Overweight women who ate a lower-calorie diet and fasted 3 days a week lost more weight and had better cardiometabolic markers than women who only reduced their calorie intake, or only fasted, or did neither in a small, 8-week randomized trial.

"Obese women who followed a diet in which they ate 70% of their required energy intake and fasted intermittently lost the most weight," said lead author Amy T. Hutchison, post-doctoral researcher, Adelaide Medical School, University of Adelaide, Australia, in a statement from her university.

"Other women in the study," she noted, "who either fasted intermittently without reducing their food intake, who reduced their food intake but did not fast, or did not restrict their diet at all, were not as successful in losing weight."

The new findings from the Effects of Periodic Fasting Versus Daily Energy Restriction on Metabolic Health (PREFER) study were published in the January issue of Obesity.

In this cohort of close to 90 middle-aged and older overweight or obese women who were randomized to the four different strategies, the most successful participants lost about 0.5 to 1 kg per week.

"This study is adding to evidence that intermittent fasting, at least in the short term, may provide better outcomes than daily continuous diet restriction for health and potentially for weight loss," said senior author Leonie Heilbronn, PhD, associate professor, University of Adelaide and South Australian Health and Medical Record Institute.

Invited to comment, Dorothy D. Sears, PhD, associate professor of medicine, University of California, San Diego, who coauthored a review article about the metabolic effects of intermittent fasting, told Medscape Medical News: "This represents another...study of intermittent fasting providing suggestive evidence of benefit." However, she pointed out that it was "small and underpowered."

The researchers agree, saying more research is needed and acknowledging that these findings cannot be generalized to a longer intervention or other populations.

"While the study confirms that intermittent fasting is more effective than continuous diet restriction, the underlying signal for limiting people's appetite, which could hold the key to triggering effective weight loss, requires further research," Heilbronn noted.

The group plans to investigate the effectiveness of long-term fasting on men and women in further trials.

Intermittent Fasting, Reduced Calories, or Both?

A continuous reduced calorie diet remains "the cornerstone lifestyle intervention to reduce the risk of developing type 2 diabetes and cardiovascular disease" in overweight people, Hutchison and colleagues write in their article.

However, intermittent fasting might be a better strategy, because people find it difficult to stick to a low-calorie eating plan.

Results from studies of transient fasting have been mixed, however, with some showing greater weight loss and improved metabolic markers, while others have reported weight loss but no improvement in metabolic markers.

Notably, five studies lasting 2 to 12 months showed that intermittent fasting and reduced caloric intake produced similar reductions in body weight and cardiovascular risk markers, Hutchison and colleagues write.

But it has not been clear if "metabolic switching" between fed and fasted states, rather than weight loss, might underlie the health benefits from intermittent fasting.

They therefore conducted a randomized controlled trial in overweight to obese women to compare how intermittent versus continuous food intakes at two energy levels affected peripheral insulin sensitivity, weight, body composition, and cardiometabolic markers, and to examine acute metabolic changes when participants switched from a "fed" to a "fasted" state.

After a 2-week lead-in, 88 women, aged 35 to 70 years, with a body mass index of 25 to 42 kg/m2 who did not have diabetes and were not physically active, were randomized to four groups for 8 weeks:

No reduced calories or fasting (100% of calories needed to maintain baseline weight), control group (12 women);

Intermittent fasting and reduced calories (70% of calories needed to maintain baseline weight) (26 women);

Intermittent fasting, no reduced calories (25 women);

Continuous reduced calories (70%), no fasting (25 women).

In the fasting groups, participants fasted from 8 AM to 8 AM on three nonconsecutive weekdays and were only allowed water and small amounts of calorie-free foods and beverages (black coffee or tea, diet drinks, chewing gum, or mints) and 250-mL of a 20-calorie broth.

All foods were delivered to the women every 2 weeks, and their diets had the same nutrient composition (35% fat, 15% protein, and 50% carbohydrate).

They completed a daily checklist, which they submitted at weekly clinic visits.

Fasting Plus Reduced Calories Produces Best Metabolic Outcomes

Insulin sensitivity, weight, body composition, and plasma markers were assessed at baseline, and at 8 weeks following a "fed" day (after a 12-hour fast, at night, for all participants) and following a 24-hour fast (in the fasting groups).

Women in the intermittent fasting, reduced calorie group had greater reductions in weight, fat mass, total- and low-density lipoprotein cholesterol, and non-esterified fatty acids compared with women in the reduced calories alone or intermittent fasting alone group (all P ≤ .05).

"Intermittent fasting was more effective than diet restriction for reducing body weight and improving metabolic health when prescribed with a similar energy deficit, but it did not differentially impact insulin sensitivity assessed by hyperinsulinemic-euglycemic clamp," say Hutchison and colleagues.

And when intermittent fasting was prescribed without energy restriction, there were transient elevations in diabetes risk markers "and no overall improvements in metabolic parameters compared with other groups, despite minor weight loss," they observe.

"This study demonstrates that intermittent fasting approaches using repeated 24-hour fasts improve metabolic health when in energy deficit but not when in energy balance," they conclude.

The research was funded by a National Health and Medical Research Council project grant. The authors have reported no relevant financial relationships.

Obesity. 2019;27:50-58. Full text

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