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") that plays a fundamental role in our cells and there v.a. within the framework of Respiratory chain (also called electron transport chain) plays a role in the mitochondria (“powerhouses of our cells”).

Absorption of NADH from food is hardly possible. The highest NADH concentrations in the animal kingdom are found in poultry, specifically in the heart and the muscle tissue under the wings. However, because NADH is such a labile substance, it is almost completely destroyed by stomach acid during consumption, meaning the body actually absorbs very little NADH from food.

NADH, provided all starting materials and cofactors are present, is synthesized by the body from macronutrients (carbohydrates, proteins, fats) via the citric acid cycle. It then reacts with the oxygen present in every cell to form H₂O. &½ cellular energy in the form of adenosine triphosphate (ATP). The reaction of hydrogen and oxygen is the one some may remember from chemistry lessons. "oxyhydrogen 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 concept of the redox gradient within the respiratory chain.

The respiratory chain

• = “chemiosmotic coupling” or “Mitchell hypothesis” with oxidative phosphorylation (OxPhos)
• used for the formation of ATP (from ADP + Pi)
  • 5 Enzyme Complexes IV
  • 2 electron carriers
  • The electron transport chain (enzyme complexes I-IV) with redox gradient provides energy for proton transport.

• NADH/H+ and FADH2 donate H to O (are reoxidized) and H2O is formed.
• Energy is released during this reaction (oxyhydrogen reaction)
• In a direct reaction of NADH/H+ + ½ O2 to H2O + NAD+, a very large amount 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.
• 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 should be supplemented, and not, for example, NAD+..

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 is.This includes:

• Chronic fatigue (also known as Long COVID)
  • In a clinical study, the administration of 20 mg of NADH per day was investigated in 73 patients suffering from chronic fatigue. After the eight-week study period, it was found that—compared to the placebo group—total NAD and, in particular, the NADH content in 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 additional supplementation with 200 mg of coenzyme Q10, which may have also 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).
  • A similar result was also shown in another study with a comparable design and 144 women suffering from chronic fatigue. This study observed a reduction in chronic pain and an improvement in sleep quality (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).
  • Furthermore, a study on chronic fatigue in 77 patients showed a reduction in anxiety and a lower heart rate after an exercise test following 60 days of taking 20 mg of 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 patients, taking 200 mg of coenzyme Q10 and 20 mg of NADH over eight weeks resulted in a significant improvement in quality of life and a reduction in the FIS (Fatigue Impact Scale) 40 total score, which measures physical, cognitive, and psychosocial exhaustion. Furthermore, improvements in sleep duration and subjective sleep quality were 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 (see 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 by Georgetown University showed that patients treated with 10 mg of NADH daily exhibited a significant increase in brain performance after six months compared to baseline.
• Patients with chronic fatigue and lack of motivation developed greater enjoyment of life and increased willingness to perform. Furthermore, an improvement in motor symptoms was observed in Parkinson's patients after NADH supplementation (see Gröber, 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 developing Alzheimer's took 10 mg of NADH daily for a period of 6 months and showed statistically better results in the area of ​​language and spatial perception at the end of the study.This experiment suggests only 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, in which they were administered NADH: 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 norepinephrine, as well as modulate the uptake and release of these 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 (see 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 heartStudies at the Medical University of Graz Studies in Austria have shown 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.aThree phenomena are responsible: a decrease in energy production (ATP) in the cells, damage to DNA (u.a(e.g., due to 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 powerful antioxidant, it is currently receiving special attention in longevity research.
• Jet lagNADH is also used to improve the symptoms of jet lag. Both cognitive functions and sleep requirements 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 energy, and loss of libido. Some of these symptoms can be caused by an ATP deficiency in addition to hormonal factors.
• Immune system and chronic inflammationAccording to studies, NADH can increase the biosynthesis of interleukin-6 in the blood many times over. 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 cortisol, somatotropin, glucagon, and adrenaline.
• blood pressureNADH stimulates nitrite production, thereby improving blood flow to all organs. A small study at Georgetown University demonstrated that administering 5 mg of NADH per day lowered blood pressure by an average of 10%.
• glaucoma (increased intraocular pressure) and Macular degeneration (Visual field changes)
• In both cases, treatment consisted of administering 450 mg L-arginine and 10 mg NADH over a period of four weeks.
• The application study resulted in a reduction in eye pressure and an improvement in reading ability of 2.5 lines.Night 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 macula (the central part of the eye responsible for sharp, central vision). Macular degeneration was present in 70% of cases when [the medication] was administered. o.gThe combination of active ingredients decreased over 4 weeks.