60:14And here's a study done by Dan Fige,
60:16at the University of Texas San Antonio,
60:18where he took obese adolescents with hypertension,
60:21and he gave them the drug Allopurinol.
60:24And Allopurinol is the drug that you treat gout with,
60:27to lower the uric acid.
60:28And look what happened to the blood pressure.
60:30Systolic, diastolic, went down.
60:33Showing that, in fact, uric acid
60:36is an important part of hypertension.
60:40We have a hypertension epidemic in this country.
60:44Here it is.
60:47It's the sugar.
60:50Okay, so, so far we have high blood pressure.
60:53Let's keep going.
60:55The fructose will get metabolized
60:56down to pyruvate, the pyruvate
60:58will enter the mitochondria just like before,
61:01throwing off a lot of citrate.
61:03And here's a little trick that fructose
61:04does that glucose doesn't.
61:06'Cause these to can reform this stuff
61:08over here called fructose 1 6 bisphosphatase,
61:11which can then reform with glyceraldehyde
61:14to form this guy, over here, called xylulose-5-phosphate.
61:17And I get to xylulose-5-phosphate in a moment.
61:19But I wanna point out this asterisk.
61:21That's there to remind me to tell you something.
61:24That's there to remind me to tell you
61:26that this is why the sports drink companies
61:29put high fructose corn syrup in the sports drinks.
61:33Because if you are glycogen depleted,
61:37in other words, if you just ran a marthon,
61:39and you have no glycogen left in your liver
61:41because you burned it all, and you take in
61:43a sports drink with high fructose corn syrup,
61:45you can replete your glycogen faster
61:49than with glucose alone.
61:50That's true.
61:52So, for elite athletes, a high fructose corn syrup
61:56containing sports drink actually makes sense.
62:00And so, indeed, sports drinks
62:01have high fructose corn syrup.
62:04The question is who drinking the sports drinks?
62:08Any elite athletes you know?
62:11Who's drinking the sports drinks?
62:13The kids, right?
62:15Why are they drinking it?
62:18Because it's cool, right?
62:21'Cause it's cool and it tastes good.
62:24So, before we go on, I just wanna,
62:26now, digress for a moment.
62:291967, University of Florida patents Gatorade.
62:36Everybody remember Gatorade?
62:38Okay, 1970, the Florida Gators win
62:41the NCAA Championship in football. 62:44 Gatorade makes a big splash.
62:47 Okay, big deal.
62:48 Anybody ever taste the original Gatorade?
62:52 Yeah?
62:53 What'd it taste like?
62:55 Tasted horrible.
62:57 It tasted like something that you might find
63:02 coming out of you instead of going into you.
63:04 (audience laughs)
63:07 It tasted awful.
63:101992, Pepsi buys Gatorade, and they say, 63:15"How are we gonna market this swill?" 63:19So, what did they do?
63:21They added the high fructose corn syrup.
63:24So, now who drinks it?
63:27Fat kids, right?
63:29Not even skinny kids, fat kids drink it.
63:32Okay, so there's a problem here.
63:34Okay, and we're gonna show you how that works.
63:35Okay, so xylulose-5-phosphate, just to show you,
63:38if you take a rat, and you glycogen deplete him
63:40by making him run on an exercise wheel,
63:43and then you re-feed them with starch
63:45or with sucrose, the xylulose-5-phosphate
63:47goes way up with the sucrose.
63:49So you get more xylulose-5-phosphate
63:51through this pathway here, going over here.
63:53So why do we care about xylulose-5-phosphate?
63:55Well, here's why.
63:56Because it stimulates this guy, over here,
63:58called PP2A, which then activates
64:00this transcription factor here,
64:01carbohydrate response element binding protein,
64:04which then activates what three enzymes?
64:09New fat making right, the novo lipogenesis.
64:12So here's the citrate, we got lot's of that.
64:15And here we've got acetyl-CoA, which is the way into fat,
64:20which then gets packaged to the VLDL,
64:25and now you've got the dyslipidemia
64:27of obesity of fructose consumption,
64:30which has, been known for many years.
64:32So, here's normal medical students,
64:36if you can call them normal,
64:39taking in a glucose load.
64:41Notice, almost none of it ends up as fat.
