Who Should Not Take An NAD⁺ Supplement?

NAD+ declines with age and with metabolic disorders like obesity, so young and healthy individuals may not benefit from NAD+ boosting supplements.

By Griffin Dean

Key Points: 

  • NAD+ declines with age and contributes to chronic age-related diseases like heart disease, neurodegenerative disease, and diabetes. 
  • NAD+ can be replenished with precursor supplements like NMN and NR, or diet and exercise. 
  • Individuals below the age of 32, those who are not overweight or obese, and those who do not suffer from addiction, anxiety, or depression may not benefit from supplementing with NAD+ precursors. 

In recent years, NAD+ has seen a rise in popularity with scientists like Dr. David Sinclair touting its anti-aging benefits. Contributing to this popularity is a rise in scientific research revealing the underlying causes of aging, which includes a decline in NAD+

What is NAD+?

Nicotinamide adenine dinucleotide (NAD+) is a naturally occurring molecule necessary for life. Each of our cells depend on NAD+ to function and survive. It participates in key cellular processes like energy production, DNA repair, and enzyme reactions (as a coenzyme). 

Chemical structure of NAD (Nicotinamide Adenine Dinucleotide).
NAD+ Chemical Structure.

NADH is the reduced form of NAD+, meaning it has an extra negatively charged electron (and a hydrogen atom, denoted by “H”). In contrast, NAD+ is the oxidized form of NADH, meaning it has lost an electron (and hydrogen). Thus, relative to NADH, NAD+ has a positive charge, represented by a plus sign. 

Carrying electrons is one of the major roles of NAD+. When we eat food, proteins, fats, and sugars are broken down in our cells, and electrons are released. NAD+ captures these electrons and carries them to a structure within our mitochondria that leads to cellular energy (ATP) production. 

NAD+ and Aging 

NAD+ declines with aging in humans, including in the skin, brain, and liver, as well as in immune cells. Age-related NAD+ decline may be due to decreased NAD+ synthesis  and increased NAD+ breakdown from chronic inflammation, or other age-related conditions. 

Measurement of NAD+ levels in skin samples across various age groups, from newborns to adults up to the age of 77, indicating age-dependent NAD+ decline.
(Massudi et al., 2012 | PLOS ONE) Age-Dependent NAD+ Decline. NAD+ levels were measured from the skin samples of newborns and adults up to the age of 77.

There are several chronic diseases for which age is the primary risk factor, including heart disease, neurodegenerative disease, cancer, and diabetes. Many of these diseases are associated with high mortality rates and may shorten the lifespan of individuals who otherwise would have lived longer. These chronic diseases are referred to as age-related diseases. 

Scientists have begun to identify the processes that underlie age-related diseases, including DNA damage, mitochondrial dysfunction, and chronic inflammation. Remarkably, deficits in NAD+ metabolism are involved in nearly all of these processes. Therefore, replenishing NAD+ could counter age-related diseases and potentially extend human lifespan.  

How to Increase NAD+ Levels 

Because of its promising benefits, boosting NAD+ has become highly sought after, and some would say overhyped within certain sectors, such as the health, tech, and longevity communities. For this reason, many NAD+ boosting products have exploded onto the market, many of which are backed by little to no quality scientific evidence. 

Essentially only two categories of NAD+ boosting methods are supported by surmounting peer-reviewed literature: NAD+ precursors and healthy lifestyle choices. NAD+ intravenous (IV) therapy deserves an honorable mention based mostly on anecdotal evidence. However, this method is rather invasive, requiring being stuck with a needle. 

NAD+ Precursors 

NAD+ precursors occur naturally within our cells but can be taken in supplement form to boost NAD+ levels. When supplemented, these molecules are metabolized into NAD+ upon entering our cells, effectively increasing intracellular NAD+ levels. 

Most NAD+ precursors are different forms of vitamin B3, and include niacin (a.k.a. nicotinic acid), nicotinamide, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). Tryptophan, which is an amino acid, is also a precursor but does not increase NAD+ levels to the same extent as other precursors. 

Of the precursors, only NR and NMN have more than a handful of studies testing their age-related effects on humans. Namely, in older, but not younger adults NR has been shown to improve exercise performance. Additionally, in obese adults, NR has been shown to improve body composition. Besides these studies and other studies that combined NR with other compounds, NR has shown little positive results in humans. 

On the other hand, NMN studies have had more positive results. NMN has been shown to improve physical performance and sleep qualitystrength and walking speedinsulin sensitivity, and skin aging, as well as cholesterol levels, blood pressure, and weight. This is in addition to the many animal studies showing that NMN reverses aspects of age-related diseases, including cardiovascular disease and neurodegenerative disease

Visualization of the process of increasing NAD+ levels and its associated anti-aging benefits.
(Rajman et al., 2018 | Cell Metabolism) Increasing NAD+ and Its Anti-Aging Benefits.

