Be Wary Of Vitamin D Supplementation

[somuch4food]

Do you consume a lot of dairy? If calcium is already high, D3 could push absorption too high. It certainly is the case for me. I can enjoy dairy as long as I avoid D3. I even tried transdermal D3 with only olive oil as an additional ingredient and the result was the same.

High calcium does cause brain fog, anhedonia. In some alternative health circle, it's dubbed the calcium shell.

 

[iso1]

Do you consume a lot of dairy? If calcium is already high, D3 could push absorption too high. It certainly is the case for me. I can enjoy dairy as long as I avoid D3. I even tried transdermal D3 with only olive oil as an additional ingredient and the result was the same.

High calcium does cause brain fog, anhedonia. In some alternative health circle, it's dubbed the calcium shell.

I do consume a lot of milk and my calcium is borderline high. D3 induced calcium brain fog would make sense to me, but why do I get shedding is a big question. Increased calcium influx in cells and as a result suppression of parathyroid hormone ?

 

[somuch4food]

I do consume a lot of milk and my calcium is borderline high. D3 induced calcium brain fog would make sense to me, but why do I get shedding is a big question. Increased calcium influx in cells and as a result suppression of parathyroid hormone ?

I am not familiar with hair loss, but there seems to exist a link with calcification (from a quick Google search): Scalp Calcification & Hair Loss: Is There a Connection? - Hair Science

 

[Amazoniac]

- Modified-release oral calcifediol corrects vitamin D insufficiency with minimal CYP24A1 upregulation

"Significant percentages of CKD patients receiving vitamin D supplements do not attain targeted levels of serum 25-hydroxyvitamin D [9,10]. Recommended repletion [11] comprises intermittent high dose regimens which may trigger accelerated vitamin D catabolism [12]."

"The impact of rate of administration on effectiveness of vitamin D therapies has been poorly investigated. In this paper, we present results from parallel studies in which calcifediol was delivered either rapidly as an IV bolus, or gradually via an oral MR [MISTER] formulation, to vitamin D deficient rats or patients with stage 3 or 4 CKD, SHPT and vitamin D insufficiency. Our findings suggest that rate of delivery is an important determinant of vitamin D hormone production, and therefore of therapeutic efficacy, and that gradual delivery allows more effective treatment of both vitamin D insufficiency and SHPT in CKD patients."​

- Vitamin D twice a day may keep vertigo away

 

[Amazoniac]

Saving for later. If this is true, it's one more toxin to mind.
- Vitamin D3 Itself Creates Profound Anti-Inflammatory Effects | GrassrootsWealth
↳ Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium

@??

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- A Comprehensive Review of Infectious Granulomatous Diseases of the Gastrointestinal Tract

 

[Amazoniac]

- Natural Epigenetic Modulators of Vitamin D Receptor

Vitamin D plays an important role in every tissue due to its differentiating properties and the control of calcium homeostasis. The reversion of the epigenetic repression of the vitamin D receptor (VDR) could lead to an increased sensitivity of the cells to the beneficial activity of the hormone and could be exploited in many vitamin D-resistant diseases. In this study we analyzed the effects of three natural epigenetic modulators: sulforaphane, curcumin, and the products of the fermentative activity of probiotics. Sulforaphane and curcumin are inhibitors of the DNA methyltransferases (DNMT) and of the histone deacetylases (HDAC); it has been demonstrated that sulforaphane and curcumin increase VDR expression in intestinal epithelial cells and in a human liver cancer cell line, respectively. The anti-inflammatory properties associated with the probiotic administration in vivo can be linked to the increased activity of intestinal VDR. Butyrate, an inhibitor of HDAC and a known modulator of VDR expression, is the candidate byproduct of fermentation by gut microbiome that could mediate the enhanced expression of VDR triggered by probiotics in vivo. Many other natural compounds wait to be investigated and recognized as epigenetic modulators of VDR, thus opening promising therapeutic avenues for many diseases by natural means.

 

[Amazoniac]

- Conjugated forms of [3H]1α,25-dihydroxyvitamin D3 in rat bile

Spoiler

"Apart from neutral metabolites, taurine conjugates and fractions of glucuronides and monosulphates were the most abundant anionic metabolites (Table 1). However, hydrolysis and solvolysis, respectively, revealed a significant degree of mixed conjugation: e.g. glucuronide/glycine and monosulphate/taurine (Table 2)."

 

[Amazoniac]

- Hypercalcaemia due to isolated elevation of 1,25-dihydroxyvitamin D in patients with Crohn’s disease

Spoiler

"Crohn's disease as a cause of hypercalcaemia is a rare clinical entity. We conducted a systematic literature search in order to access the available studies for hypercalcaemia due to elevated 1,25-dihydroxyvitamin D in the setting of Crohn’s disease." "After a comprehensive review of full-text papers, a total of four articles on increased 1,25-dihydroxyvitamin D-associated hypercalcaemia in Crohn’s disease were identified.[9–12]"

"The most frequent presentation of hypercalcaemia is increased serum calcium levels detected on a laboratory evaluation. In symptomatic cases, typical symptoms are ‘moans, bones, stones and groans’ indicating depressed mood, musculoskeletal pain, renal colic and abdominal pain.[13] Neuropsychiatric disturbances such as anxiety and depression as well as cognitive disturbances have also been reported. Renal abnormalities like polyuria, polydipsia and dehydration can also be encountered. These manifestations can be independent or may be a result of associated diabetes insipidus, distal renal tubular acidosis and nephrolithiasis. Musculoskeletal involvement may lead to bone pain, osteopenia, osteoporosis and muscle weakness. Cardiovascular complications include but not limited to hypertension, bradycardia and shortening of the QT interval.[13] In this comparative review, most patients with hypercalcaemia in setting of Crohn’s disease presented with gastrointestinal symptoms such as abdominal pain (n=3), diarrhoea (n=3), weight loss (n=2) and vomiting (n=2). Of note, in cases with chronic hypercalcaemia, higher serum calcium levels can be tolerated without any clinical symptomology."

