What is known about the mechanisms of different GLP-1RAs?
The podcast has touched on the subject of the promise of GLP-1 receptor agonists as a treatment of obesity with a number of different guests. In particular, I think the results seen with the semaglutide, and more recently, tirzepatide trials show some outstanding weight-reduction results. However, I think it would be interesting to do an AMA episode digging into what is known and what is not known about the mechanism of the various GLP-1RAs (with GIP receptor involvement in the case of Tirzepatide). The question was inspired by an observational study by Kuwata et al. out of Japan [Effects of glucagon-like peptide-1 receptor agonists on secretions of insulin and glucagon and gastric emptying in Japanese individuals with type 2 diabetes: A prospective, observational study. J. Diabetes Investig. Vol. 12 No. 12 (2021). PubMed link: https://pubmed.ncbi.nlm.nih.gov/34022121/]. In that paper they were comparing lixisenatide, liraglutide, and dulaglutide. The study has some pretty apparent methodological limitations, but if it can be replicated it would indicate that the effects of GLP-1RAs on gastric emptying and postprandial insulin/glucagon secretion are all over the place. However, they observed all three led to improved HbA1C and 2/3 drugs led to weight reduction (which seems to be even more true of high-dose semaglutide and tirzepatide). Interestingly, they observed that "[p]ostprandial ApoB48 levels were significantly suppressed by all three GLP-1RAs (Figure 4b)." Unless I'm understanding this wrong, this seems to me to indicate that there is potentially less postprandial chylomicron activity with these drugs (potentially across the board?) and therefore less postprandial lipid storage in adipose tissue. I'm generally curious as to what we know about the mechanisms driving weight loss with the GLP-1RAs. How much of it is increased satiety due to the delayed gastric emptying (in some of the drugs), how much of it is potentially improved insulin/glucagon regulation, how much of it might be something else like less postprandial chylomicron activity, and what do we know about the causality arrow in some of these mechanisms? What are the open questions here?
VO2 max chart
In the podcast, Exercise, VO2 max and longevity with Mike Joyner, it is mentioned you would like your clients to be in the elite group for 10 years younger. How do I find a chart of what the VO2 max would be for people who are in the low, below average, average, above average and elite groups. I would like to measure my VO2 max and know what I need to train for. Thank you. Thank you
Do you still utilize/recommend fasting?
What is your current thoughts on fasting/IF on improved health parameters? I heard you mention recently that maybe it's only useful from a caloric management. Do you currently still utilize fasting or recommend it in general for improved health markers? Would love to get your updated view on this. Thank you!
spinal stenosis prevention
Is there any suggestions/evidence on what one can due to try to delay or minimize aging in regards to illnesses such as spinal stenosis, which in my family, tend to cause severely diminished activity and ambulation? This is in spite of good cognitive and cardiovascular health. Thanks for your excellent website/podcasts, I have learned so much.
Minimalist training -1 set per muscle: HIT (not HIIT)
Hi Peter, I’m a bit surprised that not once has the science of HIT (High Intensity Training) been discussed thoroughly. There’s lots of research showing it’s benefits for strength AND cardio. The book Body by Science did a good job on the topic and I think you Would find Doug McGuff a good guest to discuss this topic. You can hear the type of person he is in this YT video https://youtu.be/g2dAgScTXo0 or via interviews here https://corpwarrior.libsyn.com/interview-with-high-intensity-strength-training-expert-dr-doug-mcguff I myself switched over to this in 2018 and made incredible strength gains and hypertrophy in my mid 40s after being stagnant for decades on more volume (my girlfriend also). I did a quick blurb on it here http://ricky-ryan.blogspot.com/2020/05/how-i-stay-fit-and-healthy-on-less-than.html?m=1 I feel this should be looked into by yourself as it would benefit people who say they lack time to dedicate to being healthy when in reality it takes very little to get immense benefits. Finally, Clarence Bass has been doing this for decades and looks amazing in his 80s with excellent health markers.