Consumable oils and fats enriched for bioavailability and improved benefits to health

Abstract

The present invention relates to dietary and / or nutritional supplement compositions comprising oils and fats enriched with biogenic, or at least biocompatible, fat-soluble compounds comprising at least one biological property that, when consumed, provides one or more biological effects that improve the health status of an organism, preferably a mammal. Methods and kits of formulating same are also provided herein. Combinations of the disclosed supplement compositions with corresponding dosage guidance are also provided. Also provided herein are methods for dissolving the dietary and / or nutritional components, which are preferably fat and / or oil soluble and / or finely dispersible, for making the supplement compositions prior to consumption, in a manner that promotes the ensuing uptake and bioavailability of the supplements in the mammalian body.

Description

CONSUMABLE OILS AND FATS ENRICHED FOR BIOAVAILABILITYAND IMPROVED BENEFITS TO HEALTHTECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates to compositions comprising oils and fats enriched with biogenic, or at least biocompatible, fat-soluble compounds, and related methods and kits for formulating same. The compositions disclosed herein comprise at least five or more fat-soluble supplements that, when consumed, respectively provide one or more biological effects, that improve or maintain the health of an organism, preferably a mammal. The compositions herein can be consumed as a dietary and / or nutritional supplement and / or functional food. The present invention also relates to compositions comprising combinations of dietary and / or nutritional supplements at particular dosages, which optimally promote and support mammalian health.BACKGROUND OF THE INVENTION

[0002] A balanced daily diet is one of the four main pillars of healthy life and the aging process, yet for many, such a diet is often difficult to achieve and maintain. Among possible reasons for this situation is a widespread insufficient daily intake of vegetables and fruits, which are rich sources of healthy biophenols, terpenols, and bioflavonoids. Rather, modern diets commonly feature an unhealthy intake of suboptimal oils and fats. Moreover, dietary plant products and oils are also frequently not chosen carefully enough and are too often consumed in a (highly) processed form. Such dietary practices markedly lower the nutritional value of foodstuffs, for example, by destroying a meaningful proportion of vitamins and other essential food components vital for maintaining good health or by not ensuring their desirable bioavailability. The typical modern diet is also not friendly to microbiota that are essential for healthy food uptake and bioprocessing in the mammalian body.

[0003] It is well established that supplementing a nutrient-deficient diet with the consumption of inadequate dietary and / or nutritional supplements fails to adequately address or resolve the aforementioned dietary deficiencies and their impact on the mammalian body. Supplanting missing vitamins and other bioactive food components requires more than merely ingesting a pill, especially for boosting essential dietary lipidic components; rather, improved nutrient delivery systems are needed. It has been reported that bioavailability of oil componentsconsumed in the form of oil-containing seeds or capsules is lower than their ingestion in a corresponding oil used as a food product (Austria, J. A et al. (2008) J. Am. Col. Nutr. 27:214-21) or when consumed in the form of non-fried fish (Visioli, F. et al. (2003) Lipids, 38: 415-18).

[0004] However, regular intake of lipidic β-carotene and α-tocopherol (and even of hydrophilic vitamin C additives) with food has been correspondingly observed to lower diabetes risk significantly in contrast to consuming such compounds in the form of tablets or capsules alone (Lampousi et al., (2024) Adv Nutr 15:100211). Interestingly, the bioavailability of lipidic β- carotene, lutein, α-tocopherol, and lycopene is reportedly proportional to the co-ingested oil amount up to at least 32 g of fat per meal (White S.W. et al. (2017) Am J Clin Nutr 106:1041).

[0005] Gastric and pancreatic lipases hydrolyse most dietary fats and oils consumed by omnivores and carnivores, predominantly as triglycerides (TAG) in the small intestine, which enables the absorption of the resulting free fatty acids (FFA) in the organ. Conversely, less than half (~48%) of the mean daily intake of polyphenols can be accessed by the small intestine, whereas nearly the same proportion (~42%) becomes bioavailable in the large intestine, where polyphenols are exposed to microbiota that then act on them and vice versa (Saura-Calixto, F. et al. (2007) Food Chem.101: 492-501). One reason for this is that a substantial proportion of polyphenols and carotenoids present in fruit and vegetables is bound to the non-digestible food fraction of ingested foodstuffs, and most dietary polyphenols exist in a conjugated form, for example, in a glycosylated, acylated or esterified, polymerized form. Polyphenols and carotenoids therefore often need to be (co)-processed by the gut microbiota in order to become bioavailable. However, whereas gut microbiota chiefly metabolise proteins and carbohydrates, these microbiota also contain lipases, which play an important role in fat and oil metabolism, either directly or indirectly.

[0006] What is therefore needed are improved methods for providing mammals with fat and / or oil soluble dietary components that are readily available in a healthy mammalian diet, preferably in the form of a healthy carrier oil as a dietary and / or nutritional supplement or functional food, optimally beginning with the dissolution of such dietary and / or nutritional supplement or functional food in the carrier oil prior to ingestion, thus both promoting and advancing the ensuing uptake and bioavailability of these supplements in the mammalian body.SUMMARY OF THE INVENTION

[0007] The present invention relates to supplement compositions formulated based on an underlying principle that any dietary supplement is more beneficial when consumed directly in a foodstuff, or at least in direct combination with a foodstuff, for example, as a dietary supplement that is dissolved in a carrier fat, preferably an oil.

[0008] Another aspect of the present invention is that vitamins and other beneficial nutritional food components and supplements that are dissolved and consumed in such a fatty medium (a term that refers to fats and / oils collectively) can then be presented to the gut microbiota in a finely dispersed distribution, preferably a molecular distribution, as defined in accordance with the supplement compositions herein, which can improve their pharmacokinetics and hence bioavailability to the mammalian body. This improved bioavailability can improve the ultimate bioactivity of such vitamins and supplements, since many such substances can beneficially act together with other biogenic or endogenic substances, as well as with the gut microbiota (flora) of the mammalian organism. Certain oil(s) represent especially attractive food supplements carrier(s) and are also efficient and versatile promoters of an organism's health.

[0009] One preferred embodiment of such a carrier fat is olive oil, which is an unusually oxidation resistant oil and an especially rich source of oleic and linoleic acid. Moreover, olive oil comprises more than fifty known positively (bio)active polyphenols, including but not limited to the polyphenols disclosed herein.

[0010] In one preferred embodiment, the carrier fats are oils that provide a rich source of a>- 3 fatty acids, which are known to featuring multiple health benefits, and can further comprise additional health promoting substances. For instance, in one embodiment, the additional health promoting substance is linseed oil. In other embodiments, linseed oil and another oil rich in ®-3 fatty acids, including but not limited to peri Ila oil and chia oil, may further comprise biophenols and vitamins to enhance a biological effect.

