Be Wary Of Vitamin D Supplementation

InChristAlone

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Yeah it has to be based on symptoms as well, just like Dr Gominak points out that her patients had terrible symptoms when they went up to 400 mg B5. But 100 mg was a sweet spot. I am getting my vitamin D tested just to see if I land somewhere in a healthy range or that its way too low. I just need to know if it's really low or not. If it isn't it's not so useful anymore. Then I will just continue getting about 30 minutes a day of UVB from the sun.
 

Amazoniac

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- Photobiology of Vitamin D (Mike)

"7-DHC is present in all layers of human skin. Approximately 65% of 7-DHC per unit area is found in the epidermis and the remaining 35% is in the dermis. The highest concentration per unit area is found in the stratum basale and stratum spinosum (34). These epidermal layers, therefore, have the greatest potential for previtamin D3 synthesis. However, the amount of previtamin D3 produced also depends on the number and energy of the photons reaching each layer of skin." "Because most of the radiation responsible for producing previtamin D3 is absorbed in the epidermis, greater than 95% of the previtamin D3 that is produced is in the epidermis (34)."

"Determination of the subcellular localization of 7-DHC and previtamin D3 in human epidermal tissue revealed that most 7-DHC and previtamin D3 were in the membrane fraction, while only 20% was in the cytosol. Based on this finding, it has been postulated that most 7-DHC is entrapped in membrane. It is likely that the 3β-hydroxyl group [↓] of the 7-DHC molecule is near the polar head group of the membrane fatty acids and interacts with it through hydrophilic forces, while the nonpolar rings and side chain are associated with the nonpolar tail of the fatty acid by hydrophobic van der Waals interactions. Thus, when 7-DHC in the skin’s plasma membrane is exposed to UVB radiation the thermodynamically less favorable conformation of the s-cis, s-cis-previtamin D3 is preserved through hydrophobic and hydrophilic interactions with the bilayer lipid membrane fatty acids. Thus, a rotation around carbon 5 and carbon 6 to form the thermodynamically more stable s-trans, c-cis conformer is presented in the membrane and is only permissible in an organic solvent, such as hexane."

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"The isomerization of previtamin D3 to vitamin D3 is the last step in the synthesis of vitamin D3 in human skin. The reaction rate of this isomerization is temperature dependent and is enhanced by raising the temperature. Earlier studies found that this process was not affected by acids, bases, catalysts, or inhibitors of radical chain processes (40). Furthermore, no intermediate was detected during the isomerization. This led to the conclusion that the reaction was an intramolecular concerted process involving a [1,7]-sigmatropic hydrogen rearrangement (40), which is an antarafacially (opposite side of a plane) allowed and a suprafacially (same side of a plane) forbidden process (41). Much of the information about the previtamin D3 isomerization has been obtained from experiments using organic solvents for the conversion (42, 43) and assumed to be the same in human skin. There is no evidence for the existence of an enzymatic process in the skin that can convert previtamin D3 to vitamin D3. It is postulated that in an organic solvent, such as hexane, previtamin D3 preferentially exists in a s-trans, s-cis conformation, which is thermodynamically more stable and cannot be easily converted to vitamin D3. Therefore, it takes several days for the isomerization reaction between previtamin D3 and vitamin D3 to reach equilibrium at 37◦C. However, previtamin D3 in the skin is maintained in the s-cis, s-cis conformation, a conformation which greatly facilitates its conversion to vitamin D3. Thus, instead of taking 30 h for 50% of previtamin D3 to convert to vitamin D3 at 37◦C in hexane, it took only 2.5 h in the human skin at the same temperature. The results suggest that the interaction of previtamin D3 with membrane fatty acids in skin is responsible for the efficient formation of vitamin D3 in the skin. During the formation of vitamin D3, the hydrophilic and hydrophobic interactions of the s-cis, s-cis-previtamin D3 with the membrane fatty acids are disrupted, thereby facilitating the ejection of vitamin D3 from the skin cell membrane into the extracellular space. By diffusion it enters the circulation by binding to the serum vitamin D binding protein (DBP). The removal of vitamin D3 from the skin as it is being produced, thereby, changes the isomerization reaction from a reversible process to an irreversible process (34, 44). This would explain the relatively rapid rise in the serum vitamin D3 concentration after UVB exposure."

