This Is MS Multiple Sclerosis Knowledge & Support Community

it will be nice when there are large studies looking at this interaction explicitly. for the meantime:

Kampmann, U., Mosekilde, L., Juhl, C., Moller, N., Christensen, B., Rejnmark, L., ... & Orskov, L. (2014). Effects of 12weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency–a double-blind, randomized, placebo-controlled trial. Metabolism, 63(9), 1115-1124.
http://www.sciencedirect.com/science/ar ... 9514001759

regimen: oral cholecalciferol (11,200 IU (280 μg) daily for 2 weeks, followed by 5600 IU (140 μg) daily for 10 weeks)

...............................Baseline values ............................... Changes from baseline after 3 months
...............................Vitamin D group ..... Placebo group ....... Vitamin D group ..... Placebo group
Serum 25(OH)vitD2D3....31.0 ± 4.9...............34.8 ± 3.8...............+73.9 ± 20.6...........−2.6 ± 3.2
(nmol/L)
Serum magnesium.........0.91 ± 0.05..............0.91 ± 0.03.............−0.06 ± 0.04...........−0.024 ± 0.03
(mmol)

so 2.5 x greater impact on se mag from d3 supplementation compared to placebo. the starting point for both groups is not ideal, consistent with their diabetes dx and exclusion of participants with serum d3 levels above 50 nmol/L. serum mag levels are just barely into the top half of commonly used reference ranges for serum magnesium. placebo group's follow up mean mag status drops to .886 while d3 group mean drops to 0.85 mmol/L. better to be at least 0.95 mmol/L.

slight reductions in mag and d3 in the placebo group after three months are consistent with what we know about positive correlations between se mag and se d3 status.

for comparison, in this study healthy control mean serum mag converts to 0.904 (again just barely into the top half of the normal range though) while mean serum mag for ms patients converts to 0.77.
http://ijpbs.mazums.ac.ir/article-1-139-en.pdf

so from the first study above, straight d3 supplementation takes individuals towards a healthier level for serum d3 but at the same time pushes recipients in the direction of an ms patient profile for serum magnesium.

as mentioned above, need more and larger studies looking at this dynamic, but just looking at these two small studies together for now, in 3 months of d3 treatment subjects apparently lost 40% of their healthy control magnesium advantage over a typical mean serum mag level for an average ms patient.

looking at this it makes sense that i experienced serious issues with low mag after a couple years on 4000 IU per day, with two short term megadoses along the way (1st 50K/d x 10 days, 2nd 50K/d x 8 days)

Effects of a dietary magnesium deficiency and excess vitamin D3 on swine coronary arteries
https://www.ncbi.nlm.nih.gov/pubmed/2159962
"The effect of a moderate magnesium (Mg) deficiency on coronary arteries of 61 swine, fed various levels of vitamin D3, was studied by light and electron microscopy.
The effect of subnormal Mg intake on vitamin D3-induced intimal lesions of the arteries showed a trend towards increased damage.
The degree of cell degeneration and intimal thickening, which was induced by high vitamin D intakes, was as great in swine whose diet was low in Mg and moderately high in vitamin D, as it was in those on twice as much vitamin D.
Also, the degree of arterial calcification was intensified by inadequate Mg intake at the two higher vitamin D intakes.
Present findings indicate that suboptimal dietary Mg, in combination with an excess of vitamin D, has an additive effect in the initiation of ultrastructural changes in the coronary arteries. Extension of the study is indicated to ascertain the extent to which further reduction of Mg intake can potentiate vitamin-D-induced coronary lesions."

how about further extension of the study to ascertain the extent to which correcting the imbalance can repair the damage...

wonder if the full text unpacks anything to do with magnesium eg the possibly of low d3 being perhaps in part an indicator of an underlying magnesium situation.

