US 20130261183A1 (19) United States (12) Patent Application Publication (10) Pub. N6.: US 2013/0261183 A1 Bhagat (43) Pub. Date: Oct. 3, 2013

(54) OPTIMIZED NUTRITIONAL (52) US. Cl. FORMULATIONS, METHODS FOR CPC ...... A23L 1/296 (2013.01); A61K 31/202 SELECTION OF TAILORED DIETS (2013.01); A23L 1/293 (2013.01) THEREFROM, AND METHODS OF USE USPC .. 514/560; 426/648; 426/72; 426/61; 426/71; THEREOF 426/599; 426/618; 426/634; 426/632; 426/629; 426/638; 426/641; 426/643; 426/615; 426/580; (76) Inventor: Urvashi Bhagat, California, CA (U S) 426/583; 426/87; 434/127 (21) Appl. No.: 13/877,847 (22) PCT Filed: Oct. 14, 2011 (57) ABSTRACT (86) PCT No.: PCT/US11/56463 § 371 (0X1)’ Nutritional compositions and formulations that optimize (2), (4) Date: Apr. 4, 2013 nutritional contents are provided. Dietary compositions and Related US. Application Data methods for tailoring such compositions to optimize levels of nutrients that have bene?cial effects Within speci?c ranges (60) Provisional application No. 61/393,235, ?led on Oct. are provided. Dietary plans, and formulations comprising 14, 2010, provisional application No. 61/415,096, dietary products that comprise optimized levels of nutrients ?led on Nov. 18, 2010. derived from phytochemicals, antioxidants, vitamins, miner als, lipids, proteins, carbohydrates, probiotics, prebiotics, Publication Classi?cation microorganisms and ?ber. Diet plans and modular nutritional (51) Int. Cl. packages comprising food and drink items tailored according A23L 1/29 (2006.01) to consumer patterns typed by diet, age, size, gender, medical A61K 31/202 (2006.01) conditions, family history, climate and the like are provided. US 2013/0261183 A1 Oct. 3, 2013

OPTIMIZED NUTRITIONAL [0006] Therefore, it is desirable to develop a tailored nutri FORMULATIONS, METHODS FOR tional program(s) or delivery system(s) Where consumers are SELECTION OF TAILORED DIETS guided to consume naturally-occurring foods that have been THEREFROM, AND METHODS OF USE matched keeping interactions, amounts, and consumer pref THEREOF erences in perspective. Further, the program(s) need to cau tion consumers against food types and amounts that may CROSS-REFERENCE TO RELATED disrupt the nutritional optimiZation provided by the program. APPLICATIONS Within the broad parameters of personaliZation and moderate [0001] This patent application claims priority of US. Pro compliance, consumers may be at a reduced risk for chronic diseases, and With narroWer parameters in personaliZation visional Patent Application Ser. No. 61/393,235, ?led Oct. and greater compliance, greater health bene?ts may be 14, 2010 and US. Provisional Patent Application Ser. No. achieved. To date tailored programs have been dif?cult to 61/415,096, ?led Nov. 18, 2010. The contents ofthese patent applications are incorporated herein in their entirety by ref devise, particularly With regards to phytochemicals and lipid interactions and amounts. erence. [0007] The programs may be component or module based to alloW ?exibility and convenience for consumers. The ben TECHNICAL FIELD OF THE INVENTION e?ts may be incremental With greater adherence to selection [0002] This invention relates to the ?eld of nutritional com of components Within the program. For example, lipid types positions and formulations. In particular, the application and amounts are critical to health and can vary due to a relates to methods of selection of nutritional plans tailored to number of factors, thus making the calibration complex for optimiZe bene?ts derived from nutrients. More particularly, consumers to manage every day. Both the composition and the invention relates to formulations and dietary products that the amounts need to be managed. For example, lipid require provide compositions comprising optimiZed levels of nutri ment can be as much as 80 grams or 720 calories more for one ents such as phytochemicals, antioxidants, vitamins, miner family member (a 25-year-old male) than another (a 3-year als, lipids, proteins, carbohydrates, probiotics, prebiotics, old child). This is further complicated because lipids do not microorganisms and ?ber. mix homogenously With food; as such, individual portions may contain a disproportionate amount of lipids. Conse BACKGROUND OF THE INVENTION quently, When lipids are supplemented Within a given food [0003] The requirements of phytochemicals, lipids, and preparation, an individual member may consume too little or too much of the lipids. Similarly, men may have a greater need some other nutrients for human health are rather sensitive. for a nutrient than Women. A tailored dietary component There are many nutrient interactions and their range of health system may provide an effective solution. ful effectiveness is narroW and changes With diet type and/or demographic factors. [0008] As such there is a need for component based nutri tional formulations, tailored diets and diet plans that provide [0004] Formulations comprising lipids, antioxidants, phy optimiZed levels of nutrients such as phytochemicals, anti tochemicals, vitamins, minerals, microorganisms or a com oxidants, vitamins, minerals, lipids, proteins, carbohydrates, bination thereof, are traditionally provided as supplements or probiotics, prebiotics, microorganisms and ?ber. Some of randomly added to nutritional or topical formulations. The these nutrients are rarely the focus of diet plans, e.g. phy focus is often on suppressing oxidation or in?ammation, tochemicals, yet too much or too little of such micronutrient Which ignores the fact that both oxidation and in?ammation can turn an otherWise bene?cial micronutrient in the diet to have a necessary role in physiology. Further, selective, repeti have adverse effects. tive, and excessive suppression may lead to dysregulation of in?ammation With greater health consequences. Therefore, SUMMARY OF THE INVENTION current approaches have the dangers of mismanaged and/or excessive delivery, Which may be harmful particularly in [0009] This invention relates to novel strategies for devel combination With natural “nutrient rich foods,” including oping component based dietary formulations, and programs. foods such as nuts, seeds, oils, grains, legumes, fruits, veg In particular, the invention relates to generating tailored diets etables, seafood, herbs, and spices, packed With certain lipids, for consumers, Wherein the nutrient levels are balanced to antioxidants, phytochemicals, vitamins, minerals, and micro provide optimal bene?ts. organisms. Similarly, functional foods that are enriched With [0010] In certain aspects, the invention categoriZes indi sterols, stanols, calcium, vitamin E, folic acid, omega-3, ?a viduals into diet cohorts, for example, based on high meat, vonoids, etc. can also be harmful out of context. The current high plant, and high seafood diets. Consumers generally have approach leads to imbalanced or excessive consumption of a speci?c preference for the main foods such as red meat, these nutrients. As a result the prevalent approaches do not seafood, or plant food. For example, vegetarians typically alleviate the disease burden. consume more vegetables, grains, and legumes, as compared [0005] To date there are no methods for matching naturally to hi gh-meat or high- seafood consumers. These dietary habits occurring foods such as nuts, seeds, oils, grains, legumes, can help establish basic nutrients around Which effective diet fruits, vegetables, seafood, herbs, and spices to achieve opti programs may be developed. Instead of randomly adding mal results. Instead focus is on additives, often to counter nutrients to a diet, there is a need to identify a series of diet excesses. Currently there are no methods for creating delivery types, eg plant, meat, or seafood heavy, and a series of system(s) designed to deliver nutrients in an optimal range, consumer patterns typed by diet, age, siZe, gender, medical such that a consumer can reach for products Within the sys conditions, family history, climate and the like and then tailor tem, knoWing that cumulative nutrients in the delivery system nutritional compositions tailored to each series. Will keep them in a safe range. There is a need for the devel [0011] Therefore, in one aspect, the invention provides a opment of such system(s). method for customizing or selecting a nutritional formulation US 2013/0261183 A1 Oct. 3, 2013

or plan for an individual, preferably a human. The invention anhydrous butter oil, and coconut meat. Other components in this aspect comprises determining for the individual, or for the nutritional formulations are disclosed herein. categorizing the individual With respect to, a diet type (“co [0014] In certain embodiments, the individual may exhibit hort”). For example, the cohort may be high plant food, high signs or symptoms of a chronic medical condition selected meat (e.g., high red meat), or high seafood. In certain embodi from gout, diabetes (type 1 or type 2), heart disease, glycemia, ments, the cohort is determined by the relative amounts of insulinemia, metabolic syndrome, an age-related disease grains, vegetables, fruits, legumes, dairy, meats, seafood, (e.g., macular degeneration), or an infectious disease, and herbs, sWeeteners and beverages consumed by the individual, such symptoms may be ameliorated by the balanced diet (via With a focus on foods rich in phytochemicals, and certain consumption of the nutritional formulation for a period of minerals and nutrients described herein, for Which delivery time). The nutritional formulations of the instant invention should be controlled. The cohort may be determined based on are suitable for prophylaxis or treatment of a medical condi an average daily consumption of such foods (Weight, volume, tion or disease selected from menopause, aging, allergy, mus or percent of calories). A nutritional program is then selected culoskeletal disorders, vascular diseases, hypercholester to balance certain lipids and nutrients by providing one or olemia, mood sWing, reduced cognitive function, cancer, more nutritional formulations comprising natural oils, but neural disorders, mental disorders, renal diseases, endocrine ters, margarines, nuts, seeds, herbs, vitamins, and minerals. disorders, thyroid disturbances, Weight gain, obesity, diabe These formulations deliver particular nutrients, such as lipids, tes, digestive system disorders, reproductive disorders, infant phytochemicals, and minerals, to keep the individual in a safe abnormalities, pulmonary disorders, ophthalmologic disor range and thereby prevent or ameliorate the symptoms of ders, dermatological disorders, sleep disorders, dental dis chronic disease. eases, autoimmune diseases, infectious diseases, and in?am matory diseases. Other features and/or components of the [0012] In certain embodiments, the nutritional formulation nutritional plan and nutritional formulations are described is packaged and marked for diet cohort, With a coding system herein. Thus, in some embodiments, the individual is exhib for matching formulations to deliver the proper level of iting signs and symptoms of such disease, and by consuming micronutrients, for the convenience of the individual in main a customiZed nutritional formulation in accordance With the taining a balanced nutritional state. The formulations are invention (tailored to the individual’ s diet cohort as described marked to provide the frequency for consumption (e.g., three herein) for at least one Week, tWo Weeks, or one month, such times daily, tWice daily, or once daily, or a frequency of from symptoms are ameliorated. In some embodiments, medica one to ?ve times per Week). The individual’s diet is balanced ments are formulated based on a subject’s dietary habits (by virtue of the nutritional formulation) With respect to lipids around typical consumption of phytochemicals, antioxidants, (C410, C22:6 omega 3, and others), carbohydrates, protein, and other nutrients Which may be administered With the diet vitamins, minerals, antioxidants, phytochemicals, prebiotics, plan. Appropriate supplements, medications or pharmaceuti probiotics, and ?ber. In certain embodiments, the nutritional cal drugs are administered to/by such dietary cohorts because formulation is further customiZed based on the age, gender, their requirements, biochemistry, and gene expression may siZe, climactic temperature, medical condition, or lipid toler be in?uenced in a certain predictable Way. ance of the individual. In some embodiments, the nutritional [0015] In another aspect, the invention provides nutritional formulation is in the form of one or more of an oil blend, compositions that may be modular/ component systems of spread or dip, sauce or dressing, or small dessert, Which may prepared or unprepared food, e. g. drinks, snacks, meals, des be for diurnal consumption in some embodiments. serts, cereals, salad, side dish, sauces, desserts, spreads etc, [0013] In some embodiments, the diet is balanced by the such that consumers can safely select a speci?c food or drink delivery of one or more (e.g., from 2 to 10) nutritional for item, such as a bottle ofjuice, bar, a salad, a meal knoWing that mulations that collectively make up a nutritional program for the nutrients derived from the components on the Whole Will an individual. The program may collectively meet the keep them in a safe range. In certain embodiments, such description of the nutritional plan of Tables 5, 6, 7, or 8. At components are packaged and marked for a particular cohort least one formulation contains one or more of phytochemicals described herein, such that individuals can conveniently such as phytosterol or polyphenols non-limiting examples of maintain nutritional balance Without frequent nutritional Which include, curcumin, coumarins, and rosemarinic acid. counseling. The delivery may be in the form of novel dietary In these or other embodiments, the diet is also balanced by the lipid programs comprising phytochemicals, antioxidants, nutritional formulation With respect to minerals such as sele vitamins, minerals, microorganisms and ?ber designed for nium. That is, the individual’s diet is characterized by the speci?c cohorts, comprising mutually complementing daily suf?ciency of such nutrients, and customiZed nutritional for variety dosages of spread, oil blend, sauce, dressing, and mulations prepared to balance the individual’s diet by deliv dessert to ?t the daily schedules, Which could be convenient, ering or Withholding these nutrients and/or minerals. The appealing, and fun. Such programs minimiZe the possibilities formulation provides a balanced lipid pro?le for the indi and magnitude of adverse effects from inappropriate intake of vidual leading to physiologically balanced levels of essential nutrients, particularly phytochemicals and lipids and interac fatty acids, long chain polyunsaturated fatty acids tions among them. (LCPUFA), saturated fatty acids, omega-3 fatty acids, includ [0016] Fine-tuning the dietary programs can be achieved by ing docosahexaenoic acid (DHA), arachidonic acid, linoleic further tailoring for age, siZe, gender, medical conditions, acid, omega-6 fatty acid, and omega 6:omega-3 ratio. In these lipid tolerance, family history, and climactic temperature, and or other embodiments, the diet is balanced by the delivery or the like. In some aspects, such tailored programs are devel Withholding of one or more of the folloWing substances (or oped utiliZing computer modeling, Which may be provided to the oil thereof) in certain de?ned concentrations: peanuts, the consumer through a user-friendly softWare or Web inter almonds, olives, soybeans, casheWs, ?axseeds, pistachios, face, alloWing the consumer to: identify their diet cohort pumpkin seeds, sun?ower seeds, sesame seeds, Walnuts, (cohort’s being described herein); select and/or design cus US 2013/0261183 A1 Oct. 3, 2013

