WO2019166418A1

WO2019166418A1 - Nutraceutical or pharmaceutical composition

Info

Publication number: WO2019166418A1
Application number: PCT/EP2019/054701
Authority: WO
Inventors: Steffen Oesser; Stephan Hausmanns; Hans-Ulrich Frech
Original assignee: Gelita Ag
Priority date: 2018-02-28
Filing date: 2019-02-26
Publication date: 2019-09-06
Also published as: DE102018104590A1

Abstract

The present invention relates to a nutraceutical or pharmaceutical composition for use in improving endurance performance, and to a nutraceutical or pharmaceutical composition for use in stimulating lipocatabolism, and in particular for reducing body weight. The composition comprises one or more carbohydrates and collagen hydrolysate.

Description

Nutraceutical or pharmaceutical composition

The present invention relates to a nutraceutical or pharmaceutical composition for use in improving endurance performance.

The invention further relates to a nutraceutical or pharmaceutical composition for use in stimulating fat loss, in particular for reducing body weight.

It is known that in order to achieve high endurance performance, e.g. In sports activities, a high-carbohydrate diet is beneficial, and especially preferable to a high-fat diet. The essential muscle energy reserve, namely the glycogen content in the muscle cells, can be replenished to a normal level within 24 hours with a high carbohydrate intake of 7 to 10 g per kg of body mass per day (see eg A. Jeukendrup, Schweizerische Zeitschrift für Sports Medicine and Sports Traumatology 2003 (51) 17-23). According to this article, optimal levels of glycogen delay the onset of fatigue, extend the duration of an equilibrium load by approximately 20%, and improve performance by 2 to 3% at a defined distance or work to be handled.

The object of the present invention is to propose a nutraceutical or pharmaceutical composition with which the endurance capacity can be additionally increased, i. by an effect beyond the replenishment of glycogen reserves.

This object is achieved according to a first aspect of the invention by a composition for use in improving endurance performance, wherein the composition comprises one or more carbohydrates and collagen hydrolyzate.

According to a second aspect of the invention, there is provided a composition for use in stimulating fat loss, in particular for reducing body weight, which composition comprises one or more carbohydrates and collagen hydrolyzate.

The inventors have surprisingly found that collagen hydrolyzate results in an increase in mitochondrial activity in human and animal cells, i. an increase in the mitochondrial count per cell and / or an enlargement of the individual mitochondria. From this finding, it is found that collagen hydrolyzate can be advantageously combined with carbohydrates to produce nutraceutical or pharmaceutical compositions for specifically enhancing endurance performance and stimulating fat breakdown by increasing mitochondrial activity in the muscle cells.

Collagen hydrolyzate, which is produced in particular by the enzymatic hydrolysis of collagen-containing animal starting materials, consists of a mixture of peptides whose molecular weights are distributed over a certain size range depending on the starting material and production conditions. The use of collagen hydrolyzate as a dietary supplement has been known for a long time, in particular for the prevention and / or treatment of disorders associated with the bone, joints or connective tissue, in particular a stimulating effect of the collagen peptides on the synthesis the body's own extracellular matrix could be shown in these tissue types (see, eg, Bel Io et al., Curr. Med. Res. Opin. 2006 (22) 2221-2232). However, an immediate effect of collagen hydrolyzate on mitochondrial activity and / or endurance performance has not been previously described. The endurance capacity of the human or animal body correlates with the capacity of the aerobic metabolism to supply the muscles with the required energy in the form of ATP (adenosine triphosphate) over a longer period of time. Critical to the aerobic capacity is the oxygen uptake, which in turn is determined by three factors: oxygen supply via the lungs, oxygen transport via the cardiovascular system and oxygen utilization in the muscle cells. While the maximum oxygen supply is essentially predetermined by the individual anatomical conditions (total surface area of the alveoli), the oxygen transport and the oxygen utilization can be increased by training and other measures, whereby the final step is usually the decisive, limiting factor , Endurance capacity therefore depends essentially on the number of mitochondria (per muscle cell or in the total muscle) in which the oxygen-consuming and ATP-generating reactions of the respiratory chain take place.

