Improvement of muscle function in elderly males

Abstract

The present invention provides a composition comprising a protein source and an antioxidant, optionally in combination with an omega-3 fatty acid, which composition is capable of treating or preventing sarcopenia in an elderly male, reducing loss of muscle function (e.g., muscle strength, walking speed, etc. And / or improving muscle function recovery of old men after amyotrophy.

Description

[0001] This application is a divisional application of PCT application PCT / EP2015 / 073361, which was filed on October 9, 2015 and whose invention name is “Improvement of muscle function in elderly men”. The date on which the PCT application entered the Chinese national phase is April 10, 2017, and the application number is 201580054858.9. Background Art

[0002] The present disclosure generally relates to a composition for administration to an elderly male comprising a protein source and an antioxidant. More specifically, the present disclosure relates to administering a composition comprising a protein source and an antioxidant to an elderly male to treat or prevent sarcopenia, reduce the loss of muscle function (e.g., muscle strength, walking speed, etc.), increase muscle function, and / or improve muscle function recovery after muscle atrophy.

[0003] Sarcopenia is defined as the age-related loss of muscle mass and function, including muscle strength and walking speed. Muscle function and physical ability decline with the loss of muscle mass. Impaired muscle function is highly predictive of the incidence of loss of mobility, disability, and death in advanced age. Sarcopenia is becoming more and more common with the growing elderly population, with 45% of the elderly population in the United States having moderate to severe symptoms. The direct and indirect costs attributed to sarcopenia in U.S. healthcare have reached nearly $19 billion. Therefore, preventing and / or treating sarcopenia will have a huge impact on the health and quality of life of our society, and thus on the healthcare-related economy. Unfortunately, the etiology and pathophysiological mechanisms of sarcopenia remain poorly understood, making it difficult to take effective preventive or therapeutic measures.

[0004] One of the main hypotheses proposed to explain the progressive muscle loss observed with aging is a reduction in the anabolic effect of dietary intake due to a decrease in nutrient stimulation of muscle protein synthesis. This hypothesis is known as muscle anabolic resistance. In addition, oxidative stress and / or low-grade inflammation have also been shown to be associated with frailty in the elderly and may contribute in part to anabolic resistance, either directly or through reduced muscle sensitivity to insulin. Summary of the invention

[0005] Without being bound by theory, the inventors surprisingly found that when elderly males are fed a nutritional composition comprising a protein source and at least one antioxidant, the effect of reducing sarcopenia in elderly males is improved. For example, the composition can reduce the loss of muscle function (e.g., muscle strength, walking speed, etc.) or improve muscle function in elderly males administered the composition relative to a diet lacking the composition.

[0006] Therefore, in a general embodiment, the present invention provides a method for reducing the loss of muscle function in an elderly male, increasing muscle function in an elderly male, and / or improving muscle function recovery in an elderly male after muscle atrophy. The method comprises administering to the elderly male a composition comprising a protein source and an antioxidant.

[0007] In one embodiment, the composition comprises a fatty acid. The fatty acid may be an n-3 fatty acid.

[0008] In one embodiment, the antioxidant comprises a polyphenol. The polyphenol may be selected from the group consisting of curcumin, rutin, quercetin, and combinations thereof.

[0009] In one embodiment, the protein source comprises whey protein.

[0010] In one embodiment, the protein source comprises a protein selected from the group consisting of casein, pea protein, soy protein, and combinations thereof.

[0011] In one embodiment, the antioxidant comprises a polyphenol and the composition comprises n-3 fatty acids in addition to the protein source.

[0012] In one embodiment, the composition is administered at least twice per week for a period of at least one month.

[0013] In one embodiment, the muscle function comprises a characteristic selected from the group consisting of muscle strength, walking speed, and combinations thereof.

[0014] In one embodiment, the muscle function is in a skeletal muscle selected from the group consisting of the gastrocnemius, tibialis, soleus, extensor digitorum longus (EDL), biceps femoris, semitendinosus, semimembranosus, gluteus maximus, and combinations thereof.

[0015] In one embodiment, the composition is administered in an amount to provide 0.1 to 0.4 grams of protein source per kilogram of body weight of the elderly male per day.

[0016] In one embodiment, the composition is administered in an amount to provide 0.01 g to 0.04 g of leucine per kg body weight of the elderly male per day.

[0017] In one embodiment, the elderly male suffers from sarcopenia.

[0018] In another embodiment, the present disclosure provides a composition comprising a protein source and an antioxidant in an amount that is therapeutically effective for at least one of: (i) treating sarcopenia in elderly men with sarcopenia, (ii) preventing sarcopenia in elderly men, (iii) reducing loss of muscle function in elderly men, (iv) increasing muscle function in elderly men, or (v) improving recovery of muscle function in elderly men after muscle atrophy.

[0019] In one embodiment, the antioxidant comprises a polyphenol and the composition comprises n-3 fatty acids in addition to the protein source.

[0020] In one embodiment, the composition comprises the protein source in an amount of 0.2% to 100% based on the dry weight of the composition.

[0021] In one embodiment, the protein source comprises leucine, and the leucine is present in the composition in an amount up to 10% by weight.

[0022] In one embodiment, the composition is selected from the group consisting of a food composition, a dietary supplement, a nutritional composition, a nutraceutical, a powdered nutritional product to be reconstituted with water or milk before consumption, a food additive, a medicament, a beverage, and combinations thereof.

[0023] In another embodiment, the present disclosure provides a method of preventing sarcopenia in an elderly male, the method comprising administering a composition comprising a protein source and an antioxidant to an elderly male at risk for sarcopenia.

[0024] In one embodiment, the antioxidant comprises a polyphenol and the composition comprises n-3 fatty acids in addition to the protein source.

[0025] An advantage of the present disclosure is to provide a composition, such as a food product or a food supplement, for treating sarcopenia in elderly men.

[0026] Another advantage of the present disclosure is to provide a composition, such as a food product or a food supplement, for preventing sarcopenia.

[0027] Another advantage of the present disclosure is to provide a composition, such as a food product or food supplement, that reduces the loss of muscle function (e.g., muscle strength, walking speed, etc.) in elderly males relative to the loss of muscle function that would be suffered while consuming a diet lacking the composition.

[0028] Another advantage of the present disclosure is to provide a composition, such as a food product or a food supplement, that increases muscle function (e.g., muscle strength, walking speed, etc.) in elderly males relative to the muscle function (e.g., muscle strength, walking speed, etc.) that existed due to consuming a diet lacking the composition.

[0029] Another advantage of the present disclosure is to provide a composition, such as a food product or food supplement, that improves recovery of muscle function (e.g., muscle strength, walking speed, etc.) after muscle wasting in elderly males relative to the recovery that would exist by consuming a diet lacking the composition.

[0030] Another advantage of the present disclosure is to beneficially facilitate the reduction, prevention or treatment of sarcopenia in elderly men.

[0031] Another advantage of the present disclosure is to provide nutritional strategies to mitigate the progression of sarcopenia in elderly men, particularly to reduce the loss of muscle function (e.g., muscle strength, walking speed, etc.) in frail elderly men.

