The Science of Weight Loss: What You Need to Know
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- Coming up on this episode of The Doctors Pharmacy. How do we explain this? The truth is the science of weight and metabolism is complex. It's about calories for sure, but not only calories. The science is clear on this. Not all calories affect our metabolism in the same way.

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Welcome to The Doctor's Pharmacy and another edition of Health Bytes. I'm Dr. Mark Hyman. Today we're talking about weight loss, a topic millions of people struggle with and even more have questions about how to do it and what is going on and why are we all overweight and how do we fix it? Now, given all the research and the science about weight gain and weight loss, there's so much debate still and confusion about what

causes weight gain and how best to lose weight. You see, is weight loss about eating less and exercising more? Is it about cutting calories or maybe it's cutting back on carbs? What about dietary fat? Should we cut back on that too? Well, weight loss can be super confusing. When you hop on social media, it seems like everyone has the answer. And yet, despite the endless information at our fingertips, many people are suffering and are trying, but failing to shed unwanted pounds and keep them off.

Now, the government dietary guidelines and nearly all doctors, nutritionists, and all professional associations tell us that weight loss is simply about energy. You need to burn more calories than you eat. You need to eat less and exercise more. Now, this is called the energy balance hypothesis or energy balance model of weight.

Now, according to this theory, as long as you eat fewer calories than you expend, you'll lose weight, right? Well, it doesn't matter if the calories come from a thousand calories of soda or a thousand calories of broccoli. All calories are the same in this model. Now, the implicit message here is that you're overweight because you eat too much and you don't exercise enough. In other words, it's your fault because you don't have the willpower. And the subtext is that you're a lazy glutton. I don't believe that.

This is just nonsense. The story of weight gain and weight loss and metabolism is far more complicated than that. Now, Americans have been doing their best to follow this advice of eating less and exercising more for the past 50 years. And yet obesity rates have gone from 5% when I was born to 42%. How do we explain this? The truth is the science of weight and metabolism is complex. It's about calories for sure, but not only calories. The science is clear on this. Not all calories affect our metabolism in the same way.

way you see food contains calories but also the type and quality of those calories impacts the way the body functions beyond the energy they contain you see food is information it's instructions or code that impacts your hormones your immune function your brain chemistry your gene expression and your microbiome in ways that have a huge effect on weight and metabolism

If the calorie model doesn't completely explain our obesity epidemic, is there something we're missing? And the answer, my friends, is yes. The last few decades of research have shown that a calorie is not a calorie. Now, yes, in a lab when they're burned, calories are the same, but when you eat them and the information has different effects on hormones or your brain chemistry or your

immune system or your microbiome, they are not the same. So a calorie burn is a calorie burn, but a calorie eaten is not a calorie eaten, to quote my friend Robert Lustig. Now, if our current theories don't completely explain our current obesity epidemic, then we need a new theory or maybe theories. The emerging model of weight gain and weight loss that's coming out of the science is called the carbohydrate insulin model.

Now, this theory posits that refined carbs and sugar calories drive high levels of insulin. And that's the fat storage hormone that makes you store fat. It locks the fat in the fat cells and it slows your metabolism. Not a good combo if you want to lose weight. And the special type of fat that's stored, which is your belly fat, is actually a different type of fat. It's hungry fat. But is this true? And what does the research say?

Well, today we're going to discuss the functional medicine approach to weight loss. It zooms out and looks at root causes and mechanisms and includes all the variables that affect weight and metabolism. We'll see whether weight loss is simply about eating fewer calories or maybe about fixing your hormones or whether other factors such as toxins also influence weight. So let's cut through the noise and offer a science-backed holistic roadmap to weight loss and metabolic health. So whether you want to lose that extra couple of pounds around the midsection or transform your body composition completely, I

hope you'll find this episode helpful let's get started so what makes us gain weight now there are two main schools of thought for what makes us gain weight which are truly the subject of a lot of debate the energy balance model and the carbohydrate insulin model we're going to talk about them now later in discussion we'll discuss other factors that can influence weight gain it doesn't just stop with calories or diet or the carbohydrate insulin model or energy balance model there's a lot of more things that can impact your metabolism but first let's take a look at the main

diet related theories, the two of them that lead to weight gain and the pros and cons of each one. Okay, let's start with energy balance model. Now this is the one that we've all been following for decades and decades, and it's sort of not working out for us, right? Eating less, exercising more. How's that working out for you? Well, let's talk about what it says and the science behind it and what makes sense about it and what may not. The energy balance model suggests that your body weight is maintained

when the calories we take in, in eating and drinking, equals the calories we expend, right? Our basal metabolic rate plus our physical activity plus digestion, or what we call the thermic effective food, regulates your weight. And basically weight management and weight maintenance occurs when energy in equals energy out. If you want to lose weight, well, you need to take in less energy than you put out, right? If you

gain weight, you want to gain weight, you have to take in more energy than you burn, right? This considers that all calories are metabolically alike and that you can lose or gain weight on any diet. It doesn't matter where the calories come from. The dietary guidelines from America has been primarily based on this advice. The 2025 USDA dietary guidelines state, quote, losing weight requires adults to reduce the number of calories they get from foods and

and beverages and increase the amount expended through physical activity. In other words, eat less, exercise more. The Endocrine Society says, quote, the impact of diet on obesity risk is explained largely by its effect on calorie intake rather than by changes of either energy expenditure or the internal metabolic environment.

In other words, a calorie is a calorie is a calorie. Unfortunately, that's not exactly a true story according to science. So what are the pros of this energy balance model? Well, it's simple, right? Energy intake has to equal energy expenditure or you lose or gain weight if you're out of balance. And it's an easy, straightforward, universal model for weight management that basically everybody can understand. Calories in, calories out, eat less, exercise more. People say this is true because...

It's based on the first law of thermodynamics, which means energy cannot be created or destroyed, only transformed. Now, this is true, but you have to understand the definition. The definition requires a closed system. If you just look up the first law of thermodynamics, it means energy cannot be created or destroyed in a closed system. The body is not a closed system. You've got so many variables like hormones and microbiomes

your immune system, so many other things that regulate your response to energy. It also embraces physical activity that's needed to maintain a healthy weight and wellness, which is great. I think that's important exercise, but you cannot exercise your way out of a bad diet. I promise you that. Anybody who's tried will know what I'm talking about.

