 Children's Health Care in Madeira, California. He is also board certified in obesity medicine and has done original research on genetics and epigenetics of obesity and insulin resistance. Without further ado, I'd like to pass it on to Dr. Ali. Dr. Ali, you may begin. Good afternoon, everyone. And thank you for inviting me. I hope this will be a useful program for people. I'm going to start my presentation so you can see it on the screen. So I think everyone can see the presentation on the screen. Yes. So we will begin. This is going to be sort of a quick overview of basic facts and treatment options about obesity. Obviously, obesity is a very large topic and we won't be able to cover every aspect. So we will fly over some things, but there will be questions at the end and you can ask me questions and sort of look up other things in your own time. But we will start by trying to define what is obesity? So obesity basically just means an excess of fatness, right? More fat than your body needs, more fat than is healthy for you. So it's not the same as weight. It is possible to be overweight without having excess fat, right? Like bodybuilders who have 5% fat can be very overweight in terms of weight or underweight with excessive fat. Like there is a condition called Prader-Willi syndrome in which babies are born with very low lean muscle mass. So they have relatively more fat, but they are still underweight at that stage. But for most otherwise normal adults, increasing weight will mean increasing fat, right? That's normally the case when someone gains weight. But increasing weight is less reliable as a tool in children because in children, obviously, they normally gain weight as they get older because they gain height. So we have to plot their height and weight and then see if this is excessive for that age and that size. So what would be a good measure that would assess fatness and not just weight? I'm sorry, Mr. Dr. Ali. You're supposed to go to the next slide. We're still on the first... Oh, okay, sorry about that. You can see the slide that says, what is obesity? No, we're still on the first, the cover slide. Oh, really? I moved the slides here. Sorry, I don't know why it's doing that. And also the full slide. Screen is not working. Sorry, let me just go back and fix that. So I was saying obesity is not the same as weight. So we are looking for a good measure to assess fatness and not just weight, right? And we have to find a quick and easy way to measure it. There are tools for measuring fatness. There are electronic devices, for example, where you stand on them in your bare feet and they pass some electricity through your body and assess how much fat you have. But you need some tool or something and it needs to be a process. So we are looking for something simpler. And what they came up with is body mass index. So what is a body mass index or BMI? BMI is basically a ratio of weight per unit height. So we take weight and divide it by height squared. Why height squared? There's a long discussion of why height squared. It turns out that height and weight don't sort of increase linearly with each other. The height, the weight increases in relatively more. Or relatively less, sorry, as you get taller. So the correct proportion to which would capture excess fatness best is not the weight divided by height, but the weight divided by height raised to some power. That power is actually closer to 1.6, 1.7 is ideal, but that would be harder to do. So eventually the bottom line is we came up with this figure of weight divided by height squared. And what that means is that if someone weighs 120 kilograms and they are 150 centimeters or 1.5 meters tall, then what is their BMI? We divide the 120, their weight by 1.5, their height in meters, and then divide it again by 1.5, right? That's the same as dividing by 1.5 squared. And you get a number which is in this case, 53, which is a very high BMI. So there's someone who is very overweight. In adults, we can just use cutoffs of BMI to define what is normal and abnormal. A BMI of 18 to 25 would be considered normal. Anything from 25 to 30 is overweight and anything greater than 30 is considered obese. In children though, normal fatness does vary with age. So we have to rely on plotting according to age. Because as you can see on this chart, a child who is four years old, his sort of maximum fatness should be around here, but that amount would be normal in a 14-year-old, right? So whether you consider it excessive or not depends on their age also. So we have to plot it on a graph to see if it is excessive or not. So what are the guidelines? As I mentioned, adults, BMI of 25 to 29.9 is overweight, more than 30 is obese. In children, you plot them on the chart if they're below the fifth percentile, they're underweight. From fifth to 85th, they're considered normal. If a child is at the greater than the 85th percentile, we call them overweight. And if they are over the 95th percentile, we call them obese. So on these criteria, how common is it to be overweight or obese? It is, of course, very, very common, right? And all over the world, the prevalence of obesity is increasing in both adults and children. Overall, the obesity rates in the US did seem to plateau in children for a while. There was hope that after about 2000 to 2015, there wasn't a big change. So while there was a lot of weight gain in the 80s and 90s, it seems to have slowed down in the early 2000s. But unfortunately, with the COVID epidemic and the school closures, that whole thing took off again. And the obesity rate in children is going up as well as the obesity rate in adults, which never stopped rising. And the rate of extreme obesity never stopped rising either. The people who are extremely overweight, their numbers have continued to go up. So how common is it in children in the United States? About one-third are either overweight or obese. About 20% are obese and another 15% are overweight. So about a third of them, half of them in the overweight category, about half of them in the obese category. In adults, it's much worse, right? Just double what it is in children. In adults, two-thirds are overweight or obese. So if you were going by just normative data, you would have to say that it's normal to be overweight or obese in adults because most of them are overweight or obese. There's about half in each category. So half of them, half of the adults in the US are between 25 and 30 BMI. And the other half of that, or one-third