Calcirol - Liquid Vitamin D3

[Amazoniac]

Equivalent to ~250 mcg/d and then halved, each for 4 weeks:
- Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract

 

[Amazoniac]

- D-livering the message: The importance of vitamin D status in chronic liver disease

"Serum DBP levels, which play a critical role in the transport and bioavailability of vitamin D, are moderately decreased in cirrhosis [24,25]. However, as only 5% of DBP binding sites are occupied at any one time with vitamin D metabolites [2], profound liver dysfunction is required for low DBP levels to exert a significant contributing role to vitamin D deficiency in chronic liver disease."


"[..]recent evidence suggests that vitamin D may impact upon clinical outcomes and treatment response. Fundamental to this are several in vitro studies showing that vitamin D inhibits hepatitis C virus (HCV) replication in a dose-dependent manner [30,31,32]."

[30] Vitamin D: An innate antiviral agent suppressing hepatitis C virus in human hepatocytes

"Of special importance is the finding that HCV infection markedly increased the levels of calcitriol in cell cultures. This was not due to increased production of calcitriol, as the level of 1a-hydroxylase was not altered, but rather to the prevention of induction of 24 hydroxylase, the enzyme responsible for the first step in the catabolism of calcitriol. Thus, HCV increases the efficacy of the vitamin D endocrine system of the hepatocyte."​

 

[Gone Peating]

My neck and shoulders have been feeling achy and cracking a lot lately since winter started. Just put five drops on my shoulder and 15 minutes later I am noticeably less achy and tight

 

[Amazoniac]

- Vitamin D Deficiency (guess the author)

Spoiler: Decontamination reasons

 

[Arnold Grape]

I am confused by this supplement, even at low dosages. I like what I am feeling (focused, slightly androgic, good hair) when it’s working, but it seems unpredictable in the way that I get almost depersonalization type effects when it goes wrong. Taking mag and eating well, not sure?

 

[Mateo Wiechers]

Would blocking Cholesterol syntesis with statins intibit de production of Vitamin D even with adecuate sun exposure?

 

[Peatogenic]

A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis

"High-dose vitamin D3 supplementation to patients with autoimmune disorders is conceivably advantageous over 1,25(OH)2D3 treatment concerning lower calcemic effects and more efficient control of autoimmunity. Administration of 1,25(OH)2D3 or 1,25(OH)2D3 analogs overpasses critical regulatory mechanisms related to the calciotropic effects of vitamin D by directly stimulating intestinal VDR and calcium absorption. In contrast, administration of vitamin D3 increases circulating concentrations of 25(OH)D3, which then faces different renal and extra-renal control mechanisms for expression and activity of the enzyme 1 α-hydroxylase.41 Renal 1 α-hydroxylase undergoes feedback downregulation (associated with 24-hydroxylase upregulation) by 1,25(OH)2D3 and 1,25(OH)2D3 production is also under strict control of other calcium- and phosphate-regulating hormones (PTH and FGF23).51 Conversely, the availability of 25(OH)D3 to immune cells (the production of which is not tightly controlled by the liver)37 may be the primary determinant of the amount of 1,25(OH)2D3 produced for intracrine and paracrine effects at sites of inflammation,50 where the local expression of cytokines may instead facilitate the conversion of 25(OH)D3 by inducing the expression of 1 α-hydroxylase.51,52

Hypervitaminosis D is associated with upregulation of intestinal VDR and increased absorption of dietary calcium.53 A low calcium diet protects against vitamin D toxicity, not only by reducing the availability of calcium for gastrointestinal absorption, but also by facilitating vitamin D inactivation at sites related to calcium metabolism.37 Reduced intestinal calcium by dietary restriction of milk, dairy products and calcium-enriched foods (like oat, rice or soya “milk”) has contributed to minimize the calciotropic effects of high daily doses of vitamin D3 in the current study. Increased gastrointestinal absorption of calcium is partly responsible for the hypercalcemia in vitamin D intoxication and a low dietary calcium intake gradually reduces serum calcium in such patients.54 Preliminary data (not shown) obtained from patients treated with progressively higher doses of vitamin D3 up to 35,000 IU daily showed that the adoption of such easily understandable dietary recommendations reduced urinary calcium from borderline elevated levels (around 400 mg or 10 mmol per day, with serum calcium sustained at the upper normal range) to values within the normal range without changing vitamin D daily dose. Further restriction of dietary calcium (by also avoiding foods prepared with milk, such as mashed potatoes, bread, cakes and cookies) dropped urinary calcium to levels below the lower limit of the normal range adopted by the local laboratory (100 mg or 2.5 mmol per day) while serum calcium remained around the lower limit (8.6 mg/dL or 2.15 mmol/L).

