Fasting Mimicking Meals

Abstract

The fasting mimicking meal package provides breakfast, lunch and dinner meal portions for consumption during a one-day fast or a single-day fast. The one-day fasting mimicking meal package includes breakfast, lunch and dinner meal portions for a one-day fast. The FMD package includes a breakfast meal portion having a first nut-containing nutritional bar composition, a micronutrient vegetable powder composition including vitamin and mineral supplements, an algae oil composition, a lunch meal portion incorporating a first soup composition and a kale cracker composition, and a dinner meal portion having a second soup composition, any one of a kale cracker composition or an olive-containing composition, and a second nut-containing nutritional bar composition.

Description

[Technical field]

[0001] Priority Priority is claimed from U.S. patent application Ser. No. 17 / 646,718, filed December 31, 2021, which is incorporated by reference in its entirety into this disclosure.

[0002] The present invention relates generally to compositions that mimic fasting while still providing nutrients to a subject. [Background technology]

[0003] In recent years, fasting mimicking diets have been found to provide many health benefits.For example, fasting mimicking diets (FMDs) have been found to be useful in alleviating the symptoms of chemotherapy, diabetes, hypertension, and metabolic syndrome.Such fasting mimicking diets have also been found to be useful in promoting regeneration, apoptosis of senescent cells, and other therapeutic benefits.Many categories of fasting-type diets have become popular.These generally include behavioral fasting, physiological fasting, molecular or cellular fasting, and combinations thereof.

[0004] Behavioral fasting does not require the intake of food and nutrients, but may often include the intake of water. Behavioral fasting can have adverse effects on a subject due to nutritional loss, which can lead to loss of lean muscle mass and bone density, among other problems, as well as other potentially deleterious effects.

[0005] Physiological fasting involves attempting to mimic fasting by adjusting food intake to restrict carbohydrates, which induces ketosis in the body. This is accomplished by restricting carbohydrate intake while consuming protein and high amounts of fat. Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine (1). Physiological ketosis results from low glucose availability, which occurs when carbohydrates are restricted.

[0006] Ketones are always present in the blood, and ketone levels increase when glucose stores are low, signaling the liver to shift from primarily metabolizing carbohydrates to metabolizing fatty acids (2). When the liver begins to metabolize fatty acids into acetyl-CoA, some acetyl-CoA molecules are converted into ketone bodies, including acetoacetate, β-hydroxybutyrate, and acetone (2, 3).

[0007] These ketone bodies then function as an energy source to replace reduced and / or unavailable glucose, usually derived from carbohydrates (4). Ketone bodies are released by the liver into the blood for use by peripheral tissues, including the brain (3). Some call such physiological fasting, based on ketosis resulting from a dietary intake of low carbohydrates, high fat, and moderate protein, the ketogenic or keto diet. However, such physiological fasting is not a true fasting, because if too much protein is ingested, gluconeogenesis occurs and cells do not recognize protein as a nutrient and enter a fasting state (5, 6, 7).

[0008] The third general type of fasting is known as molecular and / or cellular fasting. It provides a precisely designed nutritional profile to sustain the body during one or more days of prolonged fasting. Such cellular molecular fasting provides nutrients to the subject to prevent muscle and bone loss, but limits such nutrients to levels that are not detected by the subject's cells, such that cellular molecular fasting is induced. FMD is based on this approach and includes many variations that allow many of the therapeutic benefits that come from time-restricted intermittent fasting, potentially without the unwanted discomfort or harmful loss of bone density or lean muscle mass (6, 7, 50, 51, 52).

[0009] Metabolic syndrome is defined by the co-occurrence of three of the following five conditions: abdominal obesity, elevated fasting glucose, elevated blood pressure, high serum triglycerides, and low levels of high-density cholesterol (HDL) (8). It affects 47 million Americans (9) and is associated with a substantially increased risk of cardiovascular disease and all-cause mortality (10). Although prolonged fasting or a very low-calorie fasting mimicking diet (FMD) can ameliorate the incidence of diseases such as cancer and multiple sclerosis in mice (11-13), no randomized trials have been conducted to evaluate the ability of fasting to reduce risk factors for aging and major aging-related diseases (14-16). Prolonged fasting with only water intake for 2 or more days reduces growth-promoting signaling and activates cytoprotective mechanisms in organisms ranging from single-celled yeast to mammals (17). This is accomplished in part by transiently reducing glucose and circulating insulin-like growth factor 1 (IGF-1), a hormone that has been well studied for its role in metabolism, growth, and development, as well as its association with aging and cancer (18-23). ​​Indeed, severe deficiencies of growth hormone receptor and IGF-1 have been associated with reduced risk of cancer, diabetes, and total mortality in humans (24, 25).

[0010] Mice periodically fed FMD exhibit increased health span and multi-system regeneration, reduced inflammation and cancer incidence, and improved cognitive performance.(12) Despite the potential for disease prevention and treatment, prolonged fasting is difficult to implement in human subjects and can exacerbate existing nutritional deficiencies, making it unfeasible and / or unsafe for children, elderly, and frail individuals, and even the majority of healthy adults.

[0011] Thus, there is a need for the development of additional dietary protocols that may be useful in the treatment of human diseases. Summary of the Invention

[0012] Against this background of the prior art, a Fasting Mimetic Diet (hereinafter "FMD") is provided. The FMD molecular and / or cellular fasting products and methods are enabled by a precisely engineered nutritional profile that sustains the body during such fasts and prevents muscle and bone loss over any fasting period contemplated in this disclosure.

[0013] These novel molecular and cellular fasting products allow subjects to benefit from daily fasting and / or intermittent fasting achieved over a 24-hour period. FMDs incorporating such precisely designed products with the predetermined nutritional profiles disclosed in this disclosure allow for time-restricted and / or intermittent fasting over the 24-hour time period, as well as fasting that occurs hourly, daily, weekly and other time periods.

[0014] Such a precisely designed FMD feeding profile of carbohydrates, proteins, fats, and nutrients is precisely tuned to predetermined ratios and levels. These ratios and levels, detailed elsewhere in this disclosure, are designed to be below the detection threshold of intracellular nutrient sensors. This causes the cells to enter a true fasting state that is nearly identical to when exposed to a water-only behavioral fast. The precise formulation of specific ratios and levels of carbohydrates, proteins, fats, and nutrients establishes the precisely designed food components provided by the FMD and FMD portions and packages, which allow for sustainable molecular and / or cellular fasting without adverse consequences.

[0015] The fasting mimicking diet (FMD) has been found to be more practical and safer than fasting while providing components at levels expected to enhance the effects of fasting and affect markers or risk factors of aging and disease. The FMD is based on diets previously tested in animals and is designed to achieve effects similar to those caused by fasting based on, but not limited to, IGF-1, IGFBP1, glucose, and ketone bodies (24). To prevent nutrient deficiencies, the FMD provides each human subject with 3000 kilojoules (hereafter "kJ") to 4600 kJ per day, as well as high micronutrient nutrition (12). The safety and feasibility of this intervention were previously evaluated in 19 study participants who consumed three monthly cycles of this type of FMD, each lasting 5 days (12).

[0016] In one embodiment, a fasting mimicking meal package is provided that provides daily meal portions for a given number of days. The fasting mimicking meal package includes a kale cracker composition, a first vegetable broth composition, a mushroom soup composition, a tomato soup composition, a minestrone soup composition containing quinoa, a minestrone soup composition containing beans, and a pumpkin soup composition. Characteristically, the daily meal portions are packaged in the form of individual servings or in the form of a whole daily meal that is subsequently divided into servings.

[0017] In another embodiment, another fasting mimicking meal package is provided that provides daily meal portions for a predetermined number of days.The fasting mimicking meal package includes a nut-containing nutritional bar, a cocoa-containing nutritional bar, a first olive-containing composition, a kale cracker composition, a vegetable soup composition, a first vegetable broth composition, a tea composition containing spearmint, an energy drink composition, a micronutrient composition, and an algae oil composition.Characteristically, the fasting mimicking meal package is packaged in a single serving form or in a whole daily meal form that is subsequently divided into single servings.

[0018] Further contemplated fasting mimicking meal packages provide a one-day FMD that includes three meal portions to be consumed over a one-day fasting period. In one configuration, the FMD package includes a breakfast meal portion, a lunch meal portion, and a dinner meal portion. The breakfast meal portion includes a nut-containing nutritional bar composition, two micronutrient vegetable powders including vitamin and mineral supplements, and two algae oil composition nutritional supplements. The lunch meal portion includes a soup composition and a kale cracker composition. The dinner meal portion that completes the one-day FMD package includes another soup composition, an olive-containing composition, and one-half of another nutritional bar composition.

[0019] At least one of the breakfast, lunch, and dinner meal portions may also optionally include an energy drink composition and a tea composition containing spearmint, hibiscus, and / or lemon or other ingredients. Some further variations may include alternative nutritional bars and / or soups as described elsewhere in this disclosure.

[0020] Advantageously, the fasting mimicking diet packages described herein, when administered to a subject identified as having symptoms of the disease, can be used to help alleviate symptoms of chemotherapy, promote cell regeneration, alleviate symptoms of aging, treat or prevent diabetes, treat or prevent metabolic disorders, treat or prevent hypertension, induce senescent cell apoptosis, and prevent cancer. [Brief description of the drawings]

[0021] [Figure 1A] FIG. 1A is a schematic diagram of a fasting mimicking meal package.

[0022] [Figure 1B]Figure 1B is a consort diagram. The consort diagram shows 102 people who were contacted, of whom 100 were enrolled in the two arms of the study. The "control" group, Arm 1 (N=48), maintained their normal caloric intake during the 3-month monitoring period. Data was collected at enrollment and again after 3 months. Participants in Arm 2 (N=52) started a fasting mimicking diet (FMD) after randomization. FMD was provided for 5 days / month for 3 consecutive cycles. Data was collected at enrollment, immediately after the completion of the first FMD cycle but before resuming normal diet intake, and on average 5 days after subjects resumed normal diet after the final FMD cycle. After the initial 3-month period, subjects in Arm 1 then also started FMD. All participants were offered a follow-up clinic visit for optional analysis approximately 3 months after the completion of the third FMD cycle.

[0023] [Figure 2A] Figure 2A-2O are the change analyses of metabolic variables during randomization. The effects on aging / disease markers and risk factors in all subjects who completed the randomization analysis in the control or FMD arm (5-7 days after the third FMD cycle) are shown. Change Δ represents the comparison with baseline. All data are shown as mean ± SD. Between-arm comparisons were calculated using two-tailed two-sample equal variance t-tests. For some of the 100 enrolled participants, the nurses were not able to collect all samples / measurements from all subjects. Therefore, we excluded subjects with incomplete measurements from certain marker groups. See Table 2 for details. [Figure 2B] Same as explanation for Figure 2A. [Figure 2C] Same as explanation for Figure 2A. [Figure 2D] Same as explanation for Figure 2A. [Figure 2E] Same as explanation for Figure 2A. [Figure 2F] Same as explanation for Figure 2A. [Figure 2G] Same as explanation for Figure 2A. [Figure 2H]Same as explanation for Figure 2A. [Figure 2I] Same as explanation for Figure 2A. [Figure 2J] Same as explanation for Figure 2A. [Figure 2K] Same as explanation for Figure 2A. [Figure 2L] Same as explanation for Figure 2A. [Figure 2M] Same as explanation for Figure 2A. [Figure 2N] Same as explanation for Figure 2A. [Figure 2O] Same as explanation for Figure 2A.

[0024] [Figure 3A] Figures 3A-J are post-hoc analyses of metabolic variables in subgroups identified by severity of risk factors. Subjects from both study arms who completed three FMD cycles were post-hoc stratified based on whether they belonged to normal or at-risk subgroups for factors related to aging-related diseases and conditions. Changes Δ shown represent comparisons with baseline. All data are presented as mean ± SD. Between-arm comparisons were calculated using two-tailed, two-sample, equal variance t-tests. One-way ANOVA was used for BMI groups. See Table 4 for details. [Figure 3B] Same as explanation for Figure 3A. [Figure 3C] Same as explanation for Figure 3A. [Figure 3D] Same as explanation for Figure 3A. [Figure 3E] Same as explanation for Figure 3A. [Figure 3F] Same as explanation for Figure 3A. [Figure 3G] Same as explanation for Figure 3A. [Figure 3H] Same as explanation for Figure 3A. [Figure 3I] Same as explanation for Figure 3A. [Figure 3J] Same as explanation for Figure 3A.

[0025] [Figure 4]Figure 4 shows subject self-reported adverse effects based on the Common Terminology Criteria for Adverse Effects.

[0026] [Diagram 5] Figure 5 compares participants who completed the study with those who dropped out.

[0027] [Figure 6A] FIG. 6A is a comparison of baseline and 3-month pre / post for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6B] FIG. 6B is a comparison of baseline and pre / post 3 months for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6C] FIG. 6C is a comparison of baseline and pre / post 3 months for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6D] FIG. 6D is a comparison of baseline and 3-month pre / post for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6E] FIG. 6E is a comparison of baseline and pre / post 3 months for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6F] FIG. 6F is a comparison of baseline and pre / post 3 months for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6G] FIG. 6G is a comparison of baseline and pre / post 3 months for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6H] FIG. 6H is a comparison of baseline and pre / post 3 months for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6I]FIG. 6I is a comparison of baseline and 3-month pre / post for individual subjects in the control cohort and for all subjects who completed FMD. [Figure 6J] FIG. 6J is a comparison of baseline and 3-month pre / post for individual subjects in the control cohort and for all subjects who completed FMD.

[0028] [Figure 7A] FIG. 7A is nutritional information for the fasting mimicking nutrition bar components. [Figure 7B] FIG. 7B is nutritional information for the fasting mimicking nutrition bar components. [Figure 7C] FIG. 7C is nutritional information for the fasting mimicking nutrition bar components. [Figure 7D] FIG. 7D is nutritional information for the fasting mimicking nutrition bar components. [Figure 7E] FIG. 7E is nutritional information for the fasting mimicking nutrition bar components. [Figure 7F] FIG. 7F is nutritional information for the fasting mimicking nutrition bar components. [Figure 7G] FIG. 7G is nutritional information for the fasting mimicking nutrition bar components. [Figure 7H] FIG. 7H is nutritional information for the fasting mimicking nutrition bar components.

[0029] [Figure 8-1] FIG. 8 is Table 1 providing the baseline characteristics of the subjects. [Figure 8-2] FIG. 8 is Table 1 providing the baseline characteristics of the subjects.

[0030] [Figure 9-1] FIG. 9 is Table 2 providing study arm specific biomarker and risk factor changes for adherence. [Figure 9-2] FIG. 9 is Table 2 providing study arm specific biomarker and risk factor changes for adherence. [Figure 9-3]FIG. 9 is Table 2 providing study arm specific biomarker and risk factor changes for adherence. [Figure 9-4] FIG. 9 is Table 2 providing study arm specific biomarker and risk factor changes for adherence.

[0031] [Figure 10] Figure 10 is Table 3 providing a comparison of risk factor changes by baseline subgroups.

[0032] [Figure 11-1] FIG. 11 is Table 4 providing a post-hoc analysis of risk factors for aging-related diseases and conditions, diabetes and cardiovascular disease in at-risk subjects. [Figure 11-2] FIG. 11 is Table 4 providing a post-hoc analysis of risk factors for aging-related diseases and conditions, diabetes and cardiovascular disease in at-risk subjects. [Figure 11-3] FIG. 11 is Table 4 providing a post-hoc analysis of risk factors for aging-related diseases and conditions, diabetes and cardiovascular disease in at-risk subjects.

[0033] [Figure 12-1] FIG. 12 is Table 5 giving the complete metabolic panel. [Figure 12-2] FIG. 12 is Table 5 giving the complete metabolic panel. [Figure 12-3] FIG. 12 is Table 5 giving the complete metabolic panel.

[0034] [Figure 13A-1] FIG. 13A is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2. [Figure 13A-2] FIG. 13A is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2. [Figure 13A-3]FIG. 13A is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2. [Figure 13A-4] FIG. 13A is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2. [Figure 13A-5] FIG. 13A is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2. [Figure 13B-1] FIG. 13B is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2. [Figure 13B-2] FIG. 13B is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2. [Figure 13B-3] FIG. 13B is Table 6 providing changes in arm-specific markers and risk factors for adherence, including arm 1 after crossover to FMD, and a summary of FMD arms 1 and 2.

[0035] [Figure 14-1] FIG. 14 is Table 7 providing changes in metabolic markers and risk factors for adherence after the first FMD. [Figure 14-2] FIG. 14 is Table 7 providing changes in metabolic markers and risk factors for adherence after the first FMD. [Figure 14-3] FIG. 14 is Table 7 providing changes in metabolic markers and risk factors for adherence after the first FMD.