are going to be above that 30 BMI and are going to be obese. So what causes this obesity? Why? This is a doctor saying, patient eating many sweet delicacies and fatty foods. And this is from the Yellow Emperor's Medicine Classic in 700 BC. So it's not something new, right? We know people get overweight because they eat too many sweets and fat. Sugar and fat is what makes you gain weight. But why is that happening though? It turns, there is a system for regulating weight in our body, right? You don't have to go into these details. This is really a medical school slide. But the thing I want you to take away from this is that there is a system in the body to regulate weight, right? The body doesn't, you don't just eat out of habit or eat whatever you want. Your body, your brain sort of regulates how much you eat and how much you burn. And it does this by keeping track of your fat tissue, how much fat you have in the system and keeping track of how much food is in the stomach and in the gut. And this message is passed to the brain. There are neurons in the brain, mostly in the hypothalamus that sort of integrate all this information and decide whether the person needs to gain weight or lose weight. Unfortunate part though, is that this system was designed to avoid being underweight, right? It's not really designed to be, to treat overweight or to avoid overweight. For millions of years, we have been evolving in a setting of scarcity where our ancestors or our ape ancestors as well as our hominid ancestors were always short of food. So the brain has very extensive systems for figuring out that we don't have enough fat, we need to go out and eat more. So you feel hungry, you look for food, you, every food looks like sort of desirable to you and the body, this sensation doesn't go away till your body gains the amount of fat it wanted. Human beings really did not have a great need to try and lower their weight in the so-called good old days, right? But now that we live in an environment of plenty, this has become a problem. Now we live in an obesogenic environment, so people are gaining weight. But even now, it's not like people gain weight completely uncontrollably, there is still a system in place. And to give you an idea, I just put this fact in here, in the United States, the average adult gains two pounds a year on average, right? As you get older, you gain more weight. This weight, two pounds is really just 4,000 calories of stored energy. It's not like it doesn't take a lot of calories to put on two pounds. You eat 900,000 calories a year. If you ate just 1% more, you would gain dozens of pounds, not just like one pound. So the body is regulating it. Even today, the body is regulating your weight, but it's not succeeding in overcoming the obesogenic environment because it wasn't designed for this environment. So most cases of obesity are not due to an abnormality of the regulation of the system that we can detect in a kind of mutation that we can find, right? Most people, there are such mutations, but they are not a major cause of obesity. It's not per se a genetic disorder. If it was a genetic disorder, we would expect it to have been present 100 years ago the same way it's present today because genes don't change that fast, right? But obviously the prevalence of obesity has dramatically increased. So the genes are the same, but the same genes are being expressed or the same tendency to gain weight is being expressed now that we are in an obesogenic environment, right? And there are other, they're just looking at other causes of obesity. There's thyroid problems, cortisol problems, growth problems. None of these are really common causes of obesity. Common obesity is not due to a medical condition. It's due to an environment that we are not designed for. Our overall genetic makeup does influence how easily we gain weight, though, right? There are some people who are clearly more prone to gaining weight than others. And these people, they don't have a single gene defect. It's not like there's one mutation that caused that. It's a large number of genes working together. Some of them are a little bit off and that all adds up to a tendency to eat a little bit more or to burn calories a little bit less than the other person. And a little bit is enough. As you saw in that example, you eat 900,000 calories a year. If you eat 910,000, you will gain three pounds. So there is a small excess will add up. If you put people in an obesogenic environment, there are still some people who don't gain weight. So really some people's internal regulation is so good that even in this environment, they don't gain weight. But most people in this environment, unfortunately, tend to gain weight. One way you can get an idea of what the genetic component of obesity is, is that you look at what happens if you have an obese parent. Your risk of obesity goes three or four times higher. If you have two obese parents, your risk of obesity is 10 times higher than the general population, right? So there is an inherited tendency. There's no question about that. When people tell you that I have a tendency to gain weight or I am sort of prone to gaining weight, they're not lying. It's not just like willpower or you can say even willpower is genetic, right? There is some people will genetically have more willpower than someone else, but it's not a choice in that sense. Some people really are more prone to gaining weight than others, but they won't gain weight in a non-obesogenic environment. There are some genetic syndromes that cause obesity, and I don't want to get into any details, but just to give you an idea, the most common syndrome causing obesity is a condition called Prader-Willi syndrome, and it's only one in 10,000 to one in 15,000 people. So even this most common disorder is very rare act. The others are even rarer. Lawrence Moon, Beatles syndrome, Alstom syndrome, you'll hear these names sometimes, they cause obesity, but they're all extremely rare. There are some defects in a gene called MC4 receptor, which are a little bit more common, but even those are not a common cause of obesity. They are just one of the rarer causes of obesity. Most obesity is not due to inherited genetic defects, but an inherited genetic makeup does make you more or less prone to gain weight in an obesogenic environment, right? In a lean environment, everyone would be lean. There are no obese people in concentration camps, right? But in an obesogenic environment, only