Role of Vitamin D in Uremic Vascular Calcification
https://www.hindawi.com/journals/bmri/2017/2803579/abs/
The risk of cardiovascular death is 10 times higher in patients with CKD (chronic kidney disease) than in those without CKD. Vascular calcification, common in patients with CKD, is a predictor of cardiovascular mortality. Vitamin D deficiency, another complication of CKD, is associated with vascular calcification in patients with CKD. GFR decline, proteinuria, tubulointerstitial injury, and the therapeutic dose of active form vitamin D aggravate vitamin D deficiency and reduce its pleiotropic effect on the cardiovascular system. Vitamin D supplement for CKD patients provides a protective role in vascular calcification on the endothelium by (1) renin-angiotensin-aldosterone system inactivation, (2) alleviating insulin resistance, (3) reduction of cholesterol and inhibition of foam cell and cholesterol efflux in macrophages, and (4) modulating vascular regeneration. For the arterial calcification, vitamin D supplement provides adjunctive role in regressing proteinuria, reverse renal osteodystrophy, and restoring calcification inhibitors. Recently, adventitial progenitor cell has been linked to be involved in the vascular calcification. Vitamin D may provide a role in modulating adventitial progenitor cells. In summary, vitamin D supplement may provide an ancillary role for ameliorating uremic vascular calcification.

Serum 25‐hydroxyvitamin D 3 levels are elevated in South Indian patients with ischemic heart disease
http://bit.ly/2mQ4YmT
would be very interesting to check out the raw data for this one.

would also be nice to get my supposed access working on this one - curious if they bother to touch on magnesium... (august 2017 update - they don't)

Vitamin D, Calcium, and Cardiovascular Disease: A“D”vantageous or “D”etrimental? An Era of Uncertainty
https://link.springer.com/article/10.10 ... 017-0637-2

While the function of vitamin D in regulating calcium homeostasis is well established, there has been growing interest in its role in the prevention of numerous chronic diseases, including cardiovascular disease (CVD). There is mounting epidemiological evidence suggesting that vitamin D deficiency is linked to increased CVD risk. However, the results of previous vitamin D supplementation trials have yielded mixed results in regards to cardiovascular health, and the results of ongoing large-scale randomized controlled trials are not yet available. Further complicating the issue, calcium supplementation, which is often prescribed concurrently with vitamin D, has been associated with increased CVD risk in some (but not all) studies. Thus, it is currently unclear whether vitamin D supplements, particularly for those that are deficient, can help prevent the development of CVD. In addition, there has not been uniform consensus regarding the threshold of 25-hydroxyvitamin D levels that constitutes “sufficiency” across organizational guidelines. This review will provide an update on the most recent evidence regarding the effects of vitamin D and calcium supplements on CVD clinical outcomes, summarize ongoing vitamin D trials, and discuss the current but remarkably disparate recommendations regarding vitamin D deficiency screening and supplementation.

might crop up to some extent in the (but not all) studies mentioned. will have to come back to this one.

just a case study, and it's not one with normal serum calcium by any means. however. kidney stones have come up recently on the forum, and not for the first time:

Reversible vascular calcifications associated with hypervitaminosis D
https://link.springer.com/article/10.10 ... 015-0228-7

A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D.

again, would be nice if there were even a whisper of analysis where serum magnesium is concerned... particularly among those who failed to achieve serum level increases at daily supplemental d3 intakes above 4000 IU. talk about a blind spot. smh

Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting
https://pdfs.semanticscholar.org/30ce/e ... e164fc.pdf
Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6–18 months between 2013 and 2015. Participants were supplemented with a wide range of vitamin D doses (1,000 – 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese. Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.

reposting in case anyone wasn't clear on the importance of cofactors (Luongo...!)

Vitamin D, Essential Minerals, and Toxic Elements: Exploring Interactions between Nutrients and Toxicants in Clinical Medicine
https://www.hindawi.com/journals/tswj/2015/318595/abs/
In clinical medicine, increasing attention is being directed towards the important areas of nutritional biochemistry and toxicant bioaccumulation as they relate to human health and chronic disease. Optimal nutritional status, including healthy levels of vitamin D and essential minerals, is requisite for proper physiological function; conversely, accrual of toxic elements has the potential to impair normal physiology. It is evident that vitamin D intake can facilitate the absorption and assimilation of essential inorganic elements (such as calcium, magnesium, copper, zinc, iron, and selenium) but also the uptake of toxic elements (such as lead, arsenic, aluminum, cobalt, and strontium). Furthermore, sufficiency of essential minerals appears to resist the uptake of toxic metals. This paper explores the literature to determine a suitable clinical approach with regard to vitamin D and essential mineral intake to achieve optimal biological function and to avoid harm in order to prevent and overcome illness. It appears preferable to secure essential mineral status in conjunction with adequate vitamin D, as intake of vitamin D in the absence of mineral sufficiency may result in facilitation of toxic element absorption with potential adverse clinical outcomes.

older lit, but until now only documented elsewhere on the site:

Vitamin D3 Receptor (VDR) Gene rs2228570 (Fok1) and rs731236 (Taq1) Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis
http://journals.plos.org/plosone/articl ... ne.0065487

Abstract
Background
Some epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the VDR gene and HLADRB1*1501 in the risk for MS.