And this also allows for diet flexibility, right? As long as you quantify energy intake and expenditure, basically counting calories and counting steps, basically, then you can follow any dietary approach. Low fat, low carb. You could drink Coca-Cola as your sole food. It doesn't matter as long as you monitor and track your calories. Intuitively, it just doesn't quite make sense, right? It doesn't make sense that all calories are the same because any...

kindergarten kids would say, well, gee, if you drink a thousand calories of Coca-Cola or have a thousand calories of broccoli, probably not the same. Even within this model, they do acknowledge, and this doesn't quite fit the model though, that ultra-processed, hyper-palatable, energy-dense foods impact our brain chemistry, makes it easier to overeat. Well, so they're saying, well, maybe calories aren't the same because some calories make you overeat. Well, that doesn't make sense, right? If it's just calories in, calories out.

But they also say in the same breath that there's little human evidence to suggest that hyperpalatability is related to overconsumption. Well, that's just not true. I mean, the NIH study from Kevin Hall, we've talked about before on the podcast, where he basically gave people ultra processed food or whole foods and told them to eat whatever they want. People who ate ultra processed foods

were hungrier and ate 500 calories more a day now research supporting this model this energy balance model is is there is some research about it of course it depends which studies you look at how they're looked at and just sort of sifted through but a meta-analysis of 32 controlled feeding studies argues that when calories are controlled metabolism weight loss are essentially the same on a low fat versus a low carb diet but you have to look at what defines a low carb or a low fat diet is it 10 fat is it 10 carbs is it 50 fat is it 50 carbs like

It matters, right? And so maybe some of the differences are not really that significant in order to shut down insulin. We'll talk about that. In the studies, again, a little bit contradicting the model because if all calories are the same, they should affect you the same, right? But they do acknowledge that the macronutrients account for the differences in the distribution of body weight. So for example, high carb diets promote more belly fat than high fat diets, which don't promote more belly fat. In a systematic review and meta-analysis of randomized controlled trials, it was published in the British Medical Journal,

They compared low-fat versus low-carb diets from 121 trials and approximately 22,000 adults who were overweight or obese and reported that they both had similar effects on weight loss and cardiovascular markers at six months. However, the weight loss diminished and the heart benefits disappeared at 12 months for all the diets. Now, another study randomly assigned 131 healthy, overweight, or obese adults who had lost about 8% or more of their body weight to either a moderate-fat, low-glycemic diet, a

low-fat, medium glycemic diet or a high glycemic sugar, I mean a high sugar control diet with a similar protein content and they could eat whatever they want. And they found really no difference in weight gain after 18 months. What are the things that contradict this energy balance model? Some studies show it works, some studies show it doesn't. So let's get into what the cons are. It doesn't really explain how or why weight gain happens or what's driving the process other than just energy, right?

Obesity rates have continued to climb despite Americans eating less. Now, this is really fascinating, folks. If you take the hypothesis that obesity is all about calories, it's hard to reconcile that with the fact that over the last decades, and I'll get into that, our calorie consumption has gone down, but our weight has gone up.

up. So that's a really important fact. And this is the NHANES data, which is the National Health and Nutrition Examination Survey government data, tens of thousands of people over decades and decades. And they looked at calorie and added sugar intake, and they found that it's gone down since the year 2000. But obesity and type 2 diabetes have gone up.

right? How do you explain that? It also doesn't consider the nutrient matrix or the quality or bioavailability of certain foods. For example, nuts have a high energy density, right? Because they're higher in fat. But eating nuts has been shown to help maintain a healthy weight and even lose weight. In a 2012 study published in the American Journal of Clinical Nutrition, they found that the average energy extracted from almonds is 32% less than what's written on the nutrition labels. Meaning, even if it says 100 calories, it's

32% less than that that's actually used by the body because it takes so much work to digest it. Same goes for walnuts, about 21% less and pistachios, 5% less and cashews, 16% less. So how do you explain that? Well, it's the food matrix. It's the degree of processing. It's the indigestibility of certain parts like insoluble fiber and things that feed the gut microbiome.

Cutting calories without focusing on nutrition quality can actually lead to nutritional deficiencies, which can impact mood, mental health, and metabolism. So for example, if you're on a calorie-restricted diet, but you're not on a nutrient-dense diet, you're going to end up with problems. There's also metabolic pushback that happens. You know, cutting calories makes you hungrier and it decreases your metabolism. So you're in a vicious cycle. So you eat less, but then your metabolism slows down and then you increase your hunger. So it makes it hard to push past a weight loss plateau by just adjusting calorie intake.

It's really hard to reduce your calorie intake because you're going to be hungry and that's going to overtake your body and willpower just is not enough. So you have to use science. And this whole energy balance model also doesn't account for the complexities or the differences in individuals genetically and metabolically.

Hormones, genetics, your blood sugar, your microbiome, impact of nutrition on our brain chemistry, on our metabolism, the role of environmental toxins, things like obesogens, endocrine-interrupting chemicals, stress, mitochondrial damage, free radicals, inflammation, all that is not taken into account by the energy balance

model. And just calorie restriction doesn't work a long time. Nobody can stick with it, right? Research shows that humans are really bad also at measuring their energy intake. So we can underestimate our consumption by about 50% and we overestimate our calorie expenditure from exercise by about 70%. I always said that when I worked at Canyon Ranch. So people basically underestimate the amount they eat by 50% and overestimate the amount they exercise by about 50%.

Now, people can't adhere to a calorie-restricted diet long-term. They really can't, especially low-fat diets because they're not very satisfying and fat makes you feel full and protein makes you feel full. So counting calories is kind of unsustainable. Anyway, even if you get a PhD in nutrition and you are really focused on understanding calories, it's really hard to be accurate unless you weigh and measure every single thing you eat. And also, the only problem with this model is it kind of blames the individual when they can't lose weight. Well, why did you lose weight? Well, you're just not eating the right way. You're eating too much and you're not exercising enough.