about a third of the people can seem to resist it. So why is everyone becoming obese? It's probably an imbalance of evolution, physiology, and civilization, right? We evolved because in a situation where you couldn't find food. For 2 million years, we had scarcity. Lifespan was short, survival was difficult. In this condition, our evolution favors energy storage, right? We like dessert because dessert is sugar and fat. We are designed to like sugar and fat, right? And why not? That's exactly the best ways to get energy. And for 2 million years, we were short of energy. We were never in a situation of excessive energy. So in that kind of environment, in what you might call a natural environment, human evolution naturally favored looking for food, not protecting against food. This protests against malnutrition. It doesn't protect against weight gain as much, right? On the other hand, civilization has evolved to give us more food. It has made food more easily available. It has made food more calorie dense. When you were hunters, gatherers, you were picking up foods that were not really designed as high sugar, high fat items. But over time, we have modified them. We have evolved them to become higher in sugar, higher in fat. And the way we cook them, the way we prepare them makes that aspect even more sort of sharp. So I'll just skip over this because I don't want to take it, but you can see these are the times when these things started, because the cream started, the tunnel started. We are now at the last stage, right? And everyone is prone to gain weight. So why are we growing, becoming obese? Because we are designed to look for food. If food is half as costly, we will buy two times more. So the successful but excessive evolution of civilization to serve our evolved physiologic needs is probably the underlying reason for the obesity epidemic. Other consequences of progress may be playing a role as well though, right? It's not just that food is available outside, but some other things have also changed with what you may call progress. One big change is sleep schedules, right? Abnormal circadian rhythms. We are designed to sleep at night, work by day. We are not necessarily doing that. We have artificial light keeping us going until late at night. We have TVs, screens, phones. Those changes in sleep and circadian rhythm are definitely playing a part in the obesity epidemic, and especially in the insulin resistance epidemic, in why people are becoming more diabetic, more fatty liver, so on. So these things are connected. There's no doubt about it. I don't want to go into the details right now, but they are connected. The other thing that has recently been found to play a role is the gut microbiome, right? The bacteria you carry in your gut, they also shift with how our diet changes. And as they shift, they seem to change how likely we are to become obese. So if you take the bacteria from an obese person and put them into a lean person, that lean person tends to gain weight. If you do the opposite, the obese person tends to lose weight. So the gut microbiome does have a role in this. Some commonly used medications are obesogenic, right? Especially there is an epidemic of psychiatric medication, right? In the United States, there are some subpopulations where more than half the people are on psychiatric medication, right? Like young upper class females, more than half are on some kind of medication. So in that kind of group, those side effects play a role because those medications, not all of them, but many of them make you gain weight. Other factors also play a role, stress plays a role. Endocrine disruptors may play a role, right? You'll hear about bisphenol A in plastic bottles and things like that. Even viruses may play a role. Some cases of obesity may be due to infection with a virus that causes obesity. There is a virus that causes obesity in chickens. So we think there may be viruses that cause obesity in humans as well. Central heating may play a small role also because we don't shiver as much, right? When we burn energy, when we shiver, we burn calories. Now of course we are warm all year round. So what does it matter? People are becoming more obese, evolution has made us prone to obesity. So why does that matter? It matters because obesity causes a lot of problems. First of all, obesity causes insulin resistance. The mechanism is not completely clear, but people who become, as they become more obese, their insulin doesn't work as well. One of the consequences of that is that at some point they will develop type two diabetes. That's classic insulin resistance. But even short of that, they will have issues that arise because of insulin resistance. People have dyslipidemia, their triglyceride levels go up, their good cholesterol goes down. One very common condition in women is polycystic ovary syndrome, where their testosterone levels go up because they gain weight. Coronary artery disease obviously is another common issue that is happening more because of obesity. Obstructive sleep apnea, starting with snoring and going on to completely stop breathing at night, is a common problem with extreme obesity. Low self-esteem is a huge big deal. It's not just all, if you don't have diabetes or PCOS or anything and you're overweight, you still suffer social consequences of obesity. You feel like you're not, people are constantly stressed by the fact that they are obese. Unfortunately, that stress we know makes you eat more and stress is bad for you. It causes insulin resistance. It causes your circadian rhythms to be upset. So it's a vicious cycle. You are worried about your obesity and that worrying probably contributes to more obesity. Bullying and fat shaming is a real thing, right? People, children get bullied in school when they're overweight. Adults get fat shamed. Osteoarthritis, as you can imagine, you're carrying 300 pounds on your knees. You're more likely to damage those knees than if somebody's carrying 150 pounds. Increased risk of cancers. There's all kinds of problems that can come from being overweight. So it's not a benign condition, right? It's not just that we have gained weight and become heavier. It does cause us medical issues. So at what level do these issues become a problem? On that, there is some controversy actually. The BMI cutoffs were designed to detect the level at which something starts to go wrong. And the cutoff for overweight in adults was set at 25. But if you look at the mortality data, like how