Vitamin D

[Michael Scally MD]

Highlights
· VDR is a master transcriptional regulator in pancreatic stellate cells
· VDR ligands suppress pancreatitis
· Stromal VDR activation overcomes chemotherapeutic drug resistance
· VDR ligand plus gemcitabine enhances survival in a PDA mouse model

Sherman MH, Yu RT, Engle DD, et al. Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy. Cell 2014;159(1):80-93. http://www.cell.com/cell/abstract/S0092-8674(14)01033-2

The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment.

Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA.

Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma.

We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone.

This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy.

 

[dmmark]

I took 5000 iu/day for a week then settled down at 2000 iu / day. this put me at the upper limit of the range. my initial reading was below the lower limit.. which I thought impossible.

 

[roastdawg]

I use high vitamin fermented cod liver oil for a and d... has like 1000% rda of each.

 

[Michael Scally MD]

Low Vitamin D Tied to Higher Death Risk


To test the hypothesis that genetically low 25-hydroxyvitamin D concentrations are associated with increased mortality.

For the study, researchers used data from Danish government health records on 95,766 subjects.

All were tested for a genetic variant that reduces their vitamin D levels, and 35,334 also had their vitamin D serum levels measured.

There were 10,349 deaths over the course of the study, from 1981 to 2013.

By studying two large populations, of which one has the genetic variant for low vitamin D and the other does not, researchers were able to virtually eliminate the impact of confounding factors like other diseases, habits and behaviors that might be contributing to poor health.

These traits would be evenly distributed in the populations studied, leaving only the genetic difference between them.

The scientists found that having the genes associated with lifelong low vitamin D increases the risk of cancer death by more than 40 percent and the risk of death from any cause by more than 30 percent. They found no effect on cardiovascular disease death.


Afzal S, Brondum-Jacobsen P, Bojesen SE, Nordestgaard BrG. Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts. BMJ 2014;349. http://www.bmj.com/content/349/bmj.g6330

Objective To test the hypothesis that genetically low 25-hydroxyvitamin D concentrations are associated with increased mortality.

Design Mendelian randomisation analysis.

Setting Copenhagen City Heart Study, Copenhagen General Population Study, and Copenhagen Ischemic Heart Disease Study.

Participants 95 766 white participants of Danish descent from three cohorts, with median follow-up times of 19.1, 5.8, and 7.9 years, genotyped for genetic variants in DHCR7 and CYP2R1 affecting plasma 25-hydroxyvitamin D concentrations; 35 334 also had plasma 25-hydroxyvitamin D measurements. Participants were followed from study entry through 2013, during which time 10 349 died.

Main outcome measures All cause mortality and cause specific mortality, adjusted for common risk factors for all cause mortality based on the World Health Organization’s global health status.

Results The multivariable adjusted hazard ratios for a 20 nmol/L lower plasma 25-hydroxyvitamin D concentration were 1.19 (95% confidence interval 1.14 to 1.25) for all cause mortality, 1.18 (1.09 to 1.28) for cardiovascular mortality, 1.12 (1.03 to 1.22) for cancer mortality, and 1.27 (1.15 to 1.40) for other mortality. Each increase in DHCR7/CYP2R1 allele score was associated with a 1.9 nmol/L lower plasma 25-hydroxyvitamin D concentration and with increased all cause, cancer, and other mortality but not with cardiovascular mortality. The odds ratio for a genetically determined 20 nmol/L lower plasma 25-hydroxyvitamin D concentration was 1.30 (1.05 to 1.61) for all cause mortality, with a corresponding observational multivariable adjusted odds ratio of 1.21 (1.11 to 1.31). Corresponding genetic and observational odds ratios were 0.77 (0.55 to 1.08) and 1.13 (1.03 to 1.24) for cardiovascular mortality, 1.43 (1.02 to 1.99) and 1.10 (1.02 to 1.19) for cancer mortality, and 1.44 (1.01 to 2.04) and 1.17 (1.06 to 1.29) for other mortality. The results were robust in sensitivity analyses.

Conclusions Genetically low 25-hydroxyvitamin D concentrations were associated with increased all cause mortality, cancer mortality, and other mortality but not with increased cardiovascular mortality. These findings are compatible with the notion that genetically low 25-hydroxyvitamin D concentrations may be causally associated with cancer and other mortality but also suggest that the observational association with cardiovascular mortality could be the result of confounding.

