I'm not a medical/biological expert, but my understanding is that those "better" versions (tirzapetide and retatrutide) by acting on more receptors can both a) reduce the side effects, such as stomach problems, and b) by releasing glucose from liver glycogen storages (glucagon agonism of retatrutide) can improve FFA release and using it as energy, preserving muscle mass. Retatrutide also seems to reduce non-alcoholic fatty liver disease dramatically.
My bilirubin normalized after 20 years elevated and ALT/AST better in range than ever since being on Retatrutide. Liver disease runs in our family and I’m pleasantly surprised to see how my numbers are so much better, we’ll see how that correlates to actual health and healthspan in real life over time.
Please do an episode on the mechanisms not related to appetite suppression - I had hoped that this ep. would cover them. 1) It's been a few years since GLP-1 agonists were proposed off-label for Parkinson's. 2) I saw a news report on ''Ozempic babies' that left me scratching my head since the doctor they interviewed said the fertility increases are solely due to metabolic improvements/weight loss - but it is known there are GLP-1 receptors in the ovaries.
I think Matt pretty much says it at minute 6:30. There might not be any convincing science that indicates that GLP1 agonist directly impact the hallmarks of aging, but it is increasingly clear that they do a lot of goodness for overall health, which translates into living longer. I suspect that as more and more data comes in from the tens of millions of people that have started taking these drugs in the last few years, we will see a dramatic improvement in overall liver health, and I suspect that will translate into increased life expectancy for people on GLP-1 agonist drugs. I might add, that I started taking ozempic about 2 years ago and recently switched to mounjaro. I've never been terribly overweight but I and type 2 diabetic. I'm the healthiest now that I've been since my twenties. These drugs are amazing and they go way beyond just appetite control.
The most concerning thing I've heard about GLP-1 agonists is that they increase resting heart rate and lower HRV. Is this accurate? Do we know why they do this? Do we know how serious that is? For an athlete, this seems like a big problem.
54M - I’m 10 weeks into using trizepitide and down 13Kg. My resting heart rate had slowly increased over the last 2 years reaching 62 in August which is when my weight peaked. It’s now down to 55 which is slightly lower than my long term “normal” level of 56-57. HRV has reduced a small amount. My fitness had become poor. It’s still poor but noticeably improving. My strength is down about 7.5% which is distressing to me as I compete in strength sports but I assume that much of that will come back once my weight loss levels out. I have experienced zero unpleasant side effects from the trizepitide and even its primary action has been subtle: i can still eat and I still absolutely enjoy food but for the first time in my 50+ years (for most of which I was pretty healthy) I can look at food and think “I just don’t fancy it.” Or 2/3 of the way through a plate of food I might feel “actually I’ve had enough” which is a novel experience for me.
We need studies on the optimal way to wean people off of the drugs in a way that keeps the weight off and removes the higher heart rate the drugs cause.
Tirzepatide is a once-weekly subcutaneous injectable peptide (approved by the Food and Drug Administration [FDA] for type 2 diabetes) engineered from the native GIP sequence, with agonist activity at both the GIP and GLP-1 receptors. The participants are advised to adhere to healthful, balanced meals, with a deficit of 500 calories per day, and at least 150 minutes of physical activity per week. This protocol should help keep the weight off, as they reduce the drug dose. This Peptide is available at a reduced cost, also.
We know from network analysis of biomarkers that some cluster together, with weak or no links to other parts of the biomarker network. Does improving health/biomarkers flow to aging rate makers like epigenetics? The answer isn't a clear yes or no, because it depends on causation and the links within the network. That's all without considering the influence of drugs. GLP-1 agonists hit many biomarkers at once through a reduction in appetite, and it wouldn't be surprising to see them have a net effect of slowing the rate of aging.
