Vitamin D: Scientific Studies & News

A forum to discuss the Coimbra Protocol which uses high-dose vitamin D3 to treat multiple sclerosis.
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AntonioBR
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Vitamin D: Scientific Studies & News

Post by AntonioBR »

Multiple sclerosis: Decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D

Abstract
A group of young patients having multiple sclerosis was treated with dietary supplements containing calcium, magnesium and vitamin D for a period of one to two years. The experimental design employed self-pairing: the response of each patient was compared with his/her own case history as control. The number of exacerbations observed during the program was less than one half the number expected from case histories. No side effects were apparent. The dietary regimen may offer a new means of controlling the exacerbation rate in MS, at least for younger patients. The results tend to support a theory of MS which states that calcium and magnesium are important in the development, structure and stability of myelin.

Source:
http://www.sciencedirect.com/science/ar ... 7786900101
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Re: Vitamin D: Scientific Studies & News

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In Multiple Sclerosis Study, Vitamin D Shown to Aid Myelin Repair


Early research finds vitamin's interaction with a protein retriggers nerve fiber protector

A new study in the Journal of Cell Biology suggests that vitamin D activates a receptor involved in myelin regeneration in patients with multiple sclerosis (MS). The study, entitled “Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation[1],” and was led by researchers at the University of Cambridge, United Kingdom.

In MS, the body’s own immune system attacks and destroys the myelin layer, the sheath that covers and protects nerve fibers. The body has natural mechanisms to repair myelin, however, with age these become less effective.

Researchers found that the vitamin D receptor interacts with a protein called the RXR gamma receptor, which has already been reported to play a role in myelin repair. In their experiments, researchers added vitamin D to brain stem cells (where both vitamin D and RXR gamma receptors are present) and found a significant increase (80%) in the production of oligodendrocytes, which are the cells that generate myelin. When vitamin D receptor activity was blocked, the RXR gamma protein was unable, by itself, to induce the production of oligodendrocytes.

“For years scientists have been searching for a way to repair damage to myelin. So far, the majority of research on vitamin D has looked at its role in the cause of the disease. This work provides significant evidence that vitamin D is also involved in the regeneration of myelin once the disease has started. In the future we could see a myelin repair drug that works by targeting the vitamin D receptor,” said the study’s senior author, Professor Robin Franklin, of the MS Society Cambridge Centre for Myelin Repair and the Wellcome Trust-Medical Research Council Stem Cell Institute at the University of Cambridge, in a news release.

The research team believes that vitamin D plays a role in myelin regeneration and that it can offer new approaches for remyelination therapies.

“More than 100,000 people in the UK have multiple sclerosis and finding treatments that can slow, stop or reverse the worsening of disability is a priority for the MS Society. We’d now like to see more studies to understand whether taking vitamin D supplements could, in time, be an effective and safe treatment for people with MS,” said Dr. Susan Kohlhaas, head of Biomedical Research at the MS Society. “For now though, this is early stage research that’s been done in the laboratory and more work is needed before we know whether it would hold true in people with MS. It’s not a good idea, however, to be deficient in vitamin D and we’d encourage anybody who thinks they might be to speak to their GP [general practitioner].”

A next step is to understand in more detail the biology of both vitamin D and RXR gamma receptors, so that future studies can focus on how the vitamin D receptor could be an effective target in MS patients.

Source:
http://multiplesclerosisnewstoday.com/2 ... in-repair/


[1] Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation
Source:
http://jcb.rupress.org/content/211/5/975.abstract
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Re: Vitamin D: Scientific Studies & News

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Low vitamin D levels are related to MS brain atrophy, cognitive function, studies show

Date:April 30, 2010
Source:University at Buffalo
Summary:Low vitamin D levels may be associated with more advanced physical disability and cognitive impairment in persons with multiple sclerosis, studies conducted by neurologists have shown.


Low vitamin D levels may be associated with more advanced physical disability and cognitive impairment in persons with multiple sclerosis, studies conducted by neurologists at the University at Buffalo have shown.

