Niacin, or vitamin B3, has lengthy been a U.S. public well being darling to the purpose that it’s added, by regulation, to cereal merchandise. However a brand new examine revealed Monday in Nature Medicine factors to a probably regarding impact of an extra of the vitamin: It could improve the chance of heart problems.
The examine seemed into two cohorts of sufferers with out lively coronary heart illness, 60% of whom had been handled with statins, and located a powerful affiliation between a metabolic product of extra niacin and an elevated danger of main opposed cardiovascular occasions reminiscent of a coronary heart assault or stroke. One in 4 of the individuals within the examine had extra niacin, which doubled their danger of main cardiovascular occasions to ranges comparable with diabetes or a earlier coronary heart assault.
“It’s a reasonably sizable danger. It’s on par with what we contemplate different massive dangers,” mentioned Stanley Hazen, the part head of preventive cardiology and cardiac rehabilitation on the Cleveland Clinic and senior writer of the examine. “This opens up the door; it lays the muse for brand new research and new interventions from each a diagnostic and therapeutic perspective to attempt to scale back irritation and heart problems.”
Niacin’s capacity to extend high-density lipoprotein ldl cholesterol (HDL) — also known as “good” ldl cholesterol — and decrease low-density lipoprotein ldl cholesterol (LDL) — the “dangerous” kind — made it a primary line of intervention to forestall heart problems previous to the introduction of statins. However the brand new findings recommend that extra niacin, which can be thought to help nervous and digestive system health, might have blended results on the physique, although exterior consultants warning that it’s too early to say for sure whether or not niacin really will increase cardiovascular danger.
“To attract an inference that niacin elevated cardiovascular danger in these trials shouldn’t be essentially correct,” mentioned Sanjay Kaul, a heart specialist at Cedars-Sinai Medical Middle who didn’t take part within the examine. “Coronary coronary heart illness and associated mortality weren’t considerably elevated. … So I’ve problem in connecting the dots.”
Researchers recognized the reason for elevated cardiovascular danger in N1-methyl-4-pyridone-3-carboxamide (4PY), a niacin metabolite. They argue that 4PY will increase cardiovascular danger by an inflammatory response and say they’ve recognized a beforehand unknown pathway that may trigger opposed cardiovascular occasions. In truth, mentioned Hazen, the researchers didn’t set off to review niacin within the first place. They had been initially attempting to grasp why, when conventional danger elements reminiscent of excessive ldl cholesterol, smoking, and diabetes are handled, half of sufferers nonetheless go on to have cardiovascular occasions.
“We started by trying to see if there was one thing in fasting blood samples from topics who had been adopted over time to see who went on and developed a coronary heart assault or stroke or died — and it ended up being a compound which was unknown,” mentioned Hazen, referring to 4PY. “And once we lastly discovered what it was and the place it got here from, it may possibly solely be made by extra niacin ingestion.”
Extra niacin additionally resulted within the manufacturing of N1-methyl-2-pyridone-5-carboxamide (2PY), which, nevertheless, was not linked to irritation and better danger of heart problems.
The outcomes had been in keeping with findings in two massive niacin research (HPS2-THRIVE and AIM-HIGH), which discovered that when individuals already had low ranges of dangerous ldl cholesterol, placing them on niacin led to worse cardiovascular outcomes, though the compound is understood to extend ranges of fine ldl cholesterol. “Our examine, by the again door, now helps clarify what the darkish aspect of niacin has been: It helps foster vascular irritation by the formation of 4PY, however solely in individuals who have an excessive amount of.”
Cereals reminiscent of wheat and rice are a dietary staple for billions of individuals. The authors argue that their findings recommend that it might be time to rethink the obligatory fortification of meals with niacin.
“There isn’t any doubt that mandated fortification has been probably the greatest public well being applications and was a tremendous success,” mentioned Hazen, who notes that there have been no current U.S. instances of pellagra, a probably lethal situation brought on by niacin deficiency that may result in diarrhea, dementia, and excruciating mouth sores. Nonetheless, he mentioned, it might be time to permit for non-fortified cereal merchandise to be offered within the U.S. — as they’re in most elements of the world — to supply an alternative choice to individuals who might have elevated danger of heart problems and may gain advantage from lowered consumption of niacin.
William Boden, a professor of drugs at Boston College Faculty of Drugs who didn’t take part within the examine, was hesitant to conclude niacin extra equals cardiovascular danger.
“Whereas it’s true that within the present statin period, we don’t have compelling proof that niacin therapy reduces cardiovascular loss of life, [heart attack], or stroke, I’m cautious to conclude that there’s definitive proof of hurt related to niacin primarily based on this examine,” he wrote in an electronic mail to STAT.
The examine doesn’t handle the scenario of sufferers taking prescription niacin, which is delivered in concentrations 20 occasions larger than in dietary supplements, mentioned Daniel Rader, a professor of drugs and genetics on the College of Pennsylvania who was additionally not concerned within the examine. “What are the degrees of 2PY and 4PY in people who find themselves taking pharmacologic doses of niacin? The expectation can be that they might be astronomically larger as a result of the quantity of consumption of niacin is orders of magnitude larger,” mentioned Rader. (Hazen responded by noting that whereas not one of the contributors on this examine took prescription niacin, different research have reported elevated ranges of 2PY and 4PY.)
“If 4PY actually is pro-inflammatory and will increase danger, as they recommend, I assume I simply would anticipate that pharmacologic doses of niacin can be very clearly dangerous for you,” he mentioned. Nevertheless, quite a few earlier scientific research of pharmacologic niacin have solely failed to substantiate its advantages, not discovered vital danger related to it, although a 2012 examine of a niacin drug candidate for heart problems was halted after a “critical opposed occasion” amongst sufferers handled with the medicine.
“That is very fascinating, 4PY and its results on irritation, so I’m not likely questioning these observations,” Rader mentioned.
