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Vitamina D/D3  

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benefabio
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Post: 295
25/10/2019 10:57 pm  

Era comunque troppa, perche' 5000 ui al giorno sono per quando si sta in carenza, per poi scendete a 800 ui per il mantenimento, il riferimento per le analisi e' 45 ng/ ml, in teoria bisognerebbe sembre veleggiare su quel livello.


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Tropico
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Post: 9748
26/10/2019 5:53 pm  

10mila UI effettivamente sono esagerate (ai tempi leggevo degli studi sulla vit.A e quanto apparentemente fosse innocua ad alti dosaggi)... ogni tanto leggo di qualcuno che ha esagerato intossicandosi, ricordo anche di un vecchio utente anziano amante dell'acido ascorbico che si intossicò...qualcuno avrà capito di chi parlo.

Ad ogni modo non so perché continuo a non tollerare la vitamina D presa da fonti che non siano il sole.

La medicina ha fatto così tanti progressi che ormai più nessuno è sano. Aldous Leonard Huxley | Veniamo tutti da ambienti diversi e iniziamo con alcune idee preconcette che potremmo abbandonare lungo la strada...


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Tropico
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Post: 9748
01/11/2019 11:06 am  

Anche se non credo all'integrazione ad alte dosi, ognuno ha il suo punto di vista ed il mio è influenzato dalla recente esperienza di intossicazione di vitA, il mio livello estremamente basso, 18 ng/ml, mi impone di prendere provvedimento.

Ho provato a continuare con la vit D in gocce applicata sulla cute (dorso mani), per ora a dose di 800UI, inizialmente, come sempre ho avuto palpitazioni, da un lato positivo perché anche topicamente viene assorbita, dall'altro no perché non è bella come sensazione. Per farla breve, ho continuato lo stesso sopportando questo effetto collaterale iniziale, sembra che pian piano l'effetto collaterale sparisca.

Troppa vitamina A porta a ipercalcemia sierica, quindi presuppongo che in passato la D aumentando ancora l'assorbimento del calcio portava ad eccitotossicità cellulare peggiorando la situazione.

Purtroppo vedo molte persone prendere grosse dosi senza problemi ed è difficile avere un riscontro con chi ha questi effetti secondari.

La medicina ha fatto così tanti progressi che ormai più nessuno è sano. Aldous Leonard Huxley | Veniamo tutti da ambienti diversi e iniziamo con alcune idee preconcette che potremmo abbandonare lungo la strada...


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benefabio
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Post: 295
04/11/2019 12:14 pm  

Attualmente è cambiata la normativa e lo stato non passa più la vitamina D se non si sta sotto i 20 ng/mL, quindi il tuo caso è un caso limite, nel senso che dovresti fare integrazione per arrivare a 20 ng/mL, un'inezia, il problema vero è prendere il sole come il padreterno comanda, individuare il proprio fototipo e fare l'esposizione davanti e dietro al mare nell'intervallo di tempo dalle 9.30 alle 10.30.

Se fosse stata primavera già si poteva preventivare che avevi bisogno di 44 bagni di sole (i 32 che mancano ai 18, un bagno di sole davanti e dietro a quegli UV sviluppa un punto sulle analisi + il consumo di 12 da marzo a agosto), da ottimizzare anche per l'ora pomeridiana in 22.

Sempre facendo riferimento alla app UVLens per l'indice UV medio (giallo) da 3 a 5, quindi è da evitare in ogni caso l'esposizione agli indici UV alti, con protezione solo a viso e dorso delle mani.

Per adesso fino a primavera devi tamponare, io farei così: o con olio di fegato di merluzzo (che fra l'altro per me è la scelta migliore in quanto stimola la conversione da 0-25oh a 1-25oh), un cucchiaino a giorni alterni o con una perla di softgel della solgar natural vita d3 o con 6 gocce di d3 vegan 2000 o mangiando pesce spada, salmone selvaggio e sgombro freschi di taglio piccolo.

Questo post è stato modificato 8 mesi fa 6 tempo da benefabio

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Tropico
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12/01/2020 5:55 pm  

Ho trovato interessanti le informazioni di questo gruppo privato di Facebook

SECOSTEROID HORMONE D https://www.facebook.com/groups/517807781731760/

Premetto che hanno una visione diversa rispetto a quella comune, ossia generalmente sfavorevole all'integrazione, però ho appreso diverse cose ed ho una visione più ampia, sopratutto sul recettore della vitamina D, ossia il VDR.

Data la mia scarsissima tolleranza all'integrazione orale di vitamina D ho un certo bias nel propendere a valutare la questione più dal loro punto di vista.

Riporto un sunto di un post per i novizi che entrano nel gruppo, forse non dovrei riportarlo qui ma finché nessuno protesta...

This is a post I created a few months back for another health related page. There’s not anything new in it but it was meant to be a one stop shop type post do I will share it here.

Inevitably someone is going to ask me to dumb it down. I can’t! That’s how everyone got in trouble in the first place. With a dumbed down view of the metabolism that herded everyone to pills chasing a number. But you don’t have to understand it just know it exists. Step one really. These are molecules your Dr isn’t aware of. Even if you do understand it you can’t step in and tell the body which molecules to make. EVER. PERIOD. It’s not scientifically or biologically possible. The body is wicked SMART. A million times smarter than the device enabling you to view this.

Diagram of a SCAM. The Serum 25D level OBSESSION. (“Vitamin D Deficiency”)

I can explain the high level focus. They took everyone’s 25D level. They broke them out and grouped them by disease/condition. Then they did something very unscientific and everyone fell for it. They said their D level was the cause of their disease/condition. Turned correlation into causation. A HUGE NO NO in science. The chart shows “disease incidence prevention by 25(OH)D level”. So you hit that level and avoid getting that disease. Sounds like a fairy tale. Especially considering it’s an inactive molecule.

Can we make another nifty chart for a different but also important molecule? Say red blood cell magnesium? Methylfolate, C, K, Or E?? Of course we could. And blame THAT molecule instead. It’s every bit as scientific.

Now think of the chart with 1,25D. This is what ppl low in 25D are making. They are sick. The molecule of immune response IS 1,25D. This chart would have the sick on the RIGHT, not the LEFT. The well folks would be on the LEFT.