tomiZed nutritional programs delivering optimal amounts of consumption. Further bene?t can be derived by tailoring phytochemicals, minerals, and lipids, among others; and pur these formulations to diet cohort de?ned at least in part by chase/order the individualized nutritional compositions that demographic factors including one or more of: age, gender, make up the diet plan. siZe, medical condition, family history, and climate. Such [0017] In one aspect, packages and kits of prepared or methods Would lead to reduced risk for chronic diseases, and unprepared food are provided to support speci?c aspects of achieve greater health bene?ts. the nutritional plan. In some embodiments, the packages and [0022] The folloWing description of example embodiments kits comprise component or modular systems comprising is, not to be taken in a limited sense. The scope of the present vegetable or vegetable juice packs, fruit or fruit juice packs, invention is de?ned by the appended claims. dry grain packs, cereal packs, legume/grain/nuts and/or seed [0023] Unless de?ned otherWise, all technical and scien packs, meat/seafood packs, herbs, lipids, desserts, milks, ti?c terms used herein have the same meanings as commonly yogurts and the like, or a combination thereof. In some understood by one of ordinary skill in the art to Which this embodiments, the kits comprise from 2 to 20, or from 5 to 10 invention belongs. Although any methods and materials simi nutritional formulations, Which collectively, balance the indi lar or equivalent to those described herein can be used in the vidual’s diet Within the parameters disclosed in one of Tables practice or testing of the present invention, the preferred 5 to 8. The nutritional formulations may be designed to, methods and materials are noW described. All publications collectively, comprise at least 40%, at least 50%, at least 60%, and patents speci?cally mentioned herein are incorporated by or at least 80% of the individual’s caloric intake. In some reference for all purposes including describing and disclosing embodiments, the kits and packages comprise food suitable the chemicals, cell lines, vectors, animals, instruments, sta for consumption by babies and include, but are not limited to tistical analysis and methodologies Which are reported in the soybean-based formula, milk formula, standard milk for publications Which might be used in connection With the mula, folloW-on milk formula, toddler milk formula, invention. Nothing herein is to be construed as an admission hypoallergenic milk formula, prepared baby food, dried baby concerning the content of the prior art, that the invention is not food and other baby food. entitled to antedate any particular disclosure by virtue of prior [0018] In one aspect, food items recommended in a diet invention. plan or contained in a speci?c component or module are [0024] Before the present materials and methods are selected based on the methods of cooking, processing or described, it is understood that this invention is not limited to manufacturing used in preparing the food items such that the particular methodology, protocols, materials, and optimal nutrient content is achieved, and/or desired activation reagents described, as these may vary. It is also to be under or inactivation of nutrients particularly phytochemicals is stood that the terminology used herein is for the purpose of achieved. describing particular embodiments only, and is not intended [0019] Further aspects and embodiments of the invention to limit the scope of the present invention. Will be apparent from the folloWing detailed description of the invention. DEFINITIONS

DETAILED DESCRIPTION OF THE INVENTION [0025] As used herein, the term “phytochemical” refers to any natural molecule of plant origin. They are found in fruits, [0020] Universal supplementation of monounsaturated, vegetables, beans, grains, and other plants. The terms “phy omega-6, omega-3, other fatty acids, antioxidants, phy tochemical” and “phytonutrient” are used interchangeably to tochemicals, vitamins, or minerals, and microorganisms describe the active components of plants. Commonly knoWn Without regard to the context has not been effective. Sensitive phytonutrients or phytochemicals include (but are not limited requirements are materially altered by a number of nutritional to) antioxidants, ?avonoids, ?avones, iso?avones, catechins, and demographic factors. Further, While many nutritional anthocyanidins, isothiocyanates, carotenoids, allyl sul?des, systems focus on the protein and/ or carbohydrate component polyphenols, terpenes, limonoids, lipids, phytosterols, beta of the diet, proteins and carbohydrates affect health patterns carotene, ascorbic acid (vitamin C), folic acid, and vitamin E. mostly When consumed in large amounts, e. g. a gram or more. Phytochemicals that the nutritional plan may control, and On the other hand, microgram amounts of nutrients such as exemplary sources, are listed in Table 1. These phytochemi some lipids, antioxidants, phytochemicals, vitamins, miner cals/ sources are controlled in the construction of the diet plan, als, probiotics, prebiotics, and microorganisms, can have sig and their delivery substantially controlled by virtue of a one, ni?cant effect on health. Thus, an object of the present inven tWo, or three complementing formulations of natural oils, tion is to balance nutrition based on supplementation With butters, margarines, nuts, seeds, herbs, vitamins, and miner lipids, antioxidants, phytochemicals, vitamins, minerals, pro als. Optionally, these formulations may take the form of a biotics, prebiotics, and/or microorganisms. conventional supplement, such as a capsule for oral adminis [0021] The present invention relates, in-part, to the surpris tration, or alternatively a topical formulation. ing ?nding that, While phytochemicals, lipids, antioxidants, [0026] As used herein, the term “lipid” refers to any fat vitamins, minerals, and microorganisms have a narroW Win soluble (lipophilic) molecule. These include (but are not lim doW of healthful effects, and that the requirements change ited to) components of vegetable oils, components of seed based on the complement of nutrients, individualiZed diet oils, triglycerides, Waxes of triglycerides, and phospholipids. plans can nevertheless be designed With surprising simplicity As used herein, the term “lipid” comprises a source of lipids and accuracy. Therefore, the invention provides methods for or fats comprising any suitable lipid or lipid mixture. For preparing nutritional plans, and provides nutritional formu example, the lipid source may include, but is not limited to, lations (including complementing nutritional formulations), vegetable fat (such as olive oil, peanut oil, corn oil, sun?ower such that total consumption of these key nutrients is kept in a oil, rapeseed oil, soy oil, palm oil, coconut oil, canola oil, safe range. Further bene?t can be derived by tailoring them to lecithins, Walnuts, ?axseeds, and the like) and animal fats diet cohort de?ned at least in part by protein and carbohydrate (such as milk fat), structured lipids or other modi?ed lipids US 2013/0261183 A1 Oct. 3, 2013

such as medium chain triglycerides. As used in the nutritional [0031] As used herein, the term “carbohydrate” refers to a formulations disclosed herein, the lipid is a component of a source of carbohydrates comprising any suitable carbohy dietary food item and/ or added individually as a supplement. drate, including, but not limited to, sucrose, lactose, glucose, [0027] In some embodiments, the compositions of the fructose, corn syrup solids, maltodextrin, modi?ed starch, present disclosure include one or more of the following fatty amylose starch, tapioca starch, corn starch, isomalt, isoma acids: Saturated fatty acids: butyric (C4:0), lauric (C12:0), ltulose, or combinations thereof. As used in the nutritional myristic (C14:0), palmitic (C16:0), stearic (C18:0), and formulations disclosed herein, the carbohydrate is a compo arachidic (20:0); monounsaturated fatty acids: myristoleic nent of a dietary food item and/or added individually as a (C14:1), palmitoleic (C16:1); omega-9 fatty acids: oleic supplement. (C18:1), gadoleic (C20:1), erucic (C22:1), and nervonic [0032] As disclosed herein, the nutritional composition (C24:1); omega-6 fatty acids: linoleic (C18:2), conjugated includes minerals, or supplements containing such minerals, linoleic (C18:2), gamma-linolenic (C18:3), eicosadienoic in a form that promotes metabolic alkalinity versus acidity. (C20:2), di-homo-gamma-linolenic (C20:3), and arachidonic The minerals are provided attached to various organic acids, (C20:4); and omega-3 fatty acids: alpha-linolenic (C18:3), amino or fatty acids, or naturally occurring as part of a real stearidonic (C18:4), eicosapentaenoic (C20:5), docosapen food. For example, different forms of magnesium, calcium or taenoic (C22:5), and docosahexaenoic (C22:6) fatty acids. aluminum are suitable for affecting acid-base balance. [0028] As used herein, a “prebiotic” is a food substance that [0033] The compositions/formulations disclosed herein selectively promotes the growth of bene?cial bacteria or can be included in a nutritional or nutraceutical composition inhibits the groWth or mucosal adhesion of pathogenic bac together With additional active agents, carriers, vehicles, teria in the intestines. The prebiotic can be acacia gum, alpha excipients, or auxiliary agents identi?able by a person skilled glucan, arabinogalactans, arabinoxylans, beta glucan, dex in the art upon reading of the present disclosure. trans, fructooligosaccharides, galactooligosaccharides, [0034] Subject as used herein refers to humans and non galactomannans, gentiooligosaccharides, glucooligosaccha human primates and any other organisms Which can bene?t rides, guar gum, inulin, isomaltooligosaccharides, lactosu from the agents of the present disclosure. There is no limita crose, lactulose, levan, maltodextrins, partially hydrolyZed tion on the type of animal that could bene?t from the presently guar gum, pecticoligosaccharides, resistant starches, retro described agents. A subject regardless of Whether it is a graded starch, soy oligosaccharides, sugar alcohols, xylooli human or non-human organism may be referred to as a gosaccharides, or their hydrolysates, or combinations patient, individual, animal, host, or recipient. In certain pre thereof. For example, prebiotics are de?ned by Glenn R. ferred embodiments, the subject is a human. Gibson and Marcel B. Roberfroid, “Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Abbreviations Prebiotics,” J. Nutr. 1995 125: 1401-1412. Prebiotics are [0035] The folloWing abbreviations are used throughout fermented by the gastrointestinal micro?ora and/ or by probi the application: AA, arachidonic acid (20:4n-6); ADHD, otics. attention de?cit hyperactivity disorder; ALA, alpha-linolenic [0029] As used herein, probiotic micro-organisms (herein acid (18:3n-3); YT, alpha-tocopherol; COX, cyclooxygenase; after “probiotics”) are preferably microorganisms (alive, DSD, delta-5-desaturase; D6D, delta-6-desaturase; DGLA, including semi-viable or Weakened, and/or non-replicating), dihomo-gamma-linolenic acid (20:3n-6); DHA, docosa metabolites, microbial cell preparations or components of hexaenoic acid (22:6n-3); HNF, hepatic nuclear factor; EFA, microbial cells that could confer health bene?ts on the host essential fatty acids; EPA, eicosapentaenoic acid (20:5n-3); When administered in adequate amounts, more speci?cally, GLA, gamma-linolenic acid (18:3n-6); GSHpx, glutathione that bene?cially affect a host by improving its intestinal peroxidase; YT, gamma-tocopherol; IL, interleukin; LA, microbial balance, leading to effects on the health or Well linoleic acid (18:2n-6); LCPUFA, long-chain PUFA (DGLA, being of the host. See, Salminen S, OuWehand A. BennoY. et AA, EPA, and DHA); LPO, lipid peroxidation products; LT, al. Trends Food Sci. Technol. 1999: 10 107-10. The probiotic leukotriene; LXR, liver X receptor; MUFA, monounsaturated can be of bacterial, yeast, or fungal origin, including Saccha fatty acids; NFkB, nuclear factor kB; OA, oleic acid (18:1n romyces, Debaromyces, Candida, Pichia, Torulopsis, 9); PG, prostaglandin; PPAR, peroxisome proliferator acti Aspergillus, Rhizopus, Mucor, Penicillium, Bl?dobacterium, vated receptor; PUFA, polyunsaturated fatty acid; SCD, Bacteroides, Clostridium, Fusobacterium, Melissococcus, stearoyl CoA desaturase also knoWn as delta-9-desaturase; Propionibacterium, Streptococcus, Enterococcus, Lactococ Se-GSHpx, Se-dependent glutathione peroxidase; SFA, satu cus, Staphylococcus, Peptostrepococcus, Bacillus, Pediococ rated fatty acids; SOD, superoxide dismutase; SREBP, sterol cus, Micrococcus, Leuconostoc, Weissella, Aerococcus, regulatory element-binding proteins; TNF, tumor necrosis Oenococcus, Lactobacillus or a combination thereof. factor; TX, thromboxane; UCP, uncoupling proteins. [0030] As used herein, the term “protein” comprises a pro [0036] The invention disclosed herein relates to develop tein or polypeptide obtained from a source selected from ment of nutritional compositions and/ or formulations tailored dietary protein including, but not limited to animal protein to individual preferences that balance phytochemicals, anti (such as milk protein, meat protein or egg protein), vegetable oxidants, vitamins, minerals, acid-base, lipids, proteins, car protein (such as soy protein, Wheat protein, rice protein, bohydrates, probiotics, prebiotics, microorganisms, ?ber, and canola and pea protein), or a combination thereof. In another the like. Nutritional plans are based primarily on consump embodiment, the compositions or formulations include one tion of food from preferred natural sources. Levels and types or more amino acids selected from: Isoleucine, Alanine, Leu of nutrients in each food item are considered in developing a cine, Asparagine, Lysine, Aspartate, Methionine, Cysteine, nutritional plan keeping interactions in perspective that pro Cystine, Phenylalanine, Glutamate, Threonine, Glutamine, vides nutrients at levels that have exemplary health bene?ts. Tryptophan, Citrulline, Glycine, Valine, Proline, Serine, Nutritional plans are tailored to ?t the primary dietary pref Tyrosine, Arginine, Histidine, or a combination thereof. erences of consumers. US 2013/0261183 A1 Oct. 3, 2013