likely are you to die in the next one year? The people who are around and BMI of 27 have actually the best outcome. They are sort of the healthiest in that sense. Is there are some arguments back and forth around this? Is this cutoff still good or not? But what it brings home is that mild degrees of obesity are not necessarily unhealthy for you. Or at least not so unhealthy that they are your biggest problem. You may have many problems bigger than obesity if your BMI is 27. So if that obesity obsession is then causing stress and more eating and more worrying and low self-esteem, you're probably better off not thinking of yourself as obese. So, and the other thing to keep in mind is that fitness trumps fatness, right? There is a lot of data about this. If you have a BMI of 30 and the other person has a BMI of 25, but you exercise every day for an hour and he has never been on an exercise bike at all, the outcome is better for the person with the BMI of 30 than the BMI of 25, right? BMI alone is not the only thing that matters. Fitness trumps fatness until you get to be very overweight. Once you get to a BMI of 45, then yes, that obesity is going to cause far more problems even if you do exercise every day. But at a BMI of 25, 30, 28, 30, 32, if you are fit, you have much less to worry about, not zero, but much less. We don't want to encourage obesity, but we do want to say that it does size matters. Lower degrees are not as big a deal as the bigger degrees. So how can we treat obesity? We can decrease your caloric intake by modifying taste preferences. Like we are designed to look for sugar and fat. Could we eat a pill that doesn't make us look for sugar and fat anymore? In theory, we could, but it's not happened yet. It's not practically happened yet. We can use medications to suppress the drive to eat, right? Anti-obesity medications. And we'll come to those until a couple of years ago, this was something we could touch in one slide and say there's like 10 medications, but none of them are completely safe or completely effective. And really the outcomes were not great. But in the last two years, we do have some new medications that do seem to help and we touch on those. Then you could modify the ability to eat, right? You could fire the jaw. You could put a band on the stomach so you don't have enough space in there. You could do bypass the stomach. You could modify the ability to absorb nutrients with anti-absorptive agents or with surgeries. We'll touch on all these a little bit. Or you could increase the energy output, right? There are some medications that can make you burn more calories. Unfortunately, at the level at which you'll burn enough calories to make a difference to the obesity, you will have too many side effects from these medicines because the same medicines will make your heart race fast. It will cause arrhythmias, would make you pass out. There are blood pressure could go up. There's many things that can go wrong. So they're not ideal. These are not the medicines we want to use to treat obesity. The other way to increase energy output is just to exercise, right? And that is a big deal. We should definitely all try to do some exercise, but I'll show you the figures around that as well. Finally, modifying the overall obesogenic environment will work best, right? Out of all these things, that's the one thing where individual willpower doesn't matter. If the environment is not obesogenic anymore, the lifestyle that we live in involves walking to work, going up and down or doing something physical at work, going, walking, biking to get groceries, things like that. If your life, if your environment requires you to be more active, then of course you'll lose weight, right? And if your environment doesn't have a lot of fast food, a lot of fat, a lot of sugar, a lot of cheap calories, you will definitely gain less weight. But how to get into that environment and is that an environment people are happy with? Those are actually big questions as you may imagine. So first-line treatment for obesity is then diet and exercise, right? Everyone will tell you that this is the first-line treatment. We'll touch on both of those in a little bit of detail. Then if diet and exercise is not working, we could go to medical intervention, drugs, surgeries, things like that, and we'll touch on those a little bit. And finally, we can change the obesogenic environment. We can make walking paths, bike paths, work settings, standing desks. It's amazing how much difference these small things will make. People switching from sitting at a desk to standing at a desk reliably lose some weight. And all sorts of things improve. Their insulin resistance improves just from standing around at work instead of sitting at work. It's a wonderful intervention. If any of you has that option, I would advise you to do that. It does make a difference. Having different treats and snacks, right? We have a clinic in which every day somebody brings cakes and donuts and whatever, and we love it. But maybe we should switch to something less calorie dense. Have fewer vending machines in schools. Have increased taxes on some foods. Laws to change how foods are advertised and so on. All these things are proposed. Some of them are good ideas. Some of them are not so good. And some of them have hidden risks involved, which will come out once you start to try it. So it's not straightforward. But let's start with dieting. What diet is best? The short answer is that all diets work for some people, but no diet works for everyone. And 85 to 90% of all diets fail in the sense that weight regain occurs over time. It may occur six months a year later, but people tend to regain that weight. When they go on a diet, they lose weight. In six months, they gain it back. So in that sense, dieting is not proven intervention for obesity because we have not shown it to work. It can work. In principle, it should work, but people have a very hard time sticking to any diet. In general, carb-limited diets where you lower the carbs tend to show better initial results in most people. Whether those results are sustained or not still depends on how much people can change their lifestyle long-term. And that seems very hard to do. But still when you compare diets, it's not any diet will, almost any diet will work if you stick to it. But lower carb diets tend to work more quickly. Mediterranean diet and its variants are all good because they have other advantages. They seem to be healthier