"In terms of pathogenesis, elevated serum 1,25-dihydroxyvitamin D is recognised as the cardinal abnormality. However, 1,25-dihydroxyvitamin D-induced accelerated bone resorption may also have a role.[14,15] In normal individuals, the changeover of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D occurs in the proximal renal tubular cells, under the action of 1-hydroxylase (CYP27B1) enzyme, which is regulated by parathyroid hormone (PTH), serum phosphate levels and fibroblast growth factor-23. With the rise in serum calcium levels, serum PTH levels are decreased by the feedback loop, which in turn decreases the production of 1,25-dihydroxyvitamin D and normalises serum calcium levels. In granulomatous disorders, activated macrophages produce autonomous 1,25-dihydroxyvitamin D. This PTH-independent mechanism has a pivotal role in the underlying pathology of hypercalcaemia.[15] The synthesis of 1,25-dihydroxyvitamin D increases by 30-fold under the action of THP-1 cells, which are activated by interferon-gamma, released by the activated macrophages. Furthermore, it also minimises the metabolism of 1,25-dihydroxyvitamin D by 42.2%.[16] The aforementioned changes have commonly been implicated in granulomatous diseases and lymphoma. Therefore, similar pathophysiological derangements can also be considered as possible mechanisms causing hypercalcaemia in patients with Crohn's disease."

"The patient involved in the present study developed severe hypercalcaemia secondary to elevated 1,25-dihydroxyvitamin D during Crohn’s disease exacerbation. The workup data supporting this included the inappropriate 1,25-dihydroxyvitamin D levels with the concurrent presence of hypercalcaemia and hypercalciuria, PTH in the lower normal range, normal PTH–related peptide levels, the histopathological evidence of the left descending colon showing active Crohn’s disease, and the resolution of hypercalcaemia with treatment of Crohn’s disease using corticosteroid therapy. Additionally, an increased ACE inhibitor level is a common feature and a useful therapeutic marker in patients with sarcoidosis and hypercalcaemia.[17]"

"The appropriate treatment of hypercalcaemia depends on the underlying aetiology and the severity of the imbalance. In patients with severe hypercalcaemia, intravenous hydration with normal saline remains essentially important, regardless of the underlying pathology.[20] In difficult-to-treat cases, calcitonin, mithramycin, denosumab and/or dialysis are recognised as useful adjuncts in the emergency management.[20] Long-term treatment in granulomatous disorders mainly depends on managing the underlying disorder. The calcium levels return to normal when the disease process goes into remission. Decreasing the calcium intake to <400 mg and reducing the oxalate intake to decrease the risk of oxalate stone formation in kidneys are also important.[21] Glucocorticoid therapy (10–30 mg/day of prednisone) is commonly used to treat sarcoidosis.[22] Calcium levels begin to fall in 2 days of initiation but an optimal response has usually been achieved in 7–10 days of treatment. Ketoconazole can be used as the second-line therapy in steroid non-responders and/or in order to decrease or avoid corticosteroid exposure.[23] Doty et al described a number of patients with refractory hypercalcaemia who eventually responded to anti-tumour necrosis factor monoclonal antibody, infliximab.[24]"

"Tuohy and Steinman described significant improvement in their patient’s clinical and biochemical profiles after only 1 week of budesonide therapy. They attributed it to rapid response of macrophage 1-hydroxylase enzyme activity to this oral gastrointestinal- selective corticosteroid.[10] Therefore, budesonide may serve as a better choice than prednisone for 1,25-dihydroxyvitamin D-related hypercalcaemia in active Crohn’s disease because this agent minimises the systemic side effects of corticosteroids. In patients with sarcoidosis, the medications like chloroquine and hydroxychloroquine have also been used to decrease calcium and 1,25-dihydroxyvitamin D levels.[25,26] These agents may also be safe options in hypercalcaemia due to elevated calcitriol in active Crohn’s disease, but they have not been previously tested."

↳ [9] Hypercalcemia due to endogenous overproduction of 1,25-dihydroxyvitamin D in Crohn’s disease
↳ [11] Active crohn disease and hypercalcemia treated with infliximab: case report and literature review
↳ [12] Unusual association of diseases/symptoms: Rennies, Crohn's disease and severe hypercalcaemia
↳ [10] Hypercalcemia due to excess 1,25-dihydroxyvitamin D in Crohn’s disease

Spoiler

"More commonly, Crohn’s disease is associated with hypocalcemia caused by vitamin D deficiency resulting from ileal resection and malabsorption of fat-soluble "vitamins"[10] or low calcium intake caused by patient avoidance of dairy products.[11]"

"We describe a patient with Crohn’s disease and hypercalcemia-associated acute renal failure that appeared to be mediated by an elevated 1,25-dihydroxyvitamin D level. With remission of the active bowel disease, all metabolic parameters returned to normal."

"[..]our patient had clinical evidence of active Crohn’s disease, and hypercalcemia appeared to be mediated by unregulated production of 1,25-dihydroxyvitamin D. Despite elevated serum calcium and phosphorous levels and appropriately maximally suppressed PTH, 1,25-dihydroxyvitamin D level was elevated. In addition, 25-hydroxyvitamin D level was at the low end of normal range, which may reflect decreased intake and absorption from the GI tract or consumption by unregulated 1-Diokine hydroxylase of activated macrophages. With resolution of GI symptoms, serum calcium, vitamin D, and PTH levels returned to normal."

"The improvement in our patient’s clinical symptoms and laboratory results that followed only 1 week of therapy with budesonide may indicate that macrophage 1-Diokine hydroxylase enzyme activity is rapidly responsive to this oral GI-selective corticosteroid. Budesonide may serve as a good alternative to prednisone therapy for calcitriol-mediated hypercalcemia in patients with active Crohn’s disease because this agent minimizes the systemic side effects of corticosteroids. Ketoconazole has been used effectively as an alternative agent to prednisone in the treatment of patients with hypercalcemia associated with sarcoidosis[24] and tuberculosis,[25] especially in steroid-resistant cases or as a means of decreasing or avoiding corticosteroid exposure. Both chloroquine[26] and hydroxychloroquine[27] have been used to decrease calcium and 1,25-dihydroxyvitamin D levels in patients with sarcoidosis. However, hydroxychloroquine failed to reduce either serum calcium or 1,25-dihydroxyvitamin D levels in patients with lymphoma.[28]"

Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

- Rare Causes of Calcitriol-Mediated Hypercalcemia: A Case Report and Literature Review

Spoiler

"The ability of sunlight or even low-dose vitamin D3 supplementation to precipitate hypercalcemia in sarcoidosis has long been recognized, and also witnessed in other conditions such as histoplasmosis (62), candidiasis (4), and rheumatoid arthritis (26). Our patient was initially vitamin D deficient, which may have resulted from a combination of decreased dietary or environmental supply and/or increased consumption from up-regulated 1α-hydroxylase activity. When she received supplemental vitamin D3, she subsequently developed hypercalcemia with normal, not toxic, 25(OH)D levels. Granulomatous hypercalcemia seems particularly sensitive to vitamin D exposure. However, once the underlying cause has been treated, vitamin D supplementation can be reinstituted without recurrence of the hypercalcemia (29, 39)."

