Mimicking Temporary Fasting May Reduce Metabolic Risk Factors

Tara Haelle

February 15, 2017

Following a diet that mimics sporadic fasting over the course of 3 months reduced body weight and total body fat and improved metabolic markers in healthy adults, according to a study published today in Science Translational Medicine.

"[T]hese results indicate that the periodic [fasting-mimicking diet (FMD)] cycles are effective in improving the levels of an array of metabolic markers/risk factors associated with poor health and aging and with multiple age-related diseases," write Min Wei, PhD, from the University of Southern California in Los Angeles, and colleagues.

A benefit of their diet approach, they argue, is that it is easier and safer to adhere to than other types of stricter fasting. "Despite its potential for disease prevention and treatment, prolonged fasting is difficult to implement in human subjects and may exacerbate preexisting nutritional deficiencies, making it not feasible and/or safe for children, the elderly, frail individuals, and even most of the healthy adults," the authors write.

In an interview with the American Association for the Advancement of Science, Dr Wei and coauthor Valter Longo, PhD, said, "The results indicate that the diet will help prevent and treat diabetes, cardiovascular diseases, and cancer. It is clear that the FMD reduces diseases risk factors. However, [US Food and Drug Administration] trials will be necessary to demonstrate whether the periodic FMD is effective in disease prevention and treatment."

However, Yoni Freedhoff, MD, an obesity physician and assistant professor of family medicine at the University of Ottawa in Ontario, Canada, told Medscape Medical News that the lack of any dietary or diet counseling intervention in the control group precludes the ability to fully ascribe the metabolic effects seen to the partial fasting intervention. She notes that those same benefits may have been derived from the drop in weight loss that would be expected from any dietary intervention that restricted caloric intake.

"It's a short-term study, which is interesting, but it needs a better control — at the very least, a control group that receives dietary counseling," Dr Freedhoff told Medscape Medical News.

In addition, he said, the clinical utility of the study is limited because it is short term and cannot demonstrate long-term sustainability of the intervention or the effects described.

"The only way anybody would ever be able to claim clinical benefit is to demonstrate its long-term sustainability," Dr Freedhoff told Medscape Medical News, adding that virtually any diet will lead to weight loss and, potentially, improved metabolic markers in the short-term. "If the case they're making is that this is easier than other diets and therefore is something we should be prescribing clinically, that's great, but first show me that it's better than other diets."

Dr Wei and colleagues randomly assigned 100 healthy US adults to either follow a diet that mimicked sporadic, temporary fasting or to eat an unrestricted diet for 3 months. The FMD occurred for 5 consecutive days each month and used proprietary products from L-Nutra. Day 1 of the diet cycle involved consuming approximately 4600 kJ (~1100 calories), including 11% protein, 46% fat, and 43% carbohydrates. During days 2 to 5, participants consumed 9% protein, 44% fat, and 47% carbohydrates to make up a total of 3000 kJ (~717 calories) daily. The proprietary products included "vegetable-based soups, energy bars, energy drinks, chip snacks, tea, and a supplement providing high levels of minerals, vitamins, and essential fatty acids." The diet aimed "to attain fasting-like effects on the serum levels of [insulin-like growth factor 1 (IGF-1), insulin-like growth factor–binding protein], glucose, and ketone bodies while providing both macro- and micronutrients to minimize the burden of fasting and adverse effects," the authors explain.

At baseline, the two groups were similar in terms of the following metabolic markers or risk factors for age-related conditions: body weight, body mass index (BMI), total body fat, trunk fat, lean body mass, waist circumference, fasting glucose, IGF-1, systolic and diastolic blood pressure, triglycerides, and C-reactive protein. However, total cholesterol and low-density lipoprotein values were significantly lower in the initial intervention group at baseline.

After 3 months, participants in the intervention group lost an average of 2.6 kg (P < .0001; compared with baseline) of weight when assessed a week after completing the third fasting diet cycle vs no weight loss in the control group (0.1 kg). This weight loss primarily resulted from a reduction in body fat percentage and overall total body fat and trunk fat.

In addition, the intervention group lost an average 4.1 cm in waist circumference (P = .0035), an average 21.7 ng/mL in IGF-1 concentrations (P = .0017), an average 4.5 mm Hg in systolic blood pressure (P = .023), and an average 3.1 mm Hg in diastolic blood pressure (P = .053).

However, no significant differences were seen for fasting glucose, triglycerides, total cholesterol, low- or high-density lipoprotein cholesterol, or C-reactive protein.

Then, after the first 3 months of the study, the control group participants switched in a crossover design to the dietary intervention for 3 months. Overall, 71 participants completed the diet intervention for a full 3 months, including 39 in the intervention during the first 3 months and 32 who were first in the control group before crossing over to the diet during the second 3 months. Between the two groups, the dropout rate from the intervention diet was 25%, primarily because of scheduling conflicts, personal issues, or dislike of the diet or lack of adherence to it.

Effects in the second intervention group (previously control) were comparable to those of the first intervention group except in two measures: A greater high-density lipoprotein reduction occurred in the first intervention group than in the second, and the first group showed a drop in absolute lean body mass that the second did not.

Combining results from the two groups revealed postintervention decreases in body weight, BMI, total body fat, trunk fat, absolute lean body mass, waist circumference, and all blood pressure and cholesterol values.

Assessment of the effect size based on BMI stratification showed that participants with a baseline BMI greater than 30 kg/m2 had a larger drop in BMI after the three cycles than those with a BMI below 25 kg/m2 or from 25 to 30 kg/m2. Similarly, those with a higher baseline blood pressure showed greater proportional reductions in blood pressure measures after the intervention.

The participants reported no serious adverse effects during the intervention, with the most common being mild and moderate symptoms being fatigue, weakness, and headaches.

Among 50 participants who returned for a voluntary follow-up 3 months after completing the last diet cycle, the changes in body weight, BMI, blood pressure, and IGF-1 remained, as did the drop in blood glucose seen only in at-risk participants. The authors suggest these findings may indicate lasting beneficial effects from the diet, but also reveal potential confounding.

"Although subjects were not advised to change their diet or exercise regimen after the FMD cycles ended, we cannot rule out that some of the changes after the additional 3 months may be a result of lifestyle changes such as healthier diets and/or improved physical activity after the completion of this trial," they write.

The authors also noted the possibility that the dropout rates indicated potential difficulty in adhering to the diet.

"Note that 25% of the subjects who tested the FMD dropped out of the trial, whereas 10% of the participants opted out of the control arm," the authors write. "This indicates that, despite our efforts to reduce the burden of low-calorie/protein diets, adherence to this dietary regimen requires committed study participants."

Dr Freedhoff told Medscape Medical News that any study looking at short-term diets can only be considered a pilot study unless it can demonstrate lasting adherence and benefits for several years at least.

"Before we get excited about clinical benefit, we need to show it's sustainable," he said. "Having worked for a long time on behavioral change, I've seen the greater the change in the diet, the greater the shorter-term outcomes and the harder the long-term outcomes are to sustain."

The proprietary diet products were provided by L-Nutra Inc, and the University of Southern California may have the ability to receive royalty payments from L-Nutra. Dr Longo and one coauthor have equity interest in L-Nutra. Dr Longo's equity will be 100% donated to the nonprofit foundation Create Cures. Dr Freedhoff is founder and medical director of the Bariatric Medical Institute, which focuses on weight management without surgery and has no other disclosures.

Sci Transl Med. Published online February 15, 2017. Abstract

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