Ecdysteroids May Be A Form Of Vitamin D

[LeeLemonoil]

according to this well-reputed insect-researcher:

https://atlasofscience.org/are-ecdysteroids-insect-hormones/

I have linked up a lot of publications here on RP-Forum that show a lot of beneficial effects of Ecdysteroids,
virtually every peaty-parameter seem to be modulated in a positive way.

Plants And Insects As A Source Of Steroids

There are reservations because some ecdysteroids bind to ERbeta but that does not concern me - on the contrary given that interesting steroids like the Androstanediols, DHEA and substances Tocotrienols bind them too and displace E2 and excert protective effects this way.

Others are skeptical because of the molting hormone/prolactin Connection but this author has rather convincingly explained that ecdysteroids are not insect-hormones nor are they really the initiator of molting.

And lastly, a recent publication in Nature claims a structural and activity relationship between ecdysterone and aldosterone (which really would be a cause for caution), but that seems to be true only for alpha-Ecdysone which is the non-hydroxylated form and is likely of no importance in vivo.

What do you make of the thesis that ecdysteroids might be essential Vitamin-D sterols in humans? I find it highly intriguing and especially the hydroxylation and glycoside structures hint at the possibility. The „peat“- Flavones like Apigenin are now also considered hormone-like especially their glycsosides.
Thank you for any comment or insight on the matter!

 

[LeeLemonoil]

https://www.researchgate.net/publication/283935416_An_Alternative_Look_at_Insect_Hormones

The theories of insect hormone action were created some 50-years ago by professional insect endocrinologists. Unfortunately, the scientists slowly passed out and their original results are almost inaccessible. I am one of a few old-fashioned endocrinologists who has survived. The modern topics and priorities are mostly concerned with the isolation of receptors, enzymes (e.g. esterase) and genes (e.g. Met) in the peripheral target tissues. By contrast, the most important hormones of the central neuroendocrine system (i.e. neuropeptides of the neurosecretory cells of the brain, corpora cardiaca, corpora allata) are usually neglected. I found, for example, that ecdysone and ecdysteroids, which were accidentally discovered in the search for an insect moulting hormone, are not true insect hormones. Moreover, the sesquiterpenoid JH-I, which is still believed to be the true juvenile hormone (JH), is also not an insect hormone. Indeed, JH-I turns out to be just one of 4000 juvenoid bioanalogues, mimicking the JH action. The JH-I is a trivial excretory product of exocrine, not endocrine, colleterial glands of the male Cecropia, Hyalophora cecropia (Linnaeus, 1758) silkworms. This paper describes briefly some neglected physiological problems of insect hormone action with the aim to encourage discussions about their interpretations.

 

[LeeLemonoil]

In vertebrate animals, Ecd generally exhibit effects that are similar to the vitamin D3 (calciferol), eventually combined with anabolic growth effects similar to the androgenic steroid hormones. These conclusions can be documented by the pronounced anabolic effects of Ecd in domestic animals (rabbit, swine, cattle, sheep, Japanese quails). In addition, there exists a plethora of beneficial pharmacological effects in the human body (increased growth of bone and muscles, improved physical and mental state, improved muscle strength in athletes, metabolic stimulation, tonic effects, neurogenic, psychogenic, immunogenic, antiallergenic, anti- stressoric, anti-cancerogenic and many other more or less sufficiently supported data). A retrospective look at the history of vitamin D shows that the pioneers working on the elucidation of the rickets bone disease observed long ago (during 1930-ies) that the active compound was somehow related to 7-dehydrocholesterol, which could be converted from other sterols by UV-irradiation. They looked for the antirachitic vitamin D among the purely lipophilic fish oils and animal fat.

I am convinced that Ecd represent a previously overlooked, special group of the amphoteric, both partly lipid and partly water soluble class of the esential vitamin D. Ecd possess the 7-dehydrocholesterol unsaturation, which is stabilised by the conjugated 6-keto group. In contrast to the so far known precursors of calciferol (vitamin D3), which require activation by ultraviolet radiation and metabolic incorporation of 3 additional hydroxylic groups in the liver, the Ecd type of vitamin D6 (6 comes from the latin “Hexapoda” = insects) contains not only 3, but 6 or 7 prefabricated hydroxylic groups.

