Posts made by Mauritio

Even a mild Vitamin A deficiency decreases DHEA and Pregnenolone formation by about 40% in rats.
Not surpsing, since Vitamin A is needed for the enzyme that converts cholesterol into pregnenolone ( https://bioenergetic.forum/topic/1006/vitamin-a-deficiency-impairs-gonadal-steroid-synthesis?_=1708874573052)

Even more evident was the effect on androstenedione, which suggests that the important enzyme 3bHSD was not working anymore (https://de.wikipedia.org/wiki/3β-Hydroxysteroid-Dehydrogenase)
In the testes the conversion was more than 4 times lower when the animals experienced an "acute Vitamin A deficiency".

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1264968/?page=1

Great points. You can get too much Vitamin A, but you can certainly get too little.

To clarify what you said: if your Vitamin A is low, you will get a pregnenolone deficiency, since the side chain cleaveage enzyme converts cholesterol to pregnenolone. Pregnenolone was peats one supplement he would take on a lonely island with him for a reason and he often repeated how you need T3 and Vitamin A to turn cholesterol into hormones and bile acids.

You guys should look into the RXR. Its a very interesting nuclear receptor.

I posted a lot more studies on C3G in this thread on the forum that had to do with Ray Peat.
just too lazy to post them all here.

https://raypeatforum.com/community/threads/cyanidin-3-o-glucoside-c3g-the-next-polyphenolic-star.52555/

@Milk The difference is like 10% ...

@Not_James_Bond
Depends on the cost.

Elederberry juice is good. Dried elderberries are pretty economic since they contain a lot more C3G per gram.

@Amazoniac
Thanks! I think Ill go for organic + eating peel and hope for the best.

@Lejeboca Thanks!

@Kvothe Interesting , never heard of those. But Ill get some elderberry juice and try it out.

The dose might be important. I haven't looked into the HED of all those studies and approximately how much elderberry juice that translates to , yet.

@Kvothe Interestig.
To peel or not to peel?

I peeled my apple for years because I read a study that showed lower pesticide content in the flesh than the peal but similar vitamin C and polyphenol content (I think they just looked at a single one).

But the peel contains an interesting molecule called ursolic acid which has anti-serotonin effects and also contains the most pectin, which helps with bile excretion.
So I stopped peeling for now.

These two study show that MCTs and Coconut milk increase bile acid excretion and inhibit re-absorption. It might very well be that the MCTs in coconut milk are responsbile for that effect, since it is about 50% lauric acid. I think that is an important point since many people focus on binding bile, but it also has to be excreted fastly and not get reabsorbed too much. Normally 95% of bile gets reabsorbed. So if you bind bile acids thinking you're doung a good thing for yourself, but you are constipated then the toxic bile will get reabsorbed and cause issues.
So Coconut milk and MCTs like caprylic acid can help with that.

The coconut milk study also claims that coconut milk's fatty acids activate the FXR ,which is a very interesting and pro-metabolic receptor. Interestingly PUFA antagonize that receptor. And activating FXR decreases PUFA in the liver (Activating FXR decreases PUFA in the liver )

"As expected, the fecal bile concentration of the coconut milk group had increased significantly by1.68-fold,..."

• https://www.ocl-journal.org/articles/ocl/pdf/2020/01/ocl200053.pdf

" MCT lowered serum cholesterol levels at least partially via reduction of bile acid absorption in the small intestine by inhibition of I-BABP expression."
-https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-018-0267-x

Through reading about polyphenols I discovered this interesting compound that possibly has some interesting effects. It seems to boost Progesterone,Pregnenolone and Testosterone and various steroidogenic enzymes, especially the rate limiting enzyme StAR (hence the title). It also increases the number of androgen receptors in one study.

It also increases the anti-aging gene klotho and has an anti-inflammatory effect via COX-2.

1. "...cyanidin-3-O-glucoside (C3G) and its main metabolite protocatechuic acid (PCA) significantly increased testosterone and luteinizing hormone (LH) levels in the serum of rats, and improved sperm quality."

