Composition for increasing muscle mass

Abstract

The present invention concerns a method for preventing muscle injuries and / or fatigue in a subject comprising the step of simultaneously, separately, or sequentially administrating to a subject in need thereof an effective amount of i) at least 20-Hydroxyecdysone, ii) at least rosavin, iii) at least one Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil, and iv) optionally a pharmaceutically acceptable carrier.

Description

COMPOSITION AND METHOD FOR INCREASING MUSCLE MASS

[0001] The present patent application claims the priority of provisional application US 63 / 632,746 filed on April 11th, 2024 which is incorporated herein by reference.

[0002] The present invention relates to compositions and methods for preventing muscle injuries and subject fatigue, thus increasing muscle mass.

[0003] Muscle is a soft tissue corresponding to one of the four basic types of animal tissue. Among muscles, skeletal muscles (commonly referred to as muscles) have the ability to contract and correspond to about 35% of the body weight in humans. Skeletal musclesare typically attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle tissue and are often known as muscle fibers. The muscle tissue of a skeletal muscle is striated – having a striped appearance due to the arrangement of the sarcomeres. A skeletal muscle contains multiple fascicles – bundles of muscle fibers. Each individual fiber, and each muscle is surrounded by a type of connective tissue layer of fascia. Muscle fibers are formed from the fusion of developmental myoblasts in a process known as myogenesis resulting in long multinucleated cells. In these cells the nuclei, termedmyonuclei, are located along the inside of the cell membrane. Muscle fibers also have multiple mitochondria to meet energy needs.

[0004] Muscles are predominantly powered by the oxidation of fats and carbohydrates, but anaerobic chemical reactions are also used, particularly by fast twitch fibers. These chemical reactions produce adenosine triphosphate (ATP) molecules that are used to power the movement of the myosin heads.

[0005] Now, a subject can be subjected to conditions leading to the decrease of his muscle mass.

[0006] A subject can be affected by muscle atrophy corresponding to the loss of skeletal muscle mass. Such atrophy can be caused by immobility, aging or malnutrition. Such a muscle atrophy leads to muscle weakness and causes disability.

[0007] Now, such decrease can be the result of muscle injury in a subject following one or several muscle stresses (e.g., muscle exercises).

[0008] Now, the inventor has shown that a specific combination of 20-Hydroxyecdysone, of rosavin, and of a Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil leads to a significant decrease in muscle injuries corresponding to oxidative damages to DNA and proteins generated by a high intensity and prolonged stress test.

[0009] Simultaneously, this specific combination leads to reduce the subject fatigue during muscle stress.

[0010] Thus, and by preventing muscle injuries and muscle fatigue, the combination of the invention may be used to increase muscular mass, especially following a muscle stress.

[0011] Accordingly and in a first aspect, the present invention relates to a method for preventing muscle injuries and / or fatigue in a subject comprising the step of simultaneously, separately, or sequentially administrating to a subject in need thereof an effective amount of:

[0012] i) at least 20-Hydroxyecdysone,

[0013] ii) at least rosavin,

[0014] iii) at least one Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil, and

[0015] iv) optionally a pharmaceutically acceptable carrier.

[0016] In a second aspect, the present invention relates to products containing:

[0017] i) at least 20-Hydroxyecdysone,

[0018] ii) at least rosavin,

[0019] iii) at least one Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil and

[0020] iv) optionally a pharmaceutically acceptable carrier,

[0021] as a combined preparation for simultaneous, separate, or sequential use for preventing muscle injuries and / or fatigue in a subject.

[0022] In a third aspect, the present invention relates to a pharmaceutical composition comprising:

[0023] i) at least 20-Hydroxyecdysone, and

[0024] ii) at least rosavin,

[0025] iii) at least one Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil, and

[0026] iv) optionally a pharmaceutically acceptable carrier.

[0027] The term subject refers to a human.

[0028] Preferably, the method is for preventing muscle injuries and / or fatigue in a subject during muscular exercises.

[0029] 20-Hydroxyecdysone (ecdysterone or 20E) is a naturally occurring ecdysteroid hormone, which is also a phytoecdysteroid produced by various plants, including Spinacia oleracea, Ajuga turkestanica andRhaponticum carthamoides.

