I'm not sure what you mean. If you want to increase ketone production, instead of olive oil, it's better to use
. Medium Chain Triglycerides will give you more ketones.
Here is the transcript of parts of Dr. Seyfried interview. The numbers indicate the time segment.
Dr. Thomas Seufried interview on Livin' la Vida Low-Carb with Jimmy Moore
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11:11
So what was the purpose of the CR, how is that better than allowing them unlimited amounts of this ketogenic diet?
11:20
Well, unlimited amounts of KD is extremely unhealthy. And there is no doubt about this. If someone were to sit down and eat a plate of lard or Ketocal or any of these KDs, they would suffer significant metabolic problems. The diets are overbalanced in fat. Now, the diets are extremely healthy if given in restricted caloric amounts. We did studies in both epilepsy and in brain cancer to show that unrestricted amounts of any type of KD, including Ketocal does absolutely nothing to the growth of brain cancer or prevention of epilepsy. It was only when these diets were restricted in caloric content did you find the beneficial effects. And the issue, of course, is that you can restrict any kind of a diet, a hi-carb diet or hi-protein diet. If the diet is restricted, blood glucose levels go down and ketones go up naturally. The advantages of the ketogenic diets – restricted KD of course – is that the glucose goes down while the ketones are higher, when you take in the fats. So the KDs are more effective at elevating ketones. And these ketones, when given in restricted amounts, are extremely healthy to the metabolism of the cells.
12:52
So by restricting the calories and feeding them a high fat KD you're basically starving the tumors?
12:59
Yes, absolutely. You starve the tumors and the normal cells can transition over to ketones, because the metabolism of ketones for the generation of ATP is dependent upon oxidative phosphorylation, which is the functionality of the mitochondrion. So, normal cells generate most of their energy through oxidative phosphorylation, or what we call respiration, whereas the tumor cells have defective mitochondria. They are incapable generating energy using the ketones, so they are metabolically restricted.
13:37
In your studies you refer to the specific diet that you're using with these mice as dietary caloric restriction DR and the low carbohydrate high fat ketogenic diet to ostensibly reduce the brain tumor growth. Is there any kind of translation of what number of calories that would be to be restrictive enough to help humans?
14:03 That's a good point. I mean, this is an area of great debate and confusion, because we hear a lot about CR in humans and CR in mice and monkeys and you go around and you hear about CR. And then there are these groups of the CR society and all this kind of stuff. Well, we did a study in our lab to determine precisely what does CR in the mice represent to the human, or how does CR in the human reflect the mouse.
We have to be cautious in dealing with the different species. The basal metabolic rate of the mouse, the rate at which it uses its energy, is 7 times greater than that of the human. This accounts for why they require 20 to 25% of their body weight a day consumed in food. The basal metabolic rate of the two species is greatly different. So we have to appreciate that the CR effects will be very different in the mouse and the human.
We have evolutionarily conserved biomarkers that indicate metabolic stress, and that’s basically circulating levels of glucose and circulating levels of ketones. So, to achieve the same ratio distribution in the mouse and the man under restrictive food intake we use these biomarkers, and it turns out that a 40% restriction of calories in the mouse is comparable to a full therapeutic fast in the human. In other words, humans evolved to actually handle CR much, much better than mice. We as a species can go long periods of time with only water and no food, and our bodies are well adapted to the metabolism of FAs and ketones. The mouse, on the other hand, can only do it for short period of time.
So what we found when we did our comparative analysis of CR in the mouse and CR in the human, looking at glucose and ketones as biomarkers, as well as circulating of FFAs and some other triglycerides, we found that the human would need to do a full therapeutic fast, which is a water only fast for 7 to 10 days, and that equals what we're giving these mice as a 40% CR. So you always have to keep in mind the species differences when you talk about CR.
So if humans wanted to get the health benefits that we see in the mice, that are always reported in rats and mice and things like these, humans have to do a full therapeutic fast or very close to that, say, a very low calorie diet, 400 to 600 calories per day. And of course, most people raise their eyebrows and say, I can't do that. And it's true, a lot of people either can't or will not do that, but if they ask, if they want to achieve the same health benefits, that's basically what they must do.
17:13
You're referring to the people who are dealing with brain cancers or neurological diseases. You're not talking about just the average everyday person on the streets. You're not saying that.
17:27
Well, I mean the person on the street who would like to get himself very healthy and fit metabolically, that's what they would do. This is a tremendous health benefit to the physiology of the system. When you transition from glucose to ketones, the mitochondria get very, very healthy, oxygen free radicals go down. Now if you have a brain tumor and you try that, you put tremendous metabolic stress on the brain tumor cells and they up and die, they just can't handle that level of physiological stress. All of the gene mutations that the tumor cells have are restricting those cells from making the metabolic adaptation to survive. So those cells get eliminated very quickly.
18:11
OK, Dr. Seyfried, which creates more ketone bodies, is it the CR or is it the high percentage of fat in the diet?
18:19
Well, it's a combination of both. If you fast, ketones go up naturally, because the fats in your body are mobilized to the liver and broken down to ketones. So circulating levels of FFAs and ketones go up naturally in anyone who would undergo a therapeutic fast. But if the fast is supplemented with a high fat diet, like a restricted ketogenic diet, the levels of circulating ketones go even higher. But when I say higher, this is still within the normal physiological realm. It is not ketoacidosis, which is extremely high levels of ketones that are produced in cases of diabetes.