Objectives
The aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the VDR gene in the risk for MS. A secondary objective was to address the possible interactions between VDR genes and HLADRB1*1501.

Methods
We analyzed the allelic and genotype frequency of VDR rs2228570, rs731236, and HLADRB1*1501 (rs3135388) in 303 patients with MS and 310 healthy controls, using TaqMan Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (http://www.hrc.es/investigacion/metadisc.html; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic.

Results
VDR rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. HLADRB1*1501 showed a high association with the risk of developing MS 4.76(95% C.I.  = 3.14–7.27; p<0.0001). The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. HLADRB1*1501 showed lack of interaction with VDR rs2228570 and rs731236 in increasing MS risk.

Conclusions
These results suggest that VDR rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these VDR SNPs and HLADRB1 in the risk for MS.

noting, i think, that this old article is not included specifically in this thread i'll include it here. unsurprisingly (especially for 2007), serum magnesium is not analyzed wrt serum dose response to natural d3 exposure. cmon science, you can do this - i know you can!!

Low Vitamin D Status despite Abundant Sun Exposure (2007)
fft: https://academic.oup.com/jcem/article/92/6/2130/2597445

Abstract
Context: Lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide. However, some individuals with seemingly adequate UV exposure have been reported to have low serum 25-hydroxyvitamin D [25(OH)D] concentration, results that might have been confounded by imprecision of the assays used.

Objective: The aim was to document the 25(OH)D status of healthy individuals with habitually high sun exposure.

Setting: This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21°).

Participants: The study population consisted of 93 adults (30 women and 63 men) with a mean (SEM) age and body mass index of 24.0 yr (0.7) and 23.6 kg/m2 (0.4), respectively. Their self-reported sun exposure was 28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7).

Main Outcome Measures: Serum 25(OH)D concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a circulating 25(OH)D concentration less than 30 ng/ml.

Results: Mean serum 25(OH)D concentration was 31.6 ng/ml. Using a cutpoint of 30 ng/ml, 51% of this population had low vitamin D status. The highest 25(OH)D concentration was 62 ng/ml.

Conclusions: These data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UV exposure appears to be approximately 60 ng/ml, it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation.

interesting. it would be nice if i could find the articles i'd read ages ago on somewhat higher natural levels (maybe as high as 160 ng/ml ONLY if distant memory serves) and refresh my memory on the details as well as the calibre of the academic work or works in question. in a perfect world we'd be able to compare vit d3 cofactor status between subjects from those older works and this relatively recent hawaiian study.

ooh maybe *this* one looked at the influence of magnesium status...

Major inter-personal variation in the increase and maximal level of 25-hydroxy vitamin D induced by UVB (2013)
https://www.ncbi.nlm.nih.gov/pubmed/27001558
Vitamin D influences skeletal health as well as other aspects of human health. Even when the most obvious sources of variation such as solar UVB exposure, latitude, season, clothing habits, skin pigmentations and ethnicity are selected for, variation in the serum 25-hydroxy vitamin D (25(OH)D) response to VB remains extensive and unexplained. Our study assessed the inter-personal variation in 25(OH)D response to UVR and the maximal obtainable 25(OH)D level in 22 healthy participants (220 samples) with similar skin pigmentation during winter with negligible ambient UVB. Participants received identical UVB doses on identical body areas until a maximal level of 25(OH)D was reached. Major inter-personal variation in both the maximal obtainable UVB-induced 25(OH)D level (range 85–216 nmol/l, mean 134 nmol/l) and the total increase in 25(OH)D (range 3–139 nmol/l, mean 48 nmol/l) was found. A linear model including measured 25(OH)D baselines as personal intercepts explained 54.9% of the variation. By further including personal slopes in the model, as much as 90.8% of the variation could be explained. The explained variation constituted by personal differences in slopes thus represented 35.9%.
Age, vitamin D receptor gene polymorphisms, height and constitutive skin pigmentation (a skin area not exposed to UVB) explained 15.1% of this variation. Despite elimination of most known external sources of variation, our study demonstrated inter-personal variation corresponding to an observed maximal difference of 136 nmol/l in the total increase of 25(OH)D and 131 nmol/l in the maximal level of 25(OH)D.

interesting, but nope. # times magnesium mentioned in full text: 0
le sigh! cmon science let's git er done.

