Sugar is responsible for a global health crisis!
The evidence can no longer be ignored, sugar is to blame for the continual rise in chronic disease. Prof Robert Lustig is a paediatric neuroendocrinologist, researcher, clinician and pioneer of the anti-sugar movement.
Today Prof Lustig takes us through his expansive career and how he became a global leader in teaching both peers and public of the perils of sugar, fructose and carbohydrates; and the roles they play in the pathogenesis of disease.
Covered in this episode:
[01:29] Introducing Prof Robert Lustig
[03:12] Prof Lustig discusses his professional and academic career
[06:00] What made Prof Lustig pursue sugar
[08:54] Biochemistry drives behaviour
[12:30] Insulin hypersecretion vs insulin resistance
[14:50] Personalised obesity medicine
[15:30] Alpha Melanocyte Stimulating Hormone
[17:31] Leptin resistance
[19:11] Why weightloss slows over time
[22:46] The low-fat diet doesn’t work
[23:50] The mechanisms of carbs and sugar
[24:30] Why there's a pandemic of NAFLD, even in children
[25:21] The Ansell Keys' fat legacy
[30:11] Not all sugar is created equal?
[31:06] The power of fibre
[35:08] Glycemic Index vs. Glycemic Load
[38:00] Impact of fructose for Type 1 Diabetes
[41:35] Fructose: pathology and testing to consider
[43:56] Prof Lustig's 2-Hit Theory
[47:37] Devils Advocate: Australia doesn’t have HFCS
[48:59] Mitochondrial transcription factors: sertuin 1, 3
[49:50] How practitioners can categorize the obese patient
[52:16] Teaching patients about food
[55:06] Modifiable factors
[57:32] Do we need to say goodbye to sugar?
[59:42] Final question: what resources can we direct people to?
[1:04:38] See Prof Lustig at the 5th BioCeuticals Research Symposium
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. And joining me on the line today all the way from SoCal is Professor Robert Lustig. Robert is a professor of paediatrics in the division of endocrinology, and member of the Institute for Health Policy Studies at University of California, San Francisco.
Dr Lustig is a neuroendocrinologist whose clinical research has focused on the regulation of energy balance by the central nervous system, and the role of nutrition in metabolism. Now, his bio is way too long for me to go into so rather than that, our practitioner listeners can look up Professor Lustig's profile at profiles.ucsf.edu/robert.lustig.
And I would like to warmly welcome Robert Lustig to FX Medicine. How are you, Robert?
Robert: Thank you very much, Andrew. I just want to make one correction. I'm not greeting you from SoCal, I'm greeting you from NoCal.
Andrew: NoCal...
Robert: We would never be associated with those people down there.
Andrew: So, where does SoCal stop? Is that just a...
Robert: Usually around Santa Barbara, a little bit south from there.
Andrew: Right. Okay, gotcha. Right. I'll make sure I adjust that.
Robert: Whatever you do, if you come to NoCal, make sure you bring your sweatshirt.
Andrew: Oh, yeah.
Robert: Because it's cold.
Andrew: Well, I can't wait to go up there because the last time I went there, the Big Sur was closed from a landslide.
Robert: Yes, that's right.
Andrew: Yeah.
Robert: It happens frequently.
Andrew: Mmm. So, I can't wait for you to come out to Australia in 2017 and speak at our...I think it's our 5th symposium. Because you've got a long and esteemed career, indeed controversial.
But I think firstly, we need to take our listeners through your professional and academic career because it is voluminous. Where do we start?
Robert: Well, I appreciate your saying that. I'm not sure how voluminous it is, but...
Andrew: Why into medicine, I guess, first? What was your calling?
Robert: Oh, hard to say. Obviously, these things come from parents and grandparents, and esteemed friends over all the years. Ultimately, I wanted to do something that was valuable to people, make the world a better place, you know?
Originally, I was going to be an astronomer, but I ended up settling on medicine back in college, after I took an astronomy course and said, “You know what? Better off the other way.” Probably more to the point is why I ended up going into paediatrics.
Andrew: Yeah.
Robert: And really, that was...I knew I wasn't going to be a surgeon because I'm a lefty, and if you're a lefty, you can't be a surgeon because you stand on the wrong side of the patient's body while you're operating.
Andrew: But we're too good. I'm a lefty, too.
Robert: Yeah, exactly. Oh, well you know, if you’re... if right-handed people use the left side of their brains, then the lefties are the only people in their right minds.
Anyway, paediatrics because I was on my first night on call on adult medicine, and it was 2:00 in the morning and they wheeled in a patient who had just had a stroke, and they said, "Here, go work him up." And so I went into this room of four, basically, alcoholics who had been picked up off the street, off Skid Row. And I couldn't make it through the door jamb because the stench coming from that room was so severe that it was like a force field pushing me back.
Andrew: Wow.
Robert: I thought to myself, what's the worst smell I have smelled on paediatrics? And it was stool from a patient with cystic fibrosis, and I thought, this is worse.
Andrew: Right. Yeah.
Robert: And so I went into paediatrics.
Andrew: But then endocrinology. I mean, we're not talking about light things here, we're talking, you know, like Cushing's, and...
Robert: Endocrinology is a thinking specialty, and since I have two left hands, I needed to do something which involved thinking, and endocrinology is the ultimate cognitive specialty. Of course, we didn't get paid for it, but it is definitely interesting.
My ex-boss, Walter Miller, who's one of the world's foremost endocrinologists and just won the Lifetime Achievement Award from the Endocrine Society says, "Endocrinology is that aspect of medicine which is interesting."
Andrew: Now, I've got to ask then, why sugar? What twigged you to go, listen, there's something going on here? What was it? Because I mean, you went against the grain.
Robert: You have to understand that I had been in medicine for 28 years before the notion that sugar was a problem had even pervaded my consciousness.
Andrew: Right.
Robert: It was quite a while. I certainly did not come to this with an agenda, I came completely through the back door.
So I'm a neuroendocrinologist, so I'm interested in how the brain controls hormones, and how hormones control the brain, and sort of the last frontier of this field is obesity. And we didn't really understand how obesity worked until 1994, when the hormone leptin was discovered.
