Vitamin D: Dysequilibrium in MS

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Vitamin D: Dysequilibrium in MS

Postby frodo » Sun Jun 03, 2018 10:39 am

Dysequilibrium of the PTH-FGF23-vitamin D axis in relapsing remitting multiple sclerosis; a longitudinal study

https://link.springer.com/article/10.11 ... 018-0028-3

Background

Parathyroid glands of people with relapsing remitting multiple sclerosis (RRMS) fail to respond to low serum 25-hydroxyvitamin D (25OHD) and low serum calcium, which are stimuli for parathyroid hormone (PTH) secretion. This led us to hypothesise: that there is suppression of PTH in RRMS due to higher than normal serum concentrations of fibroblast growth factor 23 (FGF23). We therefore sought evidence for dysregulation of the PTH-FGF23-vitamin D axis in RRMS.

Methods

Longitudinal study (winter to summer) with fasting venepunctures. For RRMS subjects who recruited a healthy control (HC) friend, pairs analyses were performed. For each pair, the within-pair difference of the variable of interest was calculated (RRMS minus HC). Then, the median of the differences from all pairs was compared against a median of zero (Wilcoxon) and the 95% confidence interval of that median difference (CI) was calculated (Sign Test).

Results

RRMS had lower winter PTH than HC, P = 0.005, (CI -2.4 to 0.5 pmol/L, n = 28 pairs), and lower summer PTH, P = 0.04, (CI -1.8 to 0.5, n = 21 pairs). Lower PTH associates physiologically with lower intact FGF23 (iFGF23), yet RRMS had higher iFGF23 than HC in winter, P = 0.04, (CI -3 to 15 pg/mL, n = 28 pairs) and iFGF23 levels comparable to HC in summer, P = 0.14, (CI -5 to 13, n = 21 pairs). As PTH stimulates and FGF23 reduces, renal 1-alpha hydroxylase enzyme activity, which synthesises serum 1,25-dihyroxyvitamin D (1,25(OH)2D) from serum 25OHD, we examined the ratio of serum 1,25(OH)2D to serum 25OHD. In winter, this ratio was lower in RRMS versus HC, P = 0.013, (CI -1.2 to - 0.3, n = 28 pairs).

Conclusions

This study revealed a dysequilibrium of the PTH-FGF23-vitamin D axis in RRMS, with lower plasma PTH, higher plasma iFGF23 and a lower serum 1,25(OH)2D to 25OHD ratio in RRMS compared with HC subjects. This dysequilibrium is consistent with the study hypothesis that in RRMS there is suppression of the parathyroid glands by inappropriately high plasma concentrations of iFGF23. Studying the basis of this dysequilibrium may provide insight into the pathogenesis of RRMS.
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Re: Vitamin D: Dysequilibrium in MS

Postby jimmylegs » Sun Jun 03, 2018 12:22 pm

cofactors. magnesium (low normal in typical ms patients) could be expected to lower iFGF23 and increase serum 1,25 dihydroxycholecalciferol.

A comparison of calcium acetate/magnesium carbonate and sevelamer-hydrochloride effects on fibroblast growth factor-23 and bone markers: post hoc evaluation from a controlled, randomized study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769980/

"The study showed that serum levels of FGF-23 were significantly reduced with CaMg"

Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency.
https://www.ncbi.nlm.nih.gov/pubmed/3840173

"Magnesium therapy raised mean basal serum magnesium [1.0 +/- 0.1 (mean +/- SEM) mg/dl] and calcium levels (7.2 +/- 0.2 mg/dl) into the normal range (2.2 +/- 0.1 and 9.3 +/- 0.1 mg/dl, respectively; P less than 0.001). ... After magnesium therapy, only 5 of the patients had a rise in the serum 1,25-(OH)2D concentration into or above the normal range ... These data show that serum 1,25-(OH)2D concentrations are frequently low in patients with magnesium deficiency and may remain low even after 5-13 days of parenteral magnesium administration. ... We conclude that magnesium depletion may impair vitamin D metabolism."

would have been nice if they bothered to give any detail on the form of magnesium used. also, i'd have loved to see what happened to vit D metabolites if they'd pushed serum magnesium into the 2.3-2.7 mg/dl range.

anyhoo. insight achievement unlocked ;)
odd sx? no dx? check w/ dietitian
DRI=MINIMUM eg bit.ly/1vgQclQ
99% don't meet these. meds/lifestyle can affect levels
status can be low in ms & other cond'ns
'but my results are normal'. typical panels don't test all
deficits occur in 'normal' range
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Re: Vitamin D: Dysequilibrium in MS

Postby frodo » Mon Jun 04, 2018 12:20 am

jimmylegs wrote:would have been nice if they bothered to give any detail on the form of magnesium used. also, i'd have loved to see what happened to vit D metabolites if they'd pushed serum magnesium into the 2.3-2.7 mg/dl range.

anyhoo. insight achievement unlocked ;)


Tnanks.
There is still a lot to be learned
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