- A breakdown product of excess niacin was linked to a higher risk of cardiovascular events such as heart attack and stroke.
- Niacin, or vitamin B3, is needed for a healthy nervous system. Most people get enough in their diet.
- Breads, flours and other foods are fortified with niacin. However, researchers say this may need to be reconsidered, given the new findings.
For decades, the food industry in the United States has added niacin — also known as vitamin B3 — to bread, flour and corn products to prevent pellagra, a disease caused by a deficiency of this nutrient.
The program was so successful that today pellagra is virtually unknown in the country, except among certain populations with extreme food insecurity.
While preventing deficiency is a good thing, a new study published February 19 in Nature Medicine suggests that excess niacin in the diet may have a downside — increasing the risk of cardiovascular disease.
In the study, researchers looked specifically at a metabolic byproduct of excess niacin known as 4PY.
Researchers did not set out to examine the role of niacin in cardiovascular disease. Instead, they were trying to identify why when people are treated for other risk factors — such as diabetes and high cholesterol — some still have cardiovascular events.
In their initial research, 4PY, whose full name is N1-methyl-4-pyridone-3-carboxamide, showed up as a possible marker in the blood for cardiovascular risk. Researchers then traced this compound back to excess niacin.
They found that participants in the highest quarter of 4PY levels had about a twofold increased risk of major adverse cardiovascular events such as a heart attack or stroke, compared to those in the lowest quarter.
To put it another way: “one in four people in our cohorts had high levels of 4PY, and are at significantly higher risk for adverse cardiovascular events,” study author Dr. Stanley Hazen, chair of cardiovascular and metabolic sciences at Cleveland Clinic’s Lerner Research Institute in Ohio, told Healthline.
Researchers argue that 4PY increases cardiovascular risk through inflammation in the blood vessels, known as vascular inflammation.
Mixed effects of niacin on heart
Niacin’s ability to lower low-density lipoprotein (LDL or “bad”) cholesterol and triglycerides, and raise high-density lipoprotein (HDL, or “good”) cholesterol led to it being used as a treatment for preventing cardiovascular disease prior to the development of cholesterol-lowering statins.
Some research, though, shows that taking niacin doesn’t reduce the risk of cardiovascular disease events, or offers no extra benefit when used alongside statins. One study even found that use of niacin may slightly increase the risk of dying early.
Adding to this, the findings of the new study suggest that excess niacin may counteract some of the benefits of smaller amounts of niacin, such as supporting the nervous system.
“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,” said Dr. Cheng-Han Chen, interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, Calif.
Chen was not involved in the study.
“This [new] study will put another nail in the coffin for the use of niacin in heart disease,” he told Healthline.
However, Chen cautions that more research is needed to understand the relationship between different amounts of excess niacin and cardiovascular disease, especially in people taking niacin supplements.
How much niacin is too much?
To avoid a deficiency, adults need 14 to 18 milligrams of niacin per day. This can be found in 6 ounces of tuna or 4 ounces of peanuts, among other foods, including those that are fortified with niacin.
In comparison, therapeutic levels of niacin — such as amounts used in clinical trials for lowering cholesterol — are along the lines of 1,500 to 2,500 milligrams per day, the researchers write.
People taking prescription or over-the-counter niacin products were excluded from the analysis, said Hazen. So that leaves the diet as the main source of niacin for participants.
Researchers did not have data on how much niacin participants were getting in their diet. However, Hazen pointed out that ingestion of excess amounts of niacin — or related compounds such as nicotinamide adenine dinucleotide, nicotinic acid, and nicotinamide riboside — have all been shown previously to increase the level of 4PY, as well as another breakdown product, 2PY.
In this study, 2PY, also known as N1-methyl-2-pyridone-5-carboxamide, was not linked to inflammation or a higher risk of cardiovascular disease events.
Americans tend to get more than enough niacin to prevent a deficiency, ingesting 37 milligrams per day of niacin on average, according to the 2017-2020 National Health and Nutrition Examination Surveys (NHANES). In addition, that survey shows that fewer than 4% of adults report consuming less than 15 milligrams per day, the authors point out.
So most Americans get enough niacin in their diet, some of which is coming from fortified foods, which Hazen thinks may need to be reconsidered in light of the new findings.
“The main takeaway is not that we should cut out our entire intake of niacin — that’s not a realistic approach,” he said in a release. “Given these findings, a discussion over whether a continued mandate of flour and cereal fortification with niacin in the U.S. could be warranted.”
Chen cautions against people routinely taking niacin supplements, especially if they have a higher risk of cardiovascular disease. If they are considering taking niacin or related products, they should talk to their doctor first.
“However, it may be more difficult to avoid niacin-fortified foods, given their ubiquity in the food chain,” he said. So “niacin fortification may need to be examined at a higher level as a matter of public policy.”
Takeaway
Researchers found that people with higher amounts of a breakdown product of excess niacin had a higher risk of major adverse cardiovascular events such as heart attack and stroke.
This breakdown product, known as 4PY, acts through inflammation in the blood vessels to increase the cardiovascular risk, researchers say.
More research is needed to understand the link between different levels of excess niacin and the risk of cardiovascular disease events. Researchers call for a re-examination of the fortification of foods with niacin.