[0036] [Figure 15-1] FIG. 15 is Table 8 providing the changes in metabolic markers and risk factors for adherence after 3 months of intervention. [Figure 15-2] FIG. 15 is Table 8 providing the changes in metabolic markers and risk factors for adherence after 3 months of intervention. [Figure 15-3] FIG. 15 is Table 8 providing the changes in metabolic markers and risk factors for adherence after 3 months of intervention.

[0037] [Figure 16] FIG. 16 is another view of a one-day fasting mimicking meal package.

[0038] [Figure 17A] FIG. 17A is nutritional information for a fasting mimicking meal nut-containing nutritional bar composition providing an alternative formulation of FIG. 7E. [Figure 17B] FIG. 17B is nutritional information for a fasting mimicking meal nut-containing nutritional bar composition providing an alternative formulation of FIG. 7E. [Figure 17C] FIG. 17C is nutritional information for a fasting mimicking meal nut-containing nutritional bar composition providing an alternative formulation of FIG. 7E. [Figure 17D] FIG. 17D is nutritional information for a fasting mimicking meal nut-containing nutritional bar composition providing an alternative formulation of FIG. 7E. [Figure 17E] FIG. 17E is nutritional information for a fasting mimicking meal nut-containing nutritional bar composition providing an alternative formulation of FIG. 7E. [Figure 17F] FIG. 17F is nutritional information for a fasting mimicking meal nut-containing nutritional bar composition providing an alternative formulation of FIG. 7E. [Figure 17G] FIG. 17G is nutritional information for a fasting mimicking meal nut-containing nutritional bar composition providing an alternative formulation of FIG. 7E.

[0039] [Figure 18] FIG. 18 shows nutritional information for FMD's micronutrient vegetable powder with vitamin and mineral supplements, adapted from the nutritional information in FIG. 7H.

[0040] [Figure 19]FIG. 19 shows an example formulation of the FMD algal oil composition nutritional supplement of FIG. 7G.

[0041] [Figure 20] FIG. 20 provides nutritional information for FMD's modified kale cracker composition, similar to that of FIG. 7F.

[0042] [Figure 21A] 21A-21I are nutritional information for fasting mimicking meal soup composition components that provide alternative formulations of the soup compositions of FIGS. 7A, 7B, and 7C. [Figure 21B] Same as explanation for Figure 21A. [Figure 21C] Same as explanation for Figure 21A. [Figure 21D] Same as explanation for Figure 21A. [Figure 21E] Same as explanation for Figure 21A. [Figure 21F] Same as explanation for Figure 21A. [Figure 21G] Same as explanation for Figure 21A. [Fig. 21H] Same as explanation for Figure 21A. [Figure 21I] Same as explanation for Figure 21A.

[0043] [Figure 22] FIG. 22 shows nutritional information for olive-containing compositions of FMD. [Figure 23] FIG. 23 shows nutritional information for olive-containing compositions of FMD.

[0044] [Figure 24] FIG. 24 provides certain examples of tea compositions that include spearmint, hibiscus, and / or lemon or other ingredients.

[0045] [Diagram 25] FIG. 25 shows nutritional information for an energy drink composition from FMD as an alternative example to that shown in FIG. 7D. [Figure 26]FIG. 26 shows nutritional information for an energy drink composition from FMD as an alternative example to that shown in FIG. 7D.

[0046] [Figure 27] FIG. 27 is a table of results of a one-day fasting food plan protocol in which test subjects were tested to consume an FMD breakfast, lunch, and dinner over the course of one day and measure their respective blood glucose and ketone levels at designated times.

[0047] [Figure 28] FIG. 28 depicts the average blood ketone level measurements of test subjects at selected predetermined times during the one-day fasting protocol of FIG.

[0048] [Figure 29] FIG. 29 shows the average blood glucose measurements for the same test subjects as in FIGS. 26 and 27, at the same selected times. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] Where necessary, detailed embodiments of the present invention are disclosed in this disclosure, but it should be understood that the disclosed embodiments are merely exemplary of the present invention, which may be embodied in various and alternative forms. The figures are not necessarily to scale, and some features may be exaggerated or minimized to show details of specific components. Therefore, specific structural and functional details disclosed in this disclosure should not be construed as limiting, but merely as a representative basis for teaching those skilled in the art how to use the present invention in various ways.

[0050] The term "subject" refers to a human or animal, including all mammals such as primates (especially higher primates), sheep, dogs, rodents (e.g., mice or rats), guinea pigs, goats, pigs, cats, rabbits, and cows.

[0051] The term "fasting mimicking enriched diet" refers to a diet that mimics the effects of fasting by typically providing the subject with 50-75% or less of the subject's normal caloric intake, but with nutritional ingredients that mimic fasting while the subject is not completely hungry. However, based on our current and previous knowledge, if the fasting mimicking diet composition is maintained, partial disease prevention and treatment effects are expected even if 100% of the normal caloric intake is provided to the subject. The term "fasting mimicking enriched diet" may also be simply referred to as "fasting mimicking diet".

[0052] Typically, such fasting mimicking diets are ketogenic because they cause an increase in ketone bodies and stimulate metabolism based on ketone bodies, and therefore can be called ketogenic FMD. In particular, among other benefits, FMD affects IGF-1, AKT and TOR signaling by regulating growth hormone signaling upstream of IGF-1. This also affects the level of glucose, the release of insulin, and the level of the hunger hormone leptin. Low levels of IGF-1, leptin, insulin, and glucose, and high levels of ketone bodies and IGFBP1 work together to promote the beneficial effects of FMD.

[0053] In the context of the present invention, examples of useful fasting mimicking enriched diets, as well as methods for monitoring the effects of these diets on markers such as IGF-1 and IGFBP1, are described in U.S. patent application Ser. Nos. 14 / 273,946 (filed May 9, 2014); 14 / 497,752 (filed Sept. 26, 2014); 12 / 910,508 (filed Oct. 22, 2010); 13 / 643,673 (filed Oct. 23, 2012); Nos. 13 / 982,307, filed July 29, 2013; 14 / 060,494, filed October 22, 2013; 14 / 178,953, filed February 12, 2014; 14 / 320,996, filed July 1, 2014; and 14 / 671,622, filed March 27, 2015, the entire disclosures of which are incorporated herein by reference. The fasting mimicking diets described in U.S. patent application Ser. Nos. 14 / 060,494 and 14 / 178,953 have been found to be particularly useful in the present invention.

[0054] Further informative examples of FMD diets can be found in U.S. Patent Application No. 15 / 148,251 and WIPO Publication No. WO 2011 / 050302 and WIPO Publication No. WO 2011 / 050302, the disclosures of which are incorporated by reference in their entireties into this disclosure.

[0055] In one embodiment of the present invention, a dietary package for administering a fasting mimicking diet is provided. The fasting mimicking diet package provides daily meal portions for a predetermined number of days. Typically, the predetermined number of days is 1-10 days (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days). In a particularly useful formulation, the predetermined number of days is 5 or 6 days. In some formulations, the fasting mimicking diet described in the present disclosure provides, in order of increasing preference, 75% or less, 50% or less, 40% or less, 30% or less, or 10% or less of the subject's normal caloric intake or the recommended daily caloric intake for the subject to the subject. In one refinement, the fasting mimicking diet provides, in order of increasing preference, 5% or more, 10% or more, or 20% or more of the subject's normal caloric intake or the recommended daily caloric intake for the subject.

[0056] However, based on our current and previous knowledge, if the fasting mimicking diet composition is maintained, partial disease prevention and treatment effects are expected even if, for example, 100% of the normal caloric intake is provided to the subject. The normal caloric intake of a subject is the number of kilocalories (hereinafter "kcal") that the subject consumes to maintain his / her body weight. The normal caloric intake of a subject can be estimated by interviewing the subject or by considering the subject's body weight. As a rough guide, the normal caloric intake of a subject is an average of 2600 kcal / day for men and an average of 1850 kcal / day for women. In certain examples, the fasting mimicking diet provides the subject with 700-1200 kcal / day. In a particularly useful variation, the fasting mimicking diet provides about 1100 kcal / day for a male subject of average body weight and 900 kcal / day for a female subject of average body weight. In one formulation, the diet from the diet package is administered on consecutive days. In another formulation, the daily meal portion is provided only one day per week for at least one month.

[0057] In one embodiment, the fast mimicking meal package provides daily meal portions for a predetermined number of days as described above. The fast mimicking meal package includes a kale cracker composition, a first vegetable broth composition, a mushroom soup composition, a tomato soup composition, a minestrone soup composition containing quinoa, a minestrone soup composition containing beans, and a pumpkin soup composition. Characteristically, the daily meal portions are packaged in the form of individual servings or in the form of a whole meal for a day that will be subsequently divided into individual servings. In one variation, the fast mimicking meal package includes a nut-containing nutritional bar, a cocoa-containing nutritional bar, a first olive-containing composition, a first vegetable broth composition, a tea composition containing spearmint, an energy drink composition, a micronutrient composition, and an algae oil composition. In a further variation, the fast mimicking meal package further includes a second olive-containing composition, a second vegetable broth composition, a tea composition containing spearmint and lemon, and a tea composition containing hibiscus.

[0058] In one formulation of the above-described embodiments, the fasting mimicking meal package may comprise less than 40 grams of sugar on day 1, less than 30 grams of sugar on days 2-5 and the remaining days, if any; less than 28 grams of protein on day 1, less than 18 grams of protein on days 2-5 and the remaining days, if any; monounsaturated fat in an amount of 20-30 grams or more to reach a desired caloric intake (i.e., a predetermined caloric intake) for day 1; polyunsaturated fat in an amount of 6-10 grams or more to reach a desired caloric intake for day 1; The daily meal portions include a daily meal portion providing a micronutrient composition for each day and the remaining days, if there are any, including saturated fat in an amount of 2-12 grams or more to reach a desired caloric intake, monounsaturated fat in an amount of 10-15 grams or more to reach a desired caloric intake on days 2-5 and the remaining days, if there are any, polyunsaturated fat in an amount of 3-5 grams or more to reach a desired caloric intake on days 2-5 and the remaining days, if there are any, saturated fat in an amount of 1-6 grams or more to reach a desired caloric intake on days 2-5 or the remaining days, if there are any, and a micronutrient composition for each day and the remaining days, if there are any.

[0059] In another formulation of the above embodiment, the fasting mimetic meal package includes daily meal portions providing 8-10 kcal per kilogram of body weight for each dietary day. In this formulation, the fasting mimetic meal provides less than 30 grams of sugar for each dietary day, less than 18 grams of protein for each dietary day, 9-15 grams or more of monounsaturated fat to reach the desired caloric intake for each dietary day, and 2.5-4.5 grams or more of polyunsaturated fat to reach the desired caloric intake for each dietary day, and 1-5.5 grams or more of saturated fat to reach the desired caloric intake for each dietary day. Higher FMD formulations providing up to 100% of normal caloric intake to the subject may provide higher levels of the fats listed above.

[0060] In yet another formulation of the above embodiment, the fasting mimicking meal package includes a daily meal portion providing 5-8 kcal per kilogram of body weight for each dietary day. In this formulation, the fasting mimicking meal provides less than 20 grams of sugar for each dietary day, less than 12 grams of protein for each dietary day, and 6.5-10 grams or more of monounsaturated fat to reach a desired caloric intake for each dietary day, 2.5-4.5 grams or more of polyunsaturated fat to reach a desired caloric intake for each dietary day, and 1.5-4 grams or more of saturated fat to reach a desired caloric intake for each dietary day.

[0061] In yet another formulation of the above embodiment, the fasting mimicking meal package includes a daily meal group providing 0-3 kcal per kilogram of body weight for each dietary day. In this formulation, the fasting mimicking meal provides less than 5 grams of sugar for each dietary day, less than 3 grams of protein for each dietary day, less than 2.5 grams of monounsaturated fat for each dietary day, less than 1 gram of polyunsaturated fat for each dietary day, and less than 1 gram of saturated fat for each dietary day.

[0062] In some embodiments, the nutritional requirements of the fasting mimicking diet described above can be achieved by a dietary package containing certain dietary components. In one example of a preparation shown in FIG. 1A, the fasting mimicking diet package 10 provides daily meal portions for the predetermined number of days described above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days). The fasting mimicking diet package 10 includes a kale cracker composition (item 12), a first vegetable broth composition (item 14), a mushroom soup composition (item 16), a tomato soup composition (item 18), a quinoa-containing minestrone soup composition (item 20), a bean-containing minestrone soup composition (item 22), and a pumpkin soup composition (item 24).

[0063] Characteristically, the daily meal portions are packaged in the form of individual servings or in the form of a whole daily meal that will later be divided into servings. In one variation, the fasting mimicking meal package further comprises a nut-containing nutritional bar (item 26), a cocoa-containing nutritional bar (item 28), a first olive-containing composition (item 30), a first vegetable broth composition (item 32), a tea composition comprising spearmint (item 34), an energy drink composition (item 36), a micronutrient composition (item 38), and an algae oil composition (item 40). In a further variation, the fasting mimicking meal package further comprises a second olive-containing composition (item 42), a second vegetable broth composition (item 44), a tea composition comprising spearmint and lemon (item 46), and a tea composition comprising hibiscus (item 48). It should be understood that each of the soups, broths, teas, and energy compositions described in the present disclosure is designed to be consumed with the addition of water.

[0064] In another example of a fasting mimicking meal package, the meal package 10 includes a nut-containing nutritional bar (item 26), a cocoa-containing nutritional bar (item 28), a first olive-containing composition (item 30), a kale cracker composition (item 12), a vegetable soup composition (item 14), a first vegetable broth composition (item 14), a tea composition containing spearmint (item 34), an energy drink composition (item 36), a micronutrient composition (item 38), and an algae oil composition (item 40). Characteristically, the daily meal portions are packaged in the form of individual servings or in the form of a whole daily meal that will be subsequently divided into servings. The meal package also includes daily meal portions for a given number of days as described above, the daily meal portions being packaged in the form of individual servings or in the form of a whole daily meal that will subsequently be divided into servings. In one variation, the fast mimicking meal package further comprises a mushroom soup composition (item 16), a tomato soup composition (item 18), a quinoa-containing minestrone soup composition (item 20), and a pumpkin soup composition. In a further variation, the fast mimicking meal package further comprises a second olive-containing composition (item 42), a second vegetable broth composition (item 44), a bean-containing minestrone soup composition (item 22), a tea composition comprising spearmint and lemon (item 46), and a tea composition comprising hibiscus (item 48).

[0065] As mentioned above, the fasting mimicking meal package includes certain meal components. Typically, the compositions are as follows: The nut-containing nutritional bar includes almond meal and macadamia nuts. The cocoa-containing nutritional bar includes almond butter, almonds, and brown rice crispies (e.g., puffed brown rice). The mushroom soup composition includes brown rice flour, carrots, inulin, and mushrooms. The bean-containing minestrone soup composition includes white beans, cabbage, and potatoes. The first vegetable broth composition includes carrots, maltodextrin, celery, spinach, and tomatoes. The second vegetable broth composition includes carrots, maltodextrin, celery, spinach, soy lecithin, and tomatoes. The energy drink composition includes glycerin and water. The algae oil composition includes Schizocatrium algae oil. The micronutrient composition includes beet root powder, calcium carbonate, carrots, collard greens, kale leaves, and tomatoes. In one variation, the micronutrient composition includes Vitamins (hereinafter "Vit") A, Vit C, Ca, Fe, Vit D3, Vit E, Vit K, Vit B1, Vit B2, Vit B3, Vit B5, Vit B6, Vit B7, Vit B9, Vit B12, Cr, Cu, I, Mg, Mn, Mo, Se, and Zn.

[0066] In one variation, the nut-containing nutritional bar (L-Bar (Nut Based), available from L-Nutra Inc.) comprises almond meal and macadamia nuts. In one variation, the nut-containing nutritional bar (L-Bar (Nut Based)) comprises almond meal (preferably almond meal in an amount of 20-35% by weight), coconut (preferably coconut in an amount of 2-10% by weight), coconut oil (preferably coconut oil in an amount of 1-8% by weight), flaxseed meal (preferably flaxseed meal in an amount of 1-8% by weight), honey (preferably honey in an amount of 10-30% by weight), macadamia nuts (preferably macadamia nuts in an amount of 10-30% by weight), pecans (preferably pecans in an amount of 10-25% by weight), salt (preferably salt in an amount of 0.1-0.8% by weight), and optionally vanilla (preferably vanilla in an amount of 0.3-1.5% by weight).