[0032] Additional features and advantages are described herein and will be apparent from the following detailed description and accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is a schematic diagram illustrating a method for estimating the cross-sectional area of ​​muscles used in the experimental examples disclosed herein.

[0034] Figure 2 is a data table from the experimental examples disclosed herein.

[0035] Figure 3 is a graph showing changes in left knee extension strength in the experimental example disclosed herein.

[0036] Figure 4 is a graph showing box plots of left and right knee extension strength by visit and gender and treatment group in the experimental examples disclosed herein.

[0037] Figure 5 is a graph showing a plot of mean + / - standard deviation (SD) of left and right knee extension strength by visit and treatment group in the experimental examples disclosed herein. DETAILED DESCRIPTION

[0038] All percentages are by weight based on the total weight of the composition, unless otherwise indicated. Similarly, all ratios are by weight, unless otherwise indicated. When pH is mentioned, the value corresponds to the pH measured at 25° C. using standard equipment. As used herein, “about” is understood to refer to a number within a certain numerical range, such as -10% to +10% of the mentioned number, preferably -5% to +5% of the mentioned number, more preferably -1% to +1% of the mentioned number, and most preferably -0.1% to +0.1% of the mentioned number.

[0039] In addition, all numerical ranges herein should be understood to include all integers or fractions within the range. In addition, these numerical ranges should be understood to provide support for claims involving any numerical value or numerical subset within the range. For example, the disclosure from 1 to 10 should be understood to support ranges from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, etc.

[0040] As used herein and in the appended claims, unless the context clearly dictates otherwise, the singular form of a word includes the plural form and vice versa. Thus, references to "a," "an," and "the" generally include plural forms of the respective terms. For example, reference to "an ingredient" or "a method" includes reference to a plurality of such ingredients or methods. The term "and / or" used in the context of "X and / or Y" should be interpreted as "X" or "Y," or "X and Y."

[0041] Similarly, the words "comprise", "comprises", and "comprising" are all intended to be interpreted inclusively rather than exclusively. Likewise, the terms "include", "including", and "or" should all be considered inclusive unless the context clearly prohibits such an interpretation. However, the embodiments provided by the present disclosure may not contain any elements that are not explicitly disclosed herein. Therefore, the disclosure of an embodiment defined using the terms "comprises", is also the disclosure of multiple embodiments that are "essentially composed of the disclosed components" and "composed of the disclosed components". The term "example" used herein, especially when followed by a list of terms, is for illustration only and should not be considered exclusive or comprehensive. Any embodiment disclosed herein may be combined with any other embodiment disclosed herein, unless otherwise expressly indicated.

[0042] The term "elderly" refers to a person older than 60 years, preferably older than 63 years, more preferably older than 65 years. The term "frail" refers to a person who is physically weak, ie not strong but fragile.

[0043] The terms "treatment" and "treating" include any effect that results in an improvement in a condition or disorder, such as alleviation, reduction, regulation, or elimination of the condition or disorder. Non-limiting examples of "treating" and "treatment of" a condition or disorder include: (1) inhibiting the condition or disorder, i.e., preventing the development of the condition or disorder or its clinical symptoms, and (2) relieving the condition or disorder, i.e., temporarily or permanently regressing the condition or disorder or its clinical symptoms.

[0044] The terms "prevention" and "preventing" refer to causing clinical symptoms of a referenced condition or disorder not to develop in an individual who may be exposed to or susceptible to the condition or disorder but does not yet experience or exhibit symptoms of the condition or disorder. The terms "condition" and "disorder" mean any disease, condition, symptom, or indication.

[0045] The terms "food", "food product" and "food composition" mean a product or composition intended for human ingestion and providing at least one nutrient to a human. The compositions of the present disclosure (including the various embodiments described herein) may comprise, consist of or consist essentially of the following elements: the essential elements and limitations described herein, as well as any other or optional ingredients, components or limitations described herein or useful in the diet of an elderly male.

[0046] As used herein, "complete nutrition" includes a comprehensive variety of macronutrients (protein, fat and carbohydrates) and micronutrients in sufficient amounts to be sufficient as the sole source of nutrition for the animal to which the composition is administered. From such complete nutritional compositions, an individual can obtain 100% of his nutritional requirements.

[0047] One aspect of the present disclosure is a composition comprising a protein source and an antioxidant, which is used to treat or prevent sarcopenia in elderly men, to reduce the loss of muscle function (e.g., muscle strength, walking speed, etc.) in elderly men, to increase muscle function (e.g., muscle strength, walking speed, etc.) in elderly men, and / or to improve the recovery of muscle function (e.g., muscle strength, walking speed, etc.) in elderly men after muscle atrophy. Another aspect of the present disclosure is a method, which comprises administering to elderly men a therapeutically effective amount of a composition comprising a protein source and an antioxidant to treat sarcopenia in elderly men, to prevent sarcopenia in elderly men, to reduce the loss of muscle function (e.g., muscle strength, walking speed, etc.) in elderly men, to increase muscle function (e.g., muscle strength, walking speed, etc.) in elderly men, and / or to improve the recovery of muscle function (e.g., muscle strength, walking speed, etc.) in elderly men after muscle atrophy.

[0048] Muscle atrophy as treated or prevented according to the present disclosure can be caused by many reasons. For example, it may be caused by lack of physical activity, such as loss of activity associated with aging or low physical activity (sarcopenia associated with the aging process), hip fracture recovery, or several comorbidities of disease (such as cancer, AIDS, congestive heart failure, COPD (chronic obstructive pulmonary disease), renal failure, trauma, sepsis and severe burns). Muscle atrophy may also be caused by insufficient or inappropriate nutrition or hunger. Very commonly, muscle atrophy is caused by not using the corresponding muscles or insufficient use of the corresponding muscles.

[0049] The muscles mentioned in the present disclosure are preferably skeletal muscles. For example, the compositions disclosed herein can be used to reduce the loss of muscle function in the arms and / or legs of elderly men. The muscles can be one or more of the following: gastrocnemius, tibialis, soleus, extensor digitorum longus (EDL), biceps femoris, semitendinosus, semimembranosus or gluteus maximus.

[0050] Muscle wasting can lead to sarcopenia, which is the loss of muscle mass, size and function due to aging. Muscle wasting can have different levels, such as severe muscle wasting when the elderly are extremely frail. Extremely frail elderly people may have difficulty in daily activities and taking care of themselves. Less severe muscle wasting will allow some movement and some muscle activity, but these muscle activities are not enough to maintain intact muscle tissue. The mechanisms involved in the treatment or prevention of age-related sarcopenia are different from those in the treatment or prevention of muscle function loss in young people.

[0051] The compositions disclosed herein comprise a protein source and an antioxidant, and are capable of reducing the loss of muscle function and / or improving muscle function in elderly men to whom the compositions are administered relative to a diet lacking such compositions. In one embodiment, the reduction in loss of muscle function (e.g., muscle strength, walking speed, etc.), the improvement in muscle function (e.g., muscle strength, walking speed, etc.), the improvement in recovery of muscle function (e.g., muscle strength, walking speed, etc.) after muscle atrophy, the treatment of sarcopenia, and / or the prevention of sarcopenia are achieved without changing muscle size or muscle mass.

