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Ketogenic diet comprises of a very low carbohydrate and high-fat diet, it may improve the effectiveness of an emerging class of cancer drugs, according to a study in mice by investigators at Weill Cornell Medicine, Columbia University Irving Medical Center and NewYork-Presbyterian.
Drugs that targets activated enzyme phosphatidylinositol-3 kinase (PI3K) may not be effective unless patients can maintain low blood sugar levels through diet or medication. Low blood sugar may improve the effectiveness of cancer drugs. Some of the most common genetic mutations seen in cancerous tumors affect PI3K. The frequency of mutations in the gene has made it an appealing target for cancer drugs, and more than 20 therapies that inhibit the PI3K enzyme have entered into clinical trials.
Some patients taking these drugs develop excessively high levels of blood sugar or hyperglycemia. This is often temporary because the pancreas can usually compensate by producing more insulin. But some patients’ blood sugar levels don’t return to normal and they must stop taking the drugs.
Researchers demonstrated that rising insulin levels reactivate PI3K in mice with pancreatic tumors treated with a PI3K-inhibitor called Buparlisib. Reactivating PI3K in the tumor makes the drug relatively ineffective. The rebound elevation in insulin is rescuing the tumor from death. That observation led the investigators to reach into the endocrinologist’s tool box for treatments that help control blood sugar and insulin levels.
Metformin, which increases insulin sensitivity, didn’t have much effect on the glucose or insulin spikes, or on cellular signals that promote tumor growth. The SGLT2 inhibitors, which prevent the re-absorption of glucose in kidneys so that it is removed in urine, reduced the glucose and insulin spikes in response to PI3K treatment and reduced tumor growth signals.
The ketogenic diet, which has been used in the clinic for about four decades to control insulin levels, did the best job at preventing glucose and insulin spikes and tamping down tumor growth signals. The ketogenic diet turned out to be the perfect approach, it reduced glycogen stores, so the mice couldn’t release glucose in response to PI3K inhibition. Blocking spikes in glucose and the subsequent insulin feedback can make the drugs much more effective at controlling cancer growth. Ketogenic diet alone may not necessarily control cancer growth and in some cases may even be harmful.
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