Inhibiting dopamine breakdown reverses obesity WITHOUT caloric restriction

[Nik665]

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.

This!

 

[LLight]

Does an hibernating bear suffers from metabolic downregulation from fasting?

 

[Nik665]

@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.

Sounds like increased calorie expenditure

 

[Aad]

Eat less overall, eat more protein and walk more, preferably within two hours after you wake up.

That's it.

 

[Nik665]

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

But do you exercise

 

[learnedhelpless]

Another study compared The Biggest Loserparticipants’ weight loss with gastric bypass (Roux-en-Y) patients about six months after surgery and found something surprising.

• The two groups lost a comparable amount of weight in half a year, but the gastric bypass patients experienced half the metabolic adaptation.
• After a full 12 months, and after losing even more weight, the gastric bypass group had a very slightly higher metabolism than predicted (+8 calories per day).
• What’s more, the gastric bypass group didn’t lose any more muscle (lean mass) than The Biggest Loser group, despite not having structured exercise program.

Obviously, gastric bypass is about as fast as it gets. So how fast you lose the weight isn’t likely the determining factor.

But even if The Biggest Loser study suggested that rapid weight loss is not effective, there’s no reliable data indicating that slow weight loss is more effective.

Nevertheless, it’s not impossible to sustain weight loss.​

Some people found this study — and its media interpretations — really disappointing. If the body fights back against weight loss, does that mean there’s no hope for folks who have a lot to lose?

Others found the results somewhat reassuring. It relieved some of the sense of failure or shame around re-gaining weight. It acknowledged the difficulty and proved that it’s not all mind over matter.

But, while this study does reinforce the importance of compassion, it doesn’t indicate that long-term weight loss is impossible.

The study suggests that extreme dieting comes with consequences. Reduce your calories to an extreme and your body will likely fight back. Maybe for years. Maybe forever.

But you can sustain weight loss for the long term by effectively controlling your energy intake during (and after) whatever nutrition program you choose.

Five strategies to sustain weight loss.​

1. Use a habit-based approach.​

A more sustainable, habit-based approach that doesn’t include a drastic calorie deficit could give you a better chance at adapting — physiologically and psychologically — to a healthier lifestyle, without your metabolism coming to a screeching halt.

This point of view is consistent with The Biggest Loser paper, which closes with recommendations to focus on health markers like insulin and triglyceride levels rather than weight loss, and to take a more moderate approach with exercise and calorie reduction.

In Precision Nutrition Coaching, we use a habit-based approach to gradually — over the course of a full year — introduce our clients to small, manageable daily practices that support healthy eating and movement.

We keep in touch with past clients, and in the overwhelming majority of cases we’re hearing that the habits continue working to help them regulate their energy intake after the 12-month coaching program.

We’re working on a follow-up study to quantify clients’ weight maintenance; early data are promising.

2. Eat slowly.​

This is a foundational habit in Precision Nutrition Coaching.

Many studies show that people who eat faster are heavier than people who eat slowly, and that people who train themselves to eat more slowly eat less, and lose weight as a result.

There’s a 20-minute delay in satiety hormone signaling when you eat, so if you plow through a huge plate of food in 10 minutes, you’re liable to eat it all before you realized you’re actually stuffed.

In fact, it’s proven that simply reducing the number of bites you take per minute by half is effective at reducing your energy intake by 40 percent, particularly in big eaters.

That’s why we coach our clients to eat slowly.

Play a game with yourself: Try to be the last one eating — even after your slow-as-molasses toddler). Tune into hunger and satiety cues, which tell you how much food you really need.

3. At meals, eat until you’re satisfied, not stuffed.​

If you’re saying, “I’m stuffed!” after your meals, you’re probably overeating and/or eating for the wrong reasons, which will make it very challenging to control your energy intake.

Another keystone from Precision Nutrition Coaching: Eat until 80 percent full. This helps ensure that you’re not eating more than you need by:

• Helping you connect with your physical hunger cues (good old leptin!)
• Decoupling eating from emotions
• Breaking the deprivation/binge pattern and mindset
• Regulating your appetite

Feeling full, anxious, lethargic, foggy-headed, heavy, or extremely thirsty are signs of overeating that warrant an 80-percent experiment.

Next time you eat lunch, eat slowly, take a good break after each bite, and ask yourself, “Am I still truly, physically hungry?”

If the answer is yes, take another bite, chew slowly, and repeat. If the answer is no, end the meal and start monitoring fullness/hunger cues until dinner.

4. Reduce stress.​

The Biggest Loser study authors didn’t look at the stress hormone cortisol, which is a shame.

When you experience psychological stress, cortisol shoots upward.

Research has linked increased cortisol with weight gain, likely due to poorer food choices and physiological changes.

It’s conceivable the Biggest Loser participants experience considerable psychological stress: Undergoing an intense weight-loss program on national TV; airing their traumas to the world; regaining the weight when everyone knew they’d appeared on the show; feeling the shame of “failure”.

Every day, take steps to reduce your stress level and recover from all the hard work you do — physical and otherwise.

Some ideas:

• Sit and read a book
• Go for a walk
• Play with your cat
• Get a massage
• Take a warm bath
• Meditate
• Do yoga

Of course, what you find rejuvenating might be unique to you. Just be honest with yourself: Some activities that have the reputation for being relaxing — say, watching TV or throwing back shots at the bar — may be more escapism than true stress reducers.

5. Put your environment to work.​

Change is hard for most people, and it’s partly due to our hardwiring. Research shows that most of the decisions we make are automatic, based on patterns and brain shortcuts as opposed to rational thought.