There are sufficient data which show that Ecd (Vitamin D6) can stimulate regeneration and tissue growth or enhance metabolic rates in insects, mammals and also in humans. Unfortunately, due to the limited supply of pure Ecd compounds, there are still limited pharmacological data on avitaminosis due to the lack of the vitamin D6. It is difficult to cure avitaminosis if you do not know or do not have the responsible vitamin. I have a feeling, however, that the defficiency of vitamin D6 (Ecd) could be behind the hitherto incurable diseases, especially those related to impaired regeneration, aberrant cell growth or disturbed neuromuscular functions. Investigations along these lines have been persistently hindered by an errant belief in the moulting hormones of insects.

 

[LeeLemonoil]

Phytoecdysteroids and vitamin D analogues--similarities in structure and mode of action.

Phytoecdysteroids are plant steroids with identical or analogue structures to the molting hormone in arthropods. The ecdysteroids exert several beneficial effects on mammals, from which the most cited and deeply examined one is the increase of muscle size and strength. This shows similarities with the mode of action of the androgenic steroids but the ecdysteroids do not bind to the cytoplasmic/nuclear receptor of the mammalian steroids. These findings led to the hypothesis that ecdysteroids possibly bind to membrane bound receptors and they are likely to influence signal transduction pathways. Probably because of their closely related chemical structures, ecdysteroids exert some similar effects in vertebrates to those of the hormone 1 alpha,25-dihydroxyvitamin D3 (1,25D) which is produced in the kidney from 25-hydroxyvitamin D3, after being converted in the liver from Vitamin D3. 1,25D generates biological responses via both genomic and rapid, nongenomic mechanisms. Structure-activity relationship studies with different Vitamin D analogues could open the possibility to show that the two ways of action (genomic and nongenomic) can be influenced separately. The connection between the Vitamin D status and muscle function is already well-described in clinical studies, and several efforts have been made to evaluate the effect of Vitamin D deficiency or supplementation on muscle morphological changes and the underlying molecular mechanisms. This paper aims to summarize the main structural commonalities between the ecdysteroids, 1,25D and other Vitamin D analogues. The similarities in their effects and pathways that might be involved in the mechanism of action of these compounds will also be discussed.

 

[LeeLemonoil]

The well rputed etimologist, Karel Slama, has another publication out on his Ecdysteroids= water soluble Vitamin D. I post the abstract and the link to the full publication.
He is also convinv´ced lack of Vitamin D1 (as he now toutes it) is a causative factor in many serious diseases.

European Journal of Entomology: Vitamin D1 versus ecdysteroids: Growth effects on cell regeneration and malignant growth in insects are similar to those in humans

