← Plain English with Derek Thompson
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- [00:00]
J. Kyle Mann
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- [00:40]
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- [01:11]
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- [02:00]
David Kessler
A grand Theory of Health and Chronic Disease in America in the last few weeks, I've had two conversations with doctors that really struck me, one with David Kessler and another with Eric Topol. And in this episode, I'm merging those two interviews into one show because the two doctors and I, we ended up talking about the same thing. Diet, toxic fat, inflammation, chronic disease. And I came away from both conversations with this kind of grand hypothesis kicking around in my head. A way that Western diets lead to Americans being the sickest people in the Western world, in large part because of the way that what we eat turns into fat, which turns into inflammation, which leads to chronic disease. So what you're going to hear today is three people working together to build this grand theory up from the ground level. But first, some facts. For many decades, the US has had higher rates of obesity and chronic illness than similarly rich countries. It's not just the poor. Among us, rich Americans die from heart.
- [03:14]
Eric Topol
Disease more than similarly rich Europeans. In fact, every income group, every ethnic.
- [03:20]
David Kessler
Group, and education group that reaches the age of 50 here in America arrives at that stage of their life more heavy, more unhealthy, and at higher risk for serious heart disease or metabolic diseases like diabetes. In fact, according to the nih, Americans who've seem to have won the genetic and socioeconomic and behavioral lotteries, these are Americans who don't smoke, who are insured, college educated, rich, are still in worse health than similar groups in comparison countries. Well, you might just say let's just blame Americans. This is always an easy thing for pundits to do. Let's just judge people for eating like crap, for not walking enough, for not keeping up with their health insurance payments or their medicines, for not taking care of their bodies.
- [04:09]
Eric Topol
It's very easy to judge.
- [04:10]
David Kessler
Very, very satisfying for some. But I'm not sure this blame game is very useful. While mysteries abound in health, the reason why Americans have such a high rate of obesity is, in fact, not a total mystery.
- [04:26]
Eric Topol
Americans at every age and income simply eat more calories.
- [04:32]
Derek
I gained weight and lost it repeatedly over my lifetime. I mean, I have suits in every size and I would gain the weight and then eventually I would decide to lose it. I would lose it. I thought I was done. I would go on with my life only to gain it back.
- [04:51]
Eric Topol
That's Dr. David Kessler. He was the commissioner of the Food and Drug Administration under the Bush and Clinton administrations. Between 1990 and 1997. He helped to lead Operation Warp Speed in its final months. By all accounts, this is a man of very high conscientiousness, ability, intelligence, responsibility. But for Kessler, questions of diet and weight and obesity hit very close to home.
- [05:19]
Derek
You know, why was I gaining it back? What is this mystery about weight, right, that has not been understood. And I think if you. I mean, why do we just keep on gaining it back? Why can't I control it?
- [05:32]
Eric Topol
When he turns the spotlight inward, Kessler recalls that he used food to quash every emotion.
- [05:39]
Derek
I mean, certainly for me, if I observe, when I ate, I ate to calm myself down. I ate to increase my focus. I mean, I ate through the day. Bypass that refrigerator. I mean, just the refrigerator Itself was a cue. I was grazing through the day.
- [06:01]
Eric Topol
Now he spent years, decades really thinking about the relationship between our bodies and our food environment. Why do western countries, especially the United States, have so much obesity and obesity related disease? For Kessler, the answer goes back a.
- [06:18]
Derek
Bit, way back a bit, thousands of years ago. I mean, the food environment was characterized by scarcity. In order to survive, our brains evolved to be able to focus our attention, to gate our attention on that energy dense food. That's how we survived. I mean, if you were a bird and you were flying over and you needed to identify sustenance and energy, your brains were wired. Your brains were wired and this evolved through the species.
- [06:57]
Eric Topol
The food environment of the 21st century is unusual. For one thing, calories are more available than ever. The USDA has a long running data set on total calories produced by the US food system through production of foods in the US like say Iowa corn and the import of foods like say French cheese. This isn't a measure of food consumed. To be clear, I'm talking about a different measure, not of what we're eating, but of what producers are making available for us to eat. A measure of our environment. In 1900, calories available per person per day averaged around 3,300. In 1920, still 3,300. 1940, 1960, still around 3,300. Only starting in the 1970s does this flat line board a rocket ship in the 21st century. Today, caloric availability per person now consistently averages over 4,000 calorie hungry brain meat, calorie rich environment.
