The Peter Attia Drive - #14 - Robert Lustig, M.D., M.S.L.： fructose, processed food, NAFLD, and changing the food system

00:00:00.000 Hey everyone, welcome to the Peter Atiyah Drive. I'm your host, Peter Atiyah.

00:00:10.140 The Drive is a result of my hunger for optimizing performance, health, longevity, critical thinking,

00:00:15.600 along with a few other obsessions along the way. I've spent the last several years working with

00:00:19.840 some of the most successful, top-performing individuals in the world, and this podcast

00:00:23.620 is my attempt to synthesize what I've learned along the way to help you live a higher quality,

00:00:28.360 more fulfilling life. If you enjoy this podcast, you can find more information on today's episode

00:00:33.000 and other topics at peteratiyahmd.com.

00:00:41.360 In this episode, I'll be speaking with my friend, Dr. Rob Lustig, who I suspect a good number of you

00:00:47.060 will have already heard of and certainly have been familiar with through his pretty impressive

00:00:50.940 presence on YouTube and his talk called Sugar, the Bitter Truth that went viral, I believe,

00:00:57.180 in 2011. And that's about the time when I met Rob. Now, this podcast kind of grew out of a really

00:01:03.880 interesting discussion that I think I get into in the podcast a little bit, but I think it was in

00:01:08.580 2016 when Rob and I were both invited to Hong Kong to speak at the Credit Suisse Asian Investment

00:01:16.540 Conference. And we were on a panel together and it just so happened that we were on the same flight

00:01:21.940 back to San Francisco, which was not just a long flight, but more importantly, a flight where you

00:01:26.800 weren't going to be sleeping much. And Rob and I ended up huddling together over a laptop, going over

00:01:33.580 some really interesting data on NAFLD, which we'll get into in this podcast. And I remember thinking like

00:01:40.820 that just kind of left an impression in my mind, which was, God, this is the kind of discussion I really

00:01:44.640 enjoy having with people like Rob because it gets into the nuance and away from the headlines. And

00:01:50.440 obviously, many years later, forward, fast forward to where we are now, I'm starting a podcast. One of

00:01:54.820 the first people I wanted to reach out to was Rob to have this discussion. Rob has very recently stepped

00:02:00.280 down from his clinical responsibilities as a pediatric endocrinologist at UCSF. However, he still has a very

00:02:06.960 active presence in his research department. Rob holds a bachelor's degree from MIT. He got his MD from

00:02:12.740 Cornell. And he also has a master's of studies in law from UC Hastings, something that he did probably

00:02:18.100 about four years ago, as he began to realize that only one half of the equation in educating people

00:02:24.940 about sugar was going to come from the scientific standpoint. The other half was going to have to be

00:02:29.420 policy related. In this episode, we talk about a lot of things, but among them, we talk about why Rob

00:02:33.660 believes the food business has really pushed towards having more and more sugar in it and why these have

00:02:38.860 led to the epidemics of addiction, depression, et cetera. He talks also about how you can combat

00:02:43.780 that. And I think something that people miss in Rob's headlines is that he is not just talking about

00:02:49.500 avoiding sugar. He's also talking about the importance of fiber. And we actually get into a

00:02:53.180 very nice discussion about the differences between soluble and insoluble fiber and how it's actually not

00:02:57.900 uncommon for people to load up too much through processed foods on the soluble fibers, but they're not

00:03:03.820 getting the full benefit without having the insoluble, which is really stuff that's hard to get

00:03:08.620 without looking towards real foods, particularly vegetables. This was really a fun podcast.

00:03:14.400 And I think that comes across in how often we unfortunately probably talk over each other.

00:03:18.600 So I apologize for that in advance. This is also one of the first podcasts I record. So I was still

00:03:23.060 sort of, and I'm still sort of learning the ropes of how to do this. Unfortunately, Rob had to go to,

00:03:30.620 I believe to a deposition that morning. And so we had a really hard stop that didn't give us

00:03:36.060 nearly as much time as I think we would have spent on this topic, but I do suspect that Rob and I will

00:03:42.660 talk again. We also get into some of the really, I think kind of practical stuff around what is it

00:03:47.480 like to be a parent when you're trying to balance the desire to, you know, let your kids be kind of

00:03:53.500 normal and deal with the convenience of not making every meal, something that requires a day of

00:03:58.940 planning. But how do you prevent them at the other end of that extreme from, you know, sort of

00:04:02.980 mainlining those nasty Capri suns and wheat thins and things like that. So I think some practical

00:04:09.120 advice there is helpful. We do go really deep on fructose and there is some biochemistry in there.

00:04:14.400 It does get a little nerdy. Rob can talk kind of fast and he really knows his stuff on this topic.

00:04:20.300 So he does not pull back from any of that terminology. We're going to do our best to link in

00:04:25.380 the show notes to some of the definitions and some of the things in there that we get into that will

00:04:29.140 give you a little bit of background. We also get into liver function testing, something that I

00:04:32.860 think many people take for granted when they go to their doctor, but it becomes really important

00:04:36.400 when you're trying to screen out people who might have NAFLD, non-alcoholic fatty liver disease or

00:04:41.700 NASH. It's more progressed sibling. We talk about uric acid. We talk about metabolic syndrome. We just

00:04:47.580 talk about a whole bunch of things, including we talk about heart rate variability near the end.

00:04:52.500 And at the time, Rob asked me a question I didn't know the answer to. We have since learned the answer

00:04:56.420 to that question because I was really intrigued by the discussion. And so for anybody who's interested

00:05:01.480 in that little nuance on heart rate variability, we're going to link to that as well. You'll be

00:05:05.800 able to find a lot more information about this, including information about Rob himself and what

00:05:10.780 he's doing. And also just the stuff that we talk about at peteratiamd.com forward slash podcast.

00:05:16.460 So without further delay, here is my really interesting and intense discussion with Dr. Rob Lustig.

00:05:22.180 All right, Rob. Well, thank you so much for making time today to have this discussion.

00:05:29.300 Oh, Peter is my pleasure. My pleasure.

00:05:30.260 We've known each other for, I think about six or seven years now.

00:05:33.760 Yeah, about right.

00:05:34.600 And what made me think about talking to you at this point in the podcast, which is to say very

00:05:40.920 early on, as I was thinking back to two years ago when we went to Hong Kong together and by sort

00:05:47.360 of luck, we ended up on the same flight back to San Francisco. And we were probably the two geekiest

00:05:53.200 guys on the airplane because the laptop-

00:05:54.940 You're the only ones not sleeping.

00:05:56.460 Right, right. And then the laptop came out and then it was all data, all flight. And it was awesome.

00:06:02.180 And it's experiences like that that have made me think like a podcast can be a fun way to

00:06:07.060 reproduce some of those discussions that I often find myself having and then thinking,

00:06:11.140 God, I wish everybody could have heard that because I learned a lot during that time.

00:06:15.340 Yeah. It's vice versa, by the way. And people wish they were flies on the wall. So, you know,

00:06:22.340 I'm happy to do this. This is great.

00:06:23.760 Awesome. Well, you've spoken so much and so eloquently about sugar and fructose, and certainly

00:06:29.760 we're going to talk about a lot of that stuff today. But I also want to talk about some things

00:06:34.040 that I think are a little less understood. For example, the impact of fructose on inflammation

00:06:39.440 and things like that.

00:06:41.240 Well, what data we have.

00:06:42.960 Yeah.

00:06:43.100 By the way, let me qualify. While I do know a whole lot about sugar, fructose, you know,

00:06:50.100 metabolic disease, really my issue is processed food. Processed food has several things wrong

00:06:58.200 with it. Sugar being one of them, but lack of fiber being another. And I think that that

00:07:03.100 is equally important. And I'm very willing to talk about that issue as well.

00:07:07.160 Perfect. So let's start with a very brief set of the semantics that I think it's important for people

00:07:13.820 to understand when they do confuse fructose and glucose. They're both carbohydrates. What's the

00:07:18.340 difference?

00:07:18.980 Well, they're both monosaccharides. Glucose is the energy of life. Every cell on the planet burns glucose

00:07:26.720 for energy. Glucose is so important to functioning in all eukaryotic organisms. Single cell versus

00:07:37.140 multi-cell doesn't matter. It's so important that if you don't consume it, your body makes it.

00:07:44.720 It can make it from amino acids. It can make it from fatty acids called gluconeogenesis. Those amino acids or

00:07:52.960 fatty acids will go to the liver. The liver will metabolize those and produce glucose. And so you

00:07:59.780 can consume zero glucose, but you will still have a blood glucose level. The Inuit, they didn't have

00:08:07.940 any carbohydrate. They didn't have any place to grow a carbohydrate. They had ice. They had whale blubber.

00:08:14.760 They still had a serum glucose level. And we knew that as early as 1928. So glucose is super important.

00:08:22.080 And I don't argue that. It's so important that your body has a fail-safe mechanism.

00:08:27.920 Fructose, however, is completely vestigial to all animal life. It is a storage form of energy

00:08:35.860 in plants. Plants can utilize fructose for energy. We have the capacity to metabolize a limited amount

00:08:45.680 of fructose for energy. Really, when you're consuming fructose, your gut bacteria are more

00:08:53.120 adept, since they're plants, at being able to metabolize that fructose than you are.

00:08:59.240 So when you're consuming fructose, yes, you will absorb some, but for the most part, it's actually

00:09:06.600 more plant food than it is animal food. In addition, there are some very specific biochemical differences

00:09:14.780 between the two molecules. Glucose is a six-membered ring. Fructose is a five-membered ring. Now,

00:09:21.380 that becomes important because both glucose and fructose and every monosaccharide exists in two

00:09:29.900 forms. One is called the ring form, and the other one is called the linear form. The linear form has

00:09:36.260 the capacity to bind to proteins called the Maillard reaction. It's what makes hemoglobin A1c in

00:09:42.640 diabetics, also known as the amadori rearrangement. This is a biochemical process that occurs normally.

