Methods and compositions for the prevention and treatment of migraine

Abstract

The present disclosure relates to a nutraceutical formula regimen for the prevention and treatment of migraine. Phase-specific dietary supplements comprising vitamins, minerals, Coenzyme Q10, and herbal extracts are selectively administered during specific phases of migraine disease.

Description

METHODS AND COMPOSITIONS FOR THE PREVENTION AND TREATMENTOF MIGRAINECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 656,230, filed June 5, 2024, the entire contents of which is incorporated herein by reference for any and all purposes.TECHNICAL FIELD

[0002] The present application relates generally to methods and compositions for the treatment of migraine and the symptoms thereof. The methods and compositions relate to administration to subjects in need thereof dietary supplements effective in the prevention and treatment of migraine and symptoms thereof.INTRODUCTION

[0003] The following description is provided to assist the understanding of the reader. None of the information provided or references cited herein is admitted as being prior art to the compounds, compositions, products and / or methods disclosed herein.

[0004] The present disclosure relates to a phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement regimen with three base formulas effective for the treatment and prevention of migraine by acknowledging that migraine is an oscillating threshold condition that has different phases and therefore sensitivities (Figure 1). This is a novel approach compared to the currently prevailing approach that treats and prevents migraine with the same substance regardless of the phase of the condition.

[0005] The present disclosure further relates to a phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement regimen with three base formulas effective for the treatment and prevention of migraine by acknowledging that high-potency dietary supplement formulations are based upon the interconnectedness of high bioavailability / bioaccessibility, optimal load amount, and effective dose (Figure 2), which is not only a novel approach compared to the currently prevailing view and practice of focusing on doses alone regardless of the bioavailability of the particular ingredients but italso substantially improves the efficiency, efficacy, effectiveness, and quality of migraine treatment, prevention, and relief.

[0006] The present disclosure further relates to a phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement regimen with three base formulas effective for the treatment and prevention of migraine by acknowledging an important and often overlooked aspect of dietary supplement use, namely that while water-soluble vitamins and minerals can be consumed continuously long-term, fat soluble vitamins and herbal supplements can be consumed only intermittently, on a short-term as-needed basis, because the continuous long-term consumption of fat soluble vitamins and herbal supplements (either alone or in combination) can be hazardous to a subject’s health.

[0007] Some embodiments of the present disclosure are directed to a high-potency multivitamin dietary supplement regimen comprising one or more dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0008] Some embodiments of the present disclosure are directed to a high-potency multivitamin dietary supplement regimen comprising one or more compositions selected from the group consisting of a dietary supplement composition of Formula 1, a dietary supplement composition of Formula 2, a dietary supplement composition of Formula 3, or a combination thereof.

[0009] Some embodiments of the present disclosure are directed to a method of ameliorating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement regimen of any of the embodiments disclosed herein.

[0010] Some embodiments of the present disclosure are directed to a method of reducing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement regimen of any of the embodiments disclosed herein.

[0011] Some embodiments of the present disclosure are directed to a method of treating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement regimen of any of the embodiments disclosed herein.

[0012] Some embodiments of the present disclosure are directed to a method of preventing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement regimen of any of the embodiments disclosed herein.

[0013] Some embodiments of the present disclosure are directed to a method of raising a migraine sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement regimen of any of the embodiments disclosed herein.

[0014] Some embodiments of the present disclosure are directed to a method of maintaining a healthy brain sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement regimen of any of the embodiments disclosed herein.

[0015] Some embodiments of the present disclosure are directed to a method of maintaining overall health in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement regimen of any of the embodiments disclosed herein. Dietary supplements of the present disclosure are alternatively referred to as the Dietary Supplement Intervention.SUMMARY

[0016] In some embodiments, the present disclosure relates to a regimen for the prevention or treatment of migraine or symptoms thereof in a subject in need thereof comprising administration of a dietary supplement of Formula 1, a dietary supplement of Formula 2, and a dietary supplement of Formula 3, wherein the dietary supplements are administered to the subject in a migraine phase-specific manner. In some embodiments, the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered one or more times as needed by the subject during the attack phases of migraine. In some embodiments, the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 isadministered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered as needed by the subject during the attack phases of migraine. In some embodiments, the dietary supplement of Formula 1 comprises Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B 12, Vitamin C, Coenzyme Q10, magnesium, zinc, piperine. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg. In some embodiments, the Vitamin B9 of Formula1 is in an amount of about 0.5 mg to about 1.5 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg. In some embodiments, the Vitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg. In some embodiments, the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg. In some embodiments, the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg. In some embodiments, the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of 60 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of 150 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of 25 mg. In some embodiments, the Vitamin B9 of Formula 1 is in an amount of 1. 0 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of 0.4 mg. In some embodiments, the Vitamin C of Formula 1 is in an amount of 300 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of 24 mg. In some embodiments, the magnesium of Formula 1 is in an amount of 196 mg. In some embodiments, the zinc of Formula 1 is in an amount of 30 mg. In some embodiments, the piperine of Formula 1 is in an amount of 5. 0 mg. In some embodiments, the dietary supplement of Formula 2 comprises Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract. In some embodiments, the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg. In some embodiments, the Butterbur extract of Formula2 is in an amount of 150 mg. In some embodiments, the Feverfew extract of Formula 2 is in an amount of 200 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is inan amount of 200 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of 250 mg. In some embodiments, the dietary supplement Formula 3 comprises Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Lemon Balm extract of Formula 3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of 150 mg. In some embodiments, the Lemon Balm extract of Formula 3 is in an amount of 150 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of 60 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of 60 mg.

[0017] In some embodiments, the present disclosure relates to a method for the prevention or treatment of migraine or symptoms thereof in a subject in need thereof comprising administration of a dietary supplement of Formula 1, a dietary supplement of Formula 2, and a dietary supplement of Formula 3, wherein the dietary supplements are administered to the subject in a migraine phase-specific manner. In some embodiments, the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered one or more times as needed by the subject during the attack phases of migraine. In some embodiments, the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered as needed by the subject during the attack phases of migraine. In some embodiments, the dietary supplement of Formula 1 comprises Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin Bl 2, Vitamin C, Coenzyme Q10, magnesium, zinc, piperine. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg. In some embodiments, the Vitamin B9 of Formula 1 is in an amount of about 0.5 mg to about 1.5 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg. In some embodiments, theVitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg. In some embodiments, the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg. In some embodiments, the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg. In some embodiments, the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of 60 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of 150 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of 25 mg. In some embodiments, the Vitamin B9 of Formula 1 is in an amount of 1. 0 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of 0.4 mg. In some embodiments, the Vitamin C of Formula 1 is in an amount of 300 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of 24 mg. In some embodiments, the magnesium of Formula 1 is in an amount of 196 mg. In some embodiments, the zinc of Formula 1 is in an amount of 30 mg. In some embodiments, the piperine of Formula 1 is in an amount of 5.0 mg. In some embodiments, the dietary supplement of Formula 2 comprises Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract. In some embodiments, the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg. In some embodiments, the Butterbur extract of Formula 2 is in an amount of 150 mg. In some embodiments, wherein the Feverfew extract of Formula 2 is in an amount of 200 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is in an amount of 200 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of 250 mg. In some embodiments, the dietary supplement Formula 3 comprises Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Lemon Balm extract of Formula 3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of 150 mg. In some embodiments, the Lemon Balm extract of Formula 3 is in an amount of150 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of 60 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of 60 mg.

[0018] In some embodiments, the present disclosure relates to a method of ameliorating migraine or symptoms thereof in a subject in need thereof comprising administering to the subject a dietary supplement of Formula 1, a dietary supplement of Formula 2, and a dietary supplement of Formula 3, wherein the dietary supplements are administered to the subject in a migraine phase-specific manner. In some embodiments, the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered one or more times as needed by the subject during the attack phases of migraine. In some embodiments, the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered as needed by the subject during the attack phases of migraine. In some embodiments, the dietary supplement of Formula 1 comprises Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B 12, Vitamin C, Coenzyme Q10, magnesium, zinc, piperine. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg. In some embodiments, the Vitamin B9 of Formula 1 is in an amount of about 0.5 mg to about 1.5 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg. In some embodiments, the Vitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg. In some embodiments, the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg. In some embodiments, the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg. In some embodiments, the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of 60 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of 150 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of 25 mg. In some embodiments, the Vitamin B9 of Formula 1 is in an amount of 1. 0 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of 0.4 mg. In someembodiments, the Vitamin C of Formula 1 is in an amount of 300 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of 24 mg. In some embodiments, the magnesium of Formula 1 is in an amount of 196 mg. In some embodiments, the zinc of Formula 1 is in an amount of 30 mg. In some embodiments, the piperine of Formula 1 is in an amount of 5. 0 mg. In some embodiments, the dietary supplement of Formula 2 comprises Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract. In some embodiments, the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg. In some embodiments, the Butterbur extract of Formula 2 is in an amount of 150 mg. In some embodiments, the Feverfew extract of Formula 2 is in an amount of 200 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is in an amount of 200 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of 250 mg. In some embodiments, the dietary supplement Formula 3 comprises Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Lemon Balm extract of Formula 3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of 150 mg. In some embodiments, the Lemon Balm extract of Formula 3 is in an amount of 150 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of 60 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of 60 mg.

[0019] In some embodiments, the present disclosure relates to a dietary supplement comprising Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B12, Vitamin C, Coenzyme Q10, magnesium, zinc, and piperine. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg. In some embodiments, the Vitamin B9 of Formula 1 is in an amount of about 0.5 mg toabout 1. 5 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg. In some embodiments, the Vitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg. In some embodiments, the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg. In some embodiments, the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg. In some embodiments, the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg. In some embodiments, the Vitamin B2 of Formula 1 is in an amount of 60 mg. In some embodiments, the Vitamin B3 of Formula 1 is in an amount of 150 mg. In some embodiments, the Vitamin B6 of Formula 1 is in an amount of 25 mg. In some embodiments, the Vitamin B9 of Formula 1 is in an amount of 1. 0 mg. In some embodiments, the Vitamin B12 of Formula 1 is in an amount of 0.4 mg. In some embodiments, the Vitamin C of Formula 1 is in an amount of 300 mg. In some embodiments, the Coenzyme Q10 of Formula 1 is in an amount of 24 mg. In some embodiments, the magnesium of Formula 1 is in an amount of 196 mg. In some embodiments, the zinc of Formula 1 is in an amount of 30 mg. In some embodiments, the piperine of Formula 1 is in an amount of 5. 0 mg.

[0020] In some embodiments, the present disclosure relates to a dietary supplement comprising Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract. In some embodiments, the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg. In some embodiments, the Butterbur extract of Formula 2 is in an amount of 150 mg. In some embodiments, the Feverfew extract of Formula 2 is in an amount of 200 mg. In some embodiments, the Pinus pinaster extract of Formula 2 is in an amount of 200 mg. In some embodiments, the Grape seed extract of Formula 2 is in an amount of 250 mg.

[0021] In some embodiments, the present disclosure relates to a dietary supplement comprising Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Lemon Balm extract of Formula3 is in an amount of about 75 mg to about 225 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg. In some embodiments, the Valerian Root extract of Formula 3 is in an amount of 150 mg. In some embodiments, the Lemon Balm extract of Formula 3 is in an amount of 150 mg. In some embodiments, the Passion Flower extract of Formula 3 is in an amount of 60 mg. In some embodiments, the Hops extract of Formula 3 is in an amount of 60 mg.

[0022] In some embodiments, the present disclosure relates to a dietary supplement used for the prevention or treatment of migraine or symptoms thereof according to any of the embodiments described herein.

[0023] In some embodiments, the present disclosure relates to the use of a composition in the preparation of a medicament for treating or preventing migraine or symptoms thereof according to any of the embodiments described herein.

[0024] In some embodiments, the present disclosure relates to a kit for the prevention or treatment of migraine or symptoms thereof in a subject in need thereof comprising a dietary supplement of according to any of the embodiments described herein.

[0025] Disclosed herein is a scientific evidence-based phase-specific dietary supplement system for the prevention and treatment of migraine. The regular use of this phase-specific dietary supplement system may reduce the sole reliance on pharmaceutical migraine treatments or may reduce the size of the dose and / or frequency of the dose of pharmaceutical migraine treatments or may reduce the number of concomitant pharmaceutical treatments.

[0026] The phase-specific dietary supplement system collectively contains vitamins, minerals, Coenzyme Q, and herbal extracts including: vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin Bl 2, vitamin C, Piperine, Coenzyme Q10, a magnesium, zinc, Pinus pinaster powder or extract, grape seed powder or extract, feverfew powder or extract, pyrrolizidine alkaloids free (PA-free) butterbur powder or extract, valerian root powder or extract, lemon balm powder or extract, passionflower powder or extract, and hops powder or extract. Some embodiments disclosed herein comprise Pinus extract. Some embodiments disclosed herein comprise pine bark extract.

[0027] Embodiments of the present disclosure are directed to a phase-specific dietary supplement system comprising dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein. In some embodiments the phase-specific dietary supplement system has few of the side effects commonly associated with migraine medications. In some embodiments the phase-specific dietary supplement system has negligible amount of the side effects commonly associated with migraine medications. In some embodiments the phase-specific dietary supplement system has none of the side effects commonly associated with migraine medications.

[0028] Embodiments of the present disclosure are directed to a phase-specific dietary supplement system comprising compositions selected from the group consisting of a dietary supplement composition of Formula 1, a dietary supplement composition of Formula 2, a dietary supplement composition of Formula 3, or a combination thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 depicts the place of Formulas 1, 2, and 3 of the formula regimen as they relate to the “oscillating threshold disease” nature of migraine.

[0030] Figure 2 depicts the interconnectedness of high bioavailability / bioaccessibility, optimal load amount, and effective dose.

[0031] Figure 3 depicts the 10-50 times higher bioaccessibility and bioavailability of a combination of a) 47 mg magnesium as magnesium glycerophosphate and 149 mg magnesium as magnesium oxide versus b) 420 mg magnesium as magnesium oxide alone.

