Compositions and methods for improvement and maintenance of weight loss

Abstract

To provide a nutritional composition for use in a weight loss dietary intervention or maintenance of weight, particularly following a dietary intervention, preferably a low caloric diet intervention.SOLUTION: The nutritional composition comprises one or more amino acids, or combinations thereof, selected from the group consisting of proline, histidine, glycine, and / or hydroxyproline, which can be used to help the weight loss in obese subjects that are resistant to weight loss by caloric restricted dietary interventions alone. In addition, the nutritional composition of the invention can be used to help maintain the weight loss, particularly after dietary intervention.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention provides a nutritional composition for use in dietary intervention for weight loss, or particularly for weight maintenance after dietary intervention, preferably a low-calorie dietary intervention. The nutritional composition comprises one or more amino acids selected from the group consisting of proline, histidine, glycine, and / or hydroxyproline, or a combination thereof, which can be used to support weight loss in obese subjects who are resistant to weight loss through calorie-restricted dietary intervention alone. Furthermore, the nutritional composition of the present invention can be used to support weight loss maintenance, particularly after dietary intervention. [Background technology]

[0002] Obesity is a chronic metabolic disorder that is prevalent in many parts of the world and is a major risk factor for serious comorbidities such as type 2 diabetes, cardiovascular disease, dyslipidemia, and certain cancers (World Health Organ Tech Rep Ser. 2000;894:i-xii,1-253).

[0003] It has long been recognized that hypocaloric dietary interventions can be highly effective in weight loss, and that this weight loss improves the risk of obesity-related comorbidities in general, and type 2 diabetes in particular. Empirical data suggest that a weight loss of at least 10% of initial body weight substantially reduces the risk of obesity-related comorbidities (World Health Organ Tech Rep Ser. 2000;894:i-xii,1-253).

[0004] However, weight loss performance varies widely among subjects. Several studies have shown that a certain percentage of individuals fail to successfully lose weight through calorie restriction or low-calorie diets (Ghosh, S. et al., Obesity, 2011, 19(2):457-463). This, in turn, leads to unrealistic weight loss expectations, nonadherence to dietary interventions, dropouts, and, most commonly, failure. In fact, studies have shown a 10-fold variation in weight loss among well-adhered subjects with similar BMIs undergoing the same standardized weight loss program. These observations have led to the definition of the obese phenotype: weight loss resistance (Harper et al., Diabetes, (2002) 51:2459-2466).

[0005] Some studies suggest that subjects predicted to have a weight loss-resistant or diet-resistant obesity phenotype may be considered for bariatric surgery, which includes a variety of surgical procedures that treat obesity by modifying the gastrointestinal tract to reduce nutrient intake and / or absorption.

[0006] Clearly, there is a need for simpler and less invasive compositions and methods for weight loss-resistant or diet-resistant obese subjects.

[0007] [Summary of the Invention] Nutritional Composition In some embodiments, compositions are provided, particularly nutritional compositions, for use in weight loss during a dietary intervention or for weight maintenance after a dietary intervention. In a preferred embodiment, the dietary intervention is a low-calorie diet.

[0008] In one embodiment, the nutritional composition comprises one or more amino acids for use in weight loss during a dietary intervention or weight maintenance after a dietary intervention. In a preferred embodiment, the dietary intervention is a low calorie diet.

[0009] In one embodiment, the nutritional composition comprises one or more amino acids selected from the group consisting of proline, histidine, glycine, and / or hydroxyproline, or mixtures thereof, for use in weight loss during a dietary intervention or weight maintenance after a dietary intervention. In a preferred embodiment, the dietary intervention is a low-calorie diet.

[0010] In one embodiment, the nutritional composition contains at least proline for use in weight loss during a dietary intervention or weight maintenance after a dietary intervention. In a preferred embodiment, the dietary intervention is a low calorie diet.

[0011] In one embodiment, the nutritional composition contains at least proline and histidine for use in weight loss during a dietary intervention or weight maintenance after a dietary intervention. In a preferred embodiment, the dietary intervention is a low calorie diet.

[0012] In one embodiment, the nutritional composition contains at least proline, histidine, and glycine for use in weight loss during a dietary intervention or weight maintenance after a dietary intervention. In a preferred embodiment, the dietary intervention is a low-calorie diet.

[0013] In one embodiment, the nutritional composition contains at least proline, histidine, glycine, and hydroxyproline for use in weight loss during a dietary intervention or weight maintenance after a dietary intervention. In a preferred embodiment, the dietary intervention is a low-calorie diet.

[0014] In a preferred embodiment, the nutritional compositions of the present invention improve fat mass loss in a subject following dietary intervention, hi a preferred embodiment, the dietary intervention is a low-calorie diet.

[0015] In another preferred embodiment, the nutritional composition of the present invention improves BMI in a subject following a dietary intervention. In a preferred embodiment, the dietary intervention is a low-calorie diet.

[0016] In a further preferred embodiment, the nutritional compositions of the present invention maintain the loss of fat mass in a subject following a dietary intervention. In a preferred embodiment, the dietary intervention is a low-calorie diet.

[0017] In another preferred embodiment, the nutritional compositions of the present invention maintain BMI in a subject following a dietary intervention. In a preferred embodiment, the dietary intervention is a low-calorie diet.

[0018] In other embodiments, the nutritional composition containing one or more amino acids is formulated in and administered together with a diet product that includes (i) a fat source, (ii) a carbohydrate source, and (iii) a protein source.

[0019] In one embodiment, nutritional compositions containing one or more amino acids are administered simultaneously, sequentially, or separately to a subject.

[0020] In other embodiments, the nutritional composition containing one or more amino acids is formulated in and administered together in a diet product that includes (i) a fat source, (ii) a carbohydrate source, and (iii) a protein source.

[0021] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 40% or more of the average daily calorie intake of a subject during a reduced calorie dietary intervention.

[0022] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 70% or more of the average daily calorie intake of a subject during a reduced calorie dietary intervention.

[0023] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 80% or more of the average daily calorie intake of a subject during a reduced calorie dietary intervention.

[0024] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 90% or more of the average daily calorie intake of a subject during a reduced calorie dietary intervention.

[0025] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 100% of a subject's average daily calorie intake during a reduced calorie diet intervention.

[0026] In one embodiment, the subject's average daily calorie intake is from about 600 kcal to about 1500 kcal during the low-calorie dietary intervention.

[0027] In another embodiment, the nutritional compositions containing one or more amino acids of the present invention are formulated into a diet product along with (i) a fat source, (ii) a carbohydrate source, and (iii) a protein source and provided after weight loss to help maintain the lost weight.

[0028] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 40% of a subject's daily caloric intake during weight maintenance following a hypocaloric dietary intervention.

[0029] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 30% of a subject's daily caloric intake during weight maintenance following a hypocaloric dietary intervention.

