Alternate-Day Fasting in Short Term Safe, Has Metabolic Benefits

Ricki Lewis, PhD

August 27, 2019

Alternate-day fasting (ADF) had positive effects on body weight, cardiovascular measures, and molecular markers of aging when assessed in a randomized controlled trial among healthy adults without obesity or diabetes, researchers report in a study published online August 27 in Cell Metabolism.

ADF is a different approach to control weight than the common caloric restriction (CR) or intermittent fasting (IF) that restricts daily eating to an 8- to 12-hour window. Although ADF is gaining popularity it has not been subject to randomized clinical trials.

Therefore, Slaven Stekovic, PhD, from the Institute of Molecular Biosciences at the University of Graz in Austria, and colleagues conducted a prospective cohort study with an embedded randomized controlled trial to assess the metabolic effects of ADF. The team initially recruited 30 participants who had followed ADF for at least 6 months before the study began and compared them to 60 healthy controls. Thirty members of the control group were then randomly assigned to ADF for 4 weeks and the other 30 participants ate whatever and whenever they wanted during that time.

Specifically, the 30 people who had followed ADF for 6 months or more and the 30 individuals randomly assigned to ADF alternated between 36 hours of not eating and 12 hours of eating whatever they wanted. These two groups were similar in terms of gender distribution, age, body mass index (BMI), and waist-to-hip ratio at baseline.

Before and after the intervention, participants underwent a battery of anthropometric, physiological, hormonal, metabolic, and biochemical measurements that reflect health status and possible effects of ADF. These included measures of body composition and cardiovascular function, caloric expenditure assessed using food frequency and exercise questionnaires, and bone mineral density at the lumbar spine.

No adverse effects were seen among participants in the ADF group. Their caloric intake dropped from baseline by 37.4% (95% CI, –48.3% to –24.4%), compared with 8.2% (95% CI, –32.2% to 3.6%) in the control group.

BMI among the 4-week fasters fell by 1.2 kg/m2 (95% CI, –1.515 to –0.875; P < .0001). The average reduction in belly fat was 14.5% ± 6.4% (P < .0001).

In addition to changes in body mass and composition, researchers noted metabolic trends, which is why they chose to publish in Cell Metabolism rather than a more general journal. "Cell Metabolism is very open to translational findings and there is probably no other intervention that changes the metabolism of an organism as profoundly as fasting," co-author Frank Madeo, PhD, a professor at the Institute for Molecular Biosciences at the University of Graz in Austria, told Medscape Medical News.

Co-author Harald Sourij, MD, a professor at the Medical University of Graz, summarized the metabolic findings: "Overall a number of changes associated with reduced cardiovascular risk and aging were detected, including reduction in inflammatory markers such as sICAM-1, systolic blood pressure, levels of LDL cholesterol, short-chain fatty acids, and triiodothyronine; increase in polyunsaturated fatty acids; and downregulation of potential pro-aging amino acids, such as methionine."

The metabolic findings suggest that ADF may be safer than CR, which is more widely practiced.

"CR was previously associated with concerns about bone metabolism or immune cell function. Neither in our short-term randomized, controlled study nor in the 6-months ADF cohort did we observe adverse effects on bone mass, total white blood cell count, or abundance of immune cell subtypes, red blood cell counts, or iron metabolism," Sourij told Medscape Medical News.

He cautions though that longer prospective investigations are needed to monitor these parameters over years to rule out potential adverse effects or development of nutrient deficiencies.

The study didn't compare ADF to IF. "Losing 7 pounds within 4 weeks, as in our study, is a strong weight loss effect that will probably not be achieved by shorter fasting periods. ADF has profound positive effects on body weight, cardiovascular parameters, and molecular markers of aging," Madeo concluded.

The apparent safety of ADF may arise from its mimicking eating patterns of our hunter-and-gatherer forebears, explained Madeo. "Our physiology is familiar with periods of starvation followed by food excesses," he said. For example, starvation sets in motion autophagy, in which cells dismantle and recycle damaged parts, such as organelles and proteins, associated with aging. "Autophagy improves the metabolic functions of cells, and it is switched on after 36 hours of fasting," he said.

The autophagy angle may explain the apparent inferiority of CR. "Low-calorie intake hinders the induction of the age-protective autophagy program, which is switched on during fasting breaks," Madeo continued.

But the researchers caution that we don't yet know the consequences, if any, of strict ADF beyond 6 months, and they suggest a robust comparison of "different fasting regimens with each other and across different cohort types," they write. They also warn that constant bombardment with images of food and easy access to it may hamper attempts at ADF for some individuals, and effects may be ephemeral if the pattern of fasting and eating is abandoned.

The investigators stress the importance of identifying patients who likely cannot thrive on ADF. "Appreciable clinical support and a generally healthy lifestyle should be considered before starting ADF," they write.

That caveat is consistent with a 2017 study by John Trepanowski, PhD, of the department of kinesiology and nutrition at the University of Illinois, Chicago, and colleagues that compared ADF, CR, and no intervention among 100 otherwise healthy obese adults. They found no advantage of ADF over CR for adherence, weight loss, weight maintenance, or cardioprotection.

Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, Ontario, Canada, echoes the cautionary comments.

"ADF is already a clinically relevant intervention if employing it allows a person to lose weight and consequently improve weight-responsive medical conditions, but whether or not it has any long-term risks, or benefits beyond those attributable simply to weight loss, will require long-term study. Of course, as with any intervention for a chronic disease, if the intervention is only temporary and ADF as a lifestyle is abandoned following some health improvements, those improvements are likely only to be temporary as well."

Limitations of the investigation included enrollment of a small sample of highly motivated individuals who were interested in or already doing ADF.

Sourij has reported receiving unrestricted research grants from AstraZeneca, MSD, and Sanofi-Aventis. The other authors and commentator have reported no relevant financial relationships.

Cell Metab. Published online August 27, 2019. Abstract

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