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HomeA Focus5-day fasting diet lowers risks for major diseases

5-day fasting diet lowers risks for major diseases

FastingFocusA randomised phase-II trial of a fasting-mimicking diet of five days over a three-month cycle, reduced blood pressure, signs of inflammation and decreased insulin-like growth factor-1, as well as shrinking waistlines and resulting in weight loss, both in total body fat and trunk fat, but not in muscle mass.

What if you could lose weight and reduce your risk of life-threatening disease without any changes in what you eat – other than a five-day special diet once every few months? That's what happened for 71 adults who were placed on three cycles of a low-calorie, "fasting-mimicking" diet. The phase II trial, conducted by researchers at the University of Southern California (USC) Leonard Davis School of Gerontology, demonstrated a host of benefits from the regimen.

The diet reduced cardiovascular risk factors including blood pressure, signs of inflammation (measured by C-reactive protein levels), as well as fasting glucose and reduced levels of IGF-1, a hormone that affects metabolism. It also shrank waistlines and resulted in weight loss, both in total body fat and trunk fat, but not in muscle mass.

In effect, the diet reduced the study participants' risks for cancer, diabetes, heart disease and other age-related diseases, according to the findings.

"This study provides evidence that people can experience significant health benefits through a periodic, fasting-mimicking diet that is designed to act on the aging process," said Professor Valter Longo, director of the USC Longevity Institute and a professor of biological sciences for USC Davis and Dornsife. "Prior studies have indicated a range of health benefits in mice, but this is the first randomised clinical trial with enough participants to demonstrate that the diet is feasible, effective and safe for humans. Larger US Food and Drug Adminstration studies are necessary to confirm its effects on disease prevention and treatment," he added.

One hundred people participated in the trial from April 2013 to July 2015. The participants, ages 20 to 70 and all generally healthy, were divided into two groups for the randomised trial.

Participants in the first group, the control group, were asked to continue their normal eating habits for three months. People in the second group were placed on a three-month test of the fasting-mimicking diet.

Those on the special diet were required to eat food products supplied by the nutrition company L-Nutra during the fasting periods of five days each month. The diet, which was designed to mimic the results of a water-only fast, allowed for participants to consume between 750 and 1,100 calories per day. The meals for the fast-mimicking diet contained precise proportions of proteins, fats and carbohydrates.

After three months, participants in the control group were moved onto the special diet. The researchers found that participants on the fasting-mimicking diet lost an average of about 6 pounds. Their waistlines shrank by 1 to 2 inches. Their systolic blood pressure, which was in the normal range when the study began, dropped by 4.5 mmHG, while their diastolic blood pressure dropped by 3.1 mmHg. Also, their levels of IGF-1 dropped to between 21.7 ng/mL and 46.2 ng/mL, reaching a range associated with lower cancer risk.

"After the first group completed their three months on the fasting diet, we moved over participants in the control group to see if they also would experience similar results," Longo said. "We saw similar outcomes, which provides further evidence that a fasting-mimicking diet has effects on many metabolic and disease markers. Our mouse studies using a similar fasting-mimicking diet indicate that these beneficial effects are caused by multi-system regeneration and rejuvenation in the body at the cellular and organ levels.

"Our participants retained those effects, even when they returned to their normal daily eating habits," he added.

The researchers also noted that participants considered "at risk" because they had risk factors such as high IGF-1, cholesterol, blood pressure or blood sugar levels, made significant progress toward better health.

For example, baseline fasting glucose levels for participants with high blood sugar levels (putting them at risk for diabetes) dropped into the healthy range, below 99 mg/dl – but these levels didn't drop among participants who already had healthy levels at the beginning of the study. Cholesterol was reduced by 20 mg/dl in those with high cholesterol levels, and by about 5 mg/dl in all participants.

"Fasting seems to be the most beneficial for patients who have the great risk factors for disease, such as those who have high blood pressure or pre-diabetes or who are obese," Longo said.
The researchers had invited participants in the study for one last set of tests three months later, at the end of the diet. The research team found that the beneficial effects – from weight loss, smaller waistlines and lower glucose, blood pressure and IGF-1 levels – were sustained.

The next step for researchers is a large, FDA phase III clinical trial to test the FMD on patients diagnosed with age-related diseases or at high risk for them. The researchers said further investigation will determine whether the benefits of the diet can continue for several months.

The work was funded by the USC Edna M. Jones Chair in Gerontology fund, as well as through a National Institutes of Health grant to co-author Wendy Mack at the Keck School of Medicine of USC, through the Southern California Clinical and Translational Science Institute.

Study co-authors from USC Davis were Min Wei and Sebastian Brandhorst (lead co-authors) and Mahshid Shelehchi, Hamed Mirzaei, Chia Wei Cheng, Julia Budniak, Esra Guen, Stefano Di Biase, Pinchas Cohen and Todd Morgan. Others were Tanya Dorff of USC Norris Comprehensive Cancer Center; Kurt Hong of the Keck School of Medicine; Andreas Michalsen of Charité University Medical Center in Germany; and Alessandro Laviano at IFOM, the FIRC Institute of Molecular Oncology.

Longo is the founder of L-Nutra; its food products were used in the study. His interest in L-Nutra has been disclosed and managed per USC’s conflicts of interest policies to assure objectivity and a lack of bias in the conduct and reporting of his research.

USC also has an ownership interest in L-Nutra, and the potential to receive royalty payments from L-Nutra. USC’s financial interest in the company has been disclosed and managed under USC’s institutional conflict of interest policies.

Abstract
Calorie restriction or changes in dietary composition can enhance healthy aging, but the inability of most subjects to adhere to chronic and extreme diets, as well as potentially adverse effects, limits their application. We randomized 100 generally healthy participants from the United States into two study arms and tested the effects of a fasting-mimicking diet (FMD)—low in calories, sugars, and protein but high in unsaturated fats—on markers/risk factors associated with aging and age-related diseases. We compared subjects who followed 3 months of an unrestricted diet to subjects who consumed the FMD for 5 consecutive days per month for 3 months. Three FMD cycles reduced body weight, trunk, and total body fat; lowered blood pressure; and decreased insulin-like growth factor 1 (IGF-1). No serious adverse effects were reported. After 3 months, control diet subjects were crossed over to the FMD program, resulting in a total of 71 subjects completing three FMD cycles. A post hoc analysis of subjects from both FMD arms showed that body mass index, blood pressure, fasting glucose, IGF-1, triglycerides, total and low-density lipoprotein cholesterol, and C-reactive protein were more beneficially affected in participants at risk for disease than in subjects who were not at risk. Thus, cycles of a 5-day FMD are safe, feasible, and effective in reducing markers/risk factors for aging and age-related diseases. Larger studies in patients with diagnosed diseases or selected on the basis of risk factors are warranted to confirm the effect of the FMD on disease prevention and treatment.

Authors
Min Wei, Sebastian Brandhorst, Mahshid Shelehchi, Hamed Mirzaei, Chia Wei Cheng, Julia Budniak, Susan Groshen, Wendy J Mack, Esra Guen, Stefano Di Biase, Pinchas Cohen, Todd E Morgan, Tanya Dorff, Kurt Hong, Andreas Michalsen, Alessandro Laviano, Valter D Longo

[link url="http://news.usc.edu/116479/scientifically-designed-fasting-diet-lowers-risks-for-major-diseases/"]University of Southern California material[/link]
[link url="http://stm.sciencemag.org/content/9/377/eaai8700"]Science Translational Medicine abstract[/link]

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