EP2175747A2

EP2175747A2 - Food supplement containing alpha-keto acids

Info

Publication number: EP2175747A2
Application number: EP08717471A
Authority: EP
Inventors: Andreas Karau; Matthias Kottenhahn; Karlheinz Drauz; Norbert Windhab; Adolf GRÜNERT
Original assignee: Evonik Degussa GmbH
Current assignee: Evonik Operations GmbH
Priority date: 2007-04-04
Filing date: 2008-03-06
Publication date: 2010-04-21
Also published as: CN101646358A; RU2492705C2; WO2008122473A2; BRPI0810099A2; WO2008122613A3; WO2008122473A3; RU2009140373A; DE102007016715A1; CN101646358B; WO2008122613A2; EP2129241A2

Abstract

The invention relates to a food supplement which can contain at least one amino acid, wherein the food supplement is otherwise essentially nitrogen-free and contains at least one alpha-keto acid selected from the group alpha-ketoisocaproate, alpha-ketoisovalerate and alpha-keto-beta-methylvalerate and/or a salt of these alpha-keto acids. The food supplements described support muscle build-up and simultaneously relieve metabolism in nitrogen detoxification by reduced nitrogen supply and improve nitrogen retention in the body.

Description

Food supplement containing alpha-keto acids

The present invention relates to food supplements containing alpha-keto analogues of branched-chain amino acids for supporting muscle structure, increasing muscle performance and improving general wellbeing with simultaneous relief of nitrogen detoxification metabolism by reduced nitrogen supply and improved nitrogen retention in the body.

Lack of physical movement is a risk factor which can lead to decreased physical efficiency and thus to a reduced quality of life. In order to prevent the drop in physical efficiency, and to build it up again, physical training is essential, wherein a series of cellular processes such as, for example, muscle damage and muscle breakdown, muscle regeneration, muscle hypertrophy and muscle fibre transformation proceed. In the cellular processes, energy and protein metabolism plays a decisive role. Consequently, the supply of amino acids plays a decisive role with respect to the metabolic processes proceeding in muscle tissue. In particular, the branched-chain amino acids valine, leucine and isoleucine are essential substrates and important regulators in protein biosynthesis and a main source of nitrogen for glutamine and alanine synthesis in skeletal muscle. Alanine, in addition, is an important precursor for gluconeogenesis and glutamine acts as a nitrogen transporter between organs.

The average requirement for protein is approximately 660 mg/kg of body weight which, however, can be significantly increased by physical training. The requirement for protein can generally be covered by a balanced diet, which, however, is not readily achievable. Physical training, owing to an increased protein degradation and decreased protein synthesis, leads to an altered requirement for nutrients, in addition a modified metabolic position results which, for example, is due to the effect of physical training on the hormone system and finally, there is also a lack of knowledge about a suitable diet with increasing physical load, especially in relation to age, so that malnutrition can occur rapidly.

For these reasons, the use of a food supplement appears logical in individuals which are subject to physical load. In this context, studies have already been carried out with differing results which related to the effect of a creatine supplementation on the efficiency of the subject. In addition, it is known that muscle regeneration can be promoted by a high carbohydrate supply.

The use of branched-chain amino acids (BCAA) as a dietetic substitute was studied likewise intensively in the past, but not with clear results. While in one study an increase in mental and physical performance by BCAA supplementation is reported (Blomstrand, E. et al . , Eur. J. Appl . Physiol. Occup Physiol 63: 83-88, 1991), in another study, no effect on physical efficiency was found (van HG, Raaymakers, Saris, Wagenmakers, J. Physiol 486 (Pt3) , 789-794, 1995).

Alpha-keto acids of branched-chain amino acids likewise play an important role in amino acid metabolism, especially in the skeletal muscle and liver. One-third of muscle protein consists of the branched-chain amino acids which cannot be formed by the body, but must be taken in with food. In the muscle, especially in the case of physical exertion, proteins are continuously synthesized and broken down, wherein in the breakdown of amino acids the corresponding alpha-keto acid is formed with transfer of the amino group to a carrier. The keto acid obtained can then be further oxidized enzymatically for energy production. The carrier is transported to the liver and there releases toxic ammonia, which must be converted to urea and excreted via the kidneys.

