Do NAD+ Levels Decline with Age?

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What is NAD+ and what role does it play in the aging process?

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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.

NAD+ is an essential co-factor for hundreds of enzymes, including the purported anti-aging activities of sirtuins. In this ten-part series, I will go through the alphabet soup of NAD-boosting supplements on the market: NR, NMN, NA, NAM, NADH, NMNH, NRH, and tryptophan. I will then cover the pros and cons of each, and discuss three ways to naturally boost NAD levels without supplements.

Our understanding of nicotinamide adenine dinucleotide (NAD+) arose from humble beginnings as a factor noted to enhance yeast fermentation in a 1906 paper unassumingly entitled “The Alcoholic Ferment of Yeast-Juice.” Little did they know that waves of NAD-related discoveries would go on to yield a total of four Nobel Prizes. NAD+ is now known as an essential molecule for all living organisms, required for the function of about 500 enzymes, including, notably, the extraction of metabolic energy from food. The 21st century has produced yet another scientific renaissance for NAD+ with the realization that it was critical for the activity of sirtuins, the “guardians of mammalian healthspan” I detail in my book, How Not to Age.

NAD+ is one of the most abundant molecules in our body. Once considered relatively stable, it’s now known to be in a constant state of synthesis, recycling, and breakdown. The entire pool of NAD+ in some of our tissues is turned over several times a day. To maintain cellular vitality in the face of this turnover, an adequate supply of NAD+ precursors and sufficiently high enzyme activity synthesizing NAD+ are critical. The importance of NAD+ is exemplified by the devastating consequences of a deficiency of NAD+ precursors like niacin (vitamin B3). The deficiency syndrome, called pellagra, is characterized by the 4 Ds: dermatitis, dementia, diarrhea, and, eventually, death.

Thankfully, since life as we know it couldn’t exist without it, NAD+ and its precursors are found in everything we eat—plant, animal, or fungi—but we need to know how to get at them. The niacin in corn, for instance, is tightly bound up, but it can be released by presoaking in alkaline lime-water. Maize was exported from Latin America to become a dietary staple without the requisite knowledge about traditional processing techniques, though, and an epidemic of pellagra ensued. An estimated 100,000 Americans died from pellagra in the first few decades of the 20th century before bread started to be fortified with niacin in 1938.

The pitch for NAD+ boosting as an anti-aging strategy goes as follows. All species, including humans, naturally experience a decline in NAD+ levels over time, and this decline is, in fact, one of the major reasons organisms age. By restoring youthful levels, the argument goes, these age-related disorders can be delayed or even reversed. Two leaders in the field, one from Harvard and the other MIT, have said, respectively, that NAD+ boosters may “hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan,” and that sirtuin activation by NAD+ repletion “may be the most actionable item to emerge from aging research.” Of course, they have both been involved in multimillion-dollar dietary supplement companies.

The first premise, that NAD+ levels decline with age, has been called into question. For example, this 2022 review “Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?” concluded that, despite systemic claims to the contrary, the evidence supporting the premise is very limited. Indeed, the most comprehensive study to date found significant changes in NAD+ levels in less than half of the tested tissues in old versus young mice. The human data are similarly inconsistent.

NAD+ boosting supplement shills make claims like “By middle age, our NAD+ levels have plummeted to half that of our youth,” but the cited source only shows a drop (in brain levels) of about 13 percent between about the ages 20 to 60. A similar study estimated about an 18 percent drop from age 25 to 70, both broadly consistent with a 14 percent drop in spinal tap fluid samples taken from those over age 45 (average age 71), compared to those under age 45 (average age 34). It’s unclear if such modest differences would have any consequences, and a more recent study found no significant differences at all in brain nor muscle levels between a young group (average age 21) and an older group (average age 69).

A study of skin samples found a greater than 50 percent drop in young adults, compared to the skin of newborns, and a further drop of about 60 percent from young adults to middle age. However, there did not seem to be a further decline from middle to old age. There was a small study that found the NAD+ levels in the liver samples of six older individuals (average age 66) was about 30 percent lower than that of six younger individuals (average age 39). NAD+ levels also may be lower in macrophage white blood cells in older individuals, but in the blood more generally, half the studies showed a decline with age, and the other half didn’t. By far the largest study (enrolling 10 times more people than the other studies combined) found a slight drop in NAD+ in the aging bloodstreams of men, but no drop in women.

The bottom line is that, given the conflicting results from the remarkably few studies on the subject, it’s misleading to say NAD+ universally decreases with age. Regardless, the proof is in the pudding. What about the second premise, that boosting levels late in life can improve health and longevity? We’ll address that question, next.