And that sort of blames the victim, which is not really true. I think that there's a lot of flaws with the energy balance model. Calories do matter. I'm not saying they don't matter. They're not the whole story. And I think the quality of the calories matters. And it turns out from a lot of data from Dr. Ludwig at Harvard and others, that turns out that what you eat is more important than how much you eat.

because when you choose the right foods that regulate your biology in the right way, you don't have to white knuckle your way to weight loss. It actually will automatically start to shift your body in terms of the right metabolic health. So what's this next model, this carbohydrate insulin model? And I think we try to sort of narrow things down into simple little categories, but we have to sort of understand that biology is complex and not any single theory will explain everything. But I think this one is much closer to what I've seen in my practice and also what I've seen to be more effective

clinically with many patients and what I've heard from many of my colleagues as well. Now, this offers a different perspective to this energy balance model, but I should say, just going back to energy balance model, the energy balance model was so attractive to the food industry that Coca-Cola spent $20 million paying scientists to fabricate data to show that this actually worked.

that weight loss was just about calories in, calories out. It didn't matter where the calories came from. All calories in moderation, including Coca-Cola. That's just nonsense. Sadly to say, it's nonsense. And they were actually exposed. I wrote a lot about this in my book, Food Fix, and also some other things I've written. But it's a very...

attractive model for the food industry because it basically lets them off the hook, right? If you're a big food company or a fast food company, you can feel good about yourself because it's all about just the quantity of calories you eat. So if people don't overeat, that's fine. They can eat their junk food, but it's very, very much not the case. Let's get back to the carbohydrate-insulin model. It basically suggests that the quality of the calories consumed

particularly rapidly digested calories like refined starches, sugars, and empty carbs. They play a real critical role in weight regulation and obesity because they influence your hormones, particularly insulin. Now, insulin is a very important hormone.

What is insulin and what does it do in the body? Well, insulin is a hormone that's released by the pancreas when we eat something that has a high glycemic load, meaning it raises your blood sugar. That how rapidly a meal raises your blood sugar is called the glycemic load. Now, when a meal is rich in a lot of sugar and starch, your blood sugar spikes and then insulin is released to help deliver the glucose and...

the fuel to your cells, your muscles, your liver, your fat tissue, and too many calories from each meal then, when you have high insulin levels, because it's the fat storage hormone, they're siphoned off into the fat tissue. And then too few remain in your circulation, which then makes your body perceive that you're in an energy crisis, that you have low energy states

and that makes you crave more carbs and more sugar. You know exactly what I'm talking about. If you eat sugar and carbs, you want more sugar and carbs, even though you have so much energy. I mean, people who are obese are just having enormous storage amounts of calories, but they feel like they're hungry and starving. Why?

of the role of insulin and how it works in the body by storing the fat in the fat cells, by locking it in there, by clearing the blood of a lot of the available fuel. So it's stored in the fat cells and their brain doesn't perceive that you've got enough food around. So basically obesity is a state of starvation amidst plenty. It's the feeling that you're starving in a

when you have plenty of food and calories. Now, this perceived state of starvation negatively affects all sorts of systems in your body, including your thyroid, and that slows your metabolism even more to conserve energy. Also, if you have a high-carb diet, it increases cortisol. So we know that eating sugar and starch raises stress hormones, cortisol, also epinephrine, adrenaline, and that can lead to fluctuations in blood sugar. It can lead to more insulin resistance, weight gain, hypoglycemia, and you can just get in

the terrible vicious cycle of being hungry and in the cycles of low and high blood sugar. Now we also know from the data that restricting your energy intake, meaning eating less, while consuming a high sugar starch or high glycemic diet is going to increase

your predisposition to store belly fat, okay? And liver fat. And it's going to make you hungrier. So even if you're restricting calories or eating high carbs, you actually are going to be hungry and store more belly fat. So high insulin and the low glucagon from eating a high glycemic diet also inhibits our ability to immobilize and burn fat. As long as insulin is high, it blocks our

our ability to burn fat, what we call lipolysis. And that makes weight loss difficult. So it's like a one-way turnstile. The fat gets in the cells and the sugar and the calories get in the cells, but they can't get out. It's really difficult to lose weight as long as your insulin level is high. And I've seen this over and over with my patients. The key to getting the weight down

by any mechanism is lowering insulin. And when you have higher and higher amounts of starch or sugar, your cells start to become resistant to the effects of insulin. So you need more insulin, which leads to more weight gain and more chronic diseases like type two diabetes, obesity, Alzheimer's and cancer.

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That's kind of the theory. Now, what are the pros of this carbohydrate insulin model? Well, it focuses on food quality, on what you eat, not just how much you eat. And it focuses on getting rid of these empty, fast-digesting, high-sugar, high-starch carbohydrates because they have a really bad effect on metabolism and weight gain. It also tells us that all calories are not created equal in terms of their metabolic impact.

Now they're equal in a laboratory when you burn them. If you burn a thousand calories of broccoli and a thousand calories of Coca-Cola in a lab, they release the same amount of energy. But when you eat them, they have very different effects on the body. I mean, think about that. A thousand calories or a hundred calories of broccoli versus the same amount of Coca-Cola, very different impact on your biology.

Another really important feature of the carbohydrate insulin model is that it addresses the role of insulin in fat storage and metabolic health. You see, when you have high insulin, it makes you store fat, which means lowering insulin through diet and other mechanisms can actually improve fat loss and improve metabolic health and reduce obviously the risk for insulin resistance, type two diabetes, chronic diseases without hyper fixating on calorie intake. Focusing on what you eat versus how much can make a big difference.

This also has a huge impact for type 2 diabetes, less insulin spikes, lower insulin levels, less insulin resistance, and help can prevent and even reverse type 2 diabetes. In fact, the work by Sarah Hallberg and others using a ketogenic diet, which is like 75-80% fat and 5-10% carbs, has been able to completely reverse type 2 diabetes. In essence, diabetes and insulin resistance is a carbohydrate intolerance problem. And this is what's happening in America.

We have a huge population that's carbohydrate intolerant because we weren't adapted to eating such large amounts of sugar and starch. What does it, the carbohydrate insulin model explain? Well, it doesn't quite explain the fact that overeating alone causes weight gain. Even if you are eating healthy food, if you eat too much, you will gain weight. It's

True that that's true, but it's much harder to do on a low carb diet because protein and fat and fiber actually make you feel full. So it's harder to overeat. Like who can binge on a bag of avocados? Nobody, right? No one's going to eat a dozen avocados, but you can eat a dozen cookies in a snap, right? I've done it before, trust me.

So, you know, you have to understand that the quality of the food you're eating affects your ability to want to eat it and how full you feel. Now, on a high glycemic diet, which is high sugar, there's a lot of hormones that are messed up. For example, leptin. And you get leptin resistance, which causes the body to actually gain weight.

