By Ted Wissink, MD; Craig Schneider, MD; and Booth Dargis, MD
Dr. Wissink is Assistant Professor of Family Medicine, Tufts University School of Medicine; and Associate Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center, Portland.
Dr. Schneider is Associate Professor of Family Medicine, Tufts University School of Medicine; and Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center, Portland.
Dr. Dargis is an Integrative Medicine Fellow, Department of Family Medicine, Maine Medical Center, Portland.
Dr. Wissink, Dr. Schneider, and Dr. Dargis report no financial relationships relevant to this field of study.
• Intermittent fasting led to similar weight loss as continuous energy restriction in several human trials when compared head-to-head.
• Sustainability of intermittent fasting was similar to continuous energy restriction, but not superior.
• Other markers, such as insulin resistance and fat mass, improved more with intermittent fasting than continuous energy restriction in preliminary studies, and more research in this area could clarify whether added benefits exist with intermittent fasting.
SYNOPSIS: This article explores the existing evidence for using intermittent fasting as a strategy to promote weight loss. The evidence suggests that intermittent fasting worked as well as continuous energy restriction to achieve weight loss, but was not superior.
Obesity in the United States is on the rise and contributes to significant numbers of chronic health conditions, including heart disease, hypertension, stroke, diabetes, and sleep apnea, along with an increased risk of cancer. The statistics are alarming. According to the Centers for Disease Control and Prevention, the U.S. obesity prevalence was 42% in 2018, up from 30% in 1999, and the prevalence of severe obesity increased from 5% to 9% in that same time period.1 The rise in pediatric obesity in the United States only compounds the future morbidity and mortality we will face as a healthcare system and as a society unless we can find sustainable solutions. And according to one study, only 15% of obese individuals successfully maintain weight loss in the long term.2
Many factors contribute to the growing obesity epidemic. Certainly, an increasingly sedentary lifestyle is a factor, and medical providers often include physical activity in treatment plans to address obesity. But there also is a need for dietary interventions that are both effective and safe. Continuous energy restriction (CER), defined as lowering caloric intake consistently over time, currently is the most common dietary approach recommended to promote weight loss. It has been shown to reduce body weight and improve a variety of cardiovascular risk factors.3
One critique of CER is that people have difficulty sustaining it over time. That, along with celebrity and athlete endorsements, have contributed to increased public attention for “intermittent fasting” (IF). The articles we reviewed for this summery used a variety of terminology and abbreviations to describe intermittent fasting. For clarity, we will use the abbreviation IF to describe the various intervention groups in the studies we reviewed.
IF simply is the abstinence from eating food for a defined period and consuming calories as usual during another period. Several different diets have been used under the umbrella of IF, including alternate-day fasting (consuming no calories on fasting days), alternate-day modified fasting (e.g., 5:2 weekly schedule of significant reduction of calories on only fasting days), and time-restricted fasting (restricting food intake to specific time periods of the day). Advocates suggest IF may have similar effects on weight loss as CER, but with better long-term adherence than CER.4
In this article, we chose to focus our review specifically on the effect of IF on weight loss for obese humans. Although there are numerous studies on IF and the effect on rodents, we chose to review only human studies. Our goal is to summarize any clinical recommendations that providers can use with patients based on the current evidence.
Zubrzycki et al reviewed potential weight loss diets in a recent article.5 A popular form of IF is alternate-day fasting (ADF) in which “fast days” are alternated with “feed days.” Modified ADF involves consuming a restricted number of calories on “fast days.” Other forms include 1:6 and 2:5 schedules (fasting or restricted calories one or two days per week).
Time-restricted feeding (TRF) is another form of IF in which food consumption and fasting occur during defined windows of time. IF interventions induce a metabolic shift from lipid synthesis and fat storage to fat mobilization about 12 hours after the last meal. At this point, glycogen in hepatocytes becomes depleted, lipolysis is accelerated in adipose, and tissue and ketone synthesis is increased in the liver, kidneys, etc.
