Mental wellbeing compositions

Abstract

Compositions for improving mental wellbeing and associated uses.

Description

[0001] MENTAL WELLBEING COMPOSITIONS

[0002] TECHNICAL FIELD OF THE INVENTION

[0003] The current invention relates to compositions for improving mental wellbeing, as well as to associated uses thereof.

[0004] DESCRIPTION OF THE RELATED ART

[0005] Mental discomforts are widespread among different populations. Known and standard approaches to improving mental wellbeing include the administration of pharmaceutical agents with potential side effects and the necessity for coherent medical supervision. Known alternatives to pharmaceuticals include nutrition-based approaches and nutrition supplements to improve mental wellbeing. However, current supplements typically fall short on being convenient (unappealing pill format) , and are not tailored to specific mental needs. Importantly, known supplements more often offer temporary relief of specific symptoms rather than providing a comprehensive solution that targets the neurobiological / cognitive processes of psychological disfunction at the root of mental health challenges.

[0006] SUMMARY OF THE INVENTION

[0007] It is a task of current invention to provide compositions for improving mental wellbeing.

[0008] This task is solved by a composition with the features of claims 1 to 3. Further embodiments of the composition, as well as a use of the composition are defined by the features of further claims.

[0009] In a first aspect, the present invention is directed to a composition for oral use comprising:

[0010] Vitamin B6;

[0011] Vitamin D3 ;

[0012] L- Tryptophan;

[0013] Inositol;

[0014] Taurine; Panax Ginseng extract, optionally a water-ethanol extract, e.g. 20 vol% to 40 vol% ethanol in water, e.g. about 30 vol% ethanol in water, optionally at an extract ratio of 8 / 1 to 10 / 1, optionally of the roots of Panax Ginseng, optionally comprising 10 weight! to 25 weight!, optionally 12 weight! to 16 weight! ginsenosides ;

[0015] Yerba Mate extract, optionally a water extract, optionally at an extract ratio of 1 / 1 to 5 / 1, optionally of the ariel parts of Yerba Mate, optionally comprising 15 weight! to 30 weight!, optionally about 20 weight! caffein; and

[0016] Cocoa bean extract, optionally a water extract, optionally at an extract ratio of 7 / 1 to 9 / 1, optionally about 8 / 1, optionally of the seeds of Cocoa bean, optionally comprising 5 weight! to 10 weight!, optionally about 7 weight! theobromine.

[0017] As used herein for all aspects and embodiments, the extract ratio refers to the ratio of the mass of dried herbal / plant material to the mass of the resulting extract. For example, the extracts for use in the present invention are standardized extracts as known to the skilled person and are, e.g. , prepared, i.e. extracted, according to standards utilized in extraction techniques. For example, these standards include the European Pharmacopoeia monograph 01 / 2008:20817; 02 / 2008:20816; 04 / 2019:20934, 01 / 2008:20416, 07 / 2016:20203, 07 / 2010:20612, 01 / 2008:1523 and 01 / 2014:20631 for quality control and standardization and utilize methods such granulometry, titration, HPLC (high performance liquid chromatography) , UV-VIS (ultraviolet-visible spectrophotometry) , TLC (Thin layer chromatography) , GC-MS (Gas chromatography-mass spectrometry) , LC-MS (Liquid chromatography-mass spectrometry) and ICP-OES (Inductively coupled plasma optical emission spectrometry) for determining the quantity, purity, and identification of active ingredients and impurities in plant products.

[0018] For example, the first composition can be used to improve normal psychological functioning by improving emotional well-being, motivation, resilience, happiness and / or social functioning, supporting positive mood, enhancing sensations of vitality and increasing relaxation, and / or reducing sadness and / or anger.

[0019] In a second aspect, the present invention is directed to a composition for oral use comprising:

[0020] Magnesium;

[0021] L-Glutamic acid;

[0022] L-Arginine;

[0023] Glycine;

[0024] Ashwagandha root extract, optionally a water extract, optionally at an extract ratio of 10 / 1 to 25 / 1, optionally about 20 / 1, optionally comprising 1.8 weight! to 3.5 weight!, optionally about 2.5 weight! withanolides ;

[0025] Valerian root extract, optionally a water extract, optionally at an extract ratio of 9 / 1 to 12 / 1, optionally about 11 / 1, optionally comprising 0.3 weight! to 1.6 weight!, optionally about 0.8 weight! valerian acids;

[0026] Lemon balm extract, optionally a water-ethanol extract, e.g.

[0027] 10 vol! to 50 vol! or about 30 vol! ethanol in water, optionally at an extract ratio of 3 / 1 to 7 / 1, optionally about 5 / 1, optionally of the arial parts of Lemon balm; and

[0028] Hops extract, optionally a water-ethanol extract, e.g. 25 vol! to 30 vol! ethanol in water, optionally at an extract ratio of 4 / 1 to 6 / 1, optionally of the arial parts of Hops.

[0029] Valerian acids, as used herein, include valeric acid, isovaleric acid, valerenic acid, hydroxyvalerenic acid and acetoxyvalerenic acid.

[0030] For example, the second composition can be used to improve normal psychological functioning by improving calmness, sleep quality and / or recovery, activating parasympathetic activity, reducing restlessness, relieving mental and nervous tension and promoting sleep onset / relieving difficulty in falling asleep. In a third aspect, the present invention is directed to a composition for oral use comprising:

[0031] Vitamin B12;

[0032] Vitamin B9;

[0033] Zinc;

[0034] N-Acetyl-L-Tyrosine , optionally as L-Tyrosine;

[0035] Phenylalanine;

[0036] Green tea extract, optionally a water extract, optionally of the arial parts of the green tea, optionally comprising 40 weight! to 70 weight!, optionally 44 to 66 weight! or about 60 weight! L- Theanine ;

[0037] Guarana extract, optionally a water-ethanol extract, e.g. 60 vol! to 80 vol! ethanol in water, optionally of the seeds of guarana, optionally comprising 15 weight! to 70 weight!, optionally about 30 to 50 weight! caffein;

[0038] Ginko biloba extract, optionally a water-ethanol extract, e.g. 60 vol! to 80 vol! ethanol in water, optionally at an extract ratio of 50 / 1 to 52 / 1, optionally of the ariel parts of ginkgo biloba; and

[0039] Sage leaf extract, optionally a water extract, optionally at an extract ratio of 3 / 1 to 4 / 1.