[0030] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 20% of a subject's daily caloric intake during weight maintenance following a hypocaloric dietary intervention.

[0031] In one embodiment, the nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention provides 10% of a subject's daily caloric intake during weight maintenance following a hypocaloric dietary intervention.

[0032] In another embodiment, after achieving an ideal body weight, a subject may consume a nutritional formulation of a diet product containing a nutritional composition of the present invention comprising one or more amino acids of the present invention for up to about 26 weeks during a weight maintenance period.

[0033] In one embodiment, the nutritional composition provides 1 g to 10 g of the subject's average daily proline intake during the dietary intervention or for the weight maintenance period following the dietary intervention.

[0034] In one embodiment, the nutritional composition provides 1 g to 10 g of the subject's average daily histidine intake during the dietary intervention or for the weight maintenance period following the dietary intervention.

[0035] In one embodiment, the nutritional composition provides 1 g to 10 g of the subject's average daily glycine intake during the dietary intervention or for the weight maintenance period following the dietary intervention.

[0036] In one embodiment, the nutritional composition provides a subject with a daily hydroxyproline intake of 1 g to 10 g during the dietary intervention or for weight maintenance following the dietary intervention.

[0037] In one embodiment, the subject has been diagnosed with diet-resistant obesity or weight-loss-resistant obesity prior to dietary intervention and is in need of the nutritional composition of the present invention.

[0038] In one embodiment, the subject has been diagnosed with diet-resistant obesity or weight-loss-resistant obesity prior to the dietary intervention by measuring the levels of amino acids in the blood, particularly in red blood cells, namely proline, histidine, glycine, and / or hydroxyproline, and when any of these values ​​are below a reference value, the subject may be considered to be at risk of diet-resistant or weight-loss-resistant.

[0039] amino acid In some embodiments, the nutritional compositions of the present invention comprise one or more amino acids selected from the group consisting of proline, histidine, glycine, and / or hydroxyproline.

[0040] Methods and Uses In one embodiment, the nutritional compositions of the present invention are suitable for use in weight loss during hypocaloric dietary intervention.

[0041] In one embodiment, the nutritional composition is suitable for use in improving fat mass loss during hypocaloric dietary intervention.

[0042] In another embodiment, the nutritional composition is suitable for use in improving BMI during hypocaloric dietary intervention.

[0043] In one embodiment, the nutritional composition is suitable for use in maintaining weight loss following dietary intervention.

[0044] In one embodiment, the nutritional composition is suitable for use in maintaining fat mass loss following dietary intervention.

[0045] In another embodiment, the nutritional composition is suitable for use in maintaining BMI following dietary intervention.

[0046] In one embodiment, the dietary intervention is the administration of the nutritional compositions of the present invention as part of a reduced calorie diet.

[0047] In one embodiment, the low calorie diet includes a reduction in fat intake.

[0048] In one embodiment, the reduced calorie diet includes an increased intake of low-fat foods.

[0049] In one embodiment, the nutritional compositions and reduced calorie diets of the present invention provide an average of 600 to about 1500 kcal per day to a subject.

[0050] In one embodiment, the reduced calorie diet reduces calorie intake by an average of 10% or more per day compared to the average daily calorie intake prior to administration of the reduced calorie diet.

[0051] In one embodiment, the reduced calorie diet reduces calorie intake by an average of 15% or more per day compared to the average daily calorie intake prior to administration of the reduced calorie diet.

[0052] In one embodiment, the reduced calorie diet reduces calorie intake by an average of 20% or more per day compared to the average daily calorie intake prior to administration of the reduced calorie diet.

[0053] In one embodiment, the reduced calorie diet reduces calorie intake compared to the average daily calorie intake during the two weeks immediately preceding administration of the reduced calorie diet.

[0054] In one embodiment, the reduced calorie diet is administered for a period of up to 12 weeks, hi another embodiment, the reduced calorie diet is administered for a period of up to 6-12 weeks.

[0055] Methods of making the nutritional compositions of the present invention are provided for administering the nutritional compositions in a form suitable for the administration of the compositions of the present invention, particularly to weight-resistant obese subjects or diet-resistant obese subjects.

[0056] In one embodiment, the method for weight loss using the nutritional composition of the present invention is also suitable for reducing fat mass and improving BMI during dietary intervention.

[0057] In one embodiment, the method of weight loss using the nutritional compositions of the present invention is suitable for administering a reduced calorie diet to a diet-resistant obese subject or a weight-loss-resistant obese subject.

[0058] The methods of the present invention may further include assessing one or more anthropometric measures and / or lifestyle characteristics of the subject to determine whether the subject is in need of a composition of the present invention to achieve or maintain weight loss.

[0059] The anthropometric measures may be selected from the group consisting of gender, weight, height, and age.

[0060] A lifestyle characteristic may be, for example, whether the subject is a smoker or a non-smoker, whether the subject consumes alcohol on average above the recommended daily intake, or whether the subject consumes less than the recommended daily exercise level on average.

[0061] Also provided is a method of optimizing one or more dietary interventions, comprising assessing a subject's predisposition to achievable weight loss with one or more dietary interventions and / or to maintaining achievable weight loss in the subject after one or more dietary interventions, and administering the one or more dietary interventions to the subject.

[0062] In one embodiment, the dietary intervention is a low-calorie diet.

[0063] In another aspect of the present invention, a reduced calorie diet is provided for use in a weight loss program in which the diet product is administered to a subject expected to achieve weight loss.

[0064] In another aspect, a diet product is provided for use as part of a reduced calorie diet for weight loss, wherein the diet product is administered to a subject expected to achieve weight loss or weight maintenance.

[0065] In another aspect, a diet product is provided for use as part of a reduced calorie diet for weight loss, wherein the diet product is administered to a subject expected to achieve both weight maintenance and weight loss.

[0066] In another aspect, a diet product is provided for use in treating obesity or an obesity-related disorder, wherein the diet product is administered to a subject expected to achieve weight maintenance and / or weight loss.

[0067] In one embodiment, the dietary product comprises Optifast® or Modifast® supplemented with one or more amino acids of the present invention.

[0068] Parts kit There is provided a kit of parts for use according to the present invention, the kit comprising, as parts: (i) a dietary product; (ii) a nutritional composition containing one or more amino acids of the present invention; and (iii) instructions for their use.

[0069] In one embodiment, the diet product comprises one or more of: (i) a fat source, (ii) a carbohydrate source, and (iii) a protein source.

[0070] In one embodiment, the diet product comprises two or more of: (i) a fat source, (ii) a carbohydrate source, and (iii) a protein source.

[0071] In one embodiment, a kit of parts comprising (i) a diet product, (ii) a nutritional composition containing one or more amino acids, and (iii) instructions for their use is administered simultaneously, sequentially, or separately to a diet-resistant or weight-loss-resistant obese subject.

