Inhibiting dopamine breakdown reverses obesity WITHOUT caloric restriction

[Mazzle]

OK - I will bite. What can a person do or what sups can I take to reduce serotonin ?

 

[Peatress]

I don’t know anyone either, except my two boys. I never took birth control pills, vaccines (except a tetanus shot around 11 years old), no medicines, and antibiotics a couple of times in my thirties/forties, I quit doing dental x-rays altogether 15 years ago, and before that I would only allow them ever 5 years, because I instinctively knew they weren’t a good thing, handing me a metal blanket while they left the room. I have never had a mammogram, none of it, and I am sixty and in better health than anyone I know. It wasn’t always that way though. I did have issues before discovering Ray Peat’s work, so avoidance is really key, avoidance of many things, even avoiding supplements improved my health. I try to eat as natural as possible and let my body do it’s job sorting things out.,

You see your common sense kicked in early - I waited until I was roasted before I started declining x-rays. Good on you!!!

 

[Rinse & rePeat]

.

You see your common sense kicked in early - I waited until I was roasted before I started declining x-rays. Good on you!!!

i feel for you Peatress. I never bought into the fake margarine is better than butter scam either, though I was raised on margarine in my teen years. It was hard to transition back to butter, but I love it now! I don’t understand how some people think, that lab man-made things are an improvement on how nature intended.

 

[Hans]

As @learnedhelpless also said, cyproheptadine causes weight gain through increased appetite, some of which comes from blocking histamine. Look at the studies in the post about TPH inhbition or selective serotonin blocking (5-HT3, 5-HT2B). They make it quite clear that serotonin is a (perhaps THE) cause of obesity and (as one of the study says) a major part of that effect is through increasing cortisol release and amplifying its effects.
Also, see my response to @Regina directly below. SSRI drugs are known obesogens, when used chronically. And there is this.

Serotonin Levels Linked to Obesity

A certain hormone could be linked to obesity, and that hormone just happens to be serotonin.

www.pharmacytimes.com

Frontiers | Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

Central and peripheral pools of biogenic monoamine serotonin (5-hydroxytryptamine [5HT]) exert opposite effects on the body weight regulation: increase in br...

www.frontiersin.org

"...Results showed that under standard chow diet animals from the high-5HT subline, as compared to low-5HT animals, have lifelong increased body weight (by 12%), higher absolute daily food intake (by 9%), and different pattern of fat distribution (larger amount of white adipose tissue and lower amount of brown adipose tissue). "

I've never been a dogmatic kind of guy. I'd love to find a hack for fat loss that doesn't involve watching calorie intake. I truly do. But unfortunately, things don't work out like that in reality. ...Yes, serotonin drugs do help with fat loss in the short term, and in the long run, cause fat gain (for most people). But that's not primarily due to metabolic destruction. It's due to overeating. Having high endogenous serotonin also doesn't have the exact same effects as taking SSRIs. I personally know of people (including relatives) who have elevated serotonin and have had it for many many years, but rather struggle to gain weight. My grandmother (as one example) is a very busy lady and has to be reminded to eat because she's usually too busy to think of food. So it's very likely that despite high serotonin, she still burns more calories than she consumes.

Here is an animal study:
"Within hours, Flx decreased the activity of a subset of brainstem serotonergic neurons by triggering autoinhibitory signaling through 5-hydroxytryptamine receptor 1a (Htr1a). Following a longer treatment period, Flx blunted 5-hydroxytryptamine receptor 2c (Htr2c) expression and signaling, decreased the phosphorylation of cAMP response element-binding protein (CREB) and STAT3, and dampened the production of pro-opiomelanocortin (POMC, the precursor of α-melanocyte stimulating hormone [α-MSH]) in hypothalamic neurons, thereby increasing food intake." (R)

Serotonin blunts appetite through the 5-HT2C receptor (which also promotes the release of cortisol), but then over time causes desensitization of that receptor, leading to an increase in appetite. Basically, every time it comes down to appetite control.

Animal studies are always nice in theory, but we can never combat human evidence and experience with animal studies alone.

