GLP-1 Fatigue: Why You're Tired & How to Get Your Energy Back

0:09 Hey, you're ready. This is Hunter Williams. I hope you were doing amazing wherever you are at in the world. Today's video is going to be about GLP ones and fatigue. So at this point, I wish I had a dollar for every time someone asked me or commented or sent me an email about why they get fatigued on GLT ones. They love GLB ones, they love the fat loss that comes with it. For whatever reason, it makes them super fatique. I have a lot of theories about this and today's video is going to be putting those theories together in a way.

0:39 So maybe they're right. Maybe they were wrong, but it's just my thoughts based on what I've heard from people and the response I had from. People that I suggested for them to do things to maybe help with the fatigue that they have reported back. Good. I'm sure there are many other reasons than the ones I want to talk about today, But I do feel like if there's anyone out there that has a really good sample size of feedback of people that that I've gotten from people through the years. It's me, and today is my best compilation of the reasons I think people get fatigued on GOP1.

1:10 So again, I'm sure there's other ones out there, but it's just my guest for today. That's what today's about. Before I jump into the video, remember to check out the peptide cheat sheet down in the description and join Fully Optimized Health if you want to be part of best community on the planet for peptides, hormones, biohacking, health optimization, all that good stuff. And without further ado, I'm gonna share my screen today. We're gonna learn about why people get fatigued so much on GLP-1s. All right, today's video is about GLp-one fatigue, why it happens, and what we can do about it, because I don't want to leave you guys hanging.

1:42 So, we have TurgeAptide and Reti-TrueTib. They're the two most commonly used ones right now. I am sure that will change in the future, but they were originally developed for type 2 diabetes. they obviously help regulate blood sugars, suppress appetite and induce significant weight loss. However, a lot of people get really tired and it seems to be that they get more tired on red or true tide than true appetite. And I have my speculation as to why that is, but a lotta people will get brain fog, lethargy and low motivation while on these medications, which ironically, if you use them properly, One of the benefits is that you get the opposite of those.

2:16 You get mental clarity, you give energy, and you have high motivation. But I do understand that a lot of people don't experience that, at least not right away, or sometimes long-term. Sometimes people have it right way and then long term they get fatigued. So why is about five to 7% of patients on higher doses reported for fatigue for tricep tides, obesity indication. And we also had people report that in the diabetes trials with triseptide and then approximately 8% participants on mid to high doses experienced fatigue

2:47 in phase two trials of retitrutide. So, 5 to 7% of the people are reporting it in the trials. I think it's probably a little bit larger than that in main population of these that are using it, at least based on what I have seen, but it could be dose related too. So where can we look at this? I lean more on real world reports. You can also look a difference like social media analysis studies that have been done on these. And then also to just from testimonials, people a lot of times will say that they get tired on GLPs.

3:20 And then the weight loss kind of outweighs the fatigue. So it's worth it to them. When we look at it as a side effect, medications are often prescribed to those already experiencing low energy. If you're getting a GLP, a lot of times those people are fat, they're inflamed. They're going to have low-energy to begin with. And fatigue can worsen during the dose escalation and rapid weight-loss. We have this confluence of factors. People losing weight fast, we have them automatically titrating up the dose because that's what the doctor told them to do.

3:50 And so what happens is as a compounded effect of that, they're going to get fatigue and then weight loss and better blood sugar control should lead to increased vitality eventually. But a lot of times the doses are so high to the point where they lose the weight. that they're fatigued from the dose being so high. So there's a ton of different factors. We have physiological, hormonal, nutritional, and neurological factors that could influence fatigue levels. Why do TURS and RETTA cause fatigue? One, from calorie restriction. If we look at calorie restrictions and appetite suppression, Turs and Retta dramatically reduce hunger and food intake as part of their weight loss effects.

4:26 Research shows that within the first eight weeks on TERS, people were spontaneously eating around 200 fewer calories per meal on average. And then over the course of the treatment, this can lead to a pretty large calorie deficit. So in fitness terms, many users are essentially on a strict cut without trying, sometimes far below their usual caloric needs, which is why they get weight loss, right? So the appetite suppression is one thing, but we can have this hitting the wall effect. Glucose is the primary fuel for the brain and the muscles. Eating much less, especially if carbs are reduced, what most people are doing, may lead lower blood glucose levels throughout the day.

