Intermittent Fasting: An Update by Christina Badaracco, MPH, RD
Updated: Nov 11, 2020
Intermittent fasting has continued to be a popular diet for a variety of health conditions and goals. In fact, it was the most-searched diet on Google in 2019. It has also continued to receive considerable attention among the research community—indeed, there are currently 103 clinical trials listed on clinicaltrials.gov. This post highlights new evidence and resources on intermittent fasting from the past two years. For more background on this topic—including a list of those for whom intermittent fasting would not be indicated—see the previous Insight about Intermittent Fasting.
What are the different forms of intermittent fasting?
Time-restricted feeding is likely the most common form of intermittent fasting. It does not limit caloric intake but, rather, compresses it into a specific timeframe—often 10 or 12 hours but up to 16 hours—each day. Emerging evidence suggests the optimal window may vary for men and women.
Another approach, called the 5:2 diet, involves consuming a regular diet for five days each week and then restricting to 500 calories for the other two days. Alternate-day fasting includes a day of normal eating patterns alternating with a restricted-calorie day (potentially as low as 500 calories). The one-meal-a-day (OMAD) diet comprises one meal per day, followed by 23 hours of fasting. The warrior diet is a slightly more liberal version of the OMAD, which offers a four-hour window in which to eat. A final restricted-eating pattern involves a 24-hour fast followed by a day of regular eating. As the most restrictive option, it can have the most extreme side effects. Note that, for all of these approaches, the "normal" diet on non-restricted days should still be healthy and include a variety of whole foods.
How does intermittent fasting affect metabolism?
Understanding the potential benefits of intermittent fasting requires some technical justification for its physiological impacts. Periods of intermittent fasting result in low levels of available amino acids, glucose and insulin. This pattern suppresses downstream signaling of anabolic pathways (those that promote growth and require energy input), leading to reduced synthesis of new molecules and increased autophagy (the breakdown of damaged cells). It also leads to epigenetic changes that affect which genes are expressed, promoting better resistance to cellular stressors and the creation of new mitochondria. On a macroscopic scale, these changes lead to improved health and resistance to disease.
While in a fed state, the body prefers to use glucose as a primary energy source. In a starved or fasting state, it will be forced to produce and use molecules called ketones as an energy source instead. The liver produces ketones after it breaks down available triglycerides to provide fuel for the heart, brain and muscles. High levels of ketones in the blood can become dangerous (as might result from uncontrolled diabetes), but this metabolic switch between glucose when full and ketones when starved is a normal adaptation to starvation.
What are the potential benefits of intermittent fasting?
During a short period of fasting, the decline in circulating insulin causes the body to seek internal sources of glucose, breaking down stores of glycogen and fat, which can lead to weight loss over an extended period. Many scientists also suggest that repeated pauses from eating provide a real benefit for the GI system. Repeated periods of fasting stimulate adaptive stress responses that promote improved cellular defense mechanisms, which are maintained over time (unless interrupted by periods of overeating and sedentary behavior). Evidence also suggests that ketones have beneficial effects beyond simply supplying energy; they are involved in various signaling pathways, including promoting the formation of brain-derived neurotropic factor (BDNF), which enhances brain health. It is also possible that following an intermittent eating schedule may lead to improved overall intake since it could cause people to be more mindful of what they eat and be less likely to snack on desserts, alcohol or other processed snacks before bed.
Some evidence suggests that intermittent fasting can help lower cholesterol, control blood glucose and blood pressure, and improve endurance and sleep quality, even independent of caloric restriction and weight loss. Evidence also continues to suggest that fasting can reduce tumor growth and could help prevent the recurrence of breast cancer. This may be due to the decline in insulin production, which is an anabolic hormone known to contribute to inflammation and tumor growth when elevated for extended periods. For weight loss, there doesn’t seem to be a consistent benefit compared to other diets, however. Time-restricted feeding likely has the best evidence base for improved health outcomes at this time, although a recent study by Stekovic et al. found that alternate-day fasting, including a drastic 36 straight hours of fasting, was safe to follow for several months and resulted in weight loss, improved markers of aging and improved lipid panels.
What other factors should patients consider?
Of course, exercise and a wholesome diet are still important to promote health and realize these benefits. Consuming a diversity of foods, with plenty of fruits, vegetables, whole grains, legumes, nuts, seeds and fish rich in omega-3 fatty acids, is essential, regardless of timing.
Currently, I would not actively recommend this dietary pattern to most of my patients, unless they were seeking information about it and clearly had the necessary will power and social support to follow an intermittent fasting plan. This pattern can impede social and family life, thus making it difficult to adopt or maintain when the surrounding community continues with its typical American eating schedule. It requires more advanced planning and may necessitate substantial shifts in exercise and activity schedules, which may not be feasible for many (e.g., busy parents, stressed college students or senior citizens). It is also very restrictive and difficult to maintain over time, causing most patients to return to their previous habits. It may even lead to binging and increasing weight over time. Finally, there are several groups for whom intermittent fasting would not be indicated, including people with diabetes, a history of eating disorders or a medication regimen that requires food intake; adolescents who are actively growing; or women who are pregnant or breastfeeding. However, for patients who have struggled to lose weight or control their chronic conditions such as diabetes or heart disease and who have strong willpower and flexible schedules that will allow them to successfully follow an intermittent fasting diet with support, I may consider recommending it and offering guidance.
de Cabo R, Mattson MP. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med. 2019 26;381(26):2541-2551.
de Groot S, Pijl H, van der Hoeven JJM, and Kroep JR. Effects of short-term fasting on cancer treatment. J Exp Clin Cancer Res. 2019; 38: 209.
Grajower MM, Horne BD. Clinical Management of Intermittent Fasting in Patients with Diabetes Mellitus. Nutrients 2019; 11(4): 873.
Harris L, Hamilton S, Azevedo LB, et al. Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Database System Rev Implement Rep. 2018;16(2):507-547.
Santos HO, Macedo RCO. Impact of intermittent fasting on the lipid profile: Assessment associated with diet and weight loss. Clin Nutr ESPEN. 2018;24:14-21.
Stekovic S, Hofer SJ, Tripolt N, et al. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans. Cell Metabolism 2019; 30(3): 462-476.e5.
Christina Badaracco, MPH, RD
Christina is a registered dietitian and author who aims to improve access to healthy and sustainable food and educate Americans about the connections between food and health. She loves to experiment with healthy recipes in the kitchen and share her creations to inspire others to cook.
Christina completed her dietetic internship at Massachusetts General Hospital and earned her Master of Public Health degree from the University of California, Berkeley. Previously, she graduated with a degree in Ecology and Evolutionary Biology from Princeton University, after conducting her thesis on sustainable agriculture and energy in Kenya. She has done clinical nutrition research at the National Institutes of Health, menu planning and nutrition education at the Oakland Unified School District and communications at the Environmental Protection Agency’s Office of Water. She has also enjoyed contributing to children’s gardens, farmers’ markets and a number of organic farms.