[0052] The protein source may be from an animal or plant source, such as milk protein, soy protein and / or pea protein. In a preferred embodiment, the protein source is selected from whey protein; casein; pea protein; soy protein; wheat protein; corn protein; rice protein; protein from legumes, cereals and grains; and combinations thereof. In addition or alternatively, the protein source may comprise protein from nuts and / or seeds. In one embodiment, the composition comprises protein in an amount of 0.2%-100% based on dry weight, preferably 1%-95% based on dry weight, more preferably 2%-90% based on dry weight, even more preferably 3%-80% based on dry weight, and most preferably 5%-70% based on dry weight. In one embodiment, the composition is administered to elderly men at a daily dose of 0.1 to 0.4 g protein per kg of body weight of an elderly man, preferably 0.2 to 0.35 g protein per kg of body weight of an elderly man.

[0053] The protein source preferably comprises whey protein. The whey protein may be unhydrolyzed or hydrolyzed whey protein. The whey protein may be any whey protein, for example, the whey protein may be selected from whey protein concentrate, whey protein isolate, whey protein micelles, whey protein hydrolysate, acid whey, sweet whey, modified sweet whey (sweet whey from which casein-glycomacropeptide has been removed), fractions of whey protein and any combination thereof. In a preferred embodiment, the whey protein comprises whey protein isolate and / or modified sweet whey.

[0054] As mentioned above, the protein source may be from an animal or plant source, such as milk protein, soy protein and / or pea protein. In one embodiment, the protein source comprises casein. Casein may be obtained from any mammal, but is preferably obtained from cow's milk, and is preferably micellar casein.

[0055] The composition may comprise one or more branched-chain amino acids. For example, the composition may comprise leucine, isoleucine and / or valine. The protein source in the composition may comprise leucine in free form and / or leucine bound to a peptide and / or protein (e.g., dairy, animal or plant protein). In one embodiment, the composition comprises leucine in an amount up to 10% by weight of the dry matter of the composition. Leucine may be present in the form of D-leucine or L-leucine, preferably in the form of L-leucine. If the composition comprises leucine, the composition may be administered in a daily dose of 0.01 to 0.04 g leucine per kg body weight, preferably 0.02 to 0.035 g leucine per kg body weight. Such dosages are particularly suitable for complete nutritional compositions, but a person of ordinary skill will readily recognize how to adjust these dosages for oral nutritional supplements (ONS).

[0056] Any antioxidant may be used in the composition, but preferably the antioxidant is selected from polyphenols, phenols, flavonoids, vitamins, carotenoids and combinations thereof. Particularly preferred are food grade polyphenols. A compound is considered "food grade" if it is generally accepted and considered safe for food applications.

[0057] Mixtures of antioxidants may be used. For example, the antioxidant may be provided as an antioxidant-rich food composition or an extract thereof. An "antioxidant-rich" food composition has an ORAC (oxygen radical absorbance capacity) score of at least 100 per 100 g of the composition.

[0058] Non-limiting examples of suitable vitamins include vitamin E (tocopherol), vitamin A (retinol or beta-carotene), and vitamin C (ascorbic acid). Non-limiting examples of suitable flavonoids are hesperidin-7-glucoside and catechins.

[0059] In a preferred embodiment, the antioxidant is selected from hesperidin-7-glucoside, curcumin, green tea catechins, rutin, vitamin E, vitamin A, zinc, selenium and combinations thereof. Metabolites of antioxidants can be used. In a particularly preferred embodiment, the antioxidant is a combination of two or more antioxidants.

[0060] Cocoa, coffee and tea are rich in antioxidants. Several spices or herbs rich in antioxidants can be used, such as oregano, cumin, ginger, garlic, coriander, onion, thyme, marjoram, tarragon, peppermint and / or basil. Fruit extracts or dried fruits can be used, such as pears, apples, raisins, grapes, figs, cranberries, blueberries, blackberries, raspberries, strawberries, black currants, cherries, plums, oranges, mangoes and / or pomegranates. The composition may include vegetables rich in antioxidants, such as cabbage, broccoli, beetroot, artichoke heads, black olives, black beans, celery, onions, parsley and / or spinach.

[0061] The antioxidant may be a purified compound or a partially purified compound.

[0062] In one embodiment, the weight ratio of the protein source to the antioxidant is 40:1 to 1:1, such as 35:1 to 2:1, preferably 30:1 to 5:1, such as 28:1 to 8:1, and even more preferably 25:1 to 10:1.

[0063] In a preferred embodiment, the antioxidant comprises one or more polyphenols. A mixture of polyphenols may be used, for example two or more polyphenols. The polyphenols may also be provided as a polyphenol-enriched food composition or an extract thereof.

[0064] Cocoa, coffee and tea are rich in polyphenols. Fruit extracts or dried fruits can be used as a source of polyphenols, such as pears, apples, grapes, cranberries, blueberries, blackberries, raspberries, strawberries, black currants, cherries, plums and / or pomegranates. There are also some nuts and seeds rich in polyphenols, such as chestnuts, hazelnuts and linseeds. Non-limiting examples of vegetables rich in polyphenols are cabbage, broccoli, beetroot, artichoke heads, black olives, black beans, celery, onions, parsley and spinach.

[0065] The polyphenols may be purified compounds or partially purified compounds. Non-limiting examples of suitable polyphenols are phenolic acids; flavonoids, such as flavonols, flavones, isoflavones, flavanones, anthocyanidins and flavanols; stilbenes; and lignans. In one embodiment, the polyphenols are selected from hesperidin-7-glucoside, curcumin, quercetin, green tea catechins, rutin and combinations thereof. In a preferred embodiment, the polyphenols are selected from curcumin, rutin, quercetin and combinations thereof. In a particularly preferred embodiment, the polyphenols include curcumin and / or rutin.

[0066] In one embodiment, the composition comprises one or more whey proteins and one or more polyphenols in a weight ratio of 300:1 to 2:1, such as 100:1 to 5:1, preferably 60:1 to 10:1, even more preferably 50:1 to 20:1.

[0067] The composition comprising a protein source and an antioxidant can be administered to an elderly male at a therapeutically effective dose. The therapeutically effective dose can be determined by a person skilled in the art and will depend on many factors known to those skilled in the art, such as the severity of the condition and the weight and general condition of the elderly male.

[0068] In the case where the elderly male has not yet developed symptoms of sarcopenia, the composition can be administered to the elderly male in an amount sufficient to prevent or at least partially reduce the risk of developing sarcopenia. Such an amount is defined as a "prophylactic effective dose". Again, the exact amount depends on a number of factors related to the elderly male, such as their weight, health status, and degree of loss of muscle function (e.g., muscle strength, walking speed, etc.).

[0069] The composition is preferably used as a supplement for the elderly male diet every day or at least twice a week. In one embodiment, the composition is applied to the elderly male for many consecutive days, preferably until the increase of muscle function (such as muscle strength, walking speed, etc.) is achieved relative to the muscle function before application. For example, the composition can be applied to the elderly male every day in at least 30,60 or 90 consecutive days. For example, the composition can be applied to the elderly male in a longer period of time, such as 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years or 10 years.

