Tumor cells have more insulin receptors than healthy cells, so they preferentially metabolize glucose. When you cut off the glucose supply to tumor cells, they struggle to make the fuel they need to proliferate. The ketogenic diet sharply limits the glucose that reaches tumor cells (while providing other anticancer benefits), and animal studies (and one small but seminal human study) have shown promise in using the ketogenic diet as an adjunctive treatment for cancer. Author of the new book, Keto for Cancer, Miriam Kalamian, EdM, MS, CNS, talks with Dr. Fitzgerald about the how ketogenic eating for cancer differs from other keto and low-carb protocols and outlines specific steps for pacing a keto protocol for the specific needs of cancer patients.
In this podcast you’ll hear:
- Miriam’s family’s personal journey with the ketogenic diet
- Why the ketogenic diet isn’t just about glucose
- The importance of both meal composition and meal timing
- Why the conventional cancer community resists keto and other nutritional therapies
- The unique power of short fasts immediately before and after conventional treatment
- The dangers of losing weight too fast and specific steps to moderate rapid weight loss
- Why fasting isn’t always appropriate for patients
- An explanation of the glucose-ketone index
- The best home glucose-ketone testing options for patients
Miriam Kalamian, EdM, MS, CNS is a board-certified nutrition consultant, educator, and author specializing in the implementation of ketogenic therapies. Inspired by the work of Thomas N. Seyfried, PhD (podcasted with DrS 08-2016- check it out), Miriam is a leading voice in the keto movement and draws on a decade of experience to provide comprehensive guidelines that specifically address the many diet and lifestyle challenges associated with a cancer diagnosis. Her passion for helping others implement this diet comes directly from her personal experience with her son Raffi who was diagnosed with a brain tumor in December 2004. Beyond cancer, Miriam integrates nutritional strategies with metabolic therapies and lifestyle modifications to develop personalized treatments that address a broad spectrum of conditions currently considered intractable, including age-related, neurodegenerative, and bariatric diseases. She is the author of the new and very comprehensive book Keto for Cancer (Chelsea Green Publishing October 2017)
Recommended links:
- https://www.amazon.com/Keto-Cancer-Ketogenic-Metabolic-Nutritional/dp/1603587012
- https://www.ncbi.nlm.nih.gov/pubmed/7790697
- http://www.pnas.org/content/111/47/16647.full
- https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-015-0009-2
- https://www.charliefoundation.org/
- https://keto-mojo.com/
- https://www.drkarafitzgerald.com/2016/08/02/episode-16-cancer-mitochondrial-metabolic-disease-calorie-restricted-ketogenic-diet/
- https://www.drkarafitzgerald.com/2016/06/27/cancer-low-carb-diets-tumor-keto-adaptation/
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Kara Fitzgerald: Hey, everybody. Welcome to New Frontiers in Functional Medicine. I’m Dr. Kara Fitzgerald, and today we are circling back to talk about the ketogenic diet as a therapeutic intervention in cancer. I’m with Miriam Kalamian today. She is a board certified nutrition consultant, educator, and author specializing in the implementation of ketogenic therapies.
Miriam, like myself, is inspired by the work of Thomas Seyfried, PhD. We actually podcasted with him back in August 2016, so check that out if you’re not familiar with Dr. Seyfried’s work. He’s really put this on the map with his animal studies at Boston College.
Anyway, Miriam is a leading voice in the keto movement and draws on a decade of experience to provide comprehensive guidelines that specifically address the many diet and lifestyle challenges associated with the cancer diagnosis and, folks, I know many clinicians are listening to this podcast, and we will indeed address as many issues that we as clinicians face in practice as possible today.
Miriam’s passion for helping others implement this diet comes directly from her personal experience with her son Raffi, who was diagnosed with a brain tumor in December 2004. Beyond cancer, Miriam integrates nutritional strategies with metabolic therapies and lifestyle modifications to develop personalized treatments that address a broad spectrum of conditions currently considered intractable, including age-related neurodegenerative and bariatric diseases.
She’s the author of the new and very comprehensive book, Keto for Cancer, and that’s Chelsea Green, and it will be out in October, next month. It’s a great, great, great book. We’ve had the opportunity to actually do a little bit of peer reviewing and editing with Miriam. Anyway, very warm welcome to you, Miriam. Thank you so much for joining me today.
Miriam Kalamian: Kara, I’m thrilled to be here. You know how much I respect your work.
Kara Fitzgerald: Well, it’s definitely a mutual admiration society. I’m grateful to have you in my tribe.
Miriam Kalamian: Thank you.
Kara Fitzgerald: You’ve done just endless amounts of work. I know this was really born out of your work with your son, just this personal powerful experience. You talk about it in the beginning of your book. Do you want to just give us a little bit. Hey, folks, definitely get Miriam’s book when it’s out, because it’s extremely useful for clinicians and patients alike. It’s meaty enough for clinicians and patients who want the deep drill down, but it’s also accessible for people who just want the “what to do.”
Anyway, you talk about Raffi in your book, but can you give us a little bit of background, a little bit of your story before we jump into talking about the diet itself?
Miriam Kalamian: Sure. My son was diagnosed, he was four years old, diagnosed with brain cancer in 2004. Tumor the size of an orange in this little guy’s head. We did what we were told to do. Basically, we were misled about his prognosis, and we just did what we were supposed to do, which is basically 14 months of weekly chemotherapy. That didn’t stop it, neither did anything else that we tried.
Here we are now in the spring of 2007. We’ve exhausted all the potential therapeutic options, and now they’re going to just move him to palliative treatment, but that would’ve meant hospitalizations and transfusions and infections with very little hope that it was really going to slow this down.