 

[Michael Scally MD]

Tak YJ, Lee JG, Kim YJ, et al. Serum 25-hydroxyvitamin D levels and testosterone deficiency in middle-aged Korean men: a cross-sectional study. Asian J Androl. http://www.ajandrology.com/preprintarticle.asp?id=142137

Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was to investigate whether testosterone levels are associated with serum vitamin D levels and whether seasonal variation exists.

This cross-sectional study analyzed serum 25-hydroxyvitamin D [25(OH)D], total testosterone (TT), and free testosterone (FT) in 652 Korean men over 40 years of age who had undergone a comprehensive medical examination.

The average age of the subjects was 56.7 +/- 7.9 years, and the mean serum 25(OH)D, TT and FT levels were 21.23 +/- 7.9 ng ml-1 , 4.70 +/- 1.6 ng ml-1 , and 8.12 +/- 3.3 pg ml-1 , respectively.

In the multiple linear regression model, 25(OH)D showed positive association with TT (beta =0.137, P< 0.001) and FT (beta =0.103, P= 0.008). 25(OH)D and FT showed similar seasonal or monthly variation after adjustment for age.

A vitamin D deficiency [25(OH)D < 20 ng ml-1 ] was associated with an increased risk of deficiencies of TT (<2.30 ng ml-1 ) (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.21-5.78, P= 0.014) and FT (<6.50 pg ml-1 ) (OR: 1.44; 95% CI: 1.01-2.06 P= 0.048) after adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use.

In conclusion, we demonstrated a positive correlation between 25(OH)D and testosterone, which showed similar seasonal variation in Korean men.

 

[Michael Scally MD]

Heijboer AC, Oosterwerff M, Schroten NF, et al. Vitamin D supplementation and testosterone concentrations in male human subjects. Clinical Endocrinology. http://onlinelibrary.wiley.com/doi/10.1111/cen.12711/abstract

Objective A possible association between serum 25-hydroxyvitamin D and testosterone levels has been reported, however, contradictory results have emerged.

Design To investigate a causal link between vitamin D and testosterone status, we studied the effect of vitamin D supplementation on serum testosterone concentrations in three independent intervention studies including male patients with heart failure (study 1), male nursing home residents (study 2) and male non-western immigrants in the Netherlands (study 3).

Methods In study 1, 92 subjects were randomized to either vitamin D (2000 IU cholecalciferol daily) or control. Blood was drawn at baseline, after 3 and 6 weeks.

In study 2, 49 vitamin D deficient subjects received either vitamin D (600IU daily) or placebo. Blood was drawn at baseline and after 8 and 16 weeks.

In study 3, 43 vitamin D deficient subjects received either vitamin D (1200IU daily) or placebo. Blood was drawn at baseline and after 8 and 16 weeks. Serum 25-hydroxyvitamin D levels were measured using LC-MS/MS or radioimmunoassay. Testosterone levels were measured using a 2nd generation immunoassay.

Results Serum 25-hydroxyvitamin D levels significantly increased in all treatment groups (median increase of 27, 30, and 36 nmol/L in study 1, 2, 3, respectively) but not in the control groups. The documented increase in 25-hydroxyvitamin D levels, however, did not affect mean testosterone concentrations at the end of the study (median increase of 0, 0.5, and 0 nmol/L in study 1, 2, and 3, respectively).

Conclusions In this post-hoc analysis of 3 small clinical trials of limited duration in men with normal baseline testosterone concentrations, vitamin D supplementation was not associated with an increase in circulating testosterone concentrations.

 

[Epluribusunum]

Ahhhh Dr. Holick and I heard Dr. Bhasin's name mentioned as well. This is bringing back to me Boston days.

 

[nowandagain]

long but interesting read

 

[Michael Scally MD]

Highlights

• The role of VDR in relation to the sex hormones in elderly is investigated.
• There are relations between vit. D vs testosterone in some VDR genotypes in elderly.
• The results confirm the advantages of supplementation with vit. D in elderly people.

Laczmanski L, Lwow F, Mossakowska M, et al. Association between vitamin D concentration and levels of sex hormones in an elderly Polish population with different genotypes of VDR polymorphisms (rs10735810, rs1544410, rs7975232, rs731236). Gene. https://www.sciencedirect.com/science/article/pii/S0378111915000384

BACKGROUND: Vitamin D co-regulates the synthesis of sex hormones in part by interaction with its nuclear receptor. The aim of this study was to determine whether there is an association of vitamin D concentration vs the level of sex hormones in elderly Polish individuals with different genotypes of the vitamin D receptor (VDR) gene.

