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 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), and 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 and v.a. within the framework of 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 concentrations in the animal kingdom are found in the heart of poultry and in the muscle meat under the wings. However, because NADH is such a fragile substance, it is almost completely destroyed by stomach acid upon consumption, so the body barely 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 all the starting materials and cofactors are present. It then reacts with the oxygen present in every cell to form H2O and cellular energy in the form of adenosine triphosphate (ATP). The reaction of hydrogen and oxygen is familiar to some from chemistry class. “Hydrogen reaction”.

oxyhydrogen reaction
Hydrogen (H) reacts with oxygen (O2) to form water (H2O), producing "rocket fuel" (oxyhydrogen reaction). To avoid such an oxyhydrogen reaction in our bodies, the reaction must occur 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 “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
• Caveat: The inner mitochondrial membrane is NOT for protons (positively charged particles) permeable (only for O2, H2O and CO2 and via carriers for ATP, ADP and Pi). Therefore, only NADH and not 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 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 to 73 patients suffering from chronic fatigue was investigated. After the eight-week study period, 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 also received an additional supplementation with 200 mg coenzyme Q10, which may also have contributed to the improvement (see 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.).
  • Another study with a similar design and 144 women suffering from chronic fatigue showed a similar result. 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 heart rate after an exercise test after 60 days of taking 20 mg NADH per day (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, a dose of 200 mg coenzyme Q10 and 20 mg NADH over eight weeks showed a significant improvement in quality of life and a reduction in the Fatigue Impact Scale (FIS) 40 total score, which measures physical, cognitive, and psychosocial exhaustion. Furthermore, an improvement in sleep duration and subjective sleep quality was observed (see 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 individuals 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 improved brain performance after six months compared to baseline.
• Patients with chronic fatigue and listlessness developed a greater zest for life and motivation. In Parkinson's patients, an improvement in motor symptoms was also observed after NADH supplementation (seeGröber, U. Orthomolecular Medicine. A Guide for Pharmacists and Physicians. 2002.
• In a pilot study for the prevention of Alzheimer's disease, 24 patients at risk of Alzheimer's disease took 10 mg of NADH daily for 6 months and showed statistically improved results in language and spatial perception at the end of the study. This study suggests a small but nevertheless significant effect in the prevention of Alzheimer's disease (see 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 who were given NADH: 38% observed less fatigue and more vitality, 10% reported an increase in mobility, and 28% reported periods without fatigue; these periods 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 into 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): for aging are v.a. 3 phenomena responsible: decrease in energy production (ATP) in the cells, damage to DNA (u.a. by environmental toxins) as well as oxidation and damage to the cell membrane. Because NADH is particularly important for cellular energy production, can repair damaged DNA and cells, and acts as a powerful antioxidant, NADH is currently receiving special attention in longevity research.
• jet lagNADH 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 (see Birkmayer, GD et al. 2002. Stabilized NADH improves jet lag-induced cognitive performance deficit. Wien Med Wochenschr. 152(17-18):450-4.).
• Menopausal symptomsTypical symptoms of menopause include depressive moods, hot flashes, lack of motivation, and loss of libido. Some of these symptoms can be due not only to hormonal causes but also to a lack of ATP.
• Immune system and chronic inflammation: Studies have shown that NADH can significantly increase the biosynthesis of interleukin-6 in the blood. Interleukins are endogenous messenger substances of the immune system cells. 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, thereby improving blood flow to all organs. A small study at Georgetown University demonstrated that daily administration of 5 mg of NADH 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 significantly reduced glare sensitivity.
• Macular degeneration refers to a change in the “yellow spot” in the eye, which is responsible for sharp vision. Macular degeneration was present in 70% of cases when o.g. Drug combination decreased over 4 weeks.