Welcome, everyone. I'm Monica Agarwal. I'll be moderating this session. Dr. Lee is Professor of Medicine, Linda N. Seward Rancic Endowed Chair in Human Nutrition at David Geffen School of Medicine at UCLA. She currently holds positions of Director of Center for Human Nutrition, Chief of Division of Clinical Nutrition at UCLA. Dr. Lee currently is the immediate past president of National Board of Physician Nutrition Specialist. She has served on Board of Directors for American Society of Nutrition since 2017. Her passion is to advocate for nutrition sciences research and bring nutrition to the forefront for disease prevention and treatment. For nearly three decades, Dr. Lee's research interest has focused on translational research and prevention and treatment of obesity-related chronic diseases. She has been principal investigator of over 100 investigator-initiated NIH and industry-sponsored clinical trials and has published more than 200 peer-reviewed papers. She has co-authored several books, including Primary Care Nutrition, Writing a Nutrition Prescription. Please join me in welcoming Dr. Lee. Good morning. Thank you, Dr. Agarwal, for that wonderful presentation. It is truly a pleasure here and to share nutrition with everyone here. I promise you, and my talk will be closely linked to the theme of the conference, seems like, is GLP-1 agonist. And the difference is, I'm not aiming for once a week regimen, but this is three times a day. All right? First, a few words about our team at UCLA. Clinical nutrition, it is a standing alone specialty. We're not part of an endocrine or part of a gastroenterology. And the center, it is set up for really bridging clinical practice and clinical research and basic research. And we have teams working on, number one, food. What are food? And we eat food. We don't eat carbs. We don't eat nutrients. So we're looking at, collectively, how food interacts with the human body. And that including directly or through the gut microbiome. So we've been getting into that field about 15 years. The second major focus, obviously, is how human body, how endocrinologists study hormones and metabolism interact or influenced by how we live, including nutrition. And the third major category, obviously, is looking into how nutrition can play a role. It's not only for prevention of disease, but also increase responsiveness to our conventional treatment or standing alone at the therapy. So that is how our group look like. And compared with the conventional practice, we are more like the diabetes centers across the country. We have physician lead the group. We have registered dietitians. We have nurse specialists. We have family therapists, psychologists, and physical therapists as part of our team. The goal is actually to address what I supposed to talk about. It is achieving personalized nutrition. And hopefully we're heading to precision of nutrition and precision of medicine. So that is how we set it up at UCLA. I know there are other breakout sessions that may have more people than what we have here. Part of the reason is nutrition has been so confusing. And the question is, do we know what we're talking about, right? So look at what I put up on the screen. In 1984, we're all about low-fat diet. You dare to look at the yolks out of the egg, right? And because you're going to have a heart attack. And I wanted to say a few things about the first dietary guideline. And we would think, you know, that would really based on science at the time. Actually it's not quite like that. It is truly based on observations at the time. And with high rising cardiovascular disease and observation from autopsy, those patients often have fat and cholesterol infiltrate in the arteries. And also notice those people often have overweight and obesity. Voila! They all make sense. If we lower the fat intake, we would decrease the chance for them to infiltrate the arteries. And also fat carry more calories than protein and carbohydrate, then you would be able to manage the weight. That is the reason we started all about low-fat diet. Now fast forward to 2014, we seems like waking up all of a sudden, gee, we got to do something absolutely opposite. And with everyone here, we all know jostling therapy, right? Ketogenic diet or low-carb diet is never, you know, something new discovery. That is how we started to treat diabetes before insulin was discovered. And that, no doubt, would be helpful with glycemic control. The truth is then, the question is, are we really there to say low-fat diet is all bad, we get killed by carbs, if we just have our super drink in the morning, coffee with butter, we will be living forever, right? See that it is, you know, the issues we are facing. And that is exactly the opportunities we're going to talk about today. That is precision on nutrition. What does that mean? Are we there yet? I'll start with a case. And this is a typical patient we will see in our clinic. And Mr. R is 61 years old and works as a hotel as a manager. He has a typical past medical history of BPH and had melanoma, fatty liver, NASH, and quote resolved because the transaminase has been up and down. When he was seeing me, that was in normal range. Hypothyroidism was on, thin thyroid, and had lymphocytosis, of course, sleep apnea. That was the reason he was referred to see us. Here is his data. He weighs 219 pounds, pretty tall, 5'11", with a body mass index of 30.54. And this is his 24-hour dietary recall. And he typically has two meals a day. He said, Doc, I'm almost practicing intermittent fasting, and here's what I do. Breakfast, and I would have typical, you know, potatoes, scrambled eggs. I only eat the white, no cheese, okay, no fat, tomatoes, and then toast, whole wheat. Lunch, if I have no breakfast, I would have, you know, egg sandwiches, salad, and coffee. Dinner, variable, and depends on what he get his hands on. Snacks, he