Who would not want to live a long and healthy life? A freely available food supplement could help in this respect, scientists from ETH Zurich have demonstrated in roundworms. Vitamin 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 headed by Michael Ristow, a professor of energy metabolism, has now experimentally demonstrated, niacin and nicotinamide take effect by promoting formation of so-called free radicals. "In roundworms, these reactive oxygen species prolong life," says Ristow.
"No scientific evidence for usefulness of antioxidants"
This might seem surprising as reactive oxygen species are generally considered to be unhealthy. Ristow's view also contradicts the textbook opinion championed by many other scientists. Reactive oxygen species are known to damage somatic cells, a condition referred to as oxidative stress. Particular substances, so-called antioxidants, which are also found in fruit, vegetables and certain vegetable oils, are capable of neutralising 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," says Ristow. He does not dispute that fruit and vegetables are healthy. However, this may rather be caused by other compounds contained therein, such as so-called polyphenols. "Fruit and vegetables are healthy, despite the fact that they contain antioxidants," says the ETH-Zurich professor. 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 neutralise it," says Ristow.
Substance mimics endurance sport
In earlier studies on humans, Ristow 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. Based on the present study, he concludes 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," says Ristow. Such compounds are known as "exercise mimetics."
The researchers conducted their experiments on the model organism Caenorhabditis elegans. This worm, which is merely one millimetre in length, can be easily maintained and has a lifespan of only a month, making it the ideal model organism for ageing research.
Also relevant for humans
The results of the study may also be of relevance for humans, says Ristow. After all, the metabolic pathway initiated by niacin is very similar in roundworms and higher organisms. Whether niacin has similar effects on the life expectancy of mice is the subject of Ristow's current research. Previous studies also suggest a health-enhancing effect of niacin in humans with elevated blood cholesterol levels.
Niacin and nicotinamide have been approved as dietary supplements for decades. Ristow could easily envisage the substances being used broadly for therapeutic purposes in the future. A whole series of foods naturally contain niacin, including meat, liver, fish, peanuts, mushrooms, rice and wheat bran. Whether nutritional uptake is sufficient for a health-enhancing or lifespan-extending effect, however, remains to be demonstrated, says Ristow.
Disputed impact of enzymes
The latest study on the effects of niacin and nicotinamide is based on a particular class of enzymes, the sirtuins, which convert niacin into nicotinamide. Moreover, they are also involved in gene regulation, helping to down regulate the activity of certain genes. Until today, scientists have been disputing whether sirtuins have a life-prolonging impact.
Ristow and his team's work now suggests that the activity of sirtuins actually prolongs life in roundworms. According to the study, however, the life-prolonging effect is not down to gene regulation, as has often been supposed in the past. Instead, the effect is due to the conversion of niacin into nicotinamide. Studying 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.
- Kathrin Schmeisser, Johannes Mansfeld, Doreen Kuhlow, Sandra Weimer, Steffen Priebe, Ines Heiland, Marc Birringer, Marco Groth, Alexandra Segref, Yariv Kanfi, Nathan L Price, Sebastian Schmeisser, Stefan Schuster, Andreas F H Pfeiffer, Reinhard Guthke, Matthias Platzer, Thorsten Hoppe, Haim Y Cohen, Kim Zarse, David A Sinclair, Michael Ristow. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nature Chemical Biology, 2013; DOI: 10.1038/nchembio.1352
Cite This Page: