Vitamin D

[Michael Scally MD]

Blomberg Jensen M. Vitamin D metabolism, sex hormones, and male reproductive function. Reproduction 2012;144(2):135-52. Vitamin D metabolism, sex hormones, and male reproductive function

The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

 

[Michael Scally MD]

Nseir W, Mograbi J, Abu-Rahmeh Z, Mahamid M, Abu-Elheja O, Shalata A. The association between vitamin D levels and recurrent group A streptococcal tonsillopharyngitis in adults. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. Elsevier

Objectives - To determine the association between recurrent group A streptococcal (GAS) tonsillopharyngitis and serum 25-hydroxy (25(OH)) vitamin D among adult subjects.

Methods - Adult patients with tonsillopharyngitis between January 2007 and December 2009 were reviewed and identified retrospectively. Cases with a medical history of recurrent GAS tonsillopharyngitis were compared to age- and gender-matched individuals without a medical history of GAS tonsillopharyngitis. Recurrent tonsillopharyngitis was defined as three or more episodes of GAS tonsillopharyngitis per year for a period of two consecutive years.

Results - Fifty-four cases with recurrent GAS tonsillopharyngitis and 50 controls were enrolled. There were no significant differences between cases and controls with regard to mean age (41 ± 13 vs. 42 ± 12 years; p = 0.7) and male gender (55% vs. 54%; p = 0.6). Mean serum levels of 25(OH) vitamin D among subjects with recurrent GAS tonsillopharyngitis were significantly lower from the controls (11.5 ng/ml ± 4.7 vs. 26 ng/ml ± 7; p = 0.001). Multiple regression analysis showed that a serum 25(OH) vitamin D level <20 ng/ml was associated with recurrent GAS tonsillopharyngitis (odds ratio 1.62, 95% confidence interval 1.51–1.76; p < 0.001).

Conclusions - Our findings indicate a link between vitamin D deficiency and the recurrence of GAS tonsillopharyngitis.

 

[Michael Scally MD]

Ponda MP, Dowd K, Finkielstein D, Holt PR, Breslow JL. The Short-Term Effects of Vitamin D Repletion on Cholesterol. Arteriosclerosis, Thrombosis, and Vascular Biology. The Short-Term Effects of Vitamin D Repletion on Cholesterol

Objective—Vitamin D deficiency is common and associated with dyslipidemia. However, it is unclear whether oral vitamin D supplementation improves the lipid profile. Therefore, we conducted a randomized, placebo-controlled trial to determine the short-term effects of vitamin D repletion on the lipid profile.

Methods and Results—One hundred fifty-one vitamin D?deficient (25-hydroxyvitamin D <20 ng/mL) adults with elevated risk for cardiovascular disease were randomized to receive either 50 000 IU of vitamin D3 weekly for 8 weeks or placebo. The primary outcome was the change in small low-density lipoprotein (LDL) particle number. Secondary outcomes included changes in other nuclear magnetic resonance?based and chemical lipid fractions. Vitamin D failed to improve the lipid profile. Compared with the placebo, vitamin D repletion did not change small LDL particle number (mean change, +18 nmol/L; 95% CI [?80 to +116 nmol/L]; P=0.63). There were also no changes in the chemical lipid profile: total cholesterol (+5.8 mg/dL, 95% CI [?1.4 to +13.0 mg/dL], P=0.14); LDL cholesterol (+3.8 mg/dL, 95% CI [?2.5 to +10.2 mg/dL], P=0.13); high–density lipoprotein cholesterol (+0.4 mg/dL 95% CI [?1.6 to +2.6 mg/dL], P=0.71); and triglycerides (+7.9 mg/dL 95% CI [?6.5 to +22.3 mg/dL]). In the vitamin D repletion group, exploratory multivariate regression analysis demonstrates that changes in LDL cholesterol were positively correlated with the changes in serum calcium (P<0.001) and inversely with the changes in serum parathyroid hormone (P=0.02).

Conclusion—In contrast to the association between low 25-hydroxyvitamin D levels and dyslipidemia, correcting vitamin D deficiency in the short-term does not improve the lipid profile. Repletion of 25-hydroxyvitamin D levels raised serum calcium levels and decreased serum parathyroid hormone levels. These expected physiological responses to vitamin D therapy were correlated with a significant increase in LDL cholesterol.