loves chocolate, crackers, and he got the message about having nuts for cardiovascular health. He drinks a lot of coffee and water as well. Since we're living in Los Angeles, we're crazy about water all the time. So the question is, what are you going to start, Mr. R. Oh, where are you going to start? You read an article yesterday about ketogenic diet. Is that what you're going to do? Or we should try low-fat, or otherwise, or Weight Watchers? So the first study I want to review here with everyone, it is a study finished quite some time ago in 2005. And compare four most popular diet at the time. And as you can see, Atkins, that's very close to the ketogenic diet. Zone diet is looking at body's response in insulin to food. Weight Watchers is pretty much behavior portion control. And the Dean Ornish diet, extremely low-fat diet. We're really talking about fat percentage 20 or below 20. So here are the few messages I want to deliver. If we thank everyone here today, we are all N equals 1. Meaning we are identical. If that is the assumption, that is still the case, even pharmacological studies today, then you see the average. There is no difference between all those four diet at the year end of the study. Absolutely no difference. However, if you look at carefully then, look at inside the group variations. Same diet, there are people losing a lot more weight, you see on the bottom portion of it. And there are also people gaining weight right here. Significantly gaining weight, it doesn't matter which group. There are huge variations. And also you notice, after three months, it doesn't matter what diet you were in, people start dropping out of the study. We love the intention-to-treat analysis. We would carry the weight here all the way to end of the year. Assuming that is actually going to be the case. The reason they are dropping out of those studies is because, one, it's not practical for them. They can do it for three months, that's about all doc I can do. Or it's not working for them. That is really an issue with new nutrition studies, you do intention-to-treat analysis. That is about the best time they are, and if you carry that to the end of the year. So what we're learning from that, and it is we probably are all very different. And A equals one approach really misleading all of us in nutrition studies. Genetically, we are 99.9% identical, but that is only DNA levels. Then we're looking at genetics, and look at each individual cell level, DNA. Now RNA, we're not talking about mRNA anymore. We're not just having rRNA, we have micro RNA, non-coding. And then protein, and it is not all constantly the same, because it also gotta be functional. So it's modified into functional hormones or transmitters. Each individual levels are all impacted by nutrition. So in a sense, on each individual cell, it is a dynamic process. Which protein get become, which DNA code become activated, become a functional protein, it varies by how you live. And how you expose each individual cell to the micro environment. Now, with more we know about gut microbiome, that is adding more variability to it. And if we think about all the DNA material from head to toe, now with each one of us, 99% of genetic material belong to the microbes. And human genetic material is only 1%. So in a sense, we are truly living in the ocean of microbes. So you would not wonder why they have impact on us. But with that said, it's not equal to say, hey, I'm not guilty. It's not my fault, it's all my microbes. Because the microbes are truly, the makeup, diversity is truly in control of ourselves. Because they are controlled by how we live our life. In that sense, 70% of how we live is how we feed ourself, and that is nutrition. And to summarize what I have just said, and we as a whole individual, or organ, or tissue, or cell, is really have a two-way of interaction with the nutrients. Our genetics decided we may actually process the nutrient differently. That is nutrigenetics. On the other hand, how we expose ourselves to food also changes our genetics, that's nutrigenomics. So this is really a dynamic process. As a result, we are all different. Today's me is different from yesterday's me, in a sense. So with that said, you're going to say, oh, OK, how are we going to go to know about each cell's DNA, RNA, and protein? What can we do clinically? And here's what we can do clinically to recognize each individual's difference. The first thing I want to talk about is definition of obesity. Definition of obesity never being excess body weight. The reason we're using body weight, it is because it happened to correlate with a person's body fat based on the data at the time, 1970s health insurance data. But they are not necessarily accurate to each individual, particularly like a population in the US. We're so diverse. Truly, here are the key questions you got to ask yourself when you're talking about obesity. Number one, if the fat is stored in the physiological depot, meaning that is your body's capability to store excess body fat, for example, and the hips and the legs, that's perfectly fine metabolically. You can be overweight, quote, but metabolically healthy. However, if you're like me, a Chinese woman, I really have very limited physiological fat depot. I maybe just get to 160 pounds, but already have elevated triglyceride, elevated blood glucose. So that is commonly seen in Asian country. They are not getting to the overweight, obese range, even you move the BMI lower to 23 or lower. This is really how much it is your body can store up. I often tell my patient, if I use a car as example, I am just a very little Prius, does not use much energy, and cannot carry much either. The second thing is how much excess amount, and where the fat is located. That is such an important issue. If you are storing fat subcutaneously, even to some degree, just enter abdominal