 Hey everybody, Dr. O here. Welcome back to my series called Real Talk About Loose Skin. I'm very glad you're here because I have a lot to say about this important topic. In part one of the series, we covered the causes of loose skin as well as the risk factors and lifestyle choices that make us more likely to have issues with excess loose skin after weight loss. But now it's time to fight back and see what we can do to minimize or eliminate it all together. So who will this video help? This is the picture that I keep in my wallet. Just my reminder that there's no going back. But the advice in this video will help you if you've already had loose skin. But it will be even more helpful if you're at the beginning of your weight loss journey. As they say, an ounce of prevention is worth a pound of cure. So the best way to get rid of loose skin is to never have had it in the first place. But this doesn't mean that loose skin can't get better over time. The loose skin that I do have is better now than it was a year ago, even though I've lost more weight. I've also heard from many people who see improvements in their skin over time, that being the key. But I also don't want to give you false hope. This process is a marathon. It is not a sprint. The only quick solution for loose skin is to have it surgically removed. And no condemnation, no problem with that on my end if that's something you want to end up doing. So we're going to look at autophagy and loose skin here in this video. So I want to answer the question, what is autophagy? So we're going to cover the relationship between autophagy and skin health. Then we'll ask the question, can autophagy reduce or remove loose skin? And I specifically say both, reduce and remove, because the things that we do that will decrease your loose skin while losing weight can also be used to get rid of it once you've lost the weight as well. And then we're going to look at ways to boost autophagy, including fasting. That'll be our primary focus, but then calorie restriction, ketogenic diets, exercise and quality sleep. So be sure to stick around to the end of the video. I know it's going to be a long one because there are lots of studies to talk about. But I will share how I use all of these different methods together to maximize autophagy and minimize loose skin. But before we dive in, I want to make it clear that there are no guarantees when it comes to loose skin. We talked about that in the first video. I will explain how autophagy can improve the health of your skin. I will then explain the key drivers of autophagy. But I can't tell you how each mechanism will specifically help deal with loose skin because we just don't know. I wish I could guarantee that autophagy is the answer to loose skin. I do think it plays a major role, but I never make a promise that I can't keep. But I do feel like we're following the evidence where it leads. All right, so what is autophagy? Let's start there. Autophagy, the word literally means self-eating. So autophagy is a cell recycling and renewal process that rejuvenates our cells and restores their functions. I do think it's one of the key benefits of fasting overall. This involves the cell breaking down and metabolizing broken and dysfunctional proteins and other structures that build up inside our cells over time. So here's my favorite analogy about autophagy. It's a wood-burning stove. So let's say you have a wood-burning stove like this one that you use to keep your home warm. Well, if you're regularly getting three to six wood deliveries every day, you'll keep tossing wood on the fire and your home will stay toasty warm. This is us when we always have access to food and calories, more food and more calories than we need. We're constantly getting these wood deliveries, and that's what we're going to be focusing on using. So autophagy levels are going to be pretty low if you're always in a fed state when there's resources all around. But what happens when we run out of wood? This is when our cells start looking around for other things to burn. We have big stacks of newspapers and pizza boxes that have been piling up. We've been meaning to recycle them, but we've been too busy burning wood three to six times a day. So now we go into recycle and repair mode. We use up the old and damaged cell parts for fuel, and our cells keep working while our house, right, our cells, become less cluttered. This is how lowering our fuel levels, using things like fasting, diet and exercise, increases autophagy and cleans up our old cells. Autophagy is the perfect remedy for cleaning up the cellular gunk and damaged proteins that are causing issues with collagen and elastin production that result in loose skin. Go back to part one if you need a refresher about what causes loose skin in the first place. Your skin's replaced about every 27 days, so the goal of autophagy is healthier skin cells over time. Healthier skin cells make healthier skin that naturally gets tighter and more elastic over time. There aren't any randomized controlled trials that show that autophagy limits loose skin, but all lines of evidence do point in that direction. Solid anecdotal evidence, like my own story, also indicates that autophagy can help those who have lost weight from needing skin removal surgery. Dr. Jason Fung, considered the godfather of intermittent fasting by many, is famous for saying that he has never needed to refer a patient for skin removal surgery, and he's had multiple patients that have lost 100 pounds or more. I don't know if that's true, but I sure hope it is, and I also hope that autophagy works that well for all of you. Let's look at the science behind autophagy and skin health, and then we'll focus on