Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.

OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.

The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer.

BACKGROUND: Vitamin D, specifically serum 25(OH)D has been associated with mortality, cancer and multiple other health endpoints in observational studies, but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population-wide supplementation. We have therefore launched the D-Health Trial, a randomized trial of vitamin D supplementation for prevention of mortality and cancer. Here we report the methods and describe the trial cohort. METHODS: The D-Health Trial is a randomized placebo-controlled trial, with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers. Participants aged 65-84years were recruited from the general population of Australia. The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo. The primary outcome is all-cause mortality. Secondary outcomes are total cancer incidence and colorectal cancer incidence. RESULTS: We recruited 21,315 participants to the trial between February 2014 and May 2015. The participants in the two arms of the trial were well-balanced at baseline. Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health, to be current smokers or to have diabetes than the Australian population. However, the proportion overweight or with health conditions such as arthritis and angina was similar. CONCLUSIONS: Observational data cannot be considered sufficient to support interventions delivered at a population level. Large-scale randomized trials such as the D-Health Trial are needed to inform public health policy and practice.

Multifocal papular deep bacterial pyoderma in a Boxer dog caused by Pseudomonas aeruginosa.

A young adult Boxer dog was presented with a papular dermatitis on the dorsal back and ventral neck that had developed while it was being treated with cyclosporine and cephalexin for atopic dermatitis and secondary superficial staphylococcal pyoderma, respectively. Histopathology demonstrated nodular to diffuse pyogranulomatous dermatitis with focal furunculosis. Numerous bacterial rods, free in the tissue and engulfed by neutrophils and macrophages, could be demonstrated on stained samples (haematoxylin-eosin; Giemsa). Bacterial culture from an aseptically collected skin biopsy punch sample yielded a pure growth of Pseudomonas aeruginosa, sensitive to a variety of antimicrobials. Successful treatment was accomplished following discontinuation of cyclosporine and an extended course of enrofloxacin. There has not been a recurrence of the pseudomonal pyoderma during the subsequent 2 years.

Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis.

Testicular necrosis is a sensitive endpoint for cadmium (Cd(2+), Cd) toxicity across all species tested. Resistance to Cd-induced testicular damage is a recessive trait assigned to the Cdm locus on mouse chromosome 3. We first narrowed the Cdm-gene-containing region to 880 kb. SNP analysis of this region from two sensitive and two resistant inbred strains demonstrated a 400-kb haplotype block consistent with the Cd-induced toxicity phenotype; in this region is the Slc39a8 gene encoding a member of the solute-carrier superfamily. Slc39a8 encodes SLC39A8 (ZIP8), whose homologs in plant and yeast are putative zinc transporters. We show here that ZRT-, IRT-like protein (ZIP)8 expression in cultured mouse fetal fibroblasts leads to a >10-fold increase in the rate of intracellular Cd influx and accumulation and 30-fold increase in sensitivity to Cd-induced cell death. The complete ZIP8 mRNA and intron-exon splice junctions have no nucleotide differences between two sensitive and two resistant strains of mice; by using situ hybridization, we found that ZIP8 mRNA is prominent in the vascular endothelial cells of the testis of the sensitive strains of mice but absent in these cells of resistant strains. Slc39a8 is therefore the Cdm gene, defining sensitivity to Cd toxicity specifically in vascular endothelial cells of the testis.

Phosphorus bioavailability, growth performance, and nutrient balance in pigs fed high available phosphorus corn and phytase.

Three experiments were conducted to evaluate P bioavailability, growth performance, and nutrient balance in pigs fed high available P (HAP) corn with or without phytase. The bioavailability of P in normal and HAP corn relative to monosodiumphosphate (MSP) for pigs was assessed in Exp. 1. In a randomized complete block design, 96 pigs (average initial BW 9.75 kg) were fed eight diets for 28 d. The reference and test diets were formulated by adding P as MSP, HAP, or normal corn at 0, 0.75, or 1.5 g/kg to a corn-starch-soybean meal basal diet (2.5 g/kg P) at the expense of cornstarch. Plasma inorganic P concentration responded linearly (P < 0.05) to supplemental P intake. Estimates of P bioavailability from HAP andnormal corn when plasma P was regressed on supplemental P intake were 46 and 33%, respectively. In Exp. 2 and 3, pigs were fed corn-soybean meal-based diets containing HAP corn or normal corn and 0 or 600 units of phytase per kilogram in a 2 x 2 factorial arrangement (two corn sources and two levels of phytase). In Exp. 2, 48 crossbred pigs (barrow:gilt, 1:1) averaging 9.25 kg were used to evaluate growth performance. There were no detectable interactions between corn source and phytase for any of the performance criteria measured. Pigs receiving normal corn had the lowest (P < 0.05) BW and rate of gain. Feed efficiency was lower (P < 0.05) in pigs fed normal compared with those fed the HAP corn phytase-supplemented diet. In Exp. 3, 24 crossbred barrows averaging 14.0 kg were used to evaluate nutrient digestibility. There were no detectable interactions between corn and phytase for any of the N and Ca balance criteria. Nitrogen and Ca retention were improved in pigs receiving HAP corn with phytase (P < 0.05). Retention and digestibility of P was lowest (P < 0.01) for pigs on normal corn diet without phytase. The percentage of P digested and retained was improved and fecal P excretion lowered (P < 0.05) by feeding HAP corn. The results of this study indicate that the bioavailability and balance of P in HAP corn is superior to that of normal corn. The addition of 600 phytase units (Natuphos 600, BASF) to HAP corn-based diets further improved P digestibility and reduced P excretion in pigs.

Effects of omega-3 and omega-6 fatty acid-rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma triglycerides, plasma cholesterol, relative blood viscosity, platelet count, and bleeding time.

New Zealand white male rabbits were studied to determine how supplements of soybean oil, soybean + MaxEPA oil, or MaxEPA oil affected their cardiovascular status when they were burned. Plasma triglyceride concentrations increased at 2 hours after burn injury (28 days after supplement administration) and declined by the end of the study in all three experimental groups of rabbits. These same animals showed no noticeable differences in the plasma concentrations of total cholesterol or in the high-density lipoprotein cholesterol subfractions. Plasma low-density/very-low-density lipoprotein cholesterol levels remained unchanged at 2 hours after burn injury/sham treatment but increased by the end of the study in all three experimental groups of rabbits. The mean platelet number was significantly higher in burned/sham treated rabbits given soybean oil supplement as compared with numbers in those given either soybean oil + MaxEPA oil or MaxEPA oil supplement. Plasma relative viscosity was highest in the soybean oil-supplemented rabbits, decreased in animals fed soybean oil + MaxEPA, and lowest in MaxEPA oil-supplemented rabbits. Mean bleeding time was lowest in soybean oil-fed rabbits. The bleeding time was higher in rabbits fed soybean oil+MaxEPA oil and highest in MaxEPA oil-supplemented animals. Platelet number and plasma viscosity were highest in the soybean oil-supplemented rabbits and lowest in the MaxEPA oil-supplemented group. The reverse pattern occurred when bleeding time was established. Overall results obtained suggest that supplementation with oils rich in omega-3 and omega-6 fatty acids may have significant effects on the cardiovascular health of burned male New Zealand white rabbits.

Effects of supplemented omega-3 and omega-6 fatty acid rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma and platelet fatty acids.

The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients.