Inhibiting dopamine breakdown reverses obesity WITHOUT caloric restriction

[haidut]

Yet another study showing that the dogma we have been fed for decades - eat less and move more - is little more than a fraudulent lie. Recent studies have already demonstrated that chronic caloric restriction changes body composition for the worse - i.e. despite the weight loss, most of that weight loss is lean muscle mass and is also accompanied by a dramatic drop in the resting metabolic rate (RMR). The contest aptly named "The Biggest Loser" is perhaps the best example of what happens when somebody chronically fasts and exercises at the same time. Those poor people not only regained all the weight they lost during the contest, but felt completely miserable afterwards and found themselves gaining even more weight on a caloric intake that was up to 50% lower than what they were eating before the contest. That, of course, is the guaranteed outcome when their RMR had dropped by about 50%, as a result of participation in the contest. Other human studies with less restrictive regimens demonstrated similarly (proportionally to the restrictiveness of the regimen) alarming results in regards to lean muscle loss, insomnia, cognitive dysfunction, mood changes, etc that can all be traced back to the elevated baseline cortisol that the dogma "eat less, more more" invariably leads to. So, if fasting and torturing ourselves is not the path to slimness and health then what is? Well, if we accept that obesity is an endocrine/metabolic disorder then measures to increase RMR and change the endocrine profile away from stress would be beneficial. One of the main mediators of stress is serotonin. In fact, it is serotonin that is perhaps the major controller of cortisol release (through the 5-HT2C receptor). There are multiple ongoing human studies with drugs that inhibit the synthesis of serotonin - tryptophan hydroxylase (TPH) inhibitors - or drugs that block serotonin at the receptor level, and those have shown great promise so far not only for obesity, but for diabetes, heart disease and even neurological disorders. In other words, serotonin is obesogenic and it induces those effects by lowering of the RMR. Here is just a small list of such studies, for the people who still believe serotonin is the "happy hormone".

Inhibiting serotonin reverses obesity - Nature Reviews Drug Discovery
Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease
Regulation of systemic energy homeostasis by serotonin in adipose tissues - PubMed
Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis - PubMed
Peripheral Selective Oxadiazolylphenyl Alanine Derivatives as Tryptophan Hydroxylase 1 Inhibitors for Obesity and Fatty Liver Disease - PubMed
Serotonin Regulates De Novo Lipogenesis in Adipose Tissues through Serotonin Receptor 2A
Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance
JCI - Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance
Pharmacologic inhibition of serotonin htr2b ameliorates hyperglycemia and the altered expression of hepatic FGF21, Sdf2l1, and htr2a in db/db mice and KKAy mice
Single or combined ablation of peripheral serotonin and p21 limit adipose tissue expansion and metabolic alterations in early adulthood in mice fed a normocaloric diet
https://onlinelibrary.wiley.com/doi/full/10.1111/jdi.12406

Coincidentally (or not) the recent large study refuting the "serotonin hypothesis" in depression stated the exact same thing as the findings of the Biggest Loser contest - i.e. serotonin has nothing to do with happiness, its main role is as a (negative) metabolic regulator and if it has a role in depression it must be a negative role (i.e. it causes, not relieves depression) due to lowering energy levels in the brain. But I digress, so back to weight loss and obesity. Assuming serotonin is obesogenic then what is the mechanism for its endogenous control? There must be some mechanism through which healthy people manage to keep serotonin in check and thus stay lean/healthy without dieting/exercising. Older studies from the 60s and 70s of the past century suggest that the main endogenous antagonist of serotonin is the neurotransmitter dopamine - the one we are told leads to impulsiveness, instability and craziness. You see, that "crazy" dopamine just so happens to be a potent TPH inhibitor as well, while serotonin happens to be an inhibitor of the dopamine-synthesizing enzyme tyrosine hydroxylase.