Nutritional Plans and In?uencing Factors or part of the sensitive food item can be removed (e.g. bran, husk, germ, or skin) to remove the signi?cant levels of micro [0037] In one aspect, the invention provides a method for nutrient, then the part is removed and the food item is customizing or selecting a nutritional plan for an individual. regrouped With its basic category (e.g., legume or grain). In The nutritional plan comprises from 2 to about 20 (or from 2 some embodiments, a method of processing as described later to about 10) nutritional formulations, Which are mutually is used to arrive at optimal nutrient content or activity. complementing to balance certain micronutrients described [0042] With like items grouped together, a combination of herein. In certain embodiments, the nutritional plan com prises from 4 to about 12 or from 4 to about 10 mutually grains is created, as described herein and as shoWn in one of complementing formulations (e.g., complementing With Tables 5-8 for example. In certain embodiments, grains With strong properties eg barley, spelt, quinoa, millet, spelt oats, respect to micronutrients). In certain embodiments, one, tWo, and rye are controlled. For example, collectively, in certain or three of these formulations deliver (collectively) at least 50%, or at least 75%, or at least 90% of the set of micronu formulations, these components may make up less than 70%, trients, With the remaining formulations balanced With less than 50%, less than 40%, less than 30%, or less than 20% of carb calories. These steps are repeated for legumes, veg respect to basic dietary considerations, such as protein intake, carbohydrate intake, and/ or caloric intake, for example. Lipid etables, and fruits. The amounts of soy, pink lentils, black intake is also balanced, but in-part the balance is achieved by beans, and pigeon peas are also controlled, since these items the delivery of the micronutrient formulation. For the one, are high in ?avonoids. In various embodiments, these items tWo, or three formulations comprising the substantial level of make up less than 70%, less than 50%, less than 40%, less than 30%, or less than 20% of protein calories. micronutrients, a subset of from 3 to about 10 formulations can be prepared for selection betWeen individuals, thereby [0043] For meat and seafood items, these comprise less alloWing for cost-effective individualiZation. For example, in than 70%, less than 50%, less than 40%, less than 30%, or less a particular example, the formulations delivering the micro than 20% of protein calories. nutrients may deliver polyphenols at about 5, 10, 15, 20, 45, [0044] The remaining nutrients needed to balance the nutri 70, 95, 115, 140, or 165 mg/day; and (respectively) folate at tional plan are supplied by one, tWo, or three or more formu about 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 lations comprising herbs, spices, nuts, seeds, oils, butters, and mcg/day; phytosterols (at respectively) about 150, 200, 250, sWeeteners, Which are described in detail herein. Thus, the 300, 350, 450, 550, 650, 750, or 850 mg/day; and Se at about entire nutritional plan in some embodiments meets the 5, 10, 15, 20, 35, 55, 75, 95, 115, or 135 mcg/day (respec description in one of Tables 5 to 8. For example, for this tively). In some embodiments, these values may vary by up to micronutrient formulation, grains, legumes, vegetables, 10% or 20%. fruits, herbs, seeds, or a combination thereof; in Whole, [0038] The invention in this aspect comprises determining stripped-doWn, or processed form; are prepared to arrive at a for the individual, or categorizing the individual With respect healthful dosage of phytochemicals (polyphenols, sterols, to, a diet type or “cohort.” For example, the diet type may be coumarins, iso?avones (DaidZein, Genistein, Glycitein), ?a high plant food, high meat (e.g., high red meat), or high vonoids, bran, endosperm etc.). seafood. In certain embodiments, the diet type is determined [0045] The set of formulations can be ?ne-tuned by by the relative amounts of grains, vegetables, fruits, legumes, cohorts, such as for heavy meat, vegetarian, and heavy sea dairy, meats, seafood, herbs, sWeeteners and beverages con food. For each cohort, it is important to identify Which phy sumed by the individual. A nutritional program is then tochemicals, minerals, and/or nutrients are likely to be over selected to balance certain phytochemicals including lipids or underconsumed. For example, for the meat cohort: it is and other nutrients by the delivery of one or more nutritional likely that consumption of phytosterols, polyphenols, and formulations comprising one or more of natural oils, butters, iso?avones is inadequate, and thus should be supplemented margarines, nuts, seeds, herbs, vitamins, and minerals. For accordingly. If most protein calories are met by meat, then example, the nutritional formulation may be packaged and herbs, nuts and seeds can replace added fats. If there is room marked for diet type or cohort, for the convenience of the for additional protein calories, then legumes (black beans, individual. In certain embodiments, the packaging of the kidney beans, peas, soy, pigeon peas, black gram, chickpeas) nutritional formulations may comprise components or mod can be used. For heavy seafood diets, it Will likely be neces ules each comprising all or part of a dietary cohort’s nutri sary to avoid nuts, seeds, and certain Whole grains. For veg tional requirements. In certain embodiments, the nutritional etarians, the nutritional plan must guard against excess of formulation is further customiZed based on the age, gender, phytochemicals particularly phytosterols, polyphenols, climactic temperature, medical condition, or lipid tolerance iso?avones, and make up for potential protein de?ciency. The of the individual. Balancing diet plans based on certain demo actual level for each phytochemical, mineral, or nutrient con graphics is described in WO 2009/ 131939, Which is hereby sumed too much or too little in each cohort, can be computed. incorporated by reference. [0046] By classifying an individual as meat, plant, or sea [0039] For example, diet plans and nutritional kits can be food-base cohort, the folloWing factors can be taken into prepared as folloWs. account. In certain embodiments, cohorts are speci?cally [0040] Dietary components (such as those described de?ned by the amount or presence of the folloWing factors. herein) are grouped as: legume, grain, vegetable, fruit, meat, [0047] In certain embodiments, the nutritional formulation seafood, herb, spice, nut, seeds, oil, or butter. is balanced, With respect to the individual, for essential fatty [0041] Food items from the list are selected that have a acids and their metabolites, long-chain polyunsaturated fatty signi?cant level of sensitive nutrients (see, e. g., Table 1), such acids (LCPUFA), eicosanoids, monounsaturated fatty acids, as polyphenols, phytosterols, fat soluble vitamins/ substances and saturated fatty acids, through the delivery of lipids, phy A, D, E, K, lipids, folate, and Se. These should be controlled. tochemicals, nutrients, minerals, and other components. Food sources having signi?cant levels of these micronutrients [0048] In some embodiments, the individual’ s diet cohort is are described herein, and are knoWn in the art. Where a layer de?ned, at least in-par‘t, by consumption of and requirement US 2013/0261183 A1 Oct. 3, 2013

for essential fatty acids, and Which may be implemented by siZe, age, and climactic temperature), additional in?uencing the de?ning cohorts as plant-based, meat-based, or seafood factors may optionally be considered in de?ning the diet based, in some embodiments. For example, essential fatty cohort, and these in?uencing factors are described beloW. acids (EPA) and their metabolites, long-chain polyunsatu rated fatty acids (LCPUFA) and various eicosanoids play an Desaturase Modulators important role in human health. Monounsaturated and satu rated fatty acids also have a signi?cant role in health. HoW [0053] In certain embodiments, the individual’s diet cohort ever, the latter can inhibit the activity and bioavailability of is de?ned, at least in-part, by the individual’ s consumption of, EPA and LCPUFA. Genders differ in their ability to metabo and requirement for, desaturase modulators. In these embodi liZe lipids due to sex hormones and differential gene expres ments, the individual is provided a nutritional supplement sion. Change in hormone status may also change lipid and/or program to balance the requirement. Desaturase requirements With age. Further, of the macronutrients, lipids modulators include essential fatty acids, vitamin A, cur are the most susceptible to oxidative stress, Which is one of cumin, sesamin, and phytosterols. the most likely causes of aging. Synergistic and managed use [0054] The desaturases B6B and B5B are involved in the of different antioxidants is of bene?t to human health. Sudden production of potent LCPUFA. Several nutritional, hor and Wide ?uctuations in fatty acids consumption can alter the monal, and genetic factors can in?uence the activity of the immune response, Which is dose-dependent, the excitability desaturases. In response to increase or decrease of EPA levels, of neural and muscle cells and neurotransmission, and andro the desaturases may rapidly change in activity levels. Thus, a gen production. Thus sudden and large alterations in fatty large and sudden increase in omega-6 fatty acids from de? acids consumption may cause compromised immunity and cient conditions may lead to sudden surge of LCPUFA, its physiological disturbances. metabolites, and in?ammation. The limited desaturase activ ity in certain pathological states might be due to or exacer [0049] In some embodiments, the diet cohort is de?ned, at least in-part, by the individual’s consumption of and require bated by other endogenous or exogenous factors rather than ment for omega-6, omega-3, and omega-9 fatty acids, includ an enZymatic defect. ing one or more of the omega-6:omega-3 ratio, the omega-9: [0055] Males and females differ in their ability to synthe omega-6 ratio, ratio of monounsaturated fatty acids to siZe long-chain omega-3 fatty acids from ALA as hormones polyunsaturated fatty acids, and ratio of monounsaturated play a role. Estradiol may increase, Whereas testosterone may fatty acids to saturated fatty acids. decrease the production of LCPUFA from LA and ALA. Omega-3 pathWay is more responsive to hormonal treatment [0050] In these and other embodiments, the individual’s than omega-6 pathWay. In females, the conversion from ALA diet cohort is de?ned at least in-part by the individual’s con to DHA may be as high as 9%, Whereas for males it may be sumption of antioxidants, phytochemicals, vitamins, and 0.5-4% resulting in higher DHA concentration in plasma minerals, including particular antioxidants, phytochemicals, lipids, Without signi?cant differences in their consumption of vitamins, and minerals described herein. In some of these protein, carbohydrate, total fat, alcohol, individual fatty acids embodiments, the cohort is further de?ned by gender, age, and selected nutrients. GroWth hormones have been found to siZe, and climactic temperature for the individual, Which Will increase the B6B activity and LCPUFA in animal models. affect the individual’ s requirement for such nutrients. A num VitaminA has been shoWn to doWn regulate the expression of ber of factors can in?uence metabolism, including antioxi DSD. In addition, some phytochemicals, particularly cur dants, phytochemicals, vitamins, minerals, hormones, and cumin and sesamin, have also been shoWn to in?uence DSD microorganisms as Well as the gender, genetics and age of the function. D5-desaturation of omega-6 fatty acids Was doWn individual, and climactic temperature. regulated, Whereas D5-desaturation omega-3 fatty acids Was [0051] Nutritional programs are developed based on the up regulated. Fujiyama-FujiWaraY, et al. Effects of sesamin observation that phytochemicals, antioxidants, vitamins and and curcumin on delta 5-desaturation and chain elongation of minerals, microorganisms signi?cantly alter the sensitivity of polyunsaturated fatty acid metabolism in primary cultured rat lipid requirement and metabolism. Thus, the diet cohort may hepatocytes. J Nutr Sci Vitaminol (Tokyo). August 1992; be de?ned in some embodiments by the requirement for 38(4):353-3 63. 1995; 41(2), 217-225. Phytosterols have been omega-6, omega-3, and omega-9 fatty acids, including one or shoWn to increase the activity of B6B, DSD, and SCD. more of the omega-6:omega-3 ratio, the omega-9:omega-6 [0056] The most potent regulator of desaturase activity is ratio, ratio of monounsaturated fatty acids to polyunsaturated the cellular LCPUFA availability. Under normal physiologi fatty acids, and ratio of monounsaturated fatty acids to satu cal conditions cellular LCPUFA is maintained in a narroW rated fatty acids; and this requirement used to supplement or range by regulation of desaturase transcription. WithdraW one or more of phytochemicals, antioxidants, vita mins, minerals, and microorganisms from the individual’s Phytochemicals diet, using a customiZed nutritional composition. [0052] While a number of factors can in?uence fatty acid [0057] In certain embodiments, the individual’s diet cohort metabolism such as the presence of other fatty acids, antioxi is de?ned, at least in-part, by the individual’ s consumption of, dants, phytochemicals, vitamins, minerals, hormones, and and requirement for, phytochemicals. In these embodiments, microorganisms as Well as the gender, genetics and age of the the individual is provided a nutritional supplement and/or individual consumer, and climactic temperature, the present program to balance the requirement. Phytochemicals in cer invention provides a simple yet accurate method for deter tain embodiments are one or more of those in Table 2. In mining an individual’s requirement for fatty acids, and a certain embodiments, the cohort is de?ned by the approxi convenient and effective nutritional supplementation pro mate level of consumption of the sources of such phytochemi gram. While in certain embodiments the individual’ s require cals listed in Table 2. ments are determined by identifying a basic diet cohort (e.g., [0058] A key ingredient in optimiZing dietary programs meat, plant, or seafood, and optionally one or more of gender, comprises providing the proper types and amounts of phy US 2013/0261183 A1 Oct. 3, 2013

