Compositions and methods of reducing energy intake, enhancing satiety and enhancing energy expenditure

Abstract

The present invention relates to compositions for use in reducing energy intake, enhancing satiety and / or enhancing energy expenditure. The composition of the invention comprises: (i) l- carnitine, (ii) dihydrocapsiate and (iii) yeast hydrolysate for use in reducing energy intake, enhancing satiety and / or enhancing energy expenditure. The invention provides methods of weight management comprising administration of a composition of the invention. Advantageously, the compositions and methods of the invention may be used for individuals who are overweight, obese or maintaining a desired body weight, such as after weight loss.

Description

[0001] COMPOSITIONS AND METHODS OF REDUCING ENERGY INTAKE, ENHANCING SATIETY AND ENHANCING ENERGY EXPENDITURE

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to compositions for use in reducing energy intake, enhancing satiety and / or enhancing energy expenditure. The composition of the invention comprises: (i) L-carnitine, (ii) dihydrocapsiate and (iii) yeast protein hydrolysate for use in reducing energy intake, enhancing satiety and / or enhancing energy expenditure. The invention provides methods of weight management comprising administration of a composition of the invention. Advantageously, the compositions and methods of the invention may be used for individuals who are overweight, obese or maintaining a desired body weight, such as after weight loss.

[0004] BACKGROUND TO THE INVENTION

[0005] Obesity is a global public health issue, with worldwide 38% of individuals 5 years of age and older being overweight and obese (BMI > 25kg / m2) and 14% being obese (BMI > 30kg / m2) as of 2020 (World Obesity Atlas, 2023). Obesity is also major risk factor for other disease conditions.

[0006] Obesity is a global public health issue and numerous behavioural, nutritional and pharmacological weight loss interventions have been established over the last decades. What all weight loss interventions have in common is the regain of weight, which is mostly fat mass, after the intervention has been stopped. This effect is the result of increased appetite secondary to a reduction in anorexigenic signals leading to increased calorie intake and a concomitant reduction in energy expenditure due in part to muscle loss and the reduction in the thyroid hormone axis.

[0007] The pathophysiology of obesity is complex, multifactorial, and not well understood. One key hypothesis is that obesity occurs when there is a persistent energy imbalance wherein calorie intake is greater than energy expenditure (as the measure for the energy our body uses to perform its physiological functions) leading to weight gain.

[0008] However, people who lose weight trigger a set point regulation, which is an active feedback mechanism via a set point encoded in the brain linking the adipose tissue stored energy to energy intake and expenditure, this leads to weight regain as weight and fat mass are set to be preserved (Speakman et al., 2011).

[0009] Weight regain is defined as the change in body weight over time from the peak of weight loss. Weight regains of 30 - 50% of the total weight loss have been shown to occur within 1 year and 50% of the patients will return to their baseline weight 5 years after they started their weight loss regime (Sarwer et al., 2009). Only about 15 - 25% of overweight and obese individuals can achieve and maintain a 10% or greater weight loss with lifestyle interventions (Unick et al., 2011). Recent findings from epidemiological data show that the increase in body weight over time is due to decreases in resting metabolic rate rather than decreases in activity expenditure (Speakman et al., 2023).

[0010] Landmark clinical studies have been conducted which explored the magnitude of the effect on energy expenditure following weight loss and weight maintenance via dietary and physical activity interventions. For individuals losing 9 kg of body weight in 2 years, the 24h energy expenditure is reduced by 120 kcal in Year 1 post weight loss versus baseline but was not significantly different versus ad libitum conditions without weight loss. Furthermore, it was found that the thyroxine (T4) hormone was significantly reduced in the weight loss group at Year 2 by - 0.6 pg / dL vs. baseline (Redman et al., 2018). When higher amounts of body weight are lost, such as in the “Biggest Loser Competition” trial where 50 kg were lost in 7.5 months, total energy expenditure was reduced by 1000 kcal vs. baseline (Johannesen et al., 2012).

[0011] In the context of weight maintenance, after maintaining weight lost (-10% of body weight achieved in 4 - 10 weeks) for 14 days, resting energy expenditure increased by 149 kcal vs. recent body weight lost 14 days before, whereas maintenance of 10% weight gain results in decreased resting energy expenditure by 289 kcal (Leibel et al., 1995). Another study with patients maintaining for 1 year a body weight loss of -10% of the initial body weight in 5-10 weeks, showed an increase in 24h total energy expenditure of 86 kcal vs. recent weight loss 1 year before (Rosenbaum et al., 2008). A mathematical modelling study found that for each kilogram of lost weight, energy expenditure decreases by about 20-30 kcal / day whereas appetite increases by about 100 kcal / day above the baseline level prior to weight loss (Polidori et al., 2016). The inter-day variability for appetite subjective feelings has been reported to range between 7 and 28% in healthy lean men (Gonzalez et al., 2017).

[0012] There is an unmet need for compositions, especially nutritional compositions, and methods which can reduce energy intake, enhance satiety and / or enhance energy expenditure. There is an unmet need to provide compositions and methods which address weight regain and maintenance of a desired body weight, such as after weight loss.

[0013] In particular, there is an unmet need to provide compositions which can reduce energy intake, enhance satiety and / or enhance energy expenditure by helping an individual to manage their desired body weight, especially to maintain a desired body weight after weight loss without subsequent weight gain.

[0014] REFERENCES

[0015] Evans A & Fornasini G (2003). Pharmacokinetics of L-carnitine. Clinical pharmacokinetics. 42. 941-967.

[0016] Gonzalez J et al., 2017. Postprandial suppression of appetite is more reproducible at a group than an individual level: implications for assessing inter-individual variability. Appetite (2017) 108: 375-382.

[0017] Johannsen D et al., 2012. Metabolic slowing with massive weight loss despite preservation of fat-free mass. Journal of Clinical Endocrinology & Metabolism (2012) 97(7): 2489-2496.

[0018] Juraszek B, 2019. SLC22A5 (OCTN2) Carnitine transporter — indispensable for cell metabolism, a jekyll and hyde of human cancer. Molecules (2019) 25(1): 14.

[0019] Leibel R et al., 1995. Changes in energy expenditure resulting from altered body weight. New England Journal of Medicine (1995) 332(10): 621-628.

[0020] NIH ODS, 2023. National Institutes of Health, Office of Dietary Supplements (NIH ODS, 2023). Carnitine. Fact Sheet for Health Professionals. https: / / ods.od.nih.gov / factsheets / Carnitine- HealthProfessional / Accessed 23 May 2024.

[0021] Pistone G et al. 2003. Levocarnitine administration in elderly subjects with rapid muscle fatigue. Drugs Aging (2003) 20: 761-767

[0022] Polidori D et al., 2016. How strongly does appetite counter weight loss? Quantification of the feedback control of human energy intake. Obesity (2016) 24(11): 2289-2295.

[0023] Redman L et al., 2018. Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell metabolism (2018) 27(4): 805-815. Rosenbaum M et al., 2008. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. The American Journal of Clinical Nutrition (2008) 88(4): 906-912.