the best ways to boost it. So what does the science say? Autophagy in human skin fibroblasts impact of age. This study looked at what are called dermal fibroblasts, the cells that produce collagen and elastin, which is what you need for healthy, tight skin. This study showed that aging decreases autophagy in skin, but it also leaves us some room for hope, because if we can find ways to boost autophagy. So this study found that autophagy improves the function of these dermal fibroblasts, which means they're going to make healthier proteins that make healthier skin. Younger acting skin cells make tighter skin. So here's a quote, autophagy plays a crucial role in counteracting aging, and strategies aimed at its modulation should hold promise for the prevention of skin aging. So I love that term promise. Another one, autophagic control of skin aging. So this, as we age, this review showed us that autophagy activity will decrease and our dermal fibroblasts become less capable of producing collagen. And we know how important collagen is for skin health. So a quote here, recent experimental evidence suggests that autophagy is critically involved in skin homeostasis and skin aging is associated with and partially caused by defects of autophagy. So one more, age related disruption of autophagy and dermal fibroblasts modulates extracellular matrix components. So this study looked at what happens when you inhibit autophagy. So instead of trying to enhance it and seeing improvements, they're like, what happens if we inhibit it? And a lot of bad stuff happened. So inhibition of autophagy altered the fibroblast content of type one pro collagen, hyaluronic, and elastin, and causes a breakdown of collagen fibrils. So basically inhibiting autophagy creates an environment where loose, inflamed, damaged skin is the norm. Combine these three studies and we now have evidence that autophagy should lead to healthier, tighter skin. So then how do we boost autophagy? So if we know that autophagy is good for skin health, how do we actually boost it? Well, that's what we're going to be focusing on here the rest of the video. But notice I didn't say boost, right? Autophagy is not an on off switch. It is always occurring. It's also not always a good thing. So our goal should be to maximize autophagy at times to improve the health of our skin without taking anything to the extreme. So we want to dial up autophagy and then dial it back down if we want healthy skin over time. So what are the ways that we're going to look at to boost autophagy? We're going to look at fasting, calorie restriction, ketogenic diets, exercise and quality sleep. So for most of these we see what's happening. We need the body to run low on resources or switch into repair mode, right? So fasting, calorie restriction, ketogenic diets and exercise, they're all going to run us out of wood. So we have to start to rely on the pizza boxes in the newspapers with our wood burning stove. And then sleep is just a repair mode overall. So sleep would be like, if you want to stick with that analogy, sleep would be like once a week we take the extra pizza boxes to the recycling plant. So during this time when we're boosting autophagy, the damaged goods in our cells should be cleared away, allowing the processes that keep the skin firm and elastic to function properly, right? That's our hope. Alright, so number one, fasting and autophagy. I could list dozens of health benefits that come from fasting, but check out my other videos if you want me to hear me go on and on about how much I love it. For now I just want to focus on fasting and autophagy. So the recycling and repair benefits that come with fasting are the number one reason that I think fasting will protect you from loose skin more than the rest of the things on this list. So what's the science have to say? The impact of intermittent fasting on health and disease processes. So here's a quote, the cellular and molecular mechanisms by which intermittent fasting improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair, and autophagy. So why do I think that fasting has helped? Because I have less loose skin now than after the last time I got down to this weight when I was 18 or 19 years old. This means that I have less loose skin even though I'm much older, I had way more weight to lose, and I was overweight for a much longer period of time. This isn't proof, but my personal experience points towards autophagy from fasting as part of my success. But here's the million dollar question, how long should we fast to boost autophagy? The short answer is we're still figuring this out. Some people say 16 hours, some say 24, others say 36, but let's see what this science has to say. So early time restricted feeding improves 24 hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. So early time restricted feeding just means you're eating earlier in the day. A lot of people do time restricted feeding and they eat most of their calories at the end of the day. So that's what early time restricted feeding means. So this study showed that the expression of the autophagy gene, LC3A, was increased by 22% after four days on an 18-6 eating schedule compared to the control group that was on a 12-12 eating schedule. So I think that we can safely say that 18 hours of fasting is enough to make a difference, so a 22% increase in this autophagy gene. This study looked at one month of 17-19 hours of fasting during Ramadan and saw even better results. So the effect of prolonged intermittent fasting on autophagy, in flamazon and senescence genes expression, an exploratory study in healthy young males. So what do we see here? They looked at the relative mRNA expression of autophagy genes in