What you don’t eat could be affecting your circadian behaviour
Scientists at the University of Manchester are investigating the effect of methionine deficiencies on the circadian rhythms and behaviour.
“We are what we eat” is a well-known expression, but what we consume can also affect our behaviour – give a child a whole coffee cake and you can anticipate the results. The nutrients we get from food are used in multiple internal processes, some simply burned as fuel but others are essential for brain and body functions including the regulation of gene expression, crucial to physiology and behaviour. Chronically consuming too little or too much of key nutrients has known widespread effects on health, such as scurvy if you do not eat enough vitamin C for 2-3 months, or gout if you eat an excess of purines. But inappropriate intake of nutrients may have more acute consequences on physiology and behaviour, detectable after only a few days- if we know where to look.
Dr Jean-Michel Fustin and his lab have been looking at excesses and deficiencies of nutrients and nutritional supplements involved in a fundamental metabolic pathway called 1-carbon metabolism. Most recently they have investigated the effects of methionine and choline deficiency (MCD)– a diet usually given to mice to cause and model a liver condition known as non-alcoholic steatohepatitis (NASH), a condition that takes several weeks to develop. However, after only a few days this diet causes dramatic circadian disruptions that disappear just as soon as the MCD diet is replaced with normal chow. Mice who are fed the MCD diet exhibit shortened circadian periods, irregular activity onsets and compression of the active phase to a single intense bout of activity. Somehow, this diet is throwing off the internal clock.
An actogram showing the daily activity patterns of a female mouse fed the control diet (CTL F) and a female mouse fed the methionine/choline deficient diet (MCD F). X axis depicts time. Y axis depicts day. Source: Saer et al.
Methionine appears to be the major player here, since a diet that is only deficient in methionine reproduces these findings, and without causing NASH! You might remember methionine from your early lessons in genetics – the start codon AUG codes for it and it is needed for the translation of every protein. However, methionine has other uses; it is the precursor for the synthesis of S-adenosyl-L-methionine (SAM) that is involved in several fundamental processes such as DNA and histone methylation, which are crucial for turning genes on and off.
While the mechanisms underlying the effects of methionine on circadian rhythms are still unknown, this research, using disruptions of circadian rhythms as a read-out for metabolic disruptions, further supports the case for circadian medicine. Perhaps one day there will be a prescribed optimum circadian-friendly diet, or a diet that enables you to reduce the effects of jet lag or shift work. For now, we’re still figuring out the effects of individual dietary components on circadian rhythms, but watch this space.
Who is involved in this research?
Jean-Michel Fustin, edited by Lorena Rosen
26 February 2025