tochemicals in the nutritional plan. Phytochemicals (phytoal in?ammation, e.g. transcription of NFkB, which regulates exins, plant matter, natural molecules contained in plants) broad range of cytokine genes involved in in?ammation (e.g. have powerful properties, but healthful effects are available sulforaphane, curcumin, Zerumbone); or activate PPAR within narrow ranges of amounts included in the diet particu gamma, which may modulate anti-in?ammatory genes and larly because they have cumulative effects. inhibit NFkB (e. g. curcumin, capsaicin, ginsenosides, hespe [0059] In general, phytochemicals: (a) have antioxidant ridin, and resveratrol); (i) may excessively suppress oxidation properties, change oxidation of lipids and other molecules; and/or certain in?ammatory molecules or pathways; body (b) may turn into prooxidants at high amounts or due to some may then upregulate compensatory mechanisms; (i) may interactions; (c) modulate gene expression; stimulate synthe inhibit mitochondrial function; (k) may lead to acidosis par sis of adaptive proteins/ genes for cytoprotective, detoxifying ticularly when consumed with omega-3 and unbalanced or and antioxidant enZymes; (d) maintain genome integrity; (e) inadequate lipids (xanthones have been shown to cause aci modulate cell signaling pathways and membrane, cytoplas dosis, there are quite likely other phytochemicals that cause mic, and nuclear enZymatic reactions; (f) dampen cellular acidosis); (1) may alter metabolism and activity of lipids and hyperproliferation and hyperactivity, promote apoptosis of their metabolites; (m) may increase the requirement for genetically unstable cells; (g) accumulate in cell membranes Omega-6, and some other fatty acids; and (n) may reduce the causing alterations of cell shape and modulation of the bilayer requirement or tolerance for omega-3 (e.g. certain polyphe material properties (bilayer thickness, ?uidity and elasticity) nols enhance synthesis of long-chain omega-3 from its pre that affect membrane proteins and ion channels; (h) inhibit cursor, but may impede formation of long-chain omega-6). TABLE 1

List of common/known phytochemicals and plant matter and their exemplary sources.

MONOPHENOLS: Apiole (parsley) Carnosol (rosemary) Carvacrol (oregano, thyme) Dillapiole (dill) Rosemarinol (rosemary) POLYPHENOLS: (?avonoids, phenolic acids, lignans, stilbenes) Flavonoids

Flavonols: Quercetin (onions, tea, wine, apples, cranberries, buckwheat, beans), Gingerol (ginger), Kaempferol (strawberries, gooseberries, cranberries, peas, brassicates, chives), Myricetin (grapes, walnuts), Rutin (citrus fruits, buckwheat, parsley, tomato, apricot, rhubarb, tea). Isorhamnetin, Proanthocyanidins procyanidins, prodelphinidins and propelargonidins, apples, maritime pine bark, cinnamon, aronia fruit, cocoa beans, grape seed, grape skin, red wine Flavones: Chrysin,Apigenin (chamomile, celery, parsley) Luteolin, Tricetin, Disometin etc Parsley, capsicum pepper Flavanones: Naringenin (citrus), Hesperidin (citrus), Dihydroquercetin etc Orange juice, grape fruit, lemon peel &juice etc, Eriodictyol. Flavan3ols: Catechins (white tea, green tea, black tea, grapes, wine, apple juice, cocoa, lentils, black-eyed peas), Silymarin, Silibinin, Taxifolin, (+)—Catechin, (+)—Gallocatechin, (—)—Epicatechin, (—)—Epigallocatechin, (—)—Epigallocatechin gallate (EGCG) — green tea; (—)—Epicatechin 3-gallate (ECG), Thea?avin — black tea; Thea?avin-3-gallate — black tea; Thea?avin—3'—gallate — black tea; Thea?avin—3,3'—digallate — black tea; Thearubigins etc Cocoa, chocolates, cocoa beverages, beans, cherry, grapes, red wine, cider, blackberry etc Iso?avones: Daidzein (formononetin) — soy, alfalfa sprouts, red clover, chickpeas, peanuts, other legumes. Genistein (biochanin A) — soy, alfalfa sprouts, red clover, chickpeas, peanuts, other legumes. Glycitein — soy. Chalcones: Anthocyanins and Anthocyanidins: Pelargonidin — bilberry, raspberry, strawberry. Peonidin — bilberry, blueberry, cherry, cranberry, peach. Cyanidin — red apple & pear, bilberry, blackberry, blueberry, cherry, cranberry, peach, plum, hawthorn, loganberry, cocoa. Delphinidin — bilberry, blueberry, eggplant. Malvidin — bilberry, blueberry. Petunidin Dihydro ?avonols Chalconoids Coumestans (phytoestrogens) Coumestrol — red clover, alfalfa sprouts, soy, peas, brussels sprouts. phloretin. Phenolic acids

Ellagic acid — walnuts, strawberries, cranberries, blackberries, guava, grapes. Gallic acid — tea, mango, strawberries, rhubarb, soy. Salicylic acid — peppermint, licorice, peanut, wheat. Tannic acid — nettles, tea, berries. Vanillin — vanilla beans, cloves. Capsaicin — chilli peppers. Curcumin — turmeric, mustard. (Oxidizes to Vanillin.) Lignans (phytoestrogens) — seeds (?ax, sesame, pumpkin, sun?ower, poppy), whole US 2013/0261183 A1 Oct. 3, 2013

TABLE l-continued

List of common/knoWn phytochemicals and plant matter and their exemplary sources. grains (rye, oats, barley), bran (Wheat, oat, rye), fruits (particularly berries) and vegetables. Silymarin — artichokes, milk thistle. Matairesinol — flax seed, sesame seed, rye bran and meal, oat bran, poppy seed, straWberries, blackcurrants, broccoli. Secoisolariciresinol — flax seeds, sunflower seeds, sesame seeds, pumpkin, straWberries, blueberries, cranberries, zucchini, blackcurrant, carrots. Pinoresinol and lariciresinol — sesame seed, Brassica vegetables enterolactone, enterodiol Stilbenes

Resveratrol — grape skins and seeds, Wine, nuts, peanuts, berries Pterostilbene — grapes, blueberries Piceatannol — grapes Punicalagins — pomegranates Hydroxycinnamic acids

Caffeic acid — burdock, haWthom, artichoke, pear, basil, thyme, oregano, apple, rosemary, coffee Chlorogenic acid — echinacea, straWberries, pineapple, coffee, sunfloWer, blueberries. Cinnamic acid — cinnamon, aloe. Ferulic acid — oats, rice, artichoke, orange, pineapple, apple, peanut. Coumarin — citrus fruits, maize. Tyrosol esters

Tyrosol — olive oil Hydroxytyrosol — olive oil Oleocanthal — olive oil Oleuropein — olive oil TERPENES (ISOPRENOIDS) Carotenoids (tetraterpenoids)

Carotenes — orange pigments (1-Carotene — to vitamin A, in carrots, pumpkins, maize, tangerine, orange. [3-Carotene — to vitamin A, in dark, leafy greens and red, orange and yelloW fruits and vegetables. y-Carotene 6-Carotene Lycopene — Vietnam Gac, tomatoes, grapefruit, Watermelon, guava, apricots, carrots, autumn olive. Neurosporene Phyto?uene — star fruit, sWeet potato, orange. Phytoene — sWeet potato, orange. Xanthophylls — yelloW pigments. Canthaxanthin — paprika. Cryptoxanthin — mango, tangerine, orange, papaya, peaches, avocado, pea, grapefruit, kiWi. Zeaxanthin — Wolfberry, spinach, kale, turnip greens, maize, eggs, red pepper, pumpkin, oranges. Astaxanthin — microalge, yeast, krill, shrimp, salmon, lobsters, and some crabs Lutein — spinach, turnip greens, romaine lettuce, eggs, red pepper, pumpkin, mango, papaya, oranges, kiWi, peaches, squash, legumes, brassicates, prunes, sWeet potatoes, honeydeW melon, rhubarb, plum, avocado, pear. Rubixanthin — rose hips. Monoterpenes

Limonene — oils of citrus, cherries, spearmint, dill, garlic, celery, maize, rosemary, ginger, basil. Perillyl alcohol — citrus oils, caraWay, mints. Saponins — soybeans, beans, other legumes, maize, alfalfa. Lipids

Phytosterols — almonds, casheWs, peanuts, sesame seeds, sunflower seeds, Whole Wheat, maize, soybeans, many vegetable oils. Campesterol — buckWheat. beta Sitosterol — avocados, rice bran, Wheat germ, corn oils, fennel, peanuts, soybeans, haWthorn, basil, buckWheat. gamma sitosterol Stigmasterol — buckWheat. Tocopherols (vitamin E) US 2013/0261183 A1 Oct. 3, 2013

TABLE l-continued

List of common/knoWn phytochemicals and plant matter and their exemplary sources. omega-3,6,9 fatty acids — dark-green leafy vegetables, grains, legumes, nuts. gamma-linolenic acid — evening primrose, borage, blackcurrant. Triterpenoid

Oleanolic acid — American pokeWeed, honey mesquite, garlic, java apple, cloves, and many other Syzygium species. Ursolic acid — apples, basil, bilberries, cranberries, elder floWer, peppermint, lavender, oregano, thyme, haWthorn, prunes. Betulinic acid — Ber tree, White birch, tropical carnivorous plants Triphyophyllum pellalum and Ancislrocladus heyneanus, Diospyros Zeucomelas a member of the persimmon family, Telracera boiviniana, the jambul (Syzygiumformosanum), and many other Syzygium species. Moronic acid — Rhusjavanica (a sumac), mistletoe BETALAINS Betacyanins betanin — beets, chard isobetanin — beets, chard probetanin — beets, chard neobetanin — beets, chard Betaxanthins (non glycosidic versions)

Indicaxanthin — beets, sicilian prickly pear Vulgaxanthin — beets ORGANOSULFIDES Dithiolthiones (isothiocyanates)

Sulphoraphane — Brassicates. Thiosulphonates (allium compounds)

Allyl methyl trisul?de — garlic, onions, leeks, chives, shallots. Diallyl sul?de — garlic, onions, leeks, chives, shallots. INDOLES, GLUCOSINOLATES/SULFUR COMPOUNDS

Indole-3-carbinol — cabbage, kale, brussels sprouts, rutabaga, mustard greens, broccoli. sulforaphane — broccoli 3,3'-Diindolylmethane or DIM — broccoli family Sinigrin — broccoli family Allicin — garlic Alliin — garlic Allyl isothiocyanate — horseradish, mustard, Wasabi Piperine — black pepper Syn-propanethial-S-oxide — cut onions. PROTEIN INHIBITORS

Protease inhibitors — soy, seeds, legumes, potatoes, eggs, cereals. OTHER ORGANIC ACIDS

Oxalic acid — orange, spinach, rhubarb, tea and coffee, banana, ginger, almond, sWeet potato, bell pepper. Phytic acid (inositol hexaphosphate) — cereals, nuts, sesame seeds, soybeans, Wheat, pumpkin, beans, almonds. Tartaric acid — apricots, apples, sunflower, avocado, grapes. Anacardic acid — casheWs, mangoes.