But remember, it’s been called a vitamin for generations. The thought of Rickets makes ppl tremble. And it was two genetic mutations (VDDR & VDRR) OR a pure lack of sun. Look what parents did in the “Historic Photo”. And to be quite honest we may still not have discovered the molecule that fixes that. Think about it. It could be made by the sun and remain undiscovered. It may get transferred to food sources, as well. No one is looking. It could be one of the molecules I mention but remain an action not recognized or attributed to that molecule. Like 20OHD. The D molecule we make in the sun that protects us from the sun. Or 5,6 trans-vitamin D. I cannot stress enough that NO ONE is looking. Where would that money come from??? The only reason anyone is studying D is to:
1)Make a synthetic. There are thousands of synthetic analogues. Some as simple as D5
2) Looking to piggyback their drug on the D delivery system. Serves about 33 tissue types. Great rail line.

This is likely the latest study. It was sent to me last week by a Dr friend. This is Rodenticide in rodents. In humans it’s seen as osteoporosis because it’s not lethal. It’s the same action that occurred in this study.

High-Dose Vitamin D: No Help for Bone Health
— Surprise in randomized trial: a hint of actual adverse effect from supplementation.

Vitamin D might not be much help for strengthening bones among healthy adults without osteoporosis, Canadian researchers reported, even at doses far higher than recommended daily allowances.
In a clinical trial assessing three levels of daily vitamin D supplementation -- 400 IU, 4,000 IU, and 10,000 IU -- radial volumetric bone mineral density (BMD) was significantly lower among those (ages 55-70) taking higher doses for 3 years, according to Steven Boyd, PhD, of the University of Calgary in Canada, and colleagues:

No dose of vitamin D supplementation was able to prevent bone loss, as each dose saw a drop in the percentage of radial volumetric BMD over 3 years, they reported in JAMA:
* 400 IU: -1.2%
* 4,000 IU: -2.4%
* 10,000 IU: -3.5%

Boyd's group explained that the findings were unexpected, and that the outcomes were in fact the opposite of what they were anticipating. But they cautioned that "this evidence of high-dose vitamin D having a negative effect on bone should be regarded as hypothesis generating, requiring confirmation with further research. Therefore, the appropriate interpretation of this study is that for maintenance of bone quality in healthy vitamin D-sufficient adults, these results do not support a skeletal benefit of vitamin D doses well above the recommended dietary allowance."

https://www.medpagetoday.com/endocrinolo…/osteoporosis/81832

So what is 25D? I have 15 years of researching it under my belt. I remember when I saw THREE different D3’s in the papers and I was so lost. In time I realized the D3 faction exists at the three levels we discuss in the hydrolation pathway.

D3>25(OH)D3> 1,25(OH)2D3

Same is true of D2.
D2>25(OH)D2> 1,25(OH)2D2

Repeat again for D4.
D4>25(OH)D4> 1,25(OH)2D4

There are the two 25D’s you get tested. A good test breaks out the two factions so you can evaluate D2. There are another 10, some sulfated, some in the epi form. But all that doesn’t matter because the body will make what it wants. Always. It may not be 25D.

This study mentions the two you get tested.
The ROC curve analysis revealed that measurements of circulating forms (25OHD2 and 25OHD3) without the epimers cannot predict disease state.

https://www.ncbi.nlm.nih.gov/m/pubmed/24423328/

When you supplement children they make the epi form predominantly quite often.

“Time-course analysis of 3-epi-25-hydroxyvitamin D3 shows markedly elevated levels in early life, particularly from vitamin D supplementation in preterm infants.” http://www.nature.com/pr/journal/v79/n4/abs/pr2015251a.html

I’m against taking pills of vitamin D. I want to make it perfectly clear why that’s not a sound practice.
This is chasing a number. The serum level of 25D, typically 30 or above to satisfy mainstream. If you don’t have that you will be advised to take D3. Notice, this is a different form of D. You will likely take a lot of it but you will never have it measured. There’s no test for that. (Don’t be silly by making sense). They will continue to measure 25D. What it MAY become and where they may by chance, find it (serum-it’s a fat soluble vitamin made for storage. Think of a hibernating bear).
I said may become. Here’s why.
It can stay D3 and hang in serum. Untested. It can get stored in fat, as D3. Untested. It can become 20OHD, the sun protection analogue. Untested. It can become 24R,25D. The bone builder. Untested. It can become 25D, STORED IN FAT. UNTESTED. It can become Epi-3 25D. D formed from another pathway, epimerization. There are at least 3. Hydrolation and lactonization being two others. Hydrolation is the one 25D is from. Some of these analogues can “cross over” into another pathway.
What is the take home message? The body decides what to make. Not the Vitamin D Council Psychiatrist Cannel.

The analogy I use. Inactive D (25D or storage D as some call it) they measure is the flour and the active (1,25D) is bread. That never gets checked. So they figure out you're low on flour (25D) and start giving it to you. BUT, it turns out you had so many loaves of bread (1,25D) you really didn't need any flour. Then your body makes bread out of the flour. But the pantry is full of bread so you put some of the new bread in the utility room, then in the living room. Next in the bedrooms.
When bread starts getting put in the wrong place those rooms aren't bedrooms anymore. They are messed up. Let me try now and explain why there wasn't room for all the bread you make.
The infections like EBV, HIV, and Lyme cause inflammation (cytokines) and the cytokines convert the d from inactive to active (turn flour into bread). But the Lyme is in the vit D receptor where the active d (bread) should go. So the active d (bread) goes to the wrong receptor (thyroid let's say). That's the bread being put in the bedroom.

Now why is there a problem with me? Here’s one example if a bacterial ligands stealing the Vdr.

For context: "The Epstein–Barr virus nuclear antigen 3 (EBNA-3) is a family of viral proteins associated with the Epstein–Barr virus."

Antigen. What we put in a vaccine to create antibodies.