"After vitamin D3 is formed from the thermally induced isomerization of previtamin D3 in the epidermis, it is transported into the dermal capillary bed beneath the dermoepidermal junction. Little is known about the mechanism of this translocation process. In an attempt to understand this event, Tian et al. studied the kinetics of vitamin D3 formation and the time course of appearance of vitamin D3 in the circulation after exposure of chicken to UVB radiation. Their data indicate a much faster rate of formation of vitamin D3 from previtamin D3 than the reverse reaction (return back to previtamin D3 from vitamin D3) and a relatively fast rate of translocation from skin to circulation (44). By examining the time course of appearance of vitamin D3 in circulation, they found a rapid phase of vitamin D3 appearance from 8 to about 30 h post-irradiation and a relatively slower phase of its disappearance after the circulating concentration of vitamin D3 reached its peak. No previtamin D3 could be detected 1 h after UVB irradiation. Thus, only vitamin D3 is preferentially removed from skin into circulation, leaving behind previtamin D3 in the epidermis for the continued thermoisomerization to vitamin D3."

"The role of DBP in the translocation of vitamin D3 into circulation is implicated from the work of Haddad et al. (50). They investigated the transport of cutaneously synthesized vitamin D3 into circulation in seven healthy volunteers who received whole-body irradiation with 27 mJ/cm2 dosage of UVB light (290–320 nm) by comparing the time course distribution of plasma protein-bound vitamin D3 in high- (>1.3 g/ml) and low-density (<1.3 g/ml) fractions after UVB irradiation. They found that plasma vitamin D concentration began to increase 10 h after irradiation, peaked at 24 h, and lasted for a week in the high-density layer where all the hDBP was present. When actin affinity chromatography was used to specifically bind DBP, it also removed vitamin D3 from the plasma of irradiated subjects. These observations indicate that the endogenously photosynthesized vitamin D3 circulates in serum almost exclusively on DBP, which differs from the orally administered vitamin D2 [1250 mcg] (50), which is evenly distributed between the high- and low-density layers at 4, 8, and 24 h after the ingestion. Thus, DBP is important in the translocation of vitamin D from skin into the circulation."

- The Vitamins: Fundamental Aspects in Nutrition and Health (978-0-12-802965-7)

"DBP is critical in the regulation of vitamin D metabolism, controlling the tissue distribution of vitamin D metabolites. Due to the relative excess of DBP (4–8 μM compared to 50 nM 25-OH-D3), nearly 90% of circulating vitamin D metabolites are bound to DBP in vitamin d-adequate individuals, while occupying <5% of available binding sites. Further, because of its avid binding of 25-OH-D3 in the plasma rather than other tissues, concentrations of the free metabolite are maintained at very low levels (10^−13 M). Both 25-OH-D3 and 1,25-(OH)2-D3 can also bind to albumin, albeit with much lower affinities than DBP (Table 7.7)."

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- Vitamin D toxicity related to its physiological and unphysiological supply

"If vitamin D3 formed in skin avoids being modified further by UV over-irradiation, it has to get into the blood to contribute to the total body vitamin D supply. From the concentration of 7-DHC in skin cells, it is apparent that most pre-vitamin D3 is produced in keratinocytes in the stratum basale and stratum spinosum [25,26]. The blood DBP has an essential role in transferring vitamin D3 from its site of formation into the blood circulation. Although the specificity of binding to DBP favours 25(OH)D, vitamin D3 itself can link to the binding site, albeit with about 100-fold lower binding affinity than that of 25(OH)D [27]. If DBP is absent from the extracellular environment of skin cells, as occurs in DBP-knockout mice, the transfer of vitamin D3 into the blood is completely prevented [28]. DBP also increases the isomerisation rate of pre-vitamin D3 to vitamin D3 by providing extracellular specific binding sites and thus drawing vitamin D3 out of the cells as it is formed [25]. Although vitamin D3 is transported in blood bound to DBP, in that vehicle it is unable to be internalised into hepatic cells [29–32]. Instead, vitamin D3 is transferred from DBP either to lipoprotein in blood or to a lipoprotein on the hepatic cell membrane [32]. Inside the liver cell, vitamin D3 is either 25-hydroxylated by the cytochrome P450 microsomal enzyme CYP2R1 [33] or inactivated by a range of catabolic enzymes, and the products are excreted in bile [34]. The output of excretion products in bile increases with increasing doses of vitamin D when given by mouth or by intravenous injection [34]. However, even with extensive vitamin D formation in the skin, the rate of delivery to the liver is very slow. After a single episode of skin UV exposure, the vitamin D3 formed takes at least 3 days before it all leaves the skin [25] and some of that vitamin D3 remains in the circulation 7 days later [29]. Likewise, the 25(OH)D concentration in the blood increases slowly, reaching a peak 7–14 days after a single exposure to UV radiation [35]."