[0060] See Dr. Duke’s Phytochemical and Ethnobotanical [0062] Lipids include a group of phytochemicals that Databases (available on the Web at ars-grin.gov/duke/) for include omega-3, -6, -9 fatty acids, other fatty acids, Waxes, details on phytochemicals in natural foods and their known or sterols, fat-soluble vitamins A, D, E and K. Phytosterols are a presumed activities. subgroup of lipids, more than 200 steroid compounds similar to cholesterol are found in plants. Lipids and Metabolites [0063] A large part of the human sensitivity to lipids is due [0061] In certain embodiments, the individual’s diet cohort to the actions of essential fatty acids (EPA) and their metabo is de?ned, at least in-part, by the individual’ 5 consumption of, lites. Eicosanoids, EFA metabolites, are involved in various and requirement for, omega-3, omega-6, omega-9 fatty acids, physiological and pathological processes, including blood and optionally, fat soluble vitamins including A, D, E, and K. vessel constriction, dilation, blood pressure regulation, plate In these embodiments, the individual is provided a nutritional let aggregation, and modulation of in?ammation. Generally, supplement and/ or program to balance the requirement. Opti eicosanoids of AA origins produce a vigorous response, mal levels for basic dietary cohorts of meat, plant, and sea Whereas eicosanoids of EPA origins produce a muted food heavy diets is disclosed herein (see Tables 6 to 8). response. Additionally, AA, EPA, and DHA are precursors for US 2013/0261183 A1 Oct. 3, 2013

lipoxins, resolvins, and neuroprotectins With anti-in?amma [0069] Not only omega-6 and omega-3 fatty acids but most tory properties. Though LCPUFA modulate a number of bio other fatty acids also compete in metabolic pathWays such logical functions through eicosanoids, the fatty acids are that dietary fat is re?ected in tissue composition. Total highly active as components of cell membranes in pinocyto amount of dietary fatty acids (loW-fat versus high-fat diets) sis, ion channel modulation, and gene regulation. can also in?uence the fatty acid metabolism and tissue com [0064] It is important to balance omega-6 and omega-3 position. For example, increased omega-3 fatty acid levels in fatty acids in human nutrition for optimal function of cellular plasma fatty acids from loW fat diets have been observed, membranes and for balance betWeen eicosanoids produced Which is likely due to preferential metabolism of ALA. Other from omega-6 and omega-3 fatty acids. The present con studies have shoWn that dietary fat quantity outWeighs fat sumption pattern, omega-6-to-omega-3 ratios of 15:1-17:1 in type in in?uencing blood pressure, a risk factor for vascular Western diets, has been cited as one of the dietary component disease. Thus, omega-6 and omega-3 ratios and amounts signi?cantly associated With modern chronic diseases. Simo should be considered in conjunction With the in?uencing poulos A P. Evolutionary aspects of diet, the omega-6/ factors. omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother. November 2006; Microorganisms, Prebiotics, Probiotics, Synbiotics 60(9):502-507. [0070] In certain embodiments, the individual’s diet cohort [0065] In addition to the effects of ratios of fatty acids, is de?ned, at least in-par‘t, by the individual’ s consumption of, plasma and/or serum lipids comprising high proportions of and requirement for, microorganisms, namely prebiotics, palmitic (16:0), palmitoleic (16:1), and DGLA, and a loW probiotics, and synbiotics. In these embodiments, the indi proportion of LA and PUFA are associated With type-2 dia vidual is provided a nutritional supplement and/or program to betes, myocardial infarction, stroke, left ventricular hypertro balance the requirement. phy, and metabolic syndrome. High B6B and SCD (stearoyl [0071] The nutritional program may include one or more CoA desaturase), and loW DSD activity has been indepen prebiotics and/or ?ber (soluble and/or insoluble). The nutri dently associated With cardiovascular disease risk markers, tional program may include one or more probiotics. In gen including insulin resistance and loW-grade in?ammation, and eral, it is believed that these micro-organisms inhibit or in?u cardiovascular and total mortality. Altered endogenous ence the groWth and/or metabolism of pathogenic bacteria in desaturase levels might contribute to the mortality risks. the intestinal tract. Probiotics may also activate the immune Defect in B6B and DSD may be a factor in the initiation and function of the host. progression of atherosclerosis and often associated diseases [0072] The nutritional program or formulation may include such as obesity, diabetes mellitus, and hypertension. one or more synbiotics, ?sh oils, and/or phytonutrients. As [0066] Omega-3 fatty acids of seafood origin include, but used herein, a synbiotic is a supplement that contains both a are not limited to, salmon, herring, mackerel, anchovies and prebiotic and a probiotic that Work together to improve the sardines. Omega-3 fatty acids of botanical origin include, but micro?ora of the intestine. are not limited to, chia, kiWifruit, perilla, ?axseed, lingon [0073] Gut micro?ora in?uences the capacity of an indi beny, camelina, purslane, black raspberry, butternuts, hemp vidual to obtain energy from diet. That micro?ora also in?u seed, Walnut, pecan nut, and haZel nut. ences lipogenesis and plasma lipopolysaccharide levels implicated in in?ammation, obesity, and type-2 diabetes. A Non-Essential Fatty Acids high-fat diet creates unfavorable gut micro?ora. Conversely, gut microorganisms in?uenced fat composition of ho st tissue. [0067] In certain embodiments, the individual’s diet cohort Oral administration of Bi?dobaclerium breve With linoleic is de?ned, at least in-part, by the individual’ s consumption of, acid increased the tissue composition of conjugated-linoleic and requirement for, non-essential fatty acids. In these acid and omega-3 fatty acids EPA and DHA. embodiments, the individual is provided a nutritional supple ment and/or program to balance the requirement. Optimal Oxidation and Antioxidants levels for basic dietary cohorts of meat, plant, and seafood heavy diets is disclosed herein (see Tables 6 to 8). [0074] In certain embodiments, the individual’s diet cohort [0068] Non-essential fatty acids can be synthesiZed endog is de?ned, at least in-par‘t, by the individual’ s consumption of, enously, hoWever some of them are considered conditionally and requirement for, antioxidants. In these embodiments, the essential and they may in?uence EFA metabolism. For individual is provided a nutritional supplement and/or pro example, OA can have regulatory functions in addition to gram to balance the requirement. Optimal levels for basic altering cellular fatty acid composition in select organs. Fatty dietary cohorts of meat, plant, and seafood heavy diets is acids contribute to many cellular functions including homeo disclosed herein (see Tables 6 to 8). In certain embodiments, stasis, coordinating the expression of proteins involved in the cohort is de?ned by, and the formulation designed to lipid synthesis, transport, storage, degradation, and elimina supplement or WithdraW from the diet, one or more of vitamin tion to maintain a normal physiological state. Subsequent to C, vitamin E, and/or selenium, iron, copper, and/or Zinc. meal ingestion lipids in the duodenum regulate energy and [0075] In relation to lipid metabolism, fatty acids may glucose homeostasis through a feedback mechanism to the undergo any one of the folloWing after ingestion: (1) prima central nervous system Which ultimately regulates food rily mitochondrial and peroxisomal [3-oxidation for energy intake. This sensitive neuronal circuitry canbecome defective production, (2) free-radical mediated oxidation (chain reac in response to high-fat or fat imbalance. Certain fatty acids, tions Where one free radical can oxidiZe many lipid mol palmitic, lauric, and stearic, have a role in stimulating the ecules), (3) free-radical independent, non-enzymatic oxida expression of mitochondrial uncoupling proteins, UCP2 and tion, or (4) enzymatic oxidation to produce bioactive lipid UCP3, Which reduce oxidative stress and are associated With products such as long-chain fatty acids and eicosanoids. Spe longevity. ci?c products are formed from each type of oxidation and US 2013/0261183 A1 Oct. 3, 2013

speci?c antioxidants are required to inhibit each type of reac cellular signaling messenger. In order to exert physiologically tion. The nutritional program may include antioxidants. Anti important functions as a regulator of gene expression and oxidants are molecules capable of slowing or preventing the mediator of cellular signaling, the formation of LPO products oxidation of other molecules. Non-limiting examples of anti must be strictly controlled and programmed. Niki E. Lipid oxidants include preventative enzymes such as superoxide peroxidation: physiological levels and dual biological effects. dismutase (SOD), catalase, and glutathione peroxidases Free Radic Biol Med. Sep. 1, 2009; 47(5):469-484. (GSHpx), vitamin A, carotenoids, vitamin C, vitamin E, sele [0081] An excessive and/or sustained increase in reactive nium, ?avonoids, LactoWolfberry, Wolfberry, polyphenols, oxygen species production has been implicated in pathogen lycopene, lutein, lignan, coenzyme Q10 (CoQlO), glu esis of many diseases including cancer, diabetes mellitus, tathione or combinations thereof. atherosclerosis, neurodegenerative diseases, chronic in?am [0076] Vitamin E and C Work synergistically to protect mation, rheumatoid arthritis, ischemica/reperfusion injury, lipids; vitamin C repairs the alpha-tocopheroxyl radical (vita obstructive sleep apnea. HoWever, in a study of lipid and min E radical) enabling it to resume its antioxidant function. lipoprotein pro?les, fatty acid composition, and oxidant-an Vitamin E’s antioxidant action can reverse age-associated tioxidant status in pediatric attention de?cit hyperactivity increase in Cyclooxygenase-2 (COX-2) activity and associ disorder (ADHD) patients, reduced lipid peroxidation Was ated increase in PGE2 synthesis by inhibiting the cofactors; noted. Similarly, disturbances in the lipid pro?le, in lipopro this effect also increases T-cell-mediated immune function. tein concentrations and composition, and in oxidant-antioxi Gamma-tocopherol (YT) form of vitamin E has been found to dant status Were observed in pediatric Crohn’s disease be a more effective inhibitor of PGE2, LTB4, and tumor patients. necrosis factor-0t (TNFot) an in?ammatory cytokine than alpha-tocopherol ((XT).V1I21II11I1 E requirements are partially Vitamins and Minerals dependent on PUFA consumption, because PUFA may reduce intestinal absorption of vitamin E While increasing the [0082] In certain embodiments, the individual’s diet cohort amount needed for PUFA protection. is de?ned, at least in-part, by the individual’ s consumption of, [0077] Selenium, an important component of Se-dependent and requirement for, vitamins and minerals. In these embodi glutathione peroxidase (Se-GSHpx) and it functions syner ments, the individual is provided a nutritional supplement gistically With vitamin E as an antioxidant to protect cellular and/or program to balance the requirement. Optimal levels fatty acids and enzymes for eico sanoid production. The metal for basic dietary cohorts of meat, plant, and seafood heavy ions zinc, cadmium, silver, iron, and mercury are inhibitors of diets is disclosed herein (see Tables 6 to 8). In certain embodi Se-GSHpx. GSHpx (both Se-dependent and non-Se-indepen ments, the cohort is de?ned by, and the formulation designed dent). Both copper and zinc play a role in SOD mediated to supplement or WithdraW from the diet, one or more of protection of COX, and PG and TX synthetases. Copper vitamin A, vitamin D, vitamin E, vitamin K, vitamin B12, status is also associated With Se-GSHpx status in liver and folic acid or folate, selenium, copper, iron, calcium, magne lungs. sium, phosphorus, manganese, potassium, sodium, chloride, [0078] Many of the antioxidants, phytochemicals, vita and zinc. mins, and minerals suppress oxidation of PUFA (though [0083] Some vitamins and minerals may also have poWer some minerals, such as, iron and copper are pro-oxidants) and ful properties, i.e. a narroW WindoW of healthful effects PG synthesis, thereby increasing the need for LA or omega-6 because of their prooxidants/antioxidant potential, and their family of fatty acids, and reducing the need for or tolerance of ability to modulate the antioxidant enzyme expression, omega-3 fatty acids. Reduced oxidation affects the omega-6 among other factors. Some of those are: VitaminA, Vitamin E family more than the omega-3 family because of preferential (tocopherols), Vitamin B9 (Folic acid, particularly food folate metabolism of omega-3 family. in natural form), Vitamin D, Vitamin E, Selenium, Copper, [0079] Antioxidants have poWerful properties and there Zinc. Like phytochemicals, some minerals can act as antioxi fore have a narroW WindoW of healthful effects. LoW levels of dants and pro-oxidant depending on levels and complement oxidation products (eg lipid peroxidation (LPO) products, of other nutrients. free radicals) are necessary for cellular functions. Oxidation of molecules proceed by different pathWays. Speci?c prod Dietary Fiber ucts are formed from each type of oxidation and speci?c antioxidants are required to inhibit each type of reaction. See [0084] In certain embodiments, the individual’s diet cohort Buettner G., Arch Biochem Biophys. 1993; 300: 535-543, is de?ned, at least in-part, by the individual’ s consumption of, incorporated herein by reference in its entirety. Droge W. Free and requirement for, dietary ?ber. In these embodiments, the radicals in the physiological control of cell function. Physiol individual is provided a nutritional supplement and/or pro Rev. January 2002; 82(1):47-95. gram to balance the requirement. Optimal levels for basic [0080] LPO products in plasma of healthy human subjects dietary cohorts of meat, plant, and seafood heavy diets is are beloW 1 [1M and the molar ratios of LPO products to the disclosed herein (see Tables 6 to 8). In certain embodiments, respective parent lipids are beloW 1/1000, that is, beloW 0.1%. the cohort is de?ned by, and the formulation designed to Sublethal concentrations of LPO products induce cellular supplement or WithdraW from the diet, one or more of cellu adaptive responses and enhance tolerance against subsequent lose, starch, glucans, cereal bran, and hydrocolloids. oxidative stress through upregulation of antioxidant com [0085] As used herein, “dietary ?ber” refers to indigestible pounds and enzymes. Such opposite dual functions of LPO and non-metablizable organic material contained in food. products imply that LPO, and oxidative stress in general, may LoW calorie bulking agents, such as cellulose, starch, glucans, exert both deleterious and bene?cial effects in vivo. LPO as cereal bran, and hydrocolloids (e. g., xanthan, guar, and algi Well as reactive oxygen and nitrogen species has been shoWn nate), generally are indigestible polymers that can be used in to play important roles as a regulator of gene expression and food products. These agents, often referred to as “?ber” or US 2013/0261183 A1 Oct. 3, 2013