[0024] Sarwer D et al., 2009. Behavior therapy for obesity: where are we now? Current Opinion in Endocrinology, Diabetes & Obesity (2009) 16:347-352.

[0025] Sawicka K et al., 2019. The bright and the dark sides of L-carnitine supplementation: a systematic review. Journal of the International Society of Sports Nutrition (2020) 17:49.

[0026] Speakman J et al.. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Meeh (2011) 4(6): 733-745.

[0027] Speakman J et al., 2023. Total daily energy expenditure has declined over the past three decades due to declining basal expenditure not reduced activity expenditure. Nature Metabolism (2023) 5(4): 579-588.

[0028] Subramaniam S & Fletcher C, 2018. Trimethylamine N-oxide: breathe new life. Br J Pharmacol (2018) 175(8): 1344-1353.

[0029] Unick J et al, 2011 . Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes. Results from the Look Ahead trial. Diabetes Care (2011) 34(10): 2152-2157.

[0030] World Obesity Atlas - https: / / data.worldobesity.org / publications / ?cat=19

[0031] SUMMARY OF THE INVENTION

[0032] The present invention provides a novel and inventive solution to the problems described above by providing a composition comprising ingredients: L-carnitine, dihydrocapsiate, and yeast protein hydrolysate.

[0033] All three ingredients have a history of safe use for consumption in humans, in particular, at the daily dose of the present invention. The novel and invention composition is a combination of all three ingredients which act to reduce energy intake, enhance satiety and / or enhance energy expenditure.

[0034] Advantageously, compositions and methods of the present invention can reduce energy intake, enhance satiety and / or enhance energy expenditure. Advantageously, compositions and methods of the present invention which reduce energy intake, enhance satiety and / or energy expenditure help an individual to manage their desired body weight, especially to maintain a desired body weight.

[0035] BRIEF DESCRIPTION OF FIGURES

[0036] Figure 1 - Flow chart

[0037] The flow chart is describing the recruitment of the subjects and randomised allocation to the intervention with the study product (blend) or placebo (control).

[0038] Figure 2 - Waist Circumference

[0039] Waist Circumference shows that the waist circumference of the subjects treated with the study product (blend) decreased compared to the placebo (control) group.

[0040] Figure 3 - Ad libitum energy intake

[0041] Ad libitum energy intake (kcal) was similar between the treated (blend) and the placebo (control) groups as measured at week 4. However, after taking taking the intervention for 12 weeks, the treated subjects (blend) measured a decrease in ad libitum energy intake compared to the placebo (control) subjects.

[0042] Figure 4 - Resting energy expenditure

[0043] Resting energy expenditure is higher in the subjects treated (blend) compared to the placebo (control) subjects at 4 weeks. This difference was maintained at 12 weeks.

[0044] Figure 5 - Carbohydrate oxidation

[0045] Carbohydrate oxidation increased in the subjects treated (blend) compared to the placebo (control) subjects at 4 weeks. This difference was further increased in the treated (blend) subjects at 12 weeks compared to the placebo (control).

[0046] Figure 6 - VAS measurement for Hunger

[0047] The VAS measurement for hunger demonstrated that there was a decrease in subjective feelings of hunger in the subjects treated (blend) compared to the placebo (control) subjects. This is shown be the AUC values of the treated (blend) versus the placebo (control) groups.

[0048] Figure 7 - VAS measurement for Satiety The VAS measurement for satiety demonstrated that there was a greater perception of satiety in the subjects treated (blend) compared to the placebo (control) subjects. This is shown be the AUC values of the treated (blend) versus the placebo (control) groups.

[0049] Figure 8 - VAS measurement for Fullness

[0050] The VAS measurement for fullness demonstrated that there was a greater perception of fullness. This is shown be the AUC values of the treated (blend) versus the placebo (control) groups.

[0051] Figure 9 - VAS measurements for Desire to Eat

[0052] The VAS measurement for Desire to Eat demonstrated that there was less desire to eat in the treated (blend) versus the placebo (control) group as shown in the AUC values.

[0053] DETAILED DESCRIPTION OF THE INVENTION

[0054] Various preferred features and embodiments of the present invention will now be described by way of non-limiting examples.

[0055] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0056] The terms "comprising", "comprises" and "comprised of" as used herein are synonymous with "including", "includes", "containing", or "contains", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or steps. The terms "comprising", "comprises" and "comprised of also include the term "consisting of.

[0057] Numeric ranges are inclusive of the numbers defining the range. As used herein the term “about” means approximately, in the region of, roughly, or around. When the term “about” is used in conjunction with a numerical value or range, it modifies that value or range by extending the boundaries above and below the numerical value(s) set forth. In general, the terms “about” and “approximately” are used herein to modify a numerical value(s) above and below the stated value(s) by 10%.

[0058] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that such publications constitute prior art to the claims appended hereto. This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this disclosure. The skilled person will understand that they can combine all features of the invention disclosed herein without departing from the scope of the invention as disclosed.

[0059] All publications mentioned in the specification are herein incorporated by reference.

[0060] COMPOSITIONS

[0061] In several embodiments, the present invention provides a composition comprising active ingredients: L-carnitine, dihydrocapsiate, and yeast protein hydrolysate.

[0062] In several embodiments, the present invention provides a composition comprising: (i) L- carnitine, (ii) dihydrocapsiate and (iii) yeast protein hydrolysate for use in reducing energy intake, enhancing satiety and / or enhancing energy expenditure.

[0063] In several embodiments, the present invention provides a composition wherein (i) L-carnitine is provided in the amount of 500 mg to 3000 mg; (ii) dihydrocapsiate is provided in the amount of 3 mg to 12 mg and (iii) yeast protein hydrolysate is provided in the amount of 100 mg to 1000 mg.

[0064] In several embodiments, the present invention provides a composition wherein (i) L-carnitine is provided in the amount of about 1000 mg / day, (ii) dihydrocapsiate is provided in the amount of about 6 mg / day and (iii) yeast protein hydrolysate is provided in the amount of about 500 mg / day.

[0065] In several embodiments, the present invention provides a composition wherein the composition is administered in a single dose, in two doses, three doses or four doses per day in order that (i) L-carnitine is provided in the amount of 500 to 3000 mg / day, (ii) dihydrocapsiate is provided in the amount of 3 to 12 mg / day and (iii) yeast protein hydrolysate is provided in the amount of 100 to 1000 mg / day.

[0066] In several embodiments, the present invention provides a composition which is administered in a single dose, in two doses, three doses or four doses per day in order that (i) L-carnitine is provided in the amount of about 1000 mg / day, (ii) dihydrocapsiate is provided in the amount of about 6 mg / day and (iii) yeast protein hydrolysate is provided in the amount of about 500 mg / day. In several embodiments, the present invention provides a composition which is administered (i) at least 30 minutes before a meal or snack or (ii) together with a meal or snack.

[0067] In several embodiments, the present invention provides a composition which is a food supplement selected from a solid dose form, hard capsule, soft capsule, tablet, powder, powder to be reconstituted in water, liquid, ready to drink beverage, effervescent tablet, lozenge, gummy, gel or incorporated into a food product, such as a nutritional bar.