[0072] In one embodiment, a nutritional composition containing one or more amino acids is administered to a subject with one or more particular amino acids administered simultaneously, sequentially, or separately.

[0073] In other embodiments, the nutritional composition containing one or more amino acids is administered together in a diet product containing (i) a fat source, (ii) a carbohydrate source, and (iii) a protein source.

[0074] In one embodiment, the kit is used in improving weight loss during dietary intervention, particularly during low-calorie dietary intervention.

[0075] In one embodiment, the kit is used in maintaining weight loss following dietary intervention, particularly following a low-calorie dietary intervention.

[0076] Also provided is a method for making the kit of parts of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0077] All percentages are by weight relative to the total weight of the composition unless otherwise specified.Similarly, all ratios are by weight unless otherwise specified.When reference is made to pH, the value corresponds to the pH measured at 25°C by standard equipment.As used herein, "about," "approximately," and "substantially" are understood to refer to a number within a numerical range, for example, within -10% to +10% of the referenced number, preferably within -5% to +5%, more preferably within -1% to +1%, and most preferably within -0.1% to +0.1% of the referenced number.

[0078] Furthermore, all numerical ranges herein should be understood to include all integers, whole numbers, or fractions within that range. Furthermore, these numerical ranges should be interpreted as supporting claims directed to any number or subset of numbers within that range. For example, a disclosure of 1 to 10 should be interpreted as supporting ranges of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0079] As used in this specification and the appended claims, singular words include the plural unless the context clearly indicates otherwise. Thus, "a," "an," and "the" generally include the plural of the respective term. For example, a reference to "an ingredient" or "a method" includes a plurality of such "ingredients" or "methods." The term "and / or" when used in the context of "X and / or Y" should be interpreted as "X" or "Y" or "X and Y." Similarly, "at least one of X or Y" should be interpreted as "X" or "Y" or "both X and Y."

[0080] Similarly, the terms "comprise," "comprises," and "comprising" should be interpreted as inclusive rather than exclusive. Similarly, the terms "include," "including," and "or" should all be interpreted as inclusive unless such interpretation is clearly prevented by the context. However, embodiments provided by the present disclosure may not include any element not specifically disclosed herein. Thus, disclosure of an embodiment defined using the term "comprising" is also a disclosure of embodiments "essentially comprising" and "comprising" the disclosed component. "Essentially comprising" means that the embodiment contains more than 50% by weight of the specified component, preferably at least 75% by weight of the specified component, more preferably at least 85% by weight of the specified component, and most preferably at least 95% by weight of the specified component, for example, at least 99% by weight of the specified component.

[0081] As used herein, the term "example," particularly when followed by a list of terms, is merely exemplary and illustrative and should not be considered exclusive or comprehensive. All embodiments disclosed herein can be combined with any other embodiment disclosed herein, unless expressly stated otherwise.

[0082] The relative terms "improved," "increased," and "enhanced," etc., refer to the effect of a composition containing any one or more amino acids of the invention relative to an otherwise identical composition that does not contain, or is low in, one or more of the amino acids.

[0083] The terms "dietary product," "nutritional composition," and "nutritional formulation" refer to a product or composition comprising at least one amino acid of the present invention that is intended to be ingested by an individual, such as a human, and that provides at least one nutrient to the individual. The compositions of the present disclosure, including the many embodiments described herein, may include, consist of, or consist essentially of any additional or optional ingredients, components, or limitations described herein or useful in a diet, in addition to the essential elements and limitations described herein.

[0084] As used herein, "complete nutrition" refers to a composition containing sufficient types and levels of macronutrients (protein, lipids, and carbohydrates) and micronutrients to be the sole source of nutrition for the animal to which the composition is administered, such that the individual can receive 100% of the nutrients the individual needs from such a complete nutritional composition.

[0085] "Animal" includes, but is not limited to, mammals, including rodents, aquatic mammals, domestic animals such as dogs and cats, livestock such as sheep, pigs, cows and horses, and humans. When "animal," "mammal," or their plural forms are used, these terms apply to any animal to which the context of this section may apply, or which may be intended to apply. As used herein, the term "subject" or "patient" is understood to include animals, e.g., mammals, preferably humans, that are undergoing or will undergo treatment as defined herein. As used herein, the terms "individual" and "patient" are often used to refer to humans, although the present disclosure is not limited to humans.

[0086] Accordingly, the terms "subject," "individual," and "patient" refer to any animal, mammal, or human that can benefit from the methods and compositions disclosed herein.

[0087] Compositions and Uses Thereof The "Compositions", particularly "Nutritional Compositions" and / or "Nutritional Formulations", in "Diet Products" containing the amino acids of the present invention are suitable for use in improving weight loss during dietary intervention and in maintaining weight after weight loss. Weight loss can be measured by any technique known to those skilled in the art.

[0088] "Weight loss," as defined herein, may refer to a decrease in parameters such as weight (e.g., in kilograms), body mass index (kgm-2), waist-to-hip ratio (e.g., in centimeters), fat mass (e.g., in kilograms), hip circumference (e.g., in centimeters), or waist circumference (e.g., in centimeters).

[0089] Weight loss may be calculated by subtracting the value of one or more of the aforementioned parameters at the end of the intervention from the value of the aforementioned parameters at the start of the intervention (e.g., when using an intervention according to the present invention).

[0090] The degree of weight loss may be expressed as a percentage change in one of the aforementioned phenotypic parameters of weight (e.g., a percentage change in a subject's body weight (e.g., in kilograms) or body mass index (kgm-2)). For example, a subject may lose at least 10% of their initial body weight, at least 8% of their initial body weight, or at least 5% of their initial body weight. By way of example only, a subject may lose 5-10% of their initial body weight.

[0091] In one embodiment, the risk of obesity-related comorbidities is significantly reduced if the degree of weight loss is at least 10% of the initial body weight.

[0092] As defined herein, "maintaining weight loss" can refer to maintaining a parameter such as body weight (e.g., in kilograms), body mass index (kgm), waist-to-hip ratio (e.g., in centimeters), fat mass (e.g., in kilograms), hip circumference (e.g., in centimeters), or waist circumference (e.g., in centimeters), or maintaining fat mass after an intervention such as a dietary intervention.

[0093] Typically, weight loss maintenance occurs after a period of weight loss achievement.

[0094] According to one aspect, the present invention provides a non-therapeutic use of the nutritional composition of the present invention for maintaining a healthy body composition following a period of weight loss.

[0095] Weight maintenance may be calculated by determining the change in one or more of the aforementioned parameters over a period of time, which may be, for example, at least 12, 15, 20, 26, 30, 36, 40, 46, or 50 weeks.

[0096] Weight maintenance may be expressed as weight regain during a period after weight loss has been achieved, for example, as a percentage of weight loss during weight loss achievement.

[0097] According to one aspect, the present invention provides for the inclusion of nutritional compositions and / or nutritional formulations in diet products of the present invention for use in achieving or maintaining weight loss in a subject.

