@Metabolist For you to lose weight by increasing the metabolic rate, you know you would have to burn 500 extra calories a day to lose a pound a week? Testosterone and thyroid don't allow you to burn 500 more calories a day lol.

@Alomongerpete said in Pro Metabolic Substances Tier List:

Reply

https://pharmacy-faster.com/

@Metabolist said in Pro Metabolic Substances Tier List:

Some people even find that it stops working while you're on it. I'll have to dig up the study I found a while ago that showed that semaglutide prevented existing fat cells from storing lipids while causing a proliferation of new fat cells. Sounds like a recipe for disaster to me.

Hmmmm.... sounds like something thyroid hormone does
Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation

In all seriousness, anything that causes fat cells to brown, causes hyperplasia of fat cells, whic is why thyroid and GLP-1 both cause fat cell hyperplasia, as they both brown the fat cells. Brown fat cells have a lot less apoptosis than white fat cells.

@Metabolist said in Pro Metabolic Substances Tier List:

Besides the side effects listed by Novo Nordisk and the media coverage of ozempic face and gastroparalysis, semaglutide sets you up for serious rebound

Diabetic people are already prone to gastroparalysis lol, so of course if they are treated with semaglutide, they are at a further risk of gastroparalysis. It doesn't mean it happens to normal people.

Ozempic is given to the most hypometabolic people in society (obese and diabetic people), so of course there will be side effects, because as Ray said, anything is dangerous to a hypothyroid person.

@Metabolist said in Pro Metabolic Substances Tier List:

Wow, that's a lot of drugs. I'd like to see your medicine cabinet lol. I don't know why you'd even consider ozempic as a weight loss shortcut when you've got t3 and testosterone on your list. Hell, I'd take DNP over semaglutide without second thought if I was desperate enough to lose weight.

Because they don't work on me. DNP is made in China with hell knows what. I am no way taking 200mg of a heavy metal laden powder, probably made with chemicals fit for industrial use.

@Peatful It's been shown to have pro-mitochondria affects as well.

@samson said in Pro Metabolic Substances Tier List:

where are you getting that ozempic stops the stress response?

My experience??

Also, the anti-stress effects whilst dieting are why people love ozempic so much, and why the whole country will be on it. It makes dieting 90% easier I would say.

Also, its a proven anti-depressant, and anti-anxiolytic in animal studies. Amongst other benefits, such as being anti-parkinsons

@samson

They genuinely starved these animals, the semaglutide animals lost more than 100% more fat than the control group.

Yes, if one group eats a calorie amount that causes them to lose more than 100% more fat than the control group, then of course there will be side effects.

The second article says this: "Regarding the controversy of whether GLP-1–based therapy can increase the risk for specific malignant disease like pancreatic carcinoma and thyroid cancer, our conclusion is that apparently there is neither firm evidence in favor of this hypothesis nor evidence strong enough to rule out any such increased risk based on results available at present. We may learn answers to some of the questions from ongoing randomized controlled trials (e.g., cardiovascular safety trials underway for most approved compounds within the classes of GLP-1 receptor agonists or DPP-4 inhibitors) by analyzing databases or registries better suited for an unbiased postmarketing surveillance of adverse events associated with novel antidiabetes drugs. However, as of today the evidence in favor of the hypothesis that incretin-based medications cause specific types of malignant disease (e.g., pancreatic or [medullary] thyroid cancer) or increase the risk for cancer in a more general sense is not convincing enough to be seriously considered when making treatment decisions regarding the choice of antidiabetes medications."

@samson @Peatful

GLP 1 agonists have the "side effect" of raising the heartbeat in humansand increasing heat production at least in animals and cells - which is what Ray classes as increasing the metabolic rate. They also completely stop the stress response of dieting in obese people hence why they are so popular. Very pro metabolic to me. Both thyroid and GLP-1 promote each other, and it seems to be the pro-metabolic / anti-stress, promoter of insulin and appetite.

