WO2008122613A2

WO2008122613A2 - Food supplement containing alpha-keto acids

Info

Publication number: WO2008122613A2
Application number: PCT/EP2008/054103
Authority: WO
Inventors: Andreas Karau; Matthias Kottenhahn; Karlheinz Drauz; Norbert Windhab; Adolf GRÜNERT
Original assignee: Evonik Degussa Gmbh
Priority date: 2007-04-04
Filing date: 2008-04-04
Publication date: 2008-10-16
Also published as: RU2009140373A; DE102007016715A1; BRPI0810099A2; CN101646358A; WO2008122613A3; WO2008122473A2; CN101646358B; EP2129241A2; RU2492705C2; EP2175747A2; WO2008122473A3

Abstract

The invention relates to a food supplement that can contain at least one amino acid, is otherwise essentially nitrogen-free, and contains at least one alpha-keto acid selected from among the group comprising alpha-ketoisocaproate, alpha-ketoisovalerate, and alpha-keto-beta-methylvalerate, and/or a salt of said alpha-keto acids. The described food supplements help build muscles while relieving metabolism in terms of nitrogen detoxification by reducing the nitrogen supply and improving nitrogen retention in the body.

Description

Nutritional supplement containing alpha-keto acids

The present invention relates to dietary supplements containing alpha-keto analogs of branched-chain amino acids in support of the

Muscle building, increased muscle performance and improvement of general well-being while relieving the metabolism to nitrogen detoxification by reduced nitrogen intake compared to the intake of the corresponding amino acids and an improved nitrogen metabolism in the body.

Physical inactivity is a risk factor that can lead to decreased physical performance and thus reduced quality of life. To prevent or rebuild the decay of physical performance is a physical training is essential, with a

Series of cellular processes, e.g. Muscle damage and degradation, muscle regeneration, muscle hypertrophy and muscle fiber transformation, expire. Energy and protein metabolism play a crucial role in cellular processes. Consequently, the supply of amino acids plays a crucial role with regard to the metabolic processes occurring in the muscle tissue. In particular, the branched-chain amino acids VaNn, leucine and isoleucine are essential substrates and important regulators in protein biosynthesis and the main source of nitrogen for glutamine and alanine synthesis in skeletal muscle. Alanine is also an important precursor to gluconeogenesis and glutamine acts as a nitrogen transporter between the organs.

The average requirement for protein is about 660 mg / kg body weight, which can be significantly increased by physical training. The need for protein can usually be met by a balanced diet, which is not easy to achieve. Physical training leads, caused by increased protein degradation and humiliated Protein synthesis, to a changed need for nutrients, continues to result in a changed metabolic situation, which is due for example to the influence of physical training on the hormone system and ultimately also lack knowledge about a suitable diet with increasing physical stress, especially in relation to the age, so that fast one

Malnutrition can occur.

For these reasons, the use of nutritional supplements appears to be useful in individuals who are under physical strain. In this context, studies have already been conducted with different

Performed on the effects of creatinine supplementation on subjects' performance. Furthermore, it is known that muscle regeneration can be promoted by a high carbohydrate intake.

The use of branched chain amino acids (BCAA) as a nutritional supplement has also been extensively studied in the past, but with ambiguous results. While one study reported an increase in mental and / or physical performance by BCAA supplementation (Blomstrand, E. et al., Eur. J. Appl. Physiol.

Occup Physiol 63: 83-88, 1991), no effect on physical performance could be found in another study (van HG, Raaymakers, Saris, Wagenmakers, J. Physiol 486 (Pt3), 789-794, 1995).

Branched-chain amino acids alpha-keto acids also play an important role in amino acid metabolism, especially in skeletal muscle and in the liver. One-third of the muscle protein consists of the branched-chain amino acids, which can not be formed by the body, but must be taken with the food. In muscle, especially during physical exertion, proteins are constantly being built up and broken down

Degradation of the amino acids the corresponding alpha-keto acid is formed by transfer of the amino group to a carrier. The obtained keto acid can then be further enzymatically oxidized for energy. The carrier is transported to the liver where it releases toxic ammonia, which must be converted to urea and excreted via the kidney.

