NAD+ and NADH may bring back unwanted memories of biochemistry classes in high school. NADH stands for nicotinamide adenine dinucleotide (NAD) +hydrogen (H). NAD+ is the form without hydrogen. NAD and NADH are essential for cellular respiration.

These two cofactors help enzymes produce ATP (adenine triphosphate). ATP is commonly referred to as the energy currency in your body. This is because it powers every process in every cell.  

Increasing NADH and, therefore, ATP helps ensure all body tissues have the energy they need to function optimally. This is why many people use NADH supplements when they feel tired or lack energy. Researchers are testing NADH as a supplement to treat chronic fatigue syndrome and fibromyalgia.

What does NADH stand for in cellular respiration?

NAD+ is a coenzyme that carries electrons from one reaction to another in metabolic and cellular respiration. NAD+ is the oxidizing agent. It accepts electrons from other molecules and becomes reduced with hydrogen. For this reason, NAD+ is often referred to as an electron carrier. Hydrogen, in this form, is a negatively charged hydrogen atom. Whenever electrons are transferred in your body, energy is generated. This energy can be used for movement, to repair cellular damage, and to produce compounds needed by the body.

When NAD+ accepts a negatively charged hydrogen, it forms NADH which is a reducing agent that can donate electrons. This reaction is reversible and occurs repeatedly in your body cells.

What are NAD+ and NADH for?

NAD+ is a dinucleotide made up of nicotinamide and adenine. Nicotinamide is found in many foods and can be consumed as vitamin B3 or niacin. Adenine is a nitrogenous base that is found in DNA and RNA, which make up your genetic code.

NAD+ can be produced from any of the following:

• Tryptophan
• Nicotinic acid
• Nicotinamide
• Nicotinamide riboside

NAD+ production occurs through three pathways: the de novo, Preiss–Handler, and salvage. The salvage pathway is the most commonly used. NAD+ production is continuous in your body; without it, your body cells would not be able to function. Aging and chronic disease deplete NAD+ and NADH.

What does NADPH stand for?

NADP+ and NADPH are another pair of coenzymes that participate in chemical reactions. The structural difference between them is that NAD+ has a -OH group, and NADP+ has a phosphate group. NADP+ and NADPH are important in maintaining oxidative-reduction balance, like NAD+ and NADH, but they are involved in producing fatty acids and nucleic acids.

What does NADH stand for in medical terms?

NAD+ deficiency is the underlying cause of many inherited and acquired diseases. Though scientists have known about NAD for over a century, it has only been in the last 20 years that researchers have investigated its role in health and disease.¹

NAD+ is a substrate used by sirtuins, which are a family of NAD+-dependent deacetylases that regulate energy metabolism and mitochondrial function.²

In addition to sirtuins, the poly(ADP-ribose) polymerase (PARP) protein family, the cyclic ADP-ribose (cADPr) synthases, and CD157 also consume NAD+.² Sirtuins protect against oxidative stress and can switch off genes that are linked to accelerated aging, cell death, inflammation, and degeneration.

Researchers have identified a lack of NAD+ as a cause of disease and found that supplementing with NAD+ reversed many of the disease symptoms. Most of this research has been done in animal studies.¹

What is NADH used for in the body?

NADH, along with NAD+, has many roles in the body, including the following:

• Glutathione synthesis, an important antioxidant
• Energy metabolism
• DNA repair
• Cell signaling
• Gene expression
• Cellular homeostasis
• Modulating chemical reactions

Aging is associated with a decline in NAD+ and NADH; researchers are examining the possibility of reversing some of the signs and symptoms of aging by supplementing with NAD+ or NAD+ precursors. In one study, middle-aged adults were given nicotinamide mononucleotide (NMN), a precursor for NAD+.

NMN supplementation resulted in an 11% increase in NAD+ and NADH after 30 days of supplementation and by 38% at 60 days. Other health markers did not change, except for an improvement in insulin sensitivity, and the increase in NAD+/NADH was not statistically significant compared to the increase in the placebo group. There were no adverse events reported. Trial results need to be interpreted with caution because of potential conflicts of interest. ⁴

NAD+ and NADH depletion is associated with many metabolic and neurodegenerative diseases. Supplementing with NAD+ or NADH can help improve energy metabolism and insulin sensitivity. It may also help protect against changes in cognitive function.^5,6 Research on the benefits of NAD+ is relatively new but promising. Currently, over 1,000 clinical trials are registered on ClinicalTrials.gov investigating the potential health benefits of NAD+ and NADH.

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Disclaimer

While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice.

References:

1. Zapata-Pérez R, Wanders RJA, van Karnebeek CDM, Houtkooper RH. NAD+ homeostasis in human health and disease. https://doi.org/10.15252/emmm.202113943. EMBO Molecular Medicine. 2021/07/07 2021;13(7):e13943. doi:https://doi.org/10.15252/emmm.202113943
2. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. Mar 7 2012;13(4):225-238. doi:10.1038/nrm3293
3. Xiao W, Wang RS, Handy DE, Loscalzo J. NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism. Antioxid Redox Signal. 2018 Jan 20;28(3):251-272. doi: 10.1089/ars.2017.7216. Epub 2017 Jul 28. PMID: 28648096; PMCID: PMC5737637.
4. Huang H. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Front Aging. 2022 May 5;3:851698. doi: 10.3389/fragi.2022.851698. PMID: 35821806; PMCID: PMC9261366.
5. Braidy N, Liu Y. Can nicotinamide riboside protect against cognitive impairment? Curr Opin Clin Nutr Metab Care. Nov 2020;23(6):413-420. doi:10.1097/mco.0000000000000691
6. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985

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