https://www.sciencedirect.com/science/article/abs/pii/0006295294902437
Dopamine Inactivates Tryptophan Hydroxylase and Forms a Redox-Cycling Quinoprotein: Possible Endogenous Toxin to Serotonin Neurons
Inhibition of tyrosine hydroxylase activity by serotonin in explants of newborn rat locus ceruleus - PubMed
Serotonin 5-HT1A receptors mediate inhibition of tyrosine hydroxylation in rat striatum - PubMed

So, serotonin and dopamine are largely antagonistic to each other and their levels are inversely correlated. The latter fact has already been confirmed in humans, and it is also well-known that obese people have lower baseline dopamine levels. In light of all those relationships one could surmise that elevating dopamine levels may be beneficial for obesity, by lowering serotonin and thus raising the RMR. While raising dopamine by supplying precursors such as L-DOPA has been used for decades to treat Parkinson Disease (PD), such treatments quickly lose effectiveness and thus the pharma industry started looking at alternative solutions such as inhibiting the breakdown of dopamine by blocking the dopamine-degrading enzyme monoamine oxidase type B (MAO-B). One of the oldest drugs in clinical use for PD is exactly such an MAO-B blocker under the name of selegiline/Deprenyl. That drug is already notorious for being able to delay aging and protect from chronic disease, and it is widely used by celebrities and politicians around the world as an anti-aging and life-extension drug. Well, if the findings of the study below are legit that drug will soon become an even bigger blockbuster. Namely, the study found that using a novel, patented (though identical in pharmacology to selegiline) MAO-B inhibitor lead to increase in thermogenesis/uncopling (and thus RMR), which led to loss of weight without any changes in caloric intake or exercise regimen. According to the study, the MAO-B inhibitor achieved those effects by lowering GABA levels in astrocytes (since MAO-B also synthesizes GABA), but I do not agree with that explanation and maintain that it is the lowering of serotonin by increasing dopamine (through MAO-B) that was the main mechanism of anti-obesity action in this study. Regardless of my opinion, the main takeaway (in the study's own words) is that MAO-B inhibition is a viable mechanism for reversing obesity even on highly obesogenic diet.

@ecstatichamster

Hypothalamic GABRA5-positive neurons control obesity via astrocytic GABA - PubMed
A new breakthrough in obesity research allows you to lose fat while eating all you want

"...In a diet-induced obese mouse model, the researchers observed significant slowing in the pacemaker firing of the GABRA5 neurons. Researchers continued with the study by attempting to inhibit the activity of these GABRA5 neurons using chemogenetic methods. This in turn caused a reduction in heat production (energy consumption) in the brown fat tissue, leading to fat accumulation and weight gain. On the other hand, when the GABRA5 neurons in the hypothalamus were activated, the mice were able to achieve a successful weight reduction. This suggests that the GABRA5 neurons may act as a switch for weight regulation. In a new surprising and unexpected turn of events, the research team discovered that the astrocytes in the lateral hypothalamus regulate the activity of the GABRA5 neurons. The numbers and sizes of the reactive astrocytes are increased, and they begin to overexpress the MAO-B enzyme (Monoamine Oxidase B). This enzyme plays a crucial role in the metabolism of neurotransmitters in the nervous system and is more predominantly expressed in reactive astrocytes. This ends up in the production of a large amount of tonic GABA (Gamma-Aminobutyric Acid), which inhibits the surrounding GABRA5 neurons. It was also discovered that suppressing the expression of the MAO-B gene in reactive astrocytes can decrease GABA secretion, thereby reversing the undesirable inhibition of the GABRA5 neurons. Using this approach the researchers were able to increase the heat production in the fat tissue of the obese mice, which allowed them to achieve weight loss even while consuming a high-calorie diet. This experimentally proves that the MAO-B enzyme in reactive astrocytes can be an effective target for obesity treatment without compromising appetite. Furthermore, a selective and reversible MAO-B inhibitor, 'KDS2010', which was transferred to a biotech company Neurobiogen in 2019 and is currently undergoing Phase 1 clinical trials, was tested on an obese mouse model. The new drugs yielded remarkable results, demonstrating a substantial reduction in fat accumulation and weight without any impacts on the amount of food intake."

