Can a keto diet help treat brain cancer?

Back when news broke in July of 2017 that US Senator John McCain had been diagnosed with an aggressive form of brain cancer, neuro-oncology researcher Dr. Adrienne C. Scheck, PhD, tried to get a message to the McCain family in Arizona. She posted on his daughter’s group Facebook page and linked to research she has conducted in her role as an associate professor of neurobiology at Barrow Neurological Institute in Phoenix, Arizona, where McCain lived.

Scheck’s message to McCain back then: Try the ketogenic diet along with the standard therapy of surgery, radiation and chemotherapy. Alas, neither Senator McCain, who died in August 2018, nor his family ever responded to her message.

Over the last decade, Scheck has been studying the effect of altering cancer cell metabolism, specifically with the ketogenic diet, to improve survival and minimize side effects for patients with malignant brain tumours. Senator McCain was diagnosed in 2017 with glioblastoma multiforme (GBM), a notoriously deadly cancer that arises in the glia, the connective tissue of the brain. GBM has a grave prognosis, with an average survival time of 18 months from diagnosis. This prognosis was even shorter for McCain, who died 12 months after his tumor was first found, despite a nine-hour surgery to remove the large tumor above his left eye, followed by radiation and chemotherapy.¹

The connection between keto and cancer

Says Scheck (pictured to the right): “Based on our research, I definitely think someone with a GBM should go on a therapeutic ketogenic diet as soon as possible, in addition to standard therapy. Our pre-clinical research suggests that it potentiates both radiation and chemotherapy, and can enhance the anti-tumour immune response. Even ketones alone can have this effect in cell culture. There is nothing to lose by trying it.”²

Scheck never heard from the McCain family; she feels that was likely because they were being inundated with all forms of advice and because many people — including physicians — wrongly lump the ketogenic diet in with “fad” diets that have no scientific basis. Scheck stresses the ketogenic diet for GBM is no fad. “This is not a ‘diet’ in the typical sense of the word. It is a regimented metabolic therapy with quite a bit of peer-reviewed science behind it,” she says.

There are currently a handful of ongoing clinical trials registered at clinicaltrials.gov — led by research teams around the world — studying the role of a ketogenic diet in the treatment of glioblastoma.

Although most of the data is preclinical with few clinical trials, one systematic review attempted to synthesize all the evidence to date, finding that the preclinical studies are encouraging, but clinical trials have not yet been able to clearly demonstrate a meaningful survival benefit.³

Taking into account other types of cancer — including lung, breast, pancreatic, prostate and melanoma — numerous clinical trials are currently registered at clinicaltrials.gov, investigating the ketogenic diet as an adjunct to standard cancer therapy. Over the last decade, research investigating the ketogenic’s diet role in basic cancer research and in emerging therapies has burgeoned, with more than 400 studies or theoretical papers currently in the research literature. The number is increasing each month.

How carbs can fuel cancer

At the heart of the argument for using the ketogenic diet to help combat cancer is the fact that cancers need glucose — a great deal of it — to fuel their rapid growth.⁴ In fact, it explains how a PET scan is used to diagnose cancer: an injection of radioactive sugar lights up the malignant cancer cells because they use glucose at a much higher rate than normal cells.⁵ Glutamine, an amino acid released during the breakdown of proteins, can also fuel cancer growth.⁶

Starving cancer cells of the glucose and glutamine they need to grow, and instead using ketones as fuel for our cells is the conceptual theory behind the ketogenic diet as an adjunct to cancer treatment. “Normal cells have the flexibility to switch to ketones for energy; cancer cells do not,” explains Dr. Thomas Seyfried, PhD, who is a professor of biology at Boston College (pictured to the right).

Seyfried is the author of the influential 2012 book Cancer as a Metabolic Disease. In that book, as well as in recent research papers, he sets out evidence that cancer is a disturbance of cellular energy metabolism, particularly linked to abnormalities in the structure and function of the mitochondria.⁷

In a 2015 paper, Seyfried and his colleagues specifically promote using a calorie restricted ketogenic diet as a treatment for glioblastoma.⁸ “The goal is to restrict GBM cells of glucose, their main energy substrate,” says Seyfried. This chronic starvation of the fuel they need to grow stresses and weakens the cancer cells and — if not killing them outright — makes them much more vulnerable to treatments such as radiation, chemotherapy or hyperbaric oxygen. “It is like a one-two punch, stressing them with starvation, then hitting them while they are down,” said Seyfried.

This one-two punch concept — which Seyfried and his colleagues call “Press-Pulse” theory, was detailed in a 2017 scientific paper.⁹ The conceptual framework is to stress the cancer by starving it of glucose and suppressing insulin signaling (the press), then making a sudden strike with hyperbaric oxygen, metabolic-targeted drugs or milder doses of chemotherapeutic drugs and radiation (the pulse.)

Professor D’Agostino’s lab

“Denying cancer cells glucose is like taking the foot off the gas pedal,” explains co-author Dominic D’Agostino, an associate professor of molecular pharmacology and physiology at the University of South Florida and a research scientist at the Institute for Human and Machine Cognition. D’Agostino’s extensive research on the ketogenic diet has also been featured in several Diet Doctor videos (see right and below).