Vitamin D1 versus ecdysteroids: Growth effects on cell regeneration and malignant growth in insects are similar to those in humans
Karel SLÁMA
Polyhydroxylated derivatives of 6-keto,7-dehydrocholesterol (ecdysteroids) are common constituents of various plants. In 1965, they were accidentally discovered in the search for the insect moulting hormone. These biologically important natural compounds are neither insect hormones nor inducers of insect ecdysis. Due to their strong anabolic, vitamin D-like effects in insects, domestic animals and humans, I propose the use of the arbitrary term vitamin D1. The present paper describes the effects of vitamin D1 on the growth and regeneration of excised epidermal cells of the tobacco hornworm, Manduca sexta (Sphingidae). The periods of programmed cell death and cell proliferation (histolysis and histogenesis, respectively) exactly coincide in insects with endogenous peaks of increased concentration of vitamin D1. Epidermal cells communicate with each other, creating a mutually integrated tissue, connected by mechanical, chemical, electrical, ionic or other so far incompletely known factors. After natural cell death, or after the artificial removal of some epidermal cells, the neighbouring cells that lose communication integrity, begin to divide mitotically to replace the disconnected part. Cell divisions are arrested as soon as the integrity of the living tissue is established. During insect ontogeny, the application of juvenile hormone causes regenerating epidermal cells to repeat the previous morphogenetic programme (i.e., development of patches of larval tissue on the body of a pupa, or metathetely). Conversely, the application of vitamin D1 (20-hydroxyecdysone) caused the regenerating cells to prematurely execute a future morphogenetic programme (i.e., development of patches of pupal tissue on the body of a larva, or prothetely). Among the key features of insect regeneration, is the arrest of cell divisions when tissues resume living cell-to-cell integrity. This prevents the formation of aberrant groups of cells, or tumours. It is well established that the main physiological systems of insects (e.g., circulatory, respiratory, neuro-endocrine) are structurally and functionally similar to corresponding systems in humans. Thus the basic principles of cell regeneration and the role of vitamin D1 in insects may also be valid for humans. The common vitamins D2 (ergocalciferol) or D3 (cholecalciferol), are exclusively lipid soluble secosterols, which require activation by UV irradiation and hydroxylation in the liver. By contrast, the neglected vitamin D1 is a natural derivative of polyhydroxylated 7-dehydrocholesterol of predominantly plant origin, which is both partly a water and partly a lipid soluble vitamin. It neither requires UV irradiation, nor hydroxylation due to 6 or 7 already built-in hydroxylic groups. Like other vitamins, it enters insect or human bodies in plant food or is produced by intestinal symbionts. Vitamin D1 causes strong anabolic, vitamin D-like effects in domestic animals and in humans. I am convinced that avitaminosis associated with a deficiency of vitamin D1 in human blood may be responsible for certain hitherto incurable human diseases, especially those related to impaired nerve functions and somatic growth, aberrant cell regeneration or formation of malignant tumours.

full publication:
https://www.eje.cz/pdfs/eje/2019/01/03.pdf

 

[Gone Peating]

@LeeLemonoil What experiences did you have from taking ecdysteroids?

 

[LeeLemonoil]

I don’t take it, I‘m just intrigued by the stance Karel Sláma takes on this matter. But similarity between Ecd and aldosterone concerns me -as long as there is no conclusive proof that only ecdysone acts like that I wouldn’t touch beta-ecdysterone

 

[Sativa]

I have ~200g of Suma root, which i intend to make a simple alcoholic extract tincture.
This concentrated tincture will go perfectly alongside Sodium Salicylate, Vitamin E (natural), Squalane, Rooibos tea (lowers cortisol).

A perfect pro-anabolic & anti-catabolic, anti-estrogen stack!

I also use milk thistle occasionally, alongside strategically chosen traditional Chinese botanicals, to balance the underlying energetics of my biological organism (notably Astragalus, Poria, Jiaogulan).

TCM combined with RP philosophy is significantly more effective than either alone!

(ofc, i have a minimal pufa diet, plenty of carbs & gelatin/yolk/goats cheese protein, egg shell calcium, Mg supps etc)

 

[LLight]

Thank you, that's very interesting

I'm still trying to wrap my head around the link between fasting/dehydration and vitamin D.

- 1,25D stimulates antimicrobial peptides / the innate immune system in humans.

- Fasting and dehydration probably induce an increased innate immune response via NFAT5 stimulation. For example, NFAT5 is able to upregulate antimicrobial peptides production.

- Fasting decreases vitamin D levels, by suppressing CYP2R1 ("the main vitamin D 25-hydroxylase") and "upregulating the vitamin D catabolizing CYP24A1 in the kidney".

- Following dehydration (in mice, NFAT5 involved again), the CYP3A4 enzyme seems to be upregulated several folds in the liver (1, 2). This enzyme appears to be involved in the catabolism of vitamin D: "CYP3A4 catalyzes vitamin D biotransformation down pathways that appear catabolic in nature".

- In drosophila, dehydration stimulates antimicrobial peptides production via ecdysone.

- 1,25D may decrease NFAT5 in colon cancer cells: "Consistently, miR-22 inhibition abrogates the 1,25(OH)(2)D(3)-mediated suppression of NELL2, OGN, HNRPH1, RERE and NFAT5 genes."

So fasting/dehydration antagonize vitamin D and vice versa.
Both have the potential to stimulate the immune system.
But oddly, in drosophila, the immune stimulation due to dehydration is mediated by ecdysone, a homologue of vitamin D in insects.