I am posting this because unless and until you understand how EBV does what it does you will most likely not come to understand the "Vitamin D" metabolism. In the simplest of terms EBV (it's Ligand) Docks/parks in the VDR (Vitamin D Receptor) blocking it from encoding the genes that create our Chemical and Biological warriors that would kill it had it not evolved to do just that. It's not the only one. HIV, Lyme, and many other pathogens. Some so small 4000 will fit inside ONE red blood cell. The mycoplasma. The "lab contaminants" in Mainstream. These are the things destroying human health. This gets at GcMAF. GcMAF/Vitamin D Binding Protein/VDBP/Gc-Globulin/group-specific component are all the same thing. The VDR encodes the genes that creates the Macrophages in the first place for Macrophage Activating Factor to act upon. GcMAF is the transport protein for Hormone D. “Vitamin D” is a Secosteroid Hormone, the Most Powerful human steroid in 1,25D form. For context, 25 and 1,25D are Ligands as well. Think of one Ligand taking another's target receptor away as cars and parking spots. Like cars, the Hormone D will find another parking spot, like the thyroid receptor, taking it out too.
Abstract
Epstein-Barr virus (EBV) is a human gamma herpes virus that infects B cells and induces their transformation into immortalized lymphoblasts that can grow as cell lines (LCLs) in vitro. EBNA-3 is a member of the EBNA-3-protein family that can regulate transcription of cellular and viral genes. The identification of EBNA-3 cellular partners and a study of its influence on cellular pathways are important for understanding the transforming action of the virus. In this work, we have identified the vitamin D receptor (VDR) protein as a binding partner of EBNA-3. We found that EBNA3 blocks the activation of VDR-dependent genes and protects LCLs against vitamin-D3-induced growth arrest and/or apoptosis. The presented data shed some light on the anti-apoptotic EBV program and the role of the EBNA-3-VDR interaction in the viral strategy.

http://www.ncbi.nlm.nih.gov/pubmed/20593215

What’s the risk? What are we not being told? Why does oral impact the lipid panel. Sun derived D is carried by vitamin D Binding Protein whereas oral is picked up by the lymphatic system and shuttled by lipoproteins, ldl specifically.

Steroid Hormone Vitamin D: Implications for Cardiovascular Disease.
Abstract
Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations.

https://www.ncbi.nlm.nih.gov/pubmed/29798901

Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis.
These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process.
https://www.ncbi.nlm.nih.gov/pubmed/19539290

Lipids and lipoprotein ratios: contribution to carotid intima media thickness in adolescents and young adults with type 2 diabetes mellitus.
CONCLUSIONS:
HDL cholesterol is the only lipid to independently associate with carotid IMT. Lipoprotein ratios and non-HDL did not provide additional information. The low variance in carotid IMT explained by traditional risk factors suggests nontraditional risk factors may be important to assess to better understand the contributors to early-stage atherosclerosis in adolescents and young adults with T2D.
https://www.ncbi.nlm.nih.gov/pubmed/24079285

More of what’s hidden. Another form of Vdr. Rapid response vdr. Loves nutritional ligands like rosemary and Curcumin. And lumisterol. What D3 breaks down into.

And the Receptors for the Cyp11A1 Alternative pathway molecules. RoR’s. The true circadian controller, glucose homeostasis controller too.

Over 12 years we have documented the existence of new pathways of vitamin D3 metabolism started by the action of CYP11A1 and further modified by the actions of CYP27B1, CYP27A1, CYP24A1 and CYP3A4, generating at least 21 hydroxymetabolites with additional ones still to be experimentally defined (Table 1) [43, 50]. At least 13 of them are endogenously produced [72]. These metabolites display biological activity by acting both as “biased” agonists of the VDR and/or inverse agonists of RORα and RORγ. A subset of these compounds have the potential to act on the non-genomic VDR site or less likely on 1,25D3-MARS as suggested by molecular modeling.

We propose that the identification of a number of hydroxymetabolites of D3 may offer an explanation for the pleiotropic and diverse activities of vitamin D that have previously been assigned to 1,25(OH)2D3. We suggest that these diverse phenotypic effects are also mediated by interactions with, in additional to the VDR, receptors including RORα and RORγ. Also, for selected compounds one may propose action on the non-genomic site of VDR with the possibility that just a few of the secosteroids act as low affinity agonists on 1,25D3-MARS.

New challenges in vitamin D biology

The consensus conveyed by the majority of the literature is that all biologically relevant phenotypic effects of D3 can been assigned to one molecule, 1,25(OH)2D3, and one receptor, VDR [3, 15, 17, 38]. This makes both 1,25(OH)2D3 and VDR a bioregulatory couple, which would regulate vastly unrelated or sometime contradictory effects, which is highly unusual for endogenous ligands and their respective receptor. The existence of an alternative membrane bound receptor for 1,25(OH)2D3, e.g., 1,25D3-membrane-associated, rapid response steroid-binding protein (1,25D3-MARRS), has been proposed by some authors [39, 40]. This review, supplemented by new data and molecular modelling, will offer an additional explanation for the pleiotropic phenotypic effects of D3 by identifying both a family of novel bioactive D3 hydroxy-derivatives and the retinoic acid-related orphan receptors (RORs) α and γ, which function as alternative nuclear receptors for these compounds in addition to the VDR.

the expression of CYP11A1 in peripheral tissues, albeit at low levels, has now been documented [43] and alternative substrates to cholesterol have been identified experimentally, such as 7DHC, vitamins D2 and D3, ergosterol and lumisterol [44–49]. Additionally, the possibility of other sterol/secosteroidal compounds serving as substrates has been predicted theoretically based on molecular modeling [50].

Hydroxylation of side chain of vitamin D by CYP11A1

An assumed concept that vitamins D3/2 are only activated through 25- and 1-hydroxylations [D3/2→25(OH)D3/2→1,25(OH)2D3/2] has been challenged by recent findings of CYP11A1-initiated metabolism of vitamin D: D3→ 20(OH)D3 +22(OH)D3 + 17(OH)D3→(OH)nD3 and D2→20(OH)D2→17,20(OH)2D2→(OH)nD2 [47, 48, 51–61]. The main metabolite resulting from a single hydroxylation of D3 by CYP11A1 is 20(OH)D3, with 22(OH)D3 and 17(OH)D3 also being produced [47, 51, 61]. In the major pathway, 20(OH)D3 is further hydroxylated by CYP11A1 to 20,23(OH)2D3, 20,22(OH)2D3, 17,20(OH)2D3 and 17,20,23(OH)3D3 [47, 51]. In addition the prodrug, 1α(OH)D3, is metabolized by CYP11A1 to 1,20(OH)2D3 [62] and 1,20,23(OH)3D3 (unpublished observation). A full list of the D3 hydroxymetabolites produced by CYP11A1 and their stereochemistry is presented in Table 1.

Modification of CYP11A1 derived D3-hydroxymetabolites by CYP27B1, CYP27A1, CYP24A1 and CYP3A4

20(OH)D3, 22(OH)D3, 20,22(OH)2D3 and 20,23(OH)2D3 can be hydroxylated by CYP27B1 at C1α to the corresponding di- or trihydroxyderivatives (Table 1) [54, 56, 58, 63, 64]. The main product of D3 metabolism initiated by CYP11A1, 20(OH)D3, can be hydroxylated on the side chain by CYP27A1, CYP24A1 and CYP3A4 to 20,24(OH)2D3, 20,25(OH)2D3 and/or 20,26(OH)2D3, which are further 1α hydroxylated by CYP27B1 to the corresponding trihydroxyderivatives (Table 1)[55–57, 64–66]. In addition 20,23(OH)2D3 is hydroxylated by CYP24A1 to 20,23,24(OH)3D3 and 20,23,25(OH)3D3 [55].

