MOTS-C and SS31

[wulf00777]

800 calories is hardly extreme. There are piles of studies on VLCDs or very low calorie diets of around 400 calories per day and sometimes over quite long periods of time, up to a year or so, that was the way of losing weight for those with severe obesity without surgery in the olden days before GLP's. Usually most calories are protein.

It is a low enough calorie intake to have possible issues with electrolyte imbalances, and enough to make fatigue more of an issue, so some level of medical checking up might be a good idea.

It is a very low calorie intake to only just be losing weight, unless you have already lost a lot of weight and or been on a low calorie intake for a long period of time, so that metabolic adaptation has reduced energy expenditure a lot. Or you are very small. My energy expenditure dropped in half from 145kg to 75 kg so that at the start I lost 6kg per month on 1600-1800 kcal/day, and by the time I got to 75kg, weight loss had stopped and that calorie intake was what was required to keep the weight off, but that calorie intake is lot more tolerable long term than 800, and before I started GLP's it was really very hard to stick to and involved being more or less permanently hungry. I would also face serious health risks were I to regain the weight. I assume from your comment that 800 calories is better than being dead that you might have similar issues.

I would have to disagree with the take a break concept, there is no evidence at all of tolerance to the long term weight loss effects of GLP drugs, with one possible exception, the recent animal study showing much less weight loss from stopping and starting GLP's in mice. It is one study, not replicated and not in humans, but the effect was very strong, and not expected. There have been people on this forum say they have had trouble losing weight after restarting GLP's as well, now a lot of the time that is going to be because they have already lost quite a bit of weight and at that point the GLP drugs are acting to prevent weight regain, but are not enough to cause further weight loss, so effectively a stall. But if the stop start effect is real, that would not help.

Are you on 15mg of tirz? There are metabolic advantages from higher doses that might improve weight loss or allow more calories in at the same rate of weight loss, if you are not already there. And reta is worth considering, the glucagon agonism adds an extra 1 to 200 kcal/day of energy expenditure, and every little bit helps. But it depends a lot on what you have already tried and side effects etc.

Thanks for the very thoughtful reply. I'm at 4mg tirz so yes I can titrate up but honestly if I'm losing weight at 800, I am feeling pretty good all day and I'm not hungry. I'm going with it. I've fasted 36 hours several times in the last couple of years, not to mention 24 hours even more times. I'm adding in a couple of days of 1000-1200 calorie but those extra calories can only be good fats like olive oil, avocado or small amounts of nuts. I've heard that's a good way to ramp up your metabolism and not gain weight. If I keep losing with the extra calories then I'll add more and keep trying to increase my calories. The biggest reason for the urgency is major issues with my feet (metatarsalgia) and bad arthritis in my knee. I can't do cardio hardly but I try to do lots of other activies like weights, swimming, sauna, and walking when I can. Everyone in my family can't understand why I eat less than them and yet I'm 280lbs. My weight is the same now as when I was 16 and I've stayed at that weight all my life more or less.

Also I agree there is enough evidence now making it clear that cycling is counterproductive and switching to another glp1 can set you back several months. I'm hoping to work my way up to the 12.5mg and add Reta or cagri if needed.

 

[Gt3294a]

Thanks for the very thoughtful reply. I'm at 4mg tirz so yes I can titrate up but honestly if I'm losing weight at 800, I am feeling pretty good all day and I'm not hungry. I'm going with it. I've fasted 36 hours several times in the last couple of years, not to mention 24 hours even more times. I'm adding in a couple of days of 1000-1200 calorie but those extra calories can only be good fats like olive oil, avocado or small amounts of nuts. I've heard that's a good way to ramp up your metabolism and not gain weight. If I keep losing with the extra calories then I'll add more and keep trying to increase my calories. The biggest reason for the urgency is major issues with my feet (metatarsalgia) and bad arthritis in my knee. I can't do cardio hardly but I try to do lots of other activies like weights, swimming, sauna, and walking when I can. Everyone in my family can't understand why I eat less than them and yet I'm 280lbs. My weight is the same now as when I was 16 and I've stayed at that weight all my life more or less.

Also I agree there is enough evidence now making it clear that cycling is counterproductive and switching to another glp1 can set you back several months. I'm hoping to work my way up to the 12.5mg and add Reta or cagri if needed.

Good luck! Just a note. Your swimming and walking are super important and glad you are doing that. If you actually look at how your body creates energy to burn (atp). There are 3 basic ways. Long story short, that very light cardio, while it takes a long time, is surely the best for you right now. It’s takes longer, but really good. And then if you think of your calorie deficit, you could even eat a little more. Anyway, that will really help you more than any additional peptide in my opinion, so great you are focusing on that.

 

[banditchewy]

Sorry it's just severe metabolic adaptation to years of diets, keto, fasting and very low calorie lifestyle. If you only knew my history with exercise it's even more extreme. If I'm losing at 800 then hell or high water I'm going to keep it rolling.

Is there anyway to reset or is that even something you are worried about?

 

[wulf00777]

Is there anyway to reset or is that even something you are worried about?

