Human Age Reversed By 2.5 Years By Combo Of Metformin, DHEA And GH

[LeeLemonoil]

Yes, it increases fatty acids and causes a state of pseudo insulin resistance. At nighttime. For peripheral and skeletal healing. To spare glucose for the brain. Glucose is a poor substrate for nighttime skeletal healing. GH is doing exactly what it needs to do in that circumstance. That's the same time carnitine reaches its top importance.

This is not a focus on the thymus.

I already know about the problems with metformin, but simply knowing an AMPK inducer was for some reason involved in this is potentially important information for me.

Don't worry, I prefer to keep things nice and short too, that's why I'm not going full Travis on you (he would probably hate me even more right now for promoting methylation - whatever guys I'm just following the leads :) ).

That’s interesting. I was always puzzled that many substances that are pro-AMPK in the periphery are often pro-mTor in the brain through health-promoting in both in a regenerative context. This GH->sugar nighttime thingy seems to explain it in part. Thanks

 

[Terma]

Yes, something like that will probably be involved in the hypothalamus at least. You're a smart guy :)

 

[LeeLemonoil]

Anyway, I can’t deny to feel anticipatory annoyance towards the next Met+Dhea megadose+HGH hype from doctors and laymen alike.

Well, I won’t try to save them from themselves. But DHEA will likely become more restricted because of this. Or every GP will try to prescribe Metformin to everybody, because it’s anti-aging as proven.

Here is my 5G-mobile lying under my pillow all night and here I pop my nightly Metformin, yessir. Good night, Darling.

I like being sarcastic in a language I don’t really command. Can only guess it sounds much more confused than I really am

 

[Terma]

Yeah I hope not, DHEA has become a (possibly literal lol) godsend for me.

Look at it this way: what if you removed all sources of PUFA - would you fear the fatty acid increase from GH as much?

 

[LeeLemonoil]

I‘m not fearing GH. As said, I think it’s regenerative in the right context as you do - and oral GABA at nighttime also promotes elastin and might be just a really effective anti-aging supp overlooked by most. Many state it doesn’t work per os at all, the fools.

If we integrate T3 or methylene Blue sensibly into such an anti-age stack we can probably beat those guys

 

[LeeLemonoil]

Yeah I hope not, DHEA has become a (possibly literal lol) godsend for me.

Look at it this way: what if you removed all sources of PUFA - would you fear the fatty acid increase from GH as much?

Is the FDA aware of God‘s hormone dealing-activities?

 

[Terma]

I was just thinking about elastin too :). I most likely have high cortisol in tissues and you should see my skin (maybe I'll show it someday, but I gotta make some headway first or this is gonna be too embarassing lol - I mean I've shown my failures enough here heh).

I couldn't get a clear endorphin release from Dog this time. But the threads of ideas that just popped into my mind last night blew my mind a little again. Actually, David Usher blew my mind last night. That man is a true humanist.

(Btw, did you guys know Jaminet is a religious guy? A blessed Advent and Christmas to all our readers - Perfect Health Diet | Perfect Health Diet That caught me by surprise one day and everyone went 'wtf' - but hey, the man is intelligent enough)

(Btw, has anyone heard of magnesium beta-hydroxybutyrate? Magnesium BHB Powder Just ordered some cause it sounded neat, no idea how this is gonna go)

 

[Terma]

@LeeLemonoil You might be interested in seeing the old thread on Rapamycin on Phoenix Rising ME / CFS Forums. I posted there at the time (please take all my old messages with a grain of salt) and several people tried it. I do not want it myself because of its very long half-life but some people had some results though variable.

 

[haidut]

@Terma.
Metformin is the staple-drug in anti-age and longevity circles and research, along with Rapamycin.
Reducing mTor-pathway and activating AMPK is what most of the thinking circles around yes.

In this Forum we have compiled data and publications against Metformin, especially because it is mitotoxic - life-extenders though consider it mito-hormetic and thus health-enhancing by mitophagy of defective mitos. I prefer to err on the side of caution and abstain from Metformin, my insulin sensitivity is in order and Mito health can be influenced by other more risk-free means.

