What exactly is NADH?

NADH is the abbreviation for nicotinamide adenine dinucleotide hydride and was first detected in yeast in 1906 by Arthur Harden and William John Young.

It is composed of NAD+ and hydrogen (H). The abbreviation NAD+ stands for “nicotinamide adenine dinucleotide”. The vitamin niacin (vitamin B3) is an important building block of NADH.

NADH is the reduced form of nicotinamide adenine dinucleotide (NAD), NAD+ is the oxidized form of NAD. “Reduced form” means that the oxidized form NAD+ becomes NADH by gaining two electrons and one proton.

NADH is an essential coenzyme (so-called “Coenzyme 1”), which plays a fundamental role in our cells and there especially.a as part of the respiratory chain (also called the electron transport chain) in the mitochondria (“power plants of our cells”).

It is hardly possible to absorb NADH from food. The highest NADH content in the animal world is found in the heart of poultry and in the muscle meat under the wings. But since NADH is such a labile substance, it is almost completely destroyed by stomach acid when consumed, so that the body actually hardly absorbs NADH through food.

NADH is instead synthesized by the body from the so-called macronutrients (carbohydrates, proteins, fats) as part of the citrate cycle, provided that all starting materials and cofactors are present. It eventually reacts with the oxygen present in every cell and forms H2O & cellular energy in the form of adenosine triphosphate (ATP). The reaction between hydrogen and oxygen is the “oxyhydrogen reaction”, which some people still know from chemistry lessons.

oxyhydrogen reaction
Hydrogen (H) reacts with oxygen (O2) to form water (H2O) and produces “rocket fuel” (oxyhydrogen reaction). In order to avoid such an oxyhydrogen reaction in our body, the reaction must take place in several stages. This is the idea of ​​the redox gradient within the respiratory chain.

The respiratory chain

• = “chemiosmotic coupling” or “Mitchell hypothesis” with oxidative phosphorylation (OxPhos)
• used to form ATP (from ADP + Pi)
  • 5 enzyme complexes I-V
  • 2 electron carriers
  • Electron transport chain (enzyme complexes I-IV) with redox gradient supplies energy for proton transport

• NADH/H+ and FADH2 release H to O (are reoxidized) and H2O is formed
• In this reaction, energy is released (oxyhydrogen reaction)
• In the case of a direct reaction of NADH/H+ + ½ O2 to H2O + NAD+, a lot of energy would be released at once due to the high redox potential difference between NADH/H+ and O2
• In order to prevent an “explosion”, the process is split into several individual steps (“cascade reaction”): Electrons are passed on via cascades and the energy released is used for proton transport and ATP formation
• Cave: The inner mitochondrial membrane is NOT permeable to protons (positively charged particles) (only to O2, H2O and CO2 as well as carriers for ATP, ADP and Pi). Therefore, only NADH and not, for example, NAD+ should be supplemented. The precursors of NAD+ such as nicotinamide ribosides or NMN (nicotinamide mononucleotides) cannot pass through the cell membrane because both are positively charged molecules.

 

 

What exactly is NADH needed for in the body?

Energy is required for all physiological functions in the body, but there are some specific functions for which NADH is particularly important . These include:

• Chronic exhaustion (also Long COVID)
  • In a clinical study, the administration of 20 mg NADH per day was examined in 73 patients suffering from chronic fatigue. After the study period of eight weeks it was found that - compared to the placebo group - the total NAD and especially The NADH proportion in the blood cells had also increased significantly and the exhaustion index had also decreased. Furthermore, lipid peroxidation decreased and mitochondrial function improved. However, the study participants received an additional supplement with 200 mg of coenzyme Q10, which could also have contributed to the improvement (cf. Castro-Marrero, J. et al. 2015. Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome? Antioxidant redox signal. 22(8):679–685.).
  • Another study with a comparable design and 144 women who suffered from chronic fatigue showed a similar result. A reduction in chronic pain and an improvement in sleep quality were observed (cf. Castro-Marrero, J. et al. 2021. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 13(8):2658.).
  • In addition, a chronic fatigue study in 77 patients showed a reduction in anxiety and a lower heart rate after an exercise test after taking 20 mg NADH per day for 60 days (cf. Alegre, J. et al. 2010. [Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome. Rev Clin Esp. 210(6):284–288.).
  • In a placebo-controlled study in 207 ME/CFS sufferers, taking 200 mg of Coenzyme Q10 and 20 mg of NADH for eight weeks showed a significant improvement in quality of life and a reduction in the FIS (Fatigue Impact Scale) 40 total score, which is used to record physical, cognitive and psychosocial exhaustion. Furthermore, an improvement in sleep duration and subjective sleep quality could be observed (cf. German Society for ME/CFS e.v https://www.mecfs.de/was-ist-me-cfs/ and Castro-Marrero, J. et al. 2021. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. 13(8): 2658).