- Vitamin D and Intracellular Calcium (killcitriol)

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- Vitamin D Toxicity–A Clinical Perspective

 

[gaze]

@Amazoniac

Did you post in this thread or anywhere else if vitamin D is better transdermal or orally for people with very low cholesterol levels ? Does low cholesterol only affect sunlight conversion due to cholesterol in the skin, while transdermal cholecalciferol doesn't require the skin cholesterol? Im bad with the search function

 

[Amazoniac]

@Amazoniac

Did you post in this thread or anywhere else if vitamin D is better transdermal or orally for people with very low cholesterol levels ? Does low cholesterol only affect sunlight conversion due to cholesterol in the skin, while transdermal cholecalciferol doesn't require the skin cholesterol? Im bad with the search function

The industrial production involves irradiation of 7-dehydroatherosclerol just like it would occur in the skin, so it's no longer dependent on its availability. Compromised skin barrier might facilitate absorption, whereas in the gut it's more likely to impair and lead to malabsorption issues that can coincide with dimished pool of bile acids. I would rely on transdermal use.

 

[Amazoniac]

- Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity

"[..]there is data to support that bacteria actually influence vitamin D metabolism as some bacteria express enzymes involved in hydroxylation of steroids and thus are capable of processing and activating vitamin D in a manner similar to humans (118). Bacterial CYP105A1 (Streptomyces griseolus) converts vitamin D3 into 1,25(OH)2D3, in two independent hydroxylation reactions, representing the bacterial functional equivalent of the combined activity of vitamin D metabolic enzymes CYP2R1, CYP27A1, and CYP27B1 (119). Additional review of a microbial genome database for CYP27A1 and CYP27B1 revealed homologous protein from Ruminococcus torques (Phylum: Firmicutes) Mycobacterium tuberculosis, respectively (120). Capitalizing on these microbial enzymes, there is even a patent (U.S. Patent 5474923) for a process by which hydroxylated vitamin D derivatives are obtained by incubating vitamin D with Nocardia, Streptomyces, Sphinogmonas, and Amycolata. Additional studies are needed to understand the relationship between vitamin D and gut bacteria, and the role of bacteria in maintaining adequate vitamin D levels."​

- Calcirol - Liquid Vitamin D3

- Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome– a pilot study

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases.

- Vitamin D Bioavailability: State of the Art

"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."​

 

[Amazoniac]

From Dave's Venom D book:

- Regulation of Intestinal Calcium and Phosphate Absorption

Spoiler

"Can High Vitamin D Status Increase Intestinal Calcium Absorption?

It is well established that 1,25(OH)2D treatment can increase the efficiency of intestinal calcium absorption [7,50,51]. However, there is some controversy regarding whether intestinal calcium absorption can also increase in response to improved serum 25(OH)D levels. The traditional view of the role of vitamin D status for calcium absorption is best represented in studies by Need et al. [24] who found that increasing vitamin D status was associated with increased efficiency of intestinal calcium absorption only when serum 25(OH)D levels were inadequate to support renal production of 1,25(OH)2D (i.e., all of the added 25(OH)D was converted to 1,25(OH)2D that could then act directly). In contrast, an independent effect of high serum 25(OH)D levels was first proposed by Heaney et al. [52] who reported that calcium absorption (measured by appearance of 45Ca in serum 5 h after a meal containing 300 mg calcium) was increased by 25% after 4 weeks of treatment with 50 ug 25(OH)D/d even though serum 1,25(OH)2D levels did not change. This same group later used pooled data from two separate studies to show a 65% increase in calcium absorption efficiency in postmenopausal women as serum 25(OH)D increased from 50 to 86.5 nmol/L (increased area under the curve of serum calcium 5 h after an oral load of 500 mg calcium) [53]. Several other groups have reported a positive, but more modest, relationship between serum 25(OH)D and calcium absorption. Hansen et al. [54] found that raising serum 25(OH)D from 55 to 160 nmol/L by supplementing women with 50,000 IU vitamin D2 per day for 15 days increased calcium absorption efficiency of 300 mg Ca from 24 to 27% as determined by a dual stable isotope technique. Gallagher et al. [55] found that based on a regression approach, calcium absorption efficiency increased from 52 to 58% (2 h after a single isotope dose of 100 mg Ca) as serum 25(OH)D levels increased from 50 to 160 nmol/L after a 1 year intervention of 400–4800 IU vitamin D3/d. Shapses et al. [56] reported that in postmenopausal women, a 6 week intervention with 2500 IU vitamin D3/d increased calcium absorption by 3% (dual stable isotope method, 153 mg calcium in test dose). Aloia et al. [57] use a regression approach to show that an 8 week intervention with increasing doses of vitamin D3 (4 doses, 0–4000 IU/d) increased calcium absorption by 6.7 ± 12% between 40 and 130 nmol 25(OH)D/L.

In contrast to the data supporting a strong role for high vitamin D status as a regulator of intestinal calcium absorption, several groups show no effect. Abrams et al. [58] found that higher serum 25(OH)D levels did not increase calcium absorption efficiency in a cross-sectional study of 251 school age children (dual stable isotope method, 300 mg calcium in test dose). This group later showed that although a 1000 IU/d supplement to children for 8 weeks increased serum 25(OH)D from 70 to 90 nmol/L and reduced serum PTH by 40%, there was no relationship between serum 25(OH)D and calcium absorption (dual stable isotope method, 150 mg calcium in test dose, [59]). Similarly, Lewis et al. [60] saw no improvement in Ca absorption in 323 black and white children supplemented with increasing levels of vitamin D3 for 3 months (5 doses from 0 to 4000 IU/d; single isotope test, 3 h post meal). In a large group of postmenopausal women with baseline serum 25(OH)D levels between 35 and 68 nmol/L (n = 230), Hansen et al. [61] saw no increase in calcium absorption after supplementation with either 800 IU vitamin D3/d or 50,000 IU vitamin D3 twice weekly for 1 year despite the fact that both treatments significantly increased serum 25(OH)D levels (dual stable isotope method, 300 mg calcium). Thus, the hypothesis that improving vitamin D status beyond that necessary to support adequate renal production of 1,25(OH)2 D can regulate intestinal calcium absorption is not strongly supported by the literature."

