all things vitamin D

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NHE
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Re: all things vitamin D

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jimmylegs wrote: Tue Mar 17, 2020 1:44 pm new(ish) review, in which i note the following extensively-discussed interaction:

Important drug-micronutrient interactions: A selection for clinical practice (2020)
https://www.ncbi.nlm.nih.gov/pubmed/30580552

"Magnesium supplementation substantially reversed the resistance to vitamin D treatment (de Baaij, Hoenderop, and Bindels 2015; Gröber, Reichrath, and Holick 2015)."
I may have missed something, but that first reference only mentions vitamin D once and not in the context of vitamin D resistance.

Here's a link to the full text. It looks like a good review on magnesium by the way. It just doesn't appear to have much to say about vitamin D.

https://journals.physiology.org/doi/pdf ... 00012.2014
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Re: all things vitamin D

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i imagine the author will have drawn to some degree on both studies to construct the sentence.

on this track at the moment:

Vitamin D3 supplementation and neurofilament light chain in multiple sclerosis (2019)
https://onlinelibrary.wiley.com/doi/abs ... /ane.13185

Abstract
Objectives
Low circulating vitamin D levels are associated with an increased risk of active MRI lesions and relapses in several cohorts with relapsing remitting multiple sclerosis (RRMS). Randomized controlled supplementation trials are, however, negative on their primary endpoints, while secondary MRI endpoints suggest anti‐inflammatory effects. Circulating levels of neurofilament light chain (NfL) are a biomarker of disease activity in RRMS. We explored whether 48‐week high‐dose vitamin D3 supplements were associated with lower circulating NfL levels.

Materials & Methods
Of N = 40 Dutch interferon beta‐treated participants with RRMS of the SOLAR trial, plasma samples at baseline and 48‐week follow‐up were available. Of these participants, N = 24 were supplemented with 14 000 IU/d vitamin D3 and N = 16 with placebo. Twenty‐five hydroxyvitamin D3 (25(OH)D3) levels were measured with LC‐MS/MS, and NfL levels were measured in duplicate with Simoa.

Results
Serum 25(OH)D3 levels at 48 weeks were increased in the vitamin D3 when compared to placebo group (median level 281 [IQR 205‐330] vs 72 [39‐88] nmol/L; P < .01). NfL levels at 48 weeks did not differ between the treatment groups (median level 25.4 [IQR 19.6‐32.2] vs 25.3 [17.9‐30.1] pg/mL; P = .74). Higher week 48 NfL level showed a trend toward association with a higher risk of combined unique active lesions on the week 48 MRI scan (OR 2.39 [95% CI 0.93‐6.12] for each 10 pg/mL increase; P = .07).

Conclusions
Supplementation of high‐dose vitamin D3 for 48 weeks was not associated with lower NfL levels. This study does not support an effect of vitamin D3 on this biomarker of neuro‐axonal injury.

...

4 | DISCUSSION
High-dosed vitamin D3 supplements in interferon beta 1a–treated RRMS did not result in lower plasma NfL levels. This adds to the negative findings of this intervention on clinical endpoints in this study.7
It is also in line with another study, where moderate doses of vitamin D3 supplements did not affect both clinical and NfL endpoints.3,13 These negative results are paralleled by a positive effect of supplements on MRI endpoints.2,7 Therefore, despite these data, vitamin D3 supplementation in RRMS remains a controversial issue
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Re: all things vitamin D

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2020 Feb 25
Department of Neuropathology, Institute of Neuropathology, University Medical Center, Göttingen, Germany
High-Dose Vitamin D-Mediated Hypercalcemia as a Potential Risk Factor in Central Nervous System Demyelinating Disease
https://pubmed.ncbi.nlm.nih.gov/32161591/

