Vitamin D

[Michael Scally MD]

Hofer D, Münzker J, Schwetz V, et al. Testicular synthesis and vitamin D action. The Journal of Clinical Endocrinology & Metabolism. 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(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 (RT qPCR). In addition, effects of 1,25(OH)2D3 in combination with luteinizing hormone (LH) and insulin-like growth factor 1 (IGF-1) on gene expression level of androgens were assessed.

Testosterone levels in the culture media were determined by high-resolution ELISA. The expression of vitamin D receptor (VDR) was confirmed at baseline and after 1,25(OH)2D3 stimulation using immunocytochemistry.

Results: - Microarrays depicted sixty-three genes significantly regulated by 1,25(OH)2D3, including genes related to male androgen and vitamin D metabolism, mainly triggered by VDR/RXR receptor activation. 1,25(OH)2D3 led to significant changes in the expression profiles of reproductive genes and significantly increased testosterone 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.

 

[BBC3]

I just want to ITERATE this CONCEPT as a thread to its own due to perceived importance. From what I have read. It APPEARS that the scientific world MAY be on the verge of CALLING VITAMIN D ..... A HORMONE....! , and as a technical ... Or already does..... but it kinda makes ya stop and wonder - WHERE IS THE LINE... What about Vit A? Or Vit E..?! Perhaps a revisit in WHAT actually qualifies a "HORMONE".....

 

[shaila]

It's essential to have the right amounts of Vitamin in your body at all times.Intake of certain types of foods will help in building the amount of vitamins in your body.You can visit http://healthcareathomeindia.com/ for additional information on health.

 

[Michael Scally MD]

Lerchbaum E, Pilz S, Trummer C, et al. Serum vitamin D levels and hypogonadism in men. Andrology. http://onlinelibrary.wiley.com/doi/10.1111/j.2047-2927.2014.00247.x/abstract

There is inconsistent evidence on a possible association of vitamin D and androgen levels in men. We therefore aim to investigate the association of 25-hydroxyvitamin D (25(OH)D) with androgen levels in a cohort of middle-aged men.

This cross-sectional study included 225 men with a median (interquartile range) age of 35 (30–41) years. We measured 25(OH)D, total testosterone (TT) and SHBG concentrations. Hypogonadism was defined as TT <10.4 nmol/L.

We found no significant correlation of 25(OH)D and androgen levels. Furthermore, androgen levels were not significantly different across 25(OH)D quintiles. The overall prevalence of hypogonadism was 21.5% and lowest in men within 25(OH)D quintile 4 (82–102 nmol/L).

We found a significantly increased risk of hypogonadism in men within the highest 25(OH)D quintile (>102 nmol/L) compared to men in quintile 4 (reference) in crude (OR 5.10, 1.51–17.24, p = 0.009) as well as in multivariate adjusted analysis (OR 9.21, 2.27–37.35, p = 0.002). We found a trend towards increased risk of hypogonadism in men within the lowest 25(OH)D quintile (≤43.9 nmol/L).

In conclusion, our data suggest that men with very high 25(OH)D levels (>102 nmol/L) might be at an increased risk of hypogonadism. Furthermore, we observed a trend towards increased risk of hypogonadism in men with very low vitamin D levels indicating a U-shaped association of vitamin D levels and hypogonadism.

With respect to risk of male hypogonadism, our results suggest optimal serum 25(OH)D concentrations of 82–102 nmol/L.

 

[foreveryoung]

so what is your theory as to the need for vitamin D supplementation for those that are on TRT, would it be less necessary?

 

[beedix]

My TRT/general doc puts me on vit d3...mostly due to pasty completion and working a desk gig . Good info though.

 

[Michael Scally MD]

[USANA Health Sciences, Inc., or USANA, is a Utah-based Multi-Level Marketing company that produces various nutritional products.]

Levy MA, McKinnon T, Barker T, et al. Predictors of vitamin D status in subjects that consume a vitamin D supplement. Eur J Clin Nutr. http://www.nature.com/ejcn/journal/vaop/ncurrent/full/ejcn2014133a.html

Background/Objective: Although dietary supplement use has increased significantly among the general population, the interplay between vitamin D supplementation and other factors that influence vitamin D status remains unclear. The objective of this study was to identify predictor variables of vitamin D status in free-living subjects to determine the extent to which vitamin D supplements and other factors influence vitamin D status.

