Listen now (37 mins) | A co-discoverer of GLP-1 and great explainer takes us through the big advances, mysteries, and issues surrounding this unprecedented drug class
One question I have about using these drugs for other purposes (e.g., Alzheimers, Parkinsons, diseases of inflammageing) in people who are not overweight and cannot afford to lose weight (as is the case with some older, frail folks) is whether these drugs will tip them into being underweight and perhaps malnourished. As for their use with obesity, I have mixed feelings. On the one hand, it's good that we finally have a medication that helps people lose weight and become healthier as a result, although I think more research is needed in how these drugs affect body composition in various age groups. I also think more research is needed on whether people on these drugs meet their nutritional needs for every macro and micronutrient. But I also wonder if people would be healthier if they simply ate whole, unprocessed foods. Having read "Ultra-Processed People: The Science Behind Food That Isn't Food" by Chris van Tulleken, I recognize that our current food industry purposely makes ultra-processed food that is hyperpalatable, leading many to become addicted, and it will be extremely difficult to change this environment given the money involved in Big Food. So is this the easier route to health, or at least, less overt disease? From a practical standpoint, can our society afford to pay for these drugs for all the people who might benefit from them if they continue to eat large amounts of UPF? (73% of food on American grocery shelves is UPF.) Sorry Eric, but I'm not optimistic that either Big Pharma or PBM's are likely to allow the price to decline to a level that our country can afford to pay for. Then again, if it saves a lot of money on other health care expenses, maybe they're worth the high cost. I wonder if drug companies have thought about that?! So many questions, so few answers...
The bit about leptin is interesting. I recall reading a few years ago that a cause for obesity in a particular mouse model is leptin insensitivity due to inflammation in the hypothalamus. (Not sure if it went anywhere in humans.) I wonder if combining GLP-1 drugs with leptin or other hormones could yield effects even if leptin itself doesn't reduce obesity.
I'm also curious about diets that cause more natural GLP-1 release. Is it just fiber or are there other dietary changes than can yield some of these effects without drugs?
GLP-1 tamps down MMP expression. MMP over-expression in response to chronic inflammation is a driver of various chronic conditions from osteoarthritis to diabetes to major depression to long-covid. This may offer a hint as to why GLP1 (through blunting the up-regulatory effect of chronically high circulating levels of inflammatory cytokines on MMP expression) might be having such wide-ranging health benefits. https://gregoryberkoff.substack.com/p/what-does-long-covid-have-in-common?utm_source=profile&utm_medium=reader2
One question I have about using these drugs for other purposes (e.g., Alzheimers, Parkinsons, diseases of inflammageing) in people who are not overweight and cannot afford to lose weight (as is the case with some older, frail folks) is whether these drugs will tip them into being underweight and perhaps malnourished. As for their use with obesity, I have mixed feelings. On the one hand, it's good that we finally have a medication that helps people lose weight and become healthier as a result, although I think more research is needed in how these drugs affect body composition in various age groups. I also think more research is needed on whether people on these drugs meet their nutritional needs for every macro and micronutrient. But I also wonder if people would be healthier if they simply ate whole, unprocessed foods. Having read "Ultra-Processed People: The Science Behind Food That Isn't Food" by Chris van Tulleken, I recognize that our current food industry purposely makes ultra-processed food that is hyperpalatable, leading many to become addicted, and it will be extremely difficult to change this environment given the money involved in Big Food. So is this the easier route to health, or at least, less overt disease? From a practical standpoint, can our society afford to pay for these drugs for all the people who might benefit from them if they continue to eat large amounts of UPF? (73% of food on American grocery shelves is UPF.) Sorry Eric, but I'm not optimistic that either Big Pharma or PBM's are likely to allow the price to decline to a level that our country can afford to pay for. Then again, if it saves a lot of money on other health care expenses, maybe they're worth the high cost. I wonder if drug companies have thought about that?! So many questions, so few answers...
The bit about leptin is interesting. I recall reading a few years ago that a cause for obesity in a particular mouse model is leptin insensitivity due to inflammation in the hypothalamus. (Not sure if it went anywhere in humans.) I wonder if combining GLP-1 drugs with leptin or other hormones could yield effects even if leptin itself doesn't reduce obesity.
I'm also curious about diets that cause more natural GLP-1 release. Is it just fiber or are there other dietary changes than can yield some of these effects without drugs?
GLP-1 tamps down MMP expression. MMP over-expression in response to chronic inflammation is a driver of various chronic conditions from osteoarthritis to diabetes to major depression to long-covid. This may offer a hint as to why GLP1 (through blunting the up-regulatory effect of chronically high circulating levels of inflammatory cytokines on MMP expression) might be having such wide-ranging health benefits. https://gregoryberkoff.substack.com/p/what-does-long-covid-have-in-common?utm_source=profile&utm_medium=reader2