EP3833370A1

EP3833370A1 - Compositions for use in the treatment of obesity

Info

Publication number: EP3833370A1
Application number: EP19729848.2A
Authority: EP
Inventors: Alessandro LAVIANO
Original assignee: Nutrintech Ltd
Current assignee: Nutrintech Ltd
Priority date: 2018-05-14
Filing date: 2019-05-14
Publication date: 2021-06-16
Also published as: IT201800005336A1; WO2019220335A1

Abstract

The present invention relates to compositions comprising extract of Whitania somnifera including Withaferin A and/or Withaferin A and to a cinnamon extract and the use thereof for the treatment of obesity, and generally for the loss of fat mass. Also kits of portions comprising a first composition including Withaferin A and a second composition including a cinnamon extract belong to the present invention.

Description

"Compositions for use in the treatment of obesity"

FIELD OF THE INVENTION

The present invention relates to compositions comprising Withaferin A and a cinnamon extract and the use thereof for the treatment of obesity, and in general for the reduction of fat mass. Also kits of portions, comprising a first composition including Withaferin A and a second composition including a cinnamon extract, belong to the present invention.

STATE OF ART

Obesity represents a clinical condition characterized by the increase in fat mass and the development of chronic- degenerative pathologies, such as diabetes, arterial hypertension and some forms of tumours ( Pearson-Stuttard J et al, Lancet Endocrinol Diab 2018) . The clinical relevance of obesity is underlined not only by its large prevalence and by its clinical correlations, but even by the lack of an effective medical therapy which could contribute in favouring the change of life styles.

A minimum percentage of patients is obese for precise genetic causes. On the contrary, for most part of patients, the obesity causes are to be found in the not healthy life styles, and in particular in the unbalance between energy introduced with diet and energy consumption through physical activity. Under physiological conditions, the excessive consumption of food is prevented by a series of endocrinological mechanisms, thereamong the circulating levels of leptin hormone (Pan WW et al, Nat Rev Neurosci 2018) . Leptin is a polypeptide hormone produced by the adipose tissue proportionally to its sizes. The increase in the circulating levels of leptin triggers the activation of brain areas leading to the decreased appetite and of the caloric intake per os (Pan WW et al, Nat Rev Neurosci 2018) . However, the chronic stimulation by leptin of the brain areas determines the appearance of progressive resistance by the brain areas (Pan WW et al, Nat Rev Neurosci 2018) . And in fact, most part of cases of human obesity induced by wrong life styles is characterized by leptin-resistance and hyper-leptinemia (Pan WW et al, Nat Rev Neurosci 2018) .

Even the reduced physical activity contributes to the pathogenesis of obesity. To say the truth, a moderate- intense and constant physical activity would allow to increase the energy expense and then to contrast the effects on the body composition of the increase in the caloric intake (Kang SJ et al, J Phys Ther Sci 2018) . However, an increase in the energy expense can be obtained even by transforming the white adipose tissue, a mainly storage tissue, into brown adipose tissue, characterized by high metabolic activity with energy dispersion (Thyagarajan B et al, Horm Mol Biol Clin Investig 2017) . Although the brown adipose tissue is limited in man, the transformation of the white tissue into brown tissue, phenomenon called "browning", was demonstrated after physical stimuli, such as the exposition to cold, or pharmacological stimuli (Thyagarajan B et al, Horm Mol Biol Clin Investig 2017) .

Obesity is a clinical and social problem, which does not recognize effective therapies, with the exception of the bariatric and metabolic surgery even if compositions are known which help the weight loss, such as for example the International patent application Nr. W02005/ 107779 which describes a composition for the weight loss based upon Garcinia cambogia extract, Gymnema sylvestre extract and green tea extract. However, similar compositions (such as for example those described in the patent application US 2011/0052736) are used even for the muscle recovery.

Considered the obesity pathogenesis, a medical therapy would be optimum if at the same time it had as target both a hyperphagia control and the reduced energy expense .

