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.

Effects of nebivolol in obese African Americans with hypertension (NOAAH): markers of inflammation and obesity in response to exercise-induced stress.

We sought to determine whether the antihypertensive drug nebivolol has beneficial effects on vascular markers of inflammation and oxidation in obese African-American patients with hypertension when exposed to exercise-induced stress. Forty-three obese, African-American subjects with hypertension were treated with nebivolol (5-10 mg/day) for 8 weeks. Before treatment the subjects underwent an exercise treadmill study to a level of eight metabolic equivalents. Circulating levels of soluble interleukin-6 (sIL-6), vascular cell adhesion molecule (VCAM-1), adiponectin and leptin were measured at pre-treadmill, and 1 min, 30 min, 60 min and 24 h after treadmill. After the 8-week treatment period, exercise treadmill study and the measurement of markers were repeated. Treatment with nebivolol reduced levels of sVCAM-1 at pre-exercise by 21% and at 1 and 30 min by 12.5 and 20%, respectively (P<0.005 from corresponding time point). In nebivolol-treated patients there was a reduction in sIL-6 levels by 20% and pre-exercise and at 1 and 60 min by 19.7 and 33.5%, respectively (P<0.005 from corresponding time point). Treatment with nebivolol increased levels of serum adiponectin by 28% (P=0.012) and decreased levels of leptin by 32% (P<0.005 from pre-treatment). Treatment with nebivolol improves markers of inflammation and obesity in a high-risk African-American population. Moreover, this effect is potentiated in response to exercise-induced stress. These results suggest that nebivolol differentially regulates markers of inflammation and obesity, thereby providing vascular protection.

Irbesartan, an angiotensin type 1 receptor inhibitor, regulates the vascular oxidative state in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to determine the effect of angiotensin II type 1 (AT(1)) receptor antagonists on pro-oxidant species observed in the pathogenesis of atherosclerosis. Parameters such as low-density lipoprotein (LDL) susceptibility, monocyte binding capacity, superoxide generation and lipid peroxidation were examined in the presence of the AT(1) receptor antagonist irbesartan. BACKGROUND: Low-density lipoprotein oxidation is a key component in the process of atherogenesis. This modification may involve various mechanisms, including changes in nitric oxide levels and superoxide levels. Additionally, compounds that suppress these mechanisms may retard or inhibit the pathogenesis of atherosclerosis. METHODS: Forty-seven patients with documented coronary artery disease were treated with irbesartan for a 12-week period. Patients were randomized to receive irbesartan or placebo. Lipid peroxidation, superoxide levels, monocyte binding and LDL oxidation were measured at 0, 4 and 12 weeks. Findings were statistically evaluated by two-way repeated measures analysis of variance with p < 0.05 being significant. RESULTS: Treatment with irbesartan significantly decreased the pro-oxidative environment seen in our study population. Lag time for LDL oxidation increased 32% at 12 weeks, suggesting an increased resistance of LDL modification in the serum. Thiobarbituric acid reactive substances activity indicated that lipid peroxidation decreased by 36% in comparison to placebo. In addition, superoxide levels and monocyte-binding capacity were also significantly reduced in coronary artery disease patients receiving irbesartan. CONCLUSIONS: Our results indicate that irbesartan may suppress the atherosclerotic process by inhibiting the intravascular oxidative state and the production of reactive oxygen species, compounds that may cause damage to the vasculature.