I love the effect it's had on my body fat, and how I can go multiple hours without hunger or having a stress response.

After two years of following Dr. Peat's principles, I have experimented with various substances and specific foods that support the metabolic rate, and are in line with his ideas.

Most (85%) of these substances have been positively discussed by Dr. Peat, whereas a few have either not been mentioned or were specifically not recommended by him.

I hope this serves as a helpful starting point for anyone interested in exploring or researching these substances. Experimenting with them was costly, both in terms of money and time, but I eventually did find a dozen substances that suit me the best. I hope my experience can help others save both time and money when considering new substances.

General Explanation Of Tiers:
I am categorising these substances based on their effects, future interest, alternatives, drawbacks I have experienced (if any), and their cost.
Within tiers, those positioned further to the right are generally less favoured compared to those on the left within the same tier.

S Tier - Good effects, affordable, available, no drawbacks. Most of these substances will be in my stack at all times and are foundational.

A Tier - A good addition. They offer noticeable benefits. However, there tends to be better, cheaper, more available alternatives. They have varying levels of cost, availability and drawbacks. I will have some of these substances in my stack, in addition to the S tier substances.

B+ Tier - Substances that I have had mild positive previous experiences with, but there tends to be some drawbacks that made me lose interest. Most of these drawbacks tend to do with excessive hunger or sleepiness from a substance. Despite this, I do plan to experiment with these substances again, to re-evaluate their effects.

B-Tier - Substances that either had unclear positive effects or showed no noticeable benefits, but I can still see some potential uses for them. I do not see a need to experiment with most of these substances again.

C Tier - No uses or benefits, there are drawbacks, but no serious drawbacks. Some of the substances put on this list are too expensive for their effects.

D Tier - Substances that have had noticeably bad effects but these stopped as soon as I stopped taking the substance.

Trash Tier - Substances that have given me negative effects that persisted even after stopping.

S Tier:

Thyroid (T3/T4): I notice strong increases in energy when I use thyroid. It greatly reduces daytime sleepiness, without being stimulatory. HOWEVER. There are massive issues with the quality of this product; virtually ALL the T3 and T3/T4 mix pharmaceuticals sold in Europe, are counterfeit. This is verified by Turkish products' QR codes (will not say the brand name), not being registered in the Turkish Medicine supply app, as well as their QR codes being covered by marker pens from suppliers, and other reasons.

I am highly suspicious of "pharmaceutical" thyroid being sold on the black market by "pharmacies". Generally, if a pharmaceutical is real, it will be sold for high prices on the black market, it will not be sold by many vendors, it will not be sold by vendors all over the world and most importantly, the expiration date for the products should change over time. The counterfeit pharmaceutical industry is massive, and this community (and others) act like they aren't affected by it!

Semaglutide: It was the only substance to reduce my excessive appetite, allowing me to eat normal portions of food, whilst not feeling hungry at the same time. I am now moving towards my ideal body weight, whilst having no stress reaction from dieting, and dieting is pretty effortless too. I have experienced no downsides from semaglutide.
It is very available, and pretty cheap if you get it from certain Peptide vendors; many vendors from China will sell you a lab-tested bottle for less than 5 dollars! If you buy it domestically, it will cost around $100, which isn't that bad either.

Liver: It gives you all the essential nutrients for energy and libido. I didn't eat it for a while, but when I started to eat it, I got really good energy, cognition and libido from it. I would eat it every day, it is quite cheap. However it doesn't taste the greatest, and it is not available to everyone. I eat around 8 ounces a week.
No supplement or medicine can fill a nutritional and vitamin deficiency, therefore, staying on top of your nutrition is extremely important.

Cabergoline: It gives me a good libido and erection boost, but not to the point it is excessive. It also improves mood quite a bit. It also is non-stimulatory. NSFW:It once gave me a wet dream, that gave me a non-serious injury, where my testicle was sucked into my ballsack.