[0030] 20-Hydroxyecdysone is marketed as ingredient in nutritional supplements for various sports, particularly bodybuilding since associated with an anabolic effect (Báthori et al., Current Medicinal Chemistry, vol. 15 (1), p: 75–91, 2008). A significant dose-responsive anabolic effect of 20-Hydroxyecdysone supplementation on athletes during resistance training was demonstrated. The mechanism of action of 20-Hydroxyecdysone on human muscle cells was then elucidated and corresponds to a selective activation of the estrogen receptor beta form (ERβ) known to result in muscle hypertrophy.

[0031] As used herein, the expression "effective amount" of a compound is one which is sufficient to achieve a desired biological effect, in this case increasing muscle mass. It is understood that the effective dosage will be dependent upon the age, sex, health, and weight of the recipient, kind of concurrent treatment, if any, frequency of treatment, and the nature of the effect desired. The ranges of effective doses provided below are not intended to limit the invention and represent preferred dose ranges. However, the preferred dosage can be tailored to the individual subject, as is understood and determinable by one of skill in the art, without undue experimentation.

[0032] Advantageously, the proportion of 20-Hydroxyecdysone is between 1 and 50 mg, typically between 1 and 30 mg or between 1 and 10 mg, preferably between 2 and 5 mg and, particularly preferably, around 3 mg.

[0033] 20-Hydroxyecdysone is produced as a phytoecdysteroid by various plants, includingSpinacia oleracea,Ajuga turkestanicaandRhaponticum carthamoides.

[0034] Thus, 20-Hydroxyecdysone can be in the form of a plant extract, like a dried plant extract. Typically, such plant extract is aSpinacia oleracea, anAjuga turkestanicaor aRhaponticum carthamoidesextract.

[0035] Advantageously, the plant extract is aRhaponticum carthamoidesextract, preferably aRhaponticum carthamoidesroot extract.

[0036] Now, 20-Hydroxyecdysone is also produced by other organisms such as insects, crabs or fungi (e.g. Cordycepssinensis) that can be used as alternative sources.

[0037] It should be noticed that plant extract is advantageously a 20-Hydroxyecdysone rich extract, whose 20-Hydroxyecdysone content is greater than 5% (w / w), preferably equal or greater than 10%.

[0038] According to a preferred embodiment, 20-Hydroxyecdysone is encapsulated in at least one first capsule.

[0039] Suitable materials fur such a first capsule includes hydroxy propyl methyl cellulose (HPMC), pectin, polyethylene oxide, poly vinyl alcohol, alginate, polycaprolactone, gelatin, and gelatinized starch-based materials etc. Such materials are commercially available, e.g., in the form of ribbon-like films or can be readily manufactured, e.g., by extrusion from solution.

[0040] This at least one first capsule may be a gastro-resistant capsule.

[0041] As used herein, a gastro-resistant capsule refers to a capsule whose disintegration occurs after the stomach, preferably in the small intestine.

[0042] Such gastro-resistant capsule can be obtained by coating the capsule material, e.g., with gum arabic, gellan gum, pectin, alginate (e.g., sodium alginate) to modify solubility properties, the extent of the effect varying according to coating thickness. Further, both pectin and alginate can be cross-linked, e.g., with calcium, this has the effect of making the material pH sensitive such that it will not dissolve in the mouth but will dissolve in the stomach where pH is lower. Multi-layer materials may also be used. Examples of suitable capsule materials and coatings are given in WO 97 / 35537 and WO 00 / 27367.

[0043] Still preferably, this at least one first capsule is not a gastro-resistant capsule.

[0044] Rosavin (also known as rosin or rosarin) or 2(2E)-3-Phenylprop-2-en-1-yl α-L-arabinopyranosyl-(1→6)-α-D-glucopyranoside (CAS N°: 84954-92-7) is an organic compound having the following formula.

[0045] Rosavin has been reported to display many activities including immunomodulatory effects, radiation protection, anti-cancer activities, protective effects on bleomycin-induced pulmonary fibrosis, and induced antidepressant-like effects in mouse model. Now, clinical trials of R. rosea extract, whose major active component is rosavin, have reported positive efficacy on fatigue.