[0070] In a preferred embodiment, the composition is administered to the elderly male for a period of at least 3 months, such as 3 months to 1 year, and preferably at least 6 months.

[0071] The above-mentioned administration examples do not require continuous daily administration without interruption. On the contrary, there may be some short interruptions in the administration, such as interruptions of two to four days during the administration. The ideal duration of administration of the composition can be determined by those skilled in the art.

[0072] In a preferred embodiment, the composition is administered to the elderly male orally or enterally (eg, by tube feeding). For example, the composition can be administered to the elderly male in the form of a beverage, capsule, tablet, powder or suspension.

[0073] The composition can be any kind of composition suitable for human and / or animal consumption. For example, the composition can be selected from food compositions, dietary supplements, nutritional compositions, nutrition, powdered nutritional products reconstituted with water or milk before consumption, food additives, medicines, beverages and drinks. In one embodiment, the composition is an oral nutritional supplement (ONS), a complete nutritional formula, a medicine, a medical product or a food product. In a preferred embodiment, the composition is applied to elderly men in the form of a beverage. The composition can be stored in a pouch in powder form and then suspended in a liquid such as water for use.

[0074] In some cases where oral or enteral administration is not possible or advisable, the compositions may also be administered parenterally.

[0075] In one embodiment, the composition comprises whey protein in an amount of 0.5% to 100% based on the dry weight of the composition. For example, the composition may be a nutritional supplement, which is almost entirely whey protein. Therefore, in a preferred embodiment, the composition comprises whey protein greater than 60% based on dry weight, such as greater than 70% whey protein, preferably greater than 80% whey protein, such as greater than 85% whey protein, even more preferably greater than 90% whey protein, such as greater than 92% whey protein, in particular greater than 95% whey protein, such as greater than 97% whey protein based on dry weight.

[0076] In one embodiment, the composition is a nutritional supplement comprising a protein source (e.g., whey protein) and other ingredients that are optimal for elderly men to consume, such as one or more fatty acids, preferably essential fatty acids; protein; carbohydrates; dietary fiber; vitamins; minerals; or probiotics. In such embodiments, the composition may comprise whey protein in an amount of 0.5%-50% based on dry weight, such as whey protein in an amount of 1%-40% based on dry weight, preferably 2%-35% whey protein, such as 3%-30% whey protein, more preferably 5%-20% whey protein.

[0077] The amount of protein source administered to the elderly male depends on the weight and health status of the elderly male, i.e., the severity of sarcopenia and / or the degree of loss of muscle function (e.g., muscle strength, walking speed, etc.) of the elderly male. In one embodiment, the composition is administered to the elderly male in an amount providing 0.03 to 1.0 g of whey protein per kilogram of body weight per day, such as 0.05 to 0.7 g of whey protein per kilogram of body weight per day, and preferably about 0.1 to 0.5 g of whey protein per kilogram of body weight per day.

[0078] Thus, in one embodiment, the composition is administered to provide 5-50 g whey protein per day, such as 12-40 g whey protein per day, preferably 15-30 g whey protein per day, such as 16-25 g whey protein per day, even more preferably 20 g whey protein per day. In one embodiment, a single serving of the composition provides 5-50 g whey protein, such as 10-40 g whey protein, and preferably 12-35 g whey protein, such as 15-30 g whey protein.

[0079] In one embodiment, the composition comprising a protein source and an antioxidant further comprises a fatty acid. The fatty acid can be any fatty acid, and can be one or more fatty acids, such as a combination of fatty acids. The fatty acid preferably includes essential fatty acids, such as essential polyunsaturated fatty acids, i.e. linoleic acid (C18:2n-3) and α-linolenic acid (C18:3n-3). The fatty acid may include long-chain polyunsaturated fatty acids, such as eicosapentaenoic acid (C20:5n-3), arachidonic acid (C20:4n-6), docosahexaenoic acid (C22:6n-3) or any combination thereof. In a preferred embodiment, the fatty acid includes n-3 (ω-3) fatty acids and / or n-6 (ω-6) fatty acids. The fatty acid preferably includes eicosapentaenoic acid.

[0080] The fatty acids may be derived from any suitable source containing fatty acids, such as coconut oil, rapeseed oil, soybean oil, corn oil, safflower oil, palm oil, sunflower oil or egg yolk. The source of the fatty acids is preferably fish oil.

[0081] In some embodiments, the composition is administered to the elderly male in a single dosage form, i.e., all compounds are present in one product that is provided to the elderly male in combination with a diet. In other embodiments, the composition is administered in combination in separate dosage forms, e.g., the protein source is separated from the antioxidant.

[0082] In one embodiment, the composition further comprises vitamin D.

[0083] The composition can be applied to elderly men after electrical muscle stimulation (EMS), for example, within 2 hours thereafter, preferably within 1 hour, and more preferably within 30 minutes.EMS can also be referred to as muscle electronic stimulation, muscle electrical stimulation, neuromuscular electrical stimulation (NMES) or electromyographic stimulation, and these terms can be used interchangeably.Muscle electrical stimulation is to cause muscle contraction using electric pulses.The pulse is generated by a device and transmitted by electrodes on the skin in direct contact with the muscle to be stimulated.The pulse simulates the action potential from the central nervous system, thereby causing muscle contraction.The electrode can be a pad attached to the skin, but the electrode can also be other forms.

[0084] EMS is preferably administered to the elderly male at least once a week, preferably at least twice a week, and more preferably at least three times a week. Preferably, when the elderly male is in the EMS regimen, the composition comprising the protein source and the antioxidant is administered at least twice a week, more preferably daily. The elderly male may use a device for physical stimulation or electrical muscle stimulation, such as a device or machine that forces muscle activity to enhance energy loss.

[0085] The present disclosure also provides the following specific embodiments 1-20:

[0086] 1. A method for reducing muscle function loss in elderly men, increasing muscle function in elderly men and / or improving muscle function recovery in elderly men after muscle atrophy, the method comprising administering to the elderly men a composition comprising a protein source and an antioxidant.

[0087] 2. The method of embodiment 1, wherein the composition comprises a fatty acid.

[0088] 3. The method of embodiment 2, wherein the fatty acid is an n-3 fatty acid.

[0089] 4. The method of embodiment 1, wherein the antioxidant comprises polyphenols.

[0090] 5. The method according to embodiment 4, wherein the polyphenol is selected from curcumin, rutin, quercetin and combinations thereof.

[0091] 6. The method of embodiment 1, wherein the protein source comprises whey protein.

[0092] 7. The method according to embodiment 1, wherein the protein source comprises a protein selected from the group consisting of casein, pea protein, soy protein, and combinations thereof.

[0093] 8. The method of embodiment 1, wherein the antioxidant comprises a polyphenol and the composition comprises n-3 fatty acids in addition to the protein source.

[0094] 9. The method of embodiment 1, wherein the composition is administered at least twice a week for a period of at least one month.

[0095] 10. A method according to embodiment 1, wherein the muscle function includes characteristics selected from muscle strength, walking speed, and combinations thereof.

[0096] 11. The method of embodiment 1, wherein the composition is administered in an amount providing 0.1 to 0.4 grams of the protein source per kilogram of body weight of the elderly male per day.