Generally, an increase in mitochondrial activity means that the body's basal metabolic rate increases and a higher amount of nutrients are metabolized per unit of time for energy. These nutrients are provided at least partially in the form of the carbohydrates contained in the composition according to the invention. The ingredients of the composition thus complement each other optimally to improve endurance performance in accordance with the first aspect of the invention.

A higher catabolic metabolic activity, however, also leads to an increased depletion of the body's own reserves, ie to a stimulation of fat loss. The degradation of the long-chain carboxylic acids released from the adipose tissue takes place essentially throughout the body and in particular in the liver, so that for the second aspect of the invention, in contrast to the improvement in endurance performance, not only the mitochondria in the muscle cells are relevant. More particularly, the invention relates to nutraceutical compositions intended for non-therapeutic use, ie, administration of the collagen hydrolyzate to persons or animals that are not in need of therapy in the medical sense in terms of endurance performance or body weight. Rather, the use is on the one hand with the aim of a generally desirable increase in Enduranceperformance. This can contribute to an improvement in the quality of life and is particularly relevant for athletes. On the other hand, it may be desirable to reduce body weight by stimulating fat loss, especially from a cosmetic point of view, ie to improve body proportions. An application of the composition of the invention in animals may be useful, for example, for horses, dogs or camels, especially in animal racing.

In addition, however, the invention also includes pharmaceutical compositions intended for therapeutic use, i. for the prevention and / or treatment of a pathological condition characterized by a reduction in mitochondrial activity. In particular, the pathological condition can be characterized by a reduced endurance capacity and / or by an increased body weight.

In the context of this therapeutic use, the pathological condition is preferably selected from adiposity, cardiovascular diseases, cardiac arrhythmias, cardiac insufficiency, hypotension, hypertension, metabolic disorders, diabetes mellitus, metabolic syndrome, sideroblastic anemia, functional disorders of the kidney and the liver, Neuropathy, ataxia, epileptic seizures, dementia, Alzheimer's disease, autism, depression, chronic fatigue syndrome, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke-like symptoms, migraine, myoclonic, paralysis, neuralgia, hyperpathia, hyperesthesia, dysphagia disorders, vomiting, constipation, diarrhea, degeneration of optic nerve fibers and the retina, impaired eye movement, ptosis, night blindness, obesity, deafness and inner ear disorders. In these indications can By increasing the mitochondrial or mitochondrial activity a therapeutic effect can be achieved.

It has also been found within the scope of the invention that collagen hydrolyzate leads to increased expression of the enzyme AMP-activated protein kinase (AMPK). This regulatory enzyme also affects the energy metabolism of the cell, so that an increase in the AMPK amount has a positive effect on endurance performance and fat loss. There may be a direct correlation between collagen hydrolyzate-induced increase in mitochondrial activity and increase in AMPK expression.

Regardless of the type of therapeutic or non-therapeutic use, the composition of the invention is preferably for enteral administration, especially for oral administration.

In the case of a nutraceutical composition, it is preferably a food or a dietary supplement, depending on how high the carbohydrate content is and what intake level of the composition is provided. For nutritional supplements, it is particularly advantageous to administer in the form of a solution, e.g. in the form of finished ampoules, a powder or a gel, or in the form of tablets. Due to its good solubility, collagen hydrolyzate can also be added to various drinks without causing turbidity. The use of taste-neutral collagen hydrolyzate can increase user acceptance.

The composition according to the invention may contain the collagen hydrolyzate and the carbohydrate (s) in very different weight ratios. Conveniently, the weight ratio of collagen hydrolyzate to carbohydrate (s) ranges from 1:20 to 10: 1, preferably from 1:10 to 5: 1, more preferably from 1: 5 to 3: 1, even more preferably from 1: 3 up to 2: 1, in particular from 1: 2 to 2: 1.5. In this case, compositions with a high proportion of carbohydrates are intended in particular to be administered in larger quantities, so that a considerable part of the energy requirement is covered thereby, whereas compositions with a higher proportion of collagen hydrolyzate are more suitable than typical dietary supplements, by the other energy supply is only increased.