Subjects/Methods: This was a retrospective, cross-sectional study involving 743 volunteers. Serum 25-hydroxy-vitamin D (25(OH)D) level and the variables diet, supplement usage, latitude of residence, ethnicity, age and body mass index (BMI) were used to predict vitamin D status in a summer and winter cohort.

Results: Supplemental vitamin D3 consumption was the most significant positive predictor, whereas BMI was the most significant negative predictor, of vitamin D status in each cohort. Other positive predictors were fortified beverage and dairy consumption in the summer and winter cohort, respectively.

Negative predictors were: African American, Asian and Hispanic race in the summer; latitude of residence >36 degrees N, Asian and Hispanic ethnicity in the winter. Mean(+/-s.d.) 25(OH)D levels were 101.1 (+/-42.1) and 92.6 (+/-39.0) nmol/l in summer and winter, respectively. Comparing non-supplement vs supplement users, approximately 38 vs 2.5% in the winter and 18 vs 1.4% in the summer had vitamin D levels <50 nmol/l.

Conclusions: Vitamin D supplementation was the most significant positive predictor of vitamin D status. Collectively, these data point to the practicality of utilizing vitamin D supplements to reduce hypovitaminosis D in adults throughout the United States.

 

[beedix]

Good stuff. One of the few supplementary vitamins that seems effective from the research so far.

 

[Michael Scally MD]

The effects of vitamin D on skeletal muscle strength, muscle mass and muscle power: a systematic review and meta-analysis of randomized controlled trials. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2014-1742

Context - There is growing evidence that vitamin D plays a role on several tissues including skeletal muscle.

Objective - To summarize with a meta-analyse the effects of vitamin D supplementation on muscle function.

Data Sources - A systematic research of randomized controlled trials, performed between 1966 and January 2014 has been conducted on Medline, Cochrane Database of Systematics Reviews, Cochrane Central Register of Controlled and completed by a manual review of the literature and congressional abstracts.

Study Selection - All forms and doses of vitamin D supplementation, with or without calcium supplementation, compared with placebo or control were included. Out of the 225 potentially relevant articles, 30 randomized controlled trials involving 5615 individuals (mean age: 61.1 years) met the inclusion criteria.

Data Extraction - Data were extracted by two independent reviewers.

Data Synthesis - Results revealed a small but significant positive effect of vitamin D supplementation on global muscle strength with a standardized mean difference (SMD) of 0.17 (p=0.02). No significant effect was found on muscle mass (SMD 0.058; p=0.52) or muscle power (SMD 0.057; p=0.657). Results on muscle strength were significantly more important with people who presented a 25-hydroxyvitamin D level <30 nmol/L. Supplementation seems also more effective on people aged 65 years or older compared to younger subjects (SMD 0.25; 95% CI 0.01 to 0.48 versus SMD 0.03; 95% CI -0.08 to 0.14).

Conclusions - Vitamin D supplementation has a small positive impact on muscle strength but additional studies are needed to define optimal treatment modalities, including dose, mode of administration and duration.

 

[boxcar]

will any vit d supp work? Or can anyone rec one?
I'm past the low point on the range and my doc told me to low dose a bit d supl

 

[TheWall]

will any vit d supp work? Or can anyone rec one?
I'm past the low point on the range and my doc told me to low dose a bit d supl

A nurse at my PP recommended 5000 iu a day. I have heard/read anywhere from 5000 to 10000IU a day. We get 10K+ IU from 15 min in full sun, so there is that.

I take 5000IU a day and have returned to an olive skin tone from pasty white. I was a lifeguard for years and had a great tan, then after college took an office job. From that time on, pasty and sunburned very easily.

Since I started 5000IU, I tan again and have not burned.

 

[boxcar]

A nurse at my PP recommended 5000 iu a day. I have heard/read anywhere from 5000 to 10000IU a day. We get 10K+ IU from 15 min in full sun, so there is that.

I take 5000IU a day and have returned to an olive skin tone from pasty white. I was a lifeguard for years and had a great tan, then after college took an office job. From that time on, pasty and sunburned very easily.

Since I started 5000IU, I tan again and have not burned.

Great info man.

But, what supp do you take? like what brand? is it oral? liquid?

 

[MR10X]

https://www.yahoo.com/health/clear-link-found-between-vitamin-d-deficiency-and-94074543072.html
I'm taking 4000iu D3 a day in split doses.......

 

[TheWall]

Great info man.

But, what supp do you take? like what brand? is it oral? liquid?