[0097] 12. The method of embodiment 1, wherein the composition is administered in an amount to provide 0.01 to 0.04 grams of leucine per kilogram of body weight of the elderly male per day.

[0098] 13. The method of embodiment 1, wherein the elderly male suffers from sarcopenia.

[0099] 14. A composition comprising a protein source and an antioxidant in an amount therapeutically effective for at least one of: (i) treating sarcopenia in elderly males having sarcopenia, (ii) preventing sarcopenia in elderly males, (iii) reducing loss of muscle function in elderly males, (iv) increasing muscle function in elderly males, or (v) improving recovery of muscle function in elderly males following muscle wasting.

[0100] 15. A composition comprising a protein source and an antioxidant for use in treating sarcopenia in an elderly male suffering from sarcopenia, or in preventing an elderly male from developing sarcopenia.

[0101] 16. A composition comprising a protein source and an antioxidant for use in improving muscle function recovery after muscle atrophy in elderly men.

[0102] 17. A composition according to any one of embodiments 14 to 16, wherein the antioxidant comprises a polyphenol and the composition comprises n-3 fatty acids in addition to the protein source.

[0103] 18. The composition of any one of embodiments 14 to 16, wherein the composition comprises the protein source in an amount of 0.2% to 100% based on the dry weight of the composition.

[0104] 19. The composition of any one of embodiments 14 to 16, wherein the protein source comprises leucine, and the leucine is present in the composition in an amount up to 10% by weight.

[0105] 20. The composition according to any one of embodiments 14 to 16, wherein the composition is selected from a food composition, a dietary supplement, a nutritional composition, a nutraceutical, a powdered nutritional product to be reconstituted with water or milk before consumption, a food additive, a medicament, a beverage, and combinations thereof.

[0106] Example

[0107] The following non-limiting examples provide scientific data for the development and support of the concept of administering a composition comprising a protein source and an antioxidant to elderly men to treat sarcopenia in elderly men, prevent sarcopenia in elderly men, reduce the loss of muscle function (e.g., muscle strength, walking speed, etc.) in elderly men, increase muscle function (e.g., muscle strength, walking speed, etc.) in elderly men, and / or improve recovery of muscle function (e.g., muscle strength, walking speed, etc.) in elderly men after muscle atrophy.

[0108] As detailed below, the pilot trial was designed to investigate the effects of a combined approach using electrical muscle stimulation (EMS) and whey-based nutritional supplements (+ / - polyphenols and polyunsaturated fatty acids (PUFAs)) on muscle size and function in a physically impaired population. Forty-one debilitated individuals were randomized in a 1:1:1 ratio to one of three study groups; an isocaloric (95 kcal) drink containing: (A) 20 g carbohydrates + placebo capsule (CHO), (B) 20 g whey protein isolate + placebo capsule (whey), or (C) 20 g whey protein isolate + rutin capsule (500 mg rutin per day) + w3-FA capsule (500 mg curcumin and 1.5 g w3-FA per day) (W-BIO). All individuals received EMS training twice a week for 12 weeks. For the primary outcome, the results showed that muscle thickness (in mm) and muscle cross-sectional area (in mm) of the calf and thigh were significantly different between the three groups at week 12 after the start of treatment. 2) differences were not statistically significant. In contrast, for the entire group, calf muscle thickness and thigh muscle cross-sectional area and thickness showed a significant increase trend. This finding can be attributed to EMS treatment. For most secondary outcomes (walking speed, body composition, autonomic nervous system activity and blood chemistry), no statistically significant differences were observed between any of the three treatment groups.

[0109] In contrast, at week 12, there was a statistically significant difference in knee extension strength between the W-BIO group and the whey group (4.17 kg [95% confidence interval (CI) 0.41-7.94], p = 0.0308), and there was a statistically significant difference in knee extension strength between the W-BIO group and the CHO group (5.89 kg [95% confidence interval (CI) 1.78-10.01], p = 0.0063). For right knee extension strength at week 12, there was a statistically significant difference between Group 3 and Group 1 (5.35 kg [95% confidence interval (CI) 1.13-9.57], p = 0.0145). In addition, this effect was observed in males but not in females. These data suggest that a dual approach combining EMS with specific dietary supplements has a positive effect on muscle strength and can improve quality of life in the elderly. Therefore, combining EMS with specific dietary interventions could be considered as a new approach to treat lifestyle-related diseases caused by aging and lack of exercise.

[0110] method

[0111] The primary objective was to determine whether the ingestion of a whey-based supplement and electrical muscle stimulation (EMS) improves muscle morphology and function in frail individuals during a 12-week EMS and nutritional intervention. This was a preliminary study with a parallel, double-blind, randomized study design and a single-center study with 3 groups (see below).

[0112] individual :

[0113] The 41 individuals who initially volunteered for this study were all frail elderly people (65-90 years old) who were classified as frail according to the Japanese Long-term Care Insurance (LCTI) system. All individuals included in the study were either "independently living" without any support, or were classified as care support level 1, care support level 2, long-term care level 1 (LTC1), and long-term care level 2 (LTC2) according to the LTCI system. Individuals with a walking speed between 0.6 and 1.2 m / s were included. All individuals were screened by a physician and care manager by asking orthopedic and medical questions to determine their suitability for participation in an exercise intervention involving electrical muscle stimulation.

[0114] Subjects were randomly assigned in a 1:1:1 ratio to one of three study groups; isocaloric (95 kcal) beverage containing: (A) 20 g carbohydrate (maltodextrin glucose syrup 21DE) + placebo capsule (CHO) (n=13), (B) 20 g whey protein isolate (Prolacta 95) + placebo capsule (whey) (n=15), or (C) 20 g whey protein isolate (Prolacta 95) plus rutin capsule (500 mg rutin per day) + w3-FA / curcumin capsule (daily dose: 500 mg curcumin and 1.5 g w3-FA type NAD supplied by Sofinol) (W-BIO) (n=13). Four subjects (1 in the CHO group and 3 in the W-BIO group) were excluded from the per-protocol analysis population because the subjects did not meet the inclusion criteria (n=2) or withdrew from follow-up prematurely (n=2).

[0115] Depending on the group allocation, individuals orally ingested 1 of 3 experimental beverages (AC) dissolved in 220ml of water. When using EMS treatment (twice a week), the beverage was applied immediately after EMS (maximum stimulation of protein synthesis). In order to be able to distinguish the specific effects of supplements (and not supplements from lunch), EMS was applied as soon as possible in the morning (so the supplements will be taken at least 1 hour before meals) or later in the afternoon (at least 2 hours after lunch). When EMS treatment was not performed, individuals drank the dietary supplement at the same time they used to drink dietary supplements when receiving EMS. During the study, individuals also took 7 capsules per day, 2 during breakfast, 3 during lunch, and 2 during dinner: 2 hard capsules containing 500 mg of rutin / day or placebo, 5 soft capsules containing a mixture of fish oil (1.5 grams of fish oil / day) and curcumin (500 mg of curcumin / day). All 41 individuals were subjected to a micro-nutritional assessment (MNA) to evaluate their basic nutritional status at baseline and after 12 weeks.