“roughage,” pass through the digestive system for the most also has signi?cance for men. High levels of androgens may part intact and have been shown to have a number of actual be associated With carcinogenesis, While loW levels may be and potential health bene?ts. deleterious to semen quality. Men and Women also differ in [0086] Dietary ?ber may be divided into predominantly storage, mobiliZation, and oxidation of fatty acids, and gene soluble or insoluble ?bers (depending on solubility in Water). expression relevant to fatty acid metabolism. Both types of ?ber are present in substantially all plant foods, With varying degrees of each depending on the plant. Water soluble dietary ?ber, or “soluble ?ber”, refers to dietary ?ber Genetics that is Water soluble or Water sWellable. Water soluble dietary ?bers include, for example, oligosaccharides, psyllium, beta [0090] In certain embodiments, the individual’s diet cohort glucan, oat bran, oat groat, pectin, carrageenan, guar, locust is de?ned, at least in-par‘t, by the individual’s genetic poly beau gum, gum acacia, and xanthan gum, and the like and morphisms, and/ or consumption and requirement for methyl combinations thereof. Dietary ?ber typically consists of non donor compounds. In these embodiments, the individual is starch polysaccharides, for example, cellulose and other plant provided a formulation tailored to the individual’s genetics, components including dextrins, inulin, lignin, Waxes, chitins, or requirement for methyl donor nutrients. In certain embodi pectins, beta-glucans and oligosaccharides. ments, the cohort is de?ned by, and the formulation designed [0087] Dietary ?bers affects nutrition by changing the to supplement With one or more of folate, vitamin B-12, nature of the contents of the gastrointestinal tract, and by vitamin B-6, choline, methionine, genistein, coumesterol, and polyphenol. Taking into account the knoWn existence of changing hoW other nutrients and chemicals are absorbed. The addition of such indigestible ?ber materials to food genetic polymorphisms, the individual’s diet may be supple stimulates the intestine to peristalsis, resulting in increased mented With or restricted of certain phytochemicals including digestion of accompanying food materials. Due to its effect one or more of curcumin, capsaicin, ginsenosides, hesperidin, on digestion, increased consumption of dietary ?ber has been and resveratrol. linked to decreases in the incidence of gastrointestinal dis [0091] Genetic code, the sequence of nucleotides in our eases, including boWel cancer. Prebiotic soluble ?ber prod DNA, can in?uence health status. But there is another set of ucts, like those containing inulin or oligosaccharides, may instructions that affect gene expression, and this set of contribute to relief from in?ammatory boWel disease, as in instructions can be altered by diet. Epigenetics, the study of Crohn’s disease, ulcerative colitis, and Closlridium dz?icile, heritable changes in gene function that occur independent of due in part to the short-chain fatty acids produced With sub a change in DNA sequence, represents a neW frontier in sequent anti-in?ammatory actions upon the boWel. Consis biomedical science that has important implications for dietet tent intake of fermentable ?ber through foods like berries and ics practice. For example, one Way in Which gene expression other fresh fruit, vegetables, Whole grains, seeds and nuts is is modulated is through DNA methylationithe degree to noW knoWn to reduce risk of several diseases4obesity, dia Which methyl groups are present or absent from certain betes, high blood cholesterol, cardiovascular-disease, boWel regions of our genes. Depending on the circumstances, cancer, and numerous gastrointestinal disorders including hypomethylation or hyper'methylation can be bene?cial or irritable boWel syndrome, diarrhea, and constipation. harmful depending on Which genes are turned on or off, at What point in time, and in Which tissues. DNA methylation Gender can be affected by intake of folate, vitamins B-12 and B-6, [0088] In certain embodiments, the individual’s diet cohort choline, and methionine because these nutrients are involved is de?ned, at least in-part, by the individual’s gender. In these in the generation of methyl groups through one carbon embodiments, the individual is provided a nutritional supple metabolism. Other dietary factors, such as genistein, coumes terol, and polyphenols also in?uence DNA methylation. Sto ment and/ or program customiZed for gender. ver P J, Caudill M A. Genetic and epigenetic contributions to [0089] While sex hormones can alter metabolism of dietary human nutrition and health: managing genome-diet interac fats, dietary fats can alter synthesis of sex hormones and the associated receptor organization. Increasing amount of tions. J Am Diet Assoc. 2008; 108:1480-1487. Barnes S. dietary fat increases the androgen production, depending on Nutritional genomics, polyphenols, diets, and their impact on the fatty acids administered. Higher PUFA administration dietetics. J Am Diet Assoc. 2008; 108: 1888-1895. resulted in loWer activity of steroidogenic enZymes and loWer [0092] Genetic variations can also in?uence the metabo levels of androgens as compared to MUFA or SFA adminis lism and therefore requirement of lipids. Polymorphisms in tration. Omega-3 fatty acids, particularly DHA caused less apolipoprotein E and peroxisome-proliferator-activated androgen production than omega-6 fatty acids; and omega-6 receptor-gamma (PPARY) genes may in?uence response to fatty acids caused less androgen production than MUFA or dietary fats. HoWever, dietary fats can alter many genes. SFA. The period over Which the dietary fat Was fed to an PUFA suppress lipogenic, glycolytic, and choelsterolgenic animal also altered androgen levels; initially sharp increases genes, but increase expression of genes for enZymes needed correlated With the dietary levels after 3 Weeks, folloWed by in the [3-oxidation pathWay. Simopoulos A P. The role of fatty signi?cant reductions after 6 Weeks, demonstrating an adap acids in gene expression: health implications. Ann Nutr tation mechanism. The response may be a homeostatic adjust Metab. 1996; 40:303-311. Sampath H, Ntambi J M. Polyun ment possibly due to LCPUFA’s similar actions and bene?ts saturated fatty acid regulation of genes of lipid metabolism. as sex hormones. Though the relationship is not Well under Annu Rev Nutr. 2005; 25:317-340. PUFA modulate gene stood yet, parallels have been draWn to estrogen. Both estro expression by interacting With nuclear receptor hepatic gen and PUFA enhance nitric oxide synthesis, suppress the nuclear factor (HNF-4), liver X receptors (LXR), and PPAR production of pro-in?ammatory cytokines, shoW antioxidant 0t, [3, 6, and y, and by regulating the transcription factor sterol like and anti-atherosclerotic properties, and have neuropro regulatory element-binding proteins (SREBP) 1 & 2. SREBP, tective actions. The relationship of fatty acids With androgens suppressed by PUFA, are key regulators of cholesterol, fatty US 2013/0261183 A1 Oct. 3, 2013

acid, and triglyceride synthesis. LA andAA are potent PPAR expression, and fatty acid regulation of the human delta-5 ligands, producing rapid increase in expression of genes desaturase. J Biol Chem. Dec. 24 1999; 274(52):37335 involved in lipid oxidation. 37339. [0093] Phytochemicals may also in?uence the expression [0098] As noted before, LCPUFA increase in tissue other of a range of genes. Several phytochemicals can bind to cell than the brain With age, Which may be a compensation for surface and nuclear receptors as ligands. Curcumin, capsai decline in hormones because of similarities in actions. Stud cin, ginsenosides, hesperidin, and resveratrol are knoWn ies With rats have demonstrated loWer desaturase activity With PPARy ligands, believed to attenuate cytokine production and age, Which may be reversed With GLA. HoWever, GLA Was in?ammation. Phytosterols can also alter intestinal and liver signi?cantly more effective on DHA than on AA restoration. gene expression. Since nutrients can change gene expression, Therefore, reduced AA levels With age may be of concern, it is more effective to design nutrition (feWer variables, particularly in Women and vegetarian Women. The solution greater control, and easier implementation) for optimum might lie in optimal mix of fatty acids and antioxidants With gene-expression, rather than nutrition for disease states phytosterols, Which increase desaturase activity and have caused by unhealthy nutrition. antioxidant properties and hormone-like actions, such that greater membrane ?uidity and loWer unsaturation index can Aging be achieved. Temperature [0094] In certain embodiments, the individual’s diet cohort is de?ned, at least in-par‘t, by the individual’s age. In these [0099] In certain embodiments, the individual’s diet cohort embodiments, the individual is provided a formulation tai is de?ned, at least in-par‘t, by the individual’s climactic tem lored to the individual’s age. In certain embodiments, the perature. In these embodiments, the individual is provided a cohort is de?ned by, and the formulation designed to supple formulation tailored to the individual’s climactic tempera ment With one or more antioxidants, fatty acids, and phy ture. In certain embodiments, the cohort is de?ned by, and the tosterols. formulation designed to supplement With optimal dietary lip [0095] Aging brings about a decline in sex hormones, ids and phytochemicals. increased oxidative stress, and decreased homeostatic regu [0100] In general, a greater unsaturation index of fatty acids lation and immunity. Oxidative stress is currently one of the occurs in tissues at loWer temperatures in order to maintain most accepted theories of aging, Where aging is the result of homeoviscosity and optimal membrane and cellular func lifelong and progressive damage to molecules from oxidation tions. Increased unsaturation preserves function at loW tem products and the consequential deterioration of physiological perature and decreased unsaturation preserves function at functions. HulbertA J, Pamplona R, Buffenstein R, Buttemer high temperature, but excessively loW PUFA levels also WA. Life and death: metabolic rate, membrane composition, reduce heat tolerance. Although membrane lipid composition and life span of animals. Physiol Rev. October 2007; 87(4): is the main acclimatory response to changes in climactic 1175-1213. Since fatty acids are the molecules most vulner temperature, other responses may include altered expression able to oxidation, membranes With fatty acid compositions of membrane proteins, altered composition of bilayer stabi least prone to lipoxidative damage are associated With lon liZing versus destabiliZing lipids, and altered proportions of gevity. Fatty acids differ dramatically in their susceptibility to plasmalogens compared to diacyl phospholipids. Phy peroxidation. Birds, Who have exceptionally long lifespan tochemicals can also alter membrane properties including relative to their body mass favor loWer unsaturation index of ?uidity. Thus, While the body adapts to changes in tempera omega-6 PUFA to higher unsaturation index of omega-3 ture, bene?t can be derived by customiZing dietary lipids and PUFA in membranes. phytochemicals With respect to temperature, such that raW materials conducive to self-regulation are present in optimal [0096] PUFA and unsaturation index have been shoWn to quantities. increase With advancing age in most tissue except for brain In?ammatory PathWaysiRelationship With Nutrients Where they decline; but membrane ?uidity declines uni [0101] In certain embodiments, the individual’s diet cohort formly With age because of peroxidation and possibly altered is de?ned, at least in-part, by the individual’s in?ammatory fatty acid chain composition. Unsaturated fatty acids are said state. In these embodiments, the individual is provided a to contribute to ?uidity. Oxidized lipids and LPO are greater formulation tailored to the individual’ s in?ammatory state. In cause for membrane rigidity than loW unsaturation index. certain embodiments, the cohort is de?ned by, and the formu Antioxidants are unable to increase the maximum life span of lation designed to supplement or WithdraW, dietary phy a species, but they have been shoWn to increase mean life span tochemicals, antioxidants, vitamins, and minerals, such as in select populations. one or more of ?avonoids, sulforaphane, curcumin, and [0097] A decline in brain PUFA, particularly DHA, With Zerumbone, capsaicin, ginsenosides, hesperidin, and resvera age has been shoWn to be associated With increased lipid trol, omega-3, omega-6 (including the omega-6zomega-3 peroxidation. A decline in cognitive function along With neu ratio), In some embodiments, the phytochemicals include one ronal apoptosis of cerebral cortex and hippocampus has also or more of procyanidins, epigallocatechin gallate, epicat been found to be associated With age or hyperoxia, and pre echin 3-gallate, resveratrol, apigenin, luteolin, quecetin, vented by vitamin E. Since an aging brain has been shoWn to anthocyanins and hydrocinnamic acids, curcumin, hesperi have loWer DHA, ?sh oils have been suggested to increase din, diosmin, amento?avone, bilobetin, morello?avone, tissue DHA levels because they bypass D6D and DSD and ginkgetin, and yuccaols A, B, C, D and E. In some embodi directly provide long-chain omega-3 fatty acids in form of ments, the phytochemicals are as de?ned in Table 1 and 3. The EPA and DHA. HoWever, dietary ?sh oils rich in DHA and diet cohort may be de?ned by the level of consumption of the EPA strongly suppress D6D, With implications for other sources disclosed in Table 1 and 3, and the nutritional pro LCPUFA levels. Cho H P, Nakamura M, Clarke S D. Cloning, gram may be tailored by supplementation or WithdraWal of US 2013/0261183 A1 Oct. 3, 2013