It was just by accident, Kara, totally by accident. I was looking at one of the drugs that he was coming off at that point, because it was extremely toxic. It’s Cytoxan, extremely toxic to the kidneys, and I had found something I wanted to print. I couldn’t print it that day. I go back a few days later, and on Science Daily, there’s a different story that day, and it was Thomas Seyfried’s research.
I was not looking for a cancer diet. I was not looking for an alternative treatment. I was just researching a drug he was on, and I found this study and I was just blown away, because for anybody not familiar with it, Dr. Seyfried references Linda Nebeling’s work in the mid 1990’s, which she did with two children with brain tumors. I’m looking at this and just stunned that I didn’t know about it.
Kara Fitzgerald: Give me just the thumbnail of her work, then obviously you went on to … I know we don’t have a lot of time on it, but you’ve got to answer this question. Everybody wants to know, who’s listening, so we have to just finish this and then we’ll get to questions. Give me a thumbnail.
Miriam Kalamian: Linda Nebeling was a doctoral student at Case Western. She was a registered dietician, and she knew about the ketogenic diet for epilepsy, and she had some speculation as to what it might do in terms of brain cancer. It took her a long time, but she recruited two children. PET imaging was fairly new back then, and it was what they used for brain tumors. She recruited these two children with advanced high-grade tumors, and she did an eight-week study, that’s all it was, where she put them on a ketogenic diet. One child was in treatment, one was not.
At the end of this eight weeks when they did another PET scan comparing it to the baseline scan, there was a greater than 20% reduction in the uptake of glucose to the tumor site in both children. Both children. One of them kinda got lost to follow-up, but the other one survived for at least a number of years. For all I know, that child could still be alive.
She published this work in the American College and Nutrition Journal in 1995. Then she left Case Western. She had her doctorate. She went to work for the NIH, and the two other people on the project went off to pursue other things. The whole thing just got dropped.
It wasn’t until Dr. Seyfried, in looking at the ketogenic diet originally for other purposes, found that study and was intrigued by it, and so that was part of the stimulus for him starting his research on [inaudible 00:07:23]. If I hadn’t found it that day, I would not have been aware of it, because it was just brand new out there. There had been one paper before that, well a couple papers before that, but nothing that had grabbed attention as much as that one paper did in 2007.
Kara Fitzgerald: Yes. Really. Very serendipitous. You implemented the diet with Raffi. He was your first …
Miriam Kalamian: Yeah. This is how it went down. February, I find this study. At the same week that I find out that he’s failed his clinical trial, they are keeping him in it, because they don’t want to lose numbers along the way, so they’re still gonna give him these drugs for a few weeks until they officially kick him out.
In the meantime, I’m studying up on this diet. I run it by my husband, because he could find the flaw in anything and he says, “No. Let’s just go for it. What do we got to lose?”
He came off the study, and the next day I fasted him. He immediately went into ketosis, really strong ketosis. I was scared to death to do this, because we were not being monitored and I don’t suggest that people do this not monitored, but I was in Connecticut, I live in Montana, I had nothing to help me out there. Nobody would touch us cause we were off label using this.
I was on my own basically with some information, a Johns Hopkins book and a couple of parents on a website [crosstalk 00:08:57].
Kara Fitzgerald: Your background. Your background. You were not …
Miriam Kalamian: No, [crosstalk 00:08:58]. My background was nothing. No. Uh-uh. Retail business and education early on. This was in three months. We had a scan at the end of March, then we had a scan at the end of June, and the scan at the end of June showed the tumor had finally stopped growing, had shrunk back some. Metabolic activity of the tumor was greatly reduced. This is totally unexpected.
I really didn’t expect the diet to work when conventional therapies hadn’t. We had gone through a number of them, and they hadn’t worked. I was blown away, and I really needed help, and I got Beth from the Charlie Foundation, got us set up with the diet, but I realized that if I was going to do this long term, I needed to understand it, so within a month after that …
Kara Fitzgerald: Let me just say, Charlie Foundation is a great resource for diets for epilepsy. I know they’ve branched out and you’ve been working with them, but is it Charliefoundation.com people can go and check it out?
Miriam Kalamian: Dot org.
Kara Fitzgerald: Dot org?
Miriam Kalamian: Charliefoundation.org. Great resources. They’re adding to it all the time. That’s where I got the confidence to move forward with it, but I didn’t have enough information and nobody really wanted to get into it at that point. I enrolled. Within a month I was enrolled in the graduate program at Eastern Michigan.
Here I am, starting a biochemistry course, and it just was two-and-a-half years of just intense … Totally threw myself into it. My son was doing great. He was going to school, so it allowed me time for studying. He just did wonderfully on the diet for about three years.
He had a downturn, and then he came out of that. I talk about that in my book. Because, to me, we still don’t know what put him down, what started the process, and what brought him back to us, but he was on some version of the diet the whole time. Quality of life was so much better. We were able to do things with him that we wouldn’t have been able to do if we’d been tied to an oncology clinic.
Kara Fitzgerald: Right. Right. Well you guys had already moved into basically palliative. They ran out of interventions.
Miriam Kalamian: We didn’t have to go palliative, because he didn’t need any treatment once we started the diet.
Kara Fitzgerald: Well, I mean his prognosis prior to starting the diet was that he was not …
Miriam Kalamian: Palliative.
Kara Fitzgerald: Yeah, so he was not expected to survive for many months.
Miriam Kalamian: No.
Kara Fitzgerald: Okay.