[0011] In other preferred embodiments, the carrier fats can be oils rich in medium chain triglycerides and diglycerides. One advantage of using such oils is based on their ketogenic potential (as described in pending patent application, U.S. Ser. No. 63 / 706,777, entitled "Use of unsaturated fatty acids as biogenic ketones and long-chain PUFA precursors", which is hereby incorporated by reference in its entirety). However, medium chain triglycerides and diglyceridesoils can likewise solubilise greater quantities of at least some of the polyphenol classes and other beneficial lipid-soluble substances disclosed herein.

[0012] When striving to promote health through the use of the dietary and / or nutritional supplements and / or functional food compositions according to the present invention (i.e., collectively, "supplement compositions"), it is advantageous, in some embodiments, to use at least four, preferably at least five added food ingredients and / or supplements in moderate and established practically meaningful quantities rather than to use a large amount of any single such supplement composition, with or without a carrier oil. For this purpose, a subject can instead employ a suite of judiciously chosen, well-characterised, and adequately dosed food supplements, which may be selected from carotenoids, curcuminoids, flavones, flavanols, flavanones, lignans, phenolic acids, alcohols and ketones, vaniloids, stilbenoids, squalenes, tanins, vitamins, among others.

[0013] More generally, the group of eligible additives according to the present invention encompasses any plant-derived substance having at least one measurable beneficial biological effect in a mammal and having a sufficiently high solubility or persistent dispersability in a carrier oil to achieve such biological effect(s). Since many of these nutritional supplements are highly oxidation sensitive, in preferred embodiments, the storage of the compositions should provide suitable protection against oxidation. For instance, in some embodiments, the use of a protective gas and / or lipophilic antioxidants incorporated into the carrier fat or oil can achieve this goal. If an oil contains a fraction of water, the inclusion of water-soluble antioxidants or chelators can also be beneficial for storage of the supplement compositions.

[0014] The present invention further provides for regular, preferably once or twice daily, ingestion of a selected supplement composition, that may include, in some embodiments, one or more carotenoids, polyphenols, sterols, and other lipidic dietary supplements formulated and presented as a solution, or in the case where the composition is a fine dispersion, the composition can be provided as an oil, or a combination of such oils, which can be then consumed in a foodstuff or ingested together with a foodstuff. According to the invention, providing the supplement composition as an oil is superior to the corresponding supplements intake in a tablet or capsule form in terms of providing a resulting beneficial biological effect.

[0015] In some embodiments, improved biological effects are provided by the presently disclosed supplement compositions to a mammalian body by significantly increasing the probability that the disclosed supplement compositions encounter a native fat carrier, whichthen work together to improve both the supplement bioavailability and then the improved biological effect in an organism. In preferred embodiments, the supplement composition is provided in a fine distribution form, for instance, a molecularly fine distribution form as defined herein, preferably as a solution. Moreover, in some embodiments first storing and then consuming a fat-soluble supplement composition provided as a carrier oil improves the stability of the supplement composition.

[0016] In other embodiments, combining different lipid supplements in a carrier oil as a blended combination can increase the resulting solubility of the supplements, which is subject to their relative (molar) concentration. Mutual interactions between different supplement compositions are typically responsible for this effect, especially when the resulting proximity of polar residues on the additives in the supplement compositions diminishes the energetically disadvantageous interactions between such residues and the predominantly non-polar fatty acids (FAs) of the carrier oils that are present in the compositions described herein.

[0017] In some embodiments, oils containing fluid FAs, i.e. shorter or more unsaturated fatty chains with at least one double bond in the FA middle, were observed to act as improved solvents for non-polar supplement components in the compositions, especially if the length of the non- polar component significantly deviates from a typical FA length in typical edible oils comprised predominantly of fatty acids with 18 carbon atoms per chain, which is in the 1.3-1.5 nm range. Better matching of these FA lengths improves the solubility of the supplement in the correspondingly chosen oil in the supplement composition. With these considerations in mind, the person skilled in the art can readily screen various supplement combinations to determine without undue effort which combinations and concentrations can best achieve a select biological effect following consumption of a supplement composition or a combination of supplement compositions.

[0018] In some embodiments, the dietary and / or nutritional supplement combinations in the supplement compositions according to the invention are useful for meeting at least one or even a plurality of health needs of most mammals, preferably humans, not only as a group, but also on an individual basis. Improving the health of an individual mammalian subject is accomplished, for example, by identifying the nutritional deficiencies of each individual subject in particular group. In other embodiments, the mammalian subject is provided with information relating to the dosage of the one or more supplement compositions in addition to the frequency of administration of the supplemented compositions, which can be provided based on the extentof the nutritional deficiencies identified in the mammalian subject, and / or can be provided on the basis of an established standard of the recommended daily allowance (RDA), which is the benchmark average daily intake of a nutrient sufficient to meet the needs of nearly all (97-98%) healthy individuals in a specific life stage and gender group. Established by expert committees, such as the National Academy of Sciences' Food and Nutrition Board in the United States, and the European Food Safety Authority in the EU, RDAs serve as a guideline for ensuring good nutrition at the population level by providing a target for daily average nutrient intake, helping to ensure that diets are nutritionally adequate for a majority of a healthy population. In some embodiments, the combination of supplements in the supplement composition described herein is useful for bringing an individual mammalian subject's intake of a particular component closer to, and preferably within, the range corresponding to the highest quintile for intake of that component in the general, healthy population.

[0019] In certain embodiments, a further objective of the invention is to provide formulation guidance for the fatty acid (FA)-based supplement compositions described herein. According to some embodiments, the invention encompasses a kit containing one or more assays suitable for quantifying components within the supplement composition, including without limitation assays for determining the fatty acid distribution profile in a subject's serum or blood. The subject is a mammal, preferably a human. Such assays may, for example, measure the concentration of n-3 fatty acids, including eicosa pentaenoic acid (EPA) and / or docosa pentaenoic acid (DPA), and may determine the associated omega-3 index, for which commercially available capillary blood tests utilizing finger-prick collection methods are readily accessible. In alternative embodiments, the kit may include assays for quantifying, in blood or serum, any supplemental components that are solubilized or suspended in the carrier oil of the disclosed supplement compositions, such supplemental components including, but not limited to, carotenoids, vitamin D, vitamin E, and related compounds. In further embodiments, the kits may additionally comprise assays enabling non-invasive measurement of carotenoid concentrations, and optionally other supplemental components, through dermal assessment using appropriate sensor technology, a representative example of which is disclosed in Gehlich et al., (2023) J. Biophotonics 16:e202200394).

