Be Wary Of Vitamin D Supplementation

Amazoniac

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- Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

"In normal weight adults, for every 1000 IU of vitamin D supplementation, serum 25OHD has been shown to increase by 4.8 to 20 ng/mL [5,11,14,15]. Out of the few studies investigating vitamin D status in obese populations, some researchers reported that participants receiving 1000 IU/day of vitamin D experienced an increase in serum 25OHD of approximately 10–15 ng/mL [15,18,19,24], while others reported similar or slightly greater increases in 25OHD at 2000–3000 IU/day [20,22,23]."​

- Topical vitamin D3: A randomized controlled trial (RCT)

"An informed written consent was obtained from 550 healthy patients, with vitamin D deficiency and vitamin D insufficiency." "Complete history, thorough clinical examination was done to rule out any metabolic diseases." "The patients were randomized into two groups of 350 in study arm and 200 in control arm. Participants were instructed not to change their dietary habits and increase sunlight exposure."

"Patients in the study group were given Top-D (Vitamin D3 gel made from proniosomal technology) to apply daily on the skin. Top-D 1 g contained 5000 IU of vitamin D3. The control group was given 1 g of Aloe vera gel to be applied every day. The two groups had no knowledge to which group they belong. After 4 months serum 25OHD was tested again."

upload_2019-10-23_10-32-23.png


upload_2019-10-23_10-33-14.png

Bloody killcidiol concentration in treated humans.

- Transdermal vitamin D supplementation—A potential vitamin D deficiency treatment
 

Dave Clark

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- Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

"In normal weight adults, for every 1000 IU of vitamin D supplementation, serum 25OHD has been shown to increase by 4.8 to 20 ng/mL [5,11,14,15]. Out of the few studies investigating vitamin D status in obese populations, some researchers reported that participants receiving 1000 IU/day of vitamin D experienced an increase in serum 25OHD of approximately 10–15 ng/mL [15,18,19,24], while others reported similar or slightly greater increases in 25OHD at 2000–3000 IU/day [20,22,23]."​

- Topical vitamin D3: A randomized controlled trial (RCT)

"An informed written consent was obtained from 550 healthy patients, with vitamin D deficiency and vitamin D insufficiency." "Complete history, thorough clinical examination was done to rule out any metabolic diseases." "The patients were randomized into two groups of 350 in study arm and 200 in control arm. Participants were instructed not to change their dietary habits and increase sunlight exposure."

"Patients in the study group were given Top-D (Vitamin D3 gel made from proniosomal technology) to apply daily on the skin. Top-D 1 g contained 5000 IU of vitamin D3. The control group was given 1 g of Aloe vera gel to be applied every day. The two groups had no knowledge to which group they belong. After 4 months serum 25OHD was tested again."

View attachment 15368

View attachment 15369
Bloody killcidiol concentration in treated humans.

- Transdermal vitamin D supplementation—A potential vitamin D deficiency treatment
What then would be the benefit of using D transdermal, does it change anything in the liver vis a vis retinol , etc., or is it basically just the same as taking D orally except it is done through the skin?
 

Amazoniac

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What then would be the benefit of using D transdermal, does it change anything in the liver vis a vis retinol , etc., or is it basically just the same as taking D orally except it is done through the skin?
A few advantages is mentioned below:

- Investigating Transdermal Delivery of Vitamin D3

"Transdermal delivery has many advantages compared to oral or injection administration, such as avoiding side effects on the gastrointestinal tract, providing continuous drug delivery, and being easy to apply or remove. However, there are currently no quantitative studies regarding the effectiveness of this route of administration for vitamin D3. All studies so far have only investigated topical delivery of vitamin D3."

"However, transdermal delivery of therapeutic amounts is very difficult to achieve for some compounds because of the barrier properties of the skin. There are specific requirements for a molecule in order to pass through the skin barrier, which are as follows: small molecular weight (<600 Da), an adequate solubility in both lipids and water, and a balanced partition coefficient (logP from −1 to 4) (14). The molecular weight of vitamin D3 is 384.64 g/mol, and the recommended daily dose is very small (0.01–5 mg). Vitamin D3 is soluble in ethanol, acetone, ether, and chloroform and insoluble in water (15). The measured lipid/water partition coefficient is 10.2 (16). Except for its very high lipophilicity, vitamin D3 is an excellent candidate for transdermal delivery."

"Upon application on the skin, almost any chemical compound—and especially small molecules—will diffuse to some extent in the skin and through the skin."

"There are various techniques to enhance drug delivery through the stratum corneum. Both chemical and physical methods could enhance penetration through the skin barrier. One of the most effective methods to enhance transdermal delivery consists of using chemical penetration enhancers such as fatty acids, esters and alcohols, azones, amides, polyols, essential oils, terpenes, and certain polymers (17)."

"Fatty acids have been used as penetration enhancers for several drugs such as donepezil, rivastigmine, caffeine, and propranolol. Oleic acid is a cis-unsaturated fatty acid and one of the most investigated chemical penetration enhancers. It is commonly used in many transdermal formulations. For example, oleic acid improves the penetration of both salicylic acid and 5-flurouracil through the human skin membrane (2). Oleic acid could enhance penetration across the skin by phase separation (18). There are several advantages to using oleic acid over any penetration other enhancers. Some advantages include that it is a natural compound, is recognized as safe, and is approved by FDA as inactive ingredient in some products such as Vivelle® (19)." @DavidFoster

"There are several studies that investigated the toxicity of oleic acid. According to Loftsson et al., oleic acid irritation depends on the other vehicle additives used because pure oleic acid or propylene glycol did not cause any irritation when they were applied to human skin for 6 h (20). Oleic acid did not cause irritation when it was dissolved in n-propanol or 1-ethyl-1,3-hexanediol either. In contrast, when 5% oleic acid in propylene glycol was applied, minor irritation was detected and the irritation increased with increasing oleic acid concentrations. Moreover, Boelsma and his colleagues demonstrated that oleic acid toxicity depends on the thickness of the stratum corneum (21). They found that when 5% labeled oleic acid/propylene glycol was applied to human stratum corneum for 21 h, no oleic acid was detected in the receptor medium. In the literature, concentrations of oleic acid ranging from 1 to 30% have been proposed for enhancing drug penetration across the skin (22)."

