Random, interesting studies
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I myself have been at a bit of a crossroads for how to regard AMPK since from a strict Peat perspective, AMPK is a signal of low energy availability and thus stress.
It started when I researched low protein and FGF21. I realized most of these markers like AMPK, FGF21 and Sirtuins are strongly connected to peaty things like thyroid, klotho and overall health. Like you can't strictly separate them from each other and say one is bad and the other one is good. That's the Danny Roddy trap. He simultaneously says low protein is good, while FGF21 is bad. That's an illegal chess move
Here's a list of peaty substances that activate AMPK. So either those substances are beneficial despite or because of AMPK activation. I tend towards the latter.
Question for you: Would you regard AMPK raising substances like berberine to be of net benefit?
I think every substance has to be evaluated individually. Even if something has one seemingly bad MoA the overall net effect can still be good.
Berberine could be such a substance but I haven't looked into it yet. -
DANDELION
-It reverses the effects of ionizing radiation quite effective.
Liver enzymes, inflammatory markers, MDA, testosterone, StAR are all pretty much back to baseline, with dandelion supplementation before or after radiation.
https://sci-hub.kvnp.top/10.1007/s11033-019-04939-9#-lowers weight gain, triglycerides and liver steatosis on a high fat diet, while increasing insulin sensitivity.
The affects were reliant an AMPK activation.
https://sci-hub.kvnp.top/10.1016/j.fct.2013.04.023#-reverses antibiotic resistance
https://pubmed.ncbi.nlm.nih.gov/32602832/ -
TETRAHYDROCURCUMIN
THC increases lifes span in mice by about 12%
https://link.springer.com/article/10.1007/s10522-007-9100-zTetrahydrocurcumin extends life span in fruit flies
https://pmc.ncbi.nlm.nih.gov/articles/PMC3249455/#s2It lowered weight gain, inflammation and liver steatosis on a HFD via AMPK activation.
https://pubs.acs.org/doi/10.1021/acs.jafc.8b04624THC helps NAFLD, lowered SCD1 and FAS. Increased bile acid excretion via Mrp2 and Bsep. And changed bile acid composition.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11816436/Increases CYP7A1, a key rate-limiting enzyme in cholesterol-to-bile acid conversion.
Also increases FXR receptor.
https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1576221/fullTHC inceases dopamine via MAO-B inhibition.
https://pubmed.ncbi.nlm.nih.gov/18408903/Tetrahydrocurcumin Outperforms Curcumin in Preventing Oxidative Stress
https://pubmed.ncbi.nlm.nih.gov/40649742/It inhibits tumor growth in Triple-negative breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC12789769/Curcumins inhibit 3bHSD and progesterone production. Although the more saturated verion THC is less powerfull at that. Dosage seems so high that effects should be negligible.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10187107/THC increases UCP1 and adiponectin in adipose tissue
https://www.mdpi.com/2072-6643/13/12/4552normalizes blood glucose and causes a marked improvement of altered carbohydrate metabolic enzymes
https://pubmed.ncbi.nlm.nih.gov/16438392/Radiation protective
https://pubmed.ncbi.nlm.nih.gov/10803946/ -
Cannabigerol attenuates liver fibrosis via AMPK activation
https://pubmed.ncbi.nlm.nih.gov/40818359/ -
Intracellular pathogens inhibit their xeno-autophagic degradation through over-expression of histamin receptor 1, which inhibitis phagosome maturation and fusion to autophagosomes by restraining the necessary production of cytosolic (not mitochondrial) ROS (radical oxygen species).
H1 inhibitors emerge as potent therapeutics, (HDT; host directed therapies) against such diseases (tuberculosis! salmonella! but also likely chlamydia and mycoplasma).This means cetirizine 10mg bid or ebastine 20mg once daily are valuable, perhaps even indispensable enhancers of clearance of such chronic infections.
The nice bonus about ebastine - hugely underappreciated in "Peat-world"? - is that its active form carebastine (activation through Cyp3A4) has recently been identified as a dopamine reuptake inhibitor. This makes ebastine, which acts peripheraly (very little CNS penetration) a long-acting (half-life 14-19h), wholesome alternative for e.g. specific gastrointestinal serotonin-blockers like ondansetron.For CNS activity, benztropine has emerged as the H1 inhibitor with the best overall safety profile. It's also quite anticholinergic although I'm curious about how much so in comparison to the overpraised love-it-or-hate-it cyproheptadine. The anti-cholinergic activity, however, is essential for its also specifically promoting neuronal differentiation (in Parkinson disease or Multiple Sclerosis).
Clemastine as a non-anticholinergic H1RI, which had shown tremendous CNS benefits in neurodegenerative diseases and for re-myelination etc., has surprisingly turned out be somewhat controversial. While it widely enhances neuronal restoration, in some people it drastically speeds up overall degradation by enhanced pyroptosis (inflammatory cell death) through P2RX7 signalling in the TRAP-MS Trial. Scary.
Inhibition of H1 should be very synergistic with the positive results shown of metformin as mTOR inhibitor as shown so far in ongoing MS trials. Both enhance / restore autophagy which has been impaired by whatever cause.
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Progesterone seems to have some interaction with 5ht1a.
not sure what. but seems antagonistic somehow.
could also be that it lowers serotonin and therefore lowers 5ht1a receptor density.https://pubmed.ncbi.nlm.nih.gov/12742638/
https://pubmed.ncbi.nlm.nih.gov/12062903/ -
Hesperidin
Hesperidin (and diosmin) increase FGF21 and lower MDA in mice.
https://pubmed.ncbi.nlm.nih.gov/39459367/Increases FGF21 and strongly lowers SCD1.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6180094/27% max life span increase, not bad. In C. Elegans though.