The object of the present invention is to provide composition and kit useful for the treatment of obesity and more generally for the reduction of fat mass.

SUMMARY OF THE INVENTION

The present invention is based upon the search for and identification of a new combination of natural active principles which used in association exert a synergic effect in the reduction of the fat mass as confirmed by experiments on some obese subjects.

The present invention relates to compositions comprising Withaferin A and/or an extract of Whitania somnifera including said molecule and a cinnamon extract. The present invention further relates to their use in the prevention and treatment of obesity. The association Withaferin A and/or an extract of Whitania somnifera including said molecule and cinnamon extract provides a natural solution to the clinical problem of obesity through the normalization of brain sensitivity to leptin, with consequent decreased appetite and caloric intake, and increase in energy expenditure through the "browning" of adipose tissue.

Other advantages and features of the present invention will result evident from the following detailed description .

DETAILED DESCRIPTION OF THE INVENTION

The present invention describes a composition comprising as main active ingredients the cinnamon extract in association with Withaferin A and/or with an extract of Whitania somnifera including such molecule.

Withaferin A is the main component of the extract of Withania somnifera (that is, Ashwaganda in the ayurvedic tradition), in particular of the root and/or leaves which are the portions most commonly used for the preparation of extracts from said plant. Chemically, Withaferin A is a steroid lactone with important biological properties. Withaferin A returns the normal sensitivity to leptin in experimental models of obesity induced by the diet, by reducing the body weight and improving the metabolic profile associated to obesity. Withaferin A has the following structure formula and it could be prepared according to the procedures known to the person skilled in the art .

Withaferin A, if provided as molecule, as such could be for example administered with a dosing regimen between 50 and 500 mg/die, preferably 300 mg/die (for example lOOmg x 3 times per day, for example one hour before the main meals), alternatively, if provided as extract of Whitania somnifera plant, the dosage of Withaferin A pro die could be administered with a dosing regimen from 2 to 500 mg/die, from 2 to 200 mg/die, from 2 to 100 mg/die, from 2 to 50 mg/die, from 2 to 20 mg/die, from 2 to 10 mg/die, from 2 to 5 mg/die (for example 1-1.5 mg three times per day) . According to an embodiment the composition could include Withaferin A as insulated molecule and/or an extract of Withania somnifera including such molecule (for example prepared by means of techniques commonly used in the field such as the aqueous extraction, the hydroalcoholic extraction and the like) , in particular an extract as above defined from root of Whitania somnifera preferably titrated at a certain percentage of Withaferin A.

To the purpose of the present invention, extracts of Whitania somnifera plant can be used, having a content of Withaferin A (and then titrated in Withaferin A) from about 0.2% w/w to 20% w/w. For example, an extract of Whitania somnifera plant suitable to implement the present invention can have a content of Withaferin A from about 0.2% w/w to 15% w/w, from 0.2% w/w to 10% w/w or from 0.2% w/w to 5% w/w.

Therefore, the extract used in the present invention can be an extract or one or more fractions of extract of Whitania somnifera, such as for example an aqueous extract or a hydroalcoholic extract, optionally lyophilised, with a titre in Withaferin A of about 0.2; 0.3, 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1 ; 1.5; 2 ; 2.5; 3 ; 3.5; 4 ; 4.5; 5 ; 5.5; 6 ; 6.5; 7; 7.5; 8; 8.5; 9; 9.5; 10; 10.5; 11; 11.5; 12; 12.5; 13; 13.5; 14; 14.5; 15; 15.5; 16; 16.5; 17; 17.5; 18; 18.5; 19; 19.5; 20% w/w of said extract.

The authors of the present invention have also surprisingly found that by using the extract of Whitania somnifera plant instead of the molecule of Withaferin A it is possible to administer much lower dosages of Withaferin A pro die than those required with Withaferin A as such. For example, by administering the extract of Whitania somnifera plant, the dosage of Withaferin A pro die can be comprised from 2 to 500 mg/die, from 2 to 200 mg/die, from 2 to 100 mg/die, from 2 to 50 mg/die, from 2 to 20 mg/die, from 2 to 10 mg/die, from 2 to 5 mg/die.