Andrew: yes.
Robert: And leptin tied the brain and the fat tissue together because leptin is the hormone secreted into the bloodstream, and it's interpreted by the brain, and what the brain sees is energy sufficiencies.
So as your fat cells grow, your leptin levels go up, and that tells your brain, “I've got enough energy onboard to burn energy at a normal rate, feel good about it, and engage in expensive energy prospects such as puberty and pregnancy.” So, leptin is tied to all of the things that I study as an endocrinologist.
Well, at that same time, I was faced with a stable-full of patients who become obese due to the development of brain tumours. I was working at St Jude Children's Research Hospital in Memphis, Tennessee, and these children who had developed tumours in their hypothalamus, the area that controls hormones, had either had surgery or radiation. And as soon as that occurred, they became massively obese. They would start gaining weight at the rate of five pounds a month.
Andrew: Wow.
Robert: Which was, you know, just insane. And so this form of obesity, which has a biochemical equivalent in rats, is called hypothalamic obesity because of the hypothalamic damage.
Andrew: Yes.
Robert: And I was faced with an entire stable full of these kids, you know, what to do? So I went to the literature, and I noticed that there was this biochemical phenomenon in basic science, known as the VMH lesions rat, where you basically take an electrode and you zap the hypothalamus in the rat, and they become massively obese. And it was known that the reason that that occurred in the rat was because of the hormone insulin, that something about that lesioning of the brain led to a very high release in insulin.
So we knew that these kids had high insulins, but we didn't know if it was cause or effect. We postulated back in 1995, well, maybe these kids are just like those VMH lesion rats. And if we gave them a medicine that worked at the pancreas and suppressed their ability to release insulin… in other words, if we could get their insulin down, maybe we could help these kids.
So we did a pilot trial on eight children, we gave them all this medicine that I investigated called octreotide, which has lots of side effects, is very expensive, and only given by injection so it's not for you to try at home. But lo and behold, these kids, not only did they start losing weight, but their behaviour changed.
One mother called me up, this was patient number one, and so I didn't know what to expect. And a week into the drug therapy she hadn't lost any weight yet, she hadn't had any time to lose any weight yet, but the mother called me up, frantic.
And she goes, "Dr Lustig, something's happening," and I thought, “Oh, my God, I've got an adverse event. I'm going to have to close the study down, you know, go to jail…” I go, "Well, what's the matter?" And she says, "Well before, we would go to Taco Bell, and she would eat five tacos and an enchirito, and she'd still be hungry. We just went to Taco Bell, and she ate two tacos and she was full. And she just vacuumed the house."
Andrew: Wow.
Robert: This was very strange. In fact, all the kids that we treated with this medication started exercising spontaneously. We didn't tell them to do it, they just did it.
One kid became a competitive swimmer, two kids started lifting weights at home, one kid became the manager of his high school basketball team, you know, running around, collecting all the basketballs. I mean, these were kids who sat on the couch, ate tortilla chips and slept. And now, they seemed to have the energy to burn.
So, what this demonstrated to us very clearly was that it was the biochemistry that was driving the behaviour, because when I influenced the biochemistry with this medicine, I influenced their behaviour. And so this was very interesting. We ended up doing it again as a double-blind trial, same thing happened. And then we said, “Well gee, could it be that there are adults without brain tumours who have the same insulin problem? And if we gave them this same medicine, might they end up responding the same way?"
Andrew: Right.
Robert: Now, we didn't know what these people looked like, you know? We didn't have any roadmap to go by. So we took all comers, and we did a study where we…I did a pilot trial where we took 44 obese adults who did not have brain tumours, just 44 garden variety obese people, and we gave them the drug for six months.
And what was fascinating was that 8...count them, 8 of the 44, so 18% of the total did exactly what the kids did. They lost weight, and a lot, and they started exercising spontaneously because they felt better. Now, interestingly, the other 36 did not. They didn't respond at all.
Andrew: But you could look for a cause there. You could look for a reason.
Robert: That's right. That's right. And what we found was that these eight who responded, their insulin profile was exactly the same as the kids with the brain tumours. The others were… they had high insulins, but because of a phenomenon called insulin resistance.
Andrew: Right.
Robert: So we found this phenomenon, which we called insulin hypersecretion, and it has to do with the nerve that goes from the brain to the pancreas, called the vagus nerve. And the vagus nerve is basically in overdrive in these kids and in these adults, and they're causing the beta cells which make insulin to be twitchy, that is that they fire and explode their insulin into the bloodstream at almost the slightest provocation.
Whereas the other patients, they had insulin resistance, which is what's more commonly noted in obese people, and they're the ones who go on to develop heart disease and, you know, fatty liver disease and diabetes.
So, what we had done was we had parsed a specific phenomenon out of general obesity, proving that not all obesity is the same, and that there are different causes for obesity in different people. And that if you look a priori for the cause and you can ultimately identify it, you can target the therapy to that cause, and ultimately treat the patient properly. And that the biochemistry precedes the behaviour.
Andrew: Yeah. So this is somewhere where I think obesity treatment needs to go because we lump them into obese patients. There you go, they're all the same.
Robert: Absolutely.
Andrew: And we wonder why they just… we have such poor record in, you know, re-weight gain after two to five years.
Robert: Exactly right. Because everyone thinks that all obesity is the same.
Andrew: Yeah.
Robert: Well, you eat too much and you exercise too little. Well, the question is why do you eat too much, and why do you exercise too little? And what changed to allow this to happen? And why is it that if you eat too much and you exercise too little, why weren't you obese before, now you're obese now? Something had to have altered.
Andrew: Yeah.
Robert: And if you're smart enough, and you look for the cause, you can often - often, not always - but often find the cause. And so what we do in our clinic here at UC San Francisco, is we do personalised obesity medicine.
Andrew: Right.
Robert: We parse instead of lump.
Andrew: Yeah.
Robert: We determine what is it that's actually driving the problem, as opposed to just saying, “well, you're obese, too bad, and you know, it's your fault.” And when we actually target the therapy to the pathology, our patients respond, and it's probably the most heartening aspect of my work.
