Tightrope Walking: Using Predictors of 25(OH)D Concentration Based on Multivariable Linear Regression to Infer Associations with Health Risks.
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SUBMITTER: Ding N
PROVIDER: S-EPMC4445919 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ContextThere is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D).ObjectiveThe objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status.ParticipantsHealthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study.InterventionsThe intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days.Main outcome measures25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured.Results25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country.Conclusions25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.
| S-EPMC4207933 | biostudies-literature
Project description:Background:An estimated one in two healthy adults in the United Kingdom suffer from low levels of 25[OH]D. Vitamin D is involved in modulating immune response, but there is less clarity over its role in orthopaedic infection. This study assesses the relationship between serum 25[OH]D concentration and orthopaedic infection. Methods:A total of 205 patients in a tertiary referral centre for orthopaedic infection were included in the study. They were divided into groups based on their infection status, matched by age and gender. Data were statistically analysed to determine presence and direction of relationship. Results:A total of 114 patients had an infection. There was no statistically significant difference in age or gender between the two groups. Mean serum 25[OH]D concentration was 39 nmol/L in the group with infection and 59 nmol/L in the group without an infection (p<0.01). Overall mean serum 25[OH]D concentration was 48 nmol/L. There was a correlation between low serum 25[OH]D concentration and rate of infection (odds ratio, 5.94; 95% confidence interval [CI], 3.24 to 10.92) with a bivariate correlation of -0.338 (p<0.01). Conclusion:This study demonstrates an association between low levels of serum 25[OH]D and increased orthopaedic infection. Orthopaedic inpatients suffered from vitamin D insufficiency, and there was a correlation between higher levels of serum 25[OH]D and lower rates of infection. This suggests that prophylactic supplementation of 25[OH]D may improve outcomes, and provides a foundation for randomized controlled trials to assess its effectiveness in practice.
| S-EPMC7457855 | biostudies-literature
Project description:Abstract Objectives An important point of contention is whether genetic variation has meaningful impact on vitamin D adequacy on top of known modulators like season, fat mass, skin pigmentation and geographic latitude. Answers could come from information generated by numerous published studies. As a first step towards integration of these often diverse data, the impact of the commonly measured single nucleotide variant rs4588 of the GC gene on 25-hydroxy vitamin D (25OHD) concentration in blood of healthy Caucasian adults was assessed with a systematic review and metaanalysis of published findings. Methods Selection criteria for inclusion of studies in the analyses were Caucasian healthy adults and listing of average 25OHD concentration in plasma or serum by rs4588 or the tightly linked rs2282679 genotypes. Percent differences between genotypes were extracted from included publications. A random-effects model of metaanalysis was performed using STAT 16. Results Of the studies meeting inclusion criteria, published between 2005 and 2019, 35 reported genotype-specific 25OHD concentrations in a total of 59,939 Caucasian adults. The weighted averages were 25.3, 23.2 and 20.4 ng/ml for the GC rs4588 CC, AC and AA genotypes. Relative differences are more informative than absolute concentrations since they are much less affected by calibration discrepancies. The CA carriers had 6.8% lower concentrations than CC carriers and AA carriers 15% lower concentrations when using averages weighted by cohort size. Eight of the included studies with a total number of 15,329 individuals reported standard deviations for the genotype-specific 25OHD concentrations and only these were included for the metaanalysis. The average effect size was −0.44 (95% CI; −0.89, 0.01) for carriers of a single rs4588 A allele, and −0.59 (95% CI; −0.94, −0.23) for carriers of two AA alleles. Heterogeneity was high and statistically significant. Conclusions The combined data indicate that 25OHD concentrations differ by GC rs4588 genotype in healthy adults with predominantly Caucasian ancestry with an additive effect of about 9% per allele. The much lower than average 25OHD concentrations in the about 8% GC rs4588 AA genotype carriers should draw attention to this commonly ignored group when it comes to health risks related to vitamin D deficiency. Funding Sources UNC Nutrition Research Institute internal support
| S-EPMC8181666 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1?,25(OH)?D?, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1?,25(OH)?D?, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1?,25(OH)?D? has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1?,25(OH)?D? concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 ?g/kg or 20 ?g/kg, significantly inhibited SNU308 cells' growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1?,25(OH)?D? and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA.
