By Adelaide Agyepong, MD, and Nancy Selfridge, MD

Dr. Agyepong is Clinical Skills Facilitator, Clinical Foundations, at Ross University School of Medicine, Barbados, West Indies.
Dr. Selfridge is Professor, Clinical Foundations, at Ross University School of Medicine, Barbados, West Indies.

SYNOPSIS: A randomized clinical trial comparing time-restricted eating with a 16-hour fasting interval to a structured three-meal-per-day control group resulted in equivalent weight loss in both groups and no reduction in metabolic markers in either group.

SOURCE: Lowe DA, Wu N, Rohdin-Bibby L, et al. Effects of time-restricted eating on weight loss and other metabolic parameters in women and men with overweight and obesity: The TREAT randomized clinical trial. JAMA Intern Med 2020;180:1-9.

Obesity prevalence in U.S. adults is at an alarming age-adjusted 42.4%.1 Considering even modest weight loss appears to ameliorate insulin resistance and lower cardiovascular risk, identifying effective, simple, and acceptable ways for patients to achieve this goal is desirable. Intermittent fasting has been widely promoted in popular media as a means to lose excess body weight “without dieting.” A specific type of intermittent fasting known as time-restricted eating (TRE) refers to eating within a specific period and fasting outside this period. Although TRE’s benefits have been demonstrated in animal models, particularly obese mice, the literature regarding the benefits or effects on human populations is limited in quantity and quality.2

In this randomized, controlled trial by Lowe et al, TRE was compared to consistent meal timing (CMT). Participants of the TRE group were asked to restrict eating for a 16-hour period and eat ad libitum during an eight-hour window (noon to 8 p.m.). The CMT group consumed three structured meals per day and was permitted to eat snacks between meals. The TRE group was permitted only noncaloric drinks outside the eating window. Neither groups were given a daily caloric restriction. The primary outcome assessed was weight loss for all participants. Secondary outcomes assessed for the in-person cohort included changes in weight, fat mass, lean mass, fasting insulin, fasting glucose, insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c) levels, lipids (triglycerides, total cholesterol, low-density lipoproteins [LDL], and high-density lipoproteins [HDL]), estimated energy intake, total energy expenditure, and resting energy expenditure from an in-person cohort. Participants were recruited from across the United States between August 2018 and June 2019, and data collection was completed in October 2019. The total length of the study was 12 weeks.

Out of 1,975 potential candidates, 141 met inclusion criteria and were randomized to CMT or TRE intervention groups. Data were collected from 116 participants age 18 to 64 years with a body mass index (BMI) range of 27 kg/m2 to 43 kg/m2. However, only 105 participants completed the study. Of the 11 participants who did not complete the study, eight were lost to follow-up and three discontinued the intervention. An in-person cohort of 50 participants who lived within a 60-mile radius of the University of California, San Francisco (UCSF) was randomized and enrolled for metabolic testing, with 46 participants completing the four in-person visits. Data were collected via a mobile app created for the study, and patients received a Bluetooth scale that connected to the study app. The TRE group received daily reminders of their eating window through the app. All participants were instructed to use the scale daily in the morning before eating or drinking and before structured physical activity.

Looking at the weight change in the total cohort, there was a significant decrease in weight in the TRE group (P = 0.01) and a decrease in weight in the CMT group that was not statistically significant. Weight change between groups also was not statistically significant. Percentage decrease in weight from baseline was statistically significant in both the TRE group (-1.17%; 95% confidence interval [CI], -1.89% to -0.45%; P = 0.002) and the CMT group (-0.75%; 95% CI, -1.47% to -0.04%; P = -0.04), with no significant differences in results between these groups (-0.41%; 95% CI, -1.43% to 0.60%; P = 0.43).

In the in-person cohort, there were no statistically significant within-group or between-group differences in metabolic measurements (fasting glucose, fasting insulin, HOMA-IR, HbA1c, triglycerides, total cholesterol, LDL, or HDL levels). A significant decrease in appendicular lean mass was reported in the TRE group (P < 0.001) and between groups (P = 0.009), but not in the CMT group. There also was a significant decrease in appendicular lean mass index among TRE participants (P < 0.001) and between groups (P = 0.005), but not in the CMT group. Various other body composition measurements (e.g., fat mass, lean mass, waist and hip circumference) were assessed with no significant difference found between the groups. Finally, no adverse effects of either intervention were reported.

