Random, interesting studies

Mauritio

@Kvirion said in Random, interesting studies:

@Mauritio
It also worth noticing that peppermint is a κ-opioid receptor agonist...

https://en.wikipedia.org/wiki/Κ-opioid_receptor#Natural_agonists

Uh oh..." KOR activation causes a release in prolactin,[76]"

But then :
Menthol from Mentha piperita Suppresses the Milk Production of Lactating Mammary Epithelial Cells In Vivo and In Vitro
https://pubmed.ncbi.nlm.nih.gov/33188562/

....
Doesn't add up .

alfredoolivas

@Mauritio That might be how it inhibits LH and FSH, and is anti-androgenic, because the opioid receptor inhibits GnRH secretion when activated.

Steroids such as T and DHT, increase opioid receptor expression, which could be a mechanism of how they shut down the HPG axis.

Kvirion

@Mauritio said in Random, interesting studies:

Doesn't add up .

Welcome to the real world of Complex Adaptive Systems

This means that reaction/influence/outcome is context-dependent. I.e. may be different for different sexes or certain conditions/circumstances...

BTW Before Peatiing, I was hypothyroid with IBS-D and pretty low T...
When I was using p-mint it definitely was slowing down my digestive system - in opioid-like ways.
Secondly, at first, I was feeling the influence of rising dopamine (MAO-B inhibition), but after an hour or two it always turned into an increase in prolactin and a decrease in testosterone, which unfortunately was painfully noticeable for at least half of a day or night...

Mauritio

@alfredoolivas said in Random, interesting studies:

That might be how it inhibits LH and FSH, and is anti-androgenic, because the opioid receptor inhibits GnRH secretion when activated

Like I said above : the study showed that peoermint increased LH and FSH

@Kvirion said in Random, interesting studies:

but after an hour or two it always turned into an increase in prolactin and a decrease in testosterone, which unfortunately was painfully noticeable for at least half of a day or night...

Yeah too many people reports similar experience to yours, so I think it's best to stay away from it.

Mauritio

@Mauritio said in Random, interesting studies:

Dates, olives and walnuts contain the highest amounts of the phytoprogestogen syringic acid.

http://phenol-explorer.eu/contents/polyphenol/420

https://pubmed.ncbi.nlm.nih.gov/9704030/

Not only is syringic acid a phytoprogestogens, but it also had very potent pro thyroid effects in this study.

They gave rats a known anti- thyroid drug (PTU) to induce hypothyroidism.
Then they gave them syringic acid or T4.

Syringic acid completely restored the T3 and T4 levels of hypothyroid rats.
It even increased them above baseline.

T4 levels were even higher with syringic acid compared to giving them actual T4.

It also lowered TSH quite drastically .

@cs3000 they also included a control + synstingic acid group, and even in normal animals it helped their thyroid and increased T3 by about 30% .

Syringic acid had an affinity for the thyroid receptor TRb that was twice as strong as that of T3!

Syringic acid also increased antioxidants like SOD and catalase powerfully and lowered inflammatory cytokines.

These dosages they used are not achievable by diet alone though . Maybe there is a supplement. I also read something about pomegranate peels contain syringic acid.
https://pubmed.ncbi.nlm.nih.gov/34047416/

Mauritio

Pomegranates

One of the main polyphenols of pomegranate peels, Punicalagin, seems to have anti-estrogen and pro- progesterone effects. The anti- estrogen effect should be achievable by taking a supplement the pro- progesterone effect would be difficult. But this was an in vitro study in rats , so the dosages are a bit of a gamble anyway.

"Punicalagin (at 100 microg.ml(-1)) significantly (P<0.05) increased progesterone secretion. On the other hand, the release of 17beta-estradiol was significantly (P<0.005) decreased by punicalagin addition (at 10 microg.ml(-1))."

https://pubmed.ncbi.nlm.nih.gov/26291726/

Several polyphenols of pomegranate are aromatase inhibitors.
"These studies suggest that pomegranate ET-derived compounds have potential for the prevention of estrogen-responsive breast cancers."
https://pmc.ncbi.nlm.nih.gov/articles/PMC2805471/

"PME binds ER and down-regulated the transcription of estrogen-responsive reporter gene transfected into breast cancer cells. The expressions of selected estrogen-responsive genes were down-regulated by PME"
https://pubmed.ncbi.nlm.nih.gov/21839626/

This study hints at pomegranate extract containing significant amounts of syringic acid.

"WPE indicated that syringic acid (SA), vanillic acid and caffeic acid were the predominant flavonoids..."
https://www.sciencedirect.com/science/article/abs/pii/S0377840121000973

Pomegranates peel extract increases progesterone and offspring weight and survival .