| S-EPMC5000723 | biostudies-literature
Project description:Pain and stress are both phenomena that challenge an individual's homeostasis and have significant overlap in conceptual and physiological processes. Allostasis is the ability to adapt to pain and stress and maintain homeostasis; however, if either process becomes chronic, it may result in negative long-term outcomes. The negative effects of stress on health outcomes on physiology and behavior, including pain, have been well documented; however, the specific mechanisms of how stress and what quantity of stress contributes to the maintenance and exacerbation of pain have not been identified, and thus pharmacological interventions are lacking. The objective of this brief review is to: 1. identify the gaps in the literature on the impact of acute and chronic stress on chronic pain, 2. highlight future directions for stress and chronic pain research; and 3. introduce the Pain-Stress Model in the context of the current literature on stress and chronic pain. A better understanding of the connection between stress and chronic pain could provide greater insight into the neurobiology of these processes and contribute to individualized treatment for pain rehabilitation and drug development for these often comorbid conditions.
| S-EPMC7113396 | biostudies-literature
Project description:Maintaining an optimal vitamin D concentration reduces the risk of recurrence and extends survival time in patients after breast cancer treatment. Data on vitamin D deficiency among Polish women after breast cancer therapy are limited. Thus, the aim of the study was the analysis of vitamin D status in post-mastectomy patients, considering such factors as seasons, social habits, vitamin D supplementation and its measurements. The study involved 94 women after breast cancer treatment. Serum vitamin D concentration was measured, and a questionnaire, gathering demographic and clinical data regarding cancer, diet, exposure to sun radiation, and knowledge of recommendations on vitamin D supplementation, was delivered twice, in both winter and in summer. The control group consisted of 94 age-matched women with no oncological history. In women after breast cancer treatment, 25-hydroxyvitamin D (25(OH)D) deficiency was much more frequent than in the general population. Only about half of the patients supplemented vitamin D at the beginning of the study. After the first test and the issuing of recommendations on vitamin D supplementation, the percentage of vitamin D supplemented patients increased by about 30% in study groups. The average dose of supplement also increased. None of the women that were not supplementing vitamin D and were tested again in winter had optimal 25(OH)D concentration. It was concluded that vitamin deficiency is common in women treated for breast cancer. Medical advising about vitamin D supplementation and monitoring of 25(OH)D concentration should be improved.
| S-EPMC7915136 | biostudies-literature
Project description:STUDY QUESTION:Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study? SUMMARY ANSWER:There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise. WHAT IS KNOWN ALREADY:Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist. STUDY DESIGN, SIZE, DURATION:This community-based prospective cohort study included 522 women attempting to become pregnant between 2010 and 2016. The women completed online daily and monthly diaries until a positive home pregnancy test was observed or 12 months had elapsed. PARTICIPANTS/MATERIALS, SETTING, METHODS:The study included women from central North Carolina who were aged 30-44 with no history of infertility, with no more than 3 months of attempt time at recruitment. Women recorded vaginal bleeding so that the ongoing number of attempt cycles could be counted and used to quantify a woman's pregnancy attempt time. Blood collected at the study entry was analysed for 25(OH)D using liquid chromatography tandem mass spectrometry. Associations with fecundability were estimated with a log-binomial discrete time-to-event model. MAIN RESULTS AND THE ROLE OF CHANCE:Among 522 women, 257 conceived during the study. The mean age was 33 years and the mean 25(OH)D was 36 ng/ml. There was an estimated 10% higher fecundability with each 10 ng/ml increase in 25(OH)D (fecundability ratio (FR) 1.10, 95% CI: 0.96, 1.25). The suggestive dose-response association with the continuous measure of 25(OH)D was driven by women in the lowest and the highest categories of 25(OH)D. Compared to women with 25(OH)D of 30-40 ng/ml, women below 20 ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50 ng/ml had an estimated 35% increase in fecundability (FR (CI): 1.35 (0.95, 1.91)). Across these three categories (25(OH)D of <20 ng/ml, 30-40 ng/ml and?>?50 ng/ml), the probability of taking longer than 6 months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%). LIMITATIONS, REASONS FOR CAUTION:While the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N?=?107) or low 25(OH)D (N?=?56) was small. WIDER IMPLICATIONS OF THE FINDINGS:Our findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20 ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50 ng/ml). STUDY FUNDING/COMPETING INTEREST(S):This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683 and supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, under projects ES103086, ES049003 and ES044003. ClearBlue ovulation predictor kits were generously donated to AMZJ and AJW by Swiss Precision Diagnostics. Drs Wilcox and Jukic report non-financial support from Swiss Precision Diagnostics during the conduct of the study; Dr Jukic reports non-financial support from Theralogix, LLC, outside the submitted work. Otherwise there are no competing interests. TRIAL REGISTRATION NUMBER:N/A.