cavity, but not get to the liver, you probably metabolically will be healthy. But once the fat is used in the liver as a storage place, and the dysfunction of a metabolism really starts. Now we know the fat on the top of the heart muscles really contribute to contractility of the heart as well. So where the fat is located, and to the place it's not supposed to, it plays a very important role. And lastly, it is the ratio your body weight is made up with. How much is fat, how much it is lean body mass, including your organs. And this is what we see clinically, as to body shape, and where the fat is located. And so hip and legs are more physiological depots. And as to the body composition, and the ratio of fat and lean, and we're looking at those ladies with normal or actually lower BMI. And often, post-menopausal women, and particularly Caucasians, happy with their body weight. Oh, I have not changed since the time I got married. But what are changing is body compositions. Once menopause happens, and you have accelerated muscle loss, and increased body fat. So we even have a name for the sarcopenia obesity, or normal weight obesity. So those are the clinical things we can access patients. Now I'm going to switch gears and talk about nutrition, food, how we categorize or evaluate food intake. And this is just a slide to remind everyone, as we know, the death rate, or number of deaths, is not necessarily associated with how much calorie you're taking. It is more so with a quality of diet, high sodium diet, increased metabolic rate, and number. And so does lack of whole grain intake, vegetable intake, and fruit intake, and all over here. So that's what I'm talking about, and how to evaluate food. Start with a carbohydrate. We recognize all those three groups. Sugar-sweetened beverages, whole grain, and vegetables. One of the major difference out of those, one, sugar-sweetened beverages are completely artificial. They're not natural. But they also have really different absorption rate into the blood. And we clearly know, the sugar-containing beverages have the faster rising of blood glucose. And vegetables, in particular, have a much lower rising of blood glucose, as we can see here. So the first curve is representing simple sugars. It rise quickly, and that's a high glycemic index. And also glycemic load, the whole area under the curve, it is gigantic as well. And in the middle, the orange, is the whole grain. As you can see, the rising glucose is much slower, but the glycemic load may not significantly different from the sugar beverages. And the grain represents vegetables. It not only has a low glycemic index, but has a low glycemic load as well. So the question is, yeah, we've been in glycemic index and glycemic load. Do we know everything now about the food quality? Do we know enough how those food will interact with our body? And before you even get to that, in spite of we all know what we just talked about, here is the national trend about ultra-processed food. And you can see from the end of 2010, 2018, it doesn't matter if it's man or woman. The rising of ultra-processed food conception still on the rising. Meanwhile, minimally processed food, that is vegetables and fruit, are really showing here in a decreasing trend. So we have a lot to do to really educate the public. Now I'm even going to be more provoking for the endocrinologist here. And if your patient, now you get your patient to eat brown rice, whole grains, over white rice, are you really helping the patients? If the answer is yes, how much you are helping your patients? And look at the nutrition label here. In the brown rice as a whole grain, it does have more fibers and other things come along. But calorie-wise, glycemic load-wise, really not much difference with the white rice. Why I'm saying that? Because this is our physiology with carbohydrate metabolism. If we are sitting here right now, and we only need 8.5 grams of sugar every hour. So how many of you have put two packets of sugar into your coffee before you walk in here? That is what you can break even at the end of the lecture. For those of you who happen to have one little pastry, I have a piece in my bag as well, you're loading yourself with about 60 grams. So think about 60 divided by 8, how many hours that it is going to support you. The problem becomes much more obvious that you're going to have lunch. Let's say you're going to have a sandwich. Just the sandwich alone at least load you another 50 grams of sugar, even as a whole grain. What is the problem? All of those carbohydrates are in excess. And in order to keep your blood glucose level in the normal range, your liver will convert immediately all of those excess sugars to triglyceride. That's the saturated fat. We're trying so hard not to take in. That's the reason we're not eating our steaks. We're looking away from anything, quote, has high fat content. So this is what I really want to drive home. Whole grain carbohydrate source are healthier, but does not equal healthy unless you not to exceed your body's requirement. The most dangerous thing I have seen in my practice is that my patient thinks, Dr. Lee, I am eating brown rice. I'm healthier. So I can have two cups, or I can have bacon to go with it. Or on top of that, I can have tortilla. And that just completely misleading. We're not helping our patient by just doing one step in education, not a complete two steps. So that is one thing I want to share with everyone. The second issue I want to talk about, it is what's the difference between vegetables and fruit and the whole grains are of the same category. Human being, all of us, evolved, our ancestors evolved on plant-based diet until about 250 years ago. Our body is so perfectly toned to digest predominantly vegetables and fruit. This is a cartoon to showing you just that. The plants came to the earth first. In order for them to