[0067] In one variation, a cocoa-containing nutritional bar (L-Bar (Choco Crisp), available from L-Nutra Inc.) contains almond butter, almonds, and brown rice crispies (PGP10235). In one variation, the cocoa-containing nutritional bar (L-Bar (Choco Crisp)) comprises almond butter (preferably almond butter in an amount of 10-25% by weight), almonds (preferably almonds in an amount of 3-12% by weight), brown rice crispy (PGP10235) (preferably brown rice crispy (PGP10235) in an amount of 10-25% by weight), brown rice syrup (preferably brown rice syrup in an amount of 2-8% by weight), chocolate liquor (preferably chocolate liquor in an amount of 1-4% by weight), cocoa butter (preferably cocoa butter in an amount of 0.4-1.6% by weight), cocoa powder (preferably cocoa powder in an amount of 4-12% by weight), Fiber Syrup SF75 (preferably Fiber Syrup SF75 in an amount of 18-38% by weight), flaxseed oil (preferably flaxseed oil in an amount of 1-3% by weight), salt (preferably salt in an amount of 0.1-0.4% by weight), and sugar (preferably sugar in an amount of 1-6% by weight).

[0068] In one variation, the first olive-containing composition (sea salt version) comprises olives, olive oil, and sea salt. In one variation, the first olive-containing composition (sea salt) comprises lactic acid (preferably lactic acid in an amount of 0.3-1% by weight), oil (olive) (preferably oil (olive) in an amount of 2-6% by weight), olive (raw, pitted green) (preferably olive (raw, pitted green) in an amount of 50-97% by weight), salt (regular salt, kosher salt, sea salt) (preferably salt (regular salt, kosher salt, sea salt) in an amount of 0.8-3% by weight), and thyme (preferably thyme in an amount of 0.1-0.5% by weight).

[0069] In one variation, the second olive-containing composition (garlic version) comprises olives, olive oil, and garlic. In one variation, the second olive-containing composition (garlic version) comprises garlic (preferably garlic in an amount of 0.1-0.6% by weight), lactic acid (preferably lactic acid in an amount of 0.3-1% by weight), oil (olive) (preferably oil (olive) in an amount of 2-6% by weight), olive (raw, pitted green) (preferably olive (raw, pitted green) in an amount of 50-97% by weight), salt (regular salt, kosher salt, sea salt) (preferably salt (regular salt, kosher salt, sea salt) in an amount of 0.8-3% by weight), and thyme (preferably thyme in an amount of 0.1-0.5% by weight).

[0070] In one variation, the kale cracker composition includes kale, almonds, tapioca flour, and optionally sesame seeds. In another variation, the kale cracker composition includes almonds (preferably almonds in an amount of 15-40% by weight), black pepper (preferably black pepper in an amount of 0.1-0.4% by weight), chia seeds (preferably chia seeds in an amount of 3-10% by weight), hot pepper (preferably hot pepper in an amount of 0.4-1.2% by weight), cumin seeds (preferably cumin seeds in an amount of 0.3-0.9% by weight), flaxseed (preferably flaxseed in an amount of 3-10% by weight), garlic (preferably garlic in an amount of 0.02-0.04% by weight), kale (preferably kale in an amount of 2-6% by weight), oil (sunflower) (preferably about 2-7% by weight oil (sunflower)), onion (powder, chopped) (typically onion (powder, chopped) in an amount of 0.3-0.9% by weight), oregano (preferably oregano in an amount of 0.01-0.06% by weight), salt (preferably salt in an amount of 1-4% by weight), sesame seeds (preferably sesame seeds in an amount of 15-35% by weight), sugar (coconut) (preferably sugar (coconut) in an amount of 1-5% by weight), tapioca flour (preferably tapioca flour in an amount of 10-30% by weight), vinegar (coconut) (preferably vinegar (coconut) in an amount of 1-4% by weight), water (purified) (preferably water (purified) in an amount of 2-12% by weight), yeast extract (preferably yeast extract in an amount of 0.3-1% by weight).

[0071] In another variation, the kale cracker composition includes kale, golden flaxseed, sesame seeds, and sunflower seeds. In another variation, the kale cracker composition includes apple cider vinegar (preferably in an amount of 1-3% by weight), black pepper (preferably in an amount of 0.4-1.3% by weight), cashews (preferably in an amount of 4-13% by weight), dill weed (preferably in an amount of 0.4-1.3% by weight), golden flaxseed (preferably in an amount of 13-40% by weight), hemp seeds (preferably in an amount of 0.7-2% by weight), kale (preferably in an amount of 14-42% by weight), dried white onions, and dried thyme. The composition includes green onions (powder, chopped) (preferably dried white onions (powder, chopped) in an amount of 0.5-1.6% by weight), pumpkin seeds (preferably pumpkin seeds in an amount of 0.7-2% by weight), salt (regular salt, kosher salt, sea salt) (preferably salt (regular salt, kosher salt, sea salt) in an amount of 0.7-2% by weight), sesame seeds (preferably sesame seeds in an amount of 2-8% by weight), sunflower seeds (preferably sunflower seeds in an amount of 10-30% by weight), and yeast extract (preferably yeast extract in an amount of 1-5% by weight).

[0072] In one variation, the vegetable soup composition includes onion, tomato, spinach, green tree extract, optionally rice flour, optionally brown rice flour, optionally carrot, and optionally inulin, leek. In one variation, the vegetable soup composition comprises basil (whole leaf, dried) (preferably basil (whole leaf, dried) in an amount of 0.3-0.9% by weight), brown rice flour (whole) (preferably brown rice flour (whole) in an amount of 3-12% by weight), carrot (dehydrated, puffed, powder, pieces) (preferably carrot (dehydrated, puffed, powder, pieces) in an amount of 4-14% by weight), green tea extract (preferably green tea extract in an amount of 0.02-0.06% by weight), inulin (preferably inulin in an amount of 5-15% by weight), leek (granule-10+40) (preferably leek (granule-10+40) in an amount of 1-5% by weight), oil (olive) (preferably oil (olive) in an amount of 1-6% by weight), onion (pasta). udha, chopped) (preferably onion (powder, chopped) in an amount of 4-15% by weight), parsley (preferably parsley in an amount of 0.3-0.8% by weight), red bell pepper (preferably red bell pepper in an amount of 1-5% by weight), rice flour (preferably rice flour in an amount of 18-50% by weight), salt (preferably salt in an amount of 2-7% by weight), spinach (leaf, powder) (preferably spinach (leaf, powder) in an amount of 0.4-1.5% by weight), tomato (fruit powder, sun-dried, granule) (preferably tomato (fruit powder, sun-dried, granule) in an amount of 4-14% by weight), yeast extract (preferably yeast extract in an amount of 0.5-1.8% by weight). In any of the vegetable soup compositions and compositions described herein having rice flour, the rice flour may be glutinous rice flour or non-glutinous rice flour, and may be ground or unground.

[0073] In another variation, the vegetable soup composition includes carrots, inulin, leeks, onions, and rice flour. In one variation, the vegetable soup composition includes basil (whole leaves, dried) (preferably basil (whole leaves, dried) in an amount of 0.3-1% by weight), carrots (dehydrated, puffed, powder, pieces) (preferably carrots (dehydrated, puffed, powder, pieces) in an amount of 4-12% by weight), inulin (preferably inulin in an amount of 6-18% by weight), leeks (leeks in an amount of 1-5% by weight), oil (olive) (preferably oil (olive) in an amount of 1-3% by weight), dried white onion (powder, chopped) (preferably dried white onion (powder, chopped) in an amount of 10-30% by weight), parsley (preferably 0.3 % by weight), parsley in an amount of 1-1% by weight, potato (preferably potato in an amount of 1-5% by weight), red pepper (preferably red pepper in an amount of 1-6% by weight), rice flour (rice flour in an amount of 13-40% by weight), salt (regular salt, kosher salt, sea salt) (salt (regular salt, kosher salt, sea salt) in an amount of 4-12% by weight), spinach (leaf, powder) (preferably spinach (leaf, powder) in an amount of 0.2-1% by weight), and tomato (fruit powder, sun dried granules) (preferably tomato (fruit powder, sun dried granules) in an amount of 3-13% by weight).

[0074] In one variation, the mushroom soup composition comprises mushrooms, green tea extract, optionally brown rice flour, optionally carrots, and optionally inulin. In one variation, the mushroom soup composition comprises brown rice flour (whole) (preferably brown rice flour (whole) in an amount of 10-30% by weight), carrots (dehydrated, puffed, powder, pieces) (preferably carrots (dehydrated, puffed, powder, pieces) in an amount of 3-12% by weight), green tea extract (preferably green tea extract in an amount of 0.02-0.06% by weight), inulin (preferably inulin in an amount of 3-12% by weight), mushrooms (European mix, powder, pieces) (preferably in an amount of 6-18% by weight). mushrooms (European mix, powder, pieces)), oil (olive) (preferably oil (olive) in an amount of 1-6% by weight), onion (powder, chopped) (preferably onion (powder, chopped) in an amount of 3-12% by weight), parsley (preferably parsley in an amount of 0.1-0.5% by weight), rice flour (preferably rice flour in an amount of 18-50% by weight), salt (preferably salt in an amount of 2-8% by weight), yeast extract (preferably yeast extract in an amount of 0.5-1.5% by weight).

[0075] In another variation, the mushroom soup composition comprises carrots, inulin, mushrooms, onion and rice flour. In another variation, the mushroom soup composition comprises carrots (dehydrated, puffed, powder, pieces) (preferably carrots (dehydrated, puffed, powder, pieces) in an amount of 7-22% by weight), inulin (preferably inulin in an amount of 7-22% by weight), mushrooms (European mix) (powder and pieces) (preferably mushrooms (European mix) (powder and pieces) dehydrated in an amount of 7-22% by weight), oil (olive) (preferably oil (olive) in an amount of 0.6-2% by weight), dried white onion (powdered). % by weight), parsley (preferably parsley in an amount of 0.3 to 0.9% by weight), potato (preferably potato in an amount of 0.6 to 2% by weight), rice flour (preferably rice flour in an amount of 15 to 45% by weight), salt (regular salt, kosher salt, sea salt) (preferably salt (regular salt, kosher salt, sea salt) in an amount of 6 to 18% by weight), and yeast extract (preferably yeast extract in an amount of 0.7 to 2.2% by weight).

[0076] In one variation, the tomato soup composition comprises tomatoes, green tea extract, optionally inulin, and optionally onion. In one variation, the tomato soup composition (new) comprises basil (whole leaf, dried) (preferably basil (whole leaf, dried) in an amount of 0.2-0.7% by weight), brown rice flour (whole) (preferably brown rice flour (whole) in an amount of 1-5% by weight), green tea extract (preferably green tea extract in an amount of 0.02-0.06% by weight), inulin (preferably inulin in an amount of 7-20% by weight), oil (olive) (preferably oil (olive) in an amount of 3-9% by weight), onion (powder, finely chopped), and / or other ingredients. % by weight), onion (powder, chopped) (preferably in an amount of 4-12% by weight), parsley (preferably parsley in an amount of 0.1-0.6% by weight), rice flour (preferably rice flour in an amount of 18-50% by weight), salt (preferably salt in an amount of 2-9% by weight), tomato (fruit powder, sun-dried, granules) (preferably tomato (fruit powder, sun-dried, granules) in an amount of 12-36% by weight), and yeast extract (preferably yeast extract in an amount of 0.5-3% by weight).

[0077] In one variation, the tomato soup composition comprises tomatoes, inulin, olives, onions, potatoes, and rice flour. In yet another variation, the tomato soup composition comprises dried whole leaf basil (preferably dried whole leaf basil in an amount of 0.3-1 wt %), inulin (preferably inulin in an amount of 6-18 wt %), oil(olive) (preferably oil(olive) in an amount of 4-14 wt %), dried white onion (powder, chopped) (preferably dried white onion (powder, chopped) in an amount of 8-24 wt %), parsley (preferably parsley in an amount of 0.3-0.9 wt %), potatoes ( preferably potato in an amount of 6-18% by weight), rice flour (preferably rice flour in an amount of 9-27% by weight), salt (regular salt, kosher salt, sea salt) (preferably salt (regular salt, kosher salt, sea salt) in an amount of 4-14% by weight), tomato (fruit powder, sun dried granules) (preferably tomato (fruit powder, sun dried granules) in an amount of 8-24% by weight), and yeast extract (preferably yeast extract in an amount of 0.7-2.2% by weight).

[0078] In one variation, the quinoa-containing minestrone soup composition comprises quinoa, green tea extract, optionally olive oil, optionally cabbage, optionally potato, optionally rice flour, and optionally tomato, and optionally no turmeric. In one variation, the quinoa-containing minestrone soup composition comprises basil (whole leaves, dried) (preferably basil (whole leaves, dried) in an amount of 0.7-2% by weight), broccoli powder (preferably broccoli powder in an amount of 0.6-2% by weight), white cabbage (flakes) (preferably white cabbage (flakes) in an amount of 3-10% by weight), carrots (dehydrated, puffed, powdered, strips) (preferably carrots (dehydrated, puffed, powdered, strips) in an amount of 3-10% by weight). )), celery (preferably celery in an amount of 1-4% by weight), celery seed (powder) (preferably celery seed (powder) in an amount of 0.07-0.2% by weight), garlic (preferably garlic in an amount of 0.7-2% by weight), green tea extract (preferably green tea extract in an amount of 0.02-0.06% by weight), inulin (preferably inulin in an amount of 1-5% by weight), leek (granules-10+40) (preferably leek (granules-10+40) in an amount of 0.7-2% by weight 0)), oil (olive) (preferably oil (olive) in an amount of 0.6-2% by weight), onion (powder, chopped) (preferably onion (powder, chopped) in an amount of 2-8% by weight), peas (preferably peas in an amount of 3-10% by weight), potatoes (preferably potatoes in an amount of 7-20% by weight), quinoa (preferably quinoa in an amount of 7-20% by weight), rice flour (preferably rice flour in an amount of 7-20% by weight), salt (preferably 1.0% by weight), salt in an amount of 0.5-2% by weight), spinach (leaf, powder) (preferably spinach (leaf, powder) in an amount of 0.5-2% by weight), tomato (fruit powder, sun dried, granules) (preferably tomato (fruit powder, sun dried, granules) in an amount of 2-6% by weight), yeast extract (preferably yeast extract in an amount of 0.6-2% by weight), zucchini (powder, diced) (preferably zucchini (powder, diced) in an amount of 2-8% by weight).

[0079] In another variation, the quinoa-containing minestrone soup includes quinoa, cabbage, potatoes, and rice flour. In yet another variation, the quinoa containing minestrone soup further comprises dried whole leaf basil (preferably dried whole leaf basil in an amount of 0.7-2.2% by weight), broccoli powder (preferably broccoli powder in an amount of 0.7-2.2% by weight), white cabbage (flakes) (preferably white cabbage (flakes) in an amount of 0.6-2.2% by weight), carrots (dehydrated, puffed, powder, pieces) (preferably carrots (dehydrated, puffed, powder, pieces) in an amount of 3-10% by weight), celeriac (preferably celeriac in an amount of 2-6% by weight), celery seed powder (preferably celery seed powder in an amount of 0.6-1.8% by weight), garlic (preferably garlic in an amount of 1-3% by weight), dried white onion (powder, chopped) (preferably dried white onion (powder, chopped) in an amount of 3-9% by weight), peas, and the like. (preferably peas in an amount of 3-10% by weight), potatoes (preferably potatoes in an amount of 6-20% by weight), quinoa (preferably quinoa in an amount of 8-23% by weight), rice flour (preferably rice flour in an amount of 7-22% by weight), salt (regular salt, kosher salt, sea salt) (preferably salt (regular salt, kosher salt, sea salt) in an amount of 2-7% by weight), savoy cabbage (preferably savoy cabbage in an amount of 3-10% by weight), spinach (leaves, powder) (preferably spinach (leaves, powder) in an amount of 0.7-2.2% by weight), turmeric (preferably turmeric in an amount of 0.6-1.8% by weight), yeast extract (preferably yeast extract in an amount of 3-10% by weight), and zucchini (powder, diced) (preferably zucchini (powder, diced) in an amount of 1-5% by weight).

[0080] In one variation, the bean-containing minestrone soup composition includes white beans (eg, great northern beans), great tea extract, optionally cabbage, and optionally potatoes. In one variation, the bean containing minestrone soup composition comprises beans (Great Northern) (preferably Beans (Great Northern) in an amount of 3-10% by weight), white cabbage (flakes) (preferably White Cabbage (Flakes) in an amount of 2-8% by weight), carrots (dehydrated, puffed, powder, pieces) (preferably Carrots (dehydrated, puffed, powder, pieces) in an amount of 2-8% by weight), celery (preferably Celery in an amount of 1-4% by weight), green tea extract (preferably Green Tea Extract in an amount of 0.02-0.06% by weight), inulin (preferably Inulin in an amount of 2-10% by weight), leeks (Granules-10+40) (preferably Leeks (Granules-10+40) in an amount of 2-7% by weight), oil (olive) (preferably Oil (Olive) in an amount of 2-7% by weight), onion (powder, chopped) (preferably onion (powder, chopped) in an amount of 2-7% by weight), parsley (preferably parsley in an amount of 0.2-1% by weight), peas (preferably peas in an amount of 3-9% by weight), potato (preferably potato in an amount of 15-45% by weight), rice flour (preferably rice flour in an amount of 6-18% by weight), salt (preferably salt in an amount of 2-8% by weight), spinach (leaf, powder) (preferably spinach (leaf, powder) in an amount of 0.5-1.5% by weight), tomato (fruit powder, sun-dried, granules) (preferably tomato (fruit powder, sun-dried, granules) in an amount of 2-7% by weight), and yeast extract (preferably yeast extract in an amount of 0.5-1.5% by weight).