[0046] Advantageously, rosavin is in a proportion of between 1 and 20 mg, preferably between 5 and 15 mg and, particularly preferably, around 10 mg.

[0047] Now, it should be noted that rosavin is present inRhodiolarosea.

[0048] Rhodiola rosea(commonly golden root, rose root, roseroot, Aaron's rod, Arctic root, king's crown, lignum rhodium, orpin rose) is a plant from the Crassulaceae family growing naturally in wild Arctic regions of Europe, Asia, and North America. Even if this plant has been used in traditional medicine, there is no high-quality clinical evidence of its effectiveness to treat any disease. The United States Food and Drug Administration (FDA) has issued several warnings to manufacturers ofR. roseadietary supplements for making false health claims about its safety and efficacy.

[0049] Preferably, rosavin is in the form of aRhodiola roseaextract, typically a rhizome and / or rootRhodiola roseaextract. Still preferably, theRhodiola roseaextract is aRhodiola roseadried extract.

[0050] It should be noticed that theRhodiola roseaextract is advantageously a rosavin rich extract, whose rosavin content is greater than 2% (w / w), preferably equal or greater than 5%.

[0051] Typically, theRhodiola roseaextract is between 50 and 1000 mg, 100 and 500 mg, preferably between 150 and 250 mg ofRhodiola roseaextract and, in a particularly preferred manner, around 200 mg.

[0052] According to another preferred embodiment, rosavin is encapsulated in a capsule, said capsule being the first capsule or a second capsule.

[0053] Suitable materials fur such a second capsule include hydroxy propyl methyl cellulose (HPMC), pectin, polyethylene oxide, poly vinyl alcohol, alginate, polycaprolactone, gelatin and gelatinized starch-based materials, etc. Such materials are commercially available, e.g., in the form of ribbon-like films or can be readily manufactured, e.g., by extrusion from solution.

[0054] This second capsule may be a gastro-resistant capsule or not, preferably not.

[0055] Medium-chain triglycerides (MCTs) are triglycerides with two or three fatty acids having an aliphatic tail of 6–12 carbon atoms, including caproic acid, caprylic acid, capric acid and lauric acid. As used herein a MCT enriched oil referred to an oil, whose MCTs content is greater than 40% (w / w), preferably equal or greater than 50%.

[0056] Unsaturated fatty acids are well known from the skilled person and correspond to fatty acids contains one (i.e., monounsaturated) or more (polyunsaturated) carbon-carbon double bonds and is unable to absorb additional hydrogen atoms. Example of unsaturated fatty acids includes oleic acid (i.e., monounsaturated fatty acid), linoleic acid (i.e., polyunsaturated fatty acid), linolenic acid (i.e., polyunsaturated fatty acid), etc. As used herein an unsaturated fatty acids enriched oil referred to an oil, whose unsaturated fatty acids content is greater than 8% (w / w), preferably equal or greater than 10%.

[0057] As an example of MCTs and unsaturated fatty acids enriched oil, one can cites palm kernel oil (55% MCTs and 17% unsaturated fatty acids) or coconut oil (63% MCTs and 8% unsaturated fatty acids). Now, such MCTs and unsaturated fatty acids enriched oil can be obtained from other sources by oils combination, fractionation and / or interesterification. AS an example of such commercially available oil, one can also cites LipidEnergy® commercialized by AlianzaTeam Europe.

[0058] Typically, the MCTs and unsaturated fatty acids enriched oil is between 100 and 1,000 mg, preferably between 200 and 500 mg and, in a particularly preferred manner, around 300 mg.

[0059] According to still another preferred embodiment, MCTs and unsaturated fatty acids enriched oil is encapsulated in a third capsule.

[0060] This third capsule is preferably not gastro-resistant.

[0061] According to a specific embodiment, i) 20-Hydroxyecdysone is encapsulated in a first capsule, ii) rosavin is encapsulated in a second capsule, and iii) said first capsule and said second capsules are both further encapsulated with the MCTs and unsaturated fatty acids enriched oil in a single third capsule.