[0098] Inclusion of the nutritional compositions and / or nutritional formulas in the dietary products of the present invention may also improve fat mass loss and BMI, which may be measured by any technique known to those skilled in the art.

[0099] subject The subject of the present invention is preferably a mammal. In a preferred embodiment, the subject is a human. Alternatively, the subject may be a non-human mammal, such as a horse, cow, sheep, or pig. In one embodiment, the subject is a companion animal, such as a dog or cat.

[0100] "Overweight" is defined for adult humans with a BMI of 25-30. "Body mass index," or "BMI," refers to the ratio of weight in kilograms divided by the square of height in meters. "Obesity" is a condition in which the natural energy reserves stored in adipose tissue of animals, particularly humans and other mammals, are increased to a point associated with certain health conditions or increased mortality. "Obesity" is defined for adult humans with a BMI greater than 30. For adults, "normal weight" is defined as a BMI of 18.5-25, while "underweight" can be defined as a BMI below 18.5.

[0101] Obesity-related disease refers to any condition that obese individuals are at increased risk of developing.

[0102] The obesity-related disease may be diabetes (eg, type 2 diabetes), stroke, high cholesterol, cardiovascular disease, insulin resistance, coronary heart disease, obesity syndrome, high blood pressure, or fatty liver.

[0103] The nutritional compositions for use described herein may be used to reduce fat mass and substantially maintain lean mass in a subject.

[0104] "Fat mass" refers to the portion of a subject's body that is composed of fat. Fat mass can be measured using a variety of methods, such as measuring skinfold thickness with a caliper, dual-energy X-ray absorptiometry, CT or MRI scans, or bioelectrical impedance analysis.

[0105] A reduction in fat mass can mean a reduction in fat mass of at least 1%, at least 2%, at least 5%, at least 10%, at least 15%, at least 20%, at least 30%, at least 40%, or at least 50%.

[0106] "Lean mass" or "lean body mass" refers to the portion of the body composition defined as the difference between total body weight and body fat mass. This means measuring the mass of all organs, including bone, muscle, blood, skin, and others, excluding body fat. Maintaining lean body mass is important for optimal metabolism, normal physical activity, and good health.

[0107] Substantial maintenance of lean mass can mean, for example, that the change in lean mass after or during the intervention is less than 7%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%.

[0108] Preferably, the primary weight loss is due to loss of non-lean mass or loss of fat mass, rather than lean mass.

[0109] The subject in the present invention is preferably diet-resistant obese or weight-loss-resistant obese. "Diet-resistant obese" or "weight-loss-resistant obese" can be defined as a subject in the lowest quintile of weight loss rate within a group of subjects 6 weeks after the start of a dietary intervention (Harper et al., 2002).

[0110] The degree of weight loss is preferably expressed in terms of a reduction in BMI units, where BMI reduction = ((BMI1-BMI2)*100) / BMI1, where BMI1 is the subject's body mass index before the dietary intervention and BMI2 is the subject's predicted body mass index after the dietary intervention.

[0111] Dietary intervention The term "dietary intervention" is understood to mean an external factor applied to a subject, which causes a change in the subject's eating habits. Preferably, the dietary intervention is a low-calorie diet.

[0112] A "low-calorie diet" includes an average calorie intake of about 600 to about 1500 kcal / day, more preferably about 600 to about 1200 kcal / day, even more preferably about 700 to about 900 kcal / day, and most preferably about 800 kcal / day.

[0113] In one embodiment, the reduced calorie diet may include a daily amount of vegetables, preferably up to about 400 g / day of vegetables, for example, up to about 200 g / day of vegetables. Low-fat foods include whole grain flours and breads, porridge oats, high-fiber breakfast cereals, brown rice and whole-grain pasta, vegetables and fruits, dried beans and lentils, baked potatoes, dried fruit, walnuts, white fish, herring, mackerel, sardines, smoked fish, pilchard, salmon, and lean white meats.

[0114] The reduced calorie diet may include the administration of at least one "diet product." A "diet product" may be formulated as a meal replacement product or a food supplement that may, for example, suppress a subject's appetite. Diet products may include foods, beverage products, pet food products, food supplements, nutraceuticals, food additives, or nutritional formulations.

[0115] In one embodiment, the diet product may include, for example, Optifast® or Modifast®.

[0116] The "diet product" may be supplemented with 3 portions of non-starchy vegetables for a total energy intake of approximately 2.5 MJ (600 kcal / day). The diet product may also be supplemented with at least 2 L of water or other energy-free beverage per day.

[0117] In another embodiment, a "diet product" may include, for example, a nutritional formulation containing the amino acid nutritional composition of the present invention and up to at least 46.4% carbohydrates, 32.5% protein, and 20.1% lipids, vitamins, minerals, and trace elements, and the diet product may be further supplemented with 3 portions of non-starchy vegetables to achieve a total energy intake of about 2.5 MJ (600 kcal / day) per serving, up to a total of 1500 kcal / day. The diet product may be further supplemented with at least 2 L of water or other energy-free beverage per day.

[0118] In one embodiment, the low-calorie diet has a duration of up to 12 weeks. Preferably, the low-calorie diet has a duration of 6 to 12 weeks, preferably 8 to 10 weeks, for example 8 weeks.

[0119] amino acid The term "amino acid" is a general term for organic compounds that contain both an amino group (-NH2) and a carboxyl group (-COOH).

[0120] In some embodiments of the present invention, specific amino acids and their derivatives are described.

[0121] Proline In some embodiments of the present invention, "proline" or "proline derivatives" are defined in the nutritional compositions, methods and uses.

[0122] "Proline" is an amino acid also known as L-proline; L-(-)proline; (S)-pyrrolidine-2-carboxylic acid; (2S)-pyrrolidine-2-carboxylic acid; (-)-proline, (-)-(S)-proline; prolinum; H-Pro-OH, 2-pyrrolidinecarboxylic acid; (S)-2-pyrrolidinecarboxylic acid; prolina, (-)-2-pyrrolidinecarboxylic acid; L-pyrrolidine-2-carboxylic acid; L-alpha-pyrrolidinecarboxylic acid; L-proline; and carboxypyrrolidine.