Miriam Kalamian: No, officially it was a one-in-three chance of any response, and a one-in-ten chance that the response … And just response. We got a better response with diet, but they’re just talking response. One-in-ten chance that the response would last for a year-and-a-half. This was not a pretty picture we were facing.
Kara Fitzgerald: Yes. So you moved him onto the diet, and he was able to resume school. He did well for years.
Miriam Kalamian: For years. Even after that downturn and then he came back to us, then we had another year of just bliss. We went camping in Mexico. We did all kinds of fun stuff together. I’ll tell you, that extra year of memories right in there, that’s what I hold in my heart right now.
Kara Fitzgerald: Thank you. Thank you so much for sharing that. It’s really moving. I’m like tearing up. It’s extremely moving, Miriam, and I … Just being able to look at some of the pieces of the book that you’ve asked us to just review with you, and just having you be kind of a part of our space where we talk about [crosstalk 00:12:59].
Miriam Kalamian: I so appreciate that.
Kara Fitzgerald: My point is, is that your passion, and your stick-to-itiveness and your drill down, it just comes from this deeper force that you have, that you’re bringing to it.
Miriam Kalamian: Oh yeah. I want to get this right, and I want to keep getting it righter and righter. It’s not just what we know now, it’s what we’re learning. Every day there’s new stuff coming out, and I just try to incorporate as much of it as I can into my work with people and what I put out there in writing.
Kara Fitzgerald: Yes. Wonderful. Folks, I will definitely have links to Miriam’s website and the Nebeling paper from 1995 will be on our show notes. Charliefoundation.org is there as well. You’ve talked about some of the science to support it. Why don’t you give me a little bit of an update since Nebeling.
Miriam Kalamian: I think the most significant thing that’s happened is the realization that it’s not just about starving cancer of glucose. If that was all that was going on, then it really would not be an effective approach to cancer, because we can only get levels so low. There’s a physiological norm for glucose that we have to stay in, and our bodies take care of that for us. If we’re not taking in dietary carbohydrate for fuel, we’re going to make ketone bodies, which are great brain fuel and other cell fuel, we’re going to make them in the liver, but we’re also going to make glucose in the liver, and that glucose is sufficient for everything that glucose is needed for, and without symptoms of hypoglycemia.
So there’s gotta be something else going on, and the something else going on is meal composition, but it’s also meal timing. By going to a ketogenic diet, you are inhibiting the pathways associated, some of the pathways associated with cancer progression like mTOR and IGF-1, very anabolic, and you are up-regulating pathways that are associated with the health of the cell, and by throwing in meal timing in there, you’re also encouraging autophagy, mycophagy.
You’re impacting a number of pathways. You just gotta do it right. You can’t just pick up a Atkins Diet and think you’re gonna do something as far as your cancer goes.
Kara Fitzgerald: Yeah. Okay. When articulating what the ketogenic diet is, I think that the bulk of our listeners are familiar with the calorie-restricted ketogenic diet for cancer, but really quickly, just explain maybe Seyfried’s core thesis, or what we’re thinking about why the ketogenic diet works. Just what that is, and then I’m going to ask you about timing, meal timing, and composition, kind of go from there.
Miriam Kalamian: Okay, great. What Dr. Seyfried has kinda focused on in his research and continues to focus on is fermentation. A normal cell is going to take glucose in, and it’s going to convert it to pyruvate, because it really can’t do anything with just glucose, so it has to be converted to pyruvate. So one molecule of glucose is cleaved into two molecules of pyruvate. Generally, most of that pyruvate then is transported into the mitochondria, where it’s oxidized for energy. Very efficient process.
There’s a little bit of it that stays in the cytoplasm of the cell and is fermented for energy, but it’s also important because it’s recycling some of the intermediates like [inaudible 00:17:00] specifically. Those things are going to be needed in the mitochondria, too.
It’s a pretty well-orchestrated scene in a normal cell, but in a cell that has lost some of that mitochondrial function, things start to degenerate pretty quickly. If that pyruvate for any reason, and there’s lots of reasons why it doesn’t get oxidized properly, it can be enzymatic, it can be the structure of the mitochondrial membranes, there’s a number of things going on in there that interfere with the normal process, so instead, all this pyruvate that’s in the cell, gets fermented. The fermentation process produces a lot of lactic acid.
The lactic acid in a small amount in a normal cell is okay, but this excessive amount has to be shuttled out of the cell; otherwise, it’s going to kill the cell. So shuttled out into the micro environment of the cell. Putting an acid in the micro environment of the cell is a perfect environment for disease progression. So you’re going to get this biosynthesis that’s going to help to accumulate this tumor mass, cells are going to proliferate, that are going to be spread to new areas. That’s disease progression in cancer, that acidic micro environment.
Dr. Seyfried has speculated that that’s happening with glutamine, as well, that succinate is the acid that it produces, but it has the same kind of effect in the micro environment.
What we’re doing is just lowering the availability of glucose and reducing some of those things that can be anabolic, like a rise in glucose met by a rise in insulin levels, high insulin levels associated with high IGF-1, increased receptors on cancer cells causing rapid cell proliferation.
We’re interrupting that process. That’s the primary thing to look at. There’s a lot more little things here and there going on. What’s important to know about this, too, is that the ketones, which are excellent brain fuel, can also be used by most other cells, and there are specific enzymes within the mitochondria that aid in the [inaudible 00:19:51] of ketones for energy, and they do not produce as much [inaudible 00:19:56] as the either fatty acid or glucose metabolism.