In particular, the authors of the invention have demonstrated that it is possible to use with success (see examples below) amounts equal to about 2-5 mg per day of Withaferin A if administered under the form of extract in combination with the cinnamon extract as herein described, by obtaining the wished weight loss in the treated subj ects . By pure way of example, but in no way as limiting example, 6 capsules/die can be administered including 150 mg of extract of Whitania somnifera plant titrated at about 0.5% w/w in Withaferin A which correspond to about 0.75 mg di Withaferin A per capsule, being equal to a total of 4.5 mg/die .

The person skilled in the art could adapt the amount of extract used in the preparation of the formulations to be administered depending upon the used extract of Whitania somnifera. For example, the used amount of extract can be reduced when the used extract of Whitania somnifera has a high titre in Withaferin A in the shown range, whereas the used amount of extract can be increased when the used extract of Whitania somnifera has a low titre in Withaferin A with respect to the shown range (0.2-20% w/w) . For example, still remaining in an indicative dosage of 4.5 mg/die, 3 capsules/die can be administered including 150 mg of extract of Whitania somnifera plant titrated at 1% w/w in Withaferin A which correspond to 1.5 mg of Withaferin A per capsule, being equal to a total of 4.5 mg/die. Or, 3 capsules/die can be administered including 10 mg di extract of Whitania somnifera plant titrated at 15% in Withaferin a which correspond to 1.5 mg of Withaferin A equalling to a total of 4.5 mg/die. Or, still, 8 capsules can be administered including 250 mg of extract of Whitania somnifera plant titrated at 0.2% w/w in Withaferin A which correspond to 0.5 mg of Withaferin A per capsule, equalling to a total of 4 mg/die.

The attending practitioner or the dietician will be able to identify the optimum dosage for the subject to be treated based upon age, sex, weight and general state of health. Therefore, the dosage of 4.5 mg/die of Withaferin A if formulated by using an extract of Whitania somnifera as above exemplified, can be adapted even during the period of ingestion of the composition of the invention according to the results obtained in time, by decreasing it to 4; 3.5; 3; 2.5; 2 mg/die of Withaferin A if formulated by using an extract of Whitania somnifera, or increased to 5; 5.5; 6 ; 6.5; 7 ; 7.5; 8 ; 8.5; 9 ; 9.5; 10; 15; 20; 25; 30; 50; 100; 200; 300; 400; 500 mg/die of Withaferin A if formulated by using an extract of Whitania somnifera. To the purpose of the present invention, then, compositions with different amounts of extract of Whitania somnifera can be implemented so as to allow the administration of more or less high dosages without the treated subject having to ingest an excessive number of unitary doses (for example capsule, opercle, pill, granulate, tablet etc.) per day.

The composition will include even a cinnamon extract, in particular an extract from the cinnamon bark ( Cinnamomum cassia plant or Cinnamomum Verum plant, also called Cinnamomum Zeylanicum) . Such extract induces the "browning" of the subcutaneous adipose tissue of animals with obesity induced by the diet, by producing a significant weight loss.

The extract could be prepared according to the procedures known in the state of art, for example it could be a dry or powder extract. According to an embodiment an extract of cinnamon bark will be used, prepared with ethanol extraction, in particular having 70% of water, optionally lyophilised. An example of cinnamon extract will include mainly: protocatechuic acid (for example about 17.3 mg/kg), catechin (for example about 302 mg/kg), chlorogenic acid (for example about 25.1 mg/kg), aesculetin (for example about 12.7 mg/kg), quercetin (for example about 180.9 mg/kg) and icarin (for example about 51.1 mg/kg) . The cinnamon extract could be administered for example with a dosing regimen from 50 to 2000 mg/die, in particular 1800 mg/die, preferably in 3-6 separate administrations (for example 600mg x 3 times per day, or 300 mg 6 times per day) .

