Jeffrey Thomas

A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness.

CONTEXT Vitamin D insufficiency/deficiency is commonly observed in black youth. OBJECTIVE The aim was to determine 25-hydroxyvitamin D [25(OH)D] in response to 2000 IU vitamin D supplementation over time; to evaluate the relation between 25(OH)D concentrations and total body fat mass by dual-energy x-ray absorptiometry; and to determine whether vitamin D supplementation improves arterial stiffness measured by pulse wave velocity (PWV). DESIGN We conducted a randomized, blinded, controlled clinical trial. SETTING AND PARTICIPANTS Forty-nine normotensive black boys and girls, aged 16.3 ± 1.4 yr, were randomly assigned to either the control group (400 IU/d; n = 24) or the experimental group (2000 IU/d; n = 25). RESULTS Plasma 25(OH)D values at baseline and at 4, 8, and 16 wk were 34.0 ± 10.6, 44.9 ± 9.4, 51.2 ± 11.1, and 59.8 ± 18.2 nmol/liter, respectively, for the control group; and 33.1 ± 8.7, 55.0 ± 11.8, 70.9 ± 22.0, and 85.7 ± 30.1 nmol/liter, respectively, for the experimental group. The experimental group vs. the control group reached significantly higher 25(OH)D concentrations at 8 and 16 wk, respectively. Partial correlation analyses indicated that total body fat mass at baseline was significantly and inversely associated with 25(OH)D concentrations in response to the 2000-IU supplement across time. Furthermore, carotid-femoral PWV increased from baseline (5.38 ± 0.53 m/sec) to posttest (5.71 ± 0.75 m/sec) in the control group (P = 0.016), whereas in the experimental group carotid-femoral PWV decreased from baseline (5.41 ± 0.73 m/sec) to posttest (5.33 ± 0.79 m/sec) (P = 0.031). CONCLUSION Daily 2000 IU vitamin D supplementation may be effective in optimizing vitamin D status and counteracting the progression of aortic stiffness in black youth. Plasma 25(OH)D concentrations in response to the 2000 IU/d supplementation are negatively modulated by adiposity.

Leukocyte Telomere Length in Healthy Caucasian and African-American Adolescents: Relationships with Race, Sex, Adiposity, Adipokines, and Physical Activity

OBJECTIVE To examine the relationships of race, sex, adiposity, adipokines, and physical activity to telomere length in adolescents. STUDY DESIGN Leukocyte telomere length (T/S ratio) was assessed cross-sectionally in 667 adolescents (aged 14-18 years; 48% African-Americans; 51% girls) using a quantitative polymerase chain reaction method. Generalized estimating equations analyses were performed. RESULTS Telomere length was greater in the African-American adolescents than in the Caucasian adolescents (age- and sex-adjusted T/S ratio ± SE, 1.32 ± 0.01 vs 1.27 ± 0.01: P = .014) and greater in girls than in boys (age- and race-adjusted T/S ratio ± SE, 1.31 ± 0.01 vs 1.27 ± 0.01; P = .007). None of the adiposity or adipokine measures explained a significant proportion of the variance in telomere length. Vigorous physical activity was positively associated with telomere length (adjusted R(2) = 0.019; P = .009) and accounted for 1.9% of the total variance only in girls. CONCLUSIONS This study, conducted in a biracial adolescent cohort, demonstrated that (1) race and sex differences in telomere length have already emerged during adolescence; (2) adiposity and adipokines are not associated with telomere length at this age; and (3) the antiaging effect of vigorous physical activity may begin in youth, especially in girls.

Evidence of microvascular dysfunction in patients with cystic fibrosis.

Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether microvascular function is affected in this population has yet to be elucidated. Using laser-Doppler imaging, we evaluated microvascular function through postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh). PORH [518 ± 174% (CF) and 801 ± 125% (control), P = 0.039], LTH [1,338 ± 436% (CF) and 1,574 ± 620% (control), P = 0.045], and iontophoresis with ACh [416 ± 140% (CF) and 617 ± 143% (control), P = 0.032] were significantly lower in patients with CF than control subjects. In addition, the ratio of PORH to LTH was significantly (P = 0.043) lower in patients with CF (55.3 ± 5.1%) than control subjects (68.8 ± 3.1%). Significant positive correlations between LTH and forced expiratory volume in 1 s (%predicted) (r = 0.441, P = 0.013) and between the PORH-to-LTH ratio and exercise capacity (r = 0.350, P = 0.049) were observed. These data provide evidence of microvascular dysfunction in patients with CF compared with control subjects. In addition, our data demonstrate a complex relationship between microvascular function and classical markers of disease severity (i.e., pulmonary function and exercise capacity) in CF.