5:02 Good thing. However, when you consume fewer calories and lower your blood sugar, your energy levels could potentially dip and blood is a critical fuel. So a significant reduction can cause fatigue and subsequent brain fog. You take someone that's used to having high blood and then you make them have normal blood. Well, they're going to feel different. And sometimes that can manifest as brain. Many people describe feeling out of it or mildly lightheaded during the day until their body fully adjust to their new found lower blood, which again is going be healthier for them, but it's going lower than it was before.

5:32 And this is analogous to people feeling fatigue in the early weeks of a diet or fasting regimen. So a lot of times too, it's just the nature of dieting down period. We also have metabolic adaptation. During weight loss, the body defends against perceived starvation by slowing the metabolism. And on GOP1 agonist, weight comes off relatively fast and the bodies adaptive response can be a rapid reduction in resting metabolic rate. I talked about this on my GOP1 stalling video or GOT1 plateau video, but hormones like leptin plummet as fat as loss and thyroid hormone levels may decline

6:03 to conserve energy. Indeed, because TURZ and RETTA hits multiple pathways, it may lead to a lower calorie intake, which causes your body to slow down its metabolism and preserve energy stores. So this can make us feel tired and cold and less inclined to be active. We also can have nutrient inadequacy. So fatigue can be exacerbated if the reduced food intake isn't nutritionally balanced. A lot of times people's food is not nutritionly balanced, so feeling less hungry. Some individuals skip meals or eat very little, which might mean not enough iron B vitamins or even creatine or carnitine if overall protein consumption

6:37 is less than before. If your diet lacks the necessary nutrients to support your energy levels, tiredness will worsen. And for example, if people have too little iron or B12, it can cause anemia and fatigue and too low protein can cost muscle loss. A crash in electrolytes can caused weakness as well. And thus the weight loss without proper nutrition is a recipe for low energy. So. The weight loss itself, while beneficial long-term, can make you feel temporarily drained. This is very, very common. Even if you're a bodybuilder losing weight, you know about this.

7:08 So losing a substantial amount of body mass, some TURS users lose up to 15 to 20% of the weight. Reddit True Tide users, obviously, up 24% their weight in trials. It leaves people feeling empty or physically weak during the process. So it's not unlike training in a calorie deficit. Many athletes report sluggish workouts and fatigue when cutting weights simply because the body has fewer sources. Very simple, but a lot of people don't think about that because they kind of normalize to the lower calorie amount rather than intentionally doing it. They just kind normalized to it because that's how they feel.

7:38 So we also have this dehydration and electrolyte imbalance. So, we have GI side effects, so GOP1 agonists can cause nausea, vomiting, diarrhea, and constipation, especially when not used properly or during the increase of your dose. These effects are not only unpleasant, they can lead to dehydrations and the electrolytes imbalances that directly cause fatigue. This is one of the biggest things to me that I harp on so much because most people are dehydrated in the sense of not necessarily they're dehydrate from not have enough water, but from not having enough electrolytes and minerals.

8:11 And you introduce a GLP and then all of a sudden they're losing weight. They have all these GI side effects that are making them that much more dehydrated and they wonder why they are tired. It's because they you're going to be losing fluids like sodium, like potassium, magnesium, and even mild dehydration will make you feel weak, dizzy and foggy. It's kind of funny because for years just talking about fasting, I talked to so many people that would get to like two or three in the afternoon fasting and they would say, i just can't do the fasting. I just feel so fatigued, so groggy, brain fog, tired as I will just drink some electrolytes.

8:47 They would drink electrolyte and be like, oh my goodness, can fast for so much longer now because I'm hydrated. So Obviously, trisapatite, ratatrutide, they can contribute to dehydration electrolyte imbalances, which then even exacerbate their fatigue. So, moderate dehydratation, a 1-3% loss of body water, is known to impair cognitive function and exercise performance, so it's critical to recognize and address this. There's also going to be reduced thirst, which then makes it harder for people to stay hydrated. So some people on GLPs report not only forgetting to eat, but also forgetting the drink as well.