Abstract

The exact cause of multiple sclerosis (MS) is unknown; however, it is considered to be an inflammatory disease of the central nervous system (CNS) triggered by a combination of both environmental and genetic factors. Vitamin D deficiency is also discussed as a possible disease-promoting factor in MS, as low vitamin D status is associated with increased formation of CNS lesions, elevated number of relapses and accelerated disease progression. However, it remains unclear whether this association is causal and related and most importantly, whether vitamin D supplementation in MS is of direct therapeutic benefit. Recently, we could show that in a murine model of MS, administration of a moderate vitamin D dose was of clinical benefit, while excessive vitamin D supplementation had a negative effect on disease severity. Of note, disease exacerbation was associated with high-dose vitamin D caused secondary hypercalcemia. Mechanistically dissecting this outcome, we found that hypercalcemia independent of vitamin D similarly triggered activation of disease-perpetuating T cells. These findings caution that vitamin D should be supplemented in a controlled and moderate manner in patients with MS and concomitantly highlight calcium as a novel potential MS risk factor by itself. In this review, we will summarize the current evidence from animal and clinical studies aiming to assess whether vitamin D may be of benefit in patients with MS. Furthermore, we will discuss any possible secondary effects of vitamin D with a particular focus on the role of calcium on immune cells and in the pathogenesis of CNS demyelinating disease.

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Re: all things vitamin D

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good find. i am still impatient for more research that considers d3 interactions with MAGNESIUM :)
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Re: all things vitamin D

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  • One hundred years after Vitamin D discovery: Is there clinical evidence for supplementation doses? ( Ghanaati et al)

    "...These findings reflect the need to rethink existing reference ranges and intake recommendations. Based on the analyzed range of clinically applied doses, we recommend a Vitamin D supplementation based on three different ranges, which include <40 ng/ml, >40 <80 ng/ml, and >80 ng/ml with oral Vitamin D intake of 10,000 IU/day, 5000 IU/day, and 1000 IU/day, respectively. A 25-hydroxyvitamin D blood serum monitoring is furthermore recommenced every 3 months to re-adjust the Vitamin D dose based on the above-mentioned concept..."
not bad although monitoring serum levels every three months sounds excessive, especially over time.

i also note zero occurrences of the words cofactor, recalcitrant or magnesium, maintaining the usual reiteration of calcium.

my concern is of course linked to prior personal experience with overdosing d3 via 4000 IU per day, and suffering symptoms consistent with magnesium deficit. all such symptoms resolved after taking greater care with d3 dosage and timing in relation to magnesium. i recall also the subsequent learning curve re magnesium supplementation options and potential pitfalls. i am still unsure re the extent to which identifying and correcting zinc deficiency around the same time was a factor in my d3 deficit. in general, i still wonder about the extent to which low d3 status may simply reflect a broad underlying cofactor deficit.

overall, while supplementing d3 may improve individuals' d3 levels, cofactor deficit may only be worsened. i expect in time that addressing such considerations in research will help us understand why d3 supplementation does not always lead to clinical improvement in correlated health problems.

that said i am pleased to recall, anecdotally, improved mri results and disappearing dental problems, after working on nutrition during 2018. i noted improved d3 dose response after my second round of therapeutic d3 intake compared to my first, having paid more attention to nutrition in general in the interim. (i still had my first-ever suspicious breast lump (cyst and nodule) findings after the d3 work, but follow up efforts to improve zinc status in late 2019 corresponded, by early 2020, to an all clear re breast tissue as well). all very interesting. let's hope research makes some gains on understanding apparent interactions by the end of this decade, if not sooner.
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the 60s called again

Post by jimmylegs »

Depression of serum Mg. levels in ruminants by vitamin D.
https://www.cabdirect.org/cabdirect/abs ... 9611403765

Abstract : There are conflicting reports on the effect of massive doses of vitamin D on serum magnesium values in sheep and cattle. In a trial with groups of 8 Scottish Blackface ewes matched for age, a single injection of 400, 000 I.U. vitamin D3 given early in March 1960 had little effect in ewes grazing on the north side of a hill, whereas in ewes grazing on the south side of the same hill the mean serum Mg value 2 or 3 months after injection was reduced to about two-thirds of that in untreated ewes. In another trial on a partly shaded hill, serum Mg was reduced when the injection was given early in January but not when it was given at the end of March. It is suggested that the effect on serum Mg is a manifestation of vitamin D excess.
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vit D effects on B cells