- Is Vitamin D Supplementation Even Neccessary

At the time the concern was obtaining enough killcium, but here it's the excess, for those that presuppose that there's a killcium flood from diet involved in case of a bad reaction. You can find unexpected values at every level:

⬑ [4] Vitamin D supplementation increases calcium absorption without a threshold effect

Spoiler

I believe that it's possible to feel worse with this toxin before getting "better", yet adverse effects remain a sign that something is being overwhelmed. Without changing other factors that can increase tolerance, I would dial down the intoxication because this stuff has antibiotic properties (Pina, 2021), may be working against your life.

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Another chapter:
- Pharmacology and Pharmacokinetics

There's nothing in it that we haven't discussed on the forum, but the topic was condensed in a few pages. It's a great book.

 

[gaze]

The industrial production involves irradiation of 7-dehydroatherosclerol just like it would occur in the skin, so it's no longer dependent on its availability. Compromised skin barrier might facilitate absorption, whereas in the gut it's more likely to impair and lead to malabsorption issues that can coincide with dimished pool of bile acids. I would rely on transdermal use.

what are your thoughts on taking ox bile or bile salts? what should someone with fat malabsorption focus on? If fat absorbtion is already bad, is it a bad idea to increase dietary fat in hopes it stimulates bile? seems like a strange cycle to get out of

 

[Amazoniac]

- Comprehensive Stability Study of Vitamin D3 in Aqueous Solutions and Liquid Commercial Products

Spoiler

"The initial conclusion from the performed stability study is that vitamin D3 is very unstable in aqueous media. The significantly higher vitamin D3 stability observed in organic solvents (Figure 1) is probably due to the absence of hydronium and hydroxyl ions, used in hydrolysis, and catalysts for oxidation reactions, such as metal ions [60]. Among the three different tested waters (MQ, DW, and TW), vitamin D3 was found the most stable in MQ and the least stable in DW."

"High purity Milli-Q water (MQ) was obtained through a Milli-Q A10 Advantage water purification system (Millipore Corporation, Bedford, MA, USA). Distilled water (DW) was obtained through an Elix® Water Purification System (Merck, Darmstadt, Germany). Tap water (TW) was obtained from the laboratory at the Faculty of Pharmacy, University of Ljubljana (Ljubljana, Slovenia)."​

"Metal ions, which are less likely to be present in ultrapure MQ, lower the activation energy and lead to faster vitamin D3 degradation (higher rate constant) in DW and TW." "[..]vitamin D3 in aqueous solutions may be stabilized by being stored at a lower temperature because there was a statistically significant decrease of first-order rate constants at a lower temperature. The stabilizing effect of lower storage temperature is stronger in MQ than in TW or DW."

"Vitamin D3 was found unstable in acidic media and more stable at pH values above 5 (Figure 2). These results were in contrast to the usual trend for oxidation: lower stability at higher pH [37]."

"By evaluating the concentration effect, we concluded that aqueous solutions with lower vitamin D3 concentrations were less stable (Table 5) as a consequence of the greater impact of particular destabilizing factors."

"Vitamin D3 degradation is mostly mediated through oxidative reactions [34,59–61]. Factors that could induce and influence oxidation (e.g., light, oxygen, and metal ions) were thus evaluated. Light induces oxidative reactions, mostly through the formation of free radicals, and causes isomerization. The obtained results of decreased vitamin D3 stability under the influence of light (Figure 3) are supported by several reports in the literature [31,36,38–41] although contradictory data are also found in the published literature [43,44]. Possible reasons for the conflicting data are different experimental conditions (e.g., exposure time, light sources and illumination, media, or concentration) or deficient information on the experimental conditions. In a recently published study on vitamin D3-forced degradation, its isomers were observed as degradation products under the influence of light [42], thus confirming the destabilizing effect of light on vitamin D3. Oxygen was also identified as a factor, which significantly decreased the stability of vitamin D3 (Figure 4). However, the air above the solution was not a determining factor for vitamin D3 destabilization."

"Metal ions are widespread in the environment and may also be present in finished products. Their source may be the manufacturing equipment, containers, and the used water, or they may be present as impurities in the active ingredients or excipients if used as catalysts in the synthesis processes [62]. Trace metals can act as catalysts in oxidation processes and cause active ingredient degradation [63]."

"The performed stability study in aqueous solutions indicated that vitamin D3 could be stabilized by limiting the effects of destabilizing factors (e.g., storage at a lower temperature and/or at pH >5) and active intervention by the addition of stabilizers, which was quantitatively evaluated. The addition of three well-known antioxidants: EDTA, citric acid, and ascorbic acid significantly stabilized vitamin D3 (Figure 5). The antioxidant activity of ascorbic acid is mediated through the reduction of reactive oxygen or nitrogen species or acts as a weak chelating agent [67,68]. Citric acid and EDTA effectively remove metal ions by chelation [67,68]."

"The results from the vitamin D3 stability study in three medicines and six FSs [Food Supplements], all in the form of oral drops (Table 7), are in accordance with results from the stability study of vitamin D3 in solutions [..]. Analogously as observed within the stability study in solution [..], we identified the carrier of the formulation as the main contributing factor for vitamin D3 stabilization. Contrary to the tested oil-based formulations, vitamin D3 was found to be unstable in water-based formulations, which are commonly found on the market. Among the tested water-based formulation, we observed a difference between vitamin D3 stabilization within the two tested product categories: medicines and FSs. Although unstable in aqueous solutions, vitamin D3 may be properly stabilized, which was achieved with the formulation of Products 2 and 3, both registered as medicines. The observed vitamin D3 instability in all three water-based FSs (5, 9, and 7) also confirmed our thesis that aqueous vitamin D3 solutions require proper stabilization, which had been neglected or deemed to be of lesser importance for their manufacturers. Namely, Product 7 did not contain any stabilizer or organic solvents. Vitamin D3 was the least stable in FS Product 5, leading to its total degradation after 6 months of storage at the recommended conditions (ambient temperature). Such pronounced vitamin D3 instability was in accordance with our findings, considering the acidic environment of this product (pH < 3), which was identified as one of the key destabilizing factors within the vitamin D3 stability study in aqueous solutions [..]. In comparison, the other tested water-based formulations were in the more favourable pH range according to its pH profile (between 5.6 and 7.2). Also, the composition of Product 5 did not provide stabilization because it is an aqueous vitamin D3 solution containing only one potential vitamin D3 stabilizer—citric acid. However, its presence at high concentrations had a destabilizing effect on vitamin D3 because it created an acidic environment."

- Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D3 and Its Natural Derivatives

@Jennifer, product #7 is the most similar to your current sponsor.