[0068] In several embodiments, the present invention provides a composition for use in individuals who are overweight, obese, or maintaining desired body weight, such as after weight loss.

[0069] In several embodiments, the present invention provides a composition wherein reduction in energy intake is measured by caloric intake consumed per day, by a reduction in energy intake of at least 15 kcal / day, at least 50 kcal / day, at least 100 kcal / day, at least 120 kcal / day, at least 150 kcal / day based on the daily caloric intake compared to baseline for the individual before using the composition.

[0070] In several embodiments, the present invention provides a composition wherein satiety is measured by a questionnaire administered to the individual, preferably administered at 4 weeks after the individual continuously is taking said composition, wherein there is a reduction in appetite.

[0071] In several embodiments, the present invention provides a composition wherein enhanced energy expenditure is measured by calorimetry in kcal / kg fat free mass with at least an increase in energy expenditure of at least 0.5 kcal / kg fat free mass, at least 1 kcal / kg fat free mass, at least 2 kcal / kg fat free mass, based on post-prandial energy expenditure in the individual compared to baseline before using the composition, preferably measured at 4 weeks after continuously taking said composition.

[0072] In several embodiments, the present invention provides a composition wherein enhanced energy expenditure is measured by measuring fat oxidation wherein a lower respiratory quotient indicates an increase energy expenditure based on post-prandial energy expenditure in the individual compared to baseline before using the composition, preferably measured at 4 weeks after continuously taking said composition.

[0073] In several embodiments, the present invention provides a composition for use in weight maintenance, weight loss, obesity prevention and treatment, reducing calorie intake, reducing appetite, promoting satiety, maintenance of muscle mass, auxiliary management of diabetes, auxiliary management of post-prandial blood glucose and insulin, and reducing blood cholesterol.

[0074] In several embodiments, the present invention provides a composition for administration to an individual together with a GLP-1 agonist or to an individual who has stopped using a GLP-1 agonist after weight loss or to an individual who is on another weight-loss regime or to an individual who wants to maintain a desired body weight.

[0075] In several embodiments, the present invention provides a composition for use in an individual wherein said individual is a mammal, preferably a human mammal. For domestic animals, a person skilled in the art may readily adapt the dosing of the active ingredients to the kg body weight of the mammal.

[0076] L-carnitine

[0077] L-carnitine is an amino acid which is considered a non-essential amino acid as the body can normally store enough in the kidneys due to renal conservation (Evans & Fornasini, 2003).

[0078] L-carnitine may also be known as 3-carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium inner salt, (3-carboxy2-hydroxypropyl) trimethylammonium hydroxide inner salt, 3-hydroxy-4-N- trimethylaminobutyrate, Aminocarnitine, B-hydroxy-N-trimethyl aminobutyric acid, Beta-hydroxy- gamma-trimethylammonium butyrate, Beta-hydroxyl-gamma-tributyl aminobutyrate, B(t) Factor, Carnitine, Carnitine Orotate, Carnitor, DL-Carnitine, Facteur B(t), L-3-hydroxy-4- (trimethylammonium)-butyrate, Levocarnitine, Levocarnitine, Levocarnitine Fumurate, L-b- hydroxy-c-N-trimethylaminobutyric acid, L-Carnitina, L-Carnitine Fumarate, L-Camitine L- Tartrate, L-Carnitine Tartrate, (R)-(3-carboxy-2-hydroxypropyl) trimethylammonium hydroxide, (R)-3-hydroxy-4-trimethylammonio-butyrate, Vitacarn, Vitamin B(t), Vitamine B(t)

[0079] L-carnitine plays an essential role in the transport of long-chain fatty acids into the mitochondrial matrix for their conversion in energy via the [3-oxidation process. L-carnitine has anti-oxidant and anti-inflammatory properties and plays an important role in the regulation of metabolic pathways involved in maintaining a healthy skeletal muscle protein balance (Sawicka et al., 2020; NIH CDS 2023).

[0080] After oral doses of 1 - 6 g, the absolute bioavailability of L-carnitine is 5-18%. In contrast, the bioavailability of dietary L-camitine may be as high as 75%. L-carnitine is concentrated in tissues that oxidize fatty acids as a dietary fuel. Approximately 95% of total body carnitine is stored in heart and skeletal muscle. Most of the remainder is stored in the liver and kidney, and circulating plasma contains only about 0.5% of the body’s carnitine. Excess plasma carnitine is excreted in urine (Evans & Fornasini, 2003; NIH ODS, 2023).

[0081] L-carnitine crosses the blood-brain barrier and contributes to the formation of acetylcholine, leading to benefits like reduced physical and mental fatigue syndrome (Pistone et al., 2003; Juraszek et al., 2019).

[0082] Since the bioavailability of L-carnitine is limited, part of it becomes available for fermentation in the colon by gut microbiota leading to the production of TMA. TMA can be absorbed and transformed to trimethylamine N-oxide (TMAO) in the liver (Subramaniam & Fletcher, 2018).

[0083] Human tolerance of L-carnitine-L-tartrate up to 3 g / day has been established in adults with respect to gastrointestinal symptoms, haematology and clinical chemistry, including markers of liver and kidney function; this is equivalent to approximately 2 g / day L-carnitine

[0084] The composition of the invention may be formulated such that the L-carnitine is administered in a therapeutically effective dosage. One of skill in the art would be able to adjust the amount of L-carnitine in the composition to achieve a desired dosage per day.

[0085] In some embodiments, the L-carnitine is in the form of L-carnitine-L- tartrate.

[0086] In some embodiments, the L-carnitine is in the form of L-carnitine free base equivalent.

[0087] In some embodiments, the L-carnitine is in a combination of L-carnitine-L- tartrate and L- carnitine free base equivalent.

[0088] Suitably, L-camitine is present in an amount such that the composition provides L-carnitine of about 500 to 3000 mg per day.

[0089] Suitably, L-camitine is present in an amount such that the composition provides at least about 500 mg L-carnitine per day.

[0090] Suitably, L-camitine is present in an amount such that the composition provides at least about 500 mg L-carnitine in the form of L-camitine-L-tartrate and at least about 68 mg L-carnitine in L- carnitine free base equivalent per day.

[0091] Suitably, L-camitine is present in an amount such that the composition provides about 3000 mg or less L-carnitine per day.

[0092] In some embodiments, L-carnitine is present in an amount such that the nutritional composition provides L-carnitine in a dosage of about 1000 mg / day. In some embodiments, the composition may be formulated such that the L-carnitine is administered in a suitable amount per dose. As used herein, a “dose” may refer to the recommended or typical amount of the product that is administered at one time. As used herein, "dose" on product packaging may refer to the nutritional information provided on the label and how it relates to a single dose of the product.

[0093] Suitably, the composition comprises L-carnitine in an amount of 1 dose or more, in an amount of 2 doses or more, 3 doses or more, 4 doses or more, 5 doses or more, 6 doses or more, such that the total amount of L-camitine provided is about 500 to 3000 mg per day.

[0094] In some embodiments, the composition comprises L-carnitine in 4 doses for a total of at least about 500 mg L-carnitine per day.

[0095] In some embodiments, the composition comprising L-carnitine enhances energy expenditure and / or fatty acid oxidation.