[0081] In one variation, the bean-containing minestrone soup composition includes brown beans, carrots, peas, potatoes, and rice flour. In another variation, the bean-containing minestrone soup composition includes carrots (dehydrated, puffed, powdered, pieces) (preferably carrots (dehydrated, puffed, powdered, pieces) in an amount of 4-14% by weight), celeriac (preferably celeriac in an amount of 1-5% by weight), celery (preferably celery in an amount of 0.5-1.6% by weight), leek (preferably leek in an amount of 2-8% by weight), oil (olive) (preferably oil (olive) in an amount of 2-8% by weight), dried white onion (powdered, chopped) (preferably dried white onion (powdered, chopped) in an amount of 3-10% by weight), parsley (preferably parsley in an amount of 0.5-1.5% by weight), peas (preferably 5-18% by weight). peas), potatoes (preferably potatoes in an amount of 8-24% by weight), rice flour (preferably rice flour in an amount of 5-18% by weight), salt (regular salt, kosher salt, sea salt) (preferably salt (regular salt, kosher salt, sea salt) in an amount of 4-14% by weight), spinach (leaf, powder) (preferably spinach (leaf, powder) in an amount of 0.5-1.5% by weight), tomato (fruit powder, sun dried granules) (preferably tomato (fruit powder, sun dried granules) in an amount of 0.9-2.8% by weight), turmeric (preferably turmeric in an amount of 0.3-1.2% by weight), and yeast extract (preferably yeast extract in an amount of 0.5-1.5% by weight).

[0082] In one variation, the pumpkin soup composition includes pumpkin, green tree extract, optionally rice flour, optionally carrots, and optionally brown rice flour. In one variation, the pumpkin soup composition (new) comprises brown rice flour (whole) (preferably brown rice flour (whole) in an amount of 3-9% by weight), carrots (dehydrated, puffed, powder, pieces) (preferably carrots (dehydrated, puffed, powder, pieces) in an amount of 2-8% by weight), green tea extract (preferably green tea extract in an amount of 0.02-0.06% by weight), inulin (preferably inulin in an amount of 2-10% by weight), oil (olive) (preferably oil (olive) in an amount of 1-7% by weight), onion (powder, chopped) (preferably onion (powder, chopped) in an amount of 1.0-3% by weight), pumpkin powder (preferably pumpkin powder in an amount of 20-60% by weight), rice flour (preferably rice flour in an amount of 15-45% by weight), salt (preferably salt in an amount of 2-10% by weight), and yeast extract (preferably yeast extract in an amount of 0.3-1% by weight).

[0083] In some variations, the first vegetable broth includes carrots, maltodextrin, celery, spinach, and tomatoes. In some variations, the first vegetable broth includes carrots (dehydrated, puffed, powdered, pieces) (preferably carrots (dehydrated, puffed, powdered, pieces) in an amount of 6-18% by weight), celery (preferably celery in an amount of 3-10% by weight), garlic (preferably garlic in an amount of 3-10% by weight), maltodextrin (preferably maltodextrin in an amount of 8-25% by weight), oil (canola) (preferably oil (canola) in an amount of 0.5-2% by weight), onion (powdered, chopped) (preferably tomato in an amount of 6-18% by weight). onion (powder, chopped)), parsley (preferably parsley in an amount of 3-10% by weight), potato (preferably potato in an amount of 1-3% by weight), salt (preferably salt in an amount of 7-21% by weight), spinach (leaf, powder) (preferably spinach (leaf, powder) in an amount of 3-10% by weight), tomato (fruit powder, sun-dried, granules) (preferably tomato (fruit powder, sun-dried, granules) in an amount of 6-18% by weight), and yeast extract (preferably yeast extract in an amount of 1-6% by weight).

[0084] In one variation, the second vegetable broth (chicken flavored) comprises carrots, chicken flavoring, maltodextrin, celery, spinach, soy lecithin, and tomato. In one variation, the second vegetable broth composition comprises carrots (dehydrated, puffed, powdered, pieces) (preferably carrots (dehydrated, puffed, powdered, pieces) in an amount of 3-10% by weight), celery (preferably celery in an amount of 3-12% by weight), garlic (preferably garlic in an amount of 3-9% by weight), maltodextrin (preferably maltodextrin in an amount of 8-25% by weight), oil (canola) (preferably oil (canola) in an amount of 0.5-2% by weight), onion (preferably powdered, chopped) (preferably onion (preferably powdered, chopped) in an amount of 3-12% by weight), parsley (preferably % by weight), parsley (preferably in an amount of 3-10% by weight), potato (preferably potato in an amount of 1-6% by weight), salt (preferably salt in an amount of 8-25% by weight), soy lecithin (preferably soy lecithin in an amount of 0.5-3% by weight), spinach (leaf, powder) (spinach (leaf, powder) in an amount of 3-12% by weight), tomato (fruit powder, sun-dried, granules) (preferably tomato (fruit powder, sun-dried, granules) in an amount of 6-18% by weight), xanthan gum (preferably xanthan gum in an amount of 0.5-4% by weight), and yeast extract (preferably yeast extract in an amount of 4-12% by weight).

[0085] In one variation, the energy drink composition comprises glycerin (preferably glycerin in an amount of 20-60% by weight), water (purified) (preferably water (purified) in an amount of 40-80% by weight).

[0086] In one variation, the spearmint-containing tea composition comprises organic spearmint leaf (preferably in an amount of 70-100% by weight of organic spearmint leaf).

[0087] In one variation, the lemon and spearmint tea composition comprises organic lemon myrtle (preferably organic lemon myrtle in an amount from 3 to 12% by weight), organic lemon peel (preferably organic lemon peel in an amount from 10 to 25% by weight), and organic spearmint leaf (preferably organic spearmint leaf in an amount from 50 to 95% by weight).

[0088] In one variation, the hibiscus containing tea composition comprises organic hibiscus tea leaf (preferably organic hibiscus tea leaf in an amount of 80-100% by weight).

[0089] In one variation, the algal oil composition comprises Schizocatrium algal oil (DHA omega-3) (preferably in an amount of 80-100% by weight).

[0090] In one variation, the nutrient replenishment composition (NR-1) includes beet root powder, calcium carbonate, carrots, collard greens, kale leaves, and tomatoes. In one variation, the nutrient replenishment composition (NR-1) includes ascorbic acid, preferably ascorbic acid in an amount of 1-3% by weight; beet root powder, preferably beet root powder in an amount of 6-20% by weight; β-carotene, preferably β-carotene in an amount of 0.05-0.15% by weight; calcium carbonate, preferably calcium carbonate in an amount of 6-20% by weight; carrots (dehydrated, puffed, powder, pieces), preferably carrots (dehydrated, puffed, powder, pieces) in an amount of 6-20% by weight; cholecalciferol, preferably 0. cholecalciferol in an amount of .00% by weight; chromium picolinate, preferably chromium picolinate in an amount of 0.00% by weight; collard leaf powder, preferably collard leaf powder in an amount of 6-20% by weight; cupric sulfate, preferably cupric sulfate in an amount of 0.01-0.06% by weight; cyanocobalamin at 0.00; DL-alpha tocopherol acetate, preferably DL-alpha tocopherol acetate in an amount of 0.3-1% by weight; ferrous fumarate, preferably ferrous fumarate in an amount of 0.2-1% by weight; folic acid, preferably 0.00 folic acid in an amount of % by weight; kale leaves, preferably kale leaves in an amount of 6-20% by weight; magnesium stearate, preferably magnesium stearate in an amount of 1-6% by weight; manganese sulfate, preferably manganese sulfate in an amount of 0.04-0.08% by weight; niacinamide, preferably niacinamide in an amount of 0.3-1% by weight; pantothenic acid, preferably pantothenic acid in an amount of 0.1-0.6% by weight; phytonadione, preferably phytonadione in an amount of 0.00% by weight; potassium iodide, preferably 0% by weight. potassium iodide in an amount of 0.03-0.1% by weight; pyridoxine HCl, preferably pyridoxine HCl in an amount of 0.03-0.1% by weight; riboflavin, preferably riboflavin in an amount of 0.02-0.1% by weight; sodium molybdate, preferably sodium molybdate in an amount of 0.00% by weight; sodium selenate, preferably sodium selenate in an amount of 0.00% by weight; spinach (leaf, powder), preferably spinach (leaf, powder) in an amount of 6-20% by weight; thiamine mononitrate, preferably 0.02-0.thiamine mononitrate in an amount of 1% by weight; tomato (fruit powder, sun-dried, granules), preferably tomato (fruit powder, sun-dried, granules) in an amount of 6-20% by weight; tricalcium phosphate, preferably tricalcium phosphate in an amount of 0.5-2% by weight; and zinc oxide, preferably zinc oxide in an amount of 0.2-0.8% by weight.

[0091] In one embodiment, each of the components of the fast mimicking meal package, and thus the fast mimicking meal, is substantially gluten-free (e.g., less than 20 ppm gluten in each component) or very low gluten (e.g., 20-100 ppm gluten in each component). In another embodiment, each of the components is provided in a serving size of 20-60 g. In another embodiment, the nut-containing nutritional bar is provided in a serving size of 30-60 g, the cocoa-containing nutritional bar is provided in a serving size of 15-40 g, the olive-containing composition (sea salt version) is provided in a serving size of 10-20 g, the olive-containing composition (garlic version) is provided in a serving size of 10-20 g, and the kale cracker composition is provided in a serving size of 30-60 g. In one further exemplary formulation, the kale cracker composition is provided in a serving size of 20-50 g, the vegetable soup composition is provided in a serving size of 20-50 g, the mushroom soup composition is provided in a serving size of 20-50 g, the tomato soup composition is provided in a serving size of 20-50 g, the bean minestrone soup composition is provided in a serving size of 20-50 g, the quinoa minestrone soup composition is provided in a serving size of 20-50 g, the pumpkin soup composition is provided in a serving size of 20-50 g, the first vegetable broth composition is provided in a serving size of 5-15, the second vegetable broth composition is provided in a serving size of 3-15, and the energy drink composition is provided in a serving size of 1-5 ounces.

[0092] Figures 7A-7H provide nutritional information for each meal component. It should be understood that the variation in these values ​​may vary by + / - 30 percent. In one alternative adjustment example, the meal components provided are in sufficient amounts to meet the caloric and nutritional requirements in these figures.

[0093] The table shown below provides the dosing schedules of the two FMD dietary plans administered to a subject. The Prolon® dietary plan (available from L-Nutra Inc.) is useful for weight loss, treating or preventing hypertension, metabolic disease, diabetes, etc. The Chemolieve® dietary plan (also available from L-Nutra Inc.) is useful for reducing the side effects of chemotherapy. Thus, the dietary packages described in this disclosure can include instructions providing schedules and instructions for administering FMD to treat various conditions described in the methods below.

[0094] Meal Schedule [Table 1]

[0095] In another embodiment, a method is provided for inducing differential effects on disease factors and markers associated with aging. The method includes identifying a subject in need of modification of disease factors and markers associated with aging. Expression of the factors and markers can be decreased or increased depending on which direction produces health benefits. The fasting mimicking diet provided by the diet package described above is administered to the subject for a predetermined period of time as described above. Examples of such disease factors and markers are insulin-like growth factor-1, blood glucose, systolic or diastolic blood pressure, insulin-like growth factor-1, blood glucose, systolic blood pressure, diastolic blood pressure, cholesterol, CRP, triglycerides, or abdominal / visceral fat.

[0096] In another embodiment, a method for promoting and inducing beneficial long-lasting effects on disease factors and markers associated with aging is provided. The method includes identifying a subject in need of modification of disease factors and markers associated with aging. Expression of the factors and markers can be decreased or increased depending on whether the direction of decrease or increase produces health benefits. The fasting mimicking diet provided by the diet package described above is administered to the subject for a predetermined period of time as described above. Examples of such disease factors and markers are insulin-like growth factor-1, blood glucose, systolic blood pressure, diastolic blood pressure, cholesterol, CRP, triglycerides, or abdominal / visceral fat.

[0097] In yet another embodiment, a method for promoting and inducing stem cell-based regeneration of multiple organs and systems is provided. The method includes identifying a subject in need of promoting and inducing stem cell-based regeneration of multiple organs and systems. The fasting mimicking diet provided by the dietary package described above is administered to the subject for a predetermined period of time as described above. Examples of stem cell-based regeneration of multiple organs and systems include, but are not limited to, promoting neurogenesis, hematopoiesis, or pancreatic beta cells.

[0098] In yet another embodiment, a method for promoting and inducing stem cell-based rejuvenation of multiple organs and systems is provided. The method includes identifying a subject in need of promoting and inducing stem cell-based rejuvenation of multiple organs and systems. A fasting mimicking diet provided by the dietary package described above is administered to the subject for a predetermined period of time as described above. Examples of stem cell-based regeneration of multiple organs and systems include, but are not limited to, promoting neurogenesis, hematopoiesis, or pancreatic β-cells.

[0099] The following examples illustrate various embodiments of the present invention. Those skilled in the art will recognize many variations that are within the spirit of the invention and scope of the claims.

[0100] We report the results of a randomized controlled trial of 100 subjects, 71 of whom completed three cycles of FMD either during the randomization phase (N=39) or after crossover from the control diet to the FMD group (N=32). We evaluated the effects of FMD on risk factors and markers for ageing, cancer, metabolic syndrome, and cardiovascular disease in generally healthy participants ranging from 20 to 70 years of age.

[0101] • Baseline data for all subjects.

[0102] From April 2013 to July 2015, 100 study participants were randomized and assigned to either arm 1 (N = 48) or arm 2 (N = 52). At enrollment, subjects in the two arms were comparable for age, sex, race, and weight, regardless of whether they completed the study (Figure 8, Table 1). Hispanics (27%) were underrepresented in the study population compared to their proportion of Hispanics in the greater Los Angeles area (California, USA) (approximately 45%) (49). Participants in control arm 1 were asked to continue their usual diet for 3 months, while participants in arm 2 began the FMD intervention. Two participants discontinued from arm 1 due to schedule conflicts before completing informed consent. In the randomized comparison (Figure 1B), 18 participants, or 5 of 48 (10%) in the control arm and 13 of 52 (25%) in the FMD arm, were withdrawn or discontinued from the study. Of the 48 subjects enrolled in the control arm, 2 withdrew due to schedule conflicts, 2 due to unspecified personal issues, and 1 for unknown reasons. Of the 52 subjects enrolled in the FMD arm, 6 withdrew due to schedule conflicts, 5 due to unspecified personal issues, and 2 participants were removed from the study due to noncompliance with the FMD protocol.

[0103] Adverse Effects and Safety

[0104] According to the Common Terminology Criteria for Adverse Events (CTCAE, v4.0), 54%–100% of participants (depending on the adverse event) reported no adverse effects during the FMD cycles (Figure 4). The most common self-reported grade 1 (mild) or grade 2 (moderate) symptoms experienced by participants were fatigue, weakness, and headache. No adverse effects of grade 3 or higher were reported. A comprehensive metabolic panel that measured metabolic markers and changes in liver and kidney function did not show any negative effects of the three cycles of FMD (Figure 12, Table 5). In summary, after three cycles of FMD, subjects reported only some mild side effects and almost no moderate side effects.

[0105] • Baseline risk factors and metabolic markers: Comparison of randomized controls and FMD subjects who completed the study.

[0106] At baseline, there were no significant differences in metabolic markers or risk factors for aging-related diseases and conditions, including weight (p=0.39), BMI (p=0.24), total body fat (p=0.11), truncal fat (p=0.087), lean body mass (p=0.15), waist circumference (p=0.34), fasting glucose (p=0.55), IGF-1 (p=0.51), systolic and diastolic blood pressure (p=0.60 and p=0.91, respectively), triglycerides (p=0.21), and C-reactive protein (p=0.28) between subjects who successfully completed the randomized study in arm 1 (normal diet) and arm 2 (FMD). The notable exception was that total cholesterol (p=0.014) and low density lipoprotein (p=0.024), but not high density lipoprotein (p=0.99), were significantly lower at baseline for subjects who enrolled and completed arm 2 (Figure 9, Table 2). In summary, baseline disease marker and risk factor values ​​were comparable between the control diet and FMD groups, with the exception of total cholesterol and LDL cholesterol.

[0107] ●Changes in risk factors and metabolic markers: Comparison between randomized control group and FMD group.

