Cardiologist Ethan J. Weiss, MD, followed an intermittent fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.
"I liked the way the diet was so simple," said Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco (UCSF).
But he also felt "it was too good to be true because you can eat what you want as long as it's within a narrow window."
So when, last year, he conducted a randomized controlled trial, TREAT, testing such an approach — eating during just 8 hours a day, fasting for the remaining 16 hours — versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn't lose any more weight than the other group.
The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then 'fast' at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a "normal" amount of around 2000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.
Intermittent fasting is an umbrella term encompassing all of these different approaches.
Weiss's work builds on more than a decade of research into this type of eating plan by scientists including Professor of Nutrition Krista Varady, PhD, University of Illinois, Chicago, who presented an overview of her own studies last fall at the virtual European Association for the Study of Diabetes (EASD) Annual Meeting 2020.
Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Weiss's data — published last year — throws a spanner in the works and now complicates the evidence base.
A Promise of Simplicity: "All You Have to Do Is Watch the Clock"
Varady said she, too, is intrigued by the simplicity of intermittent fasting diets.
In 2018, Varady and colleagues tested the weight loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity (Nutr Healthy Aging. 2018;4:345-353.)
Participants were permitted an 8-hour eating window (10 AM - 6 PM) followed by water-only fasting of 16 hours (6 PM - 10 AM) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.
There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.
Varady thinks this is most likely due to the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.
"One of the most beautiful things about time-restricted feeding is that it doesn't require calorie monitoring," she explains. "People get burnt out with having to constantly monitor calories. All you have to do is watch the clock."
Adherence was quite high, she reported, although most people skipped one day, often a Saturday, likely due to social engagements.
Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P < .05).
But the researchers observed little change in metabolic disease risk factors between the groups.
In the time-restricted feeding group, systolic blood pressure dropped from 128 mmHg to 121 mmHg over the 12-week period, which was significant relative to the control group (P < .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.
In contrast to Varady's findings, Weiss's randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.
As previously reported by Medscape Medical News, those who fasted for 16 hours of each day (n = 59) did lose some weight compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).
And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.
"I don't claim time-restricted eating is dead," Weiss said, "but the hope that you can eat for a limited time each day and solve metabolic disease is not there."
Does the Length of Eating Window Matter?
Following her pilot study of an 8-hour eating window, Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.
She ran a 2-month randomized controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 PM to 7 PM; n = 19) or 6-hour (1 PM to 7 PM; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-378.e3).
Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study.
"Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles," she remarked.
Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss compared with controls, and this correlated with a 550-calorie reduction in their daily consumption compared with their baseline calorie intake.
In terms of other outcomes — and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure — researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Varady reported.
Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group compared with the control group. Fasting glucose did not change in either group, however.
The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).
"These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories," Varady and colleagues conclude.
Is Intermittent Fasting Better for Weight Loss Than Calorie Restriction?
Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares to conventional daily calorie restriction.
Back in 2017, Varady published a year-long randomized controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.
Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating "feast days". For an additional 6 months, they ate 1000 calories on fasting days — aimed at weight maintenance.
Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).
However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.
"Over the first 6 months [during the weight loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss," reported Varady.
"Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight," she admitted.
Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight loss maintenance period rather than increasing calorie intake during this phase.
Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL-C decreased in the calorie-restriction group.
Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Varady, noting that these findings were in healthy people with obesity.
In people with obesity and insulin resistance — evaluated as a subgroup in a separate study by Varady of alternate-day fasting versus daily calorie restriction published in 2019 — she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group compared to the calorie-restriction group.
"For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?" she ventured.
Who Fares Best With Which Fasting Diets?
Summing up, Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.
Those who binge eater, shift-workers, and frequent snackers do not do well with fasting, she said.
The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.
"Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won't feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay."
She cautiously concluded that weight loss with "alternate-day fasting" is quicker than some other methods, at 4.5 to 7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie-counting.
"In comparison, with time-restricted feeding, for which there have been very few...studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don't need to count calories."
Weiss has reported no relevant financial relationships. Varady has reported receiving author fees from Hachette for her book, "Every Other Day Diet."
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Cite this: To Fast or Not? The New Dieting Dilemma - Medscape - Jan 12, 2021.