2. "...C3G and PCA significantly up-regulated the gene expressions of Star, Cyp11a1, Cyp17a1, Cyp19a1, Cyp7a1, Hsd3b1, Hsd3b2, Hsd17b3, Scrab1, and Ass1 in testicular. In Leydig cells"

• https://pubmed.ncbi.nlm.nih.gov/37105472/

3. " Interestingly, C3G improved the expression of LH and FSH receptor in the testis in mice exposed to Cd. Furthermore, C3G activated the signaling pathway related to the synthesis of testosterone processing."

• https://pubmed.ncbi.nlm.nih.gov/31014900/

4. "The results demonstrated that all four kinds of anthocyanins can inhibit ROS generation, alleviate mitochondrial membrane potential damage, and contribute to increased testosterone. Among them, Cy-3,5-diglu with diglycoside performed best on antioxidative ability and improved cell dysfunction and upregulated the expression of the steroidogenic acute regulatory protein (StAR). "

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952726/

5. Again it increases StAR but also CYP11A1 which converts cholesterol into pregnenolone (https://en.wikipedia.org/wiki/Cholesterol_side-chain_cleavage_enzyme) and 3bHSD which increases Progesterone.

"After being cultured in a medium containing C3G and Pb, R2C cells exhibited an increase in progesterone concentration compared with the Pb treatment, as a result of up-regulation of the expression of the steroidogenic enzymes steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 enzyme cholesterol side chain cleavage enzyme (CYP11A1).

• https://www.researchgate.net/publication/320378290_Cyanidin-3-O-glucoside_promotes_the_biosynthesis_of_progesterone_through_the_protection_of_mitochondrial_function_in_Pb-exposed_rat_leydig_cells

6. Helps against heat stress in testicles

"It was found that C3G and PCA restored the external diameter and thickness, and alleviated atrophy and vacuolation of seminiferous tubules. Simultaneously, C3G and PCA enhanced testicular heat stress tolerance through reducing superfluous eIF2α phosphorylation and stress granule formation."

• https://www.researchgate.net/publication/368393384_Cyanidin-3-O-glucoside_and_protocatechuic_acid_alleviate_heat_stress-induced_testicular_damage

7. It lowers weight gain on a high fat diet and increases klotho more than 3 fold.

"... associated with increased expression of genes that encode FGFR1 and β-klotho (>3-fold, P < 0.05)"

• https://pubmed.ncbi.nlm.nih.gov/32470979/

8. It did not have a significant effect on hormones in this study, but more importantly it increased the number of androgen receptors, which is even better since you dont have the danger of aromatization that you would get from increased Testosterone.

• https://pubmed.ncbi.nlm.nih.gov/30376326/

9. It lowers serotonin by about 30% in platelets and protects against thrombosis on HFD.

• https://pubmed.ncbi.nlm.nih.gov/28978870/

Now you might wonder where do I get this stuff from? Nature has you covered.

Blackberries are considered a major source of C3G with about a 150mg/100g, BUT out of all foods by far the most C3G has black elderberry with about 800mg/100g! (http://phenol-explorer.eu/contents/polyphenol/9).

So the easiest and cheapest way to get C3G is probably through elderberry juice, which is widely available.

Even better, the most androgenic anthocyanin from study 4 is also contained in elderberry, just less concentrated.

Other foods than those two barely contain C3G, the third best option are black grapes with about 19mg/100g.

So black- and elderberries are the way to go.

Has anybody tried elderberry juice?

@Hussle1738 I get the same effect from low dose prog and preg. Not sure why. I actually did not expect females to be so responsive to progesterone in males, but it is one of the "higher" hormones nontheless.
I think it might be because it has a beautifying effect on me, meaning my skin looks better and I have less water retention. Unfortunetly it makes me anxious, i guess a GABA-receptor thing.

These last weeks I had a rather positive experience with apple polyphenols, mostly in terms of hair health (https://raypeatforum.com/community/threads/procyanidin-b-2-extracted-from-apples-grows-hair-in-clinical-trials-of-male-pattern-baldness.40036/), but also general metabolic health.

Unfortunately, you cannot get the same polyphenols from Citrus fruits that you can get from apples. For example procyanidins (the major apple polyphenol) are only obtainable from apple and cocoa in high amounts (http://phenol-explorer.eu/contents/polyphenol/151).

They really have a wide range of pro-metabolic effects: Increase in UCP1, Akkermansia, Th and dopamine, anti-viral, anti-bacterial,lowering TLR4,NLRP3, etc...

