Study finds link between high niacin levels and heart disease

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 for lowering cholesterol.

The team, led by Stanley Hazen, MD, Ph.D., discovered a link between 4PY, a breakdown product from excess niacin, and heart disease. Higher circulating levels of 4PY have been strongly associated with the development of heart attacks, strokes, and other adverse cardiac events in large-scale clinical studies. Researchers have also shown in preclinical studies that 4PY directly triggers vascular inflammation that damages blood vessels and can lead to atherosclerosis over time.

The study, published in Natural medicine, also details the genetic links between 4PY and vascular inflammation. The findings provide a basis for potential new interventions and treatments aimed at reducing or preventing this inflammation.

“What is exciting about these results is that this pathway appears to contribute in a significant and previously unrecognized way to the development of cardiovascular disease,” said Dr. Hazen, chair of cardiovascular and metabolic sciences at the Lerner Research Institute. from the Cleveland Clinic and co-chief of the Preventive Cardiology section at the Heart, Vascular and Thoracic Institute.

“What’s more, we can measure it, which means there is potential for diagnostic testing. This information opens the way to 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 mandated the niacin fortification of staple foods such as flour, cereals and oats, to prevent diseases linked to nutritional deficiencies,” he said. said Dr. Hazen. Yet one in four subjects in the researchers’ patient cohorts appear to consume too much and have elevated levels of 4PY, which appears to contribute to the development of cardiovascular disease.

Dr. Hazen compares our niacin intake to several faucets pouring water into a bucket. Once the bucket is full, it begins to overflow. The human body must then process this fallout and produce other metabolites, including 4PY.

“The main takeaway is not that we should cut out our niacin intake entirely – that’s not a realistic approach,” Dr. Hazen said. “Given these results, a discussion about whether a continued mandate for flour and grain fortification with niacin in the United States might be warranted.”

Dr. Hazen notes that the broader use of over-the-counter supplements made from different forms of niacin has also become popular because of its purported anti-aging goals. He adds that patients should consult their doctor before taking over-the-counter supplements and focus on a diet rich in fruits and vegetables while avoiding excess carbohydrates.

The new findings could also help explain why niacin is no longer a go-to treatment for lowering cholesterol. Niacin was one of the first treatments prescribed to reduce LDL or “bad” cholesterol. However, niacin ultimately proved less effective than other cholesterol-lowering medications and has been linked to other negative effects and higher mortality rates in previous research.

“The effects of niacin have always been somewhat paradoxical,” Dr. Hazen said. “Despite the reduction of cholesterol by niacin, the clinical benefits were always lower than expected based on the degree of LDL reduction. This led to the idea that excess niacin caused unclear adverse effects that partially counteract the benefits of lowering LDL. We believe our results help “This explains why the study of residual cardiovascular risk is so crucial; We learn a lot more than we were looking for.”

The study authors note that long-term investigations are needed to evaluate 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 takes blood samples to find chemical signatures that can predict the development of heart disease. He made pioneering discoveries in the research of atherosclerosis and inflammatory diseases, including the fundamental discovery linking intestinal microbial pathways to cardiovascular disease and metabolic diseases.