The news cycle this week is full of headlines connecting high levels of niacin to coronary heart disease through pathways of accelerated inflammation based on a new study from the Cleveland Clinic Foundation.
Although many clinicians have abandoned the use of niacin in practice, there are many theoretical and trial-based arguments for the continued use of niacin. I have published on this previously.
Has the new study buried niacin permanently from clinical use despite decades of data that niacin lowers both LDL-C and lipoprotein(a)?
A Summary of the New Study
Researchers at the Clinic searched fasting plasma samples of 1,162 patients with stable cardiac disease with untargeted metabolomics and identified 2 compounds that were related, 4PY and 2PY, associated with the presence of cardiac disease.
Further work indicated that these compounds were the terminal metabolites of “excess niacin” metabolism and were associated with an increased risk of major adverse cardiac events (MACE). A genetic variant rs10496731 was associated with 4PY and 2PY as well as with the inflammatory molecule soluble vascular adhesion molecule (sVCAM-1) in various cohorts.
In studies in mice “physiological levels” of 4PY induced expression of sVCAM-1 and leukocyte adherence to vascular endothelium.
Overall, the researchers concluded that terminal breakdown products of excess niacin were associated with residual cardiovascular risk through an inflammation-dependent mechanism.
Figure 6 in the paper indicated that NAD, niacin, nicotinamide, and vitamin B3 all could cause an overflow of the “niacin pool” leading to cardiovascular disease.
What Wasn’t Studied
From the headlines, it could easily be assumed that a trial of niacin, NAD+, NMN, or nicotinamide products were administered to subjects, and levels of 4PY were elevated in response to these agents.
Indeed, the use of niacin was an exclusion criterion from the study and no one was treated with niacin and the other supplements.
The authors pointed out that there are many foods like flours fortified with niacin to prevent the development of pellagra and the excess intake of processed foods might expose certain individuals to an excess of dietary niacin.
Conclusions
The work at the Clinic is an important advance at tackling the burden of residual cardiac risk not addressed by pharmaceutical agents or even lifestyle. The same group identified TMAO as another metabolic marker back in 2011 and the literature now has over 1,000 contributions linking TMAO to various clinical pathologies.
Niacin has proven to be a useful agent to lower lipoprotein(a) cholesterol and it seems premature to abandon it in this population. Similarly, it seems premature to abandon work on the potential benefits of NMN and NR. In terms of lipoprotein(a), there are several pharmaceutical agents in Phase 3 clinical trials that appear hopeful and an FDA-approved therapy may be available to some patients in the next few years.
Until then, further research on the “niacin pool” and 4PY is likely to appear, perhaps with actual clinical trials of administering niacin agents. I will continue to use OTC niacin in my patients with elevated lipoprotein(a).
About the author: At his core, Dr. Joel Kahn believes that plant-based nutrition is the most powerful source of preventative medicine on the planet. Having practiced traditional cardiology since 1983, it was only after his own commitment to a plant-based vegan diet that Dr. Kahn truly began to delve into the realm of non-traditional diagnostic tools, prevention tactics, and nutrition-based recovery protocols.
As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before changing your wellness routine. This article is not intended to provide a medical diagnosis, recommendation, treatment, or endorsement. These statements have not been evaluated by the Food and Drug Administration.
Opinion Disclaimer: The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy of WHN/A4M. Any content provided by guest authors is of their own opinion and is not intended to malign any religion, ethic group, club, organization, company, individual, or anyone or anything.
Content may be edited for style and length.
References/Sources/Materials provided by:
https://www.kahnlongevitycenter.com/
https://www.linkedin.com/in/joel-kahn-md-757a59225/
