Clinical Context

Intermittent fasting has become a popular method for weight loss and improving metabolic outcomes, and the authors of the current study describe some of the metabolic effects of intermittent fasting that might promote these outcomes. Intermittent fasting depends on a concept labeled as “metabolic switch,” which involves a change from dependence on glucose derived from the liver during typical dieting to ketones derived from adipose cells during fasting.

The metabolic switch can improve glucose regulation and reduce inflammation. The stress state of fasting also increases autophagy, which removes damaged molecules to prevent against further metabolic stress and can also reduce oxidative stress. Given these physiologic changes, intermittent fasting may yield substantial long-term health benefits; however, there are no long-term modern randomized trials of intermittent fasting over the long term. Even short-term studies of intermittent fasting have been heterogenous in their methodology and outcomes. The current review of meta-analyses by Patikorn and colleagues was performed to draw more definitive conclusions regarding the benefits of intermittent fasting.

Study Synopsis and Perspective

Intermittent fasting can lead to weight loss and other health benefits, at least in the short term, new research suggests.

Combined results from a total of 130 clinical trials show that intermittent fasting could help reduce weight, body mass index (BMI), body fat, "bad" cholesterol, fasting blood sugar, and blood pressure (BP), among other risk factors associated with obesity.

Two specific types of intermittent fasting were associated with significant weight loss and other health benefits. One, called modified alternate-day fasting (MADF), involves alternating one day of eating as usual with consuming no more than 600 calories the next day.

The other, called the "5:2 diet" is similar but involves 2 days per week of zero calories or very low-calorie eating and 5 days of normal eating.

Less beneficial were time-restricted eating, involving fasting 12 to 24 hours per day, and "zero calorie alternate-day fasting," where no food is consumed every other day.

"Our results support the role of intermittent fasting, especially [MADF], in adults with overweight or obesity as a weight loss approach with other health benefits. But individuals have to consult their doctors first," lead author of the research, Chanthawat Patikorn, of Chulalongkorn University in Thailand said.

There is a major snag; however: Most of the studies lasted only about 3 months.

Among those lasting longer, the weight loss seemed to level off by about 6 months, either because the body adapted to the eating pattern or because the participants could not stick to the diets.

"We are still lacking data to see if these could work in the long-term. We see weight loss and improved metabolic profiles but we still don't know if intermittent fasting can lead to reduced death or cardiovascular events," Patikorn said.

On the other hand, "I would say that if the patient is interested in doing intermittent fasting, there is no evidence that it's a bad thing."

He did caution, however, that patterns where you consume nothing for long periods of time could pose a danger for people with diabetes who use insulin or are otherwise prone to low blood sugar (hypoglycemia).

Only two diets, modified alternate-day fasting and 5:2, were associated with weight loss of 5% or more of total body weight in adults with overweight or obesity.

With the 5:2 diet, the weight loss held up at 6 to 12 months. Modified alternate-day fasting was also associated with improvements at 2 to 12 months in heart disease risk factors such as total cholesterol, "bad" cholesterol, triglycerides, and BP.

The findings were published in the December 1 issue of JAMA Network Open.^[1]

Another Trial Shows Modest Effect, Similar Endurance Problem

In a separate 1-year randomized trial published Nov. 17, 2021,^[2] in PLOS One, researchers randomly assigned 300 adults with obesity to either a 5:2 diet with self-help instructions, the same diet plus 6 weekly group support sessions, or just standard advice about diet and physical activity.

The 5:2 self-help group stuck with it initially, but only a third were still following the diet by 6 months and only about a fifth by 1 year. Weight loss at 6 months and 1 year were similar between the 5:2 self-help and standard advice groups (about 4 pounds).

The 5:2 diet with group support was associated with more weight loss than 5:2 self-help at 6 weeks, but there was no difference at 1 year.

Looking at it more positively, 18% of the 5:2 self-help group had lost more than 5% of their body weight by 1 year, and participants gave the 5:2 plan favorable ratings.

The investigators of that study, Queen Mary University of London clinical psychology professor Peter Hajek and colleagues, concluded that "a suggestion to try 5:2 could be provided in a quick consultation and be useful especially for patients who had not benefitted from the standard advice."

Patikorn pointed out that thus far no studies have compared the different types of intermittent diets head-to-head, so "the best type of intermittent fasting is the one people can really stick to for the long term."

Clinical Implications

• The potential metabolic benefits of intermittent fasting depend on a switch from glucose derived from the liver during normal diet to ketones derived from adipose cells during fasting. The metabolic switch can improve glucose regulation and reduce inflammation. The stress state of fasting also increases autophagy, which removes damaged molecules to prevent against further metabolic stress and can also reduce oxidative stress.
• In the current study by Patikorn and colleagues, MADF, in particular, was associated with lower BMI and blood pressure along with improved lipid values; however, intermittent fasting was associated with lower fat-free mass as well.
• Implications for the healthcare team: The healthcare team can recommend intermittent fasting to appropriate patients as a means to reduce body weight and improve metabolic outcomes among patients with overweight and obesity.

Earn Credit