Their results, reported at the American Academy of Neurology meeting, held earlier this month, indicated that:

The majority of MS patients and healthy controls had insufficient vitamin D levels.
Clinical evaluation and magnetic resonance imaging (MRI) images show low blood levels of total vitamin D and certain active vitamin D byproducts are associated with increased disability, brain atrophy and brain lesion load in MS patients.
A potential association exists between cognitive impairment in MS patients and low vitamin D levels.
The MRI study involved 236 MS patients -- 208 diagnosed with the relapsing-remitting type and 28 with secondary progressive, a more destructive form of MS -- and 22 persons without MS.

All participants provided blood serum samples, which were analyzed for total vitamin D (D2 and D3) levels as well as levels of active vitamin D byproducts. MRI scans performed within three months of blood sampling were available for 163 of the MS patients.

Results showed that only seven percent of persons with secondary-progressive MS showed sufficient vitamin D, compared to 18.3 percent of patients with the less severe relapsing-remitting type.

Higher levels of vitamin D3 and vitamin D3 metabolism byproducts (analyzed as a ratio) also were associated with better scores on disability tests, results showed, and with less brain atrophy and fewer lesions on MRI scans.

Bianca Weinstock-Guttman, MD, UB associate professor of neurology/Jacobs Neurological Institute and director of the Baird Multiple Sclerosis Center, is first author on the study. Commenting on these results, Weinstock-Guttman said: "Clinical studies are necessary to assess vitamin D supplementation and the underlying mechanism that contributes to MS disease progression."

While lower-than-normal vitamin D status is known to be associated with a higher risk of developing MS, little is known about its relationship to cognitive impairment.

Sarah A. Morrow, MD, UB assistant research professor of neurology/Jacobs Neurological Institute and lead author on the cognitive-impairment study, compared vitamin D levels in blood samples of 136 MS patients with the results of their neuropsychological assessments that tested multiple types of cognition affected by MS.

"Results showed that MS patients who were impaired on tests of executive function -- critical reasoning and abstract thinking -- and the ability to plan and organize, were more likely to be deficient in vitamin D," said Morrow.

"This relationship held true when controlling for the season during which vitamin D was measured, as well as depression, which is known to be associated with lower vitamin D levels." Morrow noted there also was a suggestion that verbal fluency (word generation) and visual-spatial memory (learning and memory of shapes and figures) is more likely to be affected when vitamin D levels are not sufficient.

Morrow is continuing her research to clarify these relationships.

Contributors to the studies, all from UB, were: Robert Zivadinov, MD, PhD; Murali Ramanathan, PhD; Ralph Benedict, PhD; Jun Qu, PhD; Xiaotao Duan, PhD; Barbara E. Teter, PhD; David Hojnacki, MD; Eunjin Bang, Niels Bergsland, Sara Hussein, Mariya Cherneva and Laura Willis.


Source:

http://www.sciencedaily.com/releases/20 ... 153955.htm
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Re: Vitamin D: Scientific Studies & News

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Safety of vitamin D3 in adults with multiple sclerosis



Abstract

Background: Vitamin D3 may have therapeutic potential in several diseases, including multiple sclerosis. High doses of vitamin D3 may be required for therapeutic efficacy, and yet tolerability—in the present context, defined as the serum concentration of 25-hydroxyvitamin D [25(OH)D] that does not cause hypercalcemia—remains poorly characterized.

Objective: The objective of the study was to characterize the calcemic response to specific serum 25(OH)D concentrations.

Design: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D3: from 700 to 7000 μg/wk (from 28 000 to 280 000 IU/wk).

Results: Mean (± SD) serum concentrations of 25(OH)D initially were 78 ± 35 nmol/L and rose to 386 ± 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1–2.6 mmol/L and <1.0, respectively). Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test. Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03).

Conclusions: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.

Source:
http://ajcn.nutrition.org/content/86/3/645.long
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Re: Vitamin D: Scientific Studies & News

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Confirmation of association between multiple sclerosis and CYP27B1