 

[Michael Scally MD]

Haussler MR, Whitfield GK, Kaneko I, et al. Molecular Mechanisms of Vitamin D Action. Calcif Tissue Int. Calcified Tissue International, Online First™ - SpringerLink

The hormonal metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.

 

[Michael Scally MD]

Tran B, Armstrong BK, Carlin JB, et al. Recruitment and Results of a Pilot Trial of Vitamin D Supplementation in the General Population of Australia. Journal of Clinical Endocrinology & Metabolism. Recruitment and Results of a Pilot Trial of Vitamin D Supplementation in the General Population of Australia

Context: The benefits of high serum levels of 25-hydroxyvitamin D [25(OH)D] are unclear. Trials are needed to establish an appropriate evidence base.

Objective: We plan to conduct a large-scale trial of vitamin D supplementation for the reduction of cancer incidence and overall mortality and report here the methods and results of a pilot trial established to inform its design.

Design: Pilot D-Health was a randomized trial carried out in a general community setting with 12 months intervention and follow-up.

Participants: Participants were 60- to 84-yr-old residents of one of the four eastern Australian states who did not have any vitamin D-related disorders and who were not taking more than 400 IU supplementary vitamin D per day. A total of 644 participants were randomized, and 615 completed the study (two persons withdrew because of nonserious adverse events).Interventions: The interventions were monthly doses of placebo or 30,000 or 60,000 IU vitamin D3.

Main Outcomes: The main outcomes were the recruitment rate and changes in serum 25(OH)D.

Results: Ten percent of those approached were recruited. At baseline, the mean 25(OH)D was 42 nmol/liter in all three study arms. The mean change in 25(OH)D in the placebo group was 0.12 nmol/liter, compared with changes of 22 and 36 nmol/liter in the 30,000- and 60,000-IU groups, respectively.

Conclusions: The D-Health pilot has shown that a large trial is feasible in Australia and that a dose of 2000 IU/d will be needed to ensure that a large proportion of the population reaches the target serum 25(OH)D level.

 

[Michael Scally MD]

Kramer H, Sempos C, Cao G, et al. Mortality Rates Across 25-Hydroxyvitamin D (25[OH]D) Levels among Adults with and without Estimated Glomerular Filtration Rate <60 ml/min/1.73 m2: The Third National Health and Nutrition Examination Survey. PLoS ONE 2012;7(10):e47458. PLOS ONE: Mortality Rates Across 25-Hydroxyvitamin D (25[OH]D) Levels among Adults with and without Estimated Glomerular Filtration Rate <60 ml/min/1.73 m2: The Third National Health and Nutrition Examination Survey

Background - Previous studies exploring the association between 25[OH]D levels and mortality in adults with and without kidney disease utilized 25[OH]D thresholds that have recently been scrutinized by the Institute of Medicine Committee to Review Dietary References Intakes for Vitamin D and Calcium.

Objective - We explored all-cause mortality rates across the spectrum of 25[OH]D levels over an eighteen-year follow-up among adults with and without an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.

Design - The study included 1,097 U.S. adults with eGFR <60 ml/min/1.73 m2 and 14, 002 adults with eGFR ?60 ml/min/1.73 m2. Mortality rates and rate ratios (RR) across 25[OH]D groups were calculated with Poisson regression and restricted cubic splines while adjusting for covariates.

Results - Prevalence of 25[OH]D levels <30 and <20 ng/ml among adults with eGFR <60 ml/min/1.73 m2 was 76.5% (population estimate 6.2 million) and 35.4% (population estimate 2.9 million), respectively. Among adults with eGFR ?60 ml/min/1.73 m2, 70.5% had 25[OH]D levels <30 ng/ml (population estimate 132.2 million) while 30.3% had 25[OH]D levels <20 ng/ml (population estimate 56.8 million). Significantly higher mortality rates were noted among individuals with 25[OH]D levels <12 ng/ml compared to referent group (24 to <30 ng/ml): RR1.41 (95% CI 1.17, 1.71) among individuals with eGFR <60 ml/min/1.73 m2 and RR 1.32 (95% CI 1.13, 1.56) among individuals with eGFR ?60 ml/min/1.73 m2 after adjustment for covariates including co-morbid conditions. Mortality rates were fairly similar across all 25[OH]D groups with levels >20 ng/ml after adjustment for all covariates.