Kara Fitzgerald: Right. Listen. I want to just kinda summarize this for people. Normally-functioning cell in the mitochondria, glucose is converted to pyruvate, or actually in the cytosol, and then pyruvate is shuttled in and used to turn the Krebs cycle and ultimately the electrons are sent over to the electron transport chain and ATP is the product. So that’s cellular respiration in a normal-functioning cell, that’s mitochondrial action happening, cellular respiration, ATP production is the end result.
In the disease process, this is not exclusive to cancer, but there’s a breakdown in mitochondrial function. There’s an acquired mitochondropathy, I guess we could probably say, and there’s, no longer are we able to generate ATP in the same way.
When we are not in aerobic oxidative phosphorylation, we generate lactic acid. I mean, that’s normal when we’re working out really intensely and we have an accumulation of lactic acid because there’s not enough oxygen to produce some ATP versus cellular respiration, so there’s an accumulation of that. But in the case of cancer, and I think this underlying fundamental mechanism can be seen in other conditions, as well, to varying extents.
There’s that tumor micro environment where there’s so much research going on. We see this extremely acidic milieu, this accumulation of the lactic acid and all sorts of reactive oxygen, oxidative species, and so on and so forth, and the micro environment is just horribly damaged and it allows for the proliferation of the damaged cells, and the utilization of glucose for more rapid fermentation and growth and so forth, and then just the increase of tumor size and the proliferation of cancer versus wellness.
I don’t know that I’m wrapping my arms entirely, and you can clarify this better. I don’t know if I’ve said this all together before, but carbohydrates, and as you said, there are more insulin receptors on the tumor cell, so they’re just like targets for sucking up glucose and just using it preferentially, and that’s why we give glucose actually on scans, because we see that hot metabolic activity at the site of the tumor because they just so vociferously take up the glucose, but they are not efficient. Many, many cancers are not efficient at using ketone bodies, so if we switch over to using ketones as our metabolic fuel, we actually turn this dynamic around. We stop feeding the tumors.
Is there anything to add to that? Or is there clarification you need there?
Miriam Kalamian: I think you covered it. One thing that people ask me often is whether or not their particular cancer is going to respond, and quite honestly, I mean we’ve talked about that, we don’t really know for a fact whether any particular cancer is going to respond, but my thing on that is, what have you got to lose? Try it for a couple of months. If your cancer’s not responding to the diet change, then at least you gave it a try.
Kara Fitzgerald: Absolutely.
Miriam Kalamian: You made a commitment, and you gave it a try.
Kara Fitzgerald: Yes. Yes. Generally, we’re following some tumor … There’s been at least a one or maybe a couple tumor markers have been identified that we can track closely, or we can certainly track imaging, and we’ll get feedback relatively quickly.
You gave us the thumbnail, now circling back to some of the science, scientists are looking at this. There is research out now beyond Nebeling’s and beyond Dr. Seyfried, that suggests that this … So talk about that.
Miriam Kalamian: The problem with the science is that the people who are really committed to this and believe in it, if they’re within the conventional cancer care community, they are ostracized if they speak out in support of it. I know one person who didn’t get a job that he thought he was going to get, and another one that was relieved of her position, actually two that were relieved of their position for speaking out in support of the diet.
In the conventional medical world, it’s going to be a slow process, because what I hear is there’s no evidence to support it. Well, there is preclinical evidence. There are case studies, but the clinical trials just aren’t going to be there for a couple of reasons. One is finances. Who’s going to finance a diet study? But some of these really passionate people are trying to do this within just a single institution, usually a university, and the recruitment levels are just too low, so these end up being very under-powered, and I think they just aren’t dialing the diet in properly.
The IRBs, the institutional review boards, are so opposed to the thought of somebody with cancer losing weight, that the calorie restricted ketogenic diet just is not a part of most of these trials that are going on. They’re trying to do this full calorie. If you’re doing this full calorie as an adjunct to cancer, it’s really hard to deal with the effects of the chemotherapy and at the same time be taking in a ton of fat, even if you don’t need to, because you’re carrying all that excess weight around with you anyway.
There’s a lot of those institutional obstacles. Where it’s thriving more is in your world, Kara. That’s most of what I … Most of the people that contact me for direction with the diet are not medical doctors, unless they’re integrative or functional medical doctors.
Kara Fitzgerald: Yes.
Miriam Kalamian: Yeah. They’re in the naturopathic world.
Kara Fitzgerald: It takes a lot of courage for patients and patients’ families, because families are really an intimate part of this picture, to be willing to stand up to their oncology team and hold fast to this.
Miriam Kalamian: Oh yeah. I can speak from that.
Kara Fitzgerald: It’s really scary. It is. [crosstalk 00:26:52] discouraging.
Miriam Kalamian: It’s very intimidating. I have a whole presentation that I just gave in Austin this last weekend at the KetoCon. It’s about skeptics and saboteurs, and how they can get in the way, and sometimes the skeptics and saboteurs are populated among your family.
Kara Fitzgerald: Yes.
Miriam Kalamian: Or you can be your own worst enemy because you’re listening to too many sources, it’s too confusing, you don’t know, most of the diet information is for weight loss instead of for cancer, and you just don’t know what you’re supposed to be doing.
Kara Fitzgerald: Yes. Yeah, it is. There is concern around weight loss, but there’s a very strong difference between the mechanism underlying cachexia versus …
Miriam Kalamian: Exactly.
Kara Fitzgerald: The weight loss associated with taking this diet on. Listen, because I do want to talk about that, and I know people have questions around it. I just wanted to circle back. You talked about meal composition and meal timing as being a really fundamental piece to being able to get this diet right. Just say a few things about that.
