It strikes me that nutritionists who invoke the first law of thermodynamics to defend the “calorie is a calorie” idea might by implication think that a calorie of coal in a steam engine produces the same results as a calorie of diesel in a diesel engine. But the two fuels driving the two trains produce different outcomes. While calories are preserved, the energy partitioning isn’t the same. Coal in a steam engine - little useful work, lots of heat. Diesel in a diesel engine - more work, less wasted heat.
You (or rather, I) could stretch this analogy to say that the body switches between two alternative ‘engines’ (controlled by the insulin response) if fed a high fat/low carb meal vs a low fat/high carb meal. In this respect, a calorie is not a calorie; different fuels, different outcomes.
Hi David, You're not, but this is only the beginning of the calorie-is-a-calorie problems. I'll write more about this as I'll have to, particularly the idea that diets that work have to work by making you eat less.
Different things work for different people and I’m convinced obesity has many different drivers. Millions of people would be thin on the healthy diet I’ve been eating for years. Not me! But something in this medication works, because I’m eating the same diet but have moved from XL to M clothing.
Yes, it just remains to be discovered what the unintended costs, if any, might be. I'm always wary of throwing monkey wrenches into complex biological systems.
I’m not. I’m quite happy to improve my health in hundreds of ways. If a system isn’t working and something easily fixes it, FIX IT. Stop worrying that some theoretical problem might show up someday.
Also, 100 cal of fat or protein does not equal 100 calories of energy, as the body uses protein (and fat to a lesser extent) to make things like physical structures, hormones, cell membranes neurotransmitters etc. Carbs, however, are pure energy- and the joke is it's the same energy we can make ourselves in the body. Animals are not bomb calorimeters.
That's a critical point, but the key is that the hormonal responses to these different macronutrients are also different to facilitate this different usage. So we secrete growth hormone, glucagon and insulin in response to protein consumption, but only insulin in response to the carbohydrates. Considering this very different endocrine response, the question we should be asking is how the hell COULD a calorie still be a calorie when it comes to fat storage. That's the remarkable proposition. Not that different macronutrients have very different effects on fat storage.
It would be far more precise to say that a calorie is a calorie because that is by definition a precise unit of measurement, but that different foods containing different macronutrients affect the rates of calorie excretion, oxidation, and acquisition -- all of which have direct effects on energy balance.
These articles are such a joy to read. Thank you for persisting in your efforts, and please keep pushing this boulder up the hill. It’s helping so many of us keep going, too.
These are the exact types of studies I was looking forward to as a possible silver lining in the shift towards GLP-1 drugs as first-line obesity treatment. If we better understand the underlying mechanisms of a successful pharmaceutical approach, that will inform and support the rest of us out here in the trenches helping people with LCHF diets.
One “side effect” of the drugs that fascinates me — I have read on various message boards that people reportedly become depressed due to the lack of appetite. They get to experience freedom from food noise, but some also feel empty in its absence.
I haven’t observed the same thing with LCHF diets — sometimes people get “cranky” because of the inconvenience of restricting carbs, or an emotional attachment to certain eating patterns, but because they can eat as much fat and non-starchy vegetables as they want, they can still get the satisfaction of feeling “full.”
If it’s true (as it appears to be) that the drugs work by mobilizing fat for fuel, and the body is being “fed from within,” there is still a missing element — what my peers refer to as “neurolingual response,” or what foodies might call “mouth feel.” There are many stages of digestion that are inhibited by severe calorie restriction, even if those calories are being sourced from fat stores.
Thanks, Suzie. I do think these drugs have effects that are very different than what's going on with keto, although I do think the primary mechanism--changing this fuel-partitioning--is likely to be the same. It will be interesting to see what researchers learn about them as we go along, even as we'll have to disentangle what they think they've learned from what they actually observed. gt
Ugh. Please stop pushing low carb and accept these drugs as the miracle they are.
No depression here! Quite the opposite. I am sure this may vary (I expect people become fat for all different reasons and thus react to regimens differently) but I have experienced essentially no negatives to this drug.
That’s wonderful Michelle. I do think these drugs are a miracle for many people, and I’m glad to hear that you are experiencing only positive outcomes.
What about the particularly soothing effect of carbohydrate/sweets? Not just the psychological training since childhood (upset? have a cookie) but the biological effects of boosting seratonin or other neurotransmitters. Though for some people they result in a burst of excitatory neurotransmitters too and thus can be mood-disrupting.
Not a thing, in my personal experience of 9 months on tirzepatide and almost 60 pounds gone. I very seldom feel the need for a treat now. If I do, a very small bit is enough. I enjoyed a small serving of ice cream a week ago. First ice cream in ages. The knowledge that there’s more in the freezer is irrelevant.
The theory that fat people eat their feelings may be completely wrong.
I had believed it and braced myself—fearing I’d need another way to address moods. Nope. Turns out I wasn’t eating my feelings at all.
I do not know why I got fat. I “shouldn’t” be, according to my eating habits. But I’m losing now on the same habits I’ve had for a long time.
Thank you for this explanation. It answered my question of how, in a nutshell, weighloss will increase if you increase the dose without reducing your calorie intake, just eating a healthy diet. However, if these drugs have the same effect and mechanisms such as fasting or a ketogenic diet, by using your fat reserves, how can you maintain the weight loss once you have reached your goal weight and want to stop the drug,mainly for financial reasons, but also because you haven’t got any more fat to spare? Does the body ‘learn’ to work like a lean person’s body? Or will it revert to how it was once the drug is out of the system. Is it inevitable to gain weight again. I personally have had an identical experience as Michelle in how I gained weight despite a relatively healthy diet. I have only just started with this and so far I have a good experience with it. But what will happen when I stop taking the drugs and what could I do to stop reverting?