In vivo production of novel D3-hydroxyderivatives

Many of the vitamin D3 hydroxymetabolites listed in Table 1, including 20(OH)D3, 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3, 1,20(OH)2D3, 1,20,23(OH)3D3, and 17,20,23(OH)3D3 can be made by epidermal keratinocytes, adrenals, placenta, or colorectal adenocarcinoma Caco-2 cells, tissues and cells know to express CYP11A1, following incubation with D3 [58, 70]. Production of 20(OH)D3, 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3, 1,20(OH)2D3 also occurs in human dermal fibroblasts incubated with D3 substrate [71]. Similarly, production of 20(OH)D2, 17,20(OH)2D2 and 1,20(OH)2D2 was observed in human placentas ex-utero, adrenal glands ex-vivo, and isolated human epidermal keratinocytes and colorectal Caco-2 cells incubated with D2 [59].

The final proof of the in vivo production of these CYP11A1-derived hydroxyderivatives is provided by our most recent report of the detection of not only 25(OH)D3 and 1,25(OH)2D3, but also of 20(OH)D3, 22(OH)D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3 in extracts of the human serum and epidermis, and of pig adrenals, with 1,20(OH)2D3 being detected solely in the epidermis [72]. In addition, we detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in extracts of pig adrenal gland [72]. Interestingly, the serum concentrations of 20(OH)D3 and 22(OH)D3 were, respectively, 30- and 15-times lower than 25(OH)D3, but in the nM range consistent with them displaying biological activity [72]. Contingent upon firmly establishing a physiological role for these secosteroids, future monitoring of human serum samples for CYP11A1-derived D3-hydroxymetabolites may be warranted.

Detection of novel D3 hydroxymetabolites in human serum and epidermis poses new challenges in the field in relation to the biochemistry of the pathway and the attendant physiological consequences. Thus, a relationship between vitamin D levels and production of these compounds in the context of environmental factors and routes of delivery, and in a tissue/organ context, remains to be investigated. For example, since 25(OH)D3 is not metabolized by CYP11A1 [47], we can predict that oral intake of D3 will have a minor effect on the production of the novel hydroxyderivatives. However, D3 derived from skin or delivered through parenteral routes would be metabolized by tissues expressing high levels of CYP11A1 such as adrenals, gonads and placenta, with likely systemic effects. These important considerations should set a background for extensive future investigations.

Evidence has accumulated demonstrating that RORs act as ligand-dependent transcription factors [74, 76–78]. Cholesterol and cholesterol sulfate and small molecules can interact with the LBD of RORs to modulate their transcriptional activities [79]. Intermediates of the pathway of cholesterol biosynthesis can also act as endogenous agonists of RORγ [80, 81], whereas vitamin D derivatives such as 20(OH)D3/2 exhibit RORα and RORγ inverse agonist activity where binding to the receptor reduces the basal activity of the receptor resulting in the opposite pharmacological responses to the agonist [81–83]. Therefore ROR ligands may be of value in the development of novel therapeutic strategies for treatment of different inflammatory and metabolic disorders, and neuropsychiatric diseases and cancer, in which RORs are implicated.

An overview of biological activity

The biological activity of 20S(OH)D3 in the skin was the subject of a recent review [70], therefore the description below is brief. 20(OH)D3 and its hydroxymetabolites exert prodifferentiation, antiproliferative, and antiinflammatory activities on skin cells, comparable or better than that of 1,25(OH)2D3 [53, 64, 65, 67, 70, 83–92]. 20(OH)D3 shows antifibrotic properties both in vitro [87–89] and in an in vivo mouse model of bleomycin induced scleroderma [89]. Most recently it was shown that both 20(OH)D3 and 20,23(OH)2D3 enhance defense mechanisms against UVB-induced oxidative stress and DNA damage in cultured human keratinocytes [23] and murine skin in vivo [22]. 20(OH)D3 and its hydroxymetabolites also show anti-cancer properties that are cell-lineage dependent [53, 54, 64, 68, 69, 88, 90, 92–97].

We have now tested the effects of 20,25(OH)2D3, 1,20,25(OH)3D3, 20,26(OH)2D3, 1,20,26(OH)3D3, 20,24(OH)2D3, and 1,20,24(OH)3D3 on keratinocyte proliferation and found that they display similar potency (IC50) and efficacy (maximal inhibition) to 1,25(OH)2D3, both in the presence and absence of the 1α-hydroxyl group, on the inhibition of cell proliferation (Fig. 1).

CYP11A1-derived D3 hydroxymetabolites are non-calcemic

20S(OH)D3 is noncalcemic at pharmacological doses of 3 µg/kg in rats that is in contrast to 1,25(OH)2D3 and 25(OH)D3 [95]. However, C1α hydroxylation confers limited calcemic activity, similar to that of 25(OH)D3 but still less than for 1,25(OH)2D3 [95]. 20S(OH)D3 and its chemically synthesized epimer 20R(OH)D3 are also noncalcemic at extremely high doses of 30–60 µg/kg in C57BL/6 mice, and do not show any signs of toxicity in serum chemistry, liver and kidney functions, and blood morphology or histopathology of the heart, liver, spleen and kidneys [68, 93]. In addition, 20,23(OH)2D3 is noncalcemic at 3 µg/kg in C57BL/6 mice [89] and 20(OH)D2 is noncalcemic at 4 µg/kg in rats, again showing a lack of histopathological signs of kidney or heart damage [53]. Therefore, we suggest that 20(OH)D3, 20(OH)D2 and 20,23(OH)2D3 can serve as therapeutic or adjuvant agents.

CYP11A1-derived D3 hydroxymetabolites act as “partial/biased” VDR agonists

Our previous studies have documented that 20S(OH)D3 and 20,23(OH)2D3 can act as “partial agonists on the VDR (discussed in [70]). They may also be termed biased agonists, a term now commonly applied to some ligands for G-protein coupled receptors which are functionally selective (biased) for certain response pathways from a particular receptor [98, 99]. The involvement of VDR in the regulation of differentiation, proliferation and immune functions of keratinocytes was demonstrated by experiments showing that silencing of the gene encoding the VDR significantly inhibits the phenotypic effects of either 20(OH)D3/2 or 20,23(OH)2D3 [53, 84–86]. This was further substantiated by the ability of CYP11A1-derived D3 hydroxymetabolites to translocate VDR to the nucleus with high affinity [53, 61, 92]. However, they differ substantially from 1,25(OH)2D3 in that these metabolites lack calcemic activity (as described above), act as very poor activators of CYP24A1 expression [53, 84, 86, 95] and have very poor activity on a synthetic VDRE promoter construct that was however improved by hydroxylation in position C1α [64, 65].