[0032] Figure 4 depicts the significantly higher bioavailability of 100 mg of Vitamin B6 with 5 mg BioPerine® versus 100 mg of vitamin B6 alone, measured as Vitamin B6 serum levels.

[0033] Figure 5 depicts the 18-times higher bioavailability of micellarized Hydro-Q- Sorb® CoQlO versus standard CoQlO powder, measured as uptake by Caco2 cells corrected for baseline natural CoQlO amounts in the cells.

[0034] Figure 6 is a chart illustrating the reduction in migraine frequency before and after using the Dietary Supplement Intervention. The results show a statistically significant improvement (Wilcoxon p = 0.0005) in migraine frequency. Notably, 75% of participantsreported a reduction in migraine episodes. The frequency distribution shifted from most subjects experiencing migraines 1-3 times per month or at least once a week prior to the intervention, to the majority reporting migraines only once every 4-6 months or 1-3 times per month afterwards, indicating a clear trend toward lower frequency categories.

[0035] Figure 7 is a chart illustrating the reduction in migraine duration before and after using the Dietary Supplement Intervention. The results show a statistically significant improvement (Wilcoxon p = 0.003) in migraine duration. Notably, 59% of participants reported a reduction in migraine duration. The frequency distribution shifted from most subjects experiencing migraines for at least half a day or at least one day prior to the intervention, to the majority reporting migraines for only not more than a couple of hours afterwards, indicating a clear trend toward the lowest duration category.

[0036] Figure 8 is a chart illustrating the reduction in migraine severity before and after using the Dietary Supplement Intervention. The results show a statistically significant improvement (Wilcoxon p = 0.0004) in migraine severity. Notably, almost all (94%) of participants reported a reduction in migraine severity. The frequency distribution shifted from most subjects experiencing migraine severity of 7 or 8 on a scale of 1 to 10 prior to the intervention, to the majority reporting migraine severity of 3 or 4 on a scale of 1 to 10 afterwards, indicating a very strong trend toward lower severity scale values.

[0037] Figure 9 is a chart highlighting the reduction in time missed from work or school due to migraine-related disability before and after using the Dietary Supplement Intervention. The results demonstrate a statistically significant decrease (Wilcoxon p = 0.0041) in time lost due to migraines. Specifically, 59% of participants reported a reduction in missed work or school days. The frequency distribution shifted from most subjects being unable to work or attend school about half the time or nearly all the time before the intervention, to the majority reporting no disability-related absences afterwards, reflecting a clear trend toward the lowest frequency category.

[0038] Figure 10 is a chart illustrating the reduction in the number of migraine symptoms they experienced before and after using the Dietary Supplement Intervention. The results show a statistically significant improvement (Wilcoxon p = 0.0013) in migraine severity. Notably, 76% of participants reported a reduction in the number of migraine symptoms they experienced. The frequency distribution shifted from most subjects experiencing 3, 4, or 5migraine symptoms prior to the intervention, to the majority reporting only 1 migraine symptom afterwards, indicating a very strong trend toward the alleviation of the number of migraine symptoms they experienced.

[0039] Figure 11 is a chart illustrating the reduction in the number of subjects reporting various migraine symptoms before and after using the Dietary Supplement Intervention. The findings reveal a statistically significant improvement (Wilcoxon p = 0.0013) in the prevalence of reported migraine symptoms. Notably, 76% of participants experienced an improvement in their symptoms. Following the intervention, the frequency of reported symptoms decreased across 10 out of 11 symptom types, underscoring a strong trend toward the alleviation of migraine-related symptoms. The highest percentage reductions were observed in the number of individuals reporting aura and those reporting being incapacitated and confined to bed.DETAILED DESCRIPTIONPhases of Migraine

[0040] The migraine condition is defined as having five phases: three attack phases, aura phase, and the interictal phase. The three attack phases are the premonitory phase, headache phase, and postdrome phase. The aura phase is present for some migraineurs but not for others and can occur during or outside of an attack phase. The interictal phase is the period between the prior postdrome phase and the new premonitory phase.

[0041] The premonitory phase is a back-and-forth interaction between these four aspects: sleep / waking / alertness, fasting / feeding cycles, mood / stress, and trigeminal pain processing. An overwhelming majority of migraineurs experience premonitory symptoms such as alterations in sleep patterns, changes in circadian rhythms, and frequency of yawning. Therefore, providing migraineurs with sleep support not only alleviates their sleep-related migraine symptoms, but also attenuates the feedback chain that ultimately leads to the headache phase. In addition, migraineurs very often experience cognitive changes, depression, stress, mood swings, anxiety, and other psychological symptoms related to disturbed hypothalamic functions. Therefore, providing migraineurs with calming herbs also disrupts the feedback chain leading towards the headache phase. Furthermore, digestive track symptoms, including bloating, belching, nausea, and vomiting are also common during migraine attack phases. The phase-specific, high-potency, high-bioavailability , and optimal load dietary supplement regimen described herein is a combination of three formulae comprised of medicinal herbs that support sleep / waking / alertness, fasting / feeding cycles, and mood / stress symptoms during the attack phases and / or aura.Premonitory Phase

[0042] The premonitory (or in another word: prodromal) phase of a migraine is the initial, early phenomena a person experiences that indicate a forthcoming migraine attack is likely, which have been linked to irregular thalamic and hypothalamic functions. The premonitory symptoms that take place in the prodromal phase may manifest a few hours, or even a few days, prior to a migraine fully developing and are unique to each individual. Estimates have suggested that up to 90% of migraineurs may experience symptoms such as alterations in sleep patterns and appetite, increased cravings, frequency of yawning, mood swings, changes in circadian rhythms, and increased general hypersensitivity to external stimuli, for example. Hypersensitivity to sounds (phonophobia) and light (photophobia) are well known nuisances not only in the headache phase, but also in the premonitory phase of migraine. In addition, loud noises and bright light also act as migraine triggers. The basis of photophobia in the premonitory phase lies in complex interactions in the spinal trigeminal nuclei, hypothalamus, thalamus, and the visual cortex. An oversensitive perception of sounds may be the result of either increased trigeminonociceptive activity (the perception of pain through the trigeminal network) or the premonitory oversensitization of pain processing brain areas.

[0043] The hypothalamic aspect of the premonitory phase includes appetite and craving, circadian rhythm and sleep regulation, and mood status and stress reaction. Hypothalamic areas control and coordinate not only the feeding / fasting networks but also the sleep / arousal cycling. One hypothalamic area senses the presence of leptin and therefore modulates appetite. Sensory input from here to other hypothalamic areas then triggers impulses towards the spinal trigeminal nucleus, integrating sleep and arousal, feeding and fasting, and pain processing functions. Additional areas in the hypothalamus perceive blood sugar levels, and when these levels are low neurons here release orexins. The function of orexins is twofold: they promote both appetite and alertness. While promoting alertness, orexin indirectly also influences trigeminal pain processing through other neural pathways.

[0044] As such, the hypothalamus connects the sleep / arousal network with the trigeminal pain network. In other words, changes in circadian rhythms (sleeping and alertness) have a mechanism to influence eating behaviors and direct and indirect links to potential pain generation systems, that ultimately lead to the headache phase of a migraine attack. In essence, the premonitory phase is a back-and-forth interaction between these four aspects: sleep / waking / alertness, fasting / feeding cycles, mood / stress, and trigeminal pain processing.Aura Phase, Cortical Spreading Depolarization

[0045] Aura phase is not present with all migraines, only a minority (about a third) of migraineurs experience auras. In addition, not only can migraine attacks occur without aura, but aura can also occur without any accompanying headache. Aura starts mostly before and rarely during or after the headache phase, and gradually disappears. Scientists have long established that cortical spreading depolarization (also known as cortical spreading depression) is closely linked to the manifestation of migraine aura and - subsequently - the headache phase of a migraine attack.

[0046] A trigger in the brainstem or peripheral nervous system probably initiates the cortical spreading depression as a slowly spreading wave of depolarization of neurons and glial cells across the cortex, at a rate of approximately 3 mm / min. This trigger is most probably a large increase in potassium (K+) ions and glutamate outside of the cells and sodium (Na+) and calcium (Ca2+) ions inside the cells, and a disturbance of connections (gap junctions) between glial cells and neurons.

[0047] Given that migraine can occur without aura, and aura can occur without any accompanying headache, it is still debated whether cortical spreading depression triggers migraine headaches. Furthermore, some migraineurs that experience aura state that pain develops contralateral (on the opposite side) to the side of the aura symptom, while others experience aura and pain on the same side, or experience aura on both sides while pain only on one side. Moreover, migraineurs can experience aura before, during, or even after the headache phase, but headache and aura can develop independently from each other. This inconsistency questions the exclusive role of cortical spreading depression in the development of migraine pain, meaning that cortical spreading depression may occur in non-aura migraine, but it can also appear and cause aura outside the headache phase.Headache Phase

[0048] The headache phase can be as short as a few hours and as long as three days. Its length and intensity are determined by pain perception: a multifaceted process involving pain mediators, pain inhibitors, prior pain experiences, and genetic predisposition to perceive sensory stimuli. There are two main players in the headache phase of migraine: the nociceptors (pain receptors) and the trigeminovascular pathway.

[0049] Migraine attacks are believed to originate in nociceptors. Under normal circumstances nociceptors are activated by “potential warning stimuli” such as infection (e.g., the presence of proinflammatory molecules), or physical damage, and trigger a range of responses: pain, nausea, photo- and phonophobia, similar to that seen in migraine. Structurally, nociceptors have axons that contain strong neuropeptide vasodilators (blood- vessel-dilating molecules) such as serotonin, neurokinin A, glutamate, calcitonin gene- related peptide (CGRP) and substance P (SP). They are found in the highest density in the blood vessels of the dura mater (meaning the outermost layer of the three membranous meninges layers that cover the brain), which are the most significant pain-producing intracranial tissues.

[0050] The trigeminovascular pathway is a system that conveys pain-related information from the meninges to central brain areas and afterwards to the cortex. The physiology and functions of the trigeminovascular system represent the inter-relationship between the trigeminal, meningeal, and central nervous system.

[0051] The headache phase starts with the activation of the trigeminal pathway in the periphery, meaning not in the brain but in the nerves outside the brain. In this process called “peripheral sensitization”, trigeminal neurons that reach into the dura mater receive stimulating impulses from the nociceptors.

[0052] These impulses are endogenous (originating from other parts of the body), and they trigger the release of strong vasodilating (blood-vessel-dilating) neuropeptides from the trigeminal nerves into the dura. These neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) are key in the development of the pain phase of migraine attacks.

[0053] CGRP, in particular, has wide-reaching activity beyond its vasoactive effects and has a critical role in the modulation of pain via the trigeminovascular system. One notable function is the stimulation of mast cells, which are involved in allergic inflammation responses through the release of histamine. CGRP also elicits the production of nitric oxide, an important vasodilation and inflammatory modulator, from the vascular endothelial cells.

[0054] During peripheral sensitization, the activated trigeminal nerves send signals to the trigeminal nucleus caudalis and its cervical extension, the trigeminocervical complex, in the brainstem. The trigeminal nucleus is effectively a “central relay hub” that can enhance and redirect signals to other parts of the brain.

[0055] As a result of the feedback from the trigeminal nucleus, other molecules, including noradrenalin, prostaglandins, and inflammatory cytokines are also released into the dura. These trigger further pain and inflammation responses of the brain membrane and causing the sensation of throbbing headache. The internal cascade response of the trigeminovascular system and the release of CGRP is known as a “sterile inflammation”, as it is an internal inflammation that has no external cause through infection.

[0056] A vicious cycle is thus established, where the trigeminal nerves respond to internal stimuli by sending signals back to the trigeminal nucleus, further releasing substance P and CGRP and triggering additional responses not only in the trigeminal nerve but also in central areas deep in the brain. In an escalating positive feedback loop via the thalamus and autonomic nervous system, called “central sensitization”, the release of serotonin and glutamate produces additional pain and inflammation responses.

[0057] As the trigeminal nucleus receives ongoing and repetitive nociceptive stimulation (meaning: constant perception of feeling pain), its neurons respond to lower threshold stimuli from additional sources, exaggerating and prolonging their response.Postdrome Phase, Interictal Phase

[0058] The postdrome phase is the period between the headache phase and the interictal phase (the latter being the phase between migraine attacks when things become “normal” again). Symptoms during the postdrome phase are similar to those during the premonitory phase: neuropsychiatric symptoms (such as confusion, difficulty with concentration, irritability), sensory (such as sensitivity to light, noises, and smells, speech disturbance),gastrointestinal symptoms (such as nausea, food cravings, thirst), and general symptoms (such as general malaise, tiredness, limited activities). Since the symptoms of medication overuse and side effects resemble symptoms of the postdrome phase, it is difficult to say which is which. The postdrome phase usually lasts between 18 and 25 hours.Migraine as a threshold condition

[0059] The migraine condition is much more than just a really bad headache. Changes in mood, appetite, and sleep / alertness, as well as changes in sensitivity to sensory experiences are also central and key components of the migraine condition.

[0060] The rapidly induced cognitive and mood changes as well as symptoms such as photophobia (sensitivity to light), phonophobia (sensitivity to sound), allodynia (feeling pain from stimuli that do not normally cause pain) all suggest a lower threshold is present in migraineurs not only compared to non-migraineurs in general, but also during the different migraine phases compared to the interictal phase (the interval between two headache attacks) in particular. As such, migraine may be understood best as an oscillating threshold condition.

[0061] Photophobia is such a specific symptom of migraine - between 80-90% of migraineurs experience photophobia during a migraine attack - that it is now one of the screening criteria for migraine diagnosis. In addition, many migraineurs also show a low threshold of light sensitivity between migraine attacks: visual discomfort was measured at 95 Lux among migraineurs compared to 200 Lux in non-migraineurs.

