Non-therapeutic use of an nadh preparation combined with sports

Abstract

The invention relates to the use of an NADH preparation combined with physical activity to increase the cognitive performance or to improve general health levels. The daily NADH dose supplied by administration of the NADH preparation is preferably 1 mg - 100 mg. The physical activity can comprise cardiovascular training and strength training.

Description

[0001] Non-therapeutic use of an NADH preparation in combination with exercise

[0002] The field of the present invention is that of the uses of food supplements, in particular NADH preparations.

[0003] The reducing equivalent NADH (nicotinamide adenine dinucleotide hydride) is involved in numerous metabolic reactions and serves as an electron and proton donor. As a coenzyme and temporary interaction partner for oxidoreductases, the water-soluble NADH forms reversible bonds with these enzymes and plays a key role in the regulation of numerous biological processes. In its function as an electron transporter, it accepts electrons from metabolic processes such as the citric acid cycle, beta-oxidation, and glycolysis and transfers them in the mitochondria via NADH dehydrogenase as part of oxidative phosphorylation to ubiquinone-10 and ultimately to respiratory oxygen. Therefore, NADH is significantly involved in energy metabolism through its participation in the formation of adenosine 5'-triphosphate (ATP), the "biochemical universal currency."

[0004] Arenas-Jal, et al. (European Journal of Pharmacology 879 (2020): 173158.) discusses the therapeutic potential of nicotinamide adenine dinucleotide (NAD). Covarrubias, et al.

[0005] (Nature Reviews Molecular Cell Biology 22.2 (2021): 119-141) is a review article on NAD metabolism and its role in cellular processes during aging. Rex et al. (Behavioural Brain Research 154.1 (2004): 149-153) investigates the influence of NADH supplementation on water maze performance in elderly rats.

[0006] NADH supplements are used as dietary supplements because they help increase the body's natural NADH levels. While the role of NADH in human metabolism is generally well understood, the effects of NADH supplements on the human body remain the subject of ongoing research. NADH supplements are often used to improve cognitive function. NADH supplements can also help reduce the age-related decline in energy production in the body's cells.

[0007] DE 103 26 822 A1 concerns an NADH preparation and its use. Example 1 of the document describes its use to increase physical performance and concentration in a 52-year-old man.

[0008] US 2023 / 000888 Al concerns the use of NAD+ precursors with caloric restriction for the treatment of age-related diseases.

[0009] EP 1 562 613 B1 relates to a composition comprising an isolated antioxidant A such as NADH or NADPH, and an isolated antioxidant B stabilising the antioxidant A, namely chlorophyll and / or a reduced ferredoxin.

[0010] NADH preparations have established themselves as dietary supplements on the German market and are offered in various forms, including tablets and capsules. These preparations are available in various dosages, with some products containing, for example, 1, 2, 5, 10, or 20 milligrams of NADH per tablet or capsule. The choice of dosage may vary depending on individual needs and recommendations from healthcare providers.

[0011] For example, the NADH preparation PANMOL® NADH is used, among other things, to improve memory and concentration and to increase alertness and attention.

[0012] However, there is a general need to further increase the effectiveness of NADH preparations. Therefore, the object of the present invention is to provide a novel use that enhances the positive effects of NADH preparations. The present invention provides the (non-medicinal) use of an NADH preparation (in healthy individuals) in combination with a sports intervention to increase cognitive performance (in particular motor-cognitive performance) or to improve general health.

[0013] In the course of the present invention, it was found that the combination of NADH supplementation with a sports intervention in a synergistic manner leads to excellent results both in improving cognitive performance (in particular reaction time, as determined, for example, by the so-called Shape Jump test, see the example below) and in improving general health (as determined, for example, by the established SF-36 health questionnaire).

[0014] This was not known in the literature. The review by Custodero et al. (Experimental Gerontology 137 (2020): 110972) examines the preclinical and clinical evidence on the effects of nicotinamide riboside supplementation strategies alone and in combination with physical activity on mobility and function of skeletal muscle and the cardiovascular system, but not on cognitive performance and improvement in general health.