The intended administration of the composition according to the invention may thus advantageously be from 0.1 to 5 g per kg body weight per day, preferably from 0.5 to 1.5 g per kg body mass. At the upper end of this range, a carbohydrate-rich diet can thus be realized, in which the composition according to the invention makes up a substantial portion of the total carbohydrates supplied. This variant can e.g. be sensible for competitive athletes as part of a special diet.

The mixing ratio in the composition and the amount to be administered are desirably coordinated so that the composition is administered with an amount of collagen hydrolyzate of from 1 to 40 g per day, preferably from 2.5 to 25 g per day preferably from 5 to 20 g per day, and especially from 10 to 15 g per day.

The carbohydrate (s) in the composition according to the invention may be selected from monosaccharides, disaccharides and polysaccharides, preferably from glucose, fructose, sucrose, trehalose, isomaltulose, lactose, starch and mixtures thereof, more preferably from the glycemic carbohydrates glucose, fructose and sucrose. Particularly favorable is a glucose / fructose mixture in the ratio of about 2: 1.

According to a preferred embodiment of the invention, the composition contains no further proteins, protein hydrolysates or amino acids in addition to the collagen hydrolyzate. Various proteins are used in known food supplements for muscle building and muscle maintenance, in particular especially in athletes, with the aim of replacing carbohydrates and fats as energy suppliers to a large extent by proteins. However, the composition according to the invention is not based on the function of collagen hydrolyzate as an energy source, but on its specific effect on mitochondrial activity as described above. This supplements the effect of the carbohydrate (s) as an energy source to replenish the muscular glycogen stores.

Accordingly, in another embodiment of the invention, in addition to the collagen hydrolyzate and the carbohydrate (s), the composition contains no other physiologically active ingredients.

Alternatively, however, the invention also encompasses the case in which the collagen hydrolyzate and the carbohydrate or carbohydrates are administered as constituents of a foodstuff with various further constituents. In particular, the nutraceutical compositions according to the invention may be chocolate bars, protein bars or cereal bars, or rubber or pastry products (so-called functional foods), or drinks (eg isonic drinks or energy drinks), milk products (eg milkshakes , Jog-hurt) or milk substitutes (eg soymilk, almond milk and coconut milk).

In a further embodiment of the invention, the collagen hydrolyzate and the carbohydrate or carbohydrates are combined with water and electrolytes, in particular in the form of an isotonic solution. Such a composition is particularly advantageous as a drink for athletes to simultaneously allow effective rehydration.

If the composition according to the invention comprises, in addition to the collagen hydrolyzate and the carbohydrate or carbohydrates, further physiologically active constituents, these are preferably one or more components which have a positive effect on the general health and in particular on endurance performance. Such components are preferably selected from vitamin C, vitamins of the B, D, E and K series, conjugated linoleic acids, caffeine and its derivatives, guarana extract, green tea extract, beetroot extract, lemon verbena extract, orange peel, epigallocatechin gallate, epicatechins from cocoa, creatine including its derivatives, L-carnitine, L-citrulline, L-arginine, nitric oxide, nitrates, amino acids including branched chain amino acids, omega-3 and omega-6 fatty acids, lipoic acids including α-lipoic acid, N-acetylcysteine, NADH, D-ribose, magnesium aspartate, antioxidants such as anthocyanins, Polyphenols, carotenoids, flavonoids, resveratol, quercetin, glutathione and superoxide dismutase; Xanthans including mangiferin; Adaptogens including those of Rhodiola, Eleutherococcus and Schisandra; Minerals such as iron, magnesium, calcium, zinc, selenium and phosphorus; and other proteins, hydrolysates or peptides such as soy, wheat or whey protein.

