The ketogenic, or “keto,” diet may have benefits beyond a whittled waistline. The low-carbohydrate, high-fat diet that helps your body to use fat as fuel may also be beneficial in the fight against cancer. Memorial Sloan Kettering medical oncologist Vicky Makker is studying the effects of this diet in women with endometrial cancer.
Why would a keto diet make a difference in endometrial cancer?
Trial participants receive three keto-friendly packaged meals and snacks per day for four to five weeks, according to Katie Hootman of Weill Cornell Medicine’s Clinical and Translational Science Center. Some of the foods on the menu are:
- salad greens with dressing
- fresh vegetables
- casseroles, such as a keto chicken enchilada casserole
- desserts, including cookies
Obesity is a major factor in the development of endometrial cancer. You can’t control your genetics or getting older, but weight is something that can be modified. The issue is not so much the obesity itself but the chronic inflammation it causes. Inflammation kickstarts the wound-healing process, but chronic inflammation sends that process into overdrive, injuring healthy cells in its wake. In addition, a growing body of research at MSK suggests that cancer cells take advantage of the wound-healing process to spread to new places in the body. Being overweight puts the body into chronic inflammation and causes other changes that are linked to cancer. One way to prevent chronic inflammation is to reduce the intake of carbohydrates. The keto diet is very low in carbohydrates.
Also, many women with endometrial cancer have a mutation in the PIK3 pathway. Cancer cells need access to this pathway to start a chain of events that can promote cancer growth. Targeted drugs called PIK3 inhibitors can put a roadblock in that path. But it’s a bit of a double-edged sword: The drugs block the pathway cancer cells need, but they also lead to insulin resistance and a buildup of blood glucose. It’s like a traffic jam: When glucose rises, insulin spikes, which stops the PIK3 inhibitors from working. So, the theory is that a keto diet prevents insulin spikes and therefore helps the targeted drugs work more effectively.
How are you studying this?
Our pilot study at MSK is evaluating whether newly diagnosed endometrial cancer patients can tolerate a keto diet for three to four weeks before surgery. We are also evaluating whether the diet can help stabilize the body’s insulin and blood sugar levels and have positive effects at the actual tumor site. We started this research after reviewing preliminary data from a study involving mice conducted by the Cantley Lab at Weill Cornell Medical Center.
We have two clinical trials in the works. Both incorporate a ketogenic diet and target the PIK3 signaling pathway. The difference is that in one trial, we target the pathway with a pill, and in the other, we give that drug in intravenous form. In these trials, we’re targeting endometrial cancer because we have seen a lot of PIK3 mutations in this disease, but we are also investigating this approach in lymphoma and plan to study this strategy in more cancers.
What we’ve learned so far is that the diet has been well tolerated, people are sticking to it, and that the diet is resulting in mild weight loss. We hope to be able to present our preliminary data soon.
What might a “diet prescription” look like one day?
It won’t be one-size-fits-all. It may depend on many factors including how well the patient is doing, underlying health conditions, BMI, and how resistant the body is to the insulin it produces. There are questions we need to answer: Should we take it to the extreme, prescribing a strict keto diet so that people get the bulk of their energy from fat reserves? Or would a modified keto diet work over time?
What would you tell someone who is skeptical about the impact of diet on cancer treatment?
I look to the data. A lot of patients are already looking for ways to modify their weight. If you combine diet with the science behind cancer signaling pathways, this is a novel idea worth pursuing.