[0108] Next, we evaluated the effect of FMD by assessing the changes in marker / risk factor values ​​between baseline and 5-7 days after the end of the third cycle of FMD and compared them to those occurring in the control arm within the same 3-month period (Figure 2 and Tables 2 (Figure 9) and 6 (Figure 13)). Participants in the FMD arm (arm 2) lost an average of 2.6 ± 2.5 kg (± SD) (p < 0.0001), which was accompanied by a decrease in total body fat (absolute and relative % of total mass) and truncal fat (absolute) (Tables 2 (Figure 9), Table 6 (Figure 13)). Subjects on the control diet did not lose weight (0.1 ± 2.1 kg). Controlling the false discovery rate at 0.05 between the control and FMD groups, absolute lean body mass was decreased in arm 2 (p=0.004), but no change in the percentage of lean body mass was observed (relative to total mass; p=0.07) (Table 2 (Figure 9), Table 6 (Figure 13)). Waist circumference measured after three FMD cycles was reduced by 4.1±5.2 cm (p=0.0035 between groups). FMD cycles also led to a reduction in IGF-1 concentration of 21.7±46.2 ng / mL (p=0.0017 between groups). Systolic blood pressure was reduced by 4.5±6.0 mmHg (p=0.023 between groups) and diastolic blood pressure was reduced by 3.1±4.7 mmHg (p=0.053 between groups). Fasting glucose (p=0.27), triglycerides (p=0.27), cholesterol (p=0.81 for total; p=0.50 for LDL; p=0.90 for HDL) and the acute phase inflammatory marker C-reactive protein (CRP; p=0.27) were not significantly different between groups. A graphical summary of these data is shown in Figure 2. In conclusion, three cycles of FMD reduced body weight, truncal and total body fat, blood pressure and IGF-1 compared to a standard diet.

[0109] Changes in risk factors and metabolic markers for aging-related diseases and conditions: Comparison of observations before and after FMD

[0110] After 3 months, 43 subjects from the control arm were crossed over to the FMD intervention. Eleven of these subjects (26%) discontinued before completing three FMD cycles (Figure 1B). Five of these participants discontinued due to scheduling issues, and two subjects chose to withdraw from the study for unspecified personal reasons. We also excluded four participants based on nonadherence to the FMD protocol. Causes for discontinuation / exclusion were comparable between arms. Considering both FMD treatment arms, 24 of 95 participants (25%) were removed from the study or discontinued before the completion of 3 FMD cycles (N=13 FMD in arm 2; N=11 in arm 1 FMD post-crossover) due to schedule conflicts (N=11 total; N=6 FMD in arm 2; N=5 in arm 1 FMD post-crossover), personal problems (N=7 total; N=5 FMD in arm 2; N=2 in arm 1 FMD post-crossover), or diet aversion and / or non-adherence to the dietary protocol (N=6 total; N=2 FMD in arm 2; N=4 in arm 1 FMD post-crossover) (Figure 1B).

[0111] The 25% dropout rate in participants during FMD is higher than the 10% dropout rate observed during the control diet in arm 1, but this is expected considering that subjects in the control diet group were allowed to continue their diet and only dropped out due to schedule conflicts. Ninety-five subjects (95%) completed one cycle of FMD and 71 (71%) completed three cycles of FMD. Compared to the 71 participants who completed three FMD cycles in arms 1 and 2, the 24 subjects who dropped out did not differ in age (42.5±11.6 vs. 43.3±13.1 years) or BMI (27.1±4.9 vs. 26.9±4.7), but were mostly female (18% male vs. 82% female, p=0.0045 by Fisher's exact test) (Figure 5).

[0112] Because differential dropout rates during FMD treatment (25% in FMD randomized arm 2 and / or arm 1 (after crossover) vs. 10% in randomized arm 1 (control)) could have biased the estimates of FMD treatment effect, we used sensitivity analyses to compare changes in study outcomes between the two groups that completed three FMD cycles (N=39 for FMD randomized arm 2, N=32 for arm 1 after crossover to FMD). Three FMD cycles had comparable effects between subjects in arm 1 (after crossover) and arm 2 (randomized) except for HDL, which underwent a greater decrease in arm 2 (p=0.03) and the decrease in absolute lean body mass, which was observed in arm 2 but not in arm 1 (Table 6 (Figure 13)).

[0113] Since FMD had similar effects in both arms, we combined the results from the two arms to evaluate changes in metabolites and risk factors during the first FMD cycle (day 5 of FMD and before refeeding, Table 7 (Figure 14)) and after completion of the third FMD cycle (5-7 days after finishing the third FMD cycle, Table 6 (Figure 13)).

[0114] At the end of the first FMD cycle and before resuming normal diet, weight (p<0.0001), BMI (p<0.0001), absolute lean body mass (p<0.0001), waist circumference (p<0.0001), fasting glucose (p<0.0001), IGF-1 (p<0.0001), diastolic blood pressure (p<0.0003), triglycerides (p<0.0001), and LDL (p<0.0026) were significantly decreased compared to baseline. In contrast, relative lean body mass (p=0.02), β-hydroxybutyrate (p<0.0001), and IGFBP-1 (p<0.0001) were increased. Both absolute and relative total body fat (p=0.075 and p=0.047, respectively), systolic blood pressure (p=0.076), and CRP (p=0.75) were not significantly changed after completion of the first FMD cycle compared to baseline (Table 7 (FIG. 14)). These results confirm that subjects followed and responded to the dietary changes imposed by FMD as expected.

[0115] In subjects who completed three FMD cycles (both FMD arms combined) and returned to normal diet for 5-7 days, there were no significant changes in body weight (p<0.0001, N=71), BMI (p<0.0001, N=71), total body fat (absolute and relative p<0.0001, N=70), truncal fat (p<0.001 for absolute and p=0.0002 for relative, N=70), and absolute lean body mass (p=0.0001, N=70). There were significant decreases in systolic and diastolic blood pressure (p<0.0001 and p<0.0004, respectively, N=70), waist circumference (p=0.0001, N=52), IGF-1 (p<0.0001, N=69), systolic and diastolic blood pressure (p<0.0001 and p<0.0004, respectively, N=70), total cholesterol (p=0.004, N=55), LDL (p<0.0011, N=55), and HDL (p=0.02, N=55), and increases in relative lean body mass (p=0.0002, N=70). Fasting glucose (p=0.28, N=66), β-hydroxybutyrate (p=0.23, N=69), IGFBP-1 (p=0.84, N=69), triglycerides (p=0.16, N=55) and CRP (p=0.052, N=69) were not significantly changed 5-7 days after the third FMD cycle compared to baseline (Table 6 (Figure 13)). In summary, the combined FMD groups from arms 1 and 2 confirmed that the FMD cycle promoted robust effects on many metabolic markers and disease risk factors that were maintained after subjects returned to their normal diet.

[0116] ●FMD effect stratified by baseline risk factor values: Comparison before and after FMD with post hoc observations.

[0117] Before disease can be diagnosed, physiological changes associated with aging occur that result in increased risk factors (26, 27). We utilized the aggregated FMD data from both study arms and performed a post-hoc analysis of FMD effects on risk factors for cardiovascular disease and metabolic syndrome, defined as 3 of the following 5 conditions: abdominal obesity, elevated fasting glucose, elevated blood pressure, high serum triglycerides, and low HDL cholesterol (8). We selected clinically valid cut-offs to compare normal and at-risk subjects for each risk factor: total cholesterol >199 mg / dL and LDL cholesterol levels >130 mg / dL are associated with increased risk of cardiovascular disease (CVD) (28), fasting glucose >99 mg / dL indicates impaired fasting glucose / prediabetes (29), and triglyceride levels >100 mg / dL (30) as well as CRP >1 mg / L are associated with increased risk of CVD (31). Although no clinically meaningful risk level has been established for serum IGF-1, several epidemiological studies have associated IGF-1 levels above 200 ng / ml with various cancers (24, 32). Therefore, we compared the effect of FMD cycles on subjects in the highest quartile of IGF-1 expression (>225 ng / ml) with the effect on subjects with IGF-1 levels ≤225 ng / ml.

[0118] In post-hoc analyses, we examined how changes in normal and at-risk subgroups of FMD compared with changes in those on the control diet, defined by their baseline levels of various risk factors (Table 3). A significant benefit of FMD on BMI was seen in all BMI subgroups, but not on the control diet (p-value for interaction=0.03), and FMD was particularly beneficial in subjects who were obese (BMI>30) at baseline. The FMD-dependent reduction in IGF-1 was also significantly greater in those with baseline IGF-1 ≥ 225 ng / mL (p-value for interaction=0.018), although no similar events were observed in the two control diet groups.

[0119] Next, we evaluated the effect size, i.e., efficacy in normal and at-risk subjects in subjects stratified by risk factors (Table 4). Subjects with a BMI over 30 (obese) showed a greater reduction in BMI by the end of three FMD cycles than subjects with a BMI below 25 (between-group p=0.011) and than subjects with a BMI between 25 and 30 (between-group p=0.0011). Systolic blood pressure was reduced by 2.4±6.3 mmHg in subjects with a baseline systolic blood pressure ≦120, but by 6.7±6.9 mmHg in subjects with a systolic blood pressure >120 (between-group p=0.013), and diastolic blood pressure was reduced by 1.5±5.1 mmHg in subjects with a diastolic blood pressure ≦80, but by 5.5±6.4 mmHg in subjects with a baseline level above 80 (between-group p=0.01). Fasting glucose did not change from baseline levels in participants with baseline levels ≤ 99 mg / dl, but decreased by 11.8 ± 6.9 mg / dL in participants with baseline fasting glucose > 99 mg / dl (between groups p < 0.0001); notably, this decrease resulted in glucose within the healthy range in these subjects. IGF-1 levels decreased by 55.1 ± 45.6 ng / mL in subjects with baseline levels > 225 ng / mL, which was nearly four times greater than the decrease of 14.1 ± 39.9 ng / mL observed in participants with IGF-1 concentrations < 225 ng / mL (between groups p < 0.001). Triglyceride levels decreased more in participants with baseline levels > 100 mg / dL (between groups p = 0.0035).

[0120] Total cholesterol was significantly more reduced in participants with total cholesterol above 199 mg / dL at baseline (between groups p=0.015). LDL was reduced by 14.9±21.7 mg / dL in participants with total cholesterol baseline levels above 199 mg / dL, but was not reduced by the FMD cycle in subjects in the normal range (between groups p=0.013). There was no reduction in HDL levels in study participants with HDL levels below or above 50 mg / dlm at baseline (between groups p=0.094). CRP was not reduced in subjects with levels below 1 mg / L, but most subjects with baseline CRP levels above 1 mg / L reduced by 1.6±1.3 mg / L, returning to normal levels (between groups p=0.0003). A graphical summary of these data is shown in FIG. 3; before and after dot plots of individual subjects in the control cohort and normal and at-risk subjects in the FMD cohort are shown in FIG. 6.

[0121] This post-hoc analysis shows that FMD had a more pronounced effect in participants at risk than in subjects with risk factor values ​​within the normal range, except for HDL. Larger randomized trials are needed to confirm the results regarding the effectiveness of FMD in treating patients at risk for disease.

[0122] Spontaneous follow-up after 3 months of FMD

[0123] We invited participants to return, on a voluntary basis, approximately 3 months after their third and final FMD cycle (mean actual follow-up time, 3.2±1.3 months; N=50). In these subjects, the effects of FMD on weight, BMI, waist circumference, glucose (in at-risk subjects), IGF-1, systolic (in at-risk subjects), and diastolic blood pressure persisted for at least 3 months after the final FMD cycle (Table 8 (FIG. 15)). Subjects with low HDL levels at baseline showed increased HDL levels at 3-month follow-up, whereas CRP levels remained significantly lower in study participants with baseline CRP levels above 1 mg / L. Of note, some of the at-risk groups included only small numbers of subjects, and therefore larger studies are needed to establish the long-term effects of FMD on disease risk factors.

[0124] These results indicate that some of the beneficial effects of multiple cycles of FMD may persist for several months. Although subjects were not advised to change their nutritional or exercise regimens after the FMD cycle was completed, it cannot be excluded that some of the changes after the additional 3 months may be the result of lifestyle modifications such as a healthier diet and / or improved physical activity after completion of the study.

[0125] ●Consideration

[0126] This randomized Phase 2 study shows that three cycles of 5-day / month FMD is feasible, safe, and effective in reducing body weight, waist circumference and BMI, absolute total and truncal fat mass, systolic blood pressure, and IGF-1. Metabolic markers such as fasting glucose, triglycerides, CRP, and total, HDL, and LDL cholesterol that were within the normal range at baseline were not significantly affected in the randomized comparison after three FMD cycles. After three months, subjects from the control arm were crossed over to the FMD intervention. Our post-hoc analysis of aggregate data from all 71 subjects who completed three FMD cycles confirmed the effect of FMD on truncal and total body fat, blood pressure, and IGF-1. The post-hoc analysis also allowed us to analyze subjects with elevated risk factors or metabolic markers associated with metabolic syndrome and aging-related diseases, such as high BMI, blood pressure, fasting glucose, triglycerides, CRP, cholesterol, and IGF-1. FMD had a more pronounced effect on all of these markers in at-risk participants than in subjects with risk factor values ​​within the normal range, except for HDL. Some of these metabolic markers, namely CRP, systolic / diastolic blood pressure, and serum lipids, have been proposed as markers of biological aging (33). However, other markers affected by FMD, including IGF-1 and glucose, have been strongly implicated in aging and aging-related diseases (12, 25, 34).

[0127] Study participants were instructed not to change their lifestyle habits during the study and were allowed to consume foods of their choice during the normal diet period; i.e., subjects were not placed on a pre-specified or calorie-restricted diet. There were no changes in weight, BMI, body fat, or lean mass, but there were both positive (total cholesterol and LDL) and negative (HDL) changes in arm 1 subjects during the control diet period; this may be explained by changes in dietary habits in preparation for FMD. Similarly, the sustained effects of FMD we observed 3 months after study completion may be due to changes in dietary habits and / or physical activity. The composition of the diets tested in this study was based on FMD, which is known to extend healthy lifespan in mice. As with studies in mice (12), we expect the FMD effects to be largely independent of overall calorie restriction, since both groups likely consumed similar levels of calories / month. For example, estimating a 2000 kcal diet for each of the 25-26 non-restricted days and approximately 4000 kcal for the 5-day FMD per month, the between-group difference in calorie intake is expected to be approximately 10%. Furthermore, this difference may be overestimated because, as we have shown for mice (12), subjects are likely to have elevated calorie intake after the FMD period. Fat and complex carbohydrates are the major sources of calories in the FMD, since day 1 of the FMD provides approximately 4600 kJ (11% protein, 46% fat, 43% carbohydrate), whereas days 2-5 provide approximately 3000 kJ per day (9% protein, 44% fat, 47% carbohydrate).

[0128] Our studies in cells and mice indicate that both glucose and protein interfere with the protective and regenerative effects of fasting (35). Because our previous data indicate that dietary composition may be as important as or even more important than caloric restriction, it will be important to test the effects of similarly restricted diets providing higher proportions of carbohydrate and / or protein. It remains to be established whether some of the effects of FMD we observed are mediated by stem cell-based regeneration or rejuvenation, as indicated by our mouse studies (12).

[0129] The reduction in serum glucose and IGF-1 induced by FMD is intriguing given their role in pro-senescence signaling pathways and cancer (24, 36-39). In addition to being a marker of insulin resistance and a metabolic input to cancer cells, glucose has been linked to cellular sensitization to toxins and senescence (34, 40, 41). Growth hormone receptor deficiency, which results in reduced IGF-1 levels, is associated with a greater reduction in pro-senescence signaling, cancer, and diabetes in humans (25). The reduction in IGF-1 observed in our study, but not after 6 months of intermittent energy restriction (IER) (42) or 6 years of 20% caloric restriction (CR) (43), is likely related to the long-lasting effect of the lower protein / amino acid content of FMD (on average, 11.5% with 5-day FMD vs. 21% with IER or 24% with long-term CR). Indeed, 28 vegans who consumed a moderately protein-restricted diet (10%) for approximately 5 years had decreased IGF-1 levels compared to a group who consumed a chronically 20% calorie-restricted diet (43). We also previously showed that IGF-1 levels were positively associated with protein intake in 2,253 participants of the NHANES cohort (24). Certain components, such as high levels of unsaturated fats and micronutrients, may also positively contribute to some of the beneficial effects of FMD.

[0130] It is noteworthy that 25% of subjects who tested FMD dropped out of the study, whereas 10% of participants opted out of the control arm. This indicates that despite our efforts to reduce the burden of the low-calorie / protein diet, adherence to this dietary regimen requires committed study participants. Furthermore, compared to the control diet arm, the FMD arm additionally required a full-day visit to the clinic, which may have contributed to reduced compliance. Compliance with the prescribed treatment regimen, even placebo, may be an identifiable marker of the overall health behavior of study participants (44). Thus, this type of volunteer would not drop out due to a perceived benefit, which could introduce potential bias into the analysis of our study. The overall comparability at baseline between the control and both FMD arms, as well as the comparable response to FMD (arm 2 and arm 1 after crossover), suggests that there is no significant difference in response for subjects who completed the study. Furthermore, subjects who dropped out of the study did not differ in age or BMI compared to subjects who completed the study.

