Dr. Stephen Phinney on the Safety and Benefits of a Ketogenic Diet (Part 2)

– Nutritional ketosis is a very powerful tool. And it can be used to achieve metabolic health and well-being in people who have diseases associated with insulin resistance or inflammation. Now, there are lots of myths and misunderstandings about ketogenic diets and about nutritional ketosis and I wanna really focus on the scientific evidence around safety and efficacy of this approach to nutrition. And I realize it’s hard for people to commit to this kind of endeavor if people around you are saying, “Oh, this is dangerous so you shouldn’t be doing it.” So you need to be confident that if you undertake this that you’re doing it in a safe and efficacious way.

In study after study, not just ours but others, a well-formulated ketogenic diet when compared to a standard calorie restricted low fat diet has a greater effect on weight loss and particularly loss of abdominal adipose tissue and it’s the adipose tissue or a fat mass within the abdomen that is the most dangerous fat that we carry in our body. For instance, a study that I did with Dr. Jeff Volek and Dr. Cassandra Forsythe, one of his graduate students, we compared a high carbohydrate low-fat calorie restricted diet to a ketogenic diet that people followed where their instruction was to eat to satiety, that is not count calories and don’t restrict calories but eat enough to feel like they had had enough food and they weren’t hungry.

And we ran the study for 12 weeks.

And at the end of 12 weeks, the weight loss in the high carbohydrate low-fat group was about half the weight loss in the ketogenic diet group. Now, some critics will say that well, when you go into a ketogenic diet, a lot of your weight loss is water. But we actually did careful measurements of body fat and the water loss on the ketogenic diet was only about 1/5 of the difference so five kilograms on the carbohydrate rich low-fat diet and 10 kilograms on the ketogenic diet and only about 1/5 of that difference was water, the rest was body fat. More importantly, we used the dual x-ray absorptiometry so called DEXA technique to measure body fat content.

There is a significantly greater reduction in abdominal fat, so it’s not just total fat, it’s not fat from under the skin, but it’s some of the most dangerous fat that is more rapidly mobilized when someone gets the ketogenic diet right.

The next most common effect is for people who have either slightly or markedly elevated blood glucose levels, so either prediabetes or diabetes, a prompt response of the ketogenic diet is a reduction in blood glucose. Now, that makes sense because if you eat less carbohydrate in a diet, there’s going to be less glucose produced by digestion and the level of sugar coming into the blood is gonna be reduced, that’s what we commonly see.

However, in Dr. Forsythe’s study..

. Now, these are people with prediabetes but their blood sugars are still slightly elevated. We saw a marked reduction in blood glucose in the people on the ketogenic diet and no change in blood glucose in the people who were on the high carbohydrate low-fat diet. What’s more interesting is that we also measured blood insulin levels. And insulin a hormone that makes glucose go into cells, so if the blood sugar came down, you’d think that the body was making more insulin to make it go into the cells.

But it was the opposite of what we saw. And that is that insulin level came down dramatically, blood glucose came down. And the only way you can make sense out of that is that the ketogenic diet improves insulin sensitivity, that is the body’s response to any one molecule of insulin is markedly greater.

And that’s a consistent finding we’ve seen across multiple studies and that’s the finding that has led us to the concept that we can actually reverse the root cause of Type 2 diabetes. Another effect of a well-formulated ketogenic diet is to change the blood lipid values that are characteristic of metabolic syndrome.

And, by the way, metabolic syndrome is also referred to as prediabetes.

Typically we’d see with metabolic syndrome a reduced good cholesterol, an increase in triglycerides and a greater proportion of the small dense or bad LDL cholesterol. And when we looked at that in this cohort, we saw that triglycerides plummeted. Now, they went down in both groups but they went down more than twice as much in the patients on the ketogenic diet. And by the way, they were eating more fat, and yet the blood fat levels dropped.

HDL went up about 13% which is greater than any HDL response we can get from any drugs that we have available that we can write as a prescription. So this is a pretty much unique benefit to a well-formulated ketogenic diet. And then the small dense LDL which is the most dangerous didn’t go down. If anything they went down slightly in the group who were eating the high carb low-fat diet and went down sharply in the group on the ketogenic diet. So again, all the lipid changes are going in the right direction in favor of the ketogenic diet.