[0123] The "proline derivative" is preferably L-proline and / or cis-4-hydroxy-L-proline (CHP), trans-4-hydroxy-L-proline (THP), 4-hydroxy-1-methyl-proline, 1-methyl-4-phenylaminecarbonyloxy-proline, 1-methyl-4-phenylaminecarbonyloxy-proline, cis-4-hydroxymethyl-1-proline, trans-4-hydroxymethyl-D-proline, trans-4-hydroxymethyl-1-proline, trans-4-methyl-1-proline, cis-3-amino-1-proline, 1-methyl-4-phenylaminocarbonyl-oxy-proline-ethyl ester, 1-methyl-4-phenylaminocarbonyl-oxy-proline-isobutyl ester, 4-hydroxy-1-methyl-proline-ethyl ester, 4-hydroxy-1-methyl-proline-isobutyl ester, 4-hydroxy-1-methyl-proline-ethyl ester, 4-hydroxy-proline-ethyl ester, 4-hydroxy-proline-isobutyl ester, cis-4-hydroxy-L-proline-ethyl ester, cis-4-hydroxy-L-proline-iso-butyl ester, 4-hydroxy-1,1-dimethyl-proline-ethyl ester-iodide, hydroxyproline-ethyl ester, 4-hydroxy-1,1-dimethyl-proline-iso-butyl ester-iodide, 4-hydroxy-1-cyclohexyl-proline-isobutyl-ester, 4-hydroxy-1-diphenylmethyl-proline-isobutyl ester-hydrobromide, 4-hydroxy-1-methyl-proline, 4-hydroxy-1-alkyl-proline esteramides (alkyl: methyl, ethyl, propyl, pentyl, hexyl, heptyl, octyl, and nonyl), 4-hydroxy-1-diphenylmethyl-proline-isobutyl-ester-hydrobromide. The present embodiment encompasses salts, esters, isomers, racemates, enantiomers, or prodrugs thereof.

[0124] histidine In some embodiments of the present invention, "histidine" or "histidine derivatives" are defined in the nutritional compositions, methods and uses.

[0125] "Histidine" is an amino acid also known as (S)-4-(2-amino-2-carboxyethyl)imidazole, (S)-α-amino-1H-imidazole-4-propanoic acid, (S)-α-amino-1H-imidazole-4-propionic acid, (S)-1H-imidazole-4-alanine, (S)-2-amino-3-(4-imidazolyl)propionic acid, (S)-histidine, (S)1H-imidazole-4-alanine, 3-(1H-imidazol-4-yl)-L-alanine, amino-1H-imidazole-4-propanoate, amino-1H-imidazole-4-propanoic acid, amino-4-imidazolepropionate, amino-4-imidazolepropionic acid, and glyoxalin-5-alanine.

[0126] Histidine is preferably L-histidine and / or a derivative thereof. L-histidine exists in nature and can be easily obtained from natural sources.

[0127] The "histidine derivative" is preferably selected from one or more of peptides of histidine (particularly dipeptides and tripeptides of histidine), peptides of histidine and one or more additional amino acids (particularly dipeptides and tripeptides, e.g., carnosine), and pharmaceutically acceptable salts of histidine.

[0128] glycine In some embodiments of the present invention, "glycine" or "glycine derivatives" are defined in the nutritional compositions, methods and uses.

[0129] "Glycine" is an amino acid also known as aminoacetic acid, aminoessigsaeure, aminoethanoic acid, glycocol, glycokoll, glycine, Leimzucker, 2-aminoacetate, aminoacetic acid, glycoamine, glycoxyl, glycosthene, Gyn-hydralin, and Padil.

[0130] Glycine is preferably L-glycine and / or L-glycine ethyl ester. Non-limiting examples of suitable functional derivatives of glycine include D-allylglycine, N-[bis(methylthio)methylene]glycine methyl ester, Boc-allyl-Gly-OH (dicyclohexylammonium) salt, Boc-D-Chg-OH, Boc-Chg-OH, (R)-N-Boc-(2'-chlorophenyl)glycine, Boc-L-cyclopropylglycine, Boc-L-cyclopropylglycine, (R)-N-Boc-4-fluorophenylglycine, Boc-D-propargylglycine, Boc-( Examples of suitable glycine include S)-3-thienylglycine, Boc-(R)-3-thienylglycine, Da-cyclohexylglycine, La-cyclopropylglycine, N-(2-fluorophenyl)-N-(methylsulfonyl)glycine, N-(4-fluorophenyl)-N-(methylsulfonyl)glycine, Fmoc-N-(2,4-dimethoxybenzyl)-Gly-OH, N-(2-furoyl)glycine, La-neopentylglycine, D-propargylglycine, sarcosine, and Za-phosphonoglycine trimethyl ester.

[0131] Hydroxyproline In some embodiments of the present invention, "hydroxyproline" is defined in the nutritional compositions, methods and uses.

[0132] "Hydroxyproline" is also known as (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid, or L-hydroxyproline. Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the gamma carbon atom.

[0133] diet products In addition to one or more amino acids of the present invention, the dietary product may include (i) a protein source, (ii) a fat source, and (iii) a carbohydrate source.

[0134] protein As used herein, the term "protein" includes free form amino acids, molecules of 2-20 amino acids (referred to herein as "peptides"), as well as longer amino acid chains. Small peptides, i.e., chains of 2-10 amino acids, are suitable for the present compositions, either alone or in combination with other proteins. "Free form" amino acids are the monomeric form of amino acids. Suitable amino acids include both natural and unnatural amino acids. The present compositions may include a mixture of one or more proteins, for example, a mixture of one or more of (i) peptides, (ii) longer amino acid chains, or (iii) free form amino acids; the mixture is preferably formulated to obtain a desired amino acid profile / content.

[0135] The composition can include at least one portion of one or more amino acids and / or a protein providing at least one portion of the one or more amino acids, where the at least one portion of protein can be of animal or plant origin, e.g., one or more milk proteins, e.g., a dairy protein such as a milk protein concentrate or a milk protein isolate; a dairy protein such as one or more of caseinate or casein, e.g., a casein micelle concentrate or casein micelle isolate; or a whey protein, e.g., a whey protein concentrate or whey protein isolate. Additionally or alternatively, at least a portion of the protein can be a vegetable protein, such as one or more of soy protein or pea protein.

[0136] Mixtures of these proteins are also suitable, such as mixtures in which casein constitutes a majority but not all of the protein, mixtures in which whey protein constitutes a majority but not all of the protein, mixtures in which pea protein constitutes a majority but not all of the protein, and mixtures in which soy protein constitutes a majority but not all of the protein. In one embodiment, at least 10% by weight, preferably at least 20% by weight, and more preferably at least 30% by weight of the protein is whey protein. In one embodiment, at least 10% by weight, preferably at least 20% by weight, and more preferably at least 30% by weight of the protein is casein. In one embodiment, at least 10% by weight, preferably at least 20% by weight, and more preferably at least 30% by weight of the protein is vegetable protein.

[0137] The whey protein can be, for example, any whey protein selected from the group consisting of whey protein concentrate, whey protein isolate, whey protein micelles, whey protein hydrolysate, acid whey, sweet whey, denatured sweet whey (sweet whey from which the caseinoglycomacropeptide has been removed), a whey protein fraction, and any combination thereof.

[0138] The casein can be obtained from any mammal, but is preferably obtained from cow's milk, and preferably as casein micelles.

