The effects of NAD+ boosters on aged rodents have been described in the medical literature as “profound,” “dramatic,” and “remarkable,” but do they help people?
Can NAD+ Boosters Increase Lifespan and Healthspan?
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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
The effects of NAD+ boosters on aged rodents have been described in the medical literature as “profound,” “dramatic”…“remarkable….” Treated mice had increased physical activity, improved vision, and strengthened bones, while delaying or preventing muscle loss, hearing loss, cognitive decline, and ovarian aging. Benefits to nearly every organ system have been documented, including improved artery function, brain function, heart function, immune function, kidney function, liver function, and muscle function. For example, a single week of an NAD+ booster was sufficient to restore key markers of muscle health in a 22-month-old mouse to levels similar to that of a six-month-old mouse. That’s roughly the equivalent of reverting the muscle health of a 70-year-old person back to when they were just 20.
NAD+ boosters can also extend the lifespans of animals, presumed to be due to the elevation of sirtuin activity dependent on NAD+. This longevity effect was first demonstrated more than 20 years ago in yeast cells. An overexpression of the genes involved in NAD+ synthesis extended replicative lifespans by as much as 60 percent. In the microscopic worm C. elegans, NAD+ boosting compounds have been shown to extend lifespans by up to 16 percent. In mice, one NAD+ booster was able to extend lifespan by a more modest five percent––but this was accomplished even when supplementation was started late in life, which is unusual for longevity treatments. No wonder people are excited about all manner of NAD+ boosting supplements. The big question is: do any of these healthspan or lifespan effects translate to benefitting humans?
There are four major NAD+ boosting supplements on the market these days: nicotinic acid (NA), also known as niacin, nicotinamide (NAM), also known as niacinamide, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). NAD+ can also be given directly, as well as its hydrogenated form, NADH. There are also hydrogenated forms of NMN and NR, also known as dihydronicotinamide riboside. So, there is quite the alphabet soup: NA, NAM, NMN, NR, NAD, NADH, NMNH, and NRH. The body can also make NAD+ “from scratch” from the amino acid tryptophan.
Given the critical nature of NAD+, it is perhaps unsurprising that the body has so many different pathways utilizing a panoply of precursors.
Converting tryptophan to NAD+ requires eight steps, whereas NA, NAM, and NR can be turned into NAD+ in only two or three steps. NMN is a direct precursor of NAD+, but when NMN or NR is taken orally, it appears to just turn into NA or NAM, via rapid degradation in the bloodstream or active conversion in the liver. So, why take the more expensive NMN or NR if it’s just going to end up as NA or NAM? Bought in bulk, NA or NAM would just cost pennies a day, versus more like a dollar a day for NR or NMN. That would add up to hundreds of dollars a year for NR or NMN, compared to closer to only five bucks for a whole year’s worth of NA or NAM. But cost aside, what are the risks and benefits of all these NAD boosters? That’s exactly what I’ll cover, next.
Please consider volunteering to help out on the site.
- Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 2018;27(3):529-547.
- Mills KF, Yoshida S, Stein LR, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016;24(6):795-806.
- Fang EF, Lautrup S, Hou Y, et al. NAD+ in aging: molecular mechanisms and translational implications. Trends Mol Med. 2017;23(10):899-916.
- Yang Q, Cong L, Wang Y, et al. Increasing ovarian NAD+ levels improve mitochondrial functions and reverse ovarian aging. Free Radic Biol Med. 2020;156:1-10.
- Mendelsohn AR, Larrick JW. Partial reversal of skeletal muscle aging by restoration of normal NAD + levels. Rejuvenation Res. 2014;17(1):62-69.
- de Picciotto NE, Gano LB, Johnson LC, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522-530.
- Yao Z, Yang W, Gao Z, Jia P. Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Neurosci Lett. 2017;647:133-140.
- Tong D, Schiattarella GG, Jiang N, et al. NAD+ repletion reverses heart failure with preserved ejection fraction. Circ Res. 2021;128(11):1629-1641.
- Takeda K, Okumura K. Nicotinamide mononucleotide augments the cytotoxic activity of natural killer cells in young and elderly mice. Biomed Res. 2021;42(5):173-179.
- Tran MT, Zsengeller ZK, Berg AH, et al. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature. 2016;531(7595):528-532.
- Mukherjee S, Chellappa K, Moffitt A, et al. Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration. Hepatology. 2017;65(2):616-630.
- Chi Y, Sauve AA. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 2013;16(6):657-661.
- Gomes AP, Price NL, Ling AJY, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624-1638.
- Dutta S, Sengupta P. Men and mice: Relating their ages. Life Sci. 2016;152:244-248.
- Giblin W, Skinner ME, Lombard DB. Sirtuins: guardians of mammalian healthspan. Trends Genet. 2014;30(7):271-286.
- Anderson RM, Bitterman KJ, Wood JG, et al. Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J Biol Chem. 2002;277(21):18881-18890.
- Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154(2):430-441.
- 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(6292):1436-1443.
- Conlon N, Ford D. A systems-approach to NAD+ restoration. Biochem Pharmacol. 2022;198:114946.
- Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr. 2008;28:115-130.
- Liu L, Su X, Quinn WJ, et al. Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metab. 2018;27(5):1067-1080.e5.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
The effects of NAD+ boosters on aged rodents have been described in the medical literature as “profound,” “dramatic”…“remarkable….” Treated mice had increased physical activity, improved vision, and strengthened bones, while delaying or preventing muscle loss, hearing loss, cognitive decline, and ovarian aging. Benefits to nearly every organ system have been documented, including improved artery function, brain function, heart function, immune function, kidney function, liver function, and muscle function. For example, a single week of an NAD+ booster was sufficient to restore key markers of muscle health in a 22-month-old mouse to levels similar to that of a six-month-old mouse. That’s roughly the equivalent of reverting the muscle health of a 70-year-old person back to when they were just 20.