- [08:08]
Derek
It's not that there's something wrong with our brains. If anything, our brains are working too well.
- [08:14]
Eric Topol
Some scientists refer to this phenomenon as disevolution. We were evolved for one world, we live in another. Our biochemistry is outfitted for scarcity and yet we're overrun with caloric abundance.
- [08:28]
Derek
What we did was we took this energy dense food, fat, sugar and salt. You know, fat and sugar, fat and salt, fat, sugar and salt. This perfect trifecta that affects the brain's reward circuits. We put it on every corner. We made it available 24, 7. We made it socially acceptable to eat. Any time we're living in a food circus, I mean, what did we expect to happen? I mean, we live in an environment of abundance, right? And so our brains are wired to, you know, find that energy dense food. And you know, we put all this energy dense food, made it available and made it socially acceptable to eat anytime. So we played right into those circuits.
- [09:12]
Eric Topol
Kessler is most concerned about one Category of our diet, ultra processed food. As we explained in our previous episode in this series, the NOVA food classification system has four categories. Category one is minimally processed food, say raw broccoli. Nova two is food ingredients, butter, salt, sugar. Nova three, or processed foods is most of what you might cook at home, say, marinated chicken or a homemade cookie. Nova 4 is ultra processed food. This often includes industrial ingredients, artificial flavorings, food dyes, and other additives. This category is broad, containing everything from unsweetened almond milk, two Twinkies. But Kessler is worried that most of the food that's most bad for us mostly lives in this ultra processed category. In fact, he says, a lot of this category four stuff, it's barely even food.
- [10:18]
Derek
Food has a certain structure to it. It has cellulose, it has fiber, shortache. I mean, it can have sweetness, it can have glucose, it can have fructose. But if you look at the rate of absorption, the structure of food slows down that absorption of that glucose. So the rate of rise into the bloodstream is not constant, spike after spike. And when we took these, call them ultra processed or ultra formulated foods, took out the structure. They go down into whoosh. They are rapidly absorbed in the GI tract. They are, in essence, creating metabolic chaos.
- [11:02]
Eric Topol
When somebody habitually eats more calories than.
- [11:04]
David Kessler
They burn, those extra calories get stored as fat.
- [11:08]
Eric Topol
Initially, most stored fat ends up under the skin. This is called subcutaneous fat.
- [11:13]
David Kessler
But as weight gain continues, more fat accumulates under and around internal organs in the stomach.
- [11:20]
Eric Topol
This is what David Kessler calls toxic fat.
- [11:24]
Derek
Toxic fat. It's the fat that is metabolically active. I'm not looking to give a clean bill of health to all other kinds of fat, but it's there. There's certainly this fat in our abdomen that gets into our liver, into our pancreas, into layers of the heart. That is, you know, that's causal in those chronic diseases.
- [11:48]
Eric Topol
This visceral fat is not just a passive storage depot. It behaves differently than the fat right under your skin. Visceral fat cells release a flood of acids into the veins that lead directly to our liver, where they wreak havoc on our metabolism. At the same time, scientists have found that visceral fat secretes different proteins that throw our immune system out of whack.
- [12:12]
Derek
This accumulation of fat in the liver and fat in these vital organs, it's been staring us in the face. I think, increasingly, cardiologists, nephrologists, neurologists, endocrinologists, some of the oncologists, possibly Some of the neurodegenerative diseases. But I think the medical community is beginning to wake up.
- [12:38]
Eric Topol
Many ultra processed foods have a quality that nutritionists sometimes call energy density. A full bite of broccoli has about three calories. That's category one. A full bite of marinated chicken breast might have 30, 35 calories. That's category three. A hostess ho ho. One bite, 130 calories. As food companies have gotten better at packing sugary, fatty, salty calories into single bites of food, each chew now sends our insulin levels surging again.
