Martin P Wegman, Michael H Guo, Douglas M Bennion, Meena N Shankar, Stephen M Chrzanowski, Leslie A Goldberg, Jinze Xu, Tiffany A Williams, Xiaomin Lu, Stephen I Hsu, Stephen D Anton, Christiaan Leeuwenburgh, Mark L Brantly
Journal: Rejuvenation research 2016;18(2):162-72
PMID: 25546413
It has been repeatedly shown that calorie restriction is beneficial for health by delaying the onset of age-related diseases. Long term calorie restriction is difficult to maintain. It is thought that benefits are due to increased oxidative stress which triggers expression of protective genes, resulting in an overall health benefit. Intermittent fasting (IF), where days of fasting and feasting are alternated, can result is similar benefits. In this double-crossover, double-blinded, randomised clinical trial seventeen young, healthy adults followed either IF + placebo or IF + antioxidants for three weeks each. The provided food was based on American Dietary Guidelines and the antioxidant supplements were vitamins C and E. Participants ate 25% of calories on fast days and 175% of calories on feast days to achieve overall neutral calorie balance. The aim of the trial was to show if benefits were due to intermittent periods of fasting rather than overall calorie reduction commonly seen with other IF trials. Further, if antioxidant supplements would reduce expression of the protective genes. Markers of oxidative stress and gene expression were measured. Results showed that IF decreases insulin, but IF + antioxidants did not, suggesting that the insulin lowering effect might be triggered by IF oxidative stress. Results also suggested IF mildly raised measured gene expression, including expression of sirtuin 3 (SIRT3), but IF + antioxidant reduced or reversed rises. However, none of the gene expression results were statistically significant, SIRT3 was closest. The authors stated that the findings suggest that IF may have some benefits on metabolism and potentially longevity, even in healthy individuals.
Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.
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