Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin (vitamin B3) is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. According to a new study, excess amounts of breakdown products of niacin may be linked to an increased risk of mortality, heart attacks and stroke.
Niacin is an essential micronutrient fortified in food staples beyond dietary requirements. Image credit: Ferrell et al., doi: 10.1038/s41591-023-02793-8.
CVD is a leading cause of morbidity and mortality worldwide, but only a portion of attributable risk is accounted for by established risk factors.
Despite substantial advances in therapies, residual CVD risk remains high, suggesting that additional, yet unrecognized factors are involved in CVD.
Research has previously shown that niacin (vitamin B3) can lower levels of low-density lipoprotein cholesterol.
However, the vitamin seemingly does not have the expected effects on decreasing CVD risk — the so-called ‘niacin paradox.’
“Our study provides a potential explanation for this paradox by showing that a breakdown product of niacin may promote inflammation in blood vessels,” said Dr. Stanley Hazen, a researcher at Cleveland Clinic.
In the study, the authors analyzed plasma samples from 4,325 people in three patient cohorts that included both men and women from the United States and Europe.
They found that two breakdown products of niacin — the metabolites N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3- carboxamide (4PY) — are associated with an increased CVD risk.
In subsequent human genetic and mouse studies, the team showed that this increased risk may be mediated by the ability of one of these breakdown products (4PY) to increase the abundance of the pro-inflammatory protein VCAM-1 in the endothelial cells that line blood vessels.
“Further work in larger studies is needed to explore the links between niacin and its breakdown products and CVD,” the researchers said.
Their findings were published in the journal Nature Medicine.
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M. Ferrell et al. 2024. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nat Med 30, 424-434; doi: 10.1038/s41591-023-02793-8
Source : Breaking Science News