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Enjoy your bacon sandwich, while we walk you through the facts and fictions of what science can -- and maybe someday, will -- do to help people lose weight safely.

Annotations:
Caffeine: https://youtu.be/Xl1XBJLfIDU
Circadian Rhythm: https://youtu.be/UbQ0RxQu2gM

Hosted by: Hank Green
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Sources:
http://health.howstuffworks.com/medicine/medication/diet-pill1.htm
http://science.howstuffworks.com/life/cellular-microscopic/fat-cell1.htm
http://abcnews.go.com/Health/WellnessResource/story?id=6770131
http://www.straighthealthcare.com/orlistat.html
http://www.sciencedirect.com/science/article/pii/S0031942210002967
https://ods.od.nih.gov/factsheets/WeightLoss-HealthProfessional/
http://ajcn.nutrition.org/content/98/6/1682S.long
http://www.nature.com/nature/journal/v481/n7382/full/nature10777.html
http://www.livescience.com/51845-irisin-exercise-hormone.html
http://www.theatlantic.com/health/archive/2012/01/irisin-the-muscle-hormone-linked-to-the-health-benefits-of-exercise/251501/
http://www.the-scientist.com/?articles.view/articleNo/43738/title/Irisin-Redeemed/
http://www.nature.com/nm/journal/v19/n8/full/nm.3213.html
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http://jap.physiology.org/content/107/6/1972
http://nymag.com/scienceofus/2014/12/glorious-fat-burning-drug-may-be-in-our-future.html
https://www.joslin.org/diabetes-research/turning-up-the-heat-on-brown-fat.html
http://breakingmuscle.com/health-medicine/can-you-teach-fat-cells-to-burn-calories-new-research-about-brown-fat
Hank: I'm gonna guess that you've been on the internet before, and thus you've seen plenty of ads for treatments that will supposedly help you lose weight using "1 weird trick," or you might've seen recent news about research claiming to have discovered what's been described as "exercise in a pill," sign me up!

If those things really worked, I would be speaking for everybody when I said, "Shut up and take my money!" Unfortunately, there's very little scientific evidence that any drug will make you lose weight in a significant amount safely and healthily. However, there really are some promising treatments in development right now that do at least something to help people lose weight based on new insights into how your body absorbs nutrients and uses energy. So sit down, enjoy your little bacon sandwich there while we walk you through the facts and fictions of weight loss in a pill. 

(Intro)

Let's start out with what your doctor could do for real today. Because you actually can get medications for weight loss by prescription and they come in two basic categories: appetite suppressants, and fat blockers. Appetite suppressants work by blocking your body's ability to reabsorb the chemical signals that your brain uses, called neurotransmitters, to regulate hunger. You've probably heard of a couple of these neurotransmitters: serotonin and norepinephrine, they're released by your hypothalamus to make you feel full. So if a chemical can block your body's ability to reabsorb those chemicals, you would feel more full and eat less.

Do they work? Well, sort of, and only for a while. When combined with diet and exercise, studies have shown that prescription appetite suppressants can lead to losing around one and a half to maybe a little over two kilograms of extra weight. But after 6 to 8 weeks the appetite control center in your brain adjusts to the new levels of these neurotransmitters and the weight loss benefits disappear.

Fat blockers work differently. They inhibit an enzyme known as lipase. When you eat food that has fat in it, those fat molecules need to be broken down into their constituent parts -- glycerol and fatty acids -- before they can pass through the walls of your intestines. That's because fat molecules are too big to pass through the membranes of your cells on their own. Lipases are the enzymes that break down those fat molecules and in order to do that, they need to bind with them. Fat-blocking drugs work by bonding with lipases which prevents them from bonding with fat, and without lipases to break it down, fat passes through your intestines and out of your body without ever being absorbed.

So, do they work? Pretty well, actually. Studies have shown that they stop about 30% of the fat in your food from getting taken into your body, and over the course of two years, people who took a fat blocking drug lost on average about two and a half kilograms more than people who didn't. But there can be some serious and kind of gross side effects because fat blockers keep the fat in your intestines, using the toilet can become a messier, oilier business.

So those are your current prescription options. Then, you've got your over-the-counter weight loss supplements and, I'm gonna be honest with you here, nearly all of the these are bogus. There's very little good science that suggests that any of them will help you lose weight at all. According to the Office of Dietary Supplements of the National Institutes of Health, the only -- yes only one of these that stood up to reputable trials and is legal in the United States is green tea. Green tea contains both caffeine and an organic compound known as catechin. Separately these two things don't contribute to any statistically-significant amount of weight loss but when you put them together, they appear to act synergistically.

Caffeine stimulates the nervous system which has a thermogenic effect -- basically heating your body up by getting your nervous system to tell everything to go a little faster -- and catechins inhibit the action of lipases which gives them a minor fat-blocking effect. They also stimulate the production of norepinephrine which helps control hunger. So together these compounds have a mild appetite suppressant effect that works the same way as prescription appetite suppressants, and there are apparently other mechanisms that seem to be affected by green tea as well but we don't understand them all yet.