Andrew: So there's about 20 questions springing from the last couple of sentences. There's a few burning questions in my mind. Seeing as we're talking about biochemistry, can I ask you first a chemical that interests me, and that was alpha-melanocyte-stimulating hormone, alpha-MSH. Why melanocyte? What has that got to do with weight?
Robert: Oh...well, it doesn't really. So, alpha-melanocyte-stimulating hormone is a breakdown product of a larger protein in the brain called proopiomelanocortin. And it does stimulate melanocytes, that's true, but it's not what stimulates melanocytes in your skin because it's a different receptor.
Andrew: Got you.
Robert: So, the hormone that stimulates melanocytes in the skin acts on the melanocortin-2 receptor whereas...I'm sorry, I take that back, it's melanocortin-1 receptor in the skin. The one that stimulates the adrenal gland is the melanocortin-2 receptor, and the melanocortin-4 receptor is the one that's in the brain. And so the substance in the brain never sees your skin.
Andrew: Yeah, that always interested me.
Robert: Right. Well, what the body does is it repurposes certain things for other purposes. So, it's not a big deal that…
Andrew: No. But you mentioned also POM, there. What's the correct acronym for it?
Robert: POMC, so proopiomelanocortin. So this is a 191 amino acid mega protein that gets cleaved in the brain, and also in the pituitary to make different peptides that are necessary to do different functions.
So, one of the pieces is beta-endorphin, which is our endogenous morphine that works in our brain to suppress pain. One of them is ACTH, which goes to your adrenal glands to stimulate the adrenals to produce cortisol. And one of them happens to be alpha-melanocyte-stimulating hormone, which helps control energy balance at the level of the brain.
Andrew: Right. Well, I definitely can't wait for you to come and speak to us, and re-learn… Because look, I remember learning about this myself from the Thieme books, I'll give a shout out to them, the Thieme FlexiBooks. And I was just in awe about this because everybody was talking about leptin at the time, and leptin resistance.
Robert: Right. Well you know, leptin is very interesting. But the fact is, what we've learned is that people who are obese have relatively high leptin levels, not low leptin levels.
Andrew: Mm-hmm...but they've got a resistance.
Robert: You know, everybody was thinking, “Well, leptin levels would be low.” It turns out they're high. But they're not seeing the leptin, they're not transducing the leptin signal. They have what we call leptin resistance.
And what we determined from these studies in these adults was that when we got their insulin down, these people lost weight. Again, they started exercising spontaneously. And this was really the key and the crux to the whole thing, we measured their resting energy expenditure using a metabolic cart.
So you know, they would breathe in oxygen, they would breathe out carbon dioxide, and from that, you can actually measure how fast, in terms of calories per day, people are burning energy. And it turned out that these eight people who responded to the drug, their energy expenditure at baseline, at rest was the lowest of all of the 44 people we studied. And when we gave them the medicine, their energy expenditure went up.
Andrew: Yeah.
Robert: Now, if you're losing weight, your brain is supposed to see starvation, your energy expenditure goes down. And that's one of the reasons why people slow their weight loss as they start losing weight, is because the brain senses that they're in starvation mode because their leptin levels have declined. And so their hypothalamus basically says, “Well, I have to ratchet down how fast I'm burning,” the same way your thermostat would work. Well, these people...
Andrew: And that's just a survival mechanism, yeah?
Robert: Absolutely.
Andrew: Yeah, yeah.
Robert: It's a total survival mechanism. But these people, we gave them this drug, they lost 12.6 kilos in 24 weeks, a pound a week, right? And their energy expenditure went up. Now, how do you explain that?
Andrew: Yeah. So, all right… another 20...
Robert: The only way we explained it is that their leptin is now working.
Andrew: Okay, so...
Robert: So they weren't working before, but now they're working. And that means that their leptin resistance went away, they now became leptin sensitive.
Andrew: Now, I have to...
Robert: And the reason that... Sorry, go ahead.
Andrew: Sorry. Well, I just have to ask about that. Is it as simple as saying that that leptin resistance was driven by inflammation, or is there just a whole host of other things going on?
Robert: Well, no. The leptin resistance was being driven by the insulin. So when we got their insulin down with the medicine, their leptin sensitivity came back.
Andrew: Right.
Robert: And we then proved that it's the insulin that's blocking leptin from working in the level of the brain. And other people, using basic science models have since shown that.
So, insulin blocks leptin. Insulin is an endogenous leptin antagonist. So the question is, why would God do that to us? Why does nature make insulin block leptin? And the answer is because there are two times in your life when your leptin should not work. There's two times when you actually have to gain weight for survival of the species...
Andrew: Infants and puberty?
Robert: ...those in puberty, and pregnancy.
Andrew: Oh, pregnancy. Right.
Robert: Right. If you don't gain weight, the species dies out.
Andrew: Yeah.
Robert: So if your leptin worked right all the time, you could never gain the weight, the species would die out. So doesn't it make sense that the same hormone that causes the weight gain, delivers the energy to the fat cells, should be the same hormone that would block the thermostat from ratcheting down at the level of the brain?
Andrew: Yeah.
Robert: So it makes perfect sense that insulin should end up doing both. So, insulin is an endogenous leptin antagonist. And when you understand that, you understand why, number one, obesity exists, because now everyone's hyperinsulinemic.
And number two, you also understand why it's so hard for people to lose weight. Because they lose weight, as soon as they start trying to lose weight, as soon as they reduce their total energy intake, as soon as they start dieting, their leptin levels go down before their weight does.
Andrew: And that's your plateau.
Robert: So all the brain sees is now they're leptin-deficient on top of being leptin resistant, so that's the recidivism of obesity. And when you understand that, and you understand that the insulin has to go down first, then patients can be treated. And that's what we do in our clinic every single day.
Andrew: But as you say, it's not a one size fits all, so this sort of answers the… not only does it answer the plateau of weight loss, but it also answers the varying results we get from the chosen diet, if you like, the fad of the day.
Robert: Exactly. And this also explains why the low-fat diet didn't work.
Andrew: Mm-hmm.