The Role of Vitamin D in Multiple Sclerosis: Biology and Biochemistry, Epidemiology and Potential Roles in Treatment (2018)
https://www.ncbi.nlm.nih.gov/pubmed/28933265

BACKGROUND:
Multiple sclerosis (MS) is a progressive, demyelinating condition of the central nervous system, manifesting in loss or alterations in function of sensory, motor and cognitive function. Of the various environmental and behavioural risk factors identified as playing a role in MS onset and progression, perhaps none has been as consistent as vitamin D.

OBJECTIVE:
In this review, we will endeavour to present a general background on the role of vitamin D in human health and particularly in MS, as well as the substantial epidemiological evidence in support of vitamin D's role in MS.

RESULTS:
Initially identified via the oft-noted latitudinal gradient in MS prevalence and incidence, vitamin D has since been demonstrated to have a strong and consistent inverse association with MS risk and clinical course. Cases have much lower levels of the diagnostic metabolite of vitamin D, 25- hydroxyvitamin D (25(OH)D) compared to healthy controls, while those with more active disease have lower levels of 25(OH)D than other cases with less active disease. These case-control and crosssectional study results led the way to cohort studies which indicated significant inverse associations between serum 25(OH)D and clinical activity in MS. The combined weight of indirect and direct observational evidence have been the impetus for completed and ongoing randomised trials of vitamin D supplementation, alone or in addition to standard immunomodulatory medications, as an intervention in MS onset and clinical course. Moreover, in addition to being a distinct factor in MS aetiology, vitamin D has been demonstrated to interact with a variety of other risk factors, from genetic predictors like HLA-DR1 genotype to behavioural factors like smoking.

CONCLUSION:
There is an abundance of epidemiological evidence, both direct and indirect, as well as significant biological plausibility substantiating a role for vitamin D in the onset and progression of multiple sclerosis.

no full text for me as yet. and not even hinting at vit d3 cofactors in the abstract :S le sigh

Evidence for a U-Shaped Relationship Between Prehospital Vitamin D Status and Mortality: A Cohort Study
https://academic.oup.com/jcem/article/99/4/1461/2537578
Objective:
The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D]and the risk of mortality after hospital admission.

Design:
We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011.

Setting:
The study was conducted at two Boston teaching hospitals.

Patients:
A total of 24 094 adult inpatients participated in the study.

Intervention:
There was no intervention.

Measurements:
All patients had serum 25(OH)D measured before hospitalization. The exposure of interest was 25(OH)D categorized as less than 10 ng/mL, 10–19.9 ng/mL, 20–29.9 ng/mL, 30–49.9 ng/mL, 50–59.9 ng/mL, 60–69.9 ng/mL, and 70 ng/mL or greater. The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders.

Results:
After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH)D draw, and the Deyo-Charlson index, patients with 25(OH)D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30–49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D <10 ng/mL, 10–19.9 ng/mL, 20–29.9 ng/mL, 50–59.9 ng/mL, 60–69.9 ng/mL, and ≥70 ng/mL was 2.01 (1.68–2.40), 1.89 (1.64–2.18), 1.34 (1.16–1.56), 0.94 (0.69–1.26), 1.52 (1.03–2.25), and 1.69 (1.09–2.61), respectively, compared with patients with 25(OH)D levels 30–49.9 ng/mL].

Limitations:
A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study.