[0020] In certain embodiments, the kit includes instructions that guide a subject user in formulating the fatty acid-based supplement compositions disclosed herein. The composition may be packaged in one or more containers, each container having a volume selected from the group consisting of 100 ml, 250 ml, 500 ml, and 1000 ml. According to preferred embodiments,the container housing the supplement composition comprises glass, and more particularly dark- tinted glass that attenuates ultraviolet (UV) light transmission, thereby protecting the supplement composition from photodegradation and preserving its stability and biological efficacy throughout storage and handling. This container configuration ensures that the supplement composition retains its functional integrity over extended periods.

[0021] The present invention provides a number of novel dietary and / or nutritional supplement solutions with the supplement compositions described in the embodiments herein. For example, the following aspects of the supplement compositions can exist as independent embodiments, or as combinations in a single embodiment:• The dietary supplement that are soluble or very finely dispersible in a fat carrier are typically formulated and consumed as an oil-based (oily) solution or at least as a sufficiently fine and persistent dispersion in the supplement compositions disclosed herein, which should also be preserved in a condition that prevents the supplement degradation exceeding 10%, with allowance for experimental error, during storage and before use, for instance, at room temperature for at least 12 months, preferably for at least 18 months and more preferably for at least 24 months;• The fat carrier oil(s) of the disclosed supplement compositions can provide a health benefit(s) or biological effect on their own, without the presence of a vitamin or a nutritional supplement;• The oily solutions and / or dispersions disclosed herein are typically ingested on a regular basis, preferably on a daily basis, even more preferably as part of a foodstuff or consumed with the intake of food;• The resulting delivery of the disclosed supplement composition that are provided in a molecularly or otherwise finely distributed form can promote mutual interactions between the gut flora and the supplement compositions described herein, to improve bioprocessing and uptake of the supplements while further increasing their bioavailability;• The oily solution provided in the supplement composition can contain diverse and well characterised, bioactive co-supplements, for example, 4, 5, and preferably 6 or more bioactive co-supplements, each co-supplement being provided in a particular dosage according to the dietary needs of a mammalian subject, or group of mammalian subjects, and, in preferred embodiments, at a dosage according to the body statusand / or age of the subject that can be assessed according to the relevant RDAs for that subject; and• The dose of consumed oils and supplements in the supplement composition can be commensurate to the quantity of the dissolved supplements, and preferably dosed to the needs of the subject, as described herein.

[0022] The present invention therefore beneficially provides a number of embodiments relating to dietary supplement formulations, the resulting products as the instant supplement compositions, in addition to a recommended typical daily dose of the supplement compositions for an average subject, or a group of subjects, preferably comprising the oils described herein, which are preferably enriched with carefully selected and dosed co-supplements.

[0023] According to the invention, in some embodiments methods are provided for facilitating and expediting the amount of dissolving of the co-supplements in a solution, or in the case of a dispersion, in such oils. In some embodiments methods are provided for increasing the amount of the dissolved co-supplements in such oils.DETAILED DESCRIPTION OF THE INVENTION

[0024] Unless defined otherwise, all technical and scientific terms used herein have their plain, general meaning as understood by one of ordinary skill in the art in the relevant technical field.

[0025] The term "about", or "around" when used with a numerical value, means a range surrounding the corresponding numerical value, including the typical measuring error associated with a particular experiment. Unless specifically stated, this value is understood to be, e.g., ± 1%, ± 2%, ± 3%, ± 4%, ± 5%, ± 7.5%, ± 10%, ± 12.5%, ± 15%, ± 17.5%, ± 20%, ± 25%, ± 30%, ± 35%, ± 40% or any other percentage of the numerical value. The term "about" or "around" used in connection with a particular numerical value normally means ± 25%, unless specified otherwise. For the imprecisely known or not uniquely defined quantities, this term implies a range of ± 50%.

[0026] In the broadest terms, the health benefits, or improved "biological effect" as described herein, resulting from the regular use of a composition according to the invention, for example, when treating a condition or disease, can relate to the following, interconnected indicia of aging and / or disease: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrialdysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis.

[0027] A person skilled in the art will be well-acquainted with conventional measuring, testing, and quantification protocols for assessing each of the aforementioned biological effect metrics to identify an improvement, either as a baseline measurement exercise, orfor evaluating a change in the condition over time. For instance, the starting point will typically provide the measurement baseline value(s), relative to which the change of the metric following administration of the composition use can be readily determined and evaluated.

[0028] For instance, for assessing the condition of dysbiosis or gut-status, various testing protocols can be employed, including but not limited to, specific indices reflecting microbial diversity and composition in the gut microbiome. The most common markers can be used to evaluate inflammation and the closely related oxidative stress (OS), which may include, but are not limited to, assessing acute-phase proteins, e.g., CRP, serum amyloid A, fibrinogen and procalcitonin, and cytokines, predominantly TNFα, interleukins 1β, 6, 8, 10 and 12 and their receptors and IFNγ; notably certain cytokines can be disease-specific. OS biomarkers appear less disease or tissue-specific and include lipid peroxidation products, e.g., F2-isoprostanes and malondialdehyde, DNA breakdown products (e.g., 8-OH-dG), protein adducts (e.g., carbonylated proteins), or antioxidant status. More novel OS markers include also -omics related ones, as well as non-invasive, questionnaire-based measures, such as the dietary inflammatory-index. Inflammation markers can moreover be useful to assess altered intercellular communication; even more telling are measurements of various biomarkers and signaling pathways that indicate changes in cell communication, particularly those related to inflammation and cellular senescence.

[0029] To assess mitochondrial dysfunction, at least three biomarker classes are commonly evaluated (Hubens et al. (2022) Mitochondrion 62: 187-204): functional markers measured in blood cells (including but not limited to measuring OXPHOS function, mitochondrial membrane potential, mtDNA copy number, germline mtDNA mutations and deletions) biochemical markers of serum / plasma (including but not limited to determination of lactate, pyruvate, Creatine and creatine kinase, acylcarnitine, etc.), and DNA markers. While no single biomarkers is likely to reveal all underlying mitochondrial dysfunction, combining biomarkers that cover different aspects of mitochondrial impairment addresses this problem. Deregulated mutrient sensing can involve four associated key protein groups, IGF-1, mTOR, sirtuins, and AMPK, and can lead tovarious age-related conditions, including diabetes, obesity, and cognitive decline. It can be detected and monitored, for example, by measuring various biomarkers, including but not limited to altered levels of insulin and insulin-like growth factor (IGF-1), changes in mTOR activity, variations in AMP-activated protein kinase (AMPK) signaling, etc.