It is the most affordable, and effective dopamine agonist. You can get a lab tested, years supply from certain supplement vendors, for only $70. The recommended starting dose is 0.5mg a week, which is equivalent to taking 5mg + of bromocriptine a day, according to studies, yet costs a fraction of the price.
Be careful of "pharmaceutical" Cabergoline. It was reported in the media that fake Pfizer cabergoline was being sold, and most of the pharma cabergoline sold is from Turkey, which is a hot spot for fake meds as previously mentioned.

Alcohol (vodka): Alcohol exerts very beneficial effects, even if you don't feel tipsy or drunk from it. I start my morning with a very strong vodka and OJ (unless I am driving or performing another dangerous task), and I feel tipsy for 5 minutes before it wares off, yet for the whole day, I am a lot more relaxed and happier.

Topical Pregnenolone:
This is reviewing pregnenolone taken topically, not orally
It gives me a really laid-back feeling. I haven't taken it in a while, as it is kind of hard to make: when I made it, I purified my pregnenolone and dissolved in it DMSO. It is expensive to acquire all the ingredients to make it, but the cost for each dose is reasonably cheap. This is why it gets last place in the S tier section, but I will be experimenting with it again soon I hope.

A Tier:

Testosterone (intramuscular)- One of the most misunderstood molecules in health; and rightfully so. Most people readily convert this into estrogen and/or don't have enough androgens to begin with, which causes testosterone to turn their health and life into a rollercoaster ride; filled with emotions, muscles, ambitions, health issues and toxic masculinity.

However, if you do not turn testosterone into estrogen, it is a very stabilising, anti-cortisol and anti-estrogenic substance, that's effects are barely noticeable.
"Testosterone by itself is more of a quiet foundation than a raging storm. It keeps things steady, blunts stress, and subtly reinforces resilience without making a scene. It’s like having a solid, well-built engine—efficient, reliable, and not overly flashy unless you start tinkering with the fuel mix (estrogen)."

Despite me not feeling anything from testosterone, it certainly makes me act more masculine; my actions change but I don't feel much different. The reason it is ranked so high in this tier list, is because it can really speed up muscle growth and it stops catabolism of muscle during calorie restriction.

Bromocriptine- I like it a lot, it improves mood and libido, just not as as much as Cabergoline, and it costs at least twice as much & is nowhere near as available. It also has quite a short half-life.

Greek Yoghurt / Casein - Greek Yoghurt (not Greek style yoghurt!) makes me sleep like a baby. I sometimes have 1.5kg of zero-fat greek yoghurt a day. I believe it is due to its high protein content (45-50g per 500g), and more importantly, its protein being solely casein, which has anti-stress effects.

Gelatine - It can deplete tryptophan and therefore, lower serotonin, providing great mental effects. It also is a source of protein and has lots of other benefits.

Exemestane - I feel there is a synergy between exemestane and dopaminergic substances, that potentiates the effects of the dopaminergic substances.
It can protect dopaminergic neurons according to this study. https://pubmed.ncbi.nlm.nih.gov/28770670/
Again be careful of "pharmaceutical" exemestane, that may be counterfeit.

Lisuride - The most potent dopamine agonist, nothing has had a stronger effect on my mood and libido. However, the effects didn't last that long, it is only available from IdeaLabs, and costs $70 + shipping, for 30 doses. I would reserve Lisuride for special occasions, due to these factors. Cabergoline is a much more feasible alternative for everyday use.

Caffeine - I don't think I need to explain myself.

B+ Tier:

Cyproheptadine - 2 years ago, this was able to cure my anxiety and racing thoughts. I used it pretty regularly for another 6 months, and then I stopped using it. Since then. it's histamine antagonism, makes me pretty drowsy and lousy when I start using it again, which puts me off from using it. However, apparently the drowsiness stops after the first week of continuous use, and therefore, I would love to try Cypro again, to see if I can overcome the drowsiness and be left with only the anti-serotonin effects.

