AU2020101019A4 - A provider-supervised and individualised method for weight management that includes nutritional compositions and therapeutic dietary techniques to improve the key physiological processes involved in weight management, namely gut microbial composition, gut wall integrity, immune function, mitochondrial function, nutrient status, detoxification, appetite-regulation, metabolic hormones, neurotransmitter synthesis and neurogenesis . - Google Patents

Abstract

The present innovation relates to a custom provisional model of nutritional compositions and dietary methods for improving the physiological processes involved in weight management. It includes dietary methods of periods of low calorie, low carbohydrate intake alongside self-directed intermittent fasting and periods of self-directed calorie and carbohydrate intake, intermittent ketosis to produce initial rapid fat loss followed by gradual fat loss.

Description

Editorial Note 2020101019 There is only fifty-four pages of the description

• Description Innovation Patent Ref no. INNOV290595

• Title: A provider-supervised and individualised method for weight management that includes nutritional compositions and therapeutic dietary techniques to improve the key physiological processes involved in weight management, namely gut microbial composition, gut wall integrity, immune function, mitochondrial function, nutrient status, detoxification, appetite-regulation, metabolic hormones, neurotransmitter synthesis and neurogenesis.

• Technical area The present innovation, in general, relates to a custom provisional model of nutritional compositions and dietary methods for improving the physiological processes involved in weight management. It includes dietary methods of periods of low calorie, low carbohydrate intake alongside self-directed intermittent fasting and periods of self-directed calorie and carbohydrate intake, intermittent ketosis to produce initial rapid fat loss followed by gradual fat loss. Other dietary recommendations pertaining to specific food choices, combined with three powdered nutritional compositions that are free from harmful excipients or additives, help to improve the composition of the gut microbiome, reduce inflammation and regulate the innate and adaptive immune responses, promote the regeneration of the intestinal wall and supporting the physiological processes relevant to weight management such as mitochondrial function, hepatic and enterocyte detoxification reactions, glucose and lipid metabolism, appetite control and energy balance as well as improving brain function by modulating the stress response, assisting the synthesis of neurotransmitters and providing a neurological environment conducive with neurogenesis.

The innovation is available through accredited providers who via a health questionnaire assess suitability for participation and identify the need for individual modifications tailored to those with disordered gut, inflammatory, metabolic or brain function.

The term "weight management" refers to weight loss and/or maintaining weight after weight loss and/or maintaining a healthy weight.

The term "nutritional compositions" refers to compositions containing, but not limited to micronutrients, minerals, vitamins, antioxidants, polyphenols, probiotics, prebiotics, amino acids, phospholipids, fruit and vegetable extracts and/orjuices, herbs, anti-inflammatory nutrients with or without the addition of macronutrients and/or harmful excipients, in any combination thereof.

Any discussion of the prior art throughout this specification should in no way be considered as an admission that such prior art is widely known or forms part of general knowledge in the field.

Background details and previous artwork

Weight management, which includes losing weight and maintaining a healthy weight long-term, has a complex and multifactorial aetiology.

Energy homeostasis is maintained by a feedback mechanism between peripheral organs such as the gut, pancreas and liver, and the central nervous system. This mechanism regulates food intake and energy expenditure according to physiological needs and is the premise of the calorie balance model for weight loss. This model is based on the theory that weight management is a process dependent on the number of calories consumed versus the number of calories expended. Under this model, in order to lose weight an individual must burn more calories than they consume. These have been the standard recommendations for weight loss for several decades. However, despite the judicious use of this model, long-term weight loss success rates remain low and obesity rates continue to rise. In 2014, the number of obese people in worldwide was approximately 1.9 billion, in 2019 this figure was 2.1 billion. Currently about 30% of the total population is obese.

Over the last two decades research into the gut microbiota is revealing its integral role in regulating a number of physiological processes that are relevant for weight management. Studies show that the gut microbiota influences the number of calories absorbed from a meal as well as how the macronutrients are managed in the body, that is, whether they are used for energy, stored as fat and even whether our brain is able to detect them. (220)

Microbial composition varies between individuals which is why individual responses to dietary interventions vary. Therefore, improving microbial diversity and supporting the functions relevant to weight management, may in fact be the key tosuccess.

The gut microbiota consists of over 2000 different microbial species whose genetic material, termed the microbiome, is 150 times greater than that of human genome. It is now known that these genes encode for proteins that serve a number of essential functions throughout the body. (4,5).

The gut microbiota consists of five main phyla, with Firmicutes and Bacteroides making up seventy percent of the entire gut microbiota. Each phylum contains a number of species with functional similarities. The more diversity amongst these species, the better the metabolic capacity. Alterations to the main phyla and a reduction in microbial diversity have been associated with obesity, insulin resistance and a range of metabolic disorders. (4,5).

The key function of gut microbiota is to digest dietary fibre, their main source of energy, and convert it into a number of metabolites. short chain fatty acids are the predominant metabolites through which the microbiota exerts many of its benefits are. There are three main short chain fatty acids; butyrate, propionate and acetate and they attach to g-protein coupled receptors found on host cells throughout the body. This interaction influences a range of cellular functions and the production of host proteins, hormones and peptides. Butyrate is also an epigenetic regulator and can therefore directly the expression of host genes. (9,11,14).

Other microbial metabolites include vitamins, polyphenols and neurotransmitters. (6,7,8,9). These metabolites combined with the action of short chain fatty acids have been shown to influencethe following microbial and host functions;

• Supporting the growth of gut microbiota (11-14) • Maintaining the integrity of the gut wall by stimulating the synthesis of tight junctions and the mucus layer and supplying energy to enterocytes (11-14) • Maintaining a state of immune tolerance throughout the body (11-14) • Processing and absorption of nutrients (15) • Extraction of calories from food (15) • Assisting mitochondrial function and fatty acid oxidation (16,17) • Increasing the bioavailability of dietary antioxidants (20). • Supporting detoxification and elimination of xenobiotics (21-23) • Upregulating endogenous antioxidant systems in enterocytes and hepatocytes. (21-23) • Regulating thermogenesis in metabolically active tissue. (10-14)

* Regulating glucose, lipid and amino acid metabolism in the liver, adipocytes and skeletal muscle. (10-14) • Stimulating the production of gut peptides and neurotransmitters in enterocytes to modulate appetite and energy balance. (24-28) • Production and regulation of molecules, hormones, neurotransmitters and various metabolites involved in gut-brain communication via the Vagus nerve and the neuroendocrine system. (28,29)

Studies show that a number of factors influence the composition of the gut microbiota. These include diet, medications, lifestyle, stress, genes, exposure to xenobiotics, living conditions and other environmental exposures.

Dysbiosis is the term used to describe detrimental alterations to microbial composition, whereby the proportions of the main phyla are disrupted and there is lower diversity of species, with a predominance of pathobionts. Several causative factors have been identified and these include dietary components such as food additives and xenobiotics, saturated fats, refined sugar and artificial sweeteners and non-dietary factors such as genetic predisposition, environmental xenobiotics, stress, insomnia, sedentary lifestyle, over exercising, over-eating, under-eating and medications such as antibiotics, antacids or anti-inflammatory drugs (30-34).

Dysbiosis is associated with a reduction in beneficial (symbiotic) bacteria and an increase in pathogenic Gram-negative bacteria such as E.coli.

The reduction in symbionts is associated with a decrease in microbial metabolites which leads to a disruption of all the functions they would normally support.

Endotoxin, a component of the cell wall in Gram negative bacteria, is released when the bacteria die. In states of dysbiosis there is increased turnover of this bacteria and therefore an increase in endotoxin. Endotoxin has been shown phosphorylate tight junctions, resulting in gaps between enterocytes and a disruption in the integrity of the gut wall, commonly termed leaky gut. Endotoxin is also a potent activator of the inflammatory response. It attaches to toll-like receptor 4 on macrophages and T-cells which leads to the production of pro-inflammatory cytokines such as IL-1, IL-6 and TNFa. These cytokines recruit other inflammatory cells such as neutrophils and activate T-cell and B cells. Endotoxin produces this inflammatory response within the gastrointestinal tract and in organs throughout the body. (43)

Studies show that endotoxin in the bloodstream, termed endotoxemia, occurs after consuming a meal high in saturated fats and/or refined carbohydrates. (65) Endotoxemia is associated with systemic inflammation and a range of metabolic and inflammatory conditions including obesity, insulin resistance, mitochondrial dysfunction, non-alcoholic fatty liver disease and autoimmune conditions in both humans and mice (35-44).