In a further advantageous embodiment of the invention, the composition further comprises ubiquinone-10 and / or ubiquinol, ie the oxidized or reduced form of the coenzyme Qi ₀ , with ubiquinol being preferred because of its better bioavailability. Even with a daily intake of 50 to 100 mg ubiquinol, a positive effect on the physical performance was observed, whereby a promotion of mitochondrial activity is assumed by the antioxidant effect of ubiquinol. Thus, the effect of the collagen hydrolyzate in the above-mentioned indications associated with mitochondrial dysfunction can be promoted in this way. Alternatively or additionally, a combination with pyrroloquinoline quinone (PQQ) is possible, which has recently been discovered as an important redox cofactor.

In a particular embodiment of the invention, the administration of the composition is provided in combination with endurance training or altitude training. Endurance training can increase the aerobic capacity of the metabolism. It is also known that a physical training under relative hypoxia (hypoxia training) has a strong effect on the endurance performance, so that when given at the same time of collagen hydrolyzate is to assume in each case of a synergistic effect. This is of particular interest to athletes.

On the other hand, within the scope of the invention, it is equally possible and also expedient if the administration of the composition is provided in the absence of endurance training, altitude training or muscle training.

In particular, it has been shown in animal experiments (see below) that the effects according to the invention on mitochondrial activity etc. are already shown in combination with normal physical activity.

The molecular weight of the collagen hydrolyzate contained in the composition can vary over a wide range according to the invention, with an upper limit being that, unlike denatured collagen or gelatin, collagen hydrolyzate has a sufficiently high degree of hydrolysis to be water-soluble at room temperature and not to gel. The soluble peptides of the collagen hydrolyzate can be well absorbed in the body. Typically, the collagen hydrolyzate has an average molecular weight of from 200 to 25,000 Da, preferably from 1,000 to 15,000 Da, more preferably from 1,200 to 12,000 Da, even more preferably from 1,500 to 8,000 Da, and most preferably from 1,800 to 5,500 Da.

The collagen hydrolyzate is conveniently prepared by enzymatic hydrolysis of a collagen-containing starting material. In particular, endopeptidases and / or exopeptidases of microbial or plant origin are used for this hydrolysis.

The collagen-containing starting material is usually selected from the skin or bones of vertebrates, preferably from mammals or birds, and in particular from the skin of cattle or pigs (cattle split or pork rind). The collagen of marsupials such as kangaroos is also suitable as starting material. Alternatively, the collagen-containing starting material may be selected from the skin, bones and / or scales of fish, in particular cold or hot water fish. The collagen hydrolyzate can either be prepared from these starting materials in a one-step process or gelatin via the intermediate, in which case both Type A and Type B gelatin can be used.

Alternatively, the collagen hydrolyzate for the composition according to the invention can be produced by recombinant gene expression. Through the use of natural collagen sequences, in particular from cattle or pigs, and their expression in genetically modified cells (eg yeasts, bacteria or plant cells, especially tobacco), products can be prepared which are substantially identical to the hydrolysis products of the corresponding collagen-containing raw materials , It is possible to obtain a narrower or exactly predetermined molecular weight distribution. Alternatively, the sequences can be altered by mutations to affect certain properties of the product.

An object of the present invention is also a method for improving the endurance performance and / or for stimulating the fat reduction, and in particular for reducing the body weight, by means of increasing the mitochondrial activity. The method comprises administering to a human or an animal a composition comprising one or more carbohydrates and collagen hydrolyzate. The method can be both a therapeutic and a non-therapeutic method.

Particular advantages and preferred embodiments of the method according to the invention have already been described in connection with the composition according to the invention.

The invention will be explained in more detail by means of experimental results in vitro and in vivo, which are described in the context of the following examples. Show it :

Figure 1: fluorescence micrographs of SH-SY5Y cells, which were incubated in the presence of collagen hydrolyzate; and

Figure 2: Diagram for Lactatdiagnostik in a clinical study for

Improvement of endurance performance.