That's why I also have two human studies here, both showing that people who use SSRIs gain weight.
"Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users" (R)
And this one:
"Compared with non-users, high antidepressant users had higher energy intake (9160 vs 8628 kJ/day) and higher Western dietary pattern scores after adjusting for age and gender." (R)
The more they used, the more weight they gained: "The mean annual weight gain was 0.12, 0.18 and 0.28 kg in non-users, low (1–2 prescriptions/year) and high (>2 prescriptions/year) antidepressant users, respectively."

Interestingly: "No association was found between TCA and other antidepressant use and weight gain." (R)

When they boost dopamine and noradrenaline alongside serotonin, no weight gain is seen.

Ultimately, it comes down to controlling calorie intake. My main goal with these messages is to help people not waste years of their lives. Years looking for "the secret hack" for fat loss, when it mainly comes down to controlling calorie intake. I always wanted to believe that there is some "magic sauce" to fat loss and that we can somehow work our way around CICO. And even if certain things can help here and there, the most reliable and dependable way of controlling weight gain, always comes down to calories... and ofc NOT JUST calories, but the quality of those calories.

When I first discovered Peat's work and came on this forum, I also started to believe that serotonin was the bad guy. But the more I did research and the more I worked with clients, the more it became evident that focusing on serotonin alone isn't the solution. In most cases, it's the dysregulation of the serotonin system that causes issues.

I myself have had many health and metabolism problems in the past... have been both underweight and chunky (more than once)... but no matter what, CICO always wins. Even when I was at my very worst state of health (hypothyroid, catabolic, low T, low dopamine, high cortisol, etc.) I didn't just "blow up" (put on weight) because I was still controlling calories.

Years later and I have worked with many men who have had similar health issues (and were overweight), and I've helped them lose that weight by giving them the right kinds of food and providing them with the right guidelines to not overeat and only consume what is necessary. Not once has this method failed, because once the body gets what is required and calories aren't overconsumed, it can't help but lose the excess fat and create a new baseline.

 

[Peatress]

.

i feel for you Peatress. I never bought into the fake margarine is better than butter scam either, though I was raised on margarine in my teen years. It was hard to transition back to butter, but I love it now! I don’t understand how some people think, that lab man-made things are an improvement on how nature intended.

To my shame I came to butter late

 

[Rinse & rePeat]

I've never been a dogmatic kind of guy. I'd love to find a hack for fat loss that doesn't involve watching calorie intake. I truly do. But unfortunately, things don't work out like that in reality. ...Yes, serotonin drugs do help with fat loss in the short term, and in the long run, cause fat gain (for most people). But that's not primarily due to metabolic destruction. It's due to overeating. Having high endogenous serotonin also doesn't have the exact same effects as taking SSRIs. I personally know of people (including relatives) who have elevated serotonin and have had it for many many years, but rather struggle to gain weight. My grandmother (as one example) is a very busy lady and has to be reminded to eat because she's usually too busy to think of food. So it's very likely that despite high serotonin, she still burns more calories than she consumes.

Here is an animal study:
"Within hours, Flx decreased the activity of a subset of brainstem serotonergic neurons by triggering autoinhibitory signaling through 5-hydroxytryptamine receptor 1a (Htr1a). Following a longer treatment period, Flx blunted 5-hydroxytryptamine receptor 2c (Htr2c) expression and signaling, decreased the phosphorylation of cAMP response element-binding protein (CREB) and STAT3, and dampened the production of pro-opiomelanocortin (POMC, the precursor of α-melanocyte stimulating hormone [α-MSH]) in hypothalamic neurons, thereby increasing food intake." (R)

Serotonin blunts appetite through the 5-HT2C receptor (which also promotes the release of cortisol), but then over time causes desensitization of that receptor, leading to an increase in appetite. Basically, every time it comes down to appetite control.

Animal studies are always nice in theory, but we can never combat human evidence and experience with animal studies alone.