[0096] In some embodiments, the composition comprising L-carnitine, dihydrocapsiate and yeast hydrolysate enhances energy expenditure and / or fatty acid oxidation.

[0097] Capsinoid (Dihydrocapsiate)

[0098] Capsinoids include dihydrocapsiate, capsiate and nordihydrocapsiate:

[0099] Dihydrocapsiate is also known as 4-hydroxy-3-methoxybenzyl 8-methylnonanoate (CAS No. 205687-03-2)

[0100] Capsiate is also known as 4-hydroxy-3-methoxybenzyl (E)-8-methyl-6-nonenoate (CAS No. 205687-01-0)

[0101] Nordihydrocapsiate is also known as 4-hydroxy-3-methoxybenzyl 7-methyloctanoate (CAS No. 220012-53-3)

[0102] Capsinoids are less polar than capsaicinoids, due to their ester bond that replaces the amide bond of capsaicinoids. Although they are structurally similar to capsaicin, the substance that causes pungency in hot peppers, they largely lack that characteristic pungency. Capsinoids have an estimated "hot taste threshold" which is about 1 / 1000 that of capsaicin.

[0103] The main pungent capsaicinoid is capsaicin. Capsaicin is an active component of red chili peppers from the plant genus Capsicum that found uses for flavoring, coloring, and preserving food, as well as for medical purposes. Capsicum and its properties have been well studied. Capsinoids are a group of compounds which are naturally present in foods like chilli pepper, cayenne pepper or paprika and sweet peppers. In contrast to capsaicin, capsinoids are non- pungent and relatively tasteless and thus are more palatable for most consumers. This is an advantage of formulating the composition of the invention with a capsinoid, in particular, dihydrocapsiate.

[0104] Dihydrocapsiate is a capsinoid which is 1 ,000 times less pungent than capsaicin due to an ester bond instead of an amide bond, which is a characteristic of capsaicin, between the vanillyl moiety and the fatty acid chain. Dihydrocapsiate has been shown to have effects on energy expenditure and fatty acid oxidation.

[0105] The available data on absorption, distribution, metabolism and excretion (ADME) suggest that ingested dihydrocapsiate is rapidly metabolised in the gut of rats and humans to form vanillyl alcohol, vanillic acid and 8-methylnonanoic acid. After absorption, the first two are converted into glucuronide and / or sulphate conjugates in the liver and eliminated predominantly by the kidneys into the urine. Total excretion in the urine, faeces and expired air after 72 hr was 98.0 %. The methyl-branched fatty acid 8-methylnonanoic acid is likely to be subject to a degradation via B-oxidation. Terminal co-oxidation might constitute an alternative pathway.

[0106] The composition of the invention may be formulated such that the dihydrocapsiate is administered in a therapeutically effective dosage. One of skill in the art would be able to adjust the amount of dihydrocapsiate in the composition to achieve a desired dosage per day.

[0107] Suitably, dihydrocapsiate is present in an amount such that the composition provides dihydrocapsiate of about 3 to 12 mg per day.

[0108] Suitably, dihydrocapsiate is present in an amount such that the composition provides at least about 3 mg diydrocapsiate per day.

[0109] Suitably, dihydrocapsiate is present in an amount such that the composition provides about 12 mg or less dihydrocapsiate per day.

[0110] In some embodiments, dihydrocapsiate is present in an amount such that the composition provides dihydrocapsiate in a dosage of about 6 mg / day.

[0111] In some embodiments, the composition may be formulated such that the dihydrocapsiate is administered in a suitable amount per dose. As used herein, a “dose” may refer to the recommended or typical amount of the product that is administered at one time. As used herein, "dose" on product packaging may refer to the nutritional information provided on the label and how it relates to a single dose of the product.

[0112] Suitably, the composition comprises dihydrocapsiate in an amount of 1 dose or more, in an amount of 2 doses or more, 3 doses or more, 4 doses or more, 5 doses or more, 6 doses or more, such that the total amount of dihydrocapsiate provided is about 3 to 12 mg per day.

[0113] In some embodiments, the composition comprises dihydrocapsiate in 4 doses for a total of at least about 6 mg dihydrocapsiate per day.

[0114] In some embodiments, the composition comprising dihydrocapsiate enhances energy expenditure and / or fatty acid oxidation.

[0115] In some embodiments, the composition comprising L-carnitine, dihydrocapsiate and yeast protein hydrolysate enhances energy expenditure and / or fatty acid oxidation.

[0116] Yeast protein hydrolysate (DNF-10)

[0117] Yeast protein hydrolysate is obtained from autolysis catalyzed by enzymes and concentration or drying of the raw material-baker's yeast (Saccharomyces cerevisiae). Hydrolyzed yeast is different from autolyzed yeast.

[0118] In both autolyzed and hydrolyzed yeast, the cell walls are discarded and the contents of the cell are combined. In autolyzed yeast, the enzymes found in the yeast itself are used to break down the proteins. However, in hydrolyzed yeast, these enzymes are added to the yeast.

[0119] Yeast hydrolysate peptide complex derived from Saccharomyces cerevisiae has been hydrolyzed and ultra-filtered to contain peptides with a molecular weight smaller than 10 kDa.

[0120] In some embodiments, the composition comprises yeast hydrolysate peptide complex also known as DNF-10.

[0121] DNF-10 is a yeast hydrolysate peptide complex resulting from the hydrolysis of yeast cells. The hydrolysate is filtered through a 10 k Dalton cuff-off membrane to collect peptide fractions smaller than 10 kDa. Upon ingestion, the fractions that are bigger than tri-peptides are digested by pepsin in the stomach and by pancreatic proteases in the small intestine. Furthermore, the peptidases present at the brush border of the small intestine further hydrolyze the luminal peptides, converting them to free amino acids and very small peptides which are now ready for absorption. The absorbed amino acids and peptides would be similar to those obtained when consuming commercial yeast and yeast derived products. DNF-10 has been demonstrated to have appetite suppressing properties shown in randomised clinical trials.

[0122] The composition of the invention may be formulated such that the yeast hydrolysate is administered in a therapeutically effective dosage. One of skill in the art would be able to adjust the amount of yeast hydrolysate in the composition to achieve a desired dosage per day.

[0123] In some embodiments, the yeast hydrolysate is in the form of yeast hydrolysate peptide complex.

[0124] In some embodiments, the yeast hydrolysate is in the form of yeast hydrolysate peptide complex DNF-10.

[0125] Suitably, yeast hydrolysate is present in an amount such that the composition provides yeast hydrolysate of about 100 to 1000 mg per day.

[0126] Suitably, yeast hydrolysate is present in an amount such that the composition provides at least about 100 mg yeast hydrolysate per day.

[0127] Suitably, yeast hydrolysate is present in an amount such that the composition provides about 1000 mg or less yeast hydrolysate per day.

[0128] In some embodiments, yeast hydrolysate is present in an amount such that the nutritional composition provides yeast hydrolysate in a dosage of about 1000 mg / day.