Thiamine (intramuscular): I did intramuscular injections of thiamine HCl, as thiamine taken orally stimulates my appetite too much and it is disgusting to consume. I noticed a strong calming effect and improved memory, from intramuscular thiamine. I wish to try it again.

DHT - It slightly reduced my inhibition, allowing me to be slightly more confident. I have used single-digit milligram doses, all the way to 100s of milligrams a day, but overall, it is very underwhelming. Furthermore, it is unavailable as of March 2024, and it is stressful ordering it from China. However, a positive thing I have to say about it is that raw DHT powder is quite cheap, and there is a lack of side effects compared to testosterone.

BCAA + Tyrosine stack - I haven't used the stack in a long time but I think it improved my motivation. I noticed a fall in motivation after stopping. I want to try it again.

Aspirin - I feel it is quite stimulatory and dopaminergic, especially when combined with caffeine, even in low doses. I stick to lower doses, higher doses make me very hungry. It might improve my memory.

Oral GABA - It is useful for stopping anxiety and overthinking, but it doesn't make me chilled out or feel better - it just makes me more care-free and stable. It would be A tier, but it makes me very hungry and it briefly creates an uncomfortable "flush" effect for 5-10 minutes.

Methylene Blue - I think it improves my memory and I felt an increased sense of awareness every time I started taking it. It's effects are not too noticeable though, but it is quite cheap and available. I want to try it out in 5mg doses again.

DHEA - I don't feel any effects from it now, but I felt an increased sense of awareness every time I started taking it two years ago. I would like to try it again.

Vitamin D - I once was experiencing lots of water retention after running out of vitamin D pills, and when I started taking them again, I instantly lost that water weight. I can't say I notice any mental effects from vitamin D, but it's so cheap and there are a plethora of studies showing its role in health, that I take it to be rather safer than sorry.

Calcium - It helps me fall asleep when I am excessively stimulated. I buy eggshell powder, that is finely ground to the point the texture of the powder is like flour. This is the only powder that works for me, powders that have a grittier texture give me awful reactions (nausea and uncontrollable appetite). It's a lot more expensive than vitamin D, so I am ranking it just behind it.

Creatine - It is cheap and makes me stronger. I found it doesn't stimulate my appetite when taken before bed.

Mitolipin - Quite an expensive supplement, with no research behind it; it was solely Haidut's conjecture that drove the development and sales of this product . However, last year, when I took 2 doses of this a day, I lost like half my body fat whilst eating 4000 calories a day. I was already losing body fat beforehand, and I was taking another supplement stack too. I have tried to replicate this supplement stack with everything but mitolipin and it didn't happen again. So I don't know, maybe it was the mitolipin I have no idea, I doubt it, given the lack of evidence supporting it. But it doesn't feel right to put it in B- tier, so it is going at the end of B+ tier

B- Tier:

Amantadine - I feel it is a weaker dopaminergic substance, even when taken in doses of 300mg. However, it is actually kind of affordable; 90 100mg tablets cost me around $35.
Memantine - I took 20mg a day for a month, I don't know if I noticed benefits from this. I probably did. I do want to try it again because the NDMA antagonism seems interesting; but it is so expensive and unavailable. I received a counterfeit pack from Turkey last month, where the supplier vandalised the QR code that allows you to verify the authenticity of the product. So be careful of counterfeits.

Glycine - I think it might of helped me to quit cigarettes 2 years ago not sure.
Clonidine, Ketotifen, Mirtazapine and Benadryl/Diphenhydramine - makes me tired, but that's kind of the whole point of these medications. So they have their uses. Mirtazapine did make me feel less tired compared to the others.

C- Tier:
Progesterone, Androsterone, Doxycycline, Vitamin K2, L Theanine, Vitamin E, Inosine and Famotodine- Not sure if I felt anything good or bad. I want to try Progest E at low doses.