Examples

J _ Increase of mitochondrial count by collagen hydrolyzate

The effectiveness of collagen hydrolyzate to increase the mitochondrial count could be shown in vitro using human nerve cells (neuroblastoma cell line SH-SY5Y).

The SH-SY5Y cells were incubated in culture media with different concentrations of collagen hydrolyzate of 0.05% by weight, 0.2% by weight and 2.5% by weight. For this purpose, a collagen hydrolyzate of pork swine gelatin having an average molecular weight in the region of 3,000 Da was used, which was prepared by enzymatic hydrolysis (referred to below as collagen hydrolyzate A). The molecular weight distribution of the peptides, which was determined by means of gel permeation chromatography, is given in the following Table 1:

Table 1: MG distribution collagen hydrolyzate A

To allow a direct evaluation of the mitochondrial count, the mitochondrial protein component TOM20 was fluorescently labeled. TOM20 is a subunit of a receptor complex in the outer membrane of the mitochondria, which has the function of transferring cytosolic precursor proteins (prepeptides) into the mitochondria. There, the proteins, which are enzymes of the respiratory chain or of the citric acid cycle, are activated by cleavage of the presequence.

The amount of fluorescently labeled TOM20 visible in the fluorescence microscope is thus a measure of the mitochondrial number in the cell. The cells incubated with 0.05% by weight, 0.2% by weight and 2.5% by weight of collagen hydrolyzate are shown in FIGS. 1A, 1B and 1C respectively, with an increase of the light (in the original green) with increasing concentration. Fluorescence in the areas around the nucleus (blue in the original) is clearly visible. The collagen hydrolyzate thus causes an increase in the mitochondrial count in the SH-SY5Y cells, and thus an increase in the total mitochondrial activity.

2. _ Activation of the enzyme AM PK by collagen hydrolyzate in vitro

AMP-activated protein kinase (AMPK) is involved in energy delivery in both adipose tissue and muscle. Since AMP is formed when consuming ATP, it can be considered as an indicator of lack of energy. The expression of AMPK thus serves to activate energy reserves from the fat depot and in the context of glycolysis.

To determine the effect of collagen hydrolyzate on AMPK expression, human myocytes were incubated in a medium containing 0.5 mg / ml collagen hydrolyzate over a period of 24 hours. After removal of the medium, the RNA was extracted from the cell lawn and the amount of AMPK RNA was determined by PCR using specific primers. Compared to a control without collagen hydrolyzate, AMPK RNA was significantly increased (by a factor of over 600). This finding also results in a stimulating influence of collagen hydrolyzate on the energy metabolism of the cell.

3, _ activation of the enzyme AMPK by collagen hydrolyzate in vivo

The positive effect of collagen hydrolyzate on AMPK expression could also be confirmed in an animal study in vivo.

For this purpose, mice were fed daily with a quantity of collagen hydrolyzate corresponding to a human equivalence dose of 10 g over a period of 3 months. After the mice had been euthanized, the quadriceps were completely excised, snap frozen and ground. From the muscle tissue, the soluble proteins were extracted and the amount of AMPK determined by means of an immunoassay (ELISA).

Compared to a control group that had not received any collagen hydrolyzate, the amount of AMPK was increased by a factor between 1.5 and 2.

4. Influence of collagen hydrolyzate on NADH delivery in vitro

The formation of the high-energy form NADH + H ⁺ of nicotinamide adenine dinucleotide from the low-energy form NAD ⁺ is equivalent to the provision of energy in the form of ATP. It is thus an indirect measure of mitochondrial activity in muscle cells.

For this experiment, human myocytes were incubated in a medium containing 0.5 mg / ml collagen hydrolyzate for a period of 6 days. After removal of the medium, the triglycerides were extracted, and with the aid of the enzymes glycerol kinase and glycerol-3-phosphate dehydrogenase, the energy contained in the triglycerides or glycerol was determined in the form of the released NADH + H ⁺ . Compared to a control without collagen hydrolyzate the amount of NADH was increased by a factor of about 2.