[0129] In some embodiments, the composition may be formulated such that the yeast hydrolysate is administered in a suitable amount per dose. As used herein, a “dose” may refer to the recommended or typical amount of the product that is administered at one time. As used herein, "dose" on product packaging may refer to the nutritional information provided on the label and how it relates to a single dose of the product.

[0130] Suitably, the composition comprises yeast hydrolysate in an amount of 1 dose or more, in an amount of 2 doses or more, 3 doses or more, 4 doses or more, 5 doses or more, 6 doses or more, such that the total amount of yeast hydrolysate provided is about 100 to 1000 mg per day.

[0131] In some embodiments, the composition comprises yeast hydrolysate in 4 doses for a total of at least about 500 mg yeast hydrolysate per day.

[0132] In some embodiments, the composition comprising yeast hydrolysate enhances appetite suppressing properties and / or reduces energy intake in kcal / day consumed. In some embodiments, the composition comprising L-carnitine, dihydrocapsiate and yeast hydrolysate enhances energy expenditure and / or fatty acid oxidation.

[0133] In some embodiments, the composition comprising L-carnitine, dihydrocapsiate and yeast hydrolysate enhances appetite suppressing properties and / or reduces energy intake in kcal / day consumed.

[0134] Formulation of composition

[0135] A composition of the invention may be a nutritional composition prepared in any suitable manner. The nutritional composition is not particularly limited as long as it is suitable for administration (e.g. oral, enteral, or parenteral administration). Examples of suitable nutritional compositions include powder formulas, foodstuffs, beverages, and nutritional supplements.

[0136] In some embodiments of the invention, the composition is a supplement.

[0137] The "supplement", “food supplement” or “dietary supplement” of the invention may be used to supplement the diet of an individual. The composition of the invention may be added to a beverage or food product and mixed to provide the final form of the supplement.

[0138] A supplement according to the invention can vary in shape, size and colour.

[0139] For example, the supplement may be in a solid dose form, hard capsule, soft capsule, tablet, powder, powder to be reconstituted in water, liquid, ready to drink beverage, effervescent tablet, lozenge, gummy, gel or the active ingredients of the invention may be incorporated into a food product, such as a nutritional bar.

[0140] The supplement may contain in addition to the active ingredients: L-carnitine, dihydrocapsiate and yeast hydrolysate; an organic or inorganic carrier material suitable for oral or enteral administration, such as maltodextrin or cellulose, as well as other vitamins, minerals, trace elements and other micronutrients in accordance with the recommendations of government recommended daily allowances (RDAs).

[0141] The supplement may contain in additional ingredients in addition to the active ingredients: L- carnitine, dihydrocapsiate and yeast hydrolysate, further fibers, lipids and carbohydrates. An example of such a supplement is given in the Examples of the present invention.

[0142] The composition of the invention provides a constant controlled amount of active ingredients with a desired physiological effect to reduce energy intake, enhance satiety with appetite suppression and / or increase energy expenditure and / or fatty acid oxidation. A composition of the invention may be suitably in a “solid dosage form” consists of a shell and a filling with the active ingredients of the invention. The shell is composed of two halves that are closed off at one end. Capsule shells may be made from gelatine, starch, cellulose, pullulan or other suitable materials and are filled with dry powers, pellets or liquid ingredients.

[0143] A composition of the invention may be suitably in a “soft gel” which is a type of soft capsule that is suitable for liquid or semi-solid fillings. Compared to hard capsules, in addition to the active ingredients of the invention, they require additional ingredients such as glycerine, to obtain their soft texture. They are manufactured and sealed in a single process.

[0144] In several embodiments of the invention, the composition is a capsule.

[0145] A composition of the invention may be suitably in a “tablet” which is composed of a mixture of the active ingredients of the invention, usually in powder form, that are moulded and pressed into the form of a tablet, which may be circular, oblong or other shapes. The tablet ingredients can be blended uniformly or separated into different layers within the tablet. They can also be coated to improve the product’s stability, mask unpleasant taste, and protect the tablet and its ingredients from the stomach’s acidity.

[0146] In several embodiments of the invention, the composition is a tablet.

[0147] A composition of the invention may be suitably a “powder” which contains the active ingredients of the invention that can be reconstituted by dissolving into a liquid, such as water, or sprinkled on food. The serving could be, for example, a sachet, stick or measuring scoop.

[0148] In several embodiments of the invention, the composition is a tablet.

[0149] A composition of the invention may be suitably a “liquid” includes a wide range of solutions, syrups, mixtures and may contain sweeteners and flavours to mask any taste of the active ingredients of the invention so that they are more palatable. They are generally presented in bottles or vials. When they contain more than one single dose, they are accompanied by, for example, a dropper or measuring spoon. Liquids may need to be diluted in water.

[0150] In several embodiments of the invention, the composition is a liquid.

[0151] In several embodiments of the invention, the composition is a liquid in a ready to drink beverage format.

[0152] A composition of the invention may be suitably an effervescent tablet which contains the active ingredients of the invention and are designed to dissolve when placed in water to release carbon dioxide and create a drink. They generally include colours and flavours to mask the taste of the active ingredients and provide a good consumer experience.

[0153] In several embodiments of the invention, the composition is an effervescent tablet.

[0154] A composition of the invention may be suitably a lozenge which is a solid dosage forms that are intended to dissolve or disintegrate slowly in the mouth. They contain the active ingredients of the invention and are typically flavoured and sweetened to be pleasant tasting.

[0155] In several embodiments of the invention, the composition is a lozenge.

[0156] A composition of the invention may be suitably in a chewable form such as gummies and chewable tablets contain the active ingredients of the invention and they come in a variety of shapes, colours, flavours and textures, both hard or soft. They are often taken by people who have difficulty swallowing tablets or capsules.

[0157] In several embodiments of the invention, the composition is a gummy or chewable table.

[0158] A composition of the invention may be suitably in a gel form may be contained in a squeezable pouch or administered in a dispenser. They may be added to liquids such as water or used directly.

[0159] In several embodiments of the invention, the composition is a gel.

[0160] A composition of the invention may be suitably incorporated together in a food matrix which can contain the active ingredients of the invention. In particular, the composition of the invention may take the form of a foodstuff including but not limited to a nutritional bar, biscuits, crackers, cookies, pudding, soup or sauce.

[0161] In several embodiments of the invention, the composition is formulated into a foodstuff.

[0162] In several embodiments of the invention, the composition is a nutritional bar.

[0163] In several embodiments of the invention, the composition is a snack.

[0164] A “meal” may be considered to be different from a snack in that meals are generally larger, more varied, and more filling than snacks. The type of food that is served or consumed at any given time depends on regional customs. Typically, three main meals are often eaten in the morning, early afternoon, and evening. These may correspond to breakfast, lunch and dinner.

[0165] A “snack” may be considered to be smaller than a meal and eaten between meals. In several embodiments of the invention, the composition is administered at least 30 minutes before a meal or snack.

[0166] In several embodiments of the invention, the composition is administered together with a meal or snack.

[0167] Energy intake

[0168] In several embodiments of the invention, energy intake is measured using dietary or food recalls questionnaires.

[0169] A 24-hour dietary recall (24HR) is a structured questionnaire or interview intended to capture detailed information about all foods, beverages, and dietary supplements and the amounts consumed by the respondent in the past 24 hours.