9:17 That's not uncommon when you slow gastric emptying. The normal cues that drive us to consume fluids, Which are often tied to meals, might be blunted. And if you're eating less, you might also be drinking less water overall,which even worsens the dehydration. Additionally, persistent low grade nausea can make drinking water or electrolyte beverages less appealing,Which does happen to people because I've talked to People like that. Signs to watch out for is a dry mouth, dark urine, dizziness, and headache can all accompany dehydration-related fatigue. And again, if this is what you're experiencing on GOP1, this should be the first thing that you address.

9:48 On the other hand, overcoming this factor often yields quick wins for people. Like I said, a lot of times they can knock out the fatigue in the butt with that. So we can also have hormonal and metabolic changes. We've got blood sugar fluctuations, like I hinted at earlier. Ters and Reta help stabilize blood glucose by increasing insulin. and in terjeptides case also enhancing GIP action when you eat. So they generally don't cause low blood sugar on their own if you aren't on other diabetes medications or taking insulin or something like that. However, some non-diabetic users might experience symptoms of relative hypoglycemia.

10:20 If you are accustomed to higher blood sugar spikes for meals and frequent snacking, the new steady state lower glucose due to eating less and slower gastric emptying can subjectively feel like a crash, like I was talking about before. So in some cases, rapid drops in blood Sugar can occur, especially if you go a long time between small meals, which may lead to true hypoglycemia and susceptible individuals. And hypoglycemias known to cause tiredness, dizziness, confusion and brain fog until corrected. So it's a particular concern if someone is combining a GLP-1 agonist with insulin. Like I talked about, careful monitoring is needed.

10:50 So the good thing is, hopefully, GLPs make the use of exogenous insulin, for the most part, become obsolete. But we can also look at some of the GIP and gluconol aganism as a reason for fatigue. The G.I.P. agganism in TERS is thought to complement GLp-I's effects on weight loss, but When we look at the receptors in the brain, they might play a role in fat metabolism, possibly in circadian rhythm or other neurohormonal signaling. So there's speculation that terzaptide could affect the hypothalamus sleep-wake cycle, making some people feel unusually tired as the brains adjust,

11:25 which is very interesting. Retruchide's glucagon activation also tends to increase energy expenditure and fat burning, which means that it can raise metabolic rate and even slightly increase blood glucose as glucagon triggers the liver to release sugar. So some of these from the GIP and glucogon could potentially be adding to the fatigue as well. I talked about leptin a little bit. Leptin levels drop substantially as you lose fat, which is happening in most cases when people are on these drugs. Low lepton triggers increased hunger and reduced energy expenditure, essentially the body's attempt to regain the weight.

11:57 On GLP-1s, hunger may not increase thanks to the drug, but the fatigue from low lepton can still hit. So when we lower leptin, even if our appetite isn't going up, which in a lot of cases it does with low lepton, but even our appetites doesn't go up we can still get the fatigue and the thyroid slow down from the lepton. So lower testosterone and thyroid hormones can also contribute to fatigue because anytime we're calorically restricted typically those hormones are going to down regulate given enough time as well. And so just remember that extreme calorie deficiency can cause these hormonal side effects which sometimes might not be reversible until you supplement

12:36 with the hormones, which I would recommend to do anyway, but that is something to be aware of. We also have some neurological factors. So if we look at the GLP-1 receptors in the brain, GLPs ones obviously act beyond the pancreas and the gut. They act in brain and GLp-one receptor regions of the that regulate appetite, reward, mood, and even sleep can target the brains dopamine reward system which tampens down the release of dopamine in areas linked to motivation, pleasure, or reward. GLP-1s can be investigated or are being investigated for addiction.

13:07 They work really, really well to normalize overactive ward circuits. But the flip side is that by dampening dopamine spikes, some users feel a general blunting of motivation. So many describe a apathy or lack of drive, not just toward food, but sometimes towards work, exercise or hobbies they used to love. And this dopamine downshift can manifest as low motivation and mental fatigue. So again, this isn't for everyone, but I do think when people experience like the depression that they're talking about, that's what's going on. There is like dopamine down regulation that there are just not used to.