"Dodecylamine, another common enhancer, is a typical unsaturated fatty amine which is known to increase the skin permeation rate of various drugs (e.g., testosterone (23) and fluorouracil (24)). Dodecylamine has been used as a penetration enhancer for a calcitriol transdermal patch (12)."

"Several transdermal delivery formulations are available, such as gel, cream, lotion, ointment, microemulsion, liposomes, niosomes, transfersomes, ethosomes, and nanocarriers."

"Ointment was chosen as the best transdermal delivery system for the current investigation because the ointment base increases the contact time with skin, which is vital for this highly lipophilic compound (25). Moreover, ointment bases usually increase skin hydration and drug permeability, which are very important advantages over any other type of delivery system (17). Many drugs have been used with ointment bases for transdermal delivery, such as salicylic acid and ketoprofen (26)."​

It can be difficult to find an agreement in transdermal experiments because the formulations used tend to be more complex than those where it was ingested to make up for the impediment, each find their unique way overcoming the skin and complicate the already existing differences. For example, the gurus above were selected for deficiency (more responsive) and the product in question could've contained something to disrupt the skin barrier to potentiate the vehicle. People here use it from simple formulations, how to expralotate?


Regarding changes depending on the route, I don't know for sure, probably yes.

An eventual interference in antidote K uptake would disappear:
- What Are Your Best Fat Soluble Vitamins Combinations From Personal Experience?

Poison/"vitamin" A is supposed to concentrate in the liver and harm it, yet if it's supplemented topically, there are differences in distribution.

In case you missed:

And possibly a smoother delivery:
- Retinil - Liquid Vitamin A

Therefore a fat-soluble vitamin complex taken orally or transdermally should have different effects. But it may be more due to the others than venom D itself, so I don't know what happens when it's isolated.

This is from the previous post:
- Advanced Nutrition and Human Metabolism (978-1-133-10405-6)

"In contrast to vitamin D from the diet, vitamin D3 that is made in the skin slowly diffuses from the skin into the blood and is picked up for transport by the hepatically synthesized DBP. About 60% of plasma vitamin D is bound to DBP for transport. The vitamin D bound to DBP is delivered primarily to the liver but may be picked up by other tissues, especially muscle and adipose tissue, before hepatic uptake. Thus, the difference in the transport mechanisms for the vitamin formed in the skin (i.e., going directly from the skin into the blood bound to DBP) and that absorbed from the digestive tract (i.e., incorporating into chylomicrons, entering the lymphatic system, and then entering the blood) affects the distribution of the vitamin in the body."​

Oral route kills us faster, and this is good because it doesn't prolong suffering, I guess it should be preferred whenever possible.


Since venom D can enhance the adsorption of toxic minerals, favoring its use with fruit juices for example is a good idea because of their purity and the hydrating aspect of it.
 
Last edited:

Dave Clark

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A few advantages is mentioned below:

- Investigating Transdermal Delivery of Vitamin D3

"Transdermal delivery has many advantages compared to oral or injection administration, such as avoiding side effects on the gastrointestinal tract, providing continuous drug delivery, and being easy to apply or remove. However, there are currently no quantitative studies regarding the effectiveness of this route of administration for vitamin D3. All studies so far have only investigated topical delivery of vitamin D3."

"However, transdermal delivery of therapeutic amounts is very difficult to achieve for some compounds because of the barrier properties of the skin. There are specific requirements for a molecule in order to pass through the skin barrier, which are as follows: small molecular weight (<600 Da), an adequate solubility in both lipids and water, and a balanced partition coefficient (logP from −1 to 4) (14). The molecular weight of vitamin D3 is 384.64 g/mol, and the recommended daily dose is very small (0.01–5 mg). Vitamin D3 is soluble in ethanol, acetone, ether, and chloroform and insoluble in water (15). The measured lipid/water partition coefficient is 10.2 (16). Except for its very high lipophilicity, vitamin D3 is an excellent candidate for transdermal delivery."

"Upon application on the skin, almost any chemical compound—and especially small molecules—will diffuse to some extent in the skin and through the skin."

"There are various techniques to enhance drug delivery through the stratum corneum. Both chemical and physical methods could enhance penetration through the skin barrier. One of the most effective methods to enhance transdermal delivery consists of using chemical penetration enhancers such as fatty acids, esters and alcohols, azones, amides, polyols, essential oils, terpenes, and certain polymers (17)."

"Fatty acids have been used as penetration enhancers for several drugs such as donepezil, rivastigmine, caffeine, and propranolol. Oleic acid is a cis-unsaturated fatty acid and one of the most investigated chemical penetration enhancers. It is commonly used in many transdermal formulations. For example, oleic acid improves the penetration of both salicylic acid and 5-flurouracil through the human skin membrane (2). Oleic acid could enhance penetration across the skin by phase separation (18). There are several advantages to using oleic acid over any penetration other enhancers. Some advantages include that it is a natural compound, is recognized as safe, and is approved by FDA as inactive ingredient in some products such as Vivelle® (19)." @DavidFoster

"There are several studies that investigated the toxicity of oleic acid. According to Loftsson et al., oleic acid irritation depends on the other vehicle additives used because pure oleic acid or propylene glycol did not cause any irritation when they were applied to human skin for 6 h (20). Oleic acid did not cause irritation when it was dissolved in n-propanol or 1-ethyl-1,3-hexanediol either. In contrast, when 5% oleic acid in propylene glycol was applied, minor irritation was detected and the irritation increased with increasing oleic acid concentrations. Moreover, Boelsma and his colleagues demonstrated that oleic acid toxicity depends on the thickness of the stratum corneum (21). They found that when 5% labeled oleic acid/propylene glycol was applied to human stratum corneum for 21 h, no oleic acid was detected in the receptor medium. In the literature, concentrations of oleic acid ranging from 1 to 30% have been proposed for enhancing drug penetration across the skin (22)."

