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Vitamin B paradox: Supplement linked to heart disease risk

A new study from the Cleveland Clinic has revealed a link between high levels of niacin and the development of cardiovascular disease. Niacin is a B vitamin that is commonly found in the Western diet. It is also used to treat high cholesterol and triglyceride levels.

Previously unknown pathway

The researchers have identified a previously unknown pathway involving 4PY – a byproduct of excess niacin intake. This metabolite plays a critical role in heart disease progression.

Niacin, also known as vitamin B-3, has been a staple in food fortification practices in the United States for decades. However, the research suggests that excess niacin contributes to cardiovascular diseases through the elevation of 4PY levels in the bloodstream. 

Elevated levels of 4PY have been strongly associated with an increased risk of heart attacks, strokes, and other adverse cardiac events.

Direct damage to blood vessels

In preclinical studies, Dr. Stanley Hazen and his team demonstrated that 4PY contributes to vascular inflammation. The experts also found that 4PY directly damages blood vessels, potentially leading to atherosclerosis over time. 

The study further explores genetic links between 4PY and vascular inflammation. It lays the groundwork for potential new interventions and therapeutics aimed at reducing or preventing this inflammation.

Study significance 

“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,” said Dr. Hazen. 

“What’s more, we can measure it, meaning there is potential for diagnostic testing. These insights set the stage for developing new approaches to counteract the effects of this pathway.”

“For decades, the United States and more than 50 nations have mandated niacin fortification in staple foods such as flour, cereals and oats to prevent disease related to nutritional deficiency.”

Critical insights

However, one in four study subjects in the researchers’ patient cohorts appear to be getting too much niacin. These individuals had high levels of 4PY, which appears to contribute to cardiovascular disease development.

“The main takeaway is not that we should cut out our entire intake of niacin – that’s not a realistic approach,” said Dr. Hazen. “Given these findings, a discussion over whether a continued mandate of flour and cereal fortification with niacin in the U.S. could be warranted.”

Dr. Hazen noted that broader use of supplements made with niacin have also become popular because of presumed anti-aging purposes. He said 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.

Study implications 

The implications of this research are far-reaching. They challenge long-standing practices and beliefs regarding niacin supplementation and dietary intake. For years, niacin was a favored treatment for lowering LDL, or “bad” cholesterol, due to its presumed benefits. 

However, this study sheds light on why niacin may no longer be the preferred treatment for cholesterol management. The adverse effects of excess niacin could detract from its cholesterol-lowering benefits.

Paradoxical effects

“Niacin’s effects have always been somewhat of a paradox,” said Dr. Hazen. “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 is published in the journal Nature Medicine.

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