[0040] For example, the third composition can be used to improve normal psychological function, by improving vigilance and / or focus, stimulating mental alertness, supporting memory performance, improving reaction time and / or relieving fatigue.

[0041] Also disclosed herein is a fourth composition for oral use comprising :

[0042] Vitamin B3 ;

[0043] Vitamin Bl;

[0044] Manganese;

[0045] L-Glutamine;

[0046] L-Carnitine;

[0047] Caffeine; and Rhodiola Rosea extract, optionally a water-ethanol extract, e.g. 65 vol% to 75 vol% ethanol in water, optionally at an extract ratio of 1 / 1 to 2 / 1, optionally of the roots of Rhodiola Rosea.

[0048] For example, the above composition can be used to improve normal psychological functioning by reducing tiredness and fatigue, relieving sensations of weakness, improving an energy-yielding metabolism and protecting cells from oxidative stress.

[0049] It was surprisingly found that the compositions detailed above share a common functional mechanism and are all effective in improving interrelated aspects of normal psychological function, thereby contributing to enhanced mental wellbeing. These aspects include cognitive focus, vigilance, emotional calmness, recovery, autonomic balance, and positive affect and social-emotional engagement. Without wishing to be bound by theory, it is believed that the compositions positively influence the function of different neuronal pathways and their associated neurotransmitters, which underlie these varying aspects of psychological functioning. It is believed that by targeting multiple aspects of neuronal pathway function (production, transduction and release / response of associated neurotransmitters) by using a diverse and highly specific group of ingredients (vitamins, minerals, amino acids and phytochemicals) , a more effective improvement of pathway function and mental well-being is achieved compared to the administration of individual ingredients. In other words, it is believed to be the combination of the ingredients that achieves the effect of improving mental wellbeing, which goes beyond the individual effect of each component, as shown in the experiments below.

[0050] The features of the above-mentioned embodiments of the compositions can be used in any combination within the scope of the claims, provided they do not contradict each other.

[0051] In an embodiment of the first composition according to the present invention which may be combined with any of the embodiments and aspects preaddressed or still to be addressed unless in contradiction, the composition, in particular a daily dose, a single dosage form and / or 60 mL thereof wherein water is added to a volume of 60 mL, comprises:

[0052] 0.5 mg to 5 mg, optionally 1 mg to 2.5 mg, optionally about 1.5 mg or 1.4 mg Vitamin B6;

[0053] 1 pg to 50 pg, optionally 1 pg to 10 pg, optionally 2 pg to 7 pg, optionally about 5 pg Vitamin D3 ;

[0054] 150 mg to 850 mg, optionally 300 to 500 mg, optionally about 400 mg L-Tryptophan;

[0055] 200 mg to 100 mg, optionally 300 to 700 mg, optionally about 500 mg Inositol;

[0056] 200 mg to 100 mg, optionally 300 to 700 mg, optionally about 500 mg Taurine;

[0057] 10 mg to 100 mg, optionally 20 mg to 60 mg, optionally about 40 mg Panax Ginseng extract;

[0058] 100 mg to 1000 mg, optionally 200 mg to 600 mg, optionally about 400 mg Yerba Mate extract; and 50 mg to 270 mg, optionally 80 to 150 mg, optionally about 100 mg Cocoa bean extract.

[0059] As defined herein, the reference to 60 mL means that a total volume of 60 mL comprises the components as indicated, wherein the volume is typically a liquid, in particular an aqueous solution. It is noted that any multiple or fracture of 60 mL is within the scope of the present invention, provided that the amounts of the ingredients are adjusted by the same factor. The 60 mL volume is, for example, generally considered a daily dose of the composition which can be safely and effectively consumed once a day to achieve an improvement in mental wellbeing while each component of the composition is within the daily dose limits set forth by health authorities, e.g. , by the European Food Safety Authority (EFSA) . In other words, the definition "60 mL" can be replaced by the term "a daily dose of the composition" or a "a dosage suitable for daily administration" . In an embodiment of the second composition according to the present invention which may be combined with any of the embodiments and aspects preaddres sed or still to be addres sed unles s in contradiction, the composition, in particular a daily dose , a single dosage form and / or 60 mL thereof wherein water i s added to a volume of 60 mL, compri ses :

[0060] 80 mg to 400 mg, optionally 100 to 250 mg, optionally about 190 mg or 188 mg Magnesium;

[0061] 50 mg to 450 mg, optionally 100 to 300 mg, optionally about 200 mg L-Glutamic acid;

[0062] 150 mg to 850 mg, optionally 300 to 500 mg, optionally about 400 mg L-Arginine ;

[0063] 150 mg to 850 mg, optionally 300 to 500 mg, optionally about 400 mg Glycine ;

[0064] 150 mg to 250 mg, optionally 180 to 220 mg, optionally about 200 mg Ashwagandha root extract ;

[0065] 15 mg to 60 mg, optionally 25 to 35 mg, optionally about 30 mg or 28 mg Valerian root extract ;

[0066] 45 mg to 180 mg, optionally 60 mg to 120 mg, optionally about 90 mg Lemon balm extract ; and

[0067] 5 mg to 50 mg, optionally about 10 mg to 30 mg, optionally about 20 mg Hops extract .

