You can naturally get your body to make more NAD+ by boosting the NAD+ synthesizing enzyme NAMPT.
Which NAD+ Booster Is Best?
4.2/5 - (29 votes)
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.
So, which NAD+ boosting supplement is best? There’s no clear standout, as hardly any of the preclinical effects found in the lab have translated into evidence of human clinical benefit. Perhaps this failure is to be expected, given the complexity of NAD+ physiology with its juggling of multiple precursors, production pathways, and recycling routes. The bottom line is that it’s just too early to say if NAD+ booster supplementation will ever live up to even a fraction of the hype. Many more, larger, and longer-term studies are necessary to establish safety and efficacy.
The problem is that because NA, NAM, NR, and NMN are all natural products, they can’t be patented; so, the money for well-designed clinical trials is not as available. The reason there have been comparatively more trials done on NR than NMN is that patents were originally issued for NR before being invalidated as unpatentable.
Perhaps blindly overloading the system with NAD+ precursors is not the best way to go about NAD+ restoration. The body seems too smart to allow such blunt incursion to affect tissue levels. Maybe these supplements are just profit-making distractions from more natural approaches.
Broadly, there are three main ways to increase NAD+ levels. Increasing the supply of NAD+ precursors is just the first. The other two are having the body make more, by activating NAD+ synthesizing enzymes, or have the body use less, via an inhibition of excess NAD+ degradation. The primary determinant of NAD+ synthesis is the enzyme NAMPT. An abundance of NAMPT tends to decrease with age in human muscle, dropping steadily by about 40 percent between the ages of 20 and 80. In our liver, it drops by half. However, age-related diseases, such as atherosclerosis, cancer, diabetes, and rheumatoid arthritis, have been found to exacerbate NAMPT decline, raising a chicken-or-the-egg question. There’s where interventional trials come in.
Similar NAMPT declines have been noted in aging rats and mice. Does boosting NAMPT help? Increasing NAMPT or its species equivalent increases the lifespans of yeast, fruit flies, and rodents. An NAMPT boost also increases aerobic capacity and exercise endurance in mice, in addition to helping them live longer.
Enhanced expression of NAMPT increases the NAD+ levels in the muscles in mice comparable to feeding them dietary NAD+ precursors. But if you remember, NAD+ precursors don’t seem to able to affect NAD+ muscle levels in most people. In fact, such supplements can actually suppress NAMPT, while boosting that methylating enzyme to rid the body of the excess. In addition to methyl depletion, chronic administration of these supplements could potentially then leave people worse off should they ever stop them.
There is, however, a way to naturally boost NAMPT and NAD+ levels in humans without any supplements: exercise. Athletes have about twice the NAMPT expression in their musculature compared to sedentary individuals. To prove cause and effect, sedentary men and women started a stationary bike exercise protocol, and within three weeks, NAMPT levels increased by 127 percent. Resistance training can also increase NAMPT, and this can also translate into a 127 percent increase in muscle NAD+ levels and a rise in sirtuin activity. In other words, exercise can do what NAD+ boosting supplements can’t.
Please consider volunteering to help out on the site.
- Chini EN. Of mice and men: NAD+ boosting with niacin provides hope for mitochondrial myopathy patients. Cell Metab. 2020;31(6):1041-1043.
- Conlon N, Ford D. A systems-approach to NAD+ restoration. Biochem Pharmacol. 2022;198:114946.
- McReynolds MR, Chellappa K, Baur JA. Age-related NAD+ decline. Exp Gerontol. 2020;134:110888.
- Katsyuba E, Romani M, Hofer D, Auwerx J. NAD+ homeostasis in health and disease. Nat Metab. 2020;2(1):9-31.
- ChromaDex, Inc. v. Elysium Health, Inc., 2022-1116, (Fed. Cir. Feb. 13, 2023).
- Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 2018;27(3):529-547.
- de Guia RM, Agerholm M, Nielsen TS, et al. Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiol Rep. 2019;7(12):e14139.
- Zhou CC, Yang X, Hua X, et al. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol. 2016;173(15):2352-2368.