[0170] The types of food and beverages are recorded and it may capture portion sizes, cooking methods, time of consumption, and brand names.

[0171] To estimate usual dietary intake distributions accurately, it is best to conduct two or more non- consecutive 24-hour diet recalls, usually on two weekdays and one weekend. This approach is recommended, especially when analyzing diet and health or other related factors.

[0172] Based on a 24-hour diet recall, the total caloric intake can be calculated per 24-hour period.

[0173] In several embodiments of the invention, the food recall is preferably taken on three consecutive days at the beginning of the administration of the composition and after at least 4 weeks of taking the composition of the invention.

[0174] In several embodiments of the invention, energy intake per day by the individual is ad libitum.

[0175] In several embodiments of the invention, the method of determining a reduction in energy intake is by comparing the values of the initial caloric intake in kcal / day consumed at the start of administering the composition of the invention and then the caloric intake in kcal / day after at least 4 weeks of administration of the composition of the invention to determine the difference.

[0176] In several embodiments of the invention, the composition of the invention is provided to reduce energy intake which is measured by caloric intake consumed per day, by a reduction in energy intake of at least 15 kcal / day, at least 50 kcal / day, at least 100 kcal / day, at least 120 kcal / day, at least 150 kcal / day based on the daily caloric intake compared to baseline at the start of the intervention with the composition with the daily caloric intake after using the composition, preferably after 4 weeks of administration of the composition of the invention.

[0177] In several embodiments of the invention, the method of weight management of the invention comprising administration of a composition of the invention results in a reduction of energy intake by at least 15 kcal / day consumed after 4 weeks of administration of the composition of the invention compared to baseline for the individual before taking the composition.

[0178] Satiety

[0179] Satiety is defined as a state of noneating, characterized by the absence of hunger, which follows post-prandially after consumption of a meal or snack and arises from the consequences of food ingestion. Satiety involves post-ingestive processes that inhibit eating. Satiation is the result of the collective processes that stop one from eating the current meal of snack. Satiation may be measured by calculating how many calories one eats on an ad libitum meal or snack. Many signalling molecules and hormones control appetite and satiety in the cellular, peripheral and central nervous systems.

[0180] In several embodiments of the invention, satiety is enhanced by administration of a composition of the invention.

[0181] In several embodiments of the invention, satiety is measured by questionnaires such as the (VAS) which measure subjective appetite feelings at different timepoints via a visual analogue scale

[0182] Ratings of subjective appetite sensations, which reflect the motivational drive to eat, can be made using visual analogue scales (VAS). VAS are typically used to measure subjective ratings of hunger, fullness, desire to eat and prospective food consumption, but a range of scales have been employed, and a composite score can be created from individual scales. Uses for visual analog scale (VAS) questionnaires in ingestive behavior research include the assessment of pre- and postprandial hunger, fullness, desire to eat, and prospective food consumption (PFC) before and during acute controlled nutritional intervention studies.

[0183] In several embodiments of the invention, satiety is measured by a questionnaire administered to the individual, preferably administered at 4 weeks after the individual continuously is taking said composition, wherein there is a reduction in appetite. In several embodiments of the invention, the method of weight management of the invention comprising administration of a composition of the invention enhances satiety as measured by a questionnaire to the individual after 4 weeks of the individual continuously taking said composition and the questionnaire measures a perceived decrease in appetite and / or increase in satiety.

[0184] In several embodiments of the invention, the energy intake is ad libitum and compared before and after administration of the composition of the invention may be indicative of enhanced satiety.

[0185] Energy expenditure

[0186] Total energy expenditure can be defined in terms of the following three components: basal and resting metabolic rates; thermic effect of food (dietary thermogenesis) and via brown adipose tissue; and physical activity (spontaneous physical activity and other physical activities of daily living).

[0187] Energy expenditure may be calculated using indirect or direct calorimetry.

[0188] Indirect calorimetry calculates an individual’s energy expenditure by measuring oxygen consumption and carbon dioxide production. Typically, the Resting Energy Expenditure (REE) is what is calculated.

[0189] Measurements of Vo2and Vco2are used to calculate REE using the modified Weir equation: REE = [Vo2(3.941) + Vco2(1.11)] x 1440.

[0190] Direct calorimetry provides a measure of energy expended in the form of heat. The subject is placed in an insulated chamber and heat produced by the body is absorbed by a known volume of water. The change in water temperature is the heat lost from the subject and represents expended metabolic energy. While this method is the gold standard, it is less feasible for monitoring energy expenditure in a clinical setting.

[0191] In several embodiments of the invention, energy expenditure is measured post-prandially

[0192] In several embodiments of the invention, the composition of the invention enhances energy expenditure measured by calorimetry in kcal / kg fat free mass with at least an increase in energy expenditure of at least 0.5 kcal / kg fat free mass, at least 1 kcal / kg fat free mass, at least 2 kcal / kg fat free mass, based on post-prandial energy expenditure in the individual compared to baseline before using the composition, preferably measured at 4 weeks after continuously taking said composition.

[0193] In several embodiments of the invention, the measurement of energy expenditure is preferably measured by indirect calorimetry.

[0194] In several embodiments of the invention, the method of weight management of the invention comprises administration of a composition of the invention to enhance energy expenditure which is measured by an increase in energy expenditure of at least 2 kcal / kg fat free mass per day measured post-prandially, compared to baseline for the individual before using the composition.

[0195] In several embodiments of the invention, energy expenditure is preferably measured using indirect calorimetry at Week 4 and Week 12 after intervention with the composition of the invention.

[0196] Fat Oxidation

[0197] Fat oxidation may be assessed clinically by measuring respiratory quotient (RQ), which is the ratio of the carbon dioxide expired to the oxygen consumed during indirect calorimetry. One way of measuring this may be done using a respirometer.

[0198] Fat oxidation may be assessed by means of a13CO2-breath test. After administration of a [U-13C]algal lipid mixture, exhaled air is collected and13C abundances were measured by nondispersive infrared spectroscopy. This method also measures the ratio of carbon dioxide expired to oxygen consumed.

[0199] In several embodiments of the invention, fat oxidation is enhanced after administration of a composition of the invention.

[0200] In several embodiments, the present invention provides a composition wherein enhanced energy expenditure is measured by measuring fat oxidation wherein a lower respiratory quotient indicates an increase energy expenditure based on post-prandial energy expenditure in the individual compared to baseline before using the composition, preferably measured at 4 weeks after continuously taking said composition. Blood biomarker measurements

[0201] In several embodiments of the invention, blood samples may be obtained and blood biomarkers measured at different time points during the intervention with the administration of a composition of the invention.

[0202] In several embodiments of the invention, blood samples are preferably obtained during the fasting stage.

[0203] Analysis of blood samples may include measurements of biomarkers such as acylcarnitine (marker of intake); TMAO (Trimethylamine N-Oxide) (marker of intake and safety); glucose, insulin, liver function markers, derivates of carnitine, adiponectin, GDF-15 and blood lipid profile.

[0204] In several embodiments of the invention, blood biomarkers are measured at baseline, Week 4 and Week 12 in fasting stage.