these sources. Some phytochemicals, antioxidants, vitamins action, other factors such as sudden change in excitability of and minerals interactions can lead to harmful health effects. neural and muscle cells may be another complicating factor. Phytochemicals and antioxidants can suppress a number of At such instances the host may become vulnerable to infec in?ammatory pathways. Excessive suppression may be prob tions, myocardial infarction, stroke, and induction of psoria lematic in that some in?ammation may be necessary, and that sis depending upon the rest of the body chemistry and the compensatory mechanisms may be put in motion. Phy presence of infectious agents. In less severe manifestations, tochemicals, particularly ?avonoids have been found to have due to moderate ?uctuations in fatty acids and in otherWise antimicrobial, antiviral, anti-ulcerogenic, cytotoxic, antine salubrious condition, the host may experience sleep distur oplastic, mutagenic, antioxidant, antihepatotoxic, antihyper bances, headaches, muscle cramps, confusion, melancholia, tensive, hypolipidemic, anti-aging, antiplatelet and anti-in and rage resulting from changes in neurotransmission, excit ?ammatory activities. They also have biochemical effects, ability of muscle and neural cells, and ?uctuating eicosanoids Which inhibit a number of enZymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca+2-ATPase, lipoxy and androgens.As a nutritional strategy, cumulative effects of genase, cycloxygenase, etc. Additionally, they also have a all dietary in?ammation modulation should be beloW the regulatory role on different hormones like estrogens, andro threshold Where self-regulation of the immune system is gens and thyroid hormone. materially blunted or in?ammation is dysregulated. [0102] Excessive phytochemicals, inadequate or imbal [0105] Different ?avonoids display anti-in?ammatory anced lipids and/or their impaired metabolism, and/or their mechanisms of action. For example (from Rathee et al. interactions may dysregulate cytokines involved in in?am Mechanism of Action of Flavonoids as Anti-in?ammatory mation: TGF-Bl, TNF-ot, IL-1[3, IL4, 1L5, IL6, 1L8, IL10, Agents: A revieW. In?ammation & Allergy-Drug Targets, IL13, and y-IFN. Particular diseases that may be implicated 2009, 8, 229-235.) are disorders of the immune system, for example systemic lupus erythematosus (SLE), allergy, asthma, Crohn’s disease [0106] ProcyanidinsiInhibits transcription and secretion and rheumatoid arthritis, but particularly multiple sclerosis, of IL-1 and also neurodegenerative diseases such as sequelae of [0107] Epigallocatechin gallateiInhibits the expression stroke, head trauma, bleeds, AlZheimer’s and Parkinson’s of iNOSiReducing the activity of NF-kB and AP-1. disease, and sepsis, coronary heart disease (CHD), and infant abnormalities. [0108] Epicatechin 3-gallateiAttenuates adhesion and [0103] LCPUFA play an important role in in?ammation migration of peripheral blood CD8+T cells. and immunity. At loW levels AA augments or is neutral to [0109] ResveratroliInhibits stimulation of caspase-3 and certain immune function, but at high levels it has an inhibitory cleavage of PARP induced by IL-1alpha. Suppressing the effect. Intakes of long-chain omega-3 appear to be inhibitory expression of iNOS mRNA and protein by inhibiting the on a Wide range of immune functions: autoantibody produc tion, T-lymphocyte proliferation, apoptosis of autoreactive activation of NF-kB Inhibiting NO generation. Upregulating lymphocytes, and cytokines and leukotrienes. Many of the MAP kinase phosphatase-5 effects of long-chain omega-3 appear to be due to the inhibi [0110] ApigeniniBlocks the expression of intercellular tion of transcription factor, NFkB, Which regulates broad adhesion molecule-1 (ICAM-1), VCAM-l, and E-selectin. range of cytokine genes involved in in?ammation. Calder P Inhibiting prostaglandin synthesis and IL-6, 8 production. C. Polyunsaturated fatty acids and in?ammatory processes: NeW tWists in an old tale. Biochimie. June 2009; 91(6):791 [0111] LuteoliniInhibits the upregulation of THP-l adhe 795. Long-chain omega-3 also activate transcription factor sion and VCAM-1 expression. Inhibiting the activity of the PPARY, Which can modulate anti-in?ammatory genes and NF-kB. inhibit NFkB. Therefore, in the short run omega-3 may ame [0112] QuercetiniInhibits NO production and iNOS pro liorate the symptoms of diseases associated With loW-grade tein expression. Inhibits both cyclooxygenase and lipoxyge in?ammation; but in the long run they may compromise host nase activities. immunity. Further, the effects may be compounded by certain phytochemicals Which also inhibit NFkB (e. g. sulforaphane, [0113] Anthocyanins & Hydroxycinnamic acidsiLocal curcumin, and Zerumbone) or activate PPARY (e. g. curcumin, iZes into endothelial cells. Reducing the upregulation of IL-8, capsaicin, ginsenosides, hesperidin, and resveratrol). Sudden MCP-1, and ICAM-1 and Wide ?uctuations in phytochemicals and or fatty acids [0114] CurcuminiDecreases MPO activity and TNF-al intake can change the immune response and rest of the physi pha on chronic colitis. Reducing nitrites levels and the acti ology. Withdrawing a phytochemical or Omega-3 or any vation of p38 MAPK. DoWnregulating COX-2 and iNOS immunosuppressive/in?ammation suppressive nutrient may expression. unleash excessive in?ammation. [0115] Hesperidin, DiosminiInhibits prostaglandin for [0104] Depending upon fatty acids and phytochemical tis mation. sue stores, a sudden WithdraWal of a habitual high long-chain omega-3 fatty acids or immunosuppressive or antiin?amma [0116] Amento?avone, Bilobetin, Morello?avone, tory phytochemical supply from the ho st, or a sudden increase GinkgetiniInhibits phospholipase C1 and A2. in omega-6 fatty acids or other fatty acids may result in [0117] Yuccaols A, B, C, D and EiInhibit the nuclear unrestrained cytokine response, With severe consequences involving systemic in?ammatory response (capillary leak transcription factor NF -kB. age, pyrexia, tachycardia, tachypnoea), multi-organ dysfunc [0118] The activities of the nutrients may be mediated by tion (gastrointestinal, lungs, liver, kidney, heart), and joint interactions With one or more of cell-derived mediators (listed tissue damage. In addition to sudden increases in cytokine in Table 2, from Rathee et al.). US 2013/0261183 A1 Oct. 3, 2013 15

TABLE 2

Cell-derived mediators

Name Type Source Description Lysosome granules Enzymes Granulocytes contain a large variety of enzymes Which act as inflammatory mediators Histamine Vasoactive Mast cells, Stored in preformed granules, histamine amine basophils, is released in response to a number of platelets stimuli IFNgamma Cytokine T-cells, NK Antiviral, immuno-regulatory, and anti cells tumour properties. This interferon Was originally called macrophage-activating factor, and is especially important in the maintenance of chronic in?ammation IL-8 Chemokine Macrophages Activation and chemo-attraction of neutrophils, With a Weak effect on monocytes and eosinophils Leukotriene B4 Eicosanoid Leukocytes Mediates leukocyte adhesion and activation. In neutrophils, it is also a potent chemo-attractant, and induces the formation of reactive oxygen species and the release of lysosome enzymes by these cells. Nitric oxide Soluble gas Macrophages, Potent vasodilator, relaxes smooth endothelial muscle, reduces platelet aggregation, aids cells, some in leukocyte recruitment, direct neurons antimicrobial activity in high concentrations. Prostaglandins Eicosanoid Mast cells A group of lipids Which cause vasodilation, fever, and pain. TNFalpha & IL-1 Cytokines Macrophages Affect a Wide variety of cells to induce inflammatory reactions: fever, production of cytokines, endothelial gene regulation, chemotaxis, leukocyte adherence, activation of ?broblasts.

[0119] Several nutrients are known to have cardiovascular Massaro et al., Nutraceuticals and Prevention of Atheroscle disease (CVD) related activities as shown in Table 3 (from M. rosis; Cardio vascular Therapeutics; 28 (2010), Table 2) TABLE 3

KnoWn CV disease related actions of different nutrients

Bioactive compound Examples Sources Putative effects Flavonols Quercetin, Onion, apple, tea, ,LTC, lLDL-C oxidationT HDL-C, kaempferol, berries, olives, AOx, lplatelet aggregation, catechin broccoli, lettuce, leicosanoid synthesis, lathero red Wine, ELAMs, langiogenesis, lMMPs cocoa/chocolate Flavonols Epicatechin, Green/black tea, AOx, lapoptosis, lLDL-C oxidation, epigallocatechin, cocoa/chocolate lplatelet aggregation, lathero epicatechin-3- ELAMs, langiogenesis, lMMPs gallate, epigallocatechin 3-gallate Lignans Enterolactone, Flaxseed oil, ,LLDL-C, AOx, enterodiol lucerne, clover estrogen/antiestrogen; latherosclerosis in vivo but may shoW adverse CVD effect (pro oxidant activity With partially defatted flaxseed) Isoflavones Genistein, Soybeans, legumes ,LTC and LDL-C, lLDL-C oxidation, daidzein ,LTG, THDL-C, lthrombosis, AOx, estrogen/antiestrogen, lathero ELAMs, langiogenesis, l atherosclerosis in vivo, lMMPs Stilbenoids Resveratrol Grapes, red Wine, lLDL-C oxidation, lplatelet p eanuts aggregation/thrombosis, leicosanoid synthesis, AOx, lathero-ELAMs, langio genesis but promotes angiogenesis in the ischemic US 2013/0261183 A1 Oct. 3, 2013 16

TABLE 3-c0ntinued

Known CV disease related actions of different nutrients

Bioactive compound Examples Sources Putative effects heart, latherosclerosis in vivo, iMMPs Carotenoids Lycopene Tomatoes, tomato lLDL-C and LDL-C oxidation, AOx, products lathero-ELAMs, ,LMMPs, but no effects Was shoWn in animal models of ATS and dietary intervention studies using Well-de?ned subjects population did not provided a clear evidence of lycopene in the prevention of CVD Carotenoids (1-Carotene, [3- Carrots, pumpkins, Inconsistent data. [3-carotene has carotene, y- maize, tangerine, shoWn adverse CVD effect because carotene, 6- orange and yelloW its prooxidant activity carotene fruits and vegetables Organosul?lr Allicin, diallyl Garlic, onion, leek ,LTC and LDL-C, ,LTG, lcholesterol compounds sul?de, diallyl and FA synthesis, ,LBP, lthrombosis, disul?de, allyl AOx, lathero-ELAMs, mercaptan langio genesis, latherosclerosis in vivo, ,LMMPs Soluble dietary Glucan, pectin Psyllium, oats, ,LTC, ,LTG, lLDL-C ?bers barley, yeast, fruit, vegetables, psyllium seed, forti?ed cereals and grains Isothiocyanates Phenethyl Cruciferous no relevant effects (PEITC), benZyl vegetables (e.g., (BITC), Watercress, sulforaphanes broccoli) Monoterpenes d-Limonene, Essential oils of ,LTC and LDL-C, ,LHMGCoAR, perillic acid citrus fruit, langiogenesis cherries, mint, herbs Plant sterols Sitostanol, Tall oil, soybean ,LTC and LDL-C, AOx, lcholesterol stigmasterol, oil, rice bran oil absorption; campesterol adverse effect: lcarotenoid absorption Phenolic acids Tyrosol, Extra virgin olive lLDL-C oxidation, lplatelet hydroxytyrosol, oil aggregation/thrombosis, leicosanoid oleoeuropeine, synthesis, AOx, lathero-ELAMs, caffeic acid, latherosclerosis in vivo, ,LMMPs cumaric acid 03-3 PUFA DHA, EPA, (ILA Fish and ?sh oil, ,LTC, suppression of cardiac green leaves arrhythmias, ,LBP lplatelet aggregation, leicosanoid synthesis, lathero-ELAMs, langiogenesis; ,LMMPs Prebiotics Inulin-type Fruit and ,LTC and ,LTG fructans vegetable, puri?ed extract from chicory root Probiotics Selected strains Fermented milk ,LTC, LDL-C and BP ofLaclobaciZZus products acidophilus, Bz?dobaclerium bz?dum and LaclobaciZZus bulgaricus

AOx, antioxidant activity; BP, blood pressure; CVD, cardiovascular disease; HIDL-C, high density lipoprotein cholesterol; LDL-C, loW density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; MMIPs, metalloproteinases; ELAMs, endothelial leukocyte adhesion molecules. US 2013/0261183 A1 Oct. 3, 2013