I have heard that allulose, a "rare sugar", functions like a GLP 1-RA, and indeed, if I put a big spoonful in a big cup of morning coffee, it sloshes around for a long time, so you gotta be careful. But does allulose make it past the liver into the blood, where it might interact with the GLP receptor elsewhere, or does the liver block that?
If one ascribes to the idea that it is inflammation that ultimately does the damage of aging and aging diseases (and I do) then anything that reduces inflammation is the bottom line I think. So less inflamation from fat cells, less damage that contributes to all the disease of aging.
@@Icarianbrother This episode was a good example of how scientists brainstorm new projects/avenues of future research. What was discussed was never meant to be backed up by an extensive list of scientific studies. Thr GLP-1 story is to be continued...
I really think if people just cut their carbs down under 20 grams a day, ate plenty of quality protein, got at least 8k steps a day, and did some resistance training two or more days a week, the need for GLP1 agonists would be completely eliminated.
You skipped over the endocrine disrupters, disagreements over what a “healthy “ diet consists of, addictions and pharmaceuticals that increase insulin.
No I actually think it's as simple as cutting out carbs and ultra processed foods, moving throughout the day, getting enough fully absorbable quality protein, and a couple days a week or so of even bodyweight resistance training. Maybe I'm just naive 🤔
I have a friend who's on Ozempic. He doesn't do what is required to keep at a good weight. Ozempic merely takes his appetite away..... He spends $900 a month for a drug to take his appetite away. It's psychological in my opinion. Someone that sets their mind to be at a healthy weight can do it naturally.
You could just fast 16 hours a day and fill up on protein 3 times in 8 hours. With 1 big meal. Got ripped at 6' 205 doing this and lifting 6 days a week. Fasting increases growth hormone levels so you will synthesize more protein into muscle aswell as burn off fat. Also fasting will decrease insulin resistance overtime.
I'm not a medical/biological expert, but my understanding is that those "better" versions (tirzapetide and retatrutide) by acting on more receptors can both a) reduce the side effects, such as stomach problems, and b) by releasing glucose from liver glycogen storages (glucagon agonism of retatrutide) can improve FFA release and using it as energy, preserving muscle mass. Retatrutide also seems to reduce non-alcoholic fatty liver disease dramatically.
interesting, thanks for posting
My bilirubin normalized after 20 years elevated and ALT/AST better in range than ever since being on Retatrutide. Liver disease runs in our family and I’m pleasantly surprised to see how my numbers are so much better, we’ll see how that correlates to actual health and healthspan in real life over time.
this channel should be alot bigger! great stuff
Please do an episode on the mechanisms not related to appetite suppression - I had hoped that this ep. would cover them. 1) It's been a few years since GLP-1 agonists were proposed off-label for Parkinson's. 2) I saw a news report on ''Ozempic babies' that left me scratching my head since the doctor they interviewed said the fertility increases are solely due to metabolic improvements/weight loss - but it is known there are GLP-1 receptors in the ovaries.
I think Matt pretty much says it at minute 6:30. There might not be any convincing science that indicates that GLP1 agonist directly impact the hallmarks of aging, but it is increasingly clear that they do a lot of goodness for overall health, which translates into living longer. I suspect that as more and more data comes in from the tens of millions of people that have started taking these drugs in the last few years, we will see a dramatic improvement in overall liver health, and I suspect that will translate into increased life expectancy for people on GLP-1 agonist drugs. I might add, that I started taking ozempic about 2 years ago and recently switched to mounjaro. I've never been terribly overweight but I and type 2 diabetic. I'm the healthiest now that I've been since my twenties. These drugs are amazing and they go way beyond just appetite control.
The most concerning thing I've heard about GLP-1 agonists is that they increase resting heart rate and lower HRV. Is this accurate? Do we know why they do this? Do we know how serious that is? For an athlete, this seems like a big problem.