"Fppee improved homeothermy, progesterone concentration, and pregnancy outcomes."
"Lambs born to Fppee ewes had the highest birth weights and survivability. "
https://www.sciencedirect.com/science/article/abs/pii/S030645652400261

Pomegranate extract increased Energy expenditure, V02, VCO2 and increases body temp after cold exposure.
Which probably means that it restores shivering cold thermogenesis, which is lost in unhealty people, meaning they can't mount an adaptive response to a stressor (cold). This is corroborated by the fact that Ucp, is increased in the Pomegranate group by 3- told, but only after cold exposure. It also increased SIRTI a lot and a protein called BMPB8, which stops preadipocytes from maturing into fully functional adipocytes.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9499678/#ijms-23-10460-f006

Pomegranate contains 7 (!) Carbonic anhydrase inhibitors, leading to increased CO2.
https://www.jstage.jst.go.jp/article/bpb1993/16/8/16_8_787/_article

Pomegranate polyphenols inhbit mTOR (similar to protein restriction) . Mango too.
https://pubmed.ncbi.nlm.nih.gov/27028006/

Pomegranate peel polyphenols lower adrenaline and cortisol induced by chronic, mild stress. It also I I it's MAO, strongly favoring MAO-B, leading to an increase in the dopamine/serotonin ratio.
https://onlinelibrary.wiley.com/doi/10.1111/pcn.12100

It reduces brain lead concentrations by about 90% in animals consuming high lead amounts.
https://scholar.google.com/scholar_lookup?journal=Pol. J. Nat. Sci.&title=Algerian pomegranate peel decreases lead concentration in brain and improves neurological disorders&author=L. Gadouche&author=N. Djebli&author=Z. Khayra&volume=35&publication_year=2020&pages=97-107&#d=gs_qabs&t=1738438268566&u=%23p%3DvYGsC48cmZEJ

Ellagic acid (one of the major active molecules in pomegranate). Decreases brain NO and NMDA receptors.
https://www.sciencedirect.com/science/article/abs/pii/S0143417919300204

In this study pomegranate juice increased plasma catalase by 2x, vitamin C by 3X and and vitamin E by 5x, also increased testosterone by about 30% .
https://pubmed.ncbi.nlm.nih.gov/18222572/

Mauritio

Vitamin A supplementation in third world countries drastically reduces mortality.

"Among children aged 12-71 months at baseline, mortality in control villages (75/10 231, 7·3 per 1000) was 49% greater than in those where supplements were given (53/10 919,4·9 per 1000) (p<0·05). "

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(86)91157-8/fulltext

(Mild)Vitamin A deficiency still affects almost a billion people

"In 2019, VAD and mVAD affected 333.95 million (95% CI = 253.00-433.74) and 556.13 million..."
https://pmc.ncbi.nlm.nih.gov/articles/PMC10416138/

92% ofChildren with measles had Vitamin A deficiency. Giving them Vitamin A reduced their mortality by 50%!
https://pubmed.ncbi.nlm.nih.gov/2194128/

From: "Endocrine Physiology" by Constance R. Martin, Ph.D. :

"Laboratory mammals maintained on Vitamin A-
deficient diets stop growing, acquire numerOuS epi·
the]ial cell and connective tissue disorders. and be·
come blind and sterile. "

"However. retinol or a precursor is needed for
spermatogenesis, for the ability to sustain preg·
nancy, and for the formation of visual pigments. "

"Vitamin A supports bone remodeling. In defi·
ciency states. the passageways for nerves and blood
vessels do not enlarge sufficiently. Infants deprived
of the vitamin have detective loolh formation_"

Mauritio

This post is deleted!

Mauritio

Vitex Agnus castus:

TLDR:

very strong evidence on pro-progesterone effect
strong evidence on anti-prolactin effect, esp. In high doses
few studies on estrogen and testosterone, effects ranging from low antagonism to slight agonism in both

PROGESTERONE:

In this human study on women with hyperprolactinemia it increased progesterone by almost 4-fold ,while increasing estrogen 1.13 fold.
So there's a very strong increase in progesterone and a comparably insignificant increase in estrogen.

