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What the research says about nicotinamide adenine dinucleotide
What is NAD+?
NAD+, or nicotinamide adenine dinucleotide, is a coenzyme – or enzyme “helper” that supports important reactions in the body.
NAD+ is needed to help turn nutrients into energy, and is thus a key player in mitochondrial health. NAD+ also helps repair damaged DNA and facilitates hundreds of other metabolic reactions in the body.
NAD+ is found in all of our cells – but that doesn’t mean we have an endless supply of the coenzyme. NAD+ levels vary depending on the time of day and other factors, and decline with age. In general, higher NAD+ levels are associated with better health,1 and problems with NAD+ production and function can lead to illness.2 Specifically, prolonged NAD+ deficiency compromises normal physiology, leading to a host of health problems like metabolic diseases, chronic fatigue, addiction, cancer, rapid aging, and neurodegenerative conditions.3
Where does NAD+ come from?
Our bodies get NAD+ from a few main sources:
(1) The body can synthesize NAD+ out of the essential amino acid tryptophan. Tryptophan can be found in foods like whole milk, tuna, chicken, and turkey.4 (Side note: Some people think that it’s the tryptophan in turkey that makes people drowsy after Thanksgiving dinner, but the carbs and sugars consumed at dessert are more likely to be the culprit.5)
(2) NAD+ can be made in the body from vitamin B3. “Vitamin B3” is actually a collective term that refers to several NAD+ precursors, namely: niacin (or nicotinic acid), niacinamide (or nicotinamide), or nicotinamide riboside.6
(3) The body can salvage vitamin B3 or nicotinamide mononucleotide from other reactions and recycle it back into NAD+ for use.
(4) NAD+ can also be administered intravenously (IV) or taken as a nasal spray, sublingual lozenge, or oral capsule. It works best when given alongside other nutritional cofactors, like iron, vitamin B2 (riboflavin), ribose, CoQ10, and proline.7
NAD can exist in two forms: NAD+ or NADH. When the molecule goes through a reaction in which it loses electrons (known as oxidation), it forms NAD+. When it gains electrons (in a process known as reduction), it is turned into NADH. NAD+ and NADH are converted into each other via oxidation and reduction in many different metabolic activities throughout the body, and are thus known as a “redox couple.”7 (While both NAD+ and NADH are important for health, this article will focus primarily on NAD+.)
What does it help with?
NAD+ and NADH play important roles in protecting us against a variety of seemingly unrelated illnesses.8 Every cell in the body contains NAD+, and the coenzyme facilitates hundreds of chemical reactions. Some of the better known and researched applications of NAD+ supplementation and support include the following:
Alcohol abuse diminishes the body’s synthesis of NAD+ cofactors, thereby wreaking havoc on physical and mental health. NAD+ deficiency triggers unwanted behaviors and addictive tendencies, in effect driving the vicious cycle of alcohol abuse. NAD+ deficiency is therefore not only a result of alcoholism, but also a cause of it.9 In fact, individuals who regularly consume alcohol are more likely to have vitamin B3 deficiency than non-drinkers.10
Fortunately, supplementation with niacin and other NAD+ precursors has been shown to reduce alcohol cravings in those with alcohol use disorder.11,12,9
Supplementation with niacin and other NAD+ precursors has been shown to reduce alcohol cravings in those with alcohol use disorder.
Some sources recommend a dose of 500mg of niacin daily for those with alcohol use disorders; others argue for the higher dose of 1 gram three times daily with meals.
Yet another approach is to use NAD+ intravenously (IV) to support alcohol detoxification. This must be done under the direct supervision of a healthcare professional trained in both NAD+ administration and detox. The treatment entails infusing high doses of NAD+ – plus other amino acids, antioxidants, and nutritional cofactors – into a vein at least five days per week. The super-saturation of NAD+ involved in this treatment is thought to force the brain into producing catecholamines (the neurotransmitters dopamine, epinephrine, and norepinephrine) so that the dopamine circuits (the brain’s reward centers) are satisfied.7 A similar approach may also be useful in helping patients stop using opioid drugs.
NAD+ can also protect the liver against alcohol-related injury. The liver enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) use NAD+ to breakdown the ethanol found in alcoholic drinks and turn it into a less toxic compound.13 NAD+ has also been shown to support liver regeneration in mice who had had part of their livers removed,14,15 which could suggest positive benefits for humans with liver injury as well.
Fatigue syndromes and mitochondrial dysfunction
Because of the important role it plays in mitochondrial health and ATP (energy) production,16,17 NAD+ may be helpful in conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Lyme disease.
