Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults - A Randomized Clinical Trial
John F. Trepanowski, Cynthia M. Kroeger, Adrienne Barnosky, et al. (2017) JAMA Intern Med. http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2623528
Intermittent fasting diets, involving days of fasting and days on which foods are consumed ad libitum in varying patterns, have recently increased in popularity as a weight loss strategy and have been promoted in several bestselling books. Advocates suggest that it may be easier to adhere to intermittent rather than the more conventional daily calorie restriction. One such intermittent plan is alternate day fasting in which individuals consume 25% of their usual energy intake (around 500 kcals) every other day, and eat a regular diet allowing unrestricted consumption in between (non-fast days), aiming to reduce overall calorie intake. Another popular intermittent plan is the 5:2 diet, with 5 regular days and 2 fast days a week. There have been some short term human studies that suggest intermittent fasting leads to more weight loss than conventional daily low calorie diets, but there have been no longer term studies evaluating its efficacy.
The aim of the study was to compare the effects of alternate day fasting with daily calorie restriction on adherence, weight loss, weight maintenance and cardiovascular disease (CVD) risk markers.
A randomised controlled trial of overweight and obese adults in Chicago, USA, recruited participants aged 18-65 years with a BMI between 25.0 and 39.9 kg/m2, a sedentary lifestyle (defined as <60 minutes/week light activity) and free from CVD and diabetes. The trial involved a 6 month weight loss phase followed by a 6 month weight maintenance phase. Subjects were asked not to change their level of physical activity during the study and were randomised to one of three groups, two intervention groups and a control group, with the intervention groups instructed to reduce calorie intake by 25% as follows:
Alternate day fasting
Weight loss phase: Consume 25% of baseline energy intake as lunch on fast days and 125% of baseline energy intake split over three meals on feast days. All meals provided for the first 3 months and subjects meet with a dietitian weekly during months 4-6.
Weight maintenance phase: Consume 50% of energy needs as lunch on fast days and 150% of energy needs split over three meals on feast days.
Daily calorie restriction
Weight loss phase: Consume 75% of baseline energy intake every day. All meals provided for the first 3 months and subjects meet with a dietitian weekly during months 4-6.
Weight maintenance phase: Consume 100% of energy needs.
Maintain typical diet without the provision of meals or dietary counselling.
The primary outcome was change in body weight. Other outcomes assessed were percentage energy restriction in the weight loss phase (measured via doubly labelled water) and cardiovascular risk indicators, including blood pressure, heart rate, blood cholesterol (total, LDL, HDL) and fasting glucose.
Sixty nine percent of the subjects completed the study. Among the 100 participants (86 women and 14 men; mean [SD] age, 44  years), the dropout rate was highest in the alternate day fasting group (13 of 34 [38%]), vs. the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]).
Both intervention groups, alternate day fasting and daily calorie restriction, lost weight in comparison to the control group. Mean weight loss in both the alternate day fasting and daily calorie restriction groups was similar i.e. these were not significantly different from each other.
Table 1: Percentage weight loss in intervention groups versus the control group
|6 months||12 months|
|Alternate day fasting||-6.8% (95% CI -9.1% to -4.5%)||-6.0% (95% CI -8.5% to -3.6%)|
|Daily calorie restriction||-6.8% (95% CI -9.1% to -4.6%)||-5.3% (95% CI -7.6% to -3.0%)|
Both weight regain during the maintenance period and body composition at 6 and 12 months did not significantly differ between the intervention groups.
The mean calorie restriction achieved during the intervention phase was 21% in the alternate day fasting group and 24% in the daily calorie restriction group. Overall, subjects in the alternate day fasting group consumed more calories than prescribed on fasting days and less than prescribed on feast days, whereas subjects in the daily calorie restriction group were more adherent to their prescribed energy goals.
Cardiovascular risk markers
Blood pressure, total cholesterol, fasting glucose, fasting insulin, HOMA-IR, hsCRP, homocysteine and TAG were not significantly different between the intervention groups or versus controls at month 6 or 12. HDL cholesterol was significantly higher in the alternate day fasting group versus the daily calorie restriction group at month 6 but there was no difference at month 12. LDL cholesterol was significantly higher in the alternate day fasting group at month 12 versus the daily calorie restriction group.
