New study finds too much vitamin B3 may contribute to heart disease

NATION — Researchers recently found that high levels of a common B vitamin called niacin in the body may contribute to cardiovascular disease. They saw that excess niacin can trigger vascular inflammation, which in turn may lead to atherosclerosis — or plaque buildup on artery walls.
About 20.5 million people around the world died from cardiovascular disease in 2021, making it responsible for a third of all deaths globally.
While there are some unmodifiable risk factors for heart disease, including gender, family history, and ethnicity, there are several preventable causes for cardiovascular disease, including obesity, high cholesterol levels, high blood pressure, smoking, eating an unhealthy diet, and not getting enough physical activity.
Now, researchers from the Cleveland Clinic Lerner Research Institute have added to the list of potentially modifiable risk factors with a new study reporting high levels of a common B vitamin called niacin in the body may contribute to cardiovascular disease. The study was recently published in the journal Nature Medicine.
Searching for new heart disease pathways
Finding a potential link between niacin and heart disease was not the original intention of this study, Dr. Stanley Hazen, The Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis, director of the Center for Cardiovascular Diagnostics & Prevention, and director of the Center for Microbiome & Human Health at the Cleveland Clinic Lerner Research Institute, and lead author of this study told Medical News Today.
“Our initial goal was to identify new pathways that contribute to heart disease. Even when treating cardiovascular disease risk factors to goal (e.g. cholesterol, blood pressure, diabetes, etc.), the majority of events (heart attack, stroke, death) continue to occur, or at best, we reduce the event rate by 50%. This means there are other pathways we are not addressing,” Dr. Hazen explained.
Dr. Hazen said he and his team were looking for compounds in the blood that might contribute to the future development of heart attack, stroke, or death independent of traditional risk factors.
“The compound 4PY was identified that is linked to future CVD events — in a U.S. cohort initially, then replication in a U.S. cohort, and further validation in a European cohort,” he continued.
“We then performed preclinical studies (animal model) and cell-based studies — all of which showed this compound contributes to vascular inflammation. 4PY, it turns out, is a breakdown product made from excess niacin,” he said.
What is niacin?
Niacin — also known as vitamin B-3 — is one of eight different B vitamins. Niacin helps the body convert foods eaten into energy. It also helps keep the skin healthy and the nervous system running smoothly. As the body cannot make niacin, it needs to get it from the foods we eat or via a supplement. For example, the body converts the amino acid tryptophan — found in most animal products, including meat and dairy — into niacin.
Niacin can also naturally be found in legumes, whole grains, nuts, and seeds. And there are also some foods, such as cereals and breads, fortified with niacin.
The body does not store niacin — any excess not used is removed from the body via urine.
Higher levels of 4PY associated with adverse cardiac event
For this study, Dr. Hazen and his team studied the fasting plasma from about 1,100 people with stable cardiac health.
Upon analysis, researchers discovered that higher circulating levels of N1-methyl-4-pyridone-3-carboxamide, or 4PY, were strongly associated with the development of a heart attack, stroke, or other unhealthy cardiac events.
“Our studies found high levels of 4PY in the blood predict future cardiac disease. These new studies help identify a new pathway that contributes to heart disease,” Dr. Hazen said.
However, Dr. Hazen said the main takeaway for readers is not that we should cut out our entire intake of niacin — that’s not a realistic or healthy approach.
OTC niacin supplements
“Given these findings, a discussion over whether a continued mandate of flour and cereal fortification with niacin in the U.S. could be warranted. 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.” — Dr. Stanley Hazen
Excess 4PY triggers vascular inflammation
Scientists also found that 4PY directly triggers vascular inflammation, which can damage blood vessels and lead to a buildup of plaque on artery walls, known as atherosclerosis.
“Atherosclerosis is caused by both high cholesterol and inflammation. We know how to treat the high cholesterol side of the equation, but not the inflammation side. This pathway appears to be a major participant in vascular inflammation,” Dr. Hazen said.
“(Our) research uncovered that excess niacin fuels inflammation (and) cardiovascular disease through a newly discovered pathway. (These) findings are significant because they provide a foundation for potential new interventions and therapeutics to reduce or prevent inflammation,” said Dr. Hazen.
Dr. Hazen said that now with the discovery of this link, there is much more research to do.
“On the one hand, we need to explore what other cardiovascular diseases/phenotypes are linked to 4PY since vascular inflammation is a fundamental contributor to many diseases/phenotypes — e.g. heart failure, stroke, (and) other forms of vascular disease,” he explained.
“Beyond this, we then want to focus on how to disrupt this pathway to leverage the newly gained knowledge to develop a therapeutic,” he added.
Should I stop using niacin supplements?
Dr. Cheng-Han Chen, a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, was asked about this study.
“This study identifies excess niacin, specifically its breakdown metabolite 4PY, as a risk factor for major adverse cardiovascular events such as heart attack and stroke,” Dr. Chen explained.
“While niacin was previously prescribed as a cholesterol-lowering medication, its use has fallen out of favor as multiple studies did not find as much benefit to cardiovascular health as initially thought. This study will put another nail in the coffin for the use of niacin in heart disease.” — Dr. Cheng-Han Chen
Meanwhile, Dr. Charles Brenner, Ph.D., Alfred E. Mann Chair in Diabetes and Cancer Metabolism, and cardiovascular expert with a special interest in NAD+, pointed out that this was an observational study that only assessed associations and did not determine causality.
“In other words, this was not a randomized, controlled intervention study (niacin or other B3 was not administered), so no conclusions of cause and effect can be drawn from it. Further, it inappropriately links common B vitamins and other NAD+ precursors to heart disease and omits key contextual information,” he said.
Dr. Brenner said the study results are contradicted by previous research showing that other forms of niacin, such as NR, may not increase the risk for cardiovascular disease and/or increase inflammation.
Dr. Chen said more studies need to be performed to better understand the dose relationship between niacin supplementation and cardiovascular disease.
“For now, I would caution against routine intake of niacin supplements in the average person,” he continued. “It may be more difficult, however, to avoid niacin-fortified foods given its ubiquity in the food chain; niacin fortification may need to be examined at a higher level as a matter of public policy.”
– Corrie Pelc