Endotoxin induces inflammation within adipose tissue by activating resident macrophages and recruiting immune cells into the tissue. This has been shown to change the function and hormonal output of fats cells leading to insulin resistance and fat storage. In addition, leptin release is increased and while this would normally signal fullness to the brain, leptin receptors become downregulated and it is therefore no longer detected by the brain. This is known as leptin resistance and is common in obesity. This is the reason why some people report that they never feel satisfied or that they have no "off switch" when it comes to food, despite carrying excess weight (45-46).

In the liver, endotoxin activates resident Kupffer cells which initiates the inflammatory response. This results in impaired function of hepatocytes leading to altered metabolism of glucose and lipids, impaired detoxification and the development of non-alcoholic fatty liver disease. Hepatocyte dysfunction leads to oxidative stress and an increase of toxins in the body. These toxins are lipophilic and therefore become stored within adipose tissue, leading to further metabolic derangements. (66-78).

Endotoxin travel to the brain where it damages tight junctions in the blood brain barrier allowing antigens to cross through into the brain matter. Endotoxin, cortisol and saturated fatty acids have been shown to activate microglia leading to inflammation in the brain, termed neuroinflammation. This process alters the function a several brain regions that are involved with homeostatic regulation of appetite and energy balance as well as the stress response, cognitive function and decision-making, memory, reward and impulse control. All of these functions are crucial to weight management (47-53).

The hypothalamus is an area of the brain involved in appetite control, energy balance and the stress response. Hypothalamic inflammation impairs our ability to detect signals of fullness, resulting in increased hunger and food intake, and a reduction in energy expenditure (54-58).

The corticolimbic system includes areas of the brain that are involved in cognitive function, learning, emotional control and the stress response (to name a few). When these areas are altered, our ability to manage stress, employ cognitive restraint and overcome urges is impaired. (59-61)

In addition, neuroinflammation alters the production of neurotransmitters responsible for mood, sleep and appetite. It also impairs neurogenesis, the process by which the brain remodels to form new neural pathways. (61) This is important when it comes to developing and maintaining new behaviours and lifestyle patterns related to weight management. If neurogenesis is impaired it is difficult, if not impossible, to develop new behaviours and sustain them long term.

It is important to note that dietary saturated fatty acids have been shown to produce the same inflammatory processes and consequences as endotoxin. (62,63,64)

Research has found a number of microbial aberrations commonly associated with obesity and systemic inflammation. These include a reduced diversity of species, a higher Firmicutes to Bacteroidetes ratio, lower Akkermansia mucinophilia and an increase in pathogenic species. (35, 36, 79-83)

Fortunately, research also shows that the gut microbiota is malleable and can change from meal to meal. The Mediterranean diet has consistently been shown in research to improve microbial composition and reduce systemic inflammation. (218) Prebiotics, probiotics, polyphenols, amino acids and a range of other nutrients have been shown to improve microbial composition, metabolic capacity and reduce inflammation. (34, 84-86).

Through the use of diet, lifestyle and nutrients, a well-designed weight management protocol can improve the diversity of the gut microbiota and support the physiological processes involved in weight management.

Certain dietary techniques such as intermittent fasting, calorie restriction, carbohydrate restriction and ketosis, have also been shown to have a wide range of health benefits and assist with many of the processes involved in weight management. (98-103, 223) Some of these benefits appear to be mediated by their beneficial effects on the gut microbiota (222). However, some studies have shown that these dietary techniques may cause adverse effects such as dysbiosis, hormonal disruptions and weight regain. Certain individuals are more likely to experience adverse events and therefore require a more individualised approached. (98-103)Given the wide range of health benefits, these techniques have a place in a well-designed weight loss system, however they must be implemented correctly in order to avoid complications.

There are many weight management systems that focus on improving the gut microbiota, however there do not appear to be any methods or systems that provide comprehensive nutritional compositions and incorporate a range of evidence-based dietary recommendations and techniques for improving the gut microbiota while assisting the physiological processes involved in weight management as per items 2.d,i to 2.d, vi, and addressing individual needs.

Many weight management programs that focus on the gut microbiota contain dietary information without the use of nutritional compositions. Such examples include The Clever Guts Diet by Michael Mosely, The Microbiome Diet by Dr Raphael Kellman and The Total Well-being Diet for Gut Health by the CSIRO.

In contrast, there are many individual nutritional compositions that are sold separately and address one or more aspects of gut health or weight management however, many of these contain excipients that may disrupt the microbiota and they do not addresses the whole spectrum of physiological processes involved in gut health and weight management, nor do they address individual needs. Total Gut Restoration by Microba is a twelve-week protocol for improving the gut microbiota and the integrity of the gastrointestinal tract. It includes three nutrient compositions that contain probiotics, prebiotics, amino acid and immunoglobulins. These nutrients help improve the gut microbiota and the production of their metabolites. In this way the nutritional compositions may influence many physiological processes relevant to health however, there are no components or nutrients that specifically support the processes relevant to weight management as per items 2.d,i to 2.d, vi under Disclosure of the Innovation. Total Gut Restoration provides a 2-page handout with instructions on how to use the compositions however does not include any dietary advice. Diet has the greatest impact on the gut microbiota, therefore failing to address this factor is less likely to produce favourable results beyond the twelve-week protocol.

In addition, the large majority of nutritional compositions include a range of excipients such as food additives, emulsifiers, artificial or natural sweeteners or common food allergens to improve stability and palatability; however, many of these excipients have been associated with dysbiosis. (103,104, 221)

In contrast, other plans encourage prolonged periods of fasting or extreme and prolonged calorie restriction which can lead to over-eating and therefore dysbiosis and rebound weight gain.

Many plans also endorse foods that are commonly believed to improve microbial composition such as fermented foods and bone broth. However, the addition of these foods too early in the program may actually perpetuate the problem. Fermented foods and bone broth are high in histamine which can exacerbate inflammation in those with dysbiosis, leaky gut and/or an over active immune response. (225, 226) In addition, fermented foods contain probiotics, and although only a small amount survive passage through the gastrointestinal tract, these bacteria have the potential to stimulate an overly active immune system in those with dysbiosis. It is suspected that supplemental probiotics may have the same effect.

Another downfall of many popular diet plans is they fail to consider the subjects genetic predisposition to immune-driven conditions such as allergies, food intolerances, autoimmune conditions and insulin resistance, which are commonly associated with weight gain. There is a large body of anecdotal evidence suggesting that symptoms of these conditions may be triggered by many foods that are commonly considered healthy, such as eggs, nuts and grains.

Accordingly, there is a need for improved methods of weight management, in particular for addressing individual needs while improving gut microbial diversity and metabolic capacity, addressing the underlying inflammation, as well as supporting the physiological processes that assist with weight loss and long-term weight maintenance such asdetoxification, mitochondrial function, appetite and energy balance and, of course, brain function.

As such, provided herein are methods and compositions of improving the gut microbiota and supporting these physiological processes relevant for weight management in a subject, by providing nutritional compositions that are free from excipients, combined with specific and safe dietary recommendations and techniques. In addition, individual needs are addressed for those with certain medical conditions or symptoms.

Disclosure of the Innovation

1. Before innovation embodiments are disclosed and described, it is to be understood that no limitation to the particular structures, process steps, or materials disclosed herein is intended, but also includes equivalents thereof as would be recognized by those ordinarily skilled in the relevant arts. It should also be understood that terminology employed herein is used to describe particular examples only and is not intended to be limiting.