"Dodecylamine, another common enhancer, is a typical unsaturated fatty amine which is known to increase the skin permeation rate of various drugs (e.g., testosterone (23) and fluorouracil (24)). Dodecylamine has been used as a penetration enhancer for a calcitriol transdermal patch (12)."

"Several transdermal delivery formulations are available, such as gel, cream, lotion, ointment, microemulsion, liposomes, niosomes, transfersomes, ethosomes, and nanocarriers."

"Ointment was chosen as the best transdermal delivery system for the current investigation because the ointment base increases the contact time with skin, which is vital for this highly lipophilic compound (25). Moreover, ointment bases usually increase skin hydration and drug permeability, which are very important advantages over any other type of delivery system (17). Many drugs have been used with ointment bases for transdermal delivery, such as salicylic acid and ketoprofen (26)."​

It can be difficult to find an agreement in transdermal experiments because the formulations used tend to be more complex than those where it was ingested to make up for the impediment, each find their unique way overcoming the skin and complicate the already existing differences. For example, the gurus above were selected for deficiency (more responsive) and the product in question could've contained something to disrupt the skin barrier to potentiate the vehicle. People here use it from simple formulations, how to expralotate?


Regarding changes depending on the route, I don't know for sure, probably yes.

An eventual interference in antidote K uptake would disappear:
- What Are Your Best Fat Soluble Vitamins Combinations From Personal Experience?

Poison/"vitamin" A is supposed to concentrate in the liver and harm it, yet if it's supplemented topically, there are differences in distribution.

In case you missed:

And possibly a smoother delivery:
- Retinil - Liquid Vitamin A

Therefore a fat-soluble vitamin complex taken orally or transdermally should have different effects. But it may be more due to the others than venom D itself, so I don't know what happens when it's isolated.

This is from the previous post:

Oral route kills us faster, and this is good because it doesn't prolong suffering, I guess it should be preferred whenever possible.


Since venom D can enhance the adsorption of toxic minerals, favoring its use with fruit juices for example is a good idea because of their purity and the hydrating aspect of it.
Hmm, I guess I will continue with sun or my Sperti- D lamp for vitamin D. The one link about topical A not raising plasma levels, does that mean it was not absorbed, or that it was absorbed and went to other areas of the body? I'm really on the fence about the vitamin A thing as well. Part of me says don't take any, because my diet is grass-fed meat , eggs, and dairy, and then the other half of me says I am not sure if I should have more, or not. Needless to say, this forum doesn't help any with making up one's mind, poison or elixir, who knows?
 

Amazoniac

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

"Vitamin D is absorbed from the small intestine by nonsaturable passive diffusion that is dependent on micellar solubilization and, hence, the presence of fat[39] and bile salts. The fastest absorption appears to be in the upper portions of the small intestine (duodenum and ileum); however, the greatest amount of vitamin D is probably absorbed in the distal region where food has a longer transit time. Like other hydrophobic substances absorbed by micelle-dependent diffusion in mammals, vitamin D enters the lymphatic circulation[40] predominantly (90% of the absorbed amount) in association with chylomicra (or portomicra), with most of the balance being associated with a-globulins.[41] The efficiency of enteric absorption of dietary vitamin D appears to be about 50%. Newly absorbed vitamin D is released by enterocytes into the lymphatic circulation in chylomicra. The polar metabolites (25-OH-D; 1,25-[OH]2-D) appear to be transported by DBP (vitamin D-binding protein) in the portal blood; only small amounts (13% of 25-OH-D; 1% of 1,25-[OH]2-D) appear in the lymph in chylomicra."

"Like other sterols, vitamin D is transported in the plasma largely in association with protein. While some birds and mammals transport vitamin D in association with albumin, and fishes with cartilaginous skeletons (e.g., sharks and rays) transport it in association with plasma lipoproteins, most species[43] use a protein that has been called transcalciferin or, more commonly, DBP (Table 7.6)."

upload_2019-10-30_7-15-54.png

"In adequately nourished individuals, DBP binds some 88% of the 25-OH-D3 in serum with an affinity and order of magnitude greater than those of 1,25-(OH)2-D. The concentration of DBP in the plasma, typically 4–8 µM, greatly exceeds that of 25-OH-D3 (c.50 nM) and is remarkably constant, as it is unaffected by sex, age, or vitamin D status. The excess binding capacity means that only 5% of DBP actually carries the vitamin. That DBP can also bind the plasma actin monomer and fatty acids, which suggests that the vitamin D transport protein may also have other functions in metabolism.[45] The turnover of DBP in the plasma is much shorter than that of 25-OH-D3 (1–3 days[46] versus 45 days[47]), indicating that the ligand is recycled."

"Being synthesized by the liver, DBP is depressed in patients with hepatic disease. Its expression is increased by trauma, estrogen therapy, and pregnancy. It does not appear to cross the placenta; fetal DBP is immunologically distinct from the maternal protein."

"In addition to facilitating the peripheral distribution of vitamin D obtained from the diet, DBP functions to mobilize the vitamin produced endogenously in the skin. Indeed, vitamin D3 found in the skin is bound to DBP.[50] It has been suggested that the efficiency of endogenously produced vitamin D3 is greater than that given orally for the reason that the former enters the circulation strictly via DBP, whereas the latter enters as complexes of DBP as well as chylomicra. This would indicate that oral vitamin D remains longer in the liver and is, thus, more quickly catabolized to excretory forms. In support of this hypothesis, it has been noted that high oral doses of vitamin D can lead to very high levels of 25-OH-D3 (>400 ng/ml) associated with intoxication; whereas intensive UV irradiation can rarely produce plasma 25-OH-D3 concentrations greater than one-fifth that level, and hypervitaminosis D has never been reported from excessive irradiation."