NAD+ boosters can also extend the lifespans of animals, presumed to be due to the elevation of sirtuin activity dependent on NAD+. This longevity effect was first demonstrated more than 20 years ago in yeast cells. An overexpression of the genes involved in NAD+ synthesis extended replicative lifespans by as much as 60 percent. In the microscopic worm C. elegans, NAD+ boosting compounds have been shown to extend lifespans by up to 16 percent. In mice, one NAD+ booster was able to extend lifespan by a more modest five percent––but this was accomplished even when supplementation was started late in life, which is unusual for longevity treatments. No wonder people are excited about all manner of NAD+ boosting supplements. The big question is: do any of these healthspan or lifespan effects translate to benefitting humans?
There are four major NAD+ boosting supplements on the market these days: nicotinic acid (NA), also known as niacin, nicotinamide (NAM), also known as niacinamide, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). NAD+ can also be given directly, as well as its hydrogenated form, NADH. There are also hydrogenated forms of NMN and NR, also known as dihydronicotinamide riboside. So, there is quite the alphabet soup: NA, NAM, NMN, NR, NAD, NADH, NMNH, and NRH. The body can also make NAD+ “from scratch” from the amino acid tryptophan.
Given the critical nature of NAD+, it is perhaps unsurprising that the body has so many different pathways utilizing a panoply of precursors.
Converting tryptophan to NAD+ requires eight steps, whereas NA, NAM, and NR can be turned into NAD+ in only two or three steps. NMN is a direct precursor of NAD+, but when NMN or NR is taken orally, it appears to just turn into NA or NAM, via rapid degradation in the bloodstream or active conversion in the liver. So, why take the more expensive NMN or NR if it’s just going to end up as NA or NAM? Bought in bulk, NA or NAM would just cost pennies a day, versus more like a dollar a day for NR or NMN. That would add up to hundreds of dollars a year for NR or NMN, compared to closer to only five bucks for a whole year’s worth of NA or NAM. But cost aside, what are the risks and benefits of all these NAD boosters? That’s exactly what I’ll cover, next.
Please consider volunteering to help out on the site.
- Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 2018;27(3):529-547.
- Mills KF, Yoshida S, Stein LR, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016;24(6):795-806.
- Fang EF, Lautrup S, Hou Y, et al. NAD+ in aging: molecular mechanisms and translational implications. Trends Mol Med. 2017;23(10):899-916.
- Yang Q, Cong L, Wang Y, et al. Increasing ovarian NAD+ levels improve mitochondrial functions and reverse ovarian aging. Free Radic Biol Med. 2020;156:1-10.
- Mendelsohn AR, Larrick JW. Partial reversal of skeletal muscle aging by restoration of normal NAD + levels. Rejuvenation Res. 2014;17(1):62-69.
- de Picciotto NE, Gano LB, Johnson LC, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522-530.
- Yao Z, Yang W, Gao Z, Jia P. Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Neurosci Lett. 2017;647:133-140.
- Tong D, Schiattarella GG, Jiang N, et al. NAD+ repletion reverses heart failure with preserved ejection fraction. Circ Res. 2021;128(11):1629-1641.
- Takeda K, Okumura K. Nicotinamide mononucleotide augments the cytotoxic activity of natural killer cells in young and elderly mice. Biomed Res. 2021;42(5):173-179.
- Tran MT, Zsengeller ZK, Berg AH, et al. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature. 2016;531(7595):528-532.
- Mukherjee S, Chellappa K, Moffitt A, et al. Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration. Hepatology. 2017;65(2):616-630.
- Chi Y, Sauve AA. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 2013;16(6):657-661.
- Gomes AP, Price NL, Ling AJY, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624-1638.
- Dutta S, Sengupta P. Men and mice: Relating their ages. Life Sci. 2016;152:244-248.
- Giblin W, Skinner ME, Lombard DB. Sirtuins: guardians of mammalian healthspan. Trends Genet. 2014;30(7):271-286.
- Anderson RM, Bitterman KJ, Wood JG, et al. Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J Biol Chem. 2002;277(21):18881-18890.
- Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154(2):430-441.
- 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(6292):1436-1443.
- Conlon N, Ford D. A systems-approach to NAD+ restoration. Biochem Pharmacol. 2022;198:114946.
- Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr. 2008;28:115-130.
- Liu L, Su X, Quinn WJ, et al. Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metab. 2018;27(5):1067-1080.e5.
Motion graphics by Avo Media
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Title
Can NAD+ Boosters Increase Lifespan and Healthspan?
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
This is the second video in my NAD+ series. If you missed the first one, check out Do NAD+ Levels Decline with Age?. Stay tuned for:
- Risks and Benefits of Nicotinic Acid (NA), a NAD+ Booster
- Risks and Benefits of Nicotinamide (NAM), a NAD+ Booster
- Risks and Benefits of Nicotinamide Riboside (NR), a NAD+ Booster
- Risks and Benefits of Nicotinamide Mononucleotide (NMN), a NAD+ Booster
- Lesser-Known NAD+ Boosting Supplements—Tryptophan, NADH, NMNH, and NRH
- Risks of NAD+ Boosting Supplements
- Which NAD+ Booster Is Best?
- The Third Way to Boost NAD+
For more on aging, go to your local public library and check out my longevity book, How Not to Age, available in print, e-book, and audio. (All proceeds I receive from the book are donated directly to charity.)
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