We probably can never stop taking this medication. I’ve accepted I’ll need some version of it forever to maintain. I hope I can split or stretch doses.
During my first year of strict keto, the most remarkable thing that occurred was the 4 month period when a leftover pint of ice cream from Thanksgiving sat untouched in the freezer, until I finally gave it away. Absolutely unheard of in my pre-keto (or incomplete keto) life!
I understand that not everyone gets the same results from diet changes alone, and I am glad that the GLP-1 drugs are allowing more people to experience freedom from food noise. It is truly a blessing.
GT’s audience is mostly made up of people who have experienced wonderful changes from keto diets and want to exchange thoughts and ideas about that topic. The discussion can come off as anti-drug, but I honestly don’t get that from GT himself. He seems genuinely interested in how the GLP-1 story is unfolding and how that can inform our knowledge of keto and low carb diets.
I will certainly admit to an anti-medication bias, but I have heard first hand accounts from people who have benefitted from the GLP-1 drugs (I particularly enjoyed Johann Hari’s book Magic Pill) and have an appreciation for them. I have also heard less enthusiastic accounts by people who had negative outcomes. So I’m glad the discussion continues and we are able to develop multiple approaches to address obesity.
Hi, I am not anti-drug in the least. I do worry, though, about using any such powerful drug for decades and what complications and consequences might arise. I wrote about this for the Atlantic last year. (Here's an archived version you can read without a subscription: https://archive.ph/IKMGj ) I get that this drug is a wonder drug and for many people frees them up from a lifetime of struggle. I might take it myself if I didn't find that a ketogenic diet does work for me. But if I did, I would worry about the consequences of longterm use. Would I find myself with a new health issue and not know whether the drug was the reason why. And if I went off the drug to find out, would that create yet other problems. We've seen this issue play out most conspicuously with benzodiazipines for anxiety, depression, insomnia, etc. It's always something that we have to worry about and it's why I think dietary solutions, if possible, are preferrable. I could, of course, be wrong.
I am not really worried about theoretical long-term problems because I am stacking them against serious present-day problems, and this drug has helped them all.
My blood pressure is great. My blood sugar, which kept creeping up and was one cupcake away from pre-diabetes, is now fine. My cholesterol is slightly high but better than before (I expect it to be better at next check).
Hip and knee pain were starting to make themselves known, but that has receded. I no longer have reflux. I suspect I no longer have sleep apnea. God only knows what else was going on in my body unmeasured and unknown.
My main fear is that someday I will not be able to obtain these drugs (I'm a low-income writer who is taking extreme measures to get them now) or that someday they'll stop working.
I cannot go back to spending every waking hour feeling hunger, wanting desperately to eat, denying myself most of the time and inevitably giving in and eating at some point and then gaining weight. I never want to live like that again; I am simply unwilling to.
Nothing else has ever worked. Not IF, not Whole 30, not low-carb, not keto, not any other diet or supplement or exercise program or anything else. I have lost weight in the past through various extreme means but it wouldn't stay off, but nothing has worked in recent years -- I'm 59.
I myself cannot understand why anyone gives these up. Perhaps they reached their goal weight and didn't understand they still needed to keep taking it, perhaps they could no longer afford to purchase the drug. I know some people have side effects, but I haven't had any serious ones. I have always still had an appetite at mealtime, and I am still able to eat my regular, normal, healthy diet. I will say I cannot let up on the fiber for even one day; I generally eat plenty of fiber but now I can't ever have an off day or there are ... consequences. But I can live with that. I generally get way more fiber than most.
I understand, and I would be doing the same thing if I were you.
We humans do have a habit of oversimplifying and digging in to our own perspectives. Your experience is important and I’m sure you’re helping people broaden their understanding.
The idea that some people’s metabolism can prioritize fat deposition over other presumably more vital metabolic needs fits perfectly with a remarkable experience I had with a severely overweight patient during my critical care fellowship in the early 80’s. She had survived a car accident with extensive sternal and rib injuries and a large area of scalp avulsion. The flail chest meant she was dependent on mechanical ventilation. She was stable with this treatment and had no infectious or other complications, but after two weeks she was still completely dependent on the ventilator: the chest fractures remained unstable, with no sign of healing, and the scalp wound had not contracted at all. With no other ideas to try, we began gradually increasing her tube feeding far beyond what the nutritionist recommended. Once we had exceeded 5000 calories per day, suddenly the wound began to contract and the fractures began to heal. She weaned from the ventilator a few days later. The key fact is that she gained weight—put down more fat—BEFORE any healing began. This experience changed my perspective of obesity forever. I could never again view it as a “failure of will power.” I am so glad that medical science is beginning to catch up.
Very interesting. If these individuals are able to access fat as fuel, why are we seeing higher rates of muscle loss among many individuals? I'm not a scientist just a coach, but have seen from DEXA scan reports measurable loss of muscle mass from GLP-1 users, with noticeable fat gain when drugs are discontinued.
The evidence I've seen says, yes, greater muscle loss with the drugs than with similar weight loss by calorie restriction. (Of course, they don't compare it to weight loss by ketogenic diets because they assume the ketogenic diets work merely by getting people to eat less.) That alone suggests to me that the drugs are doing something profound in the body, in the periphery, that is independent from whatever effect they're having in appetite. Again, I haven't seen any discussion i the academic literature making this point. To these folks, all these other observations are treated as interesting epiphenomena of the drug, relevant perhaps to treatment--per Jackie J's comment below--but not to understanding fundamental mechanisms.
Thanks so much for the insight Gary. Let’s hope they don’t let the ‘experiment’ go as long as the low-fat one in asking the right questions that might lead to more knowledge of the fundamental mechanisms.
