Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs).

RATIONALE: Asthma exacerbations are commonly precipitated by viral upper respiratory infections (URIs). Vitamin D insufficiency associates with susceptibility to URI in patients with asthma. Trials of vitamin D in adults with asthma with incidence of exacerbation and URI as primary outcome are lacking. OBJECTIVE: To conduct a randomised controlled trial of vitamin D3 supplementation for the prevention of asthma exacerbation and URI (coprimary outcomes). MEASUREMENTS AND METHODS: 250 adults with asthma in London, UK were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 (n=125) or placebo (n=125) over 1 year. Secondary outcomes included asthma control test and St George's Respiratory Questionnaire scores, fractional exhaled nitric oxide and concentrations of inflammatory markers in induced sputum. Subgroup analyses were performed to determine whether effects of supplementation were modified by baseline vitamin D status or genotype for 34 single nucleotide polymorphisms in 11 vitamin D pathway genes. MAIN RESULTS: 206/250 participants (82%) were vitamin D insufficient at baseline. Vitamin D3 did not influence time to first severe exacerbation (adjusted HR 1.02, 95% CI 0.69 to 1.53, p=0.91) or first URI (adjusted HR 0.87, 95% CI 0.64 to 1.16, p=0.34). No clinically important effect of vitamin D3 was seen on any of the secondary outcomes listed above. The influence of vitamin D3 on coprimary outcomes was not modified by baseline vitamin D status or genotype. CONCLUSIONS: Bolus-dose vitamin D3 supplementation did not influence time to exacerbation or URI in a population of adults with asthma with a high prevalence of baseline vitamin D insufficiency. TRIAL REGISTRATION NUMBER: NCT00978315 (ClinicalTrials.gov).

The contribution of muscle hypertrophy to strength changes following resistance training.

PURPOSE: Whilst skeletal muscle hypertrophy is considered an important adaptation to resistance training (RT), it has not previously been found to explain the inter-individual changes in strength after RT. This study investigated the contribution of hypertrophy to individual gains in isometric, isoinertial and explosive strength after 12 weeks of elbow flexor RT. METHODS: Thirty-three previously untrained, healthy men (18-30 years) completed an initial 3-week period of elbow flexor RT (to facilitate neurological responses) followed by 6-week no training, and then 12-week elbow flexor RT. Unilateral elbow flexor muscle strength [isometric maximum voluntary force (iMVF), single repetition maximum (1-RM) and explosive force], muscle volume (V(m)), muscle fascicle pennation angle (θ(p)) and normalized agonist, antagonist and stabilizer sEMG were assessed pre and post 12-week RT. RESULTS: Percentage gains in V(m) correlated with percentage changes in iMVF (r = 0.527; P = 0.002) and 1-RM (r = 0.482; P = 0.005) but not in explosive force (r ≤ 0.243; P ≥ 0.175). Percentage changes in iMVF, 1-RM, and explosive force did not correlate with percentage changes in agonist, antagonist or stabilizer sEMG (all P > 0.05). Percentage gains in θ(p) inversely correlated with percentage changes in normalized explosive force at 150 ms after force onset (r = 0.362; P = 0.038). CONCLUSIONS: We have shown for the first time that muscle hypertrophy explains a significant proportion of the inter-individual variability in isometric and isoinertial strength gains following 12-week elbow flexor RT in healthy young men.

Diet-induced vitamin D deficiency reduces skeletal muscle mitochondrial respiration.

Vitamin D deficiency is associated with symptoms of skeletal muscle myopathy including muscle weakness and fatigue. Recently, vitamin D-related metabolites have been linked to the maintenance of mitochondrial function within skeletal muscle. However, current evidence is limited to in vitro models and the effects of diet-induced vitamin D deficiency upon skeletal muscle mitochondrial function in vivo have received little attention. In order to examine the role of vitamin D in the maintenance of mitochondrial function in vivo, we utilised an established model of diet-induced vitamin D deficiency in C57BL/6J mice. Mice were either fed a control diet (2200 IU/kg i.e. vitamin D replete) or a vitamin D-deplete (0 IU/kg) diet for periods of 1, 2 and 3 months. Gastrocnemius muscle mitochondrial function and ADP sensitivity were assessed via high-resolution respirometry and mitochondrial protein content via immunoblotting. As a result of 3 months of diet-induced vitamin D deficiency, respiration supported via complex I + II (CI + IIP) and the electron transport chain (ETC) were 35 and 37% lower when compared to vitamin D-replete mice (P < 0.05). Despite functional alterations, citrate synthase activity, AMPK phosphorylation, mitofilin, OPA1 and ETC subunit protein content remained unchanged in response to dietary intervention (P > 0.05). In conclusion, we report that 3 months of diet-induced vitamin D deficiency reduced skeletal muscle mitochondrial respiration in C57BL/6J mice. Our data, when combined with previous in vitro observations, suggest that vitamin D-mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.

