Vitamin D

[Michael Scally MD]

McKibben RA, Zhao D, Lutsey PL, et al. Factors associated with change in 25-hydroxyvitamin D levels over longitudinal followup in the ARIC study. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2015-1711

Context: A single measurement of 25-hydroxyvitamin D [25(OH)D] may not accurately reflect long-term vitamin D status. Little is known about change in 25(OH)D levels over time, particularly among blacks.

Objective: To determine longitudinal changes in 25(OH)D levels among Atherosclerosis Risk in Communities (ARIC) study participants.

Design: Longitudinal study.

Setting: General community.

Participants: 9890 white and 3222 black participants at visit 2 (1990–1992), 888 whites and 876 blacks at visit 3 (1993–1994), and 472 blacks at the brain visit (2004–2006).

Main Outcome Measure: 25(OH)D levels were measured, and regression models were used to assess associations between clinical factors and longitudinal changes in 25(OH)D.

Results: Vitamin D deficiency [<50 nmol/L (<20 ng/ml)] was seen in 23% and 25% of whites at visits 2 and 3, and in 61%, 70%, and 47% of blacks at visits 2, 3, and the brain visit, respectively. 25(OH)D levels were correlated between visits 2 and 3 (3–year interval) among whites (r=0.73) and blacks (r=0.66). Among blacks, the correlation between visit 2 and brain visit (14-year interval) was 0.33.

Overall, increasing 25(OH)D levels over time were associated with male gender, use of vitamin D supplements, greater physical activity, and higher HDL-C (p<0.001).

Decreases in 25(OH)D levels over time were associated with current smoking, higher body mass index, higher education, diabetes, and hypertension (all p<0.05).

Conclusions: Among U.S. blacks and whites, 25(OH)D levels remained relatively stable over time. Certain modifiable lifestyle factors were associated with change in 25(OH)D levels over time.

 

[Michael Scally MD]

Spiller HA, Good TF, Spiller NE, Aleguas A. Vitamin D exposures reported to US poison centers 2000-2014: Temporal trends and outcomes. Hum Exp Toxicol. http://het.sagepub.com/content/early/2015/10/26/0960327115595685.abstract

There has been an increased use of vitamin D both by prescription and by the public as a widely available supplement. We evaluated 15 years of single-substance vitamin D exposures to US poison centers.

METHODS: Retrospective analysis of data from the National Poison Data System (NPDS) to evaluate clinical effects, trends, and outcomes of exposures to vitamin D over the period January 1, 2000 through June 30, 2014. Cases were limited to exposures involving vitamin D as a single substance. Multiple vitamin products that may have included vitamin D were not included in this study.

RESULTS: From 2000 through June 30, 2014, there were 25,397 human exposures to vitamin D reported to NPDS. There was a mean of 196 cases per year from 2000 to 2005, followed by a 1600% increase in exposures between 2005 and 2011 to a new annual mean of 4535 exposures per year. The mean and median ages were 23.4 years and 10 years, respectively. There were no fatalities, but five (0.02%) major effect outcomes. Serious medical outcomes (major or moderate outcome) were infrequent, ranging from 2 patients/year to 22 patients/year. Clinical effects were primarily gastrointestinal (0.7-1.5%) and mild neurological effects (0.2-0.4%). There was a decline in the percentage of patients treated in a health care facility and of patients with serious medical outcome.

CONCLUSION: Despite the enormous increase in number of exposures, there was not a significant increase in patients with a serious medical outcome. Rare severe outcomes may occur.

 

[Michael Scally MD]

Johnson K, Sattari M. Vitamin D deficiency and fatigue: an unusual presentation. Springerplus 2015;4:584. http://www.springerplus.com/content/4/1/584

Fatigue is a vague but common complaint that is poorly characterized by physicians as well as patients.

While fatigue may result from a number of different etiologies, at the present time, a comprehensive approach to each patient with fatigue does not include routine measurement of serum vitamin D levels.

A 61-year-old man was evaluated for excessive daytime fatigue.

No features characteristic for depression, sleep apnea, or narcolepsy were present.

A comprehensive work-up, including thyroid function tests and testosterone levels, did not reveal any abnormalities.

However, serum 25-hydroxyvitamin D level was low, at 18.4 ng/mL.

Vitamin D supplementation was initiated. At follow-up in 3 and 12 months, the patient reported complete resolution of daytime fatigue, corresponding to an increase in his vitamin D levels.