Please consider volunteering to help out on the site.

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.

NAD+ is an essential co-factor for hundreds of enzymes, including the purported anti-aging activities of sirtuins. In this ten-part series, I will go through the alphabet soup of NAD-boosting supplements on the market: NR, NMN, NA, NAM, NADH, NMNH, NRH, and tryptophan. I will then cover the pros and cons of each, and discuss three ways to naturally boost NAD levels without supplements.

Our understanding of nicotinamide adenine dinucleotide (NAD+) arose from humble beginnings as a factor noted to enhance yeast fermentation in a 1906 paper unassumingly entitled “The Alcoholic Ferment of Yeast-Juice.” Little did they know that waves of NAD-related discoveries would go on to yield a total of four Nobel Prizes. NAD+ is now known as an essential molecule for all living organisms, required for the function of about 500 enzymes, including, notably, the extraction of metabolic energy from food. The 21st century has produced yet another scientific renaissance for NAD+ with the realization that it was critical for the activity of sirtuins, the “guardians of mammalian healthspan” I detail in my book, How Not to Age.

NAD+ is one of the most abundant molecules in our body. Once considered relatively stable, it’s now known to be in a constant state of synthesis, recycling, and breakdown. The entire pool of NAD+ in some of our tissues is turned over several times a day. To maintain cellular vitality in the face of this turnover, an adequate supply of NAD+ precursors and sufficiently high enzyme activity synthesizing NAD+ are critical. The importance of NAD+ is exemplified by the devastating consequences of a deficiency of NAD+ precursors like niacin (vitamin B3). The deficiency syndrome, called pellagra, is characterized by the 4 Ds: dermatitis, dementia, diarrhea, and, eventually, death.

Thankfully, since life as we know it couldn’t exist without it, NAD+ and its precursors are found in everything we eat—plant, animal, or fungi—but we need to know how to get at them. The niacin in corn, for instance, is tightly bound up, but it can be released by presoaking in alkaline lime-water. Maize was exported from Latin America to become a dietary staple without the requisite knowledge about traditional processing techniques, though, and an epidemic of pellagra ensued. An estimated 100,000 Americans died from pellagra in the first few decades of the 20th century before bread started to be fortified with niacin in 1938.

The pitch for NAD+ boosting as an anti-aging strategy goes as follows. All species, including humans, naturally experience a decline in NAD+ levels over time, and this decline is, in fact, one of the major reasons organisms age. By restoring youthful levels, the argument goes, these age-related disorders can be delayed or even reversed. Two leaders in the field, one from Harvard and the other MIT, have said, respectively, that NAD+ boosters may “hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan,” and that sirtuin activation by NAD+ repletion “may be the most actionable item to emerge from aging research.” Of course, they have both been involved in multimillion-dollar dietary supplement companies.

The first premise, that NAD+ levels decline with age, has been called into question. For example, this 2022 review “Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?” concluded that, despite systemic claims to the contrary, the evidence supporting the premise is very limited. Indeed, the most comprehensive study to date found significant changes in NAD+ levels in less than half of the tested tissues in old versus young mice. The human data are similarly inconsistent.

NAD+ boosting supplement shills make claims like “By middle age, our NAD+ levels have plummeted to half that of our youth,” but the cited source only shows a drop (in brain levels) of about 13 percent between about the ages 20 to 60. A similar study estimated about an 18 percent drop from age 25 to 70, both broadly consistent with a 14 percent drop in spinal tap fluid samples taken from those over age 45 (average age 71), compared to those under age 45 (average age 34). It’s unclear if such modest differences would have any consequences, and a more recent study found no significant differences at all in brain nor muscle levels between a young group (average age 21) and an older group (average age 69).

A study of skin samples found a greater than 50 percent drop in young adults, compared to the skin of newborns, and a further drop of about 60 percent from young adults to middle age. However, there did not seem to be a further decline from middle to old age. There was a small study that found the NAD+ levels in the liver samples of six older individuals (average age 66) was about 30 percent lower than that of six younger individuals (average age 39). NAD+ levels also may be lower in macrophage white blood cells in older individuals, but in the blood more generally, half the studies showed a decline with age, and the other half didn’t. By far the largest study (enrolling 10 times more people than the other studies combined) found a slight drop in NAD+ in the aging bloodstreams of men, but no drop in women.

The bottom line is that, given the conflicting results from the remarkably few studies on the subject, it’s misleading to say NAD+ universally decreases with age. Regardless, the proof is in the pudding. What about the second premise, that boosting levels late in life can improve health and longevity? We’ll address that question, next.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Doctor's Note

This is the first video in my NAD+ series. Stay tuned for:

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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