MATERIALS AND METHODS: Rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum sex hormone level, free estrogen index (FEI) and free androgen index (FAI) as well as vitamin D, were evaluated in 766 persons (362 women and 404 men) selected from 5695 Polish population, aged 65-90 years from the PolSenior survey.

RESULTS: We observed that women with GG (rs731236), TT (rs7975232), BB (rs1544410) and FF (rs10735810) genotypes were characterized by a significant correlation between vitamin D vs testosterone concentration and FAI value.

We found a significant correlation between testosterone level and FAI vs vitamin D concentration in men with heterozygote AG in the rs731236 polymorphism and in the GG (rs7975232), the BB (rs1544410), and the Ff (rs10735810) genotypes.

CONCLUSION: In elderly selected Polish population with different genotypes of VDR polymorphisms, a statistically significant relationship between vitamin D concentration vs testosterone level was observed.

 

[Michael Scally MD]

Hofer D, Munzker J, Schwetz V, et al. Testicular synthesis and vitamin D action. J Clin Endocrinol Metab 2014;99(10):3766-73. http://press.endocrine.org/doi/abs/10.1210/jc.2014-1690

CONTEXT: The vitamin D system has pleiotropic effects not only in bone metabolism. Its role in testicular steroidogenesis is new and deserves intensive research.

OBJECTIVE: We hypothesize that vitamin D, especially 1,25 dihydroxyvitamin D3 [1,25(OH)2D3 (calcitriol)] induces male steroidogenesis and intend to identify its impact on genes and pathways in testicular androgen regulation.

METHODS: Human adult primary testicular cells were isolated, treated with 1,25(OH)2D3, and their gene expression levels profiled by microarray analysis. Highly regulated genes were confirmed by real-time quantitative PCR. In addition, the effects of 1,25(OH)2D3 in combination with LH and IGF-I on the gene expression level of androgens were assessed. T levels in the culture media were determined by a high-resolution ELISA. The expression of vitamin D receptor was confirmed at baseline and after 1,25(OH)2D3 stimulation using immunocytochemistry.

RESULTS: Microarrays depicted 63 genes significantly regulated by 1,25(OH)2D3, including genes related to male androgen and vitamin D metabolism, mainly triggered by the vitamin D receptor/retinoid X receptor activation. 1,25(OH)2D3 led to significant changes in the expression profiles of reproductive genes and significantly increased T synthesis in human testicular cell cultures.

CONCLUSIONS: Data from our human primary testicular cell culture model suggest that vitamin D plays a major role in male steroidogenesis in vitro.

 

[Michael Scally MD]

Al-Hendy A, Diamond MP, El-Sohemy A, Halder SK. 1, 25-dihydroxyvitamin D3 Regulates Expression of Sex Steroid Receptors in Human Uterine Fibroid Cells. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2014-4011

Context: Uterine fibroids (UF) are the most common benign tumors in premenopausal women. In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 {1, 25(OH)2D3} for the treatment of UF.

Objective: To determine the role of 1, 25(OH)2D3 on the expression of sex steroid receptors in human uterine fibroid cells.

Design: Human UF and their adjacent myometrium were analyzed for expression of estrogen receptor (ER-α), progesterone receptors (PR-A and PR-B), as well as members of the steroid receptor co-activator (SRC) family. Immortalized human uterine fibroid (HuLM) cells were treated with 1, 25(OH)2D3, and assayed for the expression and localization of the aforementioned receptors and SRCs using western blot, immunohistochemistry, immunofluorescence as well as immunoprecipitation assays.

Main Outcome measures: We discovered a correlation between reduced levels of vitamin D receptor (VDR) and increased levels of ER-α, PR-A and PR-B in these tissues. We evaluated the effects of 1, 25(OH)2D3 on the regulation of the aforementioned sex steroid receptors.

Results: We observed an inverse correlation between the up-regulated ER-α, PR-A, and PR-B and expression of VDR in UF. Treatment with 1, 25(OH)2D3 significantly decreased levels of ER-α, PR-A, PR-B as well as SRCs in HuLM cells (p<0.05).

