UC experts research going keto to fight cancer

Scientists are studying whether an Atkins-type ketogenic diet could help make treatments for glioblastoma more effective

Every living thing needs food, but to Rekha Chaudhary, MD, food is life. Literally.

The adjunct associate professor at the UC College of Medicine and UC Health oncologist, who specializes in treating brain cancers, has spent much of her career trying to prove that we are what we eat, and that if we eat the proper things, we can prevent or even reverse the detrimental and often deadly effects of cancer.

“Personally, I’m plant-based with whole foods, which basically means that I am a vegan who eats non-processed foods,” she says. “Studies have shown a plant-based diet could prevent the onset of a number of cancers; however, I wouldn’t recommend this type of diet to someone who has already been diagnosed with a cancer like glioblastoma who, for instance, is undergoing radiation treatment for that cancer.”

This is where Chaudhary’s latest research endeavor comes in as she and co-investigator Tammy Ward, clinical dietitian and specialist in oncology nutrition at UC Health, begin studying whether or not a modified Atkins-type ketogenic diet could help make treatments for a common, but dangerous, type of brain cancer called glioblastoma more effective.

This unique clinical trial, only being offered at UC, will allow Chaudhary and Ward to follow patients with glioblastoma to see if a ketogenic diet coupled with standard treatment (chemotherapy and radiation) improves outcomes and quality of life.

This sort of research is exemplary of the innovation agenda highlighted in UC's Next Lives Here strategic direction. 

Video link: https://www.youtube.com/embed/UpCRrysea1E?rel=0

“Gliomas are among the most invasive and lethal tumors, and there aren’t a lot of effective treatments,” Chaudhary says. “Glioblastoma multiforme, commonly called GBM, is the most aggressive primary brain tumor — five-year survival rates for this type of cancer are dismal. To date, the standard of care is chemotherapy and radiation therapy which increases the two-year survival rates by around 10%. But still, just 3% of patients are surviving at the five-year mark.

“We know that cancerous glioma cells rely on glucose, or sugar, for their division and survival. The ketogenic diet is low in sugar and because of that, the body produces ketones for energy. Normal glial or brain cells can survive on ketones alone, but it is thought that cancerous glioma cells cannot use ketones for energy.”

Ketones are chemicals made in the liver, and a person produces them when they don’t have enough insulin to turn sugar into energy. Since the body needs another source, it uses fat instead, and the liver turns this fat into ketones, a type of acid, and sends them into the bloodstream.

Chaudhary says a ketone metabolism has been used to control childhood epilepsy for many years but not much is known about what ketones do in the brain — only that they seem to help brain disorders. It’s also among the newest weight loss methods showing up on the news and internet in the last decade. 

Doing the homework

Ward says she tried the diet for the first time in 2015, after patients at the UC Health Barrett Cancer Center began asking about it.

“I realized I needed to educate myself and the staff about the diet because patients were starting to ask about it,” she says. She and Chaudhary hosted a ketogenic symposium for staff which was led by Beth Zupec-Kania, a consulting ketogenic diet therapies dietitian for The Charlie Foundation; the primary focus was on implementation of ketogenic diet therapies.

“The version of ketogenic diet we’re using for our adult cancer patients is called the modified Atkins diet, which is very similar to Phase I of Atkins, a low carbohydrate diet,” she says, adding that most patients are recommended to eat 20 net carbs or less a day on this particular phase of the diet.

She tried it herself, the first time for six weeks, and says it was phenomenal learning experience. 

Tammy Ward speaks to a patient

In order to see what her patients might experience, registered dietitian Tammy Ward decided to try the keto diet for the first time in 2015. She still remains on a form of it to this day. Photo credit: Colleen Kelley / UC Creative Services

“I missed my carbs, but I learned a lot about substitutions and about changing habits, including the fact that I needed to meal prep more on this diet,” she says, adding that since then, she’s maintained a non-ketogenic but lower-carb lifestyle. “Most importantly, as a care provider, I learned some of the hurdles our patients would encounter so that I could advise them on ways to further modify their diets to meet their nutritional needs.

“This particular diet is not about losing weight; it’s using food to help with treatment — a much different goal; often we want patients to gain or maintain weight. This diet can be a struggle with certain patients who have been taught over the years that fat is bad. We have to teach them about the benefits of good fat, and we also want to avoid concerns such as hypoglycemia, dehydration or lack of proper sodium levels during the first weeks of the diet, all while helping patients reach maximum therapeutic benefit.”

After putting together educational materials and going through the proper channels to approve them for use, Chaudhary, Ward and the rest of the team began overseeing patients who requested the diet. It was an 11-week regimen, beginning before the first radiation treatment and continuing until the first after-treatment MRI scan. Ward says the diet is completely safe for patients, when done correctly, which is why she so closely monitors the process.

 Chaudhary is hoping it will be a game changer.  

I believe in in the power of medicine, and I believe in the power of food as medicine. Combining the two is an exciting step because anything we can do to improve the lives of a group of patients with minimal options is a step in the right direction.