"Compared with that of the control group, the average and maximum lifespans of C. elegans treated with 75 μM Hst were extended by 16.28% (p < 0.05) and 27.27% (p < 0.01), respectively."
https://pmc.ncbi.nlm.nih.gov/articles/PMC11642050/#sec2-ijms-25-13148It mitigated the damage that endotoxin causes to the uterus by activating AMPK and PGC-1A.
https://pubmed.ncbi.nlm.nih.gov/40886876/It increases the protein level of Klotho, SIRT1 and MnSOD
https://pubmed.ncbi.nlm.nih.gov/41463028/There's a lot of studies showing benefits on skin health. So I thought about making a topical solution of hepseredin. It's not very soluble in many things.
This study used 70% ethanol and it worked.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4366273/
The alcohol might be drying to the skin so not sure if that makes sense.Anti-Fibrotic and Anti-Inflammatory Effects of Hesperidin in an Ex Vivo Mouse Model of Early-Onset Liver Fibrosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC12840767/ -
What is going on with Chia seeds ??
Randomly stumbled upon this.
A casual 7x increase in testosterone while it decimates prolactin. Not bad.
https://link.springer.com/article/10.1007/s11250-025-04391-x
In this study it restored testosterone and thyroid hormones that were suppressed from heavy metal exposure. Also increases antioxidants quite strongly.
It has a pretty high polyphenol content (see image above)
https://pmc.ncbi.nlm.nih.gov/articles/PMC10817305/#sec3-life-14-00109
In this study in female animals it increased Progesterone and LH significantly.
https://www.sciencedirect.com/science/article/abs/pii/S0040816623001441
Chia seeds arevery high in PUFA, especially Omega 3s . So not sure how they help so much with hormones, since PUFA usually is anti-androgenic.
Maybe it's a short term effect ?
Maybe Chia seeds help with transit and reduce gut inflammation ?
In this study after thyroidectomy, Chia seeds extract was given.
It completely restored thyroid hormones, testosterone and sperm parameters. Also lowered MDA, and increased antioxidants.
https://arccjournals.com/journal/asian-journal-of-dairy-and-food-research/DRF-413Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio a distinction is its powder. I don’t think the seeds are digested and stay intact. Awesome find regardless
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@alfredoolivas
Nice catch, this might be important. So it's actually something in the seeds, not the laxative effect.Just saw you can also buy Chia seeds as powder.
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Plant Pregnenolone
The Malaysian plant Holarrhena curtisii contains actual pregnenolone. Its properties also sound somewhat anti-serotonergic.
It also contains alkaloids with steroidal activity
https://pubmed.ncbi.nlm.nih.gov/9834146/
Another alkaloid from the same genus can convert into Pregnenolone in vivo
https://www.researchgate.net/publication/248216582_In_vivo_conversion_of_a_steroidal_alkaloid_holaphyllamine_to_pregnenolone
This paper shows that plants con convert steroids into each other and contain different ratios of known steroids.
Digitalis grandiflora for example contains pregnenolone, progesterone, 17α-hydroxypregnenolone, DHEA, and testosterone
https://pure.mpg.de/rest/items/item_3524574_6/component/file_3528676/content
Holarrhena pubescens another plant from the same genus has anti malarial effects, which rely on the pregnene-type steroidal alkaloids
https://pubmed.ncbi.nlm.nih.gov/29172699/Interesting effects of Holarrhena pubescens on diabetes, also anti-microbial and anti-inflammatory
https://www.mdpi.com/2218-273X/10/9/1341#Conessine, a steroidal alkaloid from Holarrhena pubescens has antiviral, antiplasmodial, anti-inflammatory, and neuroprotective effects.
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=6496801Conessine is a histamine H3-antagonist
https://pubmed.ncbi.nlm.nih.gov/26924015/ -
Hormones activate one of the bitter Taste receptors.
". androsterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate with 0.1 µM and adrenosterone as well as pregnenolone with 0.3 µM, respectively, showed threshold concentrations in the submicromolar range."
https://pmc.ncbi.nlm.nih.gov/articles/PMC12915477/#nyas70172-sec-0080
Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio they taste awful unless dissolved in tocopherol lol
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That is interesting about Chia seeds. Especially from a Peat perspective. (Or maybe I should say from my novice understanding of Peat.) Anything with seeds I've avoided since learning of Peat.
Could the powder of a Chia seed even be different from simply grinding the seeds?
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@Mossy Peat even said he can't see any value whatsoever in chia seeds, which is weird because they contain a lot of polyphenols, fiber and minerals, so there is at least some nutritional value there.
And he said if someone feels better from them it's probably the laxative effect, which is more or less ruled out in the above study.
So I still dont understand how it has these effects.
And it doesnt seem to be just the grounded seeds. There's another study I posted which used chia seed extract, which was very beneficial as well.
And IIRC another one used whole chia seeds.I think the powder and grounded seeds should be very similar. Unless the powder is somehow defattened. But suppose they would state that.
There was a thread on here recently that Omega 3s are essential and you need them for certain things. Ive only skimmed it, but maybe it has something to do with that.
So following the true method of knowledge I will order some grounded chia seeds and see for myself.
Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio Appreciate your thoroughness. It will be interesting to see what effect they have on you. I don't like the taste and feel of chia seeds, but maybe they could be used as a food supplement, like I do with liver.
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