| S-EPMC7209776 | biostudies-literature
Project description:OBJECTIVE:The aim of the study was to examine the associations between 25-hydroxyvitamin D (25(OH)D) and biomarkers of ovarian reserve in a large community-based sample of women. METHODS:In 2010 to 2016, women aged 30 to 44 years without any known fertility problems were recruited from the Chapel Hill, NC area for a prospective time-to-pregnancy cohort study. At enrollment 561 women provided a blood sample that was used to measure 25(OH)D, anti-Müllerian hormone (AMH), follicle-stimulating hormone, and inhibin-B. Unadjusted associations were estimated with Spearman correlation coefficients. Multivariable linear regression was used to estimate associations of 25(OH)D with ovarian reserve biomarkers, after adjusting for age, race, body mass index, smoking history, and recent use of hormonal birth control. RESULTS:The mean 25(OH)D was 36?ng/mL (SD?=?11?ng/mL). 25(OH)D was not correlated with AMH, follicle-stimulating hormone, or inhibin-B (all r?<?0.03). Multivariable results with continuous hormonal outcomes were also null. For dichotomous outcomes, there was a tendency for insufficient 25(OH)D (<30?ng/mL) to be associated with low AMH (<0.7?ng/mL) (odds ratio [95% CI]: 1.8 [0.9-4]). CONCLUSIONS:For the most part, 25(OH)D was not associated with ovarian reserve biomarkers in a group of women trying to become pregnant. We found some evidence that low 25(OH)D (<30?ng/mL) was associated with low AMH, but this should be confirmed in studies with a higher prevalence of low 25(OH)D.
| S-EPMC6014875 | biostudies-literature
Project description:ContextThe optimal measure of vitamin D status is unknown.ObjectiveTo directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans.DesignCross-sectional analysis.SettingSeven academic sites.PatientsA total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79).InterventionsMerge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype.Main outcome measuresDistribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates).ResultsFree 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype.ConclusionsTotal 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.
| S-EPMC6126881 | biostudies-literature
Project description:Representative clinical case. A 74-year-old male patient was diagnosed with stage 3 mantle cell lymphoma in 2012. Because he was ineligible for intensive treatment (age, previous myocardial infarction [MI]), he received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy for 6 cycles (reaching complete response) and then rituximab maintenance (RM) for 2 years. One year after the end of RM, he relapsed with disseminated disease. He was started on ibrutinib 560 mg/day. Two weeks after the start of ibrutinib, he developed grade 3 diarrhea that required interruption of ibrutinib. Two weeks after the regular dose was restarted (month 3), the patient had repeated bleeding (patient was receiving aspirin for previous MI) and had to stop ibrutinib again. Because the patient was in partial response (PR) with lack of disease-associated symptoms, he was restarted on ibrutinib 280 mg/day with no further adverse events, and he had maintained PR at last follow-up (month 9 on ibrutinib).
| S-EPMC6142482 | biostudies-literature