Abstract
Multiple sclerosis, MS (OMIM No. 126200), is a complex inflammatory disease that is characterized by lesions in the central nervous system. Both genes and other environmental factors influence disease susceptibility. One of the environmental factors that has been implicated in MS and autoimmune disease, such as type 1 diabetes, is vitamin D deficiency, in which patients have lower levels of 25-hydroxyvitamin D3 (25-OHD3) in blood than do controls. Previtamin D3 is produced in the skin, and turned into 25-OHD3 in the liver. In the kidney, skin and immune cells, 25-OHD3 is turned into bioactive 1,25(OH)2D3 by the enzyme coded by CYP27B1 (cytochrome P450 family 27 subfamily B peptide 1) on chromosome 12q13.1–3. 1,25(OH)2D3 binds to the vitamin D receptor, expressed in T cells and antigen-presenting cells. 1,25(OH)2D3 has a suppressive role in the adaptive immune system, decreasing T-cell and dendritic cell maturation, proliferation and differentiation, shifting the balance between T-helper 1 (Th1) and Th2 cells in favor of Th2 cells and increasing the suppressive function of regulatory T cells. Rs703842 in the 12q13–14 region was associated with MS in a recent study by the Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). We show associations with three SNPs in this region in our Swedish materials (2158 cases, 1759 controls) rs4646536, rs10877012 and rs10877015 (P=0.01, 0.01 and 3.5 × 10−3, respectively). We imputed rs703842 SNP and performed a joint analysis with the ANZgene results, reaching a significant association for rs703842 (P=5.1 × 10−11; odds ratio 0.83; 95% confidence interval 0.79–0.88). Owing to its close association with 25-OHD3, our results lend further support to the role of vitamin D in MS pathology.


Source:
http://www.nature.com/ejhg/journal/v18/ ... 0113a.html
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Re: Vitamin D: Scientific Studies & News

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Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis

Abstract

Background
Multiple Sclerosis is associated with low serum levels of 25-hydroxyvitamin D (25(OH)D). We investigated the association between serum levels of 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active metabolite, and clinical MS severity as expressed by EDSS-score and relapse rate.

Study-design

Cross-sectional study.

Patients and Methods
Serum samples from 267 MS patients were collected for 25(OH)D and 1,25(OH)2D measurement. Clinical MS parameters at the date of serum sampling were determined. Results: Both metabolite levels were significantly lower in the progressive forms compared to the relapsing remitting (RR)MS phenotype. In RRMS patients (disease course ≤ 5 years), high 25(OH)D levels were associated with a high chance of remaining relapse-free. Low 25(OH)D levels were associated with high EDSS-scores. 1,25(OH)2D was not directly associated with relapse rate or EDSS-score, and was dependent of age and 25(OH)D level.

Conclusion
Serum levels of 25(OH)D were associated with both relapse rate and disability in MS patients. These results are suggestive for a disease modulating effect of the serum concentrations of 25(OH)D on MS. The low circulating 1,25(OH)2D levels in progressive MS are due to older age and lower 25(OH)D levels. The potential consequences for vitamin D supplementation in MS will be discussed.

Source:
http://msj.sagepub.com/content/14/9/1220
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Re: Vitamin D: Scientific Studies & News

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Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women

Abstract
The aim of this study was to investigate modifiable predictors of vitamin D status in healthy individuals, aged 55–74, and living across the USA. Vitamin D status [serum 25-hydroxyvitamin D (25(OH)D)] was measured along with age and season at blood collection, demographics, anthropometry, physical activity (PA), diet, and other lifestyle factors in 1357 male and 1264 female controls selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Multivariate linear and logistic regression analyses were used to identify associations with vitamin D status. Three%, 29% and 79% of the population had serum 25(OH)D levels <25, <50 and <80 nmol/L, respectively. The major modifiable predictors of low vitamin D status were low vitamin D dietary and supplement intake, body mass index (BMI) >30 kg/m2, physical inactivity (PA) and low milk and calcium supplement intake. In men, 25(OH)D was determined more by milk intake on cereal and in women, by vitamin D and calcium supplement and menopausal hormone therapy (MHT) use. Thus targeting an increase in vigorous activity and vitamin D and calcium intake and decreasing obesity could be public health interventions independent of sun exposure to improve vitamin D status in middle-aged Americans.

Source:
http://www.sciencedirect.com/science/ar ... 6010001901
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Re: Vitamin D: Scientific Studies & News

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A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution

Abstract
Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to diverse disorders, remain poorly understood. We determined VDR binding throughout the human genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After calcitriol stimulation, we identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D. VDR binding sites were significantly enriched near autoimmune and cancer associated genes identified from genome-wide association (GWA) studies. Notable genes with VDR binding included IRF8, associated with MS, and PTPN2 associated with Crohn's disease and T1D. Furthermore, a number of single nucleotide polymorphism associations from GWA were located directly within VDR binding intervals, for example, rs13385731 associated with SLE and rs947474 associated with T1D. We also observed significant enrichment of VDR intervals within regions of positive selection among individuals of Asian and European descent. ChIP-seq determination of transcription factor binding, in combination with GWA data, provides a powerful approach to further understanding the molecular bases of complex diseases.