[0062] Sensitivity to sound is also common in migraine, with 70-83% experiencing phonophobia especially during attacks, but sometimes also between migraines. Indeed, in a study non-migraineurs experienced discomfort at 111 dB, while migraineurs at 97 dB during the interictal phase, and 82 dB during the pain phase. These data provide additional measurable evidence to the existence and oscillating nature of thresholds in migraineurs compared to non-migraineurs and within migraineurs during the attack phases compared to the interictal phases.

[0063] The finding that migraineurs with phonophobia are very likely to also have photophobia and allodynia strongly suggests that there is a single mechanism behind them. Research has identified that the response to pain stimulation of the trigeminal nucleioscillates during different phases of the migraine cycle - although of course in addition to natural daily oscillations. Neuroimaging has also shown that the hypothalamo-thalamo- brainstem network is central to the manifestation of migraine and is the most plausible source of this oscillation of pain perception, which, however, is not restricted to this network. As such, the “migraine brain” is different from the “non-migraine brain” in that certain pain processing brain networks create, process, and forward information differently.

[0064] Migraineurs already seem to have a built-in (either genetic or acquired) trait towards hypersensitivity, which though changes through the migraine phases as the sensitivity threshold decreases in the premonitory phase, bottoms during the headache phase, and increases during the postdrome phase. Thus, there are sensitivity threshold differences not only between non-migraineurs and migraineurs, but also within the same migraineurs depending on the migraine phase that they are in - See Figure 1.

[0065] As the external stimuli do not drastically change in general, the changes in stimuli perception appear to be the result of altered central processing of the signals arriving at the hypothalamus and the excitability of neurons in the linked trigeminal nerve and / or trigeminal pain-processing pathways. These changes, which appear and reappear in a cyclical fashion, may be the result of genetically determined modulation of a specific receptor or neurotransmitter transport, or changes in network connectivity. In addition, as migraineurs over their lifetime learn to associate their appearing and reappearing ailments as symptoms of migraine, there is also a notable learned component in stimuli processing.

[0066] In summary, the scientific evidence — however limited it may be — suggests that migraine attacks represent “a cycling of neuronal excitability”, leading to constantly changing sensory thresholds. More specifically, the excitability is due to another factor (e.g. malfunctioning ion channels) and the cyclical nature of changing sensory perception thresholds is due to the cyclical nature of these underlying factor(s). However, oscillations in sensory response are not unique to migraine, but migraine reflects a condition where such oscillations are expressed and perhaps enhanced by a combination of mainly genetically determined, environmentally triggered, and / or to some extent learned neuronal excitability.The interconnectedness of high bioavailability / bioaccessibility, optimal load amount, and effective dose

[0067] Pharmaceutical treatment options for migraine have only moderate efficacy for some patients and no effect for others, and their use is associated with a large prevalence of unwanted side effects. Accordingly, migraineurs seek effective alternative relief and prevention options for migraine. The embodiments described herein are directed to a phasespecific, high-potency, high-bioavailability, and optimal load dietary supplement system specific to treating the different phases (the interictal and the attack [premonitory, headache, and postdrome] phases, and aura), and that migraine is an oscillating threshold condition in that not only do migraineurs have overall lower sensory thresholds than non-migraineurs, but they also have lower thresholds compared to the interictal phase during the attack phases of the migraine, bottoming during the headache phase. In addition, this disclosure provides the necessary nutraceuticals in unprecedented best bioavailability / bioaccessibility, most efficient absorbable load amount, and least side effects combination.

[0068] A high-potency dietary supplement formulation or formulation system is based not only upon the notion that it has to be specifically formulated for a particular condition and / or phases of the particular condition based on scientific evidence, but also upon the interconnectedness of high bioavailability / bioaccessibility, optimal load amount, and effective dose (Figure 2). High bioavailability and bioaccessibility refers to how the body can access and absorb a particular substance. More specifically, bioaccessibility is the proportion of a compound that is released from the food matrix in the gastrointestinal lumen and thereby made available for intestinal absorption, and bioavailability is the proportion of a substance which is absorbed by entering the circulation when introduced into the body and thereby being able to have an active effect.

[0069] One example is the bioavailability differences of different elemental magnesium salts, despite same or higher amounts of elemental magnesium in them. A cutting edge SHIME® experimental setup compared the bioavailability of 15 different magnesium formulations and doses. The study found that that elemental magnesium provided in a combination of organic and inorganic magnesium salts (more specifically, 47 mg elemental magnesium in the form of magnesium glycerophosphate plus 149 mg elemental magnesium in the form of magnesium oxide) had 10-50 times the bioaccessibility and over 20 times the bioavailability of supplements containing only inorganic magnesium (more specifically 450 mg of elemental magnesium in form of only magnesium oxide even though it contained double the amount of elemental magnesium), and superior bioaccessibility to magnesiumcitrate (Figure 3). (Blancquaert L, Vervaet C, Derave W. Predicting and TestingBioavailability of Magnesium Supplements. Nutrients. 2019 Jul 20; 11(7): 1663, which is incorporated by reference in its entirety)

[0070] Another example is that certain additives increase the bioavailability of nutraceuticals. Piperine is one of these substances that has major bioavailability enhancing properties due to its ability to inhibit gastric emptying and gastrointestinal transit. Piperine (sold under the name Bioperine®) considerably increases the bioavailability of Vitamin B5 by increasing serum vitamin B6 levels by over 250% two hours after ingestion (Figure 4).

[0071] Moreover, the synthetic coenzyme Q10 used in supplements has a crystalline form that cannot be readily absorbed by the human body, and it has to be pulverized for consumption. Most CoQlO on the market therefore comes in powder form, which still has very little bioavailability. To change that, there are now a number of different CoQlO high- bioavailability formulations available on the market, including solubilized forms, oil dispersions, colloidal-based formulas, nano-emulsion formulations, and P-cyclodextrin powders or liquids. Hydro-Q-Sorb® (U.S. Patent No. 6,861,447, which is incorporated by reference in its entirety) is a CoQlO-y-cyclodextrin complex that has shown superior bioavailability. When corrected for endogenous levels of CoQlO, the percent cellular uptake of Hydro-Q-Sorb® relative to the standard CoQlO powder used is most CoQlO formulations on the market was 1800%, that is, 18-times as high (Figure 5). (Craft NE, Failla M: In Vitro Assessment of Coenzyme Q10 Bioavailability in Three Products using Caco-2 Cells. Tishcon research report 2006, which is incorporated by reference in its entirety)

[0072] The novelty of this invention therefore is that it utilizes two aspects of migraine treatment and prevention currently overlooked in connection with other existing dietary supplements addressing the migraine disease, namely that 1) migraine is an oscillating threshold condition that has different phases and therefore sensitivities that require different treatment regimens, and that 2) high bioavailability / bioaccessibility substantially improves the efficiency, efficacy, effectiveness, and quality of migraine treatment, prevention, and relief. Moreover, while water-soluble vitamins and minerals can be consumed continuously long-term, fat soluble vitamins and herbal supplements can be consumed only intermittently, on a short-term as-needed basis, because the continuous long-term consumption of fat soluble vitamins and herbal supplements (either alone or incombination) can be hazardous to a subject’s health, and the system of the present invention allows for the controlled consumption of vitamins, minerals, and herbal supplements in a healthy manner.

[0073] Various aspects will be described in detail hereinafter. Such aspects may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey its scope to those skilled in the art. For convenience, certain terms employed in the specification, examples, and claims are collected here. Unless defined otherwise, all technical and scientific terms used in this disclosure have the same meanings as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0074] Where a range of values is provided, it is intended that each intervening value between the lower and upper limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure. For example, if a range of 1 wt % to 8 wt % is stated, it is intended that 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, and 7 wt % are also explicitly disclosed, as well as the range of values greater than or equal to 1 wt % and the range of values less than or equal to 8 wt %.

[0075] It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural reference unless the context clearly dictates otherwise. As well, the terms “a” or “an”, “one or more” and “at least one” can be used interchangeably herein.

[0076] As used herein, the term “about” means plus or minus 20% of the numerical value of the number with which it is being used. Therefore, about 50% means in the range of 30%-70%.

[0077] The term “migraine” may refer to the neurological condition of migraine, or a migraine attack, or various phases of migraine (either ictal or interictal).

[0078] The term “administer” or other forms of administer, such as “administering” and “administration,” as used herein refers to directly administering a nutritional composition to a subject, typically orally, through feeding, or parenteral (including, but not limited to, subcutaneous, intradermal, intramuscular, intravenous, intraarticular, and intramedullary).

[0079] The term “ameliorate” or other forms of ameliorate, such as “ameliorating,” is meant to administer a dietary supplement disclosed herein or to perform a method disclosed herein in order to reduce or improve a particular characteristic or event (e.g., migraine or related symptoms).

[0080] The term “derivative,” used in the context of describing a compound or nutrient (e.g. “myricetin or derivative thereof’) refers to a chemical or biochemical modification, isomer, or analog of such molecule. The term “derivative” includes glycosides or other conjugated forms of the compound or nutrient typically found in nature or as a result of extraction or purification processes. For simplicity and clarity, “derivative” may also include the free form or aglycone form of a compound or nutrient.

[0081] As used herein, the term “dietary component” refers to a food, food product, or food group.

[0082] The term “dietary supplement” refers to any combination of compounds or micronutrients that can be administered to or taken by a subject to provide, supply, or increase the levels of vitamins, minerals, essential trace elements, amino acids, peptides, nucleic acids, oligonucleotides, lipids, cholesterols, steroids, carbohydrates, and combinations thereof. “Dietary supplement” is to be interpreted as meaning any substance, extract, or mixture of substances that: may supplement the human diet; is a concentrated source of a vitamin or mineral or other substances with a nutritional or physiological effect, alone or in combination; is taken orally as a powder, pill, capsule, tablet, food, or liquid. “Dietary supplement” offers health benefits, including reduction in the risk of a disease or health-related condition, provides a structure / function claim, or provides a nutrient claim. The term “dietary supplement” includes the definition of dietary supplements as stated by the US Food and Drug Administration (FDA), according to the Dietary Supplement Health and Education Act (DSHEA) of 1994: a dietary supplement is a product taken by mouth that contains a "dietary ingredient" intended to supplement the diet, whereas the "dietary ingredients" in these products may include vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites. Per FDA, dietary supplements can also be extracts or concentrates and may be found in many forms, such as tablets, capsules, softgels, gelcaps, liquids, or powders.

[0083] An “effective amount” of a nutritional composition is a predetermined amount calculated to achieve the desired effect, e.g., to maintain or support brain health or to prevent, reduce risk of, inhibit, block, or reverse the effect of medical, neurological or neurodegenerative condition, disorder, or disease, or decline in mental cognitive, sensory, or homeostatic qualities or capacities. The activity contemplated by the present methods includes maintenance or support of health, maintenance or support of structure or function at the cellular, tissue, or whole body levels, reduction of risk of disease, and both medical treatment and / or prophylactic treatment, as appropriate. The specific dose of a nutritional composition administered, according to the embodiments described herein, to obtain such effects will, of course, be determined by the particular circumstances surrounding the case. The desired effect may be demonstrated by any of the following alone or in combination: maintained or enhanced brain function or mental or cognitive qualities, comprising measures of cognitive ability, concentration, mental acuity, mental alertness, cognitive wellbeing, quality of life, patient reported outcomes (including but not limited to pain and malaise), sensory perception, or reduction of risk, prevention, or delay of medical, neurological or neurodegenerative condition, disorder, or disease.

[0084] The term “improve” or other forms of improve, such as “improving” or “improvement,” as used herein refers to the ability of the dietary supplement to make the subject better or healthier, e.g. to increase a subject’s mental capacity, memory, or sensory perception levels or increase levels of biomolecules or biomarkers to beneficial or optimal levels, or increase the quality of life or patient reported outcome measures.

[0085] The terms “maintain” or other forms of maintain, such as “maintenance” or “maintaining,” and “support” or other forms of support, such as “supporting,” as used herein refer to the ability of the dietary supplement to provide the necessary levels of nutrients to promote health and wellness, to keep steady-state levels, or to attain optimal levels of nutrients, biomolecules, or biomarkers to support health in the subject’s cells and tissues; such terms also refer to the ability of the dietary supplement to provide the necessary levels of nutrients to promote relevant molecular mechanisms of action (MO A), structure, and / or function at the cellular, tissue, or whole body levels for the subject. The effect of such maintenance or support may include promotion and sustainment of brain health and wellness, reduced risk of neurodegenerative disease or neuropathology, ordelayed onset or prevention of medical, neurological, or neurodegenerative condition, disorder, or disease or neuropathology.

[0086] The term “maintaining overall health” as used herein refers to promoting in an individual general good health as well as the absence of pain, discomfort, feebleness, etc. Maintaining the overall health may result in avoiding the occurrence of a migraine and / or preventing the occurrence of a migraine.

[0087] The term “migraineur” as used herein refers to an individual who suffers from migraines.

[0088] The term “migraine sensory threshold” as used herein refers to the sensory level at which a migraineur begins to become intolerant of sensory inputs and reports discomfort and / or pain. Some embodiments described herein relate to methods for raising a migraine sensory threshold in a subject. Subjects in whom a migraine sensory threshold has been raised possess an increased tolerance of pain or discomfort compared to that possessed before the sensory threshold was raised.

[0089] The term “sensory threshold” as used herein refers to the sensory level at which a person begins to become intolerant of sensory inputs and reports discomfort and / or pain. Some embodiments described herein relate to methods for raising a sensory threshold in a subject. Subjects in whom a sensory threshold has been raised possess an increased tolerance of pain or discomfort compared to that possessed before the sensory threshold was raised.

[0090] The term “healthy brain sensory threshold” as used herein to the sensory level at which a non-migraineur begins to become intolerant of sensory inputs and reports discomfort and / or pain. Some embodiments described herein relate to methods for raising a healthy brain sensory threshold in a subject. Subjects in whom a healthy brain sensory threshold has been raised possess an increased tolerance of pain or discomfort compared to that possessed before the sensory threshold was raised.