I'm not familiar with reports of muscle loss. To what extent could that muscle loss be the result of the weight loss? E.g. my obese husband has really impressive leg muscles to move himself around. As he loses weight, I would naturally expect his legs to get less muscular because they don't have to move 330 lbs.
I see muscle loss as a whole separate issue. Muscle is very much "use it or lose it," and if they don't resistance train hard enough to elicit an adaptive response, everyone loses muscle as they age regardless of whether they take a weight loss drug. Dieting without intense resistance training produces the same muscle loss, and eating to satiety without intense resistance training has the same result.
I don’t have the answer but due to this muscle loss, my doctor will no longer prescribe these drugs unless the patient has adequate testosterone levels and lifts weights.
just goes to show that the researchers don't know why the drugs work either. they say it "reduces appetite," somehow. but it obviously releases stored fat. which is why it doesn't work forever. the hypothesis you're suggesting here actually explains all the observations, instead of resulting in "paradoxes" and "mysteries."
Of course, I agree, but the problem is getting the researchers to care. They have grown up in a world in which everyone they respect thinks like they do, so if someone comes along who doesn't, the kneejerk response is simply to ignore the opinion. We all do it in other areas of our lives. The problem is when we're on the receiving end of the ignoring.
Sometimes it seems like the researchers are little better than witch doctors. I mean, “the Gods are angry,” or “the Gods appreciate your sacrifices” can explain every phenomenon just as well.
This is fantastic. Context: I’m 59 and have fought my weight ever since I got pregnant in 1989. I eat a very healthy diet — lots of veggies, beans, whole grains, nuts, some fruits, chicken and fish. Some nuts. No dirt has worked for long. Keto did nothing at all (except cause brutal constipation). I began Tirzepatide in July and am down almost 60 pounds. I haven’t changed my diet but I have reduced my volume of intake and I seldom feel a craving for sweets. I always wondered why I was so hungry even though I clearly had plenty of energy available in my butt! My body was like, “No, no. We wanna keep that butt fat just in case. Go eat something right now.”
Now, my body is like, “No need to eat anything just now. We can go grab some energy from your butt.”
I do get hungry at mealtime, but I become full and satisfied with much less food.
Study of one here but I’ve been on a glp-1 for 4 months and I’ve lost 15% of my body weight. I’m eating more than I had before I started taking glp-1s. I have MCAS so that might have something to do with it, but it’s definitely something other than just appetite suppression going on.
Interesting! I wouldn’t say I’m eating more, but I’m only hungry at mealtime now. I was always hungry before, and all I could think about was resisting food.
I have been on the lower-carb bandwagon for about 20 years. Hard to stick to it but otherwise it works well to keep down my glucose, cholesterol, and cravings.
Have been on Ozempic for about a year and am approaching a great weight and have had obvious fat-reduction. Would love to not be on such a strong medication forever. With this study, seems like we would see people on GLPs plateau once they have achieved low body fat. Does that happen? If it’s only appetite suppression, do those on GLPs just kind of waste away?
Hi Sheryl - you might be interested in part 2 of GT’s Diet or Drugs series, where this question is addressed. There does seem to be a point at which weight loss plateaus and appetite resumes on the GLP drugs.
I was going to say the same, but Suzie beat me to it. That post is behind a paywall, though. (I can use the paid subscribers...). Hope that's not a problem.
I assume she means something like ketovore or carnivore. It may not be everyone's cup of tea, but it works for a lot of people, which is great for them, just as what is working for you is great for you.
I'm not doing it for weight loss, though I'm down 50lbs which is nice (20 or so to go I suppose). I'm doing it for arthritis, bad joint pain, inflammation, and to heal my gut (which took about a year). I thought I'd have to lose a lot of weight for the joint pain to go away but that happened in days - a total shock, really - so must have been inflammation. Another bonus was food noise going away, which is great, 40 years of that was enough :-) I like eating this way and don't miss anything, so I'll keep doing it. I don't think of it as a diet, it's just what I eat to feel my best.
So you say lower carb bandwagon, and it’s helped lower cholesterol. I’m confused . Losing weight on a low carb regimen requires you to eat lots of fat. That’s how you create the change in the fuel your body burns. That’s how you will lose weight. So I assume you are not really low carb?
I was speaking broadly about changes that my body has undergone, different ways of eating, different health consequences, over the years since around age 40.
I realized in my early forties that low-carb was key. It was not well-known at the time. I educated myself and observed that my appetite was suppressed and that weight came off relatively easily when eating lower carb.
It’s not that easy to maintain that way of eating though, and one is tempted to eat just a few more potatoes etc and eventually I gained weight again. Also had a very high-stress career.
A random health check when I was 55 shocked me by revealing that I had developed Type II diabetes. Knowing what I know NOW, I would have understood a decade sooner that “low carb” wasn’t just about a better weight, but that the very fact that my body had responded so dramatically to it was a symptom of the fact that I was predisposed to metabolic syndrome. I do not think that I would have developed diabetes if I had continued to eat lower carb.
With the diagnosis, I threw myself into basically a keto diet, and my A1C plummeted, along with my cholesterol. My doctor could literally not believe her eyes when she saw the change over three months.
Fantastic, keep it up. My wife and I in our late 70’s attended a local seminar on longevity. A local physician renowned for his work in this field, came out and said, no grains, no sugar, moderate exercise, lift something heavy, have good social connections and get 8 hrs sleep. This was about 6 years ago, we looked at each other and said we could do that. That was our introduction into the LCHF / Keto community. That together with time restricted eating have changed our lives, not only lost some weight, but primarily all our inflammatory markers are way down, no aches, no pains, great mental clarity, lots of energy, and for us it is the easiest lifestyle ever. So just keep it up, remember to make sure to prioritize fats, I think that’s where a lot of folks struggle, keep the fat intake high.