[0015] Cardiovascular exercise, also known as endurance or cardio training, is a type of physical activity that strengthens the cardiovascular system and improves overall physical endurance. It involves activities performed for a sustained period of time and involving multiple large muscle groups, such as running, cycling, swimming, or hiking.

[0016] Strength training, also known as resistance or weight training, is a type of physical activity that aims to improve muscle strength and size through various exercises that involve specific muscle groups working against a resistance. This can be achieved by lifting weights, working with resistance bands, or performing bodyweight exercises.

[0017] In a preferred embodiment, the exercise intervention includes cardiovascular training and / or strength training. It has been found that these two forms of training work particularly well synergistically with the NADH preparation to achieve the effects of the invention.

[0018] It is particularly advantageous if the sports intervention comprises several training units. Preferably, at least 4 units within 4 weeks are involved (or simply: at least one unit within 4 weeks), more preferably at least 6 units within 4 weeks, even more preferably at least 8 units within 4 weeks. One training unit preferably comprises at least 30 minutes, preferably at least 50 minutes, of sports training, for example, both cardiovascular training and strength training (e.g., 20 minutes of cardiovascular training and 35 minutes of strength training).

[0019] According to a preferred embodiment, the NADH preparation is administered to an adult. Adults particularly benefit from the use of the NADH preparation in conjunction with an exercise intervention.

[0020] Preferably, the person on whom the NADH preparation is administered is healthy. In the context of the invention, this means that at least no metabolic disorder (such as diabetes mellitus) and no underlying neurological disease (such as Parkinson's disease) is present. In particular, it means that the person has no disease or disorder at all. As has been shown, untrained (healthy) people particularly benefit from the use according to the invention.

[0021] A person is considered "untrained" if they do less than 90 minutes of exercise per week, preferably less than 60 minutes, and especially less than 30 minutes. Therefore, in a preferred embodiment, the person on whom the NADH preparation is administered is untrained (and healthy). The age group 30 and over particularly benefits from the combination of NADH preparation and exercise intervention. With increasing age, changes in energy balance and cognitive performance can occur. Therefore, the person on whom the NADH preparation is administered is preferably over 30 years of age, preferably over 40 years of age, and especially over 50 years of age.

[0022] In a preferred embodiment, the daily NADH dose administered by taking the NADH preparation is between 1 mg and 100 mg - particularly good results are achieved in this range (this applies in particular to the range of 1 mg - 20 mg daily NADH dose). Preferably, the administered daily dose is 2 mg - 75 mg, more preferably 5 mg - 50 mg, even more preferably 6 mg - 25 mg, in particular 7 mg - 15 mg or even 8 mg - 12 mg. In a further preferred embodiment, the administered daily dose is 1 mg - 20 mg, more preferably 2 mg - 18 mg, even more preferably 4 mg - 16 mg, even more preferably 6 mg - 14 mg, in particular 8 mg - 12 mg.

[0023] In another preferred embodiment, the person taking the NADH preparation is not given any other dietary supplements. This can be particularly advantageous to avoid unwanted interactions with other dietary supplements as much as possible and thus maximize the effects of the NADH preparation.

[0024] The NADH preparation is preferably administered orally.

[0025] According to a further preferred embodiment, the NADH preparation comprises at least one further antioxidant (to stabilize the NADH preparation). Suitable antioxidants are, for example, vitamin C (ascorbic acid), vitamin E (tocopherol), beta-carotene or flavonoids such as resveratrol or quercetin. Chlorophyll or (reduced) ferredoxin are particularly suitable. Chlorophylls have derivatized porphyrin rings with magnesium (Mg 2+) from chelated minerals. Chlorophylls have structural similarities to the iron-containing hemes, which fulfill elementary metabolic functions in animal and human organisms as hemoglobin, myoglobin, and cytochromes. While hemes primarily serve to transport oxygen and electrons, chlorophylls are the only representatives of these porphyrins capable of absorbing light quanta from solar radiation and thus, using the energy of the light, stimulating the plant organism to synthesize organic molecules and oxygen from CO2 and H20 (photosynthesis).While the energy production of animal and human cells occurs through the breakdown of these plant, organic molecules and the gradual build-up and breakdown of stored electron energy (via the so-called reduction equivalents NADH / H+ and FADH2) analogous to the biochemical energy gradient of the calorie carriers, chlorophyll has the task of transforming the energy of sunlight into electronic energy and thus making it available for the construction of new organic substance. Chlorophyll fulfills a role as an electron donor that is physiologically similar to NADH, although electrochemically diametrically opposed to it, in the plant, and perhaps also in the human, organism. Numerous plant physiological publications point to the connections between chlorophyll content and activity and the dynamics of plant growth. More recent publications also point to connections between chlorophyll supply and the metabolism of catecholamines.