13:38 Now there's this ozempic brain fog, there is ozepic bud, ozipic face, whatever, and now we have ozymic brainfog. But it's kind of popped up in the communities of being something that people experienced. It could be partly neurological. So some research in Frontiers and Pharmacology found that malaise and fatigue were among the top complaints in semen glutide users and a general feeling of being unwell can translate to cognitive dullness. Another 2023 study found using social media data noted that insomnia and mood changes were commonly mentioned side effects of GOP1s.

14:11 If you're not sleeping well or feeling down, obviously you are going to be fatigued or it's going compound into a feeling fatigue. Again, sleep disturbance is very real and this can come from a lot of things. It can from being dehydrated, it can coming from in a calorie deficit that you don't realize you're inducing on yourself because that's what the drugs tend to do but it may seem paradoxical but along with fatigue, Many GOP1 users report poorer sleep quality. So some people get insomnia or very light fragmented sleep. And then again, could be the GI discomfort at night.

14:42 It could also be central signals to the brain sleep centers or even blood sugar dips overnight. That's another big one that can cause people not to sleep as well, which again makes them tired. You can also look at mood motivation. So while many individuals feel happier as they lose weight and get healthier, a subset report a new or worsened depression or anxiety. And this might be due to the physiological changes or even just the adjustment to a lifestyle. It's kind of funny. I was joking with Taylor the other day that a lot of fat people are actually happy. There's actually some science or credence to that because if you get to eat whatever you want all the time and you're not pushing yourself to do hard things

15:19 like exercise, You might be happier in the short term, not in a long term in my opinion, because I'm much happier being lean and exercising and eating healthy and doing those things. But I think it shouldn't be ignored that sometimes you're just happy when you are eating a pizza. Let's be honest. But it's important to recognize that depression and fatigue go hand in hand. So low mood can make the simplest task feel exhausting or reduce motivation to exercise or socialize. It's not just laziness in all cases. This is the big thing I want to talk about in this video is detoxing because this is very real and I don't think anyone's really mentioned this yet,

15:55 at least not that I've seen. But when we detox and we have rapid fat loss, that can cause fatigue. So why does this happen? So fat cells are storage depots for more than just energy. Over time, they accumulate fat, soluble toxins, metabolic byproducts, persistent organic pollutants, and even excess hormones like estrogen metabolites. When you lose fat rapidly, which is common on GOP1s due to suppressed appetite and significant calorie deficit, these substances are released into the bloodstream and fat is broken down. The liver and the kidneys are responsible for processing and eliminating these compounds.

16:27 And if the rate of release outpaces the body's ability to neutralize and excrete them, you may experience a transient toxic overload, which I think in a lot of cases people are happening. So how does this feel? You get mild headaches, get fatigue, heavy muscles, achiness, and especially brain fog are all classic detox symptoms. Just like if you weren't fat, but you were had a toxic load that you were detoxing, you're going to feel tired when you are getting rid of that. So a lot of GOP1 users notice that as the pounds drop, there can be periods of unexplained tiredness or malaise, even if diet and hydration are dialed in.

17:00 Some report waves of fatigue that seem to coincide with periods with most rapid weight loss. What's actually happening there? In my opinion, the inflammatory cytokines may be released as fat is broken down, triggering a mild systemic inflammatory response. We also have toxin mobilization, So these endocrine-disrupting chemicals, pesticides, phthalates, and all these other things and other fat-soluble toxins are literally dumped into circulation, forcing the liver to work overtime and the livers eventually hit a bottleneck. And so if the live is overloaded or under supported due to nutrient deficiencies, dehydration, or genetics, detoxification slows and symptoms worsen.