"Unlike the other fat-soluble vitamins, vitamin D is not stored by the mammalian liver except in some fishes. It reaches the liver within a few hours after being absorbed across the gut or synthesized in the skin, but from the liver it is distributed relatively evenly among the various tissues, where it resides in hydrophobic compartments. Therefore, fatty tissues such as adipose show slightly greater concentrations. However, in that tissue the vitamin is found in the bulk lipid phase, from which it is only slowly mobilized. About half of the total vitamin D in the tissues occurs as the parent vitamin D3 species, with the next most abundant form, 25-OH-D3, representing 20% of the total. In the plasma, however, the latter metabolite predominates by several fold.[53] Tissues including those of the kidneys, liver, lungs, aorta, and heart also tend to accumulate 25-OH-D3.[54] It is thought that the uneven tissue distribution of vitamin D, in its various forms, relates to differences in both tissue lipid content and tissue-associated vitamin D-binding proteins, the latter fraction being the smaller of the two intracellular pools of the vitamin."​
 

Amazoniac

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The original publications for their remarks above:

- Human plasma transport of vitamin D after its endogenous synthesis (!)

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upload_2019-11-5_11-6-37.png

- Effects of Vitamin D on Bone and Natural Selection of Skin Color: How Much Vitamin D Nutrition are We Talking About?

"If venom D is consumed orally, it is absorbed as if it were cholesterol, in chylomicrons that deliver lipids to adipose tissue, and from which chylomicron remnants are cleared by the liver, making vitamin D available for metabolism (Haddad et al., 1993)."​

You can search for the process of venom D activation, then 'extrahepatic' with any of the enzymes involved in the conversion of killciol to -diol, and 'extrarenal' for -diol to -triol. It's possible to metabolize the toxin independently of these organs.

- CYP2R1 (vitamin D 25-hydroxylase) semiactivates vitamin D in many places in the body | Vitamin D Wiki
 
Last edited:

Amazoniac

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Vitamin D (978-0-12-381978-9)
"The concentrations of vitamin D and its metabolites are so low that some basic paradigms for control of it are very different from the regulation of other steroid hormones. For the metabolism of conventional steroid hormones, the concentration of substrate (cholesterol) is far higher than the substrate in the vitamin D system. Figure 57.2 illustrates the effective, in vivo Km of 1-hydroxylase, in relation to the physiological concentration range of its substrate. In contrast to a typical human circulating cholesterol concentration in the order of 5 million nmol/liter (this is simply another way of saying 200 mg/dl); the 25(OH)D typically circulates at less than 200 nmol/liter. Cholesterol concentration is so high that it is not a rate-limiting aspect of the body's capacity to generate steroid hormones; however, 25(OH)D concentration can be absolutely rate limiting for 1,25(OH)2D production. Circulating 1,25(OH)2D can remain stable through a fairly large range of 25(OH)D concentrations because megalin facilitates renal access to 25(OH)D, as discussed above, but the paracrine production of 1,25(OH)2D beyond the kidneys, and which underlies the non-calcemic effects of vitamin D suffers from limited access to 25(OH)D."

upload_2019-11-6_19-52-35.png

"There are many reports that obese individuals exhibit lower serum 25(OH)D concentrations than reference subjects with a lower body mass index [124-129]. The explanation that this is because greater amounts of adipose tissue sequester more fat-soluble vitamin D, thereby increasing requirements for the nutrient simply due to greater adiposity, is not convincing. One obvious problem with the explanation is that women, who average 50% higher adiposity per unit body weight than men, do not seem to suffer inordinately from low 25(OH)D levels, and they do not require higher intakes of vitamin D per unit body mass than men. More plausible is that lower 25(OH)D levels with obesity simply reflect a larger volume of distribution -- greater body mass -- and not adiposity per se. Furthermore, all the obesity studies cited about this are cross-sectional [124-127], and they fail to account for outdoor activity, and the proportion of skin subjects exposed to sunshine, both of which are more plausible explanations of low 25(OH)D concentrations in obese persons." [¿]

"The effects of vitamin D supplementation on 25(OH)D levels are only moderately less for people with higher percent body fat [125,127]. At physiological doses, cholecalciferol (unmetabolized vitamin D3) distributes widely into adipose tissue, skeletal muscle, and organs [109,121,123]. The turnover of vitamin D exhibits a long biological half-life of about 2-3 months [1,117,121,128]. As stored vitamin D gradually returns into the circulation, it is converted into 25(OH)D. The result is that when vitamin D treatment is discontinued, the level of serum 25(OH)D is sustained by the returning phase of the equilibrium between vitamin D in its various body compartments back into the circulation. When supplies of vitamin D are stopped, the serum 25(OH)D declines with a biological half-life of about 2 months [117,118,121]. Even though the half-life of molecules of 25(OH)D per se exhibit a half-life of only 2 weeks [32], the functional half-life of 25(OH)D is 2-3 months."

upload_2019-11-6_19-52-42.png


"In 1990, [Reinaldo] proposed the theory that the mechanism of vitamin D toxicity involves saturation of circulating vitamin-D-binding protein (DBP) to the point that the percent of vitamin D and its metabolites that are free and accessible to target tissues increases inappropriately [133]. The theory was subsequently confirmed through laboratory testing of serum from patients intoxicated with vitamin D [1,134]. At toxic doses, the freely circulating vitamin D, along with its metabolites, accumulates in both adipose [112] and muscle [123]. The average capacity of human plasma DBP to bind vitamin D and its metabolites is 4700 nmol/l [30], and this exceeds by 20 times the physiologic total concentration of its vitamin-D-derived ligands. The 100 mg (4000 IU)/day of vitamin D that is starting to be used in adult clinical trials [49-51,60] is physiologic and far below what would be needed to change the free fraction of vitamin D or its circulating metabolites [30]."​

Sounds familiar? Extremely toxic!!1
 

JudiBlueHen

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After all these MS patients got better with the high doses of vitamin D, what then was their maintenance dosages?
Btw, I appreciate that you posted these results. The evidence seems pretty compelling to me that Vitamin D therapy works for many diseases.
Regarding the Coimbra protocol, not all MS patients get better! My friend has had MS for over 10 years and has a very severe case. She has been on this Coimbra protocol under medical supervision for over a year, and tells me she is getting much worse over the course of the year. She now cannot walk or transfer without assistance. I asked her if she had had genetic testing (VDR-related genes) but she has not. I suggested (as a friend, not a medical expert) she stop the protocol for several months and see if there is any change, but she relies on her doctor's orders (while refusing other prescription MS drugs).
 