[0205] These blood biomarkers undergo a metabolomics data analysis which involves the compound identification, statistical analysis and interpretation of any differences in these biomarkers at the different time points at baseline and after different time points after administration of a composition of the invention.

[0206] In several embodiments of the invention, metabolomic analysis compares the blood biomarker measurements at baseline, Week 4 and Week 12 after administration of a composition of the invention.

[0207] Gut hormone measurements

[0208] In several embodiments of the invention, gut hormone biomarkers such as GLP-1 , PYY, CCK, ghrelin, leptin, oxyntomodulin, NEFA, and FFA may be measured.

[0209] In several embodiments of the invention, these gut hormone biomarker measurements are preferably obtained during the fasting stage.

[0210] In several embodiments of the invention, gut hormone biomarkers are measured at baseline, Week 4 and Week 12 after administration of a composition of the invention.

[0211] In several embodiments of the invention, metabolomic analysis compares the gut hormone biomarker measurements at baseline, Week 4 and Week 12 after administration of a composition of the invention. EXAMPLES

[0212] Example 1 - Clinical Trial

[0213] The clinical trial was designed to demonstrate the effects of a composition of the invention comprising the three active ingredients: L-carnitine tartrate, dihydrocapsiate, and the yeast hydrolysate peptide complex DNF-10 with microcrystalline cellulose as excipient in the format of hard vegetable capsules. The matching placebo was microcrystalline cellulose in capsules.

[0214] The clinical trial was a single center, double-blind, randomized, placebo-controlled, 2-arm, parallel-design trial.

[0215] Subjects were recruited aged 21 - 65 years with a BMI of 28-32 kg / m2 for Western individuals or 25-30 kg / m2 for South Asians who were weight stable (no weight changes greater than 3kg in the last 6 months). The subjects received over the 12 week study, 4 capsules per day of the composition of the invention or the placebo.

[0216] Figure 1 represents the recruitment of the subjects and the randomised allocation to the intervention with the product blend of ingredients or the placebo group as described in Tables 1 and 2 below.

[0217] Composition

[0218] The composition of both the placebo and the study product can be found in Table 1 below.

[0219] Table 1

[0220] The composition of the invention and the placebo control were administrated in the form of non- gastric resistant capsules to be swallowed with a glass of water. The capsules selected are vegetable hard capsules (Vcaps®) matching in color and appearance between the composition of the invention and placebo.

[0221] The composition of the invention product and the placebo were self-administered at home for the duration of the study (12 weeks). Participants consumed a total of 4 capsules a day during 2 different intake occasions (2 capsules per intake).

[0222] The targeted dosage of the active components in the study product is shown in the Table 2 below:

[0223] Table 2 The products were kept in their original pack and stored at room temperature (between 15°C and 25°C). Participants were asked to return any remaining products for safe disposal when they returned at the site on visit week 4 and at the end of study.

[0224] The products were manufactured at a Nestle Research facility which is accredited with FSSC 22000, ISO 22000, ISO 9001 , GMP and HACCP certificates. The expiry date (EXP) and manufacturing date (MAN) were printed on the label of the different bottles. The products were released according to Nestle internal standards and provided with a Certificate of Analysis.

[0225] L-carnitine was supplied by Lonza, ON; Dihydrocapsiate was supplied by Ajinomoto, JP; and Yeast hydrolysate, DNF-10® was supplied by Flytexia.FR.

[0226] Data Collection

[0227] The primary outcome of the study was the energy intake (via 3 consecutive day food recalls) at the beginning of the study and at Week 4 of the study.

[0228] The secondary outcomes at Week 4 and Week 12 of the study included energy expenditure (using indirect calorimetry), fat oxidation (using respiratory quotient), subjective appetite feelings (VAS), body weight, waist circumference, and body composition (bioelectrical impedance).

[0229] In addition to the standard continuous monitoring of adverse events, gastrointestinal side effects and nausea were recorded using VAS on Week 4 and Week 12.

[0230] Blood biomarkers were measured in fasting stage at Week 4 and Week 12 of the study.

[0231] These included: acylcarnitine (marker of intake); TMAO (Trimethylamine N-Oxide) (marker of intake and safety); glucose, insulin, liver function markers, derivates of carnitine, adiponectin, GDF-15 and blood lipids.

[0232] Gut hormone biomarkers were measured post-prandially at Week 4 and Week 12 of the study.

[0233] These included: GLP-1 , PYY, CCK, ghrelin, leptin, oxyntomodulin, NEFA, and FFA.

[0234] Results

[0235] Anthropometric measurements

[0236] Body weight, waist circumference, body mass index (BMI), body composition (bioelectrical impedance) were measured at week 1 (baseline), week 4 and week 12. Figure 2 shows that the waist circumference of the subjects treated with the study product (blend) decreased compared to the placebo (control) group as measured at 4 weeks and this was maintained until 12 weeks. There were no differences in the other anthropometric measurements.

[0237] Energy intake

[0238] Energy intake was measured using 3 x 24h dietary recall of intake. Ad libitum energy intake was measured via an ad libitum homogeneous meal at 180 min timepoint at week 4 and 12. Food was weighed before and after to calculate how much food was consumed and converted to kcal.

[0239] Figure 3 shows that energy intake was decreased as measured in total kcal consumed per day at week 4 in the subjects treated with the study product (blend) compared to the placebo (control) group and this decreased energy intake was maintained at 12 weeks.

[0240] Energy expenditure

[0241] Energy expenditure was measured post-prandially (following a mixed meal tolerance test via standard breakfast) energy expenditure and substrate oxidation (respiratory quotient, fat and carbohydrate oxidation) at time points of 40 - 60min, 100 - 120mins, 160 - 180 min relative to standard breakfast intake (SP was taken 30 min before breakfast intake) using indirect calorimetry at week 4 and week 12.

[0242] Indirect calorimetry is a known gold-standard, non-invasive technique which is clinically recommended. It measures energy expenditure and substrate oxidation by measuring pulmonary gas exchange (i.e. the production of carbon dioxide and the oxygen inspired). This allowed calculation of rates of energy expenditure and substrate oxidation. The endpoint was the incremental Area Under the Curve (iAUC) at 3h. Overnight fasted energy expenditure and substrate oxidation was measured using indirect calorimetry at week 4 and 12.

[0243] Figure 4 shows a higher resting energy expenditure in the subjects treated (blend) compared to the placebo (control) subjects at 4 weeks which was maintained at 12 weeks.

[0244] Figure 5 shows increased carbohydrate oxidation in the subjects treated (blend) compared to the placebo (control) subjects at 4 weeks which was further increased in the treated (blend) subjects at 12 weeks.

[0245] There was no difference between groups in the measurements of fat oxidation. Composite Appetite Score

[0246] Composite Appetite Score (CAS) was measured using a questionnaire for subjective appetite feelings. Subjective appetite feelings (individual questions and composite appetite score) were measured using a 100mm-visual analogue scale (VAS) at -50, -40,15, 30, 60, 90, 120, 180 min relative to breakfast intake at week 4 and 12.

