Should advice on intake change?

Recent studies linking niacin derivatives to an increased risk of cardiovascular events have raised questions about the safety of this B vitamin, which is added to many staples of the Western diet and taken in supplement form.

The research results published in natural medicineit may also help explain why intake of niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events. Major clinical trials.

But can this essential micronutrient really have a negative impact on cardiovascular risk, and what effect does niacin intake have?

Stanley Hazen, M.D., lead author of the new study, believes some caution may be warranted in overdosing on niacin.

“I'm not saying we should avoid niacin completely. It's an essential nutrient, but our results suggest that too much can be harmful,” Hazen said. Ta.

Niacin supplements are also sold with claims of anti-aging effects, reducing arthritis, and improving brain function, but none of these claims have been proven. A related compound, nicotinamide, has also been recommended to prevent skin cancer in high-risk patients. however, Recent research raises questions That guidance.

“While these findings will be investigated further, we would like to tell the public that avoiding supplements containing niacin or related compounds may be a prudent approach at this time.”

Other experts are unsure whether such action is warranted based on this single study.

Residual cardiovascular risk

said Hazen, director of the Division of Cardiovascular and Metabolic Sciences at the Lerner Institute at the Cleveland Clinic in Cleveland, Ohio. heart.org | Medscape Cardiology They didn't start researching niacin.

“This study began as a search for new pathways involved in the residual risk of cardiovascular disease, that is, the risk of cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

Researchers began searching for compounds in plasma that predict future adverse cardiovascular events in individuals undergoing elective cardiac diagnostic evaluation. Two of the main candidates identified were niacin derivatives (2PY and 4PY) that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts: a 2,331-person American cohort and a 832-person European cohort. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling of cardiovascular risk in the highest and lowest quartile level groups.

Beyond these observational studies, to investigate potential causal relationships, Hazen's team will continue to conduct genome-wide association studies, finding that genetic variations that track higher levels of 4PY, an inflammatory marker, are associated with blood vessel cells. It was also found to be associated with levels of adhesion molecule 1 (VCAM-1).

Then, in cell culture and animal experiments, we discovered that 4PY is a driver of inflammation, upregulating VCAM-1 and inducing a vascular inflammatory response.

“Thus, we have shown in several different ways that 4PY, a niacin derivative, is associated with increased cardiovascular risk,” Hazen commented.

Serious health effects?

Hazen believed these discoveries could have significant health implications.

He noted that Westerners have been consuming large amounts of niacin since World War II, when many foods began fortifying the essential vitamin to avoid diseases caused by deficiency. Niacin was added to foods to prevent pellagra. Pellagra is an often fatal disease characterized by skin inflammation, diarrhea, and dementia.

“We may have eliminated pellagra, but did that result in an increased prevalence of cardiovascular disease years later?” Hazen asked.

This may provide a clue as to why niacin does not reduce cardiovascular risk as much as expected given the degree of cholesterol-lowering it provides. “This is the niacin paradox, and it leads to the idea that there may be some negative effects that niacin promotes. I think we may have found something that contributes to the niacin paradox,” he said. Ta.

However, the niacin pathway is complex. Niacin is a major source of nicotinamide adenine dinucleotide (NAD), an essential molecule that allows cells to produce energy. “It's so important that our bodies are designed to collect and retain NAD, but when storage capacity is exceeded, 4PY and 2PY derivatives are produced,” Hazen explained. . “But for this to happen, you really need to eat a lot of niacin-rich foods.”

He does not claim that niacin causes cardiovascular disease. “The likely driver of vascular inflammation is 4PY, and 4PY is a breakdown product of niacin. However, there is more than one pathway that may lead to the production of 4PY. There is an entire interconnected network of compounds that exchange with each other. “Taking one or more of these compounds, known as the niacin pool, increases pool levels and ultimately increases 4PY levels. But by far, niacin is the major source. It's one of those things,” Hazen commented.

Does a high protein diet have something to do with it?

Other sources of NAD include tryptophan, which is found in proteins. And one of the genetic variations associated with changes in 4PY levels has to do with how dietary protein is directed into niacin pools, suggesting that a high-protein diet may be a cause for concern in some people. It can increase vascular risk, Hazen said.

Professor Hazen estimates that approximately 3% of the niacin pool in a normal diet comes from protein intake, but that proportion can increase significantly in very high protein diets.

“Our data support the concept that lowering 4PY levels over the long term will lead to reduced cardiovascular disease. However, this is still only a hypothesis. Lowering niacin intake will also lower 4PY. “Yes,” Hazen said. .

He said it was too early to make firm recommendations about what the study would mean for consumers.