2. The present innovation solves one or more problems of the prior art by providing a method for assisting weight management by: a. Ensuring providers of the method are accredited through the completion five education modules related to the underlying physiological factors responsible for weight management. b. Providing a method of assessment to identify individual needs. c. Improving the composition of the gut microbiota d. Improving the integrity of the intestinal wall. e. Reducing inflammation in the gastrointestinal tract and target organs. f. Supporting the physiological processes relevant to weight management such as; i. Nutrient status ii. Mitochondrial function and thermogenesis iii. Hepatic and enterocyte detoxification iv. Glucose and lipid metabolism, glycaemic control v. Appetite control and energy balance vi. Neurological function including the stress response, the synthesis of neurotransmitters and neurogenesis; g. Addressing certain individual presentations that are commonly associated with microbial, immune, metabolic and neurological disruptions. h. Safely incorporating a range of dietary techniques, including intermittent fasting and calorie and carbohydrate restriction in order to produce effective fat loss while preventing the potential risks and adverse events that have been associated with the prolonged or inappropriate implementation of these techniques. i. Incorporating lifestyle recommendations that have been shown to improve microbial diversity and support the above physiological processes. 3. The present disclosure relates to a number of different methods that improve gut microbial composition and support any or all of the physiological processes relevant to weight management as per items 2.d,i to 2.d, vi, by administering the nutritional composition combined with the dietary recommendations and techniques of the present disclosure to an individual in need of such treatment. 4. The present method includes administering nutritional compositions and safely incorporating specific dietary recommendations and techniques, for a total period of six weeks to a subject who is having difficulty achieving and/or maintaining a healthy weight or who is experiencing various symptoms related to inflammation and metabolic derangements. 5. In the present disclosure, the weight management system is divided into two stages, with the first stage being two weeks duration and the second stage being four weeks. 6. In other embodiments, the system may be divided into two or three stages, with each stage ranging from one to six weeks.

Detailed description of the present disclosure

Nutritional Compositions

7. In the embodiment of the present disclosure, the weight management system includes a novel nutritional or nutraceutical composition divided into three separate formulations. The compositions are administered orally in a dry powdered formulation and do not contain any excipients that are known to contribute to dysbiosis and/or inflammation. The present method also includes a combination of probiotic and digestive enzymes in a capsule form. The present disclosure also includes a program manual and five modification handouts if required, this will be discussed below. 8. In certain embodiments, the nutritional or nutraceutical compositions can be in either a powder form, paste or capsules. 9. In some embodiments the nutritional or nutraceutical compositions may contain certain excipients that have no known negative impact on the gut microbiota such as stevia or tapioca maltodextrin. 1O.In certain embodiments the nutritional or nutraceutical compositions may be provided in sachets, syringes or capsules. 11.In other embodiments the method may include one or more nutritional compositions containing any combination of the components or nutrients, listed in 14a to 14i below. 12.Other embodiments may not include a probiotic and/or digestive enzyme component. 13.In the present method, nutritional compositions include components that contain nutrients to improve the composition of the gut microbiota and assist with physiological processes relevant to weight management, as per items 2.d,i to 2.d, vi. See also Table 1, Table 5 and Table 6

14.These nutritional compositions include:

a. An effective amount of a prebiotic component to improve the composition of the gut microbiota, this includes, but is not limited to inulin, pectin, curcumin and green tea extract. i. In certain embodiments this component may also include of fructo-oligosaccharides, green banana flour, glucomannan, konjac, galacto-oligosaccharides, burdock root, guar gum, acacia gum, arabinogalactan, tapioca, cranberry extract or juice, pomegranate extract or juice, concord grape extract or juice, or combinations thereof. References:23,24, 39,105-109

b. A an effective amount of nutrients to support the integrity of the gut wall that includes, but is not limited to inulin, pectin, glutamine, glycine, proline, vitamin D, curcumin, green tea extract, quercetin, vitamin A, a probiotic component that includes Lactobacillus spp. and Bifidobacterium spp, and a digestive enzyme component consisting of amylase, protease, lipase, bromelain and papain, or combinations thereof. i. In certain embodiments this component may also include effective amounts of butyrate, acetate, threonine, a probiotic component that includes Lactobacillus spp., Bifidobacterium spp and/or Akkermansia mucinophilia and a digestive component that includes cellulase and tilactase, flaxseed oil and grapeseed oil, or combinations thereof. References: 109-125

c. An effective amount of an antioxidant/phytochemical component that includes, but is not limited to curcumin, quercetin, zinc, green tea extract, Coenzyme Q10, selenium, berberine, pycnogenol and ginseng, a vitamin component that includes vitamins A, B1, B6, B12, C, D and E, or combinations thereof. i. In some embodiments this component may also include effective amounts of antioxidants and herbs. Non-limiting examples include resveratrol, fisetin, pyrroloquinoline quinone, lycopene, alpha-carotene, beta-carotene, lutein, xanthophylls, lignans, stilbenoids, phenolic acids, hesperidin, terpenes, hydroxycinnamic acids, lignans, flavonoids, black tea extract, sulfurophanes which may be in the form of broccoli sprout powder or extract, and phytoestrogens such as genistein, slippery elm bark powder, Silybum marianum extract (milk thistle), glycyrrhiza glabra root extract (licorice), mastic gum, orange oil, peppermint oil, lemon oil, vanilla extract or powder, cacao extract or powder, aloe vera extract, powder or juice, or combinations thereof. References: 126-131 d. An effective amount of an anti-inflammatory component that includes, but is not limited to Vitamins D, C, A and E, curcumin, quercetin, zinc, green tea extract, berberine, pycnogenol and ginseng, or combinations thereof. i. In other embodiments this component may also include effective amounts of omega-3 fish oil or a vegan omega-3 fatty acid source such as flaxseed oil or algae, a probiotic component, glutathione, resveratrol, butyrate, rice bran extract such as arabinoxylan and medicinal mushrooms such as turkey tail mushroom, maitake mushroom, reiishi mushroom, caterpillar mushroom and shitake mushroom, blackseed oil or grapeseed oil, or combinations thereof. References: 126-131 e. A component that includes, but is not limited to, an effective amount of nutrients to support mitochondrial and metabolic function consisting of vitamins C, D, E, B1, B2, B3 (niacinamide), B5, B6, Zinc, Magnesium, Choline, Biotin, iron, copper, Calcium, phosphate, manganese, alpha-lipoic acid, CoQ10, ascorbic acid , Tocopherol, the essential and non-essential amino acids phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine.curcumin, quercetin, EGCG, berberine, ginseng and pycnogenol, or combinations thereof. i. In certain embodiments this component may also include effective amounts of a probiotic component, butyrate, glutathione, resveratrol, nicotinamide ribonucleoside, nicotinamide adenine dinucleotide (NADH), L-carnitine, L- tyrosine, L-tartrate, alpha-ketoglutaric acid, ubiqionol, Membrane phospholipids, unsaturated fatty acids dichloroacetate, creatine, gluosamine, pyruvate, nicotinic acid, schisandrin, phosphatidylcholine and phosphatidyl nutrients, glycolipids and exogenous ketones, or combinations thereof. References:16,132-149 f.A component containing an effective amount of nutrients to support microbial, enterocyte and liver detoxification that includes, but is not limited to vitamins B2, B3, B5, B6 and B12, folinic acid, vitamin A, ascorbic acid , tocopherol, Selenium, copper, Magnesium, Zinc, Manganese, Iron, alpha-lipoic acid, N-acetylcysteine, molybdenum, Co-enzyme Q10, cysteine, methionine, taurine, glycine, glutamine, arginine, the essential and non-essential amino acids phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine, choline, curcumin, quercetin, green tea extract and ginseng, or combinations thereof. i. In some embodiments this component may also include effective amounts of ubiquinol, butyrate, glutathione and an antioxidant phytochemical component that may include resveratrol, lycopene, alpha-carotene, beta-carotene, lutein, ellagic acid, hesperidin, sulfurophanes which may be in the form of broccoli sprout powder or extract, and phytoestrogens such as genistein, or combinations thereof. References:134,135,141,150-167 g. A component containing an effective amount of nutrients to support appetite regulation and energy balance that includes, but is not limited to Vitamin D, Zinc, Calcium, Magnesium, taurine, chromium, EGCG, berberine, ginseng and green tea extract. i. In other embodiments this component may also include effective amounts of butyrate, cinnamon, ashwagandha, rehmannia, saffron extract, glucomannan, gymnema sylvestre and caffeine, or combinations thereof. ii. Certain embodiments may include a protein source that contains but is not limited to a plant-based protein powder such as pea protein isolate or brown rice isolate to make up all or part of the daily protein requirements as per proportions discussed in point 11. References: 168-186 h.A component containing an effective amount of nutrients to support neurological function and the synthesis of neurotransmitters that includes, but is not limited to a probiotic component as in 2., a prebiotic component as per 1., curcumin, quercetin, EGCG, berberine, ginseng, pycnogenol, phosphatidylserine, B-group vitamins, Vit C, Fe, Mg, Zn, Cu, green tea extract, tyrosine, taurine, tryptophan and phenylalanine, or combinations thereof. i. In some embodiments this component may also include effective amounts of phosphatidylcholine, caffeine, apigenin, resveratrol, rodeola rosea, ashwaghanda, ginkgo biloba, rhodiola, melatonin, bacopa monnieri, pyrroloquinoline quinone, S-adenosyl methionine, acetate, butyrate, creatine, L-carnitine, carnosine, a probiotic component that may include Lactobacillus spp., Bifidobacterium spp and/or Akkermansia mucinophilia, a prebiotic component that may include inulin, pectin, curcumin and green tea extract, fructo-oligosaccharides, green banana flour, glucomannan, konjac, galacto-oligosaccharides, burdock root, guar gum, tapioca, cranberry extract or juice, pomegranate extract or juice, concord grape extract or juice, or combinations thereof. References: 187-194 i. In certain embodiments of the disclosure the nutritional composition may include a longevity component that contains effective amounts of combination of the nutrients listed in items 14.a to 14.h. as well as but not limited to nicotinamide riboside, pyrroloquinoline quinone, d ribose, apigenin, nicotinamide mononucleotide and oxaloacete, in any combination thereof.