- [13:15]
Derek
I'm going to use a scientific term here. There's been a doubling in hyperinsulinemia in this country, and that is a result of these sweeteners coming in, being absorbed relatively rapidly. Scientists have not quite figured out it happens very fast. You know, does the visceral fat cause the hyperinsulinemia, this toxic fat, or does the hyperinsulinemia cause the visceral fat, which comes first? Right. But if you look metabolically, you have these. We're hyperinsulinemic. And that is causing enormous amounts of chronic disease. It's the environment where certain cancers get stimulated, mean it's pounding the endothelial cells of our arteries.
- [14:05]
Eric Topol
In sum, western diets are filled with food that is packed with calories per bite. Food that is so rich with sugars, salt, and fat that we eat it in excess before our bodies can send us the signal that we're full, or the signal that we're full is, for some, overwhelmed by a compulsion to keep eating. All this eating and visceral fat is having a further effect on our bodies and inflammation.
- [14:33]
And this is really the whole ball of wax for why we have chronic disease through chronic inflammation that is unchecked.
- [14:42]
This is Eric Topol. He's a cardiologist and the founder and director of the Scripps Research Translational Institute. And if overeating and visceral fat are the first two steps in this grand theory, the third stage is inflammation.
- [14:58]
Well, I mean, a way to consider it, you know, for a more familiar way, would be if you really banged up your knee, and I mean, pretty badly banged it up, and it now had fluid in it, and it was hot because it's inflamed, might even be red because basically what's happened is there's been a cellular response driving inflammation, releasing. These white cells of different types are releasing all sorts of proteins that get your body, that's that knee joint and its surrounding tissue into a hot zone. I mean, if you measure temperature of the Tissue, it gets hot.
- [15:44]
So that's inflammation in a joint. Topol says it's the sort of inflammation that most people like you and me, know and recognize. But now picture something a little bit different. Picture inflammation happening in an artery. Your artery didn't bang its knee on a chair. I don't even know what that would mean. But rather it's reacting to a smaller set of smaller bangs, perturbations brought on by our own behavior. This leads to chronic inflammation, the sort of inflammation that doesn't go away. Like a swollen knee that heals. This is inflammation that lingers.
- [16:20]
So it's the same process as that kind of simplified knee model of trauma. But this is going on in tissue, whether it be the arteries, not just of the heart, but you know, the arteries in the neck that go to the brain or, or the aorta or other arteries. That's atherosclerosis or it's in the brain. That is the same type of thing where you're having these cells releasing chemicals that are basically proteins that are, basically, they're, they're trying to react, but in so doing, in their reaction, it's an untoward response because they're, they're destroying, they're damaging tissue. You don't really want to have your brain cell damaged or destroyed, right? So the inflammation isn't good, it's untoward or adverse.
- [17:14]
Our diet is full of these tiny little knee bangs. Whether it's eating energy dense food, not exercising, not getting enough sleep, or perhaps being exposed to toxic chemicals, over time these little perturbations add up. Topol says they keep our arteries chronically inflamed, our tissues chronically inflamed, our brains chronically inflamed. The modern world hijacks our own immune system to attack our very bodies.
- [17:44]
You know, there's so many of these perturbations that are promoting inflammation at these different tissues that over time, as we age, you know, gets even more accentuated. We're, we're much more prone to this process. That's why it's called inflammaging. You know, we, we do better when we're young not to over overdrive inflammation or keep our immune system at its highest level of protection. But as we get older, it's not as competent. It's just losing its kind of delicate, kind of Goldilocks balance or too much, too little. And that's really what is the fine tuning the regulation, if you will, that changes as we get older.
- [18:34]
Today, inflammation plus aging. Inflammaging is one of the hotter fields in medicine. Researchers are testing whether anti inflammatory medications, the sort we typically use to treat rheumatoid arthritis or allergies or eczema, can slow cancer and dementia in older patients by fighting what Topol calls untoward inflammation. For him, inflammaging is a major factor behind most age related diseases.
- [19:04]
Okay, this is the underpinning, the common thread to the big three age related diseases. Cancer, atherosclerotic cardiovascular, heart disease, and neurodegenerative diseases. And basically, it's the model that explains everything.
- [19:24]
That might sound a little oversimplified, but not much. Topol says the more we learn, the more it seems that chronic inflammation in the body is a leading factor for cancer, heart disease, and Alzheimer's.
