Alternate Day Fasting and Calorie Restriction Produce Similar Outcomes in Humans

Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study, we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after more than 6 months.

ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.

Study published in Cell Metabolism 2019, 30 (3); p462-476.

So is alternate day fasting just calorie restriction? In animal studies there are significant differences in gene expression profiles between these two approaches, which is enough to suspect that perhaps fasting and feeding versus a consistent low calorie intake are two different beasts. The effects on metabolism are sweeping in either case, which makes analysis challenging, but the important mechanisms, the upregulation of cellular stress response systems such as autophagy, appear the same. More recent research into fasting mimicking diets has attempted to find the point at which low calorie intake triggers benefits, and quantify how long the low calorie diet must be sustained. The results there suggest that additional benefits emerge after three to four days, in terms of a culling of immune cells. That work also suggests that the process of refeeding after a fast is necessary in order to obtain the full benefits.

Article and commentary first published on FightAging.org