survive, and in order to survive oxidation, that's the final pathway of the cell. And they developed their own systems to survive. One of the key system is what we called, and it produces antioxidants. The reason they have different colors, it is because they have different way to deal with oxidative stress. For example, the purple color, and there's a reason given by resveratrol. That is the reason we eat blueberries. That's the reason we drink wine and for all the health. And the orange color, we know even better. That is given by beta-carotene. So that's also the very reason human being on the top of the food chain developed color visions. God knows we're going to have iPhones one reason only. The other reason, it is for us to get diverse diet and take advantage of what the plants have gained during evolution of their own for our own better health. To summarize, vegetables, compared with whole grains even, not only have a carbohydrate, it has carbohydrate in a totally different natural backgrounds. I'm going to give you examples to demonstrate that. And it also contains vitamins, minerals, including calcium. And we forgot the fact, one cup of broccoli has exactly the same amount of calcium as a cup of milk. But the calories are 25 to 30 instead of 120 to 150 or 200. And also, it got fibers. That's what we all know. But more importantly, we realize the fiber is not just there to keep ourselves regulated. More importantly, the fiber, most of it, if not all of it, are actually prebiotics. That is how we feed our gut microbiomes. I tell my students, and now I think at this time of my career after UCLA for 33 years, I start to appreciate small bowel, large bowel, probably are two different organs. Small bowel's purpose is to digest food, get the nutrients to the blood. Large bowel actually is where our gut microbiome would take in the environmental cue, the food we feed them, and then directly interact with our not only GI cells, not just the GI endocrine cells, but with our whole immune system in the gut. And also produce metabolites. We call bacteria metabolites or postbiotics. And those small molecules then get into our body, regulate every single organ of ours. And we actually have recent data we have now published and clearly demonstrate serotonins in our blood is predominantly made in the GI tract. And by our gut microbiome, in response to the food, and also by our interchromosome endocrine cells, neuroendocrine cells in the gut in interaction with food and the gut microbiome. So those are the field is evolving very, very rapidly. And also, we talked about the phytonutrients only existing in plants. Now I'm going to give you examples about why the natural backgrounds come along with the sugar matters. This is one of the study and we have done with gestational diabetes women. And we compared the same calorie pistachios with whole wheat bread. Same woman, different time to come into the clinic. You clearly see the rising of glucose after consumption of whole wheat bread. But if you consume pistachios and there is hardly any change of glucose and hardly any change of insulin as well. I did not put a slice there. Clearly demonstrate and calorie does not tell it all. And here is a study done by Dr. Jenkins group in Canada to looking at white bread consumption with a rising glucose. And then have different amount of pistachio consumed at the same time. You look at the lower panel. That's the amplified section of that. In a dose responsive way, if you consume white bread with the pistachio, your glucose metabolism is clearly regulated. The arising of glucose, it is attenuated. That is not just with white bread. Same effect you are seeing here. Consume rice with pistachio, pasta, or mashed potatoes. So this is a kind of more uniform interactions. This is our own study published not long ago. And looking at sugar existing in the form of grapes. I'm from California. And California supply most of the grapes in the United States. And there's three varieties. This is our very first study. We decide not to do just the purple with resveratrols. We decided just make a powder, frozen powder, out of the three varieties. And we gave individual 1 and 1 half, equivalent to 1 and 1 half, cups of grapes every day for four weeks. And the calorie is about 180, predominantly the sugar. To our surprise, what we see here, after four weeks, with this additional calorie intake, sugar intake, we see significant decrease of cholesterol. And we did not see any change of elevation of triglyceride, which we expect to see with a high additional glucose load. And to look at further, and we really observed significant microbiome change. And that probably is from the grapes, the skin, and other nutrients or compound come along in the grapes. And we actually now have more data to show it. And during this process, it's not just cholesterol that get impacted. It actually have impact on sex hormone as well. So this is a much more complex interaction between the nutrients you take and how your body would interact or respond. Now I'm going to give you examples about something have no calories, and that is the spices. And I believe every one of us have had in our life some spices. But I do want to say, spices does not equal pungent. And let me just start a question. What is the most consumed spices in United States? Pepper. Pepper. What else? How about vanilla? So I'm talking about how spices are classified. Spice are very, very ancient as to the relationship with a human being. Silk road was not initially started with really transporting silk from Far East to the West New World. The silk road started with actually introduce or transport spices all the way to the West. And that is how ancient we being have interact with spices. Number one, and spices are often have large molecules, compounds, made up of most of their molecular profiles. From that point of