The use of alpha-keto acids which are derived from branched-chain amino acids for pharmaceutical purposes has long been known. For instance, alpha-keto isocaproate (ketoleucine) , in particular, can be used for reducing the protein breakdown in muscle and for a reduction of the formation of urea resulting from protein breakdown after muscle operations (US 4,677,121) . The use of ketoleucine in malnutrition, muscular dystrophy or uraemia and in other disorders which are a secondary consequence of protein breakdown in muscle is also described there. Ketoleucine is administered in this case intravenously. In addition, it has been proposed to administer the alpha-keto acids of leucine, isoleucine and valine to patients who must maintain a protein-reduced diet, for example because of renal failure (US 4,100,161). The role of alpha-keto acids within protein metabolism with respect to various medical indications is also described in Walser, M. et al., Kidney International, Vol. 38 (1990), pp. 595-604.

In the functional food sector, in contrast, the branched-chain amino acids are used directly for supporting muscle build-up, for example in athletes (Shimomura, Y. et al . , American Society for Nutrition) . The use of alpha-keto acids of leucine, isoleucine and valine for improving muscle performance and also for supporting muscle recovery after fatigue is described in US 6,100,287, wherein salts of the corresponding anionic keto acids with cationic amino acids as counterion, such as, for example, arginine or lysine, are used. As a result, however, polyamines are also formed of which it is known that they can lead to apoptosis (programmed cell death) . The excretion of the breakdown products of polyamines proceeds via the kidneys which are further stressed as a result.

Proceeding from the prior art, there is a need for food supplements which promote wellbeing after sporting activities, increase muscle synthesis and efficiency of the muscle and permanently lower the nitrogen burden of metabolism.

The object is achieved by providing food supplements which contain at least one alpha-keto acid selected from the group alpha-ketoisocaproate (KIC) , alpha-keto- isovalerate (KIV) and alpha-keto-beta-methylvalerate (KMV) and/or a salt of these alpha-keto acids, wherein the supplement if appropriate can additionally contain one or more amino acids, in particular leucine, isoleucine and/or valine, but is otherwise nitrogen- free .

Food supplements are considered "essentially nitrogen- free" which, in addition to the said amino acids, do not contain nitrogenous formulation aids, in particular do not contain nitrogenous cations, such as, for example, cationic amino acids or dibasic amino acids from the group arginine, lysine, histidine or ornithine, or other nitrogenous additives to a significant extent. However, food supplements are essentially nitrogen-free which comprise nitrogenous additives which can be added to the food supplement in a very small amount of less than 5 mg (daily dose) such as, for example, nitrogenous vitamins. However, preference is given to food supplements which do not have nitrogenous components, in particular do not have cationic amino acids. In this case the expression "nitrogen-free" relates to the supplement itself. Foods (functional foods) which contain the claimed food supplements, of course, can in addition have nitrogenous components. Preferably, in the foods which are modified with the food supplements of the invention, no further food supplements are present, in particular those supplements which comprise an additionally increased supplementation with nitrogenous compounds. In particular, no artificial increase in the content of cationic amino acids should proceed in the food.

In addition to the alpha-keto acids KIC, KIV and KMV, their salts, provided that they contain nitrogen-free cations, can also be present in the food supplement of the invention. Suitable salts in this case are, in particular, the alkali metal salts or alkaline earth metal salts, in particular the Na⁺, K⁺, Ca²⁺ and Mg²⁺ salts of the said alpha-keto acids.