Dietary intake is independently associated with the maximal capacity for fat oxidation during exercise.

Background: Substantial interindividual variability exists in the maximal rate of fat oxidation (MFO) during exercise with potential implications for metabolic health. Although the diet can affect the metabolic response to exercise, the contribution of a self-selected diet to the interindividual variability in the MFO requires further clarification.Objective: We sought to identify whether recent, self-selected dietary intake independently predicts the MFO in healthy men and women.Design: The MFO and maximal oxygen uptake ([Formula: see text]O2 max) were determined with the use of indirect calorimetry in 305 healthy volunteers [150 men and 155 women; mean ± SD age: 25 ± 6 y; body mass index (BMI; in kg/m2): 23 ± 2]. Dual-energy X-ray absorptiometry was used to assess body composition with the self-reported physical activity level (SRPAL) and dietary intake determined in the 4 d before exercise testing. To minimize potential confounding with typically observed sex-related differences (e.g., body composition), predictor variables were mean-centered by sex. In the analyses, hierarchical multiple linear regressions were used to quantify each variable's influence on the MFO.Results: The mean absolute MFO was 0.55 ± 0.19 g/min (range: 0.19-1.13 g/min). A total of 44.4% of the interindividual variability in the MFO was explained by the [Formula: see text]O2 max, sex, and SRPAL with dietary carbohydrate (carbohydrate; negative association with the MFO) and fat intake (positive association) associated with an additional 3.2% of the variance. When expressed relative to fat-free mass (FFM), the MFO was 10.8 ± 3.2 mg · kg FFM-1 · min-1 (range: 3.5-20.7 mg · kg FFM-1 · min-1) with 16.6% of the variability explained by the [Formula: see text]O2 max, sex, and SRPAL; dietary carbohydrate and fat intakes together explained an additional 2.6% of the variability. Biological sex was an independent determinant of the MFO with women showing a higher MFO [men: 10.3 ± 3.1 mg · kg FFM-1 · min-1 (3.5-19.9 mg · kg FFM-1 · min-1); women: 11.2 ± 3.3 mg · kg FFM-1 · min-1 (4.6-20.7 mg · kg FFM-1 · min-1); P < 0.05].Conclusion: Considered alongside other robust determinants, dietary carbohydrate and fat intake make modest but independent contributions to the interindividual variability in the capacity to oxidize fat during exercise. This trial was registered at clinicaltrials.gov as NCT02070055.

Whey protein does not enhance the adaptations to elbow flexor resistance training.

PURPOSE: It is unclear whether protein supplementation augments the gains in muscle strength and size observed after resistance training (RT) because limitations to previous studies include small cohorts, imprecise measures of muscle size and strength, and no control of prior exercise or habitual protein intake. We aimed to determine whether whey protein supplementation affected RT-induced changes in elbow flexor muscle strength and size. METHODS: We pair-matched 33 previously untrained, healthy young men for their habitual protein intake and strength response to 3-wk RT without nutritional supplementation (followed by 6 wk of no training) and then randomly assigned them to protein (PRO, n = 17) or placebo (PLA, n = 16) groups. Participants subsequently performed elbow flexor RT 3 d · wk(-1) for 12 wk and consumed PRO or PLA immediately before and after each training session. We assessed elbow flexor muscle strength (unilateral 1-repetition maximum and isometric maximum voluntary force) and size (total volume and maximum anatomical cross-sectional area determined with magnetic resonance imaging) before and after the 12-wk RT. RESULTS: PRO and PLA demonstrated similar increases in muscle volume (PRO 17.0% ± 7.1% vs PLA 14.9% ± 4.6%, P = 0.32), anatomical cross-sectional area (PRO 16.2% ± 7.1% vs PLA 15.6% ± 4.4%, P = 0.80), 1-repetition maximum (PRO 41.8% ± 21.2% vs PLA 41.4% ± 19.9%, P = 0.97), and maximum voluntary force (PRO 12.0% ± 9.9% vs PLA 14.5% ± 8.3%, P = 0.43). CONCLUSIONS: In the context of this study, protein supplementation did not augment elbow flexor muscle strength and size changes that occurred after 12 wk of RT.