Investigating the effects of eating every other day on body composition and aging-related factors

For decades, studies in diverse animal species have shown^[1] that calorie restriction (CR) prolongs lifespan and reduces the development of chronic diseases associated with aging. Figure 1 summarizes this evidence.

The life-extending effects of CR have not been directly demonstrated in humans. However, long-term normal weight CR practitioners have shown similar metabolic characteristics as those of animal models, suggesting that CR could be a viable option to prevent modern chronic diseases, even in the absence of obesity and weight loss. But, there are some downsides to long-term CR: loss of lean mass, reduced immune function, as well as potentially reduced quality of life. The protocol itself may also be difficult to follow for many people. An alternative to constant CR that has shown promising effects in animal models is alternating periods of fasting and feasting. One way to do this is through time-restricted feeding (TRF). However, original research in animal models has suggested that an alternate-day fasting (ADF) protocol, in which feeding is restricted to every other day, might have comparable^[2] benefits. Current available studies have mostly tested fasting paradigms in people with obesity or participants with metabolic abnormalities using modified^[3] ADF paradigms (with consumption of about 25% of calories on fasting days) or in a non-controlled^[4] fashion; and metabolic parameters haven’t been measured extensively. Additionally, there is no data on long-term ADF.

The current study attempted to fill this gap in the literature by performing a short term randomized controlled trial (RCT) of ADF compared to a baseline diet in people without obesity, and a long term analysis of a cohort of participants doing ADF for at least six months.

Calorie restriction has been shown to reduce markers associated with aging in diverse animal models. However, it may have potential downsides such as loss of lean mass, reduced immune function, and reduced quality of life. Alternate-day fasting has shown to be promising in animal models as an alternative to calorie restriction, but no study to date has analyzed the effects of a “true” ADF (100% calorie restriction on fast days) on normal weight participants in the long term, as well as its effects on diverse metabolic parameters.