 

[Hans]

1. A caloric deficit only changes body recomp for the worse if someone doesn't lift and eat enough protein.

2. If serotonin was the cause of weight gain, people would drop lots of weight on cyproheptadine, which just doesn't happen.

3. Dopamine does help with fat loss primarily because people eat less and move more.

 

[Regina]

Yet another study showing that the dogma we have been fed for decades - eat less and move more - is little more than a fraudulent lie. Recent studies have already demonstrated that chronic caloric restriction changes body composition for the worse - i.e. despite the weight loss, most of that weight loss is lean muscle mass and is also accompanied by a dramatic drop in the resting metabolic rate (RMR). The contest aptly named "The Biggest Loser" is perhaps the best example of what happens when somebody chronically fasts and exercises at the same time. Those poor people not only regained all the weight they lost during the contest, but felt completely miserable afterwards and found themselves gaining even more weight on a caloric intake that was up to 50% lower than what they were eating before the contest. That, of course, is the guaranteed outcome when their RMR had dropped by about 50%, as a result of participation in the contest. Other human studies with less restrictive regimens demonstrated similarly (proportionally to the restrictiveness of the regimen) alarming results in regards to lean muscle loss, insomnia, cognitive dysfunction, mood changes, etc that can all be traced back to the elevated baseline cortisol that the dogma "eat less, more more" invariably leads to. So, if fasting and torturing ourselves is not the path to slimness and health then what is? Well, if we accept that obesity is an endocrine/metabolic disorder then measures to increase RMR and change the endocrine profile away from stress would be beneficial. One of the main mediators of stress is serotonin. In fact, it is serotonin that is perhaps the major controller of cortisol release (through the 5-HT2C receptor). There are multiple ongoing human studies with drugs that inhibit the synthesis of serotonin - tryptophan hydroxylase (TPH) inhibitors - or drugs that block serotonin at the receptor level, and those have shown great promise so far not only for obesity, but for diabetes, heart disease and even neurological disorders. In other words, serotonin is obesogenic and it induces those effects by lowering of the RMR. Here is just a small list of such studies, for the people who still believe serotonin is the "happy hormone".

Inhibiting serotonin reverses obesity - Nature Reviews Drug Discovery
Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease
Regulation of systemic energy homeostasis by serotonin in adipose tissues - PubMed
Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis - PubMed
Peripheral Selective Oxadiazolylphenyl Alanine Derivatives as Tryptophan Hydroxylase 1 Inhibitors for Obesity and Fatty Liver Disease - PubMed
Serotonin Regulates De Novo Lipogenesis in Adipose Tissues through Serotonin Receptor 2A
Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance
JCI - Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance
Pharmacologic inhibition of serotonin htr2b ameliorates hyperglycemia and the altered expression of hepatic FGF21, Sdf2l1, and htr2a in db/db mice and KKAy mice
Single or combined ablation of peripheral serotonin and p21 limit adipose tissue expansion and metabolic alterations in early adulthood in mice fed a normocaloric diet
https://onlinelibrary.wiley.com/doi/full/10.1111/jdi.12406

Coincidentally (or not) the recent large study refuting the "serotonin hypothesis" in depression stated the exact same thing as the findings of the Biggest Loser contest - i.e. serotonin has nothing to do with happiness, its main role is as a (negative) metabolic regulator and if it has a role in depression it must be a negative role (i.e. it causes, not relieves depression) due to lowering energy levels in the brain. But I digress, so back to weight loss and obesity. Assuming serotonin is obesogenic then what is the mechanism for its endogenous control? There must be some mechanism through which healthy people manage to keep serotonin in check and thus stay lean/healthy without dieting/exercising. Older studies from the 60s and 70s of the past century suggest that the main endogenous antagonist of serotonin is the neurotransmitter dopamine - the one we are told leads to impulsiveness, instability and craziness. You see, that "crazy" dopamine just so happens to be a potent TPH inhibitor as well, while serotonin happens to be an inhibitor of the dopamine-synthesizing enzyme tyrosine hydroxylase.