So again, the concern about eating a high fat diet, eating eggs and meat and dairy which contains cholesterol, the actual, the cholesterol in the blood and the blood lipids are changing all in a beneficial way when one gets this diet right. If you’re eating low carbohydrate and moderate protein, the majority of your dietary calories come from fat. And a lot of the fats that people eat typically come from animal products or from dairy and cocoa butter and things, which are saturated fats.

And so the question is is eating a lot of saturated fat dangerous when you’re on a ketogenic diet? And the reason people propose it as dangerous is that we know that when you measure blood levels of saturated fat, that the higher the blood level of saturated fat, the greater the risk of diabetes, a heart attack and overall mortality.

And so if you assume that eating saturated makes the blood level go up, that would suggest this is dangerous. But people hadn’t ever actually looked at what happens to the blood levels with saturated fat when they’re going on a ketogenic diet, so we did. And what we found was, even though the people on the high fat diet, the ketogenic diet were eating three times as many grams of saturated fat per day, their blood levels of saturated fat actually were lower than the group eating the lower saturated fat intake high carb diet.

And again, this is a head scratcher. It appears that we’ve disconnected intake from blood levels.

And that violates the law that all dietitians tell you that you are what you eat. In actuality, you are what you save from what you eat. And the neat thing about the ketogenic diet is it teaches your body to burn fat more effectively. How effectively? Well, we did a study where we looked at highly trained athletes some of whom were following a traditional high carbohydrate loading diet regimen and the other half of them were following a well-formulated ketogenic diet.

And these people had been following these diets for at least six months or longer, which means that they were fully keto-adapted for the ones on the low carbohydrate or ketogenic diet. And when we looked at the resting rate of fat oxidation, it was about double as much on the low carbohydrate ketogenic diet as it was on the high carbohydrate diet.

So again, highly trained athletes, theoretically, their bodies are highly conditioned to burn fat for fuel during exercise and yet, just the difference of diet doubled the bodies’ ability to burn fat for fuel. And then as they..

. We had them do greater and greater levels of exercise, the people on the ketogenic diet demonstrated remarkable ability to use fat for fuel. The athletes like that because they can run on body fat stores much better than trying to eat and load with carbohydrate which means that when you’re keto-adapted, your body has a capability of getting rid of saturated fat and so the amount you eat is not important, it’s how much your body saves from what you eat. And clearly, the body doesn’t save saturated fat when you’re keto-adapted, which means that saturated fats are not harmful when consumed, if you’re keto-adapted.

Another very important area of current research is in the topic of inflammation because we know that when we measure biomarkers of inflammation, and there have been some that we’ve measured over the last century, like white blood cell count and some that are more recent additions to our ways of measuring inflammation.

That those levels predict the later onset of diseases like heart disease, Type 2 diabetes, Alzheimer’s disease and many of the common forms of cancer. And so in doing the study with Dr. Volek and Forsythe, we actually measured every biomarker we could think of and we came up with 14 different biomarkers of inflammation.

And when we compared them for the people in the high carb diet versus people adapted to the low carb high fat diet, none of the levels of inflammation went down more in the people who were on the high carb low fat diet. In contrast, 7 of those 14 were significantly reduced for the people on the well-formulated ketogenic diet.

That is on average there was a marked reduction in inflammation with the ketogenic diet, indicating that this has a wide-ranging antiinflammatory effect. Now, up until recently, that’s been what we scientists call a phenomenon. We see it’s happening but we don’t know why. And it turns out that there is a particular gene, it’s kind of like a traffic cop gene, it regulates the flow of traffic around inflammation. And this gene is targeted directly by the ketone that we have circulating.


A primary ketone in our blood which is called β-hydroxybutyrate, or BHB. And this is a place where ketones talk to your genes and your genes turn down the heat, if you will, through a regulated series of events to reduce inflammation of the body and that has the likelihood of having very positive effects not just on reducing insulin resistance but also reducing other common chronic diseases, as well. Now we not only know that the inflammation goes down, but we know why it goes down and why it is so effective and even modest levels of ketones, the levels that you achieve just by restricting carbohydrates to less than 5% of total calories and keeping protein moderate.

