Early time-restricted fasting confers health benefits in humans

fx1.jpgCalorie restriction (CR), in which an organism is allowed to eat only a fraction of the food it would normally consume, reliably extends healthspan and lifespan in a variety of model organisms, and the preliminary results of clinical trials in humans are promising. An alternative strategy, intermittent fasting (IF), is also gaining traction in basic research, and has even emerged into popular culture as a fad diet for weight loss.

Each approach can be further subdivided in terms of degree (85% of ad libitum calories, or 70%?), timing (alternate-day fasting or 5:2?), and duration (just for a month, or for life?). Each variant is likely to have a different efficacy in terms of health improvement and extension of the healthspan. An important aspect of efficacy is compliance: a regimen that is effective only if the subject is closely supervised is unlikely to be useful in the population at large.

Finally, the source of the benefits of CR and IF remains in question. For example, IF has been shown to improve various aspects of cardiometabolic health, but it remains unclear whether those were simply due to weight reduction—in which case we’re simply left with the age-old question of how best to encourage humans to lose weight.

A recent study has shed light on these issues. Sutton et al. report that that early time-restricted feeding (eTRF), in which the subject eats a normal amount of calories during a specific time interval early in the day, confers health improvements in human beings. Notably in regard to the questions raised above, the benefits were not dependent upon weight loss.

The benefits were diverse but not entirely comprehensive: eTRF improved certain aspects of cardiac health, such as blood pressure, but had no effect on cardiac stiffness or blood lipoprotein levels. Similarly, some markers of aging were downregulated (specifically, those related to oxidative stress), whereas inflammatory signals were unchanged. (Given that the regimen did not result in significant weight loss, this is not surprising: overall inflammatory tone is largely driven by factors produced by abdominal fat. No loss of fat,  no decrease in inflammation.)

The “e” in “eTRF” is important: the body’s hormone profile changes with the circadian rhythms; we are more insulin-sensitive in the morning than in the evening. Consistent with this, TRF is effective in rodent models only when feeding occurs in the early part of the waking day. (Pardon the elliptical construction; I deliberately avoided  saying “morning” in the previous sentence because rodents are, as we know, nocturnal).

Importantly, the eTRF regimen decreased the participants’ appetite later in the day, thus reducing the temptation to cheat. This has major implications for compliance: Humans eat when we shouldn’t for a lot of reasons, but mostly because some signal is telling us that we’re hungry. Eating a full daily complement of calories early in the day seems to attenuate the relevant hunger pathways, likely making it easier for subjects to stay with the program. (Although the authors don’t mention this, I would speculate that allowing the subject to live the same way every day, rather than eating on some days and not on others, would also make compliance easier.)

Indeed, the subjects reported that they found it more challenging to eat a day’s worth of food in 6 hours than to avoid food for 18 — in other words, it was easier to fast than to feast. Therefore, one wonders whether adopting eTRF might also induce some degree of CR, simply because the subjects aren’t hungry enough to eat even when they’re allowed to.

Sutton et al. “Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.” Cell Metabolism (2018). DOI: 10.1016/j.cmet.2018.04.010