[0026] Ferredoxins, on the other hand, are iron-containing proteins that play a crucial role in biochemical redox processes in cells. They serve as intermediate electron carriers in a variety of metabolic reactions, including photosynthesis, respiration, and nitrogen fixation. In photosynthesis, for example, ferredoxins transfer electrons generated by light energy to other molecules in the process of carbon dioxide reduction. Ferredoxins are found in all organisms, from bacteria and algae to plants and animals.

[0027] According to another embodiment, the NADH preparation contains beeswax. Beeswax is a natural wax produced by honeybees. Beeswax serves as a natural stabilizer and can thus increase the shelf life of the preparation. Furthermore, beeswax can, among other things, enhance the release of NADH in the person's body, leading to increased effectiveness.

[0028] In another preferred embodiment, the NADH preparation contains vegetable fat. This, among other things, improves the bioavailability of NADH in the person's body and leads to increased effectiveness.

[0029] According to a further preferred embodiment, the NADH preparation is in solid form, in particular as a capsule or tablet. This solid dosage form enables simple and precise dosing of the NADH preparation, resulting in consistent absorption of the substance over the duration of use and thus an even more reliable effect over time.

[0030] In a further preferred embodiment, the NADH preparation has a microencapsulated formulation. This further increases stability by protecting NADH from environmental influences such as moisture, heat, or light. Furthermore, the microencapsulated formulation can enable controlled release of the NADH. During microencapsulation, the active component—in this case, at least the NADH—is embedded in microcapsules whose diameter is typically in the range of 1 pm to 500 pm (determined, for example, by electron microscopy).

[0031] In another preferred embodiment, the NADH preparation is formulated to be enteric-coated. This ensures that the NADH survives the aggressive environment of the stomach undamaged and is only released in the small intestine, further increasing its effectiveness.

[0032] In a further preferred embodiment, the use of the NADH preparation lasts for at least 5 days, more preferably for at least 10 days, even more preferably for at least 20 days, and especially for at least 30 days. This has been shown to achieve more sustainable health and cognitive benefits.

[0033] There are several recognized methods for assessing an individual's general health. One of the most commonly used methods is the SF-36 health questionnaire, specifically the "General Health Perceptions" subset (scale). The SF-36 health questionnaire is a generic instrument for measuring health-related quality of life. It consists of 36 questions divided into eight different scales: Physical Functioning, Physical Role Functioning, Bodily Pain, General Health Perceptions, Vitality, Social Functioning, Emotional Role Functioning, and Mental Health. The answers to these questions are then converted into a total score. The SF-36 is known for its high reliability and validity and is frequently used in clinical trials and research projects to evaluate the effectiveness of interventions (Ware Jr, John E., and Cathy Donald Sherbourne)."The MOS 36-item short-form health survey (SF-36) : I. Conceptual framework and item selection." Medical care (1992): 473-483.) .

[0034] There are also other methods for assessing health status, such as biomarker tests such as blood sugar levels, cholesterol levels, or red and white blood cell counts. These measurements can also be used to assess a person's overall health. However, the SF-36 health questionnaire, particularly the "General Health Perception" scale, is preferred.