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- A review of metal-induced effects on vitamins A, E and D3 in birds

- Vitamin D3 Transactivates The Zinc and Manganese Transporter SLC30A10 Via The Vitamin D Receptor
- Analysis of 1,25-Dihydroxyvitamin D3 Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids

- Misconceptions — Vitamin D insufficiency causes malabsorption of calcium
- Increased intestinal phosphate absorption, an often‐overlooked effect of vitamin D

- Effect of vitamin D supplementation on 24-hour urine calcium in patients with calcium Urolithiasis and vitamin D deficiency

what are your thoughts on taking ox bile or bile salts? what should someone with fat malabsorption focus on? If fat absorbtion is already bad, is it a bad idea to increase dietary fat in hopes it stimulates bile? seems like a strange cycle to get out of

I know little about the condition, can't add anything unique without sidetracking. It would be interesting to have a quantified notion about poison and venom on the regulation of bile synthesis.

 

[Jennifer]

Thank you for the heads-up, @Amazoniac. I finished up my last bottle of the D3 in water last week and went back to using one that’s in oil.

 

[Amazoniac]

- 25-Hydroxyvitamin D3 induces osteogenic differentiation of human mesenchymal stem cells

"Recent studies have demonstrated that 25(OH)D3 at physiological concentrations is as potent as 1α,25-(OH)2D3 at pharmacological concentrations in terms of regulating the behaviour of various types of cells both in vitro and in vivo[9,10,11,12,13,14,15,16,17,18,19,20]."​

 

[Amazoniac]

⬑ [12] 25-Hydroxyvitamin D3 is an agonistic vitamin D receptor ligand

"[..]the in vitro effective concentrations of 25OHD3 are within physiological range or slightly higher, from 100 to 250 nM in primary human prostate stromal cells [9] to 500 nM in human LNCaP prostate cancer cells [40] and 250–400 nM in the present study. The optimal serum concentrations of 25OHD3 and its safety issue are still under discussion [48]. In some human studies, serum 25OHD3 concentrations increased by 643 nM [49] without causing hypercalcemia. More importantly high dietary vitamin D accompanied by serum 25OHD3 concentration of 500 nM did not cause hypercalcemia in wild-type mice [47]."​

​

"In vivo, both 25OHD3 and 1,25(OH)2D3 are most likely acting in concert. When mouse Cyp27b1−/− skin cells co-treated with 25OHD3 and 1,25(OH)2D3 at various concentrations, their effects are synergistic. This not only further supports that 25OHD3 is an agonistic VDR ligand, but also indicates that the total effect of both at physiological concentrations may be enough to mediate cell proliferation and differentiation in vivo. The synergism of 25OHD3 and 1,25(OH)2D3 is rather interesting and requires further studies."​

 

[Amazoniac]

- Intestinal calcium absorption: a vitamin D-hormone-mediated adaptive response
⬑ [42] Transcaltachia (the Rapid Hormonal Stimulation of Intestinal Calcium Transport): A Component of Adaptation to Calcium Needs and Calcium Availability

"One of our early efforts in assessing the physiological importance of transcaltachia in the process of intestinal Ca2+ absorption was to learn what consequences hypercalcemia might have on transcaltachia. We found that perfusion of the duodena with elevated concentrations of Ca2+ (concentrations equivalent to a plasma Ca2+ of 12 mg/100 ml) effectively blocked the response to a physiological and pharmacological concentration of 1Dio,25(OH)2D3 (Yoshimoto et al., 1986). This is an important result in that it provides evidence for the adaptability of the process of transcaltachia in accordance with the ongoing physiological reality. In circumstances of hypercalcemia, it would be disadvantageous for 1kine,25(OH)2D3 to stimulate the further absorption of Ca2+. This result is in accordance with the J. C. Waterlow definition of adaptation, "the good fit of the organism to the environment" (Waterlow, 1985)."​

 

[Amazoniac]

- Vitamin D toxicity redefined: vitamin K and the molecular mechanism

Mito proposed in his popular article that poison A and venom D (through poisonoic acid and killcitriol) control the expression of "vitamin" K-dependent proteins in an antagonistic way.

- Molecular mechanisms mediating vascular calcification: Role of matrix Gla protein

Spoiler

- Legend Max™ Human Uncarboxylated Osteocalcin ELISA Kit | BioLegend

Spoiler

"Osteocalcin is the most abundant non-collagenous protein found in the bone. It is produced by osteoblasts as a 49 amino acid protein, which contains 3 glutamine acid residues (Glu 17, 21, and 24) that are gamma carboxylated in a vitamin K dependent manner. While fully-carboxylated osteocalcin has a high affinity for the extracellular matrix of the bone; decreases in pH, caused by the process of bone resorption, result in decarboxylation of this protein. This generates both partially decarboxylated (undercarboxylated) and fully decarboxylated (uncarboxylated) osteocalcin molecules which are released into the circulation due to decreased affinity for the extracellular matrix.

Fully carboxylated osteocalcin requires high calcium concentrations for proper protein folding; however, under/uncarboxylated osteocalcin has no calcium requirement to maintain its structure within the blood. These under/uncarboxylated forms can bind the receptor GPCR6a and act as hormones promoting insulin sensitivity, glucose tolerance, and testosterone biosynthesis. In patients with diabetes, reduced serum levels of osteocalcin are negatively correlated with obesity and insulin resistance. Furthermore, supporting studies in mice have suggested potential therapeutic applications for osteocalcin in both obesity and insulin resistance."

He suggested that having more of these proteins synthesized without being able to crapoxylate them properly may be worse than respecting the capability.

There can be a lack of "vitamin" K or poor recycling. In case of the latter, I wonder if (reduced) methylene blue could help a 'compromised' "vitamin" K cycle. A higher efficiency for a limited pool would increase tolerance to venom D.

- Interactions of Methylene Blue with Human Disulfide Reductases and Their Orthologues from Plasmodium falciparum
- VKORC1 and the Vitamin K Cycle

Spoiler

The metabolism of the epoxide form is not shown, but I think that it's similar.

 

[Amazoniac]

- Sarcoidosis and calcium homeostasis disturbances—Do we know where we stand?

Spoiler

"The majority of hypercalcemia cases in sarcoidosis are explained by the overproduction of 1,25(OH)2D3 (calcitriol) by activated macrophages. Despite quite convincing evidence supporting this hypothesis, some questions have yet to be completely answered. Moreover, some recent studies suggest that vitamin D supplementation may improve not only calcium homeostasis but also the course of sarcoidosis.[3] Naturally, many authors are at odds with this opinion and do not recommend cholecalciferol supplementation in patients with sarcoidosis. Still, it is unknown what factors predispose to calcium homeostasis disorders and how its occurrence changes the outcome. Those, among many other doubts, encouraged us to create a summary and analysis of the knowledge connected with this subject."