00:09:51.420 It is the browning reaction. It causes bananas to brown. It causes humans to brown. In fact,

00:10:01.520 we're all browning right now because our mitochondria in our cells are engaged in the

00:10:08.320 amadori rearrangement. It is what makes people age. It is the aging reaction. And I show a slide

00:10:16.060 which shows newborn rib cartilage nice and white and 88-year-old rib cartilage nice and brown. Okay,

00:10:22.960 we're all browning. So you can roast your meat in an oven for 375 degrees for an hour, or you can roast

00:10:31.640 your meat at 98.6 degrees for 75 years. Ultimately, the answer is the same. You brown. Why do I bring

00:10:38.360 this up? Because glucose causes that browning reaction at a relatively low rate. Fructose makes

00:10:46.360 that reaction occur at seven times faster rate. Now, this starts with this shift reaction, correct?

00:10:53.620 So it forms a shift base. Okay. Right. So it starts with, and it's non-enzymatic. It happens

00:10:59.540 just in a test tube with no enzymes needed. You just put it in the sunlight. It will happen.

00:11:05.820 What happens is that the aldehyde moiety of the glucose in the linear form will bind to an epsilon

00:11:12.940 amino group of lysine, which is at position one in hemoglobin, and form a shift base, which then

00:11:19.520 spontaneously decomposes to form a covalent linkage, which won't come off and basically will

00:11:25.860 stay there until that hemoglobin molecule is recycled by the spleen. So this is why you can measure

00:11:34.280 glucose levels through hemoglobin A1C is because the higher the glucose level in the blood,

00:11:40.660 the more this reaction occurs. And therefore the higher the hemoglobin A1C.

00:11:46.120 Turns out fructose does it seven times faster. And not only that, every time it happens, it's

00:11:51.760 causing those proteins to become less flexible, so less functional. And every time it happens,

00:11:57.280 it throws off a reactive oxygen species, an oxygen radical, a hydrogen peroxide, which then can do

00:12:04.900 damage unless it's quenched by an antioxidant. So in the face of antioxidant deficiency, which is

00:12:12.260 called processed food, it can actually cause inflammation and non-alcoholic steatohepatitis and

00:12:19.680 many other problems related to the inflammatory response. So fructose does that seven times faster

00:12:28.040 than glucose. A third thing that is different is that when you put glucose in the stomach,

00:12:33.080 your hunger hormone called ghrelin goes down. When you put fructose in the stomach, it doesn't

00:12:38.280 change. So when you consume a lot of fructose, your brain doesn't know you've eaten. And so you end up

00:12:45.240 consuming more. And lastly, glucose is metabolized in the brain. The areas that basically metabolize

00:12:54.480 glucose and give you a functional MRI signal are areas that have to do with the sensory motor cortex for

00:13:02.140 the most part and for the basal ganglia. Fructose specifically lights up the reward center and has

00:13:10.100 been now been shown to induce the same physiology in the brain that cocaine, heroin, nicotine, alcohol,

00:13:17.940 any hedonic substance also generates. It is the reward signal. And in fact, we treat it as a reward

00:13:26.280 signal. It's called dessert. So fructose and glucose are not the same. The food industry would

00:13:34.260 have you believe a calorie is a calorie. A sugar is a sugar. You need sugar to live. Those are all

00:13:40.320 food industry mantras. They're all out in the cybersphere and in the blogosphere. It is absolute

00:13:48.280 garbage. They are quite different and it does matter.

00:13:52.180 I want to go back to just something very minor that you mentioned. I get asked this question

00:13:56.240 all the time and I've never had a compelling answer, but we use hemoglobin A1c as sort of a

00:14:01.640 surrogate proxy for average glucose levels. Now, for reasons we won't get into today just for time,

00:14:07.120 I'm not particularly convinced hemoglobin A1c in an absolute sense provides great insight.

00:14:11.380 Oh, I agree.

00:14:12.100 On a relative basis, it can be somewhat helpful, but at least directionally it's helpful.

00:14:16.360 Within any given patient, a lowering of a hemoglobin A1c from point A to point B would

00:14:22.240 be a good thing. I won't argue that.

00:14:24.500 So the question becomes, do we have comparable biomarkers that can give us some indication

00:14:30.840 of average exposure to fructose over a given period of time?

00:14:34.480 Right. Awfully good question. So fructose also binds to hemoglobin, but it does not bind at position

00:14:40.680 one. Therefore you don't measure it in hemoglobin A1c. So it binds at positions 66 and 110. Now the

00:14:49.280 hemoglobin A1c assay is not set up to look at 66 and 110. This requires a major research lab. It

00:14:57.000 requires tandem mass spec. It's a huge undertaking. It's only done as a research tool. And the only lab

00:15:04.080 I know that does it is in Japan. So that's not a rational thing to expect right now. People are

00:15:12.320 looking for long-term biomarkers of fructose consumption. And there have been several papers

00:15:20.320 that have come out that are pointing to individual options, but none have been put into clinical

00:15:26.800 practice. None have been shown to really validate consumption in a meaningful way. So at this point in

00:15:32.860 time, we don't have that for consumption. What we do have are some indirect measures of fructose,

00:15:41.520 shall we say, biotoxicity. Yeah. Like uric acid or ALT would be two examples. Exactly. Those are the

00:15:47.140 ones I was going to bring up. Exactly. Uric acid and ALT. So we know that the more sugar you consume,

00:15:53.900 the higher your serum uric acid goes and the more risk you have for gout. Benjamin Franklin knew that

00:16:01.680 and wrote about it. The reason that happens is because since fructose can only be metabolized in

00:16:10.180 the liver because the liver has the GLUT5 transporter, every time a fructose molecule enters

00:16:17.120 a liver cell, it has to be phosphorylated. So it goes from fructose to fructose 1-phosphate,

00:16:23.140 and the enzyme that does that is called fructokinase. Well, the phosphate has to be donated and ATP is the

00:16:30.740 donor. So ATP becomes ADP. Adenosine triphosphate becomes adenosine diphosphate. Now, there is a

00:16:39.280 scavenger enzyme in the liver called adenosine diaminase 1. And what it does is it then takes

00:16:46.900 ADP down to AMP, monophosphate, then to IMP, inositol monophosphate, and finally to uric acid.

00:16:54.420 So the uric acid concentration in the blood is a proxy for total fructose consumption. Now,

00:17:01.700 there are other things that make uric acid go up too, like protein. But all things being equal,

00:17:07.060 they do correlate with each other. And we've shown that serum uric acid in children and adolescents

00:17:11.600 correlate with sugar beverage consumption, for instance. And other people have shown that that

00:17:16.840 uric acid matters because uric acid is the inhibitor of endothelial nitric oxide synthase.

00:17:23.740 That's an enzyme that exists in your vascular tree that vasodilates the blood vessels. And that

00:17:31.880 keeps your blood pressure down. And we have shown that every increase by 10% in fructose consumption

00:17:40.220 increases your blood pressure by 2 millimeters of mercury consistently. And that increases your

00:17:47.600 risk of stroke by 10%. We have data. And it's also been shown by Dan Feig at UT San Antonio that if you

00:17:55.960 give an inhibitor of uric acid synthesis, allopurinol, which is what we give to gout patients, you can

00:18:01.840 actually lower adolescents' blood pressures when they have essential hypertension. So this is a

00:18:07.500 mechanistically valid problem. And it is a surrogate proxy biomarker sort of for sugar consumption.

00:18:20.580 ALT is also a surrogate marker in a similar way. ALT goes up when your liver stores fat.

00:18:29.380 What's the difference between... I mean, patients are sort of familiar with the difference between ALT

00:18:33.500 and AST, but they both show up as liver function tests. But guys like you and I tend to spend a

00:18:38.680 little more time looking at ALT.

00:18:40.380 Right. So AST, which is aspartate aminotransferase, is a biomarker for mitochondrial

00:18:46.980 function. And ALT is alanine aminotransferase, and it is a biomarker for degree of liver fat.

00:18:55.580 So they're both important, but in different ways. AST is much more minute-to-minute.

00:19:01.640 Like, what did you eat at your last meal? ALT is a little bit more, shall we say,

00:19:08.020 stable over time. So we tend to use ALT. However, we've shown that when you cut sugar back,

00:19:13.280 AST changes, suggesting mitochondria are actually getting better.

00:19:17.660 And the ranges on these things keep drifting upward for what people deem acceptable.

00:19:22.720 I tell my patients, I want their ALT below 20. And they say, but Peter, the range says up to 42.

00:19:28.500 Indeed. This is huge, and I'm glad you brought it up. So I entered medical school in 1976.

00:19:37.740 And at that time, the upper limit for normal for ALT was 25. Now, when we talk about upper limits

00:19:46.220 for normal, where do those calculations come from? Basically, you take a bunch of, quote,

00:19:53.000 normal people, and you figure out the mean, and you look at two standard deviations around the mean,

00:19:59.280 and that's how you decide what is normal. So in 1976, 25 was two standard deviations above the mean.

00:20:09.900 Today, 40 years later, 40 is two standard deviations above the mean. Did something happen to the assay?

00:20:17.460 No. Something happened to us. Because now everyone has fatty liver disease. In fact,

00:20:24.760 the Dallas Heart Study showed that 40% of normal people have hepatic steatosis, liver fat. Well,

00:20:31.980 that makes your ALT go up. So what I say is 25 was the upper limit of normal. 25 should still be the

00:20:41.800 upper limit of normal, despite what it says on the lab slip, because that's just looking at two standard

00:20:47.140 deviations above the mean. So we use that very specifically in clinic to show parents and kids

00:20:56.020 what is happening to them and why sugar is the bad guy, because when we get them off sugar, the ALT

00:21:02.080 drops within a month. Yeah. And going back to the uric acid thing, I was very influenced by the work of

00:21:08.660 Rick Johnson. And Rick has been always incredibly generous with his time and insights. And one of

00:21:14.420 the things I started doing probably about three years ago was just basically saying it's non-negotiable.

00:21:20.460 All my patients need a uric acid below five, even though the assay says we will consider normal up

00:21:25.880 to 7.0. Exactly. Same issue. So in clinic, we basically said 5.5 is sort of the break point.