In fact, individuals with ME/CFS have been observed to have low NADH levels.8,18 Upon examination of pairs of twins in which one sibling has CFS and the other did not, NADH metabolism was found to be closely linked with fatigue.19
NAD+ is cofactor for enzymes that recycle coenzyme Q10 (CoQ10), and thus helps keep CoQ10 in its active (ubiquinol) form.20 Because CoQ10 is also important for mitochondrial health, it pairs well with NAD+ for addressing fatigue conditions. In fact, taking 20mg of NADH with 200mg of CoQ10 has been shown to improve both physical functioning and mental clarity in those with CFS after eight weeks. The supplement combination has also been shown to increase ATP blood levels.21,22,23
Mitochondrial dysfunction is seen not only in CFS, but also in many cases of Lyme disease.24 Perhaps unsurprisingly, supplementation with NADH and CoQ10 was shown to significantly reduce intractable fatigue in a pilot study of patients with chronic Lyme disease.25
NAD+ plays important roles in cancer metabolism by regulating cellular signaling, energy production, and oxidation/reduction (redox) activity.26
NAD+ may further protect against cancer by helping our cells adapt to infections, inflammation, circadian disorders, and nutritional imbalances. NAD+ also helps our bodies cope with exposures to genotoxins (chemicals that damage DNA) and xenobiotics (chemicals that are foreign to animal life, such as cosmetics, food additives, drugs, pesticides, industrial chemicals, and environmental pollutants).3
As helpful as NAD+ supplementation may be in some cases, nutrition expert Paul Anderson, NMD warns that it’s important to consider the type of cancer being treated when deciding whether or not to use NAD+. He explains that the ratio of NAD+ to NADH is important in tumor biology, and that the ideal ratio changes depending on the type of cancer a person has. Driving the ratio in the wrong direction could potentially push tumorgenesis (tumor growth).7,26
Like many health-protecting nutrients, NAD+ levels steadily decline as we grow older, increasing our risk of a variety of age-related health conditions.27,28 Fortunately, restoring NAD+ levels in old and/or diseased animals (humans included) has been shown to improve health, control the body’s stress response, and extend lifespan.29,30,31
Restoring NAD+ levels can dramatically reduce the severity of age-related conditions, including neurodegenerative diseases.
Restoring NAD+ levels can also dramatically reduce the severity of age-related conditions, including neurodegenerative diseases.32 NAD+ plays important roles in the health of neurons (the cells of the brain and nervous system), thus stalling or even counteracting processes associated with neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington diseases, as well as in amyotrophic lateral sclerosis (ALS).33,34
NAD+ is a ubiquitous coenzyme, found in every human cell. Our bodies use NAD+ for a variety of important biochemical reactions throughout all stages of life. While we don’t have an endless supply of the coenzyme, we can support its synthesis with proper nutrition, and even supplement with NAD+ directly in a variety of forms.
ReferencesClick here to see References
- Arenas-Jal M, Suñé-Negre JM, García-Montoya E. Therapeutic potential of nicotinamide adenine dinucleotide (NAD). Eur J Pharmacol. 2020;879. doi:10.1016/j.ejphar.2020.173158
- Sultani G, Samsudeen AF, Osborne B, Turner N. NAD+: A key metabolic regulator with great therapeutic potential. J Neuroendocrinol. 2017;29(10). doi:10.1111/jne.12508
- Xie N, Zhang L, Gao W, et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5(1):1-37. doi:10.1038/s41392-020-00311-7
- 9 Foods High in Tryptophan and Why You Need It. Nourish by WebMD. https://www.webmd.com/diet/foods-high-in-tryptophan#1. Accessed November 2, 2021.
- Ballantyne C. Does Turkey Make You Sleepy? Scientific American. https://www.scientificamerican.com/article/fact-or-fiction-does-turkey-make-you-sleepy/#. Published 2007. Accessed November 2, 2021.
- Niacin. Linus Pauling Institute, Oregon State University. https://lpi.oregonstate.edu/mic/vitamins/niacin. Accessed November 2, 2021.
- Anderson PS. NAD+. In: ; 2018.
- Mikirova N, Casciari J, Hunninghake R. The assessment of the energy metabolism in patients with chronic fatigue syndrome by serum fluorescence emission. Altern Ther Heal Med. 2012;18(1):36-40. https://pubmed.ncbi.nlm.nih.gov/22516851/. Accessed November 2, 2021.
- Prousky JE. The Treatment of Alcoholism with Vitamin B 3. Int Soc Orthomol Med. 2014. https://www.semanticscholar.org/paper/The-Treatment-of-Alcoholism-with-Vitamin-B-3-Prousky/7defac05e55e21d3eed44a02b37564aab650b932. Accessed November 2, 2021.