"In the context of sarcoidosis, vitamin D and its turnover are interesting because of its important role in the regulation of the immune system and the process of granulomatous inflammation. It is now known that 1-α-hydroxylase expression is present in many tissues. However, only hydroxylation in kidneys, activated macrophages, and the placenta can influence plasma 1,25(OH)2D3 levels.[4]"

[Killcitriol actions was summarized in Figure 2 (aux).]

"Increased expression of TREM-2 (a receptor playing an important role in cell fusion and granuloma formation) on myeloid cells has been found in pulmonary sarcoidosis and, interestingly, compared to subjects with 25(OH)D3 deficiency (<30 ng/μl), patients with a level between 30 ng/ml and 50 ng/ml had higher total numbers and percentages of TREM2 positive cells in bronchoalveolar lavage fluid.[11] Expression of vitamin D receptors has only been found in the alveolar lymphocytes of subjects with sarcoidosis, and not in healthy controls.[12,13] Data about polymorphisms of vitamin D receptor in sarcoidosis are inconsistent."

"Hypercalcemia occurs in 0.2–4% of the general population. Primary hyperparathyroidism and malignancies are responsible for about 80–90% of all cases.[19] Donovan et al. retrospectively analyzed 101 cases of vitamin D3-mediated hypercalcemia and concluded that sarcoidosis was an underlying cause of almost 50% of them. Calcitriol serum concentration above 300 pmol/l was suggestive of another etiology of hypercalcemia.[20] Moreover, sarcoidosis is the reason behind about 0.5% of cases of hypercalcemia in patients with a history of malignancies.[21] Depending on the studies and population studied, hypercalcemia affects from 7% up to 18% of patients with sarcoidosis.[22–25] In a case–control etiologic study of sarcoidosis (ACCESS), a multicenter prospective study with 736 enrolled patients, incidence of sarcoidosis-associated hypercalcemia was 3.7%.[26] However, such a low prevalence could be the result of ethnic composition—44% of the study group consisted of African-Americans. It is suggested that hypercalcemia is less common among these individuals.[27,28] The biggest up-to-date study found, a single-center retrospective study by Baughman et al. (n = 1606), reports that hypercalcemia appeared in about 6% of sarcoidosis patients.[29] Interestingly, the incidence of hypercalcemia in the Japanese population has been progressively rising between 1974 and 2012.[30] No similar reports regarding the European population have been found."

"A more frequent sign of dysregulated calcium homeostasis in sarcoidosis comes in the form of hypercalciuria which may affect between 20%[40] and even 40%[41] of patients. Also, nephrolithiasis is more common in sarcoidosis than in the general population. This complication will occur in 10–14% of patients in the course of the disease. Asymptomatic stones can be found in 2.7% of subjects at the moment of establishing the diagnosis and in approximately 1% of cases, it can be the first symptom of sarcoidosis.[42]"

"Increased production of 1,25(OH)2D3 is considered to be the main cause of calcium homeostasis disorders in sarcoidosis (Figure 3)."

"Studies in patients with tuberculosis revealed that macrophages activated via toll-like receptor (TLR) 2/1 present increased expression of 1-α-hydroxylase (CYP27B1) and vitamin D receptor.[49] In healthy subjects, pulmonary alveolar macrophages synthesize 1,25(OH)2D3 from 25(OH)D3 after activation by IFN-γ and LPS. Meanwhile, in pulmonary alveolar macrophages harvested from patients with sarcoidosis (including those without hypercalcemia), this process occurs without previous activation. However, exposure to LPS, IFN-γ, IL-2, or leukotriene C4 induces intensification of 1-α-hydroxylation of 25(OH)D3.[50–53] In turn, Lawrence et al. observed hypercalcemia in three out of four patients, who presented the highest concentrations of soluble receptors for IL-2.[54] There has also been a case of sarcoidosis exacerbation with the occurrence of hypercalcemia in the course of treatment with IL-2.[55] Interestingly, despite overexpression of CYP27B1 in pulmonary alveolar macrophages of patients with lung cancer (irrespective of histopathological type), no differences in calcium, 25(OH)D3 or 1,25(OH)2D3 levels have been found (in comparison with the control group).[56]"

"It is known that JAK-STAT, NF-κB, and p38 MAPK pathways play a role in the activation of 1-α-hydroxylase. After inhibiting any of them, CYP27B1 expression decreases.[57] Calcitrol synthesis is tightly regulated in healthy subjects. However, its synthesis in morbid conditions is not so strictly controlled. This has been noted via a couple of different mechanisms. Firstly, 1-α-hydroxylase from macrophages is less susceptible to feedback inhibition by 1,25(OH)2D3 (this resistance is enhanced by IFN-γ). Secondly, 1,25(OH)2D3 deactivation by 24-hydroxylase is inhibited.[50,52] Because of this, there may be two effects on circulating calcitriol: firstly, it may exceed reference values. Secondly, and more frequently, it may stay within normal range but be inadequate to circulating serum calcium level. Arguments for “inadequate normal” 1,25(OH)2D3 concentration as the main cause of sarcoidosis-associated hypercalcemia are presented and commented in Table 1."

"PTHrP expression is stimulated by factors such as LPS, prostaglandin E (PGE), IL-1, transforming growth factor β (TGF-β), and it most likely acts as an anti-inflammatory agent, which would explain its presence in granuloma cells.[70]"

"It is important to remember that sarcoidosis does not exclude other causes of hypercalcemia, beginning with the most common cause: hyperparathyroidism. Such conditions should be excluded during the diagnostic process to enable the introduction of optimal treatment."

"The influence of sarcoidosis on the skeletal system is mediated by two main etiologies, both of which are risk factors for osteoporosis. Firstly, it is mediated by calcium homeostasis disorders, including frequent 25(OH)D deficiency. Secondly, by treatment with corticosteroids."