[0035] Cognitive performance (especially motor-cognitive performance) is preferably determined using the SKILLCOURT® system (Friebe, David, et al. "Reliability and Usefulness of the Skillcourt as a Computerized Agility and Motor-Cognitive Testing Tool." Medicine and Science in Sports and Exercise (2023) .; Hülsdünker, Thorben, et al. "Validity of the SKILLCOURT® technology for agility and cognitive performance assessment in healthy active adults." Journal of Exercise Science & Fitness (2023) ). The "Shape Jump" test of this system has proven particularly useful in this regard. The "Shape Jump" test assesses the reaction speed with which a person correctly responds to new stimuli (shapes displayed on a screen) by making a movement (jump). Another method for determining cognitive performance is, for example, the D2 test of attention (D2R), cf. Bates & Lemay."The d2 Test of attention: construct validity and extensions in scoring techniques." Journal of the International Neuropsychological Society 10.3 (2004): 392-400.

[0036] In the following, the invention is explained in more detail using preferred, non-limiting examples and figures.

[0037] Fig. 1 shows the results of the "Shape Jump" test in the SkillCourt® system, which measures the motor-cognitive abilities of the subjects, at the beginning and, four weeks later, at the end of the study for the verum (NADH supplementation and exercise intervention) as well as the placebo group (exercise intervention without NADH supplementation). The points are arbitrary units.

[0038] Fig. 2 shows standard values ​​(SW) for error rate (F%), speed (BZO), and concentration performance (KL) of both test groups (NADH supplementation and exercise intervention, exercise intervention without NADH supplementation) after age adjustment. The test period was four weeks. Example - Randomized double-blind study

[0039] The aim of this prospective, randomized, placebo-controlled, double-blind study was to evaluate the efficacy of a four-week NADH supplementation with exercise intervention on cognitive performance and health status in an untrained population. Twenty-seven untrained healthy adults were recruited to participate in a targeted exercise program for four weeks and simultaneously take either 10 mg / day of chlorophyll-NADH (n = 13; age: 40.31 ± 10.49 years) or a chlorophyll-containing comparator (n = 14; age: 43.71 ± 12.96 years).At the beginning of the study and after four weeks, the participants underwent several tests: the D2-R test assessed their attention and concentration skills, cognitive-motor skills (Shape Jump) were measured using SkillCourt®, a digital testing system with scanner technology, and health status was assessed using the valid SF-36 test. In the D2-R test, the chlorophyll-NADH group performed better than the control group. In particular, the error rate (reduction in error rate: 6.43%; starting value: 89.62 ± 4.46; final value: 95.38 ± 4.61) was reduced in this group compared to the control group. In the comparison group, the improvement was only 3.17% (starting value: 84.5 ± 3.93; final value: 87.18 ± 3.60).Improved performance in the "Shape Jump" test procedure, which the subjects in the verum group developed, confirms the effect of the inventive combination on cognitive performance: In the verum group, the initial score of 6,475 ± 453.18 increased to 12,347.73 ± 1,289.81 points within four weeks, which corresponded to a performance improvement of 90.70%, whereas participants in the comparison group only experienced an improvement of 76.74% (initial score: 6,072.92 ± 528.17; final score: 10,733.33 ± 1,075.43). The improvement in overall health status was higher in the chlorophyll-NADH group with an increase of 5.7% (starting score: 125.3 ± 2.51; ending score: 132.45 ± 2.05) compared to the placebo group (improvement: 4.6%; starting score: 126.35 ± 2.76; ending score: 132.16 ± 2.1).The inventive combination of NADH supplementation and exercise intervention resulted in an additional improvement in overall health status as well as an increase in cognitive abilities.

[0040] Methods

[0041] Study design and subjects

[0042] In a randomized, double-blind pilot study, the effect of four weeks of chlorophyll-NADH supplementation compared to chlorophyll supplementation alone in combination with a four-week exercise program on cognitive performance and health status was investigated in 28 healthy adults. The guidelines of the Declaration of Helsinki were observed. Study participants were verbally informed about the project and consented to the project in writing via a signed informed consent form.