I take Nature's Made D3 5000IU Liquigels.

http://www.naturemade.com/vitamins/vitamin-d/vitamin-d-lsg-5000-iu

 

[Michael Scally MD]

Singh G, Bonham AJ. A Predictive Equation to Guide Vitamin D Replacement Dose in Patients. The Journal of the American Board of Family Medicine 2014;27(4):495-509. http://www.jabfm.org/content/27/4/495.full

Background: Vitamin D is essential for bone health and probably the health of most nonskeletal tissues. Vitamin D deficiency is widespread, and recommended doses are usually inadequate to maintain healthy levels. We conducted a retrospective observational study to determine whether the recommended doses of vitamin D are adequate to correct deficiency and maintain normal levels in a population seeking health care. We also sought to develop a predictive equation for replacement doses of vitamin D.

Methods: We reviewed the response to vitamin D supplementation in 1327 patients and 3885 episodes of vitamin D replacement and attempted to discern factors affecting the response to vitamin D replacement by conducting multiple regression analyses.

Results: For the whole population, average daily dose resulting in any increase in serum 25-hydroxyvitamin D level was 4707 IU/day; corresponding values for ambulatory and nursing home patients were 4229 and 6103 IU/day, respectively.

Significant factors affecting the change in serum concentrations of 25-hydroxyvitamin D, in addition to the dose administered, are (1) starting serum concentration of 25-hydroxyvitamin D, (2) body mass index (BMI), (3) age, and (f) serum albumin concentration.

The following equation predicts the dose of vitamin D needed (in international units per day) to affect a given change in serum concentrations of 25-hydroxyvitamin D: Dose = [(8.52 − Desired change in serum 25-hydroxyvitamin D level) + (0.074 × Age) – (0.20 × BMI) + (1.74 × Albumin concentration) – (0.62 × Starting serum 25-hydroxyvitamin D concentration)]/(−0.002). Analysis of the dose responses among 3 racial groups—white, black, and others—did not reveal clinically meaningful differences between the races.

The main limitation of the study is its retrospective observational nature; however, that is also its strength in that we assessed the circumstances seen in usual health care setting.

Conclusions: The recommended daily allowance for vitamin D is grossly inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients. About 5000 IU vitamin D3/day is usually needed to correct deficiency, and the maintenance dose should be ≥2000 IU/day. The required dose may be calculated from the predictive equations specific for ambulatory and nursing home patients.

 

[Linna123]

Hi,
One of the best way to prevent Vitamin D deficiency is to eat foods that are rich in the vitamin. Best sources are fish such as salmon, mackerel, and herring. Cod liver oil which used to be the cure for rickets many years ago is also a great source.

 

[Michael Scally MD]

Mechanisms By Which Vitamin D Deficiency May Confer Cardiovascular Risk

Potential effects of vitamin D metabolism on the cardiovascular system are divergent, but share common initial steps of nuclear and plasma membrane VDR activation.

VDR, vitamin D receptor; 1, 25-OH D2, 1, 25-dihydroxyvitamin D; RXR, retinoid-X receptor; Ca+, calcium cation; ANP, atrial natriuretic peptide; MMP, matrix metalloproteinases; VDRE, vitamin D response elements (promoter region of target genes); RAS, renin–angiotensin system; VEGF, vascular endothelial growth factor; VSMC, vascular smooth muscle cells.




Al Mheid I, Patel RS, Tangpricha V, Quyyumi AA. Vitamin D and cardiovascular disease: is the evidence solid? Eur Heart J 2014;34(48):3691-8. http://eurheartj.oxfordjournals.org/content/34/48/3691.long

Vitamin D deficiency, prevalent in 30-50% of adults in developed countries, is largely due to inadequate cutaneous production that results from decreased exposure to sunlight, and to a lesser degree from low dietary intake of vitamin D.

Serum levels of 25-hydroxyvitamin D (25-OH D) <20 ng/mL indicate vitamin D deficiency and levels >30 ng/mL are considered optimal.

While the endocrine functions of vitamin D related to bone metabolism and mineral ion homoeostasis have been extensively studied, robust epidemiological evidence also suggests a close association between vitamin D deficiency and cardiovascular morbidity and mortality.

Experimental studies have demonstrated novel actions of vitamin D metabolites on cardiomyocytes, and endothelial and vascular smooth muscle cells. Low 25-OH D levels are associated with left ventricular hypertrophy, vascular dysfunction, and renin-angiotensin system activation.

Despite a large body of experimental, cross-sectional, and prospective evidence implicating vitamin D deficiency in the pathogenesis of cardiovascular disease, a causal relationship remains to be established.

