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Diets limiting lipid intake effectively reduce cancerous tumor growth compared to ketogenic diets

According to a new study out of Massachusetts Institute of Technology (MIT), cutting off lipid supply to cells can limit tumor growth in mice.

Throughout the last few years, a handful of published studies have shown some evidence that dietary modifications can assist in decreasing tumor development. A new study from MIT demonstrates how two distinct diets influence cancer cells in mice, and provides an explanation for why calorie restriction may decrease tumor development.

While observing mice with pancreatic tumors, the researchers looked at the effects of a calorie-restricted diet versus a ketogenic diet. While both diets lower the amount of sugar accessible to tumors, the researchers discovered that only the calorically restricted diet decreased the availability of fatty acids, which was associated with a slowing of tumor development.

To be clear, according to the researchers suggestions, the findings do not imply that cancer patients should strive to adopt any of these diets. Instead, they feel the findings call for more research into how nutritional treatments may be coupled with existing or new medicines to assist cancer patients.

Matthew Vander Heiden, director of MIT’s Koch Institute for Integrative Cancer Research and one of the author’s of the new study added, “There’s a lot of evidence that diet can affect how fast your cancer progresses, but this is not a cure. While the findings are provocative, further study is needed, and individual patients should talk to their doctor about the right dietary interventions for their cancer.”

Past research has shown that a calorie-restricted diet may decrease tumor growth in some circumstances, and such a diet has been proven to increase longevity in mice and a variety of other animals. The findings of a limited number of studies looking at the effects of a ketogenic diet on cancer have been unclear.

The paper’s primary author is MIT postdoc, Evan Lien, who shared some of his thoughts on the conception of the question addressed by the study saying, “A lot of the advice or cultural fads that are out there [that] aren’t necessarily always based on very good science. It seemed like there was an opportunity, especially with our understanding of cancer metabolism having evolved so much over the past 10 years or so, that we could take some of the biochemical principles that we’ve learned and apply those concepts to understanding this complex question.”

Because cancer cells use a lot of glucose, some researchers thought that decreasing the quantity of glucose accessible by a ketogenic diet or calorie restriction might limit tumor development. However, the MIT team’s early tests in mice with pancreatic tumors revealed that calorie restriction has a significantly higher effect on tumor development than the ketogenic diet, indicating that glucose levels were not a major factor in the slowing. The researchers looked at tumor development and nutrient content in mice with pancreatic tumors that were fed a normal, ketogenic, or calorie-restricted diet to learn more about the process. Glucose levels decreased in both the ketogenic and calorie-restricted mice. Lipid levels decreased in calorie-restricted mice, but increased in mice on the ketogenic diet.

Lipid deficiency slows tumor development because cancer cells require lipids to build their cell membranes. When lipids aren’t present in a tissue, cells can usually synthesize their own. They must maintain the proper balance of saturated and unsaturated fatty acids as part of this process, which necessitates the use of an enzyme called stearoyl-CoA desaturase (SCD). Saturated fatty acids are converted into unsaturated fatty acids by this enzyme. SCD activity is reduced by both calorie-restricted and ketogenic diets, however mice on the ketogenic diet have lipids accessible from their food, so they didn’t need to employ SCD.

“The purpose of these studies isn’t necessarily to recommend a diet, but it’s to really understand the underlying biology,” Lien says. “They provide some sense of the mechanisms of how these diets work, and that can lead to rational ideas on how we might mimic those situations for cancer therapy.”

For future studies, the researchers want to examine how different fat sources, such as plant or animal-based fats with specified saturated, monounsaturated, and polyunsaturated fatty acid content, affect tumor fatty acid metabolism and the unsaturated/saturated fatty acid ratio.

The study was published in Nature, on October 20th, 2021.

Abstract. Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels, we found that only CR inhibits the growth of select tumour allografts in mice, suggesting that other mechanisms contribute to tumour growth inhibition. A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumours. Upregulation of stearoyl-CoA desaturase (SCD), which synthesises monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumour SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumour growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR. By contrast, although KD also impairs tumour SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumours, and changing the KD fat composition to increase tumour saturated fatty acid levels cooperates with decreased tumour SCD activity to slow tumour growth. These data suggest that diet-induced mismatches between tumour fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycaemic diets impair tumour growth.

Lien, E.C., Westermark, A.M., Zhang, Y. et al. Low glycaemic diets alter lipid metabolism to influence tumour growth. Nature (2021).

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