64:45Taking in a fructose load, same number of calories,
64:4830% of it ends up as fat.
64:51So when you consume fructose,
64:53you're not consuming a carbohydrate, you're consuming fat.
64:59So everybody talks about a high fat diet.
65:02Well, high sugar diet is a high fat diet.
65:05That's the point.
65:07That's exactly the point. 65:11This is a study where they gave
65:13acute administration of fructose,
65:14and you can see the triglycerides 65:16going up compared to the control.
65:18Serum triglyceride, right there.
65:20Here's normal medical students, again,
65:22six days of high fructose feeding. 65:25Triglycerides doubled, de novo lipogenesis
65:28went up five times higher, and here's free fatty acids, 65:32which then cause insulin resistance, doubled. 65:35Six days. 65:38So, here's the dyslipidemia of fructose consumption.
65:42We're not done. 65:44Some of the fat won't make it out of the liver,
65:45just like with ethanol. 65:47And now you've got a lipid droplet, 65:48so now you've got this nonalcoholic steatohepatitis. 65:52So, this is work that we did in our clinic
65:54looking at sugar sweetened beverage consumption 65:57against the liver enzyme marker ALT,
66:01alanine aminotransferase, which tells you about fatty liver. 66:05And sure enough, here's sugar sweetened beverages
66:07against ALT, and you can see a nice 66:10linear relationship in Caucasians.
66:12African Americans, it's a different relationship,
66:15and that' a' whole 'nother story all by itself. 66:18So, there's the lipid droplet
66:19of nonalcoholic steatohepatitis. 66:22Some of it will come out as free fatty acids 66:24and populate the muscle, will also tell 66:26the insulin to go up higher.
66:29Remember that JNK1? 66:30So, here's what JNK1 does.
66:31So, the acetyl-CoA and the fructose can all activate JNK1.
66:35And what JNK1 does is, remember when we 66:38used glucose, this IRS became tyrosine IRS-1
66:41and that was good? 66:42Remember that?
66:43Well, JNK1, what it does, is it's 66:45serine phosphorylated IRS-1. 66:47And serine IRS-1 is inactive. 66:50So now, the insulin can't even do it's job in the liver.
66:54So, now you have liver insulin resistance as well. 66:57That's gonna make the pancreas work that much harder
67:00generating higher insulin levels, 67:01which raise your blood pressure even further,
67:04cause further fat making, cause more energy 67:08to go into your fat cell. 67:11There's your obesity. 67:13And finally, our research has shown
67:16that the higher the insulin goes, 67:18the less well your brain can see it's leptin.
67:21And so there you've got continued consumption 67:23because your brain thinks it's starving. 67:25And it's been shown in many different ways
67:28that fructose consumption changes 67:30the way your brain recognizes energy.
67:33All in a negative fashion, so that you, 67:35basically, think you're starving. 67:37Your brain gets the signal that you're starving
67:40even though your fat cells are generating
67:43a signal that says, "Hey, I'm full like all get out." 67:48So, this just shows you how it goes.
67:50So, the high insulin generates the obesity 67:52because this is that, remember the first
67:54law of thermodynamics, the biochemical force
67:57generating the energy storage 68:01as the primary phenomenon, remember,
68:03if you're gonna store it, and you expect to burn it
68:06then you're gonna have to eat it.
68:07So, here's the store it. 68:09Normally, that would make leptin,
68:10and the leptin should feed back
68:12and turn everything off, but it doesn't,
68:14because the insulin gets in the way,
68:16and the high fat diet gets in the way. 68:18Also, the hyperinsulinemia stops the leptin
68:20from acting on that nucleus accumbens,
68:23and so you get an increased reward signal.
68:25So that continues your appetite, 68:27continues more fructose, more carbohydrate,
68:30generating more insulin resistance than you can see.
68:32You generate a vicious cycle of consumption
68:35and disease, and no stopping. 68:39So, here we are, hypertension, inflammation, 68:42hepatic insulin resistance, hyperinsulinemia,
68:44dyslipidemia, muscle insulin resistance, 68:46obesity, and continued consumption.
68:50Looks like metabolic syndrome to me.
68:54So, here are the phenomena associated 68:58with chronic ethanol exposure.