Studies have shown there really isn't a reset with glp1s. Once you have taken them and lost weight it's better to stay on and titrate up. I'm only at 4mg tirzepitide so I could keep going up but I'm losing weight and feel pretty great at 800 calories a day especially now that my dependence on carbs has worn off. You start getting that endless energy like from keto.

 

[lessthanhalf]

My experience of metabolic adaptation is that the effect is very real, thank god not down to 800 calories a day, but in 2012-2014 and 2022 - now, I got to normal or near normal weights, but staying there required a fairly low calorie input, and there is no indication of it easing over time, staying at around 1600-1800 kcal/day to be weight neutral since late 2023.

There are no approved medical therapies that increase energy expenditure except SLGT2i's, which can make you pee out up to 200 kcal/day of sugar, but due to the normal response to weight loss or extra calories out people usually only lose a couple of kilos on them, due to just eating more to compensate. The next closest is probably reta, given it is up to stage 3 human studies now, which can increase energy expenditure by 1-200 kcal/day, but does not have the automatic increase in appetite as it suppresses appetite.

It would be great if they would do a stack more research on less dangerous mitochondrial uncoupling agents like Bam15, which could be a long term solution, if the research ever gets to the stage that suggests it might be safe, and a couple of small short studies in mice or rats is nowhere near enough to imply it might be safe for human testing.

If hunger control is not a problem and you are losing weight , then increasing doses is not really needed. The biggest issue really is long term tolerability of the drug and of the diet etc so that staying with a lower calorie intake long term allows weight loss and even more importantly weight loss maintenance.

 

[wulf00777]

Good luck! Just a note. Your swimming and walking are super important and glad you are doing that. If you actually look at how your body creates energy to burn (atp). There are 3 basic ways. Long story short, that very light cardio, while it takes a long time, is surely the best for you right now. It’s takes longer, but really good. And then if you think of your calorie deficit, you could even eat a little more. Anyway, that will really help you more than any additional peptide in my opinion, so great you are focusing on that.

As I have seen my whole life exercise has very little role in weight loss for me no matter how much I do and trust me I rode a $50 bicycle from the Pacific to the Atlantic and from Canada to Mexico.

My experience of metabolic adaptation is that the effect is very real, thank god not down to 800 calories a day, but in 2012-2014 and 2022 - now, I got to normal or near normal weights, but staying there required a fairly low calorie input, and there is no indication of it easing over time, staying at around 1600-1800 kcal/day to be weight neutral since late 2023.

There are no approved medical therapies that increase energy expenditure except SLGT2i's, which can make you pee out up to 200 kcal/day of sugar, but due to the normal response to weight loss or extra calories out people usually only lose a couple of kilos on them, due to just eating more to compensate. The next closest is probably reta, given it is up to stage 3 human studies now, which can increase energy expenditure by 1-200 kcal/day, but does not have the automatic increase in appetite as it suppresses appetite.

It would be great if they would do a stack more research on less dangerous mitochondrial uncoupling agents like Bam15, which could be a long term solution, if the research ever gets to the stage that suggests it might be safe, and a couple of small short studies in mice or rats is nowhere near enough to imply it might be safe for human testing.

If hunger control is not a problem and you are losing weight , then increasing doses is not really needed. The biggest issue really is long term tolerability of the drug and of the diet etc so that staying with a lower calorie intake long term allows weight loss and even more importantly weight loss maintenance.

I had originally started with Reta and a side of trt but I then had a tachycardia probably due to high red blood cells but I had just hit 4.5mg of Reta so after the incident I managed my testosterone use better and dropped Reta because of the effects on the heart potentially. I was off glp1s for a month and didn't gain weight after losing 15lbs so now I've been on tirz for 3 weeks and dropped another 12lbs due to tirz appetite control which I absolutely love. Then I added motsc and BPCl57 after first doing 4 weeks of Ss31 5 days a week.

As if today I woke up singing, enthusiastic, perfectly content at my 800 calories and I did add 200 calories extra of high omega foods. My need for carbs I think is broken and as autophagy kicks in usually there is more energy. I feel invincible right now with this Combo.

 

[Gt3294a]

As I have seen my whole life exercise has very little role in weight loss for me no matter how much I do and trust me I rode a $50 bicycle from the Pacific to the Atlantic and from Canada to Mexico.

I had originally started with Reta and a side of trt but I then had a tachycardia probably due to high red blood cells but I had just hit 4.5mg of Reta so after the incident I managed my testosterone use better and dropped Reta because of the effects on the heart potentially. I was off glp1s for a month and didn't gain weight after losing 15lbs so now I've been on tirz for 3 weeks and dropped another 12lbs due to tirz appetite control which I absolutely love. Then I added motsc and BPCl57 after first doing 4 weeks of Ss31 5 days a week.

As if today I woke up singing, enthusiastic, perfectly content at my 800 calories and I did add 200 calories extra of high omega foods. My need for carbs I think is broken and as autophagy kicks in usually there is more energy. I feel invincible right now with this Combo.