In contrast, 1, 25(OH)2D3 self-induced its own VDR, which resulted in an induction of VDR-RXR-α (retinoid X receptor-alpha) complex in HuLM cells. Together, these results suggest that 1, 25(OH)2D3 functions as an antagonist of sex steroid hormone receptors in HuLM cells.

Conclusions: 1, 25(OH)2D3 functions as a potent anti-estrogenic/anti-progesteronic agent that may have utility as a novel therapeutic option for UF.

 

[Michael Scally MD]

Durup D, Jorgensen HLv, Christensen J, Tjonneland A, Olsen A, et al. A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality - the CopD-study. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2014-4551

CONTEXT: Cardiovascular disease is the major cause of death in the Western World, but the association between 25-hydroxyvitamin D levels and the risk of cardiovascular disease mortality remains unclear.

OBJECTIVE: To determine the association between cardiovascular, stroke and acute myocardial infarct mortality and serum levels of 25(OH)D.

DESIGN: Observational cohort study, the CopD Study, data from a single laboratory center in Copenhagen, Denmark. Follow-up 2004 to 2011.

SETTING: Serum 25(OH)D was analyzed from 247,574 subjects from the Copenhagen general practice sector.

PARTICIPANTS: Examination of the association 25-hydroxyvitamin D levels and mortality from cardiovascular disease, stroke and acute myocardial infarct among 161,428 women and 86,146 men.

MAIN OUTCOME MEASURES: Multivariate Cox regression analysis was used to compute hazard ratios for cardiovascular, stroke and acute myocardial infarct mortality.

RESULTS: Out of 247,574 a total of 16.645 subjects died in the ensuing 0–7 years. 5,454 died from cardiovascular disease including 1,574 from stroke and 702 acute myocardial infarct. 25-hydroxyvitamin D level of 70 nmol/L was associated with the lowest cardiovascular disease mortality risk.

Compared to that level the hazard ratio for cardiovascular disease mortality was 2.0(95% CI 1.8–2.1) at the lower extreme (∼12.5 nmol/L) with higher risk for men 2.5(95% CI 2.2–2.9), than for women 1.7(95% CI 1.5–1.9). At the higher extreme (∼125 nmol/L), the hazard ratio of cardiovascular disease mortality was 1.3(95% CI 1.2–1.4), with similar risk among men and women. Results were similar for stroke and acute myocardial subgroups.

CONCLUSIONS: In this large observational study low and high levels of 25-hydroxyvitamin D were associated with cardiovascular disease, stroke and acute myocardial mortality in a non-linear, reverse J-shaped manner, with highest risk at lower levels.

Whether this was a causal or associational finding cannot be determined from our data.

There is a need for randomized clinical trials which include information on the effects of 25-hydroxyvitamin D levels above 100 nmol/L.

 

[MR10X]

https://www.yahoo.com/health/too-much-vitamin-d-could-be-as-bad-for-you-as-too-113339394967.html
Getting a check up next week and since i dont get in the sun much any more i have been taking 5000 iu of D3 for a few months now and get mine checked...It was 33 last time it was checked....

 

[Michael Scally MD]

[Mice] Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis

Highlights
· Myeloid VDR deletion induces hepatic macrophage deposition and gluconeogenesis
· Myeloid VDR deletion enables M2 monocytes to transport cholesterol into plaques
· Impaired VDR-SERCA2b interaction results in macrophage ER stress and foam cells
· Bone marrow transplant of VDR into KODMAC mice rescues the metabolic phenotype

Oh J, Riek AE, Darwech I, Funai K, Shao J, et al. Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis in Mice. Cell Reports. 2015;10(11):1872-86. http://www.cell.com/cell-reports/fulltext/S2211-1247(15)00201-6

Intense effort has been devoted to understanding predisposition to chronic systemic inflammation because it contributes to cardiometabolic disease.

We demonstrate that deletion of the macrophage vitamin D receptor (VDR) in mice (KODMAC) is sufficient to induce insulin resistance by promoting M2 macrophage accumulation in the liver as well as increasing cytokine secretion and hepatic glucose production.

Moreover, VDR deletion increases atherosclerosis by enabling lipid-laden M2 monocytes to adhere, migrate, and carry cholesterol into the atherosclerotic plaque and by increasing macrophage cholesterol uptake and esterification.

