Growth activity requires energy, so cancer cells metabolize nutrients in different ways than the healthy cells around them. In an attempt to kill the tumor without killing normally functioning cells, chemotherapy drugs target these pathways within cancer cells. This is notoriously difficult, expensive, and prone to the toxic side effects that account for much of the suffering associated with the disease.
Now doctors are beginning to think more about the specific nutrients that feed tumor cells. That is, how what we eat affects cancer growth, and if there is a way to “starve” cancer cells without leaving a person malnourished, or even hungry.
“For a long time, the prevailing thought was that altered metabolism in cancer cells was the result of genes and mutations that determined metabolism,” says Jason Locasale, an oncology biologist at Duke University. “Now, as we know, it’s a complex interaction of environment and genes, and one of the main factors at play is nutrition.”
Importance of nutrition
The importance of nutrition has long been accepted for diseases such as diabetes and hypertension, diagnoses that come with well-known dietary prescriptions. Even the most commonly used type2 diabetes drug, metformin, has been found in clinical trials to be inferior to diet and exercise. Cell biologists like Locasale see extending that line of thinking to cancer as a logical step, because at the cellular level it’s also a disease of metabolic pathways.
Suggesting that people fast or starve to kill a tumor has been the domain of dubious and exaggerated claims over the years, and that’s not the suggestion now. In recent trials, metabolic pathways have been targeted through various approaches to change what people eat.
Some research has involved minimizing sugar intake. In fact, some cancer cells metabolize glucose at higher levels than normal (to support the aerobic glycolysis process), and depleting their access to sugar can slow growth.
Last year, Siddhartha Mukherjee, a Columbia University researcher and author of “The Emperor of All Diseases,” and his colleagues found that at least one particular chemotherapy drug may be more effective when combined with a “ketogenic” diet, low in sugar, protein and fat. In the Nature article, the researchers suggest that the effect was related to decreased levels of insulin that the pancreas releases into the blood in response to food.
Cancer and sugar
Around the same time, an international team concluded in the journal Science that “only some cancer cells are highly sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear.” In other words, a low-sugar diet might help fight some cancers, but it’s certainly not as simple as cancers “eat sugar,” so a low-sugar diet stops cancer.
Although the angle of sugar and insulin has shown promise, research has focused on dietary protein, or, specifically, the individual amino acids that make up that protein.
Studies have shown that restriction of the amino acids serine and glycine can modulate cancer outcomes. According to a 2018 study in Nature, the chemotherapy drug methotrexate is affected by the amino acid histidine. Another, asparagine, is involved in the progression of breast cancer metastasis.
Most interest has been directed at methionine, which is found in high levels in eggs and red meat. In 2018, a review of existing evidence from the Rutgers Cancer Institute in New Jersey found methionine restriction to be “a promising antitumor strategy.” That promise has also been shown in brain tumors and melanomas, as UC San Diego surgeon Robert Hoffman detailed in February.
Methionine
Methionine is produced in normal cells, from homocysteine, folate and vitamin b12. However, many types of cancer cells lack methionine. Therefore, they need extra methionine outside the field – through the food we eat – to survive. Cut off that supply, and it should help slow the tumor without starving the person.
This month, Localase and colleagues at Duke published findings showing that methionine restriction reduced tumor growth in mice and human subjects. In particular, it uses huge data sets to quantify metabolic activity. This allows the controversial field of nutritional research to operate with new levels of precision, where specific metabolic pathways can be monitored. Most of the nutrition research is based on self-reported data, where people who say they eat almonds have lower rates of some form of cancer, and the best we can do is assume these cases are related.
Locasale’s work, by contrast, is full of complex statistical calculations involving “Euclidean distances” and “multidimensional scaling. “It basically says that you can quantify what is happening in the cells”. What really complicates Locasale’s image is the closest thing to a strict low-methionine diet is a vegan diet.
This may seem at odds with the cancer-fighting effects reported by Mukherjee and colleagues involving a “ketogenic” diet. But contrary to the diet wars that fill the pages of popular media. Mukherjee supported the Locasale research “More evidence on the fascinating connection between diet and cancer” he tweeted about the Duke study. This is not about “starving” cancer, but about finding the precise vulnerabilities that make metabolic therapies feasible.
Metabolic strategies
Because cancer is a term that encompasses (encapsulates) many different diseases with different changes and metabolic pathways in different cells in different parts of the body: no one metabolic therapy is right for everyone. What makes one cancer grow more slowly might speed up another. Just as avoiding excessive consumption of sugar is crucial for diabetics, they lose their vision and feet, sugar can save the life of a person in a critical situation due to hypoglycemia.
For example, a study on vitamin B12 supplements, which can prevent anemia in people who do not assimilate it well through food. In excess, however, these supplements were linked to higher rates of lung cancer. Once again, it appeared that this was via a metabolic pathway that feeds tumor cells.
Nutrients or vitamins are not just good or bad, they cause or fight cancer. If a book or blog recommends a single “cancer diet” or even supplements that promise to beat cancer. This could end up making things worse.
For now, unless an oncologist recommends a specific diet tailored to your tumor, the most general recommendation is to eat a healthy diet. None of this questions the principle that staying well fed is part of the healthy approach to any disease; there is no evidence that general starvation is good or even safe.
But targeting specific eating patterns will likely be part of many cancer treatment guidelines in the years to come. Food is medicine or metabolic therapy. And no metabolic therapy is good or bad for everyone in all conditions.