Possible mechanisms for clinical improvement include effects of vitamin D on components of inflammatory cascades, including tumor necrosis factor-alpha and prostaglandin D2, which result in decrease in central nervous system homeostatic sleep pressure.

While more research is needed to determine if patients presenting with fatigue should be routinely screened for vitamin D deficiency, clinicians should consider obtaining vitamin D levels in patients with unexplained fatigue, nonspecific musculoskeletal pain, and risk factors for vitamin D deficiency.

 

[Michael Scally MD]

Associations of Vitamin D Status and Vitamin D-Related Polymorphisms with Sex Hormones

Highlights
· Vitamin D might influence sex hormone and gonadotropin levels.
· We studied relationships between 25(OH)D, gene polymorphisms and sex hormone levels.
· Lower Vitamin D status is associated with lower testosterone levels.
· There was no association between gene polymorphisms and sex hormone levels.

Rafiq R, van Schoor NM, Sohl E, et al. Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men. J Steroid Biochem Mol Biol. https://www.sciencedirect.com/science/article/pii/S0960076015301394

OBJECTIVE: Evidence regarding relationships of serum 25-hydroxyvitamin D (25(OH)D) with sex hormones and gonadotropin concentrations remains inconsistent. Polymorphisms in vitamin D-related genes may underly these relationships. Our aim was to examine the relationship of vitamin D status and polymorphisms in vitamin D-related genes with sex hormone and gonadotropin levels.

DESIGN AND MEASUREMENTS: We analysed data from the Longitudinal Aging Study Amsterdam, an ongoing population-based cohort study of older Dutch individuals (65-89 years).

We included data of men with measurements of serum 25-hydroxyvitamin D (25(OH)D) (n=643) and determination of vitamin D-related gene polymorphisms (n=459). 25(OH)D concentrations were classified into four categories: <25, 25-50, 50-75 and >75 nmol/L.

Outcome measures were total testosterone, calculated bioavailable and free fraction testosterone, SHBG, estradiol, LH and FSH concentrations. Hypogonadism was defined as a total testosterone level <8.0 nmol/L.

RESULTS: Serum 25(OH)D was positively associated with total and bioavailable testosterone levels.

After adjustments for confounders, men with serum 25(OH)D less than 25 (n=56), 25-50 (n=199) and 50-75 nmol/L (n=240) had lower total testosterone levels compared to men with serum 25(OH)D higher than 75 nmol/L (n=148) (Beta(95% confidence interval): -2.1(-3.7 to -0.4 nmol/L), -0.8(-1.9 to 0.4 nmol/L) and -1.4 (-2.4 to -0.3 nmol/L), respectively).

For bioavailable testosterone the association was significant only for men with serum 25(OH)D less than 25 nmol/L (-0.8 (-1.4 to -0.1 nmol/L)) compared to men with serum 25(OH)D >75 nmol/L.

Serum 25(OH)D was not related to SHBG, estradiol or gonadotropin levels.

Hypogonadism (n=29) was not associated with lower serum 25(OH)D.

No significant differences were found in hormone levels between the different genotypes of the vitamin D-related gene polymorphisms. Also, the polymorphisms did not modify the relationships of serum 25(OH)D with sex hormones or gonadotropins.

CONCLUSION: Vitamin D status is positively associated with testosterone levels. No association was found between vitamin D-related gene polymorphisms and hormone levels.

 

[Michael Scally MD]

[Open Access] Vitamin D Deficiency In Europe: Pandemic?

BACKGROUND: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys.

OBJECTIVE: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe.

DESIGN: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked sera.

These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data.

RESULTS: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively.

According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations.

CONCLUSIONS: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population.

Cashman KD, Dowling KG, Skrabakova Z, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. http://ajcn.nutrition.org/content/early/2016/02/10/ajcn.115.120873.abstract

 

[Michael Scally MD]

Vitamin D and Gonadal Function in Men: A Potential Inverse U-Shaped Association?

Accumulating evidence from animal and human studies suggests that vitamin D, apart from its regulatory effects on musculoskeletal health, is involved in reproductive function in both genders.

The basis of the interplay between vitamin D and reproduction lays on the presence of both vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1) enzyme in reproductive organs.

