Intermittent fasting (IF) is a general term describing a patterned eating routine that includes a period of restricted caloric consumption.1 Also known as time-restricted eating and time-restricted feeding, numerous variations exist. For example:
- 25% of a normal caloric intake day alternating with 125% of a normal caloric intake day
- Fasting two days each week without any food (5:2), eating without changes the rest of the week
- Six- to eight-hour window for food consumption each day
Intermittent fasting has become popular recently as more studies are published that highlight the potential merit of these strategies.
The foundation rests upon observations in rodents demonstrating longevity and a shift toward ketogenesis (called metabolic switching) with prolonged daily fasting intervals.1 As early as the 1930s, researchers identified an inverse relationship between caloric restriction and longevity in rodents.²,³ In one remarkable study using genetically obese mice with twice the body fat of control mice, caloric restriction allowed the lifespan of the obese mice to surpass that of control mice.⁴ Importantly, the nutritional composition did not seem to be the predominant factor. Subsequent studies of caloric restriction in rodents consistently demonstrated improvement in resilience toward many age-related diseases.
In humans, ketone production from triglyceride-derived fatty acids in the liver during a fasting state is detectable within eight hours and may remain elevated for up to twenty-four hours.5 During this fasting state, ketones become the predominant energy source for the brain and several other organs. The result is two-fold: improved metabolic efficiency using ketones as an energy source with a reduced respiratory exchange ratio (compared with glucose)6 and potent direct downstream signaling effects of several proteins critical in metabolism and brain health.7-10
Currently, there are no trials consistently demonstrating greater weight loss with intermittent fasting over calorie restriction in humans. However, fasting periods have beneficial effects beyond the potential for weight loss.11,12 Findings in mice and some human trials include less free radical production, integrated adaptive cellular responses involving reduced anabolism, heightened stress resistance, and anti-inflammatory pathways, along with improved glucose, blood pressure, and heart rate regulation. Ongoing studies are also necessary to further elucidate whether humans will have the same longevity and disease mitigation as rodents.
Thus, appropriately timed intermittent fasting as a structured, recurrent lifestyle intervention coupled with continued education on nutrition, exercise, and stress reduction is a potentially beneficial health tool for patients. Caution is advised for patients with diabetes or patients prescribed anti-hyperglycemic agents given the potential risk for hypoglycemia or ketoacidosis.13
- de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease. NEJM. 2019;381(26):2541-2551.
- McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size: One figure. J Nutr. 1935;10(1):63-79.
- McCay CM, Maynard LA, Sperling G, Barnes LL. Retarded growth, life span, ultimate body size and age changes in the albino rat after feeding diets restricted in calories: Four f J Nutr. 1939;18(1):1-13.
- Harrison DE, Archer JR, Astle CM. Effects of food restriction on aging: separation of food intake and adiposity. PNAS. 1984;81(6):1835-1838.
- Cahill Jr GF. Starvation in man. NEJM. 1970;282(12):668-675.
- Di Francesco A, Di Germanio C, Bernier M, de Cabo R. A time to fast. Science. 2018;362(6416):770-775.
- Newman JC, Verdin E. β-Hydroxybutyrate: a signaling metabolite. Annu Rev Nutr. 2017;37:51-76.
- Fisher FM, Maratos-Flier E. Understanding the physiology of FGF21. Annu Rev Physiol. 2016;78:223-241.
- Gälman C, Lundåsen T, Kharitonenkov A, Bina HA, Eriksson M, Hafström I, Dahlin M, Åmark P, Angelin B, Rudling M. The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARα activation in man. Cell Metab. 2008;8(2):169-174.
- Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci. 2018;19(2):63.
- Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. PNAS. 2003;100(10):6216-6220.
- Harvie M, Wright C, Pegington M, McMullan D, Mitchell E, Martin B, Cutler RG, Evans G, Whiteside S, Maudsley S, Camandola S. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013;110(8):1534-1547.
- Alejandra Fernandez-Cardona, Dejanira Gonzalez-Devia, Carlos O Mendivil. Intermittent fasting as a trigger of ketoacidosis in a patient with stable, long-term type 1 diabetes. J Endocr Soc. 2020; 4(10).