That's why I also have two human studies here, both showing that people who use SSRIs gain weight.
"Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users" (R)
And this one:
"Compared with non-users, high antidepressant users had higher energy intake (9160 vs 8628 kJ/day) and higher Western dietary pattern scores after adjusting for age and gender." (R)
The more they used, the more weight they gained: "The mean annual weight gain was 0.12, 0.18 and 0.28 kg in non-users, low (1–2 prescriptions/year) and high (>2 prescriptions/year) antidepressant users, respectively."

Interestingly: "No association was found between TCA and other antidepressant use and weight gain." (R)

When they boost dopamine and noradrenaline alongside serotonin, no weight gain is seen.

Ultimately, it comes down to controlling calorie intake. My main goal with these messages is to help people not waste years of their lives. Years looking for "the secret hack" for fat loss, when it mainly comes down to controlling calorie intake. I always wanted to believe that there is some "magic sauce" to fat loss and that we can somehow work our way around CICO. And even if certain things can help here and there, the most reliable and dependable way of controlling weight gain, always comes down to calories... and ofc NOT JUST calories, but the quality of those calories.

When I first discovered Peat's work and came on this forum, I also started to believe that serotonin was the bad guy. But the more I did research and the more I worked with clients, the more it became evident that focusing on serotonin alone isn't the solution. In most cases, it's the dysregulation of the serotonin system that causes issues.

I myself have had many health and metabolism problems in the past... have been both underweight and chunky (more than once)... but no matter what, CICO always wins. Even when I was at my very worst state of health (hypothyroid, catabolic, low T, low dopamine, high cortisol, etc.) I didn't just "blow up" (put on weight) because I was still controlling calories.

Years later and I have worked with many men who have had similar health issues (and were overweight), and I've helped them lose that weight by giving them the right kinds of food and providing them with the right guidelines to not overeat and only consume what is necessary. Not once has this method failed, because once the body gets what is required and calories aren't overconsumed, it can't help but lose the excess fat and create a new baseline.

Then how do you explain the rat Coke study?

Drinking Coke Freely Quadruples Calorie Intake WITHOUT Weight Gain

The study was designed to actually show that ad libitum consumption of fructose-rich drink like Coke has undesirable changes on some lipid parameters. It did manage to show that rats drinking Coke freely as part of their diet had higher levels of TG. However the cholesterol of the Coke-drinking...

raypeatforum.com

 

[aliml]

...in contrast to the traditional belief, MAO-A and MAO-B have profoundly different roles: MAO-A regulates dopamine levels, whereas MAO-B controls tonic GABA levels.

Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis - PubMed

Monoamine oxidase (MAO) is believed to mediate the degradation of monoamine neurotransmitters, including dopamine, in the brain. Between the two types of MAO, MAO-B has been believed to be involved in dopamine degradation, which supports the idea that the therapeutic efficacy of MAO-B inhibitors...

pubmed.ncbi.nlm.nih.gov

...both MAO-A and MAO-B show an excess of the low-activity genotypes in obese individuals. Additionally, the MAO-A genotype was significantly associated with both weight and BMI.

Obesity is associated with genetic variants that alter dopamine availability - PubMed

Human and animal studies have implicated dopamine in appetite regulation, and family studies have shown that BMI has a strong genetic component. Dopamine availability is controlled largely by three enzymes: COMT, MAOA and MAOB, and by the dopamine transporter SLC6A3, and each gene has a...

pubmed.ncbi.nlm.nih.gov

 

[Herbie]

@Hans I lost 4kgs last summer only thing that changed in my life was lisuride. (one bottle in one month)

 

[Hans]

@Hans I lost 4kgs last summer only thing that changed in my life was lisuride. (one bottle in one month)

Thanks for sharing. Have you been tracking your diet intake (weighing and measuring) and energy expenditure before and after the use of lisuride?

 

[Elie]

@Hans I lost 4kgs last summer only thing that changed in my life was lisuride. (one bottle in one month)

Other than weight loss, have you noted other changes?

 

[Herbie]

@Hans No I don't track anything but I know that my diet was the same before and after. I put the 4kgs back on after stopping so it's just from lisuride. I thought about it heaps and realised that is why it occurred.