blood samples. So here we see this was the autophagy gene ATG5, and it increased by 45.62% after one month of fasting every day for 17-19 hours. This one was ULK1, which is another autophagy-related gene, and increased 540.21% after one month. But notice, at the far right of both these images, that the levels return to baseline within one week of returning to normal food consumption. So the benefits of fasting occur if you continue to fast, but if you go back to eating on a regular schedule, the gene expression will drop down, which means autophagy was increased by fasting, and then it would go back down. What about longer fast? Here's another study that is quoted quite often. Short-term fasting induces profound neuronal autophagy. Like I said, this study is quoted and cited all over the place. It showed that 36-48 hours of fasting can lead to a 300-400% increase in autophagism, so one of the structural components needed for autophagy, as well as a 300% or more increase of autophagy gene expression, specifically LC3. So that's pretty exciting stuff, but this is a big but. It's important to keep in mind this was a study done in mice. We are similar to mice, but our metabolisms are quite different. For example, studies show that mice can lose between 11% and 21% of their body weight when they fast for 24-48 hours. We certainly wish that we had their metabolisms, but we don't. The research still matters. We just don't know exactly how to translate this to humans very well. It would take somewhere between three and seven days to see this big of an increase in autophagy in us humans. And by the way, I do know that these aren't mice. If you look at the picture there, they're guinea pigs. I just wanted a chance to show off our guinea pig named Theo and her babies. So if you're wondering why her name is Theo, it's actually Theodore, we were told that she was a he when we got her. So boy, we were surprised when he was pregnant and had four babies. All right. Let's switch gears a little bit because we've been talking about autophagy, but I also do want to mention the effect that fasting has on growth hormone because growth hormone has effects on your skin. So the effects of short-term fasting on grayling, growth hormone, insulin-like growth factor one, axis and healthy humans, the role of grayling in the thrifty phenotype. So this study found a 500% increase in growth hormone with 24 hours of fasting. Then this one, augmented growth hormone, secretary boost frequency and amplitude, mediate enhanced growth hormone secretion during a two-day fast in normal men. This study found that two days of fasting also induced a 500% increase in the 24-hour production of growth hormone. So why does this matter? Well, this is why. So growth hormone system, skin interactions. Here's a quote. Clinical observations and analysis have shown the important role played by the growth hormone system in the development, maintenance and repair of the skin, which is what we're trying to do. And this one, the effects of human growth hormone in men over 60 years old. This study found that boosting growth hormone levels led to a 7.1% increase in skin thickness after six months. All right, so you put this all together. So what do we do with this information? So we know that fasting anywhere between 17 and 19 hours and three to seven days can boost autophagy in humans. We also know that 24 to 48-hour fasts have a profound impact on growth hormone levels. So shorter fasts like 16.8 and OMAD or one meal a day should have a modest impact on autophagy. But I personally feel like 36-hour fasts are the sweet spot for autophagy. 36 hours is long enough to crank up the autophagy dial, but not long enough to have a major impact on muscle loss and metabolic rate as long as you refeed properly. I also like the idea of mixing in a three-day fast every few months to really crank up the autophagy dial. We'll come back to my protocol at the end. But, and you knew this but was coming. Watch my entire fat loss sweet spot series before you do any aggressive fasting and take notes on this video here. If you're showing signs that you are losing lean mass, cut back on your fasting. I'm the biggest fan of fasting, but so people are often surprised when I tell people to do it less often, but I would never trade my muscle and my metabolic rate for a little less loose skin. The juice just ain't worth the squeeze at that point. And don't worry, there are lots of other ways to boost autophagy yet to come. It's number two, calorie restriction and autophagy. So fasting isn't the only way to boost autophagy. One of the main benefits of fasting though is that it's an easy way to restrict calories for lots of people, but that's not the only way to restrict calories. We know that. The science is clear that autophagy is boosted any time you are in a calorie deficit. So let's look at this. The fact of fasting or calorie restriction on autophagy induction, a review of the literature. Here's a quote. We conclude that both fasting and caloric restriction have a role in the up-regulation of autophagy. The evidence overwhelmingly suggests that autophagy is induced in a wide variety of tissues and organs in response to food deprivation. So fasting is a great way to induce autophagy, but calorie restriction will do it as well. I think this is also the category that modified fasts, like the 5-2 diet and modified alternate-day fasting would fit into. You see some videos I've made about those topics there as I've tried these different types of fasts. These types of fasts will lead to some of the benefits of fasting as well as the benefits seen with calorie restriction. All right, number three. Ketogenic diets and autophagy. So speaking of