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A ketogenic diet is a high-fat, low-carbohydrate diet that has some specific neurological effects. In today’s podcast, Annette Goldberg talks with Dr. Roy Strowd about this diet, its history, and its potential benefits in people with certain types of brain tumors. Dr. Strowd is an Assistant Professor of Neurology and Oncology, and a neurologist and neuro-oncologist at the Wake Forest Baptist Medical Center. Annette Goldberg is an Outpatient Dietitian at the Boston Medical Center Cancer Care Center.

ASCO would like to thank Dr. Strowd and Ms. Goldberg for discussing this topic.

Annette Goldberg: Hi everybody. My name is Annette Goldberg. I'm a registered dietitian working at Boston Medical Center's Cancer Care Center. BMC is a 500-bed medical center located in Boston's south end, and we are the largest safety net hospital in the area. Therefore the patient population is quite diverse, and inspiring. And please let me introduce Dr. Roy Strowd.

Dr. Strowd: Thanks Annette. I'm delighted to be here with you. I am an academic neuro-oncologist, a brain tumor doctor. I work at the Comprehensive Cancer Center at Wake Forest University in Winston-Salem, North Carolina. And I'm a clinical and translational researcher. So I spend most of my days in the clinic seeing and treating brain tumor patients, and I do translational research. We look to take new drugs into the clinic, understand how they work, how to assess their response, and walk patients through some of the side effects that may occur during or after treatment.

One of my areas of interest is in cancer metabolism: how cancers grow, how they hijack the energy in the body, and around the cancer to live in the hostile environment of the tumor micro-environment of where cancers live. And we'd love to have a lot of drugs that target metabolism and target cancers and cancer metabolism. We don't. But 1 of the therapies that we have and have had for a long time are ketogenic diets. So 1 of the trials that I'm running is a ketogenic diet as a maintenance therapy for patients with brain tumors. And so I'm delighted to be here and talk with you more about this.

Annette Goldberg: That sounds very exciting. Allow me to jump right into some questions. Dr. Strowd, tell us a little bit about what is the ketogenic diet, and please explain how this diet originated.

Dr. Strowd: Yeah. So the ketogenic diet is a high fat, low carbohydrate, and typically a protein-restricted diet. It simulates a fasting state. So the food that you and your audience will know that we all eat is composed of 3, what are called, macronutrients: carbohydrates, proteins, and fats. And pretty much everything we eat is composed of a carbohydrate, a protein or a fat. The carbohydrates are breads, the sweets, the pastas, and even some of the fruits and vegetables that we eat. Protein is found a lot of the meats and the dairy products, and high-fat foods is all the good stuff. The bacon, the eggs, peanut butter, heavy creams, avocado oils, coconut milk, and those sorts of things.

The average American diet is about 50 to 75% of carbohydrates. That's what we eat and that's the energy currency that our body normally uses to live, work, and play, and do the things we need to do. In a ketogenic diet—these are high-fat diets—so about 90% of what a patient takes in is fat. There is very little protein and almost no carbohydrates. And this changes what the body uses for energy. And instead of carbohydrates as the energy currency in the body, the body uses what are called ketone bodies to run.

So when I'm talking to my patients, I tell them it's kind of like using a credit card instead of cash. You walk up to the register. It may take a few extra steps. You stick the card in. You have to hit a few buttons, and sign a receipt, but at the end of the day you can still make just about any purchase you need, buy the shirt, get your laundry, those sorts of things. And the same is true for the body. The body can use ketone bodies to run just like it were using carbohydrates, sugars, or other energy sources, but that may not be true of cancers. And certain cancers, specifically brain tumors or brain cancers, may have a harder time using these ketone bodies. And so that's something we're excited to explore and to exploit to treat certain types of cancers and specifically brain cancers.

In terms of history, this is a great question and ketogenic diets have really been around for eons. There's descriptions of these diets being used even back into antiquity, and for many, many years before then. In modern medicine we see that ketogenic diets have really been described in clinical trials in clinical application for over about the last 100 years or so. In the last 20-30 years, there's been a lot of interest, a lot written, a lot described, and a lot of studies looking at applying ketogenic diets to various medical conditions. And I'm a neurologist by training, a neurology-based neuro-oncologists, and neurologists are very familiar with these ketogenic diets. They've been used again for over 100 years to treat again children with medically refractory epilepsy. That's seizures that aren't responding to medications.