15.In the present disclosure, the nutritional compositions are considered nutraceuticals and are compounded in a compounding pharmacy. Each ingredient has undergone testing and quality control. The nutritional compositions are compounded and distributed to approved practitioners who meet the criteria of account holders of the compounding pharmacy.

a. In certain embodiments, the nutritional compositions may be produced in other accredited facilities and may be supplied through individuals or organisations approved by the inventor.

Dietary recommendations and techniques

16.The embodiment of the present disclosure includes dietary recommendations and techniques to addresses and support physioloigical processes listed in items 2.d,i to 2.d, vi as follows:

a. Improve microbial diversity in a subject by recommending a Mediterranean-style diet with an unlimited intake of non-starchy vegetables due to their high prebiotic and polyphenol content, combined with a moderate intake of protein mainly in the form of plant proteins which have been shown to improve microbial profiles, and a moderate intake of mono- and poly-unsaturated fats that help to reduce inflammation in immune cells of the gastrointestinal tract. i. The present method also recommendations avoiding processed foods, refined sugar, trans-fats, vegetable oils and all food additives and it advises to includes a range of gut-specific foods such as, but not limited to, bone broth, green banana flour, collagen, gelatin and fermented vegetables. ii. In the first stage of the method, which is two weeks in duration, the present method, includes a low carbohydrate intake of less 50g per day in the form of non-starchy vegetables and low sugar fruit. iii. The second stage of the method allows the addition of fruit, gluten-free wholegrains and starchy vegetables ranging from 50g to 200g total weight per serve to a maximum of three servings per day. This is expected to provide a carbohydrate intake of between 5g to 50g per serving. iv. In other embodiments the recommended total daily carbohydrate intake may range from 20g to 200g. References:104,195-198

b. Regulate immune function and assist detoxification in a subject by recommending a high intake of immune-regulatory, anti-inflammatory and antioxidant foods such as, but not limited to, green-leafy and coloured vegetables, fresh herbs and spices such as turmeric, garlic, ginger, and foods high in omega-3 fatty acids such as fish, flaxseed, avocados and olive oil. i. The present method recommends avoiding processed foods, refined sugar, trans-fats, vegetable oils and all food additives. ii. This embodiment also includes intermittent fasting with periods of abstinence from food ranging between twelve to fourteen hours overnight, between the times 6pm to 6am. iii. The embodiment of the present method includes a dietary fat portion ranging from 30 to 60% of the subjects' daily energy needs. This fat portion comes mainly from mono- and polyunsaturated fatty acids. iv. In the present method, the recommended intake of unsaturated fats is less than 20g per day for women and 30g for men. v. In other embodiments, abstinence from food may range between twelve to twenty-four hours. vi. In certain embodiments the dietary fat intake may range from 20% to 80% of the subjects' daily energy needs. References:152,199-201 c. Accelerate weight loss, increase satiety. improve metabolic and mitochondrial function, improve glycaemic control and assist with several relevant aspects of brain function in a subject, by incorporating a number of dietary techniques. i. The embodiment of the present method includes a combination of intermittent fasting, periods of calorie restriction, a low carbohydrate, moderate protein and fat intake and specific meal timing. This combination is expected to achieve the desired effects of sustained weight loss, and intermittently lead the subject into the beneficial state of ketosis, without disrupting the gut microbiota or increasing the risk of weight regain. ii. In Stage 1 of the present embodiment, this is achieved by recommending no more than three meals a day, without snacks, within a specified time frame between the hours of 6am to 6 pm. It is recommended that breakfast is consumed between 6am to 8am, lunch at 1pm and dinner at 6pm. In addition, the subject will consume a variety to dietary fibres and polyphenols at each meal aim to maintain microbial diversity, and a total daily macronutrient composition that assists with all processes listed above In Stage 1, this is achieved with a carbohydrate intake of less than 50g per day and a protein intake between than 0.7-2mg per kg of body weight and fat intake of 30g to 120g per day. iii. In Stage 2, the carbohydrate intake becomes self-directed with a maximum intake of 150g per day, while the remaining recommendations remain the same. iv. In other embodiments the subject may consume less than 20gs of carbohydrates per day for a period ranging between three and six weeks. v. In certain embodiments the recommendations include intermittent fasting with periods of abstinence from food ranging between twelve to twenty-four hours. vi. In some embodiments the macronutrient intake may calculated as percentage of the subjects' energy need with carbohydrate intake ranging from 10% to 40%, protein intake ranging from 15% to 40% and fat intake ranging from 30% to 80% of the total energy needs. vii. In certain embodiments the nutritional compositions may contain a protein component that may contain but is not limited to ingredients such as pea protein isolate or brown rice isolate to make up all or part of the daily protein requirements. viii. In some embodiments the nutritional compositions may include a fat source that may contain but is not limited to ingredients such as a as medium-chain triglyceride oil or flaxseed to make up all or part of the daily fat requirements. ix. In certain embodiments the nutritional compositions may include a carbohydrate component that may contain but is not limited to ingredients such as coconut sugar or palm sugar to make up all or part of the daily carbohydrate requirements. x. Other embodiments may include short-term calorie restrictions ranging from 30 percentage to 70 percent of the standard recommended calorie intake for the subject according to their sex, age and/or Basal Metabolic Rate, the daily calorie intake may range from 600 and 2400 calories and the duration of each stage of the method may range from two and twelve weeks. References:87-90,92,94,96,98,100,101,202-219.

17.Prevent homeostatic responses to weight loss and improve long-term weight maintenance in subjects by recommending consistency in meal timing and food choices to ensure the development of new habits. This is combined with a long-term low carbohydrate diet that allows a self-directed intake of carbohydrates ranging from 50g to 200g, depending on the subjects' glycaemic control, as determined by their weight. a. The present method recommends incorporating various forms of intermittent fasting for continued weight loss beyond the six-week method. Subjects are encouraged to incorporate either; i. An alternate-day fast schedule with a modified fast regimen during which the subject consumes approximately 600 calories a day on the fasting days, on a rotating basis for a period of no longer than two weeks followed by a period of four weeks when the subject eats to satiety. ii. Daily periods of abstinence of 16 hours duration on a rotating basis for a period of no longer than two weeks followed by a period of four weeks when the subject eats to satiety. b. In the present disclosure, other recommendations include the long-term avoidance of cheat meals, processed foods, refined sugar, trans-fats, vegetable oils, gluten-containing products and food additives. c. In the present disclosure, subjects are instructed on the careful reintroduction of certain foods on completion of the method in order to identify food intolerances. d. In certain embodiments the recommendations on completion of the six-week method, may include intermittent fasting with periods of abstinence from food ranging between twelve to twenty-four hours and/or alternate-day fasts with fasting days during which the subject consumes approximately 500 calories or less. e. In certain embodiments the recommendations on completion of the six-week method, may include intermittent fasting of twenty four hours to 36 hours. In some embodiments the recommendations on completion of the six-week method, may include intermittent fasting with periods of abstinence from food ranging between twelve to twenty-four hours f. In other embodiments the recommendations on completion of the six-week method, may include a once-a-week fasting day during which the subject consumes approximately 200 calories or less. References:87-90,92,94,96,98,100,101,202-219.