“Based on these findings, I would advise people to avoid taking niacin, nicotinic acid, or nicotinamide supplements and to eat a sensible, balanced diet, perhaps including a high-protein type of diet. Please don’t overdose, that’s all we can really say at this point.”

Note that niacin may also be one of the following symptoms: Main ingredients of energy drinksand suggested that it may be wise to limit consumption of these products.

What is the optimal intake of niacin?

Mr. Hazen pointed out that: Recommended Dietary Allowance (RDA) for Niacin It is well known that the average American intake is 14 to 18 mg, but the average American consumes four times that amount, and up to 50 times the RDA when taking supplements. He said some people are taking too much.

While fortifying foods with niacin may have been useful in the past, Hazen questioned whether it should still be mandatory.

“In the United States, you can't buy flour, cereal, or rice that isn't fortified. And if you look closely, some products contain levels much higher than the mandated levels. Food companies… They tout this as a benefit, but it doesn't do any good.'' There's data to back it up. What if decades of excessive niacin intake led to an increase in cardiovascular disease? ”

He is not suggesting that all niacin fortifications be discontinued, but “perhaps there is an option to choose a non-fortified option.”

no causal relationship has been proven

To comment heart.org | Medscape CardiologyJohn Guyton, M.D., professor emeritus of medicine at Duke University Medical Center in Durham, North Carolina, has been involved in niacin research for many years. natural medicine Although the study presents “interesting and important results,” it does not currently demonstrate a causal relationship between niacin intake and cardiovascular disease risk.

“While these findings need to be investigated further and more research is certainly warranted, this study alone does not suggest limiting niacin intake or considering discontinuing fortification of foods with niacin. “I don't think that's a good enough basis for that,” Guyton said.

He pointed out that niacin is found in large amounts in many fast foods and suggested that researchers may just be recognizing the effects of an unhealthy diet.

“If you look at foods that contain high amounts of niacin, red meat is at the top of the list. And if you think about hamburgers, niacin is found in relatively high amounts in both the hamburger and the bun. So these “The findings probably just reflect an overall unhealthy diet,” he commented.

Guyton also noted that major clinical trials using niacin have shown mixed results, and niacin's impact on cardiovascular risk is not yet fully understood. on the other hand, HPS2-THRIVE and aim higher In early studies, trials showed no benefit in reducing cardiovascular events. Coronary artery disease treatment drug project When this drug is administered with food, it does show a positive effect, with a significant reduction in myocardial infarctions and strokes. long-term mortality A few years after the trial ended, a study was conducted on the niacin group.

Nicotinamide in skin cancer prevention

What about the use of nicotinamide in the prevention of skin cancer?

Addressing this question, Kristin Bibby, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine in Baltimore, Maryland, suggests that although nicotinamide is closely related to niacin, it may have different effects. He pointed out that there is. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, Professor Dermatology He spoke at the University of Sydney in Camperdown, Australia. heart.org | Medscape Cardiology stated that these findings regarding basal levels of niacin in the heart cohort are difficult to extrapolate to the administration of supraphysiological doses of nicotinamide for skin cancer prevention.

Professor Damien said the effects of niacin supplements may have a different effect compared to nicotinamide, which does not have the vasodilatory effect seen in niacin, giving patients with and without heart disease a higher level of treatment. It would be interesting to see the results of administering higher doses of nicotinamide, he added.

She pointed out that high and low supplementation levels of nicotinamide can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. In high doses, nicotinamide has anti-inflammatory effects on the skin.

Damian is involved in two Phase 3 studies (on track and on trance) Nicotinamide 500 mg twice daily for skin cancer prevention was not associated with a significant increase in cardiovascular events compared to placebo over a 12-month period.

“Oral nicotinamide has been shown to reduce non-melanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. Skin Cancer Prevention Doses used for skin cancer far exceed daily dietary levels, and treatment must be continued to maintain preventive effects. “Although it should not be recommended as a preventive drug, it should be reserved for people with a high burden of skin cancer,” she commented.

“At this time, it makes sense to balance the potential effects on inflammatory markers in patients with cardiac risk factors with the benefits of reducing skin cancer when determining whether nicotinamide therapy is appropriate for patients. “That's true,” he added.

Meanwhile, Professor Hazen said the most exciting aspect of this new study was the discovery of new pathways contributing to cardiovascular disease and the potential for new targets to treat residual cardiovascular risk.

“I think our results show that 4PY levels need to be measured and that people with high levels need to be especially careful about reducing cardiovascular risk.”

The next step is to confirm these results in other populations and develop diagnostic tests to identify people with elevated 4PY levels, he said.