17:35 So this is why it's really good. to use things like glutathione. So how do we reduce this? One, support the liver. Use injectable glutothione, do what you can to help the lever, ease the toxic burden. that it is experiencing when you are losing fat and these things are being liberated in your bloodstream and being dumped in you're blood stream and causing you to be tired. Obviously, hydration is important. I think you want to lose weight as fast as possible. You want lose fat as soon as it's possible, but sometimes it can come at a cost and this is one of the things like the faster you lose it,

18:07 the more pronounced this detox experience is going to probably. It can also use NAC, milk thistle, and then glutathione like I talked about. And then also sauna and sweating is really good. So gentle, regular sauna sessions, or even just exercise and do sweating can support the toxin elimination. I think that's really important to do as you're losing weight. Think about how many people lose weight on a GOP-1 because they're eating less, but they are not sweating enough. And they get fatigued because there are no sweating out the toxins that are now being dumped in their bloodstream from the fat coming off of them. Most detox related fatigue is temporary and resolves as the weight loss pace slows and the body catches up with the elimination But I think this is something

18:43 that most people don't realize is going on and then there's the mitochondrial slowdown So mitochondria are the power plants of ourselves. They're responsible for converting food into usable forms of energy in the form of ATP and Anything that compromises mitochondrion function can lead to profound sense fatigue weakness and exercise intolerance So how do GLP-1s contribute to actually mitochondrial slowdown? One, the reduced calorie and nutrient intake affects mitochondria. So GLp- 1s sharply reduce appetite, leading to significant decreases in calorie in nutrient consumption.

19:14 And if fuel and co-factors are in short supply, mitochondrion cannot run at full capacity. Then this decreases substrate availability. Less glucose and fatty acids coming in means that mitochondry have turned down ATP production to match what's available like running your car on half a tank. You're going to run out faster. And you're not going be running optimally. So this is compounded during long fasting windows or skip meals, which are more likely on potent GLP-1 agonists. Then we have this adaptive energy conservation response.

19:46 The body sensing energy scarcity may intentionally down-regulate mitochondrial biogenesis and function, a process mediated by lower thyroid hormone. and reduce leptin during weight loss. So this is basically the body going into survival mode. And then that manifests as less energy output, cold intolerance and sluggishness. Long before I lost weight without using GLP-1s, or I would not lost wait, but like get really shredded, this happens. We also can look at the direct effect of the GLP-1 agonism. So some preclinical data suggests that GLPR receptors in certain tissues can directly modulate mitochondrial activity, though human deity is limited.

20:24 But we do know that in chronic undernutrition, mitochondria gene expression shifts away from growth in energy towards repair and conserve when we are losing weight. This manifests as profound tiredness, disproportionate to activity level, hitting the wall early on workouts and slow recovery, and then mental fatigue, the inability to concentrate and feeling flat. So what do we do about it? One, we can eat for our mitochondria. Obviously the more appropriate micronutrients that we eat, this is going to help with mitochondrial function. We can also supplement wisely.

20:55 So creatine, carnitine CoQ10, alpha-lipoic acid are all mitochondrial boosters, urolithin A. But obviously I'm a big fan of MotC, SS31, BAM15, and SLU. That is going to be the best way to help support mitochondria if we are in a aggressive fat loss phase. And you can look at the bodybuilding world. They're using all these things. I didn't put methylene blue on here, but you could use methylenine blue. There's using these all things to make those last few weeks of prep, which are usually torture, really be like not even that hard for people in a really,

21:28 really big calorie deficit. So we can also do resistance and interval training. Short intense bursts of exercise can stimulate mitochondrial biogenesis, even in calorie deficits. We just want to make sure that we're not overtraining. And then cycling calories can be huge too. So occasional higher calorie or higher carb days may provide enough substrate for mitochondria to upshift. And we can obviously manage our thyroid health. Keep an eye on thyroid labs, especially T3, and then use desiccated thyroid when appropriate. Mitochondrial slowdown is the body's way of conserving energy during times of scarcity, but with support, we could do it even better.

22:01 Another thing too to mitigate fatigue is just maintain a nutrient-dense diet even when appetite is low. So prioritize quality nutrition, focus on protein, because a lot of people don't eat enough protein. I'm not going to talk about the sugar diet, but the diet could be a great alternative for people to help with this. And then avoid the trap of eating barely anything or just highly processed food because our body still needs micronutrients. So much of the food that people eat is processed. They don't realize they're fatigued because they don' have any micronutsrient, so they are not supplementing with the vitamins and minerals they need or getting them from their food. And we also want to make sure that you can eat smaller frequent meals to spread the intake across the day.