00:21:33.620 So we're pretty close. ALT at 25, uric acid of 5.5. We can argue about the, we're within an order of

00:21:43.180 magnitude of each other. And that point is the same. And I think it's interesting because when we think

00:21:47.800 about cardiovascular disease, one of the things that the endothelial story gets overlooked a

00:21:53.060 little bit, the inflammation story is now getting its day based on these two very recent trials. Well,

00:21:58.340 one recent trial and one that was halted likely because of a significant improvement in the

00:22:04.180 outcome of using methotrexate. But when you look at the impact of uric acid on nitric oxide synthase,

00:22:11.300 when you look at the impact of homocysteine on asymmetric dimethyl arginine, which also then in

00:22:16.840 turn inhibits nitric oxide synthase, these things start to make a bit more sense, which is we always

00:22:24.000 kind of knew having high uric acid was bad. And we always kind of knew having high homocysteine was

00:22:28.400 bad. But now we're seeing these mechanistic reasons why all of a sudden, oh, wow, like that's a bad

00:22:34.740 thing to have, you know, vasoconstriction in your coronary arteries.

00:22:38.220 I couldn't agree more. The fact of the matter is we didn't have the empiric data. We always had the

00:22:45.260 plausibility argument, but we didn't know how important it was. Now we have the empiric data and

00:22:49.980 we have interventional data to say that this phenomenon is quite important. And it's not

00:22:56.420 its own phenomenon. It is a another manifestation of this global phenomenon we call metabolic syndrome.

00:23:04.660 And when you look at it that way and say, well, if it's doing this, what else is it doing?

00:23:10.440 All of a sudden things start piecing together. You know, it's like the puzzle, you know, and you sort

00:23:15.520 of needed the piece in the middle to fit all the other things together to be able to tell what's

00:23:21.800 really going on. And uric acid is part of that puzzle. Now, Rob, is there any situation under

00:23:28.320 which fructose consumed in its natural state, which is to say with water, with fiber, i.e. in fruit,

00:23:34.760 poses an advantage over glucose? Because clearly glucose has many advantages in terms of how

00:23:41.000 metabolically flexible, like, you know, every organ can basically consume it. You don't have a lot of

00:23:46.360 these other negative reactions. Is there something that fructose does better than glucose?

00:23:50.420 Yes. One thing. So if your liver is glycogen depleted, for instance, if you're a football player,

00:23:57.060 three hours on the gridiron, and you have depleted your glycogen stores from your liver,

00:24:02.220 and you consume a, say, energy drink or sports drink, you will replete your glycogen faster.

00:24:11.880 It will do that. I won't argue that. The reason being...

00:24:16.540 But this, to be clear, is only liver glycogen, not muscle glycogen.

00:24:20.000 Absolutely.

00:24:20.720 And muscle glycogen is a much bigger store.

00:24:22.900 Absolutely. You will replete your liver glycogen faster. There is a back door where you can turn

00:24:30.360 fructose back into glucose, which can then restore your liver glycogen. Now, the sports drink industry

00:24:38.760 makes a huge deal about this. I think this is truly a tempest in a teapot. I think this is

00:24:45.160 really irrelevant. And the reason is because after you've spent three hours on the gridiron,

00:24:50.440 you're not going to spend another three hours on the gridiron. Okay. And you will, by tomorrow,

00:24:55.980 have repleted those glycogen stores anyway, just from eating real food. So the idea that somehow

00:25:03.660 you have to replete your glycogen rapidly, just to me, does not hold water. Yeah. It's fine to

00:25:10.700 expend your glycogen stores in your liver and real food will get you back to the same place by tomorrow.

00:25:18.800 It also doesn't even make sense physiologically because the limit to performance is not liver

00:25:23.120 glycogen. It's muscle glycogen. Well, I'm not even sure that's true.

00:25:26.960 Well, that's right. When you hit people with glucagon who claim that they've sort of bonked

00:25:31.380 and hit the wall and there is no more glucose left, you'll still see a transient glucose spike.

00:25:36.180 Absolutely. Plus we have all these people who are now on high fat diets, ketogenic diets.

00:25:41.400 And how about the Ethiopians? They're not eating carbohydrates. The fact is you actually have

00:25:47.480 better sports performance using fatty acids and ketones than you do with carbohydrate. And the

00:25:53.980 reason is insulin. So I don't buy that for a minute as being important. Yes, it is true. You will

00:26:02.540 replete your liver glycogen faster. And that's true, true, and unrelated. It's like, so what?

00:26:08.780 Yeah. You very recently retired. Clinically, yeah. You're nowhere near retiring.

00:26:14.060 No, no. I've got a lot to do.

00:26:15.500 But you spent a lot of time, you're a pediatric endocrinologist, you spent a lot of time in

00:26:18.920 clinic with children who had diabetes, have been overweight, have been obese, have had NAFLD,

00:26:26.320 NASH, et cetera.

00:26:27.160 You bet.

00:26:27.420 Do you have a concern that children who undergo such metabolic transformation suffer an epigenetic

00:26:37.780 hit that makes it harder for them later in life?

00:26:41.200 What I know about epigenetics suggests that that is possible. I would even go so far as to say,

00:26:49.220 likely.

00:26:50.700 And it's frightening if it's, I mean, it's one of these things you hope is so untrue.

00:26:54.560 Right. But I don't know that. Here's what I

00:26:57.340 do know. And it's related, but not exactly the same. We know from animal work from both

00:27:07.180 Children's of Philadelphia and also from the Liggins Institute in New Zealand, that maternal

00:27:12.780 hyperglycemia causes epigenetic changes.

00:27:16.560 This is in utero.

00:27:17.400 In utero. Causes changes in H19, the different epigenetic markers that we have on chromosomes

00:27:24.860 that then portend metabolic dysfunction later on. So if that's true in humans, and no one's proven

00:27:34.620 that that's true in humans, it could explain a lot of the things that we do see. We know from a

00:27:41.700 biochemical standpoint, animals that are stressed or animals that consume large amounts of sugar during

00:27:48.840 pregnancy, end up with offspring that will manifest various aspects of the metabolic syndrome later.

00:27:56.560 Do we know that that's through epigenetics? Not yet. But if the rodent studies are similar to,

00:28:03.660 you know, what happens in primates and humans, it's not too far afield and it's not too much of a jump.

00:28:10.180 Yes. I'm very concerned about it because as you know, epigenetics is the gift that keeps on giving.

00:28:16.740 You can change the F1 generation and still find that epigenetic change and therefore the

00:28:23.660 metabolic alterations in the F4 generation. So it might explain why things keep getting worse year

00:28:33.020 after year is because we're adding on all the time and more people are entering this epigenetic

00:28:41.240 disaster. But I don't know that. That's a guess.

00:28:44.580 I mean, it's sort of one of those things where we have to sort of take a little bit of the

00:28:47.620 precautionary principle, right? So you say, well, if there is an epigenetic reprogramming that occurs,

00:28:54.620 then as parents, we need to be thinking a little bit more about the food environment our kids are in

00:29:00.240 because this is one of those things. We're pretty familiar with the notion that if you don't

00:29:04.440 discipline your kid, you're really not doing them a favor 20 years down the line. And this would be

00:29:09.840 another variant of that. And of course you would say, well, what if this turns out to be untrue?

00:29:14.000 What if there is no epigenetic signature? It's like, okay, well, what was the downside of trying

00:29:19.700 to get your kids to eat well? No argument. There's one downside and it's-

00:29:25.600 It's the effort that's required.

00:29:26.860 Exactly. That's the downside. So we have these data. How many times do you have to introduce

00:29:33.680 a savory food to an infant before they will accept it?

00:29:37.900 Oh, I don't know. Three, four?

00:29:39.740 Median 13.

00:29:40.720 Wow.

00:29:41.600 How many times do you have to introduce a sweet food to an infant before they will accept it?

00:29:46.820 Let me tell a funny story for that. When my daughter, who is now 10, turned six months old,

00:29:52.260 and I have this on video. We took her down to Del Mar for a walk on the beach and got an ice cream

00:29:58.360 cone. And we were like, all right, she's had nothing but breast milk and some formula for the

00:30:02.520 last six months. What will she do with some soft vanilla ice cream? And our thought was the cold

00:30:07.720 would turn her off. It was a foreign substance, whatever. And it's one of the funniest videos I've

00:30:14.000 ever seen because she puts her face into this vanilla ice cream and I've never seen her eyes

00:30:19.420 open so much. And I joked about it. I was like, holy shit, look at the dope. You can almost see

00:30:26.380 the dopamine firing.

00:30:27.900 You needed to put her in the functional MRI right then and there. Michael Pollan describes this in

00:30:33.760 The Omnivore's Dilemma, the first time he introduced birthday cake to his son. And he looked at him

00:30:41.140 like, you've been holding out on me. This exists in the world. And this is the first time I'm getting

00:30:47.820 it. I'm going to devote my entire life to sequestering all this stuff just to spite you.

00:30:54.780 It's incredible. Actually, my youngest son turns one on Wednesday of this week.

00:31:00.520 Congratulations.

00:31:00.800 So thank you. So he's going to get a cupcake. That'll be his first junk food.

00:31:05.840 You sure you want to do that?

00:31:07.520 Just because I love watching this reaction. Going back to this thing, I'll tell you something.

00:31:11.800 Get the MRI.

00:31:12.740 Yeah, yeah, yeah. When my daughter was growing up, so before she got to school, all she drank was milk

00:31:18.380 and water. And when she was about five years old, she was at a birthday party and they had these

00:31:24.400 things called Capri Sun, which are like, I don't even know how these things are legal because

00:31:28.420 they're basically syrup in a tinfoil bag. They're really gross. I mean, they take it to a new level.

00:31:34.220 They do.

00:31:34.920 She took one sip of one and pitched it.

00:31:37.600 Good.

00:31:37.740 And I was like, oh, Olivia, why didn't you drink that? She's like, it's really gross.

00:31:41.280 It is gross.

00:31:41.780 It was okay. Well, fast forward five years later, she drinks that stuff anytime she's at a kid's house.

00:31:47.260 Right.

00:31:47.480 Like even something that seemed so physiologically nauseating at one point in time, she's acclimated

00:31:54.020 to.