So great news right! Just start drinking lots of green tea. I like green tea! Well, don't go expecting a miracle, especially if you put a bunch of sugar in it like I do. Even the most optimistic studies suggest that drinking green tea leads to losing a couple extra kilos over about 12 weeks and even so, lots of caffeine can be dangerous.

So when it comes to what's on the market today, that's it. What about the stuff that isn't on the market? Most scientists involved in making the fat-busting drugs of the future believe a commercially-viable option is at least 10 years away, but we do know a bit about how they might work. One weight loss treatment currently in development aims to work by targeting your body's circadian rhythm. We've talked about this before, your circadian clock regulates rhythms in many of your body's processes including food intake as well as fat and sugar metabolism. And when your circadian clock says it's time to burn fuel, it activates a protein in your body called rev-erb-alpha. This protein works by boosting the number of mitochondria in your cells. Mitochondria are like your cell's power plants, they take in fuel and turn it into energy that your body can use, and your body breaks down fat molecules in your fat cells to fuel your mitochondria.

So to figure out what role rev-erb-alpha could play in weight loss, researchers injected it into some super wimpy mice. I don't know what else to call them, these mice were just not athletic. They had poor endurance, their muscles were 60% weaker than normal mice, and their muscle cells had fewer mitochondria. They were like basically what we'd be like if we were sitting on the couch all day eating chips. The researchers injected these mice with rev-erb, and all of their cells began producing lots of mitochondria. Soon, the mice could run significantly further and longer than untreated mice, obese mice given rev-erb lost weight too, and their cholesterol even improved. Essentially, rev-erb provided a whole body boost to their metabolism, like what happens when you get lots of regular exercise. It made it so that the mice's bodies just burned calories at a faster rate even when they were doing nothing. 

Excellent! Put that in a pill, give it to me, I want to take it. So there's a problem, right, just tell me what the problem is. Well, in low doses, rev-erb doesn't seem to do anything and in high doses it's toxic. While it speeds up the development of mitochondria in the short term, it impairs your cell's ability to produce healthy mitochondria in the long term and your cells need healthy mitochondria to stay alive. Since rampant cell death is something we want to avoid, a weight loss treatment based on rev-erb is going to need more work. 

Other treatments in development seek to take advantage of the calorie-burning wizardry of brown fat. Brown fat is good fat. Uh, yes, there is good fat. You actually have two different kinds of fat cells in your body. White fat cells hang on to fat for whenever your body needs it. It's the kind of fat that gives you love handles and makes you jiggle.

Brown fat cells are different. They aren't supposed to store fat, they're supposed to burn it. Brown fat raises your body temperature when it gets cold by breaking down fat into chemicals that release heat. They can do that because they are packed with mitochondria, which are brown, and that's why they're called brown fat cells. The mitochondria and brown fat have a protein called UCP 1, which tells them to act like tiny fat-burning furnaces. So what if there were a way to turn white fat cells into brown fat cells?

Actually, there is! Maybe. The key is a hormone whose existence in the body was only confirmed in early 2015. It's called irisin. irisin turns out to be one of the many hormones released by your body when you exercise, along with the more well-known ones like testosterone and adrenaline. But while testosterone stimulates muscle growth and repair, and adrenaline stimulates the breakdown of sugar and fat in your bloodstream for energy, irisin stimulates the production of mitochondria and UCP1 in your white fat cells, which turns them into brown fat cells.

So if scientists can figure out how to stick that stuff into a pill or a syringe, they'd theoretically be able to kick your brown fat cell production into overdrive which would mean lots of fat being burned without you needing to do a thing. But since they've only just figured out that irisin in humans exists, that's a long way off.

Another treatment involves developing a way to inject brown fat stem cells into white fat cells to teach the white fat cells how to produce more mitochondria on their own. Researchers at Harvard have developed a compound that lets the brown fat stem cells do this, and I'd really love to tell you how or even what that compound is, but since it's probably worth billions of dollars, it's kind secret.

And we do already know at least one downside to this possible fat-burning drug, the compound also happens to be an immunosuppressant, it interferes with your body's natural inflammatory responses. Which is really bad because you need your inflammatory response to let your immune cells reach invading bacteria and stuff. Without that response, even minor infections potentially could become really serious.

But other scientists elsewhere are working on lots of other things that might allow you someday to be both lazy and have a healthy weight at the same time. Still, you shouldn't hang up your running shoes any time soon. For now, we're stuck getting and staying in shape the old fashioned way: more running, and less bacon.

But thanks for watching this episode of SciShow which was brought to you by our patrons on Patreon. If you want to help support this show, you can go to patreon.com/scishow and don't forget to go to youtube.com/scishow and subscribe.