Imo, Cyproheptadine makes people lazy and stupid where lisuride makes people more adventurous and curious so that they do more like you said.

 

[ecstatichamster]

@Hans I lost 4kgs last summer only thing that changed in my life was lisuride. (one bottle in one month)

what was it? Eating less? diminished appetite? Metabolic advantage?

 

[TAG145]

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.

Hi! I was Searching prior posts about starch & you mentioned you were going to try no starch years back because you wanted to lose some weight. How did you transition to your current high starch way of eating? What do you eat now? Just wondering about your process that helped you lose weight. Thank you

 

[ecstatichamster]

Hi! I was Searching prior posts about starch & you mentioned you were going to try no starch years back because you wanted to lose some weight. How did you transition to your current high starch way of eating? What do you eat now? Just wondering about your process that helped you lose weight. Thank you

minimize sugar. I drink coconut water with a little juice. I eat fruit. Use a little sugar in coffee. But that is all the sugar. The rest of my diet is mostly white rice and masa harina. Some cheese and milk. A bit of muscle meat.

 

[apr]

minimize sugar. I drink coconut water with a little juice. I eat fruit. Use a little sugar in coffee. But that is all the sugar. The rest of my diet is mostly white rice and masa harina. Some cheese and milk. A bit of muscle meat.

Is it low fat? Butter on rice? Low fat milk?

 

[Runenight201]

@Hans No I don't track anything but I know that my diet was the same before and after. I put the 4kgs back on after stopping so it's just from lisuride. I thought about it heaps and realised that is why it occurred.

Imo, Cyproheptadine makes people lazy and stupid where lisuride makes people more adventurous and curious so that they do more like you said.

How much did you use per application? I’m assuming topically?

Idk about “lazy and stupid” and in fact that whole paragraphs language is too speculatively opinionated but I will say that when I took Cypro it did hardcore make me super drowsy so it’s probably best suited for specific applications (someone with pathologically high serotonin which is wreaking havoc on their physiology) and not for those who need to be engaged in high energy mentally/physically demanding tasks.

 

[Pete Rey]

When I was young, I didn't understand anything about food or stress. I was fed McDonalds at least 3x/week. So when I went to college 20 years ago, I kept eating nothing but junk food, and started drinking beer, and quickly put on 20 lbs. Once I got through that phase and moved off campus, I committed to getting lean and started fasting. I wanted a flat belly like many of the kids I grew up with, or almost every young man in videos from the 1950s. I ate once a day, still junk food, and starved myself down to 145lbs (5'10"). It got to the point where I was getting comments on my face looking like a skeleton. I had become frail and yet...I still had a gut! At age 22! And I still do to this day at 39. Not a huge one, just puffy. I only quit and let myself come back to my natural 180lbs because I realized it was pointless. I did it one more time when I discovered keto at age 27 with the exact same result. Seems to me this is all in line with the Minnesota experiment.

That's when I realized that losing weight and getting lean are not the same thing. We all want better health, and we have empirical evidence that generationally that has been worsening, so that tells me it can't just be the calories. Cutting calories and moving more will lead to weight loss, but I'm convinced that getting lean is something only a metabolically healthy person can do. Which is why people on here swear by their experience, whether it be high starch, high protein, low vitamin A, the usual RP recommendations, etc., and others see no difference with any of it. Some of us are just digging out of a much deeper hole which we may never fully get out of, but if someone offers us a backhoe instead of a shovel, naturally we're going to be interested in that.

 

[Rinse & rePeat]

When I was young, I didn't understand anything about food or stress. I was fed McDonalds at least 3x/week. So when I went to college 20 years ago, I kept eating nothing but junk food, and started drinking beer, and quickly put on 20 lbs. Once I got through that phase and moved off campus, I committed to getting lean and started fasting. I wanted a flat belly like many of the kids I grew up with, or almost every young man in videos from the 1950s. I ate once a day, still junk food, and starved myself down to 145lbs (5'10"). It got to the point where I was getting comments on my face looking like a skeleton. I had become frail and yet...I still had a gut! At age 22! And I still do to this day at 39. Not a huge one, just puffy. I only quit and let myself come back to my natural 180lbs because I realized it was pointless. I did it one more time when I discovered keto at age 27 with the exact same result. Seems to me this is all in line with the Minnesota experiment.