- [19:38]
So for cancer, it's critical that our immune system keeps up its guard, its integrity to guard against these alien cells that have these foreign proteins of cancer cells, and to react against that and squash it before it ever gets to grow. Now, with respect to the plaque of a cholesterol buildup in an artery wall, what you have there is basically an inflammation that's unhelpful. It's making that plaque grow more. It's making it susceptible to cracks that cause heart attacks and blood clots. So that's untoward inflammation. And then for Alzheimer's, you know, all of us as we get older, will have some of this misfolded proteins in our brain, like amyloid and tau. But it's really the inflammation to these proteins that is what's causing the trouble where we have loss of our brain cells and loss of brain function, which leads to Alzheimer's and other neurodegenerative conditions. So all three of these, which, by the way, Derek, it takes 20 years for these three conditions typically to take hold. So we have chronic inflammation over many years that are leading to gradual compromise of the tissue of the organs that are involved in these three processes.
- [21:09]
David Kessler
What is dadication?
- [21:10]
Dariona
The thing that drives me every day as a dad is Dariona. We call him day date for short. Every day he's hungry for something, Whether it's attention, affection, knowledge. And there's this huge response, responsibility, in making sure that when he's no longer under my wing that he's a good person. I want him to be able to sit back one day and go, we worked together. We did a good job.
- [21:30]
Eric Topol
That's dedication.
- [21:32]
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- [21:34]
Eric Topol
The U.S. department of Health and Human Services and the Ad Council. It's a compelling theory you can see it almost like dominoes clicking into one another. From an environment that's super abundant in calories to a diet that's too rich in calories. Click. From eating too many calories to weight gain. Click. From weight gain to visceral fat. Click. From visceral fat to metabolic disorder and inflammation. Click. From inflammation to disease. Final click. Now, this theory is not like gravity. This is not 1, 1, 2. It's not proven beyond all doubt.
- [22:09]
David Kessler
You should think of it as a.
- [22:10]
Eric Topol
Kind of grand hypothesis, but you have to admit it's elegant as hell. And if true, it's a frustrating reality for patients today because, as Topol admits.
- [22:22]
Like I said, we don't have readily available inflammation markers. I wish we did. I hope we will soon. But we're still talking about at least a couple of years from now.
- [22:32]
In the meantime, there are things we can do right now to track proxies for our inflammation, like glucose.
- [22:40]
You know, one way to get at this is a glucose sensor to see if you develop spikes. How big are the spikes? I mean, normally you'd like to see your glucose be steady, you know, 80, 90, less than 100 all the time. But if you have a spike to 250 after eating something, you say, huh, this is really giving me my pancreas a challenge here. Something is a little off track because you shouldn't, as a healthy person, have glucose spikes that are really high or really long, like, you know, lasting an hour, hours, whatever. So that's one way to do it.
- [23:15]
And the theory that we're building up to in this episode, this relationship between caloric surplus, which leads to visceral fat, which leads to inflammation, it has to account for something else. The fact that different human bodies process food differently.
- [23:31]
You and I, Derek, we ate the exact same thing, the same amount, the exact same time. We might have a very different respons learning about our unique metabolic responses to what we eat, when we eat. These are things, and even the sequence of what we eat, these are things that we're going to get more handle on. But whether it will come out with specific individualized recommendations, it isn't clear. There's a big investment at an NIH program that's doing that right now in over 10,000 people. But we're years away from having an individualized diet recommendation.
- [24:09]
As I was listening to Topol explain the dangers of inflammation, I thought about the times when I felt most swollen or blood hot. Yeah, that one time I ate too much steak, or maybe when I go to the gym and it Made me.
- [24:23]
David Kessler
Think of something else.
- [24:24]
Eric Topol
If exercise is inflammatory, why is it so good for us?
- [24:30]
When you exercise, it's like a test run to induce inflammation. And your body then gets groomed, if you will, trained to have your immune system and your inflammation response in the highest integrity. So when you don't exercise, you don't get the advantage of all this training. This kind of, these, this exercise can induce a low level inflammation, but then ultimately, if you're doing this on a repetitive basis, it gets your immune system function and your inflammation into its highest functionality. So it's really the exercise that does good rather than the sedentary that does bad.