The use of alpha-keto acids, which are branched-chain

Derive amino acids, for pharmaceutical purposes has long been known. For example, alpha-ketoisocaproate (ketoleucine) can be used to reduce protein breakdown in muscle and to reduce urea formation resulting from protein degradation after muscle surgery (US Pat. No. 4,677,121). Also, the use of ketoleucine in malnutrition, muscular

Dystrophy or uremia or in other diseases that result in a secondary sequence protein breakdown in the muscle is described there. The administration of ketoleucine takes place intravenously. Furthermore, the administration of the alpha-keto acids of leucine, isoleucine and VaNn has been proposed in patients who have a protein-reduced diet, e.g. due to kidney failure (US 4,100,161). The role of the alpha-keto acids within protein metabolism with respect to various medical indications is also discussed in Walser, M. et al., Kidney International, Vol. 38 (1990), pp. 43-39. 595-604.

In the functional food area, on the other hand, especially the branched-chain amino acids for supporting muscle building, e.g. in athletes, used directly (Shimomura, Y. et al., American Society for Nutrition). The use of alpha-keto acids of leucine, isoleucine and VaNn to improve muscle performance or to aid recovery of muscle after exercise is described in US 6,100,287 wherein salts of the corresponding anionic keto acids with cationic amino acids as the counterion, e.g. Arginine or lysine. However, this also produces polyamines which are known to cause apoptosis (programmed cell death). Also the excretion of

Degradation of polyamines takes place via the kidney, which is thereby subjected to increased stress. Based on the state of the art, there is a need for dietary supplements that promote well-being after sports activities, strengthen the muscle structure or the performance of the muscle and permanently reduce the nitrogen load of the metabolism.

The object is achieved by the provision of dietary supplements which contain at least one alpha-keto acid selected from the group alpha- ketoisocaproate (KIC), alpha-ketoisovalerate (KIV) and alpha-keto-beta-methylvalerate (KMV) and / or a salt thereof alpha-keto acids, wherein the supplement may optionally additionally contain one or more amino acids, in particular leucine, isoleucine and / or VaNn, but otherwise is nitrogen-free.

Dietary supplements which, in addition to the abovementioned amino acids, contain no nitrogen-containing formulation additives, in particular no nitrogen-containing cations, such as, for example, cationic amino acids or dibasic amino acids from the group arginine, lysine, histidine or ornithine, or other nitrogen-containing additives, are to be considered as "substantially nitrogen-free" Extent. However, essentially nitrogen-free are

Nutritional supplements comprising nitrogenous additives which may be added to the dietary supplement in a very low amount of less than 5 mg (daily dose), e.g. nitrogenous vitamins. However, dietary supplements which have no nitrogen-containing constituents, in particular no cationic ones, are preferred

Amino acids. The term "nitrogen-free" refers to the supplement itself. Of course, functional foods containing the claimed dietary supplement may also contain nitrogen-containing ingredients contain, in particular, no supplements that increased an additional Include supplementation with nitrogenous compounds. In particular, there should be no artificial increase in the content of cationic amino acids in the food.

In addition to the alpha-keto acids KIC, KIV and KMV, their salts, if they contain nitrogen-free cations, can also be present in the dietary supplement according to the invention. Suitable salts are in particular the alkali or alkaline earth metal salts, in particular the Na ⁺ , K ⁺ , Ca ²⁺ and Mg ²⁺ salts, of the stated alpha-keto acids.