Edit:

"In addition, it was recently shown that CYP3A4 can catalyze 25OHD3 monohydroxylation, generating nine different isomeric metabolites [54]. Interestingly, the major product generated by CYP3A4, 4β,25(OH)2D3, was detected in human plasma at concentrations comparable to that of 1α,25(OH)2D3 and its formation was induced by rifampin"

Maybe the metabolites mentioned could have roles.

 

[HealthisWealth]

@Sativa

Can you identify photos o chinese herb?

I have ~200g of Suma root, which i intend to make a simple alcoholic extract tincture.
This concentrated tincture will go perfectly alongside Sodium Salicylate, Vitamin E (natural), Squalane, Rooibos tea (lowers cortisol).

A perfect pro-anabolic & anti-catabolic, anti-estrogen stack!

I also use milk thistle occasionally, alongside strategically chosen traditional Chinese botanicals, to balance the underlying energetics of my biological organism (notably Astragalus, Poria, Jiaogulan).

TCM combined with RP philosophy is significantly more effective than either alone!

(ofc, i have a minimal pufa diet, plenty of carbs & gelatin/yolk/goats cheese protein, egg shell calcium, Mg supps etc)

 

[LeeLemonoil]

@LLight

Ecdysone is not beta-Ecdysterone, maybe that helps your riddle

 

[LLight]

@LLight

Ecdysone is not beta-Ecdysterone, maybe that helps your riddle

Thanks
So ecdysone is not exactly an ecdysteroid but a precursor metabolite for vitamin D1/ 20-hydroxyecdysone?

 

[LeeLemonoil]

Yes

 

[LLight]

@LLight

Ecdysone is not beta-Ecdysterone, maybe that helps your riddle

After reading the publication more precisely, dehydration seems to increase 20-hydroxyecdysone production too:

Ecdysone titers measured from aged flies were also significantly elevated relative to young females in control (food) conditions, while desiccation increased 20E in both young and old animals (Fig. 4c).
​

I also found that dehydration/NFAT5 may favor a different metabolism pathway of vitamin D:

Ok. That may be too much. You should try to reduce your fluid intake in order to see if it helps further.

My reasoning (which is highly hypothetical):

1. the enzyme CYP11A1, also called CYP450scc, is in charge of converting cholesterol: "P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reaction in the process of steroidogenesis in all mammalian tissues that specialize in the production of various steroid hormones. " (wikipedia)
2. It seems like the transcription factor NFAT5 could have a link with this enzyme, RNA-Seq analysis of high NaCl-induced gene expression:
   • "Categories of NFAT5 Target Genes Upregulated after Adaptation to High NaCl, but Not after as Little as 24 h of High NaCl.
   • Steroid hormones. Cyp11a1 protein localizes to the mitochondrial inner membrane and catalyzes the conversion of cholesterol to pregnenolone, the first and rate-limiting step in the synthesis of the steroid hormones."
3. NFAT5 is downregulated by hypotonicity, which I think could be caused by drinking too much. Note that while it seems like NFAT5 upregulates this enzyme, it could be false to think that by downregulating NFAT5, you would necessarily downregulate its target, the enzyme CYP11A1. Additionally, this is proven in one kind of cell.

Metabolism of vitamin D:

By the way, the enzyme CYP11A1 seems to redirect vitamin D3 towards an alternative form to the classic vitamin D metabolites 25(OH) and 1,25(OH).

I guess that if you have naturally high steroids, then you should have (relatively) high amounts of this form of vitamin D.

@LeeLemonoil Do you know if 20-hydroxyVD3 could be a sort of 20-hydroxyecdysone produced by mammals?

 

[Cloudhands]

any updates on the safety and efficacy of ecdysterone @LeeLemonoil ? im considering taking it but also question its reliability

 

[LeeLemonoil]

any updates on the safety and efficacy of ecdysterone @LeeLemonoil ? im considering taking it but also question its reliability

Haven’t followed the research last couple of month. Safety is still a but debatable to me and available supp-quality even more so

 

[LLight]

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00560-6/fulltext

The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19.

BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19.