Studies of IF vary based on regimen type and duration, but most demonstrate reduced body weight. Interestingly, weight loss does not seem to be necessary to obtain the positive metabolic outcomes in TRF, and it may produce greater weight loss than other forms.6
Harvie et al compared a 25% energy restriction delivered either through 5:2 IF or CER for weight loss and insulin resistance.7 They recruited and randomized 107 premenopausal overweight or obese women from a clinic for women with a family history of breast cancer. The CER group received 25% restriction based on a Mediterranean-type diet (30% fat, 15% monounsaturated fatty acids [MUFA], 7% saturated fat, 7% polyunsaturated fatty acids [PUFA], 45% low glycemic load carbohydrate, 25% protein).
The IF group (5:2) followed 75% restriction on two consecutive days and then a diet calculated for weight maintenance the remaining five days, comprised of part-skim milk, vegetables, fruit, salty low-calorie drinks, and a multivitamin and mineral supplement.
By the end of the study, 30% of the IF group and 33% of the CER group lost 5-10% body weight, while 34% of IF and 22% of CER lost 10% or greater of body weight (X2 = 1.89; P = 0.39). Both groups had reductions in fasting insulin and improvement in insulin sensitivity P = 0.001). There were no major adverse effects of the diets. Intention-to-treat analysis demonstrated that IF and CER were equally effective for weight loss, but IF was not any easier to adhere to.
Harvie et al then compared a 5:2 intermittent energy and carbohydrate restriction (IF), a similar diet with unrestricted protein and fat (MUFA, PUFA) (IF + PF), to a daily energy restriction (CER) for change in weight, adiposity and insulin resistance.8 One hundred fifteen overweight or obese women ages 20-69 years who reported weight gain more than 7 kg since age 20 were assigned randomly to a diet.
For CER, the authors used a Mediterranean-type diet similar to that described in the 2011 article. The IF group restricted energy to 70% and carbohydrate to 40 g on two consecutive days, and subjects were instructed to consume a Mediterranean-type diet estimated to meet their caloric needs for weight maintenance the remaining five days. The IF + PF group consumed the same diet but were permitted unlimited lean meat, fish, eggs, tofu, MUFA, and PUFA on restricted days. After three months, the CER group had calories increased to meet their daily weight maintenance requirements, and the IF and IF + PF groups were limited to just one restricted day weekly.
All groups were advised to increase their exercise gradually, with the goal of 45 minutes of moderate activity five times weekly. Intention-to-treat analysis was used, and during the weight loss period (three months), 5% or greater weight loss was achieved by 65% of intermittent energy and carbohydrate restriction (IECR), 58% of IECR + PF, and 40% of CER (X2 = 5.2; P = 0.076), but weight reduction was comparable.
IF and IF + PF reduced adiposity compared to CER (IECR P = 0.007; IECR + PF P = 0.019). IF and IF + PF experienced significantly greater reductions in serum insulin (P = 0.017) and homeostatic model assessment (HOMA) (P = 0.02) from baseline compared to CER. All groups maintained the improvements during the one-month weight maintenance phase. In the short-term, IF performed better than CER for loss of body fat and improved insulin sensitivity. Unlimited protein and fat did not improve the acceptability of the IF diet. Interestingly, those on both IF diets spontaneously restricted their energy and carbohydrate intake on nonrestricted days as well. No serious adverse effects of the diets were reported.
A 2017 review by Harvie and Howell summarized available randomized trials up to that point and found six small, short-term (fewer than six months) trials among the overweight or obese that met inclusion criteria.9 All of the trials demonstrate comparable weight loss between intermittent energy restriction (IF, not including time-restricted feeding) and CER for weight loss. One of these found IF superior for body fat loss, two for greater reductions in HOMA (a measure of hepatic insulin sensitivity) insulin resistance, and no clear evidence of harm.