Robert: Okay? The low-fat diet does not work, okay? And now the USDA, who promoted the low-fat diet for the last 40 years, has finally taken it back.
Andrew: Yeah. Yeah.
Robert: Because the data is just incontrovertible. Well, in fact, the low-fat diet is a high-carb diet, and in particular, a high sugar diet.
Andrew: Sugar diet, yeah.
Robert: Because when you take the fat out of the food, the food tastes like cardboard, and so you have to put something back in to make the food palatable. And what was it? It's sugar. Like salad dressing, low-fat salad dressing, take a look at the label, half the fat, double the sugar.
Andrew: Yeah.
Robert: So it turned out that that's what made the insulin go up. Remember I said everyone's hyperinsulinemic? It's the carbs. And in particular, the sugar.
So carbs and sugar, it turns out, act through two different mechanisms. So carbs are glucose, and glucose causes insulin release. Sugar is glucose and fructose, fructose being the sweet molecule in sugar and the reason we like it so much, because it's also addictive.
And it turns out that fructose is metabolised in the liver to fat. And so that fat gunks up the workings of the liver, causes insulin resistance, and tells your pancreas you have to make more.
And so it was the realisation that the liver insulin resistance mattered more. And the fact that we now have a pandemic of non-alcoholic fatty liver disease, even in children, that drew me to sugar. And this occurred about a decade ago, when I finally pieced together the similarity in metabolism and also in terms of what the brain does, between sugar and alcohol.
And this is why children now get the diseases of alcohol, type 2 diabetes and fatty liver disease, without the alcohol. Because the fructose molecule is being metabolised in the liver, just like alcohol. And it was that realisation that led me to the last 10 years of my career.
Andrew: What really interests me is looking back at the NHANES one and two, the increasing prevalence of obesity, and that was sort of tied inexorably with the… it was almost like an agribusiness rescue by the US Senate to support the farmers, but turning towards...
Robert: Well, indeed...
Andrew: ...yeah, corn and sugar.
Robert: That's right. So in the 1960s and 1970s, there was this big fight going on between the people who thought fat was the bad guy, and the people who thought sugar was the bad guy.
Now, on the sugar is the bad guy side was the British physiologist, nutritionist then, ultimately physician John Yudkin, and he was the one who said sugar was the problem. And on the other side, we had this guy, Ancel Keys, and he was the one who said saturated fat was the problem.
Now, both of them said what they said based on correlational studies. We now know that correlation is not causation. So to be honest with you, knowing what we know today, both of them were wrong, because both of them shouldn't have said anything. But back then, we didn't have those kinds of time-lapse studies where we could infer causation, we only had correlation.
Keys won the fight, in part because of three scientific discoveries of the 1970s. The first was the molecule called LDL, low-density lipoprotein. And we knew about children and young adults who died of heart attacks at 18 years of age, and they ended up having a disease called familial hypercholesterolemia, and they had a defect in their LDL receptor. So they couldn't clear their LDL, they had LDL levels in the thousands, and they would die of heart attacks, and this is what won Brown and Goldstein the Nobel Prize back in 1973.
The second piece of information was that dietary fat raises your LDL. And that is true, dietary fat definitely raises your LDL. And then the third piece of information was that LDL levels in large populations correlated with heart disease. So the assumption was if dietary fat raises your LDL, LDL correlates with heart disease, get rid of the dietary fat, LDL levels will go down, and heart disease will go away.
Andrew: And we lower the LDL...yeah. So does the heart disease. Yeah.
Robert: And Yudkin was thrown under the bus, Keys won the argument. We also now know that part of the reason people accepted that was because there were two scientists, professors at the Harvard School of Public Health, who had written two review articles back in 1967 in The New England Journal of Medicine, which exonerated sugar as being a cause of heart disease, and placed the blame squarely on saturated fat.
We now know, based on the work of my colleagues at UCSF, Cristin Kearns, Laura Schmidt and Stan Glantz, that those two review articles in The New England Journal in 1967 were faulty.
Andrew: Were faulty, yeah.
Robert: They were put-up jobs. They were paid off. To the tune of $6,500.
Andrew: Now, this has been recently exposed, yes, by looking at the sugar industries...?
Robert: Just last month, that's right.
Andrew: Is that right? Yeah.
Robert: The sugar industry had basically propagandised this issue to exonerate their product.
Andrew: Yeah.
Robert: So, we now know that the sugar industry had its thumb on the scale of this tenuous balance from the get-go. Nonetheless, Yudkin lost the argument, Keys won, and we all went low-fat. And when we went low-fat, we also went high sugar.
Andrew: Yeah, that's the problem.
Robert: Because the food would have tasted like crap. And in the process of going high-carb and high-sugar, which is what we did back in 1980, we have now had this pandemic of obesity, diabetes, heart disease, which we didn't get rid of, and now a new disease, fatty liver disease, which we didn't have before. And the rise of this new phenomenon, which now is called metabolic syndrome.
Andrew: Yeah.
Robert: And my job is to, number one, lay out the process by which metabolic syndrome occurs, and number two, reverse it. Which is what we do every single day.
Andrew: Now, I have to ask, sugar, probably the most widely used drug in the world...
Robert: Indeed.
Andrew: But sugar isn't one thing. It's like an apple, which sugar? Surely it isn't all bad, and what's the relevant dose? Because even fruit has sugar in it, right?
Robert: Well, of course. But fruit also has fibre, and the fibre is what mitigates the negative aspects of fruit. So, there's a big difference between fruit and fruit juice, and the difference is the fibre.
So, here's the way to think about it. Which would you rather have, an apple, which has, say, 30 calories and boatloads of fibre, or an eight-ounce glass of apple juice, which has 120 calories and no fibre? What do you think is going to do more damage to your liver?
So, here's the issue. You consume sugar, but if you consume it with its inherent fibre, that is fruit, the soluble and insoluble fibre that's within that apple or orange or whatever fruit you consume will form a barrier, a secondary barrier on the inside of your duodenum, inside your intestine.
It's a whitish gel, and you can actually see it on electron microscopy. And it acts as a secondary barrier, keeping a significant portion, anywhere from 25% to 30% of the nutrients, of the carbohydrate, of those simple monosaccharides, glucose and fructose from even being absorbed in the duodenum, and that protects your liver.