Taken together, those data suggest that partial dietary calcium restriction efficiently prevents hypercalcemia and hypercalciuria by controlling the gastrointestinal availability of calcium under the calciotropic effect of the treatment paradigm employed in patients with psoriasis and vitiligo in this study."

"serum concentration of PTH may be the best biological indicator for the individual setting of the optimal therapeutic dose of vitamin D3 for the treatment of autoimmune disorders"

"A period of at least 2 mo should be allowed between the two serum PTH measurements, considering that 25(OH)D3 has a half-life of 15 d.48 Using the PTH level as an ancillary index of therapeutic response requires a diet only partially restricted in calcium (like the one described in this study) since excessive restriction of calcium intake would maintain increased bone resorption to preserve normocalcemia, thereby limiting or preventing vitamin D3-induced PTH drop."

The guru also advocates maintaining PTH value close to the lowest of the normal range.

"all patients excluded milk and dairy products (as well as calcium-fortified foods like soy, oat or rice milk) from their diet and ingested at least 2.5 L of fluid per day to prevent, respectively, excessive absorption of intestinal calcium and concentrated urinary calcium. Calcium supplementation was not allowed. The onset of symptoms suggestive of hypercalcemia (increased thirst, constipation, nausea, vomiting) would require performing extra laboratory tests."​

__
Have you ever searched for ""vit d" isotretinoin"?

I'm having difficulty understanding the difference between different D3s. Do you know if the Coimbra protocol D3 is the same or needs to be the same as the D3 in calcirol?

 

[Peatogenic]

The point about infections causing low 25-OH-D and high 1,25-OH-D is probably accurate. As I mentioned many times before, testing 25-OH is probably inadequate to draw conclusions about vitamin D status. It should always be tested with 1,25-OH, PTH, calcium, phosphorus and maybe even WBC, CRP, and ESR.

Is Calcirol 25-OH-D? If so, does this mean it doesn't affect 1,25-OH-D?

 

[Amazoniac]

I'm having difficulty understanding the difference between different D3s. Do you know if the Coimbra protocol D3 is the same or needs to be the same as the D3 in calcirol?

Yes, it's the same toxin being used, not the derivatives that you mentioned next. Both killciol and killcidiol can be found in significant amounts in foods. This should clarify:
- Calcirol - Liquid Vitamin D3

 

[Peatogenic]

Yes, it's the same toxin being used, not the derivatives that you mentioned next. Both killciol and killcidiol can be found in significant amounts in foods. This should clarify:
- Calcirol - Liquid Vitamin D3

Your reply makes no sense to me.

 

[Amazoniac]

Your reply makes no sense to me.

I don't understand why the current confusing nomenclature prevailed; calciol (vitamin D3), calcidiol and calcitriol are much clearer. The core of the molecule is almost relegated when the derivatives are abbreviated as 25(OH)D, worse when it's 1a,25(OH)2D.

Calciol (as in Jorge's product) metabolism to calcidiol is poorly controlled, so the excess is supposed to reflect in calcidiol levels. However, there's still a backup system to prevent too much of it having to go the classical route (passing through calcitriol) to be degraded, it can be diverted to.. we can call it saviol.

 

[Peatogenic]

Since it was cleared up to me by Haidut that the topical antibacterial properties of D3 (referenced in newer posts) pertain to that contained in Calcirol, I'm going to experiment on an undiagnosed mild rosacea-like skin condition where I occasionally get folliculitis-like rash on forehead. I actually first used Calcirol a year ago on my wrists and began taking riboflavin during that time (I only take about 4000IU a week, spread out)...and my face had a two week period where it had transformed similar to as if I'd taken antibiotics.

When I came across a folliculitis study showing worsening with antibiotics and rapid remission with the prescription of topical fluconazole (antifungal), I began wondering if this requires a topical intervention. On top of this, starting 25D has had a major impact on my well being. I already use a lot of magnesium oil and get enough vitamin A, so I'm sure this helps. Other comments on the forum even mention the importance of riboflavin for Vit D activation.

A couple days ago I had a large pimple on my arm with blood pooling behind it. It was kind of alarming, as it speaks to this fear of having some type of infection going on. I put some Calcirol on it and within 10 hours, the blood pooling was gone, it had shrunk to half the size and was scabbing. It had seemed fully active and bright red for about three days prior. So I'm going to experiment with it topically on my face and see how it goes.

 

[Amazoniac]

Jorge, I heard that it's your cousin's birthday and you want to buy him something fancy. Let's ramp up the sales.