[0068] In an embodiment of the third composition according to the present invention which may be combined with any of the embodiments and aspects preaddres sed or still to be addres sed unles s in contradiction, the composition , in particular a daily dose , a single dosage form and / or 60 mL thereof wherein water i s added to a volume of 60 mL , compri ses :

[0069] 1 pg to 6 pg, optionally 1 . 5 pg to 4 pg, optionally about 2 . 5 pg Vitamin B12 ;

[0070] 100 pg to 500 pg, optionally 120 pg to 300 pg, optionally about 200 pg Vitamin B9 ;

[0071] 1 mg to 10 mg, optionally 2 to 7 mg, optionally about 5 mg Zinc ; 200 mg to 100 mg, optionally 300 to 700 mg, optionally about 500 mg N-Acetyl-L-Tyrosine ;

[0072] 100 mg to 500 mg, optionally 150 to 350 mg, optionally about 250 mg Phenylalanine ;

[0073] 200 mg to 1000 mg, optionally 250 to 800 mg, optionally about 330 mg green tea extract ;

[0074] 80 mg to 600 mg, optionally 150 to 300 mg, optionally about 200 mg Guarana extract ;

[0075] 50 mg to 350 mg, optionally 90 to 180 mg, optionally about 120 mg Ginko biloba extract ; and

[0076] 50 mg to 250 mg, optionally 60 mg to 150 mg, optionally about 100 mg Sage leaf extract .

[0077] In an example , the fourth composition, in particular a daily dose , a single dosage form and / or 60 mL thereof wherein water is added to a volume of 60 mL , compri ses :

[0078] 5 mg to 35 mg, optionally 8 mg to 25 mg, optionally about 15 or 16 mg Vitamin B3 ;

[0079] 0 . 5 mg to 3 mg, optionally 0 . 8 mg to 2 mg, optionally about 1 . 0 mg or 1 . 1 mg Vitamin Bl ;

[0080] 0 . 3 mg to 5 mg, optionally 1 mg to 3 mg, optionally about 2 mg Manganese ;

[0081] 100 mg to 500 mg, optionally 150 to 350 mg, optionally about 250 mg L-Glutamine ;

[0082] 100 mg to 500 mg, optionally 150 to 350 mg, optionally about 250 mg L-Carnitine ;

[0083] 30 mg to 200 mg, optionally 50 mg to 130 mg, optionally about 90 mg caf feine ; and

[0084] 25 mg to 150 mg, optionally 40 mg to 85 mg, optionally about 65 mg Rhodiola Rosea extract .

[0085] In an embodiment of the compositions according to the present invention which may be combined with any of the embodiments and aspects preaddres sed or still to be addres sed unles s in contradiction, the composition is a food, food additive , drink, or drink additive . For example, the composition may either be pre-dissolved as a drink, or it may be in the form of a powder to be dissolved in a drink, in particular to be dissolved to a volume of 60 mL or a multiple or fraction thereof, while adjusting the amounts of the components accordingly.

[0086] In an embodiment of the compositions according to the present invention which may be combined with any of the embodiments and aspects preaddressed or still to be addressed unless in contradiction, the composition further comprises at least one of a flavoring, optionally a natural flavoring or a sweetener, a colorant, carbon dioxide, a stabilizer, optionally guar gum, a preservative, optionally citric acid and a combination thereof.

[0087] Guar gum can be used in the composition as a stabilizer, an emulsifier, a thickener, and as a soluble dietary fiber.

[0088] In an embodiment of the compositions according to the present invention which may be combined with any of the embodiments and aspects preaddressed or still to be addressed unless in contradiction, the composition is a dry product for dissolution, optionally for dissolution in water. As noted above, the composition may, for example, be dissolved to a volume of 60 mL or a multiple or fraction thereof, while adjusting the amounts of the components accordingly.

[0089] In an embodiment of the compositions according to the present invention which may be combined with any of the embodiments and aspects preaddressed or still to be addressed unless in contradiction, the composition is a water-based solution, optionally a water-based solution that is packaged in a container, optionally a solution with a volume of 50 to 150 mL, optionally of about 60 mL .

[0090] In an embodiment of the compositions according to the present invention which may be combined with any of the embodiments and aspects preaddressed or still to be addressed unless in contradiction, the composition is a pharmaceutical composition. The pharmaceutical composition may be in any suitable dosage form such as a liquid, a powder, a capsule or a tablet.

[0091] In an aspect which may be combined with any of the aspects and embodiments preaddressed or still to be addressed unless in contradiction, the invention is directed to the composition as defined herein for use as a medicament, optionally as a nutritional supplement .

[0092] In an aspect which may be combined with any of the aspects and embodiments preaddressed or still to be addressed unless in contradiction, the invention is directed to the composition as defined herein for use in the therapy of mental health problems and / or for use in the improvement of mental wellbeing, optionally for use in the treatment of depression, stress, fatigue, insomnia and / or mood fluctuations.

[0093] The term "mental wellbeing" as used herein, in particular in the context of improving mental wellbeing, refers to, a state of comfort, health, or happiness that integrates various aspects of central nervous system function (e.g. neuronal activity and neurotransmitter balance) , cognitive processes (e.g. thought patterns, memory, attention, and problem-solving) and psychological functioning (e.g. emotional regulation, stress responsiveness and behavior) . This includes both subjective and physiological dimensions of wellbeing, such as positive affect, emotional stability, and autonomic nervous system balance.

[0094] Improving mental wellbeing can further include, e.g. , the improvement of mental and / or psychological illnesses or mental health problems, in particular the improvement of depression, depressive mood, anxiety-related symptoms, stress reactivity, sleep disorders, mood disorder, fatigue syndromes, attention deficit problem or disorder, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social anxiety disorder, phobias, and dementia. In this context, improved mental wellbeing may be reflected, e.g. , in enhanced mood, increased sustained attention, reduced physiological stress markers, improved sleep architecture, and more adaptive emotional engagement .