[0131] Why there was a gender difference (82% of dropouts were female) remains to be established. The overall dropout rate of 25% (all causes) of study participants before completing the third FMD cycle is within the range observed in other studies aimed at evaluating dietary interventions in adults. For example, 16 weeks of dieting combined with physical exercise resulted in a discontinuation rate of approximately 30% (45), and a hypocaloric diet in 28 overweight / obese women resulted in a dropout rate of 40% after 6 months (46). In a study evaluating the effects of intermittent energy / carbohydrate restriction and daily energy restriction on weight loss and metabolic disease risk markers in overweight women, Harvie et al. reported a dropout rate of 23% (47). Nevertheless, our study has limitations that should be considered: 1) the relatively small number of subjects in the randomized comparison; 2) despite providing nutrients and calories during the FMD period, we experienced a higher dropout rate during the FMD intervention than in the control arm; and 3) the finding that FMD more effectively reduced metabolic markers in at-risk subjects is based on a non-randomized post-hoc analysis of individual factors in largely healthy participants and therefore requires further evaluation in subjects with diagnosed disease.

[0132] Other less restrictive diets, such as those requiring very low calorie intake twice a week, impose severe restrictions for 8 days per month compared to 5 days per month or months in the less restrictive intervention tested here (47). However, the advantage of these diets is that they may not require as much medical supervision as longer FMDs. FMDs or any type of long-term fasting intervention lasting more than 12 hours, especially those lasting for several days, require supervision, preferably from a medical professional familiar with long-term fasting. Our results suggest that cycling a plant-based FMD may be safe for older adults, but further studies are needed to determine its safety in subjects 70 years of age or older.

[0133] Taken together, despite the limitations outlined above, these results indicate that periodic FMD cycles are effective in improving the levels of a range of metabolic markers / risk factors associated with poor health and aging, as well as multiple aging-related diseases. As suggested by preclinical studies, interventions that promote longevity should also increase healthspan. Further investigation is needed in larger clinical trials focusing on subjects diagnosed with metabolic syndrome, diabetes, and cardiovascular disease, as well as subjects at high risk of developing cancer and other aging-related diseases.

[0134] ●Method

[0135] ● Target

[0136] One hundred participants with no medical conditions diagnosed within the past 6 months were enrolled (clinicaltrials.gov NCT02158897). All participants provided written informed consent, and the University of Southern California Institutional Review Board (IRB) approved the protocol. Subject recruitment was based on flyers, the clinicaltrials.gov and usc.com websites, and / or word of mouth. Because this was a dietary intervention trial, it was not possible to blind participants or all investigators to group assignment. However, investigators involved in data collection and sample analysis were blinded to group assignment.

[0137] ● Test design

[0138] Participant enrollment and participation flow were arranged according to the Consort criteria for randomized clinical trials with a crossover design. All data were collected at the University of Southern California Diabetes and Obesity Institute. Subjects were recruited from April 2013 to July 2015 under a protocol approved by the USC IRB (HS-12-00391), based on established inclusion (generally healthy adult volunteers, age 18-70 years, body mass index: 18.5 or greater) and exclusion (any major medical or chronic illness, psychiatric illness, drug dependence, hormone replacement therapy (DHEA, estrogen, thyroid, testosterone), pregnant or lactating women, special dietary requirements or food allergies, alcoholism, medications known to affect body weight) criteria. Intention-to-treat analysis was performed by including all available observations.

[0139] Eligible participants were randomly assigned to either arm 1 or arm 2 of the study using a random number generator. All participants completed a health habits questionnaire. Pre-specified outcome measures included safety and feasibility, as well as assessment of changes in metabolic risk factors for diabetes and cardiovascular disease and metabolic markers associated with age-related disease and mortality; these outcomes were measured at baseline, during the intervention, and after completion of the intervention. Laboratory tests included height, weight, body composition measured by dual-energy X-ray absorptiometry (DEXA) (including total and truncal body fat, lean soft tissue, and bone mineral content), oscillometric blood pressure measurements, and overnight fasting blood sampling by venipuncture.

[0140] Arm 1 (control): Participants completed physical measurements and blood draws at enrollment and after 3 months to provide estimates of non-diet-related changes (Figure 1). Participants were instructed to maintain their usual eating habits. After 3 months, subjects were crossed over to the experimental fasting-mimicking diet (FMD) group (Figure 1).

[0141] Arm 2 (fasting mimicking diet): Participants were instructed to consume the FMD provided in a box for 5 consecutive days and, upon completion, to return to their normal diet until the next cycle, which began approximately 25 days later. Participants completed 3 cycles of this 5-day FMD (Figure 1). Participants completed baseline and follow-up examinations at the end of the first FMD (but before resuming normal diet to measure acute FMD effects) and after a washout period of 5-7 days of normal caloric intake following the third FMD cycle. An optional follow-up assessment was provided 3 months after the third FMD cycle.

[0142] Experimental Fasting Mimicking Diet

[0143] The fasting mimicking diet is a plant-based diet designed to achieve fasting-like effects on serum levels of IGF-1, IGFBP1, glucose and ketone bodies while providing both macro- and micronutrients to minimize the load and adverse effects of fasting (12). Day 1 of the FMD provides approximately 4600 kJ per day (11% protein, 46% fat, 43% carbohydrate), and days 2-5 provide approximately 3000 kJ (9% protein, 44% fat, 47% carbohydrate). The FMD includes a proprietary formula of vegetable-based soups, energy bars, energy drinks, chip snacks, tea, and supplements that provide high levels of minerals, vitamins and essential fatty acids (Figure 7). All items consumed per day were individually boxed to allow subjects to choose when to eat while avoiding accidentally ingesting the next day's components.

[0144] Common Terminology Criteria for Adverse Events

[0145] Study participants were asked about adverse events at each study visit, and events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) guidelines (see Supplementary Material for details).

[0146] ●Blood tests and serum markers

[0147] A complete metabolic and lipid panel (overnight fast) was completed in the clinical laboratory at the Keck Medical Center of the University of Southern California (USC) and analyzed immediately after blood draw at each visit (see Supplementary Material for details).

[0148] ●Statistical analysis

[0149] Primary comparisons of randomized groups included changes in outcomes observed in the control period in arm 1 versus changes observed in the FMD group (arm 2) after completion of three FMD cycles. Secondary observational analyses included (1) comparing FMD effects in arm 2 (randomized to FMD) versus arm 1 (received FMD after completion of the randomized control period) and (2) pooling changes for arms 1 and 2 combined after completion of the first and third FMD cycles. Changes from baseline were normally distributed. Comparisons of changes from baseline within treatment arms were performed using paired two-tailed Student's t-tests, with p-values ​​<0.05 considered significant. Between-arm comparisons of changes from baseline by treatment were performed using two-tailed two-sample equal variance t-tests, with p-values ​​<0.05 considered significant. The Benjamini-Hochberg false discovery rate (FDR) method was used to control for multiple testing. All reported p-values ​​are nominal two-sided p-values; those that met the FDR criterion and remained "significant" at p<0.05 are marked with an asterisk.

[0150] One of the researchers involved in the study generated the random allocation sequence, enrolled participants, and assigned them to the intervention; however, this researcher was not involved in outcome assessment. For this first randomized trial, the sample size of 100 subjects in total was based on detecting a 25% decrease in mean IGF-1, with a two-sided alpha of 0.05 and a power of 70%. An estimated control group mean (SD) IGF-1 of 194 (97) was used using published data on men and women aged 26–40 years (48). Statistical analyses were performed on de-identified data. Baseline information and change from baseline were summarized using the mean ± standard deviation for subjects randomized to control (arm 1, N = 48) and dietary groups (arm 2, N = 52). All subjects were included in the assigned arm regardless of treatment adherence (intention to treat), and no attempt was made to impute missing values ​​(mainly because other measurement time points were not usually available when data after completion of the third FMD cycle were not available).

[0151] In post hoc subgroup analyses, we compared FMD-control differences across the randomized study period (3 FMD cycles vs. control) within high / low risk subgroups to test whether the treatment effects differed in high vs. low risk groups. This subgroup analysis was completed using ANOVA with main effects of treatment (FMD, control) and risk group (high, low), and tested for treatment by risk group interactions if the randomized FMD effects differed in high vs. low risk groups. In observational analyses of pre-post FMD changes pooled across the two treatment arms, pre-post changes of markers within risk subgroups were tested using paired t-tests, and pre-post changes between risk subgroups were compared using two-sample t-tests or ANOVA.

[0152] With continuing reference to the materials, data, and figures discussed above, attention is now also drawn to Figures 16-29, which depict further new testing and analyses conducted using further variations and modifications of the dietary packages and methods of use discussed above. These new testing and analyses are directed to single or day fasting dietary packages and methods of use, and also contemplate the use of such FMD packages and methods for fasting having other durations and intermittent fasting uses.

[0153] As contemplated in this disclosure, the FMD molecular and / or cellular fasting products and methods are enabled by a precisely designed nutrient profile designed to sustain the body during fasting and specifically prevent loss of lean muscle and bone mass over fasting periods that may span hours, a day, a week, and other time periods. For example, periodic and intermittent fasting can be achieved with the FMD packages disclosed in this disclosure during one-day fasts (plural), where a subject fasts for one day and then resumes normal eating the next day.

[0154] Such intermittent fasting can utilize the disclosed FMD package for a "5-2" fast, where subjects eat normally for five days and then fast for two days using the novel FMD package of the present disclosure (51). One variation involves using the new FMD package during a single fast, alternating with eating normally on day one, followed by fasting on day two, and this is repeated for subsequent days or days as may be desired or appropriate. In one variation, the described FMD package is used during a one-day intermittent fast, where feeding occurs within a short time window and fasting over a longer period is achieved. These include, for example, 2-22, 4-20, 6-18, 8-16, 10-14, and other split period intermittent fasting, where a subject utilizes the FMD packages disclosed herein to eat normally during a first short time window and fast for a second time window that is of longer duration than the first (50, 51, 52).

[0155] Here, as a non-limiting example, a subject engages in "8-16" intermittent fasting, utilizing the envisioned FMD package, eating normally for a first short 8 hour window, and fasting for a second 16 hour window located before or after this, occurring over the course of a day. Similar approaches utilize the 1 day fasting FMD packages disclosed in this disclosure for shorter 2, 4, 6, 10, and other feeding periods, and longer 22, 20, 18, 14, and other fasting periods (50, 51, 52).

[0156] The novel molecular cellular fasting FMD products of the present disclosure allow subjects to benefit from daily fasting and / or intermittent fasting achieved during a 24-hour period. FMDs incorporating such precisely designed products with the predetermined nutritional profiles disclosed in the present disclosure allow for time-restricted and / or intermittent fasting within a 24-hour period, as well as time-restricted and / or intermittent fasting between fasts occurring over hourly, daily, weekly and other time periods (50, 51, 52).

[0157] Such a precisely engineered FMD feeding profile of carbohydrates, proteins, fats, and nutrients is precisely tuned to predetermined ratios and levels. These ratios and levels, detailed elsewhere in this disclosure, are designed to be below the detection threshold of intracellular nutrient sensors. This causes the subject's cells to enter a true fasting state nearly identical to when exposed to a water-only behavioral fast. The precise formulation of specific ratios and levels of carbohydrates, proteins, fats, and nutrients provided by the FMD and by the FMD portions and packaging establishes a precisely engineered food component that allows for sustainable molecular and / or cellular fasting without adverse consequences.

[0158] These tests and analyses have revealed unexpected beneficial effects similar to those already described elsewhere in this disclosure, even though the product and method are limited to a single or one-day fasting protocol.For example, one such test includes eight participants, all of whom have no medical conditions diagnosed in the past six months, who are informally invited to participate in the controlled feeding of a one-day fasting diet package.The assumed one-day fasting diet package is depicted diagrammatically in Figure 16.

[0159] An exemplary one-day fasting diet package 200 (FIG. 16) includes multiple components and / or compositions that may be grouped into meal portions, such as meal portions 205, 210, and / or 215 or the like, which may be consumed together at one time or in meal portions spaced apart over time during the day, for example and without limitation. Such meal portions may be grouped as breakfast meal portion 205, lunch meal portion 210, and / or dinner meal portion 215 for separate consumption during the expected fasting period of the day.

[0160] In further arrangements, meal portions 205, 210, and 215 may incorporate separate, sub-packaged meal items or components or components. For example, meal portion 205, which in one example may be a breakfast meal portion, further includes other possible items such as a nut-containing nutritional bar composition 220, a micronutrient vegetable powder composition incorporating a vitamin and mineral supplement 225 (also referred to in this disclosure as an "NR-1" supplement), an algae oil composition 230, and tea or other components 235 and 240. These examples also relate to meal portion 210 including many additional, and potentially preferred, items such as a first soup composition 245, a kale cracker composition 250, and an olive composition or tea or other components 255, 260, and 265.

[0161] In another exemplary arrangement of a one-day FMD package, meal portion 215, which may be a dinner meal portion, includes a second soup composition 270, one of a kale cracker composition 275 and / or an olive-containing composition 280, a second nut-containing nutritional bar composition 285, and tea and other predeterminable items or components 290.

[0162] 17-26 further illustrate many different and interchangeable components and / or compositions that may be utilized in a contemplated one-day fasting diet package and may be grouped into meal portions as further described below.

[0163] ● 1-day fasting FMD test design

[0164] Participant enrollment and participation for this 1-day fasting diet package study was informally arranged for initial analysis. Subjects were recruited and enrolled during November 2021 using an informal protocol based on the inclusion of 4 men and 4 women who were generally known to be healthy, aged 31-56 years, and generally free of any major medical or chronic illness, psychiatric illness, drug dependency, hormone replacement therapy (DHEA, estrogen, thyroid, testosterone), pregnant or breastfeeding women, special dietary requirements or food allergies, alcoholism, or taking medications known to affect weight.

[0165] The pre-specified outcome measures during the one-day fast and intake of the dietary package composition under study included only blood glucose and ketone testing. The testing was done using a consumer test device including the Precision Xtra® Blood Glucose & Ketone Monitoring System available from Abbott Corporation, https: / / abbott.com, under SKU or product number 9881465. Each glucose and ketone test utilized the device and corresponding blood ketone and glucose test strips that are compatible for use with the Precision Xtra® System. Five test data points were recorded for each participant over the 24-hour one-day fasting test period. The recorded test data is depicted in FIG. 27, which is described in more detail below.

[0166] Informal screening of each participant included the participant's height, weight, and body composition or body mass index (BMI), calculated using the participant's height and weight and methods published by the Centers for Disease Control and Prevention, where BMI is equal to the participant's weight in pounds divided by the square of the participant's height in inches multiplied by 703. BMI calculations were performed using the average weight of each participant. Figure 27 represents the average calculated from participants' weight measurements taken before starting the 1-day fast (Day 1), at the completion of the 1-day or 24-hour fast (Day 2), and the following day (Day 3).

[0167] Participants were instructed to consume the 1-day fasting FMD meal portion at a predetermined time and to consume no other food during the 24-h period of the 1-day fast. The 1-day fasting FMD package was provided in meal portions that grouped the FMD package components into three meal portions, one each for breakfast, lunch, and dinner.

[0168] As in Figures 27, 28, and 29, prior to consuming each of the meal portions, participants each completed five measurements of blood glucose and ketones during the day of fasting and use of the FMD package.

[0169] Experimental 1-day fasting mimicking diet

[0170] Similar to the previously described formulations, the 1-day FMD is a plant-based diet designed to achieve, among other benefits, a fasting-like effect on serum levels of IGF-1, IGFBP1, glucose, and ketone bodies while providing both macronutrients and micronutrients to minimize the burden and discomfort, and possible adverse effects, of fasting. (12) The composition of the package is portioned as described in this disclosure and in the accompanying figures to achieve a fasting-like effect on serum levels of IGF-1, IGFBL1, glucose, and ketone bodies without starvation of the subject while providing both macronutrients and micronutrients to minimize the burden and adverse effects of fasting.

[0171] The daily FMD package includes a unique blend of vegetable-based soups, energy bars, energy drinks, chip snacks, teas, and supplements providing high levels of minerals, vitamins, and essential fatty acids, and these items or components are described in Figures 17A-17G, 18, 19, 20, 21A-21I, and 22-26. During the one-day fast, all items consumed per day were individually apportioned and packaged according to the depictions in these noted figures, and grouped into meal portions for breakfast, lunch, and dinner, respectively, as described in one exemplary arrangement depicted in Figure 16 and shown in "Daily FMD Meal Schedule" Tables A and B below.

