Risks and Benefits of Nicotinic Acid (NA), a NAD+ Booster

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Given niacin’s decades of use as a cholesterol drug, we have a good idea of its safety profile.

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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 name nicotinic acid was changed to niacin in the 1940s to avoid any confusion with nicotine. Either name has to be better than the original moniker, though: vitamin PP (for pellagra preventing).

In the 1950s, NA became the world’s first cholesterol-lowering drug. This led to more than 20 trials involving tens of thousands of individuals taking high doses of NA for up to six years, resulting in by far the most robust safety data we have on any of the NAD+ precursors. The most striking benefit was found in the Coronary Drug Project, a trial carried out in the pre-statin drug era of the 1960s and 70s. The 15-year follow-up found that those who had been randomized to years of high-dose NA ended up with a 6.2% drop in absolute mortality (52 percent had died in the NA group, versus 58 percent in the placebo group). This sparked major clinical trials that, sadly, failed so spectacularly that one was even stopped prematurely.

All in all, a Cochrane meta-analysis concluded that “no evidence of benefits from niacin therapy” was found. One possible explanation for the contrasting results is that the early promising trials used immediate-release niacin, while the newer failed trials used slow-release formulations (also known as extended or sustained release). At high doses, regular niacin commonly causes an intense flushing redness and prickly heat sensation, similar to a menopausal hot flash. A slow-release version was developed to reduce this flushing reaction, catapulting it into a billion-dollar blockbuster drug. But it simply doesn’t work as well to lower cholesterol.

The major clinical trial failures led to the withdrawal of the drug in Europe, and the removal from U.S. clinical guidelines for cardiovascular disease prevention. There still may be a role for niacin preparations in the treatment of heart disease among patients who cannot tolerate statin drugs, but what about use for the general public as an NAD+ booster? There is a series of rare genetic defects that can lead to a condition called mitochondrial myopathy that’s characterized by low NAD+ levels in the blood and muscles. In 2020, researchers demonstrated that these levels could be repleted with 750 to 1,000 mg a day of NA, which led to a significant improvement in muscle strength. This was the first and only study to show improvements in muscle NAD+ levels and performance with any sort of NAD+ booster. In a control group of individuals without the genetic defect, blood levels of NAD+ were raised by NA––but not muscle levels, suggesting that NAD+ levels are already “topped off” in normal muscles. As you’ll see, this is a recurring theme among NAD+ boosters.

We know that large doses of NA can boost NAD+ levels in human blood, but a corresponding increase in sirtuin activity has yet to be demonstrated. Why not give it a try? Because of the side effects unearthed in the cholesterol-lowering trials. NA raises blood sugars, and may increase your risk of developing diabetes. Based on studies of tens of thousands of people on high-dose NA who were followed for years, one would expect that one in 43 people taking NA for five years would develop diabetes who otherwise wouldn’t have. It’s unclear if this risk is only limited to slow-release formulations.

The safety buffer, the ratio between the tolerable upper limit and the RDA, is the lowest for NA compared to half a dozen other common vitamins. However, the upper limit is just based on the flushing reaction, which, although uncomfortable, is considered harmless and tends to dissipate over time. Long-term use can have other adverse consequences, though, including stomach ulcers, vomiting, abdominal pain, diarrhea, and jaundice, a sign of liver toxicity, which is worse with slow-release formulations. There is also a theoretical concern that excessive NA intake may contribute to the development of Parkinson’s disease. Due to the unpleasant flushing and risk of more serious side effects, interest has moved towards other NAD+ enhancers.

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.

The name nicotinic acid was changed to niacin in the 1940s to avoid any confusion with nicotine. Either name has to be better than the original moniker, though: vitamin PP (for pellagra preventing).

In the 1950s, NA became the world’s first cholesterol-lowering drug. This led to more than 20 trials involving tens of thousands of individuals taking high doses of NA for up to six years, resulting in by far the most robust safety data we have on any of the NAD+ precursors. The most striking benefit was found in the Coronary Drug Project, a trial carried out in the pre-statin drug era of the 1960s and 70s. The 15-year follow-up found that those who had been randomized to years of high-dose NA ended up with a 6.2% drop in absolute mortality (52 percent had died in the NA group, versus 58 percent in the placebo group). This sparked major clinical trials that, sadly, failed so spectacularly that one was even stopped prematurely.

All in all, a Cochrane meta-analysis concluded that “no evidence of benefits from niacin therapy” was found. One possible explanation for the contrasting results is that the early promising trials used immediate-release niacin, while the newer failed trials used slow-release formulations (also known as extended or sustained release). At high doses, regular niacin commonly causes an intense flushing redness and prickly heat sensation, similar to a menopausal hot flash. A slow-release version was developed to reduce this flushing reaction, catapulting it into a billion-dollar blockbuster drug. But it simply doesn’t work as well to lower cholesterol.

The major clinical trial failures led to the withdrawal of the drug in Europe, and the removal from U.S. clinical guidelines for cardiovascular disease prevention. There still may be a role for niacin preparations in the treatment of heart disease among patients who cannot tolerate statin drugs, but what about use for the general public as an NAD+ booster? There is a series of rare genetic defects that can lead to a condition called mitochondrial myopathy that’s characterized by low NAD+ levels in the blood and muscles. In 2020, researchers demonstrated that these levels could be repleted with 750 to 1,000 mg a day of NA, which led to a significant improvement in muscle strength. This was the first and only study to show improvements in muscle NAD+ levels and performance with any sort of NAD+ booster. In a control group of individuals without the genetic defect, blood levels of NAD+ were raised by NA––but not muscle levels, suggesting that NAD+ levels are already “topped off” in normal muscles. As you’ll see, this is a recurring theme among NAD+ boosters.

We know that large doses of NA can boost NAD+ levels in human blood, but a corresponding increase in sirtuin activity has yet to be demonstrated. Why not give it a try? Because of the side effects unearthed in the cholesterol-lowering trials. NA raises blood sugars, and may increase your risk of developing diabetes. Based on studies of tens of thousands of people on high-dose NA who were followed for years, one would expect that one in 43 people taking NA for five years would develop diabetes who otherwise wouldn’t have. It’s unclear if this risk is only limited to slow-release formulations.

The safety buffer, the ratio between the tolerable upper limit and the RDA, is the lowest for NA compared to half a dozen other common vitamins. However, the upper limit is just based on the flushing reaction, which, although uncomfortable, is considered harmless and tends to dissipate over time. Long-term use can have other adverse consequences, though, including stomach ulcers, vomiting, abdominal pain, diarrhea, and jaundice, a sign of liver toxicity, which is worse with slow-release formulations. There is also a theoretical concern that excessive NA intake may contribute to the development of Parkinson’s disease. Due to the unpleasant flushing and risk of more serious side effects, interest has moved towards other NAD+ enhancers.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Doctor's Note

​​This is the third video in my NAD+ series. If you missed the first two, see Do NAD+ Levels Decline with Age? and Can NAD+ Boosters Increase Lifespan and Healthspan?. 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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