[0139] Proteins may be unhydrolyzed, partially hydrolyzed (i.e., peptides with a molecular weight of 3 kDa to 10 kDa and an average molecular weight of less than 5 kDa), or extensively hydrolyzed (i.e., 90% of the peptides have a molecular weight less than 3 kDa), e.g., in the range of 5% to 95% hydrolyzed. In some embodiments, the peptide profile of a hydrolyzed protein may be within different molecular weight ranges. For example, the majority of the peptides (greater than 50 mol% or greater than 50 wt%) may have a molecular weight within 1 to 5 kDa, or 5 to 10 kDa, or 10 to 20 kDa.

[0140] fat In one embodiment, the composition comprises a fat source. The fat source can comprise any suitable fat or fat mixture. Non-limiting examples of suitable fat sources include vegetable fats (e.g., olive oil, corn oil, sunflower oil, high oleic sunflower oil, rapeseed oil, canola oil, hazelnut oil, soybean oil, palm oil, coconut oil, black currant seed oil, borage oil, lecithin, etc.), animal fats (e.g., dairy fat), or combinations thereof.

[0141] carbohydrates In one embodiment, the composition comprises a carbohydrate source. Any suitable carbohydrate may be used in the composition, including, but not limited to, starch (e.g., modified starch, amylose starch, tapioca starch, corn starch), sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrin, xylitol, sorbitol, or combinations thereof.

[0142] The carbohydrate source preferably comprises no more than 50% of the energy of the composition, more preferably no more than 36% of the energy of the composition, and most preferably no more than 30% of the energy of the composition.

[0143] Nutritional preparations The composition can be any type of composition formulated to be suitable for human and / or animal consumption. For example, the composition can be selected from the group consisting of food compositions, dietary supplements, nutritional compositions, nutraceuticals, powdered nutritional formulations to be reconstituted with water or milk before ingestion, food additives, pharmaceuticals, beverages, and drinks. In one embodiment, the composition is an oral nutritional supplement (ONS), a complete nutritional formula, a pharmaceutical, a drug, or a food product. In a preferred embodiment, the composition is administered to an individual as a beverage. The composition may be stored as a powder in a sachet and then suspended in a liquid such as water for use.

[0144] In some embodiments, the compositions are administered to an individual in a single dosage form, i.e., all compounds are present in one formulation given to the individual with a meal. In other embodiments, the compositions are co-administered in separate dosage forms, e.g., at least one component is co-administered separately from one or more of the other components of the composition. [Example]

[0145] The following non-limiting examples present scientific data that develop and support the concept of administering a composition comprising one or more amino acids of the present invention, which further comprises one or more amino acids in an effective amount such that the composition is useful for weight loss or weight maintenance after weight loss. It should be understood that various modifications and variations to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such modifications and variations can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such modifications and variations be encompassed within the scope of the appended claims.

[0146] Example 1: Cohort of dietary interventions with the meal replacement OPITIFAST The OPTIWIN clinical trial tested the effectiveness of the comprehensive meal replacement dietary intervention OPTIFAST Program (OP) compared with a food-based (FB) diet plan for weight loss (Ard et al., Obesity (Silver Spring). 2019 January;27(1):22–29).

[0147] OPTIWIN was an open-label, multicenter, randomized controlled clinical trial. Nine participating sites in the US included five private clinics and four academic hospitals. Participants were non-smokers aged 18-70 years with a BMI of 30-55 kg / m². Key exclusions included recent weight loss or use of weight-loss medications, previous bariatric surgery, organ failure, type 1 diabetes, or hemoglobin A1C. 1c Eligibility criteria included >10%, incident cardiovascular disease or mental health hospitalization within the past 6 months, alcohol or drug dependence, a positive screen for an underlying eating disorder, or uncontrolled depression. Participants were screened by phone to assess initial eligibility, followed by a follow-up clinic visit to confirm eligibility and provide written consent. Eligible individuals completed a 7-day induction diet that included the use of a meal replacement product (OPTIFAST; Nestle Health Science, Bridgewater, New Jersey) once daily to assess tolerance to the product. A final screening visit was completed after the induction period to assess adherence to the diet, self-monitoring tasks, and final eligibility. This study was overseen and approved by a central Institutional Review Board after review by local Institutional Review Boards and is registered with ClinicalTrials.gov under NCT02635698.

[0148] treatment group Participants were randomized to either the OPTIFAST (OP) or food-based (FB) group.

[0149] Optifast group (OP): Participants with a BMI below 45 were instructed to use five meal replacements per day, including Optifast (800 kcal total), with 40% of calories from protein, 40% from carbohydrates, and 20% from fat. Participants with a BMI between 45 and 49.9 received six meal replacements per day (960 kcal). Participants with a BMI of 50 or greater received six meal replacements (1100–1200 kcal) in addition to one daily meal of lean protein (3–4 oz) and one meal of non-starchy vegetables. Participants followed the regimen for 12–16 weeks, based on provider discretion and patient preference, and then gradually reintroduced foods over the course of 26 weeks. After 26 weeks, participants' calories were gradually increased to stabilize their weight. During this time, participants were advised to use meal replacements once or twice daily to facilitate weight loss maintenance.

[0150] Participants met regularly with their physicians to address health concerns, arranging a total of 11 health care provider monitoring visits during the first 26 weeks and four health care provider monitoring visits from weeks 27 to 52. Medical monitoring laboratory tests, including either a basic or comprehensive metabolic panel, were obtained at weeks 2, 4, 6, 8, 10, 12, and 16. Participants received a total of 16 individual counseling visits with trained counselors during the first 26 weeks and 11 individual counseling visits from weeks 27 to 52.

[0151] Food-based group (FB): During active weight loss (weeks 0–26), FB participants were prescribed a calorie-restricted diet to enforce low-fat intake (25%–30% of total calories). Participants were advised to reduce calories to achieve an estimated total energy expenditure of 500–750 kcal, calculated based on resting metabolic rate measured by indirect calorimetry (MedGem; Microlife USA, Clearwater, FL) and activity factor (Af) based on self-reported physical activity. To balance the incentive for voluntary MR in the OP group, FB participants received gift cards totaling $800 to offset food expenses during the active weight loss phase. Participants had two monitoring visits with a health care provider at week 26 and seven individual counseling visits. During the maintenance phase (weeks 27–52), participants had two monitoring visits with a health care provider and five individual counseling visits.

[0152] analysis Sample size was primarily calculated to demonstrate the efficacy of OP compared with FB based on percent weight change at 52 weeks. Based on a two-sided test assuming α = 0.05, 113 participants per study arm were required to detect a mean difference in weight change of 5% with an estimated standard deviation (SD) of 11.5% for 90% statistical power. With an estimated dropout rate of 30%, 300 participants were recruited, with a planned provision of 150 participants per study arm.