view, in the past, we feel they are not bioavailable. Therefore, they can't really have much of impact on our body. And many of you also know curcumin. And if you read literature, you hear all about how to increase the blood levels of curcumin. It's a large molecule. And many different ways, use liposome, use fat, and many different ways try to increase that. But the truth is, with now we knowing how gut microbiome work, and those large molecules often, if not all the time, is impact on our body by change the gut microbiome, and then indirectly have impact on our body's metabolism. And this is one of the examples we have done. We have tested culinary dose of common user spices. And all of them have impact on your gut microbiomes. And we also tested mixed spices we bought from Costco and doing a very simple, actually, experiment. We cooked patty burgers, 10% fat, very lean, and gave to patient with diabetes. We only took the patient with oral agents. At two different occasions, one time you come in, eat the patty burger, just has the salt in it. Another time you come in, it has salt and culinary dose of mixed spice in it. What we have seen is that by adding spices to the patty burger, it actually decreased the patty and induced post-brandial inflammation. More importantly, and the change of our blood vessels mediated with nitric oxide, and it is also being protected by adding spices to the burger. So protected the endothelium from damage made by the post-brandial inflammation. This is a way measured by looking at the peripheral arterial tonometry to looking at the endothelium function. By adding spices, we can well preserve its function compared with you eating a patty alone. So that is about carbohydrate we talked about. And I really wanted to impress you, number one, and glycemic index, glycemic load are important, but they're not complete. And we need not to exceed our carbohydrate need. We need to really appreciate more what natural fruit and vegetables would bring us. And also to recognize sugar in different compounds, different combination when we're eating meal in reality, and they are very different than you consume a sugar beverage alone. So that is what I talked about, carbohydrate. Now I'm going to switch gear to talk about protein. And protein we are all very familiar with. And we have amino acid pool, and that's only about 70 grams. It's very dynamic, and that is predominantly the reason we needed to intake a minimum 70 grams every day to keep the pool in balance. We also have our protein as part of our body, but that is rapidly turned over every day as well in the range of 300 grams. So this is the area when we have illness, does not matter if it's COVID or any other things, it would have significantly changed, will require much more protein from the diet. And one thing I do want to point out in this field, it is recognition of anabolic resistance along with aging. That is, when we're getting older, the capability of us and break down the protein to amino acid and absorb them and also simulate that into our organs capability is decreasing along aging. So for this group of people, the dietary recommendation for protein, it is definitely not 0.8 grams per kilogram. The minimum should be 1.2. And to avoid this group of population get protein deficiency. And 1.7 is definitely safe for elderly as well. So how much is the 1.2? It's pretty much about three ounces of meat every meal. So that is the range minimum to start with. The second issue I want to address as to protein quality are particularly to those patient are now more consumed plant-based diet. That can be vegetarian or vegan for health or environmental reasons. And the consequences we do not want, we need to be well aware so we can help our patient. Number one, it is plant-based protein other than soy are incomplete proteins. What do I mean? They are lacking of essential amino acids. Even soy has a pretty low methionine. When the population need more methionine, disease, illness, or pregnancy, and this can become insufficient. So the best approach would be necessary to combine different protein source to avoid protein deficiency of a limited amino acid source. The second issue is when you talking about plant-based protein source, they are not as pure as animal-based. For example, we need about 2.5 grams of leucine every meal to stimulate our skeletal muscle protein synthesis. In order to achieve that goal, if we take whey protein, the highest biological value protein, and we only need about 128 calories because whey protein is pretty pure. On the other hand, if we take from bread or pasta, wheat products, it would carry 1,057 calories. So protein come from plant-based is not just protein. It often carries significant amount of carbohydrate. So the patient need to be educated. Beans are fine. They have a good protein amount, but they have a high load of carbohydrate as well. If you eat the beans for the meal as your protein and carbohydrate, it's perfect. If you're going to have a tortilla to carry the bean on top of them, add rice and cheese and all other goodies, you are way overload yourself with the carbohydrate and beyond what your body really need. So this is the second issue with protein source and for vegetarian and vegan. And here's a quick summary on the top, an animal source of the protein and plant-based. And those four are kind of, you know, near complete. And the best approach would be have variable protein source from different plant. And also remember, again, the older we gets and the more protein we will need. And to take adequate amount of protein, it is very important. Last group I'm going to talk about, it is a fat. And that is straightforward. We know the trans fat is no good and saturated fat is not good either. And definitely high fat content intake cannot be coupled with a high carbohydrate load because carbohydrate load wouldn't