22:38 I'm a bigger fan of that, especially on training days when I am not fasting. But weight loss should be fat loss, not muscle and water. So again, ensure sufficient protein and just make sure that you are doing everything right. I'm not going to go to a ton of that on this video. Obviously staying hydrated is very important. Proper hydration is essential for maintaining energy levels. I can't stress that enough. When we look at a dose, we want to make sure that we're not dosing or escalating the dose too fast.

23:12 too much. So when starting medications, titrate very slowly. I don't think you should titrait if you don' need to, but if have to do it slowly and then lean on other pathways before you blast the GLP to a super high dose. Again, many side effects, fatigue included, tend to improve after a few weeks once your body adjusts to each dose, so just understand if your going to titratate the dose expect that to be a byproduct because of what's going on. The good news is that fatigue is usually temporary for most people because usually within a week or two, in my experience, you'll adjust to the higher dose.

23:43 And obviously, physical activity is very, very important. So just making sure you're working out throughout the day. staying active, resistance training, cardio, again, that's going to help kickstart the mitochondria, which is going be really good. Sleep is very important. So we would just want to make sure that we're sleeping properly. Again, like I said, you can potentially have some of these things that cause you to impair sleep. When you're doing everything right from a foundational and lifestyle perspective, sleep and stress management is a very, very to us with fatigue and obviously limit caffeine.

24:16 We also want to potentially adjust the injection timing. So some users have found that when timing they take their weekly GLP-1, when they do their week dose, it can influence fatigue patterns. If you're doing a weekly dose you might have more of a roller coaster. This is why I like microdosing doing every other day or Monday, Wednesday, Friday. for my dose so you can take the same total dose and break it up into three injections or every other day injections and get a much better response without some of the drawbacks, which would be fatigue. So if you tend to experience fatigue or side effects the day after your injection, consider taking your shot before a day when you rest.

24:49 If you notice that the days you inject, you're more fatigued, maybe do it the night before, and then you time up your experience. Everyone's going to be a little bit different, but you want to make sure that if notice a crash based on when your injecting, kind of augment the injection time to maybe coincide. And again, I think microdosing solves that for a lot of people because you don't go on the roller coaster of doing one big bolus dose and then having the side effects come along with that. So maybe like where day three or four, you're really, really fatigued as the body is like peaking at the time of the.

25:21 Injection. Just make sure you're smart. Again, I've got videos on microdosing, how to do that and all that stuff, but it is something that is relevant to consider. And then lastly, circadian sunlight. So getting morning sunlight can obviously help set the circadian ribbon. I think this is important to obviously for everyone, But just on a GLP it's important. Remember that because a lot of times we forget that. Then just remember that your mood and mental health can affect fatigue. Just makes sure that as you are doing everything from a A lifestyle standpoint, a supplementation standpoint diet standpoint to make sure that your mental

25:54 health is priority journaling, meditating, doing all those things are always something that I make. Sure is a high, high priority in my life. So remember that mental fatigue is as real as physical fatigue and treating the psychological side can restore your drive and motivation and help with energy levels. That is it for the slides. And that is my comprehensive review of why people get so fatigued on GLP-1s. I think one of the biggest ones that people don't realize is that toxic load. So many people lose weight fast and they're dumping toxins in the bloodstream because they are getting rid of adipose tissue and don t do anything to address it.

26:27 The liver is running overtime to try to get those toxins out. And I think electrolytes and dehydration are very, very important to recognize as well. So those are the two big ones, but everything we talked about today can play into why you are fatigued.

26:57 need to lose weight and that is something that's very important to you that there are ways around this and if you're smart and you can do it that, there're other people out there like myself that have used these strategies to improve their energy throughout the day and ultimately maximize the effectiveness of these because I do think they're not only the best fat loss drugs of all time, but the anti-aging and longevity drugs at all times. So I'll close out. Thank you guys so much from the bottom of my heart. It means the world to me that I have support from The Amazing People in the audience. The channel is growing so much and that's thanks to you guys because you help support the channel in all the ways that I talk about liking,

27:32 commenting, subscribing, sharing the videos, being on the email list, helping support with products. So thank you, guys, so, much. It's a dream come true that i could do this and I promise each and every day it is my mission to get up and bring the best content to, you to help change your lives and make the world a better place. I appreciate you. Much love and i will talk to