[0095] In an aspect which may be combined with any of the aspects and embodiments preaddressed or still to be addressed unless in contradiction, the invention is directed to a use of the composition as defined herein for improving mental wellbeing.

[0096] In an aspect which may be combined with any of the aspects and embodiments preaddressed or still to be addressed unless in contradiction, the invention is directed to a use of the composition of the first aspect or a composition comprising the composition of the first aspect, for improving motivation, resilience, happiness and / or social functioning, and / or reducing sadness and / or anger. Such improvements may manifest, e.g. , through more positive emotional bias, faster recognition of positive social cues, and improved self-reported affective state.

[0097] In an aspect which may be combined with any of the aspects and embodiments preaddressed or still to be addressed unless in contradiction, the invention is directed to a use of the composition of the second aspect or a composition comprising the composition of the second aspect, for improving sleep quality, calmness and / or recovery, activating parasympathetic activity, and / or reducing restlessness. Such improvements may manifest, e.g. , through enhanced vagal tone and physiological downregulation of stress systems during sleep.

[0098] In an aspect which may be combined with any of the aspects and embodiments preaddressed or still to be addressed unless in contradiction, the invention is directed to a use of the composition of the third aspect or a composition comprising the composition of the third aspect, for improving vigilance, focus, reaction time. Such improvements may manifest, e.g. , through more consistent and accurate cognitive performance, increased sustained attention, and reduced attentional fatigue. In an aspect which may be combined with any of the aspects and embodiments preaddressed or still to be addressed unless in contradiction, the invention is directed to a use of the composition as disclosed herein for the treatment, or for the manufacture of a medicament for treatment of attention deficits depression, stress, tiredness, sleeping disorders and / or mood fluctuations .

[0099] BRIEF DESCRIPTION OF THE DRAWINGS

[0100] Embodiments of the current invention are described in more detail in the following with reference to the figures. It shows

[0101] Figure 1. Placebo-adjusted effects (A) and supra-additive contrast (S) on ratings of self-reported positivity;

[0102] Figure 2. Placebo-adjusted effects (A) and supra-additive contrast (S) for EBT Bias Point (EBTBP) ;

[0103] Figure 3. Placebo-adjusted effects (A) and supra-additive contrast (S) for EBT Response Count Angry (EBTRCA) ;

[0104] Figure 4. Placebo-adjusted effects (A) and supra-additive contrast (S) for ERT median reaction time to happy faces (ERTRTH) ;

[0105] Figure 5. Placebo-adjusted effects (A) and supra-additive contrast (S) for Self-reported Change in Sleep Quality;

[0106] Figure 6. Placebo-adjusted effects (A) and supra-additive contrast (S) for overall sleep score;

[0107] Figure 7. Placebo-adjusted effects (A) and supra-additive contrast (S) for deep sleep duration in minutes.

[0108] Figure 8. Placebo-adjusted effects (A) and supra-additive contrast (S) for High Frequency (HF) Heart Rate Variability (HRV) power (ms2)

[0109] Figure 9. Placebo-adjusted effects (A) and supra-additive contrast

[0110] (S) for High Frequency (HF) / Low Frequency (LF) Heart Rate Variability (HRV) ratio.

[0111] Figure 10. Placebo-adjusted effects (A) and supra-additive contrast (S) for RVP accuracy (RVPA) ; Figure 11. Placebo-adjusted effects (A) and supra-additive contrast (S) for RVP probability of hit (RVPPH)

[0112] Figure 12. Placebo-ad usted effects (A) and supra-additive contrast (S) for RVP total hits (RVPTH) ;

[0113] Figure 13. Placebo-adjusted effects (A) and supra-additive contrast (S) for RVP latency standard deviation (RVPLSD) ;

[0114] Figure 14. Placebo-adjusted effects (A) and supra-additive contrast (S) for RVP median latency (RVPML) ;

[0115] Figure 15. Placebo-adjusted effects (A) and supra-additive contrast (S) for RVP mean latency (RVPTM) ;

[0116] Figure 16. Placebo-adjusted change in self-reported energetic efficiency in the Composition 4 cohort.

[0117] DETAILED DESCRIPTION OF THE INVENTION

[0118] Demonstration of synergistic (non -additive) effects

[0119] The inventors have found that combining the ingredient classes described herein, in particular in a single, optionally pH- stabilised, 60 ml shot produces a synergistic improvement in psychological and physiological outcomes— an effect that significantly exceeds the arithmetic sum of two separate partial compositions :

[0120] (i) an amino-acid / vitamin / mineral fraction and

[0121] (ii) a phytochemical fraction.

[0122] Figure 1 shows the change in sel f-reported positivity in the Composition 1 cohort . The y-axi s plots the placebo-adj usted change in sel f-reported positivity ( A ) ; for every participant the self- reported positivity score ( 1 = Never 2 = Very rarely 3 = Occasionally 4 = Qui te often 5 = Very often) recorded after each shot was first corrected by subtracting that participant' s own placebo value ; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line . The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino- acid / vitamin / mineral fraction minus placebo , and S = the supraadditive contrast defined as S=AA- (AB+AC) . The thickest dashed line inside each violin marks the group mean . Higher sel f-reported positivity reflects improved emotional tone and subj ective well-being, both of which are linked to enhanced motivation, resilience, and social functioning. S = +0.77, and its two-sided 95 % confidence interval ( + 0.024 > +1.51) 1 ies wholly above zero; the paired t-test gives P = 0.044. Because the complete formulation raises self-reported positivity by more than the summed improvements of the two partial formulations, Figure 1 demonstrates a supra-additive (synergistic) effect. Numerical summary listed in Table 1.