Health Effects of Whole/Natural Food Items the compositions or formulation may be delivered in one-part or multiple parts as various components of a meal or to [0120] Whole foods have different health effects than one complement a meal, for example. Would predict from the sum of the parts. Nutrients have dif [0124] In some embodiments, the kits and packages com ferent properties in one form versus another, e.g. conjugated prise food suitable for consumption by babies and include, versus free. This is due to alteration in metabolism, presence and/or composition of other nutrients and/or absorption; but are not limited to soybean-based formula, milk formula, standard milk formula, folloW-on milk formula, toddler milk nature of connection betWeen nutrients and context is crucial. formula, hypoallergenic milk formula, prepared baby food, Flavonoids Which are mainly present as glycosides in food dried baby food and other baby food. (With the exception of catechins) are expected to be poorly absorbed, but quercetin glycosides are absorbed in appre [0125] In some embodiments, the compositions/formula ciable amounts in the small intestine. For instance, the ?a tion disclosed herein may be administered to an individual in vonoid quercetin Was shoWn to be more bioavailable as an any orally accepted form. In some embodiments, they may be aglycone than quercetin glucosides When ingested as onion part of an enteral or parenteral formula, or a combination ?esh, While quercetin glycosides Where more available When thereof. In some embodiments, they may be administered ingested as dried onion skin. Bene?cial or harmful effects of topically via a liquid, cream or patch formulation. The for nutrients including phytochemicals can be explained by addi mulations may be packaged in one, tWo, three, four or more tive and synergistic effects, as vegetables and fruits contain mutually complementing daily dosages. In some embodi multiple different phytochemicals Which seem to in?uence ments, they may be contained in any one or more of, but not and potentiate each other. Synergistic effects increase bio limited to, a single dosage or sustained and controlled release availability. For example quercetin is an inhibitor of resvera capsule, soft-gel capsule, hard capsule, tablet, poWder, lOZ trol sulfation in the liver and small intestine and increases the enge, or pill prepared in some instances With carriers such as bioavailability of resveratrol. The synergistic effect of pip starches, sugars, diluents, granulating agents, lubricants, erine on curcumin is driven by its inhibiting effect on cur binders, disintegrating agents, a granule, and the like. In some cumin conjugation. Further, absorption of phytochemicals embodiments, the compositions may be delivered using a can be enhanced by complexing With lipids or by nanopar gelatinous case, a vial, a bottle, a pouch or a foil, or plastic ticles that increase the Water solubility of hydrophobic drugs. and/or card-board box, and the like, or a combination thereof for containing such compositions. In some embodiments a Development of Novel Dietary Programs one-day, one-Week, tWo-Week, bi-Weekly, bi-monthly, or monthly diet plan may be formulated comprising various [0121] The invention relates to development of nutritional formulations described herein, With varying compositions compositions and/ or formulations that balance phytochemi administered each day. cals, antioxidants, vitamins, minerals, acid-base, lipids, pro [0126] In some embodiments, each pack contains speci?c teins, carbohydrates, probiotics, prebiotics, microorganisms, nutritional content suitable for a balanced and optimiZed diet. ?ber, and the like. Levels and types of nutrients in each food For example, a grain or cereal pack may contain polyphenols, item are considered in developing a nutritional plan that pro antioxidants, omega fatty acids and/or saturated fatty acids vides nutrients at levels that have exemplary health bene?ts. Within speci?c ranges Wherein each range is suitable for a In some aspects, nutritional plans are tailored to ?t the pri speci?c dietary cohort. LikeWise, a fruit, legume or vegetable mary dietary preferences of consumers. pack or drink package may be similarly classi?ed. In some [0122] To be effective, the nutritional plans are designed embodiments, each pack comprises identi?cation of the such that at least 25%, 50%, 60%, 70%, 80% or 100% of ranges of speci?c critical nutrients and nutrients. In some calories in the diet are provided by the foods speci?ed in the embodiments, each pack or module is identi?ed by the spe plan over an extended period of time. ci?c dietary cohort it is suitable for. In some aspects, each [0123] In one aspect, packages and kits are provided to module can effectively ?t into a nutritional plan When each support speci?c aspects of the nutritional plan. In some component or module individually provides less (or greater) embodiments, the packages and kits comprise component or than 100, 200, 300, 400, or 500 calories and/or less (or modular systems comprising vegetable, fruit, grains, cereals, greater) than 10%, 20%, 25%, 30%, or 40% percent of an legumes, meats, seafood, nuts, seeds, herbs, lipids, milks, individual’s daily caloric need. yogurts and the like, and any combination thereof. In some [0127] In some aspects, the formulations described herein embodiments, the packages and kits comprise unprepared, or have high antioxidant and phytochemical content and prop ready to cook foods, such as fruit, vegetable, legume, dry erties that render extra omega-3 unnecessary, or enhance grain, meat, seafood, herbs, fat, nuts and seeds, milks, bioavailability, and/or endogenous synthesis of long-chain yogurts, and the like. In some embodiments, the packages and omega-3. In speci?c embodiments, nuts, legumes, grains, kits comprise processed or cooked foods such as a nutritional sWeeteners (such as honey), and herbs/spices (such as cur bar; a bakery food product such as a bread, a dessert, a pastry, cumin) included in the compositions can render extra a truf?e, a pudding or cake; a salad, a drink, a yogurt, a milk, omega-3 unnecessary. a side dish, a snack, a meal; a gel, a puree, a sauce, a dressing, [0128] In one aspect, food items recommended in a diet a spread, a butter, drops, or the like; a sealed single dosage plan or contained in a speci?c component or module are packet or resealable packaging containing a liquid, semi selected based on the methods of processing or manufactur liquid, semi-solid, or a solid. In some embodiments, they may ing used in preparing the food items such that optimal nutrient be unsealed and taken orally, or added as part of a cooking is achieved, and/ or desired activation or inactivation of nutri ingredient to previously cooked or uncooked food prepara ents is achieved. Such processes include steps in preparing the tion With or Without added fat. For example, they can be made food items such as hulling, removing a layer or part, peeling, into an oil blend, or a special cooking oil such as a frying oil, drying versus providing fresh or froZen, and method of cook a pan-frying oil, a parting oil or the like. The components of ing such as soaking, sprouting, grinding, roasting, baking,

US 2013/0261183 A1 Oct. 3,2013 19

TABLE 4-continued isms, ?ber, and proteins, the perishability of certain essential fresh products may raise dif?culties. However, some pre Schematic representation for developing tailored dietary formulated products such as lipids, nuts, seeds, dry herbs or programs and for optimizing dietary nutrients herbal extracts, grains, and legumes have greater shelf life, Antioxi Compute ranges as above and are less cumbersome to tailor. Some vegetable, fruit, dants meat, and seafoodpacks can also be developed, which require Step 3. Develop nutritional programs/formulations similar processing facilities and storage, i.e. produce/meat/ Develop programs/formulations to complement the nutrients above, from seafood processing facilities with refrigeration. In addition to natural oils, nuts, seeds, and herbs; additional vitamins and minerals may manufacturing and production advantages and industrial util be used. Deliver as diurnal mutually complementing individual dosages; ity, this approach also retains a level of ?exibility and grati daily variety may strengthen compliance. ?cation for the consumer in selecting the main dietary com Monday Oil blend-A + sauce-A + spread-A + dessert-A Tuesday Oil blend-B + sauce-B + spread-B + dessert-B ponents. Other days Oil blend-X + sauce-X + spread-X + dessert-X [0141] Nutrients are selected from foods such as veg

“Based on average daily consumption. etables, fruits, grains, legumes (including lentils, peas, bFurther customizations may address age, gender, climactic temperature, and medical con beans), herbs, spices, teas, cocoa, coffee, sweeteners, nuts, ditions/lipid tolerance. seeds, and oils; grains are selected from wheat, rice, com, [0134] Similar cohorts can be de?ned by age, gender, barley, spelt, oats, rye, buckwheat, millet, and quinoa; the genetic pro?le, climactic temperature, and medical condi vegetables are selected from asparagus, bell peppers, cucum tions such as lipid tolerance. In case of infants, formulations ber, eggplant, green beans, green peas, kale, romaine, spin and diet plans may be de?ned based on mother’s diet, genetic ach, squash summer and winter, tomato, carrots, romaine pro?le, and/or medical conditions. In some embodiments, a lettuce, radish, bitter gourd, okra, fenugreek leaves, broccoli, feedback system is used to ?ne tune the dietary program brussels sprout, cabbage, chard, cauli?ower, mustard greens, according to results achieved. collard greens, turnip greens, turnip, beets, potatoes, fungi, [0135] Dietary cohorts can be based on main foods pre yams and sweet potatoes; the fruits are selected from apple, ferred in the diet of an individual or a group. For example: (a) apricot, orange, pear, plum, banana, cantaloupe, grapes, vegetable based comprising 2, 3, 4, 6, or more servings per grapefruit, papaya, mango, pineapple, blueberries, cranber day of herbs, legumes, fruits, and vegetables; (b) seafood ries, ?gs, kiwi, prune, raspberries, pomegranate, strawberries based comprising 1, 2, 3, 4, 6, or more servings per week of and watermelon; the legumes are selected from black beans, seafood; (c) meat based comprising 3, 4, 6, 8, 10, 12, 14 or dried peas, mung beans, garbanzo, kidney beans, lentils, lima more servings per week of meat (red meat) and less than 2, 3, beans, navy beans, pinto beans, pigeon peas, and soybeans; 4 or 6 servings per day of herbs, legumes, fruits, and/or the herbs or spices are selected from asafetida, basil, bishop’ s vegetables. weed, black pepper, cayenne pepper, chili pepper, cinnamon, [0136] Dietary cohorts can also be de?ned based on folate, cloves, coriander, cumin, dill, ginger, mustards seeds, polyphenols, phytosterols, antioxidants, vitamin A, E, Se in oregano, peppermint, rosemary, sage, thyme, turmeric, fen the diet. For example, one or more polyphenols greater (or nel, garlic, onion, leeks, parsley, celery, cardamom, saffron, less) than 5, 10, 15, 20, 45, 70, 95, 115, 140, or 165 mg/day; lime, lemon, tamarind, and mint, and the sweeteners are and/or folate greater (or less) than 100, 200, 300, 400, 500, selected from molasses, cane juice, honey, maple syrup, 600, 700, 800, 900, or 1000 mcg/day; and/or one or more dates, raisins, dried berries, ?gs, and sugar. phytosterols greater (or less) than 150, 200, 250, 300, 350, [0142] In some embodiments, the nutrients from the foods 450, 550, 650, 750, or 850 mg/day; and/or Se greater (or less) are extracted, and incorporated in a nutritional formulation in than 5, 10, 15, 20, 35, 55, 75, 95, 115, or 135 mcg/day can be liquid, dry powder, or in topical cream or patch. Thus, formu used to classify dietary cohorts. lations that provide the micronutrients to complement the [0137] In one embodiment, the tailored dietary program is remaining diet, may be oral compositions or topical in some presented as a diet plan for an individual; infant, child, teen, embodiments. adolescent, adult, mature, senior; 0-1, 1-3, 2-5, 4-8, 7-12, [0143] In one aspect, the disclosure provides compositions 13-15, 14-20, 18-30, 25-45, 40-50, 45-60, 60-70, 70+ years of that include seeds, nuts, and/or oils. In one embodiment the age, male or female. composition can include one or more edible oils, culinary [0138] In one embodiment, the tailored dietary program is nuts and/or seeds in their whole form or their oils such as, but prepared according to climatic condition and ambient tem not limited to acai oil, amaranth oil, apple seed oil, apricot perature range. Temperature ranges may be classi?ed as hot kernel oil, argan oil, artichoke oil, avocado oil, babassu oil, (90°-135°), warm) (70°-99°), cool (50°-75°), cold (33°-55°, ben oil, blackcurrant seed oil, borage seed oil, borneo tallow below freezing (0°-37°), arctic (—50°-5°), or polar (—100°-— nut oil, bottle gourd oil, buffalo gourd oil, butter oil (anhy 45°). drous), canola oil (rapeseed), cape chestnut oil, carob pod oil, [0139] In one aspect, the tailored dietary program is mani cocklebur oil, cocoa butter oil, cohune oil, coriander seed oil, fested in packages, kits or modular food components that are corn oil, cottonseed oil, dika oil, evening primrose oil, false used to complement the diet of the cohort or replace the ?ax oil (camelina sativa), ?sh oil (cod liver), ?sh oil (herring), caloric intake of the subject. The daily consumption of food ?sh oil (menhaden), ?sh oil (salmon), ?sh oil (sardine), according to plan may vary, but over a period of 1, 2, 4, 6, 8, grapeseed oil, household lard, kapok seed oil, lallemantia oil, 12, or more weeks, or as a lifestyle change, the tailored plan manila oil, meadowfoam seed oil, mustard oil, nutmeg butter, according to the invention provides at least 25, 50, 60, 70, 80, okra seed oil, palm oil, papaya seed oil, pequi oil, perilla oil, 90 or 100% of the total caloric intake of an individual. prune kernel oil, quinoa oil, ramtil oil, rice bran oil, royle oil, [0140] Although it is important to deliver balanced com sacha inchi oil, sa?lower oil, sheanut oil, soybean lecithin oil, plete diets balanced with respect to lipids, antioxidants, phy tea oil, thistle oil, tomato seed oil, ucuhuba butter oil, wheat tochemicals, vitamins, minerals, carbohydrates, microorgan germ oil, acorns, almonds, beech nuts, brazilnuts, breadnuts,