The more leptin resistance you have, the more you don't feel full, the more you eat, and you get in this vicious cycle. This kind of model doesn't completely explain everything related to weight, because there's obviously toxins, the role of the microbiome, and many other things we'll talk about. And so it oversimplifies weight gain. It's simply related to carbs and insulin. And it doesn't really consider total calorie intake, overall diet quality,

saturated fat, physical activity, genetics, environmental toxins, obesogens. So we have to sort of use a broader range of theories to explain what we're seeing. But everybody likes to focus on their theory, but it's just more complicated than that. Now, the research is mixed. Some studies show that low-fat and low-carb diets have no difference in terms of weight loss. Others show the opposite, that actually low-carb diets outperform

low-fat diets when given to people to eat. Now, the other thing the model doesn't quite explain is that obesity is typically associated with normal or high glucose and triglycerides. And this carbohydrate insulin model says that when you have a high glycemic diet, it leads to low metabolic fuel concentrations about two to five hours after eating, which increases cravings. So, you know,

you can't explain everything with this model. The counter argument from the carbohydrate insulin folks is that fat cells hit their limit and eventually do not expand anymore. And at that stage, the weight gain plateaus and circulating fuel concentrations rise. Meaning after a while, you know, you're going to see the insulin working and getting your blood sugar and your free fatty acids in your blood down. But eventually,

you're gonna just fill up the tank and you're gonna spill over and there'll be higher amounts of fuel in the blood. In other words, higher levels of glucose and free fatty acids. What does the research tell us? Well, there was a 2023 multicenter randomized controlled trial that looked at about 300 overweight obese individuals and they randomized them to a low carb diet

a calorie restricted diet or a low carb and a calorie restricted diet or just a normal controlled diet for 12 weeks. So they basically could either low carb, low carb, low calorie or a 12 week normal diet. Now, the results showed that the low carb and low calorie diets was more effective than the low carb or calorie restricted diet alone. But they also found that the low carb

plus the calorie restricted diet or just a low carb diet alone reduce body weight, waist circumference and body fat more than the calorie restricted diet. So just calorie restriction alone wasn't enough when you added low carb to it or you just did low carb alone, you did better than on calorie restriction. Now it's easier to lose weight on a low carb calorie restricted diet when you keep

your insulin low than a calorie restricted diet because your insulin can still be high if you're doing calorie restriction and eating a lot of carbs. In 2008, and this was a very impressive study, it was a two year randomized controlled trial published in the top tier journal, New England Journal of Medicine. They assigned about 322 moderately obese people

to a low-fat calorie restricted diet, a Mediterranean plus calorie restricted diet, or a low carb and not calorie restricted diet. You either were calorie restricted on Mediterranean low fat or just low carb with no calorie restriction. You could eat as much as you want. Now here's really the interesting data. The low carb group that wasn't calorie restricted lost the most weight

Okay, and then a 20% reduction in total cholesterol to HDL ratio versus 12% in a low-fat group. That's pretty amazing. So basically, not restricting calories and just using low-carb actually had the most weight reduction and the best improvement in cholesterol. Another review, a systematic review and meta-analysis of randomized controlled trials. Again, the highest level of evidence is from Dr. William Ludwig from Harvard. They looked at 53 trials with over 68,000 participants and they compared low-fat and

versus low carb diets. And they found that low carb diets outperformed low fat diets for weight loss every time. So that's a lot to take in. I know a lot of studies, a lot of information, but basically if you look at the data, it seems that calorie restriction can work. It's hard to maintain, but the best approach is a low carb diet, which is not going to be spiking insulin and actually works better than a low fat diet. So which theory is correct?

Well, the truth is they're both right and they're both wrong. We are eating less calories than we did and we're gaining weight as a society. Total sugar consumption has gone down a little bit, but high fructose corn syrup has gone up. So calories from sugar are still higher than it was before. Protein and fat intake have not really changed since the 1970s, but guess what? Refined carb and sugar intake has increased, although it's sort of hitting a plateau. But we were told to eat six to 11 servings of bread, rice, cereal, and pasta a day and we've added sugar to almost everything.

And that was in the 1992 food pyramid. And we listened and it's led to the greatest obesity and diabetes epidemic in human history. The other thing that's really happened in the last 20, 30 plus years is the intake of ultra processed food has just skyrocketed. And it's now 60 to 70% of Americans diet. In the adult population, the consumption of ultra processed foods went from about 53% in 2000 to about 57% in

2018, and it's now by some estimates well over 60%. And even looking at what's sold in stores, it's about 73% of foods. And this is even worse in kids. A study analyzing total energy intake from ultra-processed food in adolescents showed that they increased from 61% to 67%. That's 67%

of foods that our kids eat is essentially highly processed junk food. There's been a big increase in ready-to-eat meals and various kind of foods we eat that are pre-processed and ready to eat from about 2.2% to 11.2%. We are having less soda, that's good, but still we're eating more processed food. So, you know, one thing goes up, one thing goes down, but at the end of the day, we're eating more...

processed food and ultimately more refined sugars and starches. Also, we're having a lot of other things that are affecting us. Additives, preservatives, emulsifiers, gums, which in the gut cause a lot of problems. They cause dysbiosis, leaky gut, they cause inflammation, and they make us gain weight because of the role of leaky gut. And we're going to explain that a little bit. When the microbiome is affected and the quality of the food we eat affects the microbiome, it leads to more weight gain. So what can we all agree on? Well,

Cheap, convenient, energy dense, ultra processed food that's high in starch, high in sugar and full of low quality fats are bad for metabolism and our health and our risk for chronic disease.

So no argument there. I don't think any camp will say that we should really be eating more processed food, ultra processed food. I mean, the energy balance model does support that at some level, particularly the food companies are happy about it because it means there's no good and bad foods. But I hate to break the news to you folks. There are good and bad foods, right? Coca-Cola is just a bad food.