Additional components and inclusions of the weight management system

18.The present disclosure is sold as a product through accredited providers. The provider must assess the subjects medical and symptom history based on their responses to a 2-page questionnaire. This assessment can be performed without the subject being physically present, which means the method can be provided online through company websites or social media pages. 19.In other embodiments the method does not require a provider, but assessment can be automated through online sources or is assessed by the subject themselves 20.In the embodiment of the present method, the health questionnaire identifies subjects who have contraindications to the weight management system. These include chronic kidney, liver or heart disease (excluding fatty liver disease), TB, HIV, hepatitis, an eating disorder, cancer or undergoing chemotherapy or radiotherapy, pregnant or breast-feeding, anaphylaxis to or toxicity to vitamins, nutrients or supplements in the compositions. Type 1 Diabetes is not an absolute contraindication however requires strict medical supervision. 21.Certain embodiments may include additional contraindications as guided by emerging or new scientific evidence. 22.Other embodiments may have no contraindications. 23.The health questionnaire also identifies subjects who have a medical condition or symptoms that may benefit from dietary modifications. These subjects may be provided with a Modification Handout according to their needs. There are five Modification Handouts, each one relevant to medical conditions or symptoms related to a particular system. See Table 3. 24.In certain embodiments there may be a separate Modification Handout for all or some of the conditions listed in the middle column of Table. 3. 25.In other embodiments there may not be any modification handouts. In other embodiments there may be modification handouts for peri-menopause or menopause, longevity, cancer, neurological or psychiatric conditions such as dementia, bipolar disease or autoimmune conditions such as multiple sclerosis. 26.In the embodiment of the present weight management system, when the assessment is complete, the method is ordered directly from the relevant supplier.

27.In other embodiments the weight management system may be ordered through the inventor or their company, or through an appointed producer and/or supplier and/or distributer of nutritional or nutraceutical products.

28.In the embodiment of the present disclosure, the subject receives the weight management system, which contains;

a. The nutritional compositions. b. A hard copy of the program manual containing comprehensive educational material, dietary guidance for both stages of the method, as well as guidance for long-term weight maintenance. i. The manual also includes lifestyle recommendations such a minimum of 30 minutes of daily exercise, approximately 20 minutes of daily meditation and exposure to sunlight as well as instructions on sleep hygiene. ii. To assist with exercise, the manual includes a 12-minute work-out and an interval training program. See Table 4. c. And, if needed, no more than two (2) modification handouts. 29.In other embodiments the program manual may be accessed online or emailed to the subject in a soft copy. 30.In certain embodiments, the program manual may not contain all of the inclusions in table 4. 31.In other embodiments the program manual may contain the all of the modifications and the subjects determines which one is appropriate based on self-assessment of their health questionnaire. 32.Other embodiments may not include modifications to the program, should research deem them unnecessary or should all aspects be covered within the program manual.

While this innovation has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the innovation encompassed by claims made in appended points 13, 14, 15, 16 and 17.

Table 1. Treatment areas and main actions of the nutrients used in the nutritional compositions in the present disclosure.

Table 1. Nutrients included in the nutritional formulations to support weight management

Microbial diversity Microbial metabolites Inulin, pectin, glutamine, glycine, proline, Vit D, Curcumin, EGCG, V Git integrity Energy supply quercetin, Vit A

Immune regulation Anti-inflammatory Vitamin D, C, A, E, Curcumin, Quercetin, ECGC, berberine, ginseng,

' Inhibit NFkb

Nutrient Status Fat oxidation B1, B2, B3 (niacinamide), B5, B6, Zinc, Mg, Choline, Biotin, Fe, Cu, Ca, J Mitochondrial Biogenesis/ mitophagy phosphate, manganese ALA, CoQ10, ascorbic acid, Tocopherol, Amino function Antioxidant/4,ROS acids, Curcumin, quercetin, EGCG, berberine, ginseng, pycnogenol Detoxification t Phase I & 11 B2, B3, B5, B6, Folinic acid, B12, Vit A, ascorbic acid, Tocopherol, Se, Cu,

/ t NF2rF Mg, Zn, Manganese, Fe, ALA, NAC, Molybdenum, CoQ1O, Cysteine, T Phase III elimination Methionine, Taurine, Glycine, Glutamine, Arginine, Choline, Curcumin, quercetin, EGCG, ginseng Energy Balance Satiety signals Vit D, Zinc, Ca, Mg, taurine, chromium, EGCG, berberine, ginseng V Appetite control Metabolism Thermogenesis Neurotransmitters Anti-inflammatory Curcumin, quercetin, EGCG, berberine, ginseng, pycnogenol, V HPA-axis Inhibit NFkb phosphatidylserine, B-group vitamins, Vit C, Fe, Mg, Zn, Cu, tyrosine, Neurogenesis Antioxidant/, ROS tryptophan, phenylalanine

Table 2. Treatment areas addressed by the dietary recommendations and techniques used in the present disclosure.

Table 2. Dietary recommendations and techniques to support weight management

V V eieraer-t V

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partptentheweghtlsssVtem

Table 3. Criteria for provision of Modification handouts Modification Sheet Medical Condition Svstems Review score

Gut Health Food intolerances Gut Health Crohn's Disease Ulcerative Colitis Irritable Bowel Disease

Immune Health Psoriasis, eczema, dermatitis Immune Health Psoriatic arthritis Rheumatoid arthritis Ankylosing spondylitis Fibromyalgia Metabolic Health Adrenal fatigue Metabolic Health Chronic fatigue syndrome Hypothyroidism Subclinical thyroid dysfunction Hormone Health Insulin Resistance Hormone Health Type 2 diabetes Polycystic Ovarian Syndrome Brain Health Mood disorders Brain Health Food addiction Cognitive decline

Table 4. Presents the Table of Contents in the manual provided to subjects who participate in the present method.

Table of Contents The Balanced Body Key Factors • Gut Health and the Microbiome • Nutrients and Mitochondria • Detoxification • Appetite Regulation and Weight Homeostasis • The Gut-Brain Connection

The ACPHARM Blome Protocol • Summary • General Information • Meal Plans • Allowed Food List * Forbidden Food List • The Formulas • How to take the Formulas • Frequently Asked Questions

Stage I • Restore Gut Health and ReduceInflammation • Meal Plan and Menu • Allowed Food List for Stage 1 &Stage 2 • Forbidden Food List for Stage 1 & Stage 2

Stage 2 • Replenish Nutrients, Remove Toxins and Rebalance Hormones • Meal Plan and Menu

Maintenance * Maintaining a new weight long-term • Re-introducing new foods • Finding your ideal carbohydrate intake level • Intermittent fasting for on-going weight loss

Lifestyle • Movement • Rest • Sleep • Sunlight

Appendices • Shopping List: Stage I &2 • Interval Training Plan • 12-Minute Workout • Recipes

Table 5. The daily total dose range for nutrients (in alphabetical order) used in the nutritional compositions of the present method. All doses are in milligrams.