[0123] Figure 2 illustrates the change in Emotion Bias Test Bias Point (EBTBP, defined as the proportion of trials in which the subject chose 'Happy' over 'Sad' in response to emotionally ambiguous facial expressions) in the Composition 1 cohort. The y-axis shows the placebo-adjusted change in bias point (A) ; for each participant the raw Bias Point was rescaled to a 0-15 metric and corrected by subtracting their own placebo score. A A value of zero thus denotes no change versus placebo and is indicated by the dotted horizontal line. The x-axis presents four conditions: AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino acid / vitamin / mineral fraction minus placebo, and S, the supra-additive contrast, defined as S = AA - (AB + AC) . Thickest dashed lines within each violin indicate the group mean.

[0124] The EBT Bias Point reflects a participant's implicit emotional bias: higher values indicate a stronger tendency to interpret ambiguous expressions as 'Happy' , which is considered a biomarker of more positive affective processing. A higher positivity bias in turn has been linked to reduced perceived negativity in social interactions and more adaptive emotional engagement.

[0125] S~ = +1.60, and its two-sided 95% confidence interval (+0.037 -► +3.12) lies wholly above zero; the paired t-test gives P = 0.045. Because the complete formulation increases positivity bias beyond the summed partial fractions, Figure 2 demonstrates a supra- additive effect. Numerical summary listed in Table 1.

[0126] Figure 3 illustrates the change in Emotion Bias Test Response Count - Angry (EBTRCA, defined as the number of trials in which the subject selected 'Angry' over 'Happy' in response to emotionally ambiguous facial expressions) in the Composition 1 cohort. The y- axis shows the placebo-adjusted change in angry responses (A) ; for each participant, the raw count was corrected by subtracting their own placebo score. A A value of zero thus denotes no change versus placebo and is indicated by the dotted horizontal line. The x-axis presents four conditions: AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino acid / vitamin / mineral fraction minus placebo, and S, the supraadditive contrast, defined as S = AA - (AB + AC) . Thickest dashed lines within each violin indicate the group mean.

[0127] The EBTRCA endpoint reflects the frequency with which participants interpret facial expressions as 'Angry' , offering a proxy for threat-related emotional processing. A reduction in 'Angry' responses indicates a shift towards a more positive emotional bias, which has been linked to improved mood, lower stress reactivity, and more adaptive affective functioning. S” = -4.73, and its two- sided 95% confidence interval (-9.40 -► -0.0547) lies wholly below zero; the paired t-test gives P = 0.048. Because the complete formulation reduces 'Angry' responses beyond the summed effects of its partial fractions, Figure 3 demonstrates a supra-additive effect. Numerical summary listed in Table 1.

[0128] Figure 4 illustrates the change in Emotion Recognition Task Reaction Time - Happy (ERTRTH, defined as the median response time for correctly recognizing happy facial expressions compared to recognition times for other emotional expressions such as Angry, Sad, or Surprised faces) in the Composition 1 cohort. The y-axis plots the placebo-ad usted change in ERT reaction Time (A) ; for every participant the raw reaction time recorded after each shot was first corrected by subtracting that participant' s own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino-acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as S=AA-(AB+AC) . The thickest dashed line inside each violin marks the group mean.

[0129] Faster reaction time for recognizing happy faces reflects more efficient processing of positive emotional cues, facilitating quicker social cue recognition and emotional responsiveness— factors associated with enhanced well-being and positive affect. S” = - 386.0 ms, and its two-sided 95% confidence interval (-742.2 - - 29.71) lies wholly below zero; the paired t-test gives P = 0.035. Because the complete formulation reduces reaction time more than the summed effects of its partial fractions, Figure 4 demonstrates a supra-additive effect. Numerical summary listed in Table 1.

[0130] Figure 5 shows the change in self-reported sleep quality in the Composition 2 cohort. The y-axis plots the placebo-adjusted change in self-reported sleep quality (A) ; for every participant the selfreported sleep quality (1 = Very Bad, 2 = Fairly Bad, 3 = Fairly Good, 4 = Very good) recorded after each shot was first corrected by subtracting that participant's own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino-acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as S=AA- (AB+AC) . The thickest dashedline inside each violin marks the group mean.

[0131] Higher self-reported sleep quality reflects deeper rest, improved recovery, and better overnight restoration. S” = 0.47, and its two- sided 95 % confidence interval (0.031 -> 0.911) lies wholly above zero; the paired t-test gives P = 0.0368. Because the complete formulation improved perceived sleep quality more than the summed partial fractions, Figure 5 demonstrates a statistically significant supra-additive effect. Numerical summary listed in Table 1.

[0132] Figure 6 shows the change in overall sleep score in the Composition 2 cohort. The y-axis plots the placebo-ad usted change in sleep score (A) ; for every participant the sleep score recorded after each shot was first corrected by subtracting that participant's own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino- acid / vitamin / mineral fraction minus placebo, and S = the supraadditive contrast defined as S=AA- (AB+AC) . The thickest dashedline inside each violin marks the group mean.

[0133] The sleep score is calculated using a proprietary algorithm that integrates multiple physiological and behavioral parameters, including sleep duration, time spent in deep and REM stages, restlessness, and heart rate variability. A higher sleep score reflects higher physiological sleep quality, with the final score ranging from 0 to 100. S’ = 4.8, and its two-sided 95 % confidence interval (0.21 -> 9.39) lies wholly above zero; the paired t-test gives P = 0.041. Because the complete formulation increases the sleep score more than the summed partial fractions, Figure 6 demonstrates a supra-additive effect. Numerical summary listed in Table 1.

[0134] Figure 7 shows the change in deep sleep minutes in the Composition 2 cohort. The y-axis plots the placebo-adjusted change in deep sleep (min) (A) ; for every participant the minutes of deep sleep recorded after each shot was first corrected by subtracting that participant's own placebo value; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino- acid / vitamin / mineral fraction minus placebo, and S = the supra- additive contrast defined as S=AA- (AB+AC) . The thickest dashedline inside each violin marks the group mean.