That’s wonderful, pretty much where we are in terms of goals and strategies. Husband has lost 20 and has set up a nice little gym in the basement to lift. Hope he can lose another 10-15. He eats once a day, after work, typically a strip steak and a very large portion of veggies or salad. I am doing middling on the lower carb stuff.
John, is your confusion about reduction in cholesterol on a low carb, high fat diet? Because this actually happens quite often. Elevated total cholesterol, while not in itself unhealthy, can be a reflection of poor liver health, often due to insulin resistance.
When insulin resistance is corrected via LCHF diet, sometimes this will actually reduce total cholesterol. It happened to me — my TC dropped from 265 to 205 after 6 months of strict keto (<20g net carbs per day), IF and resistance training.
In my experience working with patients, it tends to be the genetically lean who more commonly see cholesterol elevations with LCHF diets.
No, my confusion was with someone claiming to be LCHF and not losing any weight. However your comment was interesting. In my experience most people on either LCHF, Ketogenic, or even Carnivore typically see elevated total cholesterol, in particular LDL. I would also take issue with your comments about elevated cholesterol as a result of regaining insulin sensitivity indicting poor liver health. But perhaps I misunderstood your meaning
The level of "LC" needed to lose weight varies depending on the individual. I can only lose weight if I stick to 20g carbs, maintain on up to 35g and gain if I consume more than 35g. All on no grains, no legumes & no sugar.
Yes, I think you’re misunderstanding my comment — I was explaining how regaining insulin sensitivity could lead to a reduction in cholesterol (either TC, LDL, or both), if the elevated cholesterol was due to poor liver health.
My point was that we can’t always tell whether someone is adhering to a LCHF by their cholesterol levels, as there is variation in blood lipid response per biochemical individuality.
I see it with enough frequency to know it’s not an outlier — LDL and TC reduction, along with HDL increase, with LCHF.
And sadly, I’ve seen plenty of people strictly adhere to a LCHF who are still unable to lose weight. There are many other factors in weight-loss resistance besides carb consumption. This actually aligns with the fuel-partitioning model, as there are myriad hormones involved with that process, beyond insulin alone.
Additional confounding factor: my blood glucose levels went down IMMEDIATELY after starting Oz.
So does that mean it would be best if I continued on GLPs even if they no longer suppress appetite?
I have to say that I feel so much better being thinner. Was always muscular and slender (5’7”, 135 lbs) until around age forty after having two kids. Still looked and felt great at 145-155. Been averaging about 185 since then, plus developed Type II.
Remember that Dr. Richard Bernstein in his Diabetes Solution (1996?) discussed prescribing Liraglutide (an early glp-1 r/a) to his diabetic patients in order to curb their carbohydrate cravings, which totally supports your theory. Why after all does someone have carbohydrate cravings? Aside from the psychological underpinnings I would argue that it's difficulty in mobilizing energy from fat stores or a tendency to over-store what is consumed rather than using it for energy, an endocrine defect that is remedied by this class of drug. Dr. Bernstein has all the answers.
Your point “An important point, though, is that they only measured RER after body weights had plateaued, not during the active weight-loss phase” is contradicted by Figure 3A in the paper which shows the human tirzepatide group to still be actively losing weight at the 18 week mark.
I’ve heard that many people report having lower psychological cravings of all kinds when taking GLP-1s, and that it appears to curb addiction in general. Is that mistaken? It would appear to be at least slightly inconsistent with the idea that the reduced food cravings are purely a result of the body being satiated by existing fat storage.
I think there isn’t just one reason people get fat.
I don’t have an issue with alcohol or shopping for fun etc, so curbing those impulses was not a thing for me. It is for some. Maybe some people do eat their feelings, but I haven’t found that to be accurate for me. Maybe some people did ingest a lot of fast food and soda, but I didn’t. I can’t explain why I was fat, because I did everything “right” generally. And I’ll note I raised two kids with healthy weights, which suggests my cooking habits aren’t to blame. All I know is now I’m more than 60 pounds down and I’m only a touch overweight, and I’m grateful.
So what exactly does this imply for obesity prevention? It's something I worry about since I have kids in a family quite prone to obesity. Other than trying to educate them that it's much easier to maintain a healthy weight than it is to lose it once you've gained more than you should, I'm not really sure what concrete steps I can take to prevent them gaining too much weight in adulthood.
It strikes me that nutritionists who invoke the first law of thermodynamics to defend the “calorie is a calorie” idea might by implication think that a calorie of coal in a steam engine produces the same results as a calorie of diesel in a diesel engine. But the two fuels driving the two trains produce different outcomes. While calories are preserved, the energy partitioning isn’t the same. Coal in a steam engine - little useful work, lots of heat. Diesel in a diesel engine - more work, less wasted heat.
You (or rather, I) could stretch this analogy to say that the body switches between two alternative ‘engines’ (controlled by the insulin response) if fed a high fat/low carb meal vs a low fat/high carb meal. In this respect, a calorie is not a calorie; different fuels, different outcomes.
Or am I off the rails?
Hi David, You're not, but this is only the beginning of the calorie-is-a-calorie problems. I'll write more about this as I'll have to, particularly the idea that diets that work have to work by making you eat less.
I don’t think a high-fat diet is the fix you think it is. I never lost an ounce on any version of low-carb. Tirzepatide is working very well, though.
It works for a lot of people. The question would be, why not for some.
Different things work for different people and I’m convinced obesity has many different drivers. Millions of people would be thin on the healthy diet I’ve been eating for years. Not me! But something in this medication works, because I’m eating the same diet but have moved from XL to M clothing.
