A team at the Cleveland Clinic has discovered a new factor in cardiovascular disease: 4PY, a byproduct of excess niacin (vitamin B-3). Their research shows that high levels of 4PY increase the risk of heart disease, stroke, and inflammation of blood vessels, leading to atherosclerosis.
Excess niacin can exacerbate inflammation, Cardiovascular diseases Through new discovery pathways.
Cleveland Clinic researchers have discovered a new pathway to cardiovascular disease linked to high levels of niacin, a common B vitamin previously recommended for lowering cholesterol.
A research team led by Stanley Hazen, MD, found a link between 4PY, a breakdown product of excess niacin, and heart disease. In large-scale clinical studies, higher circulating levels of 4PY have been strongly associated with the occurrence of heart attack, stroke, and other adverse cardiac events. Researchers have also shown in preclinical studies that 4PY directly triggers inflammation in blood vessels, damaging them and leading to atherosclerosis over time.
Impact on diagnostic and therapeutic approaches
The study was published on February 19 nature drug, The genetic link between 4PY and vascular inflammation is also detailed. These findings lay the foundation for potential new interventions and treatments to reduce or prevent inflammation.
“What is exciting about these results is that this pathway appears to be a previously unrecognized but important contributor to the development of cardiovascular disease,” said Dr. Contributors.” Preventive Cardiology at the Heart, Vascular, and Thoracic Institute. “What’s more, we can measure it, which means diagnostic tests may be possible. These insights lay the foundation for developing new methods to counteract the effects of this pathway.”
Reevaluating niacin fortification and use
Niacin (vitamin B-3) is common in the Western diet. “For decades, the United States and more than 50 countries have mandated the addition of niacin to staple foods such as flour, cereals and oats to prevent diseases related to nutritional deficiencies,” said Dr. Hazen. However, in the researchers’ patient cohort, a quarter of the subjects appeared to consume too much and had higher levels of 4PY, which appears to contribute to the development of cardiovascular disease.
Dr. Hasson likens the niacin we ingest to pouring water into a bucket from the faucet multiple times. Once the bucket is full, it starts to overflow. The body then needs to process this overflow and produce other metabolites, including 4PY.
“The main takeaway is not that we should completely stop niacin intake—that’s not a realistic approach,” Dr. Hasson said. “In light of these findings, there is a need for continued discussion of the need for mandatory niacin in flour and grains in the United States.”
Cleveland Clinic researchers led by Dr. Stanley Hazen have discovered a new pathway that contributes to cardiovascular disease associated with high levels of niacin.Image source: Cleveland Clinic
Dr. Hasson notes that the widespread use of over-the-counter supplements made from different forms of niacin has also become popular for their presumed anti-aging purposes. He added 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 may also help explain why niacin is no longer the go-to treatment for lowering cholesterol. Niacin was one of the first treatments used to lower low-density lipoprotein, or “bad” cholesterol. Ultimately, however, niacin was less effective than other cholesterol-lowering drugs and was associated with other negative effects and higher mortality. previous studies.
“The effects of niacin are always a bit paradoxical,” Dr. Hasson said. “Although niacin can lower cholesterol, its clinical benefit has always been less than expected based on the degree of LDL reduction. This has led to the idea that excess niacin causes unspecified side effects that partially offset the reduction in Benefits of LDL. We believe our findings help explain this paradox. This illustrates why investigating residual cardiovascular risk is so important; we learned much more than what we were looking for.”
The study authors note that long-term studies are needed to evaluate the impact of chronically elevated 4PY levels on atherosclerosis and other phenotypes.
The study is part of Dr. Hazen’s ongoing investigation into factors that contribute to residual cardiovascular risk. His team follows patients over time and collects blood samples to look for chemical signatures that could predict the development of heart disease. He has made groundbreaking discoveries in the study of atherosclerosis and inflammatory diseases, including groundbreaking discoveries linking gut microbial pathways to cardiovascular and metabolic diseases.
Reference: “Nicotinic acid’s final metabolite promotes vascular inflammation and increases cardiovascular disease risk,” February 19, 2024 natural medicine.
DOI: 10.1038/s41591-023-02793-8
Dr. Hazen also leads the Cleveland Clinic Center for Microbiome and Human Health and holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis.
Marc Ferrell, formerly M.D., Ph.D. student in Dr. Hazen’s laboratory and in Case Western Reserve University’s medical scientist training program and is the first author of the manuscript.The research reported in this publication was supported in part by National Institutes of Health Award numbers are R01HL103866, P01HL147823, R01HL133169, R01HL148110, R01HL168493 and U54HL170326.