The above findings led us to further test a number of the CYP11A1-derived secosteroids using the commercially available LanthaScreen TR-FRET Vitamin D receptor Coactivator kit assay (Fig. 2). The assay showed that only the 1α(OH) derivatives of CYP11A1-derived D3 hydroxymetabolites increase the affinity of the co-activator peptide to the VDR-LBD suggesting that the conformational change induced by the secosteroids lacking a 1α(OH) is different or less than that induced by 1,25(OH)2D3. Therefore we carried out ligand-induced VDR translocation assays using VDR-GFP (Fig. 3), which showed that CYP11A1-derived hydroxyderivatives, both with and without the 1α(OH) group, cause translocation of the VDR to the nucleus with high potency, however potency was greater with the 1α(OH) group present. This is in agreement with previous data demonstrating the high efficiency of D3 hydroxyderivatives with a full-length side chain for stimulating VDR translocation, with higher potency being seen for the 1α(OH) derivatives and is also consistent with our molecular modeling studies [92]. Thus, our conclusion that novel CYP11A1-derived D3 hydroxymetabolites act as partial or “biased” agonists on the VDR has been correct, however, the nature of the interaction with the receptor requires further analyses with in silico modeling being presented below.

Future directions in identifying receptors for vitamin D metabolites

The functional assays and molecular modeling clearly indicate that novel CYP11A1-derived D3 hydroxymetabolites can act both as partial/biased agonists on VDR and inverse agonists for RORα and RORγ. Their activities on the VDR can be modified by hydroxylation of their side chain and additional hydroxylation at C1α, setting a background for further studies as indicated in 5.1.2 that are necessary to dissect which phenotypic effects, aside of calcemia and CYP24A1 activation, are dependent on the 1α(OH) group. Since it is clear that novel D3 hydroxyderivatives can interact with RORs, it must be clarified which effects are strictly or partially dependent on RORs using RORα/γ−/− and VDR−/− cells. It is interesting that 20(OH)D3 and 20,23(OH)2D3 show higher docking scores on RORγ than previously established natural ligands represented by cholesterol and 20-hydroxycholesterol (Table 2), consistent with their inverse agonist activity reported previously [83]. This suggest a potential beneficial use of these compounds in inflammatory and autoimmune diseases with other secosteroids serving as additional candidates.

The list of compounds potentially acting on the non-genomic site of the VDR is shorter and aside of 1,25(OH)2D3 includes 1α,24S,25(OH)3D3, 23S(OH)D3 and surprisingly calcitroic acid. The in silico modeling with the novel secosteroids indicates that they are not perfect ligands for 1,25D3-MARRS with predicted candidates (1,20,24(OH)3D3, 1,24,25(OH)3D3, 17,20,23(OH)3D3) probably acting as low affinity ligands for this receptor that could be better or similar to the classical 1,25(OH)2D3. A surprising finding is the prediction of cholesterol and 20(OH)cholesterol binding to the genomic VDR pocket, with respective Glide XP scores of −9.99 and −9.78,. It suggests that further careful studies on the role of cholesterol and its metabolites on VDR activity are required, since these are abundant in cells, and related bile acid metabolites can act on the VDR [107–109].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373926/o

You might find the Alternative pathway and the cyp11A1 molecules of interest. This is their forte. Glucose, insulin etc.

Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity.
https://www.ncbi.nlm.nih.gov/m/pubmed/23355833/

Another sun produced molecule at play.

Abscisic acid is an endogenous stimulator of insulin release from human pancreatic islets with cyclic ADP ribose as second messenger

https://scholar.google.com/scholar…

ABSCISIC ACID (ABA).

Abstract
UV‐B is an abiotic environmental stress in both plants and animals. Abscisic acid (ABA) is a phytohormone regulating fundamental physiological functions in plants, including response to abiotic stress. We previously demonstrated that ABA is an endogenous stress hormone also in animal cells. Here, we investigated whether autocrine ABA regulates the response to UV‐B of human granulocytes and keratinocytes, the cells involved in UV‐triggered skin inflammation. The intracellular ABA concentration increased in UV‐B‐exposed granulocytes and keratinocytes and ABA was released into the supernatant. The UV‐B‐induced production of NO and of reactive oxygen species (ROS), phagocytosis, and cell migration were strongly inhibited in granulocytes irradiated in the presence of a monoclonal antibody against ABA. Moreover, presence of the same antibody strongly inhibited release of NO, prostaglandin E2 (PGE2), and tumor necrosis factor‐α (TNF‐α) by UV‐B irradiated keratinocytes. Lanthionine synthetase C‐like protein 2 (LANCL2) is required for the activation of the ABA signaling pathway in human granulocytes. Silencing of LANCL2 in human keratinocytes by siRNA was accompanied by abrogation of the UV‐B‐triggered release of PGE2, TNF‐α, and NO and ROS production. These results indicate that UV‐B irradiation induces ABA release from human granulocytes and keratinocytes and that autocrine ABA stimulates cell functions involved in skin.

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.22987

Look at this. Woah.

PreDia works by controlling the presence of glucose (sugar) in the blood either by delaying or reverting the onset of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), which classifies the prediabetic condition. PreDia's main function revolves around Abscisic acid (ABA) contained in its Grape Seed extract ingredient. Our unique and patent pending dosage of ABA significantly reduces fasting glycemia and glycated hemoglobin and also the glycemic profile after a meal (which means causing glucose in the blood). In other words, PreDia helps reduce the glucose in the blood independent of insulin (where normally it is needed to reduce the blood sugar). By doing this, not only is insulin saved, but the pancreas no longer produces excess insulin, thus preventing insulin resistance. Studies have confirmed this by showing that the dose of ABA contained in PreDia can replace the insulin action by stimulating the skeletal muscle glucose uptake. The ability of saving insulin secretion to control glycemia represents the most important function of PreDia.*

https://www.wynnpharm.com/predia-offer-quiz…
"Results showed a strong positive association between these autoimmune conditions and levels of 1,25-D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25-D are a sensitive measure of the autoimmune disease state. Rather, These findings support the use of 1,25-D as a clinical marker in autoimmune conditions. High levels of 1,25-D may result when dysregulation of the VDR by bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25-D in a normal range."

https://www.ncbi.nlm.nih.gov/m/pubmed/19758177/

The IOM (New York Academy of Sciences) does NOT agree with the Vitamin D Council's high serum 25D recommendations. They aren't scientific in any way.