Conclusions - Regardless of presence of eGFR <60 ml/min/1.73 m2, mortality rates across groups with 25[OH]D levels 20–40 ng/ml are similar.

 

[Michael Scally MD]

Major JM, Graubard BI, Dodd KW, et al. Variability and Reproducibility of Circulating Vitamin D in a Nationwide U.S. Population. Journal of Clinical Endocrinology & Metabolism. Variability and Reproducibility of Circulating Vitamin D in a Nationwide U.S. Population

Context: Most studies examining associations between circulating vitamin D and disease are based on a single measure of vitamin D, which may not reflect levels over time, particularly because vitamin D concentrations vary by season. Few studies evaluated how well multiple 25-hydroxyvitamin D [25(OH)D] measures track within the same individual over time.

Objective: This study examined variability and reproducibility of vitamin D by evaluating repeat measurements of plasma 25(OH)D concentrations while accounting for determinants of circulating concentrations including dietary supplement use and latitude of residence from a population of U.S. radiologic technologists.

Design and Participants: We analyzed circulating 25(OH)D in blood samples taken from 538 men and women from a prospective, nationwide study at two time points within a 1-yr period, most measured in different seasons. Inter- and intra-individual variability, reliability coefficients, and measurement error were examined.

Results: The spearman rank correlation between two measurements of 25(OH)D concentrations was moderate (r = 0.75, P < 0.001) and did not vary significantly by participant characteristics including age, race, or latitude. The intraclass correlation coefficient was 0.72 (95% confidence interval = 0.68-0.76). The deattenuation factor of plasma 25(OH)D levels was 1.39, suggesting that a single measure of vitamin D on a continuous scale in regression analyses may result in attenuated relationships of about 40%.

Conclusion: Our results suggest that a single blood sample obtained in spring or fall provides a reasonable average for 25(OH)D over a 1-yr period, but additional studies are needed to estimate variability and agreement in plasma 25(OH)D measurements over longer intervals and younger populations.

 

[JakeZ]

Are you aware of this study here?

http://www.cfids-cab.org/rc/Blaney.pdf

Sounds as if too much 1,25 OH is bad.
My 1,25 OH is a bit elevated while my D3 is normal. Not sure
if I need to be worried now.

 

[Michael Scally MD]

Karakas M, Thorand B, Zierer A, et al. Low Levels of Serum 25-Hydroxyvitamin D Are Associated with Increased Risk of Myocardial Infarction, Especially in Women: Results from the MONICA/KORA Augsburg Case-Cohort Study. Journal of Clinical Endocrinology & Metabolism. Low Levels of Serum 25-Hydroxyvitamin D Are Associated with Increased Risk of Myocardial Infarction, Especially in Women: Results from the MONICA/KORA Augsburg Case-Cohort Study

Context and Objective: A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system. Therefore, we thought to prospectively assess the association between serum 25-hydroxyvitamin D, the most commonly used index of vitamin D status, and incident coronary heart disease.

Design, Setting, and Patients: We measured serum levels of 25[OH]D in 1783 healthy middle-aged subjects (964 men, 819 women) in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg studies. A total of 298 coronary heart disease cases were identified over a mean follow-up period of 11 yr.

Results: After adjustment for age, survey, and season of blood sampling, the hazard ratio (HR) and 95% confidence interval comparing tertile extremes of serum levels of 25[OH]D was 0.32 (0.16–0.65) (P for trend = 0.001) in women and 0.56 (0.38–0.82) (P for trend = 0.005) in men. Further adjustment for traditional cardiovascular risk factors slightly attenuated the association in women [HR 0.39 (0.18–0.84);P for trend = 0.013], whereas it became nonsignificant in men [HR 0.76 (0.49–1.17); P for trend = 0.215]. After additional adjustment for C-reactive protein, IL-6, soluble intercellular adhesion molecule-1, and interferon-?-inducible protein-10, the association still remained significant in women [HR 0.42 (0.19–0.93); P for trend = 0.028], and it was further reduced in men [HR 0.84 (0.52–1.35); P for trend = 0.461].