[0043] Healthy, untrained men and women who exercised less than 3 x 30 minutes of regular exercise per week but declared their willingness to participate in a training program with 10 units of 60 minutes of exercise each over a four-week period met the inclusion criteria. Exclusion criteria included low compliance (< 90%), taking medication (with the exception of contraceptives) or vitamin, mineral, or fatty acid supplements that could distort the study results in the last four weeks, ongoing nutritional therapy, an existing metabolic disorder, known malabsorption, an underlying neurological disease, or severe motor limitations of the musculoskeletal system. Regular exercise (> 3 x 30 minutes / week), intolerance to the test substance, pregnancy, or the lack of informed consent also led to exclusion from the study.The fitness program comprised ten units over a four-week period. Each training session lasted 60 minutes. This included 20 minutes of moderate cardiovascular training, 35 minutes of strength training, and 5 minutes of cognitive training. 32 test subjects were recruited for the study. 28 participants met the inclusion criteria and were randomly assigned, using a validated system, to either the verum group, which received the test substance with a daily dose of 10 mg NADH (in a microencapsulated formulation), or the placebo group, which was given a corresponding placebo preparation. With a ratio of 14:13, the group size of the intervention group roughly corresponded to the group size of the control group (placebo). The participants were anonymized using serial numbers. One test subject contracted COVID-19 during the final phase, meaning his data could not be used.

[0044] The two test substances were visually indistinguishable. The chlorophyll-NADH preparation (PANMOL® NADH micro) contained excipients from pea fiber and medium-chain coconut triglycerides. It was encapsulated in a size 2 bovine gelatin capsule shell; one capsule corresponded to a daily dose of 10 mg NADH and 10 mg chlorophyll. The reference substance, however, contained only 10 mg chlorophyll. The reference preparation was visually indistinguishable from the verum preparation. 30 capsules each of the test substances (either chlorophyll-NADH or chlorophyll) were packaged in white containers. The containers for the verum and placebo preparations were visually identical.

[0045] One capsule of the stabilized, enteric-coated chlorophyll-NADH mix or the corresponding comparator product was taken orally in the morning with sufficient liquid. The first dose was taken the day after enrollment in the study. Consumption of the test substance was continued for the next 30 days.

[0046] At time TI, the day before the first intake of the test substance, the initial check was conducted. This included assessing physical and mental health using the standardized SF-36 questionnaire. Concentration and attention were assessed using the D2-R concentration test. Reaction, concentration, and motor skills parameters were determined using the Ski U CourtO system.

[0047] The test subjects were then given the test substances (active substance or placebo) and were given detailed information beforehand about their effects and how to take them. A trained fitness trainer gave the test subjects detailed instructions on the correct use of the fitness equipment and explained the fitness program. A trainer also supervised the participants during the exercise sessions. The goal was ten training sessions over the next four weeks. After this period (after 28 days), a final check was carried out which again included an inquiry into health status using the SF-36, the administration of the D2-R concentration and attention test and the analysis of motor skills and reaction time (using the Skill Court®).

[0048] D2-R

[0049] The D2-R Attention and Concentration Test is a validated test procedure for measuring individual attention and concentration skills (cf. Bates, Marsha E., and Edward P. Lemay. "The d2 Test of attention: construct validity and extensions in scoring techniques." Journal of the International Neuropsychological Society 10.3 (2004): 392-400.). The test consists of 14 test lines, each with 57 characters. Participants were instructed to distinguish between similar visual stimuli by identifying and crossing out the target objects ("d" with two lines), while ignoring all other characters ("p" or "d" with fewer or more than two lines). The time for processing one line was limited to 20 seconds (total time for the test: 4 min 40 s).The D2-R test's parameters include the total number of items completed, the total number of errors (omissions and errors made), the percentage of errors relative to the number of items completed, and an overall performance score for attention / concentration. Reliability depends on the age group being tested and ranges between alpha = 0.89 and 0.95. Age correction is performed by comparing the results with a norm table that provides standard scores.