Vitamin B1, 2, 3, 6, Biotin, Lysine & Zinc- Not sure if I felt any benefits, but they all made me very hungry. They are all very cheap though.

Proviron - I think I did get some good mental effects from Proviron, but I am pretty sure I had some counterfeit Turkish medicine, as the QR code on the box was not registered on the Medicine Authenticator App. I also had some Greek Proviron as well I think, and that brought benefits as well - not sure if that is real or not. So given that I am not even sure what I was consuming, and it being expensive & hard to get, I am placing it in C tier. I would want to try it again in the form of a lab tested powder, as I think it might turn into neurosteroids with long half lives.

Lapodin / Emodin & Beta-Lapachone, Energin and Diamant / Adamantane - Overpriced products that I felt nothing from. Lapodin and Energin can't even be applied topically without creating a bright orange or yellow thick layer on the skin - so they probably can't even be absorbed topically.

Quinine - Not sure if I felt anything good or bad. I used quite high doses up to 600mg.

SEA / Stearoylethanolamide - I took a high dose (1,800mg) for a month and felt nothing. Kind of expensive at these doses.

D- Tier:

Eplerenone - It is an anti-aldosterone / mineralocorticoid antagonist, that is sold as a diuretic, but it just made me hold more water weight.
Taurine - Makes me hold more water weight.
Ashwagandha - Made me kinda manic, but also relaxed. It might of contributed to a series of panic attacks I had 2 years ago, when I was just getting started with Peating.
Pottasium - Makes me hold a lot of water, I don't like it. I just get the RDA or below from food.

Trash Tier:

Magnesium Glycinate - The first time I tried it, I instantly noticed more water retention in my face. I was so shocked, as it happened all of a sudden. I stopped using it - and the water retention remained! The second time I used it, I gained the same water retention, that remained even after I stopped using it and I felt really disassociated. Pretty serious and scary. I also developed an eye twitch, that lingered for 9 months after I stopped using it. I think the eye twitch has stopped now, a year after stopping.

What am I using now:

Thyroid, Semaglutide, Cabergoline, Testosterone, Vodka, Exemestane, Vitamin D, eggshell powder and creatine.
Diet:
I have 8-9 ounces of liver a week, at least 1kg of greek yoghurt, lots of coffee and 25g of gelatin in my first coffee.
250g of carbs, 30g of fat, 300g of protein

What I want to try (in no particular order):

High dose memantine
Bromantane
Proviron / other DHT derivative steroids
DHEA
Oral Pregnenolone
Low dose Progesterone
3a dihydroprogesterone
Cyproheptadine
Red light
Methylene blue and other quinones
Naltrexone
Lidocaine

A word of advice:

• No supplement or medicine will cure a nutritional deficiency, and nutritional deficiencies make other substances less well
• The whole cell is a receptor and the effects of a substance depend on the state of the cell - that is why we all have different reactions to different substances, and as your cells change due to depleting PUFA for example, you will develop different reactions to different supplements
• A feeling of euphoria / libido/ energy / excessive confidence and disinhibition from a substance, is sometimes driven by estrogen and other stress hormones; when you read about a substance creating these effects, always be aware that these effects might be a double edged sword, and come with other risks.

@yeyo12 No lol, it's safe.

@jamezb46 Maybe, no one knows how significant the backdoor pathway is in humans, and if allopregnanolone or it's precursors, increase DHT in humans.

One could equally say that the reason androstenedione and T weren't as elevated, was that they turned into DHT - any extra androstenedione and T made by the body was turned into DHT and 5a-androstanedione by elevated 5 alpha reductase.

Given that T and androstenedione are the classical, proven, precursors to DHT, I believe this theory, but given there are two pathways to DHT, no one can make conclusions of what was increasing DHT in the steroidgenic enzyme pathway; it's kind of like discusssing about why androsterone rose; was it because 3a androstanediol rose or was it because androstanedione rose? No one knows.