Amazoniac

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Extremely toxic!!1

- A randomized clinical trial in vitamin D–deficient adults comparing replenishment with oral vitamin D3 with narrow-band UV type B light: effects on cholesterol and the transcriptional profiles of skin and blood

"We conducted a randomized controlled trial to determine whether vitamin D repletion through UVB radiation had a distinct metabolic effect compared with that with intake of oral vitamin D3. Both methods significantly raised serum 25(OH)D concentrations into an acceptable range, thereby effectively doubling pretreatment values. However, UVB treatment over a 6-mo period did not improve LDL-cholesterol concentrations or other lipid variables, which was similar to the effect of oral vitamin D."

"Men and women between the ages of 18 and 70 y were recruited."

"The inclusion criterion was a 25(OH)D concentration <20 ng/mL. Exclusion criteria were as follows: a history of melanoma or nonmelanoma skin cancer; intentional UV exposure (e.g., tanning bed use) in the 2 wk before enrollment or planned use during the study period; active pregnancy; use of >400 IU vitamin D/d; a serum calcium concentration >10.5 mg/dL, phosphorus concentration >5.5 mg/dL, PTH concentration <12 pg/mL, or LDL-cholesterol concentration >190 mg/dL; a change in the dose of statin, fibrate, niacin [?], or ezetimibe ≤1 mo of enrollment; or an estimated glomerular filtration rate <30 mL ⋅ min^(−1) ⋅ 1.73 m^(−2)."

"For the oral vitamin D3 group ☣, subjects were provided with an 8-wk supply of vitamin D3 (BTR Group Inc.) and were instructed to take 50,000 IU/wk as 5 capsules of 10,000 IU taken at the same time and to record doses in a medication log, which was reviewed along with pill counts to determine compliance. Serum concentrations of 25(OH)D were checked monthly, and after the first 2 mo, subjects received an additional 50,000 IU before the next 25(OH)D assessment if their serum concentration of 25(OH)D was <35 ng/mL."

"For the UVB group, subjects received the treatment according to their Fitzpatrick skin type [from type I (very fair, burns easily) to type 6 (very dark, never burns)] with the use of a phototherapy unit (Daavlin) that was fitted with 37 narrow-band UV type B (NB-UVB) TL100W tubes (Philips) (11). The irradiance of the phototherapy unit was set to 2.5 mW/m² and was checked weekly with the use of a radiometer. Subjects were unclothed with the exception of undergarments and were provided with goggles and a shield to prevent any eye or facial exposure but otherwise received wholebody radiation. The initial dose according to skin type was as follows: skin types I and II, 45 s; skin types III and IV, 60 s; and skin types V and VI, 75 s. Subjects received a mean of 2 treatments/wk for 8 wk. Thereafter, serum concentrations of 25(OH)D were checked monthly, and subjects received an additional 4 NB-UVB treatments before the next 25(OH)D assessment if their serum concentration of 25(OH)D was <35 ng/mL. The duration of exposure increased by 10% with each subsequent treatment as tolerated, which was similar to the protocols that have been used for psoriasis phototherapy (12). The maximum exposure time was limited to 4.5 min. For subjects who experienced an adverse event that was related to NB-UVB (e.g., skin erythema), treatment was held until symptoms resolved, and the treatment was resumed at a lower dose."

upload_2019-12-16_21-1-4.png

"As a steroid hormone, vitamin D regulates the expression of a broad array of genes by binding to the vitamin D–receptor transcription factor (23). Therefore, we determined the effect of oral vitamin D3 and UVB on the transcriptional profile of peripheral blood and skin (characteristics of these participant subgroups are shown in Supplemental Table 1). RNA-seq was used for peripheral blood samples, and data were subsequently analyzed with the use of a gene set enrichment analysis to determine changes in signaling pathways. Gene sets that were curated on the basis of canonical vitamin D–receptor binding sequences were significantly affected by oral vitamin D3 and UVB treatments in both the blood and skin (Table 3). To explore other well-established signaling pathways, we used the collection of hallmark gene sets in the GSEA program, which included 50 defined biological processes (24). Several gene sets showed similar directional changes with oral vitamin D3 and UVB (Supplemental Tables 2 and 3)."
upload_2019-12-16_21-1-20.png


"We measured serum oxysterol concentrations as a proof of concept that transcriptionally active metabolites, aside from vitamin D, are produced by dermal UVB exposure and detected in the circulation. Mean serum concentrations of 25-hydroxycholesterol rose in UVB-treated individuals after 2 mo of treatment but fell in the oral vitamin D3 group (1.5 ± 9.3 ng/mL in the UVB group compared with −2.6 ± 10.2 ng/mL in the oral vitamin D3 group; P-UVB compared with oral vitamin D3 < 0.05).""

"A survey of transcriptional activity in blood and skin showed that oral vitamin D and UVB exposures have overlapping although distinct biologic effects. Interferon signaling was consistently upregulated with oral vitamin D and downregulated with UVB. More generally, several other immune signaling pathways were downregulated in blood after UVB treatment including complement, inflammatory-response, and IL-6 signaling pathways; meanwhile complement signaling and IL-6 signaling were upregulated with oral vitamin D in the skin. Therefore, although some measures, such as declines in serum PTH, may be independent of the mode of repleting 25(OH)D concentrations, other physiologic responses behave diametrically."

"Dermally synthesized vitamin D and oral vitamin D may differ in terms of tissue exposure. Vitamin D that is synthesized in the epidermis may have a much greater influence over skin immune cells, whereas oral vitamin D would likely have a stronger effect on enterohepatic metabolism. Another plausible explanation for the disparate actions of the 2 modes of raising 25(OH)D concentrations is that UVB exposure generates bioactive molecules that, similar to vitamin D, can exert systemic effects. Oral vitaminD does not mimic this activity. For example, UV can convert trans-urocanic acid to cis-urocanic acid, which is an immunosuppressant (25). In a targeted approach that was focused on oxysterols, we detected a significant increase in serum concentrations of the liver X receptor agonist 25-hydroxycholesterol in UVB-treated compared with oral vitamin D-treated subjects. Indeed, 25-hydroxycholesterol and other oxysterols are produced by keratinocytes in response to UVB (26). Therefore, multiple mechanisms may differentiate oral vitamin D from UV exposure."