A preferred embodiment represents food supplements which have a combination of alpha-ketoisocaproate and alpha-ketoisovalerate or alpha-keto-beta-methylvalerate or a combination of alpha-ketoisovalerate and alpha- keto-beta-methylvalerate or a combination of all three alpha-keto acids or salts thereof. Preferably, a KMV/KIV weight ratio or KIC/KIV weight ratio or a KIC/KMV weight ratio of 50:1 to 1:50, preferably from 5:1 to 1:5, is set in the food supplement. Preferred weight ratios are, for KIC/KIV, between 3:1 and 1:1, for KIC/KMV, between 3:1 and 1:1, and for KIV/KMV, between 2:1 and 1:2. Corresponding quantitative ratios are also advantageous for a KIC/KIV/KMV mixture. A particularly suitable combination of KIC/KIV/KMV is a weight ratio of 2:1:1, wherein the said fractions can be varied ± 10%. The said weight ratios are particularly suitable for a rapid regenerative muscle build-up. The daily dose of the alpha-keto acids taken in via the food supplement should not exceed the amount of 2000 mg/kg of bodyweight for KIC, of 1000 mg/kg of bodyweight for KIV, and 1500 mg/kg of bodyweight for KMV, preference is given to doses of between 2.5 mg/kg and 500 mg/kg of bodyweight for each of the three alpha-keto acids. Particularly preferred doses are in the range from 25 mg/kg to 250 mg/kg of bodyweight for KIC, KIV and KMV, so that with adults (for example for a bodyweight between 50 and 100 kg) , an approximate preferred total amount per alpha-keto acid taken in of 1.25 g to 25 g results. Individually, for the alpha- keto acids, the following preferred doses result: for KIC between 50 mg/kg and 200 mg/kg, for KIV between 25 mg/kg and 150 mg/kg, and for KMV between 25 mg/kg and 100 mg/kg. Customary daily doses are in the range from 0.5 g to 50 g per alpha-keto acid per day. With respect to the amount of cations present, in the food supplement, preferably no more than 10 g, better between 0.5 g and 2 g, of Na⁺, K⁺ ions should be present, preferably no more than 5 g, better between 0.2 and 2.5 g of Ca²⁺ ions and no more than 2 g, better between 0.2 and 1 g, of the corresponding Mg²⁺ ions should be present.

In addition, the branched-chain amino acids leucine, isoleucine and valine can also be added to the food supplements described here. Preferably, the said amino acids, however, are used in low amounts. With respect to the present invention, the amount added to the food supplement should not exceed a ratio of 1:0.5, better 1:0.1 (alpha-keto acid: conjugate amino acid). Particularly preferred food supplements however, do not contain leucine, isoleucine or valine.

Particularly preferred food supplements contain further keto acids derived from naturally occurring amino acids, or salts thereof, particularly preferably alpha- ketoglutaric acid, of salts thereof, in particular alpha-ketoglutarate (AKG) . In this case, likewise the use of the abovementioned alkali metal salts and alkaline earth metal salts of alpha-keto acids is of particular interest. The abovementioned dosages likewise apply to the alpha-keto acids additionally present, or salts thereof. By adding AKG, the ammonia detoxification can be further increased, wherein the transport of ammonia out of the muscle in blood and liver is forced. In this case the administration of AKG does not appear to have an adverse effect on the protein synthesis rate. In addition, AKG has an antioxidative effect. Therefore, food supplements which contain a combination of KIC, KIV and/or KMV and AKG are a particularly preferred embodiment of the present invention .

In addition, preferred food supplements additionally contain creatine as component.

In addition, further nitrogen-free additives can be added to the food supplement. Those which may be stressed in particular are energy-giving compounds, preferably from the group of carbohydrates, such as, for example, glucose, but also additives which promote the regeneration process, such as, for example, vitamins, in particular vitamin A, vitamin Bi, B₂, Be and Bi₂, vitamin C, vitamin D, vitamin E, vitamin K, pantothenic acid, niacin, folic acid, biotin, choline and inositol. In addition, antioxidants can be present in the food supplement such as, for example, beta- carotene, potassium citrate, citric acid, lactic acid, tocopherol, sodium ascorbate or potassium ascorbate or ascorbic acid. Minerals and trace elements from the group sodium, potassium, magnesium, calcium, iron, zinc, manganese, copper, selenium, chromium, phosphorus and iodine are likewise possible as additives. The said additives in this case are added in the amounts conventional for the food sector.