00:31:54.500 Right. And there's data on desensitization of taste buds. And one of the reasons why you keep

00:31:59.520 wanting more and more sweet is because the taste buds get downregulated and there's data now that

00:32:05.480 actually supports that in humans. So there's this desensitization issue. There's also the desensitization

00:32:11.640 of dopamine receptors because dopamine receptors go down in response to constant bombardment by

00:32:18.020 dopamine. It's the phenomenon of tolerance.

00:32:20.260 This would be very, is this a controversial point?

00:32:23.240 No.

00:32:23.340 Because this is the sin qua non of what makes cocaine so dangerous. I mean, I have a number

00:32:28.160 of patients who recreationally use cocaine and I don't want to be like the alarmist who just says,

00:32:32.620 don't do drugs because drugs are bad. I want to make the point that says, look, not all drugs are

00:32:36.300 necessarily bad, but cocaine has two problems, at least as far as I can see. The first is,

00:32:41.640 you have a nonlinear asymmetric risk of something really bad happening as far as cardiac dysrhythmia.

00:32:47.380 So why would you take that risk? But the second issue is this downregulation of dopamine receptors

00:32:53.360 that develops this tolerance and therefore makes it actually harder for you to experience joy

00:32:59.140 subsequently.

00:33:00.340 Indeed. So here's the deal. Neurotransmitters are either excitatory or inhibitory. Now neurons like

00:33:08.480 to be excited. That's why they have receptors in the first place. But neurons like to be tickled,

00:33:13.740 not bludgeoned. They like to receive the neurotransmitter, fire, and then come back to

00:33:20.520 baseline. Chronic overstimulation of any neuron leads to neuronal cell death, period. And we know

00:33:29.700 this because we take care of all these kids with chronic seizure disorders in the ICU and we're doing

00:33:35.000 our best to try to stop those seizures, not because of the seizure, but because of the brain damage that

00:33:40.740 occurs from continued overstimulation. So any neuron that is an excitatory, that's downstream of an

00:33:51.840 excitatory stimulus, it wants to protect itself. It has a plan B. It has a fail safe. What it does is it

00:33:58.460 down-regulates the receptor. That means that there's less likelihood that any given molecule

00:34:04.040 will find a receptor to bind to, thereby reducing the risk for cell death. So what does this mean

00:34:11.220 in human terms? You get a hit, you get a rush, receptors go down. Next time you need a bigger hit

00:34:17.480 to get the same rush and the receptors go down and then a bigger hit and a bigger hit and a bigger hit

00:34:21.660 until finally you get a huge hit to get nothing. That's called tolerance. And then when the neurons

00:34:27.080 actually do start to die because chronic stimulation causes neuronal cell death, that's called addiction.

00:34:34.540 And those neurons don't come back. Once they're dead, they're dead. And that actually limits your

00:34:40.060 ability even after rehab of being able to experience that same level of reward because now you don't even

00:34:47.300 have the dopamine to be able to do it because those neurons are dead. So not every drug is

00:34:54.820 stimulatory. There are drugs that are inhibitory. If you're inhibiting the next neuron, do you have to

00:35:01.120 down-regulate the receptor? No. So like a benzodiazepine, for example. Benzodiazepines are inhibitory.

00:35:06.880 Turns out, psychedelics are inhibitory. So serotonin, 2A and 1A are inhibitory. So when

00:35:16.500 the DEA clamped down in 1970 with the Controlled Substances Act that made marijuana and psychedelics

00:35:25.200 and, you know, everything, Schedule 1 and, you know, unavailable, there were a whole bunch of people

00:35:29.480 using psychedelics. They didn't end up in the emergency room. They didn't end up with withdrawal.

00:35:35.800 And the reason was because they didn't have down-regulation of their receptors because those

00:35:41.160 were inhibitory. So not every drug fries neurons. But cocaine does.

00:35:47.480 Yeah. Help me understand how alcohol fits into this because alcohol is, of course, a gab...

00:35:51.060 Ethanol, per se, is a GABA agonist. So it should be at least depressing in that sense. But yet ethanol

00:35:56.480 has some of these negative properties in the brain that you've just alluded to.

00:36:00.120 Well, the problem is ethanol in the brain also because it's polar and it dissolves lipids.

00:36:06.860 It also creates acetaldehyde. So that's the first step in terms of metabolism of ethanol,

00:36:13.400 which then can cause that Maillard reaction because you've made an aldehyde,

00:36:17.220 which then generates reactive oxygen species. So you can kill neurons, not necessarily from

00:36:23.100 excitation, but from the biochemistry of the molecule.

00:36:27.040 So we talk a lot, and we might not even get into it today because you've spoken so eloquently

00:36:30.840 about it elsewhere, about the similarities between ethanol and fructose in the liver.

00:36:34.800 In the liver, yes. How are they similar in the brain, if at all?

00:36:38.040 So they both stimulate the reward center.

00:36:40.300 Though it seems through different mechanisms.

00:36:41.920 Yes, likely through different mechanisms. There are a lot of different dopamine stimulators.

00:36:47.420 There are substances, and they're all different, cocaine, alcohol, nicotine, sugar, heroin.

00:36:55.500 They have different mechanisms, but they all ultimately impact on dopamine the same way.

00:37:01.640 We also have behaviors that are addictive, gambling, shopping, internet, social media,

00:37:09.560 pornography, okay? There's an aholic next to every one of those too, right? Chocoholic,

00:37:15.460 sexaholic, whatever, because they're stimulating dopamine also, but they're not chemicals.

00:37:20.060 They're behaviors, but they still generate that same dopamine response, and therefore,

00:37:25.260 they still induce the same phenomenon of tolerance. Now, they don't have withdrawal. Withdrawal is the

00:37:32.620 effects of these substances on the peripheral body, not the brain, but the peripheral body,

00:37:39.120 because cocaine has effects at every adrenergic synapse. Morphine has effects on other places

00:37:45.840 other than the brain, et cetera, et cetera. Caffeine too, you know?

00:37:49.280 And it's interesting how withdrawal can sometimes be physiologically deadly. For example, ethanol,

00:37:54.760 you know, we know this stuff. I mean, we used to, when we'd operate on patients who

00:37:58.900 were alcoholics, we would actually just continue giving them ethanol throughout surgery.

00:38:03.660 I got it.

00:38:04.080 You'd keep them on alcohol the whole time they're in hospital.

00:38:05.820 Sure.

00:38:06.420 So you can kill a patient if you take alcohol away from them too abruptly.

00:38:10.240 Right.

00:38:10.620 Whereas opiates, the withdrawal is unbearable, but you won't kill the patient by removing it.

00:38:15.480 I find the physiology of withdrawal to be quite interesting.

00:38:17.960 Well, it's true. In fact, the way to deal with opiate withdrawal is get rid of the opiates or

00:38:23.760 give naloxone, you know, to counteract the opiates, which, you know, is now going on,

00:38:28.660 you know, everywhere. And now the police, you know, carry Narcan when they find opiate overdoses

00:38:34.320 in the field. And they're even having it at schools, which is really bizarre and horrible.

00:38:41.160 But this speaks to your earlier point, right? Which is, and Gabor Maté, who has written about

00:38:45.380 this quite eloquently stated, that we're all addicts.

00:38:47.900 Oh, yeah.

00:38:48.500 And so it's-

00:38:49.180 Yeah, you just get to choose your substance

00:38:51.180 of abuse or your behavior of abuse.

00:38:53.180 That's right. And as you said, it's not, and it can be work.

00:38:56.180 The point is sometimes it can be things that are not socially punished.

00:38:59.520 Right.

00:38:59.740 And sometimes those are the hardest addictions to treat.

00:39:02.920 I'm going to admit to you right now, I'm a caffeine addict. I've already had four cups of coffee this

00:39:07.920 morning. And as soon as we're done with this, I'm going to have my next. And, you know, if you take

00:39:13.400 my Starbucks away from me, I will kill you. On the other hand, caffeine is not dangerous unless

00:39:21.480 you mix it with alcohol, in which case then you have four loco and you end up with arrhythmias and

00:39:27.080 other things. So, and it's still socially acceptable. Nicotine is now not socially acceptable,

00:39:33.520 but it took a long time. It took an entire generation of teaching kids why cigarettes were

00:39:40.740 bad before it became not socially acceptable. So we have a long way to go with sugar because

00:39:46.900 it's still socially acceptable.

00:39:48.940 I want to get into some more geeky biochemistry stuff, but I also know that there's probably at

00:39:52.640 least one person listening to this who's a parent who's thinking, oh man, do I have to simmer down

00:39:57.840 how much sugar my kids are eating? So when you saw kids in the clinic, obviously you're seeing

00:40:02.920 their parents. That's one of the advantages of pediatrics is-

00:40:05.480 It's also one of the disadvantages.

00:40:06.440 That's right. That's right. You have two patients.

00:40:08.500 Two patients. And I don't get paid for both.

00:40:11.000 But the beauty of it is you have a patient who you need to take care of, which is this

00:40:15.280 child, but then you also have another caregiver who for the most part wants what's best for

00:40:19.360 that child.

00:40:20.060 Mostly.

00:40:20.820 And how would you counsel a parent who would say, look, Dr. Lustig, there's no way my kid's

00:40:26.900 going to have no sugar in their life. Can you give me a way to create a sustainable

00:40:31.800 environment and set of rules that's going to prevent my kid from having the metabolic derangement

00:40:36.560 that hoses them for the rest of their life, but allows them to still be a kid?

00:40:39.900 Yes. So that's what we did in clinic every single day. Here's the problem. It's not the

00:40:46.300 added sugar you know. It's the added sugar you don't know.

00:40:50.900 It's almost like a Rumsfeld tone to that, right?

00:40:53.340 Well, yeah. I mean, there's the known knowns and then there's the unknown knowns. And the fact

00:40:57.560 is when you look at the amount of sugar that is in sodas, it's bad. When you look at the

00:41:05.900 amount of sugar that's in candy, cake, ice cream, it's about half as much. That adds up

00:41:14.620 to 50% of the added sugar consumed by children.

00:41:18.960 And what is that number, by the way, in grams per day approximately?

00:41:21.740 Oh, it runs the gamut, but the median is 18 teaspoons.

00:41:26.080 So that's about 90 grams of sugar per day.