"Low vitamin D may be a marker of ill health

To minimise the impact of reverse causation, a recent systematic review examining the relationship between 25(OH)D concentration and ill health analysed prospective and nested case–control studies where the disorder of interest was not previously diagnosed and only studies that measured 25(OH)D concentrations, rather than predicted vitamin D status according to sunlight exposure or dietary intake, were included, to limit classification bias.7 The authors confirmed that most prospective observational studies showed an inverse association between 25(OH)D concentrations and a number of diverse health outcomes. However, to minimise residual confounding and determine causality, analysis of the randomised trials of vitamin D supplementation was also undertaken. This showed, almost universally, that vitamin D supplementation had little or no effect on the occurrence, severity and clinical course of these illnesses — even after subgroup analyses of subjects with vitamin D deficiency who received adequate dose supplementation. The discrepancy between the observational and interventional trial findings suggests that low 25(OH)D may be a marker, rather than a cause, of ill health — perhaps reflecting the effects of inflammation and the negative acute phase response of vitamin D-binding protein."

https://www.mja.com.au/…/controversies-and-consensus-regard…

Once again true science prevails. It’s a MARKER, NOT the cause.

Summary

Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

https://www.ncbi.nlm.nih.gov/m/pubmed/24622671/

MARKER, NOT the cause!”

Vitamin D studies. Nobody doubts the important role of vitamin D in the body. But are higher levels of a hormone like vitamin D–whether or not provided as a supplement– always a good thing? Well, that is far from clear. In a review of vitamin D studies in The End of Illness, David Agus, professor of medicine at University of Southern California, cites both positive and negative consequences of increased vitamin D levels. On the positive side, a 2009 study presented by the Intermountain Medical Center in Utah, following 27,686 men older than 50 years over the course of a decade, found that those with the lowest levels of vitamin D had:

90% higher incidence of heart failure
81% higher incidence of heart attack
51% higher incidence of stroke
Pretty impressive association! And yet Agus also cites two negative studies worthy of comment:

A 2010 double-blind, placebo-controlled study, published in the Journal of the American Medical Association, found that older women who received annual oral high-dose vitamin D had an increased risk for falls and fractures.
A 2008 study, published in the Journal of the National Cancer Institute, found that vitamin D does not reduce the risk of prostate cancer, and furthermore that higher circulating levels of 25-hydroxyvitamin D may be associated with an increased risk of more aggressive forms of prostate cancer.
Correlation vs. causation. Agus points out that most of the vitamin D studies are “observational studies” that show associations. They uncover a correlation bertween vitamin D levels and some other condition. But they don’t show cause and effect. The few mechanistic studies of vitamin D action were mostly carried out in cell culture, for example adding vitamin D to breast cancer cell cultures suppressed their growth. But in real humans, vitamin D is part of a homeostatic regulation system. Vitamin D doesn’t just do one thing, like promote bone growth. It is involved in as the regulation of as many as 2000 genes, turning up the expression of some, turning down the expression of others.

So how do we interpret these associations? As Agus points out, in regard to the Utah study:

An association, however, does not prove cause and effect. Another way of looking at this study is to say it’s quite possible that a heart condition lowers vitamin D levels, directly or indirectly— by keeping people with health challenges indoors and out of the sun. Also, obesity throws another wrench into the problem because excess fat absorbs and holds on to vitamin D so that it cannot be properly used in the body. Hence, is low vitamin D in this study just a marker for those who were obese? It’s the old chicken-and-egg conundrum. The same can be said for hundreds of other such studies that link the health (or lack thereof) of an individual to levels of vitamin D.

This is the key point: Low vitamin D levels may be a biomarker for other problems. It may be the consequence, rather than the cause, of certain conditions such as heart disease or obesity. For the same reason, high vitamin D levels may be a biomarker for good health. Agus quotes Dr. JoAn Manson, chief of preventive medicine at Brigham and Women’s Hospital:

People may have high vitamin D levels because they exercise a lot and are getting ultraviolet-light exposure from exercising outdoors. Or they may have high vitamin D because they are health conscious and take supplements. But they also have a healthy diet, don’t smoke, and do a lot of the other things that keep you healthy.

If vitamin D level in the blood is merely a biomarker, a consequence of good or bad health, then adding vitamin D to the diet will not necessarily improve your health. To really know whether vitamin D supplementation is beneficial, we need to look at interventional studies, where supplements are provided, and the outcomes are compared with those of control subjects who don’t get the supplement. In fact the two above-cited studies on the effects of supplementation on bone fractures in older women, and prostrate cancer in older men are two such interventional studies. And they showed that vitamin D supplementation was harmful in both cases. And note that the positive Utah study I cited above–showing a correlation between low vitamin D levels and elevated incidence of cardiovascular disease and stroke–was an observational study, not an interventional one. The men in that study with the higher vitamin D blood levels and lower incidence of heart disease were not given supplements.

Vitamin D levels are homeostatically regulated in our bodies, and this process varies with your genetics and health. As one examlple of this, people with lighter skin color and less melanin in the skin evolved to make higher vitamin D levels even with reduced sun exposure; the converse is true of those with darker skin. (This may explain why African Americans are at much higher risk for vitamin D “deficiency”, particularly if they live in higher latitudes and work indoors). People vary widely in the level at which they regulate vitamin D levels in their blood — it tends to be homeostatically controlled in a given individual, but the “normal” level may vary between 8 and 80 ng/ml, or even more widely than that. Vitamin D levels are are genetically controlled by 3 or 4 genes, and are under control of the vitamin D receptor. (This homeostatic regulation of vitamin D levels will sound familiar to those who read my previous post, “Change your receptors, change your set point“). As Agus notes,

When your cells are deluged with vitamin D…they will pull back on their sensitivity to vitamin D by reducing their number of receptors for vitamin D. But if there’s a perceived shortfall of vitamin D in the bloodstream, your cells will up-regulate— create more receptors for vitamin D— to become more sensitive to every vitamin D molecule that passes by. What happens, then, when we consume lots of vitamin D from unnatural sources such as supplements? (I use the term unnatural to imply that it’s not coming from the sun, which is a source of vitamin D that has built-in regulatory mechanisms.) No doubt our bodies are adept at adjusting using their feedback loops as I just described, and the constant surplus of vitamin D means our cells are constantly down-regulating. If we took the supplemental vitamin D away, our cells would up-regulate to make up the difference. Vitamin D has multiple downstream signaling molecules, for the vitamin D receptor signals several reactions.