Conclusion: Our findings suggest that higher vitamin D levels are associated with decreased risk of coronary heart disease. This effect is more pronounced in women than in men. Further clinical and experimental studies are needed to investigate the sex differences and whether vitamin D supplementation could contribute to the prevention of coronary heart disease.

 

[JakeZ]

What exactly are low levels? When do they start?

I also read in a book about vitamin D, that D could be toxic in itself between levels of 50ng/ml and 100ng/ml. The author wrote that low levels are bad but at the same time it's not clear if levels between 50 and 100 might not also be bad. This would mean that D itself has toxic potential. Pretty scary.

 

[idmd]

Pretty scary.

Not really....zombies are scary...not Vit D

 

[JakeZ]

No I mean it's scary not to know if vitamin D itself can be unhealthy.

 

[idmd]

No I mean it's scary not to know if vitamin D itself can be unhealthy.

Almost EVERYTHING in excess is unhealthy. Every medication, supplement, vitamin....what makes vit D any different other than they are trying to figure out the optimal range?

Too little = bad
Too much = bad

 

[JakeZ]

The problem is that the optimal range is very slim if this is true!
20 is too low and over 50 is already too high, according to what I read.
This makes it very hard to stay in the green zone.

 

[idmd]

That's actually a pretty wide range and it's not like Vit D fluctuates all that much. It took me a few months to go from 30 to 54 taking 10000UI a day. Now I only take 5000UI and guess what it's been stable for 3 months.

 

[cj123]

idmd check the penile shrinkage thread I asked you a question . couldnt figure out how to pm you

 

[Michael Scally MD]

Levin GP, Robinson-Cohen C, de Boer IH, et al. Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical Outcomes. JAMA.2012;308(18):1898-1905. JAMA Network | JAMA: The Journal of the American Medical Association | Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical OutcomesVitamin D Concentrations and Clinical Outcomes

Context - Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D.

Objective - To investigate whether common variation within genes encoding the vitamin D–binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes.

Design, Setting, and Participants - Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n = 835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies.

Main Outcome Measure - Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up.

Results - Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism.

Conclusion - Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor.

 

[techlogik]

No I mean it's scary not to know if vitamin D itself can be unhealthy.

How is vitamin D unhealthy?

If you go out in to the sun, your body/skin will produce Vit D...that is how it works naturally. You also get it from other natural food sources.

Taking 10,000ius a day, yes, that can be bad, as others have posted, anything in excess can be bad for you.

 

[Michael Scally MD]

Gorham E, Garland C, Burgi A, et al. Lower prediagnostic serum 25-hydroxyvitamin D concentration is associated with higher risk of insulin-requiring diabetes: a nested case–control study. Diabetologia 2012;55(12):3224-7. Diabetologia, Volume 55, Number 12 - SpringerLink

Aims/Hypothesis - Low serum 25-hydroxyvitamin D [25(OH)D] concentration may increase risk of insulin-requiring diabetes.

Methods - A nested case–control study was performed using serum collected during 2002–2008 from military service members. One thousand subjects subsequently developed insulin-requiring diabetes. A healthy control was individually matched to each case on blood-draw date (±2 days), age (±3 months), length of service (±30 days) and sex. The median elapsed time between serum collection and first diagnosis of diabetes was 1 year (range 1 month to 10 years). Statistical analysis used matched pairs and conditional logistic regression.

Results - ORs for insulin-requiring diabetes by quintile of serum 25(OH)D, from lowest to highest, were 3.5 (95% CI 2.0, 6.0), 2.5 (1.5, 4.2), 0.8 (0.4, 1.4), 1.1 (0.6, 2.8) and 1.0 (reference) (p trend <0.001). The quintiles (based on fifths using serum 25(OH)D concentration in the controls) of serum 25(OH)D in nmol/l, were <43 (median 28), 43–59 (median 52), 60–77 (median 70), 78–99 (median 88) and >/= 100 (median 128).

Conclusions/interpretation - Individuals with lower serum 25(OH)D concentrations had higher risk of insulin-requiring diabetes than those with higher concentrations. A 3.5-fold lower risk was associated with a serum 25(OH)D concentration >/= 60 nmol/l.

 

[idmd]

From everything I've read 60 seems like a good goal. Not too high and not too low. I was around 54 last time I checked and haven't been sick a single time since bumping vit D up....this is in spite of three school ages kids who constantly have some disease.