Increased foam cell formation results from lack of VDR-SERCA2b interaction, causing SERCA dysfunction, activation of ER stress-CaMKII-JNKp-PPARγ signaling, and induction of the scavenger receptors CD36 and SR-A1.

Bone marrow transplant of VDR-expressing cells into KODMAC mice improved insulin sensitivity, suppressed atherosclerosis, and decreased foam cell formation.

The immunomodulatory effects of vitamin D in macrophages are thus critical in diet-induced insulin resistance and atherosclerosis in mice.

 

[Michael Scally MD]

Heaney R, Garland C, Baggerly C, French C, Gorham E. Letter to Veugelers, P.J. and Ekwaru, J.P., A statistical error in the estimation of the recommended dietary allowance for vitamin D. Nutrients 2014, 6, 4472-4475; doi:10.3390/nu6104472. Nutrients. 2015;7(3):1688-90. http://www.mdpi.com/2072-6643/7/3/1688/htm

Recently Veugelers and Ekwaru published data [1] indicating that, in its dietary reference intakes for calcium and vitamin D, the Institute of Medicine (IOM) had made a serious calculation error [2]. Using the same data set as had the IOM panel, these investigators showed that the Recommended Dietary Allowance (RDA) for vitamin D had been underestimated by an order of magnitude. Veugelers and Ekwaru, using the IOM’s data, calculated an RDA of 8895 IU per day. They noted that there was some uncertainty in that estimate, inasmuch as this value required an extrapolation from the available data, which did not include individuals receiving daily vitamin D inputs above 2400 IU/day.

In this communication, we present data from a different cohort entirely, including many individuals with vitamin D intakes spanning a range from zero to above 10,000 IU per day. The data presented here are derived from the GrassrootsHealth (GRH) database, which had been characterized elsewhere [3]. Here we examine the probability range for the previously published GRH data at all supplement intakes across the relevant range.

Figure 1 plots the 25(OH)D values for 3657 individuals as a function of their own intakes of vitamin D, showing both the best fit regression line through the data [3] and the 95% confidence limits for the total data set. The horizontal dashed lines in the figure are for serum 25(OH)D values of 20, 30, and 40 ng/mL (50, 75, and 100 nmol/L). The points at which these lines intersect the lower bound of the 95% probability band for serum 25(OH)D reflect the inputs necessary to ensure that 97.5% of the cohort would have a vitamin D status value at or above the respective 25(OH)D concentration. These three values represent, respectively, the recommended values of the IOM, the Endocrine Society [4], and GrassrootsHealth. The precise inputs corresponding to these serum 25(OH)D values are 3875, 6201, and 9122 IU/day.

While the 3875 IU intake value needed to achieve at least 20 ng/mL (50 nmol/L) in 97.5% of the population is lower than the estimate of Veugelers and Ekwaru, it should be noted first that, as Veugelers and Ekwaru had stated, both estimates are roughly an order of magnitude higher than the published IOM value. Also, it must be stressed that this input is explicitly supplemental, i.e., it presumes a daily, basal input from food and sun of some non-zero magnitude. The best-fit regression line through the data, as can be seen in the figure, intersects the Y-axis at a value of 34 ng/mL (85 nmol/L), reflecting an intake from food and sun amounting to somewhat more than 3000 IU per day (5). Since an RDA, by definition, relates to intake from all sources, it is clear that total intake required to achieve 20 ng/mL in 97.5% of the cohort must be close to 7000 IU per day, not substantially different from that calculated by Veugelers and Ekwaru.

Thus, we confirm the findings of these investigators with regard to the published RDA for vitamin and we call for the IOM and all public health authorities concerned with transmitting accurate nutritional information to the public to designate, as the RDA, a value of approximately 7000 IU per day from all sources. We note that this conclusion applies specifically to the IOM’s designation of 20 ng/mL as the lower bound of adequacy, and that higher values, such as that of the Endocrine Society and GRH, would mandate the higher RDA values cited above.

With regard to possible safety concerns related to such a recommendation, we note that:
(a) as the figure shows, the mean 25(OH)D and the upper bound of the 95% probability range for the supplemental intake of 3875 IU/day are less than 50 ng/mL and 100 ng/mL, respectively;
(b) the correctly calculated RDA is well below the cutaneous production of vitamin D from summer sun [5]; and
(c) the total, all-source intake of 7000 IU/day is below the no observed adverse effect level (NOAEL) of both the IOM and the Endocrine Society, below the tolerable upper intake level (UL) of the Endocrine Society, and well within the safe range delineated by Hathcock et al. [6], who had generated that range using the IOM’s method of hazard identification.