- Vitamin D alleviates lead induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats

This study measured the effects of vitamin D (VD) supplementation on the underlying molecular pathways involved in renal and testicular damage induced by lead (Pb) toxicity. Thirty two adult male Wistar rats were divided equally into four groups that were treated individually or simultaneously, except the negative control, for four weeks with lead acetate in drinking water (1,000 mg/L) and/or intramuscular VD (1,000 IU/kg; 3 days/week). Pb toxicity markedly reduced serum VD and Ca2+, induced substantial renal and testicular injuries with concomitant significant alterations in the expression of VD metabolising enzymes, its receptor and binding protein, and the calcium sensing receptor. Pb also significantly promoted lipid peroxidation and pro-inflammatory cytokines (IL-4 and TNF-α) in the organs of interest concomitantly with declines in several anti-oxidative markers (glutathione, glutathione peroxidase and catalase) and the anti-inflammatory cytokine, IL-10. The co-administration of VD with Pb markedly mitigated renal and testicular injuries compared with positive controls. This was associated with restoration of the expression of VD related molecules, promotion of anti-oxidative and anti-inflammatory markers, but tissue Pb concentrations were unaffected. In conclusion, this report is the first to reveal potential protective effects for VD against Pb-induced renal and testicular injuries via anti-inflammatory and anti-oxidative mechanisms.

Important:

"VD3 was administrated intramuscularly in the present study to prevent any potential effect on the absorption rate of lead and/or VD3 if both were administrated orally."​

 

[Amazoniac]

Why would killciol be metabolized differently depending on the route if it remained intact? Rate of appearance must play a rôle. In this case, the use of absorption enhancers is questionable.

Returning to this experiment, I think that the oral dose used was large, so it could have influenced the distribution.
- Be Wary Of Vitamin D Supplementation

- Be Wary Of Vitamin D Supplementation
- Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system

A sluggish uptake must favor a better regulation because it gives the body time to distribute the optimal way. In the lack of absorption enhancer, if no effect is noticed, simply up the dose; but changing the rate in the presence of an enhancer is more challenging.

Dividing the daily dose has to be tried by those who suspect that they benefit from the insult, but can't detoxify it right.

Inflammation at the skin or intestine may lead to local activation (last part from first link).

- Vitamin D Bioavailability: State of the Art

"It is assumed that vitamin D3 is solubilised in mixed micelles (Rautureau and Rambaud, 1981) and absorbed by the lymphatic route, while 25OHD3, being more polar, is less dependent on bile acids, and being water-soluble, is mainly absorbed via the portal route (Maislos et al., 1981). This has been confirmed by an Israeli team who studied the effect of absence of bile salts on the absorption of non-hydroxylated and hydroxylated vitamin D forms. Their results showed that 1,25(OH)2D3 absorption was unaffected by the lack of biliary salts. Conversely, absorption of 25OHD3 was decreased and that of vitamin D3 was fully impaired (Maislos and Shany, 1987)."

"Fat-soluble entities can be theoretically solubilised in structures other than micelles in the gut. More precisely, as vesicles have been observed in the human duodenal lumen during digestion (Staggers et al., 1990), it is hypothesised that they can incorporate fat-soluble substances in their phospholipid membranes (Urano et al., 1987; Kirilenko and Gregoriadis, 1993). However, it is not known whether a significant proportion of the different forms of vitamin D is incorporated in vesicles, and whether this has any effect on their absorption."

"The main site of vitamin D absorption in humans is not accurately known, but in the rat, uptake was observed in both jejunum and ileum (Hollander et al., 1978; Reboul et al., 2011), the ileum being the main site of absorption (Reboul et al., 2011). Absorption efficiency of vitamin D3 given in peanut oil was found to range between 55% and 99% (mean 78%) in healthy subjects (Thompson et al., 1966). These rates are similar to those from animal experiments, where rates between 66% and 75% were reported. Vitamin D is detected in the bile. However, the significance of a conservative enterohepatic circulation of vitamin D is controversial."

"Dietary vitamin D is non-esterified, but because some supplements may contain vitamin D esters (Hollis et al., 1996), the question arises of whether esterification affects vitamin D bioavailability. Only one study is dedicated to comparing the relative absorption efficiency of free vitamin D and vitamin D esters (Hollis et al., 1996). In this study, performed at various postnatal ages, the abilities of vitamin D3-palmitate and non-esterified vitamin D2 to elevate circulating vitamin D3 and vitamin D2, respectively, were compared. It was concluded that the two forms approached equivalence when the gastrointestinal tract was mature. Conversely, vitamin D3-palmitate bioavailability was lower below age 10 days, probably due to the lack of maturation of the digestive tract. This confirms the need for an efficient digestion of lipids to efficiently absorb vitamin D, in particular vitamin D esters."