[0062] According to another specific embodiment, i) 20-Hydroxyecdysone and rosavin are encapsulated in a first capsule, and iii) said first capsule is further encapsulated with the MCTs and unsaturated fatty acids enriched oil in another single capsule.

[0063] Advantageously, the administrating step is a daily administrating step, which is preferably done in the morning.

[0064] Still advantageously, the administrating step is done for a period of at least 4 weeks, preferably at least 6 weeks and, most preferably, for at least 8 weeks.

[0065] The phrase "pharmaceutically acceptable" refers to molecular entities and compositions that are physiologically tolerable and do not typically produce an allergic or similar untoward reaction, such as gastric upset, dizziness and the like, when administered to a human. Preferably, as used herein, the term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.

[0066] The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the compound is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water or aqueous solution saline solutions and aqueous dextrose and glycerol solutions are preferably employed as carriers, particularly for injectable solutions. Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E.W. Martin.

[0067] Other embodiments and advantages of the present invention are illustrated in the following non-limiting examples.EXAMPLES

[0068] Preparation of theHR15 formulationcorresponding to a capsule

[0069] 3mg of 20-Hydroxyecdysone in the form of a dried plant extract is encapsulated with 200 mg ofRhodiola rosearhizome extract comprising at least 5% of rosavin (w / w) in a first gastro-resistant capsule.

[0070] This first capsule is further encapsulated with 300mg of MCTs and unsaturated fatty acids enriched oil (LipidEnergy® commercialized by AlianzaTeam Europe) in another single capsule which is not gastro-resistant.

[0071] Preclinical studies

[0072] The activity of components of HR15 on theC. eleganslifespan was studied. The agar plates (NGM) used for theC. elegansfeeding experiments were prepared with 2 mg / mL ingredients by adding the product directly to the agar surface (200 μL of the stock at 100 mg / mL). TheC. eleganswild-type strain was age-synchronized by recovering adult eggs on the corresponding agar plates, already seeded withEscherichia coliOP50. NG medium was used as a control diet, the HR15 ingredients were mixed obtaining a 100 mg / mL solution and added to the agar surface at 2 mg / mL (200 μL). Worms were incubated at 20°C for 26 days in the different media, periodically moved to new plates, and scored as dead if they did not respond to a platinum wire. The experiments were performed in duplicate. Survival curves were compared using the log-rank survival significance test, provided by the GraphPad Prism 4 statistical software package.

[0073] The conclusion of this study was that ingredients in HR15 produce an increase in the lifespan ofC. elegansin the dose of 2 mg / mL.

[0074] The second preclinical study on HR15 ingredients determined antioxidant activity in theCaenorhabditis elegansmodel. TheC. eleganswild-type strain was age-synchronized by recovering adult eggs on the corresponding agar plates, already seeded withEscherichia coliOP50. NG medium was used as a control diet, NGM supplemented with vitamin C (10 μg / mL) and NG with 2 mg / mL of HR15 ingredients. The worms were incubated at 20ºC for 7 days in the different media, transferring them every two days to new fresh plates. Subsequently, the worms were treated with hydrogen peroxide (2 mM) and after 5 h, the survival of the worms in each feeding condition was analyzed. The experiments were performed in triplicate.

[0075] HR15 ingredients showed a significant antioxidant effect (23.5% increase in worm survival versus control conditions), allowing us to conclude that these ingredients significantly protect acute oxidative stress in theC. elegansmodel.

[0076] In the third study, C. elegans was analyzed transcriptomically to study the genes, processes and metabolic pathways affected by HR15 ingredients. Agar plates (NGM) used forC. elegansfeeding experiments were prepared with 2 mg / mL of HR15 ingredients by adding the product directly to the agar surface (200 μL of the stock at 100 mg / mL). Transcriptomic profiling ofC. elegansfed HR15 ingredients revealed changes related to protein metabolism, energy metabolism, glutathione metabolism, fatty acid metabolism, and xenobiotic metabolism. Some of these transcriptomic changes would explain the antioxidant activity of these ingredients and the ability to increase the lifespan ofC. elegans.

[0077] Clinical trials

[0078] In a first clinical trial, the effects of ingredients present in HR15 were investigated in healthy volunteers. This was a single center, randomized, placebo-controlled, double-blind, month-long study with 3 groups: placebo (group A), once-daily supplement (group B), and twice-daily supplement (group C).