[0030] Loss of proteostasis is linked to several human conditions involving deterioration of the organism, particularly neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). However, loss of proteostasis can also contribute to metabolic disorders, cardiac diseases, and various age-related diseases, due to the accumulation of misfolded proteins. Studying and quantifying a loss of proteostasis requires complex, but established procedures (Lim & Vendrusco (2025) PLoS Comput Biol 21(6): el013155). To measure epigenetic alterations associated with these conditions, numerous commercially assays ("genetic clocks") are available, which individually yield different results (Bergsmal & Rogaeval (2022) Neuroscience Insights 15:1-11) and hence should best be used in combination and repeatedly to gain robust result. Telomere length, and thus attrition, can be measured directly in cells. Genomic instability markers can include specific mutations in DNA repair genes, chromosomal rearrangements, and aneuploidy, suitable for identifying and characterizing, often cancerous, tissues addressed by an intervention.

[0031] In addition, known biomarkers characteristically associated with a certain condition can be measured with readily available techniques. For example, in case of diabetes, such protocols include but are not limited to, monitoring glucose and, in the case of insulin, concentrations in the blood (both highlighting the acute situation) or HBA1C concentration in blood (as a longer term and thus trend indicator) can be readily determined.

[0032] In case of a cardiovascular condition, blood pressure and / or blood lipid measurements can provide valuable assessment of the health status of a subject, and are hence useful for determining the treatment success; less common but also useful for the purpose are pulse wave-velocity measurements.

[0033] Various neurological conditions can be assessed, for example, by using one of the known validated tests that monitor and asses cognition, the shortest of which not taking more than only a few minutes (Zhang et al. (2019) Aging Disease 6:1258-1269); to gain a deeper insight on the health status of a subject, MRI imaging can be used.

[0034] To assess bone density and to monitor its changes, dual wavelength X-ray is useful, for example, but also telling can be studying relative frequency of fractures in a study population.

[0035] Many conditions are moreover associated with an increased level of inflammation markers that can be readily assessed by the skilled person using a variety of conventional means by selecting a test method suitable for assessing the beneficial biological effect(s) provided by the compositions according to the invention following administration to a mammalian subject, preferably a human.

[0036] Total daily energy requirement calculations and activity level assessment for a mammalian subject can be established using a number of conventional methods. For example, the estimated total daily energy requirement of an individual can be calculated using well- established predictive equations that calculate basal metabolic rate (BMR) based on demographic and anthropometric parameters. The preferred method employs the Mifflin-St Jeor equation, which has demonstrated superior accuracy compared to alternative formulations, correctly predicting resting metabolic rate within 10% of measured values in approximately 82% of individuals with normal body mass index. For male subjects, the BMR is calculated as: (10 x weight in kilograms) + (6.25 x height in centimeters) - (5 x age in years) + 5, while for female subjects the calculation is: (10 x weight in kilograms) + (6.25 x height in centimeters) - (5 x age in years) - 161. Alternatively, the revised Harris-Benedict equation may be employed, utilizing the formulations: BMR = 88.362 + (13.397 x weight in kg) + (4.799 x height in cm) - (5.677 x age in years) for males, and BMR = 447.593 + (9.247 x weight in kg) + (1.736 x height in cm) - (4.330 x age in years) for females. The calculated BMR represents the minimum energy expenditure required for basic physiological functions at rest and is subsequently multiplied by a physical activity level (PAL) factorto determine total daily energy expenditure (TDEE). The physical activity level multipliers follow established guidelines: sedentary lifestyle (BMR x 1.2 for minimal physical activity beyond basic daily living activities), lightly active (BMR x 1.375 for light exercise or sports 1-3 days per week), moderately active (BMR x 1.55 for moderate exercise or sports 3-5 days per week), very active (BMR x 1.725 for hard exercise or sports 6-7 days per week), and extremely active (BMR x 1.9 for very hard physical work or training twice daily). The resulting TDEE value represents the total calories required to maintain current body weight under the specified activity conditions.

[0037] There are also well-known methodologies for activity level assessment and related classification of same. The determination of whether an individual is sedentary or active can be immediately evaluated using standardized physical activity assessment protocols that quantify both the duration and intensity of weekly physical activity engagement. According to establishedWorld Health Organization guidelines and validated screening instruments, adults are classified as sedentary / inactive when they perform less than 150 minutes of moderate-intensity physical activity per week or less than 75 minutes of vigorous-intensity activity per week, essentially engaging in no structured physical activity beyond basic movements required for daily living such as household activities, occupational tasks, or personal care. Conversely, individuals are classified as active when they achieve or exceed the minimum recommended physical activity guidelines of 150-300 minutes of moderate-intensity aerobic activity per week (such as brisk walking at 3-4 mph, recreational swimming, or doubles tennis), or 75-150 minutes of vigorous-intensity activity per week (such as running, competitive sports, or high-intensity interval training), or an equivalent combination thereof. The assessment can be rapidly conducted using validated screening tools such as the General Practice Physical Activity Questionnaire (GPPAQ), which provides a four-level physical activity index, or the International Physical Activity Questionnaire Short Form (IPAQ-SF), which categorizes individuals based on metabolic equivalent (MET) minutes per week calculations. For immediate clinical assessment, practitioners can employ simple screening questions that evaluate: (1) frequency of moderate-to-vigorous physical activity sessions per week, (2) average duration of each activity session, (3) nature of occupational physical demands, (4) time spent in sedentary behaviors such as sitting or screen time (with >8 hours daily indicating high sedentary behavior regardless of exercise habits), and (5) use of active transportation methods. Individuals reporting fewer than 3 sessions of moderate activity per week lasting less than 30 minutes each, combined with predominantly sedentary occupational and recreational activities, are classified as inactive and would receive a physical activity level factor of 1.2 in energy calculations, while those meeting or exceeding activity recommendations receive correspondingly higher PAL factors of 1.375-1.9 depending on the intensity and frequency of their reported physical activity engagement.

[0038] This systematic approach to energy requirement calculation and activity level assessment provides a standardized, reproducible method for determining appropriate dosing regimens for ketogenic energy compositions, ensuring that the administered quantities align with individual metabolic demands and activity-adjusted energy expenditure patterns while maintaining therapeutic efficacy across diverse patient populations with varying physical activity profiles and metabolic requirements.

[0039] The term "carotenoid" herein refers to simple hydrocarbon carotenes (including α-, β -, γ-, δ-, ε- and ζ-carotene and the more complex lycopene, lycopersene, and phytofluene, etc.),their corresponding alcohols (including e.g., alloxanthin, γ-caroten-16-ol, crypto-monaxanthin, cynthiaxanthin, gazaniaxanthin, lutein, lycoxanthin, rhodopin and rhodopinol, zeaxanthin, etc.), ethers (rhodovibrin and spheroidene) as well as epoxides (e.g., citroxanthin, diadinoxanthin, luteoxanthin, mutatoxanthin, neo-, folia- and trolli-chrome, etc.), their corresponding aldehydes (e.g. rhodipinal and warmingone), acids and acid esters (torularhodin and its methyl-ester), ketones (e.g., astacene, astaxanthin and canthaxanthin, capsanthin and capsorubin, cryptocapsin, echinenone and its 3'-hydroxy version, flexi- and 3-OH-canthaxanthin, okenone, pectenolone, phoeniconone, phoenicopterone, etc.), esters of alcohols (e.g., astacein, fucoxanthin, physalien, etc.), apocarotenoids (e.g., apo-2- and apo-6'-lycopenal, azafrinaldehyde, citranaxanthin, crocin and crocetin, paracentrone, sintaxanthin, etc.), norcarotenoids, secocarotenoids and retrocarotenoids as well as retro-apo-carotenoids, and higher carotenoids.

[0040] The term "dosage" herein relates to the dietary needs of a mammalian subject, or group of mammalian subjects. In a preferred embodiment of the invention, "dosage" refers to the amount of the supplement compositions disclosed herein that are required to meet the dietary needs established by expert committees. In another preferred embodiment, the dosage is chosen so as to bring the intake of the reference substance for the dosage closer to and preferably into the range of the highest quintile of the substance intake in the general, healthy population, as published in one or more peer-reviewed publications in broadly respected scientific journals. In a further preferred embodiment, the dosage is selected by a trained dietitian or a physician to meet a specific dietary or health need of a mammalian subject. The dosage selection should consider the body status and / or age of the subject, which can be assessed according to the relevant RDAs for that subject.

[0041] The term "fat" in its broadest meaning as used herein refers to an oil, a fat, or a mixture thereof. Most frequently, this term refers to tri- and / or, but less preferably, diglycerides of fatty acids that can be saturated, which is typical of solid fats, such as lard, but including also triglycerides that are fluid at mammalian body (or room) temperature if their average fatty acid chain has fewer than around 10 carbon atoms or 12 C-atoms, as in the medium chain triglycerides. Fatty acids can be, alternatively, mono-, di-, tri-, or poly-unsaturated, i.e., comprising 1, 2, 3 or ≥ 4 double bonds per chain (as in fluid oils), or else contain one or more side branches (e.g. methylene groups), etc. Monoglycerides and (for example, various sugar) derivatives of di- and monoglycerides may be used as fats in these embodiments so long as regulatory provisions, supplement solubility limits, and compatibility with other productcomponents (e.g. water) justify and permit their inclusion, which would be known to the skilled person.

[0042] The term "fat-soluble supplement" herein refers to any supplement to a foodstuff that is soluble or at least finely dispersible in fat or miscible with fat to the extent needed for purposes of this invention. In addition to the originally fat-soluble vitamins, this term includes, but is not limited to, biopolyphenols, as defined herein, and to fatty derivatives of otherwise water-soluble dietary supplements in the range of their respective solubility and / or very fine dispersability in carrier oil(s). Fat-soluble supplements thus also include, but are not limited to, fatty acids and other acids and polyacids, amides and polyamides, or amines and polyamines, many of which are originally insufficiently fat-soluble (i.e., insufficiently lipidic) biogenic active substances that can be made more soluble by derivatisation into the corresponding fatty ethers or preferably esters (exemplified herein by acyl gallates), various essential oils components, including but not limited to, borneol and its acetate, bisabolol, bornyl acetate, δ-cadinene, camphene, camphor, carvacrol, 3-carene, carvone, caryophyllene and its oxide, 1,8-cineole, citral (or geranial), citrol, citronelol, p-cymene, β-elemene, ethyl maltol, eudesmol, elemol, estragole, α-eudesmol, eugenol, genchone, farnesene, geraniol, and geranyl acetate, germacrene D, guaiol, humulene, laevo-perillaldehyde, linalool and its oxide, linalyl acetate, limonene, menthol, menthone, menthyl acetate, myrcene, nerone acetate, ocimene, octanal, perillaldehyde, α- pinene, piperitenone and its oxide, pulegone, sabinene, safrole, selinene, terpinen-4-ol, alpha- terpineol, γ-terpinene, terpinolene, thujene, thymol, valerianol, zhymol, etc., many of which are from the class of terpenoids and may be included in the present supplement compositions according to the invention to provide a desirable biological effect and / or to improve the organoleptic and sensory properties of the resulting products, as claimed herein.

[0043] The term "fat-soluble vitamin" herein generally refers to vitamins A, D, E and K. For example, the term "vitamin A" includes retinol and retinyl ester, as well as provitamin A carotenoids alpha-, beta-, gamma-carotene, and the xanthophyll beta-cryptoxanthin. The term "vitamin D" typically refers to either D2(ergocalciferol) or the D3subtype (cholecalciferol), or both, but herein also comprises the entire vitamin D group of secosteroids that includes subtypes D1(a 1 / 1 ergocalciferol / lumisterol mixture), D4(22-dihydroergocalciferol), and D5(sitoca Iciferol). The term "vitamin E" encompasses alpha-, beta-, gamma, delta- tocopherols and the corresponding four, more unsaturated and therefore less preferred, tocotrienols, as well as their derivatives including, but not limited to, tocopherol acetate. The term "vitamin K" refers tovitamin K1(phytomenadione) and the vitamin K2group (menaquinones, typically with 4-12 carbon atoms per side chain and preferably 4 or 7 such C-atoms), or vitamin K3(menadione).

[0044] The terms "finely distributed" or "molecularly distributed", and the corresponding terms relating to "distribution" refer herein to a grouping, e.g., an aggregation, of oil components with an average diameter of the largest of co-supplement groups, for instance, predominantly in the range up to 150 nm, preferably smaller than 100 nm, more preferably smaller than 75 nm, even more preferably smaller than 50 nm. In some embodiments, the grouping comprises one co-supplement molecule. In other embodiments, the grouping comprises 2, 3, 4, 5, or 6 co- supplement molecules, corresponding to a solution.

[0045] The term "lipidic" herein means a molecule having an affinity for hydrophobic, and hence oily, surroundings.

[0046] The term "mechanical stress" herein means the mechanical stress exerted on the supplement compositions of the invention by a suitable device. In some embodiments, the device can be a rotor-stator shearing device (e.g. an in-line or vessel homogeniser), a high- pressure homogeniser, a French-press, or the like. The device can diminish the starting size of the co-supplement(s) aggregates (whether in crystalline or fluid form) for achieving a fine or molecular final distribution, and in preferred embodiments, a complete or near complete dissolution of the co-supplement(s) during a practically and / or commercially acceptable time period.