"Although NB-UVB did not improve the lipid profile, broadening the light spectrum of phototherapy beyond NB-UVB more closely mimics exposure to sunlight. Indeed, previous studies have shown an inverse correlation between 25(OH)D concentrations and LDL cholesterol with an independent effect of solar UV radiation (32). To this end, additional studies are required to identify metabolites that are produced throughout the spectrum of natural light. For example, UV type A radiation can lower blood pressure by mobilizing epidermal nitric oxide into the circulation, which may explain why higher 25(OH)D concentrations that are caused by solar radiation are associated with better cardiovascular health (33). Metabolites such as nitric oxide have activities that may have been erroneously ascribed to vitamin D because of the association of 25(OH)D concentrations with UV exposure. The study of the effects of solar spectrum-light exposure may help resolve the paradox of why correcting vitamin D deficiency does not improve many of the same conditions with which the deficiency itself is so strongly associated."

"In conclusion, in the era of evidence-based medicine, it is difficult to overlook the shortfall in the efficacy of vitamin D supplementation. A logical step toward reconciling the association of higher 25(OH)D concentrations with better health that is not reproduced by supplementation is to entertain the hypothesis that the association is noncausal but an epiphenomenon of exposure to sunlight including UV. Perhaps the beneficial effects of vitamin D on health are not due to vitamin D itself but to the sunlight required to generate the vitamin D. By studying the comparative effect of vitamin D repletion through oral vitamin D and UVB exposure, we show these modalities to be nonsynonymous and highlight the potential to identify systemic bioactive metabolites to complement the activity of vitamin D."​

It's important to clarify that if I were to read these out loud, I would try not to gesticulate to indicate the quotation marks. In case I had to for some reason, it wouldn't make no sense to do it twice with two fingers on each hand. When it's only done once, it's less silly for being a concise gesture, and we don't end up with punctuation that's as ""superfluous"" as this paragraph.
 
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Amazoniac

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Grossary:
Killciol, venom D3, and candy are synonyms.

Some of the reported effects was measured too early, so it's worth paying attention to this aspect when reading because they could've been at a time when the animals' bodies were under the acute and protective effect of DSS; it's inflammatory but helps in getting rid of toxins since there was right away a drop in the circulating metabolites of our candy, tending to reverse afterwards.

It's interesting to compare only the control groups first (solid bars) to get a sense of the impact of graded killciol without more variables. It's all more detailed in the publication, I recommend you to ignore this post and click on the link.

- High Dose Vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis

"Vitamin D has been suggested as a possible adjunctive treatment to ameliorate disease severity in human inflammatory bowel disease. In this study, the effects of diets containing high (D++, 10,000 IU/kg), moderate (D+, 2,280 IU/kg) or no vitamin D (D−) on the severity of dextran sodium sulphate (DSS) colitis in female C57Bl/6 mice were investigated."​

Not sure how much they ated, but..

"At ten weeks of age, the mice in the three groups were not significantly different in weight (data not shown)."​


"The group on high dose vitamin D (D++) developed the most severe colitis as measured by blinded endoscopic (p < 0.001) and histologic (p < 0.05) assessment, weight loss (p < 0.001), drop in serum albumin (p = 0.05) and increased expression of colonic TNF-α (p < 0.05). Microbiota analysis of faecal DNA showed that the microbial composition of D++ control mice was more similar to that of DSS mice. Serum 25(OH)D3 levels reduced by 63% in the D++ group and 23% in the D+ group after 6 days of DSS treatment. Thus, high dose vitamin D supplementation is associated with a shift to a more inflammatory faecal microbiome and increased susceptibility to colitis, with a fall in circulating vitamin D occurring as a secondary event in response to the inflammatory process."

upload_2019-12-17_8-14-20.png


sFigure 1. The extent of histological inflammation as determined by grading the distal colons at A. Day 7 and B. Day 14, post-initial DSS treatment. n=7-9/grp.

"The drop in 25(OH)D3 was associated with a greater than five-fold increase in gene expression of kidney CYP24A1 among D+ mice, an enzyme responsible for the catabolism of both 25 and 1,25(OH)2D. This suggests that vitamin D metabolites drops in response to inflammation. We did not observe this increase in kidney CYP24A1 expression in the D++ group which had the greatest drop in 25(OH)D, likely due to increased expression at baseline as a counter-regulatory mechanism to the higher 25(OH)D levels. An alternative mechanism must exist to explain the fall in vitamin D levels in this group. It is well established that 1,25(OH)2D can be produced by colonic epithelial cells[30] and monocytes[31], and this is also regulated by local CYP27B1 and CYP24A1. In fact, a study by Liu et al., demonstrated increased Cyp24A1 expression from the proximal, but not distal, colon with DSS colitis[15]. Thus, it is possible that with the colon inflammation, colonic epithelial cell and monocyte CYP24A1 expression is upregulated leading to the fall in serum 25(OH)D levels. The recovery of 25(OH)D3 was slow and did not return to baseline by day 35 in the D++ group despite resolution of colitis. This is likely due to this group having the greatest drop in 25(OH)D3, thus the time taken for 25(OH)D3 to return to baseline would be expected to take the longest even after the colitis has resolved."

upload_2019-12-17_8-14-31.png
- Clinical and Biochemical Features of Patients with CYP24A1 Mutations

upload_2019-12-17_8-14-39.png

The authors below was considerate in putting the graphs in sequence of metabolism.

upload_2019-12-17_8-14-58.png

"In critical illness, reduced 25(OH)D and 1,25(OH)2D levels have been observed, however this has been in association with reduced concentrations of the VDBP[32]. In our model we observed an increase in VDBP levels. While this could simply be a discrepancy between mouse and human vitamin D metabolism, it may also be unique to intestinal inflammation. In our previous work examining over 300 patients with CD in remission, high VDBP concentrations were independently associated with a 20% increased risk of subsequent clinical relapse of disease[33]. Thus, subclinical inflammation may lead to increased VDBP levels and subsequent disease flare. VDBP has an important role in actin scavenging such that in the case of acute tissue damage, cellular actin will bind plasma VDBP for subsequent rapid clearance of the complex[34]. It is possible that in response to intestinal tissue damage, VDBP was upregulated and thus is a biomarker of subclinical disease activity."

