Cardiovascular disease (CVD) is the leading cause of death in the United States, but its risk factors are not fully understood. An NIH-funded research team led by Cleveland Clinic inventor Stanley Hazen, MD, investigated risk factors for CVD by analyzing plasma from more than 1,100 people. They identified two molecules, 2PY and 4PY, that are produced when excess niacin is broken down, and found that elevated levels of either molecule were associated with an increased risk of major cardiac events. . These findings suggest that excess niacin may be a risk factor for his CVD and may lead to a better assessment of CVD risk.

via article NIH research matters

Cardiovascular disease (CVD) is a disease of the heart and blood vessels. CVD is the leading cause of death for both men and women in the United States. Despite advances in prevention and treatment, it remains prevalent. This suggests that there may be risk factors that are not yet recognized.

To investigate, an NIH-funded research team led by Dr. Stanley Hazen of the Cleveland Clinic looked for metabolites that may contribute to CVD risk. The results were: natural medicine February 19, 2024.

The research team analyzed plasma from more than 1,100 people to look for molecules associated with serious adverse cardiac events such as heart attacks and strokes. They identified two such molecules, 2PY and 4PY. Both of these are produced when the body breaks down excess niacin.

Niacin, also known as nicotinic acid or vitamin B3, is an essential part of your diet. Many countries require that staple foods such as cereals, flour, oats, and grains be fortified with niacin to prevent deficiency diseases. In the United States, “fortified” foods must have niacin added to them. The recommended amount of niacin for adults is 14 to 18 mg/day.

High-dose niacin (1,500 to 2,000 mg/day) was also one of the first cholesterol-lowering drugs. But the study found that niacin, unlike newer cholesterol-lowering drugs, does not lower the risk of heart attack or stroke. Researchers didn’t understand why.

The researchers looked at 2PY and 4PY levels in two other groups, Americans and Europeans, totaling more than 3,000 people. They confirmed that elevated levels of either molecule were associated with an increased risk of major cardiac events. People with levels in the top 25% of 2PY or 4PY have a 1.6 to 1.6% risk of a major cardiac event over the next 3 years compared to people with levels in the bottom 25%, even after controlling for other CVD risk factors. There were twice as many.

Levels of both 2PY and 4PY were associated with mutations in a gene called . ACMSD. The researchers also found that levels of another protein called VCAM-1 ACMSD Subspecies. Additionally, VCAM-1 levels correlated with 2PY and 4PY levels.

VCAM-1 is known to help white blood cells adhere to blood vessel walls as part of the inflammatory response. This contributes to the formation of plaque in the arteries. Injecting mice with 4PY, but not 2PY, increased the amount of VCAM-1 on blood vessel walls and the number of attached leukocytes.

These findings suggest that excess niacin may be a risk factor for CVD. When excess niacin is broken down to 4PY, this breakdown product activates inflammatory pathways known to promote plaque formation in arteries. This can increase your risk of serious cardiac events.

“Niacin’s effectiveness has always been somewhat contradictory,” Hazen says. “Although niacin lowers cholesterol, the clinical benefit has always been less than expected based on LDL severity.” [cholesterol] reduction. This led to the idea that excess niacin causes obscure side effects that partially negate the LDL-lowering benefits. We believe that our findings help explain this discrepancy. ”

The results of this study may lead to better assessment of CVD risk. They also highlight the importance of further research into the health effects of niacin supplements.

—Written by Dr. Brian Doctorow