Eating in Line with Circadian Clock Restores Insulin Sensitivity, Prevents Breast Cancer

Somi Igbene PhD ANutrOctober 20, 2021

Eating in line with the circadian (internal body) clock restores insulin sensitivity, reduces breast cancer risk, its growth and spread in postmenopausal obese mice, a new preclinical study reports. 

“Previous research has shown that obesity increases the risk of a variety of cancers by negatively affecting how the body reacts to insulin levels and changing circadian rhythms,” Nicholas Webster, PhD, professor at UC San Diego School of Medicine and senior research career scientist at VASDSH said in a press release

“We were able to increase insulin sensitivity, reduce hyperinsulinemia (excess blood insulin), restore circadian rhythms and reduce tumour growth by simply modifying when and for how long mice had access to food,” Webster added. 

The study, “Time-restricted feeding normalises hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models,” was published in Nature Communications

Obesity is a strong risk factor for type 2 diabetes, cardiovascular disease and at least 13 types of cancer, including postmenopausal breast cancer. While scientists do not fully understand how obesity drives breast cancer, studies show that hyperinsulinemia (excessive insulin production) and insulin resistance may play a role. 

Obesity disrupts the circadian clock – 24-hour rhythms present in all mammals that regulate essential functions and processes in the body. Emerging evidence from animal and human studies show that circadian clock disruptions can contribute to metabolic diseases, including insulin resistance and cancer. 

Time-restricted feeding (TRF) is a form of intermittent fasting that encourages limiting meals to within a four to ten-hour window in harmony with the circadian clock. Many mice studies show that TRF causes weight loss, lowers inflammation, and improves insulin sensitivity and metabolic health. In humans, the little evidence available shows that time-restricted eating (the TRF equivalent) reduces blood pressure, promotes fat loss and improves insulin sensitivity. 

Based on the available evidence, a team of scientists investigated if TRF could prevent or reduce breast cancer growth in mouse models of postmenopausal obesity. 

The researchers induced menopause in the mice either by removing their ovaries or depleting their follicles. They then fed them a high-fat diet for ten weeks to cause obesity. Subsequently, they randomised them to either continue eating an unrestricted high-fat diet (ad libitum group) or restricted them to eat the same amount of food within a short window at night when they were most active (TRF group). 

All mice fed the ad libitum diet gained weight throughout the study period, whereas TRF-fed mice maintained their weight. Strikingly, the TRF group improved their glucose and insulin tolerance by eight weeks, displaying decreased fasting blood glucose levels and insulin resistance than the ad libitum group.

In contrast to ad libitum feeding, TRF also significantly reduced the number and size of fat cells in the liver, fat mass in breast tissue and around the organs and suppressed the activation of several inflammatory genes.

The researchers injected Py230 cells or more aggressive ER/PR/HER2- cancer cells into mice breast tissue to induce breast cancer and investigated whether TRF could block breast cancer growth. Compared to ad libitum feeding, TRF significantly reduced tumour growth in these mice and others with pre-established breast cancer.

The researchers then proceeded to investigate if insulin alone could drive tumour growth by Injecting lean mice with Py230 breast cancer cells and high doses of insulin. Notably, insulin sped tumour growth, showing that hyperinsulinemia alone could drive cancer. Remarkably, TRF lowered insulin levels and reduced tumour growth in these mice. 

Previous studies have shown that obesity disrupts circadian rhythms in tissues, raising the risk of metabolic diseases, including cancer. Consistent with past results, the researchers found circadian clocks disruptions in many liver and breast tissue genes in ad libitum-fed obese mice. However, TRF restored the circadian rhythms; it also restored circadian rhythms in tumour cells to similar patterns in normal cells. 

“We confirmed and extended prior reports that TRF normalises hyperinsulinemia, improves metabolic deregulations, and restores circadian rhythms. We found that TRF inhibited tumour growth, delayed tumour initiation and reduced breast cancer [spread] to lungs in models of postmenopausal obesity driven breast cancer,” the researchers wrote. 

“Time-restricted eating has a positive effect on metabolic health and does not trigger the hunger and irritability that is associated with long-term fasting or calorie restriction,” Manasi Das, PhD, a postdoctoral fellow at the Webster lab and lead author of the study, said. 

“Through its beneficial metabolic effects, time-restricted eating may also provide an inexpensive, easy to adopt, but effective strategy to prevent and inhibit breast cancer without requiring a change in diet or physical activity,” Das added. 

Although insulin-lowering drugs effectively reduce tumour growth in mouse models of cancer, they have not shown similar results in human trials. However, this study suggests that TRE may be an effective and simple strategy to improve insulin sensitivity and reduce tumour growth. 

“The increase in risk of breast cancer is particularly high in women who are overweight and have been through menopause. For this reason, doctors may advise women to adopt weight loss strategies to prevent tumour growth,” Das said. 

“Our data suggest that a person may benefit from simply timing their meals differently to prevent breast cancer rather than changing what they eat,” Das added. 

A Nutritionist’s Perspective

This study was done in mice, but the results may apply to humans going by previous human TRE studies. TRE is an exciting area of research, I will explore TRE in greater detail in future posts. Stay tuned

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