Evaluating Continuous versus Intermittent Methionine Restriction in Mice
Researchers here show that intermittent methionine restriction (four days off, three days on, alternating) produces the same metabolic benefits as continuous methionine restriction, though to a lesser degree. Methionine sensing is one of the major mechanisms by which cells respond to low calorie intake, so it is possible to trigger this response without reduced calorie intake by reducing only levels of the essential amino acid methionine in the diet. To my eyes, the most interesting outcome here is that there is a large difference in metrics between the groups placed on a zero methionine diet for three days versus those placed on a low methionine diet for three days.
From a practical point of view, the difficulty in practicing methionine restriction lies in organizing the diet, as near all staple foods contain a lot of methionine. Thus intermittent methionine restriction is going to be just as challenging as methionine restriction: it would require about the same amount of work to adopt this lifestyle choice either way. Further, any period of complete methionine restriction would require a manufactured diet. Those medical diet products exist, but are very expensive and/or not available to the public at large.
A sustained state of methionine restriction (MR) dramatically extends the healthspan of several model organisms. For example, continuously methionine-restricted rodents have less age-related pathology and are up to 45% longer-lived than controls. Promisingly, MR is feasible for humans, and studies have suggested that methionine-restricted individuals may receive similar benefits to rodents. However, long-term adherence to a methionine-restricted diet is likely to be challenging for many individuals. Prompted by this, and the fact that intermittent variants of other healthspan-extending interventions (i.e., intermittent fasting and the cyclic ketogenic diet) are just as effective, if not more, than their continuous counterparts, we hypothesized that an intermittent form of MR might produce similar healthspan benefits to continuous MR.
Accordingly, we developed two increasingly stringent forms of intermittent MR (IMR) and assessed whether mice maintained on these diets demonstrate the beneficial metabolic changes typically observed for continuous MR. To the best of our knowledge, we show for the first time that IMR produces similar beneficial metabolic effects to continuous MR, including improved glucose homeostasis and protection against diet-induced obesity and hepatosteatosis. In addition, like continuous MR, IMR confers beneficial changes in the plasma levels of the hormones IGF-1, FGF-21, leptin, and adiponectin. Together, our findings demonstrate that the more practicable intermittent form of MR produces similar healthspan benefits to continuous MR, and thus may represent a more appealing alternative to the classical intervention.