September 17, 2018 | 8 minute read

The ketogenic diet is a hot topic these days, with news stories and multiple health claims spurring interest in this extremely high-fat and low-carb diet plan. One major area of activity centers around how the ketogenic diet may help individuals diagnosed with cancer.

The theories behind this potential health benefit are not new; they go back nearly 100 years. But emerging research in cellular metabolism and a handful of recent studies – including an AICR-supported study published in August – are adding insights into the possible effects of the ketogenic diet during cancer treatment.

“This is an important area of research that has the potential to significantly improve treatment responses,” said AICR’s Director of Research Nigel Brockton, Ph.D. “There are plausible mechanisms by which the ketogenic diet could help make treatment more effective, but, as we see many times, plausibility alone is not enough; it has to be tested. That’s why we are supporting research in this area.”

Currently, no major cancer health organizations, including AICR, recommend the ketogenic diet for cancer patients – or for cancer prevention.

Note: The ketogenic diet was developed in the 1920s to curb seizures. Today, it is an accepted medical option for children with epilepsy who do not respond to standard treatment. Other disease-related health claims continue to be investigated.

About the ketogenic diet

Take a high-fat, low-carbohydrate diet to the extreme and you have the basics of the ketogenic diet.

The average American eats close to half of our calories – 47 to 50 percent – from carbohydrates, 33 percent from fat and 16 percent from protein.

The classic ketogenic diet is composed of 5 percent or fewer of daily calories from carbohydrates, 80 percent from fat, and 15 percent from protein. For someone on a 2,000 calorie diet that means eating less than 25 grams of carbs per day – about the amount in one apple.

This diet is challenging for many individuals to follow long-term. There are versions of it that contain more carbs, especially the plans targeted in the popular press. For someone undergoing cancer treatment, even proponents of the ketogenic diet note that it should be closely supervised by one’s health-care team.

How the diet relates to cancer

All of our cells need the energy to survive and the fuel for that energy comes from the digestion and metabolism of food. The fuel of choice for most cells is glucose (sugar); it is delivered to cells from the blood, primarily from the digestion of carbohydrates.

A healthy cell pulls in glucose that then goes through a series of reactions with oxygen to produce usable energy.

In the 1920s, German scientist Otto Warburg found that cancer cells fuel their growth through metabolizing a large amount of glucose. Unlike the average healthy cell, he saw that cancer cells were converting glucose into energy without using oxygen, even when oxygen was readily available. Now called the Warburg effect, this phenomenon is seen in about 80 percent of cancers.

The oxygen-free pathway used by cancer cells needs a lot more glucose to produce the same amount of energy as an oxygen-using cell. This realization led to imaging techniques where cancer cells can be detected by spotting where large amounts of a glucose tracer accumulate in the body. The glucose used in this technique contains a small amount of radioactive material that lights up in the image.

If our body doesn’t have access to glucose, it will eventually start to produce ketones in the liver from fatty acids and amino acids.

Healthy cells can use ketones for energy but cancer cells may not be able to as easily. Fasting for several days or extended aerobic exercise are both ways that can shift the body towards using ketones for fuel; a ketogenic diet is another. The ketogenic diet attempts to deprive cancer cells of their primary energy source – glucose.

The ketogenic-cancer evidence

Cancer is increasingly being studied as a metabolic disorder, not just a genetic one. This has renewed interest in the Warburg effect and the ketogenic diet.

The vast majority of claims regarding the ketogenic diet and cancer are drawn from lab and animal studies. Findings from animal studies are revealing. A study published in July’s Nature found that in mice, the ketogenic diet enhanced the effects of a specific cancer treatment. The drugs in that treatment targeted a signaling network guided by an enzyme (abbreviated P13K), which is commonly mutated in cancers.

Consuming foods with carbohydrates increases sugar levels in the blood, which leads to insulin production. Insulin could then activate P13K signaling in tumors. By feeding mice a ketogenic diet, insulin levels were kept low and the drug was more effective, the study concluded.