As can GH. Taking Gaba plain and simple before sleep for example.
GABA - An Effective Sleep Aid W/ GH Boosting Effects that Works Within 30 Minutes - Only 100 mg Pre-Bed Will Suffice - SuppVersity: Nutrition and Exercise Science for Everyone

If you are interested, there is much recent research and screening going on for Metformin and Rapamycin - mimetics.
Allantoin is a potent Metformin-mimetic and freely available.
Interestingly, Withaferin A was found to mimic both Rapa and Met. It’s a steroidal lactone and might be interesting from a peaty perspective. Don’t know if it’s possibly estrogenic though, i think not but not read up on it

@haidut
Those indications on GH being pro-cancerous are concerning, though I take it as always context matters. 100mg of GABA seem to triggers GH and also elastin synthesis, both seems pro-regenerative and probably also cancer protective when used sensibly

Most human GABA studies used massive doses (2g-3g in a single sitting), often on an empty stomach. Here is one that is referenced by one of the links you included. I would not take that study as a good example of what the role/effect of physiolgical levels/doses of GABA have.
Growth hormone isoform responses to GABA ingestion at rest and after exercise. - PubMed - NCBI

Btw, most amino acids taken on an empty stomach will raise GH but some aminos do have a more pronounced effect. Arginine and glutamic acid are two of them. As far as the effects of GABA on HGH - as I suggested above, I would not jump to conclusions just yet. In physiological doses, which limit GABA's effetcs to agonism at the GABA receptors, it actually inhibit GH release.
GABA supplementation and growth hormone response. - PubMed - NCBI
The inhibitory effects of (gamma)-aminobutyric acid (GABA) on growth hormone secretion in the goldfish are modulated by sex steroids

In support of that, synthetic GABA agonists block GH release.
Effects of a Gamma Aminobutyric Acid (GABA) Derivative, Baclofen, on Growth Hormone and Prolactin Secretion in Man

Further corroborating that view are studies showing that GABA antagonists greatly increase GH release.
410 EVIDENCE FOR TONIC GAMMA-AMINOBUTYRIC ACID (GABA) MEDIATED INHIBITION OF GROWTH HORMONE (GH) SECRETION IN THE OVINE FETUS

@Terma - as far as GH release during sleep, I really don't see why this has to be categorized as beneficial and not simply as a result of hypoglycemia due to the unfed state for 8+ hours. No need at all to invoke some kind of "sparing" of glucose. If you don't eat, and it is dark then after your glycogen stores get depleted HPA gets activated and fatty acids flood the circulation. GH is needed to increase the oxidation of those extra fats in the bloodstream, but I would certainly not categorize that increase in GH as beneficial. Again, the very authors of the OP study cautioned about GH diabetogenic effects and we know those effects are driven through increased FAO.
Hypoglycemia: a potent stimulus to secretion of growth hormone. - PubMed - NCBI

Furthermore, if you do more digging you will see that GH is actually an indispensable part of the stress-cascade and is in fact BOTH a very reliable biomarker of chronic stress and an actual promoter/mediator of the maladaptations that occur with chronic stress.
A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear. - PubMed - NCBI
"...We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and growth hormone in maladaptive changes following prolonged stress."

So, nothing at all surprising that its levels rise during sleep. Btw, GH levels only rise during night sleep, where in the absence of light and food the serotonin / melatonin / cortisol / estrogen / ghrelin field dominates. Daytime sleep does not induce GH release/rise, despite increased GABA.

 

[Terma]

Skeletal restructuring and repair is an energy-expensive process. It you want to truly heal it's not sufficient to stick to "sufficient for adult health". To achieve better healing the body needs that extra push so that 1) the brain gets as much glucose as possible for as long as possible during the night (i.e. 9 hours) and 2) the skeletal tissues have an abundant source of ATP to do their work with - I am talking about energy more than fat as a structural element although that it also necessary in regenerating phospholipids etc. Again this is while also aiming for no or low PUFA, with the assumption that I am intentionally trying to keep my gut empty during the night (so as to let LPS levels drop and allow tissues to relax and recover**). Ghrelin is supposed to get ablated at nighttime - GH is a stress hormone only during the day. It fits way, way too perfectly for me. I respect a lot of Ray's ideas (hope you liked that hourglass comment) but (consider the health of children he's trying to say is "in spite of" GH - prove it definitely) that was his weakest article.