[0116] Electrical Muscle Stimulation (EMS) Procedure :

[0117] Although the use of EMS is reduced mainly due to the discomfort of stimulation, the new technology enables the application of strong contractions without pain. This activation can be applied at higher exercise doses and greater effectiveness than what people can achieve through exercise. The muscle electrical stimulation procedure has been fully described elsewhere (Hasegawa et al., 2011 (Hasegawa et al., 2011); Kimura et al., 2011 (Kimura et al., 2011); Miyamoto et al., 2012 (Miyamoto et al., 2012); Moritani et al., 2005 (Moritani et al., 2005)). In short, all individuals received EMS training twice a week for 12 weeks. Individuals were required to install belt-type electrodes around the waist and both knees and ankle joints to stimulate deep muscles and gluteus maximus, quadriceps femoris, hamstrings, calf triceps and tibialis anterior at a stimulation frequency of 20Hz (muscle hypertrophy mode). The stimulation intensity of EMS is adjusted to the maximum tolerable level of each individual without causing discomfort. Provide 20 minutes, 2 times a week, and 12 weeks of EMS training to individuals. Check the physical condition of individuals before each EMS. EMS training is carried out in a sitting position during rest to minimize the risk of mild dizziness, dizziness, falls and syncope caused by rapid movement. In this study, a specially designed muscle stimulator (Auto Tens pro, Homer Ion Co. Ltd., Tokyo, Japan) was used to carry out EMS training. The stimulator current waveform is designed to produce a co-contraction of the lower limb muscle groups with a frequency of 20 Hz and a pulse width of 250 μs. The duty cycle is 5 seconds stimulation, 2 seconds pause, and the cycle is 20 minutes. In addition, exponentially rising pulses are used to reduce discomfort during muscle stimulation.

[0118] The reason and rationale for using these EMS procedures described above is that high-frequency fatigue is evident when effective force is suppressed at a frequency that previously induced maximal force. High-frequency fatigue induces excessive force loss, which may be caused by electrical transmission failure and a rapid decrease in the amplitude of the evoked action potential. During this period of high-frequency force fatigue, considerable force is generated at 20 Hz stimulation (Moritani et al., 1985). Therefore, high-frequency fatigue can be largely explained by electrical transmission failure, which may be due to reduced sarcolemmal excitability, resulting in a decrease in evoked potential amplitude and conduction time (Jones et al., 1979; Moritani et al., 1985).

[0119] Most previous studies have reported the efficacy of EMS using either very high frequency (2500 Hz) or high frequency (50 or 80 Hz) stimulation. Eriksson et al. (1981) found that muscle enzyme activity, fiber size, and mitochondrial properties in the quadriceps femoris did not change during 4 to 5 weeks of 50 Hz EMS training. Therefore, patients trained with high frequency (50 or 80 Hz) EMS in previous studies may have experienced high frequency fatigue, and therefore the target muscles failed to contract effectively. This evidence suggests that 20 Hz EMS has the potential to induce muscle improvements (combined adaptation of neural factors and morphological changes) more effectively than high frequency (50 or 80 Hz) EMS.

[0120] Muscle morphology assessment :

[0121] Muscle thickness of the quadriceps, hamstrings, and triceps was assessed by ultrasound at baseline, week 4, week 8, and week 12 of the intervention. A close correlation between muscle thickness measured by B-mode ultrasound and site-matched skeletal muscle mass measured by MRI has been reported (Dupont et al., 2001; Fukunaga et al., 2001). Therefore, it seems reasonable to use muscle thickness measurements to estimate muscle size and muscle hypertrophy. Previous studies have demonstrated the reliability of measuring muscle thickness using ultrasound techniques (Kellis et al., 2009; Reeves et al., 2004). In addition, the reliability of ultrasound measurements was also measured in this study. The intraclass correlation coefficients of RF, VL and CA were 0.97 (0.88-0.99), 0.96 (0.85-0.99) and 0.99 (0.96-1.0), respectively.

[0122] The muscle thickness measurement using ultrasound examination is standardized as follows: all scans are performed at baseline and every four weeks after treatment. Each individual is examined by the same operator using a real-time scanner (SSD-900, ALOKA, Tokyo, Japan) with a 5MHz broadband transducer. A water-based gel is applied to the probe before the imaging procedure. During imaging, the transducer is kept perpendicular to the skin surface, with special attention to avoid excessive pressure. The measurement site is the thickest part of the muscle, and is measured using a standardized procedure using carefully positioned bone landmarks. When the individual is in a sitting position, the muscles of the quadriceps and triceps surae are imaged and measured on their unilateral side, respectively, because these muscles are the main determinants of walking speed. The images obtained are stored in situ, and all data are subsequently analyzed by using the National Institutes of Health (NIH) image program. Each imaging data is analyzed by a blind method for individual and date information to avoid any experimental bias. The measurement of muscle volume using ultrasonography was also standardized in the following manner: In addition to measuring muscle thickness, the circumference of the thigh and calf muscle groups was measured using standardized procedures to estimate the variation in these muscle groups. Subcutaneous fat thickness was determined ultrasonographically at four sites for each muscle group and averaged. The volume of each muscle group was then calculated algebraically using the method of Moritani and deVries (1979). (See Figure 1 ).

[0123] Assessment of autonomic nervous system activity :

[0124] Power spectrum analysis of heart rate variability (HRV) is a widely recognized and useful noninvasive method that allows for comprehensive, quantitative, and qualitative assessment of autonomic function in a variety of research and clinical settings (Conny et al., 1993; Moritani et al., 1995). In general, power spectrum analysis of HRV will show at least two distinct periodic regions in the RR intervals of the electrocardiogram (ECG). The high-frequency component (>0.15 Hz) is the main factor reflecting the activity of the parasympathetic nervous system (PNS), while the low-frequency component (<0.15 Hz) is associated with the activity of both the sympathetic nervous system (SNS) and the PNS (Akselrod et al., 1981; Moritani et al., 1993).

[0125] The RR interval power spectrum analysis procedure has been fully described elsewhere (Moritani et al., 1993; Matsumoto et al., 1999, 2001). Briefly, the analog output of the ECG monitor (Life Scope, Nihon Kohden, Tokyo, Japan) was digitized at a sampling frequency of 1000 Hz using a 13-bit analog-to-digital converter (HTB 410, Trans Era, South Orem, UT). The digitized ECG signal was sorted, and the resulting ECG QRS peaks and pulse intervals (RR intervals) were stored sequentially on a hard disk for subsequent analysis. Prior to RR spectral analysis, the stored RR interval data were displayed sequentially and aligned to obtain equally spaced samples with an effective sampling frequency of 2 Hz and displayed on a computer screen for visual inspection. The DC component and linear trend were then completely eliminated by digital filtering with a bandpass between 0.03 Hz and 0.5 Hz. The root mean square value of the RR interval was calculated, representing the average amplitude. After passing through a Hamming-type data window, the RR interval data of a continuous 256-second time series obtained during the test were subjected to power spectrum analysis by fast Fourier transform. The spectral power in the frequency domain was quantified by integrating the area under the curve for the following bandwidths: low frequency (LF: 0.03 Hz and 0.15 Hz), an indicator of SNS and PNS activity; high frequency (HF: 0.15 Hz and 0.5 Hz), reflecting only PNS activity; and total power (TP: 0.03 Hz and 0.5 Hz), representing overall ANS activity.