A preferred embodiment is nutritional supplements comprising 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 their salts. 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 set in the dietary supplement. Preferred weight ratios for KIC / KIV are 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 ratios are also for a KIC / KIV / KMV mixture advantageous. A particularly suitable combination of KIC / KIV / KMV represents a weight ratio of 2: 1: 1, wherein said proportions can be varied +/- 10%. The weight ratios mentioned are particularly suitable for rapid regenerative muscle growth. The daily dose of alpha-ketoacids taken up by the dietary supplement should not exceed the levels of 2000 mg / kg body weight for KIC, 1000 mg / kg body weight for KIV and 1500 mg / kg body weight for BMV, preferably doses of between 2.5 mg / kg and 500 mg / kg body weight for each of the three alpha keto acids. Particularly preferred dosages are in the range of 25 mg / kg to 250 mg / kg body weight for KIC, KIV and KMV, so that at

An adult (eg at a body weight between 50 and 100 kg) has an approximate preferred total amount per ingested alpha-keto acid of 1, 25 g to 25 g. Specifically, the following preferred dosages are given for the alpha-keto acids: for KIC between 50 mg / kg to 200 mg / kg, for KIV between 25 mg / kg to 150 mg / kg and for KMV between 25 mg / kg to 100 mg / kg. Usual daily dosages range from 0.5 g to 50 g per alpha-keto acid per day. In terms of the amount of cations contained should be in

Nutritional supplement preferably not more than 10g, more preferably between 0.5g and 2g, of Na ⁺ , K ⁺ ions, preferably not more than 5g, more preferably between 0.2 and 2.5g Ca ²⁺ ions and not more than 2g better between 0.2 and 1 g, containing the corresponding Mg ²⁺ ions.

Furthermore, the branched-chain amino acids leucine, isoleucine and VaNn can also be added to the dietary supplement described here. However, the amino acids mentioned are preferably used in small amounts. In view of the present invention, the amount added to the dietary supplement should not exceed a ratio of 1: 0.5, more preferably 1: 0.1 (alpha-keto acid: corresponding amino acid). However, particularly preferred dietary supplements do not contain leucine, isoleucine or VaNn.

Particularly preferred dietary supplements contain further keto acids derived from naturally occurring amino acids or salts thereof, particularly preferably alpha-ketoglutaric acid or its salts, in particular alpha-ketoglutarate (AKG). The use of the abovementioned alkali metal and alkaline earth metal salts of alpha-keto acids is also of particular interest. The above-mentioned dosage information also applies to the additionally contained alpha-keto acids or their salts. By adding AKG, ammonia detoxification can be further enhanced, forcing the transport of ammonia out of the muscle into the blood and liver. The administration of AKG does not seem to have a negative effect on the protein synthesis rate. In addition, AKG has an antioxidant effect. Therefore ask

Dietary supplements containing a combination of KIC, KIV and / or KMV and AKG include a particularly preferred embodiment of the present invention.

Furthermore, preferred dietary supplements also contain creatine as an ingredient.

In addition, the dietary supplement can be added to other nitrogen-free additives. Particularly noteworthy are energy-giving compounds, preferably from the group of carbohydrates, such. Glucose, but also additives that promote the regeneration process, such. Vitamins, especially Vitamin A, Vitamin Bi, B2, B & and B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, Pantothenic acid, Niacin, Folic Acid, Biotin, Choline and Inositol. Furthermore, antioxidants, e.g. beta-carotene, potassium citrate, citric acid, lactic acid, tocopherol, sodium or potassium ascorbates or ascorbic acid may be included in the dietary supplement. Minerals and

Trace elements from the group sodium, potassium, magnesium, calcium, iron, zinc, manganese, copper, selenium, chromium, phosphorus and iodine are also possible as additives. The additives mentioned are added in the usual amounts for the food industry.

Preferred dietary supplements may be e.g. contained (the quantities represent the preferred daily dose):

10 - 500 mg sodium, 10 - 500 mg potassium,

50-500 mg calcium,

10 - 300 mg magnesium,

1 - 20 mg zinc,

5-50 mg of iron, 0.1-1 mg of iodine,

5-100 μg selenium,

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

Other additives include saturated or unsaturated fatty acids, in particular C ₆ -C ₂₂ -fatty acids, as an additive. Fats and oils from the group sunflower, sesame, rape, palm, castor,

Coconut, safflower, soybean oil, lard and beef tallow. In addition, preservatives, food colors, sweeteners, flavor enhancers and / or flavorings in the dietary supplement may also be included in the usual amounts known to those skilled in the art. In particular, flavoring substances are considered as additives, since e.g. free alpha-keto acids acidic or their salts can taste unpleasant. If the additives used are used in larger quantities, nitrogen-free additives are used. However, particularly preferred dietary supplements do not contain nitrogenous additives.

