@DavidPS
I've thought along the same lines but struggled to fit those concepts coherently together.

expression of Hmgcs2, the gene encoding rate-limiting enzyme of ketogenesis, decreases significantly in Leydig cells from aged mice. Additionally, the concentrations of ketone bodies β-hydroxybutyric acid and acetoacetic acid in young testes are substantially higher than that in serum, but significantly diminish in aged testes. Silencing of Hmgcs2 in young Leydig cells drives cell senescence and accelerated testicular aging.

So what I'll do is shower you and the others with my open questions:

First in line for me is the question: Why is (testicular) Hmgcs2 being downregulated in aging?

Obviously feeding BHB as the end product of ketogenesis increased testosterone. Therefore the underlying mechanism can't be about sex hormone substrate availability (cholesterol). Rather, it's about a decline in ketogenesis, i.e. a tissue energy depletion: "suppression of ketogenesis impairs steroidogenic function of LCs"

Is it locally or systemically/predominantly hepatically?

--> The study tells us it's locally, because testicular tissue concentrations are higher than serum and "BHB andAcAc concentrations in serum were comparable between the young
and the aged group (Fig. 2k, l)."
"Remarkably, the concentration of ketone bodies in the testes were more than tenfold higher than that in serum (Fig. 2i–l), implying ketone bodies might have testis-specific functions"

Is there a decline in peripheral fatty acid circulation as a reason for declining tissue ketogenesis? In contrast to ketone bodies, free fatty acids don't really cross the blood--brain-barrier. Do they significantly cross the blood-testis-barrier? If it's not about fatty acids as a ketogenesis substrate, is it about peripheral protein circulation levels? If it's about neither upstream substrates, is there perhaps a tissue-specific decrease of utilization to Acetyl-CoA? Is the HMGGCS2-decreasing cause founded in a lack of carnitine or a lack of CoA? Will supplementation of carnitine or stimulation of CoA then attain similar results to exogenously supplying BHB for that matter?

--> The authors have followed this strain of thought and injected AAV vectors to deliver and overexpress the Hmgcs2 gene, demonstrating "that Hmgcs2 overexpression increased the levels of H3K9ac and FOXO3a in aged testicular tissue, similar to the levels in young testes"
--> So it's not immediately about any substrate levels but HMGCS2 activity itself.

Does this lead back to epigenetic downregulation of bodily functions, in this case HMGCS2, and the concepts of DNMTi and HDACi?

--> Clearly there's a positive association between acetylation of H3K9 and HMGSC2 expression in rats in that HMGSC2 induced higher H3K9ac.

Is this reciprocal, i.e. would H3K9ac also induce HMGCS2? Or does H3K9ac come about by increased concentrations of the products of HMGCS2, like BHB, and the cellular energy abundance provided by it?

--> The authors followed this and found: "Consistent with in vitro results, Western blot analysis revealed that BHB increased the levels of H3K9ac and FOXO3a in aged testicular tissue, similar to the levels observed in young testes (Fig. 7d, e)."

Is this then a course of gradual decline, wherein a decrease of testicular ketone energy in turn decreases its own synthesis? Just as the observation that more BHB increases its own synthesis? I.e. a positive / negative feedback loop? Would, therefore, a one time course of exogenous BHB or induced Hmgcs2 overexpression "reset" testicular ketogenesis back to a youthful level, wherefrom it may once again gradually decline?

--> Well, the authors fed exogenous BHB in addition to the control diet to 18-months old rats for a duration of 2 months. Those were then 20-months old rats. Unfortunately, no subgroup to follow up on wrt to their physical activity and testicular findings has been kept and reported on beyond that.

"Last, we validated the changes in FOXO3a-related inflammation genes through quantitative RT-PCR analysis, revealing that inflammation-related genes were significantly upregulated in aged mice, and Hmgcs2 overexpression reduced the expression of these genes (Supplementary Fig. 9b–e).
Overall, these data suggest that enhancing ketogenesis is sufficient to alleviate LCs senescence and testicular aging in aged mice."

@yerrag
Wow. Those are some additional challenges. Coincidentally, my brother just survived a 4 day hospital stay for congestive heart failure.