- Koltai E, Szabo Z, Atalay M, et al. Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats. Mech Ageing Dev. 2010;131(1):21-28.
- Liu LY, Wang F, Zhang XY, et al. Nicotinamide phosphoribosyltransferase may be involved in age-related brain diseases. PLoS One. 2012;7(10):e44933.
- Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature. 2003;423(6936):181-185.
- Balan V, Miller GS, Kaplun L, et al. Life span extension and neuronal cell protection by Drosophila nicotinamidase. J Biol Chem. 2008;283(41):27810-27819.
- Yoshida M, Satoh A, Lin JB, et al. Extracellular vesicle-contained enampt delays aging and extends lifespan in mice. Cell Metab. 2019;30(2):329-342.e5.
- Brouwers B, Stephens NA, Costford SR, et al. Elevated nicotinamide phosphoribosyl transferase in skeletal muscle augments exercise performance and mitochondrial respiratory capacity following exercise training. Front Physiol. 2018;9:704.
- Costford SR, Brouwers B, Hopf ME, et al. Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance. Mol Metab. 2018;7:1-11.
- Frederick DW, Davis JG, Dávila A, et al. Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism. J Biol Chem. 2015;290(3):1546-1558.
- Okabe K, Yaku K, Uchida Y, et al. Oral administration of nicotinamide mononucleotide is safe and efficiently increases blood nicotinamide adenine dinucleotide levels in healthy subjects. Front Nutr. 2022;9:868640.
- Dollerup OL, Chubanava S, Agerholm M, et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. J Physiol. 2020;598(4):731-754.
- Costford SR, Bajpeyi S, Pasarica M, et al. Skeletal muscle NAMPT is induced by exercise in humans. Am J Physiol Endocrinol Metab. 2010;298(1):E117-126.
- Lamb DA, Moore JH, Mesquita PHC, et al. Resistance training increases muscle NAD+ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals. Aging (Albany NY). 2020;12(10):9447-9460.
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.
So, which NAD+ boosting supplement is best? There’s no clear standout, as hardly any of the preclinical effects found in the lab have translated into evidence of human clinical benefit. Perhaps this failure is to be expected, given the complexity of NAD+ physiology with its juggling of multiple precursors, production pathways, and recycling routes. The bottom line is that it’s just too early to say if NAD+ booster supplementation will ever live up to even a fraction of the hype. Many more, larger, and longer-term studies are necessary to establish safety and efficacy.
The problem is that because NA, NAM, NR, and NMN are all natural products, they can’t be patented; so, the money for well-designed clinical trials is not as available. The reason there have been comparatively more trials done on NR than NMN is that patents were originally issued for NR before being invalidated as unpatentable.
Perhaps blindly overloading the system with NAD+ precursors is not the best way to go about NAD+ restoration. The body seems too smart to allow such blunt incursion to affect tissue levels. Maybe these supplements are just profit-making distractions from more natural approaches.
Broadly, there are three main ways to increase NAD+ levels. Increasing the supply of NAD+ precursors is just the first. The other two are having the body make more, by activating NAD+ synthesizing enzymes, or have the body use less, via an inhibition of excess NAD+ degradation. The primary determinant of NAD+ synthesis is the enzyme NAMPT. An abundance of NAMPT tends to decrease with age in human muscle, dropping steadily by about 40 percent between the ages of 20 and 80. In our liver, it drops by half. However, age-related diseases, such as atherosclerosis, cancer, diabetes, and rheumatoid arthritis, have been found to exacerbate NAMPT decline, raising a chicken-or-the-egg question. There’s where interventional trials come in.
Similar NAMPT declines have been noted in aging rats and mice. Does boosting NAMPT help? Increasing NAMPT or its species equivalent increases the lifespans of yeast, fruit flies, and rodents. An NAMPT boost also increases aerobic capacity and exercise endurance in mice, in addition to helping them live longer.