Post by jimmylegs »

brought this one over from the cladribine topic

Illuminating vitamin D effects on B cells – the multiple sclerosis perspective (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754614/
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2020 review: vit D fx on MS

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this looks very good so far - I still need to finish reading it thoroughly

A Brief Review of the Effects of Vitamin D on Multiple Sclerosis (2020)
fft: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218089/
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Re: all things vitamin D

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2020 Aug 31
Department of Cellular and Molecular Nutrition, Tehran University of Medical Sciences, Tehran, Iran
The effect of calcitriol and all-trans retinoic acid on T-bet, IFN-γ, GATA3 and IL-4 genes expression in experimental autoimmune encephalomyelitis
https://pubmed.ncbi.nlm.nih.gov/32865844/

Abstract

Multiple sclerosis (MS) is an immune-mediated inflammatory disease which affects the central nervous system (CNS). In the present study, the in vivo effects of ATRA, calcitriol, and their combinations on the expression of murine CD4+ T cell cytokines and their specific transcription factors in experimental autoimmune encephalomyelitis (EAE)-induced mice were explored. Thirty-two EAE induced inbred C57BL/6 female mice with an age ranged from 8 to 10 weeks were divided into four categories in a random manner. The first, second, and third groups received ATRA, calcitriol, ATRA+ calcitriol, respectively, and the fourth group received vehicle. The treatment started on the day prior to immunization and through the IP injections every other days for 21 days. The dosages of administration for calcitriol, ATRA, and calcitriol+ ATRA were 100 ng, 250 μg, and 50ng + 125 μg, respectively per mouse. An equal volume of excipient was administered for the vehicle group. T-bet, IFN-γ, GATA-3, and IL-4 genes expression were assessed in the splenocytes of EAE -induced mice. The expression of T-bet and IFN-γ genes in the splenocytes of ATRA, calcitriol and combination- treated mice were significantly reduced compared to vehicle group (p < 0.05). A significant decrease in T-bet expression was observed in the combination-treated group compared to the ATRA-treated group (p < 0.05). The expression of GATA3 and IL-4 genes was significantly increased in the ATRA-, calcitriol-, and combination-treated mice when compared with the control group (p < 0.05). Furthermore, the effect of calcitriol alone and in combination with ATRA was more considerable than that of ATRA alone. The nutraceutical approaches may be promising in the prevention and/or treatment of MS.
---------------------

wiki https://en.wikipedia.org/wiki/Retinoic_acid
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Re: all things vitamin D

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2021 Feb 3
Molecular and Cell Biology, Emeritus, University of California, Berkeley, USA
Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?
https://pubmed.ncbi.nlm.nih.gov/33546262/

Abstract

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.
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Re: all things vitamin D

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2021 Feb 12
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Vitamin D Changes Expression of DNA Repair Genes in the Patients with Multiple Sclerosis
https://pubmed.ncbi.nlm.nih.gov/33588040/

Abstract

Oxidative stress (OS) plays an essential role in demyelination and tissue injury related to pathogenesis of multiple sclerosis (MS). On the other hand, vitamin D (VD) as an antioxidant reduces oxidative stress and has been used as adjuvant therapy in autoimmune diseases. Although VD supplementation is suggested as a protective and immunomodulation factor for MS patients, the molecular mechanisms remain unclear. Given that VD may modulate the immune system of MS patients through the DNA repair pathway, we aimed to evaluate the effects of VD supplementation in DNA repair genes expression including OGG1, MYH, MTH1, and ITPA. Transcript levels were measured using the RT-qPCR method in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) patients before and after two months of VD supplementation. Furthermore, in silico analysis and correlation gene expression analysis was performed to find the biological binding sites and the effect of NRF2 on the regulation of DNA repair genes. Our data revealed that in MS patients, 2-month VD treatment significantly altered the expression of MYH, OGG1, MTH1, and NRF2 genes. A significant correlation was observed between DNA repair genes and NRF2 expression, which was confirmed by the presence of antioxidant response element (ARE) binding sites in the promoter of OGG1, MYH, and MTH1 genes. This study demonstrated that the impact of VD on MS patients may be mediated through the improvement of DNA repair system efficiency. This finding brought some new evidence for the involvement of DNA repair genes in the physiopathology of MS patients.
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so-called vit d3 'resistance'

