June 18, 2015

expert reaction to effects of fasting diet in mice and humans

A study published in Cell Metabolism looked at the effects of feeding a calorie-restricted diet to mice for a few days each month, and reported subsequent tissue regeneration and an increased number of stem cells. A similar calorie-restricted diet was then piloted in a small randomised clinical trial with human participants, with a reported decreased risk factors for ageing, diabetes and heart disease.

Prof Lynne Cox, Associate Professor of Biochemistry, University of Oxford, said:

“This new study reports how a special diet that mimics the effects of fasting can extend healthspan (time spent in good health). For many years, caloric restriction (cutting out 30-40% of your calories each and every day) has looked the best bet for improving health outcomes during ageing, but this new diet appears much easier to stick to than caloric restriction – in humans, it involves taking low protein plant-based meal replacements that provided a third to a half of normal calorie intake for five days every month over a cycle of three months.

“What is noteworthy here is that the study incorporates a whole host of experiments from model organisms as simple as yeast cells, through mice and into a small controlled clinical trial in humans. All of the results point in one direction: periodically mimicking fasting (i.e. very low calorie intake whilst maintaining micronutrients) leads to marked decreases in risk factors for diseases such as diabetes and heart disease, and, in mice, improved short and long term memory were observed. Most notably, cancer incidence dropped by 45% in the mice; we’re not mice and their cancer rate is vastly higher than ours, but the finding that the diet may increase cells’ capacity to recycle worn out components (a process called autophagy) and also reduces inflammation is potentially important, not least because inflammation is thought to contribute both to ageing and cancer.

“The authors stress that the diet should only be administered under clinical supervision, and they rightly exclude from their study anyone with underlying health conditions. It is certainly not something to be undertaken lightly and the calorie intake is likely to make most active people feel tired, and sick people possibly sicker. In fact, the regime was shortened as mice got older because there appeared to be some additional risk of death on abrupt changes to feeding patterns. The human fasting diet was also surprisingly high in fat as a percentage of total calorie intake – far more than current government guidelines. Some of the changes after dieting were akin to age-related muscle loss and liver atrophy, but these did appear to be restored to normal after refeeding. In addition, the two arms of the trial (normal feeding and on the cyclical fasting diet) had a different percentage of men and women and the treatment group on average were six years older than those in the control arm, making comparisons more complex. As to the position of the authors, a couple of them have already branched out into the commercial sector making the diet formulation – but this doesn’t necessarily mean that the science is biased; perhaps it simply shows how important they believe their own findings to be.

“There have been many claims of diets that improve health, but the difference here is the wealth of scientific data from across species and the fact that the human study set out to establish a proper trial comparing the effects of the diet with normal eating patterns; it is based (in the main) on sound science. Yes, it needs more tests and in some cases different ways of measuring outcomes. And as far as the mice were concerned, the diet meant fewer younger mice died, though the rate of death accelerated later. The numbers in the human trial are small so it really needs to be done for much longer and with a far larger sample size, but the trends look interesting. If over a longer time human findings match up to the results in mice (which cover the whole lifecourse) then this type of intervention has the potential to improve health – though it is likely to be more relevant to young and middle-aged people as drastic metabolic changes may not be well-tolerated in older people.”

Declared interests

Prof Lynne Cox: “I work on the molecular basis of biological ageing. I am a full time employee of the University of Oxford (Associate Professor of Biochemistry). I co-hold a BBSRC grant on ageing, and a Glenn award for medical research. I am co-founder of OxAgeN (Oxford ageing Network), am a member of the British Society for Research on Ageing (BSRA), Biochemical Society and Genetics Society, and senior associate member of the Royal Society of Medicine. ‎I used to serve on the exec committee of the BSRA but am not currently on any decision making bodies external to my university appointment. I have no competing financial interests.”