Nutrient Daily dose (mg) Daily dose (mg) MINIMUM MAXIMUM -HTP 75.00 500.00 Acetylcysteine 500.00 600.00 Alpha-lipoicacid 600.00 1000.0 Arginine 90.0 130.00 Ascorbic Acid 1600.00 2000.00 Berberine 300.00 1000.0 Betaine 30.0 150 Biotin (mg) 0.03 1.0 Calcium 150.00 2000.0 Choline 225.00 400.0 Chromium 0.015 0.050 Copper 1.43 1.60

CoO 150.00 200.00 Cystine 150.00 160.00 Iron 8.00 15.00 Folinic Acid (mg) 0.45 0.50 Gingseng 200.00 1000.0 Glutamine 875.00 5000.0 Glutathione 50.00 600.00 Glycine 875.00 1000.0 Green tea extract 50.00 500 Histidine 75.00 700.00 Inositol 225.00 2000.0 Inulin 700.00 300.00 Iodine 0.1 0.16

Isoleucine 225.00 800.00 L-carnitine 600.0 1000.0 Leucine 225.00 1000.00 Lysine 225.00 1000.00 Magnesium 150.00 400.0 Manganese 1.00 2.00 Methionine 75.00 700 Methylcobalamin/Vit B12 0.45 0.60 Niacin 15.00 30.00 Niacinamide 75.00 150.00 P5P 1.00 30.00 Pectin 1000.00 3000.00 Phenylalanine 150.00 800.00 Phosphatidylserine 200.00 1000.00 Potassium 75.00 150.00 Proline 500.00 800.0 Pycnogenol 100.00 900.00 Quercetin 800.00 1000.00 Riboflavin 1.00 30.00 Selenium 0.015 0.070 Molybdenum 0.01 0.045 Taurine 500.00 1000.0 Threonine 150.00 800.00 Tyrosine 150.00 1000.00 Turmeric 1000.00 4000.00 Valine 300.00 1000.00 Vit E 7.00 20.00 Vitamin A 0.40 0.70 Vitamin B1 1.00 30.00 Vitamin B5 5.00 75.00

Vitamin D 0.01 0.1 Vitamin K2 0.10 0.15 Zinc 8.00 40.00

Table 6. Nutrients and ingredients (in alphabetical order), that may be included in the nutritional compositions of certain embodiments of present disclosure, in any combination thereof. This list is not limiting.

Nutrients Nutrients Nutrients Acetate Fructo-oligosaccharides Omega-3 fish oil Algae Galacto-oligosaccharides Orange oil Aloe vera extract, Genistein Pea protein powder powder or juice Alpha-carotene Ginkgo biloba Peppermint oil Alpha-ketoglutaric acid Glucomannan Phenolic acids Apigenin Glucosamine Phosphatidyl nutrients Ashwagandha Glutathione Phosphatidylcholine Bacopa monnieri Glycolipids Phytoestrogens Beta-carotene Glycyrrhiza glabra root Pyrroloquinoline quinone extract (licorice) Bifidobacterium spp Grape extract or juice Pyruvate Black tea extract Grapeseed oil Rehmannia Blackseed oil Green banana flour Reiishi mushroom Broccoli sprout powder Guar gum Resveratrol or extract Brown rice isolate Gymnema sylvestre Rhodiola Burdock root Hesperidin Rice bran extract (arabinoxylan) Butyrate Hydroxycinnamic acids Rodeola rosea Cacao extract or powder Konjac S-adenosyl methionine Caffeine L-tartrate Saffron extract Carnosine Lactobacillus spp. Schisandrin Caterpillar mushroom Lemon oil Shitake mushroom Cellulase Lignans Silybum marianum extract (milk thistle) Cinnamon Lutein Slippery elm bark powder Coconutsugar Lycopene Stilbenoids Cranberry extract or juice Maitake mushroom Sulfurophanes Creatine Mastic gum Tapioca Dichloroacetate MCT oil Terpenes Ellagic acid Melatonin Threonine Exogenous ketones Membrane phospholipids Tilactase Flavonoids Nicotinamide adenine Turkey tail mushroom dinucleotide (NADH)

Flaxseed oil Nicotinamide Ubiquinol ribonucleoside Nicotinic acid Vanilla extract or powder

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Editorial Note 2020101019 There is only thirty-eight pages of the claim

Claims For Innovation Patent Application Ref No. Innov290495

Claims 1to 9 refer to how specific components of the nutritional formulations benefit the key physiological processes relevant to weight management, as per items 2.d,i to 2.d, vi in the "Description" and Table 1, Table 5 and Table 6.

1. CLAIM 1 (References: 23,24, 39, 105-109)

i) The nutritional compositions include an effective amount of a prebiotic component to improve the composition of the gut microbiota, this includes, but is not limited to inulin, pectin, curcumin and green tea extract.

ii) In certain embodiments this component may also include of fructo oligosaccharides, green banana flour, glucomannan, konjac, galacto oligosaccharides, burdock root, guar gum, acacia gum, arabinogalactan, tapioca, cranberry extractor juice, pomegranate extract or juice, concord grape extract or juice, or combinations thereof.

2. CLAIM 2 (References: 109-125)

i) The nutritional compositions include an effective amount of nutrients to support the integrity of the gut wall that includes, but is not limited to inulin, pectin, glutamine, glycine, proline, vitamin D, curcumin, green tea extract, quercetin, vitamin A, a probiotic component that includes Lactobacillus spp. and Bifidobacterium spp, and a digestive enzyme component consisting of amylase, protease, lipase, bromelain and papain, or combinations thereof.

ii) In certain embodiments this component may also include effective amounts of butyrate, acetate, threonine, a probiotic component that includes Lactobacillus spp., Bifidobacterium spp and/or Akkermansia mucinophilia and a digestive component that includes cellulase and tilactase, flaxseed oil and grapeseed oil, or combinations thereof.

3. CLAIM 3 (References: 126-131) i) The nutritional compositions include an effective amount of an antioxidant/phytochemical component that includes, but is not limited to curcumin, quercetin, zinc, green tea extract, Coenzyme Q10, selenium, berberine, pycnogenol and ginseng, a vitamin component that includes vitamins A, B1, B6, B12, C, D and E, or combinations thereof.

ii) In some embodiments this component may also include effective amounts of antioxidants and herbs. Non-limiting examples include resveratrol, fisetin, pyrroloquinoline quinone, lycopene, alpha carotene, beta-carotene, lutein, xanthophylls, lignans, stilbenoids, phenolic acids, hesperidin, terpenes, hydroxycinnamic acids, lignans, flavonoids, black tea extract, sulfurophanes which may be in the form of broccoli sprout powder or extract, and phytoestrogens such as genistein, slippery elm bark powder, Silybum marianum extract (milk thistle), glycyrrhiza glabra root extract (licorice), mastic gum, orange oil, peppermint oil, lemon oil, vanilla extract or powder, cacao extract or powder, aloe vera extract, powder orjuice, or combinations thereof.

4. CLAIM 4 (References: 126-131)

i) The nutritional compositions include an effective amount of an anti inflammatory component that includes, but is not limited to Vitamins D, C, A and E, curcumin, quercetin, zinc, green tea extract, berberine, pycnogenol and ginseng, or combinations thereof.

ii) In other embodiments this component may also include effective amounts of omega-3 fish oil or a vegan omega-3 fatty acid source such as flaxseed oil or algae, a probiotic component, glutathione, resveratrol, butyrate, rice bran extract such as arabinoxylan and medicinal mushrooms such as turkey tail mushroom, maitake mushroom, reiishi mushroom, caterpillar mushroom and shitake mushroom, blackseed oil or grapeseed oil, or combinations thereof.

5. CLAIM 5 (References: 16, 132-149) i) A component that includes, but is not limited to, an effective amount of nutrients to support mitochondrial and metabolic function consisting of vitamins C, D, E, B1, B2, B3 (niacinamide), B5, B6, Zinc, Magnesium, Choline, Biotin, iron, copper, Calcium, phosphate, manganese, alpha-lipoic acid, CoQ10, ascorbic acid , Tocopherol, the essential and non-essential amino acids phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine,curcumin, quercetin, EGCG, berberine, ginseng and pycnogenol, or combinations thereof.

ii) In certain embodiments this component may also include effective amounts of a probiotic component, butyrate, glutathione, resveratrol, nicotinamide ribonucleoside, nicotinamide adenine dinucleotide (NADH), L-carnitine, L-tyrosine, L-tartrate, alpha-ketoglutaric acid, ubiqionol, Membrane phospholipids, unsaturated fatty acids dichloroacetate, creatine, gluosamine, pyruvate, nicotinic acid, schisandrin, phosphatidylcholine and phosphatidyl nutrients, glycolipids and exogenous ketones, or combinations thereof.