"It is generally assumed that like other vitamins, the absorption efficiency of vitamin D decreases with increasing dose. The effect of the dose of vitamin D on its absorption efficiency was studied in the rat. In both the jejunum and ileum, a linear relationship was found between the absorption rate of the vitamin and its intraluminal concentration (Hollander et al., 1978). This suggests that at least in the range of the studied concentrations, vitamin D absorption efficiency does not significantly decrease with dose. This result is supported by the result of a clinical study in which 116 subjects were placed in nine treatment groups that ingested vitamin D3 (25, 250 or 1250 μg/d for 8 weeks), 25OHD3 (10, 20, or 50 μg/d for 4 weeks) or 1,25(OH)2D3 (0.5, 1.0, or 2.0μg/d for 2weeks). Results showed that serum levels of all three forms increased linearly with the dietary dose, showing a similar efficiency of absorption, at least in the range of doses studied (Barger-Lux et al., 1998). A recent study, performed in the human intestinal cell line Caco-2, has shown that at low concentrations of vitamin D3 in micelles, i.e., between 0.1 and 2–3 μmole/L, higher than the physiological concentration in the human duodenum, calculated to be about 0.01 μmole/L (Reboul et al., 2011), the uptake of both vitamin D3 and D2 was saturable, while it was linear at high pharmacological concentrations, i.e., up to 10 μmole/L. This result supports the involvement of intestinal proteins in vitamin D absorption at dietary concentrations and a passive diffusion that becomes preponderant at pharmacological concentrations."​

--
@Jorge, have you thought about running your own human experiment attempting to detect the activity of this toxin in blood from topical use? Testing the main metabolites regularly at first and sparingly later on. It must not be expensive and there aren't many studies of this kind, I'm sure you can do much better than the ones available.

 

[Peatogenic]

I asked Ray if oral or topical 25-OH D3 was best for skin conditions and he said oral. So I think I'm going to experiment with both. I take a really low dose anyway, about 2000iu every other day. (Making sure to also be replete with Magnesium, B2, calcium, K, and A)

 

[baccheion]

I asked Ray if oral or topical 25-OH D3 was best for skin conditions and he said oral. So I think I'm going to experiment with both. I take a really low dose anyway, about 2000iu every other day. (Making sure to also be replete with Magnesium, B2, calcium, K, and A)

You need 300-500 IU/kg/day. Adjust down calcium intake if necessary. IIRC, it worsens rosacea (or eczema, forgetting which) and clears psoriasis.

 

[Peatogenic]

You need 300-500 IU/kg/day. Adjust down calcium intake if necessary. IIRC, it worsens rosacea (or eczema, forgetting which) and clears psoriasis.

Rosacea usually has lower vitamin D, but higher cathelecidin in skin.

 

[Amazoniac]

With doses that is not pharmacological, the majority absorbed initiates the destruction from the portal vein:

- Comparison of vitamin D and 25-hydroxyvitamin D absorption in the rat

"[Our studies demonstrated] that physiological amounts of vitamin D are transported out of the intestine by both lymph and portal blood. The amount recovered in the lymph was only about one-third the total vitamin D absorbed, as determined by the sac digestion experiments, indicating that the portal route of absorption is important at [] physiological concentrations."

Spoiler

That's the percentage of the administered dose under low-fat condition.

"Schachter et al. (22) studied the intestinal absorption of vitamin D in the rat using labeled vitamin D of low specific activity, requiring 1,000 times the dose of vitamin D used in this study. They found that, under those conditions, most of the absorbed vitamin D was recovered in the lymph and mainly in the chylomicron fraction."

"The difference between our results and those of Schachter et. al. (22) may simply reflect differences between physiological and pharmacologic concentrations of vitamin D. McDonald et al. (17) have recently reported that at low concentrations long-chain fatty acids are transported predominantly by the portal venous route, whereas at high is predominant."

Progesterone Oral Vs Topical​

"In both our experiments and those of Schachter et al. (22), most of the vitamin D in lymph chromatogramed as the unmetabolized vitamin."

"In our studies, we also found that 25(OH)D was absorbed more rapidly than vitamin D from all test solutions studied. The portal venous route was particularly important and predominant for the intestinal absorption of 25(OH)D."

"In our study, only 53% of lymph vitamin D was found in chylomicrons. In contrast, under identical conditions, more than 80% of retinol was found in the chylomicron phase. An even smaller fraction of 25(OH)D is carried in lymph chylomicrons (13%). Distribution of vitamin D in lymph may be affected by exchange of vitamin between lipoprotein particles after release from the enterocyte."