Brain / Memory / Neurodegenerative Diseases

• Increased NADH intake showed good results in cognitive and verbal parameters in people with Alzheimer's disease and Parkinson's disease (cf. Demarin, V. et al. 2004. Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide. Drugs Exp Clin Res. 30(1):27-33.).
• A study at Georgetown University showed that patients treated with 10 mg NADH daily had significantly increased brain performance after six months compared to baseline.
• Patients with chronic fatigue and lack of motivation developed more joy in life and motivation. An improvement in motor symptoms after NADH supplementation was also observed in Parkinson's patients (cf. Groeber, U. Orthomolecular medicine. A guide for pharmacists and doctors. 2002.).
• In a pilot trial to prevent Alzheimer's, 24 patients at risk of Alzheimer's took 10 mg NADH daily over a period of 6 months and showed statistically better results in the areas of language and spatial perception at the end of the study. This experiment suggests only a small but still significant effect in the prevention of Alzheimer's disease (cf. Demarin, V. et al. 2004. Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Drugs Exp Clin Res. 30(1):27–33.).
• On St. Georgs Hospital in Székesfehérvár, a study was carried out on patients with MS in which this NADH was administered: 38% observed less fatigue and more vitality, 10% reported an increase in mobility, 28% reported phases without fatigue; these were significantly longer than in the control group.
• NADH can increase the production of the neurotransmitters dopamine and norepinephrine and modulate the uptake and release of neurotransmitters into the synaptic cleft (cf. Pearl, S. M et al. 2000. Effects of NADH on dopamine release in rat striatum. Synapse 36(2):95-101 and Ying, W. 2007. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 12:1863-88)

• As a central component in the antioxidant system of brain cells, NADH plays an essential role in slowing down aging processes (cf. Ying, W. 2008. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxidant redox signal. 10(2):179-206).

• Protection of the heart: Studies at the Medical University of Graz in Austria show that NADH can prevent heart disease: https://www.medunigraz.at/news/detail/herzschwaeche-nikotinamid-als-neuer-wirkstoff-fuer-zukuenftige-therapie-untersucht )

• “Longevity” (healthy aging): v. are responsible for aging.a 3 phenomena are responsible: decrease in energy production (ATP) in the cells, damage to DNA (e.g.a through environmental toxins) as well as oxidation and damage to the cell membrane. Since NADH is of particular importance for cellular energy production, can repair damaged DNA and cells and acts as a strong antioxidant, NADH is currently enjoying particular attention in longevity research.
• Jet lag: NADH is also used to improve the symptoms of jet lag. Both cognitive functions and the need for sleep seem to benefit from increased dopamine synthesis (cf. Birkmayer, G. D et al. 2002. Stabilized NADH improves jet lag-induced cognitive performance deficit. Vienna Med Weekly. 152(17-18):450-4.).
• Menopausal symptoms: Typical side effects of menopause are depressive moods, hot flashes, listlessness or loss of libido. In addition to hormonal causes, some of these symptoms can also be due to a lack of ATP.
• Immune system and chronic inflammation: According to studies, NADH can increase the biosynthesis of interleukin-6 in the blood many times over. Interleukins are the body's own messenger substances in the cells of the immune system. Interleukin-6 is relevant as an anti-inflammatory substance and also increases the secretion of cortisone, somatotropin, glucagon and adrenaline.
• Blood pressure: NADH stimulates nitroxide production and thereby improves blood circulation in all organs. A smaller study at Georgetown University showed that administering 5 mg of NADH per day reduced blood pressure by an average of 10%.
• Glaucoma (increased eye pressure) and macular degeneration (change in visual field)
• The treatment in both cases was with the administration of 450 mg L-arginine and 10 mg NADH over a period of four weeks.
• In the application study there was a reduction in eye pressure and an improvement in reading ability by 2.5 lines. Twilight vision improved to 100% in all cases. 80% of the test subjects showed a significantly reduced sensitivity to glare.
• Macular degeneration refers to a change in the “yellow spot” in the eye, which is responsible for sharp vision. Macular degeneration was eliminated in 70% of cases with administration orG combination of active ingredients decreased over 4 weeks.