Influence of Vitamin D Supplementation by Simulated Sunlight or Oral D3 on Respiratory Infection during Military Training.

PURPOSE: This study aimed to determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1) and then to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated sunlight or oral D3 supplementation in winter (study 2). METHODS: In study 1, 1644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received placebo, simulated sunlight (1.3× standard erythemal dose, three times per week for 4 wk and then once per week for 8 wk), or oral vitamin D3 (1000 IU·d-1 for 4 wk and then 400 IU·d-1 for 8 wk). URTI was diagnosed by a physician (study 1) and by using the Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA), and cathelicidin were assessed by liquid chromatography-mass spectrometry LC-MS/MS and enzyme-linked immunosorbent assay. RESULTS: In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D-sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D <50 nmol·L-1 (OR = 0.6, 95% confidence interval = 0.4-0.9), an association that remained after accounting for sex and smoking. Each URTI caused, on average, three missed training days. In study 2, vitamin D supplementation strategies were similarly effective to achieve vitamin D sufficiency in almost all (≥95%). Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (P < 0.05). These reductions were similar with both vitamin D strategies (P > 0.05). Supplementation did not affect salivary secretory immunoglobulin A or cathelicidin. CONCLUSION: Vitamin D sufficiency reduced the URTI burden during military training.

Vitamin D and the hepatitis B vaccine response: a prospective cohort study and a randomized, placebo-controlled oral vitamin D3 and simulated sunlight supplementation trial in healthy adults.

PURPOSE: To determine serum 25(OH)D and 1,25(OH)2D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D3 supplementation in wintertime (study 2). METHODS: Study 1 involved 447 adults. In study 2, 3 days after the initial hepatitis B vaccination, 119 men received either placebo, simulated sunlight (1.3 × standard-erythema dose, 3 × /week for 4 weeks and then 1 × /week for 8 weeks) or oral vitamin D3 (1000 IU/day for 4 weeks and 400 IU/day for 8 weeks). We measured hepatitis B vaccination efficacy as percentage of responders with anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/mL. RESULTS: In study 1, vaccine response was poorer in persons with low vitamin D status (25(OH)D ≤ 40 vs 41-71 nmol/L mean difference [95% confidence interval] - 15% [- 26, - 3%]; 1,25(OH)2D ≤ 120 vs ≥ 157 pmol/L - 12% [- 24%, - 1%]). Vaccine response was also poorer in winter than summer (- 18% [- 31%, - 3%]), when serum 25(OH)D and 1,25(OH)2D were at seasonal nadirs, and 81% of persons had serum 25(OH)D < 50 nmol/L. In study 2, vitamin D supplementation strategies were similarly effective in achieving vitamin D sufficiency from the winter vitamin D nadir in almost all (~ 95%); however, the supplementation beginning 3 days after the initial vaccination did not effect the vaccine response (vitamin D vs placebo 4% [- 21%, 14%]). CONCLUSION: Low vitamin D status at initial vaccination was associated with poorer hepatitis B vaccine response (study 1); however, vitamin D supplementation commencing 3 days after vaccination (study 2) did not influence the vaccination response. CLINICAL TRIAL REGISTRY NUMBER: Study 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895 ; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103 .

Influence of Vitamin D Supplementation by Sunlight or Oral D3 on Exercise Performance.

PURPOSE: To determine the relationship between vitamin D status and exercise performance in a large, prospective cohort study of young men and women across seasons (study 1). Then, in a randomized, placebo-controlled trial, to investigate the effects on exercise performance of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol·L) by a unique comparison of safe, simulated-sunlight and oral vitamin D3 supplementation in wintertime (study 2). METHODS: In study 1, we determined 25(OH)D relationship with exercise performance in 967 military recruits. In study 2, 137 men received either placebo, simulated sunlight (1.3× standard erythemal dose in T-shirt and shorts, three times per week for 4 wk and then once per week for 8 wk) or oral vitamin D3 (1000 IU·d for 4 wk and then 400 IU·d for 8 wk). We measured serum 25(OH)D by high-pressure liquid chromatography tandem mass spectrometry and endurance, strength and power by 1.5-mile run, maximum dynamic lift and vertical jump, respectively. RESULTS: In study 1, only 9% of men and 36% of women were vitamin D sufficient during wintertime. After controlling for body composition, smoking, and season, 25(OH)D was positively associated with endurance performance (P ≤ 0.01, ΔR = 0.03-0.06, small f effect sizes): 1.5-mile run time was ~half a second faster for every 1 nmol·L increase in 25(OH)D. No significant effects on strength or power emerged (P > 0.05). In study 2, safe simulated sunlight and oral vitamin D3 supplementation were similarly effective in achieving vitamin D sufficiency in almost all (97%); however, this did not improve exercise performance (P > 0.05). CONCLUSIONS: Vitamin D status was associated with endurance performance but not strength or power in a prospective cohort study. Achieving vitamin D sufficiency via safe, simulated summer sunlight, or oral vitamin D3 supplementation did not improve exercise performance in a randomized-controlled trial.

Addition of novel degenerate electrical waveform stimulation with photodynamic therapy significantly enhances its cytotoxic effect in keloid fibroblasts: first report of a potential combination therapy.

BACKGROUND: We recently reported use of photodynamic therapy (PDT) for treating keloid disease (KD). However, in view of high recurrence rates post any treatment modality, adjuvant therapies should be considered. Additionally, we previously demonstrated the effect of a novel electrical waveform, the degenerate wave (DW) on differential gene expression in keloid fibroblasts. OBJECTIVE: In this study, we evaluated the in vitro cytotoxic effect of PDT at 5J/cm(2) and 10J/cm(2) of red light (633 ± 3nm) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) with and without DW, on keloid fibroblasts compared to normal skin fibroblasts. METHODS: The rate of intracellular photosensitizer (protoporphyrin IX, PPIX) generation and disintegration, reactive oxygen species (ROS) generation, LDH cytotoxicity, WST-1 cytoproliferation, apoptosis by Caspase-3 activation, mitochondrial membrane potential assessment by JC-1 aggregates, qRT-PCR, flow cytometry and In-Cell Western Blotting were performed. RESULTS: PPIX accumulation and disintegration rate was higher in keloid than normal fibroblasts after incubation with MAL compared to ALA. Increased cytotoxicity and decreased cytoproliferation were observed for keloid fibroblasts after PDT+DW treatment compared to PDT alone. ROS generation, mitochondrial membrane depolarization, apoptosis (Caspase-3 activation) and collagens I and III gene down-regulation were higher in keloid compared to normal skin fibroblasts after MAL-PDT+DW treatment. An increase in the number of cells entering apoptosis and necrosis was observed after PDT+DW treatment by flow cytometry analysis. All positive findings were statistically significant (P<0.05). CONCLUSION: The cytotoxic effect of PDT on keloid fibroblasts can be enhanced significantly with addition of DW stimulation, indicating for the first time the utility of this potential combinational therapy.