6. CLAIM 6 (References: 134, 135, 141, 150-167)

i) The nutritional compositions include a component containing an effective amount of nutrients to support microbial, enterocyte and liver detoxification that includes, but is not limited to vitamins B2, B3, B5, B6 and B12, folinic acid, vitamin A, ascorbic acid , tocopherol, Selenium, copper, Magnesium, Zinc, Manganese, Iron, alpha-lipoic acid, N-acetylcysteine, molybdenum, Co-enzyme Q10, cysteine, methionine, taurine, glycine, glutamine, arginine, the essential and non-essential amino acids phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine, choline, curcumin, quercetin, green tea extract and ginseng, or combinations thereof.

ii) In some embodiments this component may also include effective amounts of ubiquinol, butyrate, glutathione and an antioxidant phytochemical component that may include resveratrol, lycopene, alpha-carotene, beta-carotene, lutein, ellagic acid, hesperidin, sulfurophanes which may be in the form of broccoli sprout powder or extract, and phytoestrogens such as genistein, or combinations thereof.

7. CLAIM 7 (References: 168-186)

i) The nutritional compositions include a component containing an effective amount of nutrients to support appetite regulation and energy balance that includes, but is not limited to Vitamin D, Zinc, Calcium, Magnesium, taurine, chromium, EGCG, berberine, ginseng and green tea extract.

ii) In other embodiments this component may also include effective amounts of butyrate, cinnamon, ashwagandha, rehmannia, saffron extract, glucomannan, gymnema sylvestre and caffeine, or combinations thereof.

iii) Certain embodiments may include a protein source that contains but is not limited to a plant-based protein powder such as pea protein isolate or brown rice isolate to make up all or part of the daily protein requirements as per proportions discussed in point 11.

8. CLAIM 8 (References: 187-194)

i) The nutritional compositions include a component containing an effective amount of nutrients to support neurological function and the synthesis of neurotransmitters that includes, but is not limited to a probiotic component as in 2., a prebiotic component as per 1., curcumin, quercetin, EGCG, berberine, ginseng, pycnogenol, phosphatidylserine, B-group vitamins, Vit C, Fe, Mg, Zn, Cu, green tea extract, tyrosine, taurine, tryptophan and phenylalanine, or combinations thereof.

ii) In some embodiments this component may also include effective amounts of phosphatidylcholine, caffeine, apigenin, resveratrol, rodeola rosea, ashwaghanda, ginkgo biloba, rhodiola, melatonin, bacopa monnieri, pyrroloquinoline quinone, S-adenosyl methionine, acetate, butyrate, creatine, L-carnitine, carnosine, a probiotic component that may include Lactobacillus spp., Bifidobacterium spp and/or Akkermansia mucinophilia, a prebiotic component that may include inulin, pectin, curcumin and green tea extract, fructo oligosaccharides, green banana flour, glucomannan, konjac, galacto oligosaccharides, burdock root, guar gum, tapioca, cranberry extract or juice, pomegranate extract or juice, concord grape extract or juice, or combinations thereof.

iii) In some embodiments the nutritional compositions may include a fat source that may contain but is not limited to ingredients such as a as medium-chain triglyceride oil or flaxseed to make up all or part of the daily fat requirements.

9. CLAIM 9 (References: 187-194)

i) In certain embodiments of the innovation the nutritional composition may include a longevity component that contains effective amounts of combination of the nutrients listed in items 14.a to 14.h. as well as but not limited to nicotinamide riboside, pyrroloquinoline quinone, d ribose, apigenin, nicotinamide mononucleotide and oxaloacete, in any combination thereof.

ii) Claims 10 to 9 refer to how the dietary recommendations and techniques in the innovation benefit the key physiological processes relevant to weight management, as per items 2.d,i to 2.d, vi in the "Description" and Table 2.

10.CLAIM 10 (References: 104, 195-198)

i) The dietary recommendations and specific techniques advised in the innovation improve microbial diversity in a subject by recommending a Mediterranean-style diet with an unlimited intake of non-starchy vegetables due to their high prebiotic and polyphenol content, combined with a moderate intake of protein mainly in the form of plant proteins which have been shown to improve microbial profiles, and a moderate intake of mono- and poly-unsaturated fats that help to reduce inflammation in immune cells of the gastrointestinal tract.

ii) The present method also recommends avoiding processed foods, refined sugar, trans-fats, vegetable oils and all food additives and it advises to includes a range of gut-specific foods such as, but not limited to, bone broth, green banana flour, collagen, gelatin and fermented vegetables.

11.CLAIM 11(References:152, 199-201)

i) The dietary recommendations and specific techniques advised in the innovation regulate immune function and assist detoxification in a subject by recommending a high intake of immune-regulatory, anti inflammatory and antioxidant foods such as, but not limited to, green leafy and coloured vegetables, fresh herbs and spices such as turmeric, garlic, ginger, and foods high in omega-3 fatty acids such as fish, flaxseed, avocados and olive oil.

ii) The present method also recommends avoiding processed foods, refined sugar, trans-fats, vegetable oils and all food additives.

iii) This embodiment also includes intermittent fasting with periods of abstinence from food ranging between twelve to fourteen hours overnight, between the times 6pm to 6am.

iv) The embodiment of the present method includes a dietary fat portion ranging from 30 to 60% of the subjects' daily energy needs. This fat portion comes mainly from mono- and polyunsaturated fatty acids.

v) In the present method, the recommended intake of unsaturated fats is less than 20g per day for women and 30g for men.

vi) In other embodiments, abstinence from food may range between twelve to twenty-four hours.

vii) In certain embodiments the dietary fat intake may range from 20% to 80% of the subjects' daily energy needs.

12.CLAIM 12 (References: 87-90, 92, 94, 96, 98, 100, 101, 202-219.) i) The dietary recommendations and specific techniques advised in the innovation accelerate weight loss, increase satiety. improve metabolic and mitochondrial function, improve glycaemic control and assist with several relevant aspects of brain function in a subject, by incorporating a number of dietary techniques.

ii) The embodiment of the present method includes a combination of intermittent fasting, periods of calorie restriction, a low carbohydrate, moderate protein and fat intake and specific meal timing. This combination is expected to achieve the desired effects of sustained weight loss, and intermittently lead the subject into the beneficial state of ketosis, without disrupting the gut microbiota or increasing the risk of weight regain.

iii) In Stage 1 of the present embodiment, this is achieved by recommending no more than three meals a day, without snacks, within a specified time frame between the hours of 6am to 6 pm. It is recommended that breakfast is consumed between 6am to 8am, lunch at 1pm and dinner at 6pm. In addition, the subject will consume a variety to dietary fibres and polyphenols at each meal aim to maintain microbial diversity, and a total daily macronutrient composition that assists with all processes listed above. In Stage 1, this is achieved with a carbohydrate intake of less than 50g per day and a protein intake between than 0.7-2mg per kg of body weight and fat intake of 30g to 120g per day.

iv) In Stage 2, the carbohydrate intake becomes self-directed with a maximum intake of 150g per day, while the remaining recommendations remain the same.

v) In other embodiments the subject may consume less than 20gs of carbohydrates per day for a period ranging between three and six weeks.

vi) In certain embodiments the recommendations include intermittent fasting with periods of abstinence from food ranging between twelve to twenty-four hours.

vii)In some embodiments the macronutrient intake may calculated as percentage of the subjects' energy need with carbohydrate intake ranging from 10% to 40%, protein intake ranging from 15% to 40% and fat intake ranging from 30% to 80% of the total energy needs.

(1) Other embodiments may include short-term calorie restrictions ranging from 30 percentage to 70 percent of the standard recommended calorie intake for the subject according to their sex, age and/or Basal Metabolic Rate, the daily calorie intake may range from 600 and 2400 calories and the duration of each stage of the method may range from two and twelve weeks.