[0172] These tables represent two exemplary arrangements that may be selected from an infinite number of possible possible meal schedules. Those skilled in the art will understand that these schedules may be adapted using any of the other equivalent components and components described in the referenced figures, any of which may replace each of those items in the exemplary schedule examples. Participants consumed each meal portion only after testing their blood glucose and ketone levels.

[0173] Table A: Daily FMD Meal Schedule [Table 2]

[0174] Table B: Daily FMD Meal Schedule [Table 3]

[0175] As shown in Figures 27, 28, and 29, from the one-day fasting study data, it was observed that blood ketone levels beneficially but unexpectedly increased in each participant, while blood glucose levels decreased. More specifically, it was observed that the average blood ketone levels of all participants increased from 0.2 mM to 0.5 mM over the 24-hour one-day fasting period, demonstrating a ketogenic effect. The average glucose levels of all participants decreased from about 85 mg / dL to as low as about 75 mg / dL, but returned to only about 78 mg / dL at the end of the 24-hour fast.

[0176] In certain exemplary arrangements of these one-day fasting examples, various arrangements of meal portions and their constituent parts are contemplated, as generally represented in Figure 16 and the previously described meal schedules A and B. For example, one arrangement of fasting mimicking meal package 200 includes breakfast 205, lunch 210, and dinner 215 meal portions for a one-day fast.

[0177] Exemplary breakfast meal portion 205 includes a first nut-containing nutrition bar composition 220 (see, e.g., any of the nut-containing nutrition bar compositions depicted in Figures 17A-17G), a micronutrient vegetable powder composition 225 including vitamin and mineral supplements (see, e.g., Figure 18), and an algae oil composition 230 (see, e.g., Figure 19). Exemplary lunch meal portion 210 includes a first soup composition 245 (see, e.g., one of the soup compositions depicted in Figures 21A-21I) and a kale cracker composition 250 (see, e.g., Figure 20). Exemplary dinner meal portion 215 includes a second soup composition 270 (see, e.g., any of the soup compositions described in Figures 17A-17G), a kale cracker composition 275 (see, e.g., Figure 20), or an olive-containing composition 280 (see, e.g., one of the olive-containing compositions in Figures 22 and 23), and a second nut-containing nutritional bar composition 285 (again, see, e.g., one of the nut-containing nutritional bar compositions in Figures 17A-17G).

[0178] The modified FMD package 200 (FIG. 16) also includes tea compositions (see, e.g., FIG. 24), each including at least one of lemon, hibiscus, and spearmint tea, and combinations thereof and others, which may be consumed at any time during the 24 hour period of the day fast. In one variation, tea compositions such as the tea composition of FIG. 24 may be consumed as breakfast items 235, 240, lunch items 255, 260, and 265, and dinner item 290. In one other arrangement, an energy drink may be consumed as a different breakfast component 235, 240, lunch items 255-265, or dinner component 290.

[0179] Further formulation examples include a first nut-containing nutrition bar 220 containing almond, macadamia, and pecan (FIGS. 17A and 17C-17G) with a predetermined nutritional profile of fat, carbohydrate, and protein, and / or an algal oil composition (FIG. 19) with a nutritional profile including DHA omega-3 fatty acid and optionally an algal oil of at least one of Aurantiochytrium and Schizocatrium. In one other application, the FMD diet package 200 incorporates a second nut-containing nutrition bar composition 270 with a nutritional profile including inulin, almonds, almond butter, brown rice crispy, cocoa powder, chocolate chips, rolled oats, flaxseed oil, rice dextrin, grape juice, and salt (see, e.g., FIG. 17B).

[0180] These arrangements also contemplate a variant in which the second nut-containing nutrition bar composition 270 is sized to half the portion size of the first nut-containing nutrition bar and includes almonds, macadamia, pecans, honey, flaxseed, coconut flour, and rosemary extract (see, e.g., FIG. 17A). The nut-containing nutrition bar may also optionally include almonds, macadamia, and pecans, and in other variants, may include honey, flaxseed, coconut flour, and rosemary extract (see, e.g., FIGS. 17A and 17C-17G). These examples may be further modified to include half-sized nut-containing nutritional bars 270 containing almonds, macadamias, and pecans, and / or one or more of chicory root fiber, tocopherols, acai, blueberries, cacao nibs, cocoa powder, raspberries, strawberries, and lemon juice (see, e.g., Figures 17A and 17C-17G).

[0181] In one formulation example, the first and second FMD nut-containing nutritional bar compositions 220, 285 are formulated to provide about 90 kcal to about 350 kcal per serving, or about 90 kcal to about 260 kcal per serving (see, e.g., Figures 17A, 17B), or optimally about 200 kcal to about 210 kcal per serving (see, e.g., Figures 17C-17G).

[0182] In one variation, the first and second FMD nutrition bar compositions are precisely formulated to provide about 10 grams to about 35 grams of total fat per serving, and in one embodiment, about 5 grams to about 22 grams of total fat per serving. In a further variation, the first and second FMD nutrition bars are formulated to provide less than about 20 grams of saturated fat, and optionally less than about 5 grams of trans unsaturated fatty acids (hereinafter "trans fat") (optimally less than 1 gram of trans fat) per serving. A further variation contemplates the first and second FMD nutrition bars having about 17 grams to about 18 grams of total fat per serving.

[0183] Each of these variations further contemplates the first and second FMD nut-containing nutritional bar compositions having no trans fat and about 1-4 grams of saturated fat per serving, more preferably about 2-3.5 grams of saturated fat per serving. A further variation contemplates that each of the first and second nut-containing nutritional bar compositions contains polyunsaturated fat in the range of about 2.5 grams to about 3.5 grams, and monounsaturated fat in the range of about 9 grams to about 11 grams.

[0184] In one variation, each of the first and second FMD nutrition bar compositions is formulated to provide less than about 10 grams of protein per serving. In a further variation, the first and second FMD nutrition bar compositions are precisely formulated to provide about 1 to about 8 grams of protein per serving. In a further variation, the first and second FMD nut-containing nutrition bar compositions are formulated to provide about 2 to 6 grams of protein per serving, or about 4 to 5 grams of protein per serving.

[0185] In yet another variation, each of the first and second FMD nut-containing nutrition bar compositions is precisely formulated to provide less than about 30 grams of carbohydrate per serving. In a further variation, the nutrition bar compositions are formulated to provide between about 8 grams and about 25 grams of carbohydrate per serving. In yet another variation, each of the first and second FMD nutrition bar compositions is formulated to provide between about 10 and 18 grams of carbohydrate per serving.

[0186] Yet other variations contemplate each FMD nut-containing nutritional bar composition having about 13 grams to about 14 grams of total carbohydrate per serving. Other arrangements of the first and second FMD nutritional bar compositions provide about 3 grams to about 9 grams of total sugars per serving, or about 5 grams of total sugars per serving. In any of these arrangements, the first and second FMD nut-containing nutritional bar compositions are precisely formulated to have about 1 gram to about 7 grams, or up to about 3 grams of added sugars per serving.

[0187] The first and second FMD nutrition bar compositions may be formulated within these limits with any combination of macadamia nuts, honey, pecans, almonds, almond butter, coconut flour, sea salt, mixed tocopherols (vitamin E), citric acid, and ascorbic acid. Some variations also include first and second nut-containing nutrition bar compositions precisely formulated within these limits with any combination of inulin, almond butter, brown rice crisps, cocoa powder, almonds, chocolate chips (cane sugar, unsweetened chocolate, cocoa butter), rolled oats, brown rice syrup, flaxseed oil, rice dextrin, grape juice, and salt.

[0188] The one-day fasting FMD package 200 also includes a micronutrient vegetable powder composition 225 that includes vitamin and mineral supplements containing Vitamin A, Vitamin C, Ca, Fe, Vitamin D3, Vitamin E, Vitamin K, Vitamin B1, Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B7, Vitamin B9, Vitamin B12, Cr, Cu, I, Mg, Mn, Mo, Se, and Zn (see, e.g., FIG. 18). Similarly, optionally, the micronutrient vegetable powder composition 225 including vitamin and mineral supplements preferably contains ascorbic acid, beet root powder, beta carotene, calcium carbonate, carrot, cholecalciferol, chromium picolinate, collard greens powder, cupric sulfate, cyanocobalamin, Dl-alpha tocopherol acetate, ferrous fumarate, folic acid, kale leaf, magnesium stearate, manganese sulfate, niacinamide, pantothenic acid, phytonadione, potassium iodide, pyridoxine HCl, riboflavin, sodium molybdate, sodium selenate, spinach, thiamine mononitrate, tomato, tricalcium phosphate, and zinc oxide (FIG. 18).

[0189] The micronutrient vegetable powder composition 225 including vitamin and mineral supplements may also otherwise include, as further examples, Vitamin A, Vitamin C, Vitamin D, Vitamin E, Vitamin K1, Vitamin B1, Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B12, folic acid, biotin, pantothenic acid, calcium, iron, iodine, magnesium, zinc, selenium, copper, manganese, chromium, molybdenum, kale leaves, beet root, carrot root, spinach leaves, and tomato (FIG. 18).

[0190] Any of the one-day fasting FMD packages 200 may also be prepared having almonds, kale, sesame seeds, and tapioca flour, and / or a kale cracker composition 250 including almonds, kale, sesame seeds, tapioca flour, chia seeds, flax seeds, sunflower oil, salt, coconut sugar and vinegar, onion, cayenne pepper, cumin seeds, black pepper, garlic, tocopherol, oregano, and citric acid (see, e.g., FIG. 20).

[0191] In one variation, each FMD soup composition, such as exemplary soup compositions 245 and 270, is formulated to provide about 80 kcal to 150 kcal, optionally about 110 kcal to 120 kcal per serving (see, e.g., FIGS. 21A-21I). In the context of formulation, "providing" also means "containing" and "comprising." In a variation, each FMD soup is formulated to provide about 1 to 5 grams of total fat per serving, and optionally about 1.5 to 2.5 grams of total fat per serving. In a further variation, each FMD soup is formulated to provide less than about 1 gram of saturated fat and less than about 5 grams of trans fat (optimally less than 1 gram of trans fat) per serving. Variations include making such FMD soups substantially free of saturated or trans fat.

[0192] In some variations, each FMD soup composition is precisely formulated to provide less than about 10 grams of protein per serving. In further variations, each FMD soup is formulated to provide about 1-8 grams of protein per serving. In further variations, each FMD soup is formulated to provide about 2-6 grams of protein per serving, and optimally about 2-5 grams of protein per serving.

[0193] In other variations, each FMD soup is precisely formulated to provide less than about 40 grams of carbohydrate per serving. In a further variation, each FMD soup is formulated to provide about 10-35 grams of carbohydrate per serving. In yet another example formulation, each FMD soup is formulated to provide about 20-30 grams, more preferably about 22-25 grams of carbohydrate per serving. In any of the contemplated precisely designed FMD soup formulations, further modifications are directed to limiting the total carbohydrate sugar content to about 1-4 grams per serving, optimally substantially free of added sugars.

[0194] FMD soups can be formulated within these exemplary limits from any combination of ingredients selected from the group consisting of black beans, butternut squash, quinoa, tomatoes, mushrooms, white beans (e.g., great northern beans), brown beans, spinach, green tea extract, rice flour, onion, brown rice flour, carrots, inulin, leeks, olive oil, cabbage, potatoes, olives, peas, pumpkin, maltodextrin, and celery, chicory root fiber, sea salt, yeast, basil, parsley, garlic, rosemary extract, coriander, oregano, potato starch, potato flakes, zucchini squash, turmeric.

[0195] In some variations, FMD soups can also be precisely formulated within these limits from a first component selected from the group consisting of black beans, butternut squash, quinoa, tomatoes, mushrooms, white beans (e.g., great northern beans), brown beans, spinach, and combinations thereof, and a second component selected from the group consisting of green tea extract, rice flour, onion, brown rice flour, carrots, inulin, leeks, olive oil, cabbage, potatoes, olives, peas, pumpkin, maltodextrin, and celery, chicory root fiber, sea salt, yeast, basil, parsley, garlic, rosemary extract, coriander, oregano, potato starch, potato flakes, zucchini squash, turmeric, and combinations thereof. Typically, FMD soups are provided as powders that can be combined with water to form a soup, typically upon heating.

[0196] Exemplary FMD soups include, for example, but are not limited to, vegetable soup, minestrone soup containing quinoa, mushroom containing soup, tomato containing soup composition, bean containing minestrone soup composition, pumpkin soup composition, white bean and spinach soup, buckbean soup, butternut squash soup, butternut squash and quinoa soup, and vegetable broth. One example of a vegetable soup composition includes onion, tomato, spinach, green tree extract, optionally rice flour, optionally brown rice flour, optionally carrot, leek, and optionally inulin. One example of a quinoa-containing minestrone soup composition includes quinoa, green tea extract, optionally olive oil, optionally cabbage, optionally potatoes, optionally rice flour, and optionally tomatoes, and optionally no turmeric.

[0197] An example of a vegetable soup composition includes carrots, inulin, leek, onion, and rice flour. A specific example of a mushroom-containing soup composition includes mushrooms, green tea extract, optionally brown rice flour, optionally carrots, and optionally inulin. A specific example of a mushroom-containing soup composition includes carrots, inulin, mushrooms, onion, and rice flour.

[0198] A specific example of a tomato-containing soup composition includes tomato, green tea extract, optionally inulin, and optionally onion. An example of a different tomato-containing soup composition includes tomato, inulin, olive, onion, potato, and rice flour. A specific example of a quinoa-containing minestrone soup composition includes quinoa, green tea extract, optionally olive oil, optionally cabbage, optionally potato, optionally rice flour, and optionally tomato, and optionally does not include turmeric. A variation of a quinoa-containing minestrone soup composition includes quinoa, green tea extract, optionally olive oil, optionally cabbage, and optionally potato, optionally rice flour, and optionally tomato, and optionally does not include turmeric.

[0199] An exemplary bean-containing minestrone soup composition includes white beans (e.g., great northern beans), great tea extract, optionally cabbage, and optionally potatoes. In one variation, the bean-containing minestrone soup composition includes brown beans, carrots, peas, potatoes, and rice flour. One example of a pumpkin soup composition includes pumpkin, green tree extract, optionally rice flour, optionally carrots, and optionally brown rice flour. One specific example of a first vegetable broth includes carrots, maltodextrin, celery, spinach, and tomatoes. Another example of a vegetable broth includes carrots, maltodextrin, celery, spinach, and tomatoes.

[0200] An exemplary composition of white bean and spinach soup includes white beans, whole grain black rice, rice flour, chicory root fiber, olive oil, spinach leaves, sea salt, celery, onion, yeast extract, and garlic. One specific example of a black bean soup composition includes black beans, chicory root fiber, whole grain brown rice, olive oil, potato starch, rosemary extract, sea salt, onion, yeast extract, garlic, coriander, and oregano.

[0201] One specific example of a butternut squash composition includes butternut squash, rice flour, whole grain brown rice, chicory root fiber, sea salt, carrots, olive oil, potato starch, rosemary extract, onion, and yeast extract.One specific example of a butternut squash and quinoa composition includes butternut squash, quinoa, whole grain brown rice, rice flour, chicory root fiber, olive oil, potato starch, rosemary extract, sea salt, onion, yeast extract, garlic, and chives.

[0202] An even more exemplary arrangement of the one-day fasting FMD package 200 of FIG. 16 incorporates a first soup composition and a second soup composition, each including at least rice flour, chicory root fiber, onion, olive oil, and yeast extract. These variations may also include the first and second soup compositions 245, 270 in other forms, such as the first and second soup compositions 245, 270 including rice flour, chicory root fiber, onion, olive oil, salt, and yeast extract, and / or one or more of basil, parsley, whole brown rice, sweet red pepper, leek, spinach, cabbage, tomato, celery, turmeric, quinoa, potato flakes, peas, carrots, zucchini squash, broccoli, celery seed, mushroom powder, white beans, black beans, garlic, coriander, oregano, butternut squash, and chives.

[0203] The 1-day FMD also contemplates that the first soup composition and the second soup composition in the modified formulation each include rice flour, chicory root fiber, onion, olive oil, salt, and yeast extract, wherein the first soup composition and the second soup composition each include:

[0204] (a) a mushroom soup component including parsley, whole grain brown rice, rice flour, carrots, and mushroom powder;

[0205] (b) a tomato soup component containing tomatoes, basil, parsley, and whole brown rice;

[0206] (c) a vegetable soup component including basil, parsley, whole brown rice, sweet red pepper, leek, spinach, tomato, and carrot;

[0207] (d) minestrone soup components including parsley, leeks, spinach, cabbage, tomatoes, celery, turmeric, potato flakes, peas, carrots, and white beans;

[0208] (e) a minestrone soup component having quinoa, basil, parsley, whole brown rice, leeks, spinach, cabbage, tomatoes, celery, turmeric, potato flakes, peas, carrots, zucchini squash, broccoli, celery seeds, and garlic;

[0209] (f) a white bean and spinach soup component containing whole brown rice, spinach, celery, white beans, and garlic;

[0210] (g) a black bean soup component comprising whole brown rice, black beans, garlic, coriander, and oregano;

[0211] (h) A butternut squash soup component, which comprises whole grain brown rice, carrots, butternut squash, and chives; and

[0212] (i) a butternut squash and quinoa soup component that includes whole grain brown rice, quinoa, butternut squash, garlic, and chives.