So if you take vitamin D supplements, and vitamin D is regulated homeostatically, your body will turn down its endogenous production of vitamin D. If you believe that vitamin D is a “biomarker” of good health, do you really want to turn down the upstream processes that synthesize vitamin D? Think about that before you pop a vitamin D capsule.

Unintended consequences. Even worse, taking vitamin D supplements may actually suppress the immune system. This “alternative hypothesis” of vitamin D has been put forward by Trevor Marshall and Paul Albert. Supplementation with vitamin D will tend to increase levels of the inactive form of vitamin D–that is, 25-D. Conversion of inactive 25-D to active 1,25-D in the kidneys is not immediate, and may not be efficient, particular if kidney function is less than optimal. Now here is the problem: While both the inactive 25-D and active 1,25 bind to the vitamin D receptor (VDR), only the 1,25-D turns on the VDR, allowing it to perform its beneficial functions; the inactive 25-D actually inhibits the VDR. This is a problem because the VDR is the “gate-keeper” of the innate immune system, regulating over a thousand genes. So elevated levels of 25-D can result in immunosuppressive effects. As Albert writes in Vitamin D: the alternative hypothesis:

Indeed, the secosteroid 25-D may exert palliation on the innate immune system not unlike the way corticosteroids exert palliation on the adaptive immune system. So is it possible then that supplemental vitamin D is now perceived as a wonder substance simply because it effectively palliates the inflammation associated with diseases across the board? If so, this would certainly explain why its effects are most noticeable in the short-term and why efficacy often diminishes in the long-term.

And we need to also take into account the regulation of vitamin D levels through homeostatic feedback processes. Consider that it is typically the 25-D form of vitamin D–not the biologically active 1,25-D– that is measured in blood tests. And there is very little correlation between the active and inactive forms, as shown in the the figure below, from a 2009 study by Blaney et al., published in the Annals of the New York Academy of Sciences in a sample of 100 Canadian patients. As the authors note, while many of the subjects had very low levels of 25-D–the type reported in most blood tests–most of them had levels of 1,25-D elevated above the normal range. Can those subjects with low levels of 25-D but elevated levels of the biologically active 1,25-D truly be considered vitamin D deficient?

Because low levels of 25-D are often associated with inflammatory conditions such as cardiovascular disease and autoimmune disease, people jump to the conclusion that low 25-D levels are a cause of the inflammatory condition. On this point, listen again to Albert:

Yet, the alternative hypothesis must be considered – that the low levels of 25-D observed in patients with chronic disease could just as easily be a result rather than a cause of the inflammatory disease process. Our research suggests that this is the case. Indeed we have found that 1,25-D tends to rise in patients with chronic disease and that these high levels of 1,25-D are able to downregulate through the PXR nuclear receptor the amount of pre-vitamin D converted into 25-D, leading to lower levels of 25-D. I describe this finding further in my paper. So are we really facing an epidemic of vitamin D “deficiencey” or are we simply beginning to note more signs of an imminent epidemic of chronic disease – an epidenmic which would be exacerbated by increasing the amount of vitamin D added to our food supply?

So the body is making enough active vitamin D to deal with inflammation–maybe even too much, leading to downregulation of the inactive 25-D precursor. Trevor Marshall has also pointed out that elevated levels of 1,25-D may result from impaired activity of the VDR, which is essential for innate immunity. The excess 1,25-D can cause problems with other secosteroid receptors in the body, such as the thyroid receptor. But adding more 25-D, beyond what is needed, will tend to only further inhibit the VDR, interfering with its beneficial anti-inflammatory actions, and impairing innate immunity. In other words, well-intended supplementation with Vitamin D3 may actual backfire. Something to think about!

https://gettingstronger.org/…/why-i-dont-take-vitamin-d-su…/

The ROC curve analysis revealed that measurements of circulating forms (25OHD2 and 25OHD3) without the epimers cannot predict disease state.

https://www.ncbi.nlm.nih.gov/m/pubmed/24423328/

La medicina ha fatto così tanti progressi che ormai più nessuno è sano. Aldous Leonard Huxley | Veniamo tutti da ambienti diversi e iniziamo con alcune idee preconcette che potremmo abbandonare lungo la strada...


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benefabio
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Post: 295
13/01/2020 4:22 pm  

Che l'integrazione blocca i vdr e li manda in immunosoppressione già lo sapevo, essendo stato uno dei primi a tirare fuori lo studio di Trevor Marshall, ma a livello renale la produzione di 1-25OH è regolata dalle informazioni delle paratiroidi in base alla presenza di calcio, quindi questa questione dei vdr sarebbe importante solo a livello periferico oltre i 20 ng/mL, infatti attualmente l'integrazione si dovrebbe fare fino a 20 ng/mL e dopo prendere il sole perché sarebbe quella quota che va da 20 ng/mL a 45/50 ng/mL (livello rilevato negli uomini primitivi e nelle popolazioni del centro africa) ad essere suscettibile di immunosoppressione dei vdr in quanto trasformazione extrarenale di 1-25OH.

Nel tuo caso stando vicino ai 20 ng/mL risulta inutile l'integrazione ma rimane il segno evidente che fai una serie di cose che tiene bassa la vitamina D tra cui da analizzare: il fumo, lo smog, il contatto con le plastiche, il contatto con i detersivi, lavori in cui si sta a contatto con veleni chimici tipo meccanici o anche parrucchiere, mancata esposizione solare, alimentazione non biologica, utilizzo di medicine o prodotti di sintesi. Intanto al primo posto metterei la mancata o non corretta esposizione solare e mi preoccuperei di prendere il sole nella maniera giusta da UV 3 a UV 5, e se fototipo basso tipo 1 o 2 da UV 2.5 a UV 3.5.

Quello importante da sapere è che fino a 20 ng/mL di 25OH non c'è trasformazione in 1-25OH a livello extrarenale perché il corpo invia una specie di black-out, visto che la 25OH livellata a 20 ng/mL serve per il metabolismo renale.

Sui secosteroidi ritorniamo ai prodotti di sintesi.