Unfortunately, all of these trials were small, brief, and underpowered. Generally, adherence to IF and CER was similar. Interestingly, IF was not associated with compensatory hyperphagia during the nonrestrictive eating days. Larger studies of longer duration, including broader population and real world conditions, still are needed.
Because most diets achieve maximal weight loss around six months followed by a period of gradual weight regain, the purpose of a 2016 review was to look at long-term effects (six months or longer) of intermittent energy restriction (IF) on weight and biological markers.10
Starting with 968 records, nine studies met inclusion for qualitative synthesis and six for the meta-analysis. Studies ranged from six to 24 months and included modified ADF, a 5:2 regimen, intermittent continual energy restriction (a week-on, week-off strategy), and very low energy diets (VLED) as the IF interventions.
Each of these IF diets led to weight loss comparable to CER, and weight loss (although less so) was demonstrated at the end of each trial lasting up to 24 months. Each IF diet was successful in achieving significant weight loss (P < 0.05) compared to baseline but was not superior to CER. No associations among gender, body mass index (BMI), and weight loss were noted. There were no significant differences reported between industry- or non-industry supported studies. Dropouts for IF and CER/control groups were similar. There were no serious adverse events reported.
Trepanowski et al recently evaluated 100 people, mostly women, comparing alternate day fasting/feasting type IF (25% baseline calories/125% baseline) vs. daily CER (75% baseline daily) vs. control.11 They found weight loss in both groups compared to control, but none between groups. They found increased dropouts in the alternate day IF. IF was not superior to CER, but this IF protocol appeared to be more difficult to tolerate.
Another interesting prospective study in 2019 compared effects from three different diets that participants were allowed to choose.12 This was a 12-month, five-arm (control and four intervention arms), randomized, controlled trial with overweight, but otherwise healthy, adults.
Those who participated chose between a Mediterranean (n = 68), IF (n = 136), or Paleo diet (n = 46). To represent a realistic patient population, those with managed anxiety/depression, hypertension (HTN), prediabetes, hyperlipidemia, and controlled asthma were allowed to participate in the study. The IF diet used the 5:2 method, with normal calorie intake five days/week, and markedly reducing intake two days/week (500 kcal/day for women and 600 kcal/day for men). The Paleo diet emphasized less-processed foods, consuming animal protein, fruits and vegetables, butter, coconut products, and extra virgin olive oil.
Participants recorded three-day diet records at baseline, six, and 12 months. IF was the most popular diet option, with 54% of participants choosing this over Mediterranean (27%) or Paleo (18%). Overall retention was 82% at six months, and 68% at 12 months, but only half of those who chose the Mediterranean or IF diets were still adhering, while only one-third of those who chose Paleo reported adherence by 12 months. Most of the IF group were still fasting for two days per week (76% at six months, 73% at 12 months), but only one-third were meeting the calorie targets.
Energy intake was decreased in all groups at 12 months compared to baseline, with IF participants having lower energy intakes than the other groups. However, there were no significant differences among the three diets in terms of physical outcomes over time. All the groups lost weight by six months, and continued weight loss at 12 months was seen in the IF and Mediterranean groups. The IF group did show a greater overall energy deficit and weight loss (average, 4.2 kg), even with only modest adherence to the fasting recommendations, but the differences were not statistically significant.
We set out to evaluate whether IF represents an advance from the conventional CER approach to weight loss. Although IF repeatedly has demonstrated equivalent weight loss to CER, it is not superior. There also is no evidence that weight loss is sustained for longer in IF, nor that IF is easier to adhere to than a conventional CER approach. However, there are markers of health other than weight that favor IF, and demonstrated weight loss is not inferior. Taken together, this makes IF a valid option for weight loss and an advance in conventional thinking.
