Niacin Found to Promote Formation of Free Radicals, May Lead to Longer Life Span

B3 (also known as niacin) and its metabolite nicotinamide in the worms’ diet caused them to live for about one-tenth longer than usual.

As an international team of researchers from ETH Zurich (Switzerland), led by Michael Ristow, a professor of energy metabolism, has now shown in their research, niacin and nicotinamide take effect by boosting formation of so-called free radicals. “In roundworms, these reactive oxygen species prolong life,” said Prof. Ristow.

This might seem surprising as reactive oxygen species (ROS) are typically considered to be unhealthy. Prof. Ristow’s hypothesis also challenges the general scientific consensus maintained by many other scientists. ROS are known to injure somatic cells, a condition referred to as oxidative stress. Specific compounds, so-called antioxidants, which are also found in vegetables, fruit, and various vegetable oils, are capable of neutralizing these free radicals. Many scientists believe that antioxidants are beneficial to health.

“The claim that intake of antioxidants, especially in tablet form, promotes any aspect of human health lacks scientific support,” stated Prof. Ristow. He does not argue that fruit and vegetables are healthy. However, this may instead be caused by other compounds they contain, such as so-called polyphenols. “Fruit and vegetables are healthy, despite the fact that they contain antioxidants,” he said.

Based on the current and many previous findings he is convinced that small amounts of reactive oxygen species and the oxidative stress they trigger have a health-promoting impact. “Cells can cope well with oxidative stress and neutralize it,” stated Prof. Ristow.

In earlier studies on humans, the investigators demonstrated that the health-enhancing effect of endurance sports is mediated via an increased formation of reactive oxygen species--and that antioxidants abolish this effect. Prof. Ristow concluded, based on the present study that niacin brings about a similar metabolic condition to exercise. “Niacin tricks the body into believing that it is exercising—even when this is not the case,” he stated. These substances are known as “exercise mimetics.”

The researchers conducted their research on the organism Caenorhabditis elegans. This worm, which is just 1 mm in length, can be easily maintained and has a lifespan of only one month, making it the ultimate model organism for aging research. The study’s findings may also be of significance for humans, according to Prof. Ristow. The metabolic pathway triggered by niacin is very similar in roundworms and higher organisms. Whether niacin has similar effects on the life expectancy of mice is the topic of Prof. Ristow’s current research. Moreover, earlier research suggests a health-enhancing effect of niacin in humans with elevated blood cholesterol levels.

Niacin and nicotinamide have been approved as dietary supplements for a long time. Prof. Ristow could easily envisage the substances being used broadly for therapeutic purposes in the future. A whole series of foods naturally contain niacin, including liver, other meats, fish, peanuts, wheat bran mushrooms, and rice. Whether nutritional uptake is adequate for a health-enhancing or lifespan-extending effect, however, remains to be seen, according to Prof. Ristow.

The latest study on the effects of niacin and nicotinamide is based on a specific type of enzymes, the sirtuins, which convert niacin into nicotinamide. Furthermore, they are also involved in gene regulation, helping to down-regulate the activity of specific genes. Until now, scientists have been disputing whether sirtuins have a life-prolonging impact.

This study now suggests that the activity of sirtuins really does prolong life in roundworms. According to the study, however, the life-prolonging effect is not caused by gene regulation, as has frequently been supposed in the past. Instead, the effect is caused by the conversion of niacin into nicotinamide. Examining genetically modified roundworms that were unable to convert nicotinamide into certain other metabolic products, the scientists did not observe any lifespan extension, even after overexpression of sirtuins, which otherwise lead to an increased life expectancy.

The study’s findings were published September 2013 in the journal Nature Chemical Biology.

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