Intermittent fasting (IF) practices have been linked to beneficial health effects, such as increased insulin sensitivity and reduced body weight.

A research team led by Dr. Kyoung-Han Kim at The Hospital for Sick Children and the University of Ottawa Heart Institute demonstrated that the effects of IF without caloric restriction include fat shedding and protection against metabolic dysfunction. The team hopes that the mechanism by which IF works can be studied to treat metabolic conditions such as obesity and type 2 diabetes.

The effects of IF were tested on mice, which were subjected to a two-day unrestricted feeding period followed by one day of fasting. In the first six weeks, the IF mice demonstrated an improved metabolic state and a better ability to regulate blood sugar.

After 16 weeks of the regime, the IF mice weighed less than the control mice who ate the same total volume of food. The researchers noticed that this weight loss corresponded to a loss of white adipose tissue (WAT) and increased thermogenesis, or heat production.

WAT stores energy in the form of fat in your body. In the process of ‘browning,’ it can turn into brown adipose tissue, which is responsible for heat production from fat.

Positive effects were seen in the mice following IF, including WAT browning, which have been linked to a protein called vascular endothelial growth factor (VEGF). It turns out that an IF-induced increase in VEGF triggers the ‘alternative activation’ of a group of cells called macrophages. This increases the level of M2 macrophages in the body, which then are involved in the browning process.

According to the study, it is now accepted that thermogenesis by fat tissues improves metabolism and that VEGF plays a role in this process. Increased levels of VEGF in the WAT of IF mice amplified M2 macrophage activation and thermogenesis.

Obese mice were then subjected to IF without caloric restriction and a high-fat diet, and they displayed similar results after six weeks. This included improved liver function and glucose homeostasis as well as WAT breakdown. These results suggest that IF can also be used to treat obesity, in addition to preventing it.

The researchers also found that IF-induced increases in VEGF were reversible. During fasting, VEGF levels peaked, and during feeding, they decreased to their original concentrations.

When they analyzed the activity of VEGF and M2 macrophages in human tissues, they found a similar correlation.

It must be noted that comparing the effects of IF on mice and on humans is difficult. Periods of fasting lead to both mental and physiological stress, and humans have fundamental differences in baseline metabolic rates and required food intake. However, IF appears to improve both eating behaviour and mood in humans.

The researchers have stated that further rigorous studies are required to examine whether the beneficial effects of IF last after the fasting has been discontinued, the potential harms that may be associated with IF, and whether IF is age- or disease-state dependent. Future studies aim to determine the precise response of human adipose tissues to IF and its association with circadian rhythm, gut microbiome changes, and sleep regulation.

“We plan to investigate the effect of IF on human clinical setting. Based on the results seen from human trials of IF, this could be an alternative treatment method for human obesity and diabetes. However, human study will take some time to initiate,” said co-author Hoon-Ki Sung.