13.CLAIM 13 (References: 87-90, 92, 94, 96, 98, 100, 101, 202-219.)

i) The dietary recommendations and specific techniques advised in the innovation Prevent homeostatic responses to weight loss and improve long-term weight maintenance in subjects by recommending consistency in meal timing and food choices to ensure the development of new habits. This is combined with a long-term low carbohydrate diet that allows a self-directed intake of carbohydrates ranging from 50g to 200g, depending on the subjects' glycaemic control, as determined by their weight.

ii) The present method recommends incorporating various forms of intermittent fasting for continued weight loss beyond the six-week method. Subjects are encouraged to incorporate either; (a) An alternate-day fast schedule with a modified fast regimen during which the subject consumes approximately 600 calories a day on the fasting days, on a rotating basis for a period of no longer than two weeks followed by a period of four weeks when the subject eats to satiety. (b) Daily periods of abstinence of 16 hours duration on a rotating basis for a period of no longer than two weeks followed by a period of four weeks when the subject eats to satiety.

iii) In the present disclosure, other recommendations include the long term avoidance of cheat meals, processed foods, refined sugar, trans fats, vegetable oils, gluten-containing products and food additives.

iv) In the present disclosure, subjects are instructed on the careful reintroduction of certain foods on completion of the method in order to identify food intolerances.

v) In certain embodiments the recommendations on completion of the six-week method, may include intermittent fasting with periods of abstinence from food ranging between twelve to twenty-four hours and/or alternate-day fasts with fasting days during which the subject consumes approximately 500 calories or less.

vi) In certain embodiments the recommendations on completion of the six-week method, may include intermittent fasting of twenty-four hours to 36 hours. In some embodiments the recommendations on completion of the six-week method, may include intermittent fasting with periods of abstinence from food ranging between twelve to twenty-four hours

vii) In other embodiments the recommendations on completion of the six-week method, may include a once-a-week fasting day during which the subject consumes approximately 200 calories or less.

Table 1. Nutrients included in the nutritional formulations to support weight management

Microbial diversity Microbial metabolites Inulin, pectin, glutamine, glycine, proline, Vit D, Curcumin, EGCG, Git integrity Energy supply quercetin, Vit A

Immune regulation Anti-inflammatory Vitamin D, C, A, E, Curcumin, Quercetin, ECGC, berberine, ginseng, Inhibit NFkb

Nutrient Status Fat oxidation B1, B2, B3 (niacinamide), 85, B6, Zinc, Mg, Choline, Biotin, Fe, Cu, Ca, V Mitochondrial Biogenesis/ mitophagy phosphate, manganese ALA, CoQ10, ascorbic acid, Tocopherol, Amino function Antioxidant/4.ROS acids, Curcumin, quercetin, EGCG, berberine, ginseng, pycnogenol Detoxification t Phase I &Il B2, B3, B5, B6, Folinic acid, B12, Vit A, ascorbic acid, Tocopherol, Se, Cu, %/ T NF2rF Mg, Zn, Manganese, Fe, ALA, NAC, Molybdenum, CoQ10, Cysteine, t Phase II elimination Methionine, Taurine, Glycine, Glutamine, Arginine, Choline, Curcumin, quercetin, EGCG, ginseng Energy Balance Satiety signals Vit D, Zinc, Ca, Mg, taurine, chromium, EGCG, berberine, ginseng i Appetite control Metabolism Thermogenesis Neurotransmitters Anti-inflammatory Curcumin, quercetin, EGCG, berberine, ginseng, pycnogenol, /

HPA-axis Inhibit NFkb phosphatidylserine, B-group vitamins, Vit C, Fe, Mg, Zn, Cu, tyrosine, Neurogenesis Antioxidant/4,ROS tryptophan, phenylalanine

Table 2. Treatment areas addressed by the dietary recommendations and techniques used in the present disclosure.

Table 2. Dietary recommendations and techniques to support weight management

(mg Daily dose/ g

TableThdaily~ it Wta oernger fntrin1ts(naabe tial order) use i 01

NurintDiltds VV v

% etane 150

Aemtystein 50.0I000

Alh-ipiai 600.00 100. Table 5. The daily total dose range for nutrients (in alphabetical order) used in the nutritional compositions of the present method. All doses are inmilligrams. Bererin 30000100. Nutrient Daily dose (mg) Daily dose (mg) ________________MINIMUM MAXIMUM -HTP 75.00 500 Acetylcysteine 500.00 600.00 Alpha-lipoicacid 600.00 100.0 Arginine 90.0 130.00 Ascorbic Acid 1600.00 2000.00 Berberine 300.00 10. Betaine 30.0 150 Biotin (mg) 0.03 1.0 Calcium 150.00 20. Choline 225.00 400.0

Chromium 0.015 0.050 Copper 1.43 1.60

CoO 150.00 200.00 Cystine 150.00 160.00 Iron 8.00 15.00 Folinic Acid (mg) 0.45 0.50 Gingseng 200.00 1000.0 Glutamine 875.00 5000.0 Glutathione 50.00 600.00 Glycine 875.00 1000.0 Green tea extract 50.00 500 Histidine 75.00 700.00 Inositol 225.00 2000.0 Inulin 700.00 300.00 Iodine 0.1 0.16 Isoleucine 225.00 800.00 L-carnitine 600.0 1000.0 Leucine 225.00 1000.00 Lysine 225.00 1000.00 Magnesium 150.00 400.0 Manganese 1.00 2.00 Methionine 75.00 700 Methylcobalamin/Vit B12 0.45 0.60 Niacin 15.00 30.00 Niacinamide 75.00 150.00 P5P 1.00 30.00 Pectin 1000.00 3000.00 Phenylalanine 150.00 800.00 Phosphatidylserine 200.00 1000.00

Potassium 75.00 150.00 Proline 500.00 800.0 Pycnogenol 100.00 900.00 Quercetin 800.00 1000.00 Riboflavin 1.00 30.00 Selenium 0.015 0.070 Molybdenum 0.01 0.045 Taurine 500.00 1000.0 Threonine 150.00 800.00 Tyrosine 150.00 1000.00 Turmeric 1000.00 4000.00 Valine 300.00 1000.00 Vit E 7.00 20.00 Vitamin A 0.40 0.70 Vitamin B1 1.00 30.00 Vitamin B5 5.00 75.00 Vitamin D 0.01 0.1 Vitamin K2 0.10 0.15 Zinc 8.00 40.00

Table 6. Nutrients and ingredients (in alphabetical order), that may be included in the nutritional compositions of certain embodiments of present disclosure, in any combination thereof. This list is not limiting.

Nutrients Nutrients Nutrients Acetate Fructo-oligosaccharides Omega-3 fish oil Algae Galacto-oligosaccharides Orange oil Aloe vera extract, Genistein Pea protein powder powder or juice Alpha-carotene Ginkgo biloba Peppermint oil Alpha-ketoglutaric acid Glucomannan Phenolic acids

Apigenin Glucosamine Phosphatidyl nutrients Ashwagandha Glutathione Phosphatidylcholine Bacopa monnieri Glycolipids Phytoestrogens Beta-carotene Glycyrrhiza glabra root Pyrroloquinoline quinone extract (licorice) Bifidobacterium spp Grape extract or juice Pyruvate Black tea extract Grapeseed oil Rehmannia Blackseed oil Green banana flour Reiishi mushroom Broccoli sprout powder Guar gum Resveratrol or extract Brown rice isolate Gymnema sylvestre Rhodiola Burdock root Hesperidin Rice bran extract (arabinoxylan) Butyrate Hydroxycinnamic acids Rodeola rosea Cacao extract or powder Konjac S-adenosyl methionine Caffeine L-tartrate Saffron extract Carnosine Lactobacillus spp. Schisandrin Caterpillar mushroom Lemon oil Shitake mushroom Cellulase Lignans Silybum marianum extract (milk thistle) Cinnamon Lutein Slippery elm bark powder Coconutsugar Lycopene Stilbenoids Cranberry extract or juice Maitake mushroom Sulfurophanes Creatine Mastic gum Tapioca Dichloroacetate MCT oil Terpenes Ellagic acid Melatonin Threonine Exogenous ketones Membrane phospholipids Tilactase Flavonoids Nicotinamide adenine Turkey tail mushroom dinucleotide (NADH) Flaxseed oil Nicotinamide Ubiquinol ribonucleoside Nicotinic acid Vanilla extract or powder

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