Preferred food supplements can contain, for example, (the quantities in each case are the preferred daily dose) : 10-500 mg of sodium,

10-500 mg of potassium,

50-500 mg of calcium, 10-300 mg of magnesium,

1-20 mg of zinc,

5-50 mg of iron,

0.1-1 mg of iodine,

5-100 μg of selenium, 5-100 μg of chromium, up to 100 mg of vitamin Bi, up to 100 mg of vitamin B₂, up to 100 mg of vitamin B₆, up to 200 mg of vitamin B12, up to 5 g of vitamin C, up to 500 mg of vitamin E, up to 300 mg of pantothenic acid, up to 1 g of niacin, up to 10 mg of folic acid, up to 1 mg of biotin.

Further additives which come into consideration as an addition are saturated or unsaturated fatty acids, in particular C6-C22 fatty acids. In addition, use can be made of fats and oils from the group sunflower, sesame, rapeseed, palm, castor oil, coconut, safflower, soyabean, pork lard and beef tallow. In addition, preservatives, food dyes, sweeteners, flavour enhancers and/or aroma substances can be present in the food supplement in the customary amounts known to those skilled in the art. In particular, as additives, taste- masking substances come into consideration since, for example, free alpha-keto acids can taste acidic or their salts can taste unpleasant. If the additives employed are used in relatively large amounts, recourse is made in this case to nitrogen-free additives. Particularly preferred food supplements, however, do not contain nitrogenous additives. The claimed food supplements can be used, for example in the form of a powder, a tablet, or in the form of a solution or suspension. In tablet form, the alpha-keto acids or salts thereof are preferably formulated with approximately 30 to 80 per cent by volume in the food supplement, preferably using nitrogen-free additives, in particular carbohydrates, fats and oils, and if appropriate also amino acids, such as, for example, leucine, isoleucine and valine, which can be present in the food supplement at approximately 70 to 20 per cent by volume.

If direct administration of the food supplement in the form of a powder or a tablet is desired, the addition of conventional carriers can be advantageous. Suitable carriers are, for example, linear or (hyper) branched polyesters, polyethers, polyglycerols, polyglycolides, polylactides, polylactide-co-glycolides, polytartrates and polysaccharides or polyethyleneoxide-based dendrimers, polyether dendrimers, coated PAMAM dentrimers, such as, for example, polylactide-co- glycolide coating, or polyaryl ethers.

The powder or the tablet can in addition be provided with a coating, in order, for example, to permit the release of the food supplement first in the intestinal tract. The following encapsulating materials are preferably used in this case: carboxymethylcellulose, nitrocellulose, polyvinyl alcohol, shellac, carrageenan, alginates, gelatin, cellulose acetate, phthalates, ethylcellulose, polyglycerols, polyesters or Eudragit®.

If, in contrast, a solution or suspension of the food supplement is administered, the addition of emulsifiers or colloids can be useful, in order to be able to take up all desired components as well as possible in an aqueous system. Suitable additives are, for example, polyvinyl alcohols, glycerides of edible fatty acids, their esters of acetic acid, citric acid, lactic acid or tartaric acid, polyoxyethylene stearates, carbohydrate esters, propylene glycol esters, glycerol esters or Sorbitan esters of edible fatty acids or sodium lauryl sulphate.

The present invention further relates to foods (functional foods) which contain the claimed food supplement. These can be, for example, drinks or bars which are particularly suitable for consuming the food supplement .

The foods in this case can be admixed with the claimed food supplement during their production, or a formulation of the food supplement can be added later to the food, for example in the form of a powder or a tablet. The dissolution of effervescent tablets or of a powder in mineral water can be mentioned here by way of example .

The use of the described food supplements or food can in principle be possible all day, but in particular during or after physical exertion is advisable. Physical training causes a muscular adaptation including muscle damage, muscle hypertrophy and muscle transformation. In this case a training unit is considered a combination of a training phase and a regeneration phase. A suboptimal design of the training unit can lead, for example, to an overtraining syndrome which is expressed in a long-lasting tiredness with reduced physical efficiency. Such an overtraining syndrome is frequently caused or amplified by malnutrition.

