High dose vitamin D exacerbates CNS autoimmunity

A forum to discuss the Coimbra Protocol which uses high-dose vitamin D3 to treat multiple sclerosis.
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Petr75
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High dose vitamin D exacerbates CNS autoimmunity

Post by Petr75 » Sat Sep 21, 2019 11:15 am

2019 Sep 1
Institute of Neuropathology, University Medical Center, Göttingen, Germany
High dose vitamin D exacerbates central nervous system autoimmunity by raising T-cell excitatory calcium.
https://www.ncbi.nlm.nih.gov/pubmed/31302671

Abstract

Poor vitamin D status is associated with a higher relapse rate and earlier disability in multiple sclerosis. Based on these associations, patients with multiple sclerosis are frequently supplemented with the vitamin D precursor cholecalciferol, although it is unclear whether this regimen is of therapeutic benefit. To model consequences of this common practice, mice were fed for more than 3 months with a low, medium or high dose of cholecalciferol, representative of vitamin D deficiency, modest and disproportionally high supplementation, respectively, in patients with multiple sclerosis. Compared to vitamin D-deprived mice, its moderate supplementation reduced the severity of subsequent experimental autoimmune encephalomyelitis, which was associated with an expansion of regulatory T cells. Direct exposure of murine or human T cells to vitamin D metabolites inhibited their activation. In contrast, mice with 25-(OH) vitamin D levels above 200 nmol/l developed fulminant experimental autoimmune encephalomyelitis with massive CNS infiltration of activated myeloid cells, Th1 and Th17 cells. When dissecting this unexpected outcome, we observed that high, but not medium dose vitamin D had caused mild hypercalcaemia, which rendered T cells more prone to pro-inflammatory activation. Exposing murine or human T cells to equivalent calcium concentrations in vitro enhanced its influx, triggering activation, upregulation of pro-inflammatory gene products and enhanced transmigration across a blood-brain barrier model. These findings suggest that vitamin D at moderate levels may exert a direct regulatory effect, while continuous high dose vitamin D treatment could trigger multiple sclerosis disease activity by raising mean levels of T-cell excitatory calcium.

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Re: High dose vitamin D exacerbates CNS autoimmunity

Post by clarentine » Tue Oct 01, 2019 12:42 pm

I'm not following the Coimbra protocol, but this study should be taken with a grain of salt.

Rodants are very sensitive to vitamin D, which is why it's used as a ratpoison. In the experiment they fed mice about 2mg/kg of vitamin D, which is between 1/20th and 1/10th the known lethal dose (40mg/kg) for the animals for 2 months, daily.

The lethal dose for humans isn't really known, but with dogs it's observed to be a single 88mg/kg. For an adult human weighing 75kg this amount would be 6,600mg or 264,000,000 IU.

Assuming humans are as sensitive as dogs to vitamin D, this would be an equivalent of 13,200,000 (1/20th) to 26,400,000 IU (1/10th) of vitamin D daily for 2 months.

Most Coimbra doses, as far as I know, are up to 200,000 IU daily and many are much lower. The highest I read was 350,000 IU daily. That's typically far lower than what was used in the study.

And even if humans are as sensitive to vitamin D as nocturnal animals (which seems unlikely), the Coimbra doses are still nowhere near as high as used in the study (in relative terms).

I'm not sure if Comibra is the right way to got, but I'm pretty sure, that this study isn't reliable in terms of possible high dosage therapies in humans. The people responsible in putting it together mainly showed what happens if you poison mice slowly.

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NHE
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Re: High dose vitamin D exacerbates CNS autoimmunity

Post by NHE » Tue Oct 01, 2019 10:07 pm

I thought that it was about blood concentration and not dosage.
In contrast, mice with 25-(OH) vitamin D levels above 200 nmol/l developed fulminant experimental autoimmune encephalomyelitis with massive CNS infiltration of activated myeloid cells, Th1 and Th17 cells.

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Re: High dose vitamin D exacerbates CNS autoimmunity

Post by clarentine » Sat Oct 05, 2019 10:11 am

Yes, they are talking about blood levels. But comparing the effects is really not conclusive, because rodans are likely to be more sensitive to vitamin D than humans.

Blood levels of 200 nmol/l aren't really that high and are still well within the healthy range for humans. If there were neurological pathologies happening in that range, we would have seen the effects a long time ago - and certainly in Coimbra patients.

Barts MS blog also had a look at the raw data here: https://multiple-sclerosis-research.org ... d-in-mice/
The effects mentioned in the abstract don't even seem to be significant.

I'd be careful with high dose vitamin D too - in fact I haven't tried it because I'm not convinced it's safe. But I doubt the results of this study can be applied to humans because of the dosage reasons I mentioned.

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