69:00Hematologic disorders, electrolyte abnormalities,
69:02hypertension, cardiac dilation, cardiomyopathy, 69:04dyslipidemia, pancreatitis, malnutrition,
69:06obesity, hepatic dysfunction, 69:08that's alcoholic steatohepatitis,
69:10fetal alcohol syndrome, and addiction.
69:14Here's fructose. 69:16Eight out of twelve.
69:19Why? 69:22'Cause they do the same thing.
69:23'Cause they metabolize the same way. 69:25Because they are the same.
69:26They come from the same place, right. 69:28How do you make ethanol? 69:30Naturally. 69:32Right, you ferment sugar.
69:35Hasn't changed, 'cause it has all the same properties.
69:38Because it's basically taken care of by the liver 69:40in exactly the same way, and for the same reason. 69:43Because sugar and ethanol are the same,
69:46every which way you turn.
69:49So, here's our clinic intervention. 69:52This is what we do in our clinic.
69:53It's as simple as you can imagine.
69:55We write this on the back of a matchbook. 69:58It's just as simple as you can make it. 70:00We have four things we teach
70:01the kids to do, and the parents.
70:03Get rid of every sugared liquid in the house, bar none.
70:06Only water and milk, there is no
70:09such thing as a good sugar beverage, period.
70:12Eat your carbohydrate with fiber.
70:14Why?
70:14Because fiber is good.
70:16Fiber is supposed to be an essential nutrient.
70:18And we can talk later, if you want,
70:20after the cameras turn off,
70:22as to why fiber is not an essential nutrient.
70:25Because the government doesn't want it to be. 70:28'Cause then they couldn't sell food abroad.
70:31Wait 20 minutes for second portions, 70:34to get that satiety signal.
70:35And finally, buy your screen time 70:37minute-for-minute with physical activity. 70:39That's the hardest one to do. 70:41So, if you play for half an hour, 70:43you can watch TV for half an hour.
70:45You wanna watch TV for an hour, play for an hour. 70:47That one's a hard one, but anyway. 70:48We follow our patients every three months.
70:50So, here's my question. 70:51Does it work?
70:53What do you think? 70:55Yeah, it works. 70:57So, this is BMI z-score time from initial visit.
71:01It works.
71:02But, we were interested in what made it work, 71:04and made it didn't work, so we did
71:05a multivariate linear regression analysis. 71:08The thing that made it not work, 71:11sugared beverage consumption.
71:13The more sugar beverages the patient drank at baseline, 71:16the less well lifestyle intervention worked 71:20for all the reasons I just showed you.
71:24So, why is exercise important in obesity. 71:28Because it burns calories?
71:31Come on. 71:3220 minutes of jogging's one chocolate chip cookie.
71:35You can't do it. (audience laughs) 71:36Are you joking me? 71:38So, why is exercise important?
71:42I'll tell you why, here's why. 71:43Number one, it improves that skeletal muscle 71:46insulin sensitivity because you're insulin 71:48actually works better at your muscle, 71:50which then brings your insulin levels down.
71:52Which is good for you. 71:53Number two, it's your indigenous stress reducer.
71:57It's the single thing that actually stress reduces. 72:01And if you stress reduce, 72:02what do you think your appetite does?
72:04Goes down, because stress and obesity go hand in hand, 72:08for all sorts of reasons which are beyond
72:10the scope of this lecture today. 72:12But, we can talk about it in
72:13the question period, if you want.
72:15And then finally, remember that de novo lipogenesis?
72:18Remember those three nasty enzymes?
72:21What if you burned the stuff off before you made the fat?
72:27That's what exercise does, 'cause it makes
72:29that TCA cycle run faster, so you don't get
72:31the citrate leaving the mitochondria,
72:33so it doesn't get turned into fat,
72:35so it doesn't precipitate and cause
72:36all the problems you just saw.
72:39(speaking away from microphone)
72:41That's what they mean by a higher metabolism, yes.
72:45But it has nothing to do with burning of calories.
72:47That is the stupidest reason
72:49that I've every heard of for exercise.
72:52You gotta be joking me.
72:54You can't do it.
72:55I mean one Big Mac and you gotta
72:58mountain bike for ten hours.