In addition, because you don't absorb them in the duodenum, they go further down to the jejunum. And what's in the jejunum that's not in the duodenum? Bacteria. There's virtually no bacteria in the duodenum because the pH just changed from the stomach, you have to wait for the pancreatic juices that come in via the sphincter of Oddi, into the duodenum to mix with everything before the pH will change to allow for bacterial growth.
So, the jejunum has all these bacteria in it. Now, each of us is 10 trillion cells, but we have 100 trillion bacteria in our intestine, they outnumber us 10 to 1. Each of us is really a big bag of bacteria with legs.
And those bacteria matter because the bad bacteria tend to make proteins called cytokines, which cause disease, and they have to be buffered by what seem to be fragile bacteria, which need more energy in order to proliferate, what we call bacterial or microbial diversity, this concept of the intestinal microbiome. Well, if you're absorbing all of your nutrients up in your duodenum because there's no fibre in your diet, what are the bacteria in your jejunum supposed to eat?
Andrew: Yeah.
Robert: So what happens is the bacteria that are more hearty and tend to be more disease-causing will proliferate. The other bacteria, which are more fragile, will tend to dwindle. This is the whole concept by which, you know, probiotics are being utilised. The problem is, if you don't fix the environment, you expect those probiotics to last?
Andrew: No.
Robert: So what's really neat, it's not probiotics, but prebiotics.
Andrew: Oh, yeah. Absolutely.
Robert: You need to change the environment in the intestine to allow for the good bacteria to grow. And the single most important prebiotic? Fibre. By far and away.
So if you eat your food with fibre, which is called real food, you're going to reduce your sugar consumption, you're going to increase your fibre consumption, you're going to reduce your absorption of nutrients that can potentially overload your liver, and you're going to increase your microbial diversity, thereby promoting metabolic health. It's called real food.
Andrew: Yeah, you just answered my next frame for questioning. And that was, basically, just look at the argument, if you like, between which one out, the sugar or the fat? And you know, both of those have issues.
And then you think in a simplistic view, one would say, “Kkay well, let's decrease both of those potential baddies” So what's left in our diet? Well, that would normally, most people would think, “Oh, protein.” So then you've got high protein, but if you have too much protein without other stuff, that will also change the conditions…
Robert: You get renal failure.
Andrew: So, the missing ingredient there is fibre. And that's the thing that can help fill us up, and…yeah.
Robert: That's right. Exactly. Exactly. And this is actually why I am not a fan of glycaemic index.
Andrew: Right.
Robert: Because glycaemic index ignores the issue of fibre. It also ignores the issue of fructose. So, the way to explain what's really good is not glycaemic index. I know glycaemic index is a big deal down in Australia.
Andrew: It was.
Robert: And I'm here to tell you that glycaemic index is a sham, it's a canard. What we should be talking about is something called glycaemic load.
Andrew: Load, yeah.
Robert: Now, what's the difference between glycaemic index and glycaemic load? The answer, everything. So a perfect example of how this works, let's take carrots. So carrots, they're good for you, right?
Andrew: But they're evil if you look on the glycaemic index load...glycaemic index, right.
Robert: That's right, that’s right. So if you consume 50 grams of carbohydrate from carrots, your blood sugar will go pretty high, so it has a high glycaemic index. However, how many carrots do you have to eat to get 50 grams of carbohydrate from carrots? The answer is you have to eat 700 grams of carrots. That's a lot of carrots.
Andrew: Yeah, it's kind of, it’s exactly like apples versus apple juice.
Robert: Absolutely, of course.
Andrew: Try and get the same caloric intake from eating apples as a glass of apple juice.
Robert: Absolutely. So, nobody eats 700 grams of carrots. So, every food is a low glycaemic load food if it comes with its inherent fibre.
Andrew: Yeah.
Robert: So if you eat real food, you're eating a low glycaemic load diet. Whereas if you're eating processed food, because there's no fibre, you're eating a high glycaemic load diet.
The other problem with glycaemic index is the molecule fructose itself. Now, glycaemic index is how high does your blood glucose level rise? Fructose is not glucose. So when you consume a fructose load, it doesn't raise your blood glucose, it raises your blood fructose. Which is seven times worse, because it binds to proteins seven times faster, causes seven times the denaturation of those proteins, and releases seven times the number of oxygen radicals, oxidative stress in order to damage cells and cause cell death and dysfunction.
Andrew: Right.
Robert: And it's not captured in the concept of glycaemic index because it raises your fructose level, not your glucose level. So, glycaemic index is, and in French, bullshit. It is garbage.
Andrew: Right. Right.
Robert: It is to be ignored. And I cannot stress that more than for the Australian audience that has been led astray over the past two decades.
Andrew: Oh, and more. I have to ask here, something that's just entered my mind is when you're measuring… if you're looking at diabetics, for instance, type 1 diabetics, and they're looking at insulin control, and they're looking at...they're measuring that with HbA1c for a three-month average of glycaemic control, how does fructose effect that measurement?
Robert: Well, that's exactly right, it doesn't affect that measurement because haemoglobin A1c does not measure fructose binding to the haemoglobin molecule. Because haemoglobin A1c only measures the glycation, the addition of a glucose to position one.
Andrew: Right.
Robert: That is why it's called haemoglobin A1c, because it's at position one on the haemoglobin A molecule.
Andrew: Right.
Robert: It turns out fructose, because of its stereochemistry, doesn't bind there. It doesn't bind to position 1, it binds at positions 66, 110.
Andrew: Right.
Robert: So you don't see it in your haemoglobin A1c, you would see it in your haemoglobin A66, 110, but no one measures that.
Andrew: And that's...
Robert: We actually have data that show that this fructosylation of proteins is part of the ageing reaction that drives diabetics, in particular who consume fructose because they're told to, because it doesn't raise their serum glucose.
Andrew: Yeah...I'm sorry, I don't understand this. When it's biochemistry, and it's there and it's known, I don't get the blinkers. I don't get this. I don't understand why it's not being raised in normal diabetic and endocrinological circles in all countries.