5, increase of rat mitochondrial density in vivo

In a preclinical study, a marked increase in mitochondrial density (i.e., an increase in the number and / or size of mitochondria) in skeletal muscle of rats could be demonstrated by the administration of different collagen hydrolysates.

The study was performed on ^CD® IGS male rats (Charles River Laboratories, Sulzfeld), who were 64 days old at the beginning of the study period and had a body weight of between 300 and 400 g. The test group and the control group each comprised six animals.

At the beginning of the study (t = 0), a fine needle biopsy was taken from the four-headed thigh muscle (quadriceps femoris) in each rat. The animals of the test groups were then given a daily dose of 200 mg of the respective collagen hydrolyzate (see below) per kg of the current body weight (corresponding to a daily dose of 15 g in a person weighing 75 kg) over a period of four weeks. The collagen hydrolyzate was dissolved at a concentration of 20 mg / ml in an appropriate amount of tap water and administered via gavage. The animals of the control group each received the identical amount of tap water without collagen hydrolyzate. In addition, all rats received daily 25 g of feed with a carbohydrate content of 41.2% by weight, namely 36.5% by weight of high-glycemic starch and 4.7% by weight of sucrose.

In addition to the collagen hydrolyzate A described above, a collagen hydrolyzate B from bovine cleavage gelatin having an average molecular weight of 2,000 Da and a collagen hydrolyzate were used in further test groups C from bovine cleavage gelatin with an average molecular weight of 3,500 Da, each produced by enzymatic hydrolysis. Furthermore, a collagen hydrolyzate D from bovine cleavage gelatin having an average molecular weight of 12,000 Da and a collagen hydrolyzate E from fish collagen having an average molecular weight of 1,300 Da was also used, which was also enzymatically hydrolyzed.

The molecular weight distributions of all five hydrolysates are given in the following Table 2:

Table 2: MG distribution of collagen hydrolysates in% by weight

After the end of the study period (t = 4 W), all rats were euthanized and again a fine needle biopsy of the quadriceps femoris was taken. During the four weeks there was an average weight gain Rats of about 30%, with no significant difference between the test group and the control groups.

To determine the mitochondrial density, the biopsies taken before and after the study period were prepared for transmission electron microscopy as described in the literature (see A. Lasts and P. Lewis: Biological Specimen Preparation for Transmision Electron Microscopy, Princeton Legacy Library , 2014). In each case, individual surface sections of the muscle biopsies were 15.17 x 15.17 pm

(230 pm ² ) digitized and semi-quantitatively evaluated. Ten samples from each biopsy were used to determine the average area of the mitochondria in relation to the total area. The mitochondria could be localized by the clearly visible, characteristic structure of the inner membrane with its cristae.

The following Table 3 shows the development of the mitochondrial density (pm ² mitochondria per 230 pm ² total area) in the animals of the test group with the collagen hydrolyzate A:

Table 3: Development over time Test Group A

As a result, the four-week administration of collagen hydrolyzate A resulted in a very significant increase in mitochondrial density by an average of 78.5%, which is also statistically significant (p = 0.001). A similar finding is also shown by the comparison of the mitochondrial density between the test groups with the collagen hydrolysates A to E and the control group in each case after four weeks according to the following Table 4:

Table 4: Comparison of test groups A, B, C, D and E with control group

The mitochondrial density was at least 40% higher in the test groups (test group D) than in the control group, which was also statistically significant (p = 0.001); in test groups C it was even lower about 90% higher. The value "Cohen's d" as a measure of the effect size is more than 2.5 for all test groups, which is a very strong effect.

In summary, this study clearly demonstrates that the administration of collagen hydrolyzate leads to a significant increase in mitochondrial density in muscle cells, and thus to a corresponding increase in mitochondrial activity. This effect can be confirmed with collagen hydrolysates of various origins (pig or cattle) and molecular weight distribution.

6. Clinical Study to Improve Endurance Ability

In a randomized, double-blind study, the impact of orally administered collagen hydrolyzate on endurance performance, lactate threshold and anaerobic threshold was investigated.