"The various transport mechanisms of vitamin D from oral input not only differ from those that process vitamin D formed in skin, but the rate of delivery to the liver is also much faster. Rapid uptake of vitamin D by the intestinal mucosa cells is promoted by dietary fat, and it may cross the brush border membrane passively in mixed micelles. However, absorption is also facilitated by binding to transmembrane cholesterol transporter proteins [36,37]. Inside the mucosal cell, vitamin D is packaged with triglycerides, phospholipids, and cholesterol and secreted across the basolateral membrane as chylomicrons. Some may also be secreted as high-density lipoproteins [36]. During transit through lymph and blood, some of the chylomicron vitamin D is apparently transferred to DBP [38]. The peak vitamin D concentration in blood is found at 10–12 h after ingestion, but it may take 1 week after a single oral dose for all of the vitamin D in the blood to be cleared [36]. Nevertheless, the bulk of an oral dose of vitamin D is delivered as a bolus to the liver in chylomicron remnants and up to 50% is incorporated into hepatocytes by 1 h after entering the circulation [30,38]."

⬑ [38] Plasma clearance, transfer, and distribution of vitamin D3 from intestinal lymph

"In contrast to poison A, 30-95% of vitamin D3 recovered in plasma was present in the protein fraction (d > 1.019) within 2 min after injection of radiolabeled intestinal lymph. This indicates a rapid transfer of vitamin D3 from chylomicrons to DBP. At the same time, about 60% of the injected vitamin D3 was recovered in the plasma. It can thus be calculated that at least 20-57% of the vitamin D3 was not cleared from the circulation as chylomicron remnants. This proportion probably represents an underestimate of the nonchylomicron remnants removal because it is unlikely that the entire 40% of radioactive vitamin D3 not recovered in plasma after 2 min was removed by the liver as chylomicron remnants during this short period of time."​

"The conversion of oral-input vitamin D to 25(OH)D in the liver and its secretion into the blood occurs rapidly, like that derived from formation in skin. However, the quantity of vitamin D supplied to the liver from oral input can be considerably greater and its rate of delivery is certainly considerably faster than the vitamin D trickling in from skin. Although the peak concentration of 25(OH)D in blood from a single oral dose of vitamin D is reached in 7–14 days [?] [37,39], the quantity of 25(OH)D is greater and its initial rate of output from the liver is much faster than that coming from skin [40,41]. The high concentration of apo-DBP, with its high binding affinity for 25(OH)D in the extracellular fluid around the hepatocytes [27], would draw 25(OH)D from the cells as it is being produced, in a similar way to its mobilisation of vitamin D formed in skin cells."
 

Amazoniac

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Both by Heccie and friends:

- Vitamin D and Citrate Oxidation

- Vitamin D and the Incorporation of [1-14C]Acetate into the Organic Acids of Bone

"The administration of vitamin D to the rachitic rats only 2 days before they were killed was considered to be the most favourable condition for study of the alleged effect of vitamin D on citrate synthesis. This technique would allow sufficient time for the metabolic effects of vitamin D to appear and still minimize secondary changes such as those indicated in the preceding paragraph. This technique would allow sufficient time for the metabolic effects of vitamin D to appear and still minimize secondary changes such as those indicated in the preceding paragraph. It appears likely that the changes reported by Meyer et al. (1959) to be due to vitamin D might be at least in part explicable in terms of secondary morphological and cytological differences between the tissues from the rachitic rats and those from animals given a continual supply of vitamin D. For example, the uncalcified area in the ends of long bones from rachitic rats is made up of resting, proliferating and hypertrophic cartilage cells as well as osteoid tissue, whereas the same area in a rat receiving a continual supply of vitamin D contains predominately resting and proliferating cartilage. It would not be surprising if these cell types differed in their metabolism of citrate and other intermediates."

"As our results demonstrate, the epiphysis, spongiosa, cartilage and trabecular bone from vitamin D-deficient animals incorporated, within the limits of experimental error, as much radioactivity from [1-14C]acetate into the organic acids as do the corresponding tissues from animals that had received vitamin D on the fifteenth day. Thus it appears that the administration of vitamin D only shortly before the rats were killed has not greatly changed the distribution of cell types and therefore the overall metabolic activity of the tissue."