[0047] The term "ω-3 fatty acid rich oils" refers herein primarily but not exclusively to oils extracted from linseed or camelina or peri Ila or chia seeds, each of which contains a relatively high proportion of the essential alpha-linolenic acid (= C18:3(n-3)). The term also refers to oils extracted from other plants or algae that abound in even more unsaturated and / or longer ω-3 = n-3 = α-unsaturated fatty acid(s). One such example is Echium plantagineum, which provides stearidonic or moroctic acid (= C18:4(n-3)) and can also be extracted from leaves or borage (Borago officinalis) in a glycolipid or monogalactosyl-diacylglycerol form. Cyanobacterium Spirulina is another potential source of stearidonic acid. Even longer and more unsaturated, but therefore also more oxidisable, n-3 fatty acids are employed in some embodiments of the compositions disclosed herein, including C20:5(n-3) or EPA, C22:5(n-3) or DPA, and C22:6(n-3) or DHA, which can all be sourced from fatty fish (especially their liver), but which gain such fatty acids from krill that in turn receives them from algae, especially the Nannochloropsis, Phaeodactylum, Schizochytrium and Thraustochytrium algae varieties. In other embodiments,algae, and the oils obtained from them, represent another possible source of ω-3 polyunsaturated fatty acids according to the present invention, as are transgenic versions of plants, algae, or potentially other suitable related organisms.

[0048] The terms "food" or "foodstuff" are used interchangeably herein, and include but are not limited to baked confectionery foods, cakes, cereals, smoothies, salads, drinks, dressings or mayonnaise, fried cakes or other kinds of fried foods, ice creams, meats, margarine or fat spreads on breads, oils, powder containing coffee or tea, or concentrate in fluid or dry form suitable for incorporation or transformation into any nutritional product used by ingestion.

[0049] The terms "ingestion" and "consumption" are used interchangeably herein, and refer to the intake of a substance by an organism, typically through the mouth into the gastrointestinal tract (populated by flora, microbiota), for example, through eating or drinking.

[0050] The term "oil" refers to any edible fat that is fluid at room temperature, or at least at mammalian body temperature.

[0051] The term "polyphenol" or "biophenol" as used herein refers generally to "phenols", "terpenoids", and "flavonoids". Phenols are a class of substances comprising at least one aromatic ring bearing at least one hydroxyl group and includes, but is not limited, to, phenolic acids, in particular benzoic and cinnamic acids and their derivatives (e.g., respectively, gallic and caffeic acid and their alkyl esters, etc.) and their corresponding analogues, such as curcuminoids (i.e. curcumin and derivatives, etc.), vanilloids (e.g. acetovanilon or apocynin, capsaicin, and their derivatives, etc.), paradol and derivatives, hydroxytyrosol and biphenyls (e.g., honokiol and magnolol); furthermore stilbenes (including resveratrol, and its derivatives including, piceid, pterostilbene, etc.), chaicones (including xanthohumol and isoxanthohumol, etc.), tannins (polymers of gallic acid, phloroglucinol or flavan-3-ol, including tannic and ellagic acid, rugosin E, punicalagin, etc.), the condensed tannins, or proanthocyanidins. The class of terpenoids, or isoprenoids, stemming from the five-carbon compound isoprene and its derivatives, includes, for example, hemiterpenoids (such as isoprenol, isovaleramide, isovaleric acid, prenol, etc.), monoterpenoids (such as several of the essential oils components including e.g., bornyl acetate, citral, geraniol, linalool, thymol, etc.), sesquiterpenoids (such as farnesol, geosmin, humulone), diterpenoids (such as abietic acid, ginkgolides, retinol, steviol), sesterterpenoids (such as amyrin, limonoids, sterols, squalene, etc), and tetraterpenoids ("carotenoids"). The class of flavonoids shares a flavan skeleton with at least hydroxyl groups and includes, but is not limited to, flavones (preferably flavone, but also crysin, wagonin, acacetin, oroxylin A, and less preferably apigenin,baicalin, hispiludin, luteolin, eupalitin, etc.), isoflavones (e.g., genistein, daidzein and its methylated version formononetin, equol, biochanin A, etc.), the flavanols (e.g., kaempferol, quercetin, myricetin, fisetin, isorhamnetin, etc), flavanones (pinocembrin, naringenin or 8- prenylnaringenin, etc.), flavanes and isoflavanes (e.g., catechol and vestitol, etc.), silybin or silibinin, which is the main ingredient of a bioactive silymarin mixture, theaflavins, thearubigins, and theasinensins, propolis polyphenols (e.g., propolins C, D, F and G), anthocyanins (esp. rosinidin, europinidin, pelargonidin and malvidin, but also cyanidin, peonidin delphinidin, petulidin), coumarins (e.g., 4-methyl coumarin and its precursor 7,8-Dihydroxy-4- methylcoumarin, auraptene and fraxin, etc.), lignans, and the like.

[0052] With at least 3 OH groups on two rings, flavonoids are typically relatively less soluble in oils than phenols, but low solubility in oils and water is a challenge for most polyphenols and even phenols. According to the present invention, one should therefore consider using any of the more lipophilic derivatives of these compounds, which are most often but not necessarily of an alkyl-ester type. Employing propyl- or octyl-gallate instead of gallic acid exemplifies one such solution.

[0053] The terms "polyphenol" or "biophenol" also refer to substances that are neither phenols, nor terpenoids, nor flavonoids but are both lipophilic and bioactive, such as α-lipoic or thioctic acid, bioactive fatty amines and amides, very long chain alcohols or policosanols, some phospholipids, etc. When referring to olive oil biophenols, the term includes specifically oleuropein, oleoeuropein acid, 3,4-DHPEA-EA and 3,4-DHPEA-EDA or oleuropein aglycone mono- and dialdehyde, oleacein, oleaceinic acid, 3,4-DHPEA or hydroxytyrosol, ligstroside, p-HPEA-EA and p-HPEA-EDA or ligstroside aglycone mono- and dialdehyde; oleocanthal, oleocanthalic acid, tyrosol, p-HPEA, methyloleoside, nuzhenide, (e)-3-(l-oxobut-2-en-2-yl) glutaric acid, vanillin, elenolic acid, p-salicylic acid, p-coumaric acid, gallic acid, caffeic acid, ferulic acid, protocatechuic acid, vanillic acid, syringic acid, homovanillic acid, sinapic acid, chlorogenic acid, verbascoside, rutin, apigenin, apigetrin, isorhoifolin, glucocyanidin, antirrhinin, luteolin, luteolol, cynaroside, veronicastroside, diosmetin, hesperidin, quercetin, quercitrin, dihydroquercetin, (+)-l- acetoxypinoresinol, (+)-l-pinoresinol, trans-cinnamic acid, gentisic acid, a-resorcylic acid, catechol, hydroquinone, 2-naphthol, or o-coumaric acid.

[0054] The term "practically meaningful" means herein reaching or exceeding, with the referred to substance or treatment, a concentration or dose threshold identified herein, with the lowest of 0.0001% of the substance dose resulting in a No Observed Adverse Effect Level('NOAEL'), or refers to the maximum dose or level ('ADL') allowed by a competent national regulatory agency (e.g. European Food Safety Agency (EFSA), Norwegian Food Safety Agency, the US Food and Drug Administration (FDA), UK Nutrition and Health Claims Committee, (UKNHCC), Joint FAO / WHO Expert Committee on Food Additives (JECFA), or an alternative desirable dose justified by the scientific reasoning to be practically valuable.

