In the early 20th century, the worst nutrition-related disease in U.S. history hit the American South. Pellagra is a disease caused by a deficiency of niacin and/or tryptophan and is characterized by the four “D’s”: diarrhea, dermatitis that causes horrible skin spots, dementia, and death. At its peak during the Great Depression, pellagra killed nearly 7,000 Southerners a year. Researchers estimate that between 1906 and 1940, the epidemic affected about 3 million Americans and killed about 100,000.

The deadly epidemic led to voluntary and eventually mandatory fortification of wheat and other grains with niacin (also known as vitamin B3). By mid-century, pellagra had all but disappeared from the United States. But decades later, the public health victory may be backfiring. Federal health surveys show that Americans’ diets are more dependent than ever on processed foods fortified with niacin, and the average intake of niacin in the United States is now approaching what is considered the nutrient’s tolerable upper limit. ing. And an extensive study recently published in Nature Medicine suggests that these excess amounts of niacin may worsen cardiovascular disease and increase the risk of heart attack, stroke, and death. doing.

The study, led by Stanley Hazen, director of the Division of Cardiovascular and Metabolic Sciences at the Lerner Institute at the Cleveland Clinic, found that high blood levels of niacin breakdown products (and to a lesser extent tryptophan) and Associated with increased risk of adverse cardiovascular events (mace). And this increased risk appears to be independent of known risk factors for those events, such as high cholesterol.

“What is interesting about these results is that this pathway, previously unrecognized, appears to contribute significantly to the development of cardiovascular disease,” Dr. Hazen said in the study presentation. It is measurable and could one day lead to new avenues of treatment and prevention, he added.

metabolite fishing

Hazen and his colleagues did not initially suspect that niacin might be a cause of cardiovascular disease. They arrived at that point by examining the patient’s plasma. The researchers carefully looked at metabolites in the fasting plasma of 1,162 patients who were evaluated for cardiovascular disease. They were looking for anything that might be associated with an increased risk of heart attack, stroke, or death over a three-year period that wasn’t completely explained by other risk factors. Despite advances in the identification and treatment of cardiovascular disease, some patients remain at risk for serious cardiovascular events despite treating and managing traditional risk factors. Researchers point out that. Hazen and his colleagues wanted to know why.

An unknown metabolite was discovered through metabolomics trol fishing (signature C)₇H₉○₂N₂), which was significantly associated with 3-year incidence of MACE. Those with higher levels of this metabolite circulating in their bodies were in the top 75th percentile of relative MACE risk within the cohort. Further research revealed that this metabolite is actually two related molecules: 2PY (N1-methyl-2-pyridone-5-carboxamide) and 4PY (N1-methyl-4-pyridone-3-carboxamide). It was determined that Both are final breakdown products of niacin.