all things vitamin D

[Petr75]

2018 Aug 31
Department of Neurology, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Low vitamin D-25(OH) level in Indonesian multiple sclerosis and neuromyelitis optic patients
https://www.ncbi.nlm.nih.gov/pubmed/30195201

Abstract
BACKGROUND:
Vitamin D deficiency is commonly found in multiple sclerosis (MS) and Neuromyelitis Optic (NMO) patients and can impair the immunological status. As a tropical country, Indonesia has a lot of sunshine throughout the year as a source of vitamin D. The aim of this study was to evaluate and compare the serum vitamin D-25(OH) level in Indonesian MS and NMO patients to healthy individuals.
METHODS:
A cross-sectional study was conducted in Dr. Cipto Mangunkusumo General Hospital Jakarta from November 2016 to May 2017. Forty-eight patients (29 MS and 19 NMO) and 33 healthy controls were enrolled. We assessed the dietary recall, vitamin D supplementation, sunshine exposure, medication, annual relapse rate, and Expanded Disability Status Scale (EDSS). Vitamin D level was measured using direct competitive chemiluminescence immunoassay.
RESULTS:
Vitamin D deficiency was found in 48.4% of MS and 56.2% of NMO patients. The serum vitamin D level in MS and NMO groups was not significantly different from the healthy controls. Vitamin D level was not associated with EDSS and the annual relapse rate. Positive significant correlation was observed between sunshine exposure and vitamin D level in healthy control, but not evident in MS and NMO groups. MS and NMO subjects who still treated with corticosteroid had lower vitamin D level.
CONCLUSION:
Vitamin D deficiency is commonly found in Indonesian MS and NMO patients, but not associated with EDSS and annual relapse rate. Despite living in a country with adequate sunshine exposure, the physician should anticipate low serum vitamin D level, especially in MS or NMO patients who received corticosteroid.

[jimmylegs]

interesting - can't get into full text yet to see what is meant by low. still wish there were more studies analysing cofactor interactions.
i'm glad there are at least a handful out there, eg
http://www.thisisms.com/forum/chronic-c ... ml#p224503

[jimmylegs]

Can adverse effects of excessive vitamin D supplementation occur without developing hypervitaminosis D? (2018)
https://www.sciencedirect.com/science/a ... 6017301711

Highlights
•Hypovitaminosis D status usually reflects reduced sunlight exposure.
•Vitamin D status is more likely to be a consequence rather than a cause of a disease.
•Extreme vitamin D supplementation may impair organ function even in hypovitaminosis D.
•Serum 25(OH)D levels may not be true reflection of total vitamin D status of the body.
•Supplementation may be useful who are at high-risk of developing vitamin D deficiency.

Abstract
Vitamin D is a fat-soluble hormone that has endocrine, paracrine and autocrine functions. Consumption of vitamin D-supplemented food & drugs have increased significantly in the last couple of decades due to campaign and awareness programs. Despite such wide use of artificial vitamin D supplements, serum level of 25 hydroxyvitamin D does not always reflect the amount of uptake. In contrast to the safe sunlight exposure, prolonged and disproportionate consumption of vitamin D supplements may lead to vitamin D intoxication, even without developing hypervitaminosis D. One of the reasons why vitamin D supplementation is believed to be safe is, it rarely raises serum vitamin D levels to the toxic range even after repeated intravenous ingestion of extremely high doses of synthetic vitamin D analogs. However, prolonged consumption of vitamin D supplementation may induce hypercalcemia, hypercalciuria and hyperphosphatemia, which are considered to be the initial signs of vitamin D intoxication. It is likely that calcium and phosphorus dysregulation, induced by exogenous vitamin D supplementation, may lead to tissue and organ damages, even without developing hypervitaminosis D. It is needed to be emphasized that, because of tight homeostatic control of calcium and phosphorus, when hypercalcemia and/or hyperphosphatemia is apparent following vitamin D supplementation, the process of tissue and/or organ damage might already have been started.

[jimmylegs]

Vitamin D Toxicity in Young Breastfed Infants: Report of 2 Cases
fft: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607921/

Vitamin D toxicity in infants is not uncommon, and has been reported as early as the 1930s, usually due to antirachitic treatment with very high doses of vitamin D. This usually involves administration of 600 000 IU vitamin D2 oral or intramuscularly (termed “stoss therapy”) resulting in vitamin D toxicity symptoms related to hypercalcemia.1-4 Most of these case reports occurred outside the United States.

Recently, there are reports of vitamin D toxicity in very young breastfed infants, mostly in the United States, from inadvertent overdose with highly concentrated vitamin D formulation obtained over-the-counter or from free-standing stores (Table 1).