[0135] The number of minutes spent in deep sleep is calculated using a proprietary algorithm that analyzes physiological signals captured, including movement (actigraphy) , heart rate, and heart rate variability. A higher value indicates greater physiological sleep quality and recovery during sleep. S" = 17.2, and its two-sided 95 % confidence interval (3.29 -► 31.11) lies wholly above zero; the paired t-test gives P = 0.0171. Because the complete formulation increased deep sleep duration more than the summed partial fractions, Figure 7 demonstrates a supra-additive effect. Numerical summary listed in Table 1.

[0136] Figure 8 shows the change in high-frequency heart rate variability (HF-HRV) in the Composition 2 cohort. The y-axis plots the placebo- adjusted change in HF-HRV power (ms2) (A) ; for every participant, the HF-HRV power recorded after each shot was corrected by subtracting that participant's own placebo value. Hence, a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis displays AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as S = AA - (AB + AC) . The thickest dashed line inside each violin marks the group mean.

[0137] High-frequency HRV reflects parasympathetic (vagal) activity and is a physiological marker of relaxation, calm, and recovery. It is calculated using a proprietary algorithm that analyzes beat-to-beat heart rate intervals derived from photoplethysmography. A higher HF-HRV value during sleep indicates a more relaxed state of the nervous system and is associated with deeper, more restorative sleep and overall improved sleep quality S” = 228.9, and its two- sided 95 % confidence interval (70.34 -> 387.46) lies wholly above zero; the paired t-test gives P = 0.0065. Because the complete formulation increased HF-HRV more than the summed partial fractions, Figure 8 demonstrates a statistically significant supra- additive effect. Numerical summary listed in Table 1.

[0138] Figure 9 shows the change in high-frequency to low-frequency heart rate variability ratio (HF / LF) in the Composition 2 cohort. The y- axis plots the placebo-adjusted change in HF / LF ratio (A) ; for every participant, the HF / LF ratio recorded after each shot was corrected by subtracting that participant's own placebo value. A A value of zero thus indicates "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis displays AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as S = AA - (AB + AC) . The thickest dashed line inside each violin marks the group mean.

[0139] The HF / LF ratio reflects the balance between parasympathetic (vagal) and sympathetic nervous system activity. It is calculated using a proprietary algorithm that analyzes beat-to-beat heart rate intervals derived from photoplethysmography. A higher HF / LF ratio indicates a shift toward parasympathetic (vagal) dominance, which is associated with a calmer physiological state and improved relaxation. During sleep an elevated HF / LF ratio indicates an enhanced vagal tone and effective downregulation of stress systems, supporting more restorative and higher-quality sleep. S” = 0.127, and its two-sided 95 % confidence interval (0.054 -> 0.200) lies wholly above zero; the paired t-test gives P = 0.0014. Because the complete formulation increased HF / LF more than the summed partial fractions, Figure 9 demonstrates a statistically significant supra- additive effect. Numerical summary listed in Table 1.

[0140] Figure 10 shows the change in Rapid Visual Processing accuracy (RVPA) in the Composition 3 cohort. The y-axis plots the placebo- adjusted change in RVP accuracy (A) ; for every participant the raw accuracy recorded after each shot was first corrected by subtracting that participant's own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino-acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as S=AA- (AB+AC) . The thickest dashed line inside each violin marks the group mean.

[0141] Higher RVPA values indicate better sustained-attention accuracy. S~ = +0.040, and its two-sided 95 % confidence interval ( + 0.015 -► +0.0654) lies wholly above zero; the one-sample paired t-test gives P = 0.0034. Because the complete formulation improves RVPA by more than the summed improvements of the two partial formulations, Figure 10 demonstrates a supra-additive (synergistic) effect. Numerical summary listed in Table 1.

[0142] Figure 11 shows the change in Rapid Visual Processing probability of hit (RVPPH) in the Composition 3 cohort. The y-axis plots the placebo-adjusted change in RVP probability of hit (A) ; for every participant the raw probability of hit recorded after each shot was first corrected by subtracting that participant's own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino-acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as

[0143] S=AA— (AB+AC) . The thickest dashed line inside each violin marks the group mean.

[0144] A higher probability of hit reflects improved vigilance. S” = + 0.124, and its two-sided 95 % confidence interval ( + 0.023 -> +0.224) lies wholly above zero; the one-sample paired t-test gives P = 0.0182. Because the complete formulation raises RVPPH more than the summed partial fractions, Figure 11 demonstrates a supra-additive (synergistic) effect. Numerical summary listed in Table 1.

[0145] Figure 12 shows the change in Rapid Visual Processing total hits (RVPTH) in the Composition 3 cohort. The y-axis plots the placebo- adjusted change in RVP total hits (A) ; for every participant the raw counts of total hits recorded after each shot was first corrected by subtracting that participant's own placebo value; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino-acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as S=AA-(AB+AC) . The thickest dashed line inside each violin marks the group mean.

[0146] More hits correspond to greater sustained-attention accuracy. S~ = + 6.848, and its two-sided 95 % confidence interval ( + 1.50 -> +12.20) lies wholly above zero; the one-sample paired t-test gives P = 0.0145. Because the complete formulation increases total hits more than the summed partial fractions, Figure 12 demonstrates a supraadditive effect. Numerical summary listed in Table 1.

[0147] Figure 13 shows the change in Rapid Visual Processing latency standard deviation (RVPLSD) in the Composition 3 cohort. The y-axis plots the placebo-adjusted change in RVP latency standard deviation (A) ; for every participant the raw latency standard deviation recorded after each shot was first corrected by subtracting that participant's own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino- acid / vitamin / mineral fraction minus placebo, and S = the supraadditive contrast defined as S=AA- (AB+AC) . The thickest dashed line inside each violin marks the group mean.