00:41:28.660 Yeah. It used to be 120. It's actually come down because of the obesity epidemic. 90 to

00:41:33.280 94 grams of added sugar per day. Half of the sugar is in foods you didn't know had it.

00:41:40.640 Bread. Pasta sauce.

00:41:42.380 Pretzels. Why do pretzels have sugar in them? Okay. Bread. Right. Why do they put sugar in

00:41:48.100 bread? Any idea? I guess. It probably helps with preserving it, doesn't it?

00:41:53.020 Exactly. So if you buy a loaf of bread at the bakery, how soon before it stales?

00:41:58.260 Two days, typically.

00:41:59.420 Two days. If you buy a loaf of bread at the grocery store, how long before it stales?

00:42:04.280 10 days.

00:42:04.880 Three weeks.

00:42:06.100 Okay. Why? They're both bread, right? Well, what they did in the grocery store bread was they added

00:42:13.180 sugar very specifically because the sugar doesn't boil off when you put it in the oven. Water

00:42:19.980 does. So it acts as a humectant. It keeps-

00:42:24.840 That's why it's so much moister when you have store-bought bread.

00:42:28.280 Exactly. That's why if you threw a loaf of bread at my head, it would just bounce off is

00:42:35.600 because it's kind of spongy, right? But there are also breads like German fitness bread,

00:42:40.960 which don't have that. They're real bread. They use whole grains. They're lumpy, bumpy,

00:42:46.760 and they're small, the loaves. They're the size of a brick.

00:42:49.840 They're weapons.

00:42:50.560 And they're weapons, right? You could kill somebody if you threw a German fitness bread at their head.

00:42:55.620 Okay? It is dense. They're both bread, but the store-bought bread had sugar added very specifically

00:43:04.260 to hold on to water because sugar's polar. And so the water stays in and therefore the bread

00:43:10.760 doesn't stale as quickly. Therefore, you can put a sell-on by date way later, decreased depreciation,

00:43:18.820 increased profit.

00:43:20.220 So if a kid came in and a kid's got NAFLD and you've surmised that this child's eaten about 100

00:43:25.400 grams of sugar a day, do you say to the parent, our target is what, 20 grams per day?

00:43:30.360 What we say is we don't worry about target numbers. What we say is processed food is the

00:43:36.940 problem because processed food is high sugar, low fiber. What you want is a low sugar, high fiber

00:43:44.760 diet. That's called real food. Every diet out there that works, and there are a whole bunch

00:43:51.720 of diets that work, okay? Certain vegan diets work. Remember, Coke is vegan, so it's not like

00:43:57.700 every vegan diet's okay.

00:43:59.380 The college vegan diet doesn't necessarily work.

00:44:01.060 Yes, the college vegan diet does not work. Exactly right. The traditional Japanese diet,

00:44:06.100 the Atkins diet, ketogenic diet, paleo diet, Mediterranean diet, all of these diets work.

00:44:12.680 Plant-based diets.

00:44:13.860 Sure. They all work because they're all real food. Every diet that works is real food, and

00:44:20.580 every diet that doesn't is because it's processed food. The problem is parents don't know the

00:44:26.660 difference. They don't understand that grocery store bread is processed food. They think it's

00:44:31.740 food. They think if it's sold in the supermarket, it's food. No, there's real food, and you know

00:44:38.780 what that is, but the parents don't. And what we teach them in clinic is if there's a label

00:44:45.180 on the food, that's a warning label because that means it's been processed because real food doesn't

00:44:52.620 need a label. Is there a nutrition facts label on broccoli? Is there a nutrition facts label on

00:44:58.960 carrots? No. Is there a nutrition facts label on the meat in the meat case? No. The reason is because

00:45:07.220 it's all real food. Now, when we get to meat, there's ways of making meat a problem too. It's

00:45:13.840 called corn-fed. But the bottom line is at least they're real food because that means-

00:45:20.180 You don't necessarily fixate on targets. You say, look, we're going to make a conceptual change.

00:45:25.980 We don't ask them to do meth. We ask them to purchase and consume real food. Now, we have

00:45:34.440 to teach them what that is. So what we do, we bring all of the new patients in on the same day.

00:45:40.860 We see all the new patients on one day. It's like chaos. And they all meet with a dietician. They come

00:45:48.300 in fasting and we draw their blood and we evaluate them. And then they all sit down at a communal table

00:45:55.560 and we do an hour-long teaching breakfast. And the dietician narrates why those foods are available

00:46:04.880 for breakfast. So whole grain bread, natural peanut butter, you know, not Skippy, Jif, Peter Pan,

00:46:12.560 but you know, the real stuff, plain yogurt, et cetera. And we explain why these foods were chosen

00:46:19.460 and how they meet the criteria of real food as opposed to what they're currently buying.

00:46:25.540 Most parents get it. Now, there are some who don't. There are some who say, I'm sorry,

00:46:30.180 that takes too long. I can't spend the time preparing real food. And then-

00:46:35.940 Is there an economic consideration also?

00:46:37.980 Oh, absolutely.

00:46:38.860 Do you have a sense of what it costs, all things equal?

00:46:41.860 Yeah, double.

00:46:42.920 So a parent's going to basically have to double their food budget if they want to start eating

00:46:46.220 real food.

00:46:46.800 That's right. They're going to have to double their food budget and they're also going to

00:46:49.500 have to double their food time in terms of preparation.

00:46:53.080 That's a big ask for, I mean, when the CDC last looked at this, the estimates of NAFLD,

00:47:00.220 which we'll get into in a moment so we can let you explain that in some detail. But when you look

00:47:05.240 in particular along ethnic lines, at the time I last looked at this, 50% of Hispanic boys who were

00:47:13.700 obese had NAFLD. My guess is that's a gross underestimation.

00:47:17.300 Likely. The fact is that Latinos are more risk of developing NAFLD.

00:47:22.340 Right. There's a genetic predisposition.

00:47:24.900 They have a specific polymorphism of a specific gene called PNPLA3,

00:47:32.580 patatin-like phosphoprotein domain A3. And it's been shown that if you have the homozygous form,

00:47:40.980 the GG mutation of polymorphism of this gene, a little sugar in your diet makes a

00:47:47.280 lot of liver fat. And 19% of Latinos have it. So this is particularly worrisome for the Latino

00:47:55.840 population. And yes, they have fatty liver like nobody else. So there are people at more risk.

00:48:01.800 And so it becomes even more important to get the sugar out of their diet. And we explain all of this

00:48:07.020 to them. We explain why this is. And we show them the lab data. We show them the acanthosis

00:48:12.980 nigra cans on the back of the kid's neck to explain how the environment changes the biochemistry.

00:48:20.600 We also then explain how the biochemistry changes the behavior. We know from our study where we

00:48:27.420 actually substituted starch for sugar, that kids actually couldn't even eat as much food as we had

00:48:34.580 to supply. They all of a sudden got satiety back.

00:48:37.380 Let's talk for a moment about that. This is the isocaloric substitution of fructose or glucose

00:48:42.440 for fructose. That's right.

00:48:43.840 So let's take a step back and explain what NAFLD is. Let me start with one anecdote before we get,

00:48:47.740 which you'll appreciate. When I was in my residency, so we're talking about 18, 20 years ago,

00:48:54.360 one of the questions if you're a young surgical resident, you're always asking the patient during

00:48:58.300 pre-op is how much alcohol do you consume? And the reason is, going back to the DT thing,

00:49:02.680 we don't want to ever get into a situation where two days post-op, a patient's having DTs.

00:49:08.600 So I remember on at least three occasions, but probably more, where a patient claimed they did

00:49:14.820 not consume alcohol or that they're, you know, they consume like a beer twice a week. And then

00:49:19.740 we'd get in there to do the case and they'd have fatty liver. And we would look at each other and go,

00:49:24.740 God damn it, this guy lied to me. I can't believe this. You know, I wasn't there to judge him. I just

00:49:29.360 needed to know he clearly is drinking like his life depends on it. And he was in denial. Well,

00:49:35.080 it never registered to me what was going on until 10 years later when I learned about NAFLD. And I

00:49:39.780 said, wait a minute, those patients weren't lying to me. They had non-alcoholic fatty liver disease.

00:49:45.640 And you can't tell the difference under the microscope. They look the same. So my first NAFLD

00:49:51.620 patient was in 1996. I had just moved to Memphis, Tennessee. And I had a patient who had ALTs in the

00:50:04.800 300s and the liver was enormous. And they were just sure this, and it was a kid, you know, so it wasn't

00:50:12.340 an alcohol thing, you know, but they were sure this kid had hepatitis or something else. And it turned

00:50:17.020 out, you know, they went and did a liver biopsy and it was, you know, fatty liver disease. And I said,

00:50:22.140 what the hell is this? And soon all my patients had it. Same thing with type 2 diabetes. I saw my

00:50:28.880 first pediatric type 2 diabetic back in 1992. And now one third of all new diabetes diagnoses in kids

00:50:38.720 is type 2. What's going on? You know, we were at the beginning. We, both of us were seeing this at the

00:50:45.900 beginning of this epidemic. And now everyone's got it. You know, this can't be genetic. This is an

00:50:54.280 environmental insult. And the good news is we figured out what the insult is. The bad news is

00:51:00.440 there are dark forces on the other side keeping it that way.

00:51:04.100 Let's talk for a moment about that. About four or five years ago, there was certainly a controversy

00:51:09.240 around the etiology of NAFLD. There were camps that said, look, it's got to be the fructose for

00:51:15.620 reasons that you'll articulate. There were other camps that said, actually, it's fatty acids. It's

00:51:20.840 kids that are consuming too much fat. Others said, actually, it's just a proxy for obesity.

00:51:26.600 In other words, quote unquote, caloric excess leads to adiposity, which leads to NAFLD.

00:51:33.460 I'd like to hear your thoughts on, in the most unbiased way we could, how do you make the case

00:51:39.720 that it's fructose that is disproportionately driving this versus some of these other factors?

00:51:45.160 It's very easy to imagine how you get liver fat. There's production, and then there's clearance.

00:51:55.760 Okay. And the amount of liver fat is the equilibrium between those two phenomena. There are two

00:52:02.880 methods for production. One is through diet. So dietary fat can contribute to hepatic fat,

00:52:12.080 fat. But there's also de novo lipogenesis, which is new fat making. It's the process of turning sugar

00:52:20.140 into fat. Now that had been discounted for years because of a one study.