- Badawy AAB. Pellagra and alcoholism: A biochemical perspective. Alcohol Alcohol. 2014;49(3):238-250. doi:10.1093/alcalc/agu010
- Narasimha VL, Ganesh S, Reddy S, et al. Pellagra and alcohol dependence syndrome: Findings from a tertiary care addiction treatment centre in India. Alcohol Alcohol. 2019;54(2):148-151. doi:10.1093/alcalc/agz004
- Lewis MJ. Alcoholism and nutrition: A review of vitamin supplementation and treatment. Curr Opin Clin Nutr Metab Care. 2020;23(2):138-144. doi:10.1097/MCO.0000000000000622
- What’s the Difference Between NAD+ and NADH? Elysium Health. https://www.elysiumhealth.com/blogs/science101/what-s-the-difference-between-nad-and-nadh. Accessed November 3, 2021.
- Mukherjee S, Chellappa K, Moffitt A, et al. Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration. Hepatology. 2017;65(2):616-630. doi:10.1002/hep.28912
- Wan HF, Li JX, Liao HT, et al. Nicotinamide induces liver regeneration and improves liver function by activating SIRT1. Mol Med Rep. 2019;19(1):555-562. doi:10.3892/mmr.2018.9688
- Cantó C, Menzies KJ, Auwerx J. NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53. doi:10.1016/j.cmet.2015.05.023
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. doi:10.1038/s41580-020-00313-x
- Forsyth LM, Preuss HG, MacDowell AL, Chiazze L, Birkmayer GD, Bellanti JA. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy, Asthma Immunol. 1999;82(2):185-191. doi:10.1016/S1081-1206(10)62595-1
- Ciregia F, Kollipara L, Giusti L, et al. Bottom-up proteomics suggests an association between differential expression of mitochondrial proteins and chronic fatigue syndrome. Transl Psychiatry. 2016;6(9):e904. doi:10.1038/tp.2016.184
- Ross D, Siegel D. Functions of NQO1 in cellular protection and CoQ10 metabolism and its potential role as a redox sensitive molecular switch. Front Physiol. 2017;8(AUG). doi:10.3389/fphys.2017.00595
- Castro-Marrero J, Cordero MD, Segundo MJ, et al. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxidants Redox Signal. 2015;22(8):679-685. doi:10.1089/ars.2014.6181
- Castro-Marrero J, Sáez-Francàs N, Segundo MJ, et al. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome – A randomized, controlled, double-blind trial. Clin Nutr. 2016;35(4):826-834. doi:10.1016/j.clnu.2015.07.010
- Castro-Marrero J, Segundo MJ, Lacasa M, Martinez-Martinez A, Sentañes RS, Alegre-Martin J. 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. 2021;13(8). doi:10.3390/nu13082658
- Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015;5:66-70. doi:10.1016/j.redox.2015.03.002
- Nicolson GL, Settineri R, Ellithorpe R. Glycophospholipid formulation with NADH and CoQ10 significantly reduces intractable fatigue in western blot-positive “chronic lyme disease” patients: Preliminary report. Funct Foods Heal Dis. 2012;2(3):35-47. doi:10.31989/ffhd.v2i3.100
- Hong SM, Hwang SW, Wang T, et al. Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level. Cancer Sci. 2019;110(2):629-638. doi:10.1111/cas.13886
- Poljsak B, Kovač V, Milisav I. Healthy Lifestyle Recommendations: Do the Beneficial Effects Originate from NAD+Amount at the Cellular Level? Oxid Med Cell Longev. 2020;2020. doi:10.1155/2020/8819627
- De Barcelos IP, Haas RH. Coq10 and aging. Biology (Basel). 2019;8(2). doi:10.3390/biology8020028
- Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547. doi:10.1016/j.cmet.2018.02.011
- Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science (80- ). 2015;350(6265):1208-1213. doi:10.1126/science.aac4854
- Yaku K, Okabe K, Nakagawa T. NAD metabolism: Implications in aging and longevity. Ageing Res Rev. 2018;47:1-17. doi:10.1016/j.arr.2018.05.006
- Imai S ichiro, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. doi:10.1016/j.tcb.2014.04.002
- Lautrup S, Sinclair DA, Mattson MP, Fang EF. NAD+ in Brain Aging and Neurodegenerative Disorders. Cell Metab. 2019;30(4):630-655. doi:10.1016/j.cmet.2019.09.001
- Fang EF, Lautrup S, Hou Y, et al. NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med. 2017;23(10):899-916. doi:10.1016/j.molmed.2017.08.001
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Dr. Erica Zelfand
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