for you in other ways. Even when you don't lose weight, they seem to be healthier for you. Maybe they have more antioxidants. Maybe they have different fats. Olive oil is maybe a healthier fat than the fat we, than margarine or palm oil or something. Butter is actually a better fat than the fruit. Intermittent fasting became popular, reached a peak. It's probably now it's sort of all these things have a hype cycle now sort of falling out of fashion a little bit, but it does work. It does help. In many people, it does seem to be better than the alternatives. Compared to many other diets, intermittent fasting seems to help people. Skipping breakfast is a dietitians for some reason that made it a big deal that you must eat breakfast because there were studies showing that people who don't eat breakfast gain more weight. But this on closer sort of examination doesn't turn out to be a big deal. Whether you skip it or eat it, more depends on the rest of the, how about your total intake? Extreme low calorie diets also work. So if somebody tells you they're like on a one week fast and going to lose 20 pounds, it's doable. It's not that these things don't work. It's just that they're very hard to do and very hard to stick to. Junk food and processed foods are not good for you in general, right? So whatever diet you're trying to do, it's very good if you can cut down on quote unquote junk food. What is junk food is an open question also, but really most fast foods outside when you go to McDonald's, Chick-fil-A, whatever, the secret of success in the food business is fat and sugar. And this makes complete sense, right? Because that's what our evolution has designed us to look for. So there's no way a restaurant is deliberately going to cut down on fat or butter or something because that's what makes their food more delicious. So you're always better off eating at home and processed foods will frequently have trans fats. Those are really bad fats for you. So the bottom line is if you can cut down on those, it's generally going to be good for you. But any diet that the patient can follow and lose weight on is a good diet. If there is this thought in the background also, low-fat diets may actually have made things worse. This isn't controversial. I don't want to give you the impression that this is something we know for sure. We don't. There's constant argument about this. But it's interesting to see that the American population was actually not very obese when the American government decided to give them dietary guidelines. Before dietary guidelines, they were doing fine. They were eating steaks and potatoes and butter and they were really not that obese. But after the dietary guidelines came in and the dietary guidelines said eat less fat, they started gaining weight. And they have continued to gain weight ever since. Now there's many other things that changed at the same time, right? So maybe it's just progress in other areas that made the environment so obesogenic. But there is a thought out there that the low-fat diets made things worse because people started to substitute carbs for fat. And carbs have a little less calories, less than half the calories of fat, weight for weight. But if you eat more of them, you are going to gain weight. And they turned out to be bad for you in other ways. In many ways, fats are healthier than carbs. The sugar rush is involved in producing the insulin resistance and problems that we talked about. So what practical advice can we give in like a short, some presentation like this is try to read more labels, right? Try to see how many calories are in various things. You will be surprised at some of the things that you eat on a very regular basis, how many calories are in there. How many calories are in Cheetos, for example, is a shock to most people. So reading labels definitely helps. Knowing how many calories are in there gives you a better sense of what we eat and what not to eat. Try to be more active, try to avoid mindless snacking. No regular soda and no juice, right? These liquid calories really bring nothing but bad things to the table. So try to stay away from all of that. Now people switch to diet soda and it turns out that doesn't always work either, right? People still gain weight. In fact, in some cases gain more weight. Maybe there's something bad about the diet soda itself, but it may also just be that that wasn't there. With the diet soda, they're still having their french fries and their burgers and whatever. It hasn't really made the difference they thought it was. Fast food and processed food we already mentioned. So a practical carb limited diet would be to avoid all simple sugars, right? This is easy to say, but you'll see how much it cuts out. No sugar in tea, no sugar in coffee, no sugary desserts, no cakes, no donuts. If you just decide you won't eat simple sugar anymore, it will cut out a lot of things that make you gain weight. No regular soda, right? No sweetened juices. No foods with more than five grams of sugar. Make that a rule and just stick to that. Try to limit other carbs to smaller helpings, right? Everybody eats bread, potatoes, rice, but try to eat smaller helpings of those and don't worry about the fat and the protein part. If you can do this, you will actually lose weight. More lean protein is better, more fish and selfish is better. Low carb or non-carb snacks are best, right? It's the carbs and sugar are an enemy. And exercise at least 30 minutes, five times a week. It's a very, very minimal exercise goal here. The idea is that this is something most people can follow, right? They can stop eating sugar and drinking soda and they can start doing 30 minutes every day to a lot of people, even this will make a difference. And the problem is that even sticking to this is hard. It's not easy. On the exercise size, what can you do? How much would it take to lose weight? Well, the short answer is it would take a lot more than an average adult or child will voluntarily do. It's actually not easy to lose weight on just exercise. You have to cut down the calories because exercise is not sort of magic. It is good. As I said, fitness trumps fatness. There are huge advantages to being fit beyond even the obesity issue. But still people overestimate how much difference it makes to weight gain. If you are doing heavy exercise, and this is not walking, this is like doing swimming, proper biking, something like that, you're burning about 500 calories an hour. One burger fries and