Conclusions:
Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients.

my friend who is fighting advanced breast cancer recently went against her medical team's advice, which was to take 4000 IU per day of D3, to address her low serum level (under 50 nmol/l ie less than 20 ng/ml, and mine was only a little better)
together she and i completed a 10 day, 50K IU per day regimen. this is a protocol that is meant to boost serum levels by 50 nmol/l but personally having been around this block a couple times i know my own dose response has been much higher. triple the expected dose response was okay by me, because i'd still be at 150 nmol/l, which i'm fine with as long as i have all my cofactors in order.

i have not yet had a chance to request follow-up bloodwork for my own recent megadose, but her results came in yesterday.
her levels climbed just 30 nmol/l. she has just barely squeaked into the range of sufficiency in terms of protection against osteoporosis, never mind anything more serious.
but that lab paperwork is god. it says >75 nmol = desirable. so who cares if her level isn't even 80, never mind that the next level in the rubric is >250 = excess
circling the drain is, apparently, 'desirable'.

one of her applicable risk factors for breast cancer, aside from the obvious, is obesity.
while the literature does not seem to show a clear relationship between d3 status and risk of her cancer in particular, this research is relevant:

The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers (2014)
https://journals.plos.org/plosone/artic ... ne.0111265
Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body's vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation.
We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets.

comments:

first, for clarity results describe a *negative* exponential curve, ie a plateau
https://journals.plos.org/plosone/artic ... 11265.g001

a clear "diminishing returns" scenario.

also, re "12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day",
if you check out the figure, the y axis seems to indicate on average subjects went from say 63 nmol/l taking no daily d3, to 85 nmol/l if taking 1000 IU/day
also looks like 5000 IU per day puts the group mean serum level above 100 nmol/l - with typically large dose response variation around the line of best fit (... and as usual no analysis of or discussion about any cofactor other than calcium.. )

i note with interest one of the outliers, with 150 nmol/l serum d3 level at around 2000 IU/d supplemental intake. wonder what else that person has going on in their day to day routine and/or gene pool!

anyway. i hope my friend has let her docs know about the 10 day megadose, and that her team is not under the mistaken impression that her recent 30 nmol/l gains were made as a result of their 4000 IU per day instruction. she definitely has gotten nowhere near the 100 nmol/l level that the above study's chart suggests for a 4000 IU/day intake, even *with* the megadose in the mix.

i'll be very interested to see my own results, so that we can compare notes on dose-response!!

no time to dig in yet, but anticipate some questions re study design

Vitamin D Levels and Clinical and OCT measures in Progressive Multiple Sclerosis (2018)
http://n.neurology.org/content/90/15_Supplement/P2.352

Abstract
Objective: To examine the association between vitamin D levels and clinical/optical coherence tomography (OCT) features in progressive multiple sclerosis subjects (primary progressive [PPMS] and secondary progressive [SPMS]) from the ibudilast phase II clinical trial (NN201/SPRINT-MS).

Background: Vitamin D deficiency is a risk factor for multiple sclerosis (MS). Low vitamin D levels are associated with increased risk of brain lesions, relapses and early progression of disability in relapsing forms of MS.

Design/Methods: 25 OH vitamin D levels (D3 and total D) were conducted on baseline serum samples from the subjects enrolled into the NN102/SPRINT-MS trial along with clinical and disease data. The validated clinical measures included the Expanded Disability Status Scale (EDSS), 25-foot timed walk (T25FW), 9-hole peg test (9HPT), Symbol Digit Modality Test (SDMT) and the 2.5% low contrast visual acuity test (LCVA). OCT measurements included retinal nerve fiber layer thickness (RNFL) and ganglion cell layer thickness (GCL).

Results: The sample included 267 patients (Age 55.6±7.4, 47.2% male, and 51.3% PPMS) who had both baseline clinical/OCT data along with vitamin D levels. No difference was found between PPMS and SPMS for mean D3 (40.7 vs. 39.9 ng/ml) and total D (43.8 vs. 42.9 ng/ml). There was no significant association between D3 or total D and the clinical/OCT measures. Compared to PPMS, SPMS had worse/lower 2.5% LCVA (19.3 vs 22.9, p=0.01) and OCT measures including RNFL (79.5 vs 85.7, p=<0.001) and GCL (68.6 vs 71.8, p=<0.02). The differences were not significant between D3/total D sufficient and insufficient (<30) groups. There was no difference in other clinical measures between the two vitamin D stratification.

Conclusions: Vitamin D levels were not significantly correlated with clinical/OCT measures. The OCT changes seen between PPMS and SPMS may support the chronic nature of SPMS and do not appear to be mediated by vitamin D.