In males, VDR are present in testis, epididymis, prostate, and seminal vesicles. In Sertoli cells, whose secretory activities are ion channel-dependent, vitamin D has been shown to stimulate calcium uptake through a nuclear receptor activity.

Epidemiological studies support a positive association between serum 25-hydroxy-vitamin D [25(OH)D] concentrations and sperm motility in both fertile and infertile men.

In addition, large multi-center, cross-sectional studies from Europe and USA have shown positive, linear association between 25(OH)D and androgen concentrations. On the contrary, there are studies that support an inverse U-shaped association, that is, men with both low and high 25(OH)D concentrations demonstrate poorer gonadal function compared with those with intermediate concentrations.

Given the rapid increase in over-the-counter use of vitamin D supplements by men that anticipate advantageous health outcomes, the aim of the present commentary is to provide an overview of the studies that present either U-shaped or linear association between 25(OH)D concentrations and male gonadal function.

Karras S, Anagnostis P, Kotsa K, Goulis DG. Vitamin D and gonadal function in men: a potential inverse U-shaped association? Andrology. Vitamin D and gonadal function in men: a potential inverse U-shaped association? - Karras - 2016 - Andrology - Wiley Online Library

 

[Michael Scally MD]

Anic GM, Albanes D, Rohrmann S, et al. Association between serum 25-hydroxyvitamin D and serum sex steroid hormones among men in NHANES. Clinical Endocrinology. Association between serum 25-hydroxyvitamin D and serum sex steroid hormones among men in NHANES - Anic - 2016 - Clinical Endocrinology - Wiley Online Library

Background: Recent literature suggests that high circulating vitamin D may increase prostate cancer risk. Although the mechanism through which vitamin D may increase risk is unknown, vitamin D concentration could influence circulating sex steroid hormones that may be associated with prostate cancer; an alternate explanation is that it could be associated with prostate-specific antigen (PSA) concentration causing detection bias.

Objective: We examined whether serum vitamin D concentration was associated with sex steroid hormone and PSA concentrations in a cross-sectional analysis of men in the National Health and Nutrition Examination Surveys (NHANES).

Design: Testosterone, oestradiol, sex hormone binding globulin (SHBG), androstanediol glucuronide, and 25-hydroxyvitamin D (25(OH)D) were measured in serum from men ages 20 and older participating in NHANES III (n=1,315) and NHANES 2001-2004 (n=318). Hormone concentrations were compared across 25(OH)D quintiles, adjusting for age, race/ethnicity, body fat percentage, and smoking. PSA concentration was estimated by 25(OH)D quintile in 4,013 men from NHANES 2001-2006.

Results: In NHANES III higher testosterone (quintile (Q) 1=17.2, 95% confidence interval (CI)=16.1-18.6; Q5=19.6, 95% CI=18.7-20.6 nmol/L, p-trend=0.0002) and SHBG (Q1=33.8, 95% CI=30.8-37.0; Q5=38.4, 95% CI=35.8-41.2 nmol/L, p-trend=0.0005) were observed with increasing 25(OH)D. Similar results were observed in NHANES 2001-2004. PSA concentration was not associated with serum 25(OH)D (p-trend=0.34).

Conclusion: Results from these nationally representative studies support a positive association between serum 25(OH)D and testosterone and SHBG. The findings support an indirect mechanism through which vitamin D may increase prostate cancer risk, and suggest the link to prostate cancer is not due to PSA-detection bias.

 

[Michael Scally MD]

McDonnell SL, Baggerly C, French CB, et al. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. PLoS ONE 2016;11(4):e0152441. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

Background - Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations.

Objectives - To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations.

Methods - Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer.

Results - Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12–0.90).

Conclusions - 25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined.

 

[Michael Scally MD]

[OA] Assessment of Vitamin D Status - A Changing Landscape

In recent years it has been shown that vitamin D deficiency is associated with an increased incidence as well as the progression of a broad range of diseases including osteoporosis, rickets, cardiovascular disease, autoimmune disease, multiple sclerosis and cancer. Consequently, requests for the assessment of vitamin D status have increased dramatically.

Despite significant progress in the analysis of vitamin D metabolites and an expansion of our pathophysiological knowledge of vitamin D, the assessment of vitamin D status remains a challenging and partially unresolved issue. Current guidelines from scientific bodies recommend the measurement of 25-hydroxy vitamin D (25-OHD) in blood as the preferred test.