"The effectiveness of Vitamin D3 and calcium supplementation in improving BMD in patients with sarcoidosis remains unconfirmed.[75,79] Surprisingly, Saidenberg-Kermanac’h et al., in a cross-sectional study of 142 patients, showed that vitamin D supplementation paradoxically caused BMD reduction and a higher occurrence of bone fractures.[78]"

"[..]there is currently a discussion about supplementation with vitamin D and calcium and its potential in bringing about hypercalcemia and hypercalciuria.[36,62,83,84]"

"In a randomized trial over 1 year that studied a group of 27 subjects with sarcoidosis taking cholecalciferol supplementation of 50,000 IU/month, there were relevant differences observed in the mean concentration of 25(OH)D3 ranging from suboptimal average <50 nmol/l to average >75 nmol/l. The authors also observed a small, but statistically significant difference in concentrations of 1,25(OH)2D3. One patient from the study group developed hypercalcemia.[79] Similarly, in a prospective study, in which a group of 16 African-Americans with average 25(OH)D3 concentration <75 nmol/l were given 50,000 IU/month for 12 weeks, a comparable rise in 25(OH)D3 occurred with no changes in mean concentrations of Ca and Ca2+. Also, no calciuria had been observed. Surprisingly, in the majority of the subjects, 1,25(OH)2D3 concentration decreased by half.[86] When supplementation was limited to Ca, increased excretion of calcium in urine was observed, without any effect on calcium and vitamin D metabolites serum concentration.[62]"

"The management of hypercalcemia depends mostly on the level of calcium. Patients with moderate elevations in serum calcium (12.0–14.0 mg/dl) may develop symptoms when levels rise rapidly. This group of symptomatic patients requires immediate intervention. Intensive treatment is usually necessary when serum calcium concentration exceeds 14 mg/dl. Intravenous rehydration and loop diuretics are the treatment of choice."

"Our clinical observations suggest that in cases of progressive kidney failure, when dual etiology (hypercalcemic and sarcoidosis of kidneys) could not be excluded, IV methylprednisolone was effective. Other drugs successfully (but rarely) used in the treatment of calcium homeostasis disorders are (hydroxy) chloroquine and ketoconazole.[93–96] Both drugs suppress 1-α-hydroxylase and chloroquine additionally stimulates calcitriol deactivation by 24-hydroxylase.[50,93]"

"In the case of hypercalciuria, thiazide diuretics are contraindicated due to their potential to induce hypercalcemia. Some authors suggest a low-calcium diet, but studies seem to question this recommendation. Hypercalciuria persisted in 30% of patients despite calcium restriction in their diet. Further, the use of pharmacotherapy to limit calcium absorption did not improve calcium concentration control.[102,103] In a 4-year observational study, a lower incidence of nephrolithiasis was observed in patients with higher dietary calcium intake, which may be related to inhibition of oxalates absorption. While renal calculi in patients with sarcoidosis consist mainly of calcium oxalates, calcium restriction in the diet may produce unexpectedly harmful results.[104–106]"

"The complex action of vitamin D on the immune system coupled with the pathophysiology of granulomatous inflammation seen in sarcoidosis could possibly provide new therapeutic targets in the future."

⬑ [3] Calcium and Vitamin D in Sarcoidosis: Is Supplementation Safe?

Spoiler

"In our study, sarcoidosis patients without CAD supplementation were at higher risk for developing hypercalcemia, without having a significant difference of serum level of 25‐(OH)D between the CAD and non‐CAD–treated group (Fig. 3). As mentioned [..], vitamin D deficiency could possibly increase the disease activity of sarcoidosis. Thus, the results of our study suggest that vitamin D–deficient sarcoidosis patients should be supplemented with CAD to potentially lower disease activity."

"Patients in our study used mostly 400 IU daily of vitamin D. Thus, vitamin D intoxication is not expected if normal doses of CAD supplementation are used."

- Vitamin D Supplementation in Patients Treated for Sarcoidosis: Controversy or Consensus?

Spoiler

"Vitamin D supplementation in patients treated for sarcoidosis is a controversial issue in the medical community. Most physicians involved in the management of sarcoidosis argue against vitamin D supplementation based on early evidence of a link between vitamin D intake and hypercalcemia. Experts have developed recommendations supporting this view (1). Rheumatologists play only a secondary role in managing the organ damage caused by sarcoidosis. However, they are called on to manage other complications, most notably bone loss related to the need in some patients for long-term high-dose glucocorticoid therapy, and may therefore be more favorable to vitamin D supplementation. These two apparently conflicting positions may find common ground in recently published data."

"Early studies emphasized the risk of hypercalcemia in patients with sarcoidosis. Depending on the study population, 2% to 63% of patients with sarcoidosis had hypercalcemia. The true prevalence is probably closer to 10%-15%. Hypercalciuria is more common but seems directly related to the serum level of 1,25(OH)2D (calcitriol), which is the active form of vitamin D. The rise in serum 1,25(OH)2D in response to calcium or vitamin D supplementation is greater in patients with sarcoidosis compared to healthy controls. In addition, 1,25(OH)2D decreases in response to high-dose calcium in normal individuals (via regulatory mechanisms) but not in patients with sarcoidosis. Serum 1,25(OH)2D levels are often elevated in patients with sarcoidosis and hypercalcemia (2). Moreover, hypercalcemia has been reported after vitamin D supplementation (3) or sunlight exposure (4). Studies have established that macrophage activation by activated T cells leads to the production of interferon gamma (IF-y) and interleukin-2 (IL-2). The result is extrarenal 1-alpha hydroxylation within the sarcoid granulomas with elevation of 1,25(OH)2D levels responsible for hypercalcemia (5). Whether this mechanism is deleterious or protective remains unclear. The enzyme 1-alpha hydroxylase, which is required for the hydroxylation of 25(OH)D, is now generally recognized to be present within immune system cells (macrophages and dendritic cells), which also carry the vitamin D receptor, a feature shared by T cells. In vitro, 1,25(OH)2D tends to exert beneficial effects, with decreased production of Th1 pro-inflammatory cytokines by T cells (6), decreased production of IF-y and IL-2 by macrophages, and diminished antigen presentation by dendritic cells to lymphocytes. Nevertheless, the mechanism that regulate serum calcium levels seem impaired in patients with sarcoidosis."

- Calcirol - Liquid Vitamin D3

- Precipitation of hypercalcaemia in sarcoidosis by foreign sun holidays: report of four cases​

"[..]there is some evidence of an increased fracture risk in patients with sarcoidosis. The most likely cause is exposure to glucocorticoids."

"Vitamin D supplementation is among the measures recommended to prevent glucocorticoid-induced osteoporosis."

"1,25(OH)2D elevation is classically associated with greater disease activity (11,12) and, more specifically with a requirement for chronic treatment. Nevertheless, in several studies higher 25(OH)D levels were associated with lower disease activity (9, 13[↑]). In a recent study, serum ACE levels declined after vitamin D supplementation (14)."

