Excess Niacin and Cardiovascular Risk

Cardiovascular disease (CVD) is a serious condition affecting the heart and blood vessels, leading to numerous deaths every year. Despite advancements in treatment and prevention, there are still unknown risk factors contributing to its prevalence.

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A recent study led by Dr. Stanley Hazen and his team at the Cleveland Clinic, funded by the National Institutes of Health (NIH), delved into potential factors associated with CVD risk. Their findings, published in Nature Medicine on February 19, 2024, shed light on the role of excess niacin in promoting cardiovascular disease.

Niacin, also known as vitamin B3, is a vital nutrient found in various foods. It’s added to staple foods in many countries to prevent deficiency. However, the study revealed that when the body breaks down excess niacin, it produces molecules called 2PY and 4PY, which were linked to major adverse cardiac events like heart attacks and strokes.

Despite being one of the first cholesterol-lowering drugs, high doses of niacin did not show significant benefits in reducing the risk of heart attacks or strokes compared to newer medications. This puzzled researchers until now.

Analyzing data from over 1,100 individuals and confirming their findings with more than 3,000 people, the team discovered that elevated levels of 2PY and 4PY were associated with a higher risk of major cardiac events over the next three years.

Further investigations revealed a connection between these molecules and a gene called ACMSD. They also found that another protein called VCAM-1, known to promote plaque formation in arteries, correlated with 2PY and 4PY levels.

When injected into mice, 4PY increased the presence of VCAM-1 on blood vessel walls, suggesting a potential mechanism by which excess niacin contributes to cardiovascular disease.

Dr. Hazen explained, “Niacin’s effects have always been somewhat of a paradox. Despite its cholesterol-lowering properties, its clinical benefits have been less than expected, hinting at unclear adverse effects. Our findings offer insight into this paradox.”

These discoveries highlight the importance of further research into the health effects of niacin supplementation and its potential role in assessing cardiovascular disease risk. Understanding how excess niacin impacts heart health could lead to better prevention strategies and treatment approaches in the future.