Use of the claimed food supplements promotes ammonia detoxification in muscle which is necessary, inter alia, as a result of the protein and amino acid breakdown in muscle. By transferring amino groups which are released to the keto acids, the conjugate amino acids are generated and are again available for muscle build-up and the energy-consuming nitrogen detoxification and nitrogen excretion via liver and kidney is decreased. Correspondingly, the throughput of nitrogenous breakdown products such as, for example, urea, in the blood or urine is reduced. At the same time the efficiency of the musculature is increased and muscle build-up is supported by the food supplements, since by transamination the keto acids which are administered can be converted in the muscle into the corresponding amino acids which are there available for anabolic reactions. Finally, a more rapid regeneration of the muscle tissue is established, and the physical efficiency and also general wellbeing is improved. Not only the support of protein synthesis in the muscle but also ammonia detoxification is particularly supported by the said alpha-keto acids, since these are selectively taken up by the muscle tissue. Ammonia detoxification proceeds particularly efficiently when the claimed food supplements additionally contain alpha-ketoglutarate (AKG) .

Consequently, the nitrogen balance of the body which is under a physical stress, is improved in two aspects by the food supplements of the invention: firstly, the loss of nitrogen by muscle breakdown processes in the case of physical stress is reduced, which leads to muscle regeneration and muscle repair, secondly ammonia detoxification is accelerated which leads to a more rapid muscle recuperation or reduced tiredness of the musculature. By a more rapid regeneration, an increased training scope or increased training intensity or frequency may also be achieved, without provoking the abovementioned adverse effects of overtraining. In summary, it may be stated that substitution of the food supplements according to the invention prevents malnutrition, leads to satisfaction of the increased nutrient requirement, promotes muscular regeneration and prevents overtraining, which leads to strengthening of the musculature and increases the efficiency and wellbeing of a person.

In the said aspects, the food supplement of the invention is directed, in particular, to athletes, in this case both recreational and top athletes, including power athletes, and also those interested in health and fitness. The use of food supplements by older persons who, as is known, frequently have a restricted nitrogen economy and restricted nitrogen excretion capacity, is likewise particularly advantageous.

Therefore, the present invention further relates to the use of the claimed food supplements for producing products which can be taken orally such as, for example, functional foods, in particular drinks, gels, creams, broths, energy bars, etc., and also tablets, powders which, for example, can be offered in sachets, bags, tubes, and for supporting muscle build-up, the efficiency of the musculature, for protection of the musculature against cell damage under stress, for increasing general wellbeing, general physical efficiency and for supporting muscle regeneration after physical stress with simultaneous relief of metabolism with respect to nitrogen detoxification.

Accordingly, the present invention further relates to the use of the described food supplements or foods in combination with targeted nutrition, in particular a reduced-calorie diet, slimming diets or fitness diets.

In addition, the claimed food supplements can also be used for producing animal food. The higher efficiency of the musculature which is achieved by the intake of food supplements or the foods modified thereby, can be demonstrated, firstly, in an improved endurance, secondly, however, in an increased takeoff power and other performance parameters. For testing the increased efficiency, subjects can be placed into a state of overtraining (intense training with insufficient regeneration) . The keto acid substitution can be performed, for example, by effervescent tablets which are dissolved in water, wherein the amount of alpha-keto acids should be adapted to the bodyweight of the subject. The freshly stirred drinks are preferably supplied during or shortly after the respective training unit.

A preferred formulation for such a test is the use of 0.2 g/kg/d of calcium alpha-ketoglutarate or sodium alpha-ketoglutarate or of the corresponding free acid, or of 0.2 g/kg/d of calcium alpha-ketoisocaproate or sodium alpha-ketoisocaproate or of the corresponding free acid or of 0.2 g/kg/d of calcium alpha- ketoisovalerate or sodium alpha-ketoisovalerate or the corresponding free acid, or 0.2 g/kg/d of calcium alpha-ketomethylvalerate or sodium alpha-ketomethyl- valerate or of the corresponding free acid, or 0.2 g/kg/d of a mixture of these components, in particular of the calcium or sodium salts of KIC (for example 95 mg/kg/d) , MIV (for example 60 mg/kg/d) and KMV (for example 45 mg/kg/d) . As placebo, use can be made of, for example, calcium glucose and/or sodium glucose or free glucose. The appearance and taste should as far as possible be identical for all formulations .