Limitations of the study
The final number of subjects completing the study was small (21 in the alternate day fasting group, 25 in the daily calorie restriction group and 23 in the control group). The subjects were mostly obese (85%) and from the same area of the US, and about two thirds were from ethnic minorities. The participants were mostly women (86%) and metabolically healthy so the results may not be applicable to men, overweight (but not obese) individuals and those with raised CVD risk markers. Overweight individuals with raised CVD risk markers are likely to show improvements in these outcomes with sustained weight loss.
Alternate day fasting did not produce greater adherence, weight loss, weight maintenance or improvement in CVD risk markers compared to daily calorie restriction.
- Previous short term studies have reported weight loss of 3-7% and improvements in CVD risk markers after 2-3 months of alternate day fasting.
- A 2016 systematic review and meta-analysis comparing 12 studies of 3-12 weeks duration found no significant difference in amount of weight loss between studies prescribing alternate day fasting and those prescribing very low calorie diets (<800 kcal/day) after adjustment for BMI and study duration, though adjusted loss of fat mass was significantly greater for alternate day fasting studies (Alhamdan et al., 2016). However, some non-randomised studies were included in this analysis due to the small number of publications.
- A 2015 systematic review of studies comparing intermittent fasting regimes with daily energy restriction found that 9 out of 12 studies (of 5-50 weeks duration) reported no difference in weight loss and all studies measuring body composition reported no differences (Seimon et al., 2015). Dropout rates between the two regimes differed among the studies, providing no clear indication that either is easier to adhere to. The majority of the studies measuring effects on glucose homeostasis reported no difference versus daily energy restriction. Similarly to Trepanowski et al., the review concluded that intermittent fasting represents an equivalent alternative to continuous energy restriction.
- A further systematic review and meta-analysis (Headland et al. 2016) including only studies of at least 6 months duration, six of which compared intermittent fasting and daily energy restriction, also reported no difference in weight loss, blood lipids, glucose and insulin between the two regimes.
- Reviews in this area highlight the fact that most studies are of short duration and have small numbers of subjects completing them therefore further research is needed.
Two thirds of adults in the UK are currently overweight or obese and considering the associated health implications and wider impact on society, effective weight loss strategies are needed. NICE guidance suggests that approaches should be multicomponent, addressing dietary intake, physical activity and behaviour change with achievable weight loss goals tailored to the individual. The NHS promotes safe and sustainable weight loss of 1-2 pounds per week using daily calorie reduction and exercise. However, in recent years diets incorporating fasting days have increased in popularity, and intermittent fasting dietary plans such as the 5:2 diet have been studied in the short term with some positive benefits reported. The important message from this study is that adherence is key – the ability to adhere to a diet is a crucial aspect of weight loss and maintenance. Certainly from this study it would appear that fasting based diets result in similar weight loss to more traditional daily calorie restricted diets and therefore are not superior, but fasting diets may suit the lifestyle of some individuals and the important thing is to find a method of weight loss that suits the individual.
Alhamdan, B. A., Garcia-Alvarez, A., Alzahrnai, et al. (2016) Alternate-day versus daily energy restriction diets: which is more effective for weight loss? A systematic review and meta-analysis. Obesity Science & Practice, 2(3): 293–302.
Headland, M., Clifton, P. M., Carter, S., et al. (2016) Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Intermittent Energy Restriction Trials Lasting a Minimum of 6 Months. Nutrients, 8(6): 354.
NHS Choices (2016) 12 week weight loss plan http://www.nhs.uk/Livewell/weight-loss-guide/Pages/losing-weight-getting-started.aspx
NICE (2014) Weight management: lifestyle services for overweight or obese adults https://www.nice.org.uk/guidance/ph53
Seimon, R. V., J. A. Roekenes, J. Zibellini, et al. (2015) Do intermittent diets provide physiological benefits over continuous diets for weight loss? A systematic review of clinical trials. Molecular and Cellular Endocrinology.153-172.