https://www.sciencedirect.com/science/article/abs/pii/0006295294902437
Dopamine Inactivates Tryptophan Hydroxylase and Forms a Redox-Cycling Quinoprotein: Possible Endogenous Toxin to Serotonin Neurons
Inhibition of tyrosine hydroxylase activity by serotonin in explants of newborn rat locus ceruleus - PubMed
Serotonin 5-HT1A receptors mediate inhibition of tyrosine hydroxylation in rat striatum - PubMed

So, serotonin and dopamine are largely antagonistic to each other and their levels are inversely correlated. The latter fact has already been confirmed in humans, and it is also well-known that obese people have lower baseline dopamine levels. In light of all those relationships one could surmise that elevating dopamine levels may be beneficial for obesity, by lowering serotonin and thus raising the RMR. While raising dopamine by supplying precursors such as L-DOPA has been used for decades to treat Parkinson Disease (PD), such treatments quickly lose effectiveness and thus the pharma industry started looking at alternative solutions such as inhibiting the breakdown of dopamine by blocking the dopamine-degrading enzyme monoamine oxidase type B (MAO-B). One of the oldest drugs in clinical use for PD is exactly such an MAO-B blocker under the name of selegiline/Deprenyl. That drug is already notorious for being able to delay aging and protect from chronic disease, and it is widely used by celebrities and politicians around the world as an anti-aging and life-extension drug. Well, if the findings of the study below are legit that drug will soon become an even bigger blockbuster. Namely, the study found that using a novel, patented (though identical in pharmacology to selegiline) MAO-B inhibitor lead to increase in thermogenesis/uncopling (and thus RMR), which led to loss of weight without any changes in caloric intake or exercise regimen. According to the study, the MAO-B inhibitor achieved those effects by lowering GABA levels in astrocytes (since MAO-B also synthesizes GABA), but I do not agree with that explanation and maintain that it is the lowering of serotonin by increasing dopamine (through MAO-B) that was the main mechanism of anti-obesity action in this study. Regardless of my opinion, the main takeaway (in the study's own words) is that MAO-B inhibition is a viable mechanism for reversing obesity even on highly obesogenic diet.

@ecstatichamster

Hypothalamic GABRA5-positive neurons control obesity via astrocytic GABA - PubMed
A new breakthrough in obesity research allows you to lose fat while eating all you want

"...In a diet-induced obese mouse model, the researchers observed significant slowing in the pacemaker firing of the GABRA5 neurons. Researchers continued with the study by attempting to inhibit the activity of these GABRA5 neurons using chemogenetic methods. This in turn caused a reduction in heat production (energy consumption) in the brown fat tissue, leading to fat accumulation and weight gain. On the other hand, when the GABRA5 neurons in the hypothalamus were activated, the mice were able to achieve a successful weight reduction. This suggests that the GABRA5 neurons may act as a switch for weight regulation. In a new surprising and unexpected turn of events, the research team discovered that the astrocytes in the lateral hypothalamus regulate the activity of the GABRA5 neurons. The numbers and sizes of the reactive astrocytes are increased, and they begin to overexpress the MAO-B enzyme (Monoamine Oxidase B). This enzyme plays a crucial role in the metabolism of neurotransmitters in the nervous system and is more predominantly expressed in reactive astrocytes. This ends up in the production of a large amount of tonic GABA (Gamma-Aminobutyric Acid), which inhibits the surrounding GABRA5 neurons. It was also discovered that suppressing the expression of the MAO-B gene in reactive astrocytes can decrease GABA secretion, thereby reversing the undesirable inhibition of the GABRA5 neurons. Using this approach the researchers were able to increase the heat production in the fat tissue of the obese mice, which allowed them to achieve weight loss even while consuming a high-calorie diet. This experimentally proves that the MAO-B enzyme in reactive astrocytes can be an effective target for obesity treatment without compromising appetite. Furthermore, a selective and reversible MAO-B inhibitor, 'KDS2010', which was transferred to a biotech company Neurobiogen in 2019 and is currently undergoing Phase 1 clinical trials, was tested on an obese mouse model. The new drugs yielded remarkable results, demonstrating a substantial reduction in fat accumulation and weight without any impacts on the amount of food intake."