[0126] Physical performance test :

[0127] Muscle strength measurement. The measurement procedure has been reported elsewhere (Watanabe et al., 2012a, 21012b (Watanabe et al., 2012a, 2012b)). In brief, isometric knee extensions were performed on a custom-made dynamometer equipped with a force transducer (LU-100KSE, Kyowa Electronic Instruments, Tokyo, Japan). During the contraction, the hip and knee joint angles were flexed 90° each (180° is full extension). Maximum voluntary contraction (MVC) involves a gradual increase in the knee extension force applied by the knee extensors from baseline to maximum within 2-3 seconds, and then maintained at maximum for 2 seconds. The timing of the task was based on verbal counts given at 1-second intervals, with researchers giving positive encouragement when the force began to plateau. At least two MVC tests were performed on each knee of the individual, with a 2-minute rest between tests. The highest MVC force was used for comparison.

[0128] Walking speed As part of the performance assessment, walking speed was measured at baseline, before any EMS or supplementation, after 12 weeks, and after the last EMS treatment and supplementation during the screening period by measuring the time (in seconds) taken to walk along a 6-meter straight path marked with a tape measure on the ground using a custom-made stopwatch with a trigger attached. During the assessment, the individuals were asked to walk normally as they would in daily life. The use of common walking aids (e.g., sticks, walkers) was allowed. The walking speed of each individual was evaluated three times and the average was taken.

[0129] Body composition Body composition (fat mass, lean body mass, expressed as Kg and %) was assessed by using bioelectrical impedance analysis at baseline and at week 12 of treatment. These measurements were performed on all individuals using a state-of-the-art bioelectrical impedance analysis device (Tanita BC-118D, Tanita Ltd., Tokyo, Japan) using handheld leads and flat-foot plantar electrodes with an excitation current of 500 microamperes at 50 KHz. The measured impedance values ​​were used to calculate lean body mass and fat mass for the arms, legs, trunk, and whole body, respectively.

[0130] Blood Chemistry. Blood samples were collected from the antecubital vein into evacuated tubes after an overnight fast. Blood tests were performed for markers of insulin sensitivity (changes in blood glucose, glycated hemoglobin, plasma insulin, and C-peptide concentrations), red blood cell count, white blood cell count, plasma fatty acid profile, inflammatory markers (CRP, transthyretin, fibrinogen, and serum mucoid), and blood chemistry for CPK, HDL and LDL cholesterol, albumin, total protein, and triglycerides. Blood tests for coagulation parameters (platelet count, prothrombin time, and partial thromboplastin time) were measured at baseline, week 2, week 6, and week 12 to ensure the safety of the nutritional intervention. For other parameters, measurements were performed at baseline and after 12 weeks of intervention with EMS and nutritional supplementation.

[0131] Statistical analysis :

[0132] Primary analyses were performed on the full analysis set (FAS) and per-protocol (PP) analysis populations, comparing group 2 with group 1. Muscle thickness (in mm) was analyzed using a repeated measures mixed model with baseline measurements, sex, age at randomization, and time as covariates. 2 ). The least square means for each muscle location and treatment group at week 12 will be given.

[0133] The O'Brien OLS test between Group 1 and Group 2 was used as a global test to assess the effect of the product on both muscle locations at Week 12. The O'Brien OLS statistic was determined as follows:

[0134] T-test statistical tests were calculated for treatment effect at Visit 8 for each individual muscle location (ie, calf and thigh).

[0135] The OLS statistic is then determined as follows:

[0136]

[0137] where t is the vector of t-test statistics for the calf and thigh measurements, j is a vector of 1s, is the sample correlation matrix of the original observations.

[0138] t OLS The degrees of freedom (df) is approximately defined as df = 0.5*(n1+n2-2)*(1+1 / m 2 ), where m is the number of endpoints analyzed (i.e., calf + thigh), and n1 and n2 are the number of individuals in Group 1 and Group 2 for whom calf and thigh measurements were available at Visit 8, respectively.

[0139] Secondary analyses were performed on the FAS population only. The analyses performed are described in detail in Section 11.2 of the SAP.

[0140] Mixed effects linear models were used to analyze longitudinal data in order to account for correlations between repeated measures. Fixed effects linear models were used to analyze changes from baseline to one time point. Multiple comparisons were performed when necessary (W-BIO vs. placebo (PLACEBO), and whey vs. placebo). For these multiple comparisons, adjusted p values ​​using a single step adjustment are recorded. O'Brien global tests were performed to test the hypothesis of the directionality of the combined effects on muscle cross-sectional area and thickness. This was only done to compare the calf and thigh muscles in the W-BIO group with the placebo group separately. All data analyses were performed using R version 3.0.1.

[0141] result

[0142] Table 1 (below) presents a description of the population parameters at baseline. The majority of individuals randomized in the trial were female. The individuals included in the W-BIO group were slightly heavier (BMI of 22.7 kg / m 2 , while the CHO group and whey group were 20.3 and 21.3 kg / m 2 ), and their calf muscles are larger (cross-sectional area, mm 2 ). The right and left knee extension forces were worse in individuals randomized to the CHO group compared to the measurements obtained from individuals randomized to the whey and W-BIO groups, respectively.

[0143] Table 1. Description of population parameters at baseline

[0144]

[0145]

[0146] Muscle shape :

[0147] Longitudinal analysis of muscle surface area and thickness Global tests were performed to compare the W-BIO group with the placebo group for the cross-sectional area (CSA) and total thickness of the calf and CSA, and similarly to compare these parameters for the thigh of these two groups. These comparisons were not found to be statistically significant.

[0148] Effects of dietary treatment on muscle surface area and thickness at the end of the intervention . Comparing the different groups at the end of the treatment period (after 3 months), no statistically significant differences were found in thigh and calf muscle thickness or cross-sectional area between the three groups. There were no statistically significant differences in thigh and calf muscle cross-sectional area between any of the study treatment groups at any time point. Therefore, considering the results on muscle morphology together, it is suggested that the treatment induced the increase in muscle surface area and thickness observed in the three groups and may therefore be more related to EMS treatment than to specific nutritional interventions.

[0149] Physical performance :

[0150] Walking speed Table 2 shows the descriptive results of walking speed (m / s) at baseline and week 12 in the three treatment groups ( Figure 2 The greatest improvement in walking speed was observed in the W-BIO group, from 1.15 ± 0.45 to 1.26 ± 0.46 m / s (an increase of nearly 9.5%). Only moderate increases in walking speed were observed in the CHO and whey groups, from 1.20 ± 0.32 to 1.24 ± 0.37 m / s (an increase of 3.3%) and from 1.12 ± 0.33 to 1.16 ± 0.31 m / s (an increase of 3.6%), respectively. However, these differences did not reach statistical significance.

[0151] Muscle Strength . Figure 3 Shown are the changes in left knee extension muscle strength for the three treatment groups at baseline and week 12. At week 12, there were statistically significant differences in left knee extension between the W-BIO group and the whey group (4.17 kg [95% confidence interval (CI) 0.41-7.94], p=0.0308), and between the W-BIO group and the CHO group (5.89 kg [95% confidence interval (CI) 1.78-10.01], p=0.0063).

