What Do We Know About the Ketogenic Diet in People With Cancer
- February 04, 2021
The ketogenic diet or “keto diet” is now being evaluated for its potential role in both cancer prevention and treatment. There are several questions to consider, however. Cancer is not a single disease but a broad collection of diseases, and the keto diet may be helpful with one type (or molecular subtype) but harmful in another. The answers may vary as well depending on how it may affect risk (prevention), treatments (such as chemotherapy and radiation), survival, or risk of recurrence. We will look at the research to date, potential benefits, side effects, risks, and contraindications. Importantly, if you are living with cancer it’s essential to talk to your oncologist before beginning any type of diet.
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The ketogenic diet (also called the “keto diet”) is a diet that is high in fat, low in carbohydrates, and is protein “neutral,” often having a slightly higher amount of protein than the typical Western diet. Specifically, the ketogenic diet is made up of:
- Fat: 55% to 60%
- Protein: 30% to 35%
- Carbohydrates: 5% to 10% (for a person consuming a 2000 calorie daily diet, this translates to 20 grams to 50 grams of carbohydrates)
This is in contrast to 2015-2020 USDA Dietary Guidelines which recommend:
- Fat: 20% to 35% (with an emphasis on healthy fats)
- Protein: 10% to 35%
- Carbohydrates: 45% to 65%
Even though it restricts carbohydrates very significantly, the ketogenic diet differs from many low carbohydrate diets that are made up of 20% to 30% carbs.
The goal of the ketogenic diet is to burn fat instead of sugar (glucose) for the body’s energy source. When carbohydrate intake is significantly reduced, the body switches to burning fat, a process (keto-adaptation) that produces ketone bodies. (This nutritional ketosis differs from the diabetic ketoacidosis, a dangerous condition many people are familiar with.)
The ketogenic has been found to lead to weight loss, at least over the short term. It has also proven helpful in reducing the number of seizures in people with medication-resistant epilepsy and is being studied for a potential role in conditions ranging from Parkinson’s disease to autism.
Since the research looking at the ketogenic diet in cancer is young, it’s helpful to look at how the diet may affect cancer cells and normal cells in the body.
There are a few ways in which a ketogenic may have benefits for at least some cancers.
One is by essentially “starving” cancer cells. Many years ago, Otto Warburg postulated the notion that sugar feeds cancer (the Warburg effect), earning the 1931 Nobel Prize in Physiology and Medicine. This has subsequently led to sugar being demonized in many circles as the cause of cancer growth, and indeed, PET scans rely on the fact that many types of cancer cells consume sugar to identify tumors. Rather than simply being cells that are bullies and grabbing onto sugar before normal cells are able, however, the theory behind the ketogenic diet with cancer is that it exploits a cancer’s dependence on glucose.
Cancer cells are different from normal cells in many ways, including their ability to adapt to changes in their environment. From lab studies, it appears that at least some cancer cells have difficulty using ketones as a source of energy (they are less likely to go through the process referred to as keto-adaptation due to down-regulation of enzymes needed to use ketones or because of mitochondrial dysfunction.). The theory is that inducing ketosis gives normal cells an advantage as they can adapt more readily to metabolize ketones.
In a different way, the ketogenic diet, in theory, might play a role in cancer due to its effect on lowering insulin levels. It’s known from research that both insulin and insulin-like growth factors can stimulate the growth of cancers.
In order for cancers to grow, they need to develop new blood vessels to support the tumor, a process referred to as angiogenesis. In a mouse model of glioma, the ketogenic diet was found to reduce angiogenesis.
Finally, it’s thought that ketone bodies might actually have a direct toxic effect on cancers. One study looked at the effect of ketone supplementation both on cancer cells grown in the lab and on mice with metastatic cancer. In the lab, ketone supplements were found to decrease both the health and growth of the cancer cells. In mice with metastatic cancer, ketone supplementation was associated with longer survival (50% to 68% longer depending on the specific ketone bodies used).
The ketogenic diet may also function in ways that could theoretically reduce the risk of at least some cancers.
Cancer begins when a series of mutations occur in a normal cell. A hereditary predisposition may be present, but most mutations are acquired over time via oxidative stress. Free radicals are unstable molecules that can be produced by carcinogens or by normal metabolic processes in the body. The theory behind eating an antioxidant-rich diet is that antioxidants work to “neutralize” free radicals by providing them with an electron. Oxidative stress, in turn, is a phrase that refers to an imbalance of free radicals and antioxidants, such that free radicals outnumber the antioxidants.
Ketone bodies reduce the production of free radicals while at the same time increasing antioxidant capacity in the body. Free radicals are implicated in causing the mutations that can lead to cancer, but this is also important for people who are living with cancer. Cancers continually change and develop new mutations. It is, in fact, these new mutations that lead to resistance to chemotherapy and targeted therapies that had previously been effective. That said, and as will be discussed below, restricting fruits and vegetables as may occur in the ketogenic diet could counteract this effect, but the true effect is not known at this time.
In another study, the ketone body B-hyroxybutyrate has been shown to suppress oxidative stress.
The research into the effect of a ketogenic diet on both cancer prevention and treatment is in its infancy. Since there are relatively few human studies to date, we will also look at the mechanism by which ketosis may play a role in cancer, as well as animal and lab studies to date.
While human cancer cells grown in the lab and animal studies don’t necessarily translate into what will happen in humans (and we will share an example below), they do shed light on a potential role in cancer.
Overall, animal studies suggest that the ketogenic diet may have an anticancer effects with most cancers. A 2017 review of studies found that 72% of the studies showed an anti-tumor effect of the ketogenic diet on cancer in animals. In this review, a pro-cancer effect (worsening of a tumor due to the ketogenic diet) was not seen.