Thanks for these insights and links.

My only thought, some what akin to Han's reply, is that the most serotonergic people I know are super skinny.

 

[learnedhelpless]

2. If serotonin was the cause of weight gain, people would drop lots of weight on cyproheptadine, which just doesn't happen.

Serotonin and histamine are huge appetite suppressants, so when you block it, you will gain appetite. This leads people to eat more than they are expending, causing weight gain. Cyproheptadine is prescribed in numerous countries, for appetite issues. We really only see this will cyproheptadine / other anti histamines. TPH inhibitors, pure serotonin antagonists do not have this effect, and really have the opposite effect - weight loss. Histamine is involved in insulin sensitivity, as you have posted before on your blog, so I don't see why you are using an antihistamine to prove a point about serotonin.

 

[Hans]

Serotonin and histamine are huge appetite suppressants, so when you block it, you will gain appetite. This leads people to eat more than they are expending, causing weight gain. Cyproheptadine is prescribed in numerous countries, for appetite issues. We really only see this will cyproheptadine / other anti histamines. TPH inhibitors, pure serotonin antagonists do not have this effect, and really have the opposite effect - weight loss. Histamine is involved in insulin sensitivity, as you have posted before on your blog, so I don't see why you are using an antihistamine to prove a point about serotonin.

Let's use metergoline or lisuride as examples then. There are no success stories with them either. Using collagen (which lowers serotonin production) also doesn't help with fat loss.

The serotonergic system is much more complex and there are a lot of nuance; some people have normal to high serotonin and they struggle to gain weight and vice versa. There are 14 known receptors of serotonin and each has a different function and response in the body (all of which are important).

Yes, excess serotonin is bad, but the answer isn't to try and abolish it. In my experience, (working with clients and looking at their labs) the ratio of dopamine to serotonin is more important than looking at serotonin alone.

Another similar example is estrogen. Estrogen is not a problem (and in fact necessary for male health) AS LONG AS it's balanced with high androgens (high T and DHT).

 

[ecstatichamster]

Let's use metergoline or lisuride as examples then. There are no success stories with them either. Using collagen (which lowers serotonin production) also doesn't help with fat loss.

The serotonergic system is much more complex and there are a lot of nuance; some people have normal to high serotonin and they struggle to gain weight and vice versa. There are 14 known receptors of serotonin and each has a different function and response in the body (all of which are important).

Yes, excess serotonin is bad, but the answer isn't to try and abolish it. In my experience, (working with clients and looking at their labs) the ratio of dopamine to serotonin is more important than looking at serotonin alone.

Another similar example is estrogen. Estrogen is not a problem (and in fact necessary for male health) AS LONG AS it's balanced with high androgens (high T and DHT).

There is an inverse relationship between prolactin and dopamine, and perhaps things like cyproheptadine raises prolactin and lowers dopamine even though it may lower serotonin, and that may block serotonin-lowering effects on weight.

 

[learnedhelpless]

Let's use metergoline or lisuride as examples then. There are no success stories with them either. Using collagen (which lowers serotonin production) also doesn't help with fat loss.

The serotonergic system is much more complex and there are a lot of nuance; some people have normal to high serotonin and they struggle to gain weight and vice versa. There are 14 known receptors of serotonin and each has a different function and response in the body (all of which are important).

Yes, excess serotonin is bad, but the answer isn't to try and abolish it. In my experience, (working with clients and looking at their labs) the ratio of dopamine to serotonin is more important than looking at serotonin alone.

Another similar example is estrogen. Estrogen is not a problem (and in fact necessary for male health) AS LONG AS it's balanced with high androgens (high T and DHT).