In an embodiment, the composition does not comprise at least two, at least three, at least four, at least five or at least six of the following components: Garcinia cambogia extract, Gymnema sylvestre extract, green tea extract, curcumin, resveratrol and aspartic acid, or derivatives thereof.

In an additional embodiment, the composition comprises an extract of Withania somnifera plant (preferably from root and leaves) and a cinnamon extract as unique active ingredients for the reduction of the body weight. Therefore, the composition can include other components, such as for example carriers, excipients, stabilizers, preservatives, and the like, but it does not comprise other principles or compounds active in the weight loss or control.

In an embodiment then, the composition of the invention, comprises cinnamon extract in any herein defined form, Withaferin A and/or extract of the Whitania somnifera plant comprising Withaferin A (preferably from root) in any herein defined form and at least one or more pharmaceutically acceptable substances selected among excipients, stabilizers, preservatives, glidants, fillers, humectants, disintegrants , binders, retardants, absorption accelerators, adsorbents, lubricants and the like.

For example, the composition according to the invention can include cinnamon extract in any herein defined form, Withaferin A and/or extract of the Whitania somnifera plant including Withaferin A (preferably from root) in any herein defined form and one or more pharmaceutically acceptable excipients.

The compositions according to the present invention according to anyone of the embodiments provided in the present description can be formulated under any form and administration route and associated to any other component, in a variety of ways, preferably they will be formulated for oral use for example as capsules, soft capsules, tablets, pills, gelatines, powders or granules. Such excipients can be selected for example among those normally used in the state of art and include, but they are not limited thereto: a) carriers, such as for example sodium citrate and calcium phosphate, b) fillers such as for example starch, lactose, microcrystalline cellulose, sucrose, glucose, mannitol, triglycerides and colloidal silica, c) humectants, such as for example glycerol, d) disintegrants , such as alginates, calcium carbonate, starches, derivatives of starch, of cellulose and of polyvinylpyrrolidone, silicates and sodium carbonate e) binders such as carboxymethylcellulose, alginates, gelatine, polyvinylpyrrolidone, sucrose, polymeric derivatives of cellulose, starch derivatives f) retarding agents such as paraffin, cellulose polymers, esters of fatty acids g) absorption accelerators, such as quaternary ammonium compounds, h) wetting agents and surfactants such as cetyl alcohol and monostearate glycerol, i) adsorbents, such as benthic clays and kaolin, k) lubricants such as talcum, calcium stearate, magnesium stearate, polyethylene glycol, sodium lauryl sulfate, sodium stearyl fumarate j) glidants such as talcum, colloidal silica.

The forms of solid dosage, such as tablets, capsules, soft capsules, gelatines, pills and granules, could be coated with enteric, gastric coatings or coatings of other type known in the state of art. They can include opacifers and can be of the type to allow the release of the active ingredients only or preferably in a certain tract of the intestine, in case, in a delayed manner. Substances which can allow such delayed use include, but they are not limited thereto, polymers and waxes.

The soft capsules could house the antioxidant substances in liquid forms alone or in solutions, suspensions or emulsions of the active substances in a liquid solvent. The soft capsules could be characterized by a casing qualitatively similar to that of the stiff ones but thicker and soft.

Liquid forms suitable to an oral administration are for example emulsions, solutions, prepared or extemporaneous suspensions, syrups and elixirs. Excipients suitable to the formulations according to the present invention in liquid forms for oral use include, but they are not limited thereto, diluents such as water or other solvents, solubilizing agents and emulsifying agents selected from ethyl alcohol, polyalcohols, propyl glycol, glycerol, polyethylenglycol and sorbitan esters. These formulations can even include sweeteners and flavours.

The compositions will be for example a medical device, a food supplement, a nutraceutical , dietetic and nutritional composition, a food product, a beverage, a neutraceutical , a medicament, a medicated food, food for special medical purposes, food, a pharmaceutical composition. The compositions will be mainly intended to be used by the human beings, but they could also be used on animals.