In order to be able to evaluate the results better, likewise a diet protocol should be carried out, wherein resource is made to a diet as standardized as possible (for example Prodi programme diet protocol) .

The general health status and stress recovery can be determined by questioning the subjects. Further conclusions as to the change in general efficiency result from the change in bodyweight and body fat percentage .

To be able to assess muscle function generally, the maximum oxygen intake (Vθ2maχ) is measured with a subject under stress. For this the stress is increased on a bicycle ergometer by means of a ramp protocol (for example at the start 0 watt, continuous increase in performance at 50 watt/min, until subjective exhaustion occurs) . In addition, the heart rate can be determined synchronously by means of electrocardiography. The oxygen intake is calculated from the ventilation rate per minute measured on-line and the difference between oxygen concentration between inspired and expired gases .

To determine the improvement in stamina, the individual anaerobic-aerobic threshold (IAAT) is determined. This is achieved on the basis of measuring a lactate performance curve with a running belt test (training phase protocol: start 6 km/h, increased 2 km/h, which corresponds to an increase of approximately 25- 50 watt/min, stage time 3 min) and with a bicycle ergometer (initial stage 50 watt, increase 25 watt, stage time 3 min, until subjective exhausted state is achieved) . In this case, before and after a training stage, blood samples are taken in a 30 second interval (for example whole blood (haemolysed) from hyperaemized capillary blood (earlobe) ) and the glucose and lactate concentration were determined by means of a YSI 2300 STAT plus analyser from YSI Life Sciences, Yellow Springs, USA and the maximum oxygen intake (VO2 max value) determined spirometrically using a K4 measuring instrument from Cosmed (Rome, Italy) .

The improvement in takeoff power can be measured by means of a takeoff power measuring plate from Kistler, Winterthur, Switzerland. For determining the explosive power by means of the takeoff power test, the "squat jump" and "count movement jump" protocol specific to the instrument is used. The takeoff power is measured on the basis of contact time on the measuring plate and the jump height and calculated with equalization for body weight. To determine the maximum force, for example the leg musculature can be stressed at a defined angle and the maximum force measured.

Metabolic parameters such as, for example, the concentration of BCKA and AKG or the urea or uric acid concentration in blood can be measured by HPLC measurements. To determine the damage of muscle cells, for example during physical stress, the uric acid level in blood or urine or the creatine kinase activity in blood is determined. The rise in creatine kinase activity correlates with the extent of muscle damage and can be determined by an enzymatic reaction using the kit No. 1087533 from Roche Diagnostics, Mannheim, Germany. The uric acid concentrations can be determined photometrically using the "Fluitest UA®" kit from Biocon Diagnostics, Vδhl/Marienhagen, Germany.

The effects of the claimed food supplement on protein metabolism may be detected by measuring urea concentrations in blood or urine. Determining the urea concentrations can be performed by photometric end point determination at a wavelength of 334 nm using the urea S test combination (reagent kit No. 777510 from Boehringer Mannheim, Germany) . A supporting action by the claimed food supplement with respect to muscle build-up can proceed by determining the expression of the myogenic factors Myo D and myogenin by RT-PCR. For this, tissue samples are taken from the subject before and after the training phase from the muscle by biopsy, using a biopsy needle (for example 13 gauge biopsy needle from Peter Pflugbeil Medizinische Instrumente GmbH, Zorneding, Germany, or a 16 gauge biopsy needle from Manan Medical Products, Northbrook, IL, USA) . In this case approximately 3 mg of tissue are taken which are immediately cooled with liquid nitrogen and stored at approximately -70⁰C. PCR is carried out using a LightCycler® from Roche Applied Science, USA, using established primers, wherein the product identity can be performed via a melt-curve analysis and quantitative determination by means of gel electrophoresis and densitometric determination of the RT-PCR product. In this case the increase in myo D-mRNA indicates the proliferation of satellite cells in muscle tissue, while the increase in myogenin-mRNA indicates differentiation of the cells in muscle cells. The muscular adaptation can also be tested by analysing the myocin-heavy chain (MHC) isoforms and by determining the stress protein Hsp70 (inducible form) (analytical methods, for example, according to

