Cleveland Clinic researchers have identified a new pathway that contributes to cardiovascular disease associated with high levels of niacin, a common B vitamin that was previously recommended for lowering cholesterol.
A research team led by Stanley Hazen, M.D., Ph.D., discovered a link between 4PY, a breakdown product of excess niacin, and heart disease. In large clinical studies, high circulating levels of 4PY were strongly associated with the development of heart attacks, strokes, and other adverse cardiac events. The researchers also showed in preclinical studies that 4PY can directly cause vascular inflammation, damaging blood vessels and causing atherosclerosis over time.
This research Nature medicine, We also detail the genetic link between 4PY and vascular inflammation. This discovery provides the basis for potential new interventions and treatments to reduce or prevent inflammation.
“What’s interesting about these results is that this pathway, previously unrecognized, appears to contribute significantly to the development of cardiovascular disease,” said Dr. said Dr. Hazen, chair of the Department of Metabolic Sciences and co-chair of the center. Cardiovascular Thoracic Institute Preventive Cardiology. “Furthermore, being able to measure it means there is potential for diagnostic tests. These insights set the stage for developing new approaches to counteract the effects of this pathway.”
Niacin (vitamin B-3) is very common in the Western diet. “For decades, the United States and more than 50 countries have required staple foods like flour, cereals, and oats to be fortified with niacin to prevent diseases related to nutritional deficiencies,” Dr. Hazen said. said. However, one in four subjects in the researchers’ patient cohort appeared to be overdosing, having high levels of 4PY, which is thought to contribute to the development of cardiovascular disease.
Dr. Hazen compares our niacin intake to pouring water into a bucket from multiple taps. Once the bucket is full, it will start spilling. The human body must then process the spill and produce other metabolites, including 4PY.
“The main point is not that you should completely stop taking niacin; that’s not a realistic approach,” Dr. Hazen said. “Given these findings, there will be a debate as to whether continuing mandates to fortify flour and grains with niacin in the United States are justified.”
Dr. Hazen points out that over-the-counter supplements using various forms of niacin have become widely used for anti-aging purposes. He added that patients should consult their doctor before taking over-the-counter supplements and focus on a diet rich in fruits and vegetables while avoiding excessive carbohydrates.
This new discovery may also help explain why niacin is no longer the go-to treatment for lowering cholesterol. Niacin was one of the first treatments prescribed to lower LDL or “bad” cholesterol. Ultimately, however, previous studies found that niacin was less effective than other cholesterol-lowering drugs and was associated with other adverse effects and higher mortality rates.
“Niacin’s effectiveness has always been somewhat of a paradox,” Dr. Hazen says. “Although niacin lowers cholesterol, the clinical benefit has always been less than expected based on the degree of LDL reduction. We believe our findings help explain this discrepancy. It shows why research is so important. We learn much more than we set out to find.”
The study authors note that long-term studies are needed to assess the impact of chronically elevated 4PY levels on atherosclerosis and other phenotypes.
This study 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 the study of atherosclerosis and inflammatory diseases, including seminal discoveries linking gut bacterial pathways with cardiovascular and metabolic diseases.
Dr. Hazen directs the Center for Microbiome and Human Health at the Cleveland Clinic and holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis.
Mark Ferrell, retired physician, Ph.D. A student in Dr. Hazen’s lab, Case is a student in his program at Western Reserve University Medical Scientist Training and is the first author of this manuscript. Research reported in this publication was supported in part by the National Institutes of Health under award numbers R01HL103866, P01HL147823, R01HL133169, R01HL148110, R01HL168493, and his U54HL170326.