The combination of the above-mentioned active ingredients could be used formulated in one single composition according to the various above-described embodiments or in a kit including the different separate ingredients, for example in single compositions such as capsules, pills tablets for sequential or contemporary administration of the different ingredients.

The above-described compositions could be used/administered/ingested for preventing and/or treating obesity, in particular in female subjects. They could also be used by not obese patients to reduce the fat mass. Preferably, independently from the used formulation type, the combination of active ingredients according to the present invention will be administered with a daily dosing regimen according to the above-mentioned amounts.

Generally, then, compositions for oral use will include for example between 10 and 5000 mg of Cinnamon extract per dosage unit and between 10 and 5000 mg of insulated Withaferin A, or 2-500 mg of Withaferin A if formulated by using an extract of Whitania somnifera per dosage unit, preferably between 50 and 500 mg of Cinnamon extract per dosage unit and between 50 and 500 mg of insulated Withaferin A, or 2-100; 2-50; 2-20; 2-10; 2-5 mg of Withaferin A if formulated by using an extract of Whitania somnifera .

EXAMPLES

Some not limitative examples of compositions of the present invention are shown hereinafter.

The examples are provided in formula of capsule or pill but obviously they can be adapted to an administration by means of opercle, granulate, tablet or the like.

EXAMPLE 1

Composition for oral use in form of capsule

EXAMPLE 2

Composition for oral use in form of pill

EXAMPLE 3 Composition for oral use in form of pill, capsule, opercle, granulate or tablet

EXAMPLE 4

Composition for oral use in form of pill, capsule, opercle, granulate or tablet

EXPERIMENTS

The available literature highlights that the supplementation with extract from bark of Cinnamomum Verum in 42 overweight-obese women (BMI average of 30.715, 0) at the dose of 1500 mg/die does not lead to weight loss during a period of 8 weeks (Borzoei A et al . J Tradit Complement Med 2018.

Similarly, 2 overweight subjects (that is, BMI 25-29.9) received for 4 weeks Withaferin A at the dose of 300 mg/die, with a weight loss of 3%. At last, 2 overweight volunteers received a supplementation with Withaferin A 300 mg/die and extract of bark of Cinnamomum Verum 1800 mg/die for 4 weeks and showed a weight loss of 5%. These results confirm that the action of the integrated supplementation of Withaferin A and extract of cinnamon bark determine a synergic effect, greater than the additive action of the single components.

Moreover, with the purpose of evaluating the effectiveness of the composition, the invention relates to, the inventors performed a clinical study by following the protocol described hereinafter. The study was performed with consenting and informed patients and the medical protocol was approved by the ethics committee of the University "SAPIENZA" in Rome.

ADMISSIBILITY

Age comprised between 25 years old and 75 years old

Both sexes

INCLUSION CRITERIA

Overweight and obese patients (BMI between 26 and 35), not subjected to therapy with anorectics nor drugs reducing the digestion and the food absorption in the 3 months preceding the inclusion and who have given their written informed consent to the inclusion in the study.

EXCLUSION CRITERIA

The recruitment will exclude the patients having: symptomatic chronic cardiac deficiency (NYHA class III- IV); congenital heart diseases; tacho-brady arrhythmias with poor pharmacological control; neoplasia in progress; acute heart attack or acute coronary syndrome within 3 months preceding the inclusion in the study; acute infections or inflammations in progress; valvulopathy; cognitive deficit or poor compliance to the treatment; concomitant treatment with thyroid hormones or other drugs interfering with metabolism. Pregnant or fertile women, not using adequate contraceptive methods, will be excluded from inclusion.

MATERIALS AND METHODS

Statistical analysis

The demographic and clinical features will be synthetized by means of descriptive statistics (average, standard deviation, median, interquartile range) in case of continuous variables and by means of absolute frequencies and percentages in case of categoric variables. The distribution normality of all variables will be tested by using Kolmogorov-Smirnov test. The comparison between percentages will be performed by means of chi-square test or with the exact test of Fisher (if n<5) . The correlation coefficients of Pearson or Sperman will be used for analysing the dependence between variables.