Rekha Chaudhary, MD

A new promise

“Results for a modified keto diet in animal models were really hopeful,” she says. “Researchers in previous studies implanted animal model brains with cancerous glioma cells to study the effect of ketosis on their survival and to monitor what happened to the glioma cells; the models had a modest increase in survival with ketogenic diet as compared to controls not on the ketogenic diet. However, when radiation was added to the treatment of ketogenic diet there was a significant increase in survival, so much so that 9 out of the 11 animal models were cured of their tumors.”

“This is why we think that ketones may act as a radiation sensitizing agent, and this would explain the significantly increased survival in the animal models on the ketogenic diet with radiation as compared to the models on the ketogenic diet alone,” Chaudhary adds. “Initially, this was thought to work because of the low sugar state; however, other animal model studies have shown that not only do the brain tumors implanted in animals take up the ketones, but also they use them for energy. This led us to the hypothesis that perhaps the ketones are being taken up in the tumors and are making the tumors more sensitive to radiation. There is limited data in humans with ketogenic diets and cancer but because of the preliminary data in animal models and retrospective data in humans with glioblastoma, trials are beginning to pop up.

“Now, we’re adding radiation to the mix to see if outcomes can improve even more.”

Cody Woodhouse in front of a scientific poster

Cody Woodhouse, third-year medical student at the UC College of Medicine, presented results from a UC retrospective study via poster at the 2019 American Association of Clinical Oncology Annual Meeting in early June. The paper has been accepted for publication in an upcoming journal issue of Current Oncology. Photo provided by Woodhouse.

Cody Woodhouse, third-year medical student at the UC College of Medicine, presented results from a UC retrospective study via poster at the 2019 American Association of Clinical Oncology Annual Meeting in early June. The paper has been accepted for publication in an upcoming journal issue of Current Oncology. 

“In 2017, as part of my studies, I had to shadow a registered dietician who recommended a ketogenic diet for epilepsy, which really interested me,” he says. “I was always interested in oncology and nutrition so it was recommended that I team up with Dr. Chaudhary because of her expertise of food-based medicine practices in oncology.”

As Woodhouse continued working with Chaudhary and Ward, the idea formed to put together a retrospective study based on Dr. Chaudhary’s experience with patients being treated for glioblastoma while on the ketogenic diet. Woodhouse began pulling information from patient charts, starting in 2015 when Ward began advising patients on this diet.

“We combed through patient charts to look at MRI results as well as β-hydroxybutyrate (BHB) levels, a predominant ketone, and reviewed their outcomes,” he says. “There were 30 patients included in the study and all of them achieved ketosis which is the goal of the diet. Only one couldn't complete the diet throughout the entirety of treatment because it was too restricting which indicates the diet is feasible to maintain through treatment.”

The results were promising.

“It is too early to assess survival,” says Dr. Chaudhary.  “However, we did see a significant increase in the amount of pseudoprogression on the MRI. Pseudoprogression is a sign of radiation sensitization, meaning the tumors may have become more sensitive to the radiation because of the diet. There was an increase in radiation sensitization showing on MRI scans within patients on the ketogenic diet as compared to historical control populations. Pseudoprogression or radiation sensitization has been traditionally associated with increased survival.”

Rekha Chaudhary smiling in front of her computer

Rekha Chaudhary, MD, adjunct associate professor at the UC College of Medicine and UC Health oncologist. Photo credit: Colleen Kelley / UC Creative Services

What's next?

The latest trial will run in a similar fashion, with 30 patients being evaluated over 11 weeks. They’ll meet with Ward one to four weeks prior to their first radiation and chemotherapy treatments to be educated about the diet and what is needed for it. The diet will begin approximately seven days prior to treatment, and the patient will continue the study diet until the first post-radiation MRI, a time period of approximately 10 weeks.

“We will obtain blood to assess serum BHB, fasting insulin and glucose and other chemistries as well as body weight weekly, according to the standard of care, while on chemotherapy and radiation therapy,” Chaudhary says. “Participants will receive weekly phone calls from a registered dietician to address any questions or concerns regarding the diet, and a food diary will be used to assess adherence during the 10-week period. All info from food diaries will be entered into nutrient analysis software and will be used to identify potential problematic intake which may be preventing patients from achieving ketosis.

“We are also doing special MRI scans called MR spectroscopy to measure the amount of ketones in the brains of the patients. This will tell us if the ketones are really getting into the brains of these patients to help test our theory.” 

“Prevention is one thing, but this is using nutrition to try to enhance therapy in these patients,” Woodhouse says. “This patient group has some of the worst prognostic outcomes, and hopefully, this is something we may be able to use to give them some control over their situation and give them a better quality of life with minimal complications.”

Chaudhary agrees.

“I believe in in the power of medicine, and I believe in the power of food as medicine. Combining the two is an exciting step because anything we can do to improve the lives of a group of patients with minimal options is a step in the right direction,” she says. “We often think of diet as a prevention tool to thwart diseases, but here, we are using diet and modern medicine to treat one of the most devastating diseases of all.”

Featured photo: Colleen Kelley/UC Creative Services 

Get involved

To find out more about enrolling in the study, call 513-584-8195.