have your liver making even more triglyceride and saturated fat. And monounsaturated, polyunsaturated are associated with lower mentalities. I will give one example about a quality of fat. And this is an avocado, carry about 300 calories or so, average about 270 to 300 range. It is predominantly monounsaturated fatty acid. We actually have just finished a multicenter study with 500 patient taking one avocado every day and the other half do their usual habitual diet. After six months, we did MRI on every single subject. They did not gain weight. And we also see a decrease of cholesterol as well. So just the calorie alone, just the fat content does not tell you the whole story. And the other very important study we did is we check what we did in a clinical trial in a acute setting. Again, we see the same as we see with spices. Adding 300 calories to the burger did not elevate your triglyceride, but offered your protection to your blood vessels. And so I actually missing a slide about the fat. One more thing I want to talk about the fat is long chain omega-3s. And that is one of the fatty acid we really need for our essential health. And I also want to point out the second issue with long-chain fatty acid, that is many of our patients are taking ALA and the 18-carbon from flaxseed and feel good about they have given themselves omega-3s. The research has clearly demonstrated human being, us, converting 18-carbon to EP and DHA, the capability is very low, average about 1% to 2%. Particularly for men, you do not convert much at all. So if you really want to give yourself long-chain fatty acid, omega-3, you got to go for the algae directly. They are the one making it. Or fish. Fish is a concentrator. They eat the algae. They store the omega-3s in their body. So the algae is also vegetarian-friendly. So that is I want to end with the fact. So now I'm going to quickly go over how human being as a whole. And nutrition would not really complete if you're just talking about what you have put inside of you. As to the fact, how much stayed with you, it needs a driver. That is your physical activity. And that can be any shape or form. And you like to do. It is not just for your muscles. It's not just about control your sugars. It's about your aging process. And very simple. If you are active about 150 minutes every day, and when you are even at 90 years old, you can preserve your muscle really well. If you are sedentary, the marble starts very early. And even the size of the legs is the same. But the quality, it is definitely different. Another issue is the patient does not exist alone. All of us living in a society, we're social beings. We often, counseling the patient, feel like they are an independent individual. That's not the case. We have to help the whole family, the whole social connection, in order to help our patients. And you have to consider that, and what it is feasible for an individual. And we, human beings, evolved as a social group. And the best show of love is to offer your survival benefit, and that is food. That only until 250 years ago. That is the reason we love someone, we feed them. And that's still true today with my parents, particularly for my kids. So this is one example and how important social group would be. This is a study we done at the VA. Looking at, in the middle, the average response. Look at the veterans and their weight trajectory. And one year before they enroll in the MOVE program. It's a peer-supported group. And looking at their weight reduction, and one year after, even five years out. And this is very important, to have buddy system and social support. And this, I don't need to really elaborate. We all have this moment. And stress used to be all survival related. Related to scarce of food and nutrition. But today, and stress come in all shape and forms. But our body, our brain, react the same way. We thinking, as long as we get calories, we will be stress-free. And also, there's a special connections with carbohydrate and dopamine system. And satiety, you know, the pleasure system as well. So those are evolving research. And the newest one is chrononutrition. That is looking at when to eat, what is the best intervals to eat, to have the best interaction of our metabolism and food intake. And I can quickly give you quick examples to look. Night eating is definitely associated with more calorie intake. And if you're looking at 500 calorie excess a day, that's weight gain of a pound every week. That is happening during the pandemic. The other issue related to chrononutrition is window of eating. So for, you know, animals and they eat either nocturnal or during the day. But look at human being, we're pretty much 24-7. So this is also another issue we need to look at how we address that. And one thing for sure, for behavior purpose, intermittent fasting is a very functional tool. As to whether intermittent fasting would reset your metabolic rate, the jury's still out. In animal studies, it has been shown, and intermittent fasting can reset your metabolism, including beta cell function. But that has yet to be proved true in human. So really, I use this slide to illustrate one thing. It doesn't matter we're dealing with glucose or weight management. And it is no longer just energy balance and genetic risk. And there are so many other confounding factors and really impact on the success of our therapy and the success for the patients. So nutrition should not be existing alone, just calories or physical activity. We really do have to look at nutrition's impact on stress, mood, sleep, and everything else. And in order to really help our patients. And this is a study I think we all know, an endocrinologist, we clearly know now, even just us, ourself, if we take exactly same amount of rice or bread, repeatedly testing ourself, our postprandial glucose would vary. And that is actually physiological