coke can be a thousand calories, right? You would have to swim for two hours just to work off that one McDonald's meal. And nobody except like competitive swimmers is going to swim two hours every day. So what I'm trying to say is that the exercise is great, but it doesn't actually burn the number of calories you are eating. Those will still exceed the exercise unless you cut down on the intake side also. You have to cut down on that, otherwise it doesn't work. And just to give you an idea of what the energy expenditure is going to, 60% of our daily calories are just going to resting energy expenditure. That's the basic functions of the body, the cells all sort of humming along inside your body. That takes up 60% of your, so that doesn't change day to day anyway, right? The big change is the non-resting energy expenditure. That's where you are walking, running, sports, activities, fidgeting, all of that. Sometimes there is a subset or I put NEAT, it should be NEAT of that, which is the kind of activity you do, which is not formal exercise. Like I'm sitting on my chair and just fidgeting or shaking my foot or something. This is also burning calories. It is non-resting energy expenditure, but it's not active exercise that I'm doing. That also makes a difference. Some people who are thin, maybe thin, because they are very fidgety. They never sit still. Over time, that makes a difference. There's a thermic effect of feeding, you don't have to worry about that. So the bottom line with this is that you, just going on a diet is not a very successful study. Most diets fail, but if you do want to lose weight, you do have to diet, but you also have to start exercising more and you have to make both the diet and the exercise a part of your lifestyle. Not something you took up for a month or a week or something. It has to be that this is going to be your life. So pick something that you can do lifelong doing or pick something very drastic to lose weight initially, but then pick something that will go lifelong. You can't sort of go back to your old ways because that will mean you just gain that weight back. Now, coming to medications. All these appetite suppressants and things, you don't have to sort of even look at, all of them had side effects, they didn't work very well or they were not even approved for prolonged use. The big change that has happened in medication side is that there's a class of medications called GLP-1 agonists. These are medications used initially to treat diabetes. They are hormones, they are sort of, they're analogs of hormones that our gut makes when it's exposed to food. And these hormones basically tell the brain to slow down eating because there's already enough food in the system. And they slow down the emptying of the stomach. They have other effects, then more insulin is produced, better beta cell function improves, but the effects on weight loss come mostly from the fact that these medicines suppress appetite and reduce gastric emptying. The stomach doesn't empty as quickly. So you feel full more quickly. These medications initially used for diabetes seem to be causing a fair amount of weight loss in those diabetic patients. So in 2021, they were also approved for weight loss. And now more of them have been approved and we'll look at them in detail. There's another new medication called Set Melanotide. This you may not have heard of because it's a very fringe niche medicine right now, but it's a medication that blocks that you saw that circuit that makes you hungry. It blocks that circuit in a crucial place. So it blocks your drive to eat. In theory, it should make everyone lose weight. Till now, it's only been approved for some genetic forms of rare genetic forms of obesity. There are side effects. We will see how it goes with those rare forms, but in time, it may be that this medication will become more widely available and will also be a big sort of boost to our medical and momentary illness. Then if the medications don't work, you can go to bariatric surgery. Surgery is not much of an option in children. They generally don't recommend bariatric surgery until you've finished your growth. But in adults and older adolescents, it's definitely an option. It does work, right? People lose weight after bariatric surgery. Almost everyone loses weight after bariatric surgery. But it can have complications including fatal complications. It is major surgery. It's not like a joke. So it's our last choice after everything else is failed. So coming back to GLP-1 agonists, these are incretin hormones that tell your body that we already have food in the system. You don't have to eat any, right? Initially found to treat type 2 diabetes, then approved in 2021 as a once a week injection for weight loss. It's an injection. There is a pill now. The pill doesn't seem to have the same drastic effect as the dramatic benefit as the injection does. So till now it's really mostly the injection that's working. But we will see if the higher doses of the pill work that will make life much easier for people who don't like shots. So the results of these drugs have been much better than any previous drug. And so these drugs are now being produced in higher concentrations for weight loss specifically. Previously they were produced really for diabetes. They're not for everyone, right? They are contraindicated in pregnancy or in someone who has had pancreatitis because in some rare cases they will cause pancreatitis. And there's a rare form of thyroid cancer that these drugs when they were tested in mice seem to increase the risk in mice at least. We don't know for sure if they actually increase the risk in humans, but obviously we don't want to test that or risk that. So people who have a family history of that particular cancer are also not candidates. But otherwise most people can try these medications. And this is the result. You don't have to worry about the detail, but look at this. This is the group that got placebo injection and this is the group that got the semaglutide injection. And there is a huge difference, right? These are the first medications that could cause 15, 20% weight loss. That's very impressive weight loss for a medication, especially since all the medications we had in the past, none of them could do this. So this is very dramatic. This is another one of the same group of medicines. You can see again, the higher the dose, the more the weight loss. This is the mechanism of action. I left it in there just because