[0148] Lower latency variability indicates more consistent reaction times, which is linked to greater focus and sustained concentration. S” = -85.23 ms, and its two-sided 95 % confidence interval (-140.84 -> - 29.62) lies wholly below zero; the paired t-test gives P = 0.0043. Because the complete formulation reduces latency variability beyond the summed partial fractions, Figure 13 demonstrates a supraadditive effect. Numerical summary listed in Table 1.

[0149] Figure 14 shows the change in Rapid Visual Processing median latency (RVPML) in the Composition 3 cohort. The y-axis plots the placebo-ad usted change in RVP median latency (A) ; for every participant the raw median latency recorded after each shot was first corrected by subtracting that participant's own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino-acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as

[0150] S=AA— (AB+AC) . The thickest dashed line inside each violin marks the group mean.

[0151] Shorter median latency reflects faster correct responses. S” = - 71.94 ms, and its two-sided 95 % confidence interval (-126.997 -► - 16.88) lies wholly below zero; the paired t-test gives P = 0.0168. Because the complete formulation shortens median latency more than the summed partial fractions, Figure 15 demonstrates a supra- additive effect. Numerical summary listed in Table 1.

[0152] Figure 15 shows the change in Rapid Visual Processing mean latency (RVPTM) in the Composition 3 cohort. The y-axis plots the placebo- adjusted change in RVP mean latency (A) ; for every participant the raw mean latency recorded after each shot was first corrected by subtracting that participant's own placebo score; hence a A value of zero denotes "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis display AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino-acid / vitamin / mineral fraction minus placebo, and S = the supra-additive contrast defined as S=AA- (AB+AC) . The thickest dashed line inside each violin marks the group mean.

[0153] A shorter mean latency signals faster overall reaction speed, benefiting task performance. S” = -6.870 ms, and its two-sided 95 % confidence interval (-12.21 -► -1.525) lies wholly below zero; the paired t-test gives P = 0.0141. Because the complete formulation accelerates mean latency more than the summed partial fractions, Figure 15 demonstrates a supra-additive effect. Numerical summary listed in Table 1.

[0154] Figure 16 shows the change in self-reported energetic efficiency in the Composition 4 cohort. The y-axis plots the placebo-ad usted change in perceived energetic efficiency (A) ; for each participant the self-reported energy efficiency (0 = very efficient, 10 = not at all efficient) were first corrected by subtracting that participant's own placebo score. A A value of zero thus indicates "no change vs placebo" and appears as the dotted horizontal reference line. The x-axis displays AA = complete formulation minus placebo, AB = phytochemical fraction minus placebo, AC = amino acid / vitamin / mineral fraction minus placebo, and S = the supraadditive contrast defined as S = AA - (AB + AC) . The thickest dashed line inside each violin marks the group mean. Lower values on this scale reflect greater perceived efficiency and improved energy utilization. S’ = -1.57, and its two-sided 95 % confidence interval (-3.07 -> -0.06) lies wholly below zero; the paired t-test gives P = 0.042. Because the complete formulation decreased inefficiency ratings more than the summed partial fractions, Figure 16 demonstrates a statistically significant supra-additive effect.

[0155] Numerical summary listed in Table 1.

[0156] Table 1. Placebo-Adjusted Changes (A) and Supra-Additive Contrasts

[0157] (S ) Across Endpoints

[0158] * AA, AB, AC are placebo-adjusted means for the A = complete, B = phytochemical fraction and C= amino-acid / vitamin / mineral fraction, respectively. AA = A"-D", AB= B--D-, AC = C"-D".

[0159] ** Within-sub ect supra-additive contrast: S” = AA - (AB + AC) .

[0160] + Two-sided 95 % confidence interval for S .

[0161] Two-tailed paired t-test for S =0.

[0162] The results from the three independent crossover studies demonstrate that the compositions share a unifying mechanism that supports multiple, interrelated dimensions of mental wellbeing. Each composition contributes to improved cognitive, emotional, and physiological functioning. The synergistic action of their ingredients enables a broader and more effective impact on mental wellbeing than could be achieved by individual components alone.

[0163] Compositions for Study

[0164] The following compositions were made for conducting the study disclosed herein. The compositions were dissolved in water to a total volume of 60 mL.

[0165] 1. Composition 1

[0166] Complete composition A:

[0167] : calculated to yield 80 mg caffeine

[0168] Phytochemical fraction B :

[0169] * : calculated to yield 80 mg caffeine Flavor-matched to Composition A.

[0170] Amino acid, vitamin, mineral fraction C :

[0171] Flavor-matched to Composition A. Placebo composition D :

[0172] Water . Flavor-matched to Composition A.

[0173] 2 . Composition 2

[0174] Complete composition A:

[0175] : calculated to yield 5 mg of withanolides

[0176] Phytochemical fraction B :

[0177] : calculated to yield 5 mg of withanolides Flavor-matched to Composition A.

[0178] Amino acid, vitamin, mineral fraction C :

[0179] Flavor-matched to Composition A. Placebo composition D :

[0180] Water . Flavor-matched to Composition A. 3. Composition 3

[0181] Complete composition A:

[0182] *: calculated to yield 198 mg L-Theanine; **: calculated to yield 66 mg caffeine

[0183] Phytochemical fraction B:

[0184] *: calculated to yield 198 mg L-Theanine; **: calculated to yield 66 mg caffeine Flavor-matched to Composition A. Amino acid, vitamin, mineral fraction C :

[0185] Flavor-matched to Composition A.

[0186] Placebo composition D : Water . Flavor-matched to Composition A.

[0187] 4 . Composition 4

[0188] Complete composition A: Phytochemical fraction B :

[0189] Flavor-matched to Composition A.