We know that in these children when placed on a ketogenic diet, these diets can be as effective as a medication, as a seizure drug in treating a child's seizures. Children have been managed on these ketogenic diets for many years, and they've been evaluated in multiple studies, and it's proven to be effective, and are part of the standard armamentarium that our neurologists would use to treat the child with medically refractory epilepsy seen at an academic center.

They work for kids, for kids with epilepsy. The same's not necessarily true for adults, and for the past 10-20 years, we've looked at translating these diets into adults. And the strict ketogenic diet is highly restrictive. It's really hard for adults to do. There's going to be limitations in fluid intake. Some diets are initiated during an in-patient hospitalization which can be challenging for adults. And so for about the past years our field and the neurology field has looked at alternatives to the strict ketogenic diets for adults: something that's a little bit more tolerable, and can be implemented and maintained in adults, in the busy life of an adult, and still be effective.

One of these alternatives is the modified Atkins diet, and as the name implies, it's a clinically modified version of the more popularized Atkins based diets. And there are a number of other alternatives. And in adults with epilepsy, these alternative ketogenic diets have been proven to be effective in treating seizures. So there's really been a long history of dietary therapies in medicine and primarily in neurology for managing children, and now adults with seizures. There's a lot of interest in other applications, and specifically in cancer, and in brain cancer, and in looking at applying these diets to this new indication.

Annette Goldberg: Okay. I know that the brain prefers as its fuel, carbohydrates, and so how does the brain function on the ketones? And is there any difficulty there?

Dr. Strowd: That's a really good question. And so the vast majority of trials and studies in interests in looking at ketogenic diets for cancer are looking at the application of this diet for brain cancer. The brain's a little bit different from other organs in the body. In fact, when the body is in a state of fasting, the body will shunt sugar up to the brain to live in contrast to other organs. And so the brain is really uniquely positioned in the body to potentially respond to ketogenic diets, and respond to diets that simulate this fasting state that use ketone bodies to run.

So if you think about it, these diets have really been around for a very long time, and there's a good reason that they've been primarily been used in the treatment of brain disorders, things like epilepsy, and interest in migraine, and autism, and brain cancer, and it's due to this unique property of the brain, this potential reliance on sugar, and the inability to process these ketone bodies, to use ketone bodies to run. Unfortunately, we don't yet know all of the details about how the diets work mechanistically. What they actually do to change the brain or to change other cells in the body. But there's a lot of data and the vast majority of data supports applying these diets to brain tumors. That's not the case for other types of cancers: prostate cancer, lung cancer, colon or breast cancer. The clinical trials that we see in oncology today are really focused on applying the diets to brain cancer and we're not ready for prime time even there. I don't think we are certainly ready for prime time in other types of cancers.

Annette Goldberg: Well, that's very helpful because I have definitely encountered patients with other cancer diagnoses in the clinic, and they've asked about following the ketogenic diet. I think patients need this information on the internet, and hear about it other places, and they want to follow it to hopefully make progress with their own cancer diagnosis. And I've discouraged them from trying to follow the ketogenic diet for prostate cancer or their breast cancer.

So what is the status of some of the clinical trials might be evaluating the ketogenic diet specifically for brain cancer?

Dr. Strowd: This is a really good question. I think we see this a lot as well. There's a lot written about this. There's a lot on the internet. There's a lot of excitement about these diets. And I think you're right. It's important to know where they stand. And most of the application, most of the trials are looking at these diets in brain cancer.

I'm a clinical trialist so most of what I do during the day is clinical trials, and developing new treatments, and I look at the diet the same way we would look at a new drug. And your audience may be familiar with how we typically develop a new drug for cancer. And we've got a number of jobs, and I think about them, and our field thinks about them in 3 steps. So as your audience likely knows, the first thing we do is we have to figure out what the dose of the drug is. What dose is needed to give to patients, and that's what's done in a phase I study. The second thing we have to do is, once we know the dose, we have to figure out if that dose is safe. And with the safe dose if there's some signal that the drug may work, and that's what's typically done in a phase II study. And then finally when we know that the drug is safe, and that there is some signal of activity, a phase III trial proves that it works. That it fights cancer, it kills the tumor or it's better than what we currently use, and that it works to treat cancer.

So when we think about these diets, there's a lot written about them, there's a lot of excitement about them. But they’re therapies, they’re treatments just like the drugs we're developing, and we think about developing these diets in the same way. The first thing we have to do is figure what's the right dose, and then we have to know whether it's safe, whether there's some signal that it will work in the brain tumor or in the cancer type, and then determine if it works.