Post by jimmylegs »

still annoying!

2014 called:
viewtopic.php?p=223430#p223430

"i consider the passing mention of multimineral use only in the context of those with poor d3 absorption to be irresponsible"

Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol (2021)
https://www.frontiersin.org/articles/10 ... 55739/full

search results for terms:

cofactor=0
magnesium=0
zinc=0

so in 2021, folks are still going on about high dosing d3, but now key known relevant cofactor nutrients aren't even making it into the discussion at all. smh!
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toxin uptake w Vit D3

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item 1: some vit D is good; item 2: a lot may be toxic

Correlation between vitamin D and alterations in MRI among patients with multiple sclerosis (2021)
https://pubmed.ncbi.nlm.nih.gov/34558256/

"... high serum levels of vitamin D, in this case 75 nmol/Lor higher (p=0.021) and 100 nmol/L or higher (p=0.016), were associated with lower levels of NfL in cerebrospinal fluid. NfL levels also correlated with the number of contrast-enhancing brain lesions on MRI (p<0.0005) [31].
...
patients with MS featured significantly lower vitamin D levels than healthy volunteers (15.9 nmol/L vs. 20.6 nmol/L; p<0.0001).
...
Serum concentrations below 50 nmol/L indicated higher risk of MS occurrence (p=0.024) and an increased likelihood of disease progression (p<0.001) [32].
In addition, little difference in EDSS score was observed between 2 groups of MS patients receiving either 20,400 IU or 400 IU over a period of 18 months (p=0.64), suggesting that vitamin D in excess doses does not have a differential impact on MS progression"

so modest d3 levels may be protective, and can be achievable with modest daily d3 intakes - provided of course that suitable cofactors are in the mix (doesn't seem to be any mention of such in this article, mind you). interesting:

Vitamin D, Essential Minerals, and Toxic Elements: Exploring Interactions between Nutrients and Toxicants in Clinical Medicine (2015)
https://www.hindawi.com/journals/tswj/2015/318595/

"... What has largely been forgotten, however, is that higher levels of 25(OH)D3 have been linked to enhanced absorption of toxic elements such as aluminum, cadmium, cobalt, and lead as well as radioactive isotopes including cesium and radioactive strontium [12].
...
It is important to recognize that vitamin D does not work alone but requires essential minerals to achieve its full benefit. Deficiency of minerals including magnesium, calcium, zinc, and iron is very common as outlined above. Recognizing the synergistic action of mineral deficiency with elevated vitamin D levels on the uptake of toxic elements, adequate intake of minerals needs to be ensured."
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magnesium for vit D

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Response of Vitamin D after Magnesium Intervention in a Postmenopausal Population... (2020)
https://www.mdpi.com/2072-6643/12/8/2283/htm
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cool Re: all things vitamin D

Post by jimmylegs »

Development of safe UVB-LED special lighting to support daily recommended vitamin D synthesis: convergence approach of health and UVB-LED lighting (2021)
https://link.springer.com/article/10.10 ... 21-01576-7

"The expected amount of vitamin D synthesis by distance and use duration is calculated through a performance test for the proposed lighting. The test results show that when the proposed lighting is used at a distance of 20 cm for 33–40 min, the daily recommended vitamin D synthesis can be achieved."

now for some dose response testing in different groups :)
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