Liu et al., Eur. J. Appl . Physiol. 91: 330-335, 2004, Liu et al. Int. J. Sports Med. 21: 351-355, 200, Liu et al., J. Appl. Physiol. 86: 101-104, 1999).

Claims

1. Food supplement which can also contain one or more amino acids, wherein the food supplement is otherwise essentially nitrogen-free and contains at least one alpha-keto acid selected from the group alpha-ketoisocaproate, alpha-ketoisovalerate and alpha-keto-beta-methylvalerate and/or a salt of these alpha-keto acids.

2. Food supplement according to Claim 1, characterized in that it does not contain any amino acids or any nitrogenous additives.

3. Food supplement according to Claim 1 or 2, characterized in that alkali metal salts or alkaline earth metal salts of the said alpha-keto acids are present.

4. Food supplement according to Claim 3, charactteerriizzeedd iinn tthhaatt NNaa⁺⁺,, KK⁺⁺,, CCaa²²⁺⁺ aanndd MM'g²⁺ salts of the said alpha-keto acids are present.

5. Food supplement according to one of Claims 1 to 4, characterized in that the food supplement contains a combination of alpha-ketoisocaproate and alpha- ketoisovalerate or alpha-keto-beta-methylvalerate or a combination of alpha-ketoisovalerate and alpha-keto-beta-methylvalerate or a combination of alpha-ketoisocaproate, alpha-ketoisovalerate and alpha-beta-methylvalerate and/or salts of said alpha-keto acids.

6. Food supplement according to Claim 5, charac- terized in that the alpha-keto acids KIV/KIC have a weight ratio between 50:1 and 1:50, the alpha- keto acids KMV/MIC have a weight ratio between 50:1 and 1:50 and/or the alpha-keto acids KMV/KIV have a weight ratio between 50:1 and 1:50.

7. Food supplement according to one of Claims 1 to 6, characterized in that the food supplement contains a daily amount of each of the alpha-keto acids that are present of between 0.5 g and 50 g.

8. Food supplement according to one of Claims 1 to 7, characterized in that the food supplement contains further additives selected from the group of the carbohydrates, fats and oils, vitamins, antioxidants, minerals and trace elements, preservatives, food dyes, sweeteners, flavour enhancers and aroma substances.

9. Food supplement according to one of Claim 1 to 8, characterized in that in addition, further keto acids are present.

10. Food supplement according to Claim 9, characterized in that, in addition, alpha-ketoglutaric acid or salts thereof are present.

11. Food supplement according to one of Claims 1 to 10, characterized in that, in addition, creatine is present.

12. Food containing a food supplement according to one of Claims 1 to 11.

13. Use of food supplements according to one of Claims 1 to 11 or of foods according to Claim 12 in combination with physical stress.

14. Use of food supplements according to one of Claims 1 to 11 or of foods according to Claim 12 for stimulation of insulin release and promotion of glucose uptake into the cells.

15. Use of food supplements according to one of Claims 1 to 11 or of foods according to Claim 12 in combination with low-calorie diet, slimming diets or fitness diets, or other targeted diets.

16. Use of food supplements according to one of Claims 1 to 11 for producing products which can be taken orally.

17. Use of food supplements according to one of Claims 1 to 11 for producing products which can be taken orally from the group of drinks, gels, creams, broths, energy bars, tablets or powders.

18. Use of food supplements according to one of Claims 1 to 11 or of foods according to Claim 12 for producing products which can be taken orally for supporting muscle build-up, the efficiency of musculature, for protecting musculature against cell and tissue damage, for increasing general wellbeing and/or for supporting muscle regeneration after physical stress with simultaneous relief of metabolism with respect to nitrogen detoxification.