Meal frequency and timing in health and disease

Mark Mattson

David Allison

Luigi Fontana

Michelle Harvie

Eric Ravussin+4 authors

^{Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD, 21224;}

^{Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205;}

^{Nutrition and Obesity Research Center, University of Alabama, at Birmingham, Birmingham, AL, 35294;}

^{Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63130;}

^{Department of Clinical and Experimental Sciences, Brescia University, 25123 Brescia, Italy;}

^{CEINGE Biotecnologie Avanzate, 80145 Naples, Italy;}

^{Genesis Breast Cancer Prevention Centre, University Hospital South Manchester, Wythenshaw, M23 9LT Manchester, United Kingdom;}

^{Longevity Institute, Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089;}

^{Laboratory of Experimental Hormonology, Brussels Free University, B-1070 Brussels, Belgium;}

^{British Broadcasting Corporation, W1A 1AA London, United Kingdom;}

^{Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, 32610;}

^{Pennington Biomedical Research Center, Baton Rouge, LA, 70808;}

^{Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, 02115;}

^{Biology Department, Boston College, Chestnut Hill, MA, 02467;}

^{Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, 60612; and}

^{Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037}

^{To whom correspondence may be addressed. Email:}vog.hin@nosttam.kram or ude.klas@adnap.

Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved October 7, 2014 (received for review July 23, 2014)

Author contributions: M.P.M., D.B.A., L.F., M.H., V.D.L., W.J.M., M.M., L.N., E.R., F.A.J.L.S., T.N.S., K.A.V., and S.P. wrote the paper.

Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved October 7, 2014 (received for review July 23, 2014)

Abstract

Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.

Keywords: metabolism, circadian rhythm, time-restricted feeding, feeding behavior, obesity

Abstract

Obesity and associated diseases of modern societies (diabetes, cardiovascular/cerebrovascular disease, cancers, and Alzheimer’s disease) are overwhelming health care systems. Unfortunately, the common knowledge that reducing overall calorie intake and regular exercise can help optimize body weight and reduce disease risk has, in many cases, not been implemented successfully. Some of the advice provided by physicians and dieticians to their patients is consistent with the current scientific evidence, including the benefits of vegetables, fruits, fiber, nuts, and fish, and the value of reducing or eliminating snacks. However, there are many myths and presumptions concerning diet and health, including that it is important to eat three or more meals per day on a regular basis (1, 2). Although many aspects of diet and lifestyle influence metabolic status and disease trajectory during the life course, emerging findings suggest that the influences of the frequency and timing of meals on health may be large, but are difficult to characterize with any generality. Here we describe the physiological responses of laboratory animals and human subjects to controlled variations in meal size, frequency, and circadian timing, and their impact on health and disease in modern societies. Three experimental dietary regimens are considered: (i) caloric restriction (CR), in which daily calorie intake is reduced by 20–40%, and meal frequency is unchanged; (ii) intermittent energy restriction (IER), which involves eliminating (fasting) or greatly reducing (e.g., 500 calories per day) daily intake food/caloric beverage intake intermittently, for example 2 d/wk; and (iii) time-restricted feeding (TRF), which involves limiting daily intake of food and caloric beverages to a 4- to 6-h time window. We also consider the cultural and industrial barriers to implementing evidence-based healthy eating patterns, and strategies for removing or circumventing those barriers.

Acknowledgments

This article incorporates information from a workshop on “Eating Patterns and Disease,” which can be viewed at videocast.nih.gov/summary.asp?Live=13746&bhcp=1, and was supported by the National Institute on Aging Intramural Research Program and the Glenn Foundation for Medical Research. Relevant research in the authors' laboratories are supported by NIH intramural support (to M.P.M.); NIH Grants P30DK056336 (to D.B.A.), P01AG034906 (to V.D.L.), R01NS041012 (to L.N.), P30DK072476 (to E.R.), R01DK099512 (to F.A.J.L.S.), R01NS055195 (to T.N.S.), R01HL106228 (to K.A.V.), and R01DK091618 (to S.P.); the European Union's Seventh Framework Programme MOPACT [mobilising the potential of active ageing in Europe; FP7-SSH-2012-1 Grant 320333 (to L.F.)]; a grant from Genesis Breast Cancer Prevention, UK (to M.H.); and Belgian Foundation for Scientific Medical Research Grant 3.4520.07 (to W.J.M.).

Acknowledgments

Footnotes

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Footnotes

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