[0247] The outcomes resulted in a Composite Appetite Score of iAUC3h of measurements of hunger, satiety, fullness, and desire to eat.

[0248] Overall, the Composite Appetite Score (CAS) showed a decrease in appetite in the subjects treated (blend) compared to the placebo (control) subjects.

[0249] Hunger

[0250] Figure 6 shows the VAS measurements for Hunger. The VAS measurement for hunger demonstrated that there was a decrease in subjective feelings of hunger in the subjects treated (blend) compared to the placebo (control) subjects. This is shown be the AUC values of the treated (blend) versus the placebo (control) groups.

[0251] Satiety

[0252] Figure 7 shows the VAS measurements for Satiety. The VAS measurement for satiety demonstrated that there was a greater perception of satiety in the subjects treated (blend) compared to the placebo (control) subjects. This is shown be the AUC values of the treated (blend) versus the placebo (control) groups.

[0253] Fullness

[0254] Figure 8 shows the VAS measurements for Fullness. The VAS measurement for fullness demonstrated that there was a greater perception of fullness. This is shown be the AUC values of the treated (blend) versus the placebo (control) groups.

[0255] Desire to eat

[0256] Figure 9 shows the VAS measurements for Desire to Eat. The VAS measurement for Desire to Eat demonstrated that there was less desire to eat in the treated (blend) versus the placebo (control) group as shown in the AUC values. Blood and Gut hormone biomarkers

[0257] C-reactive protein was measured at -50 min (fasted) relative to breakfast intake for the endpoint at week 4 and 12.

[0258] Liver function was measured at -50 min (fasted) relative to breakfast intake for the endpoint at week 4 and 12.

[0259] Fasting acylcarnitine and derivates, TMAO, HbA1c, liver function, CRP, blood lipid profile were measured at week 4 and 12.

[0260] Postprandial gut hormones: GLP-1 , PYY, ghrelin were measured at -50, -40,15, 30, 45, 60, 90, 120, 180 min relative to breakfast intake for the endpoint iAUCI h and iAUC3h at week 4 and 12.

[0261] Postprandial: glucose, insulin, gut hormones (Glucose-dependent insulinotropic polypeptide [GIP], CCK, leptin, Growth differentiation factor 15 [GDF-15], oxyntomodulin) were measured at -50, -40,15, 30, 45, 60, 90, 120, 180 min relative to breakfast intake for the endpoint iAUCI h and iAUC3h.

[0262] Summary

[0263] The study was able to demonstrate that a composition of the invention comprising: (i) l-carnitine, (ii) diyhydrocapsiate and (iii) yeast hydrolysate was able to reduce energy intake in kcal consumed per day, enhance satiety by improving appetite control and enhance energy expenditure.

Claims

CLAIMS1. A composition comprising: (i) l-carnitine, (ii) diyhydrocapsiate and (iii) yeast hydrolysate for use in reducing energy intake, enhancing satiety and / or enhancing energy expenditure.

2. The composition according to claim 1 wherein (i) l-carnitine is provided in the amount of 500 mg to 3000 mg; (ii) dihydrocapsiate is provided in the amount of 3 mg to 12 mg and (iii) yeast hydrolysate is provided in the amount of 100 mg to 1000 mg.

3. The composition according to Claim 1 or 2 wherein (i) l-carnitine is provided in the amount of about 1000 mg / day, (ii) dihydrocapsiate is provided in the amount of about 6 mg / day and (iii) yeast hydrolysate is provided in the amount of about 500 mg / day.

4. The composition according to claim 1 or 2 wherein the composition is administered in a single dose, in two doses, three doses, four doses, 5 doses, 6 doses per day in order that (i) l-carnitine is provided in the amount of 500 to 3000 mg / day, (ii) dihydrocapsiate is provided in the amount of 3 to 12 mg / day and (iii) yeast hydrolysate is provided in the amount of 100 to 1000 mg / day.

5. The composition according to claim 3 wherein the composition is administered in a single dose, in two doses, three doses or four doses per day in order that (i) l-carnitine is provided in the amount of about 1000 mg / day, (ii) dihydrocapsiate is provided in the amount of about 6 mg / day and (iii) yeast hydrolysate is provided in the amount of about 500 mg / day.

6. The composition of any one of claims 1 to 5 administered (i) at least 30 minutes before a meal or snack or (ii) together with a meal or snack.

7. The composition of any one of claims 1 to 6 wherein said composition is a food supplement selected from a solid dose form, hard capsule, soft capsule, tablet, powder, powder to be reconstituted in water, liquid, ready to drink beverage, effervescent tablet, lozenge, gummy, gel or incorporated into a food product, such as a nutritional bar.

8. The composition according to any one of claims 1 to 7 for use in individuals who are overweight, obese, or maintaining desired body weight, such as after weight loss.

9. The composition according to any one of claims 1 to 8 wherein reduction in energy intake is measured by caloric intake consumed per day, by a reduction in energy intake of at least 15kcal / day, at least 50 kcal / day, at least 100 kcal / day, at least 120 kcal / day, at least 150 kcal / day based on the daily caloric intake compared to baseline for the individual before using the composition.

10. The composition according to any one of claims 1 to 8 wherein satiety is measured by a questionnaire administered to the individual, preferably administered at 4 weeks4-weeks after the individual continuously is taking said composition, wherein there is a reduction in appetite.11 . The composition according to any one of claims 1 to 8 wherein enhanced energy expenditure is measured by calorimetry in kcal / kg fat free mass with at least an increase in energy expenditure of at least 0.5 kcal / kg fat free mass, at least 1 kcal / kg fat free mass, at least 2 kcal / kg fat free mass, based on post-prandial energy expenditure in the individual compared to baseline before using the composition, preferably measured at 4 weeks 4 weeks after continuously taking said composition.

12. The composition according to any one of claims 1 to 11 for use in weight maintenance, weight loss, obesity prevention and treatment, reducing calorie intake, reducing appetite, promoting satiety, maintenance of muscle mass, auxiliary management of diabetes, auxiliary management of post-prandial blood glucose and insulin, and reducing blood cholesterol.

13. The composition according to any one of claims 1 to 12 for administration to an individual together with a GLP-1 agonist or to an individual who has stopped using a GLP-1 agonist after weight loss or to an individual who is on another weight-loss regime or to an individual who wants to maintain a desired body weight.

14. The composition according to any one of claims 1 to 13 for use in an individual wherein said individual is a mammal, preferably a human mammal.

15. Method of weight management comprising administration of a composition according to any one of claims 1 to 14 wherein reduction of energy intake is measured by a reduction in energy intake by at least 15 kcal / day consumed compared to baseline for the individual before taking the composition.

16. Method of weight management comprising administration of a composition according to any one of claims 1 to 14 wherein enhanced satiety is measured by a questionnaire to the individual after 4 weeks of the individual continuously taking said composition and the questionnaire measures a perceived decrease in appetite and / or increase in satiety.

17. Method of weight management comprising administration of a composition according to any one of claims 1 to 14 wherein enhanced energy expenditure is measured by an increase in energy expenditure of at least 2 kcal / kg fat free mass per day measured post-prandially, compared to baseline for the individual before using the composition.

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