Spoiler

"Dietary triglyceride is transported from the intestine largely with chylomicron particles. Formation of chylomicrons depends on de novo synthesis of chylomicron associated apolipoproteins. Treatment of animals with inhibitors of protein synthesis such as cycloheximide or puromycin markedly decreases triglyceride absorption; the enterocytes became packed with triglyceride, which cannot be released into lymph as chylomicrons (21). Abetalipoproteinemia, a genetic disorder in which apoB synthesis is defective, is characterized by steatorrhea and a histological picture of lipid-filled enterocytes, identical to that seen in cycloheximide-treated animals (6)."

"To further study the requirement for chylomicron synthesis in vitamin D absorption, the effect of cycloheximide on intestinal absorption was determined. Cycloheximide caused a 46% reduction in intestinal absorption of vitamin D. This was significantly less than 70% inhibition of oleic acid or retinol absorption. It is interesting to note that vitamin D deficiency has only rarely been reported in abetalipoproteinemia, whereas vitamin A deficiency is quite commonly seen (14). Absorption of the 25(OH)D was even less affected by cycloheximide, with only 30% inhibition of absorption."

Spoiler

 

[Peatogenic]

With doses that is not pharmacological, the majority absorbed initiates the destruction from the portal vein:

- Comparison of vitamin D and 25-hydroxyvitamin D absorption in the rat

"[Our studies demonstrated] that physiological amounts of vitamin D are transported out of the intestine by both lymph and portal blood. The amount recovered in the lymph was only about one-third the total vitamin D absorbed, as determined by the sac digestion experiments, indicating that the portal route of absorption is important at [] physiological concentrations."

Spoiler

View attachment 16454

"Schachter et al. (22) studied the intestinal absorption of vitamin D in the rat using labeled vitamin D of low specific activity, requiring 1,000 times the dose of vitamin D used in this study. They found that, under those conditions, most of the absorbed vitamin D was recovered in the lymph and mainly in the chylomicron fraction."

"The difference between our results and those of Schachter et. al. (22) may simply reflect differences between physiological and pharmacologic concentrations of vitamin D. McDonald et al. (17) have recently reported that at low concentrations long-chain fatty acids are transported predominantly by the portal venous route, whereas at high is predominant."

Progesterone Oral Vs Topical​

"In both our experiments and those of Schachter et al. (22), most of the vitamin D in lymph chromatogramed as the unmetabolized vitamin."

"In our studies, we also found that 25(OH)D was absorbed more rapidly than vitamin D from all test solutions studied. The portal venous route was particularly important and predominant for the intestinal absorption of 25(OH)D."

"In our study, only 53% of lymph vitamin D was found in chylomicrons. In contrast, under identical conditions, more than 80% of retinol was found in the chylomicron phase. An even smaller fraction of 25(OH)D is carried in lymph chylomicrons (13%). Distribution of vitamin D in lymph may be affected by exchange of vitamin between lipoprotein particles after release from the enterocyte."

Spoiler

View attachment 16455

"Dietary triglyceride is transported from the intestine largely with chylomicron particles. Formation of chylomicrons depends on de novo synthesis of chylomicron associated apolipoproteins. Treatment of animals with inhibitors of protein synthesis such as cycloheximide or puromycin markedly decreases triglyceride absorption; the enterocytes became packed with triglyceride, which cannot be released into lymph as chylomicrons (21). Abetalipoproteinemia, a genetic disorder in which apoB synthesis is defective, is characterized by steatorrhea and a histological picture of lipid-filled enterocytes, identical to that seen in cycloheximide-treated animals (6)."

"To further study the requirement for chylomicron synthesis in vitamin D absorption, the effect of cycloheximide on intestinal absorption was determined. Cycloheximide caused a 46% reduction in intestinal absorption of vitamin D. This was significantly less than 70% inhibition of oleic acid or retinol absorption. It is interesting to note that vitamin D deficiency has only rarely been reported in abetalipoproteinemia, whereas vitamin A deficiency is quite commonly seen (14). Absorption of the 25(OH)D was even less affected by cycloheximide, with only 30% inhibition of absorption."

Spoiler

View attachment 16456

Would you say the takeaway is that it's very challenging to absorb vitamin D?

 

[Amazoniac]

Would you say the takeaway is that it's very challenging to absorb vitamin D?

No, that the liver gets most of it before other tissues (not a problem).
What I don't know is how it compares to when it's applied on the skin, one of the linked experiments above was done with irradiation.