19:12
Where is that fine line between having enough ketones and too many to reach the ketoacidosis state?
19:15
Well, the ketoacidosis state usually happens when there is severe energy imbalance due to say, diabetes. In the case of diabetes you have very high circulating glucose levels, because insulin is missing, and then the body perceives itself as starving. And then the body starts cranking out large amount of ketones. So you have this very severe situation where ketones go very high in the presence of glucose, and this is a combination that generally would never happen in a normal condition. Also, the body has an internal regulatory system where you will excrete the ketones in the urine, so anywhere from 5 to 7 mMol of ketones is about the maximum you're gonna get in a normal healthy person that would be fasting and taking the ketogenic diet or taking any kind of food that would generate the ketones. So the body would have like a regulator, a rheostat to maintain a normal physiological level that would be needed for energy metabolism. Anything excess would be excreted in urine.
20:30
Well, lets turn back to cancer, because this is a fascinating research you're doing, Dr. Seyfried. If someone is dealing with cancer...
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22:16
I know your specific expertise is with the brain cancers, but do you see this kind of ketogenic approach being used for other cancers?
22:23
You have to understand the energetic situation and the placement in the body of the tumor cells. The tumor cells in the brain are somewhat protected or restricted from the rest of the body by the BBB, so the cells behind the BBB are not exposed to the same metabolites as say cancer cells in other parts of the body, like the lung or the liver, colon, breast or these other areas. So, if the tumor cells are glycolytic, where they use a large amount of glucose to survive, they would be susceptible to killing by CR ketogenic diets. However, some of these cells can survive using glutamine, which is an alternative fuel, and restricted ketogenic diets may not be as effective in targeting those kinds of cancer cells that would be using glutamine as an alternative energy. The brain has very low levels of glutamine, so we are not too concerned about that, but outside of brain, glutamine now becomes another issue. And we think that cells that would be using considerable amounts of glutamine may not be as effectively killed as cells that are purely glycolytic. So the answer is, I think some cancers would probably respond quite well, whereas others may not respond as dramatically as some of the brain tumors respond.
24:15
And that's because the brain functions well on ketone bodies and whereas some other areas of the body, where cancers could be, maybe not so much?
24:22
Well, no. Normal cells in the body will burn ketones. The cancer cells will not be able to burn ketones in any part of the body, because their mitochondria are defective. That's a given. But they also have access to an alternative fuel besides glucose, so they could survive. Even though they are not burning ketones, they could survive on glutamine, which is converted to glutamate, which then goes into the TCA cycle, and one can generate energy through that in some cancers. You'd have to probably look at the cells to see whether or not they might be candidates. But you know, the one thing about the ketogenic diet – restricted, I always want to emphasize that – CR ketgenic diet is not a harmful diet. This does not hurt you like, say, radiation or chemotherapy would hurt you, that actually damages your cells and tissues. These diets don't do that. So, this is the non-toxic approach to the management of cancer.
25:33
So, Dr. Seyfried, if people who are listening right now want to protect themselves against brain cancer and even be healthy, is it better for them to go ahead and eat this ketogenic style type of diet, even if it is a little higher in calories than what you're recommending for the people who actually going through brain cancer or is it something else?
25:55
Well, when you say protect, that enters now into the concept of cancer prevention as opposed to cancer management. It's very clear in my mind what prevents cancer. And any damage to the mitochondria will provoke cancer. The question is, how do you prevent damage to the mitochondria. Yes, you can do low calorie diets, that would lower glucose and elevate ketones. This is the most powerful anti-cancer therapy that I know of. The problem is most people won't do this. Most people don't do any of this kind of stuff... yeah, there are some people out there, but most people don't do this. The issue is, once they have cancer, what can they do. This comes now into the management phase of the cancer. How do I kill the tumor that I have without also killing half of my body and creating all kinds of other problems. So, when you look at these diet therapies for cancer, you have to say, do I want to prevent cancer. If you want to prevent cancer, then you do a therapeutic fast once a year. Then the probability of getting cancer would be extremely low relative to those people who don't do that, simply because you're gonna purge the body of any particular cell that's going to be glycolytic and an insipient cancer cell. So you can get rid of these doing it. But very few people will do this. They are looking for a quick fix, some sort of an antioxidant, or something like this. Those will have a very minimal effect compared to a therapeutic fast. This is what we know.
27:46
Let's define what that therapeutic fast would be. Is that the 7 to 10 days?
27:49
Yes, 7 to 10 days on distilled water only. If you want to prevent yourself from getting cancer, you would probably engage in that once a year. Now who can do this? Only those people who are extremely well disciplined are capable of doing something like this.
28:12
But it's worth it if you can ward off brain cancer.
28:13
You ward off any cancer, not just brain cancer. But how many people that we know in our society today, or in any society for that matter, will do anything like this? Although the human body evolved to do these kinds of things. So, I mean, I always look at, humans evolved to starve. Our history in the past was seeking out any place you could get food. So we're supremely designed to engage in this kind of activity. But most people won't do this, so they get cancer or whatever other kind of disease and then they seek medical therapies that many times are as bad as the disease itself.
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