Other pre-clinical studies have found that different types of cancer or molecular subtypes may respond differently to the ketogenic diet. For example, while most cancer cells responded (the diet had an anti-cancer effect), the diet appeared to have a pro-cancer effect in a few cancers (kidney cancer and BRAF-positive melanoma). The fact that BRAF V600E-positive melanoma in a mouse model showed significant growth on the ketogenic diet raises concern that the ketogenic diet may have different effects not only on different cancer types, but the specific molecular alternations present that drive the growth of the tumor.
Overall, it’s important to note that, for good or bad, the ketogenic diet does have an effect on the metabolism of cancer cells. In a 2019 study, the ketogenic diet was found to have a significant inhibitory effect on the cells that appeared to go beyond simply the energy supply of the cells. What that mechanism may be, however, is unknown.
Most of the human studies looking at the ketogenic diet in people with cancer have been small, and many have focused primarily on safety at this time.
The strongest evidence has been seen for glioblastoma, the most common and aggressive type of brain cancer. There is also good evidence for a potential benefit of the ketogenic diet with a few other cancers including lung cancer, prostate cancer, colon cancer, and pancreatic cancer.
While animal studies are helpful, the situation in humans may be different. For example, while BRAF-positive melanoma in a mouse model showed significant growth with the ketogenic diet, in a small trial with only a few patients with BRAF mutation-positive melanomas, one appeared to benefit from the ketogenic diet.
A recent study of the effect of the ketogenic diet on women who had ovarian or uterine cancer primarily addressed safety, but was encouraging in other ways. It was found that the diet did not negatively impact quality of life for the women and may improve physical functioning, reduce fatigue, and decrease food cravings.
With any approach to cancer, the potential benefits must be weighed against potential risks, and it’s important to look at side effects, potential risks, and situations when the diet should not be used (contraindications).
When people begin the ketogenic diet, it’s common to experience symptoms that have been coined the “keto flu.” This can include fatigue, nausea, vomiting, a lower exercise tolerance, constipation, and other digestive system side effects.
These side effects as well as the metabolic effects of the ketogenic diet can pose some risks, including:
People should also be aware that the ketogenic diet can cause a false positive alcohol breath test.
Long term side effects may include low protein levels in the blood (hypoproteinemia), hepatic steatosis, and vitamin and mineral deficiencies. Since the diet is challenging to maintain, and research is relatively new, all of the potential long term effects are unknown.
While few studies have been done, there are several potential risks to be considered among people with cancer before using the diet.
Dietary Components and Potential Deficiencies
Due to the rigor and requirements of the ketogenic diet, it could be challenging to get all of the important nutrients needed in a healthy diet. In addition, the increase in fat could potentially be problematic. For example, a low-fat diet has been linked to a lower risk of recurrence with some types of breast cancer. On the other hand, the ketogenic diet may help some people lose weight. Obesity is associated with an increased risk of breast cancer recurrence.
When you are coping with cancer, or if you have a hereditary disorder of fat metabolism, it’s also important to note that your body may not function like that of someone who does not have cancer. Just as cancer cells may be unable metabolize proteins and fats, your healthy cells may have problems as well.
A significant concern is that of restricting foods such as fruits. There are many studies that have found a lower risk of cancer in people who eat a greater number of fruits and vegetables.
Since dairy products are restricted on some ketogenic diets, a lack of vitamin D has been raised as a concern. That said, due to the association of low vitamin D levels with poorer outcomes with some cancers, everyone with cancer should have a blood test to determine their vitamin D level, and talk to their oncologist if the level is low (or within the low end of the normal range)
Since the ketogenic diet restricts fruits and legumes, it may also reduce fiber intake. Fiber can be thought of as a “prebiotic” or a food that feeds your gut bacteria (microbiome). For people with cancer treated with immunotherapy, a diverse gut microbiome is associated with greater effectiveness. Though probiotics did not appear to help, a high fiber diet did. Fiber also helps maintain bowel function. Current USDA guidelines recommend an intake of 23 to 33 grams of fiber daily.
The fatigue associated with cancer (cancer fatigue) could be compounded by the ketogenic diet early on, and many people considered this fatigue to be one of the more annoying side effects of cancer treatment.
While praised as a method to lose weight, weight loss may be detrimental to someone living with cancer. Cancer cachexia, a syndrome comprised of unintentional weight loss and muscle wasting, is thought to be the direct cause of 20% of cancer deaths.
The ketogenic diet should be avoided by women who are pregnant, wish to become pregnant, or are breastfeeding. It should also be used with caution in people with diabetes, and only under the careful observation of a physician. There are several medical conditions for which the ketogenic should absolutely not be used (is contraindicated). Some of these include:
- Liver failure
- Certain hereditary syndromes such as primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency, pyruvate kinase deficiency, porphyrias, and other disorders of fat metabolism.
We know that what we eat is important. Just as higher octane gasoline may lead to better functioning cars, our bodies function most efficiently when we give them the right fuel. When it comes down to dietary specifics, however, the research is in its infancy. While a diet high in fruits and vegetables and low in processed meats has been associated with a lower risk of many cancers, less is known about how specific elements of our diets affect a cancer already present. Fortunately, there are currently many clinical trials in place designed to answer these questions and some answers are being found. For example, intermittent fasting (prolonged nighttime fasting) has been linked to a lower risk of breast cancer recurrence.
While there are potential mechanisms by which adopting a ketogenic diet may play a role in cancer prevention or treatment, how those theories play out in people living with the disease are uncertain. If you are asking about the role of the ketogenic diet and cancer you are in a good place. Though that’s a discussion you will need to have with your oncologist, raising the question is a sign that you are being your own advocate in your cancer care; something that can help give you back at least some control of your life, and has even been associated with better outcomes in some cases.