[0091] The terms “nutrient” and “micronutrient” are used interchangeably, and they refer to nutritional compounds, such as lettered vitamins, minerals, and polyphenolic compounds, such as flavonoids, which may be used as ingredients in a dietary supplement composition.

[0092] The term “herbal” or “plant based” as used herein refer to compounds derived from a plant or parts of a plant or extracts of a plant.

[0093] The term “prevent” or other forms of prevent, such as “preventing” or “prevention,” is meant to stop a particular event or characteristic, to stabilize or delay the development or progression of a particular event or characteristic, or to minimize the probability that a particular event, characteristic, or symptom will occur. Prevention does not require comparison to a control as it is typically more absolute than, for example, reduce or lower.

[0094] The terms “reduces” or “lowers,” or other forms of the words, such as “reduce,” “reducing,” “reduction,” or “lowering,” refer to a decrease in an event, characteristic, or symptom, or a decrease in the probability that a particular event, characteristic or symptom will occur.

[0095] The terms “slow” or “slowing” as used herein refers to the ability of the dietary supplement to inhibit the progression of an event, characteristic, or symptom.

[0096] As used herein, the use of the term “subject” refers to an individual. “Subject” includes a mammal, such as a primate or a human.

[0097] The terms "treat," "treated," "treating", or “treatment” as used herein refers to therapeutic treatment of an undesired physiological condition, disorder or disease, or to obtain beneficial or desired clinical results. For the purposes of the present disclosure, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms; diminishment of the extent of the condition, disorder or disease, or their symptom(s); stabilization (z.e., not worsening) of the state of the condition, disorder or disease or their symptom(s); delay in onset or slowing of the progression of the condition, disorder or disease or their symptom(s); and remission (whether partial or total), whether detectable or undetectable, or enhancement or improvement of the condition, disorder or disease or their symptom(s). Treatment includes eliciting a clinically significant response without excessive levels of side effects.

[0098] By hereby reserving the right to proviso out or exclude any individual members of any such group, including any sub-ranges or combinations of sub-ranges within the group, that can be claimed according to a range or in any similar manner, less than the full measureck this disclosure can be claimed for any reason. Further, by hereby reserving the right to proviso out or exclude any individual components, compounds, nutrients, or groups thereof, or any members of a claimed group, less than the full measure of this disclosure can be claimed for any reason.

[0099] Throughout this disclosure, various patents, patent applications, and publications may be referenced. The disclosures of these patents, patent applications, and publications in their entireties are incorporated into this disclosure by reference in order to more fully describe the state of the art as known to those skilled therein as of the date of this disclosure. This disclosure will govern in the instance that there is any inconsistency between the patents, patent applications, and publications cited and this disclosure.Dietary Supplement Compositions

[0100] Disclosed herein is a scientific evidence-based phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system.

[0101] The present disclosure is formulated in a novel way as a supplement system comprised of three base formulas that appropriately and selectively target the different phases of migraine (the interictal and the attack [premonitory, headache, and postdrome] phases, and / or aura): Formula 1 occurs continuously during the attack and interictal phases of the migraine, Formula 2 occurs continuously during the attack phases of the migraine, and Formula 3 occurs intermittently during the attack phases of the migraine (see Figure 1). Additionally, each formula may as well occur for either continuous or intermittent use in other phases that they are intended for, or in combination with other formulas within the presently disclosed formula system.

[0102] The present disclosure is formulated in a novel way to provide the best bioavailability / bioaccessibility, the most efficient absorbable load amount, and the least possible side effects.

[0103] Disclosed herein is a phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system that provides optimal load amounts of each component at non-toxic levels. The regular use of this phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system may reduce the sole reliance on pharmaceutical migraine treatments or may reduce the size of the dose and / or frequency of-Tithe dose of pharmaceutical migraine treatments or may reduce the number of concomitant pharmaceutical treatments.

[0104] The phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system collectively contains vitamins, minerals, Coenzyme Q, and herbal extracts in a high bioavailability and / or bioaccessibility manner and / or form, including: vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B 12, vitamin C, the bioavailability enhancer piperine to increase the bioavailability of the above, a high- bioavailable form of Coenzyme Q10, a high-bioavailable form of magnesium, a high- bioavailable form of zinc, Pinus pinaster powder or extract, grape seed powder or extract, feverfew powder or extract, pyrrolizidine alkaloids free (PA-free) butterbur powder or extract, valerian root powder or extract, lemon balm powder or extract, passionflower powder or extract, and hops powder or extract. Some embodiments disclosed herein comprise Pinus extract. Some embodiments disclosed herein comprise pine bark extract.

[0105] Embodiments of the present disclosure are directed to a phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprising one or more dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein. In some embodiments the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system has few of the side effects commonly associated with migraine medications. In some embodiments the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system has negligible amount of the side effects commonly associated with migraine medications. In some embodiments the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system has none of the side effects commonly associated with migraine medications.

[0106] Embodiments of the present disclosure are directed to a phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprising one or more compositions selected from the group consisting of a dietary supplement composition of Formula 1, a dietary supplement composition of Formula 2, a dietary supplement composition of Formula 3, or a combination thereof.

[0107] Disclosed herein is a scientific evidence-based phase-specific dietary supplement system for the prevention and treatment of migraine. The regular use of this phase-specificdietary supplement system may reduce the sole reliance on pharmaceutical migraine treatments or may reduce the size of the dose and / or frequency of the dose of pharmaceutical migraine treatments or may reduce the number of concomitant pharmaceutical treatments.

[0108] The phase-specific dietary supplement system collectively contains vitamins, minerals, Coenzyme Q, and herbal extracts including: vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin Bl 2, vitamin C, Piperine, Coenzyme Q10, a magnesium, zinc, Pinus pinaster powder or extract, grape seed powder or extract, feverfew powder or extract, pyrrolizidine alkaloids free (PA-free) butterbur powder or extract, valerian root powder or extract, lemon balm powder or extract, passionflower powder or extract, and hops powder or extract. Some embodiments disclosed herein comprise Pinus extract. Some embodiments disclosed herein comprise pine bark extract.

[0109] Embodiments of the present disclosure are directed to a phase-specific dietary supplement system comprising dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein. In some embodiments the phase-specific dietary supplement system has few of the side effects commonly associated with migraine medications. In some embodiments the phase-specific dietary supplement system has negligible amount of the side effects commonly associated with migraine medications. In some embodiments the phase-specific dietary supplement system has none of the side effects commonly associated with migraine medications.

[0110] Embodiments of the present disclosure are directed to a phase-specific dietary supplement system comprising compositions selected from the group consisting of a dietary supplement composition of Formula 1, a dietary supplement composition of Formula 2, a dietary supplement composition of Formula 3, or a combination thereof.Formula 1[OHl] Some embodiments of the present disclosure are directed to a dietary supplement composition of Formula 1 comprising water-soluble vitamins, natural cofactor, and minerals of Vitamin B2, Vitamin B6, Vitamin B12, Vitamin B9, Vitamin C, Coenzyme Q10, magnesium, zinc, piperine, optionally Vitamin B3, and optionally one or more additional components.

[0112] In some embodiments, the dietary supplement composition of Formula 1 is for continuous use during all phases of the migraine.

[0113] In some embodiments, the dietary supplement composition of Formula 1 is in a high potency form.

[0114] In some embodiments, the dietary supplement composition of Formula 1 is in a high bioavailability form.

[0115] In some embodiments the one or more additional components is selected from the group consisting of one or more additional water-soluble vitamins or a combination thereof.

[0116] In some embodiments of the dietary supplement composition of Formula 1, the one or more additional water-soluble vitamins is in a high bioavailability form.

[0117] In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B2 is in an amount of about 30 mg to about 90 mg, about 40 mg to about 90 mg, about 50 mg to about 90 mg, about 30 mg to about 80 mg, about 30 mg to about 70 mg, about 40 mg to about 80 mg, or about 50 mg to about 70 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Vitamin B2 is in an amount of about 60 mg. In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B2 is in a high bioavailability form.

[0118] In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B6 is in an amount of about 10 mg to about 50 mg, about 20 mg to about 50 mg, about 10 mg to about 40 mg, about 10 mg to about 30 mg, about 20 mg to about 50 mg, about 20 mg to about 40 mg, or about 20 mg to about 30 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Vitamin B6 is in an amount of about 25 mg. In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B6 is in a high bioavailability form.

[0119] In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B 12 is in an amount of about 0.2 mg to about 0.6 mg, about 0.3 mg to about 0.6 mg, about 0.2 mg to about 0.5 mg, or about 0.3 mg to about 0.5 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Vitamin B12 is in anamount of about 0.4 mg. In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B12 is in a high bioavailability form.

[0120] In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B9 is in an amount of about 0.5 mg to about 1.5 mg, about 0.75 mg to about 1.5 mg, about 0.5 mg to about 1.25 mg, or about 0.75 mg to about 1.25 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Vitamin B9 is in an amount of about 1 mg. In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B9 is in a high bioavailability form.

[0121] In some embodiments of the dietary supplement composition of Formula 1, the Vitamin C is in an amount of about 150 mg to about 450 mg, about 225 mg to about 450 mg, about 150 mg to about 375 mg, or about 225 mg to about 375 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Vitamin C is in an amount of about 300 mg. In some embodiments of the dietary supplement composition of Formula 1, the Vitamin C is in a high bioavailability form.

[0122] In some embodiments of the dietary supplement composition of Formula 1, the Coenzyme Q10 is in an amount of about 12 mg to about 180 mg, about 60 mg to about 180 mg, about 90 mg to about 180 mg, about 60 mg to about 120 mg, or about 90 mg to about 120 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Coenzyme Q10 is in an amount of about 120 mg. In some embodiments of the dietary supplement composition of Formula 1, the Coenzyme Q10 is in an amount of about 12 mg to about 36 mg, about 18 mg to about 36 mg, about 12 mg to about 24 mg, or about 18 mg to about 24 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Coenzyme Q10 is in an amount of about 24 mg. In some embodiments of the dietary supplement composition of Formula 1, the Coenzyme Q10 is in a high bioavailability form.

[0123] In some embodiments of the dietary supplement composition of Formula 1, the magnesium is in an amount of about 100 mg to about 300 mg, about 125 mg to about 300 mg, about 150 mg to about 300 mg, about 175 mg to about 300 mg, about 100 mg to about 275 mg, about 100 mg to about 250 mg, about 100 mg to about 225 mg, or about 175 mg to about 225 mg. In certain embodiments of the dietary supplement composition of Formula 1, the magnesium is in an amount of about 196 mg. In some embodiments of the dietary supplement composition of Formula 1, the magnesium is in a high bioavailability form.

[0124] In some embodiments of the dietary supplement composition of Formula 1, the magnesium is in the form of magnesium glycerophosphate. In some embodiments of the dietary supplement composition of Formula 1, the magnesium is in the form of magnesium oxide. In some embodiments of the dietary supplement composition of Formula 1, the magnesium is in the form of magnesium glycerophosphate and in the form of magnesium oxide. In some embodiments of the dietary supplement composition of Formula 1, the molar ratio of magnesium in the form of magnesium glycerophosphate to magnesium in the form of magnesium oxide is about 1 : 1, about 1 :2, about 1 :3, about 1 :4, about 1 :5, about 1 :6, about 1 :7, about 1 :8, about 1 :9, about 9: 1, about 8: 1, about 7: 1, about 6: 1, about 5: 1, about 4: 1, about 3: 1, or about 2: 1. In certain embodiments of the dietary supplement composition of Formula 1, the ratio of magnesium in the form of magnesium glycerophosphate to magnesium in the form of magnesium oxide is about 1 :3.17.

[0125] In some embodiments of the dietary supplement composition of Formula 1, the magnesium in the form of magnesium glycerophosphate is in an amount of about 25 mg to about 75 mg, about 35 mg to about 75 mg, about 25 mg to about 65 mg, about 25 mg to about 55 mg, or about 35 mg to about 55 mg. In certain embodiments of the dietary supplement composition of Formula 1, the magnesium in the form of magnesium glycerophosphate is in an amount of about 47 mg. In some embodiments of the dietary supplement composition of Formula 1, the magnesium in the form of magnesium glycerophosphate is in a high bioavailability form.

[0126] In some embodiments of the dietary supplement composition of Formula 1, the magnesium in the form of magnesium oxide is in an amount of about 75 mg to about 225 mg, about 100 mg to about 225 mg, about 125 mg to about 225 mg, about 75 mg to about 200 mg, about 75 mg to about 175 mg, about 100 mg to about 200 mg, or about 125 mg to about 175 mg. In certain embodiments of the dietary supplement composition of Formula 1, the magnesium in the form of magnesium oxide is in an amount of about 149 mg. In some embodiments of the dietary supplement composition of Formula 1, the magnesium in the form of magnesium oxide is in a high bioavailability form.

[0127] In some embodiments of the dietary supplement composition of Formula 1, the zinc is in an amount of about 15 mg to about 45 mg, about 20 mg to about 45 mg, about 25 mg to about 45 mg, about 15 mg to about 40 mg, about 15 mg to about 35 mg, about 20 mg to about 40 mg, or about 25 mg to about 35 mg. In certain embodiments of the dietarysupplement composition of Formula 1, the zinc is in an amount of about 30 mg. In some embodiments of the dietary supplement composition of Formula 1, the zinc is in a high bioavailability form.

[0128] In some embodiments of the dietary supplement composition of Formula 1, the zinc is zinc citrate. In some embodiments of the dietary supplement composition of Formula 1, the zinc citrate is in a high bioavailability form.

[0129] In some embodiments of the dietary supplement composition of Formula 1, the piperine is in an amount of about 2 mg to about 8 mg, about 3 mg to about 8 mg, about 4 mg to about 8 mg, about 2 mg to about 7 mg, about 2 mg to about 6 mg, about 3 mg to about 7 mg, or about 4 mg to about 6 mg. In certain embodiments of the dietary supplement composition of Formula 1, the piperine is in an amount of about 5 mg. In some embodiments of the dietary supplement composition of Formula 1, the piperine is in a high bioavailability form.