Increasing NAD+ Naturally 

Diet and exercise have always been nature’s medicine. Caloric restriction (CR) — reducing caloric intake by 25-60% — has been shown to increase the lifespan of animals, including monkeys. CR, along with eating habits like avoiding high-fat and high-sugar foods stimulate increases in NAD+ levels. Furthermore, physical activity, including aerobic exercise and resistance training also boosts NAD+ levels. 

Side Effects of Boosting NAD+ with Supplements

Human clinical studies of multiple NAD+ precursors, including niacin, nicotinamide, NR, and NMN have demonstrated that boosting NAD+ with these supplements is safe within recommended dosages. However, cellular NAD+ homeostasis is complex, and altering NAD+ levels can have anti-cancer or pro-cancer effects. For example, niacin, NR, and nicotinamide have been shown to have anti-cancer effects. And hypothetically, boosting NAD+ could enhance the survival and function of existing cancer cells, as it does with most cells. 

Niacin, specifically, is known to cause flushing of the skin. However, there are now non-flush niacin products available. Niacin and the other NAD+ precursors share similar side effects, including nausea, vomiting, and diarrhea in some individuals

Who Should Take An NAD+ Supplement?

Whether or not to take an NAD+ supplement largely depends on age. With age, our NAD+ levels decline, leading to a myriad of cellular defects that lead to chronic disease. However, a poor diet and lack of exercise can also lead to cellular metabolic defects, including diminished NAD+ levels. 

While there are no human studies that have directly tested at what age to begin taking NAD+ supplements (precursors), current studies would suggest beginning NAD+ supplementation around midlife, as early as the age of 32. Additionally, individuals who are overweight or obese could also benefit from NAD+ supplements. 

Additionally, while mostly anecdotal evidence exists, there are studies showing that boosting NAD+ can alleviate anxiety, depression, and cravings from addiction. Therefore, individuals with adverse mood-dependent behavioral issues may also benefit from NAD+ supplementation, regardless of age or weight. However, more studies are needed to confirm this.  

In contrast, those who do not have low NAD+ levels, such as healthy-weight individuals under the age of 32 are not likely to benefit from NAD+ supplements.


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.

Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357. Epub 2012 Jul 27. PMID: 22848760; PMCID: PMC3407129.

Zhu XH, Lu M, Lee BY, Ugurbil K, Chen W. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2876-81. doi: 10.1073/pnas.1417921112. Epub 2015 Feb 17. PMID: 25730862; PMCID: PMC4352772.

Zhou CC, Yang X, Hua X, Liu J, Fan MB, Li GQ, Song J, Xu TY, Li ZY, Guan YF, Wang P, Miao CY. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol. 2016 Aug;173(15):2352-68. doi: 10.1111/bph.13513. Epub 2016 Jun 27. PMID: 27174364; PMCID: PMC4945761.

Minhas PS, Liu L, Moon PK, Joshi AU, Dove C, Mhatre S, Contrepois K, Wang Q, Lee BA, Coronado M, Bernstein D, Snyder MP, Migaud M, Majeti R, Mochly-Rosen D, Rabinowitz JD, Andreasson KI. Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation. Nat Immunol. 2019 Jan;20(1):50-63. doi: 10.1038/s41590-018-0255-3. Epub 2018 Nov 26. PMID: 30478397; PMCID: PMC6768398.

Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011 Oct 5;14(4):528-36. doi: 10.1016/j.cmet.2011.08.014. PMID: 21982712; PMCID: PMC3204926.

Tirumurugaan KG, Jude JA, Kang BN, Panettieri RA, Walseth TF, Kannan MS. TNF-alpha induced CD38 expression in human airway smooth muscle cells: role of MAP kinases and transcription factors NF-kappaB and AP-1. Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1385-95. doi: 10.1152/ajplung.00472.2006. Epub 2007 Feb 23. PMID: 17322278.

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3. PMID: 36599349.

Aman, Y., Qiu, Y., Tao, J., & Fang, E. F. (2018). Therapeutic potential of boosting NAD+ in aging and age-related diseases. Translational Medicine of Aging, 2, 30-37.

Dolopikou CF, Kourtzidis IA, Margaritelis NV, Vrabas IS, Koidou I, Kyparos A, Theodorou AA, Paschalis V, Nikolaidis MG. Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Eur J Nutr. 2020 Mar;59(2):505-515. doi: 10.1007/s00394-019-01919-4. Epub 2019 Feb 6. PMID: 30725213.

Remie CME, Roumans KHM, Moonen MPB, Connell NJ, Havekes B, Mevenkamp J, Lindeboom L, de Wit VHW, van de Weijer T, Aarts SABM, Lutgens E, Schomakers BV, Elfrink HL, Zapata-Pérez R, Houtkooper RH, Auwerx J, Hoeks J, Schrauwen-Hinderling VB, Phielix E, Schrauwen P. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. Am J Clin Nutr. 2020 Aug 1;112(2):413-426. doi: 10.1093/ajcn/nqaa072. PMID: 32320006; PMCID: PMC7398770.

