Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism

Rejuvenation Res. 2015 Apr;18(2):162-72. doi: 10.1089/rej.2014.1624.


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.

Trial registration: NCT02132091.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Aging / genetics*
  • Aging / metabolism*
  • Antioxidants / administration & dosage
  • Caloric Restriction*
  • Cross-Over Studies
  • Dietary Supplements
  • Double-Blind Method
  • Energy Metabolism / drug effects
  • Energy Metabolism / genetics*
  • Fasting / metabolism*
  • Feeding Behavior*
  • Female
  • Florida
  • Gene Expression Regulation
  • Healthy Volunteers
  • Humans
  • Male
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics*
  • Patient Compliance
  • Patient Satisfaction
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism
  • Time Factors
  • Young Adult


  • Antioxidants
  • SIRT3 protein, human
  • Sirtuin 3

Associated data