Yet the study also found that the ketogenic diet alone, in some cases, had no effect on the cancer or actually accelerated the growth of leukemia in mice. It may be harmful for patients with cancer when used in isolation, the authors note.

Translating animal findings to a study of cancer patients is challenging, given each person’s unique diagnosis, treatment needs and the challenge of following such an extreme diet. The relatively few human trials completed in this field are small, lasting from days to months. Most involve advanced cancers and some deal only with adherence.

Current evidence among cancer patients is unclear and articles have reached different conclusions: A 2017 review article found the evidence of ketogenic diets on cancer and treatment side effects “missing”.

AICR-supported randomized-controlled study

One randomized-controlled trial examining the effects of a ketogenic diet in cancer patients was recently published in August. The study was AICR-supported and published in The Journal of Nutrition.

The AICR-supported study investigated whether the ketogenic diet can shift the metabolic environment to one proposed to be unfavorable for tumor growth among women diagnosed with ovarian and endometrial cancers.

In the study, Barbara A. Gower, Ph.D., and her colleagues analyzed data from 45 women diagnosed with ovarian and endometrial cancers. The women were randomly assigned to either a ketogenic or a standard, healthy diet group. The ketogenic group was asked to consume 70 percent of calories from fat, 25 percent from protein and 5 percent from carbohydrates. The comparison diet was one recommended by the American Cancer Society, high in whole grains and fruit and low in added sugar.

After three months, women in the ketogenic diet group had lower levels of insulin and an insulin-like growth factor (IGF-1) in their blood than the comparison group.

This study demonstrates not only high feasibility but also that a ketogenic diet can shift the metabolic environment among women with ovarian and endometrial cancers, said Gower, a professor at the University of Alabama at Birmingham (UAB) Nutrition Obesity Research Center. Further study in a clinical setting is needed to determine whether the ketogenic diet may be an effective non-pharmacologic adjuvant therapy for certain types of cancer, the paper concluded.

Ongoing research

More studies are coming. In Gower’s study, participants varied in cancer stage and treatment, which may have influenced the results. She is planning to follow up with a ketogenic diet study focused on ovarian cancer patients undergoing chemotherapy, investigating immune function and survival.

And the research team who published their mice findings in Nature are now carrying this research into a clinical trial for patients with lymphoma and endometrial cancers. The trial aims to include 40 patients and begin this fall.

Cancer patients, survivors and what to eat

AICR recommends that anyone who has received a diagnosis of cancer should receive specialized nutritional advice from an appropriately trained professional.

For patients interested in Ketogenic diet, it is vitally important that you talk with your health-care providers, says Alice Bender, MS, RDN, AICR’s Director of Nutrition Programs. “A dietitian is best positioned to talk with you about what is known regarding the pros and cons – especially to learn if this diet has any research showing the reasonable application with your particular type of cancer and if the ketogenic diet may even be harmful for you.”

The diet’s strict limitation on starchy vegetables, whole grains, and fruits may lead to missing out on vitamins, minerals and other healthy compounds found in plant foods, which can lead to malnutrition, Bender adds. A true ketogenic diet could also lead to digestive and other unpleasant side effects. It requires monitoring and nutritional supplements. It can be difficult to follow.

“Even for people who comply with the diet, the metabolic effects may vary and the effect on cancer treatment is still uncertain,” Brockton warns.

There is, however, clear evidence that following a diet rich in plant foods like vegetables, whole grains, fruit, and beans, choosing moderate amounts of red meat and other animal foods and limiting alcohol reduces the risk for cancer and other chronic diseases. It also provides the nutrition needed for overall health and wellness.

AICR recommends that survivors who have finished their treatment follow the diet recommended for cancer prevention, unless otherwise advised. That means a diet filled with a variety of plant foods, including whole grains, vegetables, and fruit, with healthy proteins and limited amounts of red meat and highly processed, fatty and sugary foods.

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