Metergoline increased food intake at 1, 3, and 6 months postoperatively by up to 45% again, they all increase food intake. I have yet to see an experiment, where food intake was controlled. Given that all the anti serotonin drugs improve metabolic measures, it is hard to say that serotonin is not a metabolic inhibitor.

 

[Hans]

Metergoline increased food intake at 1, 3, and 6 months postoperatively by up to 45% again, they all increase food intake.

The increased food intake is a good thing in that scenario because after an operation, appetite is low and that can slow recovery.

I have yet to see an experiment, where food intake was controlled.

Yes exactly, that's the point. In the real world, food intake is not controlled. People don't want to control their food intake. That's why there is an obesity pandemic.

Given that all the anti serotonin drugs improve metabolic measures, it is hard to say that serotonin is not a metabolic inhibitor.

Yes I get it. Excess serotonin is bad. I agree. But when it comes to fat loss, talking about blocking serotonin and boosting dopamine is a "scapegoat" not to control food intake. Anyone who wants to get lean must do some form of portion control (conscious or subconcious).

 

[Hans]

There is an inverse relationship between prolactin and dopamine, and perhaps things like cyproheptadine raises prolactin and lowers dopamine even though it may lower serotonin, and that may block serotonin-lowering effects on weight.

Trust me, I've also done everything possible not to limit food intake. I've researched the hell out of all the hormones and drugs, etc, etc. Ultimately it came down to...if you want to be lean, eat less and/or move more.

 

[ecstatichamster]

Trust me, I've also done everything possible not to limit food intake. I've researched the hell out of all the hormones and drugs, etc, etc. Ultimately it came down to...if you want to be lean, eat less and/or move more.

i found that I didn't lose fat until I went on a high starch diet, and now it's easy to regulate. I think it controlled my cortisol and really was wonderful.

 

[learnedhelpless]

The increased food intake is a good thing in that scenario because after an operation, appetite is low and that can slow recovery.

Yes exactly, that's the point. In the real world, food intake is not controlled. People don't want to control their food intake. That's why there is an obesity pandemic.

Yes I get it. Excess serotonin is bad. I agree. But when it comes to fat loss, talking about blocking serotonin and boosting dopamine is a "scapegoat" not to control food intake. Anyone who wants to get lean must do some form of portion control (conscious or subconcious).

The eat less move more rule is not sustainable. Nearly all diets are based off that and is why 80% of the people trying them fail. If you do stick to it, you are basically forcing yourself to adapt to low calories, as you will have to constantly lower your diet, to keep on having to lose weight. Hence, the metabolic rate drops, which creates a bunch of issues.

 

[Hans]

i found that I didn't lose fat until I went on a high starch diet, and now it's easy to regulate. I think it controlled my cortisol and really was wonderful.

There are so many different dietary styles out there so it's good you found something that works for you. I've just always had a big appetite. My diet (and I've tried a lot of variation) works well for my appetite, but I'd just like to eat more...but then I get fat. It's just what it is.

 

[Hans]

The eat less move more rule is not sustainable. Nearly all diets are based off that and is why 80% of the people trying them fail. If you do stick to it, you are basically forcing yourself to adapt to low calories, as you will have to constantly lower your diet, to keep on having to lose weight. Hence, the metabolic rate drops, which creates a bunch of issues.

I don't agree with that. When I was in college I was naturally lean. Didn't try at all and was sub 10% BF. Later on, I realized that I was lean because I was a poor student and didn't have much money for food. So I just didn't eat much. I didn't have any issues either. Only after I started making money and was able to eat more did I realize I needed to check myself. If no one "checks" themselves, they'll gain fat. In some rare circumstances, someone has a very fast metabolic rate and they struggle to gain weight. But that's the exception.

 

[learnedhelpless]

I don't agree with that. When I was in college I was naturally lean. Didn't try at all and was sub 10% BF. Later on, I realized that I was lean because I was a poor student and didn't have much money for food. So I just didn't eat much. I didn't have any issues either. Only after I started making money and was able to eat more did I realize I needed to check myself. If no one "checks" themselves, they'll gain fat. In some rare circumstances, someone has a very fast metabolic rate and they struggle to gain weight. But that's the exception.