- [25:22]
Exercise is critical. One scientist I spoke to last year called it the greatest medical intervention known to mankind. When it comes to weight and fat, exercise is particularly important because energy balance is about calories in, calories out. And in rich countries with our delirious food abundance, it's critical for people who can't control their calorie intake to increase their caloric burn rate, to get into what Kessler calls an energy deficit state.
- [25:52]
Derek
The only way to be in an energy deficit state, you know, was this phrase, eat less, exercise more right? But the problem was it failed for decades because no one could do it. Why could no one eat less and exercise more, right?
- [26:09]
Eric Topol
It was an absolute failure for decades. Kessler said most people dealing with obesity and weight gain felt powerless to overcome their metabolism, their stomachs, their minds, their cells. They ate when they didn't want to. They gained weight that they wanted to lose. But now a new tool has offered hope to millions of people. It's called glucagon. Like peptide 1 receptor agonists. You probably know this category as GLP1, Ozempic, Wegovy, Mounjaro.
- [26:41]
Derek
They work primarily multiple mechanisms, but primarily through something that's called delayed gastric emptying. So food stays in your stomach longer, it just doesn't move through as much.
- [26:59]
Eric Topol
Think about normal times when our stomach sort of shuts down when we're sick.
- [27:04]
Derek
You have the flu, right? You are ill, you know, your GI tract stops working fully, right? Food stays in your stomach. What's the last thing you want to do? Put anything else in your GI tract, right? Food poisoning. Have you ever had food poisoning? You eat something and you remember years later. I mean, that memory still stays with you. It's that cellular. But in food poisoning, food just continues to accumulate. Your GI tract shuts down. The food just piles into your stomach. It doesn't leave the pyloris, it doesn't leave that Sphincter into the rest of your intestines and you feel like vomiting or throwing up, you just have this sense of nausea.
- [27:50]
Eric Topol
Kessler isn't just reading the academic literature, he's describing his own firsthand experience on these GLP1 drugs.
- [27:58]
Derek
When I went on these GLP1 drugs, I didn't want to put anything else in my stomach. I started eating smaller portions and I didn't want fat and sugar in my stomach. It was just going to sit there longer. So I started first time I started eating vegetables. I just didn't want to put more amount of this ultra formulated foods in my stomach.
- [28:21]
Eric Topol
This is one of the findings in the early literature that I personally find most interesting. Being on GLP1s doesn't just get people to change how much they eat, they change what they eat. Ultra processed food intake declines, fruit and vegetable consumption goes up. How the hell is a drug doing that? Kessler has his own theory. GLP1s haven't just been found to increase satiety. There are GLP1 receptors in the brain as well.
- [28:55]
Derek
We know they get to the hindbrain, they get to the gut, they'll have this delayed gastric temperature, they get to the hymer and they get to the area of postrema, they get to the NTS nucleus solitarius.
- [29:07]
David Kessler
So altogether these drugs seem to slow.
- [29:10]
Eric Topol
Gastric emptying, increase feelings of fullness, tweak our dopamine cycles and dull our addictive circuits. Some studies have found that people on GLP1 drugs curb other compulsions like gambling and smoking.
- [29:25]
What we have learned and I would submit to you Derek, that we're only at the beginning of the gut hormone story. We're talking about the gut hormones talking to the brain and to the immune system.
- [29:38]
Eric Topol is thrilled about the future of GLP1s for their potential to reduce not only weight but also chronic inflammation. The drugs in the market have already shown their ability to be anti inflammatory. And what's to come might be even better.
- [29:56]
And we have two that are out there, injectables. We're going to have pills and tirzepatide is a double receptor. Soon we're going to have a triple receptor resurrectides. And then we're going to have all these other gut hormones, another 10 more of them in combinations with the ones we have today or even more potent ones, some that get in the brain much better directly don't rely on the gut to brain signals. So what I'm getting at here is this has turned out to be one of the most extraordinary anti inflammatory mediators that we have ever seen. They make statins look weak.
- [30:36]
David Kessler
Do you think there's a future in which a certain kind of GLP1 drug.
- [30:42]
Eric Topol
Maybe it's a double agonist, maybe it's.