There were also reports of toddlers that had vitamin D toxicity from over-the-counter (OTC) vitamin D overdose within the United States. They presented with symptoms of irritability, vomiting, constipation, and hypertension.9,10 The patients’ hypercalcemia resolved with standard treatments. One patient, a 16-month-old, had refractory hypercalcemia that was treated with pamidronate.10

Case Report
The 2 infants in this report have an identical presentation. One is a 3.5-month-old Caucasian female and the other a 2.5-month-old Caucasian male. They came to the emergency department, on separate occasions, for decreased feeding, lethargy, and inconsolable crying. Physical examination showed evidence of moderate dehydration. They are exclusively breastfed and have been receiving OTC vitamin D supplementation. Further questioning of the parents and later examination of the vitamin D bottles revealed that the infants received vitamin D supplementation way above the recommended dose, resulting in hypervitaminosis D and hypercalcemia (Table 2).

...

Conclusions
The worst reported cases of vitamin D toxicity in breastfed infants were described here. With the promotion of breastfeeding and vitamin D supplementation, more and more cases of vitamin D toxicity are being reported; therefore, efforts at its prevention need to be enhanced. Providing written instructions on vitamin D supplementation, including start schedule, brand name, concentration, and dose is recommended. Recommending only brands with vitamin D concentration of 400 IU/mL (such as D-visol, Tri-visol, or Poly-visol), and warning against highly concentrated vitamin D preparations from free-standing stores may help avoid dosing mistakes. Medication reconciliation with particular attention to vitamin D concentration and dose at the 2- and 4-month visit with the pediatrician may help identify early vitamin D toxicity. 25(OH)D may be obtained if there is suspicion for hypervitaminosis D but is not recommended for routine screening.

[Petr75]

2018 Sep 24
Department of Paediatrics, American Mission Hospital, Manama, Manama, Bahrain
Vitamin D for the management of multiple sclerosis
https://www.ncbi.nlm.nih.gov/pubmed/30246874

Abstract
BACKGROUND:
This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12). Multiple sclerosis (MS) is characterised by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system (CNS), which can result in varying levels of disability. Some studies have provided evidence showing an association of MS with low levels of vitamin D and benefit derived from its supplementation...

AUTHORS' CONCLUSIONS:
To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D₃ at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review

[jimmylegs]

definitely off the top of my head, vitamin d is among the essential nutrients for which i have felt no benefit at all via supplementation, even megadose supplementation, in spite of major improvements to levels per the lab.

as for the sun, i absolutely have seen the complete disappearance of inflammatory (but non-ms) issues, with pretty much all day every day exposure to natural uv.

also a topical synthetic version of the post-kidney d3 metabolite, 1,25 dihydroxyvitamin d3, makes a noticeable difference to those same inflammatory but non ms issues.

flip side, d3 is one of two supplements which actually made me worse. ironically, magnesium is the other one. took a while to find the balance with those two :S

all that said, when i got *really* sick earlier this year and finally got my vit d3 house in order, level was at 50 nmol/l *after* a month of i think it was 4000 IU per day. did i work to correct? absolutely. last test 91. did i feel a difference? no. will i keep working on it? absolutely.

i note with interest the low quality of evidence re risk of minor or serious adverse effects with prolonged d3 supplementation. i will have to familiarize with this GRADE system https://bestpractice.bmj.com/info/us/to ... -is-grade/

'Vitamin D₃ did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I² = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I² = 20%; eight trials; 701 participants; low-quality evidence according to GRADE)."

[ElliotB]

"low-quality evidence suggests..."

Why make conclusions based on "low-quality" evidence? A waste of time and money.


While there is no conclusive evidence as to the effectiveness of Vitamin D' treatment of with MS and other diseases, there is ample evidence to suggest that it likely is, but until 'quality' studies are completed, there is just no way to know for sure. Since Vitamin D is inexpensive, easy to take, easy to monitor the results, and not necessarily dangerous or require doctor supervision unless you get into higher and mega doses, with reasonable care based on what we do know at this time, simple blood work, and minor diet considerations it may make sense for many to take it, especially when there are no other alternatives or when conventional medicine is not working.. After all, what do you have to loose!

As with all the supplements I take, I have no idea if I am benefiting from taking higher than 'normal' doses of vitamin D. I guess because there isn't a huge amount of money in the Vitamin D treatments, this treatment option will likely never be properly investigated. AND until someone come up with a 'super' vitamin D formulation that cost $2000-$4000 a month that insurance companies will be will to pay for, we may never know!

I guess I will keep taking it for now and hope!!!