[0079] Additionally, the effects of subjects in arm B were evaluated after stopping intake (group B1) or 120 days of intake (group B2). Subjects were evaluated on days 1, 7, and 30 (37 and 44 for group B1; 60, 90, and 120 for group B2).

[0080] The evaluation included antioxidant defenses, oxidative damage, inflammatory profile and change in emotional state. A total of 73 subjects were randomized, arm A = 32, arm B = 21 (group B1 = 11, group B2 = 10), arm C = 20.

[0081] The results established that supplements significantly increased glutathione peroxidase levels (arms B and C), reduced glutathione (GSH) (arm C) and decreased oxidized glutathione (GSSG) (arms B and C). The GSH / GSSG ratio also showed a significant increase (group C). The supplement also significantly increased the levels of vitamins C (group B and C; group B1) and E (group B2). Reduced levels of oxidative damage to proteins were observed (arms B and C). The supplement had a significant positive emotional effect on anxiety (group C), positivity (groups B and C), vitality (group C) and global score (group C).

[0082] In conclusion, one month of supplementation increased antioxidant defense and reduced oxidative damage to proteins, with a good safety profile.

[0083] The second experimental nutritional study (randomized, crossover, with two study groups, double-blind and placebo controlled) was carried out to evaluate the efficacy of different components of the HR15 product in 35 male subjects who performed physical activity at least once a week for preventing muscle injuries and as an anti-fatigue.

[0084] In muscle injuries preventing, significant antioxidant differences were observed between placebo and ingredients of the HR15 product in the levels of 8 oxodG, carbonyl groups, oxidized glutathione and reduced / oxidized glutathione ratio. All the differences indicate that ingredients in the HR15 product reduce the oxidative damage generated by the stress test or improve the action of antioxidant defenses. When the levels of total antioxidant capacity of the plasma were compared under basal conditions (before performing the tests) between the two study groups, it was seen that the consumption of ingredients from the HR15 product for 15 days increased the total antioxidant capacity of the plasma.

[0085] In anti-inflammatory and muscle damage results, significant differences were observed between the placebo and ingredients of the HR15 product in the levels of creatine kinase and interleukin 6. The differences indicate that ingredients of the HR15 product reduce the muscle damage generated by the stress test.

[0086] In the fatigue study, significant differences were observed between placebo and ingredients of the HR15 product in the Borg scale score at minute 90 and in serum glucose results at the moments corresponding to minute 90 and minute 110. The differences between the groups indicate that the product contributes to reducing the fatigue generated by the stress test.

[0087] The conclusions of this study were that the consumption of HR15 ingredients for 15 days increases the total basal antioxidant capacity of the plasma, reduces the oxidative damage to DNA and proteins generated by a high intensity and prolonged stress test, reduces the damage muscle generated by said test and reduces the athlete's fatigue during the performance of that same test.