Miriam Kalamian: People get it in terms of the carbohydrate, at least on the surface. They’re looking at the weight loss world, or the fitness world, and they’re going, “Yeah, 20 or 30 grams of carbohydrate a day.” In my little cancer world, that might have to be as low as 12 grams of carbohydrate a day for somebody who has brain cancer. We really need to dial it in very differently than a diet for weight loss.
Then people get the carb part pretty easily. They don’t get the protein part as quickly. That needs a little more coaching and supervision. They generally start out with about twice the amount of protein that they need, and that can … Go ahead.
Kara Fitzgerald: Just tell me, I’m so sorry, but just give me the background on why we are restricting protein, because it’s not necessarily restricted in other ketogenic programs.
Miriam Kalamian: Right. We’re restricting protein for a couple of reasons. The mTOR and IGF-1 are critical pathways in cancer progression, and by restricting protein, that nutrient sensing that goes on, the body [inaudible 00:29:20] time to build, and it shuts down those activities including the ones related to cancer. That’s one thing that’s happening with protein.
The other is, if we’re eating an excess amount of protein, the excess is going to be recycled into glucose. In somebody losing weight, that may not be a big deal unless they have some intense issues, metabolic issues, but in cancer, it can be a big deal.
Then the third thing is, certain proteins, dairy proteins and egg proteins are meant to be anabolic. They’re taking little baby animals and growing it into big ones. You get an insulin response, even in the absence of the glucose response, you’re getting an insulin response and, again, that’s associated with IGF-1. It also suppresses ketone production.
Kara Fitzgerald: So diet is, we’re going extremely low on the carbs. We’re going low in protein for those reasons.
Miriam Kalamian: As low as we can go in protein, yeah. That’s a case-by-case basis we have to figure that one out.
Kara Fitzgerald: And then loads of fat.
Miriam Kalamian: Yeah. Only people don’t need to overeat fat if they’re carrying a lot of weight. They can eat reasonable amounts as long as they have a sustainable amount of weight loss. We don’t want to dump too much into the … too many of those toxins that are stored in fat into the body at once.
Kara Fitzgerald: Do you get that, folks? Slower weight loss if you can manage that. You’ve got somebody who presents to you with cancer, and they still have some degree of body fat that you can work with, so they’re going to be actually using that fat to produce ketones for a while, but you want to keep it slow as Miriam said so that you’re not liberating the toxins present in the adipose. Go ahead.
Miriam Kalamian: When I say that, then people say, “Well, what about fasting? I hear that fasting can cure cancer.” Boy. That’s a whole other can of worms right there, because I do believe, a lot of people that contact me want to start with a fast. They’re just so overwhelmed by this diagnosis they’ve just been handed, so they want to start with a fast. I’m totally supportive of that, but I’m very picky about the circumstances in which they should fast.
There’s a lot of caveats and disclaimers to throw in there. If they can do it, it is a way for them to get some self-control back over this diagnosis and feel like they’re really doing something. At the same time, they’re going to make the shift into ketosis a lot faster if they are fasting. Once they are done with the fast, I want them to have a plan in place so that they’re not just going back to doing what they were doing.
That first week or so is so critical, that first two or three weeks beyond that are also critical, because that’s the kind of make or break for people.
Kara Fitzgerald: Right. I know many patients come to my practice who have done the fasting or some sort of version, and then they’ve put themselves on the diet and they usually hit some sort of a wall of intolerance or challenge, and then they show up here, and I think that’s probably true with you. Give me some of the caveats. I know people, again, they’ll find this in your book, but just throw out a couple that would caution you towards supporting somebody jumping into fast immediately.
Miriam Kalamian: I think if somebody is underweight or malnourished, it’s not a good idea. Wait till you are in ketosis and have stabilized all that. Then once you’re in ketosis, a fast is not going to degrade protein, so you’re not going to degrade muscle mass as rapidly as you would just coming straight from a standard diet. That’s one consideration.
The other thing is, I’m careful in terms of is it going to be safe for this person? Or the caregiver, are they the parent of young children and there’s nobody else in the house, so what happens if they have a problem with the fasting and they’ve got little children in the house? I’m very concerned about that. It doesn’t happen very often, but it’s significant when it does.
Other than that, older people, I don’t believe that older people do well with fasting for the same reason as just coming from a standard diet, because they lose too much muscle mass, and an older person has a much harder time regaining, if they can, regaining that muscle mass.
Kara Fitzgerald: We can get people into a good robust ketosis without doing fasts.
Miriam Kalamian: We can, yep.
Kara Fitzgerald: Most of the time, it’s somewhat the exception that I’m finding people to be fit for fasting. Even though I support it theoretically full on, I hear you with regard to your precautions. We really need to pay attention to that, especially muscle loss, and just the ability to handle such a jolt.
Talk to me about meal timing. You mentioned that as being extremely important in getting this diet right.
Miriam Kalamian: Yeah. I don’t think that the diet is as effective if you eat every waking hour. I realize that there’s some people that have to eat small and frequent meals, but I’d still like to see it be done in a smaller eating window, because there is just plenty of science out there that shows that longer overnight fasting up-regulates autophagy. In the up-regulation of autophagy, that’s taken out damaged cells, and cancer is damaged cells, but it’s also taking out other damaged cells that are causing inflammation and other problems in the body.
It’s serving a really good purpose for everybody, I think, to practice that daily intermittent fasting. For more vulnerable people, keep that eating window wider, but I always suggest that people don’t eat within three to four hours of bedtime, or just even lying down, and that they wait for an hour or two, at least, after they get up in the morning before they eat real food.