Questo post è stato modificato 6 mesi fa 5 tempo da benefabio

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Tropico
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Post: 9748
14/01/2020 2:39 pm  

Nel mio caso è in buona parte dovuto alla mancanza di esposizione solare volontaria.

Da 3 anni che mi espongo poco al sole, nel 2019 addirittura mai, pur avendo il mare a pochi km. Imperdonabile.

La settimana scorsa spero di aver mitigato, sono stato al sole dell'Egitto in costume e mi sono abbronzato 😎 

@benefabio cosa ne pensi invece sull'aumentare i recettori VDR tramite olio di rosmarino/salvia? In quel gruppo si punta più su questo che sull'integrazione di vitD.

La medicina ha fatto così tanti progressi che ormai più nessuno è sano. Aldous Leonard Huxley | Veniamo tutti da ambienti diversi e iniziamo con alcune idee preconcette che potremmo abbandonare lungo la strada...


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benefabio
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Post: 295
14/01/2020 4:06 pm  

Per i VDR a livello periferico basta non fare integrazione da 20 ng/mL a 45/50 ng/mL, di fatto sarebbe solo la vitamina D sintetica a bloccarli nella conversione 1-25OH, mentre a livello centrale serve solo un po' di olio di fegato di merluzzo.

L'abbronzatura non è indicativa di produzione di vitamina D perchè bisogna vedere quanto sole hai preso senza protezione solare, nei minuti in cui ci si espone per la vitamina D, da indice UV 3 a indice UV 5 bisognerebbe mettere la crema protettiva solo a faccia e mani, ed avere bene a mente il proprio fototipo perché un fototipo 1 può esporsi 10 minuti davanti e 10 dietro, mentre un 2 - 20 minuti, un 3 - 30 minuti e un 4 - 40 minuti, quindi le cose importanti sono queste 2: controllare sempre l'indice UV e avere la consapevolezza del proprio fototipo.

In teoria un VDR non può andare in immunosoppressione se si integra solo fino a 20 ng/mL, e sto parlando di casi gravi di persone che stanno costantemente da 5 a 10 ng/mL, il problema rimane sempre quello di riempire il serbatoio di vitamina D 25OH, perché dato che è liposolubile si va ad immagazzinare nel fegato, nei depositi adiposi e nel circolo sanguigno per poi essere utilizzata dal corpo al bisogno.

L'ideale è non scendere mai sotto i 30 ng/mL e dopo in estate fare 20 esposizioni solari per tornare a fine estate a 50 ng/mL, per poi scendere a inizio primavera a 30 ng/mL.

Quindi personalmente non punterei né sull'integrazione né in nient'altro, ma solo nell'esposizione solare giusta a indice UV medio controllando sempre l'app UVLens.

Questo post è stato modificato 6 mesi fa 2 tempo da benefabio

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Tropico
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Post: 9748
14/01/2020 8:18 pm  

Non ho messo filtri solari, zero creme. Con un app ho misurato che nelle ore centrali l'indice andava da 3 a 5. Si l'abbronzatura dipende dagli UVA ma l'esposizione è stata di diverse ore totali.

La medicina ha fatto così tanti progressi che ormai più nessuno è sano. Aldous Leonard Huxley | Veniamo tutti da ambienti diversi e iniziamo con alcune idee preconcette che potremmo abbandonare lungo la strada...


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benefabio
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Post: 295
15/01/2020 7:28 am  

allora dovresti avere già risolto


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Tropico
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Post: 9748
30/01/2020 10:47 am  

...mi conforta comunque che nel gruppo sulla vitamina D sopra menzionato, ci siano persone che come me sono "intolleranti" alla vitamina D sottoforma di integratore, con gli stessi sintomi di tachicardia/extrasistole quando la assumono anche a basse dosi.

Più interessante sarebbe conoscere l'eziologia, la causa, se è una reazione del tutto normale per alcuni soggetti oppure un sintomo rivelatore di uno squilibrio. Dal momento che il normale processo attraverso il sole sulla pelle è ok, non ne faccio una priorità.

La medicina ha fatto così tanti progressi che ormai più nessuno è sano. Aldous Leonard Huxley | Veniamo tutti da ambienti diversi e iniziamo con alcune idee preconcette che potremmo abbandonare lungo la strada...


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benefabio
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30/01/2020 11:33 am  

Per me ipotizzando è da ricondurre al fatto che la vitamina D da integrazione non è poliedrica, cioè non ha la capacità all'occorrenza o di trasportare il calcio o di legarsi ai VDR per la conversione in 1-25OH nei siti extrarenali, infatti sembrerebbe esclusivamente idonea a trasportare il calcio.

Adesso bisognerebbe vedere la situazione interna delle vene, se le pareti delle vene, anche in soli alcuni punti, sono ricoperte da una buona parte di accumulo di Neu5Gc, introitata con un'alimentazione ricca di carne rossa e si fa anche un'alimentazione che va a superare una porzione di latticini al giorno, ecco che avendo un aumentato trasporto del calcio concomitante con una carenza di vitamina K2, si ha la possibilità che il calcio si perda per strada e vada ad accumularsi proprio dove si è già in precedenza accumulata la Neu5Gc, aumentando la possibilità di eventi cardiocircolatori.

No bisognerebbe quindi soltanto pensare a prendere il sole, ma anche ad evitare la vitamina D sintetica di cui sono addizionati parecchi prodotti confezionati.

Questo post è stato modificato 5 mesi fa da benefabio

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eric
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Post: 2459
04/02/2020 10:42 pm  

@tropico

Io quando prendo la vitamina D che mi ha dato Fabietto diluita nell olio di canapa, non accuso nessun sintomo.


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Yankee
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Post: 1004
31/03/2020 2:57 pm  

Ciao,

ho alcune app per il calcolo della vit. D ma non so bene di quale fidarmi.

Ad esempio, dminder è affidabile? (la versione pro dice quanto esporsi)

Ne cercavo una che, inserendo i dati mi calcolasse nella giornata odierna quanto stare esposto.

UVLens da solo l'intensità UV nella zona.


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benefabio
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Post: 295
31/03/2020 5:06 pm  

@yankee con la uvlens vedi il periodo, quando e' giallo, per il tempo ti devi regolare con il fototipo fototipo 1 - 10 minuti davanti e dietro, 2 - 20, 3 - 30, 4 - 40.


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Yankee
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Post: 1004
31/03/2020 5:36 pm  

@benefabio per periodo giallo/arancione intendi quando dice che il livello è su moderate?

perchè quando è su low, si colora di verde..

immagino poi ci sarà anche un rosso in estate..


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