[0130] In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B3, in any derivative, is in an amount of about 75 mg to about 225 mg, about 100 mg to about 225 mg, about 125 mg to about 225 mg, about 75 mg to about 200 mg, about 75 mg to about 175 mg, about 100 mg to about 200 mg, or about 125 mg to about 175 mg. In certain embodiments of the dietary supplement composition of Formula 1, the Vitamin B3 is in an amount of about 150 mg. In some embodiments of the dietary supplement composition of Formula 1, the Vitamin B3, in any derivative, is in a high bioavailability form.Formula 2

[0131] Some embodiments of the present disclosure are directed to a dietary supplement composition of Formula 2 comprising herbal ingredients — separately from the water- soluble vitamins, natural cofactor, and minerals in Formula 1 for consumer safety reasons — of Butterbur extract, Feverfew extract, Pinus pinaster extract, Grape seed extract, and optionally one or more additional components.

[0132] In some embodiments, the dietary supplement composition of Formula 2 is for continuous use during the attack phase of the migraine.

[0133] In some embodiments, the dietary supplement composition of Formula 2 is in a high potency form.

[0134] In some embodiments, the dietary supplement composition of Formula 2 is in a high bioavailability form.

[0135] In some embodiments the one or more additional components is selected from the group consisting of one or more fat soluble vitamins or a combination thereof.

[0136] In some embodiments the one or more fat soluble vitamins is in a high bioavailability form.

[0137] In some embodiments of the dietary supplement composition of Formula 2, the Butterbur extract is in an amount of about 75 mg to about 225 mg, about 100 mg to about 225 mg, about 125 mg to about 225 mg, about 75 mg to about 200 mg, about 75 mg to about 175 mg, about 100 mg to about 200 mg, or about 125 mg to about 175 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Butterbur extract is in an amount of about 150 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Butterbur extract contains a minimum of about 5% petasins, about 10% petasins, about 15% petasins, about 20% petasins, or about 25% petasins. In some embodiments of the dietary supplement composition of Formula 2, the Butterbur extract is in a high bioavailability form.

[0138] In some embodiments of the dietary supplement composition of Formula 2, the Feverfew extract is in an amount of about 100 mg to about 300 mg, about 125 mg to about 300 mg, about 150 mg to about 300 mg, about 175 mg to about 300 mg, about 100 mg to about 275 mg, about 100 mg to about 250 mg, about 100 mg to about 225 mg, about 125 mg to about 275 mg, about 150 mg to about 250 mg, or about 175 mg to about 225 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Feverfew extract is in an amount of about 200 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Feverfew extract contains at least about 0.1% parthenolide, at least about 0.2% parthenolide, at least about 0.3% parthenolide, at least about 0.4% parthenolide, at least about 0.5% parthenolide, at least about 0.6% parthenolide, at least about 0.7% parthenolide, at least about 0.8% parthenolide, at least about 0.9% parthenolide, or at least about 1.0% parthenolide. In some embodiments of the dietary supplement composition of Formula 2, the Feverfew extract is in a high bioavailability form.

[0139] In some embodiments of the dietary supplement composition of Formula 2, the Pinus pinaster extract is in an amount of about 100 mg to about 300 mg, about 125 mg to about 300 mg, about 150 mg to about 300 mg, about 175 mg to about 300 mg, about 100 mg to about 275 mg, about 100 mg to about 250 mg, about 100 mg to about 225 mg, about 125 mg to about 275 mg, about 150 mg to about 250 mg, or about 175 mg to about 225 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Pinus pinaster extract is in an amount of about 200 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Pinus pinaster extract contains about 45% proanthocyanidins, about 50% proanthocyanidins, about 55% proanthocyanidins, about 60% proanthocyanidins, about 65% proanthocyanidins, about 70% proanthocyanidins, about 75% proanthocyanidins, about 80% proanthocyanidins, or about 85% proanthocyanidins. In some embodiments of the dietary supplement composition of Formula 2, the Pinus pinaster extract is in a high bioavailability form.

[0140] In some embodiments of the dietary supplement composition of Formula 2, the Grape seed extract is in an amount of about 125 mg to about 375 mg, about 150 mg to about 375 mg, about 175 mg to about 375 mg, about 200 mg to about 375 mg, about 225 mg to about 375 mg, about 125 mg to about 350 mg, about 125 mg to about 325 mg, about 125 mg to about 300 mg, about 125 mg to about 275 mg, about 250 mg to about 350 mg, about 275 mg to about 325 mg, or about 200 mg to about 300 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Grape seed extract is in an amount of about 250 mg. In certain embodiments of the dietary supplement composition of Formula 2, the Grape seed extract contains at least about 75% proanthocyanidins, about 80% proanthocyanidins, about 85% proanthocyanidins, about 90% proanthocyanidins, about 95% proanthocyanidins, about 97.5% proanthocyanidins, or about 99% proanthocyanidins. In some embodiments of the dietary supplement composition of Formula 2, the Grape seed extract is in a high bioavailability form.Formula 3

[0141] Some embodiments of the present disclosure are directed to a dietary supplement composition of Formula 3 comprising herbal ingredients — separately from the water- soluble vitamins, natural cofactor, and minerals in Formula 1 for consumer safety reasons — of Valerian Root extract, Lemon Balm extract, Passion Flower extract, Hops extract, and optionally one or more additional components.

[0142] In some embodiments, the dietary supplement composition of Formula 3 is for intermittent use during the attack phase of the migraine.

[0143] In some embodiments, the dietary supplement composition of Formula 3 is in a high potency form.

[0144] In some embodiments, the dietary supplement composition of Formula 3 is in a high bioavailability form.

[0145] In some embodiments of the dietary supplement composition of Formula 3, the Valerian Root extract is in an amount of about 75 mg to about 225 mg, about 100 mg to about 225 mg, about 125 mg to about 225 mg, about 75 mg to about 200 mg, about 75 mg to about 175 mg, about 100 mg to about 200 mg, or about 125 mg to about 175 mg. In certain embodiments of the dietary supplement composition of Formula 3, the Valerian Root extract is in an amount of about 150 mg. In some embodiments of the dietary supplement composition of Formula 3, the Valerian Root extract is in a high bioavailability form.

[0146] In some embodiments of the dietary supplement composition of Formula 3, the Lemon Balm extract is in an amount of about 75 mg to about 225 mg, about 100 mg to about 225 mg, about 125 mg to about 225 mg, about 75 mg to about 200 mg, about 75 mg to about 175 mg, about 100 mg to about 200 mg, or about 125 mg to about 175 mg. In certain embodiments of the dietary supplement composition of Formula 3, the Lemon Balm extract is in an amount of about 150 mg. In some embodiments of the dietary supplement composition of Formula 3, the Lemon Balm extract is in a high bioavailability form.

[0147] In some embodiments of the dietary supplement composition of Formula 3, the Passion Flower extract is in an amount of about 30 mg to about 90 mg, about 40 mg to about 90 mg, about 50 mg to about 90 mg, about 30 mg to about 80 mg, about 30 mg to about 70 mg, about 40 mg to about 80 mg, or about 50 mg to about 70 mg. In certain embodiments of the dietary supplement composition of Formula 3, the Passion Flower extract is in an amount of about 60 mg. In some embodiments of the dietary supplement composition of Formula 3, the Passion Flower extract is in a high bioavailability form.

[0148] In some embodiments of the dietary supplement composition of Formula 3, the Hops extract is in an amount of about 30 mg to about 90 mg, about 40 mg to about 90 mg,about 50 mg to about 90 mg, about 30 mg to about 80 mg, about 30 mg to about 70 mg, about 40 mg to about 80 mg, or about 50 mg to about 70 mg. In certain embodiments of the dietary supplement composition of Formula 3, the Hops extract is in an amount of about 60 mg. In some embodiments of the dietary supplement composition of Formula 3, the Hops extract is in a high bioavailability form.Formula 4

[0149] Some embodiments of the present disclosure are directed to a dietary supplement composition of Formula 4 comprising the dietary supplement composition of Formula 1 of any embodiment disclosed herein, the dietary supplement composition of Formula 2 of any embodiment disclosed herein, and the dietary supplement composition of Formula 3 of any embodiment disclosed herein.

[0150] In some embodiments, the dietary supplement composition of Formula 4 is in a high potency form.

[0151] In some embodiments, the dietary supplement composition of Formula 4 is in a high bioavailability form.Formula 5

[0152] Some embodiments of the present disclosure are directed to a dietary supplement composition of Formula 5 comprising the dietary supplement composition of Formula 1 of any embodiment disclosed herein and the dietary supplement composition of Formula 2 of any embodiment disclosed herein.

[0153] In some embodiments, the dietary supplement composition of Formula 5 is in a high potency form.

[0154] In some embodiments, the dietary supplement composition of Formula 5 is in a high bioavailability form.Formula 6

[0155] Some embodiments of the present disclosure are directed to a dietary supplement composition of Formula 6 comprising the dietary supplement composition of Formula 1 ofany embodiment disclosed herein and the dietary supplement composition of Formula 3 of any embodiment disclosed herein.

[0156] In some embodiments, the dietary supplement composition of Formula 6 is in a high potency form.

[0157] In some embodiments, the dietary supplement composition of Formula 6 is in a high bioavailability form.Formula 7

[0158] Some embodiments of the present disclosure are directed to a dietary supplement composition of Formula 7 comprising the dietary supplement composition of Formula 2 of any embodiment disclosed herein and the dietary supplement composition of Formula 3 of any embodiment disclosed herein.

[0159] In some embodiments, the dietary supplement composition of Formula 7 is in a high potency form.

[0160] In some embodiments, the dietary supplement composition of Formula 7 is in a high bioavailability form.

[0161] In some embodiments, the dietary supplement compositions according to the Formulae as described herein further comprise a component to improve bioavailability. In some embodiments, the component to improve bioavailability is selected from the group consisting of a food complex, whole food matrix, delayed or controlled release technology, multi-compartment capsules or capsule-in-capsule technology, phytosome or liposome technology, nano technology, oil dispersion, crystalline formulation, solubilized formulation, colloidal-based formulation, amino acid functionalization or chelation functionalization, partition or division of oil-soluble components from the remaining components (e.g. oil-soluble components in a softgel(s) and remaining components in a two-piece capsule(s)), cyclodextrin or other encapsulation technologies.

[0162] In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated as an immediate release composition. In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated as a timed-release composition. In some embodiments, the dietarysupplement compositions according to the Formulae as described herein are formulated as a sustained release composition.

[0163] In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated as a once a day composition, a twice a day composition, a three times a day composition, an every other day composition, a once a week composition, a bi-weekly composition, or a monthly composition.

[0164] In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated as a dosage form selected from the group consisting of pill, tablet, caplet, soft gelatin or vegetarian capsule, hard gelatin or vegetarian capsule, lozenge, sachet, cachet, veggie cap, liquid drop, liquid, gel, slurry, elixirs, suspensions, emulsions, solutions, dragee, syrups, concentrated food product (for example, supplement bar), gummies, effervescent tablets, other edibles, and tea bags.

[0165] In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated as an injectable dosage form. In some embodiments the injectable dosage form is a subcutaneous injectable dosage form. In some embodiments the injectable dosage form is an intravenous injectable dosage form. In some embodiments the injectable dosage form is an intramuscular injectable dosage form. In some embodiments the injectable dosage form is an intradermal injectable dosage form.

[0166] In some embodiments, the dietary supplement compositions according to the Formulae as described herein are a liquid, lyophilized, or otherwise dried. In some embodiments, the dietary supplement compositions according to the Formulae as described herein include diluents of various buffer content (e.g., Tris-HCl, acetate, phosphate), pH and ionic strength, additives such as albumin or gelatin to prevent absorption to surfaces, detergents (e.g., Tween 20, Tween 80, Pluronic F68, bile acid salts), solubilizing agents (e.g., glycerol, polyethylene glycerol), anti-oxidants (e.g., ascorbic acid, sodium metabisulfite), preservatives (e.g., Thimerosal, benzyl alcohol, parabens), bulking substances or tonicity modifiers (e.g., lactose, mannitol), covalent attachment of polymers such as polyethylene glycol, complexation with metal ions, or incorporation of the material into or onto particulate preparations of polymeric compounds such as polylactic acid, polyglycolic acid, or hydrogels, or onto liposomes, microemulsions, micelles, lamellar or multilamellar vesicles, erythrocyte ghosts or spheroplasts. Such compositions will influencethe physical state, solubility, stability, rate of in vivo release, and rate of in vivo clearance. Controlled or sustained release compositions include formulations in lipophilic depots (e.g., fatty acids, waxes, oils).

[0167] The dietary supplement compositions according to the Formulae as described herein described herein are for oral administration and can be formulated readily by combining the components with acceptable carriers well known in the art. Dietary supplement compositions according to the Formulae as described herein for oral administration can be obtained by adding a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients include, but are not limited to, fillers such as sugars, including, but not limited to, lactose, sucrose, mannitol, and sorbitol; cellulose preparations such as, but not limited to, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidone (PVP). If desired, disintegrating agents can be added, such as, but not limited to, the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

[0168] Dragee cores can be provided with suitable coatings. For this purpose, concentrated sugar solutions can be used, which can optionally contain gum Arabic, talc, polyvinyl pyrrolidone, Carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments can be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

[0169] Dietary supplement compositions according to the Formulae as described herein may also be formulated as push-fit capsules made of gelatin or sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in an admixture with a filler such as lactose, binders, starches, lubricants, talc, magnesium stearate or stabilizers. In soft capsules, the active compounds can be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers can be added.

[0170] In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated to deliver the daily dose in a singleformulation. In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated to partition the daily dose of nutrients into separate dosage units (for example, some nutrients are contained in one capsule, while the remaining nutrients are contained in a second capsule). In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated to deliver a fraction of the daily dose and will be administered two or more times per day. In some embodiments, the dietary supplement compositions according to the Formulae as described herein are formulated to deliver a dose equal to about half of a daily dose and will be administered twice per day. In some embodiments, the dose is administered every about 12 hours.Methods

[0171] The dietary supplements administered in the following methods are as described herein.