The study was conducted with 50 men between the ages of 18 and 40 years (mean age 28 years) who were randomly assigned to a verum group and a placebo group of 25 individuals each. All participants completed a 45-minute aerobic endurance training in the form of a running workout during the study period of 12 weeks for 3 days per week. The intensity of the training was chosen so that at most 55 to 60% of the maximum oxygen uptake (V0 ₂ max) were reached.

The participants in the verum group received 15 g of collagen hydrolyzate daily throughout the study period, namely the collagen hydrolyzate C described in Example 5 with an average molecular weight of 3,500 Da (see Table 2), whereas the placebo group participants instead received silica as placebo.

In addition, all participants received a normal diet during the study period with a share of approximately 46% by weight of carbohydrates. To quantify the improvement in endurance performance, participants completed a 60-minute run before and after each study period. For the respective group, the 60 minutes course in the placebo group increased by 1.065 km (from 10.735 ± 1.448 to 11.800 ± 1.270 km, p = 0.001), and by 1.727 km in the verum group (from 10.963 ± 1.254 to 12.690 ± 1.223 km, p = 0.001). Thus, by administering collagen hydrolyzate, the distance that could be taken after the 12-week endurance exercise could be increased by more than 60%, which is a significant and notable increase in endurance performance.

Furthermore, before and after the study period lactate diagnostics were carried out, whereby the lactate concentration in the blood was measured on a treadmill as a function of the running speed. The results are shown in a diagram in FIG. There, the measured values for the placebo group are represented by triangles and the measured values for the verum group by squares. The measured values before the study period are interpolated with solid lines and the measured values after the study period with dashed lines.

The evaluation of the curves in FIG. 2 gives the following results:

There was no significant shift in the lactate threshold in the placebo group (9.5 ± 1.5 km / h before the study and 9.4 ± 1.0 km / h after the study, p = 0.629). In the verum group, the lactate threshold shifted on average by 0.7 km / h (from 9.2 ± 1.2 km / h to 9.9 ± 0.8 km / h, p = 0.099).

The individual anaerobic threshold shifted on average 0.6 km / h in the placebo group (from 12.2 ± 1.5 km / h before the study to 12.8 ± 0.9 km / h after the study, p = 0.024), while this shift in the verum group averaging 1.7 km / h (from 12.0 ± 1.2 km / h to 13.7 ± 0.9 km / h, p = 0.001).

The greater increase in lactic acid levels and, in particular, the anaerobic threshold in the verum group are also evidence of the immediate effect of collagen hydrolyzate on improving endurance performance.

Claims

Patent claims

A nutraceutical or pharmaceutical composition for use in improving endurance performance;

characterized in that the composition comprises one or more carbohydrates and collagen hydrolyzate.

2. Nutraceutical or pharmaceutical composition for use in stimulating fat loss, in particular for reducing body weight,

3. Nutraceutical composition according to claim 1 or 2, wherein the use is a non-therapeutic use, in particular a cosmetic use.

4. The pharmaceutical composition according to 1 or 2, wherein the use is a therapeutic use for the prevention and / or treatment of a pathological condition characterized by a decrease in mitochondrial activity, in particular by a decreased endurance performance and / or by a increased body weight.

5. The composition of claim 4, wherein the pathological condition is selected from obesity, cardiovascular diseases, cardiac arrhythmias, myocardial insufficiency, hypotension, hypertension, metabolic disorders, diabetes mellitus, metabolic syndrome, sideroblastic anemia, kidney dysfunction and liver, neuropathy, ataxia, epileptic seizures, dementia, Alzheimer's disease, autism, depression, chronic fatigue syndrome, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke-like symptoms, migraine, myoclonus, paralysis, neuralgia, hyper- pathia, hyperaesthesia, dysphagia, vomiting, constipation, diarrhea, degeneration of optic nerve fibers and the retina, impaired eye movement, ptosis, night blindness, deafness, deafness and inner ear disorders.