Yes, it just remains to be discovered what the unintended costs, if any, might be. I'm always wary of throwing monkey wrenches into complex biological systems.
I’m not. I’m quite happy to improve my health in hundreds of ways. If a system isn’t working and something easily fixes it, FIX IT. Stop worrying that some theoretical problem might show up someday.
Also, 100 cal of fat or protein does not equal 100 calories of energy, as the body uses protein (and fat to a lesser extent) to make things like physical structures, hormones, cell membranes neurotransmitters etc. Carbs, however, are pure energy- and the joke is it's the same energy we can make ourselves in the body. Animals are not bomb calorimeters.
That's a critical point, but the key is that the hormonal responses to these different macronutrients are also different to facilitate this different usage. So we secrete growth hormone, glucagon and insulin in response to protein consumption, but only insulin in response to the carbohydrates. Considering this very different endocrine response, the question we should be asking is how the hell COULD a calorie still be a calorie when it comes to fat storage. That's the remarkable proposition. Not that different macronutrients have very different effects on fat storage.
It would be far more precise to say that a calorie is a calorie because that is by definition a precise unit of measurement, but that different foods containing different macronutrients affect the rates of calorie excretion, oxidation, and acquisition -- all of which have direct effects on energy balance.
These articles are such a joy to read. Thank you for persisting in your efforts, and please keep pushing this boulder up the hill. It’s helping so many of us keep going, too.
These are the exact types of studies I was looking forward to as a possible silver lining in the shift towards GLP-1 drugs as first-line obesity treatment. If we better understand the underlying mechanisms of a successful pharmaceutical approach, that will inform and support the rest of us out here in the trenches helping people with LCHF diets.
One “side effect” of the drugs that fascinates me — I have read on various message boards that people reportedly become depressed due to the lack of appetite. They get to experience freedom from food noise, but some also feel empty in its absence.
I haven’t observed the same thing with LCHF diets — sometimes people get “cranky” because of the inconvenience of restricting carbs, or an emotional attachment to certain eating patterns, but because they can eat as much fat and non-starchy vegetables as they want, they can still get the satisfaction of feeling “full.”
If it’s true (as it appears to be) that the drugs work by mobilizing fat for fuel, and the body is being “fed from within,” there is still a missing element — what my peers refer to as “neurolingual response,” or what foodies might call “mouth feel.” There are many stages of digestion that are inhibited by severe calorie restriction, even if those calories are being sourced from fat stores.
Thanks, Suzie. I do think these drugs have effects that are very different than what's going on with keto, although I do think the primary mechanism--changing this fuel-partitioning--is likely to be the same. It will be interesting to see what researchers learn about them as we go along, even as we'll have to disentangle what they think they've learned from what they actually observed. gt
Ugh. Please stop pushing low carb and accept these drugs as the miracle they are.
No depression here! Quite the opposite. I am sure this may vary (I expect people become fat for all different reasons and thus react to regimens differently) but I have experienced essentially no negatives to this drug.
That’s wonderful Michelle. I do think these drugs are a miracle for many people, and I’m glad to hear that you are experiencing only positive outcomes.
What about the particularly soothing effect of carbohydrate/sweets? Not just the psychological training since childhood (upset? have a cookie) but the biological effects of boosting seratonin or other neurotransmitters. Though for some people they result in a burst of excitatory neurotransmitters too and thus can be mood-disrupting.
Not a thing, in my personal experience of 9 months on tirzepatide and almost 60 pounds gone. I very seldom feel the need for a treat now. If I do, a very small bit is enough. I enjoyed a small serving of ice cream a week ago. First ice cream in ages. The knowledge that there’s more in the freezer is irrelevant.
The theory that fat people eat their feelings may be completely wrong.
I had believed it and braced myself—fearing I’d need another way to address moods. Nope. Turns out I wasn’t eating my feelings at all.
I do not know why I got fat. I “shouldn’t” be, according to my eating habits. But I’m losing now on the same habits I’ve had for a long time.
Thank you for this explanation. It answered my question of how, in a nutshell, weighloss will increase if you increase the dose without reducing your calorie intake, just eating a healthy diet. However, if these drugs have the same effect and mechanisms such as fasting or a ketogenic diet, by using your fat reserves, how can you maintain the weight loss once you have reached your goal weight and want to stop the drug,mainly for financial reasons, but also because you haven’t got any more fat to spare? Does the body ‘learn’ to work like a lean person’s body? Or will it revert to how it was once the drug is out of the system. Is it inevitable to gain weight again. I personally have had an identical experience as Michelle in how I gained weight despite a relatively healthy diet. I have only just started with this and so far I have a good experience with it. But what will happen when I stop taking the drugs and what could I do to stop reverting?
We probably can never stop taking this medication. I’ve accepted I’ll need some version of it forever to maintain. I hope I can split or stretch doses.
During my first year of strict keto, the most remarkable thing that occurred was the 4 month period when a leftover pint of ice cream from Thanksgiving sat untouched in the freezer, until I finally gave it away. Absolutely unheard of in my pre-keto (or incomplete keto) life!
I understand that not everyone gets the same results from diet changes alone, and I am glad that the GLP-1 drugs are allowing more people to experience freedom from food noise. It is truly a blessing.
GT’s audience is mostly made up of people who have experienced wonderful changes from keto diets and want to exchange thoughts and ideas about that topic. The discussion can come off as anti-drug, but I honestly don’t get that from GT himself. He seems genuinely interested in how the GLP-1 story is unfolding and how that can inform our knowledge of keto and low carb diets.
I will certainly admit to an anti-medication bias, but I have heard first hand accounts from people who have benefitted from the GLP-1 drugs (I particularly enjoyed Johann Hari’s book Magic Pill) and have an appreciation for them. I have also heard less enthusiastic accounts by people who had negative outcomes. So I’m glad the discussion continues and we are able to develop multiple approaches to address obesity.
