Researchers at the Cleveland Clinic have uncovered a new pathway that may explain how high levels of niacin (vitamin B3), once widely recommended to lower cholesterol, could actually increase the risk of heart disease.
Their findings were published in the journal Nature Medicine.
The research team, led by Dr. Stanley Hazen, identified a substance called 4PY, which is produced in the body when there’s too much niacin. In large-scale clinical studies, people with higher levels of 4PY in their blood were more likely to have heart attacks, strokes, or other serious heart problems.
Lab tests showed that 4PY can trigger inflammation in blood vessels, which can damage them over time and lead to atherosclerosis—a buildup of plaque in the arteries.
Dr. Hazen explained that this discovery opens the door to new ways to diagnose and potentially treat inflammation in blood vessels. “What’s exciting about these results is that this pathway appears to be a previously unrecognized yet significant contributor to the development of cardiovascular disease,” he said.
Niacin is a common part of the Western diet. Since the mid-20th century, the U.S. and many other countries have required food companies to add niacin to staple foods like flour, cereal, and oats to prevent deficiency diseases. But Dr. Hazen said that one in four people in their study had niacin levels that were too high, which may be contributing to heart disease.
He likens the problem to pouring water into a bucket. Once the bucket is full, any extra water spills over, and the body must process that spillover. One result is the production of 4PY, which appears to harm blood vessels.
Dr. Hazen isn’t recommending that people stop eating all niacin-rich foods, but he believes it might be time to reconsider the rules about adding niacin to foods. He also warned against the growing use of over-the-counter niacin supplements, which are marketed for anti-aging benefits, and encouraged people to speak with their doctor before using them.
Niacin was once a popular treatment for lowering LDL (bad) cholesterol, but it fell out of favor when studies showed it was less effective than other medications and could lead to side effects and even higher death rates.
Dr. Hazen said this new study may help explain that paradox. “Niacin’s effects have always been puzzling,” he said. “Now we believe the negative effects of 4PY may have canceled out the benefits of lowering cholesterol.”
The research also adds to Dr. Hazen’s larger project aimed at understanding what causes heart disease beyond traditional risk factors. His team studies blood samples to identify chemical signs that might predict future heart problems. He is known for his earlier discoveries linking gut bacteria to heart and metabolic diseases.
Dr. Hazen holds leadership roles at Cleveland Clinic’s Center for Microbiome and Human Health and the Lerner Research Institute, and he continues to explore how inflammation, diet, and other hidden factors contribute to cardiovascular risk.
Long-term studies are still needed to better understand how 4PY affects heart health over time, but this research marks a key step in explaining how too much of even a once-recommended nutrient could be harmful.
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