"The mechanism by which high dose vitamin D supplementation increased colitis susceptibility remains unclear, but we did observe that "vi"ta"min" D had a potent effect on the microbial composition of faeces from plain-water treated, control mice. Interestingly, the microbial composition of faeces from D++ control mice approached that of DSS mice, suggesting a shift to a more pro-inflammatory microbiome even before starting DSS treatment. Some of the changes seen across vitamin D categories were confirmed by correlation with serum 25(OH)D3 levels."

"It remains unclear if the observed changes in faecal microbiota are a direct response to changes in vitamin D, or mediated indirectly through changes in mucosal immune responses. While our findings demonstrate an association between vitamin D dosing, faecal microbiota changes and susceptibility to colitis, we acknowledge that a specifically designed study would be needed to draw definitive conclusions about cause and effect."

"In conclusion, high dose vitamin D worsens the severity of murine colitis induced by DSS, and is associated with distinct changes in microbial composition that may be a direct dietary effect or as a result of dysregulation of the gut mucosal immune response. Future work needs to further explore the effects of high levels of vitamin D on gut mucosal immunity to better understand if high as well as low vitamin D levels lead to a dysregulation."​

@Jorge, check out how protective DSS wased initially, it can be deemed an antidote. D-extranon? D-extraneousin?


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After meditating on the words from the previous post, we may argue that it results in "this" instead. However the time passes, therefore it's ""doubled"" nevertheless. An alternative would be to repeat it with only one finger on each side to make up for doubleness, it looks immature but it works.. in theory; in reality it won't (either way) because the person doesn't wait for the sentence to finish, a word will be 'i'nter'r'upted by a single or double mark. It's tough to find a solution just like it is to discover which mushroom is responsible for these paragraphs.
 
Last edited:

Amazoniac

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- Ultraviolet Radiation Suppresses Obesity and Symptoms of Metabolic Syndrome Independently of Vitamin D in Mice Fed a High-Fat Diet

"Our previous studies have shown that long-term UVR exposure does not modify serum 25(OH)D levels in male mice (14), allowing us to investigate the ability of UVR to modulate obesity and MetS independent of circulating 25(OH)D levels."

"C57BL/6 male mice were purchased from the Animal Resources Centre (Murdoch, Western Australia, Australia)."

"All diets were obtained from Specialty Feeds (Glen Forrest, Western Australia, Australia) and included two semipure low-fat diets (5% fat; canola oil), which were supplemented with vitamin D3 (2,280 or 0 IU vitamin D3/kg) (LF-D+) or not (LF-D2) and two high-fat diets (23%; lard [20.7%] and canola oil [2.9%]) that were supplemented with vitamin D3 (2,280 or 0 IU vitamin D3/kg) (HF-D+) or were not (HF-D2)."

"A bank of six 40-W lamps (TL UV-B; Philips, Eindhoven, the Netherlands) emitting broadband UVR (250–360 nm), with 65% of the output in the UVB range (280–315 nm), was used to irradiate mice to deliver suberythemal (1 kJ/m2) (15) or erythemal (4 or 8 kJ/m²) UVR onto a clean-shaven 8-cm2 dorsal skin area, as previously described (16)."

upload_2019-12-17_14-14-45.png


Outcomes:

upload_2019-12-17_14-14-57.png


"The HF-D− increased circulating 25(OH)D levels; it is likely that this diet contains vitamin D, perhaps within the lard-derived fat fraction. Supplementation of this diet with vitamin D (i.e., the HF-D+) further increased serum 25(OH)D levels."

Since killcidiol levels weren't changed by ultraviolent radiation (first quote), any effect was considered independent of it.
upload_2019-12-17_14-15-35.png



upload_2019-12-17_14-16-10.png

"Here, long-term UVR exposure but not dietary vitamin D suppressed weight gain and various measures of MetS (circulating cholesterol levels, glucose intolerance, and insulin resistance). Further, while vitamin D supplementation did improve NAFLD, UVR suppressed its development even more effectively. Vitamin D supplementation suppressed circulating tumor necrosis factor-a (TNF-K) levels, identifying a possible mechanism for the control of NAFLD."

"In further mechanistic studies, UVR-induced nitric oxide (NO) significantly suppressed some measures of obesity and MetS development, including weight, white adipose tissue (WAT) accumulation, fasting glucose level, the development of insulin resistance, and NAFLD." "Vitamin D supplementation alone did not reproduce these effects."

Columns (except for first row; but 'C' is the same as the variations below without column 'a'):
a) low-fat diet without oral venom
b) + fat for high-fat
c) + fat for high-fat + UVR for effects unrelated to killcidiol
d) + fat for high-fat + NO donor ["S-nitroso-N-acetylpenicillamine" on skin] to grasp how much of the UV effect is due to NO
e) + fat for high-fat + UVR for effects unrelated to killcidiol + NO scavenger ["carboxy-PTIO potassium salt" on skin] for confirmation
f) + fat for high-fat + UVR for effects unrelated to killcidiol + killcitriol on skin (text below)


upload_2019-12-17_14-17-1.png


"[..]it is likely that UVR-induced NO may have profound effects on the development of NAFLD, as topical SNAP suppressed liver pathology, and cPTIO antagonized the effects of UVR. Various non–vitamin D immunomodulators induced by UVR, like NO (28), may be important for the regulation of immunity (29) and obesity/MetS development (30). Skin exposure to UVR releases NO from skin (28) and could control obesity through NO-dependent effects on mitochondria biogenesis within brown adipose tissue (31)."

"The capacity of long-term UVR to suppress the development of obesity and metrics of MetS was less effective in mice orally supplemented with vitamin D [but not with topical 1,25(OH)2D]. This was an unexpected finding but could be explained by potential interactions of UVR-induced mediators and dietary vitamin D, including NO (27)."