Robert: Well, I'll tell you why. Real easy. One word: money.
Andrew: Right.
Robert: Think about this. We have, in America, the American Diabetes Association. In the UK, you have Diabetes UK. And I think that that also works for Australia as well.
Andrew: Yes, Diabetes Australia.
Robert: The rest of the world has the International Diabetes Federation. Now, there's a big difference between the American Diabetes Association and Diabetes UK who are on one side, and the International Diabetes Federation on the other. Because the International Diabetes Federation member countries are so poor they can't even afford the refrigerator to keep the insulin in.
Andrew: Right.
Robert: They have to be for prevention. Prevention is essential. And so the IDF has lobbied the G20 to enact soda taxes around the world to stem the tide of diabetes type 2 around the world. Whereas the American Diabetes Association and Diabetes UK have actually come out and said that fructose plays no role in in the pathogenesis of diabetes, and in fact, it's a good thing to consume.
Andrew: What?
Robert: Why? Because of money. Because Diabetes UK and the American Diabetes Association are funded by big pharma. That's why.
Andrew: Yeah. So I have to ask then, for our listeners, our practitioner listeners out there, is the test available to be able to test for fructose effect on haemoglobin?
Robert: No. No.
Andrew: It's more of a research...
Robert: It's not immediately available. It would be a research tool, and only one or two labs around the world do it.
Andrew: Right.
Robert: There's a Japanese lab that does it, and my colleagues can do it although we're not set up for that.
Andrew: Got you. So, how do we therefore look at surrogate measures of that?
Robert: Yes. Well, so there are many things you can do in order to answer this question. And I think, based on our work, that the single two best surrogate measures, proxy measures are ALT, alanine aminotransferase, which is a marker for liver fat, and uric acid, which is a proxy for sugar consumption.
Andrew: Right.
Robert: Because when fructose enters the liver cell, it has to be phosphorylated. And since 100% of the fructose load ends up in the liver, so when you consume, say, a soda, you're going to get a big fructose load, so you're going to get a lot of fructose phosphorylation, which means a lot of ATP is going to be turned into ADP because the phosphate has to be donated.
And there's a scavenger mechanism in the liver known as adenosine deaminase 1, which then takes those ADPs and pulls the phosphates off to go to AMP, adenosine monophosphate, then to IMP, which is inositol monophosphate, and finally to the waste product, uric acid, which is then released from the liver, and then goes out in the urine. And if you put too much out in the blood, you will get gout. And you can also get uric acid stones.
Andrew: Yeah, yeah. And that explains to me why uric acid is a separate risk factor, at least in integrative circles, for cardiovascular disease as well. Because it's tied in with...
Robert: Absolutely. It's well documented, for type 2 diabetes as well. Because uric acid is a marker for metabolic syndrome.
Andrew: Right.
Robert: And the thing is that uric acid is also a marker for sugar consumption. So, this all is very internally consistent.
Andrew: Right. Okay, so I'm going to go on to a different sort of thing here, it's still all tied in with fructose consumption, and our insulin resistance sort of lifestyle. Most praccies are aware of insulin resistance, syndrome X, they're also aware of the burgeoning prevalence of non-alcoholic fatty liver disease, NAFLD. What's the link with fructose, and can you take us through what you termed the "two-hit theory of NAFLD" I read in your paper, in Nature?
Robert: Yes, absolutely. So, the bottom line is that because fructose is metabolised in the liver only, because only the liver has the GLUT 5 transporter, because fructose is not regulated by insulin and does not regulate insulin, and because fructose does not go to glycogen, it goes straight down to the mitochondria. And then the mitochondria become overwhelmed by the energy bolus because it becomes... fructose goes to acetyl-CoA, and the acetyl-CoA...
The mitochondria can only cycle at a certain rate. And if you go over that rate, then what happens is the mitochondria have no choice but to liberate the citrate that was formed. It goes out via a process called the citrate shuttle, it's now in the cytosol, and three enzymes in the cytosol act on it. Those three enzymes are ATP citrate lyase, acetyl-CoA carboxylase 1, and fatty acid synthase.
Those three enzymes together constitute what we call de novo lipogenesis, the new fat making. And so they take energy that the mitochondria should have burned but couldn't, and turns it into fat. And then that fat has one of two fates.
It will either precipitate in the liver as a lipid droplet, now you've got fatty liver disease, which then causes insulin resistance, it causes hyperinsulinemia, and it causes ultimately, type 2 diabetes.
Or it will be packaged and it will be released from the liver, and now you've increased your VLDL, very low-density lipoprotein, which you measure as your serum triglyceride. And that then can serve as a substrate for atherosclerosis. So, you can pick your poison. You basically can get type 2 diabetes, or you can get heart disease. Or both.
Andrew: Or both, yeah. Pick when.
Robert: Pick when, yeah. So the bottom line is, don't let that happen. And the easiest way to not let that happen is reduce the substrate at the level of the liver.
Well, there are four foodstuffs that are metabolised in this fashion, that is, they don't stimulate insulin, they're metabolised by the liver only, and they don't go to glycogen. Those four are trans fats, but we know that, and they're coming out of our diet, branched chain amino acids, leucine, isoleucine and valine. They are the stuff that's in protein powder that bodybuilders use to pump iron. But if you're not pumping iron, then eating extra branched chain amino acids only end up as liver fat. Alcohol, but kids don't drink alcohol. And finally, fructose.
Andrew: Yeah.
Robert: Those four foodstuffs are all independently related to the development of metabolic syndrome. And by far and away, sugar being the worst of the bunch because everyone is exposed.
Andrew: Now I have to play the devil's advocate here on a couple of things. So I guess the first one is, high-fructose corn syrup isn't prevalent in Australian foods.
Robert: That’s right.
Andrew: Tell me why we've still got the issue of obesity.
Robert: Because you have sucrose, because you have table sugar.
Andrew: Yeah.