** (including - notably - the gut itself)

 

[Herbie]

owning and starring in movie franchises worth hundreds of millions of dollars, in your 70s. yeah terrible performance. he probably looks better than you do now

LOL

 

[haidut]

To achieve better healing the body needs that extra push so that 1) the brain gets as much glucose as possible for as long as possible during the night (i.e. 9 hours)

Completely agree, however not much of that glucose in the brain will get metabolized in light of elevated free fatty acids (Randle cycle) and GH actually blocking glucose oxidation directly. So, the net effect of this "glucose sparing" would be high lactic acid. This could explain why people taking growth hormone in the evening (athletes mostly) have nightmares and poor sleep.
Acute Growth Hormone Administration Causes Exaggerated Increases in Plasma Lactate and Glycerol during Moderate to High Intensity Bicycling in Trained Young Men
"...We studied the acute effects of a single, sc GH dose on exercise performance and metabolism during bicycling. Seven highly trained men [age, 26 ± 1 yr (mean ± SEM); weight, 77 ± 3 kg; maximal oxygen uptake, 65 ± 1 ml O2·min−1·kg−1] performed 90 min of bicycling 4 h after receiving 7.5 IU (2.5 mg) GH or placebo in a randomized, double-blinded, cross-over design trial. A standardized pre-exercise meal was given 2 h before exercise. Blood was sampled at rest and during exercise and analyzed for GH, IGF-I, glucose, lactate, insulin, glycerol, and nonesterified fatty acids (NEFA). In the placebo trial, all subjects completed the exercise protocol without any difficulties. In contrast, two subjects were not able to complete the exercise protocol in the GH trial, and one subject barely managed to complete the protocol. In addition, GH administration resulted in exaggerated increases in plasma lactate concentrations during exercise (P < 0.0001). The combined lipolytic effect of GH and exercise, evidenced by increased plasma glycerol and serum NEFA concentrations, was 3-fold greater than the effect of exercise alone (P < 0.0001), but this increased substrate availability did not result in increased whole body fat oxidation (indirect calorimetry). Plasma glucose was, on average, 9% higher during exercise after GH administration compared with placebo (P < 0.0001). We conclude that a single, relevant GH dose causes exaggerated increases in plasma lactate and glycerol as well as serum NEFA during 90 min of subsequent bicycling at moderate to high intensity. The exaggerated increase in plasma lactate may be associated with substantially decreased exercise performance."

Btw, I am not asking you to or expecting that you'd agree with Peat. I myself disagree with him on quite a few things. But the role of growth hormone as a stress biomarker/mediator is solidly backed by evidence IMO. Children need GH to grow, but they also produce a lot of differentiating steroids like pregnenolone/progesterone, which mitigate the carcinogenic effects of GH. It is not GH that makes children youthful, but likely thyroid.
Bonobos Do Not Age Due To High Thyroid Hormone

Injecting/elevating GH is not much different than using estrogen as an ergogenic and anti-aging aid. They both have remarkably overlapping effects on metabolism, substrate utilization, hypertrophy or various organs, etc.

 

[Terma]

Honestly I just make that comment about Ray Peat because I know he is an important figure in your life and I don't want to disparage him or you for nothing. I just suck at not doing that :P, this is pretty new for me. It's just he's too rigid or generalized on some of these concepts and he's gonna be wrong on some details. Just like Jaminet, Travis (imo one thing or two - you need those polyamines at some point) and good ol me.

GH must be balanced by the other hormones like DHEA. It's not meant to be increased on its own like that. My goal is to control the growth induced by GH and methylation using DHEA, retinoic acid and those other protective hormones, in balance. So that's no surprise to me, but thanks for the link.

 

[LeeLemonoil]

Thanks for providing all the info @haidut, I’ll read everything carefully.

@Terma
I‘m relatively well versed in Rapamycins effect, will read it anyway.

 

[haidut]

GH must be balanced by the other hormones like DHEA. It's not meant to be increased on its own like that. My goal is to control the growth induced by GH and methylation using DHEA, retinoic acid and those other protective hormones, in balance. So that's no surprise to me, but thanks for the link.

Then why not take testosterone/progesterone/pregnenolone/DHEA instead of GH? They have shown anti-aging effects in humans too and are probably safer. Is there anything unique to GH that cannot be provided by those other hormones?
Peat Interview Jan. 24, 2019 On One Radio Network

 

[Terma]

Then why not take testosterone/progesterone/pregnenolone/DHEA instead of GH? They have shown anti-aging effects in humans too and are probably safer. Is there anything unique to GH that cannot be provided by those other hormones?
Peat Interview Jan. 24, 2019 On One Radio Network

Because I already take 3 of those hormones topically (previously huge doses orally) and it is not enough to heal me (my testosterone has always been around 'normal'). Those each have different roles (ways to partition energy, energy sources and nutrients in the body). Progesterone got a little problematic especially, I took it too many nights at 3-10mg (sometimes 200mg for "fun" - doesn't compare to this ;3).