response. And that is not just determined by what we eat, but gut microbiome, our overall stress, and physical activity, all of that. And that is the reason NIH, this year, January, awarded $170 million for precision nutrition study. It is a consortium. We are lucky to be one of the centers. The goal, actually, it is using new technology to really digitally fingerprinting every individual metabolically from all the tools we know. And we also wanted to digitalize, objectively capture nutrition intake, not just calories, but as meals. And on the other hand, we'll do the same with physical activity and also use AI to really produce a digital profile for every single individual. And hopefully in the near future, at least in five years from now, we'll know more about how food can keep our healthy, how food can really help us to improve our health or better respond to therapy. And those are the questions we intend to answer, and who is our patient, and what we need to do, and when do we need to do, and where, what setting, and understand why patient has the current metabolic situation, and how they got there. At the very last, this is our patient we started with, and Mr. R. We end up working with this patient and with one meal, basically vegetables, and proteins, and carbohydrate controlled at one single meal. The rest of time, we're giving him two, sometimes if he's hungry, three meal replacement. Basically limiting fat and carbohydrate intake, but ensure he'll have protein intake every single meal. And he's been losing weight nicely, and he's been able to maintain the weight as well. I know I talked a lot, and since I'm from UCLA, I've been there 33 years, and here's my selfish acronym for you to take something home. And really advocate fruit, vegetables, that's what our genetics best fit for, and control the starch and fat. And because we are not as active what we used to be, and make sure you get enough protein from lean source, and driving the nutrition home with activity. Thank you very much. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you so much. What a wonderful presentation. We have a few minutes for questions. Thank you, that was a really great talk, and very, very helpful. Could you comment on protein supplementation, like whey protein supplements, and what are your thoughts on that in general, if someone is not getting enough protein from their diet? Okay, the question is, can you comment on whey protein representative protein supplement? I think it's a very effective tool. Talking about whey in particular, it is almost identical to human breast milk, and is also clear liquid diet, in a sense, because it completely dissolve in water. So we use a lot for elderly. We also use a lot in the hospital setting, particularly GI surgery, immediately post-surgery. We do use a lot. I think it is a very effective way to supplement protein intake. Granted, the best is taking natural source of proteins, but if you cannot achieve that goal with food, protein supplement is a viable option. Okay, thank you. I had a question about testing. There are companies like Genova that do Nutri-Eval, that test your nutritional levels, and some companies that do custom vitamins. What are your thoughts about testing people, and then ordering custom vitamins based on their own nutritional deficiencies? Okay, so first comment is, I do not think we are there to know exactly vitamin levels on each individual at a given time, how that is associated overall body function. Vitamin level, again, it is dynamic. The levels are dynamic as well. And even, I think it's important to testing have no major deficiencies. For example, one, the vitamin we worry the most those days are vitamin D, for example. Elderly, another one is thiamine. And those deficiencies need to be ruled out. But beyond that, we actually do not know enough to customize vitamin levels for supplementation and get better health. I'll give you another example. Vitamin E was highly advocated, say 20 years ago for antioxidants until the trials are showing increased mortality, increased stroke. Why? And one thing we're now looking at is, vitamin E has eight different forms. The one you actually take, you buy from the store, are synthetic alpha-tocopherols. That actually is the minimal effective one. When you take a large dose, you actually competitively eliminate all the biological, highly functional vitamin E. And the last comment I would make is that if without good food and just vitamins, it is the sprinkles on the muffin. It is still a muffin. It did not change to whole salad or vegetable food. And also, I want to add it, the microbiome is the same. We do not know enough to really, based on the microbiome testing data, to give patient appropriate guidance. There are various places in the world where people live for a long time. I think there's even one of the places in California, I'm not sure. But when you look at those populations, I'm not sure if you're familiar, do you learn anything about their diet that has perhaps helped them? I mean, there's a length of life that may be multifactorial. Diet certainly isn't the only thing, but it certainly would be an important thing. Was there anything that's learned from these populations where people live a long time? Yes, the question is, did we learn from populations globally they live longer time? I think the top spots are Hong Kong, Singapore, Japan, Asia. Even in here, there's pockets of people live longer. And here, thumbs up, they eat a lot of natural food. And like Japan, their islands, they eat a lot of seafood, seaweeds, and even they eat, we know Japanese food is talking about sushi. They actually don't eat that much of rice. They also are very much portion controlled. On top of that, they're constantly working, even they're 89 years old. And I visit people and I feel uncomfortable shame in a sense. 