In order to grow, tumors depend on nutrients such as sugar and fats. Diets are therefore also being discussed to support cancer therapies. A study in mice now shows that a reduced-calorie diet can actually help to slow down tumor growth. A ketogenic diet, on the other hand, had no effect on tumor growth. However, diet recommendations for humans cannot be derived directly from this, as the researchers emphasize. However, the findings shed new light on the underlying mechanisms and could contribute to the development of new therapies.
Since cancer cells divide very quickly compared to other cells in the body, they need a particularly large number of nutrients as energy suppliers and as building blocks for molecules that are necessary for cell division. It is therefore discussed to what extent diets can help to “starve out” the tumor. So far, there has been a particular focus on carbohydrates. Since tumors depend on glucose, one idea was to slow down tumor growth through a low-carbohydrate diet – such as a ketogenic or low-calorie diet.
Tumor mice on a diet
A team led by Evan Lien from the Massachusetts Institute of Technology (MIT) in Cambridge has now used mice to study how various diets affect cancer cells. To do this, they implanted tumor cells from pancreatic cancer or small cell lung carcinoma in the animals and fed them in various ways: one group received a ketogenic diet with very few carbohydrates but a normal calorie content, one group received a diet with 40 percent fewer calories that was balanced on fats , Carbohydrates and proteins distributed, and a control group was fed normally.
“Both diets lowered blood sugar levels in a similar way,” the researchers report. The insulin levels of the mice also fell, more so on the ketogenic diet than on the calorie-restricted diet. However, only the reduced-calorie diet ensured that the tumor grew less quickly – even if the researchers put the tumor size in relation to the weight of the animals, which was significantly lower in mice from the low-calorie group. “The effects of calorie reduction on tumor growth cannot apparently be fully explained by the reduction in blood sugar and insulin,” the researchers said.
Fatty acid deficiency slows tumor growth
To find out how the reduced-calorie diet slows tumor growth, Lien and his colleagues investigated the availability of additional nutrients and metabolic products in the tumors. “We found that the two diets had very different effects on fatty acid levels,” they report. Only the low-calorie diet reduced the availability of important fatty acids in the tumor. The ketogenic diet, on the other hand, actually increased the levels of some fatty acids.
In cell cultures, the researchers tested how the fatty acid deficiency affects tumor growth. And indeed: if important fatty acids were missing, the tumor cells could not multiply because they need the lipids to build their cell membrane. The effect was partially absorbed in the cell cultures by an enzyme called stearoyl-CoA desaturase (SCD). This can convert saturated into unsaturated fatty acids and thus maintain the balance between saturated and unsaturated fatty acids required for cell division. If the enzyme was missing, the tumor cells could not adapt to the lipid deficiency.
Double attack on the tumor
In the mice, the researchers found that both diets reduced SCD activity. “That’s likely because SCD is usually upregulated by insulin signals and both diets lowered insulin levels,” they explain. However, since there are enough different lipids available on the ketogenic diet, the tumor does not need SCD in this case, which could explain why this diet did not slow down growth. “The calorie restriction, on the other hand, removes lipids from the tumors and also impairs the process that enables them to adapt to the diet. This combination really helps to inhibit tumor growth, ”says Lien.
In addition, Lien and his colleagues analyzed diet and survival data from 1,165 pancreatic cancer patients. The data are not complete enough to reach far-reaching conclusions, but suggest that a low-carbohydrate diet in humans is associated with longer survival times and that vegetable fats may be cheaper than animal fats.
Not recommended for human patients
However, the researchers emphasize that no recommendations for cancer patients can be derived from their results. “There is a lot of evidence that diet can affect the rate at which cancer progresses, but that’s not a cure,” says Lien’s colleague Matthew Vander Heiden. “The results are provocative, but more studies are required, and every patient should talk to their doctor about the right nutritional measures for their cancer.” Diets could have serious side effects, especially for cancer patients, warn the researchers. In the worst case, they can promote metastases and increase the risk of cardiovascular diseases. In addition, weight loss could make further therapy difficult or impossible.
“The purpose of these studies is not necessarily to recommend diet, but to really understand the underlying biology,” says Lien. “They give an impression of the mechanisms by which these diets work, and this can lead to rational ideas as to how we could mimic these situations for cancer therapy.” the tumor cells would be cut off from producing unsaturated fatty acids.
Source: Evan Lien (Massachusetts Institute of Technology, Cambridge) et al., Nature, doi: 10.1038 / s41586-021-04049-2