(Dr. Lustig’s Sugar: The Bitter Truth lecture is approaching 1,000,000 views on youtube, and justifiably so.)
During the podcast, Jimmy asked Dr. Lustig about a study he had mentioned on a prior podcast of LLVLC (Episode 378):
Lustig: That was a pilot study. Everyone got drugged. It was not controlled it was not blinded and we went on a fishing expedition in which we gave people a drug that blocked insulin release called Octreotide. Octreotide is usually used to treat acromegaly, which treats growth hormone (GH) excess because it blocks growth hormone release as well as insulin release and so people who have pituitary tumors and oversecrete GH are on this drug. We used [Octreotide] instead to block insulin release and what we found was there was a group, out of the 44 we treated, 8 of them responded amazingly well.
Lustig: Their appetites went away, they stopped snacking between meals, their carbohydrate intake went down like a stone from 900 calories a day from carbohydrate to 350. They felt better and they lost a lot of weight. 12.6 kg in 24 weeks. And we didn't tell them to change the composition of their diet or to lose weight, they just did it, all by themselves.
Lustig: This was kind of amazing. But it only happened in eight out of the 44 study participants. It was cause-and-effect in the eight, or 18% of the subjects, because we could look before and after the treatment, and it turned out that the 18% who responded, all had one thing in common: all hypersecreted insulin. Their insulin response to glucose were all the same as each other and very different from the 36 who did not.
Lustig: So what we end up doing in this study was finding a subset of people who hypersecrete insulin, who oversecrete insulin for the same amount of glucose. Now, those people are walking the streets, they don’t know who they are, they don’t know what they look like. The doctors taking care of them don’t know who they are either. But we’ve shown in a clinic, where we do OGTT, as routine in our clinic, because that’s how we sort patients.
Lustig: This is going back to the first point; not everybody’s the same. We are not the same. Obesity is not a disease, it is a phenotype of many different pathologies. What we did in the study was we found one pathology. We found one reason for obesity. And we found one treatment that worked for obesity.
Lustig: You might say that you found the data post hoc, it wasn’t randomized, it wasn’t controlled, it wasn’t blinded. To which I would say: We did it again. We did it again in a randomized, double-blind, placebo-controlled fashion in a clinical trial. … The same group of people responded; the same group of people who hypersecreted insulin to start with.
I think this is fascinating for many reasons, but something that should not be overlooked is the pattern, or arrow of causation, that appears to be occurring in the subjects who are responding to the Octreotide.
Normally, we, the proponents of the carbohydrate/insulin hypothesis, would say that a low-carbohydrate diet causes lower levels of insulin. However, what Lustig has really shown in the studies above is that the causality can be flipped: lower levels of insulin can cause a low-carbohydrate diet.
As Dr. Lustig said, “They had a change in macronutrient preference. They were carboholics. We blocked their insulin, and now, they couldn’t care less about carbohydrate. By getting their insulin down, we changed what foods they ate.”
Acutely, when we eat a meal rich in carbohydrates, our insulin goes up in response. For the uninitiated, elevated levels of insulin in the body used to be a strong clue that there are an abundance of carbohydrates in the bloodstream. Insulin tells the muscles to burn carbohydrate for fuel and for the adipocytes to store nutrients as fat and inhibit the release of fat into the bloodstream. Why waste any stored fat when we have an abundant supply of energy in the bloodstream? Also, we know that elevated blood sugar is not a state we want to be in for several acute and chronic reasons, so the priority becomes clearing carbohydrates.
I say “used to be a strong clue,” because more and more people are becoming chronically hyperinsulinemic, insulin resistant, and type-2 diabetic.
Acute 'hyperinsulinism' may be seen as something physiological and not necessarily pathological: we eat like the Kitavans for a meal, lots of carbohydrates from glucose sources, and our insulin goes up, we burn carbohydrates for fuel, we temporarily inhibit lipolysis and store fat, but over time (perhaps overnight) we are ultimately homeostatic: our weight may fluctuate, but not by much, and we remain relatively weight stable and relatively lean.
Chronic hyperinsulinemia is another, and pathological, story. If you have elevated insulin levels most of the time, our bodies don’t know the difference between our acute response to a carbohydrate-rich meal and the chronic condition of hyperinsulinemia, so the response in the body is relatively the same. Fuel is partitioning in the same manner where insulin is telling muscles to burn carbohydrate; and fat tissues to store fat and protein, and to hang on to it.
Carbohydrates become the body’s food of choice. A hyperinsulinemic state can sap glucose from the energy supply because it ‘thinks’ glucose is in high supply. But it’s not. You should be burning free fatty acids (FFAs) for fuel while glucose is in relatively short supply. Not so for people who are chronically hyperinsulinemic. They crave carbohydrates because that’s what they can utilize for fuel and it is also what happens to be in short supply because of the way their fuel is partitioned.
The obese, hyperinsulinemic, will eat; store a little more of it as fat, and their insulin remains relatively elevated for longer periods of time; and they eat a little more, and they store a little more and burn a little less than a healthy, lean individual who is relatively insulin sensitive, a ‘hypo-secreter’ of insulin, if you will. And so the fat begins to accumulate progressively on the fat person, while the lean person remains in "energy balance."
The fat person isn’t fat, and isn’t getting fatter because he’s eating more; the fat person was, and is, eating more because he’s fat, and getting fatter. (Thank you, Gary Taubes, who would like to thank George Wade, who should probably thank Hugo Rony back to 1940. This isn't a new observation, but most people, i.e. the conventional wisdom interpret it from the wrong side of the 'arrow' of causality, at least when it comes to us weak-willed humans.)
The healthy, lean individual isn’t lean because he’s eating less; he’s eating less because he’s lean. The healthy person will eat; store fat, and then burn fat, so that he is in “caloric balance,” but calories really don’t have anything to do with it.
As Lustig noted, essentially the fundamental way an obese, hyperinsulinemic individual gets fat out of the fat tissue is to lower insulin levels. Octreotide did the trick in his patients.
Low-carbohydrate, slow-carbohydrate, and safe-carbohydrate (Lustig: “I'm for safe carb, rather than low-carb, as a generalization”) diets, for example, can do the trick as well.
And, just as Lustig pointed out that when he blocked insulin secretion in subjects who otherwise secreted too much insulin and they went from “carboholics” to ostensible Atkins-dieters; the logic would hold that if you took a healthy individual and gave them a drug (insulin is on the nose) that kept insulin elevated, we would see the opposite: we would induce “carboholism.”
We're not just playing with words when we observe that, people who go on low-carbohydrate diets have lower levels of insulin, and people on high-carbohydrate diets have higher levels of insulin, and we conclude:
Lower levels of insulin cause low-carbohydrate diets...
...Higher levels of insulin cause high-carbohydrate diets.
And both may be a "vicious" cycle where lower levels of insulin leads to a lower-carbohydrate diet, which lowers insulin levels, which leads to a lower-carbohydrate diet.
The same holds true inversely: higher levels of insulin leads to a higher-carbohydrate diet, which raises insulin levels, which leads to a higher-carbohydrate diet.