The intra-subject weight variation will be evaluated by means of a t-test for paired data. The comparison analysis between the two types of intervention will make use of an analysis of the variance for repeated measurements or, if required, not parametric tests.

In order to take into consideration the longitudinal nature of the data in the secondary analyses we will use the measurement of each marker at each observation time as outcome, estimating generalized linear models with mixed effects. The casual incercept will be used to capture the dependence generated by the repeated measurements.

The statistical software R (3.3.2) will be used for the statistical analysis.

Calculation of the statistical sample

The study was performed on a sample of 40 subjects.

The performed study is a perspective, double-blind study) , cross-over with randomized AB/BA drawing: such mode was selected as at the beginning of a dietary-nutritional programme the adherence is higher and this could constitute a bias. The primary end-point of the study is the variation in the body weight with energy restricted diet and use of the association of extract of Withania somnifera and of extract of cinnamon bark with respect to the body weight with energy restricted diet and placebo.

The systemic effects of the association can also be evaluated through markers of inflammation (that is, CRP, ratio neutrophils on lymphocytes) and of sugar metabolism (that is, glycaemia) and lipidic metabolism (that is, total cholesterol and triglycerides) and/or the effects of the association on the abdominal and gluteal circumference. Each subject will be randomized at a sequence AB or BA, or at a first period of evaluation with energy restricted diet and composition of the invention (treatment A) or energy restricted diet and placebo (treatment B) . More in particular, the treatment A consists in capsules containing 300 mg of extract of cinnamon bark, 150 mg of extract of the root and the leaves of Withania sominifera plant titrated at about 0.5% in Withaferin A and 10 mg of magnesium stearate, whereas the treatment B in capsules containing an equal dose of starch and cellulose, to be ingested three times per day. Under energy restricted diet a diet is meant determining a loss of 20% of the calories usually introduced by the patient.

In order to avoid the run-in of the association, it is suitable to interrupt the ingestion of the association or of the placebo for 14 days before proceeding with the subsequent treatment.

After a clinical and nutritional evaluation, a diet is processed determining a loss of 20% of the calories usually introduced by the patient. At time of starting the diet, the amount is provided to the patient for 4 weeks of association or placebo (depending upon the results of randomization) . At the end of the 4 weeks of treatment A or B, the patient is called again for a medical examination wherein a new clinical and nutritional evaluation is performed. After 14 days of washout, the patient starts the treatment B or A by using the provided material. At the end of the 4 weeks, the patient is examined again and the results are recorded. At this point, the patient exits the study as he/she has completed the protocol, and he/she will continue to be followed by our centre.

Before including in the study, at 4, and 10 weeks from the beginning of the study each patient is subjected to a blood withdrawal apt to evaluate the routine indexes (creatinine, azotemia, uricemia, blood count, triglycerides, total cholesterol, HDL, LDL, glycaemia) . On each examination the patient is subjected to the measurement of the blood pressure, of the oxygen saturation and of the pulse frequency in addition to the medical examination and to the questions related to the adherence to therapy.

Extract of cinnamon bark

The used cinnamon extract is a dry extract of bark of Cinnamomum Cassia obtained by the extraction ethanol/water such as, for example, the dry extraction of a bark of Cinnamomum Cassia commercialized by FlaNat research.

Extract of Withania somnifera

The used extract of Withania somnifera is a dry extract of roots and leaves of Withania somnifera plant obtained by extraction in water and which has the following composition: glycosides Witanolides ³ 10% w/w, oligosaccharides ³ 32% w/w and aglycone of Witanolide (such as Withaferin A) <0.5% w/w such as, for example, the dry extract of roots and leaves of Withania somnifera plant commercialized by Natreon (Sensoril®) .