"The tissues from the rachitic rats that had been given vitamin D have 40-50% (bone and cartilage) to 100% (epiphysis and spongiosa) more radioactivity in citric acid. On the other hand, the tissues from rachitic rats not given vitamin D have more 14C in a-oxoglutaric acid and in most cases more in glutamic acid (except in cartilage). In general the administration of vitamin D has little or no effect on the appearance of 14C in the other organic acids, i.e. succinic acid, malic acid, 'unidentified' and lactic acid (except in trabecular bone). Since both types of tissues incorporate the same total amount of radioactivity, the administration of vitamin D causes a significant increase in the amount of radioactive citric acid, while causing an approximately equal decrease in the sum of the radioactivity in all the remaining acids."

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From: Caffey's Pediatric Diagnostic Imaging

- Why Ray Recommends Eating Lots Of Calcium (Sec. 4.1)



- Quantative studies of the interactions of cholecalciferol (vitamin D3) and its metabolites with different genetic variants of the serum binding protein for these sterols
 

artist

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I tolerate D3 and MK4 K2 supplements well (D3 megadoses are too destabilizing but that's not really unusual) but I can't tolerate even tiny amounts of supplemented calcium, regardless of the form (I am also dairy free due to casein intolerance so probably woefully calcium deficient) and MK7 K2 gives me heart palpitations. I also do very poorly with more than like 100% RDA type dosages of vitamin C. Weird how different everyone is. I suspect the reason many of us wind up on a board like this is due to some "unusual" genetics that lead to health hiccups and this could also be reflected in issues with various supplements.
 

Amazoniac

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Mossy

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I tolerate D3 and MK4 K2 supplements well (D3 megadoses are too destabilizing but that's not really unusual) but I can't tolerate even tiny amounts of supplemented calcium, regardless of the form (I am also dairy free due to casein intolerance so probably woefully calcium deficient) and MK7 K2 gives me heart palpitations. I also do very poorly with more than like 100% RDA type dosages of vitamin C. Weird how different everyone is. I suspect the reason many of us wind up on a board like this is due to some "unusual" genetics that lead to health hiccups and this could also be reflected in issues with various supplements.
Interesting. I react exactly the same to MK7 K2 and any dose of calcium. I can tolerate lower doses of D3 and topical MK4 K2, but oral tends to give me serotonin and histamine reactions, though rarely not. Due to how similar our reactions are, I quickly looked up some of your other posts, and if I read correctly, I find I react the same to yet two other supplements you've tried: famotidine and sodium bicarbonate. I mention all this because I'm trying to find ways to make supplements work that have not been; and, considering how similar your reactions are to mine, for most supplements, I thought it worth asking what version of D3 and MK4 you're taking, in the hopes that they'll work for me—at least the MK4.
 

artist

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Interesting. I react exactly the same to MK7 K2 and any dose of calcium. I can tolerate lower doses of D3 and topical MK4 K2, but oral tends to give me serotonin and histamine reactions, though rarely not. Due to how similar our reactions are, I quickly looked up some of your other posts, and if I read correctly, I find I react the same to yet two other supplements you've tried: famotidine and sodium bicarbonate. I mention all this because I'm trying to find ways to make supplements work that have not been; and, considering how similar your reactions are to mine, for most supplements, I thought it worth asking what version of D3 and MK4 you're taking, in the hopes that they'll work for me—at least the MK4.
I have used a variety of D3 and mk4 supplements over the years but I never noticed a big difference in effect between them (which is probably not what you’re hoping to hear, I’m sorry…). These days I have both from NOW brand and I just take the RDA.
 

Mossy

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I have used a variety of D3 and mk4 supplements over the years but I never noticed a big difference in effect between them (which is probably not what you’re hoping to hear, I’m sorry…). These days I have both from NOW brand and I just take the RDA.
Yeah, not the magic answer, but still helpful. Thank you.
 

Lejeboca

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Zinc and its role in vitamin D function

Abstract

Zinc is an essential mineral with an important relationship with vitamin D. Studies have found that reduced blood zinc levels could predict vitamin D deficiency in adolescent girls, while zinc supplementation increased vitamin D levels in postmenopausal women. In vitro studies using human peritoneal macrophages have found that zinc induced the release of calcitriol (1,25-dihydroxycholecalciferol). Zinc also acts as a cofactor for vitamin D functions, as the transcriptional activity of vitamin D-dependent genes relies on zinc to exert pleiotropic functions, including mineral ion regulation. Vitamin D could also induce zinc transporters to regulate zinc homeostasis. Together, zinc and vitamin D in adequate concentrations help maintain a healthy musculoskeletal system and beyond; however, deficiency in either of these nutrients can result in various disorders affecting almost all body systems. This brief article will focus on the role of zinc in vitamin D functions.
 

moa

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Since i am a idiot and went ahead yday to try 12k IU Vitamin D with some magnesium and Vitamin K despite the knowledge that i do not tolerate it in low dosages ...