The claimed dietary supplements may 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 their salts are preferably formulated with about 30 to 80 percent by volume in the dietary supplement, preferably using nitrogen-free additives, in particular carbohydrates, fats and oils, and optionally also of amino acids, such as leucine, isoleucine and VaNn, which may be present at about 70 to 20 volume percent in the dietary supplement

If the direct administration of the dietary supplement in the form of a powder or a tablet is desired, the addition of usual carriers of

Be an advantage. Suitable carriers are e.g. linear or (hyper) branched polyesters, polyethers, polyglycerols, polyglycolides, polylactides, polylactide-co-glycolides, polytartrates and polysaccharides, or polyethylene oxide-based dendrimers, polyether-dendrimers, coated PAMAM dendrimers, e.g. Polylactide-co-glycolide coating, or polyarylether.

The powder or tablet may further be provided with a coating, e.g. allow the release of the dietary supplement only in the intestinal tract. The following capsule shell materials are preferably used: carboxymethylcellulose, nitrocellulose, polyvinyl alcohol, shellac, carrageenan,

Alginates, gelatin, cellulose acetate, phthalates, ethylcellulose, polyglycerols, polyesters or Eudragit®.

If, on the other hand, a solution or suspension of the dietary supplement is administered, the addition of emulsifiers or colloids may be useful in order to be able to absorb all desired components as well as possible in an aqueous system. Suitable additives are e.g. Polyvinyl alcohols, glycerides of fatty acids, their acetic, citric, lactic or tartaric acid esters, polyoxyethylene stearates, carbohydrate esters, propylene glycol esters, glycerol esters or sorbitan esters of fatty acids or sodium lauryl sulfate.

Another object of the present invention are food (Functional Food) containing the claimed dietary supplement. These may be, for example, drinks or bars, which are particularly suitable for receiving the dietary supplement. The foods may be added during their production with the claimed dietary supplement or it may later be added a formulation of the dietary supplement to the food, for example in the form of a powder or a tablet. By way of example, the dissolution of effervescent tablets or a powder in mineral water can be cited here.

The use of the dietary supplements or foods described can in principle be possible throughout the day, but is especially recommended during or after a physical stress. The physical

Training causes muscular adjustment including muscle damage, muscle hypertrophy and muscle transformation. A training session is a combination of a training phase and a regeneration phase. A suboptimal embodiment of the training unit may e.g. lead to overtraining syndrome resulting in prolonged fatigue with reduced physical capacity. Such overtraining syndrome is often caused or exacerbated by malnutrition.

With the help of claimed nutritional supplements, the ammonia detoxification in the muscle, which inter alia by the protein and

Amino acid removal in the muscle becomes necessary, promoted. By transferring liberated amino groups to the keto acids, the corresponding amino acids are generated and in turn are available for muscle growth and the energy-consuming nitrogen detoxification and excretion via the liver and kidney is reduced. Accordingly, the throughput of nitrogenous degradation products, e.g. Urea, reduced in the blood or urine. At the same time the muscular capacity is increased or the muscle build-up is supported by the dietary supplements, since by transamination the administered keto acids in the muscle can be converted into the corresponding amino acids, which are used there for anabolic reactions

To be available. Finally, there is a faster recovery of muscle tissue, and physical performance and overall Well-being is improved. Both the support of protein synthesis in muscle and the ammonia detoxification is particularly supported by the mentioned alpha-keto acids, as these are selectively absorbed by the muscle tissue. Ammonia detoxification is particularly efficient when the claimed supplements additionally contain alpha-ketoglutarate

(AKG) included.

