Sonia Moreno Madrid

Madrid

Updated Monday, February 19, 2024-17:00

Excess

breakdown products of

niacin or vitamin B3

may be related to

a

higher risk of mortality from cardiovascular disease

, specifically myocardial infarction and stroke, according to

a study in

Nature Medicine

published today, Monday

.

The authors of this work, led by Stanley Hazen, head of Cardiovascular and Metabolic Sciences at the Cleveland Clinic, in the United States, have identified a molecular mechanism by which

too much vitamin B3 can be harmful

.

Where do we get that extra vitamin B3?

Niacin is an essential micronutrient naturally present in many foods, such as eggs, lean meats and legumes; The body can also produce it through tryptophan, an amino acid that is released when digesting proteins. And, in addition, flours and cereals enriched with niacin are common. The consumption of this vitamin is, therefore, sufficiently covered in the Western diet.

Previous research has shown that niacin can reduce levels of low-density lipoprotein cholesterol (LDL-C) and increase high-density lipoprotein cholesterol (HDL), as well as decrease triglycerides. However, in other studies, such as a

meta-analysis published in

The Journal of the American College of Cardiology

, it has not been found that this effect implies a lower risk of cardiovascular disease

.

"Therefore, it has been recognized that niacin has a more complex effect on cardiovascular disease or CVD events (the so-called "niacin paradox", whereby it reduces LDL cholesterol, but not the risk of cardiovascular events. CVD), presumably through cholesterol-independent mechanisms," the researchers note in the

Nature Medicine

article .

Why, if vitamin B3 is needed, can it work against us?

Their research provides an explanation for that paradox by showing that

a breakdown product of niacin

can promote

inflammation in blood vessels

.

To do this, they analyzed plasma samples from 4,325 people in three patient cohorts that include men and women from the United States and Europe. Hazen's group found that two breakdown products of niacin - the metabolites N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3-carboxamide (4PY) - are associated with an increased risk of cardiovascular disease.

This observation was corroborated with subsequent genetic analyzes and in experimental models, where the authors demonstrated that

the increased risk may be mediated by the ability of one of these degradation products (4PY)

to increase the abundance of the proinflammatory protein VCAM-1 in the endothelial cells that line blood vessels.

Niacin is used to enrich basic foods such as flour, cereals and oats, in order to prevent diseases related to nutritional deficiency, Hazen recalls. However, one in four subjects in the researchers' patient cohorts

appeared to be consuming too much and had high levels of 4PY,

which appears to contribute to the development of cardiovascular disease.

In the study, scientists use the simile of a bucket where several taps of water converge until it overflows, to convey what happens with the

surplus of the vitamin and the production of metabolites

in the body.

Elevated blood levels of 4PY were closely associated with the

development of heart attacks, strokes

, and other adverse cardiovascular events in large-scale clinical studies. Researchers also showed in preclinical studies that 4PY directly triggers vascular inflammation that damages blood vessels and can

lead to atherosclerosis over time

.

"The main conclusion is not that we should completely eliminate our niacin intake," highlights Hazen, who is in favor of controlling the fortification of certain foods, as well as consulting

with the doctor before launching into the consumption of over-the-counter supplements

, and to focus better on a diet rich in fruits and vegetables.