72:59(audience laughs)
73:01Are you joking?
73:03So, why is fiber important in obesity?
73:06So, this is my motto in clinic.
73:08When God made the poison, he packaged it with the antidote.
73:12'Cause fructose is a poison.
73:14I think I've, hopefully, shown you that.
73:16But, wherever there's fructose in nature,
73:19there's way more fiber.
73:21You ever see a piece of sugar cane?
73:23It's a stick, right?
73:25(audience laughs)
73:27You can't even chew the damn thing, right?
73:29You gotta suck the stuff out.
73:30(sucking)
73:31Like that, right?
73:32I mean, how many calories you think you're
73:33gonna get out of a piece of sugar cane?
73:36They actually did studies on the sugar plantations
73:38back in the early 1900s.
73:42All of the workers were healthy
73:44and lived longer than the sugar executives
73:47who got the processed product.
73:49How 'bout that, wonder why.
73:52So, eat your carbohydrate with fiber,
73:55that's why we say that.
73:57That includes sugar, that's why fruit's okay.
74:00Because number one, it limits
74:01how much fructose you're gonna take in,
74:03and number two, it gives you an essential nutrient
74:05which you needed in the first place.
74:06And you get some micronutrients along with it
74:08so that you actually, your liver works healthier.
74:12So, here's what fiber does.
74:14 Number one, it reduces the rate
74:15 of intestinal carbohydrate absorption.
74:18 Now, sometimes that's bad.
74:21 I'll tell you when that's bad.
74:23 Now when that's bad?
74:25 That's bad when you're at a formal function.
74:32 'Cause what happens if you reduce
74:34 the rate of carbohydrate absorption in your gut?
74:38 The bacteria get to it.
74:40 So, as far as I'm concerned,
74:42 in life you've got two choices.
74:45 It's either fat or fart.
74:47 (audience laughs)
74:50 It increases the speed of transit
74:52 of the intestinal contents to the ilium,
74:55 and that raises this hormone over here
74:57 called PYY, which goes to your brain
74:58 and tells you the meal's over.
75:00 That's your satiety signal.
75:01 So when you add fiber to your diet,
75:03 you actually get your satiety signal sooner,
75:05 because the food moves through faster.
75:07 And then, finally, it also inhibits
75:09 the absorption of some free fatty acids
75:11 all the way to the colon, and then those
75:13 get chopped up into little itty bitty fragments
75:16 called short chain fatty acids,
75:17 and those actually suppress insulin,
75:19 as apposed to long chain fatty acids
75:20 which stimulate insulin.
75:22 So there are a whole bunch of reasons why fiber is good.
75:25 Anybody ever heard of the Paleolithic Diet?
75:29 Go home and read up on it on the internet.
75:32 The Paleolithic Diet.
75:33 Basically, if you east everything as it
75:35 came out of the ground raw, with no cooking,
75:40 you would cure diabetes on a dime.
75:44 Takes about a week.
75:45 Because you're getting that 100
75:47 to 300 grams of fiber I mentioned before.
75:50 That's why, 'cause fiber is good for you.
75:53 And the more, the better.
75:54 - [Audience Member] Type 2.
75:56 Type 2, right, Type 2, not Type 1.
75:58 I stand corrected, Type 2.
76:01 Now, for some fun.
76:03 That's the end of the biochemistry.
76:05 Phew, how'd I do?
76:06 (audience applauds)
76:11 I told you I'd get you through it.
76:13 So, now comes the fun part.
76:15 The racial innuendos, and all the political stuff.
76:18 The fructosification of America,
76:21 and, of course, the world.
76:22 Ready?
76:24 Another quiz.
76:26 Can you name the seven foodstuffs
76:28 at McDonald's that don't have
76:29 high fructose corn syrup or sucrose?
76:31 - [Audience Member] Mustard?
76:33 - (laughs) No, mustard has it.
76:34 (audience chatter)
76:37 Oh, come on, come one, the big one.
76:39 French fries, but they have salt, starch, and fat.
76:42 So, they're not so good either.
76:44 Okay, what else?
76:46 We'll get to coffee.
76:47 Hash browns, for the same reason,
76:49 salt starch and fat.