A composition according to any one of the preceding claims, wherein the composition is for enteral administration, in particular for oral administration.

7. A composition according to claim 6, wherein the nutraceutical composition is a dietary supplement, especially in the form of a solution, a powder or a gel, or in the form of tablets.

8. A composition according to claim 6, wherein the nutraceutical composition is a foodstuff which is preferably selected from chocolate bars, protein bars, cereal bars, gum sugar, biscuits, drinks, dairy products and milk substitutes.

9. A composition according to any one of the preceding claims wherein the composition contains the collagen hydrolyzate and the carbohydrate (s) in a weight ratio of from 1:20 to 10: 1, preferably from 1:10 to 5: 1, more preferably from 1: 5 to 3: 1, more preferably from 1: 3 to 2: 1, in particular from 1: 2 to 2: 1.5.

A composition according to any one of the preceding claims wherein the composition is for administration in an amount of from 0.1 to 5 grams per kilogram of body mass per day, preferably from 0.5 to 1.5 grams per kilogram of body mass per day.

Composition according to any one of the preceding claims, in which the carbohydrate (s) are selected from monosaccharides, Disaccharides and polysaccharides, preferably from glucose, fructose, sucrose, trahalose, isomaltulose, lactose, starch and mixtures thereof, more preferably from the glycemic carbohydrates

Glucose, fructose, sucrose.

12. The composition according to any one of the preceding claims, wherein the composition in addition to the collagen hydrolyzate contains no further proteins, protein hydrolysates or amino acids.

13. The composition according to any one of the preceding claims, wherein the composition in addition to the collagen hydrolyzate and the carbohydrate or contains no other physiologically active ingredients.

14. A composition according to any one of claims 1 to 11, further comprising one or more components selected from vitamin C, B, D, E and K series vitamins, conjugated linolenic acids, caffeine and its derivatives, Guarana extract, green tea extract, beetroot extract, lemon verbena extract, orange peel, epigallocatechingallate, epicatechins from cocoa, creatine and its derivatives, L-carnitine, L-citrulline, L-arginine, nitric oxide, nitrates, Amino acids including branched chain amino acids, omega-3 and omega-6 fatty acids, lipoic acids including α-lipoic acid, N-acetylcysteine, NADH, D-ribose, magnesium aspartate, antioxidants such as anthocyanins, polyphenols, carotenoids, flavonoids, resveratol, quercetin, Glutathione and superoxide dismutase; Xanthones including mangiferin; Adaptogens including those of Rhodiola, Eleutherococcus and Schisandra; Minerals such as iron, magnesium, calcium, zinc, selenium and phosphorus; and other proteins, hydrolysates or peptides such as soy, wheat or whey protein.

15. The composition according to any one of claims 1 to 12 or 14, further comprising ubiquinone-10 and / or ubiquinol, which preferably in a Amount of 50 to 100 mg per day to administer, and / or with pyrroloquinoline quinone (PQQ).

16. A composition according to any one of the preceding claims, wherein the administration of the composition is provided in combination with endurance training or altitude training.

17. A composition according to any one of claims 1 to 15, wherein the administration of the composition is provided in the absence of endurance training, altitude training or muscle training, but especially in combination with normal physical activity.

18. A composition according to any one of the preceding claims, wherein the collagen hydrolyzate has an average molecular weight of from 200 to 25,000 Da, preferably from 1,000 to 15,000 Da, more preferably from 1,200 to 12,000 Da, even more preferably from 1,500 to 8,000 Da, and especially from 1,800 to 5,500 Da.

19. A composition according to any one of the preceding claims, wherein the collagen hydrolyzate is prepared by enzymatic hydrolysis of a collagen-containing starting material.

20. The composition of claim 19, wherein the collagen-containing

Starting material is selected from skin or bones of

Vertebrates, preferably of mammals or birds, in particular skin of cattle or pigs.

21. The composition according to any one of claims 1 to 18, wherein the collagen hydrolyzate is prepared by recombinant gene expression.

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