Pepsi's a bad food. Doritos is a bad food. I mean, I can go on and on. Those are just not actually food by the definition of food. So what else makes us gain weight besides calories or carbohydrates or sugars, right? Hormones. Hormones play a big role in our metabolism, including insulin. And high insulin is the biggest driver 'cause it's the fat storage hormone. And when we eat a diet that's high in sugar or starch or even high in calories,

it will spike insulin. Also, our thyroid is often playing a big role in our metabolism and low thyroid hormones do affect your metabolism. High levels of stress, which are driving more cortisol. Cortisol will make you gain weight. High leptin, which happens because of our

leptin resistance and inflammation. We also have low GLP-1, which is known as Ozempic. And there's many reasons for that, but our diet definitely causes our body not to produce as much GLP-1 because of all the ultra processed food. Other hormones are important like glucagon and GIP, which stimulates insulin secretion and promotes fat storage and it slows gastric emptying. So all that, not so good.

right? You get more insulin, more fat storage. The other factors that may play a role are genetics, particularly epigenetics. So there's a lot of environmental influences on our weight and our risk of getting weight. In fact, the social factors are huge. Christakis' work is really, really impressive. This is from Harvard where he looked at Framingham data and he found that if your friends are overweight, you're far more likely to be overweight than if your parents or your siblings are overweight.

about 171% more likely than about 40% more likely if your family member's overweight. So it's the social connections we have play a big role. There are other factors, perinatal factors, like what happens in utero. For example, if fetus is exposed to a diet high in starch and sugar or environmental toxins in utero, what we call obesogens, it makes them more susceptible to weight gain by this epigenetic factor.

imprint. And I've discussed this in my health bite called Preparing to Conceive. I'm going to put the link in the show notes. You can learn more about it, but definitely plays a role. Epigenetics play a role in setting up programming of the fetus to become overweight or diabetic or have other issues later in life. There are other factors. Our gut flora plays a huge role. For example, when they do studies on rats, when they take the microbiome of a thin, healthy mouse and put it in a overweight fat mouse, the fat mouse loses weight even though they're eating the same amount of calories. So

It's clearly way more than just calories. So dysbiosis, leaky gut, what we call metabolic endotoxemia also play a role. When you have also bad bugs in your gut, they release toxins. One of them is called lipopolysaccharides and these get absorbed in the body. The immune system creates response and that immune system response drives insulin resistance.

So anything that drives inflammation will cause insulin resistance. And of course, insulin resistance itself causes inflammation. So when you look at bacterial strains, you can actually see bacterial strains that actually are associated with more obesity. For example, high formicities and low bacteroides are associated with obesity. When you can measure that on a stool test, we do that all the time in my practice. Low levels of good bacteria, right, like lactobacillus, bifidobacteria, which are the

good guys they also affect our metabolism so when you eat an energy dense high processed fat high carb sugar diet from ultra processed food it increases these bacterial endotoxins these lps's they just increase inflammation throughout the body they increase gut lining inflammation they loosen the connections between our intestinal cells called tight junction junctions which causes leaky gut those toxins leach into circulation they cause inflammation and

and they basically cause your body to gain weight. So they lead to insulin resistance in the muscle, liver, and fat tissue, and basically just create this vicious cycle of weight gain. Obviously, there are other factors too. I mentioned ultra-processed foods and sugar-sweetened beverages, which are super easy to overconsume, are a big factor. The overall impact of excess calories is for sure a factor from refined carbs, from starches, from sugar. And when you eat those foods, they make you overeat them. So you end up eating more calories if you eat that

food. But if you eat real whole food, your body will naturally regulate and you won't be hungry and you won't want all that junk. So what are the ways in which the ultra processed food and all this crap affects us? Well, there's many pathways. One of them is called AMPK. I've written about this in my book, Young Forever.

But when your energy levels are low in a fasted state, AMPK goes up and it increases glucose and fatty acid uptake and the breakdown of fuel across various tissues like the liver, brain, and muscles. Now, when energy levels are high in a fed state, AMPK is inhibited and that increases liver triglycerides, it increases insulin resistance, and it creates metabolic dysfunctions.

So basically, when you're in a fasted state or you do overnight fasting, it actually makes you have a better metabolism. And that's what the drug metformin does. It activates AMPK, which is a good thing. But when your energy levels are high, which is most of the time for most of us, AMPK isn't activated and you end up with all this metabolic dysfunction and waking.

The other big thing in our diet that's a problem is fructose. And free fructose from high fructose corn syrup is a big problem. It's an ultra processed food. It's pretty much in everything. And this inhibits AMPK. So when you inhibit AMPK, it's not good because you end up gaining weight and having all these metabolic issues. Now in mice studies, they fed fructose rich diets to these mice and they found lots of problems with their liver metabolism of fats and their bile acid metabolism. And that led to fatty liver.

So basically fructose, which is the main thing in sugar-sweetened beverages and a lot of foods, and high fructose corn syrup basically causes fatty liver. It also leads to leaky gut because fructose requires a lot of energy to be absorbed and it takes away energy from the gut, which is needed to keep the cells stuck together and you get the breakage of these tight junctions and end up with leaky gut. And then you end up in this terrible cycle. The other thing is sugar is kind of addictive.

All right, this is a really good study. It was in the American Journal of Clinical Nutrition. And it basically showed that foods high in sugar and glycemic index or load trigger addiction-like responses in humans. Now, David Ludwig and his team from Harvard conducted a study that demonstrated that high sugar foods activate the brain in the area called the nucleus accumbens, which is a brain region associated with opioid addiction and addiction in general. Now, they did this really very elegant study

The study utilized a rigorous, randomized, blinded, crossover design test, which is the best kind of study, to test the biological basis of sugar addiction. And then by doing the study this way, they avoided bias and criticisms, which were going to come for sure from the food industry. So what did they do? Well, they took 12 overweight or obese men and they were given milkshakes with the same amount, and this is important, the same exact amount of calories and fat and carbs and protein and fiber.

Now, they were designed to taste exactly the same, but they differed only in how they affected blood sugar levels. Because one had a low glycemic starch and the other had a high glycemic starch. But they looked and tasted the same and they had the same protein, calories, carbs, and fiber and fat. So it's not just about calories, folks. This is one of the studies that really compels you to see that. Now, when they measured the brain imaging,

the brain activity, the measured blood sugar, the measured hunger. After consuming each milkshake type, the results showed that the high glycemic milkshakes, the ones with the quickly absorbed carbs, they cause significant spikes in blood sugar and insulin. They cause more hunger, more cravings. And most importantly, in my mind, it lit up the area of the brain called the nucleus accumbens, which is the addiction center in the brain.

