This new research aims to understand how diet affects tumor growth and how to improve drug treatments.
The study, published in Nature, highlights how some diets, such as those that periodically limit calories and induce metabolic changes associated with fasting, or low-carb, high-fat ketogenic diets, are emerging as nutritional interventions that can slow down the growth of cancer and increase the anticancer effect of drugs.
In particular, a study by Lien and colleagues showed how diet influences cancer growth. The results highlight the importance of the number of calories and levels of proteins, fats, and carbohydrates in the diet, as well as its duration and frequency.
The authors examined mice with two types of cancer: pancreatic ductal adenocarcinoma, (a malignant tumor of the pancreas) and lung cancer. The two types of mice were subjected to a diet that restricted calories by 40% by reducing carbohydrates for 25 days, or in alternative to a 20 day ketogenic diet consisting of a normal number of calories but made up of a 90% fat intake, 9% protein and 1% carbohydrate. The researchers found that both diets led to a similar result in decreasing glucose levels in the blood, but that the calorie-restricting diet reduced tumor growth to a greater extent than the ketogenic diet.
Glucose levels are important for the survival and growth of many types of cancer, to the point that glucose metabolism is considered a target for anticancer therapy.
However, only the calorie-restricting diet had effects on tumor growth, as it reduced the availability of glucose to cancer cells.
The authors also considered whether, in addition to glucose, other nutrients influenced the anticancer effects of the calorie-restricting diet, in particular, the concentration of fatty acids in the blood and in the tumor. As expected, the ketogenic diet led to high concentration levels, unlike the calorie restricting diet, suggesting the possibility that some fatty acids support tumor growth. Both diets reduced the activity of an enzyme necessary for cancer cells to proliferate in a fat-free environment, however, only the calorie-restricting diet reduced levels of unsaturated fats (the “healthy” fats) and affected the ratio of unsaturated and saturated fats (the “bad ones”), suggesting that their imbalance affects tumor growth.
In order to better understand this mechanism, the authors gave the mice a low-calorie diet, but high in fat, in the form of palm oil; thus the ratio of unsaturated to saturated fat returns to that of mice following the normal diet. This partially blocked the effect of calorie restriction on tumor growth. In fact, although the calorie-restricted diet was effective against pancreatic and lung cancer, the addition of palm oil (and more generally fat) stopped the effects of the diet on pancreatic cancer growth.
WHAT’S NEW ABOUT THIS STUDY
This discovery underlines the need to combine calorie restricting diets with highly effective drugs against various cancers. In fact, the long-term calorie restricting diet or the more restrictive, fasting mimicking diet (periodic cycles of a diet capable of limiting the metabolic changes induced by water-only fasting), are effective against a wide range of cancers because they reduce the levels of glucose and proteins, such as insulin, IGF-1, leptin and ferritin, and in addition, they also alter the availability of amino acids and fats.
A study in mice found that fasting cycles act in a similar way to a chemotherapy drug (gemcitabine) that delays the growth of pancreatic tumors, however, only by combining fasting and gemcitabine a strong effect in inhibiting the progression of pancreatic cancer was obtained.
Therefore, the study by Lien and colleagues highlights how low-calorie diets, but not ketogenic diets, can compromise the growth of specific tumors, paving the way for further research aimed at estimating the involvement of other metabolites in the survival of cancer cells.