[0153] Coprimary outcomes were percent weight change from baseline at weeks 26 and 52, which were tested using a hierarchical procedure. We first planned to test the outcome at week 26. This analysis was statistically significant (P<0.05). A subsequent test was performed at the end of week 52, with an alpha significance level of 0.05. However, given that the analysis at week 26 was not statistically significant, the analysis at week 52 was not conclusive and was exploratory.

[0154] The primary analysis population was the modified intention-to-treat (mITT) population, which included randomized subjects who were known to have initiated the study program and had at least one post-baseline weight assessment. For the primary analysis, a repeated measures model with both random and fixed effects was used to compare percent weight change between the OP and FB groups. A linear mixed model included a variable intercept for subject, fixed visit, fixed treatment, and fixed baseline weight effects, as well as a visit-by-treatment interaction term. The model also included age, race, sex, center, diabetes status, and gender as covariates. The final model was adjusted using the SAS PROC MIXED method with the RANDOM and LSMEANS statements (SAS Institute, Cary, North Carolina). In a sensitivity analysis, multiple imputation (MI) was employed due to missing weight values ​​at scheduled post-baseline visits (Weeks 12, 26, 40, and 52) in the mITT population. Imputation was performed separately for each treatment group (imputation = 50) using the SAS PROC MI procedure. Primary outcomes were then calculated from the imputed dataset. For secondary outcomes, including body composition and AE frequency, continuous measures were compared using standard t-tests, while categorical measures were compared using χ 2 The test was used for comparison.

[0155] result Of 463 participants screened, 330 were confirmed as eligible (164 randomized to OP and 166 randomized to FB). Fifty-seven participants either refused further participation in the study after learning of their randomization (9 OP, 16 FB) or discontinued without weight follow-up (20 OP, 12 FB). These participants were demographically similar to the mITT population, except that they were younger (42.5 years, P = 0.006) and reported lower average weight loss in previous trials (0.1 kg, P < 0.001). The remaining 273 participants (135 OP, 138 FB) comprised the mITT population (82.7% of randomized participants). In the mITT population, 19 participants (14.1%) in the OP group and 25 participants (18.1%) in the FB group discontinued. Participants were typically middle-aged (47.1 ± 11.2 years), primarily female (82%), and Caucasian (71%) (Table 1). 52% had prediabetes or diabetes, 33% were being treated for hypertension, and 21% were being treated for dyslipidemia. OP and FB participants attended weekly group behavioral sessions 53.5% and 46.2%, respectively.

[0156] [Table 1]

[0157] Continuous variables compared using standard t-tests. Due to the small number of cells, Fisher's exact test was used to compare χ excluding race. 2 Categorical variables were compared using the .DELTA. test.

[0158] a Drug use includes continued use from before the trial through the trial, or use initiated during the trial and continued throughout the trial, or use terminated before the completion of the trial.

[0159] Weight loss outcomes Both treatment groups achieved weight loss at 26 and 52 weeks (% weight loss at 26 weeks was 12.4% ± 0.6% with OP vs. 6.0% ± 0.6% with FB (difference, 6.4% ± 0.9%; P < 0.001). % weight loss at 52 weeks was 10.5% ± 0.6% with OP vs. 5.5% ± 0.6% with FB (difference, 4.9% ± 0.9%; P < 0.001). Sensitivity analyses showed similar estimates of percent weight loss. Using MI to handle missing data, OP showed weight losses of 12.1% ± 0.6% and 10.1% ± 0.7% at 26 and 52 weeks, respectively. In comparison, FB resulted in weight losses of 6.0% ± 0.6% and 5.5% ± 0.7% at 26 and 52 weeks. All differences between OP and FB remained significant at P<0.001.

[0160] There was a relative weight change by treatment group at weeks 26 and 52. Weight change values ​​(%) were calculated from least-squares means using a linear mixed model that included a random intercept subject effect, fixed visit effect, fixed treatment effect, fixed baseline body weight effect, visit-treatment interaction term, and covariates including age, race, sex, location, and reported baseline diabetes status.

[0161] At week 52, more participants in the OP group achieved a 5% (63.7%) and 10% weight loss (43.7%) compared with those in the FB group (42% and 21.7%, respectively, P<0.001). The percentage of participants who lost 15% or more of their initial body weight was more than twice as high in the OP group as in the FB group (30% vs. 12%, P<0.001). The proportion of participants who did not respond to the assigned treatment, defined as failure to lose 3% or more of their initial body weight, was also examined. At week 26, 15.6% of OP participants and 39.1% of FB participants were non-responders. By week 52, 23.7% of OP participants were non-responders, compared with 43.5% of FB participants.

[0162] Changes in body composition Changes in body composition outcomes are shown in Table 2. Changes in waist circumference paralleled weight loss in both treatment groups. However, at 26 and 52 weeks, there was a greater decrease in the OP group than in the FB group. Changes in body composition, as measured by dual-energy X-ray absorptiometry, followed a similar pattern. By week 52, mean total fat mass decreased by 9.7 ± 10.4 kg in OP participants. Total fat mass decreased by an average of 3.5 ± 6.6 kg in FB participants at week 52. Both treatment groups experienced a loss of lean mass. The absolute differences were statistically significant. However, the percentage of weight lost from lean mass at week 52 was similar (23% in OP and 25.5% in FB). There was no difference in change in total bone mineral density between treatment groups.

[0163] [Table 2]

[0164] Differences in change from baseline, defined as post-baseline values ​​minus baseline values, were compared using standard t tests.

[0165] Participants in the OP treatment group lost 10.5% of their initial body weight by week 52, nearly double the effect on body weight seen with FB. With OP, more participants lost 5%, 10%, or 15% of their body weight, and a higher percentage of participants responded to OP with at least a 3% weight loss. OP participants experienced greater fat mass loss, and OP was well-tolerated and safe. Overall, OP proved to be a more effective treatment than FB.

[0166] The OP group achieved greater weight loss and less weight regain over 12 months. Weight loss through continued use of meal replacements such as OPIFAST for weight loss maintenance may be advantageous because MR is characterized by low energy intake (e.g., protein control, low calories, reduced choice) and changes in the subject's subjective desire and craving for food. This was objectively supported by concurrent changes in brain regions corresponding to food intake control and reward on functional magnetic resonance imaging. Continuity of treatment and use of meal replacements may be important for maintaining weight loss.

[0167] Example 2: Method for measuring amino acids Plasma samples from subjects in the OP group were analyzed at baseline, 26 weeks, and 52 weeks to assess amino acid concentrations. Specifically, proline, histidine, glycine, and hydroxyproline were measured.