However, growing evidence indicates significant limitations of this test, including analytical aspects and interpretation of results. In addition, the relationships between 25-OHD and various clinical indices, such as bone mineral density and fracture risk, are rather weak and not consistent across races.

Recent studies have systematically investigated new markers of vitamin D status including the vitamin D metabolite ratio (VMR) (ratio between 25-OHD and 24,25-dihydroxy vitamin D), bioavailable 25-OHD [25-OHD not bound to vitamin D binding protein (DBP)], and free 25-OHD [circulating 25-OHD bound to neither DBP nor albumin (ALB)]. These parameters may potentially change how we will assess vitamin D status in the future.

Although these new biomarkers have expanded our knowledge about vitamin D metabolism, a range of unresolved issues regarding their measurement and the interpretation of results prevent their use in daily practice. It can be expected that some of these issues will be overcome in the near future so that they may be considered for routine use (at least in specialized centers).

In addition, genetic studies have revealed several polymorphisms in key proteins of vitamin D metabolism that affect the circulating concentrations of vitamin D metabolites. The affected proteins include DBP, 7-dehydrocholesterol synthase and the vitamin D receptor (VDR).

Here we aim to review existing knowledge regarding the biochemistry, physiology and measurement of vitamin D. We will also provide an overview of current and emerging biomarkers for the assessment of vitamin D status, with particular attention methodological aspects and their usefulness in clinical practice.

Herrmann M, Farrell CL, Pusceddu I, Fabregat-Cabello N, Cavalier E. Assessment of vitamin D status - a changing landscape. Clin Chem Lab Med. http://www.degruyter.com/view/j/cclm.ahead-of-print/cclm-2016-0264/cclm-2016-0264.xml

Vitamin D metabolism and Assessment.

In the liver vitamin D is hydroxylated in 25-hydroxy-vitamin D (25-OHD) by the enzyme CYP2R1.

Subsequently, 25-OHD is hydroxylated to bioactive 1α,25-dihydroxy-vitamin D (1,25-(OH)2D) by the enzyme CYP27B1, predominantly in the kidney.

Vitamin D catabolism is predominantly due to CYP24A1, which metabolises 25-OHD to 24,25-dihydroxy-vitamin D (24,25-OH2D) and 1,25-(OH)2D to 1,24,25-dihydroxy-vitamin D (1,24,25-OH3D).

Circulating vitamin D is bound to carriers (vitamin D binding protein (DBP), albumin and lipoproteins).

Bioavailable vitamin D (BAVD), vitamin D metabolite ratio (VMR), automated immunoassay (automated IA).

 

[Michael Scally MD]

Serum Vitamin D and Sex Hormones Levels in Men and Women

Highlights
· We examined the relationship between vitamin D and sex hormone levels among men and women.
· Low vitamin D was associated with lower sex hormone binding globulin and higher free testosterone levels in men and women.
· Low vitamin D levels was associated with lower estradiol and higher dehydroepiandrosterone levels in women.
· These associations between vitamin D and sex hormones were independent of adiposity and lifestyle.
· Future research is needed to determine whether vitamin D treatment influences sex hormone levels.

INTRODUCTION: 25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity.

AIM: To examine associations of 25(OH)D concentrations with sex hormone levels.

METHODS: Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort.

MAIN OUTCOME MEASURES: Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone.

RESULTS: The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively.

In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L).

In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity.

CONCLUSIONS: Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels.

Zhao D, Ouyang P, de Boer IH, et al. Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA). Maturitas 2017;96:95-102. http://www.maturitas.org/article/S0378-5122(16)30391-7/abstract

 

[Michael Scally MD]

Backx EMP, Tieland M, Maase K, et al. The impact of 1-year vitamin D supplementation on vitamin D status in athletes: a dose-response study. Eur J Clin Nutr 2016;70(9):1009-14. http://www.nature.com/ejcn/journal/v70/n9/full/ejcn2016133a.html

Background/Objectives: To assess the prevalence of vitamin D deficiency in Dutch athletes and to define the required dosage of vitamin D3 supplementation to prevent vitamin D deficiency over the course of a year.

Subjects/Methods: Blood samples were collected from 128 highly trained athletes to assess total 25(OH)D concentration. Of these 128 athletes, 54 male and 48 female athletes (18–32 years) were included in a randomized, double blind, dose–response study.