I just know that keto did nothing good for me and this drug is profoundly changing my life.
I want to bear witness to this, because too many people are against these drugs.
I see so many obese people who have been convinced these drugs are too scary to even try. That’s tragic.
Hi, I am not anti-drug in the least. I do worry, though, about using any such powerful drug for decades and what complications and consequences might arise. I wrote about this for the Atlantic last year. (Here's an archived version you can read without a subscription: https://archive.ph/IKMGj ) I get that this drug is a wonder drug and for many people frees them up from a lifetime of struggle. I might take it myself if I didn't find that a ketogenic diet does work for me. But if I did, I would worry about the consequences of longterm use. Would I find myself with a new health issue and not know whether the drug was the reason why. And if I went off the drug to find out, would that create yet other problems. We've seen this issue play out most conspicuously with benzodiazipines for anxiety, depression, insomnia, etc. It's always something that we have to worry about and it's why I think dietary solutions, if possible, are preferrable. I could, of course, be wrong.
That was an interesting article. Kudos.
I am not really worried about theoretical long-term problems because I am stacking them against serious present-day problems, and this drug has helped them all.
My blood pressure is great. My blood sugar, which kept creeping up and was one cupcake away from pre-diabetes, is now fine. My cholesterol is slightly high but better than before (I expect it to be better at next check).
Hip and knee pain were starting to make themselves known, but that has receded. I no longer have reflux. I suspect I no longer have sleep apnea. God only knows what else was going on in my body unmeasured and unknown.
My main fear is that someday I will not be able to obtain these drugs (I'm a low-income writer who is taking extreme measures to get them now) or that someday they'll stop working.
I cannot go back to spending every waking hour feeling hunger, wanting desperately to eat, denying myself most of the time and inevitably giving in and eating at some point and then gaining weight. I never want to live like that again; I am simply unwilling to.
Nothing else has ever worked. Not IF, not Whole 30, not low-carb, not keto, not any other diet or supplement or exercise program or anything else. I have lost weight in the past through various extreme means but it wouldn't stay off, but nothing has worked in recent years -- I'm 59.
I myself cannot understand why anyone gives these up. Perhaps they reached their goal weight and didn't understand they still needed to keep taking it, perhaps they could no longer afford to purchase the drug. I know some people have side effects, but I haven't had any serious ones. I have always still had an appetite at mealtime, and I am still able to eat my regular, normal, healthy diet. I will say I cannot let up on the fiber for even one day; I generally eat plenty of fiber but now I can't ever have an off day or there are ... consequences. But I can live with that. I generally get way more fiber than most.
I've lost about 10 more pounds since this story: https://michelleteheux.substack.com/p/overweight-and-underpaid
I understand, and I would be doing the same thing if I were you.
We humans do have a habit of oversimplifying and digging in to our own perspectives. Your experience is important and I’m sure you’re helping people broaden their understanding.
Not a thing *for you.*
I don’t think I’m very unique, judging from others’ stories. “Eating our feelings” seems to be something other people made up to judge us.
The idea that some people’s metabolism can prioritize fat deposition over other presumably more vital metabolic needs fits perfectly with a remarkable experience I had with a severely overweight patient during my critical care fellowship in the early 80’s. She had survived a car accident with extensive sternal and rib injuries and a large area of scalp avulsion. The flail chest meant she was dependent on mechanical ventilation. She was stable with this treatment and had no infectious or other complications, but after two weeks she was still completely dependent on the ventilator: the chest fractures remained unstable, with no sign of healing, and the scalp wound had not contracted at all. With no other ideas to try, we began gradually increasing her tube feeding far beyond what the nutritionist recommended. Once we had exceeded 5000 calories per day, suddenly the wound began to contract and the fractures began to heal. She weaned from the ventilator a few days later. The key fact is that she gained weight—put down more fat—BEFORE any healing began. This experience changed my perspective of obesity forever. I could never again view it as a “failure of will power.” I am so glad that medical science is beginning to catch up.
That is fascinating, and also what a gift that you all had that insight. I wonder what makes some bodies prioritize fat storage over healing.
Very interesting. If these individuals are able to access fat as fuel, why are we seeing higher rates of muscle loss among many individuals? I'm not a scientist just a coach, but have seen from DEXA scan reports measurable loss of muscle mass from GLP-1 users, with noticeable fat gain when drugs are discontinued.
The evidence I've seen says, yes, greater muscle loss with the drugs than with similar weight loss by calorie restriction. (Of course, they don't compare it to weight loss by ketogenic diets because they assume the ketogenic diets work merely by getting people to eat less.) That alone suggests to me that the drugs are doing something profound in the body, in the periphery, that is independent from whatever effect they're having in appetite. Again, I haven't seen any discussion i the academic literature making this point. To these folks, all these other observations are treated as interesting epiphenomena of the drug, relevant perhaps to treatment--per Jackie J's comment below--but not to understanding fundamental mechanisms.
Thanks so much for the insight Gary. Let’s hope they don’t let the ‘experiment’ go as long as the low-fat one in asking the right questions that might lead to more knowledge of the fundamental mechanisms.
I'm not familiar with reports of muscle loss. To what extent could that muscle loss be the result of the weight loss? E.g. my obese husband has really impressive leg muscles to move himself around. As he loses weight, I would naturally expect his legs to get less muscular because they don't have to move 330 lbs.
I see muscle loss as a whole separate issue. Muscle is very much "use it or lose it," and if they don't resistance train hard enough to elicit an adaptive response, everyone loses muscle as they age regardless of whether they take a weight loss drug. Dieting without intense resistance training produces the same muscle loss, and eating to satiety without intense resistance training has the same result.