References

1. Veugelers, P.J.; Ekwaru, J.P. A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Nutrients 2014;6:4472–5. http://www.mdpi.com/2072-6643/6/10/4472/htm

2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D; The National Academic Press: Washington, DC, USA, 2011.

3. Garland, C.F.; French, C.B.; Baggerly, L.L.; Heaney, R.P. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res. 2011;31:607–12. http://ar.iiarjournals.org/content/31/2/607.long

4. Holick, M.F.; Binkley, N.C.; Bischoff-Ferrari, H.A.; Gordon, C.M.; Hanley, D.A.; Heaney, R.P.; Murad, M.H.; Weaver, C.M. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society Practice Guideline. J. Clin. Endocrinol. Metab. 2011;96:1911–30. http://press.endocrine.org/doi/full/10.1210/jc.2011-0385

5. Heaney, R.P.; Armas, L.A.G. Quantifying the vitamin D economy. Nutr. Rev. 2015;73:51–67. http://nutritionreviews.oxfordjournals.org/content/73/1/51

6. Hathcock, J.N.; Shao, A.; Vieth, R.; Heaney, R.P. Risk assessment for vitamin D. Am. J. Clin. Nutr. 2007;85:6–18. http://ajcn.nutrition.org/content/85/1/6.long

 

[HapticFBK]

I started taking Vitamin D supplements because I was told it might help with this strange persistent cough that I've had since flu season. I just wonder how much exposure to sun do you need before supplements aren't really needed? I spend about 20 hours a week in direct, high-noon Florida sunlight when I'm cycling or running.

 

[Michael Scally MD]

Halfon M, Phan O, Teta D. Vitamin D: A Review on Its Effects on Muscle Strength, the Risk of Fall, and Frailty. Biomed Res Int. http://www.hindawi.com/journals/bmri/2015/953241/

Vitamin D is the main hormone of bone metabolism. However, the ubiquitary nature of vitamin D receptor (VDR) suggests potential for widespread effects, which has led to new research exploring the effects of vitamin D on a variety of tissues, especially in the skeletal muscle.

In vitro studies have shown that the active form of vitamin D, calcitriol, acts in myocytes through genomic effects involving VDR activation in the cell nucleus to drive cellular differentiation and proliferation. A putative transmembrane receptor may be responsible for nongenomic effects leading to rapid influx of calcium within muscle cells.

Hypovitaminosis D is consistently associated with decrease in muscle function and performance and increase in disability. On the contrary, vitamin D supplementation has been shown to improve muscle strength and gait in different settings, especially in elderly patients.

Despite some controversies in the interpretation of meta-analysis, a reduced risk of falls has been attributed to vitamin D supplementation due to direct effects on muscle cells. Finally, a low vitamin D status is consistently associated with the frail phenotype. This is why many authorities recommend vitamin D supplementation in the frail patient.

 

[Michael Scally MD]

Chin KY, Ima-Nirwana S, Wan Ngah WZ. Vitamin D is significantly associated with total testosterone and sex hormone-binding globulin in Malaysian men. Aging Male. 2015. http://informahealthcare.com/doi/abs/10.3109/13685538.2015.1034686

OBJECTIVE: Cross-sectional studies in the Caucasian population have shown a significant relationship between vitamin D and testosterone levels, but data in the Asian population are limited. This study aimed to determine the association between vitamin D and testosterone levels in Malaysian men.

METHODS: Chinese and Malay men (n = 382) aged 20 years or above residing in the Klang Valley, Malaysia were recruited. Their fasting blood was collected for serum testosterone, sex hormone-binding globulin (SHBG) and 25-hydroxyvitamin D (25(OH)D) assays. Relationship between 25(OH)D and testosterone levels was analyzed using multiple regression analysis. Testosterone and SHBG levels among subjects with different vitamin D status were compared using univariate analysis. Confounders such as age, ethnicity and body mass index (BMI) were adjusted.

RESULTS: 25(OH)D was significantly and positively associated with total testosterone and SHBG levels before and after adjustment for age and ethnicity (p < 0.05). Only association with SHBG remained significant after further adjustment for BMI (p < 0.05). Total testosterone and SHBG values displayed an increasing trend from subjects with vitamin D deficiency to those with optimal level (p < 0.05). The trend was attenuated after adjustment for BMI (p > 0.05).

