What exactly is NADH?

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

It is made up 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 absorbing two electrons and one proton.

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

It is almost impossible 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 because NADH is such an unstable substance, it is almost completely destroyed by stomach acid when consumed, so the body hardly absorbs any NADH from food.

Instead, NADH is synthesized by the body from the so-called macronutrients (carbohydrates, proteins, fats) as part of the citric acid cycle, provided that all starting materials and cofactors are present. It then reacts with the oxygen present in every cell and forms H2O & cellular energy in the form of adenosine triphosphate (ATP). The reaction of hydrogen and oxygen is the one known to some from chemistry lessons. "oxyhydrogen reaction".

oxyhydrogen reaction
Hydrogen (H) reacts with oxygen (O2) to form water (H2O), thereby producing "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)
• serves to form ATP (from ADP + Pi)
  • 5 enzyme complexes IV
  • 2 electron carriers
  • Electron transport chain (enzyme complexes I-IV) with redox gradient provides energy for proton transport

• NADH/H+ and FADH2 release H to O (are reoxidized) and H2O is formed
• During 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
• To prevent an “explosion”, the process is split into several individual steps (“cascade reaction”): electrons are passed on via cascades and the released energy is used for proton transport and ATP formation
• Cave: The inner mitochondrial membrane is NOT for protons (positively charged particles) permeable (only for O2, H2O and CO2 and via carrier for ATP, ADP and Pi). Therefore, only NADH and not NAD+ should be supplementedThe 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 needed for all physiological functions in the body, but there are some specific functions for which NADH is particularly important These include:

• Chronic fatigue (also known as Long COVID)
  • In a clinical study, the administration of 20 mg NADH per day was investigated 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 content in the blood cells had increased significantly and the fatigue index had also decreased. Furthermore, lipid peroxidation decreased and mitochondrial function improved. However, the study participants received an additional supplementation with 200 mg coenzyme Q10, which may 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? Antioxid Redox Signal. 22(8):679–685.).
  • A similar result was shown by another study with a similar design and 144 women suffering from chronic fatigue. A reduction in chronic pain and an improvement in sleep quality were observed (see 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 study on chronic fatigue in 77 patients showed a reduction in anxiety and a lower pulse rate after an exercise test after taking 20 mg NADH per day for 60 days (see 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 of 207 ME/CFS sufferers, taking 200 mg of coenzyme Q10 and 20 mg of NADH over 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 measure physical, cognitive and psychosocial exhaustion. Furthermore, an improvement in sleep duration and subjective sleep quality was observed (see German Society for ME/CFS ev 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 persons 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 of 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 willingness to perform.In Parkinson's patients, an improvement in motor symptoms was also observed after NADH supplementation (cf. Gröber, U. Orthomolecular medicine. A guide for pharmacists and doctors. 2002.).
• In a pilot study on the prevention of Alzheimer's disease, 24 patients at risk of Alzheimer's disease 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 study suggests only a small but nevertheless 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.).
• A study was conducted at St. George's Hospital in Székesfehérvár on patients with MS in which NADH was administered to them: 38% observed less fatigue and more vitality, 10% reported an increase in mobility, 28% reported periods without fatigue; these were significantly longer than in the control group.
• NADH can increase the production of the neurotransmitters dopamine and noradrenaline and modulate the uptake and release of the neurotransmitters in the synaptic cleft (see Pearl, SM 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. Antioxid Redox Signal. 10(2):179-206).

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

• "longevity" (healthy aging): Three phenomena are primarily responsible for aging: a decrease in energy production (ATP) in the cells, damage to DNA (due to environmental toxins, among other things), and oxidation and damage to the cell membrane. Since NADH is particularly important for cellular energy production, can repair damaged DNA and cells, and acts as a powerful antioxidant, NADH is currently receiving 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 appear to benefit from increased dopamine synthesis (cf. Birkmayer, GD et al. 2002. Stabilized NADH improves jet lag-induced cognitive performance deficit. Wien Med Wochenschr. 152(17-18):450-4.).
• menopausal symptoms: Typical symptoms of menopause are depressive moods, hot flashes, lack of motivation or loss of libido. Some of these symptoms can be caused by hormonal factors or 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 of 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 to all organs.A smaller study at Georgetown University showed that taking 5 mg of NADH per day reduced blood pressure by an average of 10%.
• glaucoma (increased eye pressure) and macular degeneration (visual field change)
• In both cases, treatment consisted 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 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 decreased in 70% of cases when the above combination of active ingredients was administered over 4 weeks.