this will be saved in the presentation. People can look at it later. You don't have to worry about it. This is really medical school stuff. There is a new version of these medications coming or already on the market called Zepetide. Not yet approved for kids. Approved right now just for diabetes, but it's going to be approved for weight loss very soon. This medication seems to work even more than the first one's approved. So you may see a dramatic improvement in weight loss with this kind of medicine. The other drug I mentioned is set melanotide. This is a MC4 receptor. It's the drug that works in the brain basically blocks your drive to eat, right? It's been approved for some rare genetic forms of obesity because that's the particular gene the area it's targeting. There may be more approvals in the future. If it really works and if the side effects don't turn out to be too dangerous, this may also be a good drug for weight loss. There are other things coming. There's this medicine. This is not a medicine. It's a capsule that you swallow and it grows into this giant ball of cellulose or not ball triangle of cellulose in your gut, in your stomach. So it's sort of, it acts like a gastric balloon. You can't eat anymore. And eventually it just sort of dissolves and passes out in the stool. It's not yet approved in the US but it's already approved in Europe. We'll see how well it does. But this is also coming. Bariatric surgery, as I said, I won't go into details because we'll run out of time. But there are many different procedures that are out there for older adolescents and adults, not approved for younger children. Not our first choice, but if nothing is working, it does work. These are some of the ways you can, some of the ways you can do bariatric surgery. You can make a smaller stomach. You can put a balloon in the stomach. You can bypass some of the gut. So these are, and there's many more variations on these, but really the idea in all of these is that you make it harder to eat more and you make it harder to absorb that food. Redirecting civilization, as we mentioned, you can alter the composition of prepared foods, right? Somebody in a dictatorship, maybe you can change how much sugar they put in Twinkies. But in a democracy, I think this is harder to do. You can also limit portion sizes, things like that. You can do this in schools, but I doubt you can do this in restaurants because people don't go to restaurants to eat limited portions. Public health programs make a difference. Legal penalties can make a difference, but then how do you sort of fairly target people, right? There may be some people who need those higher calorie stuff or who are not being harmed by them. But taxes hurt everyone, not just the people who are overweight. So that's why these things all help, but redirecting civilization not always easy. And finally, just sort of to go back to, this is just mortality in older adults. And you can see on this that the lowest mortality is in a region which is considered overweight right now, right? Your chances of dying then start to go up as you get heavier, but you can see they're also very heavy if you're super thin. That's not because you're thin necessarily. It's because this is just adults captured in one snapshot. These are people who probably already had some illness that's made them lose weight, right? So that's why they're dying and they're thin. But it may be that there is a healthy level below which your illness or morbidity or risk of dying does go up even with being overweight. I just wanted to show this picture because you'll see this a lot, right? People used to be unfamiliar with this thing. And if you saw this on somebody's neck, you would assume that they're dirty, they haven't bathed. But now with the obesity epidemic, you'll see this in a lot of people and it's not because they are not washing. It's because the excess, you know, the insulin resistance has chicken in their skin and it causes this kind of appearance called acanthosis, migra cans. So if you see this on somebody's neck, they are at risk for getting diabetes. So I will stop here. There's more information that we can get to, that I left in the presentation for people to sort of look at if they wanted to just details about the genetic causes of obesity and things like that. But I decided not to include them and thought we'll just leave a few minutes for questions. Thank you so much, Dr. Ali. We received a couple of questions. The first question we have is, it's obesity a result of PCOS or is PCOS a cause of obesity? And for those of us who are not familiar with the term, PCOS stands for Polycystic Overy Syndrome. So primarily PCOS is a result of obesity, right? We think that people who are overweight tend to develop higher testosterone levels because of the insulin resistance and the higher testosterone levels cause hair growth on the face, they cause acne, they cause irregular periods. So all those features of PCOS will then show up. And if they lose weight, PCOS will improve. So it means with weight loss it can be reversed. But there is a little bit of chicken and egg there too because it turns out that if you are insulin resistant you seem to have more of a tendency to gain weight. So there is a vicious cycle of sorts. If you gain weight you become more insulin resistant, but if you are insulin resistant you tend to gain weight also. And in mice and in animal studies they have shown that if you make them insulin resistant they start to gain weight. You made them artificially insulin resistant but they can start to gain weight from that. So there is some chicken and egg thing also going on but primarily we would say PCOS is the result of being overweight, not a cause of obesity. Thank you. Another question sent directly to me, it's about with overweight, do insulin resistance and testosterone levels lessen? Also does estrogen increase? Right. So insulin resistance actually goes up with weight, right? So when you gain weight you become more insulin resistant. So your insulin levels tend to go up because your body is trying to overcome that resistance. So people have higher insulin levels when they are overweight. The other part was that does it... What was the second? Does estrogen increase with weight loss? Yes. No, again it actually increases with weight gain. Estrogen levels, fat is one of the sites where the body makes estrogen. So if you have more fat you tend to make a little bit more. In women it matters less because