[0152] In addition, a mixed effects model was fitted to account for the correlation between the two measurements taken from the two knees of each individual at each time point. Figure 4 ) showed that there was a statistically significant interaction between treatment and gender. In other words, the treatment effect was different for the two genders. This was prominent in the comparison between the active treatment group (also called W-BIO) and the placebo (CHO) for males and females respectively. Thus, the treatment seemed to induce a strong improvement in knee extension force in the males of the W-BIO group, but this effect was not observed in the females.

[0153] Finally, when each individual is represented individually, the results are quite interesting ( Figure 5 ): While the progression in the other 2 groups appeared to rise and fall, almost all individuals in the W-BIO group presented a positive slope between V2 and V8 (regardless of gender). Thus, this presentation allowed a direct visualization of the specific benefits observed in the W-BIO group and demonstrated by the statistical analysis above.

[0154] Body composition Anthropometric measurements (fat mass, lean body mass, expressed in Kg and %) were performed by using bioelectrical impedance analysis at baseline and week 12 of the experimental treatment. There were no statistically significant differences between any of the study treatment groups at baseline and week 12.

[0155] Autonomic nervous system activity Power spectrum analysis of the electrocardiographic RR intervals showed no statistically significant differences between any of the study treatment groups at baseline and week 12 regarding resting heart rate, LF (sympathetic nervous system activity), HF (parasympathetic nervous system activity), and TP (global autonomic nervous system activity).

[0156] Blood analysis There were no statistically significant differences between any of the study treatment groups at baseline and Week 12 for markers of insulin sensitivity (changes in blood glucose, glycated hemoglobin, plasma insulin, and C-peptide concentrations), red blood cell count, white blood cell count, plasma fatty acid profile, inflammatory markers (CRP, transthyretin, fibrinogen, and serum mucoid), and blood chemistries for CPK, HDL and LDL cholesterol, albumin, total protein, and triglycerides. Similarly, blood tests for coagulation parameters (platelet count, prothrombin time, and partial prothrombin time) measured at baseline, Week 2, Week 6, and Week 12 showed no significant group differences.

[0157] discuss

[0158] The present study showed that after 12 weeks of administration of bioactive supplements (whey protein, rutin, w3-FA, and curcumin) and EMS training, knee extension force in frail individuals in the W-BIO group increased significantly compared to the other two groups (CHO and whey) (18.8% in the left leg and 7.3% in the right leg). In addition, the W-BIO group showed the greatest improvement in walking speed (9.6%) among the groups supplemented with carbohydrates or whey protein and trained with EMS. Interestingly, this benefit regarding muscle strength was not associated with an increase in muscle size. In fact, after 12 weeks of treatment, a small increase in muscle size was observed in all three groups, but this effect was similar in the three groups, so the increase in muscle size may be specific to EMS treatment (and not related to dietary treatment).

[0159] Interestingly, gender differences were found in the response to EMS training, with male individuals showing significant improvements in muscle thickness, whereas no such significant changes were observed in females.

[0160] These findings provide support for the importance of a "neural factor" that, although not yet clear, certainly contributes to the expression of maximal muscle force (called strength). Human voluntary strength is determined not only by the amount (muscle cross-sectional area) and quality (muscle fiber type) of muscle mass involved, but also by the degree of activation of that muscle mass (neural factors). In addition, muscle mass is also related to intramuscular lipid content, which increases with age and leads to a decrease in muscle mass. Therefore, the benefits observed in the W-BIO treatment group, which improved as the study progressed, could be a reduction in lipid content in the muscle and an increase in the number or size of muscle fibers, allowing improvements in strength to be obtained without any changes in muscle thickness or CSA (balance between lipid and protein content).

[0161] In this study, all three groups received the same EMS training, which induced "involuntary" contractions of the major lower limb muscle groups twice a week for 12 weeks. In the absence of significant differences in muscle thickness and estimated cross-sectional area of ​​the thigh and calf among the three groups, the following possibilities are proposed: the W-BIO group may have acquired the ability to activate muscles to a higher degree by enhancing central motor drive and / or by altering muscle fiber composition through bioactive supplementation to produce more tension per unit cross-sectional area. The W-BIO group may have had enhanced central nervous system integrity, thereby generating higher motor commands to activate muscles.

[0162] Another possibility to explain the increase in muscle strength observed specifically in the W-BIO group is that polyphenols may help control oxidative stress, which is known to occur in inactive elderly people. Administration of polyphenols together with protein may help to counteract anabolic resistance (by controlling oxidative stress), thus enabling restoration of the anabolic effects of nutrients and protein on muscle protein synthesis. In the same way, EPA supplementation may also induce improvements in insulin sensitivity, thus stimulating muscle protein synthesis relative to whey protein.

[0163] It should be understood that various changes and modifications made to the presently preferred embodiments described herein will be apparent to those skilled in the art. These changes and modifications may be made without departing from the spirit and scope of the subject matter of the present invention and without impairing its intended advantages. Therefore, these changes and modifications are intended to be covered by the appended claims.

Claims

1. Use of a composition comprising a protein source and an antioxidant in the preparation of a product for reducing muscle strength loss in elderly men, increasing muscle strength in elderly men and / or improving muscle strength recovery in elderly men after muscle atrophy, wherein the composition consists of n-3 fatty acids, an antioxidant and a protein source, wherein the antioxidant is a combination of curcumin and rutin, and wherein the protein source is whey protein, and wherein the composition is administered in an amount providing 0.1 to 0.4 grams of the protein source per kilogram of body weight of the elderly male per day.

2. The use according to claim 1, wherein the composition is administered at least twice a week for a period of at least one month.

3. The use according to claim 1 or 2, wherein the composition is administered in an amount providing 0.01 to 0.04 g of leucine per kg of body weight of the elderly male per day.

4. The use according to claim 1, 2 or 3, wherein the elderly male suffers from sarcopenia.

5. The use according to any one of claims 1 to 4, wherein the product is a food composition, a dietary supplement, a nutritional composition, a nutraceutical, a powdered nutritional product to be reconstituted with water or milk before consumption, a food additive, a medicament, a beverage or a combination thereof.

6. Use according to any one of the preceding claims, wherein the weight ratio of whey protein to the combination of curcumin and rutin is from 300:1 to 2:

1.

7. Use according to any one of the preceding claims, wherein the composition further comprises vitamin D.

8. A composition consisting of n-3 fatty acids, an antioxidant and a protein source, wherein the antioxidant is a combination of curcumin and rutin, and wherein the protein source is whey protein, and wherein the composition comprises the protein source in an amount of 0.2% to 100% based on the dry weight of the composition, and wherein the composition is administered in an amount providing 0.1 to 0.4 grams of the protein source per kilogram of body weight of the elderly male per day.

9. The composition according to claim 8, wherein the weight ratio of whey protein to the combination of curcumin and rutin is 300:1 to 2:

1.

10. The composition according to claim 8 or 9, wherein the composition further comprises vitamin D.

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