76:51 What else, chicken McNuggets, I was shocked.
76:55 I was shocked.
76:56 No sucrose or high fructose corn syrup in chicken McNuggets.
76:59 But, as the Circuit Court Judge in New York
77:02 called them, they are still a McFrankenstein creation.
77:05 (audience laughs)
77:07 But, nonetheless, no sucrose, I was really shocked.
77:10 Sausage.
77:12 Oh, they're terrible, they're just disastrous.
77:13 But, I mean, there's nothing good in them at all,
77:15 but there's not fructose.
77:18 Sausage, Diet Coke, Coffee, if you don't add the sugar,
77:25 and ice tea, if you don't add the sugar.
77:28 By the way, the chicken McNuggets,
77:29 we have a disclaimer, because no one
77:31 eats the chicken McNuggets without a dipping sauce.
77:35 And there's a whole bunch of high fructose corn syrup
77:38 in the dipping sauce, right?
77:40 Okay, good, all right.
77:41 So, who's really drinking this?
77:43 We talked about this before.
77:45 Gatorade AM.
77:48 So, this is an attempt by Pepsi
77:50 to capture market share on the juice market.
77:54 Do you think there are any elite athletes
77:56 who actually drink this stuff?
77:59 You gotta be kidding me.
78:00 Okay, this is for kids, right?
78:04 So, this really blew my socks off.
78:07 This was my daughter, when she
78:09 was in second grade, two years ago,
78:11 Miriam Lustig, brought these two
78:13 cartons of milk home for me, and said,
78:15 "Dad, you're not gonna believe this."
78:17 Second grade.
78:18 So, here's the calories in Berkeley Farms
78:20 1% low fat milk, 130 calories, 15 of them are sugars,
78:23 'cause it's lactose, which is okay.
78:26 And here's Berkeley Farms 1% chocolate milk,
78:29 190 calories, 29 grams of sugar,
78:33 all high fructose corn syrup.
78:36 It's like a glass of milk plus
78:38 a half a glass of orange juice.
78:41 And that's what we're giving to our kids.
78:43 And do you know what the
78:46 nutrition department at the SFUSD says?
78:48 "Well, we have to get our kids to drink milk some how."
78:52 Is that brilliant, or what?
78:54 I don't know.
78:55 Now, what about WIC.
78:58 So, we talked about the 112 pounds
79:00 of orange juice that the kid down in Salinas was drinking.
79:03 What bout WIC?
79:05 Remember what we started with?
79:07 We have an epidemic of obese six month olds.
79:11 Remember?
79:14 So, could this be the reason?
79:16 So, here's a can of formula.
79:21 43.2% corn syrup solids, 10.3% sugar.
79:29 It's a baby milkshake.
79:33 Soda, Coca Cola, is 10.5% sucrose.
79:38 Formula is 10.3% sucrose.
79:42 Any difference?
79:44 And there's a huge literature that's
79:45 now coming of age that shows that
79:47 the earlier you expose kids to sweet,
79:50 the more they're gonna crave it later.
79:53 Plus, there's a new literature that shows
79:56 the more sugar the pregnant woman drinks or eats
79:59 during the pregnancy, the more that gets
80:01 across the placenta, and actually causes
80:05 what we call developmental programming,
80:07 changing the kids adiposity even before the kid is born,
80:12 and driving this whole epidemic even further.
80:15 So, we'll close in a few minutes.
80:18 But, I just wanna point out what's the difference.
80:22 Here, we got a can of Coke.
80:24 Here we got a can of beer.
80:25 And I'm not picking on Schlitz, or anything.
80:27 It's any beer you want, okay.
80:29 So, 150 calories each, no difference
80:32 in terms of total calories.
80:33 Percent carbohydrate, so 10.5% from sucrose here,
80:37 except it's high fructose corn syrup, but who cares.
80:39 3.6% alcohol, here's the breakdown.
80:42 75 fructose, 75 glucose for the Coke.
80:45 90 alcohol 60 maltose for the beer.
80:49 Remember, the first pass GI metabolism
80:51 takes 10% of the alcohol off the table.
80:54 So, when you actually compute
80:56 the number of calories hitting the liver,
80:58 which remember was the big difference