[0055] The term "predominantly" means herein at least greater than 50%, more preferably greater than 68%, and most preferably greater than 75%.

[0056] The term "range" used in the context of ≥ 2 numerical values means that the numerical value can be any value encompassed within the specified range. For the purposes according to the present invention, "range" also means that, within the broadest range specified, any narrower range may be selected using 50%, 45%, 40%, 36%, 33%, 30%, 27.5%, 25%, 22.5%, 20%, 17.5%, 15%, 12.5%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the entire specified range. By way of example, a range of 1 to 10 is thus subdivisible and / or limited to 1 to 2, 2 to 3, 3 to 4, 4 to 5, 5 to 6, 6 to 7, 7 to 8, 8 to 9 and 9 to 10 or else to 1 to 3.33, 3.33 to 6.66 and 6.66 to 9.99 or 3.33 to 9.999, or from 1 to 4, 4 to 7, 7 to 10, 1 to 7 or 4 to 10; or else from 1 to 3.25, from 3.25 to 5.5, from 5.5 to 7.75, from 7.75 to 10, from 1 to 5.5, from 1 to 7.5, from 3.25 to 7.5 from 3.75 to 10, or from 5.5 to 10.

[0057] The term "soluble" or "dissolvable" or "dispersible" as used herein means achieving a measurable concentration of a substance indicated as 'soluble' in a specified solvent medium.

[0058] The term "supplement" refers to any substance, or a combination thereof, that can lead to a beneficial biological effect in a mammalian body following oral consumption, whether in the form of a food supplement or as a functional food.

[0059] Equivalents to the compositions and methods according to the present invention therefore fall within the contemplated scope of the invention and the corresponding claims. The contents of all cited references, patents, and patent applications are hereby incorporated by reference; the appropriate components, processes, and methods of these cited disclosures may be suitably selected for use in the embodiments of the presently disclosed invention.EXAMPLES

[0060] Supplement Compositions

[0061] The supplement compositions comprising oils and fats and enriched with biogenic, or at least biocompatible, fat-soluble dietary supplements disclosed herein, wherein thecompositions comprise at least five, preferably six, more preferably seven and most preferably eight or more fat-soluble supplements, wherein the compositions, when consumed, achieve one or more biological effects that improve or maintain the health of a mammalian subject, preferably a human.

[0062] As described herein, the particularly beneficial polyphenol-carrier fat compositions can be produced based on selecting the optimal and boundary conditions for an individual, based on the subject's body and health status, as well as the subject's typical daily nutrition intake.

[0063] The selection of the exemplary supplement compositions shown in Table 1 are therefore neither exclusive nor exhaustive. For instance, changing regulatory requirements may force, or permit, supplement composition modifications. Formulation adjustments and more complex preparation methods can, for example, use higher concentrations of the disclosed supplement compositions than otherwise specified in Table 1.

[0064] According to the present invention, the formulations shown in Table 1 provide a useful first guidance to any skilled person making the supplement compositions disclosed herein, which is advantageously enriched in oil formulations to maximize a beneficial biological effect that improves or maintains the health of the mammalian organism.

[0065] Depending on intrinsic solubility of the substances used for oil enrichment in the carrier oils described herein, as well as the form of the starting substance, e.g., a micronized or very fine powder vs. materials with relatively large diameters and hence more slowly soluble, a simple mixing procedure can be used to prepare the enriched oils exemplified in Table 1. Otherwise, it may be necessary to expose the carrier oil and the substances mixture to mechanical stress to achieve a timely, desired dissolution of all the additives to the carrier oil, which would be apparent to the skilled person. To such end it can be advantageous also to warm the oil during the process to promote dispersion, either by the 'stressing process' itself or by use of an external heat-source. To obtain at least a very fine and sufficiently stable dispersion, the carrier oil and the dispersible substance density should be matched to within a 10%, preferably 7.5%, more preferably 5% and even more preferably 2.5% range since a smaller average aggregate size permits a relatively greater densities mismatch without causing sedimentation. Care should be taken to keep the oxidation-sensitive ingredients minimally exposed to air in order to minimize oxidative degradation, typically by using stripped oil(s) and / or a protective atmosphere, for example, an atmosphere with low oxygen partial pressure of. < 0.05%.

[0066] The appropriate amounts of each and all selected supplement composition components are weighed on a suitable balance scale and then kept in a sealable container prior to their introduction into a stripped carrier oil. Exemplary, but not limiting, compositions are shown in Table 1.

[0067] The initial dispersion of the components in the carrier oil is achieved by mechanical mixing, preferably gentle mixing and for a duration sufficient to coarsely disperse the components. Unless the container is already essentially free of oxygen, the air introduced into the oil tank during the introduction of the components should be replaced with a protective gas while further stirring or otherwise more vigorously mixing the enriched oil. If deemed necessary to minimise oxidation, the flushing and mixing procedure should be continued, ideally by introducing the protective gas close to the mixing device. The combination of oil and supplement(s) components should be mixed vigorously until large particles or sedimented material are no longer visible or until the targeted concentration of each dissolved or very finely dispersed supplement in the oil has been reached. The typical time needed to meet this goal depends predominantly on the final product composition, the volume density of the energy used for mixing, the mixing chamber geometry, and the processing temperature; higher temperature (predominantly in ≤85 °C range) normally shortens the necessary processing time.

[0068] When a high-shear rotor-stator mixer (driven by an up to 8 kW engine) is used to process 1000 L of oil, the processing time for a representative supplement composition of the Table 1 is predominantly in the range ≤120 s / L, preferably ≤60 s / L, and even more preferably ≤30 s / L at processing temperature ≤40 °C.

[0069] If one or several of the supplements are used in less than a 98% pure form, or if an additive solubility limit in the carrier oil is below the additive targeted concentration, the final supplement composition should be acceptable for the contemplated use even if the oil still contains some dispersed (and ultimately sedimented) material, provided that the quantity of impurities is tolerable or else the final dispersion of the poorly soluble supplements is predominantly very fine.

[0070] Supplement composition embodiments presented in Table 1 can be based on the use of extra virgin olive oil as the selected carrier for the indicated dietary and / or nutritional supplement compositions according to the invention. Composition embodiments with a higher supplement concentration are typically based on ω-3 fatty acid rich oils, for example, linseed oil, peri Ila oil, chia oil, echium oil, or on an oil comprising primarily medium chain triglycerides as therespective fat carrier (for example, coconut oil, as a widely available source of such triglycerides), owing to higher supplement solubility in such carrier oils with more fluid chains at ambient and physiological temperature. Mixtures of olive oil and of any of the presently disclosed ω-3 fatty acid rich oils can serve the same purpose. Some embodiments comprise, for example, a 1 / 1 weight / weight mixture of enriched linseed oil, perilla oil, chia oil, echium oil, and the like.