Moreover, the cardiovascular benefits of normalizing 25-OH D levels in those without renal disease or hyperparathyroidism have not been established, and questions of an epiphenomenon where vitamin D status merely reflects a classic risk burden have been raised.

Randomized trials of vitamin D replacement employing cardiovascular endpoints will provide much needed evidence for determining its role in cardiovascular protection.

 

[Michael Scally MD]

Bouillon R, Verlinden L. Does a better vitamin D status help to reduce cardiovascular risks and events? Endocrine. http://link.springer.com/article/10.1007/s12020-014-0429-1

Vitamin D is one and maybe even the most frequently used “drug” in the world as it is recommended as supplement during the early years of life from infancy onwards, and is also recommended systematically for all elderly subjects with little exposure to sunlight.

This is mainly inspired by the essential role of the vitamin D endocrine system for bone health.

The vitamin D receptor and activating enzyme, CYP27B1, are both fairly generally expressed in most tissues and the vitamin D hormone, 1,25(OH)2D, also regulates a great number of genes, far more than needed for calcium transport.

Therefore the question and hypothesis arise that the vitamin D endocrine system would have many extra-skeletal effects and that vitamin D supplementation may help to reduce the burden of nearly all major human diseases.

The cardiovascular system may well be such non classical target tissue for vitamin D action based on a vast and rapidly increasing number of publications and reviews in basic and clinical journals, and even in the lay press.

Two manuscripts published in the present issue of endocrine add new data for this debate.

 

[Michael Scally MD]

Gill TK, Hill CL, Shanahan EM, et al. Vitamin D levels in an Australian population. BMC Public Health 2014;14(1):1001. http://www.biomedcentral.com/1471-2458/14/1001/abstract

BACKGROUND: Levels of vitamin D in the population have come under increasing scrutiny, however there are only a few studies in Australia which measure levels in the general population. The aim of this study was to measure the levels of vitamin D within a large population cohort and examine the association with seasons and selected demographic and health risk factors.

METHODS: A longitudinal cohort study of 2413 participants in the northwest suburbs of Adelaide, South Australia conducted between 2008 and 2010 was used to examine serum levels of 25-hydroxy vitamin D (25(OH)D) in relation to demographic characteristics (age, sex, income, education and country of birth), seasons, the use of vitamin D supplements and selected health risk factors (physical activity, body mass index and smoking). Both unadjusted and adjusted mean levels of serum 25(OH)D were examined, as were the factors associated with the unadjusted and adjusted prevalence of serum 25(OH)D levels below 50 and 75 nmol/L.

RESULTS: Overall, the mean level of serum 25(OH)D was 69.2 nmol/L with 22.7% of the population having a serum 25(OH)D level below 50 nmol/L, the level which is generally recognised as vitamin D deficiency. There were significantly higher levels of 25(OH)D among males compared to females (t = 4.65, p < 0.001). Higher levels of 25(OH)D were also measured in summer and autumn compared with winter and spring. Generally, mean levels of 25(OH)D were lower in those classified as obese.

Smokers and those undertaking no or less than 150 minutes/week of physical activity also had lower levels of serum vitamin D. Obesity (as classified by body mass index), season and undertaking an insufficient level of physical activity to obtain a health benefit were significantly associated with the prevalence of vitamin D deficiency.

CONCLUSIONS: Vitamin D deficiency is prevalent in South Australia, affecting almost one quarter of the population and levels are related to activity, obesity and season even when adjusted for confounding factors. Improved methods of addressing vitamin D levels in population are required.

 

[Michael Scally MD]

Garland CF, Kim JJ, Mohr SB, et al. Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Public Health 2014;104(8):e43-50. http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2014.302034

We examined the relationship between serum 25-hydroxyvitamin D (25[OH]D) and all-cause mortality. We searched biomedical databases for articles that assessed 2 or more categories of 25(OH)D from January 1, 1966, to January 15, 2013. We identified 32 studies and pooled the data.

The hazard ratio for all-cause mortality comparing the lowest (0-9 nanograms per milliliter [ng/mL]) to the highest (> 30 ng/mL) category of 25(OH)D was 1.9 (95% confidence interval = 1.6, 2.2; P < .001). Serum 25(OH)D concentrations less than or equal to 30 ng/mL were associated with higher all-cause mortality than concentrations greater than 30 ng/mL (P < .01).

Our findings agree with a National Academy of Sciences report, except the cutoff point for all-cause mortality reduction in this analysis was greater than 30 ng/mL rather than greater than 20 ng/mL.