So literally, even though people didn't know what they were eating, even though it tasted the same, even though it had the same amount of calories, even though it had the same amount of carbs, where those carbs came from mattered. And it affected their brain and their hormones and their metabolism. Now, this study suggests that the body response to calories varies a lot based on the composition of the diet. I mean, carbs, fat, protein, quality of the carbs, the quality of the food, and that foods that cause rapid blood sugar spikes are biologically addictive.

And that's pretty much all the food we're eating today in America. The other thing that's really important is our low fiber diet and our diet that's low in essential nutrients for two reasons. One, fiber is critically important, helping slow the absorption of glucose and prevent these insulin spikes and glucose spikes. It makes you feel full and it overall helps you lose weight. We used to eat about 150 grams of fiber per person per day. Now we eat about eight. The other thing is that essential nutrients are important because

because when you're low in vitamins and minerals, your body's craving more food. And so you start eating anything with junk food and fast food and ultra processed food. We're looking for love in all the wrong places, right? There are no nutrients in that food. So we keep on eating. It's like kids who are iron deficient will eat dirt, try to get iron. We just keep eating more junk food, hoping there are nutrients in there, but they're not in there. Not consciously. It's not what our brain thinks. It's what our body's actually reacting to. Also, if you eat a high sugar starch diet, it overwhelms your cells and it causes reactive oxygen species or free radicals, which basically are a byproduct of

metabolism, but when you're eating a lot of calories and food, you get a lot more of them, and that causes all sorts of issues. That damages our mitochondria, which are our energy production factories. It damages our energy sensing pathways. So high levels of free radicals can inhibit, for example, the AMPK we talked about, which senses energy in the body, and then it makes your cells just not burn calories as much. Now, over time, this imbalance in the cellular signaling and the mitochondrial damage that can

can occur from these free radicals, affects your metabolism and potentially the weight gain. Where do these reactive oxygen species come from? A lot of places, just from overeating, from eating too much sugar and starch, but also from toxins. And I wrote an article years ago called Systems Biology, Toxins, Obesity and Functional Medicine. And I wrote a lot about how the mechanisms are of these environmental toxins and how they affect our weight. Now here's the big picture. There are 80,000 new chemicals that have been introduced since the turn of the 20th century. I think it's maybe up to 100,000 now.

And most have never been tested for safety. So where do these toxins come from? Well, they're obviously the ones introduced, but they're also internal toxins, right? The gut is a great source of toxins if we have bad bugs in there. We talked about the bad bugs producing lipopolysaccharides or LPSs. That's one source of toxins. But a lot of the toxins we're talking about here are environmental toxins.

things we should not be having in our bodies but are because of industrialization and pollution and petrochemical use and there are many kinds of toxins out there like heavy metals lead mercury cadmium arsenic nickel aluminum i mean i had one woman who was a fitness trainer obsessed with her weight and health and could not lose 40 pounds no matter what she did it turned out she had high levels of mercury we got the mercury out of her system and she dropped the 40 pounds there are also something called volatile organic compounds vocs that are everywhere off gassing from paints solvents

things in cleaning materials, formaldehyde, toluene, benzene. All these things are all around us. Medications sometimes have toxins in them, alcohol, pesticides, PCBs, herbicides, air pollution, food additives, all this stuff affects us. And of course, so infections, you know, we know that weight can be caused by even infections like adenoviruses, which

create inflammation. Anything that creates inflammation will create weight gain. Mold, I had a patient who was in a moldy apartment and she was so sick from it, it caused her to gain 50 pounds. So anything that causes inflammation will cause weight gain. And of course, obviously our modern refined diet is a toxin in and of itself, right? With all the sugar, starch, high fructose corn syrup, trans fats, crap, aspartame, all the weird food we're eating. And then all the

the plastics we get in our environment, BPA, phthalates, PFAS, the forever chemicals, hormones, antibiotics in our food supply. It's a lot. So a lot of stuff we're exposed to and our bodies have to handle it. Why are they a problem? How do they affect our metabolism? When we are exposed to a lot of environmental toxins, they interfere with our metabolism. They overload our ability to detoxify them from our liver. They disrupt our central weight control mechanism. So our brain function gets disrupted and our ability to control

our weight. It promotes insulin resistance, so toxins cause insulin resistance like BPA, we know for example causes diabetes. It alters our circadian rhythms, alters our stress response because toxins are a stress just by having a toxin in your system, body perceives it as a stress and that leads to higher cortisol. Also, toxins are highly impacting the thyroid and will slow your thyroid

down. And that leads to low thyroid function, which leads to a slow metabolism and more weight gain. And people, you know, see this when you see people dropping a lot of weight, they'll plateau and often they'll plateau because their fat tissue releases all these stored toxins and it poisons their mitochondria, but also poisons their thyroid. So you get all these problems.

So what are these things called? Well, all these toxins are referred to as obesogens because they make you obese. And there's a lot of them out there. We just went through them all. One of the ones that concerns me a lot are these xenoestrogens. These are foreign molecules that mimic estrogen in the body and high estrogen levels promote fat gain and fat storage and really are bad news. So how do toxins prevent people from losing weight? Well, they're stored in our fat tissue. And then when we lose weight, they're released into our bloodstream.

that overloads our liver and our ability to detoxify these compounds. It down-regulates our metabolism, so it slows our metabolism by reducing our thyroid hormone function. It increases actually the excretion of thyroid hormones by the liver, and it competes with thyroid hormones by blocking the thyroid receptors and vying for thyroid transport proteins. So all in all, it messes up your thyroid.

in plain English. It also increases free radicals, which inhibits something called redox signaling, which then damages our mitochondria. So that's our little energy factory. So when you have damaged mitochondria, you don't burn fat very well. Toxins also inhibit the effects of leptin, the fullness hormone, right? They block the effect of leptin in the brain. They also lead to higher stress on the body because anything that's a toxin will create a stress response and high cortisol will lead to weight gain and it can lead to

insulin resistance. It's not just diet that can cause insulin resistance. It's also stress and toxins, as we were talking about. And also high cortisol affects a lot of the appetite regulating hormones like ghrelin and leptin and neuropeptide Y, and that makes you hungry, have more cravings. In fact, in a study of 59 healthy premenopausal women who were aged 30 to 45, they found that stress-induced reactivity and negative mood were associated with greater calorie intake.