I don’t have the answer but due to this muscle loss, my doctor will no longer prescribe these drugs unless the patient has adequate testosterone levels and lifts weights.
JFC, that’s so wrong.
just goes to show that the researchers don't know why the drugs work either. they say it "reduces appetite," somehow. but it obviously releases stored fat. which is why it doesn't work forever. the hypothesis you're suggesting here actually explains all the observations, instead of resulting in "paradoxes" and "mysteries."
Of course, I agree, but the problem is getting the researchers to care. They have grown up in a world in which everyone they respect thinks like they do, so if someone comes along who doesn't, the kneejerk response is simply to ignore the opinion. We all do it in other areas of our lives. The problem is when we're on the receiving end of the ignoring.
Sometimes it seems like the researchers are little better than witch doctors. I mean, “the Gods are angry,” or “the Gods appreciate your sacrifices” can explain every phenomenon just as well.
Fascinating study with a clever design! Thank you for making it so accessible to all of us.
You’ll find Dr Ben Bikman’s research on the correlation between glp-1, fat burning and ketones helpful.
I've spoken with Ben about this a lot. Although, now that you mention it, I'll ask him specifically about fat burning and ketones.
Yes, please do.
This is fantastic. Context: I’m 59 and have fought my weight ever since I got pregnant in 1989. I eat a very healthy diet — lots of veggies, beans, whole grains, nuts, some fruits, chicken and fish. Some nuts. No dirt has worked for long. Keto did nothing at all (except cause brutal constipation). I began Tirzepatide in July and am down almost 60 pounds. I haven’t changed my diet but I have reduced my volume of intake and I seldom feel a craving for sweets. I always wondered why I was so hungry even though I clearly had plenty of energy available in my butt! My body was like, “No, no. We wanna keep that butt fat just in case. Go eat something right now.”
Now, my body is like, “No need to eat anything just now. We can go grab some energy from your butt.”
I do get hungry at mealtime, but I become full and satisfied with much less food.
This drug is so miraculous.
Glad to see more discussion on mechanism of weight loss with GLP-1s.
You may have seen my recent Substack article wherein a patient of mine who tracks his caloric intake and output meticulously found no change in his intake or satiety after initiating semaglutide but lost substantial weight (https://theskepticalcardiologist.substack.com/p/modifying-lifestyle-versus-wegovy?r=1f2oz2)
I referenced your first piece on this in that article.
I also had before and after DEXA scans on him. He lost almost no muscle mass but a ton (not literally) of visceral fat with the semaglutide.
Study of one here but I’ve been on a glp-1 for 4 months and I’ve lost 15% of my body weight. I’m eating more than I had before I started taking glp-1s. I have MCAS so that might have something to do with it, but it’s definitely something other than just appetite suppression going on.
Interesting! I wouldn’t say I’m eating more, but I’m only hungry at mealtime now. I was always hungry before, and all I could think about was resisting food.
Absolutely fascinating!
I have been on the lower-carb bandwagon for about 20 years. Hard to stick to it but otherwise it works well to keep down my glucose, cholesterol, and cravings.
Have been on Ozempic for about a year and am approaching a great weight and have had obvious fat-reduction. Would love to not be on such a strong medication forever. With this study, seems like we would see people on GLPs plateau once they have achieved low body fat. Does that happen? If it’s only appetite suppression, do those on GLPs just kind of waste away?
So much yet to discover!
Hi Sheryl - you might be interested in part 2 of GT’s Diet or Drugs series, where this question is addressed. There does seem to be a point at which weight loss plateaus and appetite resumes on the GLP drugs.
https://open.substack.com/pub/uncertaintyprinciples/p/drugs-or-diet-2-lets-talk-mechanisms?r=pff55&utm_medium=ios
Thank you so much!
I was going to say the same, but Suzie beat me to it. That post is behind a paywall, though. (I can use the paid subscribers...). Hope that's not a problem.
Great questions and a concern for many. There is a natural alternative with no side effects and no need to stop.
No, there fucking is not.
I assume she means something like ketovore or carnivore. It may not be everyone's cup of tea, but it works for a lot of people, which is great for them, just as what is working for you is great for you.
It doesn’t work for most people. About 95 percent of people on any diet regain the weight. These drugs are the only thing that works for most people.
I'm not doing it for weight loss, though I'm down 50lbs which is nice (20 or so to go I suppose). I'm doing it for arthritis, bad joint pain, inflammation, and to heal my gut (which took about a year). I thought I'd have to lose a lot of weight for the joint pain to go away but that happened in days - a total shock, really - so must have been inflammation. Another bonus was food noise going away, which is great, 40 years of that was enough :-) I like eating this way and don't miss anything, so I'll keep doing it. I don't think of it as a diet, it's just what I eat to feel my best.
Then what is it?
So you say lower carb bandwagon, and it’s helped lower cholesterol. I’m confused . Losing weight on a low carb regimen requires you to eat lots of fat. That’s how you create the change in the fuel your body burns. That’s how you will lose weight. So I assume you are not really low carb?
I was speaking broadly about changes that my body has undergone, different ways of eating, different health consequences, over the years since around age 40.
I realized in my early forties that low-carb was key. It was not well-known at the time. I educated myself and observed that my appetite was suppressed and that weight came off relatively easily when eating lower carb.
It’s not that easy to maintain that way of eating though, and one is tempted to eat just a few more potatoes etc and eventually I gained weight again. Also had a very high-stress career.
A random health check when I was 55 shocked me by revealing that I had developed Type II diabetes. Knowing what I know NOW, I would have understood a decade sooner that “low carb” wasn’t just about a better weight, but that the very fact that my body had responded so dramatically to it was a symptom of the fact that I was predisposed to metabolic syndrome. I do not think that I would have developed diabetes if I had continued to eat lower carb.