[0168] Tandem mass spectrometry (UPLC-MS / MS) was used for amino acid analysis. Separation and analysis were performed on an Accela UHPLC 1250 pump (Thermo Fisher Scientific Inc., Waltham, MA, USA) coupled to a TSQ Quantum Vantage triple quadrupole equipped with a heated electrospray ionization (H-ESI) source (Thermo Fisher Scientific Inc., MA, USA). Chromatographic separation was obtained using gradient elution on a reversed-phase UPLC XSelect HSST3, 2.5 μm, 100 × 2.1 mm I.D. column (Waters Corporation, Milford, MA, USA). The injection volume was 10 μL, and the total run time for analysis was 13 min. Plasma samples were thawed and vortexed for 10 s. A volume of 50 μL of plasma was transferred to a 1.5 mL microcentrifuge tube by pipette. 10 μL of IS solution was added to the plasma. 50 μL of TCEP solution and then 140 μL of methanol + 1% FA were added to the mixture. The tube was placed in a multi-tube vortex at 1350 rpm for 15 minutes at 4°C and centrifuged at 14,500 rpm for 5 minutes. The supernatant was pipetted, filtered through a 0.22 μm filter, and placed in a vial for LC-MS / MS analysis.

[0169] Using a sparse partial least squares (sPLS) approach, changes in blood amino acids during weight loss were tested for association with changes in anthropometric variables during the entire intervention (i.e., post-WM). The sample included 71 participants with data at baseline (V1), 12 weeks (V2), and 24 weeks (V3) after the weight loss program.

[0170] The sparse partial least squares (sPLS) approach implemented in the mixOmics R package combines both integration and variable selection simultaneously for two datasets (amino acid and anthropometric variables) in a one-step strategy. It is a multivariate methodology that relates two data matrices, X (e.g., anthropometric measurements) and Y (amino acids). sPLS goes beyond the scope of traditional multiple regression by modeling the structure of both matrices. Unlike traditional multiple regression models, it is not limited to uncorrelated variables. One of the many benefits of sPLS is its ability to handle a large number of noisy, collinear (correlated), and missing variables, and its ability to simultaneously model several corresponding variables Y. Variable selection is achieved by introducing lasso penalization for pairs of weight variables. Clustered image maps (CIMs) are provided to summarize and visualize sPLS results. Missing data are imputed via bagging. The method fits a bagged tree model for each predictor (which is a function of all others). CIM is based on hierarchical clustering applied simultaneously to the rows and columns of a real-valued similarity matrix obtained via sPLS results. A network plot is also provided to represent the association between two sets of variables. These are inferred to form pairwise association scores between variables X and Y provided by sPLS. A threshold is set to represent only variables X and Y with association scores above a given cutoff.

[0171] The analysis assumed that a three-component model was applied for visualization and interpretation. The results are reported in Table 3 as CIM element values.

[0172] The analysis highlights a strong association between blood amino acid changes (V2 / V1) during weight loss and the body composition state (V3 / V1) achieved at the end of the weight maintenance period. In particular, changes in proline were positively associated with changes in lean mass and negatively associated with changes in BMI and fat mass. Furthermore, changes in glycine and histidine were negatively associated with changes in fat mass and BMI. These observations are explained by (i) the fact that greater reductions in fat mass and BMI were achieved in subjects showing no or weak depletion of proline, histidine, and glycine, and (ii) the fact that greater maintenance of lean mass was observed in subjects showing weak depletion of proline.

[0173] Hydroxyproline is produced by the hydroxylation of the amino acid proline.Hydroxyproline content is a well-known marker of collagen catabolism, particularly tissue degradation, including bone resorption or muscle damage.Changes in the ratio of proline to hydroxyproline are negatively associated with changes in lean mass, and positively associated with changes in fat mass and BMI.Specifically, the higher the conversion rate of hydroxyproline to proline, the greater the loss of lean mass.

[0174] [Table 3]

Claims

1. A nutritional composition for use in weight loss, comprising one or more amino acids selected from the group consisting of proline, histidine, glycine, and / or hydroxyproline, or mixtures thereof.

2. A nutritional composition for use in weight maintenance, comprising one or more amino acids selected from the group consisting of proline, histidine, glycine, and / or hydroxyproline, or mixtures thereof.

3. 3. The nutritional composition according to claim 1 or 2, which is used for weight loss during a low-calorie diet intervention or for weight maintenance after a low-calorie diet intervention, and which comprises one or more amino acids selected from the group consisting of proline, histidine, glycine, and / or hydroxyproline, or mixtures thereof.

4. 4. The nutritional composition of claim 3, wherein the low-calorie dietary intervention is 600 kcal / day to 1500 kcal / day for up to 12 weeks for adults.

5. A nutritional composition for use according to any one of claims 1 to 4, wherein said nutritional composition contains at least proline.

6. A nutritional composition for use according to any one of claims 1 to 4, wherein said nutritional composition contains at least proline and histidine.

7. A nutritional composition for use according to any one of claims 1 to 4, wherein said nutritional composition contains at least proline, histidine and glycine.

8. A nutritional composition for use according to any one of claims 1 to 4, wherein said nutritional composition contains at least proline, histidine, glycine and hydroxyproline.

9. 9. The nutritional composition of any one of claims 1 to 8, wherein said nutritional composition improves fat mass loss in a subject following a low-calorie dietary intervention.

10. 9. The nutritional composition of any one of claims 1 to 8, wherein said nutritional composition improves BMI in a subject following a low-calorie dietary intervention.

11. 9. The nutritional composition of any one of claims 1 to 8, wherein said nutritional composition maintains the loss of fat mass in a subject following a low-calorie dietary intervention.

12. 9. The nutritional composition of any one of claims 1 to 8, wherein the nutritional composition maintains BMI in a subject following a low-calorie dietary intervention.

13. 13. The nutritional composition for use according to any one of claims 1 to 12, wherein said one or more amino acids are administered simultaneously, sequentially or separately to a diet-resistant or weight-loss-resistant obese subject.

14. 14. The nutritional composition for use according to any one of claims 1 to 13, wherein said one or more amino acids are administered simultaneously with a low-calorie diet intervention with a diet product to a diet-resistant obese subject or a weight-loss-resistant obese subject.

15. (i) diet products, and / or (ii) 15. A kit of parts comprising the nutritional product containing one or more amino acids according to any one of claims 1 to 14, and (iii) instructions for their use for simultaneous, sequential or separate administration to a diet-resistant or weight-loss-resistant obese subject.

16. 15. A method of reducing BMI in a subject in need thereof, comprising administering to said subject in need thereof a nutritional composition comprising one or more amino acids according to any one of claims 1 to 14.

17. 15. A method of maintaining the BMI of a subject after weight loss, comprising administering to said subject in need thereof a nutritional composition comprising one or more amino acids according to any one of claims 1 to 14.

18. 15. A method for reducing fat mass in a subject in need thereof, comprising administering to said subject in need thereof a nutritional composition comprising one or more amino acids according to any one of claims 1 to 14.

19. 15. A method of maintaining fat mass in a subject after weight loss, comprising administering to said subject in need thereof a nutritional composition comprising one or more amino acids according to any one of claims 1 to 14.

Images