What does the science say about the clinical use of ketogenic diets for epilepsy and cancer?
Blood sugar, also known as blood glucose, is the universal go-to fuel for the cells throughout our bodies. Our brain burns through a quarter pound of sugar a day because “glucose is the preferred metabolic fuel.” We can break down proteins and make glucose from scratch, but most comes from our diet in the form of sugars and starches. If we stop eating carbohydrates (or stop eating altogether), most of our cells switch over to burning fat. Fat has difficulty getting through the blood-brain barrier, though, and our brain has a constant, massive need for fuel. Just that one organ accounts for up to half of our energy needs. Without it, the lights go out…permanently.
To make that much sugar from scratch, our body would need to break down about half a pound of protein a day. That means we’d cannibalize ourselves to death within two weeks, but people can fast for months. What’s going on? The answer to the puzzle was discovered in 1967. Harvard researchers famously stuck catheters into the brains of obese subjects who had been fasting for more than a month and discovered that ketones had replaced glucose as the preferred fuel for the brain. Our liver can turn fat into ketones, which can then breach the blood-brain barrier and sustain our brain if we aren’t getting enough carbohydrates. Switching fuels has such an effect on brain activity that it has been used to treat epilepsy since antiquity.
In fact, the prescription of fasting for the treatment of epileptic seizures dates back to Hippocrates. In the Bible, even Jesus seems to have concurred. To this day, it’s unclear why switching from blood sugar to ketones as a primary fuel source has such a dampening effect on brain overactivity. How long can one fast? To prolong the fasting therapy, in 1921, a distinguished physician scientist at the Mayo Clinic suggested trying what he called “ketogenic diets,” high-fat diets designed to be so deficient in carbohydrates that they could effectively mimic the fasting state. “Remarkable improvement” was noted the first time it was put to the test, efficacy that was later confirmed in randomized, controlled trials. Ketogenic diets started to fall out of favor in 1938 with the discovery of the anti-seizure drug that would become known as Dilantin, but they’re still being used today as a third- or fourth-line treatment for drug-refractory epilepsy in children.
Oddly, the success of ketogenic diets against pediatric epilepsy seems to get conflated by “keto diet” proponents into suggesting a ketogenic diet is beneficial for everyone. Know what else sometimes works for intractable epilepsy? Brain surgery, but I don’t hear people clamoring to get their skulls sawed open. Since when do medical therapies translate into healthy lifestyle choices? Scrambling brain activity with electroshock therapy can be helpful in some cases of major depression, so should we get out the electrodes? Ketogenic diets are also being tested to see if they can slow the growth of certain brain tumors. Even if they work, you know what else can help slow cancer growth? Chemotherapy. So why go keto when you can just go chemo?
Promoters of ketogenic diets for cancer are paid by so-called ketone technology companies that offer to send you salted caramel bone broth powder for a hundred bucks a pound or companies that market ketogenic meals and report “extraordinary” anecdotal responses in some cancer patients. But more concrete evidence is simply lacking, and even the theoretical underpinnings may be questionable. A common refrain is that “cancer feeds on sugar.” But all cells feed on sugar. Advocating ketogenic diets for cancer is like saying Hitler breathed air so we should boycott oxygen.
Cancer can feed on ketones, too. Ketones have been found to fuel human breast cancer growth and drive metastases in an experimental model, more than doubling tumor growth. Some have even speculated that this may be why breast cancer often metastasizes to the liver, the main site of ketone production. As you can see below and at 4:59 in my video Is Keto an Effective Cancer-Fighting Diet?, if you drip ketones directly onto breast cancer cells in a petri dish, the genes that get turned on and off make for much more aggressive cancer, associated with significantly lower five-year survival in breast cancer patients, as you can see in the following graph and at 5:05 in my video. Researchers are even considering designing ketone-blocking drugs to prevent further cancer growth by halting ketone production.
Let’s also think about what eating a ketogenic diet might entail. High animal fat intake may increase the mortality risk among breast cancer survivors and potentially play a role in the development of breast cancer in the first place through oxidative stress, hormone disruption, or inflammation. This applies to men, too. “A strong association” has been found “between saturated fat intake and prostate cancer progression and survival.” Those in the top third of consumption of these kinds of fat-rich animal foods appeared to triple their risk of dying from prostate cancer. This isn’t necessarily fat in general either. No difference has been found in breast cancer death rates based on total fat intake. However saturated fat intake specifically may negatively impact breast cancer survival, increasing the risk of dying from it by 50 percent. There’s a reason the official American Cancer Society and American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline recommend a dietary pattern for breast cancer patients that’s essentially the opposite of a ketogenic diet. It calls for a diet that’s “high in vegetables, fruits, whole grains, and legumes [beans, split peas, chickpeas, and lentils]; low in saturated fats; and limited in alcohol consumption.”
“To date, not a single clinical study has shown a measurable benefit from a ketogenic diet in any human cancer.” There are currently at least a dozen trials underway, however, and the hope is that at least some cancer types will respond. Still, even then, that wouldn’t serve as a basis for recommending ketogenic diets for the general population any more than recommending everyone get radiation, surgery, and chemo just for kicks.
“Keto” has been the most-searched keyword on NutritionFacts.org for months, and I didn’t have much specific to offer…until now. Check out my other videos on the topic in related videos below.
For an overview of my cancer work, watch How Not to Die from Cancer.
Michael Greger M.D. FACLM
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