"...and eliminated deficits in luteal
progesterone synthesis (placebo: 1.99±0.65→2.34±0.59 ng/ml; verum: 2.46±0.70→9.69±6.34) in
the verum group. The changes were significant. All other examined hormonal parameters did not change with the exception of 17ß-estradiol which increased significantly in the luteal phase in patients receiving verum (placebo: 119.5±26.0 pg/ml→131.1±33.2; verum: 131.6±25.0 pg/ml→151.6±25)"

PROLACTIN:

Here's a lot of info on it from the RPF ,with OP claiming it removed his premature ejaculation. Dosage seems to be important.
https://lowtoxinforum.com/threads/vitex-for-men.11538/

Mauritio

"Result showed 5-HT released from platelet decreased..."
https://pubmed.ncbi.nlm.nih.gov/8043997/

Mauritio

Another very impressive study about A. Melegueta a.k.a. Grains of Paradise.

Not only did rats on a high fat diet not gain weight they actually lost weight while on GoP. Rarely ever saw that.

It also increased UCP1 by more than 100% and PGC1a several fold.

https://journals.sagepub.com/doi/full/10.1177/1934578X211033744#sec-2

It can also quadruple rats testosterone , reduce prolactin and estrogen ,while not touching progesterone. For more info look at my posts on it on the former RPF.

Mauritio

The Acute Effects of a Commercially Available Caffeinated and Caffeine-Free Thermogenic Dietary Supplement on Resting Energy Expenditure, Hunger, and Hemodynamic Responses
https://www.mdpi.com/1661-3821/4/1/6

cs3000

@Mauritio nice one on the syringic acid thanks, agonises the trB receptor. so could be helpful for people with chronic inflammation having their t3 eaten up by immune cells / deiodinase 3 getting around this by hitting the receptor direct .
1,25 vit D up in poor health also has much more potent affinity for that receptor than t3 but as a blocking effect instead

Looking around at sources because of the dose i dont think u'd get enough from foods right, (they said 50mg/kg was better than 25mg/kg so wouldnt get the effect from lower by the sounds of it) ,
its reasonably priced but only seeing it on the sites not selling to individuals

so its a hydroxybenzoic acid like aspirin

wonder if ferulic or vanilic acid could be alternatives?

ferulic acid also stimulates t3 activates TPO so maybe binds thyroid receptor too ? but by other effects not as potently as syringic
https://pmc.ncbi.nlm.nih.gov/articles/PMC8151655/

https://www.researchgate.net/figure/Structures-of-aromatic-compounds_fig8_226981671

or vanillin from vanilla extract but less similar

ferulic acid can be bought as a cosmetic , not very bioavailable in cereals because its bound in polysaccharides but given to mammals by itself its very bioavailable
here in vivo it reversed hypo too
https://link.springer.com/article/10.1007/s12020-024-03818-z
50mg/kg t3 levels
(not as effective as syringic)

very liver protective in cadmium toxicity when given after established (but like most of these polyphenols dosing high could deplete too many needed metals too over time)
10.1007/s11356-019-05420-7

,
curious what the differences are agonising trA vs trB thyroid receptors

cs3000

@cs3000 also ferulic acid is a partial 5ht1a agonist without effecting 5ht2a. not active at 10mg/kg in mice orally but is 50mg/kg ~250mg-300mg human , and 250mg/kg started losing effect. maybe 150mg - 500mg

So could give a relaxing / anti anxiety effect
but maybe a short effect time / half life
(lowered the amount they moved around frantically in new environment or around new mouse, and lowered the heightened aggression, given acutely
all of the effect went when they gave them a 5ht1a antagonist
https://pubmed.ncbi.nlm.nih.gov/33829309/

50mg/kg orally in mice = enhanced exercise endurance, and prevented fatigue from consecutive days exercise
https://www.jstage.jst.go.jp/article/bbb/73/6/73_90062/_pdf/-char/en

&
fully restored brain performance in Alzheimers model by restoring brain blood flow
https://pmc.ncbi.nlm.nih.gov/articles/PMC8423929/#Sec20
cool imaging

1 way to get a better idea if ferulic acid is legit, should smell like "metallic meat" or hot dogs

CrumblingCookie

@cs3000
It's bizarre that ferulic acid hasn't been getting much more attention on these forums already long ago. In cosmetics/skin care it's a "secret" niche ingredient. It's comparatively cheap to buy and mostly extracted from rice bran.
Taken orally, ferulic acid is super powerful with noticably effects already after a few hours / half a day. For me it gives a remarkably clear head/mind. As you've brought up it has this very rare anti-serotonin profile on the specific receptors. But it's also very antiinflammatory. I.e. it may have powerful effects on lowering immunity. I can't say which effect weighs stronger and therefore stopped to take it after only a few days (+-250mg twice a day) because the effects were uncannily good.

cs3000

@CrumblingCookie cool, so did you stop alltogether or you take it a few days a week? im thinking if i notice benefits will go for 150mg - 250mg and 1 day between uses
just had a look at ant inflammatory effects yeah looks very good in the intestines at least