Source:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945184/
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Re: Vitamin D: Scientific Studies & News

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Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention.


Abstract
BACKGROUND:
Studies indicate that intake of vitamin D in the range from 1,100 to 4,000 IU/d and a serum 25-hydroxyvitamin D concentration [25(OH)D] from 60-80 ng/ml may be needed to reduce cancer risk. Few community-based studies allow estimation of the dose-response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d.

MATERIALS AND METHODS:
A descriptive study of serum 25(OH)D concentration and self-reported vitamin D intake in a community-based cohort (n = 3,667, mean age 51.3 ± 13.4 y).

RESULTS:
Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d.

CONCLUSION:
Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.


Source:
http://www.ncbi.nlm.nih.gov/pubmed/2137 ... t=Abstract
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Re: Vitamin D: Scientific Studies & News

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Vitamin D and the brain


Vitamin D is a member of the superfamily of nuclear steroid transcription regulators and as such, exerts transcriptional control over a large number of genes. Several other steroids, such as thyroid hormones, vitamin A, androgens and the glucocorticoids, are known as ‘neurosteroids’ and their role in brain development and function is well defined. It has only been in the last decade or so that vitamin D has been thought to function as a neurosteroid. In this review we have collated a diverse array of data describing the presence of vitamin D metabolites and the receptor in the brain, the evidence that vitamin D may be an important modulator of brain development, and the potential role of vitamin D in neurological and neuropsychiatric disorders.


Source:

http://www.sciencedirect.com/science/ar ... 0X11000595
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Re: Vitamin D: Scientific Studies & News

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Vitamin D status in a sunny country: Where has the sun gone?

Summary
Background & aims

Hypovitaminosis D [serum 25 vitamin D < 30 ng/ml] is related to the development of metabolic bone disease and greater risk of chronic illnesses. However, it is frequently under-diagnosed, mainly in countries where UV radiation is abundant. We prospectively determined the prevalence and the predictors of serum 25 vitamin D (s25(OH)D) in a healthy Brazilian population after the winter and after the summer.

Methods

603 (118M and 485F) healthy Brazilian volunteers aged 18–90 years from a universitary hospital were selected after the winter of 2006. From the initial sample, 209 volunteers (31M and 178F) accepted to participate in a second health check after the subsequent summer.

Results

After the winter, median s25(OH)D was 21.4 ng/mL and 77.4% of the population presented hypovitaminosis D. s25(OH)D was significantly related to age, BMI, PTH and race. In multivariate linear regression analysis, s25(OH)D was significantly and independently dependent on age, glycemia and skin color. Significant increase in s25(OH)D was verified after summer [10.6 (3.7–19.3 ng/ml); p < 0.001] and this improvement was dependent on age. We also observed a significant decrease in hyperparathyroidism prevalence (20.8% vs. 4.9%; P < 0.0001).

Conclusion

In São Paulo, at the end of winter, we observed a high prevalence of hypovitaminosis D and secondary hyperparathyroidism in healthy adults. s25(OH)D was dependent on age and skin color. After summer, we observed a decrease in the prevalence of hypovitaminosis D. This unexpected finding emphasizes the need for a strong recommendation to monitor s25(OH)D, even in a sunny country such as Brazil.


Source:
http://www.sciencedirect.com/science/ar ... 1410001111
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A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis
Dermatoendocrinol. 2013 Jan 1;5(1):222-34. doi: 10.4161/derm.24808.