Claims

Products containing::i) at least 20-Hydroxyecdysone,ii) at least rosavin,iii) at least one Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil, andiv) optionally a pharmaceutically acceptable carrier,as a combined preparation for simultaneous, separate, or sequential use for preventing muscle injuries and / or fatigue in a subject.The products of claim 1, for preventing muscle injuries and / or fatigue in a subject during muscular exercises.The products of any one of claim 1 or 2, wherein the proportion of:20-Hydroxyecdysone is between 1 and 50 mg, preferably between 1 and 30 mg, and most preferably between 1 and 30 mg,the proportion of Rosavin is between 1 and 20 mg, preferably between 5 and 15 mg, andMCTs and unsaturated fatty acids enriched oil is between 100 and 1,000 mg, preferably between 200 and 500 mg.The products of any one of claims 1 to 3, wherein the Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil has a MCTs content greater than 40% (w / w), preferably a MCTs content equal or greater than 50% (w / w).The products of any one of claims 1 to 4, wherein the Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil has an unsaturated fatty acids content greater than 8% (w / w), preferably an unsaturated fatty acids content equal or greater than 10% (w / w).The products of any one of claims 1 to 4, wherein:20-Hydroxyecdysone in the form of a plant dried extract selected in the group comprisingSpinacia oleracea,Ajuga turkestanicaandRhaponticum carthamoidesdried extract, androsavin is in the form of aRhodiola roseaextract, preferably a rhizome and / or rootRhodiola roseaextract.The products of claim 6, wherein:the 20-Hydroxyecdysone plant dried extract is a 20-Hydroxyecdysone rich extract, whose 20-Hydroxyecdysone content is greater than 5% (w / w), preferably equal or greater than 10 % (w / w), andtheRhodiola roseaextract is a rosavin rich extract, whose rosavin content is greater than 2% (w / w) , preferably greater than 5% (w / w).The products of any one of claims 1 to 7, wherein:20-Hydroxyecdysone is encapsulated,rosavin is encapsulated, andMCTs and unsaturated fatty acids enriched oil is encapsulated.The products of any one of claims 1 to 7, wherein:20-Hydroxyecdysone is encapsulated in a first capsule,rosavin is encapsulated in a capsule, being the first capsule or a second capsule, andsaid first capsule and eventually second capsule are both further encapsulated with MCTs and unsaturated fatty acids enriched oil in a third capsuleThe products of claim 9, wherein:the first capsule is a gastro-resistant capsule or not, preferably not;Eventually the second capsule is a gastro-resistant capsule or not, preferably not a gastro-resistant capsule; andthe third capsule is not a gastro-resistant capsule.The products of any one of claims 1 to 10, as a combined preparation by daily administration for simultaneous, separate, or sequential use for preventing muscle injuries and / or fatigue in a subject.The products of claim 11, as a combined preparation by daily morning administration for simultaneous, separate, or sequential use for preventing muscle injuries and / or fatigue in a subject.The products of any one of claims 1 to 12, as a combined preparation for simultaneous, separate, or sequential use for a period of at least 4 weeks for preventing muscle injuries and / or fatigue in a subject.A composition comprising:at least 20-Hydroxyecdysone,ii) at least rosavin,iii) at least one Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil, andoptionally a pharmaceutically acceptable carrier.The composition of claim 14, for use in preventing muscle injuries and / or fatigue in a subject during muscular exercises.The composition of any one of claim 14 or 15, wherein the proportion of:20-Hydroxyecdysone is between 1 and 50 mg, preferably between 1 and 30 mg, and most preferably between 1 and 30 mg,the proportion of Rosavin is between 1 and 20 mg, preferably between 5 and 15 mg, andMCTs and unsaturated fatty acids enriched oil is between 100 and 1,000 mg, preferably between 200 and 500 mg.The composition of any one of claim 14 to 16, wherein the Medium-chain triglycerides (MCTs) and unsaturated fatty acid enriched oil has a MCTs content greater than 40% (w / w), preferably a MCTs content equal or greater than 50% (w / w).The composition of any one of claim 14 or 17, wherein:20-Hydroxyecdysone in the form of a plant dried extract selected in the group comprisingSpinacia oleracea,Ajuga turkestanicaandRhaponticum carthamoidesdried extract, androsavin is in the form of aRhodiola roseaextract, preferably a rhizome and / or rootRhodiola roseaextract.The composition of claim 18, wherein:the 20-Hydroxyecdysone plant dried extract is a 20-Hydroxyecdysone rich extract, whose 20-Hydroxyecdysone content is greater than 5% (w / w), preferably equal or greater than 10 % (w / w), andtheRhodiola roseaextract is a rosavin rich extract, whose rosavin content is greater than 2% (w / w), preferably greater than 5% (w / w).The composition of any one of claim 14 to 19 in the form of a capsule.The composition of claim 20, wherein20-Hydroxyecdysone is encapsulated in a first capsule,rosavin is encapsulated in a capsule, being the first capsule or a second capsule, andsaid first capsule and eventually second capsule are both further encapsulated with MCTs and unsaturated fatty acids enriched oil in a third capsule.The composition of claim 21, wherein:the first capsule is a gastro-resistant capsule or not, preferably not;Eventually the second capsule is a gastro-resistant capsule or not, preferably not a gastro-resistant capsule; andthe third capsule is not a gastro-resistant capsule.

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