Despite widespread anecdotal stories of IF, the accumulated empirical evidence for weight loss relating to IF remains limited. With no standard definition and fasting protocols varying from study to study, even talking about IF as a monolith is problematic. The reviewed studies encompass TRF, ADF or fasting one to two days per week, total fast to caloric reduction, just to name a few. This mixing of methodologies does not allow any distinction among the contributions of meal timing, variable-day fasting, and continuous caloric reduction to weight loss. Although the current dearth of clinical trial data leaves the possibility that one of the numerous IF methodologies will emerge as superior, there is no initial indication that this will be the case.
Although no difference in weight loss is shown thus far between IF and CER, they are not completely equivalent. Reviewed studies have shown cases of improved insulin resistance, reduced fat mass, and increased growth hormone secretion of IF protocols compared to CER, despite no differences in weight loss. The difference in health markers other than weight leave open the possibility that, given longer periods of time, IF may prove to be better for health overall compared to CER, without any initial differences in weight.
Although the current available evidence indicates that IF is not superior to CER for weight loss, we are encouraged by its noninferiority. It is unlikely that there is one diet that is optimal for every person, thus searching for a “one size fits all” solution to something as complex as weight loss likely is an endeavor to end in frustration. Each individual has motivations, circumstances, and needs that are unique, and the job of a skilled clinician is to help guide patients to an approach that will lead to improved health.
In this setting, we think that IF could be beneficial. It is demonstrably safe, with weight loss equivalent to conventional CER. There have been multiple protocols leading to weight loss, which means that people have many options for making an IF approach fit into their lifestyle.
Although no one protocol has demonstrated increased adherence over another or CER across a group, it stands to reason that the more effective options available, the more likely it is for an individual to find “their” effective approach.
At this point, more questions remain than there are answers to be found regarding IF. Future investigation could elucidate whether there is a difference among various IF protocols, whether the population able to adhere to CER and IF are the same or differ, and whether it is food timing or food amount that leads to weight loss in IF, to name a few. The story of IF is in its early stages, but it may even now be a step on the path to health for some.
- Hales CM, Carroll MD, Fryar CD, et al. National Center for Health Statistics. Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS data brief no. 76. Hyattsville;2020.
- Purcell K, Sumithran P, Prendergast LA, et al. The effect of rate of weight loss on long-term weight management: A randomized controlled trial. Lancet Diabetes Endocrinol 2014;2:954-962.
- Redman LM, Ravussin E. Caloric restriction in humans: Impact on physiological, psychological, and behavioral outcomes. Antioxid Redox Signal 2011;14:275-287.
- Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: Hormesis or harm? A systematic review. Am J Clin Nutr 2015;102:464-470.
- Zubrzycki A, Cierpka-Kmiec K, Kmiec Z, et al. The role of low-calorie diets and intermittent fasting in the treatment of obesity and type-2 diabetes. J Physiol Pharmacol 2018;69:663-683.
- Gabel K, Hoddy KK, Haggerty N, et al. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: A pilot study. Nutr Healthy Aging 2018;4:345-353.
- Harvie MN, Pegington M, Mattson MP, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: A randomized trial in young overweight women. Int J Obes (Lond) 2011;35:714-727.
- Harvie M, Wright C, Pegington M, et al. 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;110:1534-1547.
- Harvie M, Howell A. Potential benefits and harms of intermittent energy restriction and intermittent fasting amongst obese, overweight, and normal weight subjects—A narrative review of human and animal evidence. Behav Sci (Basel) 2017;7:1-22.
- Headland M, Clifton PM, Carter S, et al. Weight-loss outcomes: A systematic review and meta-analysis of intermittent energy restriction trials lasting a minimum of 6 months. Nutrients 2016;8:1-12.
- Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults. JAMA Intern Med 2017;177:930-938.
- Jospe MR, Roy M, Brown RC, et al. Intermittent Fasting, Paleolithic, or Mediterranean diets in the real world: exploratory secondary analyses of a weight-loss trial that included choice of diet and exercise. Am J Clin Nutr 2019;111:503-514.