GH targets especially the regeneration of collagen in cartilage and joints via local IGF-1 and iirc other signaling. Otherwise ciprofloxacin ruined my joints permanently. If you find me something else that can do that, believe me, I'll use it. [Yes I know, I saw the BPC-157 thread]

[Reminder: the most useful hormone to me prior to this was 5alpha-DHP - but this is a brain-protective hormone that can probably offset some things that GH may trigger in the brain; you simply need one or more hormones or substances that protect the brain during this process - localized] [******* this post editor sometimes]

 

[haidut]

Because I already take 3 of those hormones topically (previously huge doses orally) and it is not enough to heal me (my testosterone has always been around 'normal'). Those each have different roles. Progesterone got a little problematic especially, I took it too many nights at 3-10mg (sometimes 200mg for "fun" - doesn't compare to this ;3).

GH targets especially the regeneration of collagen in cartilage and joints via local IGF-1 and iirc other signaling. Otherwise ciprofloxacin ruined my joints permanently. If you find me something else that can do that, believe me, I'll use it. [Yes I know, I saw the BPC-157 thread]

[Reminder: the most useful hormone to me prior to this was 5alpha-DHP - but this is a brain-protective hormone that can probably offset some things that GH may trigger in the brain; you simply need one or more hormones or substances that protect the brain during this process - localized] [******* this post editor sometimes]

Understood.
As far as cartilage regeneration, DHEA has good evidence but it needs to be either injected into the joint or done topically on the joint with a high-effectiveness solvent like DMSO/ethanol combination. I have 2 clients that reported this resolved their OA and RA respectively. One of them used progesterone/DHEA combo (1:1) and applied 5mg:5mg twice a day (morning and evening) on his knees and elbows, and the other one used only DHEA and applied 5mg x 3 daily on his knees. Both of them reported that while oral route also works it is not nearly as potent as rubbing directly on the joints and their symptoms recur when they stop it. With the topical application they claim after about a month of use they do not feel the need to use any more and get "relapses" once or twice a year and only in the winter. The one using the progesterone/DHEA combo uses our CortiNon and the one using only DHEA made his own solution with DMSO:ethanol in 80:20 ratio. He says it makes his skin itch but he says it is nothing compared to the relief he gets. Apparently it allowed him to go back to work (construction) and he was unable to walk more than 4 blocks before that. Here are the studies on DHEA and cartilage/joint health.
The effect of dehydroepiandrosterone in different stages of osteoarthritis – Atlas of Science
The disease-modifying effect of dehydroepiandrosterone in different stages of experimentally induced osteoarthritis: a histomorphometric study
Effects of dehydroepiandrosterone on articular cartilage during the development of osteoarthritis. - PubMed - NCBI

 

[Terma]

DMSO has always been problematic for me - I end up with eye pain and interferes with sleep, so I decided to abandon it - too powerful for comfort (without me really understanding everything it does).

The big difference with those people is that tendinosis from fluoroquinolone damage is not inflammatory in nature but more like premature aging and destruction. This is why progesterone is not the best for this, although I believe it will increase blood flood and therefore nutrient supply (eNOS and whatnot) and some other effects. But on its own it's nowhere near.

DHEA definitely is productive for me, even if it weren't about anti-inflammatory effects (although there is the LPS thing too - and that might affect joint health... hmmm)... I guess I'll just start by applying the topical I have straight to my joints in the evening - I mean that's what I'm talking about anyway about the localization. Thanks for that tip, it's better than nothing.

 

[MetabolicTrash]

Metformin seems too risky. Couldn't just DHEA topically and some other combination of stuff achieve the same end results? I've heard of growth hormone secretagogues (had to Google how to spell it correctly!) being sometimes less risky but potentially having similar effects over time, depending on various factors probably.

Wouldn't low stress + a good hormonal profile + good diet/gut health/etc. put you in a better direction of living longer anyways?

Any thing more would be bonuses, which I'm not against of course, but just questioning the metformin-association here. At least low dose DHEA is more conclusive/safe, but exogenous GH and metformin are both risky things I would probably would to stray away from overall -- especially the metformin.

 

[Terma]

I am sure you can find better than metformin - for example if AMPK is important then we already know a million things that induce that in better ways: 17 AMPK Benefits + Natural Supplements to Activate AMPK - SelfHacked
(but of course there is also the specific - or more generic lol? - targeting of mitophagy as Lee pointed out)
(In case you are wondering yes I am still on that cloud right now - it lets me see all this more clearly)