So toxins can for sure cause stress, but stress itself can cause stress, right? Psychological stress. And what does it do to the body? Well, a study of 59 healthy premenopausal women aged 30 to 45 found that stress-induced reactivity and negative mood were associated with greater calorie intake. So if you were stressed, you ate more, right? Stress eating makes you crave sugar and even fat when we're stressed. It's normal. Cortisol goes up when you're under stress and you want fuel when you're under stress, you can run from a tiger, right?

It also makes you store belly fat, unfortunately. It affects how the body metabolizes glucose and stores fat. We know people who are on prednisone, which is basically a medication form of cortisol, it causes diabetes. I just talked to somebody the other day who took it for some reason and his blood sugar went to like a thousand. The body thinks you're stressed and it tries to save your life by storing calories and you go into preservation mode. Now, this hormonal imbalance that happens with cortisol leads to weight gain and then it also interferes with the body's ability to lose weight effectively.

So there's a lot of things you should know about weight metabolism. It's carbohydrate insulin model, the energy balance model, obesogens, stress. There's a lot of things. The microbiome all play a role. Infections even, inflammation from any source will all play a role in affecting weight metabolism. So it's not just simple as what you're eating. It's more complex than that. And I think I've written a blog about it years ago called The 8 Reasons Why You Can't Lose Weight That Have Nothing To Do With What You're Eating.

So there's a lot of factors. You just have to pay attention to them all. There's a lot of ways to find out what's going on under the hood. And it's important to know your data. And it's really important to know your hormones. Leptin, glucose, insulin, hemoglobin A1C, lipid fractionation, which is the best kind of panel for cholesterol, your full thyroid panel, stress hormones, inflammation markers, all really important.

looking at heavy metals, toxins, lead, mercury, testing your metabolic health, your liver health, your sex hormones. All these things are really, really important to help you understand what's going on. You might even need infection testing, mold testing, testing for food sensitivities like gluten. A lot of things are really important to look at. And we can test for these things. We can test for stool and microbiome. We can test for mold. We can test for toxins. We can look at your genetic detox pathways. So when I'm working on someone who's got issues, I want to look at a lot of these things.

How do people do this? Because the average doctor isn't helping them. Well, I co-founded a company called Function Health, which is a health platform that allows you to assess all these biomarkers and lots more and learn about your numbers and how to optimize them with deep insights in science. Just $4.99 a year for twice a year testing. And if you're interested, want to learn more and get your own test done so you can see what's going on with your health and metabolism, go to functionhealth.com forward slash mark. So what is a functional medicine approach to losing weight? So what is a functional medicine approach to losing weight while supporting your detox pathways?

Well, first you want to cut out ultra processed foods, sugar sweetened beverages. Just get rid of that stuff. There's just no reason to ever consume those things. You want to basically balance your blood sugar and lower insulin. And that's a key strategy for losing weight. If you can do that, you will lose weight. Now there may be other factors sometimes, as I mentioned, that are unusual, like toxins or infections, but for most people struggling with weight, lowering insulin is a great strategy.

How do you do that? Well, you reduce your intake of refined grains, processed foods, added sugars, lots of starchy foods like rice and potatoes, foods that have a high glycemic load with low nutritional quality. You want to emphasize low glycemic carbohydrates. Non-starchy veggies, those are carbs. Beans can be okay. Non-tropical whole fruits, also good. Gluten-free grains can be fine, but lower amounts, particularly if you're insulin sensitive.

and ideally gluten-free because gluten can be very inflammatory, can cause leaky gut. I've talked a lot about this on various podcasts, but gluten in our America is not your friend. Also, you want to have the right amount of protein, which is about a pound per gram of ideal body weight. And why? Because protein makes you feel full. It also takes a lot of energy to burn protein. So you're actually burning more calories in metabolizing protein. So again, this goes...

against the whole energy balance hypothesis if if it actually takes more calories to burn protein than it does to burn carbs your net net is not the same in terms of your calorie intake and use so you kind of have to understand that it's really more complex than just calories and calories out so basically that's actually a good thing because you're when you eat more protein your body spends more energy digesting it than any other macronutrient also you want to eat the right amount of protein every meal it's really about a palm size piece of protein

About 30, 40 grams. Lots of fats. Fats are good for you. And fats actually also help you lose weight by making you feel full. I wish I could go through all the studies, but there's a lot of studies that show, for example, that eating a higher fat diet will cause less visceral fat and more muscle mass building and many things that you won't see when you eat a high carb, high starch diet. Also, you know, in the good fats, what am I talking about? Nuts, seeds, avocados, olive oil, you know the drill.

Also toxins, you want to try to reduce your exposure as much as possible by eating organic food. If you're eating animal products, make sure you have regeneratively raised ones or grass-fed ones. Also, you want to avoid pesticides, herbicides, hormones, antibiotics in your food. You want to drink filtered water, get a reverse osmosis or carbon filter to reduce the contaminants. Get an air filter like a HEPA or ALPA filter to increase quality of your air, decrease indoor air pollution like

from dust and molds and VOCs. Get houseplants. Houseplants actually help filter indoor air. They're great for that. In terms of your personal care products and your household cleaning products, make sure they're clean. Use the EWG guide called Skin Deep. There's also a guide in household cleaning products. But a lot of these things have plastics, phthalates. There are all those plug-in fragrances for Breeze.

All that crap is just not good. Also, plastic use. Not just bad for the planet, it's bad for you. Microplastics are in everything. Nanoplastics, don't drink from plastic water bottles. Don't heat food in plastic. Don't do takeout foods in plastic containers. Use glass instead. And don't use plastic cutting boards, et cetera. So all that stuff you can do yourself.