Bullet-proof coffee served in the interim, and I think that’s a wonderful way to start the morning, actually, and it will bring down that rise in glucose stimulated by cortisol, the dawn phenomenon. It will bring that down, and it’ll boost your ketones at the same time, and then you go into that first meal of the day a few hours later.
Kara Fitzgerald: Just, folks, just talking about the dawn phenomena, we’ve been dialoguing about this a lot, you, and Seyfried didn’t see this, or doesn’t see it in the animal model,
Miriam Kalamian: No. Mm-Mm (negative)-
Kara Fitzgerald: We see it in our patients. There can be, in somebody who’s adopted a really strong ketogenic diet, that can have this inexplicable morning blood sugar spike, and we think that probably what’s going on is some sort of a nighttime cortisol sort of adrenaline surge referred to as the dawn phenomena, breaking down muscle, turning it into glucose. So the bullet-proof coffee you’re talking about using in the morning, and I have to my patients recommended a little bit of a nighttime fat snack with some good result. Just something little to see if we can tie it over.
Then we’re monitoring ketones and blood sugar really carefully at this point, so you’ll get pretty immediate feedback as to whether or not what you’re doing works. I have tried complex, just a very small amount of complex carbohydrate at night, as well. How about you? Anything else on that?
Miriam Kalamian: No, I’ve been pretty straight. If somebody needs to have food in the evening, then I say have it with a high-fat snack, yeah, or if they’re not getting enough total calories in, I don’t want them breaking down more, so I will say add something at bedtime. Especially people in treatment, their appetite is so dysregulated, and their food preferences get all messed up. The sight and smells of food can often turn them off to eating.
Then you combine that with the effect of the ketogenic diet on appetite, suppresses appetite, so that’s part of what you have to monitor, especially in those first few weeks, but there’s another thing right there. Short-term fasting around chemotherapy, I am a huge fan of that. I see that in the people that I work with. They’re reluctant to do it, they might go through a cycle of chemotherapy, and then the next time around approach it with fasting before and after the chemotherapy, and they feel so much better. They feel so much better.
This one woman, she was like in bed after her first chemotherapy infusion. The next time she did it with short-term fasting, she was out walking with her daughter the next afternoon. I’ll send you that … I’m sure you’re aware of it, too, there’s a very readable case series from Panda and Longo. It sort of lays that out. They’re the ones that are really looking at that. They’re looking at it in terms of standard diets, though, so you have to put the standard diet filter on when you read their work and say, “What would it be? How more robust an effect would they get if they were doing this from a ketogenic diet rather than a standard diet?”
Kara Fitzgerald: Yes. Right, right, right. Speaking of references, send that to me and I’ll post it on your page. Also, folks, you’ll find a lot of good references on Dr. Seyfried’s page. A lot of his full texts are available for free, so there’s a bunch of links there. Fats. Let’s talk about fats and what fats you’re recommending and why.
Miriam Kalamian: Well, I believe, and this comes from following [inaudible 00:40:04] and Finney, initially, they were the only ones really writing about quality of fat in the beginning, that we really can do best with the combination of saturated fats and unsaturated fats. I watch for the balance, and that’s why I like that tool, chronometer, because there’s an option on chronometer, it has this dashboard dial that shows you if you’re faithful about putting in all of the foods and supplements that you’re using. It shows you your omega-6 to omega-3 ratio.
Once people have that dialed in, then they don’t need to use that tool all the time once they know that they’ve got that balance in check, so that’s one really important thing.
Basically, saturated fats, which of course have been vilified, are a really important part of this diet, and they are highly digestible compared to some of the oils. I really like people to think about every place they can that they can throw a little bit more saturated fat into it. They’re going to get the polyunsaturates and the monounsaturates out of their foods an on the things like nuts and seeds without having to pile on a lot of oil, which certain oils are going to be pretty inflammatory, and the ones that aren’t, you can get tired of them pretty quickly.
And the quality of fat, the best quality that you can get. If you’re eating animal fat or dairy fats, you want it from very clean animals. The lipid profiles of animals that are fed on pasture are so much better than the lipid profiles of animals that are fed or finished with grain.
Kara Fitzgerald: Perfect. We just talked about obviously dairy protein, avoiding that. However, the dairy fat is a different story. You’re going to be using it, like if you’re using butter, I’m assuming you’re recommending ghee, or maybe minimizing butter just so you’re reducing the amount of protein exposure, right?
Miriam Kalamian: If somebody’s had a problem, then I’ll minimize butter; but if they don’t like the taste of ghee, obviously ghee’s the better product, but if they don’t like the taste of it, then I don’t want to throw one more obstacle into them getting enough fat so it’s like, yeah, go for the butter. You could clarify butter. You can just melt better, and the solids will sink to the bottom, then you just drain off the butter oil, and that has virtually no protein in it. You’ve solved the problem and you’ve kept the taste.
Kara Fitzgerald: Coconut oil, you know or medium chain triglycerides, you’re using those, I’m sure.
Miriam Kalamian: Yeah.
Kara Fitzgerald: Okay, just any comments on them? I mean, obviously, we can pump them into ketones pretty quickly. What are you thinking?
Miriam Kalamian: Well, this is the problem, and I go into this in my book. I spent a lot of time on this in my book, because I think it’s really important for people to get this, and there’s a lot of misinformation floating around. You’ll see coconut oil, and it’ll say rich in MCTs, over 50% MCTs. That’s because technically, lauric acid, which is a 12-carbon chain, is considered a medium chain triglyceride, and that’s predominantly what’s in coconut oil.
