How Much Niacin is Optimal?
In a previous post, we discussed using supplemental niacin and the potential risk of increased cardiovascular events, versus lowered risks. While niacin has been found to increase HDL, how much is safe to take?
The RDA for niacin is not much- between 14 and 18 mg per day. Stanley Hazen, MD and senior author of the study linking niacin to heart disease notes the average American consumes four times the RDA for niacin. Some individuals ingest even more- up to 50 times the RDA through supplements.
Food fortification of niacin may have been necessary in the past, but Hazen wonders if mandating now is needed.
He notes, "In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin have led to an increase in cardiovascular disease?"
Hazen doesn’t advise ceasing all niacin fortification but suggests having a choice of unfortified options would be better.
Causal Link Not Proof
John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed "interesting and important results," but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.
He believes the results need to be researched more and that this solo study does not make the case for limiting niacin intake or stopping the fortification of niacin in food.
He also notes that niacin is available in large amounts in fast food, and the researchers could have chosen the results of consuming a poor diet.
"If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet," he commented.
Guyton also noted that mixed results with niacin use have been observed in large clinical trials. Its impact on cardiovascular risk isn’t completely known.
The HPS2-THRIVE and AIM-HIGH trials were not successful in reducing cardiovascular events. A previous study, the Coronary Drug Project in which the agent was given with food did demonstrate some positive effects with significant reductions in myocardial infarction and stroke. In addition, there was a potential reduction in long-term mortality in the niacin group several years after the trial had ended.
Nicotinamide and Skin Cancer Prevention
Nicotinamide, a niacin derivative, may have a role in skin cancer prevention.
Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, Maryland, indicated that nicotinamide, while closely related to niacin, may have a different impact. "This study does not specifically address nicotinamide supplementation and 4PY levels, " she said.
Diona Damian, MD, professor of dermatology at The University of Sydney, Camperdown, Australia, believes it was hard to pull these results on basal levels of niacin in a cardiac cohort to the use of very high doses of nicotinamide for skin cancer prevention.
Damian notes, “There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin.” She adds that, “it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.”
High vs low levels of nicotinamide supplements can have varying and possibly opposite effects on cell processes, including upregulating or preventing DNA repair enzymes. Nicotinamide is anti-inflammatory in skin at high doses.
What the Studies Say
In two phase 3 studies for skin cancer prevention using 500 mg of nicotinamide twice a day (ONTRAC and ONTRANS) did not result in a substantial increase in cardiovascular events compared to a placebo in a one-year trial.
According to Damian, "Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,".
She suggests, "For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,".
Hazen claims it’s exciting that this new research could discover another compound that may contribute to cardiovascular disease plus a target to use in residual cardiovascular risk.
"I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk."
He believes that what’s next is confirming the results in alternate populations and creating a diagnostic test to identify individuals with high 4PY levels.
Bottom Line
In conclusion, the use of high-dose niacin or nicotinamide supplements may or may not advised. If your risk of skin cancer is high, talk to your healthcare provider about your cardiovascular risks as well. This may determine if you should limit the use of niacin-fortified foods.
Lisa Andrews, MEd, RD, LD
References:
https://www.nature.com/articles/s41591-023-02793-8
https://www.nejm.org/doi/full/10.1056/NEJMoa1300955
https://www.nejm.org/doi/full/10.1056/nejmoa1107579
https://pubmed.ncbi.nlm.nih.gov/1088963/
https://www.sciencedirect.com/science/article/pii/S0735109786802935?via%3Dihub