Also cut down your exposure to heavy metals, right? They're in certain fish, water sources, lead paint, some medical products like thimerosal and certain vaccines like the flu vaccine. Also improve your elimination of toxins, making sure you're going to the bathroom every day, one or two times a day, bowel movement. I drink lots of water, six to eight glasses at least a day to flush out toxins. Try to sweat every day through exercise or exercise.

or a sauna or steam or even a hot bath. That really helps detox. Fiber, also really important. One, because it helps slow the absorption of glucose and sugar into your system and decrease insulin spikes and helps with weight loss that way. But also 'cause it helps detoxification. So you can have more beans, you can have some whole grains, vegetables, fruit, nuts, seeds.

that helps boost your fiber. Also feed your healthy gut bacteria. You need to feed those guys, right? Have probiotic rich foods, things like yogurt, kimchi, kefir, natto, tempeh, which help the gut flora. Also eat foods that boost detoxification. A lot of phytochemicals are in there. The broccoli family, we talked about a lot.

cabbage, broccoli, collard, kale, brussel sprouts, all that really important for boosting detox. Garlic every day is helpful because also garlic has sulfur that boosts your detox system. Green tea, also another great detoxifier. You can start your day with that. Maybe try vegetable juices. You can use cilantro, celery, ginger, parsley, beets. I don't know too many carrots or beets though. That makes it sugary, but cucumbers. Sometimes herbs can be helpful for mobilizing toxins. Things like dandelion root, ginger, cardamom, cinnamon. A lot of herbs can be very helpful.

curcumin. Make sure you have sulfur containing proteins, eggs, whey protein, garlic, onions. All these are great to help you improve your elimination of toxins because they all boost glutathione, which is really important. Other things can be helpful about flavonoids and colorful things like berries. Dandelion greens are actually one of the most, uh,

liver detoxifying plants out there. They help bowel flow and are great. Cilantro is also great. You can juice cilantro that helps remove heavy metals. Rosemary is great. It has carnosol, which boosts a lot of your detox enzymes. And curcuminoids, which is found in turmeric and curry, well, they're full of antioxidants and they're anti-inflammatory and they're detoxifying. I eat dark green leafy vegetables, which have chlorophyll, also really good for detoxifying. So there's a lot of things you can do with diet

and herbs and spices and foods to help your body boost its own detox pathways. Next, you want to obviously exercise, right? Exercise is really important. Yoga, lymphatic massages, all that helps flush out toxins from your tissues and boost circulation so you can detoxify. So you don't obviously want to only exercise for detoxification. You want to do it for your metabolism. So HIIT training, cardio, strength training, all important for metabolism.

weight management, but you can't get there alone with exercise. And then there's a lot of supplements you can use to help with blood sugar regulation and insulin sensitivity and detoxification. You know, I start with a multivitamin and mineral formula. I also use PGX. It's a polyglycoplex. It comes from cognac root, which is a Japanese root, a tuber, but it doesn't, uh,

have any calories and it absorbs 50 times its weight in water. You can take it as a supplement, either capsules or powder, two and a half to five grams, 15 minutes before every meal with about eight ounces of water. And that basically acts like a sponge and slows things down. Magnesium, really important. Vitamin D. Chromium is usually in a multivitamin. Milk thistle is great for detoxing. Omega-3 fatty acids reduce inflammation. N-acetylcysteine also helps boost glutathione.

And lipoic acid is also a really important detoxifier. It's also important antioxidant and mitochondrial support nutrient. And so is carnitine. So there's a lot of things you can take. We're going to reference all these in the show notes and give you a lot more detail. But I think basically you can help your body by getting rid of all this starch and sugar, by upregulating your detox pathways, by optimizing your microbiome,

by taking a few nutrients to help your metabolic pathways and detox system. You know, you can get your weight under control. I've seen this over and over. And without Ozempic, without drugs, without extreme calorie restriction diets, I've helped people lose literally hundreds of thousands of pounds. I hope we can all agree that weight loss is not just a simple problem, that it's not a one-size-fits-all journey. It's not just about counting calories. It's not just about carbs. It's about everything. So whether you lean toward counting calories, which good luck with that, or managing your carb intake,

The consensus for everybody is really clear. Nobody disagrees with this. Ultra processed foods are bad for your health. Don't eat them. It's literally going to cut out 60 to 70% of the foods you eat in your diet if you're average American, but you need to do it. And if you don't do it, you're going to screw up your metabolism. You're going to screw up your microbiome. You're going to screw up your hormones and you're going to screw up your health. And nobody wants that. And these are highly addictive. They're designed to make us overeat, which contributes to a lot of the weight gain we're seeing. And it's all these downstream issues. And I've talked at

nauseam about ultra processed foods on the podcast, but I encourage you to learn more about it and really understand the harm they do. Now, when we focus on whole food, on nutrient-dense food, when we optimize our detox pathways, when we get rid of environmental toxins as best we can, then we can address the root cause of waking or the causes because there's often many

And when we do that, we're going to create a sustainable path to weight loss and optimal health. And again, I've seen people over and over lose weight, maintain the weight loss simply by working with their bodies rather than against it. So remember, if you're overweight, it's not your fault. It's because of the incredible burden of things that are flooding our system today, the excess

of refined starches and sugars, the excess of calories, the excess of environmental toxins, these things that destroy microbiome, the chronic stress we're under. And it's a lot to deal with, but we can deal with it. And we just need to break it down for each individual and personalize the care. And by doing that, I think we can get people back to health. I've seen this over and over. I've done this with large groups, and I think

if you understand your body and how it works, which is the whole purpose of why I do all this and give all this free information is I want people to feel better. I know people are just literally a few days away from feeling better. And then if they had the instruction manual for their body, they can overcome a lot of the challenges they have and lead a healthy, vibrant life, which is what I want.

for all of you. Thanks for listening today. If you love this podcast, please share it with your friends and family. Leave a comment on your own best practices on how you upgrade your health and subscribe wherever you get your podcasts. And follow me on all social media channels at DrMarkHyman. And we'll see you next time on The Doctor's Pharmacy.

I'm always getting questions about my favorite books, podcasts, gadgets, supplements, recipes, and lots more. And now you can have access to all of this information by signing up for my free MarksPix newsletter at drhyman.com forward slash MarksPix. I promise I'll only email you once a week on Fridays and I'll never share your email address or send you anything else besides my recommendations. These are the things that have helped me on my health journey and I hope they'll help you too. Again, that's drhyman.com forward slash MarksPix. Thank you again and we'll see you next time on The Doctor's Pharmacist.

This podcast is separate from my clinical practice at the Ultra Wellness Center and my work at Cleveland Clinic and Function Health, where I'm the chief medical officer. This podcast represents my opinions and my guests' opinions, and neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional.

This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for your help in your journey, seek out a qualified medical practitioner. You can come see us at the Ultra Wellness Center in Lenox, Massachusetts. Just go to ultrawellnesscenter.com. If you're looking for a functional medicine practitioner near you, you can visit ifm.org and search find a practitioner database. It's important that you have someone in your corner who is trained, who's a licensed healthcare practitioner and can help you make changes, especially when it comes to your health.