And I honestly think these steps are really, really important for something like the ketogenic diet. For something that is widely circulated on the internet, and there's a lot of the interest in this. This is very different from some of the fad diets that you see out there. It's very different from some of the other weight loss diets that you see out there. This is a medical therapy, and we've got to know whether it's safe. We've got to know whether there's a sign that it works, and then we've got to know whether it actually treats the tumor. And that's really where the current trials are. So currently there are about 10 ongoing trials in the United States and elsewhere in the world that are looking at ketogenic diets, and the treatment of various brain tumors.

There is a number of trials that are also looking at ketogenic diets and other neurologic conditions; migraine, autism, cognitive dysfunction, and epilepsy. But in cancer, the interest is primarily in brain tumors. Right now, most of the trials are looking at this phase II question. We have an idea of what the dose is, and the trials are using a variety of doses, and we need to know whether it's safe. And we need to know whether there's a sign that it works, and if so, those trials could move forward to a phase III study to determining that this treatment works, and is ready for prime time. But we're really not there yet.

And I think this is really important. It's important for listeners and audience to hear and understand. We know that these diets are safe. They've been used in epilepsy patients for a long time. Seizure patients can continue on these diets for years: 5, 10, 20 years. But our cancer patients are a lot different, and different in many ways from seizure patients. Some have other medical conditions that we would worry about. Most have been treated with chemotherapy and may need further chemotherapy, and whether these diets are safe in those patients is very unclear.

In the trial that we're doing here—looking at a ketogenic-based diet for brain tumor patients—we've actually seen some changes in our patients' white blood cell counts and other circulating electrolytes and other sorts of things. And we don't know whether these diets are safe in those patients, and certainly we wouldn't want to implement the diet that could prevent a patient from getting future chemotherapy should they need it or those sorts of things.

So I think in summary, this is something that we're really excited about. And I'm not a dietitian, but got into this because this is something that our patients come into the clinic asking about, and wanting to know about. And right now, there's a lot of interest, and excitement in clinical medicine, and in clinical research. We're still at the point of making sure that these are safe. We're still at the point of understanding whether there is a sign of activity. And I think for patients who are interested, it's something to talk with your doctor about, and potentially meet with a dietitian about. And I think the best thing is to look for a trial, and there are a number of these trials, again, 10 trials out there that are currently evaluating this in brain tumors.

Annette Goldberg: Dr. Strowd, I think that was a very helpful explanation. It's great to equate the diet, and the importance of researching the diet the same way that you do with the drugs. And it shows the importance of making sure that we evaluate the diet step-by-step because it can be as helpful or as harmful, potentially, as a drug can be. For patients and caregivers that have additional questions or want to find some more information that's reliable information, could you suggest a few resources?

Dr. Strowd: God, that's a tough question. There is a ton of information out there. And when I see patients from the clinic asking these similar sort of questions, it's even hard for us to sort through some of that. There is a long history, as I mentioned, of these diets in epilepsy, so I actually think some of the better resources and some really great resources to just understand a little bit more about what these diets are, and what the patient experience is like can be found within epilepsy sites. There's the Charlie Foundation, and the Epilepsy Foundation, which have really good sections on the ketogenic diet.

If it's something that a patient is interested in, I think talking with your oncologist is always important. Again, I equate this to a therapy. And if you're interested in a new drug, or a new device, or a new surgery to treat a cancer, it's something you'd talk with your cancer doctor about. And I think that's a good idea. Dietitians are always a part of the discussion, at least here, when we discuss this with patients. And I really think this is something where—as with a new treatment and a new drug, patients will seek out clinical trials. That's the same thing. ClinicalTrials.gov and other resources to look for trials that are out there that patients may be a candidate for—always a good idea.

Annette Goldberg: Dr. Strowd, thank you so much for your time. Your explanation was very insightful, and I think will be very helpful for the audience. And again, thank you for dedicating your career to helping cancer patients.

Dr. Strowd: Absolutely. Thanks so much for giving me an opportunity to talk with you.

ASCO: Thank you, Dr. Strowd and Ms. Goldberg. For more expert interviews and stories from people living with cancer, visit the Cancer.Net Blog at www.cancer.net/blog.

Cancer.Net is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high-quality cancer care. Thank you for listening to this Cancer.Net Podcast.