Clinical evaluation

Evaluation of body mass index (BMI) and weight loss (%), abdominal circumference, beat frequency.

Results

After 4 weeks of administration an average weight loss of -3.4+/-1.3% was recorded in the patients who received the composition of the invention and of -1+/-1.4% in the patients who received placebo.

Claims

1. A composition comprising an extract of Whitania somnifera plant including Withaferin A and/or Withaferin A and a cinnamon extract and one or more excipients and/or diluents and/or carriers.

2. The composition according to claim 1 wherein said extract of Whitania somnifera plant including Withaferin A and/or Withaferin A and said cinnamon extract are the only active principles for the reduction and/or check of the body weight or wherein said composition does not comprise at least two, at least three, at least four, at least five or at least six of the following components: Garcinia cambogia extract, Gymnema sylvestre extract, green tea extract, curcumin, resveratrol and aspartic acid, or derivatives thereof.

3. The composition according to claims 1 or 2, for oral use.

4. The composition according to anyone of claims 1 to

3 wherein said cinnamon extract is an extract from the bark of the Cinnamomum cassia plant or from the Cinnamomum Verum plant.

5. The composition according to anyone of claims 1 to

4 wherein said extract of the Withania somnifera plant is titrated in Withaferin A from 0.2 to 20% w/w.

6. The composition according to claim 5 wherein said Withania somnifera plant extract is titrated in Withaferin A from 0.2% w/w to 15% w/w, from 0.2% w/w to 10% w/w or from 0.2% w/w to 5% w/w.

7. The composition according to anyone of claims 1 to

6 wherein said cinnamon extract comprises protocatechuic acid and/or catechin and/or chlorogenic acid and/or aesculetin and/or quercetin and/or icarin.

8. The composition according to anyone of claims 1 to

7 in a form chosen from capsule, soft capsule, tablet, pill, gelatine, powder, granule, emulsion, solution, syrup .

9. The composition according to anyone of claims 1 to

8 wherein the amount of cinnamon extract is between 50 mg and 5000 mg and/or the amount of Withaferin A is between 50 mg and 5000 mg if provided as insulated molecule or it is between 2 mg and 500 mg if provided in an extract of Whitania somnifera.

10. The composition according to anyone of claims 1 to 9 wherein said composition is a medical device, a food supplement, a nutraceutical , dietetic and nutritional composition, a food product, a beverage, a neutraceutical , a medicament, a medicated food, a pharmaceutical composition or a food for special medical purposes.

11. The composition according to anyone of claims 1 to 10 for use in the prevention and/or treatment of obesity .

12. A non-therapeutic use of a composition according to anyone of claims 1 to 10 for the reduction of fat mass.

13. A kit of portions comprising a first composition for oral use comprising an extract of Whitania somnifera plant comprising Withaferin A and/or Withaferin A and a second composition for oral use comprising a cinnamon extract, in particular an extract from the bark of the Cinnamomum cassia plant or of the Cinnamomum Verum plant.

14. The kit of portions according to claim 13 wherein said extract of the Whitania somnifera plant including Withaferin A and/or Withaferin A and said a cinnamon extract are the only active principles for the reduction and/or control of the body weight or wherein none of said compositions comprises at least two, at least three, at least four, at least five or at least six of the following components: Garcinia cambogia extract, Gymnema sylvestre extract, green tea extract, curcumin, resveratrol and aspartic acid, or derivatives thereof.

15. The kit of portions according to any one of claims 13 or 14 wherein said extract of the Withania somnifera plant is titrated in Withaferin A from 0.2 to 20% w/w.

16. The kit of portions according to claim 15 wherein said extract of the Withania somnifera plant is titrated in Withaferin A from 0.2% w/w to 15% w/w, from 0.2% w/w to 10% w/w or from 0.2% w/w to 5% w/w.

17. The kit of portions according to anyone of claims 13 to 16 for use in the prevention and/or treatment of obesity by means of sequential or contemporary administration of the two compositions.