I think your perspective of leaning on Peat and alternative counterculture, as a defense against status quo medical pathology, is the general perspective of most of us. But, just as you say, it's challenging, and can be daunting, because we are limited. I hope more alternative and naturopathic doctors adopt bioenergetic and similar principles to help those like us to bridge the gap, so we don't have to play doctor. There does seem to be a trend of some going that way. My thought is that it really won't be at its best until it's local, so we can have real-doctor support.

This is the fatty acid composition of the three fats. Margarine actually only has slightly higher PUFA content than olive oil and less MUFA than it. So overall margarine contains less unsaturated fats than olive oil does.

One reason olive oil performs so well despite its high UFA content, might be its polyphenol content, containing oleocanthal, hydroxytyrosol or even small amounts of policosanol.

I've talked about their pro-metabolic, testosterone enhancing effects here:
https://bioenergetic.forum/topic/3624/olive-leaf-extract-increases-t3-t4-lowers-tsh?_=1748111089619

1000015133.png

Canadian rancher Maggie is laughing at this study 😁

alt text

Maybe something to do with tonicity, vascular tone and everything thereafter. Onset in reverse, I wonder what causes that.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11293686/
(Only a sample.)

If "the next pandemic" had an energy mandate as or opposed to a vaccine mandate. I wonder what would happen.

the study in women athletes had them taking ridiculously high doses, something like 1g a day of TTFD iirc.

it is dopamingeric, the first time i took a 25mg alinamin f tablet i got pronounced euphoria. it’s popular in japan.

@haidut
I remember the announcement and recruiting for this study in 2020 iirc.
Then everything vanished and reportedly the project's budget was cut and the study shelved.
WTF was going on there. How did they finish it anyway? Who allowed them to now release their results? Too many polito-economic-corruptory questions.

@haidut Wow no surprise the SSRIS are really from the bad guys.

Do you have a recommendations for what a person with PSSD should do?
(Post ssri sexual dysfunction)
Would love to hear your thoughts…….

Thanks

@CrumblingCookie I wouldn't call it anti-serotonergic , the mood lift felt more like a neurosteroid boost. Which is a little different from a dopamine boost. Both are good though.

Not sure about it's androgenicity , I didn't experience any detrimental effects . But I only tried it twice and I was also sick with a cold so not the best test run.
I certainly would be willing to try it again if it wasn't for the constipation, but I'm sure I'll give it another go.

Ive tried the old version of gonadin today with phytol in it. that was quite nice . I'm also having great results with diosgenin in the last months.

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@CrumblingCookie said in Repairing Knee Osteoarthritis and Cartilage Degeneration with the combination of Boswellia and Celery Seed::

Both celery extract and apigenin, and flavonoids in general (?), seem to promote breakdown of calcium oxalate.

Digging into this I discovered the term Chondroprotective agents. These agents "include both endogenous and synthetic chemicals." No mention of exogenous natural sources. A quick search of 2025 pulbications:

Anthocyanins and Anthocyanidins in the Management of Osteoarthritis: A Scoping Review of Current Evidence

Potential Chondroprotective Effect of Artemisia annua L. Water Extract on SW1353 Cell

Chondroprotective effect of pomegranate seed oil in papain-induced knee osteoarthritis through animal modeling

Butchered and banned.

Why China. Why.

@Mauritio Thanks 🙏

@evan-hinkle said in Visceral fat reduction by enteric-coated lactoferrin:

@Ismail hey man, doing well! I was taking 500mg Jarrow freeze-dried lactoferrin.

And just a general update: I’ve been taking the enteric coated for a few months now, and I actually think I prefer the ones I was taking before. I replicated the study above taking 300mg of the enteric coated, and really didn’t notice anything at all, (which is odd because I respond to most everything I try, (good or bad)).

TMI: I saw an undigested enteric coated lactoferrin in my stool last week, (great, they’re making it past the stomach-bad, I’m literally shitting my money away…).

Lol! I guess the enteric coating is working erm too well!

Since this event I’ve begun chewing the enteric coated pills, (now we’re really defeating the purpose, lol) and this has not made any difference. Still not noticing any effect. I’ll swap back to my old brand for a month and see what I think.

Yes will def be interesting to see how you respond if you go back again 🙂