The study analyzed the effects of these two different dietary approaches on cancer cell growth in mice and provided an explanation for why calorie restriction slowed tumor growth.

The study examined the effects of a calorie-restricted diet and a ketogenic diet in mice with pancreatic tumors. While both diets reduced sugar availability to tumors, the researchers found that only the calorie-restricted diet reduced fatty acid availability, which was associated with slower tumor growth.

Diet affects the metabolism of cancer cells

Cancer cells consume large amounts of glucose, so some scientists had hypothesized that either a ketogenic diet or calorie restriction might slow tumor growth by reducing the amount of glucose available. However, preliminary experiments by the MIT team in mice with pancreatic tumors showed that calorie restriction had a much greater effect on tumor growth than a ketogenic diet, so the researchers suspected that glucose levels did not play a role in slowing tumor growth. play a major role.

To dig deeper into this mechanism, the researchers analyzed tumor growth and nutrient concentrations in mice with pancreatic tumors. The mice were fed a normal diet, a ketogenic diet, and a calorie-restricted diet. Glucose levels dropped in both ketogenic and calorie-restricted groups of mice. But the difference was that lipid levels also decreased in the calorie-restricted mice, and increased in the mice on the ketogenic diet.

A shortage of lipids impairs tumor growth because cancer cells need lipids to build their cell membranes. Normally, cells can make their own when lipids are not available in tissues, and as part of this process, they need to maintain the proper balance of saturated and unsaturated fatty acids, which requires a process called stearoyl-CoA desaturation (SCD) enzymes. This enzyme is responsible for converting saturated fatty acids into unsaturated fatty acids.

Both calorie-restricted and ketogenic diets reduced SCD activity, but mice on the ketogenic diet had dietary lipids, so they did not need SCD. However, mice on a calorie-restricted diet were unable to obtain fatty acids from their diet or produce their own. Tumor growth in these mice was significantly slower than in mice on the ketogenic diet.

In addition to the mouse studies, the researchers also looked at some human data. Working with oncologists at Dana-Farber Cancer Institute, the team obtained data from a large cohort study to analyze the relationship between dietary patterns and survival time in pancreatic cancer patients.

Although the study showed benefits of calorie restriction in mice, the researchers do not recommend that cancer patients follow a calorie-restricted diet because it is difficult to maintain and can have harmful side effects. However, exploiting cancer cells' dependence on the supply of unsaturated fatty acids to develop drugs that may help slow tumor growth is a new angle the study offers.

【Reference article】

Lien E C, Westermark A M, Zhang Y, et al. Low glycaemic diets alter lipid metabolism to influence tumour growth[J]. Nature, 2021: 1-6.