Consequently, the nitrogen balance of the body, which is under a physical stress, with the dietary supplements according to the invention improved in two ways: First, the loss of nitrogen by

On the other hand, the ammonia detoxification is accelerated, which leads to a faster muscle recovery or reduced fatigue of the muscles. Through a faster regeneration can also be increased training or increased

Achieve training intensity or frequency without provoking the above negative effects of overtraining.

In summary, substitution with the dietary supplements according to the invention prevents malnutrition

Satisfaction of the increased nutritional requirement promotes muscular regeneration and prevents overtraining, which leads to a strengthening of the musculature and increases a person's performance and well-being.

From the above aspects, the invention is directed

Dietary supplements especially for athletes, as well as recreational and top athletes, including strength athletes, as well as to wellness and fitness enthusiasts. The use of nutritional supplements by the elderly, who are known to often have limited nitrogen economy or limited nitrogen excretion capacity, is also particularly advantageous. Therefore, another object of the present invention is the use of the claimed dietary supplements for the production of orally absorbable products, such as functional food, in particular drinks, gels, creams, mash, power bars, etc., as well as tablets, powders, for example, in letters, Bags, tubes can be offered, and to

Support of muscle building, muscle performance, to protect the muscles against cell damage under stress, to increase the general well-being, the general physical performance or to support the muscle regeneration after physical stress while relieving the metabolism in terms of

Nitrogen detoxification contribute.

Accordingly, another object of the present invention is the use of the dietary supplements or foods described in combination with a targeted diet, in particular a calorie-reduced diet, slimming or fitness diets.

Furthermore, the claimed dietary supplements can also be used for the production of animal feed.

The higher performance of the muscles, which is achieved by taking the dietary supplements or the thus modified foods, can show on the one hand in an improved endurance ability, on the other hand also in an increased bounce and other performance. In order to test the increased performance, subjects can be put into a state of overtraining (intensive training with insufficient regeneration). The keto acid substitution can be e.g. by effervescent tablets, which are dissolved in water, the amount of alpha-keto acids should be adjusted to the body weight of the subject. The freshly mixed drinks are preferred during or shortly after each

Training session. The preferred formulation for such a test is the use of 0.2 g / kg / d calcium or sodium alpha-ketoglutarate or the corresponding free acid, or 0.2 g / kg / d calcium or sodium alpha-ketoisocaproate or the corresponding free acid or of 0.2 g / kg / d calcium or sodium alpha-ketoisovalerate or the corresponding free acid or 0.2 g / kg / d Calciumbzw. Sodium alpha-Ketomethylvalerat or the corresponding free acid or 0.2 g / kg / d of a mixture of these components, in particular from the calcium or sodium salts of KIC (eg 95 mg / kg / d), MIV (eg 60 mg / kg / d) and KMV (eg 45 mg / kg / d). For example, calcium and / or sodium glucose or free glucose can be used as placebo. The appearance and taste should be as identical as possible for all formulations.

In order to better evaluate the results, a nutritional protocol should also be used, using as standardized a diet as possible (for example Nutritional Protocol Program Prodi).

The determination of the general state of health and the stress recovery can be made by questioning the subjects. Further information about changes in overall performance can be found in the change in body weight and body fat percentage.

In order to evaluate the muscle function in general, the maximum oxygen uptake (Vθ2max) is measured under load of a subject. For this purpose, the load on a cycle ergometer is increased by means of a ramp protocol (for example beginning 0 watt, continuous increase of the power with 50)

Watt / min, until subjective exhaustion occurs). In addition, the heart rate can be determined synchronously by means of electrocardiography. Oxygen uptake is calculated from online minute ventilation and the difference in oxygen concentration between inspiratory and expiratory gases. To determine the endurance capacity, the Individual Anaerobic Aerobic Threshold (IAAS) is determined. This is done by measuring a lactate power curve with a treadmill test (training phase protocol: start 6 km / h, increase 2 km / h, which corresponds to an increase of about 25-50 watts / min, stage duration 3 min.) or with a bicycle ergometer (initial level

