Elsevier

Experimental Gerontology

Volume 153, 1 October 2021, 111506
Experimental Gerontology

Review
Evidence gaps and potential roles of intermittent fasting in the prevention of chronic diseases

https://doi.org/10.1016/j.exger.2021.111506Get rights and content

Abstract

Moderate calorie restriction (CR) has long been recognized to reduce the risk of chronic diseases that are associated with obesity and aging. Intermittent fasting (IF) has recently emerged as a viable alternative to daily CR to reduce risk markers of chronic diseases, such as type 2 diabetes and cardiovascular diseases. The majority of trials have shown that IF provides similar metabolic and weight benefits to CR, although a few suggest that IF maybe superior to CR. The type of fasting protocol that is employed varies widely and could underpin the divergence in study outcomes. This review will discuss the findings of currently available IF versus CR trials, the protocol differences that exist between studies, as well as the gaps that still exist in the field, and finally will highlight upcoming studies that will further our understanding of the metabolic effectiveness of IF diets for metabolic health.

Section snippets

Calorie modification approaches to weight loss and health

Lifestyle interventions that employ a moderate daily calorie restriction (CR) of between 20–40% and increase physical activity by around 150 min/week have been consistently advocated as first line, non-pharmacological, approaches to prevent or delay the onset of chronic diseases such as type 2 diabetes and cardiovascular diseases (CVD) (Evert et al., 2019; Cosentino et al., 2020; Uusitupa et al., 2019; Knowler et al., 2002; Ravussin et al., 2015). In fact, three large population, multi-site

Identical primary outcome among similar populations

Of the fourteen studies summarized in Table 1, ten have powered on body weight and only four have prospectively powered on glycaemic outcomes (Harvie et al., 2011; Harvie et al., 2013; Hutchison et al., 2019; Carter et al., 2018). Improvements in biomarkers of health and disease, and not body weight, should be the primary focus of research in future. Two of those four observed a greater reduction in insulin resistance by HOMA-IR in women with overweight and a family history of breast cancer (

Future directions

Future studies should compare IF protocols to identify which produce the maximal metabolic benefit, but also ascertain it is acceptable for the majority to follow, whilst achieving clinically relevant health benefits. Future trials should not only focus on body weight, but power the trials to detect clinically relevant metabolic health benefits. The majority of published studies have limited to individuals who are obese but otherwise healthy, and thus the study populations should be extended to

Conclusion

To date, IF appears to be at least as effective as CR for weight loss and health outcomes, but most studies are short-term and the populations tested are mostly limited to healthy individuals with obesity. Optimization of IF protocols could maximize metabolic benefits, whilst making the fasting strategy more sustainable to facilitate long term compliance in prevention of chronic diseases.

Declaration of competing interest

The authors declared no conflicts of interest.

Acknowledgements

XTT is supported by an Australian Government Research Training Program Scholarship from The University of Adelaide.

References (80)

  • K.L. Marlatt et al.

    Persistence of weight loss and acquired behaviors 2 y after stopping a 2-y calorie restriction intervention

    Am. J. Clin. Nutr.

    (2017)
  • M.P. Mattson et al.

    Impact of intermittent fasting on health and disease processes

    Ageing Res. Rev.

    (2017)
  • R. Schubel et al.

    Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial

    Am. J. Clin. Nutr.

    (2018)
  • T.M. Sundfor et al.

    Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: a randomized 1-year trial

    Nutr. Metab. Cardiovasc. Dis.

    (2018)
  • R.R. Wing et al.

    Long-term weight loss maintenance

    Am. J. Clin. Nutr.

    (2005)
  • S.D. Anton et al.

    Flipping the metabolic switch: understanding and applying the health benefits of fasting

    Obesity (Silver Spring)

    (2018)
  • R. Antoni et al.

    Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants

    Br. J. Nutr.

    (2016)
  • R. Antoni et al.

    Intermittent v. continuous energy restriction: differential effects on postprandial glucose and lipid metabolism following matched weight loss in overweight/obese participants

    Br. J. Nutr.

    (2018)
  • R. Antoni et al.

    Efficacy of an intermittent energy restriction diet in a primary care setting

    Eur. J. Nutr.

    (2020)
  • S. Bansal et al.

    Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women

    JAMA

    (2007)
  • S.P. Bauersfeld et al.

    The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study

    BMC Cancer

    (2018)
  • K. Beaulieu et al.

    An exploratory investigation of the impact of 'fast' and 'feed' days during intermittent energy restriction on free-living energy balance behaviours and subjective states in women with overweight/obesity

    Eur. J Clin. Nutr.

    (2021)
  • S.E. Berry et al.

    Human postprandial responses to food and potential for precision nutrition

    Nat. Med.

    (2020)
  • S. Bhutani et al.

    Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans

    Obesity (Silver Spring)

    (2013)
  • E.E. Blaak et al.

    Impact of postprandial glycaemia on health and prevention of disease

    Obes. Rev.

    (2012)
  • J. Bowen et al.

    Randomized trial of a high protein, partial meal replacement program with or without alternate day fasting: similar effects on weight loss, retention status, nutritional, metabolic, and behavioral outcomes

    Nutrients

    (2018)
  • I. Caffa et al.

    Fasting-mimicking diet and hormone therapy induce breast cancer regression

    Nature

    (2020)
  • S. Carter et al.

    Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: a randomized noninferiority trial

    JAMA Netw. Open

    (2018)
  • V.A. Catenacci et al.

    A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity

    Obesity (Silver Spring)

    (2016)
  • J.L. Chan et al.

    Short-term fasting-induced autonomic activation and changes in catecholamine levels are not mediated by changes in leptin levels in healthy humans

    Clin. Endocrinol.

    (2007)
  • L.S. Chow et al.

    Time-restricted eating effects on body composition and metabolic measures in humans who are overweight: a feasibility study

    Obesity (Silver Spring)

    (2020)
  • S. Cienfuegos et al.

    Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity

    Cell Metab.

    (2020)
  • I. Cioffi et al.

    Intermittent versus continuous energy restriction on weight loss and cardiometabolic outcomes: a systematic review and meta-analysis of randomized controlled trials

    J. Transl. Med.

    (2018)
  • D.J. Clayton et al.

    24-h severe energy restriction impairs postprandial glycaemic control in young, lean males

    Br. J. Nutr.

    (2018)
  • M. Conley et al.

    Is two days of intermittent energy restriction per week a feasible weight loss approach in obese males? A randomised pilot study

    Nutr. Diet.

    (2018)
  • F. Cosentino et al.

    2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

    Eur. Heart J.

    (2020)
  • C.S. Davis et al.

    Intermittent energy restriction and weight loss: a systematic review

    Eur. J. Clin. Nutr.

    (2016)
  • R. de Cabo et al.

    Effects of intermittent fasting on health, aging, and disease

    N. Engl. J. Med.

    (2019)
  • A. di Francesco et al.

    A time to fast

    Science

    (2018)
  • T.B. Dorff et al.

    Safety and feasibility of fasting in combination with platinum-based chemotherapy

    BMC Cancer

    (2016)
    • View full text
    © 2021 Elsevier Inc. All rights reserved.