"[..]we cannot exclude the possibility that UVR alters neuroendocrine signaling networks in the skin (35) that might have a systemic impact."

"These studies suggest that while vitamin D supplementation may be useful for preventing NAFLD development, sunlight exposure may be more effective, and have the added benefits of suppressing obesity and MetS through NO-dependent pathways."​


--
When you think that it can't get worse from the previous post, of course it can. What if the locustor decides to voice the punctuation while gesticulating? Specific characters are needed now because it's starting to get confusing even if you're tripping. It's going to be adding quotation marks to the voiced announcement: <“quo”te-“un”quote> and <the sentence that's meant to be quoted>; or put in another way: <“'”'-“'”'> and <the part that never got a single quotation mark>. I conclude with my opinion that it's better not to use them unless you want to distract the listener, but then it's preferable to juggle bowling pins while talking or make blatant mistakes on purpose to ease the unintentional ones (a virtue of prolactinese).
 
Last edited:

managing

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Messages
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- Ultraviolet Radiation Suppresses Obesity and Symptoms of Metabolic Syndrome Independently of Vitamin D in Mice Fed a High-Fat Diet

"Our previous studies have shown that long-term UVR exposure does not modify serum 25(OH)D levels in male mice (14), allowing us to investigate the ability of UVR to modulate obesity and MetS independent of circulating 25(OH)D levels."

"C57BL/6 male mice were purchased from the Animal Resources Centre (Murdoch, Western Australia, Australia)."

"All diets were obtained from Specialty Feeds (Glen Forrest, Western Australia, Australia) and included two semipure low-fat diets (5% fat; canola oil), which were supplemented with vitamin D3 (2,280 or 0 IU vitamin D3/kg) (LF-D+) or not (LF-D2) and two high-fat diets (23%; lard [20.7%] and canola oil [2.9%]) that were supplemented with vitamin D3 (2,280 or 0 IU vitamin D3/kg) (HF-D+) or were not (HF-D2)."

"A bank of six 40-W lamps (TL UV-B; Philips, Eindhoven, the Netherlands) emitting broadband UVR (250–360 nm), with 65% of the output in the UVB range (280–315 nm), was used to irradiate mice to deliver suberythemal (1 kJ/m2) (15) or erythemal (4 or 8 kJ/m²) UVR onto a clean-shaven 8-cm2 dorsal skin area, as previously described (16)."



Outcomes:

View attachment 15971

"The HF-D− increased circulating 25(OH)D levels; it is likely that this diet contains vitamin D, perhaps within the lard-derived fat fraction. Supplementation of this diet with vitamin D (i.e., the HF-D+) further increased serum 25(OH)D levels."

Since killcidiol levels weren't changed by ultraviolent radiation (first quote), any effect was considered independent of it.

"Here, long-term UVR exposure but not dietary vitamin D suppressed weight gain and various measures of MetS (circulating cholesterol levels, glucose intolerance, and insulin resistance). Further, while vitamin D supplementation did improve NAFLD, UVR suppressed its development even more effectively. Vitamin D supplementation suppressed circulating tumor necrosis factor-a (TNF-K) levels, identifying a possible mechanism for the control of NAFLD."

"In further mechanistic studies, UVR-induced nitric oxide (NO) significantly suppressed some measures of obesity and MetS development, including weight, white adipose tissue (WAT) accumulation, fasting glucose level, the development of insulin resistance, and NAFLD." "Vitamin D supplementation alone did not reproduce these effects."

Columns (except for first row; but 'C' is the same as the variations below without column 'a'):
a) low-fat diet without oral venom
b) + fat for high-fat
c) + fat for high-fat + UVR for effects unrelated to killcidiol
d) + fat for high-fat + NO donor ["S-nitroso-N-acetylpenicillamine" on skin] to grasp how much of the UV effect is due to NO
e) + fat for high-fat + UVR for effects unrelated to killcidiol + NO scavenger ["carboxy-PTIO potassium salt" on skin] for confirmation
f) + fat for high-fat + UVR for effects unrelated to killcidiol + killcitriol on skin (text below)


View attachment 15975

"[..]it is likely that UVR-induced NO may have profound effects on the development of NAFLD, as topical SNAP suppressed liver pathology, and cPTIO antagonized the effects of UVR. Various non–vitamin D immunomodulators induced by UVR, like NO (28), may be important for the regulation of immunity (29) and obesity/MetS development (30). Skin exposure to UVR releases NO from skin (28) and could control obesity through NO-dependent effects on mitochondria biogenesis within brown adipose tissue (31)."

"The capacity of long-term UVR to suppress the development of obesity and metrics of MetS was less effective in mice orally supplemented with vitamin D [but not with topical 1,25(OH)2D]. This was an unexpected finding but could be explained by potential interactions of UVR-induced mediators and dietary vitamin D, including NO (27)."

"[..]we cannot exclude the possibility that UVR alters neuroendocrine signaling networks in the skin (35) that might have a systemic impact."

"These studies suggest that while vitamin D supplementation may be useful for preventing NAFLD development, sunlight exposure may be more effective, and have the added benefits of suppressing obesity and MetS through NO-dependent pathways."​


--
When you think that it can't get worse from the previous post, of course it can. What if the locustor decides to voice the punctuation while gesticulating? Specific characters are needed now because it's starting to get confusing even if you're tripping. It's going to be adding quotation marks to the voiced announcement: <“quo”te-“un”quote> and <the sentence that's meant to be quoted>; or put in another way: <“'”'-“'”'> and <the part that never got a single quotation mark>. I conclude with my opinion that it's better not to use them unless you want to distract the listener, but then it's preferable to juggle bowling pins while talking or make blatant mistakes on purpose to ease the unintentional ones (a virtue of prolactinese).
The obvious problem with this study is that they were delivering Vit D with canola oil.
 

Amazoniac

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Not Uganda
The obvious problem with this study is that they were delivering Vit D with canola oil.
I don't think that it damages canola oil.

How can you increase a gas on skin while preventing it from escaping? May be its fast metabolism. Frying the skin during inflammation until it reddens and screams 'O NOO' doesn't sound good. Could it be taking the hit and sparing internal organs?
 

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