Random, interesting studies
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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
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-413
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 ? -
@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
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@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.
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@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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@Mauritio 5ht1a 1b both downreg sero produc
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Mauritio said:
A casual 7x increase in testosterone while it decimates prolactin. Not bad.
In the testosterone study they used 0.025g/L of chia powder in drinking water, which is an extremely low dose. This should approximately correspond to an HED of ~70mg.
Wild that even had an effect at all at that dosage.
There's another study using the same dosing protocol also in rabbits. So HED ~ 70mg.
And it shows strongly lowered cortisol, insulin, leptin and triglycerides. With a small increase in TSH.

It also drastically lowered one protein which is part of the HSP70 family. Peat used to write about the dangers of heat shock proteins, so lowering should be a good sign.
https://www.nature.com/articles/s41598-024-82175-3#Tab5
Many studies with Chia seeds use HEDs of 5/10/or even 50g. Often showing that the 10g or higher dose is most effective. While the lower dosage is relatively ineffective.
The above studies show that (at least in rabbits) a microdose might be all you need.
70mg/ day increased testosterone and lowered cortisol strongly.
If you want to replicate the study, measure 70mg with a mg scale and put in a big bottle of water and sip throughout the day. That is the closest thing to what they did in the studies.
So that way, you could get the benefits without overloading on PUFAs. -
@Mauritio I await a report of your experience
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Mauritio said:
The above studies show that (at least in rabbits) a microdose might be all you need.
70mg/ day increased testosterone and lowered cortisol strongly.
If you want to replicate the study, measure 70mg with a mg scale and put in a big bottle of water and sip throughout the day. That is the closest thing to what they did in the studies.
So that way, you could get the benefits without overloading on PUFAs.Heres another study on chia seeds. They also use an HED of 50-70mg, although this time it is an extract.
In diabetic rats that were given low dose chia seeds extract (P3), blood sugar and MDA drastically improved. They were lower than in the control group without diabetes (P0) and lower than in the positive control group that received metformin (P1).

https://www.researchgate.net/publication/373779495_Effect_of_Chia_Seed_Extract_Salvia_Hispanica_L_On_Current_Blood_Sugar_Levels_and_MDA_LevelsA plausible explanation of the benefits could be mitohormesis. A very small mitochondrial stress could activate benefical compensatory mechanisms like Nrf2, PGC-1a or AMPK. There are studies showing Chia seeds activate AMPK.
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ETIFOXINE
Has anybody tried it? It seems to be a GABAergic that strongly increases (neuro-)steroids.
Here you can see that it strongly increases Pregnenolone, Progesterone and the infamous 5aDHP in the brain, especially in higher doses. It also seems to increase andogens T + DHT in lower doses while it suppresses them in higher doses.