We react to what’s in front of us, and our actions are often impulsive and/or the result of motivations we’re not fully conscious of.

That means our environment powerfully shapes our decisions — including food decisions — more than we realize.

We eat whatever’s in front of us, finish all the food regardless of portion size, consume more when we’re multitasking… and more.

Tough to change your eating habits when those habits are based on thoughts you didn’t know you were having, huh?

But you can use this hardwiring to your advantage by putting your environment to work to control your energy intake:

• Keep fresh fruits and vegetables within view
• Park far from the office so you have to walk
• Don’t keep junk food at home
• Get a dog that needs walking

Why did you copy and paste an article from a coaching business? They are likely to be biased, and provided no sources, just their anecdotal evidence.

 

[shanny]

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.

Wow. I think we are on the same diet! I drink coconut water throughout my work day and use fruit and dairy as flavor/fat on my starch. Kind of like the "croissant diet" with rice and potatoes as my main starches. Every time I've tried to cut starch down and use more fruit/sugar, my digestion suffers and my mood isn't as stable. I've also found that I crave/need way less muscle meat eating this way.

 

[Nik665]

Why did you copy and paste an article from a coaching business? They are likely to be biased, and provided no sources, just their anecdotal evidence.

Because I agree with this. The weight loss by inhibiting dopamine breakdown WITHOUT calorie restriction has yet to be seen in humans. Even ray himself said if one is getting too fat it is a matter of calories, it was in the strong sistas podcast

 

[learnedhelpless]

Because I agree with this. The weight loss by inhibiting dopamine breakdown WITHOUT calorie restriction has yet to be seen. Even ray himself said if one is getting too fat it is a matter of calories, it was in the strong sistas podcast

So it's impossible, to increase the calorie expenditure? The only way to create a calorie deficit, is to reduce food intake, and not increase expenditure?

 

[Rinse & rePeat]

But do you exercise

I move around all day long, busy. I am busy in my garden, cooking, house chores, running errands, and I don’t watch tv, but I do not do monotonous gym type jumping around exercises. I like to do stretches when I ground on the concrete. I am very strong, lifting my own heavy bags of garden soil, I dig holes to plant trees, saw big branches just active stuff, like when I was a kid. When I am not so busy I like a brisk walk, two miles, to town for dinner, and then walk home. I do not get tired, sore or winded from any of it. I do think a lot, problem solving and I read everyday, and that makes me lose weight easily I have noticed.

 

[ecstatichamster]

Wow. I think we are on the same diet! I drink coconut water throughout my work day and use fruit and dairy as flavor/fat on my starch. Kind of like the "croissant diet" with rice and potatoes as my main starches. Every time I've tried to cut starch down and use more fruit/sugar, my digestion suffers and my mood isn't as stable. I've also found that I crave/need way less muscle meat eating this way.

That’s awesome. Works great doesn’t it.

 

[facesavant]

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.

It is as your title says learned helplessness. Taking a magic pill will not help in the long run if not doing the work changing diet and proper exercise.

 

[learnedhelpless]

It is as your title says learned helplessness. Taking a magic pill will not help in the long run if not doing the work changing diet and proper exercise.

I never said that, and I did not mean to imply that.

 

[Mathgirl]

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.

Can you expand on this? I recently started uping my potato intake. I know I have high stress hormones as i lost quite a bit of weight by fasting and after stopping fasting I gained weight back

 

[PopSocket]

Can you expand on this? I recently started uping my potato intake. I know I have high stress hormones as i lost quite a bit of weight by fasting and after stopping fasting I gained weight back

Really well boiled potatos (1h 30 min) with a bit of butter and lots of salt is great for lowering stress hormones for me too. I limit it to 1-2 times a week though and only prior to sleep. Gives me a restful happy night and the effect last well into the next day or two.

 

[EnergeticLeo]

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.

I appreciate you pushing back; do you think if someone was at caloric maintenance, and maintained that caloric intake and activity level, and then added cyproheptadine on top of that, that they would lose weight?
If RU486 causes rapid weight loss, then I would think cyproheptadine through lowering cortisol could do something similar?

 

[Hans]

I appreciate you pushing back; do you think if someone was at caloric maintenance, and maintained that caloric intake and activity level, and then added cyproheptadine on top of that, that they would lose weight?
If RU486 causes rapid weight loss, then I would think cyproheptadine through lowering cortisol could do something similar?

I would not bet much on that. Unless someone is really sick for some reason, only then will drugs work (but it's still a hit or miss). I know someone who is sick and "overweight" (mainly water retention) and used RU486 and nothing. Zero symptom resolution. Same with cypro, progesterone and most other supps. In some cases it's really hard to find the root cause without testing.

 

[EnergeticLeo]

I would not bet much on that. Unless someone is really sick for some reason, only then will drugs work (but it's still a hit or miss). I know someone who is sick and "overweight" (mainly water retention) and used RU486 and nothing. Zero symptom resolution. Same with cypro, progesterone and most other supps. In some cases it's really hard to find the root cause without testing.

Fair enough, I do agree finding the root cause is always best. I do wonder how much non-response to these supplements is due to lacking the basics, though, e.g. too much fat in the diet, or just eating too much, or missing some key nutrient etc... in which case correcting those would be way more important.

 

[Razvan]

Everybody pro exercise here
Its clear that excercise lowers lifespan.
A lot of people here are clearly metabolicly ****88 from exercise and they need to do the calories in calories out fad.
Thats what "they"want you to do...

 

[Hans]

Its clear that excercise lowers lifespan

Bruh...