NADH

Synonym(s): Nicotinamide adenine dinucleotide, Post-Covid-Syndrome, reduced nicotinamide adenine dinucleotide

Nutrient group: vitaminoids, Neurotropic agents

Sources and physiological effects

Dietary sources
NADH (nicotinamide adenine dinucleotide) is a biological substance found in all living cells and is therefore also found in plant and animal foods. Higher quantities are contained in meat and fish. However, NADH is destroyed by heating during food preparation.
Physiological effects
Energy balance	Coenzyme in numerous redox reactions of cell metabolism (e.g. citrate cycle)
Nervous system	Influence on neurotransmitter synthesis and signal transmission Increase in dopamine synthesis

Detailed information

NADH - an essential coenzyme for neurotransmitter activities

Reduced NADH is involved as coenzyme and hydrogen transmitter in many redox reactions in the cells. It is produced in the body from nicotinamide (niacin). In addition to its involvement in energy production processes in the mitochondria, NADH can increase the production of the neurotransmitters dopamine and norepinephrine (1). It can also modulate the uptake and release of these neurotransmitters in the synapse cleft (2) (3). Besides ATP, NADH appears to be a fundamental substance for multiple processes in the brain. As a central component in the antioxidative system of brain cells, it also plays an essential role in slowing down ageing processes (3).

Preventive use and therapeutic intervention

NADH is showing good success in the adjuvant treatment of neurodegenerative diseases. In people with Alzheimer's disease and Parkinson's disease, increased NADH intake showed improvements in cognitive and verbal parameters (4). In patients with chronic fatigue and listlessness, NADH treatment resulted in an increased zest for life and a willingness to perform. In Parkinson's patients, an improvement in motor symptoms after NADH supplementation was also observed (5).

NADH for treatment of jetlag

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 (6).

NADH in Alzheimer's disease

In a pilot trial for the prevention of Alzheimer's disease, 24 patients at risk for Alzheimer's disease took 10 mg of NADH daily for a 6-month time frame and showed statistically better outcomes in language and spatial perception at the end of the study. This trial suggests only a small but nevertheless significant effect in the prevention of Alzheimer's disease (7).

NADH in chronic fatigue syndrome and long-COVID

NAD (nicotinamide adenine dinucleotide) is an important cofactor for various processes in cellular energy metabolism and is therefore also used in chronic fatigue syndrome, also known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and reduced mental performance. In a clinical study, the administration of 20 mg NADH per day to 73 patients suffering from chronic fatigue was investigated. 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 additional supplementation with 200 mg of coenzyme Q10, which may also have contributed to the improvement (8). 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 (9). In addition, a chronic fatigue study in 77 patients showed a reduction in anxiety and a lower pulse rate after an exercise test after taking 20 mg of NADH per day for 60 days (10). These findings may also be relevant in long COVID patients in whom development from chronic fatigue syndrome is observed. Although exact mechanisms of Long COVID remain part of research, recent studies, however, indicate a significant disturbance in energy metabolism. In a placebo-controlled study of 207 ME/CFS sufferers, an eight-week course of 200 mg coenzyme Q10 and 20 mg NADH showed a significant improvement in quality of life and a reduction in the FIS (Fatigue Impact Scale) 40 total score, which is used to assess physical, cognitive, and psychosocial fatigue. Furthermore, an improvement in sleep duration and subjective sleep quality was observed: representing a promising approach in the treatment of Long COVID symptoms (11)(12).

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	Supportive therapy for neurological disorders for degenerative and vascular dementia and their mixed forms	10 - 30 mg/d
	Complemantary therapy for Alzheimer and Parkinson	10 - 30 mg/d
	With beginning ACE-inhibitory therapy	10 mg/d
	For short-term improvement of cognitive performance	10 mg/d
	For Alzheimer's disease	10 mg/d
	In Chronic fatigue syndrome and Long-COVID	20 mg/d

Administration

General mode of administration
When	NADH should be taken between meals.
Side effects
No side effects are known to date.
Contraindications
No contraindications are known to date.

Interactions

Drug interactions
None	No relevant interactions are known to date.
Nutrient interactions
None	No relevant interactions are known to date.

References

1) Pearl, S. M. et al. 2000. Effects of NADH on dopamine release in rat striatum. Synapse. 36(2):95-101.
2) Ying, W. 2007. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 12:1863-88.
3) 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.
4) Demarin, V. et al. 2004. Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide. Drugs Exp Clin Res. 30(1):27-33.
5) Gröber, U. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte. 2002.
6) Birkmayer, G. D. et al. 2002. Stabilized NADH improves jet lag-induced cognitive performance deficit. Wien Med Wochenschr. 152(17-18):450-4.
7) 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.
8) 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.
9) 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.
10) Alegre, J. et al. 2010. [Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome. Rev Clin Esp. 210(6):284–288.
11) Deutsche Gesellschaft für ME/CFS e.v. https://www.mecfs.de/was-ist-me-cfs/. Aufgerufen am 14.03.2022.
12) 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.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.