- [30:44]
David Kessler
A triple agonist, maybe it's some other, some other approach will be generally recommended for far more people who don't have anything like type 2 diabetes or obesity. Because at some point, if I put together everything that you're saying in this episode, which is number one, that inflammation is a major driver of the most common diseases that kill older Americans and number two, that we sort of haphazardly, accidentally, you know, looked at the Gila monster's mouth, yada yada, yada. Have GLP1 drugs accidentally made this drug that is extraordinary at reducing the thing that's driving age related diseases. Why wouldn't at some point the FDA or doctors recommend that tens of millions more patients take say a diet Coke version of these drugs that don't have an enormous amount of weight loss potential? You know, if someone's already of normal weight, you don't want them losing another 20 pounds. But has some of this anti inflammatory effect?
- [31:51]
Eric Topol
Yeah, I think eventually we're going to get there that most people will be taking some type of gut hormone mimetic, which is what these are. Because the way to the body's inflammation and immune system is. So as we've learned in recent years is through the gut. I mean we didn't think that. I never would have guessed it. We knew the gut microbiome was important, we just didn't know how important these gut hormones are. Now one of the questions I have though, Derek, is another alternative would be to manipulate the gut microbiome with prebiotics and probiotics. And so whether we do it in the years ahead, I mean, talk about years ahead, through the. The bacteria in our gut lining or it's their metabolites or whether we do it with some variety of gut hormones that we have in the. I want to say we're early in the gut hormone era. Right. Whether it's one of the two. But this will become a standard part of medicine in the years ahead. This is why I'm so keen that we are having a newfound capability of preventing these big three diseases because we're seeing some things we had never envisioned. I mean, when I went to medical school there was only one gut hormone we knew about, it's called insulin. Now we have 20 and now we're seeing these kind of Magical effects in the clinic. And still many, many more of these to come in pill form, which will be much less expensive, easy to make, and then of course, all sorts of permutations and combinations and doses. And this is just early stuff that people don't realize how big this gut hormone and gut microbiome story is to unfold.
- [33:40]
We started this miniseries with a simple why are Americans so unhealthy?
- [33:45]
David Kessler
The unified theory presented here is simple.
- [33:48]
Eric Topol
We live in an environment of extraordinary caloric abundance, including ultra formulated foods which overwhelm our natural hunt for calories and our feelings of fullness. This leaves most Americans in a state of constant caloric surplus. We consistently take in more calories than we're burning out. And the basic physics of this imbalance predicts nothing short of inevitable weight gain. But we're not just gaining weight in our subcutaneous fat just under the skin. Deposits of visceral fat in our abdomen leak toxins, proteins that cause body wide inflammation. And this chronic inflammation, this simmering fire inside our bodies, is slowly wreaking havoc on our heart, our minds, ourselves. And unless we find some way to, on our own, reverse that cycle, one of the best tools that we have right now is this new category of GLP1 drugs, which essentially work on two levels. First, they delay gastric emptying and make us feel full. And second, they seem to tweak our dopamine reward systems in a way that gives people more control over their compulsive behavior. Because these changes are so dramatic, they can make people feel nauseous or just sick enough to avoid rich foods and graze on plainer foods, which has the remarkable effect of shifting patients entire diets toward healthier fare. I want to leave you with one final image. The human body is a car finely tuned over thousands of years to have a million different parts. And two of those parts are a gas pedal and a brake. The modern food environment is a brick dropped on the gas pedal. Caloric availability makes it easy to overeat. Ultra processed foods accelerate glucose absorption. The whole food environment in this metaphor, is heavy pressure on the accelerator. GLP1s work because they slow everything down. They hit the brakes rather than accelerate glucose absorption. They slow gastric emptying rather than increase hunger. They increase feelings of fullness rather than flood us with food noise, that feeling at the back of your head that says eat, eat, eat. They turn down the volume of the food noise and return us to our regularly scheduled thoughts. Perhaps that's why research shows that these drugs improve not only weight gain, but also health across a range of outcomes. They return the car to its proper owner. They remind the body that the brake pedal exists in the first place.
- [36:32]
David Kessler
Dr. Kessler, thank you very much.
- [36:34]
Derek
Thank you.
- [36:36]
David Kessler
Eric Topol, thank you very much.
- [36:38]
Eric Topol
Thank you, Derek.
- [36:39]
Enjoyed it and thank you all.