Robert: You're right, the entire Pacific Rim, other than Japan, doesn't have high-fructose corn syrup. Korea doesn't have high-fructose corn syrup. Australia doesn't have high-fructose corn syrup. China doesn't have high-fructose corn syrup. And you all have the exact same diseases as we do because... And Malaysia doesn't have high-fructose corn syrup...because you have sucrose, you have table sugar.
You grow it there in Australia, in Queensland. And your parliamentary MP, I think his name is Boswell, read into the parliamentary record that I was a menace to Australian society. I would like to correct that.
Andrew: You're kidding.
Robert: No, I'm not kidding. I would love to debate Mr Boswell, and I will take him down…
Andrew: Yeah. Well, he's a politician. That would be...
Robert: ...in short order.
Andrew: That's all right, most Australians don't trust politicians.
Robert: Well, we don't trust our politicians either. I wonder why.
Andrew: No, I wasn't going to open up that one. Not at this stage.
So I have to ask about another… I know I'm sort of looping back to these biochemical entities, but I need to ask one which I'm totally ignorant about, and that was one that you mentioned in a couple of papers of yours, sirtuin A.
Robert: Ah. Well, sirtuin 3 and 1, 1 and 3. So, these are mitochondrial transcription factors that appear to be related to longevity. And people who have variants of sirtuin 1 and 3 seem to have reduced liver capacity to metabolise fructose. So a little sugar makes a lot of liver fat. And so it's particularly worrisome in people who might have problems in terms of liver fat metabolism.
Andrew: So then, I guess coming back to the diet, the treatment sort of thing, if you're looking at there's no one approach to obesity, what sort of testing the need to be doing? What sort of testing should practitioners be doing to categorise which sort of obese patient they have in front of them?
Robert: Right. So, I'll give you the script that we use in my clinic, and that hopefully will provide some guidance. So, a fat kid comes in, you take a look at the kid, almost always...not always, but almost always they have acanthosis nigricans, that ridging around the back of the neck that is indicative of insulin resistance.
So we point to the mother, and have the mother come over and look. You say, "See this? This is not dirt. This does not wash off. This is a sign of high insulin." So we haven't even drawn blood on your kid, and we already know your kid has high insulin. So every time your kid eats, insulin shunts a portion of that to fat, which is why they keep gaining weight. And as long as the insulin is high, we will not be able to turn this around. We have to get the insulin down.
Andrew: Right.
Robert: That insulin reduction is the directive, irrespective of calories. If we can get the insulin down, your kid wins. If we don't get it down, your kid loses. And in that way we, number one, medicalise it, and we partner with them to make it clear that they have to do something themselves.
So, we say, all right, how do you get insulin down? Well, there are three ways, diet, exercise, medicine. We never start with medicine, so that leaves us with diet and exercise.
So obviously, exercise is important. It helps burn energy, it makes you insulin sensitive, it increases muscle, and it grows mitochondria and thereby increasing burning, therefore, more insulin sensitivity. So more exercise, more better. So we impress upon them the need for their child to engage in some meaningful form of physical activity because of their insulin, not because of their weight. Then we say, “all right, now we're at diet.” How do you get insulin down with diet? Well, don't let it go up.
So, what makes insulin go up? Two things, refined carbohydrate, bread, rice, pasta, potatoes, and sugar. Now, what colour are those five things? White.
Andrew: Right.
Robert: Now, when wheat comes out of the ground, what colour is it? It's brown. But when you turn it into bread, what colour is it?
Andrew: White, yeah.
Robert: White. When rice is grown in the rice paddy, what colour is it? It's brown. But when you eat it at a Chinese restaurant, what colour is it? It's white. Where did the brown go? What was the brown? Well, the brown was the fibre.
But it was milled off at the mill, or polished, and that fibre, that whole grain, that brown rice was actually important because it supplied the fibre that makes your intestine do its job. So, we tell everyone you have to eat your carbohydrate with fibre. So you don't have to eat a low-carb diet, you have to eat a safe-carb diet.
Andrew: Right.
Robert: You have to eat brown food. So not bread, rice, pasta, potatoes, but beans, lentils, nuts, quinoa, farro, brown rice, other legumes because they contain fibre. Fibre is either brown or green, so brown and green food, that works. That supplies fibre to your intestine so that the intestinal bacteria can do their job.
And then finally, sugar. And so basically we say, your kid needs to eat a low-sugar, high-fibre diet. That's called real food. But right now, your kid is eating a high-sugar, low-fibre diet. That's called processed food. And so what we do is we teach them the difference between real and processed food. And a lot of parents don't know, a lot of parents grew up after 1980, when processed food really took over the marketplace, and they don't know that breakfast cereal is not food.
They think that a fruit-flavoured yogurt is food. And they don't understand the difference, they don't understand why these things don't work. We explain, and we explain the science behind it. Because if they understand it, then they can partner with you, and then they will actually be able to alter their home environment so as to allow for the insulin to be reduced and the weight to come down, and their metabolic health will improve. But not until they understand it.
Andrew: I have to ask two questions about… Well, I guess the first one would be there's a group of researchers, I think they're in Scotland, and what they were talking about was despite, the Scottish lay-public, a high prevalence of obesity, high prevalence...increasing prevalence of diabetes.
And what they were looking at was some sort of food that they could incorporate into, let’s say a lazy way of correcting a diet, if you like. So they're saying if they're not going to comply with a dietary change, what sort of intervention can they add that would change some sort of cardiac parameter risk? And what they came up with was, I think it was either 15 or 25 mils of olive oil.
Robert: Hmm...
Andrew: Right? So, that was one question. The second question is Dr Michael Mosley talks about high-intensity interval training or exercise, HIIT training.
Robert: Yeah. Right.
Andrew: What do you see is the relevance of these sorts of approaches long-term, given that they're not really correcting the original issue? Like, do you think it's just a Band-Aid?
Robert: Yeah, I'm not sure about the olive oil. I mean, certainly olive oil is a good thing because it stimulates...it's oleic acid, it stimulates the hepatic transcription factor PPARalpha, and that actually helps burn energy in the liver better. So there might be a value to it, although I would have to see the data in order to...
Andrew: Yeah, I think it's early days.
