A new study by researchers at MIT has provided insights into the mechanisms by which dietary changes slow tumor growth and suggests new avenues to explore for increasing survival time in cancer patients.
There have been a few studies conducted on the effect of diet on tumor growth that suggest dietary changes can help to slow down the growth of tumors. Studies on mice and other animals have shown lifespan can be increased by reducing food intake and cutting calories by between 25%-50%. Some studies have also been conducted on the effect of a ketogenic diet on tumor growth, although the results of those studies have been inconclusive.
Ketogenic diets are low in carbohydrates and high in protein and fat and, like calorie-restricted diets, reduce the amount of glucose available. Since tumors consume large amounts of glucose, reducing the level of available sugar has potential to slow down cancer growth.
The researchers conducted their study on the effect of a calorie-restricted diet and ketogenic diet on mice with pancreatic tumors to explore the impact both had on tumor growth. The researchers found that the calorie-restricted diet resulted in a slowdown in tumor growth, which suggests it is not the reduction in sugar that is having the effect but something else. The researchers found that mice that consumed 40% fewer calories than the control group had reduced body weights but found that tumor growth was still inhibited when normalized to animal body weights.
The researchers investigated the reasons for the slowdown in tumor growth and found that with both the calorie-restricted and ketogenic diets, blood glucose was reduced, but lipid levels also went down in mice on the calorie-restricted diet, whereas lipid levels increased in mice on the ketogenic diet. Mice on the calorie-restricted diet had lower lipid levels in the plasma and tumors and it is thought to be the lipid shortage, not the lower glucose levels, that is impairing tumor growth.
Lipids are needed by cancer cells as they are essential components of cell membranes. When lipids are not available, cells can make their own through a process involving stearoyl-CoA desaturase (SCD), which is an enzyme that converts saturated fatty acids into unsaturated fatty acids. Mice on both diets exhibited a reduction in SCD activity, but the mice on the ketogenic diet were able to get the lipids they needed from food, whereas the calorie-restricted mice could not.
“Not only does caloric restriction starve tumors of lipids, it also impairs the process that allows them to adapt to it,” said first author Evan Lien. “That combination is really contributing to the inhibition of tumor growth.”
The researchers also investigated the possible effect of diet on human cancer patients by comparing pancreatic survival times with dietary data from 1,165 patients from two large cohorts. They found the type of fat consumed by patients appeared to influence how patients on a low sugar diet fared after being diagnosed with pancreatic cancer.
While it was not possible to draw any conclusive results from their analysis due to the amount of data available, the data appear to indicate that a diet low in carbohydrates and higher in fat and protein was associated with longer survival time, with longer survival times were associated with diets consisting of more fat than protein, and also when fat and protein came from non-animal sources.
While the evidence suggests that dietary restrictions could be beneficial in cancer patients, there is insufficient data to support a decision to adopt a different diet to increase survival. That decision would need to be taken on a case-by-case basis. While there could be advantages to dietary changes, both diets are hard to maintain and there are also potential harmful side effects, especially with calorie-restricted diets as the associated weight loss might prevent certain treatment options from being open to patients.
The study was not conducted to determine the best diet for cancer patients, instead to identify the mechanisms by which certain dietary changes could affect tumor growth. The results of the study suggest avenues to explore in research into future cancer therapies, such as using drugs that inhibit the SCD enzyme to limit the ability of cancer cells to produce the unsaturated fatty acids they depend on for growth.
“This study shows how diet can alter tumour metabolite availability and influence cancer cell metabolism to affect growth,” explained the researchers in the paper. “A better understanding of dietary effects on tumour metabolism and progression might lead to orthogonal strategies to mimic the effects of a particular diet and provide guidance for how to incorporate dietary interventions to improve the care of patients with cancer.”
You can read more about the research in the paper – Low glycaemic diets alter lipid metabolism to influence tumour growth – which was recently published in Nature. DOI: 10.1038/s41586-021-04049-2