https://www.pismin.com/10.1016/j.psyneuen.2017.05.022Different study similar findings:
"Exposure of frog hypothalamic explants to graded concentrations of etifoxine produced a dose-dependent increase in the biosynthesis of 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone and tetrahydroprogesterone, ..."
https://pubmed.ncbi.nlm.nih.gov/25785994/Etifoxine reverses weight gain on a HFD
https://pubmed.ncbi.nlm.nih.gov/32679124/Etifoxine was as effective for treating anxiety as a Benzodiazepine!
"Etifoxine was non-inferior to Alprazolam in reducing anxiety symptoms in GAD, was well-tolerated, and can be a promising alternative for anxiety management without drug dependence risk."
https://pubmed.ncbi.nlm.nih.gov/41763071/Etifoxine restores mitochondrial oxidative phosphorylation (in vitro)
https://pmc.ncbi.nlm.nih.gov/articles/PMC8657969/It seems to increase GABA-A receptors or at least amplify its function.
https://pubmed.ncbi.nlm.nih.gov/10854897/ -
"After brushing out the effect of lifestyle factors as best as possible with statistical methods, the researchers found that during the study, participants who consumed 2 or more tablespoons of olive oil daily were 31 percent less likely to die than participants who did not consume olive oil."
https://www.ergo-log.com/this-daily-amount-of-olive-oil-may-extend-your-lifespan.html
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Benzoic acid, a known uncoupler - even in small amounts - can convert to salicylic acid inside the body.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2800778/The best source of benzoic acid are fresh cranberries.
There's also the plant Benzoe Siam which is about 20-30% benzoic acid, but not sure if theres a food grade option.
Essntial oil of plants are an inexhaustible source of interesting components, with interesting properties.
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Berberine
Berberine activates thermogenesis in white and brown adipose tissue and increases UCP1;
PMID 25423280
Berberine increases testosterone but also prolactin. There might be a sweet spot between 50-100mg/kg (rat dose) where you get minimal prolactin increase with a significant testosterone increase. Maximal T increase was almost 100%
https://link.springer.com/article/10.1007/s44345-024-00007-3#Fig2
Berberine sometimes receives criticism because some studies show that it can inhibit mitochondria.
Which is true it can:"
"...inhibit mitochondrial respiratory complex I” in vitro
PMID 18285556Although in this study it had a positive effect on mitochondria in vivo; it increases mitochondria numbers and prevented mitochondrial dysfunction, which was accomplished via AMPK and SIRT1 activation.
"Furthermore, we observe that the prevention of mitochondrial dysfunction by BBR, the increase in mitochondrial biogenesis, as well as BBR-induced AMPK activation, are blocked in cells in which SIRT1 has been knocked-down."
PMID: 22027215
"...extended the lifespan ... of naturally aged mice by ~16.49%”
PMID 31773901
This study reported an increase in the NAD+/NADH ratio.
PMID: 22027215
Berberine made someone on the RPF able to tolerate milk.
https://lowtoxinforum.com/threads/does-anyone-here-use-berberine-regularly.41514/post-669774
Increases SERT; lowers serotonin
https://pubmed.ncbi.nlm.nih.gov/21647174/
decreased HFD-induced metabolic endotoxemia. Inhibits TLR4
PMID 29202334.
Berberine activates one of the bitter receptor family, (TAS2Rs).
Interestingly that is the same receptor that Pregnenolone, DHEA and androsterone activate. (not sure if it's the same subtype)
And, it's activation increases GLP-1 signaling.
https://pubmed.ncbi.nlm.nih.gov/29363059/This bitter receptor is also partly responsible for the weight loss effects seen with berberine. That's a good counter argument when people say berberine doesn't even get absorbed much. It doesn't have to get aborbed to activate TAS2Rs.
https://pubmed.ncbi.nlm.nih.gov/36341914/
Berberine also activates the bile acid receptor FXR which has a a lot of downstream pro-metabolic effects.
"These results indicate that BBR may exert its lipid-lowering effect primarily in the gut by modulating the turnover of bile acids and subsequently the ileal FXR signaling pathway."
https://pubmed.ncbi.nlm.nih.gov/27932556/
A lot of the effects of berberine seem to be downstream from bile acid metabolism and gut effects.
"The abundance of Clostridium genera was significantly inhibited by BBR, which resulted in a significant reduction of secondary bile acids.."
https://pubmed.ncbi.nlm.nih.gov/38740003/
Berberine increases FGF21 in BAT and leads to less weight gain on a HFD.
https://pubmed.ncbi.nlm.nih.gov/30991048/
Berberine can lower adrenaline.
https://pubmed.ncbi.nlm.nih.gov/12650858/Blocks alpha2 adrenoceptors
https://pubmed.ncbi.nlm.nih.gov/1649363/
https://pubmed.ncbi.nlm.nih.gov/41039433/ -
A few studies on salicylic acid/ sodium salicylate:
Sodium salicylate induces ovulation in female mice. It also lowers Progesterone and estrogen, while increasing prostaglandins. Quite counterintuitive.
The devil's in the detail though. The dosages that have the above effects correspond to an HED of ~2.5-20mg.
If you look at the highest dose (21.2mg/kg) that's around 100mg HED, it basically had no effect on the above parameters.

You can see on the highest dose it actually lowered the protein level of COX-2 and CYP17A1, which converts pregnenolone and progesterone into cortisol-like steroids.

So I guess don't take low dose sodium salicylicate .
https://pmc.ncbi.nlm.nih.gov/articles/PMC9916436/
Interesting, old study on high dose salicylic acid. The authors say it depresses thyroid function and goiter formation. I guess they mostly mean TSH suppression by that.
They also compare thyroxin to DNP and salicylicate. Both of these thyromimetics share many characteristics of thyroxin, but not all. For example they cannot antagonize myxedema."Thyroxine, dinitrophenol (DNP), and salicyl-
ate evoke many similar responses in man or the
experimental animal (Table V). "
From:
SALICYLATES AND THYROID FUNCTION. II. THE EFFECT ON
THE THYROI-PITUITARY INTERRELATION
By J. WOLFF AND FRANK K. AUSTEN
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