We’re doing a study with Indiana University Health where we recruited over 260 people with Type 2 diabetes and put them on a well-formulated ketogenic diet.

This study will be going on for two years, but I want to show you just the early data from the first 10 weeks of the study. All these people had the diagnosis of Type 2 diabetes. Some were poorly controlled, some were pretty well controlled, some were very tightly controlled. So we divided the biomarker of diabetes control called hemoglobin A1c or HBA1c into high levels, intermediate levels and well controlled levels.

And in all three cases, after 10 weeks, there was a reduction in the level of hemoglobin A1c and this effect was greatest in the people who had the highest levels. So people who had the poorest control of their diabetes got the greatest effect, but all three groups had an effect. And the result was that over half of these people moved from having hemoglobin A1c levels in the diabetes range into the non-diabetes range. What’s really intriguing is normally in medical care diabetes, you get better glucose control by giving people more drugs. In this case, we took away most of the drugs from five of the seven classes of diabetes medications.

And the two most dangerous which are insulin and sulfonylurea, those are the two classes of drugs that are most likely to cause hypoglycemia which is probably the most threatening side effect, short-term side effect of in diabetes management that we either stopped or markedly reduced the majority of those medicines in these patients. And so here, again, we have the paradox, less medication, better control. And the reason we can get better control with less medication is β-hydroxybutyrate in ketones, in general, speak to the genes and change fundamentally how the body functions, including changing how the body responds to insulin so the body can get much greater benefit from far less insulin.

And then as a side effect of this, again, we told people to eat to satiety. It limited carbs, protein in moderation, as much fat as they needed, and again, they can put butter on their meat, they can put butter or dressing on their vegetables and dip with vegetables, things like that.

And so they were eating to satiety, and yet 75% of these patients lost more than 5% of their body weight. And on average, the body weight loss was a little bit over 7%. And that was just in the first 10 weeks. At six months in this cohort, the weight loss went from 7% to 12%. So this is not a short-term quick loss and then regain, but it appears to be a sustained long-term effect.

Because, again, people who are six months into our study are doing the same thing we told them to do at the onset and that is limit carbohydrate, protein in moderation, eat fat to satiety and that gives the body permission to burn a lot of body fat stores because the body has become so efficient in burning fat for fuel. Just to mention other conditions that we’ve seen that show improvement with the ketogenic diet, just general muscle and joint aches and pains.

Irritable bowel syndrome typically gets better. Polycystic ovary syndrome in women. People with migraine headaches mention that either their frequency is down, the intensity is down and some people get complete remission of their migraines when they get the ketogenic diet right.

As we showed from the study of Dr. Forsythe, metabolic syndrome or prediabetes has improved along with that liver fat levels go down which is a side effect of poorly controlled diabetes. And we see improvements in fluid retention and blood pressure, as well. This is a very powerful tool. It can have very beneficial effects on a number of chronic conditions, but when a person’s taking medicines for these chronic conditions, those beneficial effects usually mandate a sharp and rapid reduction in medication.

And that can be dangerous, unless you have the assistance of a physician who understands this type of diet and understands how to manage the medications. This cannot be done in a casual way, you can’t start a diet and go back and see your physician six weeks later and say, “So what do you think I should do with my diabetes medication?” Because typically we have most of the changes in the first six days when people get the diet right. The concern is finding a doctor who understands this and that is sometimes difficult, but we see increasing interest in physicians, so if you look carefully, you can probably find someone who can help you, if you need that kind of assistance when you’re following this type of regimen. So again, for our conclusion a well formulated diet is not only safe but it can be very effective in reversing disease.

These effects are so powerful. However, this has to be started with careful monitoring. Stated in this directly, you have to find a physician who can help you manage your medications in the proper way that this be done where the benefits far outweigh any potential risks involving changes in medication use..

Read More: Dr. Stephen Phinney on Nutritional Ketosis and Ketogenic Diets (Part 1)

1,740 thoughts on “Dr. Stephen Phinney on the Safety and Benefits of a Ketogenic Diet (Part 2)

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