With the diagnosis, I threw myself into basically a keto diet, and my A1C plummeted, along with my cholesterol. My doctor could literally not believe her eyes when she saw the change over three months.
Fantastic, keep it up. My wife and I in our late 70’s attended a local seminar on longevity. A local physician renowned for his work in this field, came out and said, no grains, no sugar, moderate exercise, lift something heavy, have good social connections and get 8 hrs sleep. This was about 6 years ago, we looked at each other and said we could do that. That was our introduction into the LCHF / Keto community. That together with time restricted eating have changed our lives, not only lost some weight, but primarily all our inflammatory markers are way down, no aches, no pains, great mental clarity, lots of energy, and for us it is the easiest lifestyle ever. So just keep it up, remember to make sure to prioritize fats, I think that’s where a lot of folks struggle, keep the fat intake high.
That’s wonderful, pretty much where we are in terms of goals and strategies. Husband has lost 20 and has set up a nice little gym in the basement to lift. Hope he can lose another 10-15. He eats once a day, after work, typically a strip steak and a very large portion of veggies or salad. I am doing middling on the lower carb stuff.
John, is your confusion about reduction in cholesterol on a low carb, high fat diet? Because this actually happens quite often. Elevated total cholesterol, while not in itself unhealthy, can be a reflection of poor liver health, often due to insulin resistance.
When insulin resistance is corrected via LCHF diet, sometimes this will actually reduce total cholesterol. It happened to me — my TC dropped from 265 to 205 after 6 months of strict keto (<20g net carbs per day), IF and resistance training.
In my experience working with patients, it tends to be the genetically lean who more commonly see cholesterol elevations with LCHF diets.
No, my confusion was with someone claiming to be LCHF and not losing any weight. However your comment was interesting. In my experience most people on either LCHF, Ketogenic, or even Carnivore typically see elevated total cholesterol, in particular LDL. I would also take issue with your comments about elevated cholesterol as a result of regaining insulin sensitivity indicting poor liver health. But perhaps I misunderstood your meaning
The level of "LC" needed to lose weight varies depending on the individual. I can only lose weight if I stick to 20g carbs, maintain on up to 35g and gain if I consume more than 35g. All on no grains, no legumes & no sugar.
Yes, I think you’re misunderstanding my comment — I was explaining how regaining insulin sensitivity could lead to a reduction in cholesterol (either TC, LDL, or both), if the elevated cholesterol was due to poor liver health.
My point was that we can’t always tell whether someone is adhering to a LCHF by their cholesterol levels, as there is variation in blood lipid response per biochemical individuality.
I see it with enough frequency to know it’s not an outlier — LDL and TC reduction, along with HDL increase, with LCHF.
And sadly, I’ve seen plenty of people strictly adhere to a LCHF who are still unable to lose weight. There are many other factors in weight-loss resistance besides carb consumption. This actually aligns with the fuel-partitioning model, as there are myriad hormones involved with that process, beyond insulin alone.
Cholesterol's mostly a red herring, in my understanding.
Additional confounding factor: my blood glucose levels went down IMMEDIATELY after starting Oz.
So does that mean it would be best if I continued on GLPs even if they no longer suppress appetite?
I have to say that I feel so much better being thinner. Was always muscular and slender (5’7”, 135 lbs) until around age forty after having two kids. Still looked and felt great at 145-155. Been averaging about 185 since then, plus developed Type II.
I’m now about 153 lbs and what a joy!
Remember that Dr. Richard Bernstein in his Diabetes Solution (1996?) discussed prescribing Liraglutide (an early glp-1 r/a) to his diabetic patients in order to curb their carbohydrate cravings, which totally supports your theory. Why after all does someone have carbohydrate cravings? Aside from the psychological underpinnings I would argue that it's difficulty in mobilizing energy from fat stores or a tendency to over-store what is consumed rather than using it for energy, an endocrine defect that is remedied by this class of drug. Dr. Bernstein has all the answers.
Thanks Gary for your work and information sharing 👍⛓️🐂🥩✔️
Your point “An important point, though, is that they only measured RER after body weights had plateaued, not during the active weight-loss phase” is contradicted by Figure 3A in the paper which shows the human tirzepatide group to still be actively losing weight at the 18 week mark.
I’ve heard that many people report having lower psychological cravings of all kinds when taking GLP-1s, and that it appears to curb addiction in general. Is that mistaken? It would appear to be at least slightly inconsistent with the idea that the reduced food cravings are purely a result of the body being satiated by existing fat storage.
I think there isn’t just one reason people get fat.
I don’t have an issue with alcohol or shopping for fun etc, so curbing those impulses was not a thing for me. It is for some. Maybe some people do eat their feelings, but I haven’t found that to be accurate for me. Maybe some people did ingest a lot of fast food and soda, but I didn’t. I can’t explain why I was fat, because I did everything “right” generally. And I’ll note I raised two kids with healthy weights, which suggests my cooking habits aren’t to blame. All I know is now I’m more than 60 pounds down and I’m only a touch overweight, and I’m grateful.
So what exactly does this imply for obesity prevention? It's something I worry about since I have kids in a family quite prone to obesity. Other than trying to educate them that it's much easier to maintain a healthy weight than it is to lose it once you've gained more than you should, I'm not really sure what concrete steps I can take to prevent them gaining too much weight in adulthood.
I’m fat but my (grown) kids are not. My son is extremely thin. They grew up eating the exact healthy diet of home- cooked food I myself eat.
I do not have all the answers but I do know the conventional wisdom isn’t wise.
Anyway, on tirzepatide my relationship to food is now quite similar to that of my slender son.