Yes, lauric acid has lots of benefits. It’s antimicrobial and antiviral and antifungal, too. There’s good reasons to include coconut oil, but it’s not because it’s ketogenic. Only 14% of coconut oil are the more ketogenic oils, the C8 and the C10, 8 and 10 carbon chains.
If you’re going for bang for your buck for higher ketosis, if you want to boost your ketones with a food supplement like MCT oil, then you go for either the straight C8, the caprylic acid, or you go for the C8 and C10 combo, which is more common and less expensive, but the caveat here is that a lot of people … Young people don’t have any problem with it.
Kara Fitzgerald: Yes.
Miriam Kalamian: As people get older, for each decade, they seem to be less and less tolerate of MCT, gastric distress, diarrhea, so what’s the good of it? It’s not doing any good if that’s what’s going to happen when you take it. Yeah, so just small amounts of it until you’re sure you can tolerate the small amounts and build up slowly, but boy, it’s a wonderful addition to boost the ketones, because any time you’re boosting ketones, you’re also suppressing gluconeogenesis, because you’re not needing as much glucose if you have sufficient amounts of ketones in the body. Your intake is going to be the same of carbohydrate, low, but you’re not turning on gluconeogenesis in the liver if you can keep ketones providing the bulk of the energy.
Kara Fitzgerald: You are recommending people monitor blood sugar carefully and monitor blood ketones. We use urine ketones also, just because the ketone strips for blood can be super expensive.
Miriam Kalamian: Oh, I do too, yep.
Kara Fitzgerald: Okay, so just talk about what you’re doing and maybe Seyfried’s index, and just kinda talk about monitoring your patients. What do you recommend?
Miriam Kalamian: Okay. In the beginning, I don’t want people stressing over this. I think there’s important reasons to get to where you want to be with it, so in the beginning, I just have them get used to using a glucose meter, a home meter, and testing fasting blood glucose, because in the beginning, you don’t have the dawn effect, and you don’t have the physiological insulin resistance developing that quickly. So people get an idea of what their fasting levels are, and it’s motivating, because they’ll see it come down rather quickly.
Then at the same time, using the urine ketone sticks, and I ask people to do it like three times a day: when they wake up, sometime in the afternoon, and when they go to bed. Pretty simple routine. Again, motivating. It also helps with compliance and accountability. People do things inadvertently sometimes, or just the thought that they may not get a good reading on a strip, they may be able to say no to something that isn’t keto-friendly.
Like you said, they’re inexpensive, so just use them, but at the same time, getting people up to speed with testing blood ketones, because that’s going to give you a more accurate picture of what’s going on in that individual’s body. The simultaneous testing of glucose and ketones is what Thomas Seyfried uses for what he calls his glucose ketone index.
I explain that in the book, or you could get his paper, one of his papers is specifically on that. You take glucose, which is expressed in milligrams per deciliters here in the US, you divide it by 18, you got the normals. You divide that by what you see on your ketone meter, and that gives you hopefully a number somewhere between 1.0 and 2.0.
Definitely, lower is better for brain cancer. For people with metastatic disease, I often see numbers closer to 2, or even maybe 2-1/2 to 3, because they can’t get their … Either they can’t get their glucose down as low, or they’re not getting their ketones up as much. That’s where ketone supplements can help, the new ones that are out on the market. They can give you a little boost in that department.
Kara Fitzgerald: I’m gonna actually, folks, I’ll throw the paper that Miriam just mentioned, the Seyfried paper with the [inaudible 00:48:18] ketone index calculator in it, or actually his … I don’t know if there’s a calculator in it, but he does write it out.
Miriam Kalamian: Well, it’s a calculation. The thing that I tell people is, this is a guide. It doesn’t have to hit the target every time. You’re a human, and there’s going to be variations in your body. Inflammation from treatment … People test after they’ve had radiation; of course, it’s going to be way off, because you are killing cells, and it’s creating inflammation, and that drives up glucose, and that suppresses ketones.
Kara Fitzgerald: It does. That’s right. It’s very catabolic, and you’re breaking down muscle, and then you’ve got sort of fuel to make more sugar. That’s right. It’s hard. For me, in our patient population, it’s been pretty difficult to kind of get the perfect between 1 and 2. Sometimes we’re in the low 2’s. It can be challenging to achieve.
Miriam Kalamian: With each decade that passes. Kids are below 1, and people in their 20’s and 30’s can generally hit 1, but it’s a rare person in their 70’s that hits 1.
Kara Fitzgerald: I think younger men, having testosterone, it just seems to turn the volume up on metabolism, and they can produce more ketones or more actively. Then we look at this … It just makes me think of supporting fat metabolism, beta oxidation, and we’ve talked about using a little bit of carnitine and testing for carnitine, so they get fat adapted, or keto adapted, so they’re actually able to start make ketones and then use ketones. That can be a little bit of a process with some lag time.
Miriam Kalamian: I’m very, very careful with carnitine, because we used carnitine with our son to encourage some linear growth, because the ketogenic diet in kids, a really rigorous one, does impair linear growth. We used just 2 grams a day, and we did it for eight weeks, had an MRI, and his tumor was metabolically active, so we cut it out; two months later had another MRI, and he was back to where he had been. I’m very careful.
I think that our bodies do a good job of sorting this out after the first few months. I do just replacement doses, so maybe just … It comes in like 330’s, so 330, 660. Over-the-counter might be 250 or 500. Just very carefully, if I’m going to use it at all, but I would rather see somebody just eat a couple of meat meals a week, or support with lysine, because lysine combines with methionine and will make carnitine. Lysine is a ketogenic amino acid, so you’re not going to be raising blood glucose by taking that one.