Enhanced expression of NAMPT increases the NAD+ levels in the muscles in mice comparable to feeding them dietary NAD+ precursors. But if you remember, NAD+ precursors don’t seem to able to affect NAD+ muscle levels in most people. In fact, such supplements can actually suppress NAMPT, while boosting that methylating enzyme to rid the body of the excess. In addition to methyl depletion, chronic administration of these supplements could potentially then leave people worse off should they ever stop them.
There is, however, a way to naturally boost NAMPT and NAD+ levels in humans without any supplements: exercise. Athletes have about twice the NAMPT expression in their musculature compared to sedentary individuals. To prove cause and effect, sedentary men and women started a stationary bike exercise protocol, and within three weeks, NAMPT levels increased by 127 percent. Resistance training can also increase NAMPT, and this can also translate into a 127 percent increase in muscle NAD+ levels and a rise in sirtuin activity. In other words, exercise can do what NAD+ boosting supplements can’t.
Please consider volunteering to help out on the site.
- Chini EN. Of mice and men: NAD+ boosting with niacin provides hope for mitochondrial myopathy patients. Cell Metab. 2020;31(6):1041-1043.
- Conlon N, Ford D. A systems-approach to NAD+ restoration. Biochem Pharmacol. 2022;198:114946.
- McReynolds MR, Chellappa K, Baur JA. Age-related NAD+ decline. Exp Gerontol. 2020;134:110888.
- Katsyuba E, Romani M, Hofer D, Auwerx J. NAD+ homeostasis in health and disease. Nat Metab. 2020;2(1):9-31.
- ChromaDex, Inc. v. Elysium Health, Inc., 2022-1116, (Fed. Cir. Feb. 13, 2023).
- Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 2018;27(3):529-547.
- de Guia RM, Agerholm M, Nielsen TS, et al. Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiol Rep. 2019;7(12):e14139.
- Zhou CC, Yang X, Hua X, et al. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol. 2016;173(15):2352-2368.
- Koltai E, Szabo Z, Atalay M, et al. Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats. Mech Ageing Dev. 2010;131(1):21-28.
- Liu LY, Wang F, Zhang XY, et al. Nicotinamide phosphoribosyltransferase may be involved in age-related brain diseases. PLoS One. 2012;7(10):e44933.
- Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature. 2003;423(6936):181-185.
- Balan V, Miller GS, Kaplun L, et al. Life span extension and neuronal cell protection by Drosophila nicotinamidase. J Biol Chem. 2008;283(41):27810-27819.
- Yoshida M, Satoh A, Lin JB, et al. Extracellular vesicle-contained enampt delays aging and extends lifespan in mice. Cell Metab. 2019;30(2):329-342.e5.
- Brouwers B, Stephens NA, Costford SR, et al. Elevated nicotinamide phosphoribosyl transferase in skeletal muscle augments exercise performance and mitochondrial respiratory capacity following exercise training. Front Physiol. 2018;9:704.
- Costford SR, Brouwers B, Hopf ME, et al. Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance. Mol Metab. 2018;7:1-11.
- Frederick DW, Davis JG, Dávila A, et al. Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism. J Biol Chem. 2015;290(3):1546-1558.
- Okabe K, Yaku K, Uchida Y, et al. Oral administration of nicotinamide mononucleotide is safe and efficiently increases blood nicotinamide adenine dinucleotide levels in healthy subjects. Front Nutr. 2022;9:868640.
- Dollerup OL, Chubanava S, Agerholm M, et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. J Physiol. 2020;598(4):731-754.
- Costford SR, Bajpeyi S, Pasarica M, et al. Skeletal muscle NAMPT is induced by exercise in humans. Am J Physiol Endocrinol Metab. 2010;298(1):E117-126.
- Lamb DA, Moore JH, Mesquita PHC, et al. Resistance training increases muscle NAD+ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals. Aging (Albany NY). 2020;12(10):9447-9460.
Motion graphics by Avo Media
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Title
Which NAD+ Booster Is Best?
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
This is the second-to-last video in my NAD+ series. If you missed any of the previous ones, check out:
- Do NAD+ Levels Decline with Age?
- Can NAD+ Boosters Increase Lifespan and Healthspan?
- 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
Stay tuned for 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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