[0172] Embodiments of the present disclosure are directed to a method of ameliorating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system of any of the embodiments disclosed herein.

[0173] Embodiments of the present disclosure are directed to a method of ameliorating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0174] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein.

[0175] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodimentsproviding to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs as needed.

[0176] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously during all phases of the migraine.In some embodiments of the method of ameliorating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein.

[0177] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject thedietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs as needed.

[0178] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously during the attack phase of the migraine.

[0179] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein.

[0180] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of

[0181] the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject thedietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs as needed.

[0182] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs intermittently during the attack phase of the migraine.

[0183] Embodiments of the present disclosure are directed to a method of ameliorating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments disclosed herein.

[0184] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein.

[0185] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments asdisclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs as needed.

[0186] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0187] Embodiments of the present disclosure are directed to a method of ameliorating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments disclosed herein.

[0188] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein.

[0189] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject thedietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs as needed.

[0190] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0191] Embodiments of the present disclosure are directed to a method of ameliorating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments disclosed herein.

[0192] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein.

[0193] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosedherein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs as needed.

[0194] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0195] Embodiments of the present disclosure are directed to a method of ameliorating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments disclosed herein.

[0196] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein.

[0197] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietarysupplement composition of Formula 7 of any of the embodiments as disclosed herein occurs as needed.

[0198] In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of ameliorating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0199] In some embodiments of the method of ameliorating a migraine in a subject in need thereof results in the reduction in the frequency of migraines.

[0200] Embodiments of the present disclosure are directed to a method of reducing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system of any of the embodiments disclosed herein.

[0201] Embodiments of the present disclosure are directed to a method of reducing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0202] In some embodiments of the method of reducing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein.

[0203] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of theembodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs as needed.

[0204] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously during all phases of the migraine.

[0205] In some embodiments of the method of reducing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein.

[0206] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosedherein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs as needed.

[0207] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously during the attack phase of the migraine.

[0208] In some embodiments of the method of reducing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein.

[0209] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs as needed.

[0210] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs intermittently during the attack phase of the migraine.

[0211] Embodiments of the present disclosure are directed to a method of reducing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments disclosed herein.

[0212] In some embodiments of the method of reducing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein.

[0213] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs as needed.

[0214] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0215] Embodiments of the present disclosure are directed to a method of reducing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments disclosed herein.

[0216] In some embodiments of the method of reducing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein.

[0217] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs as needed.

[0218] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any ofthe embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0219] Embodiments of the present disclosure are directed to a method of reducing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments disclosed herein.

[0220] In some embodiments of the method of reducing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein.

[0221] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs as needed.

[0222] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of themigraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0223] Embodiments of the present disclosure are directed to a method of reducing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments disclosed herein.

[0224] In some embodiments of the method of reducing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein.

[0225] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs as needed.

[0226] In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof.In some embodiments of the method of reducing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0227] In some embodiments of the method of reducing a migraine in a subject in need thereof results in the reduction in the frequency of migraines.

[0228] Embodiments of the present disclosure are directed to a method of treating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system of any of the embodiments disclosed herein.

[0229] Embodiments of the present disclosure are directed to a method of treating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0230] In some embodiments of the method of treating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein.

[0231] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs as needed.

[0232] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously during all phases of the migraine.

[0233] In some embodiments of the method of treating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein.

[0234] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs as needed.

[0235] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of themigraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously during the attack phase of the migraine.

[0236] In some embodiments of the method of treating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein.

[0237] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs as needed.

[0238] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of theembodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs intermittently during the attack phase of the migraine.

[0239] Embodiments of the present disclosure are directed to a method of treating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments disclosed herein.

[0240] In some embodiments of the method of treating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein.

[0241] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs as needed.

[0242] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of treating a migraine in a subject in need thereof,providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0243] Embodiments of the present disclosure are directed to a method of treating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments disclosed herein.

[0244] In some embodiments of the method of treating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein.

[0245] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs as needed.

[0246] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0247] Embodiments of the present disclosure are directed to a method of treating a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments disclosed herein.

[0248] In some embodiments of the method of treating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein.

[0249] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs as needed.

[0250] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0251] Embodiments of the present disclosure are directed to a method of treating a migraine in a subject in need thereof, wherein the method comprises providing to thesubject the dietary supplement composition of Formula 7 of any of the embodiments disclosed herein.

[0252] In some embodiments of the method of treating a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein.

[0253] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs as needed.

[0254] In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of treating a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0255] In some embodiments of the method of treating a migraine in a subject in need thereof results in the reduction in the frequency of migraines.

[0256] Embodiments of the present disclosure are directed to a method of preventing a migraine in a subject in need thereof, wherein the method comprises providing to thesubject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system of any of the embodiments disclosed herein.

[0257] Embodiments of the present disclosure are directed to a method of preventing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0258] In some embodiments of the method of preventing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein.

[0259] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs as needed.

[0260] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In someembodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously during all phases of the migraine.

[0261] In some embodiments of the method of preventing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein.

[0262] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs as needed.

[0263] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously during the attack phase of the migraine.

[0264] In some embodiments of the method of preventing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein.

[0265] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs as needed.

[0266] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs intermittently during the attack phase of the migraine.

[0267] Embodiments of the present disclosure are directed to a method of preventing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments disclosed herein.

[0268] In some embodiments of the method of preventing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein.

[0269] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs as needed.

[0270] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0271] Embodiments of the present disclosure are directed to a method of preventing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments disclosed herein.

[0272] In some embodiments of the method of preventing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability,and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein.

[0273] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs as needed.

[0274] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0275] Embodiments of the present disclosure are directed to a method of preventing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments disclosed herein.

[0276] In some embodiments of the method of preventing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein.

[0277] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs as needed.

[0278] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0279] Embodiments of the present disclosure are directed to a method of preventing a migraine in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments disclosed herein.

[0280] In some embodiments of the method of preventing a migraine in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein.

[0281] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any ofthe embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs as needed.

[0282] In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of preventing a migraine in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0283] Embodiments of the present disclosure are directed to a method of raising a migraine sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system of any of the embodiments disclosed herein.

[0284] Embodiments of the present disclosure are directed to a method of raising a migraine sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0285] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to thesubject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein.

[0286] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs as needed.

[0287] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously during all phases of the migraine.

[0288] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein.

[0289] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs as needed.

[0290] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously during the attack phase of the migraine.

[0291] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein.

[0292] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition ofFormula 3 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs as needed.

[0293] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs intermittently during the attack phase of the migraine.

[0294] Embodiments of the present disclosure are directed to a method of raising a migraine sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments disclosed herein.

[0295] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein.

[0296] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs as needed.

[0297] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0298] Embodiments of the present disclosure are directed to a method of raising a migraine sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments disclosed herein.

[0299] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein.

[0300] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs as needed.

[0301] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0302] Embodiments of the present disclosure are directed to a method of raising a migraine sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments disclosed herein.

[0303] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein.

[0304] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs as needed.

[0305] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0306] Embodiments of the present disclosure are directed to a method of raising a migraine sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments disclosed herein.

[0307] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein.

[0308] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs as needed.

[0309] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0310] In some embodiments of the method of raising a migraine sensory threshold in a subject in need thereof results in the reduction in the frequency of migraines.

[0311] Embodiments of the present disclosure are directed to a method of maintaining a healthy brain sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system of any of the embodiments disclosed herein.

[0312] Embodiments of the present disclosure are directed to a method of maintaining a healthy brain sensory threshold in a subject in need thereof, wherein the method comprisesproviding to the subject the dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0313] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein.

[0314] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs as needed.

[0315] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously during all phases of the migraine.

[0316] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein.

[0317] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs as needed.

[0318] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously during the attack phase of the migraine.

[0319] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high--n-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein.

[0320] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs as needed.

[0321] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs intermittently during the attack phase of the migraine.

[0322] Embodiments of the present disclosure are directed to a method of maintaining a healthy brain sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments disclosed herein.

[0323] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein.

[0324] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs as needed.

[0325] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0326] Embodiments of the present disclosure are directed to a method of maintaining a healthy brain sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments disclosed herein.

[0327] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein.

[0328] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs as needed.

[0329] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0330] Embodiments of the present disclosure are directed to a method of maintaining a healthy brain sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments disclosed herein.

[0331] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein.

[0332] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs as needed.

[0333] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0334] Embodiments of the present disclosure are directed to a method of maintaining a healthy brain sensory threshold in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments disclosed herein.

[0335] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, the providing to the subject the phase-specific, high- potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein.

[0336] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs as needed.

[0337] In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs during the attack phases of the migraine, occurs during the premonitory phase of the migraine, occurs during the headache phase of the migraine, occurs during the postdrome phase of the migraine, occurs during the aura phase of the migraine, occurs during the interictal phase of the migraine, or a combination thereof. In some embodiments of the method of maintaining a healthy brain sensory threshold in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs throughout all phases of the migraine.

[0338] Embodiments of the present disclosure are directed to a method of maintaining overall health in a subject in need thereof, wherein the method comprises providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system of any of the embodiments disclosed herein.

[0339] Embodiments of the present disclosure are directed to a method of maintaining overall health in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement compositions according to the Formulae of any of the embodiments disclosed herein.

[0340] In some embodiments of the method of maintaining overall health in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein.

[0341] In some embodiments of the method of maintaining overall health in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 1 of any of the embodiments as disclosed herein occurs as needed.

[0342] In some embodiments of the method of maintaining overall health in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein.

[0343] In some embodiments of the method of maintaining overall health in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of theembodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 2 of any of the embodiments as disclosed herein occurs as needed.

[0344] In some embodiments of the method of maintaining overall health in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein.

[0345] In some embodiments of the method of maintaining overall health in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 3 of any of the embodiments as disclosed herein occurs as needed.

[0346] Embodiments of the present disclosure are directed to a method of maintaining overall health in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments disclosed herein.

[0347] In some embodiments of the method of maintaining overall health in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to thesubject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein.

[0348] In some embodiments of the method of maintaining overall health in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 4 of any of the embodiments as disclosed herein occurs as needed.

[0349] Embodiments of the present disclosure are directed to a method of maintaining overall health in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments disclosed herein.

[0350] In some embodiments of the method of maintaining overall health in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein.

[0351] In some embodiments of the method of maintaining overall health in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject thedietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 5 of any of the embodiments as disclosed herein occurs as needed.

[0352] Embodiments of the present disclosure are directed to a method of maintaining overall health in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments disclosed herein.

[0353] In some embodiments of the method of maintaining overall health in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high- bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein.

[0354] In some embodiments of the method of maintaining overall health in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 6 of any of the embodiments as disclosed herein occurs as needed.

[0355] Embodiments of the present disclosure are directed to a method of maintaining overall health in a subject in need thereof, wherein the method comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments disclosed herein.

[0356] In some embodiments of the method of maintaining overall health in a subject in need thereof, the providing to the subject the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system comprises providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein.

[0357] In some embodiments of the method of maintaining overall health in a subject in need thereof, providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day, twice a day, three times a day, every other day, once a week, continuously, or as needed. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs once a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs twice a day. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs continuously. In certain embodiments providing to the subject the dietary supplement composition of Formula 7 of any of the embodiments as disclosed herein occurs as needed.ExamplesExample 1 : Dietary supplement formulations

[0358] The following are examples of dietary supplement compositions according to the Formulae as described herein, containing the following components in at least the amounts indicated. The dietary supplement may be presented in capsule form, powder form or other forms as previously described.Example Formula 1 :Example Formula 2:Example Formula 3 :Example 2: Use of the phase-specific, high-potency, high-bioavailability, and optimal load dietary supplement system on a migraineur.

[0359] The inventor has suffered from both episodic and chronic migraines for almost 30 years. She has tried a large number of migraine medications, including a range of NSAIDs, triptans, and opioids. As such, she has experienced an array of medication side effects, not to mention rebound headaches due to migraine medication overuse. Eventually, she had at least one or two migraine episodes per month and was in bed and incapacitated for between 48 and 72 hours during each migraine episode. Overall, her migraine disease amounted toabout 5-6 full days each month of complete bed-ridden incapacitation with excruciating head pain and a large number of severe non-pain migraine symptoms, including severe gastrointestinal symptoms and exacerbated sensitivity to light, sound, and touch.

[0360] She devised the invention and started taking the combination as individual pills or capsules, but in the same dose as described in the present disclosure. For the first three months she had no migraines. During month #4, she had a migraine attack that lasted only for three hours (instead of three days) and had the fraction of the pain intensity of her usual migraines, accompanied by just a fraction of non-pain symptoms. During month #6 she had another migraine attack that lasted for merely two hours, with virtually no non-pain symptoms. She was then completely migraine free between month #6 month #12, at the time of this patent application.

[0361] She has been taking the combination as described in the present disclosure for the past four years, and she is virtually migraine-free.

[0362] When she travels and does not have access to the combination as described in the present disclosure for an extended period of time, her migraines return, only to go away when she starts taking again the combination as described in the present disclosure.

[0363] During the month before she started taking the supplement system described in this present disclosure, she had a long flight with a 6-hour jetlag, which lead to a three-day incapacitation due to migraine each way, which she typically experienced after long flights and several hours of jet lags. Eleven months after she started taking the supplement system described in this present disclosure, she had another long flight with a 6-hour jetlag. This time, however, she did not experience any pain or non-pain migraine symptoms whatsoever.Example 3: Use of the dietary supplements of the present disclosure for the prevention and treatment of migraine.

