Warning: High Levels of Niacin (Vitamin B3) Linked to Heart Disease
A team from the Cleveland Clinic has identified a new contributor to cardiovascular disease: 4PY, a byproduct of excess niacin (vitamin B-3). Their research shows that high levels of 4PY are linked to an increased risk of heart attack, stroke, and vascular inflammation, which can lead to atherosclerosis.
Excess niacin fuels inflammation, 
Cleveland Clinic researchers, led by Dr. Stanley Hazen, have identified a new pathway that contributes to cardiovascular disease associated with high levels of niacin. Credit: Cleveland Clinic
Dr. Hazen notes broader use of over-the-counter supplements made with different forms of niacin has 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.
The new findings also might help explain why niacin is no longer a go-to treatment for lowering cholesterol. Niacin was one of the first treatments prescribed to lower LDL or “bad” cholesterol. However, eventually niacin showed to be less effective than other cholesterol-lowering drugs and was associated with other negative effects and higher mortality rates in previous research.
“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.
The research is part of Dr. Hazen’s ongoing investigation into factors that contribute to residual cardiovascular risk. His team follows patients over time and collects blood samples to find chemical signatures that can predict the development of heart disease. He has made pioneering discoveries in atherosclerosis and inflammatory disease research, including the seminal discovery linking gut microbial pathways to cardiovascular disease and metabolic diseases.
Reference: “A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk” 19 February 2024, Nature Medicine.
DOI: 10.1038/s41591-023-02793-8
Dr. Hazen also directs Cleveland Clinic’s Center for Microbiome and Human Health and holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis.
Marc Ferrell, a former M.D., Ph.D. student in Dr. Hazen’s laboratory and student in Case Western Reserve University’s Medical Scientist Training Program, is first author of the manuscript. Research reported in this publication was supported in part by the
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