"These recent data may provide grounds for a consensus. The fracture risk is probably higher in patients taking glucocorticoid therapy, and low serum 25(OH)D levels seem associated with fractures. It would therefore seem reasonable to consider supplementation for the prevention of glucocorticoid-induced osteoporosis. The most recent data suggest that vitamin D supplementation may be appropriate in patients with inactive sarcoidosis and low serum 25(OH)D levels. The ideal serum value in these patients is unknown but may be lower than in the general population, between 15 and 20 ng/mL. Furthermore, prudent supplementation regimens should be used given the increased sensitivity of patients with sarcoidosis. Concomitantly increasing the intake of calcium seems desirable, although dietary sources should be given preference. During induction therapy with high-dose glucocorticoids (0.5 to 1 mg/kg/d), the risk of hypercalcemia seems extremely low in treatment responders. However, a high level of vigilance is appropriate during dosage tapering, given the risk of rebound disease activity and exaggerated responsiveness to vitamin D."

"In patients with osteoporotic fractures and no glucocorticoid therapy, a similar strategy may be suitable. Thus, calcium and vitamin D supplements may be appropriate if the disease is controlled. Great caution is nevertheless in order, even in patients believed to be in remission. After supplementation is started, serum calcium levels should be monitored routinely and urinary calcium excretion if appropriate. Low serum 25(OH)D can indicate active sarcoidosis, and a 1,25(OH)2D assay may therefore be indicated in this situation."

"Selecting patients for supplementation based on effective sarcoidosis control, normal kidney function, and absence of prior hypercalcemia may minimize the risk of hypercalcemia, together with the use of appropriate supplementation regimens. Glucocorticoid therapy, when needed to treat the sarcoidosis, decreases the risk of hypercalcemia. Nevertheless, the best means of preventing glucocorticoid-induced osteoporosis is glucocorticoid sparing via the use of immunosuppressants whenever possible. Furthermore, the mechanisms of action of bisphosphonates suggest that adding such an agent (when useful) may confer additional protection. Under these specific conditions, calcium and vitamin D supplementation may have a favorable risk/benefit ratio."

- Goldilocks, vitamin D and sarcoidosis

Spoiler

"In tuberculosis, vitamin D supplementation has been recommended in patients because vitamin D is crucial in the granulomatous reaction against the organism. However, what may be good for tuberculosis eradication may not be good for sarcoidosis. It has been noted that excessive amounts of vitamin D are associated with a worse clinical outcome in sarcoidosis [2]. In granulomas, there may be increased activity of 1-alpha hydroxylase. As part of the Th-1 immune response, calcitriol has a paracrine effect within the granuloma. In some cases, this leads to excessive calcitriol, resulting in hypercalcuria or hypercalcemia [3]. At least 10% of sarcoidosis patients have hypercalcemia, half of whom can develop associated renal dysfunction [3, 4]. In some cases, hypercalcemic renal failure can be reversed by simply withdrawing vitamin D supplementation [3]. There are case reports of excessive vitamin D replacement leading to hypercalcemia in patients with mycobacterial infections [5]."

- Protection of Bone Density in Sarcoidosis: Can we Give Vitamin D without Causing Hypercalcemia?

Spoiler

"Saidenberg-Kermanac’h et al. (9) performed a cross sectional analysis on 142 patients to evaluate risk factors for low bone mineral density and fractures in sarcoidosis and to determine a potential link between bone fragility and calcium and vitamin D metabolism. Low dietary calcium, high current corticosteroid dose, and low creatinine clearance were associated with increased fracture risk. Similar to Kamphius et al[↑], they found an inverse relationship between vitamin D levels and sarcoid disease activity. They also noted that serum 25-hydroxyvitamin D levels between 10 and 20 ng/ml were associated with higher BMD, whereas values greater than 20 ng/ml were associated with an increased risk of fragility fracture, perhaps due to associated increase in 1,25-dihydroxyvitamin D levels; the authors note that while physiologic levels of 1,25-dihydroxyvitamin D inhibit PTH dependent bone resorption, higher levels are known to induce bone resorption."

"We assert that the targets of vitamin D supplementation should be less robust than in the general population, perhaps aiming for levels approaching 20 ng/ml (9), and we may want to get there slowly using low daily doses like 400 IU rather than high dose supplementation (5[⇈]). Clearly further studies will be needed to confirm this."

- Vitamin D: what clinicians need to know

Spoiler

"In patients with PHPT, it is advisable to treat vitamin D insufficiency cautiously to avoid hypercalcemia (133,134), especially in patients with markedly elevated serum calcium levels because vitamin D therapy may worsen hypercalcemia. In patients with PHPT, the goal is to maintain serum vitamin D levels around 25 ng/mL (62 nmol/L) (6). Replacement therapy is discontinued or the dose is lowered once the serum vitamin D level reaches the target level. To prevent exacerbation of hypercalcemia and hyper-calciuria, monitoring of serum and urine calcium levels in PHPT patients receiving vitamin D therapy is suggested (132,135-138). In most patients with PHPT, although serum PTH may decrease a bit, there are no significant increases in serum calcium levels after normalization of serum vitamin D."

"It is relatively common to find high serum PTH levels with normal or low-normal serum calcium levels in patients with osteoporosis (132,135-140). In this setting, measurement and appropriate replacement of vitamin D (132) facilitate making the right diagnosis: (A) Secondary hyperparathyroidism: PTH values will return to the normal range with replenishment of vitamin D, whereas calcium levels remain within the normal limits (141); (B) Concomitant PHPT and vitamin D deficiency: PHPT-associated hypercalcemia may be masked by co-existing vitamin D deficiency. Thus, vitamin D supplementation may uncover biochemical hypercalcemia with persistent elevation of serum PTH levels (126); or (C) Normocalcemic hyperparathyroidism, characterized by high serum PTH but normal plasma calcium in the presence of normal serum vitamin D levels (135, 141)."

⬑ [134] Preventing vitamin D toxicity in patients with sarcoidosis

Spoiler

"Due to the possible development of hypercalcemia, vitamin D supplementation should be given with caution, ideally, after the determination of 1,25(OH)2D3 levels. Table I lists recommendations on replacement of vitamin D in dark-skinned patients with sarcoidosis. Bisphosphonate therapy should be the primary prevention strategy of glucocorticoid-induced osteoporosis in these patients, supplemented with 200 to 400 IU per day of vitamin D3 and calcium (1200-1500 mg/d). Consultation with the endocrine service may be appropriate."