[0050] SkillCourt®

[0051] The SkillCourt® is a digital training facility with scanner technology suitable for measuring the motor and cognitive parameters of participants (see Friebe, David, et al. "Reliability and Usefulness of the Skillcourt as a Computerized Agility and Motor-Cognitive Testing Tool." Medicine and Science in Sports and Exercise (2023) .; Hülsdünker, Thorben, et al. "Validity of the SKILLCOURT® technology for agility and cognitive performance assessment in healthy active adults." Journal of Exercise Science & Fitness (2023) ). The cognitive characteristics and reaction times of the participants were assessed using the Shape Jump Test: One of three possible shapes (sphere, pyramid, or cube) was displayed on the monitor. This was initially located in the center of three lanes. On each of these lanes, there was an obstacle with a cutout (for a sphere, pyramid, or cube) through which only the corresponding shape could pass.The participants then had to use foot movements to guide this shape onto the correct path, where the obstacle with the appropriate cutout for the shape was located. The different colors of each shape and the corresponding tunnel required additional concentration. The time for a reaction was limited. Participants had less time to complete the task per round. The system automatically awarded points based on how accurately the participants completed this exercise. These points were recorded and used for statistical analysis.

[0052] Compatibility and acceptance of the test substances

[0053] Tolerability and acceptance of the test substances were determined as additional secondary parameters. This was done using a participant diary provided to participants. Participants were asked to note any subjective abnormalities or peculiarities that they considered to be related to the test substances.

[0054] SF-36

[0055] The SF-36 Health Survey is a cross-disease validated measurement instrument for assessing patients' health-related quality of life. It consists of 36 items (Ware Jr, John E., and Cathy Donald Sherbourne. "The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection." Medical care (1992): 473-483). It encompasses eight domains of subjective health: physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and psychological well-being, which can be assigned to the basic dimensions of "physical and psychological health." Points are awarded for each item according to the individual's health status, so that health status can be quantified using the SF-36. Higher scores indicate a better quality of life. A maximum of 155 points can be achieved.

[0056] Results

[0057] 32 participants were recruited for the current study. They were divided into two test groups (active drug or placebo) using a validated randomization system. Four people dropped out of the study prematurely, so that the final study population consisted of 28 healthy women (n = 19) and men (n = 9) between the ages of 18 and 65. One further participant had to be excluded from the final analysis due to COVID-19 illness at the time of the final test. The data of 27 participants were included in the analysis. The group sizes of both test groups were similar: 13 participants (nine women, four men) took the chlorophyll-NADH test substance and 14 subjects (nine women, five men) received the comparator preparation.The mean age of the NADH group was 40.31 ± 10.49 years, and the age of the placebo group was 43.71 ± 12.96 years. Table 1 shows the demographic characteristics of the participants. The demographic parameters were normally distributed, and there were no significant differences between the two study groups (p > 0.05).

[0058] Table 1: Age and gender distribution of both test groups. Key: M = male, F = female, MW = mean, SD = standard deviation, min = minimum, max = maximum

[0059] The primary interest of the study was to investigate the impact of one month of NADH supplementation combined with exercise training on general health and cognitive abilities. As a secondary outcome, the tolerability of the supplement was also tested.

[0060] SkillCourt® Shape Jump

[0061] Due to musculoskeletal disorders (knee pain / Achilles tendonitis) or insufficient training sessions, four of the 27 participants had to be excluded from the motor tests (Shape Jump). Eleven subjects (eight women, three men) in the active group were compared with 12 participants (eight women, four men) in the placebo group. The mean age of the NADH group was 39.91 ± 11.44 years (mean ± SD), and the age of the placebo group was 39.5 ± 9.8 years (mean ± SD).

[0062] A significant cognitive improvement was observed in the "Shape Jump" test. In the NADH group, participants initially achieved an average of 6,475 ± 453.18 points at the start and improved their performance to 12,347.73 ± 1,289.81 points after four weeks, which corresponds to a performance improvement of 90.70%. In the placebo group, participants improved by 76.74% from an initial 6,072.92 ± 528.17 points to 10,733.33 ± 1,075.43 points within four weeks. The results are shown in Fig. 1.

