Effect of genetic factors on the response to vitamin D3 supplementation in the VIDARIS randomized controlled trial.

OBJECTIVES: Supplementation provides the best means of improving vitamin D status; however, individual responses vary partly owing to genetics. The aim of this study was to determine whether 28 single nucleotide polymorphisms (SNPs) in six key vitamin D pathway genes (GC, DHCR7, CYP2 R1, CYP24 A1, CYP27 B1, VDR) were associated with differences in response to supplementation. METHODS: Participants (N = 313; n = 160 vitamin D, n = 153 placebo) were part of VIDARIS (Vitamin D and Acute Respiratory Infections Study), a double-blind, randomized controlled trial involving oral monthly supplementation of either vitamin D3 (200 000 IU each for the first 2 mo, thereafter 100 000 IU monthly) or placebo for 18 mo. Circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline and 2, 6, 12, and 18 mo, and vitamin D binding protein (Gc-globulin) and calculated free 25(OH)D concentrations at baseline and 2 mo were obtained. Multiple regression was used to model associations between genetic variants and 25(OH)D, Gc-globulin, and free 25(OH)D concentrations. RESULTS: SNPs within GC, CYP2 R1, and CYP27 B1 were associated with 25(OH)D concentrations following supplementation. However, only two GC gene SNPs (rs2282679, rs1155563) were significant after adjustment for multiple testing. This effect disappeared after more than 2 mo of supplementation. None of the SNPs were significantly associated with Gc-globulin concentrations; however, there was a significant interaction with one SNP in DHCR7 (rs12785878), which was associated with reduced free 25(OH)D concentrations in the supplemented arm. CONCLUSION: Only variants of GC were associated with 25(OH)D concentrations after supplementation. This effect was modest and disappeared after >2 mo of supplementation, suggesting it may be time/dose-dependent and saturable.

The physiological response to cold-water immersion following a mixed martial arts training session.

Combative sport is one of the most physically intense forms of exercise, yet the effect of recovery interventions has been largely unexplored. We investigated the effect of cold-water immersion on structural, inflammatory, and physiological stress biomarkers following a mixed martial arts (MMA) contest preparation training session in comparison with passive recovery. Semiprofessional MMA competitors (n = 15) were randomly assigned to a cold-water immersion (15 min at 10 °C) or passive recovery protocol (ambient air) completed immediately following a contest preparation training session. Markers of muscle damage (urinary myoglobin), inflammation/oxidative stress (urinary neopterin + total neopterin (neopterin + 7,8-dihydroneopterin)), and hypothalamic-pituitary axis (HPA) activation (saliva cortisol) were determined before, immediately after, and 1, 2, and 24 h postsession. Ratings of perceived soreness and fatigue, counter movement jump, and gastrointestinal temperature were also measured. Concentrations of all biomarkers increased significantly (p < 0.05) postsession. Cold water immersion attenuated increases in urinary neopterin (p < 0.05, d = 0.58), total neopterin (p < 0.05, d = 0.89), and saliva cortisol after 2 h (p < 0.05, d = 0.68) and urinary neopterin again at 24 h (p < 0.01, d = 0.57) in comparison with passive recovery. Perceived soreness, fatigue, and gastrointestinal temperatures were also lower for the cold-water immersion group at several time points postsession whilst counter movement jump did not differ. Combative sport athletes who are subjected to impact-induced stress may benefit from immediate cold-water immersion as a simple recovery intervention that reduces delayed onset muscle soreness as well as macrophage and HPA activation whilst not impairing functional performance.

Steroid analysis in saliva: an overview.