Robert: ...be able to say this is true or not true. In addition, high resistance interval training can also help increase mitochondrial biogenesis and increase the maximal velocity of the tricarboxylic acid cycle, thereby taking some of that acetyl-CoA that would have gotten turned into liver fat, and maybe it actually gets burned.
And there are possible repercussions that would be positive from that kind of thinking. The point is that you have to understand the mechanism. So, you need three things, you need plausibility, you need mechanism, and you need empiric data. And certainly, there's a plausibility argument, there is a mechanism, now we have to see the empiric data that says this is what's really going on.
Andrew: There's so much more to go into...and I've got to say this is going to be riveting for me, to learn about these mechanisms that drive not just insulin resistance, but also there's the resistant obesity, and why we should be looking deeper into it. And I think more so how we can treat these people to live happier, healthier lives by saying goodbye to sugar.
Robert: Well, I don't know that you need to say goodbye to it, but once upon a time, sugar was a treat. Now it's a diet staple.
Andrew: Yeah. Yeah.
Robert: Once upon a time, sugar was rare, safe, and rare, like abortion. Now, it's everywhere, and that's the problem. And the reason it's everywhere is twofold. One, we went low-fat, which was a terrible mistake. And number two, the food industry learned that when they add it, you buy more, because it's addictive. Which is also a mistake.
So, recognising those two facts, and recognising what that has done to our food supply, our global food supply, not just in America, not just in Australia, but truly around the world. And now, there's a diabetes pandemic in countries that aren't even fat, like China, Pakistan and India.
Understanding how the export of the Western processed diet has led to basically the fall of all of these healthcare systems around the world, trying to take care of chronic metabolic disease, this is what we should be focusing on and trying to remediate.
Andrew: Mmm. I think one of the saddest examples of what you're talking about there is the Okinawans. You know, a decade, not even a decade ago, they were praised, it was this hallelujah, Holy Grail of longevity, and now they've fallen by the wayside. They've got a massively increasing incidence of diabetes happening because the Western diet has gone in there.
Robert: Has taken over. Absolutely.
Andrew: Yeah. So, I can't wait, seriously Robert, for you to share with our audience at the symposium some of these…I'm going to say secrets, but you know, they're not. But I've got to ask one last thing. Where...
Robert: No, no, no, they're not secrets. They're not secrets.
Andrew: No, no, no.
Robert: But they are not what the food industry wants you to know.
Andrew: Yeah, that blindfold. Yeah. I've got to ask though, for our listeners that won't be able to attend the symposium, what sort of resources can you direct them to, to start learning about the different types of obesity and how they can treat their patients?
Robert: Well, the first place I would send them is a website that's curated by UCSF, known as sugarscience.org. This is 8,000 clinical research articles vetted by 12 independent scientists who do not take money, and distilled into five messages for the general public. And there's no policy, and it's just what you can do and what is the problem?
Andrew: Yeah.
Robert: And this is something that is very specifically catered to the average American, and potentially Australian. It's bringing the science to them. So, that's the first resource I would offer.
The second is the book I wrote called "Fat Chance," which has a lot of this information in it. We wrote a cookbook to go along with it, although the recipes are uniquely American, I'm sure, but nonetheless, are real food.
The problem is that here in America, 33% of adults don't know how to cook. They never learned. And if you don't know how to cook, then you're hostage to the food industry for the rest of your life. Which, by the way, that was their plan. So we have to fix that, we have to change that.
In terms of understanding the different types of obesity, I would say that, I wrote the textbook chapter in Sperling's textbook of Pediatric Endocrinology, which lays all of this out very completely and nicely.
Andrew: Beautiful.
Robert: It's hard to find short articles on this issue, parsing obesity, because there's so much to know. So, the chapter I wrote has all of this in it.
Andrew: Well, and I think we might put that reference up on our FX Medicine website for our listeners. So it's Sperling's textbook of endocrinology, is that right?
Robert: Oh, Paediatric Endocrinology.
Andrew: Paediatric endocrinology.
Robert: Paediatric endocrinology.
Andrew: That would be a worthwhile text.
Robert: And in addition, I don't know, do you get Netflix in Australia?
Andrew: Yeah.
Robert: Okay, well, there are two movies that you can watch. One is called "Fed Up," another is called "Sugar Coated." There's also a third movie that was made in Australia, called "That Sugar Film."
Andrew: Oh, yeah.
Robert: And also, we made a public television special here in the United States, called "Sweet Revenge." It's available by DVD. It probably doesn't play in Australia, but you can certainly buy the DVD. And it is very specifically geared to teaching people about the relationship between food, insulin, and health.
Andrew: I've got to say, like, not being a...let's say not being a total success story, but just on my starting journey on my beginnings of getting away from sugar, just decreasing by half the amount of sugar in a coffee, and wow.
It's exactly like Stephen Fry said, I'm tasting the coffee. Of course, what it's made me into as a coffee snob, but it's really amazing, you know? Like, I'm so proud now that we shop from the outside of the supermarket, and rarely do we venture into the inside aisles.
Robert: If you've gone into the aisles, you've gone off the ramp.
Andrew: Yeah, yeah...just doing these simple things, and wow. Wow.
Robert: Actually, it makes a big difference.
Andrew: Yeah.
Robert: The last thing I would suggest is that your listeners might want to log on to our nonprofits website, which is the Institute for Responsible Nutrition, responsiblefoods.org. We take no money from any food industry concern, and so everything that's on there is completely vetted and independent, not food industry propaganda. Because it's actually very hard to find information that is not controlled by the food industry, as this New England Journal debacle has demonstrated.
Andrew: Well, we'll definitely be putting all of these references and resources up on the FX Medicine website for our listeners. Professor Robert Lustig, I can't thank you enough for joining us today, and educating me in so many areas.
Robert: My pleasure.
Andrew: And I'm sure that our listeners have gotten something out of this, and I just seriously cannot wait. I'm so sorry, when I meet you I'm going to tackle you, and I'm going to take all of your time up, and suckle everything that's in your brains out. So, forgive me when I meet you at the symposium next year.
Robert: It will be my pleasure.
Andrew: Thanks, Professor Lustig. And this is FX Medicine, I'm Andrew Whitfield-Cook.
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