Knowing my levels are extremely low and reading all the positive anecdotes i felt i need to give it one more proper try and ... the experience was horrifying to say the least
Not only did my stomache feel wierd and i had bad nausea - after around 1-2 hours or so my head started feeling wierd and my eye sight was severely impaired.

It was both, part of the peripheral vision but also the direct vision that was ... clouded and not accessiable anymore. I coudn't see the things my eyes were focusing on accompanied with this wierd feeling in the head. As if the information gathered trough the eyes were not processesable anymore and this impairment caused a odd kind of headache. A awful feeling of seeing and yet not seeing with only parts visible and the rest being not there eventho it is. I would raise my left hand up to the spot i can't see and indeed i coudn't see my hand full knowing it was there.



I got realy stressed and scared for 30 mins and figured i need to absolutely get w/e is in my digestive track moving. A glass of salt water (1 teaspoon salt) does wonders for my transit time and i felt better within 10-20 minutes and my eyesight returned.

So done with vitamin d. One mans cure is another mans poision is so true. Perhaps my liver and digestive track is just damaged and impaired beyond help.

To be honest tho, i found it fascinating that this could even happen.
very interesting description of the visual feelings.

i have something similar some days and i also had bad reactions when i took one huge 20kui d3 for 2 days.

how was your story with D3, did you continue supplementing ?

what about the symptoms, did they go away ?
 

Ben.

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very interesting description of the visual feelings.

i have something similar some days and i also had bad reactions when i took one huge 20kui d3 for 2 days.

how was your story with D3, did you continue supplementing ?

what about the symptoms, did they go away ?

i stopped vitamin d3 supplementation all together. Wether it is/was a low dose or a high dose, sooner or later it all led to this "partial" blindness that feels like a headache inducing foggy no-vision sideffect.

One assumption that i have/had would be that due to possible lyme infection the conversion of vitamin D in the kidneys is impaired. "Supposedly" lyme can knock out the VDR (vitamin D receptor) using these ligands that slide inside the VDR, the space in which normal vitamin D molecules should be going in to.

From the vitamin d wiki:
Pathogenic influences are known to negatively influence the function of the Vitamin D receptor. This is especially true of:
  • EBV (epstein barr virus) (1)
  • CMV (cytomegalovirus) (2)
  • Borrelia burgdorferi (Lyme bacteria) (3)
  • Wifi radiation (electrosmog) has shown to adversely affect the VDR (4)
  • Gliotoxin, a virulence factor and mycotoxin of fungi (20). Gliotoxins are produced by numerous fungi. Though the study cited identified gliotoxin release from aspergillus fumigatus, it is known that gliotoxins can also be produced by penicillium and trichoderma
"Since the VDR is at the heart of the innate immune system, bacteria can survive by discovering how to disable it through a variety of different actions. Actions accumulate and are more powerful than individual actions. In keeping with evolutionary theory, a growing number of substances and species have been shown to downregulate the activity of the VDR, one of which is Borrelia burgdorferi. Live Borrelia burgdorferi reduced VDR expression in monocytes (phagocytes) by 50 times, and lysates (“dead” Borrelia) reduced it by 8 times 11)"
 

moa

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One assumption that i have/had would be that due to possible lyme infection

My impression is that it is due to brain being in high glutamate state, a kind of visual aura, comes with headache migraine-like and sensibility to noise, known effects of high glutamate.

but I'm not sure about the link with vitamin D ? some studies show that, in time, high vitamin D3 supplement with high calcium will reduce migraine. could initial high dose have the opposite effect and cause strange visual aura ?

i think if you're PTH is high, and you take lots of vitamin D3, it will raise calcium and maybe PTH needs time and will stay high and maybe higher calcium is causing issues when pth is high (Ray peat said this once, that high blood calcium is bad when you have high PTH, not intake).

maybe that's why it's good to start with lower dose and long term, to allow PTH to go down before increasing the vitamin D3 even more ?
 

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