diets that give you many of the benefits of fasting, I consider ketogenic diets to be a type of fasting mimicking diet. Autophagy is activated by glucose deprivation, keeping your blood glucose levels low. Ketogenic diets are glucose deprivation diets, right? You have to keep your glucose levels low in order to stimulate the production of ketones. So we know that. What's the science have to say, though? Up-regulation of hepatic or liver autophagy under nutritional ketosis. So animal studies like this make it clear that ketogenic diets do induce autophagy, at least in some structures, right? The results showed that autophagy is up-regulated in the livers of animals fed the ketogenic diet. Another one. The ketone body, beta-hydroxybutyrate, stimulates the autophagic flux and prevents neuronal death induced by glucose deprivation in cortical, cultured neurons. So this study here showed that the ketone body, beta-hydroxybutyrate, or BHB, stimulates this autophagic flux, which is a measure of the activity of the entire autophagy process. So this means that ketogenic diets stimulate autophagy in at least two ways, right? Because, number one, they deprive you of glucose and keep glucose levels low. And number two, the actual ketone body, beta-hydroxybutyrate, stimulates autophagy on its own. So all cool stuff. All right, what about number four? So now we've talked about fasting, we've talked about calorie restriction, we've talked about ketogenic diets, but now it's time to talk about exercise and autophagy. Exercise is another great way to stimulate autophagy. It stimulates more autophagy than fasting does. I think they stimulate different types of autophagy, if I'm being honest, though. But why not do both and double your chances? So autophagy, dependent beneficial effects of exercise. Sorry. Quote, the exercise-induced regulation of autophagy includes both increased autophagy flux, as well as transcriptional activation of important autophagy genes. So remember, the autophagy flux is like the level of autophagy occurring in the cells, and then transcriptional activation would mean that the genes involved in autophagy are being upregulated. Another quote. Furthermore, exercise-induced autophagy seems to be involved in mediating many of the beneficial effects of exercise. I'll show you another study in a second, but it looks like autophagy plays a major role in the health benefits that come from exercise. But when we're talking about exercise, your first question should be what kind of exercise? So I wanted to share a couple of quotes from this review. It kind of doesn't matter. So the first one. All together, there is robust evidence suggesting that autophagy is stimulated in skeletal muscle in response to acute endurance exercise. Then the second quote. Autophagy is activated during recovery from resistance exercise, similarly to endurance exercise. So it does appear that really both types of exercise are going to be beneficial. Other studies have actually shown that exercise leads to more autophagy early in the process when you're untrained. If you're just getting started with increasing your physical activity and exercising, you're going to get even more autophagy benefits than someone who's already been exercising for two or three or more years. Another one. Regulation of exercise-induced autophagy in skeletal muscle. So not only does exercise increase autophagy, it really does appear that autophagy is one of the main reasons that exercise is good for us. So another quote. A number of studies have indicated that physical exercise is non-selective autophagy and selective mitophagy, which is basically the autophagy of mitochondria in skeletal muscle in animal models and humans. The autophagy activity is required for health benefits of exercise. So I thought this is really neat. They've done studies in autophagy deficient mice and they don't get the benefits of exercise that you and I would get. So it does appear that autophagy is not only activated by exercise, but it's critically important to exercise good for you. All right. So we know that exercise can stimulate autophagy, but that's only the beginning. So I do think that the key to minimizing loose skin is maintaining healthy muscle tissue. There's nothing special about me. I'm a 45-year-old man. For decades I did nothing but sit around. Now I'm trying to make up for lost time. I do exercise, I do train and I do believe when people ask me about loose skin autophagy plays a big role, but I also believe exercise plays a big role for other reasons as well. Muscle gives skin a tighter appearance and reduces the appearance of saggy skin. This is why I always talk about or one of the reasons why I always talk about being sure you're not losing muscle while you're losing fat because losing muscle causes your arms and legs to look deflated and loose. And adding muscle. So maintaining muscle is great, but adding muscle actually will fill in that left behind. So I think that even if exercise doesn't impact your skin from an autophagy standpoint, building muscle will have an impact on at least the appearance of your loose skin. Number five, sleep and autophagy. This one might come as a surprise to you. I don't see many discussions on this topic compared to the other ones, but one of the main benefits of sleep is that it increases autophagy. This makes perfect sense. Sleep is when our body recovers and repairs from the damage that occurs while we are awake. This means that we'll be able to sleep our way to tighter skin, or at least that's our hope. So what's the science have to say? Impact of sleep on autophagy and neurodegenerative disease. Sleeping your mind clear. So I just want to read a quote here because we don't