CONCLUSION: 25(OH)D is significantly associated with total testosterone and SHBG in Malaysian men but this association is BMI-dependent.

 

[Michael Scally MD]

Association between Testosterone, Vitamin D and Cardiovascular Risk
http://www.aua2015.org/abstracts/abstractprint.cfm?id=MP51-04

Introduction and Objectives - It has been well established that Vitamin D plays in an important role in bone metabolism, but within the last decade Vitamin D has been shown be associated with the inflammatory cascade as well as immune-modulating properties. Numerous studies have implicated low Vitamin D levels in increased overall mortality, cardiovascular (CV) and cancer mortality.

In fact, Siadat et al showed that low serum 25-hydroxyvitamin D (VitD-25) is associated with prevalent coronary artery disease independent of CV risk factors. Studies have shown a complex relationship between vitamin D and androgen metabolism.

To date, there is conflicting information regarding the association of vitamin D and androgen levels in men. In this abstract, we aim to show relationship between total testosterone (TT) and serum VitD-25 independent of CV risk among asymptomatic middle-aged men.

Methods - We evaluated 824 male participants in the World Trade Center (WTC)-CHEST program from January 2011 to June 2014. Blood samples were analyzed for various laboratory parameters including VitD-25 and total testosterone. Hypovitaminosis D is defined as VitD-25 less than 30.0 ng/L. We used the Framingham 10-year CV disease risk as a proxy for general CV risk.

Results - Insufficient VitD-25 was noted in 68.3% (563) of the participants. Only 11.4% (64) of those with insufficient VitD-25 took Vitamin D supplementation. Subjects with insufficient VitD-25 were significantly younger, and have higher BMI than those with normal VitD-25 (table).

In subjects with hypovitaminosis D, TT was 319.66 +/- 108.85 ng/L which was significantly lower than those with normal VitD-25 whose TT was 341.77 +/- 132.36 (p = 0.013). When adjusted for Framingham 10-year CV Disease risk, subjects with hypovitaminosis D still had significantly lower TT than those with normal TT (p = 0.019)

Conclusions - There is a significant association between hypovitaminosis D and total testosterone among this population of asymptomatic middle-aged men independent of cardiac risk. It is important to evaluate vitamin D levels in men having low total testosterone.

 

[Michael Scally MD]

Huang Y, Jin H, Chen J, Jiang X, Li P, et al. Effect of Vitamin D on basal and Luteinizing Hormone (LH) induced testosterone production and mitochondrial dehydrogenase activity in cultured Leydig cells from immature and mature rams. Anim Reprod Sci. https://www.sciencedirect.com/science/article/pii/S037843201500113X

The objectives of this study were to investigate the potential effects of 1alpha,25-(OH)2VD3 (biologically active form of Vitamin D) on basal and LH-induced testosterone production and mitochondrial dehydrogenase activity in Leydig cells from immature and mature rams cultured in vitro.

Leydig cells were isolated from testes of immature and mature rams, treated without (control) or with increasing concentrations of LH (1, 10, 100ng/ml) and/or 1alpha,25-(OH)2VD3 (1, 10, 100nM).

After 24h, concentrations of testosterone in culture media were measured.

After 96h, mitochondrial dehydrogenase activity in Leydig cells were measured.

In immature and mature ram Leydig cells, treatment with 10 and 100ng/ml LH increased testosterone production and mitochondrial dehydrogenase activity.

Treatment with 1alpha,25-(OH)2VD3 in the absence of LH did not increase testosterone production, but 10 and 100nM 1alpha,25-(OH)2VD3 increased LH induced testosterone production for both immature and mature ram Leydig cells.

Treatment with all doses of 1alpha,25-(OH)2VD3 in the absence of LH and 10 and 100ng/ml LH in the absence of 1alpha,25-(OH)2VD3 increased mitochondrial dehydrogenase activity for cultured Leydig cells from immature and mature rams and 1 and 10nM 1alpha,25-(OH)2VD3 treatment enhanced the LH induced increase in mitochondrial dehydrogenase activity.

Result demonstrate Vitamin D3 induced regulation of function of Leydig cells from immature and mature rams cultured in the presence or absence of LH and support a potential role for Vitamin D3 in regulation of gonadal function in rams.