[0063] D2-R

[0064] The concentration performance (KL) is composed of the parameter values ​​error percentage (F%) and the number of processed target objects (BZO) (KL = BZO omission and confusion errors). F% corresponds to the relative error frequency (F% = 100 x (errors / BZO)). The age-corrected standard values ​​(SW) of F%, BZO and KL, which were determined using a norm table, were compared. Fig. 2 illustrates the start and end values ​​of the verum and the comparison group. The error rate F% improved in the chlorophyll-NADH group by 6.43% from 89.62 ± 4.46 (start value) to 95.38 ± 4.61% (end value). In the comparison group, the improvement was 3.17%. The initial value was 84.5 ± 3.93, and the final value was 87.18 ± 3.60. The initial BZO value in the chlorophyll-NADH group was 92.54 ± 3.20 and increased to a final value of 98.92 ± 3.51 within the test period. In the control group, an increase in SW was observed from 87 ± 3.09 to 93.29 ± 3.38.The SW of the KL increased in the chlorophyll-NADH group from initially 89.38 ± 3.82 to 96.31 ± 4.11 and in the control group from 83.14 ± 3.60 to 89.14 ± 3.71.

[0065] SF-36

[0066] Overall health status improved within the four weeks in both test groups: In the NADH group, the average mean ± standard error (MV ± SE) improved by 5.7% from an initial value of 125.3 ± 2.51 to 132.45 ± 2.05. In the control group, an increase of 4.60% was observed from a starting value of 126.35 ± 2.76 to the mean final score of 132.16 ± 2.10. A highly significant improvement (p = 0.004) resulted from the "General Health Perception" category: With a Cohen's d value of 1.210 and an effect size of 0.518 (the effect has a medium strength), general health perception was significantly higher in the chlorophyll-NADH group compared to the comparison group.In the verum group, the initial score was 19.37 ± 1.04 points and improved by 11.84% to 21.66 ± 0.88, whereas the score in the control group improved by only 2.17% from a starting value of 21.1 ± 0.75 to 21.56 ± 0.68. The chlorophyll-NADH group also performed better than the control group in five other domains: "Physical Functioning," "Role Physical Functioning," "Vitality," "General Health," and "Change in Health Status." Tolerability of the investigational drug.

[0067] All subjects rated the test substance as well tolerated. According to the study participants, no adverse effects occurred from taking the test drug.

[0068] Conclusion

[0069] This study investigated the influence of NADH supplementation with exercise intervention (i.e., the combination according to the invention) on cognitive performance and general health. The benefits of the combination according to the invention were primarily evident in an improvement in overall health (especially in general health perception) and in attention and reaction speed. The combination according to the invention led to a reduction in the frequency of errors in various cognitive areas.

Claims

Patent claims 1. Use of an NADH supplement in combination with an exercise intervention to increase cognitive performance or improve general health.

2. Use according to claim 1, wherein the daily dose of NADH supplied by taking the NADH preparation is 1 mg - 100 mg, preferably 2 mg - 75 mg, more preferably 5 mg - 50 mg, even more preferably 6 mg - 25 mg, in particular 7 mg - 15 mg or even 8 mg - 12 mg.

3. Use according to claim 1 or 2, wherein the sports intervention comprises cardiovascular training and / or strength training.

4. Use according to any one of claims 1 to 3, wherein the use is on an adult person.

5. Use according to claim 4, wherein the person is healthy and untrained.

6. Use according to claim 4 or 5, wherein the person is over 30 years old, preferably over 40 years old.

7. Use according to any one of claims 4 to 6, wherein no further nutritional supplements are administered to the person.

8. Use according to any one of the preceding claims, wherein the NADH preparation comprises at least one further antioxidant for stabilizing the NADH preparation.

9. Use according to claim 8, wherein the further antioxidant is chlorophyll or ferredoxin.

10. Use according to any one of the preceding claims, wherein the NADH preparation comprises beeswax.

11. Use according to any one of the preceding claims, wherein the NADH preparation comprises vegetable fat.

12. Use according to one of the preceding claims, wherein the NADH preparation is in solid form, in particular as a capsule or tablet.

13. Use according to any one of the preceding claims, wherein the NADH preparation comprises a microencapsulated formulation.

14. Use according to any one of the preceding claims, wherein the NADH preparation is formulated to be enteric-coated.

15. Use according to any one of the preceding claims, wherein the use lasts for at least 5 days, preferably at least 10 days, more preferably at least 2 weeks, in particular at least 4 weeks.

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