NAD+ 101

What is NAD+?

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every living cell in the body. NAD+ helps convert food to energy, repair DNA, and protect critical organs. 

It plays a critical role by acting as a carrier for electrons within mitochondria, a cell component responsible for energy production.¹ NAD+ is involved in over 500 enzyme reactions in the body. 

What are the health benefits of NAD+?

• Anti-Aging
  • As you age, NAD levels in your body decline. NAD+ is the active form of NAD in the body. Research is ongoing to study whether supplementing NAD+ could improve age-related conditions and complications.² One animal study shows that NAD+ improves stem cell function and enhances lifespan in mice.³

• Metabolic Health‍
  • NAD+ is believed to be involved in aiding your body’s ability to regulate blood sugar levels, insulin production and release, cholesterol levels, and other functions.⁴ A study found that NAD+ supplementation may increase a body’s capacity to exercise.

• Brain and Cognitive Health‍
  • Studies have shown that NAD+ supplements may affect cerebral blood flow in the brain. These findings may have implications for the treatment of Alzheimer’s disease or mild cognitive impairment.⁵ Low-dose NAD+ supplement may also improve fatigue symptoms in patients after a COVID-19 infection.⁶

• Skin Health‍
  • NAD+ has the ability to help your body repair DNA. That regenerative property could include repairing UV-damage to your skin. Using topical formulations of NAD+ could improve symptoms of psoriasis or other skin conditions.⁷

• Eye Health‍
  • NAD+ plays a critical role in the health of the eye. It can aid in the prevention of retinal nerve damage. NAD+ levels could play a critical role in the management of eye conditions such as glaucoma or age-related macular degeneration.⁸

• Immune Booster and Anti-Inflammatory Agent‍
  • NAD+ supplementation may be effective at supporting immune health and reducing inflammation. This study showed that during periods of inflammation and activation of the immune system, NAD+ levels declined in the body.⁹ More research is needed to determine if NAD+ supplements could be effective as an immune support and anti-inflammatory product. 

Who should consider taking NAD+ supplements?

• Elderly‍
  • The anti-aging properties of NAD+ are appealing to anyone interested in taking supplements that may counteract the decline in function seen as we get older. NAD+ can promote several antioxidant functions that can prevent cell damage and decay.

• Cognitive Impaired Patients‍
  • Patients with cognitive impairment may benefit from NAD+ supplements. Based on studies, NAD+ may improve symptoms due to anti-oxidant and anti-inflammatory effects.¹⁰

• Skin and Eye Health‍
  • Anyone interested in maintaining eye health or preventing sun UV radiation skin damage should consider NAD+ supplements. Further studies are needed to discover the exact mechanisms involved in the eye and skin health benefits of NAD+. 

Should NAD+ supplements be a part of a weight loss program?

Studies have shown that NAD+ supplementation is safe and well-tolerated with low levels of side effects.¹¹ Dosage forms may be dependent on the intended benefit or health condition being treated.

One study showed that NAD+ supplementation increased insulin sensitivity and remodeling in muscle tissue of postmenopausal women. Those women were either prediabetic or overweight.¹²

One study did show that NAD+ may enhance oxidative metabolism and protect against obesity resulting from a high-fat diet.¹³ More studies are needed to confirm that NAD+ supplements are a beneficial addition to a weight-loss program. Ask your healthcare provider if NAD+ is right for your individual goals and treatment program. 

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Resources

¹ Amjad S, Nisar S, Bhat AA, Shah AR, Frenneaux MP, Fakhro K, Haris M, Reddy R, Patay Z, Baur J, Bagga P. Role of NAD+ in regulating cellular and metabolic signaling pathways. Mol Metab. 2021 Jul;49:101195. doi: 10.1016/j.molmet.2021.101195. Epub 2021 Feb 17. PMID: 33609766; PMCID: PMC7973386.

² Palmer RD, Elnashar MM, Vaccarezza M. Precursor comparisons for the upregulation of nicotinamide adenine dinucleotide. Novel approaches for better aging. Aging Med (Milton). 2021 Aug 4;4(3):214-220. doi: 10.1002/agm2.12170. PMID: 34553119; PMCID: PMC8444956.

³ Zhang H, Ryu D, Wu Y, et al.. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352:1436–1443.

⁴ Munk SHN, Merchut-Maya JM, Adelantado Rubio A, Hall A, Pappas G, Milletti G, Lee M, Johnsen LG, Guldberg P, Bartek J, Maya-Mendoza A. NAD+ regulates nucleotide metabolism and genomic DNA replication. Nat Cell Biol. 2023 Dec;25(12):1774-1786. doi: 10.1038/s41556-023-01280-z. Epub 2023 Nov 13. PMID: 37957325; PMCID: PMC10709141.

⁵ Orr ME, Kotkowski E, Ramirez P, Bair-Kelps D, Liu Q, Brenner C, Schmidt MS, Fox PT, Larbi A, Tan C, Wong G, Gelfond J, Frost B, Espinoza S, Musi N, Powers B. A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. Geroscience. 2024 Feb;46(1):665-682. doi: 10.1007/s11357-023-00999-9. Epub 2023 Nov 23. PMID: 37994989; PMCID: PMC10828186.

⁶ Isman A, Nyquist A, Strecker B, et al. Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19. Brain, Behavior, & Immunity - Health. Published online February 1, 2024:100733. doi:https://doi.org/10.1016/j.bbih.2024.100733

⁷ Wozniacka A, Szajerski P, Adamus J, Gebicki J, Sysa-Jedrzejowska A. In Search for New Antipsoriatic Agents: NAD+ Topical Composition. Skin Pharmacol Physiol. 2006;20(1):37-42. doi:https://doi.org/10.1159/000096170.

⁸ Jadeja RN, Thounaojam MC, Bartoli M, Martin PM. Implications of NAD+ Metabolism in the Aging Retina and Retinal Degeneration. Oxid Med Cell Longev. 2020;2020:1-12. doi:https://doi.org/10.1155/2020/2692794.

⁹ Idoine R, Kwon J, Ishtiaq Y, Rosene M, Shao A, Nkrumah-Elie Y. Impact of Boosting NAD on Immune Function: Results From NR Preclinical Studies. Curr Dev Nutr. 2022 Jun 14;6(Suppl 1):983. doi: 10.1093/cdn/nzac068.012. PMCID: PMC9194018.

¹⁰ Zhao Y, Zhang J, Zheng Y, Zhang Y, Zhang XJ, Wang H, Du Y, Guan J, Wang X, Fu J. NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway. J Neuroinflammation. 2021 Sep 16;18(1):207. doi: 10.1186/s12974-021-02250-8. PMID: 34530866; PMCID: PMC8444613.

¹¹ Gindri IM, Ferrari G, Pinto LPS, Bicca J, Dos Santos IK, Dallacosta D, Roesler CRM. Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review. Am J Physiol Endocrinol Metab. 2024 Apr 1;326(4):E417-E427. doi: 10.1152/ajpendo.00242.2023. Epub 2023 Nov 16. PMID: 37971292.

¹² Mihoko Yoshino et al. ,Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 372,1224-1229(2021).DOI:10.1126/science.abe9985

¹³ Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022. PMID: 22682224; PMCID: PMC3616313.

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