50 watts, increase 25 watts, step duration 3 min, until subjective exhaustion is reached). Blood samples are taken before and after a training step in a 30-second break (eg whole blood (hemolyzed) from hyperemic capillary blood (earlobe)) and the glucose and lactate concentration using a YSI 2300 STAT plus analyzer from YSI Life Sciences, Yellow Springs, USA and the maximum oxygen uptake (Vθ ₂ max value) was determined spirometrically using a K4 measuring instrument from Cosmed (Rome, Italy).

The measurement of the bounce improvement can by means of a

Bounce plate of the company Kistler, Winterthur, Switzerland be determined. To determine the explosive power by means of the bounce test, the device's own protocols "Squat-Jump" and "Count-Movement Jump" are used. The bounce is measured based on the contact time on the measuring plate and the jump height and calculated in comparison with the body weight.

For determining the maximum force, e.g. the leg muscles are stressed at a defined angle and the maximum force is measured.

Metabolic parameters, e.g. the concentrations of BCKA and AKG or urea or uric acid concentration in the blood can be determined by HPLC

Measurements are measured. To determine the damage of muscle cells, e.g. During physical exercise, uric acid levels in the blood or urine or creatine kinase activity in the blood are determined. The increase in creatine kinase activity correlates with the extent of muscle damage and may be due to an enzymatic reaction

Use of the kit no. 1087533 from Roche Diagnostics, Mannheim, Germany. The uric acid concentrations can be determined photometrically using the "Fluitest IIA®" kit from Biocon Diagnostics, Vöhl / Marienhagen, Germany.

The effects of the claimed dietary supplement on protein metabolism can be demonstrated by measurements of urea concentrations in the blood or urine. The urea concentrations can be determined 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 supportive effect of the claimed dietary supplement with regard to muscle growth can be made by determining the expression of the myogenic factors Myo D and myogenin by RT-PCR. To do this, the subjects are given tissue samples before and after the training phase from the muscle by biopsy, using a biopsy needle (e.g., a 13-gauge biopsy needle of the

Company Peter Pflugbeil Medical Instruments GmbH, Zorneding, Germany or a 16-gauge biopsy needle from Manan Medical Products, Northbrook, IL, USA). There are taken from about 3 mg of tissue that are immediately cooled with liquid nitrogen and stored at about -70 ⁰ C. The PCR is performed with a LightCycler® from Roche Applied Science,

USA performed using established primers, wherein the product identity via a melting curve analysis and the quantitative determination can be carried out by gel electrophoresis and densitometric detection of the RT-PCR product. The increase in Myo D mRNA indicates the proliferation of satellite cells in muscle tissue, while the increase in myogenin mRNA indicates the differentiation of cells in muscle cells. The muscular adaptation can also be checked by the analysis of the myosin heavy chain (MHC) isoforms or by the determination of the stress protein Hsp70 (inducible form) (analytical method, 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). Execution of the tests:

To test the effects of branched-chain alpha-keto acids (BCKAs) on muscle growth, increased muscle performance, nitrogen metabolism, and general well-being, we performed the following human study:

We recruited two volunteer groups with 12 subjects each. The subjects were randomized. The physical training was in all two

Groups equal:

4 weeks of training, 5 days a week: Training: 30 minutes of endurance training (running) per day 3x3 minutes of high-speed running per day

1 week of regeneration without physical training.

Throughout the study phase, the two groups of subjects took each day the amount of Mix 1 (branched chain

Keto acids in the composition described below) or Mix 2 (placebo) in which a subject always took the same mix over the entire duration.

We selected the following composition of the dietary supplement for the alpha-keto-acids (Mix1):

47.6% KIC

29.7% KIV 22.7% KMV

Each subject in the clinical study consumed 0.2 g / kg body weight / day of said mixture per day. In the study, KIC was used as the sodium salt, KIV and

KMV administered as calcium salt. To improve the taste, the keto acid mixtures can be stirred into commercially available sweet or salty products such as yoghurts, whey drinks, fruit compote and dessert soups.