[0190] Amino acid, vitamin, mineral fraction C :

[0191] Flavor-matched to Composition A.

[0192] Placebo composition D :

[0193] Water . Flavor-matched to Composition A.

Claims

CLAIMS1. A composition for oral use comprising:Vitamin B6;Vitamin D3 ;L- Tryptophan;Inositol;Taurine;Panax Ginseng extract;Yerba Mate extract; andCocoa bean extract.

2. A composition for oral use comprising: Magnesium;L-Glutamic acid;L-Arginine;Glycine;Ashwaganda root extract;Valerian root extract;Lemon balm extract; and Hops extract.

3. A composition for oral use comprising: Vitamin B12;Vitamin B9;Zinc;N-Acetyl-L-Tyrosine ;Phenylalanine;Green tea extract;Guarana extract;Ginko biloba extract; and Sage leaf extract.4 . The composition according to claim 1 , wherein the composition compri ses :0 . 5 mg to 5 mg, optionally 1 mg to 2 . 5 mg, optionally about 1 . 5 mg or 1 . 4 mg Vitamin B6 ;1 pg to 50 pg, optionally 1 pg to 10 pg, optionally 2 pg to 7 pg, optionally about 5 pg Vitamin D3 ;150 mg to 850 mg, optionally 300 to 500 mg, optionally about 400 mg L-Tryptophan ;200 mg to 100 mg, optionally 300 to 700 mg, optionally about 500 mg Inositol ;200 mg to 100 mg, optionally 300 to 700 mg, optionally about 500 mg Taurine ;10 mg to 100 mg, optionally 20 mg to 60 mg, optionally about 40 mg Panax Ginseng extract ;100 mg to 1000 mg, optionally 200 mg to 600 mg, optionally about 400 mg Yerba Mate extract ; and50 mg to 270 mg, optionally 80 to 150 mg, optionally about 100 mg Cocoa bean extract , optionally wherein water is added to a volume of 60 mL .5 . The composition according to claim 2 , wherein the composition compri ses :80 mg to 400 mg, optionally 100 to 250 mg, optionally about 190 mg or 188 mg Magnesium;50 mg to 450 mg, optionally 100 to 300 mg, optionally about 200 mg L-Glutamic acid;150 mg to 850 mg, optionally 300 to 500 mg, optionally about 400 mg L-Arginine ;150 mg to 850 mg, optionally 300 to 500 mg, optionally about 400 mg Glycine ;100 mg to 300 mg, optionally 150 to 250 mg, optionally about 200 mg Ashwagandha root extract ;15 mg to 60 mg, optionally 25 to 35 mg, optionally about 30 mg or 28 mg Valerian root extract ;45 mg to 180 mg, optionally 60 mg to 120 mg, optionally about 90 mg Lemon balm extract ; and5 mg to 50 mg, optionally about 10 mg to 30 mg, optionally about 20 mg Hops extract , optionally wherein water is added to a volume of 60 mL .6 . The composition according to claim 3 , wherein the composition compri ses :1 pg to 6 pg, optionally 1 . 5 pg to 4 pg, optionally about2 . 5 pg Vitamin B12 ;100 pg to 500 pg, optionally 120 pg to 300 pg, optionally about 200 pg Vitamin B9 ;1 mg to 10 mg, optionally 2 to 7 mg, optionally about 5 mg Zinc ;200 mg to 100 mg, optionally 300 to 700 mg, optionally about 500 mg N-Acetyl -L-Tyrosine ;100 mg to 500 mg, optionally 150 to 350 mg, optionally about 250 mg Phenylalanine ;200 mg to 1000 mg, optionally 250 to 800 mg, optionally about 330 mg green tea extract ;80 mg to 600 mg, optionally 150 to 300 mg, optionally about 200 mg Guarana extract ;50 mg to 350 mg, optionally 90 to 180 mg, optionally about 120 mg Ginko biloba extract ; and50 mg to 250 mg, optionally 60 mg to 150 mg, optionally about 100 mg Sage leaf extract , optionally wherein water is added to a volume of 60 mL .

7. The composition according to any of claims 1 to 6, wherein the composition is a food, food additive, drink, or drink additive .

8. The composition according to any of claims 1 to 7, wherein the composition further comprises at least one of a flavoring, optionally a natural flavoring or a sweetener, a colorant, carbon dioxide, a stabilizer, optionally guar gum, a preservative, optionally citric acid and a combination thereof .

9. The composition according to any of claims 1 to 8, wherein the composition is a dry product for dissolution, optionally for dissolution in water.

10. The composition according to any of claims 1 to 8, wherein the composition is a water-based solution, optionally a waterbased solution that is packaged in a container, optionally a solution with a volume of 50 to 150 mL, optionally of about 60 mL .

11. The composition according to any of claims 1 to 10, wherein the composition is a pharmaceutical composition.

12. The composition according to any of claims 1 to 11 for use as a medicament.

13. The composition according to any of claims 1 to 11 for use in the improvement of mental wellbeing, optionally for use in the treatment of attention deficits, depression, stress, tiredness, sleeping disorders and / or mood fluctuations.

14. A use of the composition according to any of claims 1 to 11 for improving mental wellbeing.

15. A use of the composition according to any of claims 1 to 11 comprising the composition according to claim 1, for improving motivation, resilience, happiness and / or social functioning, and / or reducing sadness and / or anger.

16. A use of the composition according to any of claims 2 to 11 comprising the composition according to claim 2, for improving sleep quality, calmness and / or recovery, activating parasympathetic activity, and / or reducing restlessness .

17. A use of the composition according to any of claims 3 to 11 comprising the composition according to claim 3, for improving vigilance, focus, reaction time.

18. A use of the composition according to any of claims 1 to 11 for the treatment of attention deficits depression, stress, tiredness, sleeping disorders and / or mood fluctuations.

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