[0071] Further alterative combinations contain around 10% and up to 25% of a medium chain triglyceride oil, and may additionally comprise combinations of other preferred oils, especially of extra virgin olive oil and of ω-3 fatty acid rich oils, for instance, in a range of 10 / 90 to 90 / 10 weight / weight.

[0072] Table 1: Supplement compositions comprising exemplary combinations of preferred embodiments of oils, further illustrating exemplary representative supplement compositions.Table 1 (continued)Table 1 (continued)Table 1 (continued)

Claims

CLAIMS1. A consumable supplement composition comprising:(a) a consumable oil, and(b) at least five, preferably six, more preferably seven and most preferably eight or more fat-soluble supplements, wherein the components specified in (a) and (b) are dissolved in the consumable oil to form the consumable supplement composition, and optionally wherein consuming the supplemental composition by a subject causes a measurable increase in a biological effect that improves or maintains the health of the subject.

2. A consumable supplement composition comprising;(a) at least one consumable oil, and(b) at least five, preferably six, more preferably seven, and most preferably eight or more fat-soluble supplements selected from fat-soluble vitamins or polyphenols, wherein the components specified in (a) and (b) are dissolved or finely dispersed in the consumable oil to form the consumable supplement composition, and optionally wherein consuming the supplemental composition by a subject causes a measurable increase in a biological effect that improves or maintains the health of the subject.

3. The consumable supplement composition according to claim 1 or 2, wherein the composition comprises 6, 7, or eight fat-soluble supplements.

4. A consumable supplement composition comprising:(a) a consumable oil comprising a combination of carotenoids, calciferol, and vitamin E dissolved in the consumable oil, and(b) at least two additional co-supplements including a vitamin and one or more polyphenols, wherein the components specified in (a) and (b) are dissolved together in the consumable oil to form the consumable supplement composition, andoptionally wherein consuming of the supplemental composition by a subject causes a measurable increase in a biological effect that improves or maintains the health of the subject.

5. The consumable supplement composition according to claim 4, wherein the carotenoid is selected from a α-, γ-, δ-, ε- and ζ-carotene, lycopersene, phytofluene, alloxanthin, γ-caroten- 16-ol, crypto-monaxanthin, cynthiaxanthin, gazaniaxanthin, lycoxanthin, rhodopin, rhodopinol, rhodovibrin, spheroidene, citroxanthin, diadinoxanthin, luteoxanthin, mutatoxanthin, neochrome, foliachrome, trollichrome, rhodipinal, warmingone, torularhodin, astacene, canthaxanthin, capsanthin, capsorubin, cryptocapsin, echinenone, flexicanthaxanthin, 3-OH- canthaxanthin, okenone, pectenolone, phoeniconone, phoenicopterone, astacein, fucoxanthin, physalien, apo-2- and apo-6'-lycopenal, azafrinaldehyde, citranaxanthin, crocin and crocetin, paracentrone, sintaxanthin, norcarotenoids, secocarotenoids, retrocarotenoids, retro-apo- carotenoids, or a combination thereof.

6. The consumable supplement composition according to claim 4, wherein the carotenoid is β-carotene, lutein, zeaxanthin, astaxanthin, lycopene or a combination thereof.

7. The consumable supplement composition according to claims 4 to 6, wherein the polyphenol is preferably selected from antioxidants and essential oil components, and derivatives thereof.

8. A consumable supplement composition comprising:(a) one edible oil comprising a combination of carotenoids, calciferol, vitamin E dissolved in the oil, and(b) at least three additional supplements selected from vitamin K, chalkones, curcuminoids, flavanols, flavanones, phenolic acids, stilbenes, or vanilloids, wherein the components specified in (a) and (b) are dissolved in the consumable oil to form the consumable supplement composition, and optionally wherein consuming of the supplemental composition by a subject causes a measurable increase in a biological effect that improves or maintains the health of the subject.

9. The consumable supplement composition according to any of the preceding claims, wherein the consumable oil is an olive oil, preferably a virgin olive oil, and even more preferably an extra virgin olive oil.

10. The consumable supplement composition according to any of the preceding claims, wherein the consumable oil is an ω-3 fatty acid rich oil, preferably obtained from a plant.

11. The consumable supplement composition according to claim 6, wherein the ω-3 fatty acid comprises 18-22 carbon atoms and 3-6 double bonds, preferably 18 carbon atoms per chain and 3 or 4 double bonds, preferably 3 double bonds.

12. The consumable supplement composition according to claims 5, 6 or 7, wherein the consumable oil comprises concentration of olive oil phenols above 250 mg / kg, preferably above 500 mg / kg, more preferably above 750 mg / kg, and even more preferably above 900 mg / kg.

13. The consumable supplement composition according to any of the preceding claims, wherein the consumable oil comprises at least 25% ω-3 fatty acids, preferably at least 40% ω-3 fatty acids, and more preferably at least 45% ω-3 fatty acids.

14. The consumable supplement composition according to any of the preceding claims, that when consumed, causes a measurable increase in a biological effect that improves or maintains the health of the subject, preferably a human.

15. A kit for measuring concentration and distribution of a fatty acid in a subject following the consumption of supplement composition according to any of claims 1 to 14, comprising:(a) one or more assays for measuring fatty acid concentrations in a biological sample obtained from the subject, wherein the biological sample is selected from blood and serum;(b) optionally, one or more assays for quantifying a supplement component in the supplement composition, preferably carotenoids, vitamin D, and / or vitamin E in a biological sample obtained from the subject; and(c) optionally, instructions for formulating the fatty acid-based supplement composition based on measured concentrations obtained from the one or more assays.

16. The kit according to claim 15, wherein the one or more assays for measuring fatty acid concentrations comprise:(a) an assay for determining n-3 fatty acid concentration;(b) an assay for determining eicosapentaenoic acid (EPA) concentration;(c) an assay for determining docosapentaenoic acid (DPA) concentration; and / or(d) an assay for determining an omega-3 index.

17. The kit according to claim 15 or 16, wherein at least one assay utilizes a capillary blood sample obtained via finger-prick collection.

18. The kit according to claims 15 or 17, further comprising a non-invasive sensor for measuring a supplement component in the supplement composition, preferably measuring carotenoid concentration in skin of the subject.

19. The kit according to any of claims 15 to 18, wherein supplemental composition is provided in one or more containers having a volume selected from 100 ml, 250 ml, 500 ml, and / or or 1000 ml.

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