All samples performed the planned study protocol properly. For the evaluation thus 24 subjects could be consulted. With regard to the anthropometric data, as well as the training history and the training state, the study groups did not differ statistically.

The training was performed according to the above form and controlled by the subjects themselves. The training was carefully documented by the test persons in the training protocol and regularly checked in random samples. Therefore, we assume that the completed training questionnaire is essentially plausible.

Effects of supplementation on physical performance and muscle function during training

We analyzed the effects of supplementation on physical

Performance, in particular the parameter "sustained exercise time" as an expression of exercise tolerance, on general physical performance as well as on muscle function. According to our study design, the training was to be done with 5 units per week, with each training session providing 30 minutes of endurance training

Basic Endurance Zone 2 (GA2), followed by 3x3-minute high-speed so-called "power-out." This training indicated that the total weekly training time was 195 minutes, 150 minutes for endurance, and 45 minutes for high-speed.

Effects of dietary supplementation on exercise tolerance Figure 1 shows the total exercise time per week. The total training time in the 1st week did not differ between the groups.

In the second week of training, the total exercise time in the BCKA group only fell slightly, but significantly and significantly in the placebo group (P <0.05). In the placebo group, the exercise time in the third week continued to decrease significantly (P <0.05) and decreased by 51% in the fourth week compared to the first week (P <0.01). The comparison of the training time between the groups shows that the total training time between the groups did not differ significantly in the 1st or 2nd week. In the 3rd and 4th week, however, the training time was clearly and statistically significantly reduced in the placebo group, but not in the BCKA-taking group. Through these results we could clearly and statistically prove that the exercise capacity is improved by the administration of BCKAs. By BCKAs the training time of the subjects was almost doubled. The intake of BCKAs thus leads to an improved exercise capacity during training over a longer period.

Effects of interventions on urea metabolism

In order to test the effect of dietary supplementation on urea metabolism, we measured urea concentrations in the body

Blood plasma and measured in urine (Figure 2).

The urea concentration in the plasma had a similar level before training in both groups. At the end of training, the urea concentration in both groups was higher than before, but to varying degrees depending on the dietary supplement. The increased urea concentrations after the training indicated an increased urea synthesis, which resulting from a reduced due to physical training protein degradation.

The plasma urea concentration behavior was significantly different between the groups. Figure 3 shows that the increase in

Plasma urea concentration at the end of exercise in the BCKA group was significantly higher than that in the placebo group. After one week of regeneration, no further increase was found in the BCKA group, while there was a marked increase in the placebo group.

In urea metabolism, we calculated urinary excretion over 8 hours of urine. At the end of physical training, urinary urea excretion was increased compared to pre-training excretion. However, this increase in exercise excretion was higher in the BCKA group at the end of training than in the placebo group (Figure 4).

These results are consistent with plasma urea concentration. This illustrates in particular the difference in urine excretion between the measurement times (Figure 5).

Since urea synthesis is based on the protein-derived ammonia, increased urea synthesis may be explained by the fact that the ammonia produced in the working musculature, resulting from protein degradation by catabolism, is more rapidly transported to the liver; or possibly KAS has favored urea synthesis in the liver.

Effects of nutritional supplementation on muscle function

We examined the influence of BCKAs on the muscle function of subjects by determining the maximum isometric force. We measured the maximum force legs with an isokinetic device. The muscles of the legs are stressed at a defined angle and the maximum strength of the leg muscles determined.

On average, the static maximum force of m. quadriceps femoloris of

252 NM (Newton meters) to 264 NM, corresponding to about 5% in all subjects. The changes among the groups were different. While there was an increase in static maximum force in the BCKA group of 20 NM, there was no change in the placebo group (Figure 6).

So we could show that the maximal isometric force increases when taking BCKAs.