Yes I agree, people that are lean don't necessarily eat alot, but trying to replicate that with restricting food in obese people does not work, as shown with the 80% of diet statistic failing.

 

[Runenight201]

I don't agree with that. When I was in college I was naturally lean. Didn't try at all and was sub 10% BF. Later on, I realized that I was lean because I was a poor student and didn't have much money for food. So I just didn't eat much. I didn't have any issues either. Only after I started making money and was able to eat more did I realize I needed to check myself. If no one "checks" themselves, they'll gain fat. In some rare circumstances, someone has a very fast metabolic rate and they struggle to gain weight. But that's the exception.

Doesn’t the metabolic rate drop with age? Not to mention that the younger you are the more resilient to stress, whereas with aging youth hormones naturally decline and stress hormones stay chronically elevated. This is all going to make it harder to do “whatever” and stay lean as someone ages. I recall Dr. Attia state that when he was younger he was consumed a ridiculous amount of calories and never gained a pound.

Another factor also is that stress in any form, is going to raise cortisol, which is going to trigger people to want to eat to lower it, which in turn will put on weight. This is actually probably a good thing as it means that cortisol won’t stay elevated and wreak havoc on the body. If someone has raised cortisol and then doesn’t handle it somehow, it’s going to cause disease.

So really I believe the eat less and move more mentality should really be replaced with, stress less and eat mindfully.

And there’s all sorts of ways someone can stress less from realizing their androgens, raising dopamine, taking cortisol/estrogen antagonists, etc… etc…

 

[ecstatichamster]

The eat less move more rule is not sustainable. Nearly all diets are based off that and is why 80% of the people trying them fail. If you do stick to it, you are basically forcing yourself to adapt to low calories, as you will have to constantly lower your diet, to keep on having to lose weight. Hence, the metabolic rate drops, which creates a bunch of issues.

I found that cortisol control is super important. I also normalized my metabolic rate. The two together resulted in very substantial fat loss while preserving lean mass. I think sugar is very hard to use for fat loss, so it has to be starch. This may be the point of view of a man who isn't 20 years old anymore, but it has been the experience of many men I work with. Same thing. Starch and lowish fat and lowish protein along with normalizing metabolic rate creates easy fat loss.

 

[Hans]

Yes I agree, people that are lean don't necessarily eat alot, but trying to replicate that with restricting food in obese people does not work, as shown with the 80% of diet statistic failing.

Only because they don't know what they're doing or don't know how to troubleshoot when they run into problems. If you don't know anything about business, changes are you'll quit pretty soon.

 

[Peatful]

I found that cortisol control is super important. I also normalized my metabolic rate. The two together resulted in very substantial fat loss while preserving lean mass. I think sugar is very hard to use for fat loss, so it has to be starch. This may be the point of view of a man who isn't 20 years old anymore, but it has been the experience of many men I work with. Same thing. Starch and lowish fat and lowish protein along with normalizing metabolic rate creates easy fat loss.

If cortisol is up- that is thyroid suppressing for sure.
Just terrible hormonally and metabolically.

What is your daily kcal?
What macro ratios?



Im a starch addict btw
Lean
Big eater

 

[PopSocket]

Anything that raises cortisol and prolactin/lower dopamine/ causes fat and water gain, puffy face, hair loss and crappy skin. I suspect many people in the Peat world do not realize they are hyper sensitive to coffee and the metabolic boost (if it occurs) cannot override the cortisol increase. Then they wonder why they have central obesity even though they consume no pufa.

 

[learnedhelpless]

Only because they don't know what they're doing or don't know how to troubleshoot when they run into problems. If you don't know anything about business, changes are you'll quit pretty soon.

Most of the diet tricks, like high protein, saturated fats, limited pufa, help weight loss, as they increase the metabolic rate. So indirectly, improving fat loss by these things, comes down to increasing the metabolic rate, not by increasing calorie restriction.