[jimmylegs]

whoosh

[jimmylegs]

Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports (2018)
fft: https://www.mdpi.com/2072-6643/10/8/953/pdf

Abstract: Over the past two decades, vitamin D level measurements have become some of the most frequently ordered tests in the laboratory. This increase is due to a growing awareness of widespread vitamin D deficiency and scientific data suggesting the beneficial effects of vitamin D in various diseases. A literature search was carried out in PubMed for cases reporting vitamin D intoxication and overdose. Thirteen articles were included in this review. Intoxication was severe in the reported cases. Patients presented with serum vitamin D concentrations ranging between 150 and 1220 ng/mL and serum calcium concentrations between 11.1 and 23.1 mg/dL. Most of the reported patients showed symptoms of vitamin D toxicity such as vomiting, dehydration, pain, and loss of appetite. The underlying causes included manufacturing errors, overdosing by patients or prescribers, and combinations of these factors. Our literature search highlights the fact that even though vitamin D intoxication is rare, it does occur and therefore patients and prescribers should be more cognizant of the potential dangers of vitamin D overdose.

[ElliotB]

Anyone taking higher than normal doses of Vitamin D should be doing blood work every few months to monitor their D level and to avoid overdosing in order to reduce/eliminate vitamin D toxicity.

The best option if you are using moderate, high or extremely high doses is obviously to use a doctor who is trained in high dose Vitamin D therapy, but for lower doses that are above 'typical' your D level can easily be monitored without using a specialist. Regular monitoring will help you avoid vitamin D toxicity.

[jimmylegs]

including excretion, so users know exactly how much any megadose intake is disappearing down the toilet anyway.

[jimmylegs]

A Randomised, Double-Blind, Placebo-Controlled Trial with Vitamin D3 in MS: Subgroup Analysis of Patients with Baseline Disease Activity Despite Interferon Treatment (2012)
https://www.hindawi.com/journals/msi/2012/802796/abs/

We present a subgroup analysis of the first double-blind, placebo-controlled, randomised trial with vitamin D3 in MS. In the overall study population, there were 34 patients in the vitamin D arm and 32 patients in the placebo arm. All the patients were using interferon-β-1b (IFNB) therapy. The subgroup consisted of 15 patients in the vitamin D arm and 15 patients in the placebo arm, who had either at least one relapse during the year preceding the study or enhancing T1 lesions at the baseline MRI scan. We measured the total number of MRI T1 enhancing lesions, the number of new/enlarging T2 lesions and T2 lesion volume (BOD) (mm3), EDSS (Expanded Disability Status Scale), annual relapse Rate (ARR), timed 25-foot walk (T25FW), and timed 10-foot tandem walk (TT10W) at baseline and at 12 months in the vitamin D-treated and in the placebo-treated patients. There was a statistically significant reduction in the number of T1 enhancing lesions, a smaller T2 lesion volume growth and less new/enlarging T2 brain MRI lesions in the vitamin D3-treated than in the placebo-treated subgroup patients. The MRI results were slightly more pronounced in the subgroup than in the overall study population.
...
Exclusion criteria were serum calcium >2,6 mmol/L; serum 25(OH)D >85 nmol/L;
...
2.3. Study Product. 20 mg of cholecalciferol (Dekristol) corresponding to 20000 IU (500 μg) of vitamin D3 , administered as a capsule once a week, or identically appearing placebo capsules (Swiss-Caps, Switzerland) were used. A private company (Joutsen apteekki, Turku, Finland) organized the importing, packaging, and labelling procedure of the study product. Patients were given a bottle of 26 capsules of study medication and were instructed by the investigator in the weekly administration of the study medication. At month 6, a new bottle of 26 capsules of study medication was given to patients. Adherence was evaluated by capsule counting.
...
BMI (median, range) 23.8 (19.7–31.2)
...
Serum 25(OH)D levels rose from a mean of 55 nmol/L (range 35–82) to 115 nmol/L (range 78–163) in the vitamin D-treated patients after 12 months of treatment and remained unchanged in the placebo group (mean of 50 nmol/L [range 24–81] at baseline and 48 nmol/L [range 30–68] at 12 months).

interesting, that. would be interesting if the dose response had been broken down by body size. from other recent reading i would expect the higher bmi patients to have the lower dose response

and as always, i wish people would look at serum magnesium not just serum calcium

[Zyklon]

But heyyy wait, some docs say: "No evidence exists..."

[jimmylegs]

yeah i still haven't checked out this GRADE rubric to see how the above would stack up.
i am also curious what would have happened if they'd not excluded patients w levels 85 or higher, but just treated them as another subgroup for analysis. especially since as it was, the very highest serum level obtained in the treatment arm was 163 nmol/l.

[jimmylegs]

Life-threatening vitamin D intoxication due to intake of ultra-high doses in multiple sclerosis: A note of caution (2018)

"Knowledge about complications of chronic ultra-high dose vitamin D supplementation is limited. We report a patient with primary progressive multiple sclerosis (MS) who presented with generalized weakness caused by hypercalcemia after uncontrolled intake of more than 50,000 IU of cholecalciferol per day over several months. Various treatment strategies were required to achieve normocalcemia. However, renal function improved only partly and further progression of MS was observed. We conclude that patients need to be informed about the risks of uncontrolled vitamin D intake and neurologists need to be alert of biochemical alterations and symptoms of vitamin D toxicity."

be safe, folks.