Effects of supplementation on psychosomatic aspects during physical training

To record the psychosomatic effects of the intervention with physical training and nutritional supplements, we collected recovery exercise questionnaires once a week during the study period (see p.

Kellmann et al. (2001) Sports Psychologist 15: 151). A total of 76 questions from each questionnaire were answered by respondents on a Likert scale of (0: never to 6: always), which were then combined into parameters of stress and recovery as well as injury / fatigue.

The general stress varied within a group (Figure 7), the variance increased statistically significantly in the 3rd week placebo group, whereas it changed only slightly in the BCKA group (P> 0.05). This result suggests that the subjects in the placebo group generally felt more stressed. During the observation period, the parameter "emotional exhaustion" generally increased (Figure 8), this was particularly the casebo group and in the BCKA group, this parameter was only slightly and not significantly increased (P> 0.05). ,

The subjects in the placebo group felt generally stressed, especially the emotional exhaustion of physical training became apparent. These effects were successfully prevented by the administration of BCKA.

Claims

claims

1. Nutritional supplement, which may also contain one or more amino acids, wherein the dietary supplement is otherwise substantially nitrogen-free and at least one alpha-keto acid selected from the group alpha-ketoisocaproate, alpha-ketoisovalerate and alpha-keto-beta-methylvalearate and / or a Contains salt of these alpha-keto acids.

2. Dietary supplement according to claim 1, characterized in that it contains no amino acids and no nitrogen-containing additives.

3. dietary supplement according to claim 1 or 2, characterized in that alkali or alkaline earth metal salts of said alpha-keto acids are included.

4. dietary supplement according to claim 3, characterized in that Na ⁺ -, K ⁺ -, Ca ²⁺ - and Mg ²⁺ salts of said alpha-keto acids are included.

5. Dietary supplement according to one of claims 1 to 4, characterized in that the dietary supplement is 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-keto-beta-methylvalerate and / or salts of said alpha-keto acids.

6. dietary supplement according to claim 5, characterized in that the alpha-keto acids KIV / KIC a weight ratio between 50: 1 and 1: 50, the alpha keto acids KMV / KIC 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. Dietary supplement according to one of claims 1 to 6, characterized in that the dietary supplement contains a daily amount of each of the alpa-keto acids contained between 0.5 g and 50 g.

8. Dietary supplement according to one of claims 1 to 7, characterized in that the dietary supplement further additives selected from the group consisting of carbohydrates, fats and oils, vitamins, antioxidants, minerals and trace elements, preservatives, food colors, sweeteners, flavor enhancers and flavorings.

9. Dietary supplement according to one of claims 1 to 8, characterized in that additional keto acids are also included.

10. dietary supplement according to claim 9, characterized in that in addition alpha-ketoglutaric acid or its salts are included.

11. Dietary supplement according to one of claims 1 to 10, characterized in that in addition creatine is included.

12. Foodstuffs containing a dietary supplement according to one of

Claims 1 to 11.

13. Use of dietary supplements according to any one of claims 1 to 11 or of foods according to claim 12 in combination with exercise.

14. Use of dietary supplements according to any one of claims 1 to 11 or of foodstuffs according to claim 12 for the stimulation of insulin release and promotions of glucose uptake into the cells.

15. Use of dietary supplements according to one of the claims

1 to 11 or foodstuffs according to claim 12 in combination with calories reduced diet, slimming or fitness diets or other targeted diets.

16. Use of dietary supplements according to one of the claims

1 to 11 for the production of orally ingestible products.

17. Use of dietary supplements according to one of claims 1 to 11 for the manufacture of orally absorbable products from the group of drinks, gels, creams, mash, power bars, tablets or powders.

18. Use of dietary supplements according to one of claims 1 to 11 or of foodstuffs according to claim 12 for the production of orally ingestible products for supporting muscle building, the performance of the musculature, for the protection of the

Musculature against cell and tissue damage, to increase general well-being and / or to support muscle recovery after physical stress while relieving the metabolism in terms of nitrogen detoxification.