[0364] This example demonstrates the use of dietary supplements of the present disclosure for the prevention and treatment of migraine in multiple individuals.Case 1

[0365] A 68-y ear-old female reported experiencing migraines 1-3 times a month before trying the Dietary Supplement Intervention. Her average migraine attacks lasted no morethan a couple of hours, with a severity rating of 5 on a scale of 1 to 10. She did not need to take time off from work or school during these episodes. Her primary symptom was a headache, with only one symptom per episode. She did not consult any specialists for her migraines and used Tylenol and Tramadol as her medications.

[0366] After starting the Dietary Supplement Intervention, her migraine frequency decreased to once every 4-6 months, while the duration of her attacks remained unchanged — lasting no more than a couple of hours. The severity of her symptoms decreased to 3 on a scale of 1 to 10. She continued not requiring time off from work or school due to migraines. Her only symptom remained a headache, and the number of symptoms she experienced per episode stayed at one.Case 2

[0367] A 22-y ear-old male reported experiencing migraines 1-2 times a year before trying the Dietary Supplement Intervention. These attacks lasted no more than a couple of hours, with a severity rating of 3 on a scale of 1 to 10. He did not need to take time off from work or school due to these episodes. His symptoms included headache, sensitivity to light, and a general feeling of malaise, with three symptoms per episode. He did not consult a specialist and relied on general painkillers for relief.

[0368] After using the Dietary Supplement Intervention, his migraines decreased to less than once a year, with the duration of the attacks remaining at no more than a couple of hours. The severity dropped significantly to 1 on a scale of 1 to 10. He still did not require time off during migraine episodes. His symptoms were reduced to headache and sensitivity to light, with only two symptoms per episode.Case 3

[0369] A 33 -year-old female experienced migraines at least once a week before trying the Dietary Supplement Intervention. These episodes lasted for at least half a day and were rated as a 7 / 10 in severity. She had to take time off from work or school about half the time. Her symptoms included headache, nausea and vomiting, sensitivity to light, a general feeling of malaise, and being bedridden and unable to function, with five symptoms per episode. She had never seen a specialist as an adult but remembered undergoing an MRI as a child. She relied on Maxalt for relief.

[0370] After starting the Dietary Supplement Intervention, her migraine frequency decreased to 1-3 times a month, with attacks lasting no more than a couple of hours. The severity dropped to 3 / 10, and she no longer needed to take time off. Her only remaining symptom was a headache, with the number of symptoms per episode reduced to one.Case 4

[0371] An 18-y ear-old female suffered from migraines at least once a week before trying the Dietary Supplement Intervention. Her attacks lasted for at least half a day and had a severity of 8 / 10. She hardly ever took time off from work or school. Her symptoms included headache, sensitivity to light and sounds, a general feeling of malaise, and being bedridden and unable to function, with five symptoms per episode. She consulted a neurologist but did not report using specific medications.

[0372] After trying the Dietary Supplement Intervention, her migraines decreased to 1-3 times a month. The duration of her attacks remained at half a day, and the severity dropped slightly to 6 / 10. She still did not need to take time off, and her symptoms remained the same as before, with five symptoms per episode.Case 5

[0373] A 31 -year-old male experienced migraines 1-3 times a month before using the Dietary Supplement Intervention. These episodes lasted at least half a day and were rated as 7 / 10 in severity. He hardly ever took time off. His symptoms included headache, nausea and vomiting, sensitivity to light, sounds, and smell, and a general feeling of malaise, with six symptoms per episode. He consulted a primary care physician and used Excedrin for relief.

[0374] After starting the Dietary Supplement Intervention, his migraine frequency remained at 1-3 times a month, but the duration decreased to no more than a couple of hours. The severity dropped slightly to 6 / 10. He continued to rarely take time off, and his symptoms stayed the same, with six symptoms per episode.Case 6

[0375] A 62-year-old female reported experiencing migraines at least once a week before trying the Dietary Supplement Intervention. Her attacks lasted at least half a day and were rated as 8 / 10 in severity. She had to take time off from work or school about half the time.Her symptoms included headache, aura, nausea and vomiting, sensitivity to light, and being bedridden and unable to function, with five symptoms per episode. She consulted a neurologist and used Tylenol for relief.

[0376] After using the Dietary Supplement Intervention, her migraines decreased to 1-3 times a month, with the duration reduced to no more than a couple of hours. The severity dropped to 4 / 10, and she rarely needed to take time off. Her only remaining symptom was a headache, with the number of symptoms per episode reduced to one.Case 7

[0377] A 43 -year-old female experienced migraines 1-3 times a month before trying the Dietary Supplement Intervention. Her attacks lasted at least one day and were rated 7 / 10 in severity. She had to take time off from work or school about half the time. Her symptoms included headache, a general feeling of malaise, and neck and shoulder pain related to the headache, with three symptoms per episode. She consulted her nurse practitioner and used Aleve, similar OTC products, and Lexapro as part of her treatment.

[0378] After starting the Dietary Supplement Intervention, her migraine frequency remained at 1-3 times a month, but the duration decreased to at least half a day. The severity dropped to 4 / 10, and she hardly ever needed to take time off. Her only remaining symptom was a headache, with the number of symptoms per episode reduced to one.Case 8

[0379] A 42-y ear-old female reported experiencing migraines 1-3 times a month before trying the Dietary Supplement Intervention. These attacks lasted at least one day and were rated as 7 / 10 in severity. She had to take time off from work or school almost all the time. Her symptoms included headache, nausea and vomiting, and sensitivity to light, with three symptoms per episode. She had consulted many doctors for her migraines and used Tylenol for relief.

[0380] After using the Dietary Supplement Intervention, her migraine frequency decreased to once every 4-6 months. However, the duration of her attacks increased to more than three days. The severity dropped to 4 / 10, and she no longer needed to take time off.Her only symptom was a headache, with the number of symptoms per episode reduced to one.Case 9

[0381] A 57-y ear-old female experienced migraines 1-3 times a month before trying the Dietary Supplement Intervention. These attacks lasted at least two days and were rated as 10 / 10 in severity. She needed to take time off from work or school almost all the time. Her symptoms included headache, aura, nausea and vomiting, sensitivity to light, sounds, touch, and smell, a general feeling of malaise, and being bedridden and unable to function, with nine symptoms per episode. She consulted a general practitioner and a neurologist and used Excedrin, Tylenol, ibuprofen, and aspirin for relief.

[0382] After starting the Dietary Supplement Intervention, her migraines decreased to 1-2 times a year. The duration reduced to no more than a couple of hours, and the severity dropped to 3 / 10. She no longer needed to take time off. Her symptoms included headache, nausea and vomiting, sensitivity to light, sounds, and smell, with five symptoms per episode.Case 10

[0383] A 24-y ear-old female reported experiencing migraines 1-3 times a month before trying the Dietary Supplement Intervention. Her attacks lasted at least half a day and were rated as 3 / 10 in severity. She did not need to take time off from work or school during these episodes. Her symptoms included headache, sensitivity to light, and sensitivity to sounds, with three symptoms per episode. She had not consulted any specialists or used medications for her migraines.

[0384] After using the Dietary Supplement Intervention, her migraine frequency decreased to once every 4-6 months. The duration of her attacks reduced to no more than a couple of hours, and the severity dropped to 2 / 10. She continued not requiring time off, and her only symptom was a headache, with the number of symptoms per episode reduced to one.Case 11

[0385] A 36-y ear-old female experienced migraines 1-3 times a month before trying the Dietary Supplement Intervention. Her attacks lasted no more than a couple of hours and were rated as 8 / 10 in severity. She hardly ever took time off from work or school. Her symptoms included headache, aura, sensitivity to light, and sensitivity to sounds, with four symptoms per episode. She consulted her primary doctor and used ibuprofen and Excedrin for relief.

[0386] After starting the Dietary Supplement Intervention, her migraine frequency decreased to once every 4-6 months, with the duration remaining at no more than a couple of hours. The severity dropped slightly to 6 / 10. She still did not need to take time off, and her symptoms included headache, sensitivity to light, and sensitivity to sounds, with three symptoms per episode.Case 12

[0387] A 26-year-old female experienced migraines at least once a week before trying the Dietary Supplement Intervention. These episodes lasted at least half a day and were rated as 7 / 10 in severity. She had to take time off from work or school almost all the time. Her symptoms included headache, nausea and vomiting, sensitivity to light, sounds, and smell, a general feeling of malaise, and being bedridden and unable to function, with seven symptoms per episode. She consulted a neurologist and used Advil for relief.

[0388] After using the Dietary Supplement Intervention, her migraine frequency decreased to 1-3 times a month. The duration of her attacks decreased to no more than a couple of hours, and the severity dropped significantly to 2 / 10. She rarely needed to take time off, and her symptoms were nearly eliminated, with hardly any remaining.Case 13

[0389] A 40-year-old female reported experiencing migraines at least once a week before trying the Dietary Supplement Intervention. Her attacks lasted no more than a couple of hours and were rated as 6 / 10 in severity. She hardly ever took time off from work or school. Her symptoms included headache, aura, sensitivity to light, and sensitivity to sounds, withfour symptoms per episode. She consulted a neurologist and used Sumatriptan and Qulipta for treatment.

[0390] After starting the Dietary Supplement Intervention, her migraine frequency remained at least once a week, with the duration of her attacks unchanged. The severity remained at 4 / 10. She still rarely needed to take time off, and her symptoms included headache, sensitivity to light, and sensitivity to sounds, with three symptoms per episode.Case 14

[0391] This 26-year-old female had migraines 1-3 times a month before trying the Dietary Supplement Intervention. The attacks lasted at least half a day, with a severity of 6 / 10. She did not need to take time off and reported symptoms including headache, aura, sensitivity to light, and sensitivity to sounds. She only consulted a primary care doctor and used Advil, Aleve, and Excedrin.

[0392] After trying the Dietary Supplement Intervention, her migraines decreased to once every 4-6 months, lasting not more than a couple of hours. The severity remained at 4 / 10. She did not need to take time off, and her symptoms were reduced to headache and sensitivity to light.Case 15

[0393] A 35-y ear-old female had migraines at least once a week before trying the Dietary Supplement Intervention. The attacks lasted at least one day, with a severity of 8 / 10. She almost always had to take time off and reported multiple symptoms, including headache, aura, nausea and vomiting, sensitivity to light, sounds, and smell, generally feeling awful, and vertigo. She consulted Alamo Neurology Consultants and used medications such as Lamotrigine, Botox, aspirin, ibuprofen, and acetaminophen.

[0394] After trying the Dietary Supplement Intervention, her migraines decreased to 1-3 times a month, still lasting at least one day. The severity remained unchanged at 8 / 10. She continued to almost always need time off, and her symptoms persisted in full.Case 16

[0395] This 36-year-old female experienced migraines 1-3 times a month before trying the Dietary Supplement Intervention. The attacks lasted at least one day, with a severity of 5 / 10. She hardly ever needed to take time off and reported symptoms such as headache and sensitivity to sounds. She consulted her primary care doctor and used ibuprofen.

[0396] After trying the Dietary Supplement Intervention, her migraine frequency and severity reduced slightly to not more than a couple of hours and 3 / 10, respectively. She no longer needed to take time off, and her symptoms were reduced to just a headache.Case 17

[0397] This 48-y ear-old female experienced migraines 1-3 times a month before trying the Dietary Supplement Intervention. The attacks lasted at least half a day, with a severity of 9 / 10. She had to take time off about half the time and reported symptoms such as headache, sensitivity to light, and generally feeling awful. She consulted a physician and used amitriptyline.

[0398] After trying the Dietary Supplement Intervention, her migraines decreased to once every 4-6 months, lasting not more than a couple of hours. The severity dropped to 5 / 10. She hardly needed to take time off, and her symptoms were reduced to none.

[0399] Data compiled from these case studies is presented in Table 1 and Figures 6-11. The data show that dietary supplements of the present disclosure are effective for the prevention and treatment of migraine and symptoms of migraine.

Claims

What is claimed is:

1. A regimen for the prevention or treatment of migraine or symptoms thereof in a subject in need thereof comprising administration of a dietary supplement of Formula 1, a dietary supplement of Formula 2, and a dietary supplement of Formula 3, wherein the dietary supplements are administered to the subject in a migraine phase-specific manner.

2. The regimen of claim 1, wherein the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered one or more times as needed by the subject during the attack phases of migraine.

3. The regimen of claim 1, wherein the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered as needed by the subject during the attack phases of migraine.

4. The regimen of any one of claims 1-3, wherein the dietary supplement of Formula 1 comprises Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B 12, Vitamin C, Coenzyme Q10, magnesium, zinc, piperine.

5. The regimen of claim 4, wherein the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg.

6. The regimen of claim 4, wherein the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg.

7. The regimen of claim 4, wherein the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg.

8. The regimen of claim 4, wherein the Vitamin B9 of Formula 1 is in an amount of about 0.5 mg to about 1.5 mg.

9. The regimen of claim 4, wherein the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg.

10. The regimen of claim 4, wherein the Vitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg.

11. The regimen of claim 4, wherein the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg.

12. The regimen of claim 4, wherein the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg.

13. The regimen of claim 4, wherein the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg.

14. The regimen of claim 4, wherein the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg.

15. The regimen of claim 4, wherein the Vitamin B2 of Formula 1 is in an amount of 60 mg.

16. The regimen of claim 4, wherein the Vitamin B3 of Formula 1 is in an amount of 150 mg.

17. The regimen of claim 4, wherein the Vitamin B6 of Formula 1 is in an amount of 25 mg.

18. The regimen of claim 4, wherein the Vitamin B9 of Formula 1 is in an amount of 1.0 mg.

19. The regimen of claim 4, wherein the Vitamin B12 of Formula 1 is in an amount of 0.4 mg.

20. The regimen of claim 4, wherein the Vitamin C of Formula 1 is in an amount of 300 mg.

21. The regimen of claim 4, wherein the Coenzyme Q10 of Formula 1 is in an amount of 24 mg.

22. The regimen of claim 4, wherein the magnesium of Formula 1 is in an amount of 196 mg.

23. The regimen of claim 4, wherein the zinc of Formula 1 is in an amount of 30 mg.

24. The regimen of claim 4, wherein the piperine of Formula 1 is in an amount of 5.0 mg.

25. The regimen of any one of claims 1-3, wherein the dietary supplement of Formula 2 comprises Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract.

