Nature: Ketogenic diet cannot fight cancer, but calorie restriction can cut off lipid supply and inhibit tumor growth

The ketogenic-diet (KD) is a formula diet with high fat content, low carbohydrate content, and suitable protein and other nutrients

Caloric restriction (CR) refers to limiting the total daily intake of calories and reducing the total calories by 25-50% while providing sufficient nutrients such as essential amino acids and vitamins to ensure that malnutrition does not occur

Both of these diets are low glycemic index diets, because this diet does not raise blood sugar levels quickly after eating

For most cancer patients, long-term low-glycemic diet is not allowed, because this will cause them to lose weight and muscle mass, which is not conducive to disease treatment

On October 20, 2021, Matthew Vander Heiden of theMassachusetts Institute of Technology and others published a research paper titled: Low glycaemic diets alter lipid metabolism to influence tumour growth in Nature .

This study found through mouse models of pancreatic cancer that only calorie restriction can inhibit tumor growth, while ketogenic diets cannot

And further revealed the underlying mechanism: calorie restriction not only reduces the blood lipid levels in plasma and tumors, but also reduces the stearoyl-CoA desaturase (SCD) activity, resulting in cancer cells not being able to obtain lipids from the diet, but also It is difficult to produce by oneself, which leads to tumor growth restriction

Using this feature of cancer cells can inhibit tumor growth by inhibiting the activity of SCD, which may represent a new direction for cancer treatment

Cancer cells consume a lot of glucose, so it is thought that a ketogenic diet or calorie restriction may slow tumor growth by reducing the amount of glucose available to cancer cells

The research team used a mouse model of pancreatic cancer to study these two diets and found that only calorie restriction can inhibit tumor growth.

Figure a: Calorie restriction diet significantly inhibited tumor growth; Figure b: Ketogenic diet failed to significantly inhibit tumor growth

The research team conducted further analysis and found the difference between the two diets: calorie restriction not only lowered blood sugar levels, but also lowered blood lipid levels, while ketogenic diet only lowered blood sugar levels, but increased blood lipid levels

Lack of lipids will limit tumor growth, because fast-dividing cancer cells need lipids to build cell membranes.

Calorie restriction not only reduces blood lipid levels in plasma and tumors, but also reduces the activity of stearoyl-CoA desaturase (SCD), breaking the balance between saturated fatty acids and unsaturated fatty acids, and further weakening the survival of tumors.

Although the ketogenic diet will also destroy the activity of stearoyl-CoA desaturase (SCD), the ketogenic diet will increase blood lipids, thereby maintaining the ratio of saturated fatty acids to unsaturated fats at a level favorable for tumor growth

Figure a: The metabolic changes brought about by calorie restriction can inhibit tumor growth; Figure b: The metabolic changes brought about by a ketogenic diet cannot inhibit tumor growth

In addition to the mouse experiments, the research team also analyzed the relationship between the dietary patterns and survival time of 1165 pancreatic cancer patients.

Although this study shows that calorie restriction can inhibit tumor growth, the author also pointed out that this diet is not necessarily suitable for all cancer patients, because the diet model of calorie restriction is difficult to adhere to, and if it can be adhered to, it will lead to weight loss.

However, this study reveals that tumors are dependent on unsaturated fatty acids.
In the case of low blood lipid levels, inhibiting the activity of stearoyl-CoA desaturase (SCD) can cut off the ability of cancer cells to produce unsaturated fatty acids, thereby inhibiting Tumor growth
.

The author believes that further research on how diet affects the metabolic changes that interfere with tumor growth, or can guide how to add diets or therapies that mimic such effects to existing cancer treatment strategies
.

First author Evan C.
Lien (left), corresponding author Matthew Vander Heiden (right)

Original source:

Lien, EC, Westermark, AM, Zhang, Y.
et al.
Low glycaemic diets alter lipid metabolism to influence tumour growth .
Nature 599, 302–307 (2021).
https://doi.
org/10.
1038/s41586-021- 04049-2.