Cleveland Clinic researchers have identified a new pathway that contributes to cardiovascular disease associated with high levels of niacin, a common B vitamin previously recommended to lower cholesterol.

Niacin (vitamin B-3) is very common in a Western diet. Yet one in four subjects in the researchers’ patient cohorts appear to be getting too much, and had high levels of 4PY, which appears to contribute to cardiovascular disease development.

Dr. Hazen compares our intake of niacin as multiple taps pouring water into a bucket. Once that bucket is filled, it begins to spill over. The human body then needs to process that spill-over and produce other metabolites, including 4PY.

“The main takeaway is not that we should cut out our entire intake of niacin — that’s not a realistic approach,” said Dr. Hazen. “Given these findings, a discussion over whether a continued mandate of flour and cereal fortification with niacin in the U.S. could be warranted.”

Dr. Hazen notes broader use of over-the-counter supplements made with different forms of niacin have also become popular because of presumed anti-aging purposes. He adds that patients should consult with their doctors before taking over-the-counter supplements and focus on a diet rich in fruit and vegetables while avoiding excess carbohydrates.

“Niacin’s effects have always been somewhat of a paradox,” Dr. Hazen said. “Despite niacin lowering of cholesterol, the clinical benefits have always been less than anticipated based on the degree of LDL reduction. This led to the idea that excess niacin caused unclear adverse effects that partially counteracted the benefits of LDL lowering. We believe our findings help explain this paradox. This illustrates why investigating residual cardiovascular risk is so critical; we learn so much more than what we set out to find.”

The study authors note that long-term investigations are needed to assess the effect of chronic elevation of 4PY levels on atherosclerosis and other phenotypes.

Sources:

Marc Ferrell, Zeneng Wang, James T. Anderson, Xinmin S. Li, Marco Witkowski, Joseph A. DiDonato, James R. Hilser, Jaana A. Hartiala, Arash Haghikia, Tomas Cajka, Oliver Fiehn, Naseer Sangwan, Ilja Demuth, Maximilian König, Elisabeth Steinhagen-Thiessen, Ulf Landmesser, W. H. Wilson Tang, Hooman Allayee, Stanley L. Hazen. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nature Medicine, 2024; 30 (2): 424 DOI: 10.1038/s41591-023-02793-8

Materials provided by Cleveland Clinic. Note: Content may be edited for style and length.

Cleveland Clinic. “Link between high levels of niacin — a common B vitamin — and heart disease, study suggests.” ScienceDaily. ScienceDaily, 19 February 2024. <www.sciencedaily.com/releases/2024/02/240219130657.htm>.

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