00:52:28.120 This is Hellerstein's study that basically looked at-

00:52:30.460 Right. The Parks Hellerstein study from Journal of Clinical Investigation, 98.

00:52:35.080 1998. Okay.

00:52:36.060 1998. Where they said, oh, this is a minor pathway. The fractional DNL was only 3%.

00:52:42.100 Well, the reason it was only 3% was because, number one, these were healthy people. Number two,

00:52:47.800 they were fasting, which means they were glycogen depleted. And so the fructose went into repleting

00:52:53.400 the glycogen like we talked about. And there were also people who hadn't been large fructose

00:52:59.100 consumers in advance. And we now know that fructose absorption at the level of the gut is inducible.

00:53:06.320 We learn this every Halloween because the kid eats a lot of sugar and then ends up having diarrhea

00:53:13.160 like crazy because basically they've got-

00:53:16.080 Malabsorption.

00:53:16.620 They've got malabsorption because their enzyme hadn't been induced yet. But if you continue to

00:53:23.260 supply it, the process increases. And we now know the reason for that is a protein in the

00:53:30.640 intestinal epithelial cell called thioredoxin inhibitory protein or TXNIP. This is work from

00:53:35.440 Richard Lee at Harvard. There were a whole bunch of reasons why people thought that de novo lipogenesis

00:53:43.300 was a minor pathway. It's not a minor pathway. It is a major pathway. And Donnelly showed in 2005

00:53:51.880 that de novo lipogenesis was worth about 25% of the fat in the liver.

00:53:57.960 Wow. And then, I mean, you're going to get to this, but how much of that is getting exported in VLDL?

00:54:02.880 That's the clearance side. There are two ways to clear. There's oxidation, fatty acid oxidation.

00:54:09.760 This is why diseases that cause mitochondrial dysfunction like RISE syndrome end up with fatty

00:54:15.400 liver. And then there's export. And the export can be through VLDL or it can be through phosphatidyl

00:54:21.480 choline, but it's basically export out of the liver. So there's oxidation is clearance and export is

00:54:27.500 clearance. So you have two ways coming in.

00:54:30.200 Two inputs, two outputs.

00:54:31.260 Two inputs, two outputs. And so the question is, what's changed? And the answer is our dietary fat's

00:54:37.380 gone down. So that ain't it. But our de novo lipogenesis has gone up. And when you look at the

00:54:44.440 exports, we now have fatty liver, which actually makes things worse because it causes inflammation,

00:54:50.740 which ends up making mitochondria less functional, which causes less fatty acid oxidation. And we

00:54:58.080 have data on that. And we have high triglycerides in patients who consume fructose. So if that pathway

00:55:06.780 out is going up, then you know that if you've got fatty liver, it's because more is coming in.

00:55:12.080 Bottom line, the DNL is the driver.

00:55:16.000 So we could say because triglycerides typically go up with NAFLD, that says it's not a problem of

00:55:21.520 exporting. It's not ineffective exporting.

00:55:23.420 Patients who have A-beta lipoproteinemia, they can't export. They can't make the VLDL.

00:55:28.920 You know how many patients that is? Okay. That's like one in 10,000. We have a 40% NAFLD rate in

00:55:35.560 this country. It ain't one in 10,000. It's not because of the fatty acid oxidation defects.

00:55:41.640 It's not because of the export problem. It's not because of the increased saturated fat.

00:55:48.080 It's because of the de novo lipogenesis. By process of exclusion, that's the only pathway

00:55:54.400 that's gone up.

00:55:55.220 Do you believe that insulin resistance is the result of NAFLD or is NAFLD the result of insulin

00:56:02.060 resistance? Yes. The two feed off each other?

00:56:06.080 Let's talk about metabolic syndrome because the one aspect of metabolic syndrome that everyone

00:56:12.840 agrees on is this phenomenon called insulin resistance. The question is, where's the insulin

00:56:18.380 resistance come from? Everyone assumes, well, you get fat. Therefore, your fat cells make cytokines

00:56:26.560 like TNF-alpha and IL-6. Those then go via the portal system to the liver and cause the liver

00:56:32.900 to be dysfunctional. Therefore, you increase hepatic glucose output. That then causes your

00:56:38.500 beta cells to have to overproduce insulin. Then that drives the insulin resistance. That's what

00:56:44.180 you learn in medical school. Undoubtedly, there are some patients where that is the pathway.

00:56:52.200 I actually think that's actually a rare way that this happens, maybe 10%. I don't think that's the

00:57:00.420 majority, but that is one way. We'll call it the adipogenic hypothesis of metabolic syndrome.

00:57:08.560 Because clearly that patient is not insulin resistant at the adipocyte as evidenced by the

00:57:13.440 fact that they can increase the size of their adipocyte.

00:57:16.420 Exactly right. So they have liver insulin resistance, but their adipocytes are insulin sensitive

00:57:21.980 because they keep storing. And in that model, you haven't necessarily specified what's happening

00:57:27.160 at the level of the muscle, which some would argue is the harbinger of bad things. In other words,

00:57:32.700 once the muscle stops disposing of glucose, taking it in.

00:57:36.480 Yeah. In fact, muscles don't need insulin to import glucose. If they did, then every diabetic would be

00:57:45.360 paralyzed. The reason insulin works at the muscle is for import of amino acids. So for muscle growth,

00:57:52.840 but not for muscle metabolism.

00:57:54.840 So the transporter on muscle is which glute? Glute two?

00:57:57.600 It is glute.

00:57:59.240 Or four.

00:57:59.840 It's not four. That's in adipocytes. Glute two is in liver. I'm pretty sure it's three. One is in the

00:58:07.920 brain. I'm pretty sure it's three. I got to look at that again, but I'm just trying to remember.

00:58:12.260 But it's not glute four. So that's one pathway of metabolic syndrome, starting at the fat cell.

00:58:19.220 But I think that's rare. There's a second metabolic syndrome. We see it in clinical depression. Now,

00:58:26.860 clinical depression causes weight loss. So you'd think that that would actually obviate metabolic

00:58:32.160 syndrome. But in fact, clinical depression increases metabolic syndrome. It decreases obesity,

00:58:37.020 but it increases metabolic syndrome. And when you do CT scans or MRIs across the abdomen of people

00:58:44.260 with clinical depression, they have increased visceral fat. Now, why do they have increased

00:58:48.600 visceral fat? Cortisol drives visceral fat accumulation. We know that from the Cushing

00:58:53.860 syndrome patients. Okay. Glucocorticoids drive that. So the question is, why are stressed people

00:59:01.280 accumulating visceral fat, irrespective of their sub-Q fat? And the answer is because the sympathetic

00:59:07.540 nervous system normally, which is lipolytic, at least acutely, becomes lipogenic chronically.

00:59:15.260 And the reason is because of the co-factor that's released with the norepinephrine called neuropeptide Y.

00:59:23.260 Neuropeptide Y actually changes what would be a lipolytic stimulus to a lipogenic stimulus.

00:59:30.620 So chronic overstimulation of the sympathetic nervous system leads to visceral fat accumulation.

00:59:36.300 And of course, chronic stress increases cortisol. The two together increase visceral fat. Well,

00:59:41.620 that visceral fat will make the inside of kinds. But this is independent.

00:59:43.760 Independent of subcutaneous fat.

00:59:45.940 But also the cortisol and the sympathetic piece, the norepi piece, you're saying are both

00:59:51.980 basically conspiring to be both pro-lipogenic.

00:59:55.440 Yes, exactly.

00:59:57.020 It's funny. I knew about the, obviously the cortisol connection, didn't realize the

01:00:00.360 norepi connection.

01:00:01.500 So acutely, norepi will cause lipolysis through the beta-3 adrenergic receptor at the level of

01:00:07.300 the adipocyte. But it causes lipogenesis when neuropeptide Y is available.

01:00:11.480 Can neuropeptide Y be measured or is it too short-lived?

01:00:14.420 Too short-lived.

01:00:14.880 Can you measure urinary metabolites of it?

01:00:16.680 Not to my knowledge.

01:00:18.000 You know, I wear a continuous glucose monitor.

01:00:20.180 Yes.

01:00:20.440 And everybody says to me, you know, why the hell do you wear that thing? You're not diabetic.

01:00:23.740 But I will tell you the insights I gleaned from this are remarkable. And now that I wear

01:00:27.880 this thing called Bora ring, so this thing's measuring heart rate variability. So every

01:00:32.320 morning when I wake up, to me, the most interesting thing I can look at is what was my glucose over

01:00:36.540 the last eight hours? And what was my heart rate and heart rate variability?

01:00:40.700 Okay.

01:00:40.880 And the interesting correlation I've noticed, which now maybe you've provided an explanation

01:00:45.800 for, is when heart rate variability is lowest, we know that we are under-

01:00:50.480 Which heart rate variability? Low frequency or high frequency? It matters.

01:00:53.220 I'm looking at the RMSSD of the total signal.

01:00:57.940 Okay.

01:00:58.420 So the way that it's quantified here is, I don't know that it's specifying.

01:01:04.180 It matters.

01:01:04.980 Interesting. Well, let me tell you what I've noticed.

01:01:06.760 Because high frequency heart variability is vagal. And low frequency is a bunch of things thrown on

01:01:12.400 top of each other. Barrel receptor, respiratory rate, and sympathetic. So it's the low to high

01:01:17.860 ratio that gives you the sympatho-vagal balance because you cancel out the other things. So taking

01:01:24.660 your HRV and, you know, binning them into low and high frequency matters. If the-

01:01:30.100 Do you know what the frequency cutoff is?

01:01:32.600 0.3.

01:01:34.200 Okay. I'll look into this. This is interesting.

01:01:37.380 Just looking at it at the level that it's reported, the lower the HRV, obviously the imputed or

01:01:44.020 inferred higher sympathetic tone.

01:01:45.880 Right.

01:01:46.120 Well, generally the higher the glucose level.

01:01:48.280 I believe that.