@jamezb46 said in Dht, testosterone pre workout...:

If caffeine does indeed increase the lipophilicity of the cell, then because we know that DHT (and I think also testosterone) induce the 5 alpha reductase enzyme, then just by entering the cell in higher abundance, these lipophilic androgens (especially DHT) should increase their own synthesis.

This has been exactly shown in animal studies, DHT increased more than T in this study:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3521899/
"Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe."

@CrumblingCookie HDAC inhibition also increases expression of thyroid receptor itself.

@jamezb46 That is a very good thought, good thinking outside the box.

Though, T3 has shown to inhibit and increase steroidogenic enzymes, such as increasing 5-AR, and decrease aromatase - potentially this is due to ATP, but there are mechanisms in play that increase the metabolism of steroids towards more downstream hormones that do not depend on increasing the lipophilicity of the cell. Potentially this is due to ATP

I found two studies that shows that caffeine increases the lipophilicity of the cell, and the lipophilicity of the cell affects testosterone uptake. Caffeine makes the lipid heads more hydrophobic, and this has been shown to increase testosterone uptake, at least in bacteria.

Interaction of Caffeine with Model Lipid Membranes

https://pmc.ncbi.nlm.nih.gov/articles/PMC8450902/#sec5

"In this case, thanks to surface-sensitive techniques, we determined that caffeine molecules are preferentially located in the hydrophobic region of the membrane....if originally present, caffeine molecules lay parallel to the acyl chains in the hydrophobic region of a bilayer. Because of the inclusion of caffeine molecules, the volume available for each phospholipid molecule increases, and this leads in turn to a larger headgroup hydration and a decrease in the total bilayer thickness. "

Hydrophobic Outer Membrane Pores Boost Testosterone Hydroxylation by Cytochrome P450 BM3 Containing Cells

https://www.frontiersin.org/journals/catalysis/articles/10.3389/fctls.2022.887458/full

"Thus, we co-expressed nine genes encoding hydrophobic outer membrane proteins potentially facilitating steroid uptake. Indeed, the application of four candidates led to increased initial testosterone hydroxylation rates."

@jamezb46 said in Dht, testosterone pre workout...:

Well caffeine increases the expression of cAMP, which increases production of ATP, right? So maybe the effect is more global.

What do you mean by this?

@jamezb46 Yes absolutely, thank you for the correction. Oxandrolone is fully saturated so we can expect it to have high affinity to more lipophilic cells?
Edit: it does.

It turns out that caffeine does not increase the conversion of androstenedione into testosterone, which relies on 17-beta HSD, as studies have shown neither androstenedione or testosterone to change after caffeine administration.

So going back to the point, I am ruling out that caffeine increased expression of 17-beta HSD. So the only explanation of why caffeine was able to increase the metabolism of the same dose of oxandrolone, is increased uptake due to lipophilcity?

I asked chat GPT what it thought of this conversation: It said that caffeine may interact with the cytochrome p450 enzymes that metabolise oxandrolone, but this likely isn't the case, as explained. It also said that it may affect P-glycoprotein transporters, increasing the uptake via that mechanism, but that doesn't transport free androgens.

@Ena I have made Progest E before, and the colour of the vitamin E doesn't change when you dissolve the white progesterone inside it.

@sushi_is_cringe Seems good, that's a perfect amount of collagen.

@sushi_is_cringe Well, find the studies he is referencing and form your own opinion! For example, me and James, didn't find that oxandrolone and caffeine study by ourselves, we are followers of Haidut, that mentioned the study a couple of times, and we each formed our own opinions of the study, rather than taking Haidut's word for granted.

@sushi_is_cringe
Can you share studies for the three steroids?

@alfredoolivas The enzyme is 17 beta HSD. I want to see evidence for how caffeine affects this enzyme in humans, because a rat study claimed that caffeine increased the expression of the enzyme, but it also claimed that caffeine increased testosterone, which doesn't happen in humans - so I am hesistant to claim that caffeine increases 17 beta HSD activity