1. Increase UCP1 and Akkermansia

• Apple Polyphenols Extracts Ameliorate High Carbohydrate Diet-Induced Body Weight Gain by Regulating the Gut Microbiota and Appetite - PubMed

2. Reduces hepatic steatosis and increases Akkermansia

• https://pubs.acs.org/doi/abs/10.1021/acs.jafc.3c00596

3. Increases short chain fatty acids and tight junction proteins in the gut and decreases TLR4 and NF-kB expression

• Apple peel polyphenol alleviates antibiotic-induced intestinal dysbiosis by modulating tight junction proteins, the TLR4/NF-κB pathway and intestinal flora - PubMed

4. Lowers neuroinflammation, TLR4 and NLRP3 ( which is also implicated in hair loss)

• Apple Polyphenol Extract Ameliorates Atherosclerosis and Associated Cognitive Impairment through Alleviating Neuroinflammation by Weakening TLR4 Signaling and NLRP3 Inflammasome in High-Fat/Cholesterol Diet-Fed LDLR-/- Male Mice - PubMed

5. Increase tyrosine hydroxilase and thus dopamine synthesis and UCP1, reduce fat acumulation

• Apple polyphenols induce browning of white adipose tissue - PubMed

6, Increases oxygen consumption, heat production and AMPK

• Dietary apple polyphenols promote fat browning in high-fat diet-induced obese mice through activation of adenosine monophosphate-activated protein kinase α - PubMed

7. Increase hepatic FXR level,and reduce hepatic steatosis

• Apple Polyphenol Extract Improves High-Fat Diet-Induced Hepatic Steatosis by Regulating Bile Acid Synthesis and Gut Microbiota in C57BL/6 Male Mice - PubMed

8. Increase the enzyme CYP7A1 ,which coverts cholesterol into bile acids and is the rate limiting enzyme in this reaction.

• Dose-dependent hypocholesterolemic actions of dietary apple polyphenol in rats fed cholesterol - PubMed

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893479/

9. Anti-bacterial effect ,in this case, against C. difficile, plus a strong anti-inflammatory effect.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694464/

10. Increases autophagy, cytochrome c and several mitochondrial respiratory chain complexes

"...mitophagy-related protein levels were significantly increased. The enzymatic activities of mitochondrial respiratory chain complexes II, III and IV were significantly higher in the AP intake group..."

• Dietary apple polyphenols enhance mitochondrial turnover and respiratory chain enzymes - PubMed

@BlueMeth A few years ago he was convinced B2 and B3 supplementation cures every gut issue IF you only take it long enough.
What has happened to that cure-all?

@Truth I had to chuckle when reading that he eats 4 apples and 3 banans per day, while being anti-fructose.
I am pro fructose and dont eat that much fruit.

The toxic bile movement is interesting, mostly because it brings more attention to the gallbladder and bile. I have been reading a lot about it these past months and discovered that it seems to be an "upstream" thing that affects many downstream issues.

Like the FX-receptor (bile acid receptor) is as interesting as it gets in terms of receptors. The whole "X" family (FXR,PXR, RXR,LXR) of receptors is really worth looking into. Ironically Vitamin A activates the RXR, which is good for liver health.

@haidut Remarkable that biotin is so effective. I would assume that B1 can substitute for it (especially in terms of Co2 production), but that is apparently not the case.
Good Luck.

@brad
Thanks for the explanation!
Seeing all the familiar names over here is like a school reunion and makes me realize how many great people were banned over the last years.

@haidut Groundbreaking work! Were going to look back at this study to "where it all began"...hopefully.

Im wondering if the addition of biotin (and maybe aspirin) was the deciding factor? IIRC your earlier studies had less of an anti-tumor effect and did not include biotin.

@brad
Hi everyone,
I will from now on post my threads here as well as in the RPF, since it doesn't take much effort to copy and paste once they are written.

How much Im going to contribute outside of that also depends on the vibe around here, so we'll see.

BTW what's the origin story of this forum and who is the person behind it? Was it in the making for a longer period of time or a reaction to recent events? How is the power distributed?
I think those are all questions people are interested since it's become obvious that power in the hand of one person can be a bit ...tricky.

Greetings and Good luck!