01:01:49.000 And I've always assumed it was just cortisol coming along for the ride. I never actually thought-

01:01:54.060 Well, cortisol does go up 5, 6, 7, 8 a.m. You know, it's the diurnal variation. So maybe that's

01:01:59.460 adding to it.

01:02:00.320 Well, my peak glucose was at 2 a.m. yesterday. My peak for 24 hours was at 2 a.m. Now I was

01:02:08.040 sleeping in a hotel, having a shitty sleep. Who knows what I was stressed out about? I remember I

01:02:12.700 had the weirdest dreams imaginable. But it's really interesting how much cortisol plays a role in

01:02:17.940 this.

01:02:18.140 I agree. Cortisol plays a major role in it. And we know this from all the data from the Whitehall

01:02:23.000 study in terms of stress that workers are under, et cetera. And shift workers really have problems

01:02:29.560 with cortisol. So anyway, the point is you can have visceral fat, which releases cytokines and

01:02:35.360 goes to the liver. So it can come from the sub-Q fat. That would be obesity. And come from the visceral

01:02:39.520 fat. That would be stress. And then there's a third way. And that is making the liver sick straight

01:02:45.940 away, mainlining the toxin. That's called sugar.

01:02:51.500 And what is the-

01:02:52.100 And that's the one I think is the biggest problem.

01:02:54.580 It's probably the one that's increasing the most, for sure.

01:02:57.580 What is the actual mechanism by which all of those things, which lead to things we know are bad,

01:03:02.900 right? The homocysteine going up, the uric acid going up, the ALT going up, fat actually accumulating

01:03:08.480 grossly. How does that translate to a peripheral problem that actually becomes the runway to diabetes?

01:03:14.640 If you have liver dysfunction, which occurs due to those cytokines from either the sub-Q fat or the

01:03:21.540 visceral fat, or because you have primary hepatic dysfunction, as in NAFLD, what's going to happen

01:03:30.160 is you're going to have increased hepatic glucose output because now you're insulin resistant at the

01:03:35.580 level of the liver. So your liver can't inhibit the enzymes that cause gluconeogenesis. So the process

01:03:43.560 of hepatic glucose output is because the insulin phosphorylates FOXO1, which is a forkhead protein

01:03:53.680 that normally goes into the nucleus of the liver cell and transcribes the enzymes that are involved

01:04:00.900 in glycogenolysis and gluconeogenesis. That's how you raise your serum glucose when insulin is unavailable.

01:04:08.780 Insulin is supposed to suppress that by phosphorylating the FOXO1. If you're insulin resistant

01:04:15.500 because there's liver fat or because of the cytokines coming in, now you can't phosphorylate

01:04:23.040 FOXO1. You can't transduce that insulin signal. So now your hepatic glucose output goes up, which then

01:04:30.120 increases your serum glucose, which then goes to your beta cell.

01:04:33.780 But then there's no off switch.

01:04:35.680 There's no off switch. Correct. And your beta cell then has to make extra insulin and it's making

01:04:41.620 it fasting. It's not just making it in response to a meal. It's making it all the time. And insulin

01:04:47.080 is both good and bad. It's good when it lowers your blood sugar. It's bad when it does everything else.

01:04:53.600 Insulin's job is to store energy. Okay. It is not to keep your glucose normal. It is to store energy.

01:05:04.580 It keeps your glucose normal as a function of storing energy. If you're storing energy,

01:05:09.540 you're going to gain weight. In addition, insulin stimulates a different pathway in cells. That is the

01:05:18.440 proliferation pathway. It's called MAP kinase and ERK. This pathway is responsible for vascular smooth

01:05:26.480 muscle proliferation, coronary artery, vascular smooth muscle proliferation, thereby making your

01:05:32.620 coronaries tighter and less likely to be able to vasodilate when they need to, thus increasing risk

01:05:40.940 for heart attack. It also causes cell division because insulin is a mitogen. It causes cells to

01:05:47.980 divide. Well, if it causes your breast cell to divide, you might end up with breast cancer.

01:05:53.920 And so hyperinsulinemia is associated with all of the chronic metabolic diseases we know about

01:05:59.380 because of this second phenomenon that insulin does, not just lowering glucose, which it does as a

01:06:06.840 sidelight of storing energy, but in fact, because it causes both inflammation and cell division.

01:06:13.040 My hope is that as time goes on, more and more physicians will realize that hyperinsulinemia

01:06:17.800 per se, independent of what's happening at the level of glucose. In other words,

01:06:22.880 you have a patient with a quote unquote normal hemoglobin A1c, but they're hyperinsulinemic,

01:06:26.880 that that is taken as seriously as we would take diabetes.

01:06:30.780 Absolutely. And this is one of the reasons why,

01:06:33.420 if you look at all of the diabetes studies that are out there in terms of diabetes control,

01:06:39.960 they all improve hemoglobin A1c and the patient dies anyway. The UK PDS, the ACCORD study,

01:06:49.400 and several others all show that you can lower blood glucose, you can reduce microvascular complications,

01:07:01.000 diabetic retinopathy, neuropathy, nephropathy, all small vessel complications by lowering the glucose.

01:07:11.040 But what you do is you exacerbate the large vessel complications like coronary heart disease

01:07:16.160 or cancer, and you end up dying just the same. So getting your blood glucose down is only half the

01:07:24.160 job in diabetes. Getting your blood insulin down is the other half. And taking drugs that increase your

01:07:32.300 insulin ain't the way.

01:07:34.420 Yeah. Yeah. It's a backwards way to go about that.

01:07:36.220 Totally. The object is to increase your insulin sensitivity. And the only way to do that is by

01:07:42.920 diet, not even by exercise alone. You can't outrun a bad diet. You have to fix the insulin problem,

01:07:51.900 and exercise won't fix the insulin problem by itself.

01:07:55.080 It seems to me that a large part of this now becomes a policy issue, which I know

01:07:59.360 you went back to graduate school.

01:08:02.160 Law school.

01:08:02.480 Yeah. About, what, six years ago?

01:08:04.740 Five years ago, yeah.

01:08:05.360 Yeah. And I know that even though you've quote unquote retired from your clinical practice,

01:08:09.640 that's simply given you more time to focus on these other issues.

01:08:13.420 Yeah. In fact, it's one of the reasons I retired. I realized, oh, about seven, eight years ago,

01:08:19.140 that I could actually take care of a million kids easier than I could take care of one.

01:08:23.600 And so I'm devoting my time now to research. We have a study now that is ultimately, if all goes

01:08:31.880 well, and so far it is, we'll put the final nail in the coffin on a calorie is not a calorie.

01:08:38.140 And we'll basically prevent the food industry from ever saying it again. That's my goal.

01:08:43.780 And currently the food industry says, I mean, I haven't really paid much attention to this,

01:08:48.620 to be honest with you, in the last few years, but is the food industry basically still saying that

01:08:52.260 while a can of Coke is not ever deemed even by Coca-Cola to be as nutritious as a carrot,

01:08:58.960 in the end, are they basically saying that all calories contribute equally to adiposity

01:09:04.440 and insulin resistance?

01:09:06.000 Yes. They are all saying it's about obesity and therefore it's about energy balance. Therefore,

01:09:10.380 it's about calories. Therefore, all calories are the same. That's what they say. It is absolutely

01:09:16.360 not true. And we have all the reasons in the world to show why it's not true. We have empiric data,

01:09:23.280 we have mechanistic data, we have plausibility data, we have hard data that show that is just not the

01:09:30.020 case. And if you want, I'll give you examples of it. All right, let's start.

01:09:34.480 So yeah, let's talk about fiber. You eat 160 calories in almonds. How many do you absorb?

01:09:40.940 Two thirds, 130. Yeah. I mean, 75%. Okay. Well, what happened to the other 30?

01:09:47.120 Presumably it's going to drag some stuff out in your colon.

01:09:50.980 Well, no, what happens is the soluble and insoluble fiber in the almonds forms a gel on

01:09:55.300 the inside of the intestine. You can actually see it on electron microscopy, a whitish gel.

01:09:59.260 So that's going to act as a secondary barrier preventing absorption of some of those almond

01:10:05.620 calories early on. Well, if they don't get absorbed in the duodenum, where do they go next?

01:10:10.940 Jejunum.

01:10:11.160 Ilium, jejunum.

01:10:11.840 Jejunum. Well, what's in the jejunum that's not in the duodenum? The microbiome.

01:10:16.220 Yeah.

01:10:16.920 The duodenum is essentially sterile. It's got a pH of one. Only H. pylori can live there. You have to

01:10:23.300 get the bicarbonate infusion.

01:10:24.760 Wait, you're saying that that lining is formed in the duodenum?

01:10:28.000 Duodenum, yeah. Exactly. To prevent your liver from getting the whole dose because anything

01:10:35.740 that's absorbed in the duodenum goes straight to the liver.

01:10:37.600 So how much fiber is in an apple?

01:10:39.620 A lot. I mean, I can't give you a number of grams.

01:10:41.500 But directionally, I'm making this number up, but let's say there's how many grams of

01:10:45.480 fructose in an apple? 20?

01:10:46.760 There's 30 calories in a standard apple, half of which would be fructose of 15.

01:10:52.860 That seems low. An apple, like a big-ass Fuji apple?

01:10:55.740 Well, I mean, not a big mother apple, but like an apple apple.

01:10:59.740 But so based on that, you're saying only half the fructose that you would eat in a piece

01:11:04.400 of fruit might actually get to the liver?

01:11:06.140 Yeah, or less. Most of it's going to end up in the jejunum. And once it goes to the jejunum,

01:11:11.220 it's a free-for-all. Do you absorb it or do the bacteria digest it and metabolize it for their own

01:11:15.640 use? Remember, you have 10 trillion cells in your body, but you have 100 trillion bacteria

01:11:20.740 in your intestine. Every one of us is just a big bag of bacteria with legs. Those bacteria have

01:11:26.560 to survive.

01:11:27.200 If the fructose gets absorbed at the level of the jejunum, in other words, if the gut

01:11:30.860 outcompetes the bacteria, can it still get back to the liver?

01:11:33.440 Oh, yeah.

01:11:33.920 Okay.