The first report of steroid analysis in saliva was more than thirty years ago. Since that time its popularity has increased due to the attractiveness of non-invasive, repeated and simple stress-free sampling. It has proved a popular sampling fluid for psychobiology, sports medicine, pharmacology and paediatric studies as well as in the area of complementary medicine. In the diagnostic laboratory, salivary progesterone and oestradiol have been used for assessing ovarian function and 17alpha-OH progesterone for the diagnosis of congenital adrenal hyperplasia (CAH). Salivary cortisol is used for investigating adrenal function and recently there has been considerable interest in the use of bedtime salivary cortisol levels as a screening test for Cushing's disease. However, there are several caveats on the use of saliva including collection techniques, the variable matrix of saliva, sensitivity, steroid stability, the presence of binding proteins and reference range anomalies. This brief review will attempt to address these issues and provide a balanced approach to steroid analysis in saliva.

Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study.

St John's wort extract (SJW; Hypericum perforatum L.) is taken extensively as a putative herbal antidepressant. It has been shown to induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the clearance of numerous drugs and steroids such as cortisol and ethinyl estradiol. This study was conducted to determine if SJW exposure also alters the concentrations of circulating androgenic steroid hormones. The study was conducted using healthy volunteers (6M, 6F) studied before and after a 14-day treatment period with a SJW preparation previously demonstrated to induce the activity of CYP3A4. Plasma concentrations of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and the combined concentrations of androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were measured by immunoassay methods. The results of analysis demonstrated that SJW did not significantly alter the majority of the androgens studied (p > 0.05) although the combined concentrations of the 5alpha-reduced steroids, AoS and epiAoS, significantly declined following treatment in all subjects (p = 0.02), and in males (p = 0.04). Furthermore, the testosterone to DHT ratio was increased in both men and women. Although the latter increase did not reach statistical significance, it is also consistent with the possible inhibition of 5alpha-reductase by SJW. It is concluded that despite significant induction of CYP3A4, short term administration of SJW does not significantly alter the concentrations of most circulating androgens in men and women but may produce a dimunition in some of the circulating 5alpha-reduced androgens.

Effect of Ginkgo biloba extract on plasma steroid concentrations in healthy volunteers: a pilot study.

STUDY OBJECTIVE: To determine if a standardized ginkgo supplement significantly alters concentrations of circulating androgenic steroids in humans. DESIGN: Open-label, fixed-treatment order, crossover study. SETTING: University general clinical research center. SUBJECTS: Eleven healthy volunteers (six men, five women). INTERVENTION: Volunteers received ginkgo biloba 240 mg/day for 14 days. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of cortisol, 11-deoxycortisol, 17alpha-hydroxyprogesterone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, androstenedione, and free testosterone, as well as free androgen index and combined concentrations of androsterone sulfate and epiandrosterone sulfate, were analyzed in all subjects before and after their 14-day course of ginkgo biloba. Ginkgo biloba did not significantly alter endogenous steroid levels compared with baseline values (p < 0.05). CONCLUSION: A 14-day oral administration of a widely used, standardized ginkgo extract at a generally advocated dosage of 240 mg/day did not significantly alter concentrations of major circulating steroids in men and women.

A simple binding assay for the direct determination of biotin in urine.

BACKGROUND: We have devised a simple assay to detect adequate biotin intake, which uses an alternative configuration from most existing assays. METHODS: The assay depends on the competition of streptavidin peroxidase for immobilized biotin or soluble biotin in standards or samples. Immobilized streptavidin peroxidase is detected using tetramethylbenzidine, and the plates are read at 450 nm. The assay was normalised by determining the biotin/creatinine ratio in the urine of healthy adults. Urinary biotin excretion was measured in unsupplemented pregnant women. The half-life of biotin excretion after a single oral supplement was determined for healthy volunteers. RESULTS: Urinary biotin excretion in unsupplemented pregnant women was 2.9+/-1.9 micromol/mol creatinine (mean+/-S.D.) and was significantly lower (p<0.001) than those of healthy males and females, which were 9.0+/-5.4 and 7.0+/-2.1 micromol/mol creatinine (mean+/-S.D.), respectively. The half-life of a single oral biotin supplement was 30-40 h, with excretion returning to basal levels at 70 h. CONCLUSION: We have devised a novel binding assay for the direct determination of total biotin excretion in urine, which is suitable for routine clinical laboratory. The assay is inexpensive, simple, rapid, and could be fully automated.