COMMENTARY

Although the simplicity of TRE eating may make it easy to implement, Lowe et al showed there was no statistically significant difference in weight changes or cardiometabolic markers for those who fast for an extended period during the day (TRE) compared to those eating three consistent meals per day (CMT). The strengths of this study include its randomized control design, the recruitment of participants from across the United States, and inclusion of an in-person cohort to assess metabolic marker measurements. This study was conducted for a period of three months, and there was a large percentage of participants who could be analyzed at the end of the study period.

However, there were some limitations. Although the primary objective was to assess the effects of TRE on weight loss and various metabolic markers, only one eating/fasting regimen (eight hours/16 hours) was assessed. The reasoning the authors offered for the chosen TRE interval was to mimic skipping breakfast for the participants, making it easier to adopt. Thus, results from this study may not be generalizable to all TRE regimens.

In a similar study by Chow et al, TRE was compared to an ad libitum diet, and participants randomized to the TRE group were allowed to self-select an eight-hour eating window.3 In this study, the earliest end of the eating period chosen was 5 p.m. Although this was a small study population of 20 participants and did not address the contribution of TRE timing to the weight loss and metabolic improvements observed in study participants, it is reasonable to question whether alternative eating windows might affect results. Comparison of TRE to a single CMT structure of three meals daily also is a limitation of this study. Considering additional CMT eating schedules, such as six smaller, evenly distributed meals daily, would be a valuable enhancement.

Although sleep activity was recorded for participants, Lowe et al did not consider the circadian system in the intervention design. In previous animal models, researchers hypothesized the circadian system’s role in regulating glucose, lipid, and energy metabolism throughout the day requires an appropriate alignment of feeding interval to result in improvement in these outcomes.4-6 Indeed, in prior TRE trials in humans, results do appear to depend on the timing of the chosen eating window.6 Other studies of humans show eating a larger breakfast and a smaller dinner improves glycemic control, weight loss, lipid levels, and reduces hunger.4 In human studies, the association between BMI and the timing of food intake strengthens substantially when considering food intake in relation to the internal circadian time, best aligned with sleep/wake cycles as opposed to time of day.6

The in-person cohort was derived from a select population near the UCSF campus. This population most likely is exposed to similar environmental, social, and economic factors, which may contribute to dietary choices.7 It is possible that with a larger and more varied selection for the in-person cohort, results may have differed. The authors observed a significant decrease in appendicular lean mass and lean mass index in the TRE group, an observation that adds to findings from the current literature that have resulted in recommendations for protein supplementation for individuals using TRE for weight management.3

Ultimately, additional high-quality studies in human subjects are required to determine if this method of eating, or any of its variations, are safe to help with weight loss, especially those with weight- and diet-related health risks. The true test of a successful weight loss diet is long-term weight loss maintenance, and most studies to date have been conducted over a short period, often less than six months.2-6 Because of the limited effect on weight reduction over a short period, no effect on cardiometabolic markers, and potentially significant reduction in measures of lean body mass, intermittent fasting currently cannot be recommended to patients as an alternative to calorie reduction and regular exercise for weight control. Longer-term studies of intermittent fasting regimens that account for circadian rhythms, employ food diaries to assess dietary quality, and track lean body mass changes are required to determine if sustained and meaningful weight loss or metabolic improvements can result from time-restricted eating.

REFERENCES

  1. Hales CM, Fryar CV, Ogden CL. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. National Center for Health Statistics. Hyattsville; 2020.
  2. Pellegrini M, Cioffi I, Evangelista A, et al. Effects of time-restricted feeding on body weight and metabolism. A systematic review and meta-analysis. Rev Endocr Metab Disord 2020;21:17-33.
  3. Chow LS, Manoogian E, Alvear A, et al. Time-restricted eating effects on body composition and metabolic measures in humans who are overweight: A feasibility study. Obesity (Silver Spring) 2020;28:860-869.
  4. Sutton EF, Beyl R, Early KS, et al. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab 2018;27:1212-1221.e3.
  5. Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev 2017;39:46-58.
  6. Rynders CA, Thomas EA, Zaman A, et al. Effectiveness of intermittent fasting and time-restricted feeding compared to continuous energy restriction for weight loss. Nutrients 2019;11:2442.
  7. Hall KD, Kahan S. Maintenance of lost weight and long-term management of obesity. Med Clin North Am 2018;102:183-197.