D’Agostino’s research has been focused on nutritional neuroscience — how the brain changes in response to dietary influences. He started by studying the ability of the ketogenic diet and ketone supplementation to help prevent seizures associated with central nervous system oxygen toxicity, a limitation for US Navy SEAL divers who use circuit rebreathers.

Now his lab, specifically with research associate Dr. Angela Poff, is investigating the role of nutritional ketosis as an adjuvant in cancer therapy. Dr. Poff’s video about exploiting cancer metabolism using ketosis is a popular video on the Diet Doctor site.

D’Agostino says their hypothesis is that glucose, insulin, and inflammation are all closely linked to cancer growth and to cancer treatment and prevention; they are tightly associated with the metabolic health of cells. He feels a ketogenic diet with targeted intermittent fasting, with guidance from an experienced clinician, could prove effective as an add-on to conventional cancer therapy.

D’Agostino stresses that research on the ketogenic diet and cancer is still in its infancy. “We need more clinical data about how best to apply these concepts to the patient with GBM,” he cautions. “However, it is very reasonable for someone with a diagnosis of GBM — with an average 12-18 months to live — to implement a ketogenic diet (with a qualified nutritionist) to their standard therapy.”¹⁰

Stories of controlling brain cancer with keto¹¹

Pablo Kelly, 28, from Devon, UK (pictured to the right), was diagnosed with GBM in 2014 and credits the ketogenic diet with saving his life. “My GBM was declared inoperable because of its location in my brain, in the parietal lobe, with a tendril going into my motor cortex,” said Kelly, who soon after the diagnosis began a restricted calorie ketogenic diet.

He credits his strict keto eating, as well as supplementing with exogenous ketones, MCT oil and anti-inflammatory supplements, with shrinking his tumour enough so that 90 % could be removed by an awake craniotomy in 2017. Follow-up MRI scans since then have shown the cancer has not grown, says Kelly, who connects with people through his open Facebook page, Pablos Journey Through a Brain Tumour, and through media stories, which have been shared by thousands. “When I was first diagnosed I had to search really hard to find people who were doing ketogenic for GBM,” says Kelly, who these days is regularly contacted by people around the world hoping for more information about trying keto for their brain tumor. “I want to inspire as many people as possible.”

Canadian teenager Adam Sorenson’s (pictured to the right together with his father Brad)¹² journey with GBM and the ketogenic diet is another inspiring anecdotal story. He was diagnosed with Stage IV GBM in September 2013, the day after his 13th birthday. The tumor was the size of a baseball and carried a dismal prognosis.¹³

Doctors performed surgery to remove as much as possible, but his father, Brad, did extensive research to try to improve his son’s odds for survival. “The overriding rules I set was that it had to be safe, it had to have at least some clinical trial data published, and it had to be accessible.” Adam’s parents also consulted with Dr. Jong Rho, an expert in the ketogenic diet for epilepsy, and a former mentor of Dr. Scheck at the Barrow Neurological Institute; Dr. Rho had been recruited to the Alberta Children’s Hospital to the Hotchkiss Brain Institute at the University of Calgary.¹⁴ The Sorensons also consulted with Drs. Seyfried, D’Agostino and Scheck.

They came up with a protocol that included a ketogenic diet consisting of 80% fat, 15% protein and 5% carbohydrates combined with radiation treatment, hyperbaric oxygen, and the drug metformin. Four months after starting the treatment, in February 2014, Adam had an MRI scan that showed no visible tumor. Subsequent MRIs have remained clear of cancer. Adam has remained on the ketogenic diet and metformin ever since. “It is basically really low carbs with lots of whipping cream, eggs, pork, nuts and seeds,” says his dad.

In a compelling video, Adam says the diet is not always easy as a teenager, especially when out with friends. “When I realized I was not going to be able to eat some of my favourite foods like pizza and candy, I was a little sad. But I thought, it’s going to help me live.”

Adam was a keynote speaker in November 2016 at the Global Symposium on Ketogenic Therapies in Banff, Alberta and sponsored by the Charlie Foundation for Ketogenic Therapies. The foundation began as an organization focused on the ketogenic diet for epilepsy control, but has now branched into its use in brain cancer, autism and other disorders.

When asked what he would say to families dealing with GBM, Brad Sorenson said, “I am really hesitant to act in the role of a doctor. I am concerned that I could add to a stressful situation. I don’t want to give them false hope.”

Sorenson, who is the CEO and founder of two biotechnology companies, felt that starting the keto diet before radiation and avoiding steroids, which are almost uniformly given to brain cancer patients, were keys to Adam’s therapy. “Adam’s protocol invites a lot of pushback from doctors.” So Sorenson simply tells people what they did for Adam, shares a slide deck with their protocol and its rationale with references, and encourages them to find a qualified dietitian.

“I do not believe the diet alone is a game changer, but I do believe it helps improve the potency and efficacy of other cancer treatments,” says Brad. “I am very aware that Adam’s story is anecdotal. But I am totally confident that if we had gone with the standard of care, Adam would not be alive today.”

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Anne Mullens

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