26. The regimen of claim 25, wherein the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg.

27. The regimen of claim 25, wherein the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

28. The regimen of claim 25, wherein the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

29. The regimen of claim 25, wherein the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg.

30. The regimen of claim 25, wherein the Butterbur extract of Formula 2 is in an amount of 150 mg.

31. The regimen of claim 25, wherein the Feverfew extract of Formula 2 is in an amount of 200 mg.

32. The regimen of claim 25, wherein the Pinus pinaster extract of Formula 2 is in an amount of 200 mg.

33. The regimen of claim 25, wherein the Grape seed extract of Formula 2 is in an amount of 250 mg.

34. The regimen of any one of claims 1-3, wherein the dietary supplement Formula 3 comprises Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract.

35. The regimen of claim 34, wherein the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

36. The regimen of claim 34, wherein the Lemon Balm extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

37. The regimen of claim 34, wherein the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

38. The regimen of claim 34, wherein the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

39. The regimen of claim 34, wherein the Valerian Root extract of Formula 3 is in an amount of 150 mg.

40. The regimen of claim 34, wherein the Lemon Balm extract of Formula 3 is in an amount of 150 mg.

41. The regimen of claim 34, wherein the Passion Flower extract of Formula 3 is in an amount of 60 mg.

42. The regimen of claim 34, wherein the Hops extract of Formula 3 is in an amount of 60 mg.

43. A method for the prevention or treatment of migraine or symptoms thereof in a subject in need thereof comprising administration of a dietary supplement of Formula 1, a dietary supplement of Formula 2, and a dietary supplement of Formula 3, wherein the dietary supplements are administered to the subject in a migraine phase-specific manner.

44. The method of claim 43, wherein the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered one or more times as needed by the subject during the attack phases of migraine.

45. The method of claim 43, wherein the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered as needed by the subject during the attack phases of migraine.

46. The method of any one of claims 43-45, wherein the dietary supplement of Formula 1 comprises Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B 12, Vitamin C, Coenzyme Q10, magnesium, zinc, piperine.

47. The method of claim 46, wherein the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg.

48. The method of claim 46, wherein the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg.

49. The method of claim 46, wherein the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg.

50. The method of claim 46, wherein the Vitamin B9 of Formula 1 is in an amount of about 0.5 mg to about 1.5 mg.

51. The method of claim 46, wherein the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg.

52. The method of claim 46, wherein the Vitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg.

53. The method of claim 46, wherein the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg.

54. The method of claim 46, wherein the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg.

55. The method of claim 46, wherein the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg.

56. The method of claim 46, wherein the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg.

57. The method of claim 46, wherein the Vitamin B2 of Formula 1 is in an amount of 60 mg.

58. The method of claim 46, wherein the Vitamin B3 of Formula 1 is in an amount of 150 mg.

59. The method of claim 46, wherein the Vitamin B6 of Formula 1 is in an amount of 25 mg.

60. The method of claim 46, wherein the Vitamin B9 of Formula 1 is in an amount of 1.0 mg.

61. The method of claim 46, wherein the Vitamin B12 of Formula 1 is in an amount of 0.4 mg.

62. The method of claim 46, wherein the Vitamin C of Formula 1 is in an amount of 300 mg.

63. The method of claim 46, wherein the Coenzyme Q10 of Formula 1 is in an amount of 24 mg.

64. The method of claim 46, wherein the magnesium of Formula 1 is in an amount of 196 mg.

65. The method of claim 46, wherein the zinc of Formula 1 is in an amount of 30 mg.

66. The method of claim 46, wherein the piperine of Formula 1 is in an amount of 5.0 mg.

67. The method of any one of claims 43-45, wherein the dietary supplement of Formula 2 comprises Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract.

68. The method of claim 67, wherein the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg.

69. The method of claim 67, wherein the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

70. The method of claim 67, wherein the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

71. The method of claim 67, wherein the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg.

72. The method of claim 67, wherein the Butterbur extract of Formula 2 is in an amount of 150 mg.

73. The method of claim 67, wherein the Feverfew extract of Formula 2 is in an amount of 200 mg.

74. The method of claim 67, wherein the Pinus pinaster extract of Formula 2 is in an amount of 200 mg.

75. The method of claim 67, wherein the Grape seed extract of Formula 2 is in an amount of 250 mg.

76. The method of any one of claims 43-45, wherein the dietary supplement Formula 3 comprises Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract.

77. The method of claim 76, wherein the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

78. The method of claim 76, wherein the Lemon Balm extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

79. The method of claim 76, wherein the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

80. The method of claim 76, wherein the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

81. The method of claim 76, wherein the Valerian Root extract of Formula 3 is in an amount of 150 mg.

82. The method of claim 76, wherein the Lemon Balm extract of Formula 3 is in an amount of 150 mg.

83. The method of claim 76, wherein the Passion Flower extract of Formula 3 is in an amount of 60 mg.

84. The method of claim 76, wherein the Hops extract of Formula 3 is in an amount of 60 mg.

85. A method of ameliorating migraine or symptoms thereof in a subject in need thereof comprising administering to the subject a dietary supplement of Formula 1, a dietarysupplement of Formula 2, and a dietary supplement of Formula 3, wherein the dietary supplements are administered to the subject in a migraine phase-specific manner.

86. The method of claim 85, wherein the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered one or more times as needed by the subject during the attack phases of migraine.

87. The method of claim 85, wherein the dietary supplement of Formula 1 is administered daily during the interictal and attack phases of migraine, the dietary supplement of Formula 2 is administered daily during the attack phases of migraine, and the dietary supplement of Formula 3 is administered as needed by the subject during the attack phases of migraine.

88. The method of any one of claims 85-87, wherein the dietary supplement of Formula 1 comprises Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B 12, Vitamin C, Coenzyme Q10, magnesium, zinc, piperine.

89. The method of claim 88, wherein the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg.

90. The method of claim 88, wherein the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg.

91. The method of claim 88, wherein the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg.

92. The method of claim 88, wherein the Vitamin B9 of Formula 1 is in an amount of about 0.5 mg to about 1.5 mg.

93. The method of claim 88, wherein the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg.

94. The method of claim 88, wherein the Vitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg.

95. The method of claim 88, wherein the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg.

96. The method of claim 88, wherein the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg.

97. The method of claim 88, wherein the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg.

98. The method of claim 88, wherein the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg.

99. The method of claim 88, wherein the Vitamin B2 of Formula 1 is in an amount of 60 mg.

100. The method of claim 88, wherein the Vitamin B3 of Formula 1 is in an amount of 150 mg.

101. The method of claim 88, wherein the Vitamin B6 of Formula 1 is in an amount of 25 mg.

102. The method of claim 88, wherein the Vitamin B9 of Formula 1 is in an amount of 1.0 mg.

103. The method of claim 88, wherein the Vitamin B12 of Formula 1 is in an amount of 0.4 mg.

105. The method of claim 88, wherein the Vitamin C of Formula 1 is in an amount of 300 mg.

106. The method of claim 88, wherein the Coenzyme Q10 of Formula 1 is in an amount of 24 mg.

107. The method of claim 88, wherein the magnesium of Formula 1 is in an amount of 196 mg.

108. The method of claim 88, wherein the zinc of Formula 1 is in an amount of 30 mg.

109. The method of claim 88, wherein the piperine of Formula 1 is in an amount of 5.0 mg.

110. The method of any one of claims 85-87, wherein the dietary supplement of Formula 2 comprises Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract.

111. The method of claim 110, wherein the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg.

112. The method of claim 110, wherein the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

113. The method of claim 110, wherein the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

114. The method of claim 110, wherein the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg.

115. The method of claim 110, wherein the Butterbur extract of Formula 2 is in an amount of 150 mg.

116. The method of claim 110, wherein the Feverfew extract of Formula 2 is in an amount of 200 mg.

117. The method of claim 110, wherein the Pinus pinaster extract of Formula 2 is in an amount of 200 mg.

118. The method of claim 110, wherein the Grape seed extract of Formula 2 is in an amount of 250 mg.

119. The method of any one of claims 85-87, wherein the dietary supplement Formula 3 comprises Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract.

120. The method of claim 119, wherein the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

121. The method of claim 119, wherein the Lemon Balm extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

122. The method of claim 119, wherein the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

123. The method of claim 119, wherein the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

124. The method of claim 119, wherein the Valerian Root extract of Formula 3 is in an amount of 150 mg.

125. The method of claim 119, wherein the Lemon Balm extract of Formula 3 is in an amount of 150 mg.

126. The method of claim 119, wherein the Passion Flower extract of Formula 3 is in an amount of 60 mg.

127. The method of claim 119, wherein the Hops extract of Formula 3 is in an amount of 60 mg.

128. A dietary supplement comprising Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B9, Vitamin B 12, Vitamin C, Coenzyme Q10, magnesium, zinc, and piperine.

129. The dietary supplement of claim 128, wherein the Vitamin B2 of Formula 1 is in an amount of about 30 mg to about 90 mg.

130. The dietary supplement of claim 128, wherein the Vitamin B3 of Formula 1 is in an amount of about 75 mg to about 225 mg.

131. The dietary supplement of claim 128, wherein the Vitamin B6 of Formula 1 is in an amount of about 10 mg to about 50 mg.

132. The dietary supplement of claim 128, wherein the Vitamin B9 of Formula 1 is in an amount of about 0.5 mg to about 1.5 mg.

133. The dietary supplement of claim 128, wherein the Vitamin B12 of Formula 1 is in an amount of about 0.2 mg to about 0.6 mg.

134. The dietary supplement of claim 128, wherein the Vitamin C of Formula 1 is in an amount of about 150 mg to about 450 mg.

135. The dietary supplement of claim 128, wherein the Coenzyme Q10 of Formula 1 is in an amount of about 12 mg to about 180 mg.

136. The dietary supplement of claim 128, wherein the magnesium of Formula 1 is in an amount of about 100 mg to about 300 mg.

137. The dietary supplement of claim 128, wherein the zinc of Formula 1 is in an amount of about 15 mg to about 45 mg.

138. The dietary supplement of claim 128, wherein the piperine of Formula 1 is in an amount of about 2 mg to about 8 mg.

139. The dietary supplement of claim 128, wherein the Vitamin B2 of Formula 1 is in an amount of 60 mg.

140. The dietary supplement of claim 128, wherein the Vitamin B3 of Formula 1 is in an amount of 150 mg.

141. The dietary supplement of claim 128, wherein the Vitamin B6 of Formula 1 is in an amount of 25 mg.

142. The dietary supplement of claim 128, wherein the Vitamin B9 of Formula 1 is in an amount of 1.0 mg.

143. The dietary supplement of claim 128, wherein the Vitamin B12 of Formula 1 is in an amount of 0.4 mg.

144. The dietary supplement of claim 128, wherein the Vitamin C of Formula 1 is in an amount of 300 mg.

145. The dietary supplement of claim 128, wherein the Coenzyme Q10 of Formula 1 is in an amount of 24 mg.

146. The dietary supplement of claim 128, wherein the magnesium of Formula 1 is in an amount of 196 mg.

147. The dietary supplement of claim 128, wherein the zinc of Formula 1 is in an amount of 30 mg.

148. The dietary supplement of claim 128, wherein the piperine of Formula 1 is in an amount of 5.0 mg.

149. A dietary supplement comprising Butterbur extract, Feverfew extract, Pinus pinaster extract, and Grape seed extract.

150. The dietary supplement of claim 149, wherein the Butterbur extract of Formula 2 is in an amount of about 75 mg to about 225 mg.

151. The dietary supplement of claim 149, wherein the Feverfew extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

152. The dietary supplement of claim 149, wherein the Pinus pinaster extract of Formula 2 is in an amount of about 100 mg to about 300 mg.

153. The dietary supplement of claim 149, wherein the Grape seed extract of Formula 2 is in an amount of about 125 mg to about 375 mg.

154. The dietary supplement of claim 149, wherein the Butterbur extract of Formula 2 is in an amount of 150 mg.

155. The dietary supplement of claim 149, wherein the Feverfew extract of Formula 2 is in an amount of 200 mg.

156. The dietary supplement of claim 149, wherein the Pinus pinaster extract of Formula 2 is in an amount of 200 mg.

157. The dietary supplement of claim 149, wherein the Grape seed extract of Formula 2 is in an amount of 250 mg.

158. A dietary supplement comprising Valerian Root extract, Lemon Balm extract, Passion Flower extract, and Hops extract.

159. The dietary supplement of claim 158, wherein the Valerian Root extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

160. The dietary supplement of claim 158, wherein the Lemon Balm extract of Formula 3 is in an amount of about 75 mg to about 225 mg.

161. The dietary supplement of claim 158, wherein the Passion Flower extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

162. The dietary supplement of claim 158, wherein the Hops extract of Formula 3 is in an amount of about 30 mg to about 90 mg.

163. The dietary supplement of claim 158, wherein the Valerian Root extract of Formula 3 is in an amount of 150 mg.

164. The dietary supplement of claim 158, wherein the Lemon Balm extract of Formula 3 is in an amount of 150 mg.

165. The dietary supplement of claim 158, wherein the Passion Flower extract of Formula 3 is in an amount of 60 mg.

166. The dietary supplement of claim 158, wherein the Hops extract of Formula 3 is in an amount of 60 mg.

167. A dietary supplement used for the prevention or treatment of migraine or symptoms thereof according to any of the preceding claims.

168. The use of a composition in the preparation of a medicament for treating or preventing migraine or symptoms thereof according to any of the preceding claims.

169. A kit for the prevention or treatment of migraine or symptoms thereof in a subject in need thereof comprising a dietary supplement of according to any of the preceding claims.

Images