Abstract

Autoimmunity has been associated with vitamin D deficiency and resistance, with gene polymorphisms related to vitamin D metabolism frequently described in affected patients. High doses of vitamin D3 may conceivably compensate for inherited resistance to its biological effects. This study aimed to assess the efficacy and safety of prolonged high-dose vitamin D3 treatment of patients with psoriasis and vitiligo. Nine patients with psoriasis and 16 patients with vitiligo received vitamin D3 35,000 IU once daily for six months in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oat, rice or soya "milk") and hydration (minimum 2.5 L daily). All psoriasis patients were scored according to "Psoriasis Area and Severity Index" (PASI) at baseline and after treatment. Evaluation of clinical response of vitiligo patients required a quartile grading scale. All patients presented low vitamin D status (serum 25(OH)D3 ≤ 30 ng/mL) at baseline. After treatment 25(OH)D3 levels significantly increased (from 14.9 ± 7.4 to 106.3 ± 31.9 ng/mL and from 18.4 ± 8.9 to 132.5 ± 37.0 ng/mL) and PTH levels significantly decreased (from 57.8 ± 16.7 to 28.9 ± 8.2 pg/mL and from 55.3 ± 25.0 to 25.4 ± 10.7 pg/mL) in patients with psoriasis and vitiligo respectively. PTH and 25(OH)D3 serum concentrations correlated inversely. The PASI score significantly improved in all nine patients with psoriasis. Fourteen of 16 patients with vitiligo had 25-75% repigmentation. Serum urea, creatinine and calcium (total and ionized) did not change and urinary calcium excretion increased within the normal range. High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients.


Source:
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... A+24494059

Full Text:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897595/
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Re: Vitamin D: Scientific Studies & News

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AntonioBR wrote:Confirmation of association between multiple sclerosis and CYP27B1


Abstract
Multiple sclerosis, MS (OMIM No. 126200), is a complex inflammatory disease that is characterized by lesions in the central nervous system. Both genes and other environmental factors influence disease susceptibility. One of the environmental factors that has been implicated in MS and autoimmune disease, such as type 1 diabetes, is vitamin D deficiency, in which patients have lower levels of 25-hydroxyvitamin D3 (25-OHD3) in blood than do controls. Previtamin D3 is produced in the skin, and turned into 25-OHD3 in the liver. In the kidney, skin and immune cells, 25-OHD3 is turned into bioactive 1,25(OH)2D3 by the enzyme coded by CYP27B1 (cytochrome P450 family 27 subfamily B peptide 1) on chromosome 12q13.1–3. 1,25(OH)2D3 binds to the vitamin D receptor, expressed in T cells and antigen-presenting cells. 1,25(OH)2D3 has a suppressive role in the adaptive immune system, decreasing T-cell and dendritic cell maturation, proliferation and differentiation, shifting the balance between T-helper 1 (Th1) and Th2 cells in favor of Th2 cells and increasing the suppressive function of regulatory T cells. Rs703842 in the 12q13–14 region was associated with MS in a recent study by the Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). We show associations with three SNPs in this region in our Swedish materials (2158 cases, 1759 controls) rs4646536, rs10877012 and rs10877015 (P=0.01, 0.01 and 3.5 × 10−3, respectively). We imputed rs703842 SNP and performed a joint analysis with the ANZgene results, reaching a significant association for rs703842 (P=5.1 × 10−11; odds ratio 0.83; 95% confidence interval 0.79–0.88). Owing to its close association with 25-OHD3, our results lend further support to the role of vitamin D in MS pathology.


Source: http://www.nature.com/ejhg/journal/v18/ ... 0113a.html
http://www.mdpi.com/1099-4300/15/4/1416

Glyphosate's Suppression of Cytochrome P450 Enzymes
By Anthony Samsel and Stephanie Seneff
Entropy 2013, 15(4), 1416-1463, doi:10.3390/e15041416

Abstract

… "Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an overlooked component of its toxicity to mammals. …"

According to the Samsel/Seneff article above, 25-(OH)D3 would NOT be turned into the bioactive form of 1,25 (OH)2D3 in the presence of glyphosate, which suppresses the required cytochrome enzyme (CYP27B1). It is estimated that 80-90% of the American food supply contains glyphosate/Roundup residues. I understand that this herbicide is widely used in South America as well.
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Re: Vitamin D: Scientific Studies & News

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AntonioBR wrote: Source:

Code: Select all

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Re: Vitamin D: Scientific Studies & News

Post by AntonioBR »

NHE wrote:
AntonioBR wrote: Source:

Code: Select all

http://www.sciencedaily.com/releases/2010/04/100429153955.htm
Please don't put URLs within code tags. See the BBCode FAQ for information on formatting posts with BBCode.
Hi NHE,


I changed it.


Thank you.
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