[0213] Each or any of the various arrangements of the multi-day FMD package 10 described above, as well as the envisioned one-day fasting FMD package 200, may be further adapted so that the combination of the breakfast, lunch, and dinner meal portions provides a total of 75% or less of the subject's recommended daily calorie intake. In one other adjustment example, the combination of the breakfast, lunch, and dinner meal portions provides 50% or less of the subject's recommended daily calorie intake. A further exemplary variation is for the combination of the breakfast, lunch, and dinner meal portions to provide 25% or less of the subject's recommended daily calorie intake.

[0214] In one variation, the day fasting FMD package 200 is precisely formulated to provide between about 500 kcal and about 1500 kcal per package totaling the meal plan schedule and meal portions described herein. A further formulation example relates to a day fasting FMD package 200 precisely formulated to contain between about 740 kcal and about 1140 kcal total per package. Modifications also include a day fasting FMD package 200 precisely designed to have between 910 kcal and 945 kcal total per package totaling the meal portions incorporated therein. Each of the many contemplated formulation variations is contemplated for use with various types of intermittent fasting and / or time restricted fasting using the contemplated day FMD packages 200 described herein.

[0215] Certain other examples of the one-day fasting FMD package or the FMD packages described above include combinations of breakfast, lunch, and dinner meal portions that provide, in the aggregate, at least about 50 grams of fat or at least about 30 grams of fat, carbohydrates including less than about 20 grams of sugar, and at least about 20 grams of protein per package 200. Modifications are also contemplated in which the combinations of breakfast, lunch, and dinner meal portions provide, in the aggregate, about 50 grams to about 60 grams of fat, about 10 grams to about 20 grams of carbohydrates including sugar, and about 20 grams to about 30 grams of protein per package 200. Still other variations include combinations of breakfast, lunch, and dinner meal portions adapted to provide less than about 60 grams of fat, less than about 20 grams of carbohydrates including sugar, and less than about 30 grams of protein.

[0216] It is also contemplated that the combination of breakfast, lunch, and dinner meal portions provides 70%-80% of the subject's recommended daily fat intake, 25%-40% of the subject's recommended daily sugar intake, and 25 grams-30 grams of protein. A modified formulation of the one-day fasting FMD package 200 can have a combination of breakfast, lunch, and dinner meal portions formulated as described herein to provide less than 80% of the subject's recommended daily fat intake, less than 40% of the subject's recommended daily sugar intake, and less than about 30 grams of protein.

[0217] In one variation, the one-day fasting FMD package and the combination of the breakfast, lunch, and dinner meal portions 205, 210, 215 components are consumed by the subject only one day per week for at least 30 days, or four weeks, or one month, and one day per week for longer periods. In a further variation, the one-day fasting FMD package 200 is consumed by a subject who fasts intermittently and / or restricts eating to a certain period of time and fasts before and after such FMD eating period. In one other adjustment example, the subject consumes the one-day fasting FMD package 200 for two days per week and eats normally for the preceding and / or following five days of the week, which is sometimes called a 5-2 fast (51).

[0218] Each of the various FMD packages, including the 1-day fasting FMD package, also contemplates various methods of use, as described in more detail elsewhere in this disclosure. In some variations, the FMD may also be modified to be a low-sodium diet that provides less than 1000 mg of sodium chloride per day. As a further example, the 1-day fasting FMD package may be utilized in a method of inducing differential effects on disease factors and markers associated with aging, comprising administering the 1-day fasting FMD package to a subject. In this method, the disease factors and markings may be insulin-like growth factor-1, blood glucose, systolic blood pressure, diastolic blood pressure cholesterol, CRP, triglycerides, or abdominal / visceral fat.

[0219] Other variations of the method are available and may be directed to promoting and inducing stem cell-based regeneration of multiple organs and systems using any of the variously described one-day FMD package arrangements. Again, the method includes administering one of the exemplary one-day fasting FMD packages to a subject in need thereof. Methods of using the one-day fasting FMD package, where the stem cell-based regeneration of multiple organs and systems includes promoting neurogenesis, hematopoiesis, or pancreatic beta cells, are also contemplated in the present disclosure.

[0220] Although exemplary embodiments have been described above, it is not intended that these embodiments describe all possible forms of the invention. Rather, the terms used herein are terms of description rather than limitation, and it is understood that various modifications can be made without departing from the spirit and scope of the invention. Moreover, features of the various implementations of the embodiments may be combined to form further embodiments of the invention.

[0221] ●References: 1. “Healthline,” https: / / www.healthline.com / health / ketonuria#causes, Noreen Iftikhar, M.D. 2. “Ketone Body Metabolism” by C. Ward. Diapedia. https: / / web.archive.org / web / 20181111193826 / https: / / www.diapedia.org / metabolism-and-hormones / 51040851169 / ketone-body-metabolism. (2015). 3. Lori Laffel, "Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes." Diabetes / Metabolism Research and Reviews. 15(6):412-426. (November 1999). 4. MPMattson, K. Moehl, N. Ghena, M. Schmaedick, A. Cheng, “Intermittent metabolic switching, neuroplasticity and brain health.” Nature Reviews. Neuroscience. 19(2):63-80. (2018). 5.Eric C. Westman, Justin Tondt, Emily Maguire, William S. Yancy, "Implementing a low-carbohydrate, ketogenic diet to manage type 2 diabetes mellitus." Expert Review of Endocrinology & Metabolism. 13(5):263-272. (September 15, 2018). 6. “Ketogenic diet improves metabolic syndrome in multiple ways,” https: / / www.diabetes.co.uk / news / 2017 / dec / ketogenic-diet-improves-metabolic-syndrome-in-multiple-ways-99064712.html, (December 18, 2017). 7. Victoria M. Gershuni, Stephanie L. Yan, Valentina Medici, "Nutritional Ketosis for Weight Management and Reversal of Metabolic Syndrome." Current Nutrition Reports. 7(3):97-106. (August 20, 2018) / 8. K. G. Alberti et al., "Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention," National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Federation for the Study of Obesity. Circulation 120, 1640 (20 October 2009). 9. E.S. Ford, W.H. Giles, and W.H. Dietz, "Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey," Jama 287, 356 (January 16, 2002). 10. A.S. Gami et al., "Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies," Journal of the American College of Cardiology 49, 403 (January 30, 2007). 11. IY Choi et al., "A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms." Cell Reports 15, 2136 (7 June 2016). 12. S. Brandhorst et al., "A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration,Enhanced Cognitive Performance,and Healthspan." Cell Metabolism 22, 86 (7 July 2015). 13. V.D. Longo, S. Panda, "Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan." Cell Metabolism 23, 1048 (June 14, 2016). 14. A. J. Bruce-Keller, G. Umberger, R. McFall, and M. P. Mattson, "Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults." Ann Neurol 45, 8 (January 1999). 15. A. L. Hartman, J. E. Rubenstein, and E. H. Kossoff, “Intermittent fasting: a (new) historical strategy for controlling seizures?” Epilepsy research 104, 275 (May 2013). 16. H. Muller, FWde Toledo, and KLResch, “Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review.” Scandinavian journal of rheumatology 30, 1 (2001). 17. VD Rongo, M.P. Mattson, "Fasting: Molecular Mechanisms and Clinical Applications." Cell Metabolism 19, 181 (February 4, 2014). 18. C.-W. Cheng et al., "Prolonged Fasting Reduces IGF-1 / PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression." Cell Stem Cell 14, 810 (5 June 2014). 19. WESonntag et al., “Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals.” The journals of gerontology. Series A, Biological sciences and medical sciences54, B521 (December 1999). 20. Y. Ikeno, RT Bronson, G. B. Hubbard, S. Lee, A. Bartke, “Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longlife.” The journals of gerontology. Series A, Biological sciences and medical sciences58, 291 (April 2003). 21. K. Flurkey, J. Papaconstantinou, R. A. Miller, and D. E. Harrison, "Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone," Proceedings of the National Academy of Sciences 98, 6736 (June 5, 2001). 22. S.E. Dunn et al., "Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice." Cancer Research 57, 4667 (November 1, 1997). 23. MS Bonkowski, "Disruption of growth hormone receptor prevents calorie restriction from improving insulin action and longevity." PLOS ONE 4, e4567 (2009). 24. ME Levine et al., “Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population.” Cell Metabolism 19, 407 (March 4, 2014). 25. J. Guevara-Aguirre et al., "Growth hormone receptor deficiency is associated with major reduction in pro-aging signaling, cancer, and diabetes in humans." Science Translational Medicine 3, 70ra13 (February 16, 2011). 26. M.W. Gillman, "Developmental origins of health and disease." New England Journal of Medicine 353, 1848 (October 27, 2005). 27. L. Fontana, BK Kennedy, VD Rongo, D. Seals, S. Melov, "Medical research: treat ageing," Nature 511, 405 (July 24, 2014). 28. M. Nayor, R.S. Vasan, "Recent Update to the US Cholesterol Treatment Guidelines: A Comparison with International Guidelines." Circulation 133, 1795 (May 3, 2016). 29. “Diagnosis and classification of diabetes mellitus.” Diabetes Care 37 Suppl 1, S81 (January 2014). 30. M. Miller et al., "Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association," Circulation 123, 2292 (May 24, 2011). 31. T.A. Pearson et al., "Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association," Circulation 107, 499 (January 28, 2003). 32. M.N. Pollack, "Insulin, insulin-like growth factors, insulin resistance, and neoplasia," Journal of the American Academy of Clinical Nutrition 86, s820 (September 2007). 33. MELevine, “Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age?” The journals of gerontology. Series A, Biological sciences and medical sciences 68, 667 (June 2013). 34. L. Fontana, L. Partridge, and V.D. Rongo, "Extending healthy life span--from yeast to human," Science 328, 321 (April 16, 2010). 35. S. Brandhorst, M. Wei, S. Hwang, TEMorgan, VD Rongo, “Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay glioma progression.” Experimental Gerontology, (February 21, 2013). 36. A. G. Renehan et al., "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis," Lancet 363, 1346 (April 24, 2004). 37. JM Chan et al., "Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer." Journal of the National Cancer Institute 94, 1099 (July 17, 2002). 38. N.E. Allen et al., "A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk." British Journal of Cancer 92, 1283 (11 April 2005). 39. O. Fletcher et al., "Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review," Cancer epidemiology, biomarkers & prevention, American Cancer Society, in collaboration with the American Society for Preventive Oncology, vol. 14, no. 2 (January 2005). 40. K. Rapp et al., "Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria," Diabetologia 49, 945 (May 2006). 41. T. Stocks et al., "Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (ME-CAN): analysis of six prospective cohorts," Pros Medicine 6, e1000201 (December 2009). 42. M. N. Harvie et al., "The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women." International Journal of Obesity 35, 714 (May 2011). 43. L. Fontana, EP Weiss, DTVillareal, S. Klein, JO Olloszy, "Long-Term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in human." Aging Cell 7, 681 (October 2008). 44. R. D. Hays et al., "The impact of patient adherence on health outcomes for patients with chronic disease in the Medical Outcomes Study." Journal of Behavioral Medicine 17, 347 (August 1994). 45. TP Wycherley et al., "A high-protein diet with resistance exercise training improves weight loss and body composition in overweight and obese patients with type 2 diabetes." Diabetes Care 33, 969 (May 2010). 46. ​​D. Florakis et al., "Effect of hypocaloric diet plus sibutramine treatment on hormonal and metabolic features in overweight and obese women with polycystic ovary syndrome: a randomized, 24 week study," International Journal of Obesity 32, 692 (April 2008). 47. M. Harvie et al., "The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women." British Journal of Nutrition 110, 1534 (October 2013). 48. G. Brabant et al., "Serum insulin-like growth factor I reference values ​​for an automated chemiluminescence immunoassay system: results from a multicenter study," Hormone Research 60, 53 (2003). 49. www.census.gov 50. C. Patikorn et al., "Intermittent Fasting and Obesity-Related Health Outcomes, An Umbrella Review of Meta-analyses of Randomized Clinical Trials." JAMA Network Open 2021;4(12:e2139558 (17 December 2021). 51. P. Hajek et al., "A Randomized Controlled Trial of the 5:2 Diet." PLOS ONE 16(11):e0258853 (17 November 2021). 52. R. Schubel et al., "Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 weeks: a randomized controlled trial." Journal of the American Academy of Clinical Nutrition 2018;108:933-945 (2018).

Claims

1. a first meal portion comprising a first nut-containing nutritional bar, a micronutrient vegetable powder containing a vitamin and mineral supplement, and an algae oil composition; a second meal portion comprising a first soup composition and a kale cracker composition; and a third meal portion comprising a second soup composition, any one of the kale cracker composition or the olive-containing composition, and a second nut-containing nutritional bar; and A one-day fasting mimicking meal package for a continuous 12-24 hour fast, comprising predetermined compositions grouped into:

2. the first nut-containing nutritional bar contains almonds, macadamia nuts, and pecans; 10. The fasting mimicking meal package of claim 1.

3. The algal oil composition comprises DHA omega-3 fatty acid and at least one of Aurantiochytrium algal oil and Schizocatrium algal oil.

10. The fasting mimicking meal package of claim 1.

4. the second nut-containing nutritional bar contains inulin, almonds, almond butter, brown rice crispy, cocoa powder, chocolate chips, rolled oats, flaxseed oil, rice dextrin, grape juice, and salt; 10. The fasting mimicking meal package of claim 1.

5. the second nut-containing nutrition bar is sized to one-half the portion size of the first nut-containing nutrition bar and comprises almonds, macadamia, pecans, honey, flaxseed, coconut flour, and rosemary extract; 10. The fasting mimicking meal package of claim 1.

6. the kale cracker composition comprises almonds, kale, sesame seeds, and tapioca flour; 10. The fasting mimicking meal package of claim 1.

7. the first soup composition and the second soup composition comprising rice flour, chicory root fiber, onion, olive oil, and yeast extract; 10. The fasting mimicking meal package of claim 1.

8. each of the first soup composition and the second soup composition comprises one or more of basil, parsley, whole grain brown rice, sweet red pepper, leek, spinach, cabbage, tomato, celery, turmeric, quinoa, potato flakes, peas, carrots, zucchini squash, broccoli, celery seed, mushroom powder, white beans, black beans, garlic, coriander, oregano, butternut squash, and chives; 8. The fasting mimicking meal package of claim 7.

9. The micronutrient vegetable powder contains vitamins selected from vitamin A, vitamin C, vitamin D, vitamin E, vitamin K1, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, folic acid, biotin, and pantothenic acid, minerals selected from calcium, iron, iodine, magnesium, zinc, selenium, copper, manganese, chromium, and molybdenum, and vegetable ingredients selected from kale leaves, beet roots, carrot roots, spinach leaves, and tomatoes.

10. The fasting mimicking meal package of claim 1.

10. The fasting mimicking meal package of claim 1, further comprising a tea composition comprising at least one of lemon, hibiscus, and spearmint for optional consumption between 12-24 hour intervals.

11. The fasting mimicking meal package of claim 1, wherein the sum of the first meal portion, the second meal portion, and the third meal portion provides 740 kcal to 1140 kcal per day.

12. The fasting mimicking meal package of claim 1, wherein the sum of the first meal portion, second meal portion, and third meal portion provides at least 50 grams of total fat, less than 20 grams of total sugars, and 20 grams to 30 grams of protein per day.

13. 10. The fasting mimicking meal package of claim 1, wherein the first meal portion, second meal portion, and third meal portion together provide 75% or less of a subject's recommended daily calorie intake.

14. A fasting-mimicking meal package as described in claim 1, wherein the predetermined compositions are grouped into a first meal portion, a second meal portion, and a third meal portion as separate labeled portions packaged together for same-day use.

15. A fasting mimicking meal package as described in claim 1, further comprising printed instructions specifying consumption of grouped meal portions.

16. The fasting mimicking meal package of claim 15, wherein the printed instructions instruct the user to try and consume a first meal, a second meal, and a third meal during a 24-hour period to maintain a fasting metabolic state.

17. Non-medical use of the fasting mimicking meal package described in claim 16 for improving fasting-related metabolic markers for a 24-hour period, said improvement being achieved by maintaining elevated blood ketone levels and limiting blood glucose fluctuations during said period.

18. The use described in claim 17, wherein mean blood beta-hydroxybutyrate is elevated to 0.3 mM or greater during the 24-hour period, and mean blood glucose is maintained within the range of 75 to 85 mg / dL at specified pre- and post-prandial time points.

Images