Athletes with either a deficient (<50 nmol/l) or an insufficient (50–75 nmol/l) 25(OH)D concentration were randomly assigned to take 400, 1100 or 2200 IU vitamin D3 per day orally for 1 year.

Athletes who had a total 25(OH)D concentration above 75 nmol/l at baseline continued with the study protocol without receiving vitamin D supplements.

Serum total 25(OH)D concentration was assessed every 3 months, as well as dietary vitamin D intake and sunlight exposure.

Results: Nearly 70% of all athletes showed an insufficient (50–75 nmol/l) or a deficient (<50 nmol/l) 25(OH)D concentration at baseline.

After 12 months, serum 25(OH)D concentration had increased more in the 2200 IU/day group (+50±27 nmol/l) than the sufficient group receiving no supplements (+4±17 nmol/l; P<0.01) and the 1100 IU/day group (+25±23 nmol/l; P<0.05).

Supplementation with 2200 IU/day vitamin D resulted in a sufficient 25(OH)D concentration in 80% of the athletes after 12 months.

Conclusions: Vitamin D deficiency is highly prevalent in athletes. Athletes with a deficient or an insufficient 25(OH)D concentration can achieve a sufficient 25(OH)D concentration within 3 months by taking 2200 IU/day.

 

[Tinyuniverse31]

This has been very interesting. I take the jym multi with a zinc tab at night and tons of little separate vitamins but no extra d I may have to add some in

 

[Michael Scally MD]

[OA] Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol

BACKGROUND AND OBJECTIVES: Vitamin D deficiency is frequent during the winter and occurs throughout the year in the elderly or patients suffering from autoimmune diseases. The objective of this study was to evaluate the pharmacokinetic properties of oral supplementation versus a single intramuscular injection of cholecalciferol in healthy individuals.

RESEARCH DESIGN AND METHODS: Up to 8,000 I.U. oral cholecalciferol was administered daily for 84 days in a 4 week dose-escalation setting to vitamin D deficient individuals. In another cohort, a single intramuscular injection of 100,000 I.U. cholecalciferol was given.

In both cohorts, individuals without vitamin D intake served as the comparison group. 25-hydroxyvitamin D (25(OH)D) concentrations were measured in all individuals at defined time points throughout the studies.

RESULTS: The mean 25(OH)D serum concentration increased significantly after oral cholecalciferol intake compared to the control group (day 28: 83.4 nmol/l and 42.5 nmol/l; day 56: 127.4 nmol/l and 37.3 nmol/l; day 84: 159.7 nmol/l and 30.0 nmol/l). In individuals receiving 100,000 I.U. cholecalciferol intramuscular, the mean 25(OH)D serum concentration peaked after 4 weeks measuring 70.9 nmol/l compared to 32.7 nmol/l in the placebo group (p = 0.002). The increase of 25(OH)D serum concentrations after 28 days was comparable between both routes of administration (p = 0.264).

CONCLUSIONS: Oral and intramuscular cholecalciferol supplementation effectively increased serum 25(OH)D concentrations.

Wylon K, Drozdenko G, Krannich A, Heine G, Dolle S, Worm M. Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol. PLoS One 2017;12(1):e0169620. Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol

 

[Michael Scally MD]

Effects of Cholecalciferol Vs. Calcifediol On Total and Free 25-Hydroxyvitamin D

Context: Vitamin D deficiency (25-hydroxyvitamin D [25D] <20 ng/ml) disproportionately affects non-Caucasian individuals.

Controversy persists over:
1) how to best restore low 25D levels; and
2) how to best define vitamin D status (total [protein-bound + free] vs. free 25D).

Objective: To assess:
1) the effects of vitamin D3 (cholecalciferol, D3) vs. pharmacologic 25-hydroxyvitamin D3 (calcifediol, 25D3) on total and free 25D in a multi-ethnic cohort of adults; and
2) whether change in parathyroid hormone (PTH) is more strongly associated with total vs. free 25D.

Design: 16-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks.

Intervention: 60 mcg (2,400 IU)/day of D3 or 20 mcg/day of 25D3.

Setting: Academic medical center.

Participants: 35 adults >18 years with 25D levels <20 ng/ml.

Main Outcome Measures: Total and free 25D, PTH.

Results: Baseline total (16.2 + 3.7 vs. 17.0 + 2.5 ng/ml, p=0.4) and free (4.2 + 0.8 vs. 4.7 + 1.0 pg/ml, p=0.2) 25D were similar between D3 and 25D3 groups, respectively.