54M - I’m 10 weeks into using trizepitide and down 13Kg. My resting heart rate had slowly increased over the last 2 years reaching 62 in August which is when my weight peaked. It’s now down to 55 which is slightly lower than my long term “normal” level of 56-57. HRV has reduced a small amount. My fitness had become poor. It’s still poor but noticeably improving. My strength is down about 7.5% which is distressing to me as I compete in strength sports but I assume that much of that will come back once my weight loss levels out. I have experienced zero unpleasant side effects from the trizepitide and even its primary action has been subtle: i can still eat and I still absolutely enjoy food but for the first time in my 50+ years (for most of which I was pretty healthy) I can look at food and think “I just don’t fancy it.” Or 2/3 of the way through a plate of food I might feel “actually I’ve had enough” which is a novel experience for me.
Great info Thanks !
We need studies on the optimal way to wean people off of the drugs in a way that keeps the weight off and removes the higher heart rate the drugs cause.
Only semaglutide does this
Tirzepatide is a once-weekly subcutaneous injectable peptide (approved by the Food and
Drug Administration [FDA] for type 2 diabetes) engineered from the native GIP sequence, with
agonist activity at both the GIP and GLP-1 receptors. The participants are advised to adhere to healthful, balanced
meals, with a deficit of 500 calories per day, and at least 150 minutes of physical activity
per week. This protocol should help keep the weight off, as they reduce the drug dose.
This Peptide is available at a reduced cost, also.
We know from network analysis of biomarkers that some cluster together, with weak or no links to other parts of the biomarker network. Does improving health/biomarkers flow to aging rate makers like epigenetics? The answer isn't a clear yes or no, because it depends on causation and the links within the network. That's all without considering the influence of drugs. GLP-1 agonists hit many biomarkers at once through a reduction in appetite, and it wouldn't be surprising to see them have a net effect of slowing the rate of aging.
I have heard that allulose, a "rare sugar", functions like a GLP 1-RA, and indeed, if I put a big spoonful in a big cup of morning coffee, it sloshes around for a long time, so you gotta be careful. But does allulose make it past the liver into the blood, where it might interact with the GLP receptor elsewhere, or does the liver block that?
If one ascribes to the idea that it is inflammation that ultimately does the damage of aging and aging diseases (and I do) then anything that reduces inflammation is the bottom line I think. So less inflamation from fat cells, less damage that contributes to all the disease of aging.
What’s enough protein really tho
OK, Now PLEASE tell me what you-all think of GLP microdosing when weight loss is not wanted only the reduction in heart and cancer related events?
Too much guessing and thinking going on here instead of knowing the answers.
I'll do my @an impression- He's offering a lot of unscientific speculation. There are no scientific studies to back his claims.
@@Icarianbrother This episode was a good example of how scientists brainstorm new projects/avenues of future research. What was discussed was never meant to be backed up by an extensive list of scientific studies. Thr GLP-1 story is to be continued...
I really think if people just cut their carbs down under 20 grams a day, ate plenty of quality protein, got at least 8k steps a day, and did some resistance training two or more days a week, the need for GLP1 agonists would be completely eliminated.
You skipped over the endocrine disrupters, disagreements over what a “healthy “ diet consists of, addictions and pharmaceuticals that increase insulin.
No I actually think it's as simple as cutting out carbs and ultra processed foods, moving throughout the day, getting enough fully absorbable quality protein, and a couple days a week or so of even bodyweight resistance training. Maybe I'm just naive 🤔
For many people low car doesn't work.
I have a friend who's on Ozempic. He doesn't do what is required to keep at a good weight. Ozempic merely takes his appetite away..... He spends $900 a month for a drug to take his appetite away. It's psychological in my opinion. Someone that sets their mind to be at a healthy weight can do it naturally.
You could just fast 16 hours a day and fill up on protein 3 times in 8 hours. With 1 big meal. Got ripped at 6' 205 doing this and lifting 6 days a week. Fasting increases growth hormone levels so you will synthesize more protein into muscle aswell as burn off fat. Also fasting will decrease insulin resistance overtime.