High sodium intake is associated with short leukocyte telomere length in overweight and obese adolescents

Background/objectives:Telomere shortening has an important role in cellular aging. However, the impact of high sodium intake, an important risk factor of age-related diseases, on telomere shortening remains unknown. Therefore, we examined the relationship between high dietary sodium intake and leukocyte telomere length (LTL), particularly in the context of obesity, as obesity increases salt sensitivity.Subjects/methods:LTL was determined by a quantitative polymerase chain reaction method in 766 adolescents aged 14–18 years (50% females, 49% African Americans). Dietary sodium intake was assessed by seven independent 24-h dietary recalls. We divided the sample into low sodium (mean 2388±522 mg per day) or high sodium groups (mean 4142±882 mg per day) based on the median value (3280.9 mg per day).Results:In the entire cohort, there was no significant association between sodium intake and LTL (r=−0.05, P=0.24). However, there was a significant interaction between sodium intake and obesity status (P=0.049). Further multiple linear regression analyses revealed that higher dietary sodium intake was associated with shorter LTL in the overweight/obese group (body mass index ⩾85th percentile, β=−0.37, P=0.04), but not in the normal-weight group (β=0.01, P=0.93) after adjusting for multiple confounding factors. In the overweight/obese group, LTL was significantly shorter in the high sodium intake subjects vs low sodium intake subjects (1.24±0.22 vs. 1.32±0.20, P=0.02), but not the normal-weight group (1.29±0.24 vs 1.30±0.24, P=0.69).Conclusions:Higher dietary sodium intake is associated with shorter telomere length in overweight and obese adolescents.

A single bout of maximal exercise improves lung function in patients with cystic fibrosis

BACKGROUND Responses to a single bout of exercise may provide critical information for maximizing improvements in pulmonary function following exercise training in cystic fibrosis (CF). We sought to determine if acute maximal exercise improves pulmonary function in patients with CF. METHODS Thirty-three patients with CF completed a comprehensive assessment of pulmonary function to determine forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and lung clearance index (LCI) prior to and immediately following maximal aerobic exercise on a cycle ergometer. RESULTS Following exercise, FVC (∆0.08±0.14L) and FEV1 (∆0.06±0.15L) increased, while LCI decreased (∆-0.71±0.93) (all p<0.05). Changes in FEV1 (%predicted) were associated with peak work (r=0.40, p=0.02) and peak pulmonary ventilation (r=0.45, p=0.01). CONCLUSIONS A single bout of maximal exercise acutely improves pulmonary function in patients with CF and improvements may be related to peak work and peak pulmonary ventilation.

Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD

BACKGROUND: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. METHODS: Seventeen patients with COPD completed a randomized, double‐blind, placebo (PLC)‐controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow‐mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho‐ and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons. RESULTS: Treatment with BH4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH4 increased (P = .013) the ratio of phospho‐NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC. CONCLUSIONS: An acute dose of BH4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov.

BH4 improves postprandial endothelial function after a high-fat meal in men and postmenopausal women

Objective: The timing and duration of menopause is important when evaluating the risk for cardiovascular disease in postmenopausal women, likely related in part to nitric oxide (NO) bioavailability. The flow-mediated dilation (FMD) test is a noninvasive assessment of NO bioavailability in humans, and tetrahydrobiopterin (BH4) is essential for NO synthesis. A high-fat meal (HFM) has been used to increase lipemia and reduce NO bioavailability. Thus, this study sought to determine if menopausal transition has any impact on the postprandial endothelial function response to a HFM, and evaluate the effect of BH4 on postprandial endothelial function in postmenopausal women and men. Methods: Utilizing a randomized, double-blind, placebo-controlled design, sex-steroid hormones and FMD were determined in 30 older adults (10 postmenopausal women aged below 3 y [W < 3], 10 postmenopausal women aged above 10 y [W > 10], and 10 men) at baseline and 4 hours after the ingestion of a HFM alone or a HFM with BH4 (HFM + BH4; 5 mg/kg). Results: Data are presented as mean ± SEM. Independent of treatment, postprandial testosterone was significantly (P < 0.05) decreased in men (−64 ± 11 ng/dL), whereas no changes were observed in W < 3 or W > 10 group. In addition, concentrations of progesterone were higher (P = 0.019) and the testosterone/estradiol ratio was lower (P = 0.026) in all groups after the ingestion of HFM + BH4 compared with the ingestion of HFM alone. Overall, an increase in FMD was observed after the ingestion of HFM + BH4 (&Dgr;1.9% ± 0.6%), whereas no change in FMD was observed after the ingestion of HFM alone (&Dgr;−0.7% ± 0.6%). Conclusions: Co-ingestion of BH4 with a HFM not only alters the sex-steroid hormone ratio, it improves postprandial FMD after a HFM regardless of postmenopause status or sex.