Kara Fitzgerald: Okay, that’s fair enough. We test it. We can test carnitine. It’s pretty easy test to get insurance coverage on. I hear your caution, and especially if you’re not actually looking at values and confirming that, in fact, it’s rock bottom, absolutely, yeah. I think your experience speaks volumes and, yes, as you mentioned, lysine. I know we’ve talked about this before.
Miriam Kalamian: Should we say something about why people need carnitine, or what’s going on there?
Kara Fitzgerald: Yeah, Mm-Hmm (affirmative). Sure. Go for it.
Miriam Kalamian: Okay. Carnitine is used to transport long chain fatty acids across the mitochondrial membranes. So you can imagine that in fatty acid, the medium chain ones don’t need that kind of transport, the long chain ones do. With robust fatty acid oxidation, there’s enough regulation of the usage of carnitine up-regulation in the biosynthesis of it as well, but it may not keep up in the beginning.
What I see when people can test, is it may impact it in the first couple of months. You see low carnitine, but over time, it might supplement for a little bit, but test it again. Always test it again a few months after that, and you most likely will see levels back in the normal range.
Kara Fitzgerald: And it tends to be associated with the experience of fatigue before they’re really in the groove of using ketones. Then there’s actually generally, in my experience, a nice bump of energy when their body’s actually really able to utilize them.
Miriam Kalamian: Right.
Kara Fitzgerald: We are coming to a close here. I feel like I could go on with the questions. What are you using for measuring ketones and glucose? What’s the instrument that you’re recommending?
Miriam Kalamian: Okay, a good question. Personally, I have not had good experiences with the Nova Max. I don’t think it’s very accurate at the lower ranges of ketosis, so I have traditionally used the Precision Xtra. Sometimes people will have two different meters: a separate glucose meter, because the strips, the glucose strips for the Precision Xtra are pretty expensive, and the ketone strips are really expensive.
In San Diego, just last month, there’s a new meter on the market called Keto-Mojo. I signed up for one. I don’t have it yet. I should be getting it in the next week or so, and then I will be comparing as will so many of the people that I know in my world will be comparing the accuracy of this to the Precision Xtra, because those strips are just a dollar apiece.
Kara Fitzgerald: Oh, isn’t that terrific.
Miriam Kalamian: As opposed to … Right. If you want to buy them for under 5 or $6, you got to order them out of Canada or Australia, and that’s highly inconvenient with the Precision Xtra.
The other thing that is so wonderful about this Keto-Mojo, oh you’re going to love this, is that it adjusts for hematocrit. So when you’re working with somebody with cancer and they have low hematocrit, there’s a separate reagent on the strip, and it’s feeding into an algorithm that’s going to adjust the glucose level to what would be a more accurate assessment of what that person’s blood glucose level is, and not skewed by their low hematocrit.
I think that’s amazing that there are some meters out there that are better than others, but I think to have all of it in one tidy little package for people with cancer would be great.
Kara Fitzgerald: Yes. That’s right. That’s very cool. Yep. I’m looking at it right now. I put the website on the show notes, so Keto-Mojo.com. Yeah, and it looks like they’ve obtained FDA approval for it as medical [inaudible 00:55:07].
Miriam Kalamian: They have, yes. Oh god, I met the guy that developed the company. He’s passionate. He’s doing this because … He’s doing it for the greater good. He’s going to make a ton of money off of it, as well, if his product proves to be as accurate as Precision Xtra, and he’s done that internal testing himself, so he’s pretty confident, but I just can’t wait for it to get into the hands of the researchers who are using these and see what they have to say about it.
Kara Fitzgerald: Right. Right. Right. Yeah. Well, he hasn’t offered the device for research yet? They don’t have any competition yet?
Miriam Kalamian: He did not.
Kara Fitzgerald: That’s interesting.
Miriam Kalamian: He just kept it all in-house for the unveiling. He unveiled it in San Diego early August. The people that signed up then are getting theirs in the next week or so.
Kara Fitzgerald: I’ve got tons of questions, but we’re gonna wrap up now, and I’m going to just encourage you to reach out to … Go to Miriam’s website, check out what she’s doing, and without question, grab her book when it’s available and, again, it’s called Keto for Cancer, and it’s Chelsea Green. Again, thank you so much for joining me today.
Miriam Kalamian: I want to say, I welcome feedback from people, and I don’t mean something written as a review in Amazon. That’s great, too, but I welcome feedback on that book from people, because I have the opportunity to make changes in it for a second printing, and I would like to incorporate what your audience knows, what [crosstalk 00:56:42].
Kara Fitzgerald: Oh, that’s perfect. Absolutely.
Miriam Kalamian: That’s who I am, and that’s where I’m at with this, is I really want to formulate the best keto for cancer diet out there.
Kara Fitzgerald: You can start the dialog, folks, right on the comments page on the show notes, and then we’ll just shoot those comments over to Miriam, and then she’ll respond accordingly. That can be a starting. I’m sure there’s a way to access you from your website, as well.
It’s an important opportunity for all of us to dialog. There’s a lot of unknowns. We’ve got some knowns, so it’s important.
Miriam Kalamian: There is a lot of unknowns.
Kara Fitzgerald: If you’re a clinician using this in practice and you’re seeing some interesting labs, or there’s [inaudible 00:57:25] or a couple of important good anecdotes you can share with us, by all means, I would love to hear from you, as well.
Miriam Kalamian: That’s great. Thank you, Kara.
Kara Fitzgerald: Absolutely. My pleasure.