25D3 increased total (+25.5 vs. +13.8 ng/ml, p=0.001) and free (+6.6 vs. +3.5 pg/ml, p=0.03) 25D more than D3. By 4 weeks, 87.5% of 25D3 participants had total 25D levels >30 ng/ml, compared to 23.1% of D3 participants (p=0.001). These trends were consistent across race/ethnicity. Change in PTH was similarly associated with both total (p=0.01) and free 25D (p=0.04).

Conclusions: 25D3 increased total and free 25D levels more rapidly than D3, regardless of race/ethnicity. Free and total 25D were similarly associated with change in PTH.

Shieh A, Ma C, Chun RF, et al. Effects of cholecalciferol vs. calcifediol on total and free 25-hydroxyvitamin D and parathyroid hormone. J Clin End Metab. 2017. https://academic.oup.com/jcem/article/2982842/Effects-of-cholecalciferol-vs-calcifediol-on-total

 

[william12]

What about this?!
Vitamin D Supplements Are Not Effective, And Could Be Dangerous, Studies Find

 

[Dr__Jan_Itor]

Well the last part where they talk about the increase in fractures with high Vitamine D is long known that's why you should take vitamin K with it.
Also if you are in the sun alot anf your body produces alot of vit d on its own it's advised to take vitamin K.

 

[Soloshino]

Last year, before I took any vitamin D supplements and spent little time out in the sun, my level came up at 22. After one year of using 50,000 iu vitamin D2 per week, it only increased to 36. Now I am taking 100,000 iu per week in hopes of reaching 70 by the end of the year.

 

[Soloshino]

What about this?!
Vitamin D Supplements Are Not Effective, And Could Be Dangerous, Studies Find

It depends on what your level is. Not everybody absorbs it efficiently. I saw a study showing that some people only need 1/7 of the amount through supplementation as others to achieve the same increases in body levels. Only a level above 100 is ostensibly dangerous and that's extremely rare to see.

 

[ddp7]

@Michael Scally MD Dr Scally Do you have hear the problem regarding the measure of vit d and VDR?

Whats the bottom line? Thanks

 

[Michael Scally MD]

Lerchbaum E, Pilz S, Trummer C, et al. Vitamin D And Testosterone In Healthy Men: A Randomized-Controlled Trial. The Journal of Clinical Endocrinology & Metabolism. Vitamin D And Testosterone In Healthy Men: A Randomized-Controlled Trial | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic

Context: Available evidence shows an association of vitamin D with androgen levels in men. However, results from preliminary randomized controlled trials (RCTs) are conflicting.

Objective: To evaluate whether vitamin D supplementation increases total testosterone (TT) levels in healthy men.

Design: The Graz Vitamin D&TT-RCT is a single-center, double-blind, randomized placebo-controlled trial conducted between December 2012 and January 2017.

Setting: Endocrine outpatient clinic at the Medical University of Graz, Austria

Participants: 100 healthy men with TT levels ≥10.4 nmol/l and 25-hdroxyvitamn D (25[OH]D) levels <75 nmol/l. 98 men completed the study.

Intervention: Subjects were randomized to receive 20000 IU of vitamin D3/week (n=50) or placebo (n=50) for 12 weeks.

Main Outcome Measures: Primary outcome was TT measured using mass spectrometry. Secondary outcomes were free testosterone (FT), free androgen index (FAI), SHBG, estradiol, FSH, and LH, metabolic characteristics, and body composition.

Results: In healthy men (mean age, 25[OH]D, and TT were 39 [±13] years, 53.3 [±18.3] nmol/l, and 19.1 [±5.6] nmol/l, respectively) we found no significant treatment effect on TT, but a significant effect on quantitative insulin sensitivity check index (QUICKI) and a trend towards decreased MATSUDA-index. In the vitamin D group, median changes (IQR) for TT, QUICKI, and MATSUDA-index were 0.5 (-0.63-0.63) nmol/l (p=0.497), -0.02 (-0.04-0.01) (p=0.034), and -0.9 (-3.2-0.8) (p=0.051), respectively.

Conclusions: Vitamin D treatment has no effect on TT levels in middle-aged healthy men with normal baseline TT but significantly decreased QUICKI. Additional studies investigating vitamin D effects on TT and insulin sensitivity in healthy men are required.