Random, interesting studies

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 unique 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

cs3000

@Mauritio the 1st one, ferulic acid didnt increase uterus weight where quercetin did, (5mg/kg ferulic lowered it a little fitting with the other study showing anti-estrogenic activity at 5mg/kg, but lose some of the effects here),

had mild non significant effect on increasing estrogen vs quercetin that increased it 22.48%.
but thats at ~100mg - 150mg heq. with the estrogenic potential its probably more significant at higher doses. tho has some of its benefits at 150mg, so i think its probably an ok dose there. though more gained further

so milder estrogenic activity than quercetin , but it still binds receptors.
but the breast cancer 1 you posted is concerning yeh they didnt use crazy high concentrations
and potent effect

was dose dependant coming down from 1uM to 100nM to 10nM.
10 nM is ~2 ug/ml for this

good enough reason to avoid daily for long duration, or if have a tumor. will avoid going over 150mg long term

the other one you posted showing anti estrogen effect was low dose 5mg/kg, ~ 50 - 75mg human.
raised testosterone & estrogen together
lowered the elevated estrogen receptor
https://pmc.ncbi.nlm.nih.gov/articles/PMC8106114/

,
here given to male rats it restored & increased testosterone higher than controls 2.45 -> 3.8 , 50mg/kg rats
https://onlinelibrary.wiley.com/doi/abs/10.1111/and.12798

blood levels of testosterone plummet when u give male rats estrogen. so doesnt seem to be showing estrogenic effect in males for some reason,
but the other = good enough reason for some caution yeh

Mauritio

Rosmarinic acid.

Almost doubled testosterone in controls. And strongly protected against EMF damage . https://pmc.ncbi.nlm.nih.gov/articles/PMC3847387/#sec12

It also protected against different types of radiation .
https://pmc.ncbi.nlm.nih.gov/articles/PMC11053252/

cs3000

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