Vitamin D Abstracts 2

© 2012

Vitamin D-gene interactions in multiple sclerosis

            (Berlanga-Taylor, Disanto et al. 2011) Download

Vitamin D has been studied for over a century and its functions related to calcium homeostasis are well established. Over the last 30 years or so it has become increasingly clear that it has a wider role in physiology and, importantly, also in disease. Vitamin D deficiency has been linked to multiple sclerosis (MS); however the molecular mechanisms of this association were poorly understood. Recent technological advances have provided major insights as to how vitamin D may exert its role, particularly through the actions of the vitamin D receptor (VDR). In this review we aim to highlight the importance of the interaction between vitamin D and MS associated genes which provide a biological basis for the association between vitamin D and MS risk.

Use of a novel vitamin d bioavailability test demonstrates that vitamin D absorption is decreased in patients with quiescent crohn's disease

            (Farraye, Nimitphong et al. 2011) Download

BACKGROUND:: Vitamin D deficiency is a common problem in patients with Crohn's disease (CD). The aim of this study was to determine the ability of normal subjects and patients with quiescent CD to absorb vitamin D(2) using a novel vitamin D bioavailability test. In addition, we evaluated whether the location of disease or previous surgery had any influence on the bioavailability of vitamin D(2) in CD patients. METHODS:: Ten normal subjects (50% female) and 37 CD patients with quiescent disease (51% female) were included in this study. Subjects who recently received any vitamin D(2) were excluded. The vitamin D bioavailability test was performed in all subjects. After a baseline blood draw, all subjects were then given a single 50,000 IU oral dose of vitamin D(2) in a capsule formulation and had their blood drawn 12 hours later to determine serum vitamin D(2), which reflected their vitamin D(2) absorption capacity. RESULTS:: Forty-two percent and 29% of CD patients were found to be either vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] </=20 ng/mL] or insufficient [25(OH)D 21-29 ng/mL], respectively. Twelve hours after ingesting 50,000 IU vitamin D(2), vitamin D(2) levels rose from a baseline of 0.7 +/- 0.7 ng/mL (mean +/- SEM) to 49.8 +/- 3.0 ng/mL in normal subjects. In CD patients, baseline vitamin D(2) levels rose from 0 ng/mL to 34.8 +/- 2.8 ng/mL. CD patients had on average a 30% decrease in their ability to absorb vitamin D(2) (P = 0.01). Moreover, we found a wide variability of vitamin D(2) bioavailability in CD patients. Analysis of variance (ANOVA) revealed no statistical difference of vitamin D(2) bioavailability between patients in the CD subgroup stratified by the location of disease, the type of surgery, and receiving or not receiving surgery. CONCLUSIONS:: More than 70% of the patients with quiescent CD were vitamin D-deficient or insufficient. The ability to absorb vitamin D(2) in CD patients is unpredictable and the only way to determine this is to perform a vitamin D bioavailability test. Use of this test may guide clinicians in administering the appropriate therapeutic dose of vitamin D for treating vitamin D deficiency in patients with CD. (Inflamm Bowel Dis 2011;).

Symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency leading to statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle

            (Glueck, Abuchaibe et al. 2011) Download

Myositis-myalgia is the most common cause of statin intolerance, leading to cessation of statin use, with consequent failure to lower LDL cholesterol to target levels for primary and secondary prevention of cardiovascular disease (CVD). We hypothesize that symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent 25 (OH) vitamin D deficiency and statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle. In hypercholesterolemic, vitamin D deficient patients, intolerant to statins because of myositis-myalgia, three non-blinded clinical case series have uniformly demonstrated that after supplementation with oral vitamin D2 which normalizes serum 25 (OH) vitamin D levels, statins can be successfully re-instituted in >90% of patients, without recurrent myositis-myalgia, with reduction of LDL cholesterol to target levels. Empirically, in 68 hypercholesterolemic patients, unable to tolerate>/=1 statin because of myositis-myalgia, selected by low (<32 ng/ml) serum 25 (OH) vitamin D, we have prospectively assessed whether resolution of vitamin D deficiency would result in statin tolerance, free of myositis-myalgia. On no statins, 50,000 units of vitamin D2 was given twice/week for 3 weeks, and was then continued once/week. After 3 weeks on vitamin D supplementation, statins were restarted, and patients were re-assessed after 3 months on statins while continuing vitamin D supplementation. At 3 months follow-up, on vitamin D supplementation and re-instituted statins, 62 of 68 (91%) previously statin-intolerant patients now tolerated statins well and were asymptomatic without myositis-myalgia. In these 68 patients, on vitamin D supplementation and statins, mean+/-SD vitamin D rose from 22+/-7 to 43+/-13 ng/ml (p<0.0001), and LDL cholesterol fell from 162+/-55 to 101+/-35 mg/dl (p<0.0001). Despite published and new empirical evidence, the medical establishment has refused to accept the hypothesis, requiring placebo-controlled, double-blind studies, none having been reported to date. A placebo-controlled, double-blind study is needed to document that normalization of serum 25 (OH) vitamin D levels in vitamin D deficient, statin intolerant patients would facilitate re-introduction of statins with concurrent freedom from myositis-myalgia. The ability to reverse myositis-myalgia in vitamin D deficient, statin intolerant, hypercholesterolemic patients by vitamin D supplementation would be extraordinarily valuable, facilitating reinstitution of statins to lower LDL cholesterol to reduce risk of CVD events. We hypothesize that symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency producing statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle.

1alpha,25-Dihydroxyvitamin D3 exerts tissue-specific effects on estrogen and androgen metabolism

            (Lundqvist, Norlin et al. 2011) Download

It is well-known that 1alpha,25-dihydroxyvitamin D(3) and analogs exert anti-proliferative and pro-differentiating effects and these compounds have therefore been proposed to be of potential use as anti-cancer agents. Due to its effects on aromatase gene expression and enzyme activity, 1alpha,25-dihydroxyvitamin D(3) has been proposed as an interesting substance in breast cancer treatment and prevention. In the present study, we have examined the effects of 1alpha,25-dihydroxyvitamin D(3) on estrogen and androgen metabolism in adrenocortical NCI-H295R cells, breast cancer MCF-7 cells and prostate cancer LNCaP cells. The NCI-H295R cell line has been proposed as a screening tool to study endocrine disruptors. We therefore studied whether this cell line reacted to 1alpha,25-dihydroxyvitamin D(3) treatment in the same way as cells from important endocrine target tissues. 1alpha,25-Dihydroxyvitamin D(3) exerted cell line-specific effects on estrogen and androgen metabolism. In breast cancer MCF-7 cells, aromatase gene expression and estradiol production were decreased, while production of androgens was markedly increased. In NCI-H295R cells, 1alpha,25-dihydroxyvitamin D(3) stimulated aromatase expression and decreased dihydrotestosterone production. In prostate cancer LNCaP cells, aromatase expression increased after the same treatment, as did production of testosterone and dihydrotestosterone. In summary, our data show that 1alpha,25-dihydroxyvitamin D(3) exerts tissue-specific effects on estrogen and androgen production and metabolism. This is important knowledge about 1alpha,25-dihydroxyvitamin D(3) as an interesting substance for further research in the field of breast cancer prevention and treatment. Furthermore, the observed cell line-specific effects are of importance in the discussion about NCI-H295R cells as a model for effects on estrogen and androgen metabolism.


References

Berlanga-Taylor, A. J., G. Disanto, et al. (2011). "Vitamin D-gene interactions in multiple sclerosis." J Neurol Sci 311(1-2): 32-6.

Farraye, F. A., H. Nimitphong, et al. (2011). "Use of a novel vitamin d bioavailability test demonstrates that vitamin D absorption is decreased in patients with quiescent crohn's disease." Inflamm Bowel Dis.

Glueck, C. J., C. Abuchaibe, et al. (2011). "Symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency leading to statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle." Med Hypotheses 77(4): 658-61.

Lundqvist, J., M. Norlin, et al. (2011). "1alpha,25-Dihydroxyvitamin D3 exerts tissue-specific effects on estrogen and androgen metabolism." Biochim Biophys Acta 1811(4): 263-70.