01:11:34.340 Yeah, but the area under the curve will be wider, which means the insulin response will be lower,

01:11:40.520 which is what you want because it took longer. But a lot of it won't get absorbed.

01:11:45.100 It'll be digested. It doesn't come out in the stool. It gets digested by the gut bacteria who

01:11:50.900 use it for their own purposes. Now, here's the thing that I only learned about a month and a half

01:11:56.620 ago, which is absolutely essential. If you don't consume fiber, that means that your gut bacteria

01:12:04.400 are not getting the food they need because you're absorbing it all early. Well, they still have to

01:12:09.980 survive. So, what do they do? They protealize and lipolize the mucin layer.

01:12:16.780 So, auto-digest.

01:12:18.000 They auto-digest the mucin layer that sits on the surface of your intestinal epithelial cells,

01:12:23.460 protecting them. And you can actually see on electromicroscopy an increased apposition of the

01:12:30.480 bacteria with the intestinal epithelial cell, which likely causes damage, possibly a leaky gut,

01:12:39.360 and possibly GI disease like colitis and even maybe Crohn's. So, the idea is to feed your bacteria

01:12:48.680 or your bacteria will digest you.

01:12:51.620 And what sources of fiber do you think? I mean, people talk about using psyllium husk and all

01:12:56.560 these other things to sort of augment fiber. Do you think that's necessary or do you think you

01:13:00.160 can get enough of it just from...

01:13:02.000 Well, so, psyllium is soluble fiber. It's not insoluble fiber. You need both. Fiber has soluble

01:13:10.560 insoluble, like pectins, like what holds jelly together. Insoluble fiber, like cellulose,

01:13:15.980 you know, stringy stuff in celery. You need both to make that gel. So, the insoluble fiber forms the

01:13:22.100 lattice work, like the net. Let's say you put a layer of petroleum jelly on a strainer. You would

01:13:28.020 have an impenetrable water barrier, right?

01:13:30.180 Yeah. So, the insoluble is like the strainer and the soluble becomes the thing that fills in the

01:13:35.540 lattice.

01:13:36.000 That's right. Exactly. So, when you have both, it works. And there's data that shows that if you

01:13:40.800 have either one or the other, it doesn't work. You need both. Well, you get both in real food.

01:13:47.620 And this is why the food industry keeps adding soluble fiber, like psyllium husk,

01:13:52.340 to food, like fiber one bars. It doesn't make a damn bit of difference. They have insoluble fiber

01:13:58.600 in things like certain breakfast cereals. But if you don't have the soluble fiber, it also doesn't

01:14:04.220 work. You need both. Real food has both. The point is...

01:14:08.420 So, the fiber fortified stuff is... The easy way to do it is to add soluble fiber.

01:14:12.020 That doesn't work. Okay. And that's what the food industry keeps doing and keeps telling us that

01:14:15.820 it's good because it's got extra fiber. Wrong. Doesn't have functional fiber. Doesn't have the

01:14:21.360 fiber that does what you want it to do. That's the reason a calorie is not a calorie all by itself.

01:14:25.800 I know that you've got to go soon. Otherwise, we could do this for another two hours. But I do want

01:14:30.360 to ask you one sort of final question or final thought on something, which is, I looked into this a few

01:14:35.360 years ago. And maybe the numbers have changed, but directionally, I think this is still correct.

01:14:39.180 There were something like nine companies that controlled basically all of CPG, consumer packaged

01:14:45.620 goods.

01:14:46.100 10. There's 10.

01:14:46.940 Okay.

01:14:47.420 10 control 90% of the food.

01:14:49.140 Yeah. My calculation was 10 of them controlled 85% of the calories that people consumed.

01:14:54.200 Yep.

01:14:54.880 You face a very uphill battle.

01:14:56.460 Indeed.

01:14:56.700 Because you're trying to get them to change the way they do business, but they answer to shareholders,

01:15:03.220 not to you. And the way they're doing things right now is working out reasonably for their

01:15:08.840 shareholders. Not great. These aren't the most high-performing companies in the world. But

01:15:12.800 how in the world, when such a small group of companies control so much, and going back to

01:15:19.500 what you said earlier, you're asking parents to double their food budget to feed their kids

01:15:24.680 correctly and spend twice the time doing it. What does this look like in 10 years? How does

01:15:28.980 the story end?

01:15:29.600 Well, I don't know how it ends. This is a battle royal, like tobacco was. And it took

01:15:34.700 a long time to win that. And there are people who say, we haven't even won that one yet.

01:15:39.080 You know, e-cigarettes now come, but we're having another proposition here in San Francisco

01:15:42.740 tomorrow about tobacco to kids. Here's the deal. The food system needs to change. They're

01:15:50.040 not going to change it from the inside because right now sugar is their business model. It's

01:15:57.120 the thing that increases their sales. When high fructose corn syrup and the dietary guidelines

01:16:02.480 of 1977 were first available, the profit margin of the food industry went from 1% per year

01:16:11.560 to 5% per year. This is their juggernaut. This is their gravy train. They add more sugar,

01:16:16.600 they sell more food, and they know it. And that's why there's sugar in all the food because when

01:16:21.420 they add it, you buy more for all the reasons we've discussed. They have to change the food,

01:16:28.060 which means they have to change the business model. So how do you change the business model?

01:16:33.820 Well, there are four potential ways to change the business model. One is educate the public

01:16:40.000 so that they don't want that food, in which case then they won't sell it. We're trying to do that.

01:16:45.520 That's one reason I am the chief science officer of a nonprofit trying to do just that, okay,

01:16:51.480 called Eat Real. And Real is an acronym, Responsible Epicurean and Agricultural Leadership. We are trying

01:16:57.740 to change the food system by praising the good and hoping that that will induce competition amongst

01:17:03.980 restaurants, cafeterias, hospitals, schools to procure, market, and sell real food.

01:17:10.880 Or you can have executive branch efforts like the FDA or the USDA, but not in this administration.

01:17:22.620 If anything, they've rolled back opportunities for that, like the nutrition facts label.

01:17:28.220 Or you can have Congress legislate specific changes. They're not doing that because they're all paid

01:17:35.140 off from the American Legislative Exchange Council and other concerns like the Koch brothers, what have

01:17:41.980 you. Or you can have judicial impact. And so there are lawsuits against the food industry going on

01:17:49.740 as we speak in an attempt to try to, shall we say, regulate from the bench, which no one thinks is

01:17:56.040 optimal, but seems to be the only thing that's available at the moment, aside from education.

01:18:01.680 So those are the four ways to do this. My goal would be to get rid of food subsidies.

01:18:11.180 Are the food subsidies what enable the junk food to be basically half the price of real food?

01:18:16.700 Or is it that the real food is twice as much to make, not independent of the subsidy?

01:18:20.880 It's about the subsidy making junk food cheap. If you got rid of the subsidies, then the market would

01:18:27.320 work. Right now, any subsidy distorts the market. And there's no reason for food subsidies. In fact,

01:18:33.900 there's no economist worth their salt today that believe in food subsidies because they distort the

01:18:38.240 market. So the question is, would food get more expensive if we got rid of all food subsidies? The

01:18:45.060 Giannini Foundation at UC Berkeley engaged in this exercise several years ago. And they computed what would

01:18:53.220 happen to the price of food? And it turned out that the price of food wouldn't change except for two

01:18:57.220 items. Corn and sugar would go up.

01:18:59.860 But how would that not impact the cost of all other foods, given how ubiquitous they are?

01:19:05.220 It's a complex modeling, and I'm not an expert in how they arrived at this. But empirically,

01:19:12.220 this is what fell out of it, is that the price of wheat wouldn't change, the price of soy wouldn't

01:19:18.360 change. Only corn and sugar. And that is where the dietary sugar in our food comes from. So I think

01:19:26.360 that that would be a really smart way to start. You know, the farm bill is, you know, re-apportioned

01:19:34.520 every five years. And right now, there's actually tension around that farm bill. It has to do with

01:19:40.840 other things. But I would like to see the issue of the metabolic cost of food built into the farm

01:19:48.820 bill. Because right now, our government has not linked or yoked the productivity and economic costs

01:19:57.320 of Medicare, Medicaid, Social Security with food. I would like to see that link strengthened because

01:20:04.660 we have the data. And when they do, maybe they'll fix us.

01:20:07.280 Is there anything right now that you consider a victory? Because when you look at the smoking

01:20:10.360 story, you had Surgeon General's report first, you had changes in advertising next, you had

01:20:15.520 excise taxes, and then ultimately environmental changes.

01:20:18.720 We have excise taxes for soda.

01:20:20.780 Do you have any advertising rule changes yet?

01:20:23.740 Well, here in San Francisco, we have a warning label on billboards. That is, right now, there's a

01:20:31.300 temporary injunction about because the food industry did that.

01:20:33.860 But the smoking one was interesting. I didn't know this until a few years ago.

01:20:37.080 But basically, a law came out that said anytime a tobacco commercial was on TV, it had to be

01:20:43.640 followed by an anti-tobacco commercial.

01:20:45.820 Right. The fairness doctrine.

01:20:47.280 Yeah. It turned out the anti-tobacco commercials were so popular and so effective that tobacco

01:20:52.480 voluntarily withdrew from television.

01:20:55.420 Indeed.

01:20:56.180 Is there anything around creating that type of awareness?

01:20:59.520 No. What there is, is the question of marketing to children. And the thing is that many of the

01:21:06.400 conglomerates have said they voluntarily will not market to children, at least during certain

01:21:13.280 times of the day when kids are more likely to watch. But in fact, watchdogs have been looking at this

01:21:21.080 and they say that it's lip service, that they're not actually doing it. So you cannot expect the

01:21:28.040 food industry to police itself.

01:21:30.460 I hate to end on this note. I know you have to go. I want to respect your time. I hope we can come back

01:21:35.360 and do this again and talk in more detail.

01:21:37.040 Peter. Okay. There are a few people that I don't just make myself available for, but that I want

01:21:45.200 to see. And you are on that list.

01:21:47.540 That means a lot. Thank you, Rob.

01:21:49.320 My pleasure.

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The Peter Attia Drive - September 10, 2018

#14 - Robert Lustig, M.D., M.S.L.： fructose, processed food, NAFLD, and changing the food system

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