Kim M, Seol J, Sato T, Fukamizu Y, Sakurai T, Okura T. Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Nutrients. 2022 Feb 11;14(4):755. doi: 10.3390/nu14040755. PMID: 35215405; PMCID: PMC8877443.

Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, Sekine R, Fukamizu Y, Sato T, Sakurai T, Sato J, Ino K, Kubota N, Nakagawa T, Kadowaki T, Yamauchi T. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. NPJ Aging. 2022 May 1;8(1):5. doi: 10.1038/s41514-022-00084-z. PMID: 35927255; PMCID: PMC9158788.

Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021 Jun 11;372(6547):1224-1229. doi: 10.1126/science.abe9985. Epub 2021 Apr 22. PMID: 33888596; PMCID: PMC8550608.

Morita, Y., Izawa, H., Hirano, A., Mayumi, E., Isozaki, S., & Yonei, Y. Clinical evaluation of changes in biomarkers by oral intake of NMN. Glycative Stress Research. June, 2022.

Pencina KM, Valderrabano R, Wipper B, Orkaby AR, Reid KF, Storer T, Lin AP, Merugumala S, Wilson L, Latham N, Ghattas-Puylara C, Ozimek NE, Cheng M, Bhargava A, Memish-Beleva Y, Lawney B, Lavu S, Swain PM, Apte RS, Sinclair DA, Livingston D, Bhasin S. Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. J Clin Endocrinol Metab. 2023 Jul 14;108(8):1968-1980. doi: 10.1210/clinem/dgad027. PMID: 36740954.

Zhang R, Shen Y, Zhou L, Sangwung P, Fujioka H, Zhang L, Liao X. Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure. J Mol Cell Cardiol. 2017 Nov;112:64-73. doi: 10.1016/j.yjmcc.2017.09.001. Epub 2017 Sep 5. PMID: 28882480; PMCID: PMC6257991.

Hu Y, Huang Y, Xing S, Chen C, Shen D, Chen J. Aβ promotes CD38 expression in senescent microglia in Alzheimer’s disease. Biol Res. 2022 Mar 3;55(1):10. doi: 10.1186/s40659-022-00379-1. PMID: 35241173; PMCID: PMC8892694.

Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018 Mar 6;27(3):529-547. doi: 10.1016/j.cmet.2018.02.011. PMID: 29514064; PMCID: PMC6342515.

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 Dec 12;2020:8819627. doi: 10.1155/2020/8819627. PMID: 33414897; PMCID: PMC7752291.

Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4. doi: 10.1126/science.1173635. PMID: 19590001; PMCID: PMC2812811.

Reiten OK, Wilvang MA, Mitchell SJ, Hu Z, Fang EF. Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing. Mech Ageing Dev. 2021 Oct;199:111567. doi: 10.1016/j.mad.2021.111567. Epub 2021 Sep 10. PMID: 34517020.

Kirkland JB. Niacin status and treatment-related leukemogenesis. Mol Cancer Ther. 2009 Apr;8(4):725-32. doi: 10.1158/1535-7163.MCT-09-0042. PMID: 19372544.

Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, LeBoeuf SE, Gay LJ, Yagi T, Felding-Habermann B. Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest. 2013 Mar;123(3):1068-81. doi: 10.1172/JCI64264. Epub 2013 Feb 15. PMID: 23426180; PMCID: PMC3582128.

Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DL. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015 Oct 22;373(17):1618-26. doi: 10.1056/NEJMoa1506197. PMID: 26488693.

Reiten OK, Wilvang MA, Mitchell SJ, Hu Z, Fang EF. Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing. Mech Ageing Dev. 2021 Oct;199:111567. doi: 10.1016/j.mad.2021.111567. Epub 2021 Sep 10. PMID: 34517020.

Poljšak B, Kovač V, Milisav I. Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies. Antioxidants (Basel). 2022 Aug 24;11(9):1637. doi: 10.3390/antiox11091637. PMID: 36139711; PMCID: PMC9495723.

Okabe K, Yaku K, Tobe K, Nakagawa T. Implications of altered NAD metabolism in metabolic disorders. J Biomed Sci. 2019 May 11;26(1):34. doi: 10.1186/s12929-019-0527-8. PMID: 31078136; PMCID: PMC6511662.

Blum K, Han D, Baron D, Kazmi S, Elman I, Gomez LL, Gondre-Lewis MC, Thanos PK, Braverman ER, Badgaiyan RD. Nicotinamide Adenine Dinucleotide (NAD+) and Enkephalinase Inhibition (IV1114589NAD) Infusions Significantly Attenuate Psychiatric Burden Sequalae in Substance Use Disorder (SUD) in Fifty Cases. Curr Psychiatry Res Rev. 2022 Jul;18(2):125-143. doi: 10.2174/2666082218666220527114427. Epub 2022 Jun 21. PMID: 36118157; PMCID: PMC9474872.

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