Absent some odd issue your blood work should show, the only way it is physically possible for exercise to not effect weight loss is if you eat more when exercising to compensate for burning additional calories. That often happens because the body tells you to. But I don’t see how it is humanly possible to burn calories and it not effect weight loss, particular if periods for over a hour at low rate, because if you don’t eat like shit, your body will burn through available glucose and start to produce AST from stored fat. That is just how the body works. But I suppose you could have hormonal or thyroid issue that throws somewhat of a wrench in this.

 

[wulf00777]

Absent some odd issue your blood work should show, the only way it is physically possible for exercise to not effect weight loss is if you eat more when exercising to compensate for burning additional calories. That often happens because the body tells you to. But I don’t see how it is humanly possible to burn calories and it not effect weight loss, particular if periods for over a hour at low rate, because if you don’t eat like shit, your body will burn through available glucose and start to produce AST from stored fat. That is just how the body works. But I suppose you could have hormonal or thyroid issue that throws somewhat of a wrench in this.

Neither does anyone else understand it including myself. None of my doctors care enough to ask the right questions or get the right tests. But considering I didn't own a car for 7 years, was a vegan and rode 50 miles daily to school and work and never lost any weight is pretty remarkable.

 

[lessthanhalf]

Absent some odd issue your blood work should show, the only way it is physically possible for exercise to not effect weight loss is if you eat more when exercising to compensate for burning additional calories. That often happens because the body tells you to. But I don’t see how it is humanly possible to burn calories and it not effect weight loss, particular if periods for over a hour at low rate, because if you don’t eat like shit, your body will burn through available glucose and start to produce AST from stored fat. That is just how the body works. But I suppose you could have hormonal or thyroid issue that throws somewhat of a wrench in this.

This is not strictly true. And there have been high quality studies on it. Energy expenditure, especially in calorie restricted states, really does not want to increase. There are very strong evolutionary reasons for this, to improve survival of famines. So while exercise by definition has to use some calories, just for physics reasons, how efficiently your body uses those calories during and after exercise can change, and post exercise behaviour can change, so that there is typically a reduction in energy expenditure during the rest of the day to compensate for the calories used in the exercise, mainly via reduced non exercise movement.

This is consistent with my experience when I was losing weight where going from more or less total inactivity to 3 hours of walking on uneven bush trails per day, made no observable difference in rate of weight loss or calorie intake, despite the fact that it "should " have used several hundred calories per day. And this occurred midway through the process, while still losing weight so energy expenditure had not yet dropped to minimum of 1600-1800 kcal/day yet.

It is fairly likely this does not apply to the same degree in non calorie restricted states, though there is evidence that there are upper limits to energy expenditure per day, where more and more exercise does not increase energy expenditure past a certain point, the body just gets more efficient.

 

[Gt3294a]

This is not strictly true. And there have been high quality studies on it. Energy expenditure, especially in calorie restricted states, really does not want to increase. There are very strong evolutionary reasons for this, to improve survival of famines. So while exercise by definition has to use some calories, just for physics reasons, how efficiently your body uses those calories during and after exercise can change, and post exercise behaviour can change, so that there is typically a reduction in energy expenditure during the rest of the day to compensate for the calories used in the exercise, mainly via reduced non exercise movement.

This is consistent with my experience when I was losing weight where going from more or less total inactivity to 3 hours of walking on uneven bush trails per day, made no observable difference in rate of weight loss or calorie intake, despite the fact that it "should " have used several hundred calories per day. And this occurred midway through the process, while still losing weight so energy expenditure had not yet dropped to minimum of 1600-1800 kcal/day yet.

It is fairly likely this does not apply to the same degree in non calorie restricted states, though there is evidence that there are upper limits to energy expenditure per day, where more and more exercise does not increase energy expenditure past a certain point, the body just gets more efficient.

You gotta to do what works for you. And I concede it is true, say your body becomes 400 calories more efficient for a day, so if you burn 400 calories by walking 4-5 miles, there is no difference. But that breaks down when you get to higher calorie expenditures. It takes energy to move, that requires creating energy. There can’t be an upper limit. It isn’t scientifically possible. Like some dude walks 40 miles in a day and he stops burning energy at mile 30.

 

[lessthanhalf]

Research has been done on this , and in the short term in ultramarathons or cycling competitions, it can be as high as 10000 kcal/day. There was a study done in the race across the USA a 140 day race where energy expenditure started as high as 6000/day but it cannot be sustained long term and slowly drops to 2.5 times basal metabolic rate or about 4500 kcal/day, which is the same as the peak growth period in pregnancy, and is possibly limited by calorie intake and gut absorption, tissue repair and metabolic processes having limits. So the second law of thermodynamics is not being broken and someone will consume more calories walking 40km than 30 km, but the extra calories if it exceeds this limit will most likely be recovered over the next few days by being too tired to cover the 30km per day.

The process involved in limiting energy expenditure in low calorie intake situations is not going to be exactly the same, but it does indicate the body does have adaptive mechanisms to control energy expenditure over time. During weight loss energy expenditure is nowhere near this hard limit, but presumably the body can set different limits in different physiological states.