know exactly what's going on. But sleep promotes autophagy by yet poorly understood mechanisms, preventing the accumulation of proteinaceous and lipid wastes. So this is true. But if this is true, then sleep should keep your cells from accumulating this waste and debris. Another quote. Disruption of autophagy or sleep deprivation both lead to defective oxidative stress management, accumulation of cellular waste, eventually leading to disease. And that's what we're trying to get rid of, the cellular wastes that are impacting your skin health. Another one. Autophagy impairment in patients with obstructive sleep apnea modulates intermittent hypoxia induced oxidative stress and cell apoptosis via hypermethylation of the ATG5 gene promoter region. That's quite a mouthful. But I just wanted to show you this because they looked at 64 patients with untreated obstructive sleep apnea and 24 subjects with primary snoring. The obstructive sleep apnea patients have impaired autophagy activity. And remember that ATG5 is one of the autophagy genes that's turned on by fasting. So sleep and autophagy. What enhances autophagy is one of dozens of reasons why we need to make sleep a priority. Check out this video here for a long list of reasons why sleep is a critically important piece of the weight loss puzzle. I was going to say piece of the weight loss pie, but that's just rude since we're all trying to lose weight. So how do we so maximizing autophagy to minimize loose skin? So let's put it all together. Keep in mind this is an aggressive plan for someone who has serious concerns about loose skin. There are lots of reasons that this may not be something that you end up with. So step one, intermittent fasting every week. So you should fast for 17 plus hours every day or fast 36 to 42 hours several times per week based on the literature and the studies that we've looked at. The daily fasting could be OMAD, one meal a day, TUMAD, which I actually prefer, two meals a day, or Warrior fasting, which is the 24 fasting schedule. The longer the fast the greater the increase in autophagy and growth hormone, at least to a point. So we're talking about intermittent fasting here. Step two would be seasonal extended fasting. So perhaps you'll want to fast 3 to 7 days every 3 months. Longer fasts like this can function like a reset. They will enhance the benefits of fasting, like autophagy, but they can also increase the negatives associated with fasting like losing lean mass. So proceed with caution and err on the side of doing these less often if you have any concerns about lean mass and you should. And work with your doctor any time you're doing extended fasting. Step three is calorie restriction, but we're going to skip this one because your intermittent fasting program already has you in a calorie deficit for some or most of your day. So I don't think there's anything else to say about that. Step four, eat keto. You can eat any way you want, but if you're trying to maximize autophagy, there are benefits to eating a ketogenic diet. So fasting is really the original keto diet. That's when our ancestors would have been in the state of ketosis. But you can get even more benefit if you eat a ketogenic diet during your eating window. I'm going to make a lot of videos on low carb, keto, ketobor, and carnivore diets next year. So reach out if you have any questions. I'll make sure I cover them in those future videos. Speaking of keto, there isn't a direct measurement of autophagy that we can use yet. Hopefully there will be in the near future. But until then we need to look for the best clues that we have. So my favorite proxy measure for autophagy is called the glucose ketone index. So if you like data like I do, I recommend tracking your glucose ketone index with the keto mojo meter you see here on the screen. You need to test your blood glucose and blood ketone levels in order to determine your glucose ketone index. This is actually why I recently switched from the precision extra. So I used to use the precision extra meter to test my blood glucose and ketones. This is why I switched to the keto mojo. My old device was working just fine, but the keto mojo pairs with an app that changes over time. And you can see a screenshot from the app there. It also calculates the glucose ketone index for you. You see it there, right? GKI 3.8 and 4.4. I used to have to do this by hand. So actually there's a link in the description that will give you 15% off your keto mojo device if you do want to give it a try. So I'm really loving it. Step 5, exercise. So any exercise appears to be good, both endurance exercise and resistance exercise. But I would recommend focusing on building muscle if preventing loose skin is a primary goal, right? Fill the space that that fat left behind. Step 6, get better sleep. Now I know this will be the hardest step for many of you. I understand that. But aim for seven to nine hours of quality sleep every night. Your skin will thank you. Look for my entire sleep playlist on YouTube if you need help getting started. This video here is a great place to start called 10 Tips to Sleep Better Tonight. I also have an entire course on sleep, particularly important. I also do have a new series coming out on fasting and sleep. I'll cover the science behind how fasting can improve your sleep, but I'll also take a deep dive into what to do if fasting causes sleep issues as well. Excuse me. Because I know, especially when you get used to fasting there can be issues, so I'll cover all of that in this upcoming series. All right, I hope that you've learned a ton in this video. Part 3 will cover the importance of feeding any questions I'm here to help. Have a wonderful day. Be blessed.