CrumblingCookie

@cs3000
I've looked into my notes (glad I had made some!): I was taking 250mg (not 500mg) once to twice a day. I had stopped it altogether because my reasoning told me that such a strong effect could only be ascribed to strong antiinflammatory effects which I am very wary of with regard to maintaining immunity.
Some more of my notes on FA:

FA is a presynaptic 5-HT1A agonist, alleviates neuroinflammation. 
May also improve skin tone and marks long-term. 
Compared to agmatine FA felt calmly stimulating. Maybe because it also 
agonises β2-receptors and inhibits MAOs, increases ghrelin and peristalsis. 
No increases in CRH, ACTH and cortisol.
Modulation of Nurr1 expression as well as immunotoxicity by inhibiting TRAF/TAK1/NF-κB, 
Nrf2 and p53 pathways.
(Antiviral, antibacterial), antiinflammatory, promoting angiogenesis 
and activating the energy-regulating AMPK.
The increased mental clarity by FA began half a day after the first intake
and further increased over the course of three days.

AFAIK 
TRAF and TAK1 are far up the cascade of intracellular signalling from pathogen sensing.
Inhibition of those not only decrease NF-κB 
but also the pathway down AP1 essential for innate immunity.
Inhibition of Nrf2 decreases bacterial phagocytosis (less bacteria getting eaten by macrophages).

Mauritio

@cs3000 @CrumblingCookie

Ferulic and vanillic acid seem to have some estrogenic properties. Maybe gigantol and Geranylgeraniol are some alternatives.

Quercetin and Ferulic Acid Elicit Estrogenic Activities In Vivo and In Silico
https://pubmed.ncbi.nlm.nih.gov/37446770/

The authors' conclude that FA causes human breast cancer cell proliferation by up-regulation of HER2 and ERalpha expression.
https://pubmed.ncbi.nlm.nih.gov/16893382/

Ferulic acid possessed phytoestrogenic effect by up-regulating pS2 gene expression and the receptor subtype of ERalpha.
https://pubmed.ncbi.nlm.nih.gov/21246834/

Although this one says it Inhibits estrogen.
https://pubmed.ncbi.nlm.nih.gov/33987364/

I've found less evidence of vanillic acid being estrogenic so I'd be more willing to experiment with that one.

Effects are abolished by anti-estrogenic substance , which doesn't prove it to be directly estrogenic, sometimes they use weird substances with a lot of different effects.
https://pubmed.ncbi.nlm.nih.gov/25106917/
This study says that the Anti-osteoporosis effects of syringic acid and vanillic acid are not due to estrogen. Possibly even anti-estrogenic ?
https://pubmed.ncbi.nlm.nih.gov/31186185/
vanillin elevated both serotonin and dopamine levels in brain tissue.
https://pubmed.ncbi.nlm.nih.gov/25595338/

"Moreover, treatments with 10 μM gigantol increased StAR protein levels and progesterone production from MA-10 Leydig cells. However, neither ferulic acid nor isoferulic acid influenced StAR protein synthesis and progesterone production in MA-10 Leydig cells. "
https://pubmed.ncbi.nlm.nih.gov/35723385

Gigantol seems interesting. Anti-cancer, Inhibits mTOR.
https://pubmed.ncbi.nlm.nih.gov/33737087/

Geranylgeraniol is another candidate. Also increases progesterone and testosterone. Probably easier to obtain .
https://pubmed.ncbi.nlm.nih.gov/26757775/

It protects from muscle atrophy in this one.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7652489/

In this human study it slightly increases testosterone in males .
https://www.mdpi.com/1661-3821/3/4/43

cs3000

@CrumblingCookie thanks for the info , solidified another thing ive been looking for
oh right, yeah sounds reasonable , better for the tail end i guess if symptoms stick for >7 days or get too wild

its really effective at lowering neutrophils in lungs in viral infections (big part of the damage)
(found neutrophils only really needed to peak early to kickstart the process & attract other cells, unless theres a big lack of lymphocytes,
by the time symptoms are noticed theyre probably already peaking or close)
doi: 10.1055/s-2006-958060

~200mg heq, lowered neutrophil in lungs a lot , and giving it on day 0 the viral count increased only a little. but still probably better holding for a day or 2 of symptoms

should be very effective for people hit hard by symptoms in current breakout

cs3000

@Mauritio thanks will have a look through, quercetin definitely feels estrogenic to me even at low dose, and long half life. im trying it rn for a specific effect. the supplement doses are kind of crazy for where it has effects generally