That's when I realized that losing weight and getting lean are not the same thing. We all want better health, and we have empirical evidence that generationally that has been worsening, so that tells me it can't just be the calories. Cutting calories and moving more will lead to weight loss, but I'm convinced that getting lean is something only a metabolically healthy person can do. Which is why people on here swear by their experience, whether it be high starch, high protein, low vitamin A, the usual RP recommendations, etc., and others see no difference with any of it. Some of us are just digging out of a much deeper hole which we may never fully get out of, but if someone offers us a backhoe instead of a shovel, naturally we're going to be interested in that.

This that you said is exactly right Rey, and I keep saying it, losing pounds does equal healthy or even look good eventually. Losing fat in a healthy way eating is the way to go. Like Ray Peat said back off fat and starches and the weight comes off without worrying about the calories. I can wear the same outfit with a twenty pound difference, where the lower weight I lost fat AND muscle and the higher weight I lost just the fat. I show my proof in this long ago thread (linked below) I posted when I first joined this forum. I have lost pounds successfully so many ways, but each came with a negative trade off. Since losing weight per Ray Peat I lost all the fat I wanted and have continually reaped more benefits sticking with it, and I haven’t been to the gym in 30+ years.

Lose Fat Not Pounds & Seeing Is Believing (before & after pics)

"In one of the studies in which rats had been taught learned helplessness so they would drown in five or six minutes, just being able to see another rat escape would let the informed rat go for days without drowning. Just the recognition that someone else did it can make all the difference." Ray...

raypeatforum.com

 

[Pete Rey]

This that you said is exactly right Rey, and I keep saying it, losing pounds does equal healthy or even look good eventually. Losing fat in a healthy way eating is the way to go. Like Ray Peat said back off fat and starches and the weight comes off without worrying about the calories. I can wear the same outfit with a twenty pound difference, where the lower weight I lost fat AND muscle and the higher weight I lost just the fat. I show my proof in this long ago thread (linked below) I posted when I first joined this forum. I have lost pounds successfully so many ways, but each came with a negative trade off. Since losing weight per Ray Peat I lost all the fat I wanted and have continually reaped more benefits sticking with it, and I haven’t been to the gym in 30+ years.

Lose Fat Not Pounds & Seeing Is Believing (before & after pics)

"In one of the studies in which rats had been taught learned helplessness so they would drown in five or six minutes, just being able to see another rat escape would let the informed rat go for days without drowning. Just the recognition that someone else did it can make all the difference." Ray...

raypeatforum.com

I will say that I've been eating quite Peaty the past few years, with the exception of rice. Low fat in general and no PUFA other than what naturally occurs in animal sources. I even do the frozen OJ thing (which has recently gotten a lot more expensive!). And I do feel better than ever on it. RP has offered by far the best dietary advice in that regard. But in terms of body composition, there's no real difference. Which is fine by me. A flat belly is not as important to me at 39 as it was at 20. Maybe after a few more years of PUFA depletion I will see a difference, but I'm not holding my breath. I have at least 2 permanent health problems - autism and fluorosis (adult teeth came in brown at age 7), so it would not surprise me if other aspects of my health were also permanent. But a part of me obviously still hopes to be pleasantly surprised one day!

And I should also add to the CICO point, that for at least a time in my life I was no slacker on the movement part of the equation - I maintained a 405lb deadlift and 315lb back squat for several years.

 

[Mauritio]

Thanks for the links.

I'm not gonna send them to a family member this time. Said family member has had anorexia for 5 decades. Dr put her on SSRI's.
She's now a skeleton. It's hopeless.
The bone loss is scary.

Ever tried cyproheptadine? Its safe and increases apetite.