women make a lot of estrogen obviously in their ovaries. In men most of the estrogen they have is coming from their fat. So there is... If you gain weight your estrogen levels tend to go up just a little bit. It's not a big deal either way. But if anything increase your estrogen, not decrease. Okay. The last question that sent directly to me is for adolescents with obesity caused by PCOS and other physical issues who exercise and restrict calories with little positive results. Do you have any suggestion for them? They're considering biiatric surgery as well as OSAMPIC if they can get insurance to help them. Right. So we would say diet and exercise is not working for someone and they're finished with growth. We would... First we would try these new medications since the medications are working for a lot of people. So if they can get the medication I would try the ones who make shots first. And if the ones who make shots are not working or they're not able to get it. This... Our healthcare system is like so insane that $1,000 drug may not be available and that $20,000 surgery may be available. So weird things will happen. But rationally you will try the medicines first and the surgery later. Thank you, Dr. Adley. We have a question from Kevin and Kevin also raised his hand. I'll read his question then maybe he can unmute himself to explain. He said, it's plant-based organic only effective. Isn't heavier when older just giving up? I'm sorry, what was the second part? Is it what? Well, if you say your BMI is greater if you're heavier when you're older saying that that's okay, isn't that just giving up? It's not necessarily just giving up because there seems to be some normal weight gain with age in human beings in general. If you go to any country and even historically if you look back at people, whatever records they have for people in the armies and things like that, as they got older, they gained some weight. Some weight gain as you get older seems to be normal. They shouldn't become obese though. They should not become abnormally obese. They shouldn't become overweight, but they do gain some weight. So if somebody saying normal weight in a 50-year-old can be like 10, 15 pounds more than normal weight in a 20-year-old, they're probably right at least in the statistical sense that this is what human beings tend to do. They gain a little bit of weight as they get older. My other question was about plant-based. And plant-based organic and no standard American diet. Right. It will almost certainly help, right? And it doesn't have to be most of these restrictive diets even if you don't believe in their other benefits. You don't believe that vegetarians are better than meat or something. The fact is that when you go on one of these diets, you are restricting yourself in some ways, right? There are 20 things you won't eat anymore. So it automatically makes your intake a little less. But beyond that, I think there is some benefit too. I think that we do think, we do see foods are more pro-inflammatory than others. They seem to cause inflammation in your body and generally plant-based foods, vegetarians, vegans, they do better on this than people who are eating meats and processed foods. Okay, thank you. Thank you. Question from Denise. Why do children of same parents and environment very greatly in tendency to gain weight? She also wanna say she enjoyed your presentation very much and you're putting our culture in historical context. Thank you. So this, people tend to gain weight, I'm sorry, you said that because of what? Why do children of same parents and environment very greatly in tendency to gain weight? Why do they vary greatly? I think first of all, they don't vary greatly. They do have a higher risk of being obese, right? If you have two obese parents, the chances are very high that all the children are likely to be obese. Now, they may not all be the same degree of obese, but that's because the same thing with height, right? If you have two parents who are six foot and five foot four, all their children will not be at these heights, male and female. Some will be taller, some will be shorter because you don't get the exact same genes. It's a sort of a reshuffling of genes that happens when that fertilization happens. Half the genes come from one parent, half from the other. Which half you get from which parent is a random chance thing, right? And so nobody, no two siblings are going to be exactly alike. They share 50% of their genes, but there's another 50% they don't share. So this is not surprising that there's some difference. But in fact, in actual practice, it tends to go the other way more. They do resemble each other more than their children. Most of them do tend to be obese. Thank you, Dr. Ali. Another question from Denise. Would you discuss metabolism of aging? I'm an active elder with osteoporosis and finding it very frustrating to be eating better and less and it is so difficult to shed excess pounds. Right, it is difficult as you get older, metabolism slows down. So normally people would need to eat less as they get older, right? Then that's a known fact. Because their overall metabolism slows down a little bit as they get older. And their activity level slows down, right? You're not as active as you get older. So you would expect to find it harder to lose weight as you get older because you have to cut down even more to lose that weight. There may be more things going on than we know also. I mean, there are changes in hormones, obviously. Women go through menopause, men go through a sort of andropause also. What difference these things make? Are they contributing to difficulties with weight loss in older? But the bottom line is that it's difficult in every age. Yeah, it's hard to hold on to weight and our body will fight back and make it very hard to lose weight. Thank you, Dr. Ali. That's the last question I see in the chat. Anna, did you get any direct message questions? No, I did not. So with that, I'd like to thank Dr. Ali. We really appreciate you taking the time to share with us the basic facts and treatment options for obesity. And I also want to thank everyone for joining the program. I hope you all find the presentation informative and helpful to you. We will send out an evaluation survey together with the recording link and Dr. Ali's slides later today. Please give us your feedback so we can continue to improve. Again, thank you, everyone. Stay healthy and have a wonderful rest of your day. Bye-bye now.