87 years old women squatting down, start working on the piece. I can't even do that. I'm much younger than that. I think the answer to you, and there are a lot to learn, natural food, portion control, not exceed your body's need, and coupling with physical activity is really the key. Sorry, I couldn't give you more like superfood. Sorry, go ahead. Thank you for the excellent presentation. I have two questions. Number one is the, can you comment about the vinegar? The mechanism does postprandial hyperglycemia. There is also data about the cinnamon as well. Yes. This is number one. Number two, what's the different, like we do hear a lot about the intermittent fasting. People do lose weight and it's like Ramadan. Okay. But the other way, when people skip meals, for example, when they don't eat breakfast, they gain weight. And that's what we see in our clinical practice. Aha, okay. It's three questions. Number one is about rice vinegar. And initially people believe it was the pH, right? But rice vinegar's pH is not even as low as our stomach acid. And by now, they're looking at rice vinegar in particular, and they may actually have short-term fatty acid. And like the gut bacteria may make. And there are a lot of people trying to study that. Even though their commercial products on the market combine live bacteria, probiotics, and those acetic acid and stuff in it, try to mimic that effect. As to scientifically proving with large cohort study, it is not there. It have a lot to do with individual variabilities. And, but I do want to say, rice vinegar is a fermented products. So you do taking not just the compounds, you still have the fermentation started microbes. And it definitely no side effect, no harm, unless people have severe heartburns, all of that. So that's the first question. Cinnamon. Cinnamon, we actually have done quite a bit of study. Rule number one, it varies depends on the individual. It seems like most helpful for people have pre-diabetes and also overweight, and they get most of the benefit. And the cinnamon also changed the gut microbiome as well. But if you looking at cross section lump everyone together, we have not able to find any unique group. They all respond the same way. And again, it's a spice. And particularly if you replace sugar, we clearly see benefit. We use cinnamon to replace it. If you say, oh, I can add cinnamon, you know, cinnabons, oh, I'm not sure. All right. So last question about fasting and people skip meals. First thing about fasting, it is not necessary for everyone to start with, particularly not good for elderly. The reason is before we turn 50, and the metabolic process is pretty reversible. If you not eating for eight hours, your amino acid pool lasting about three hours, no problem, break down skeletal muscle and amino acid pool is taking care of it. When you get to the meal and your anabolic process starts, your protein restored. But when you become 50 or older, that process become less, less reversible. There are even studies showing if you are a senior citizen, 65 or above, if you losing weight, no activity involved, you losing half fat, half lean. But when you gain weight, you gain 100% fat. Okay. With one round of this, your metabolism is significantly lower. That is the reason when you skipping meals and often you losing muscle, even you come back to the same diet, you gaining weight and instead of able to maintain. So it's very, very important. I will not recommend people go on fasting, particularly elderly or taking diuretics and taking hypoglycemic medications. Can be done, but need you all closely monitor them. If we start someone and we lost regimental fasting or no fasting, we typically, if they're on insulin, cut at least half, if not 70% to start with for safety. And also for the feasibility for them to lose weight. If you have them in a very, very tight glucose control, they're gonna be hungry. They're gonna be eating. They're not gonna lose weight. That's another thing to just to share. Yes. That was very interesting. I think you commented on this a little bit, but could you comment a little bit more on probiotics and supplements of that sort? Okay. Probiotics are live bacterias. It is, other than IBS, there is no clear evidence at this moment probiotic will do anything at this moment for a couple of reasons. Number one, it is no evidence of showing they actually can got to larger bowel life because we have acid. We have the digestive enzyme in the small bowel. That's number one. Number two, and no evidence that they can really reside in your gut. And that is the reason they give you pills, 50 million, 50 billion, you take three times a day, continuously taking. The most concerning are the more recent studies showing probiotics actually have more negative impact on your gut microbiome because the most important thing for gut microbiome, it is not necessarily you have how much bifido, you have how many lacto, what strains. Diversity is most important. Second thing is how resilient your gut microbiome are. Let's say you have to take antibiotics for one course, how fast they can come back. And there is no clear evidence probiotics would like a drug. And we give this number of this live bacteria, we would solve whatever condition. Absolutely not. In the GI tract, we only have 500 different kind bacteria. If you're counting strains like the probiotics we're talking about, that number is gigantic. And we're talking about 100 trillion total numbers. In that context, 50 billion, it is nothing. So we are not there to tell you, ah, take the probiotics, live forever happily. Sorry about that. I know time is up and I'll stay in the front if anyone else have more experience to share. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.

nutrition

health

balanced diet

disease prevention

gut microbiome

personalized nutrition

portion control

physical activity

social support

holistic approach