Effectiveness of Vitamin D Supplementation to Reduce Injury and Illness in the UK Armed Forces With Specific Reference to Stress Fracture Risk Reduction

Study Overview:

Aim: The effect of vitamin D3 supplementation in (male) Royal Marine recruits during 32-weeks of (arduous) initial military training on stress fracture and respiratory illness risk. Volunteer recruits will initially complete a healthy history, smoking habit and alcohol consumption questionnaire. Height, body mass (from which BMI will be calculated), and calf girth/skinfold will be measured. A 20 ml blood sample will be drawn (gold and purple top vacutainers) for determination of vitamin D status, calcium and albumin concentrations, PTH concentration, markers of bone turnover, antibody responses against S. aureus or other antigens and plasma cytokine levels. A (3-5 ml) saliva sample will be taken for S. aureus culture, and for assessment of oral microbiota, cytokine and antibody levels in saliva. A dry swab would be taken from both anterior nares for enumeration of S. aureus, and stored in phosphate buffered saline. The study recruit cohort will be divided into two groups: (i) a vitamin-D3 supplementation (50,000 IU administered orally every two months - equivalent to 800 IU per day); and (ii) a placebo supplementation (administered orally every two months) control group. The vitamin D supplement and the placebo supplement will be manufactured by Pharmaterials Ltd., Unit B, 5 Boulton Road, Reading, RG2 0NH, UK. The active and placebo supplements will be presented as identical (size and appearance) tablets, indiscernible from each other for the volunteer or the study team in situ at CTC. Both groups will receive one tablet at each time point. Recruits will be randomly assigned to a study group, but the two groups will be matched for age, height, body mass and aerobic fitness. The randomisation of supplement/placebo administration to study volunteers will be undertaken by statisticians from the University of Surrey. Study team staff will monitor supplement taking and will further confirm supplement taking through exit interviews. Further 20 ml blood samples will be drawn every two months (i.e. at weeks 8, 16 and 32 of RM training), saliva samples and nasal swabs will also be taken, and the smoking habit and alcohol consumption questionnaire will be re-administered. The study team will take into consideration prevailing data on recruit attrition to inform this decision. Food Frequency Questionnaire (FFQ) will be administered in week-6 of training; this will allow the recruits' habitual RM training diet to be established following the civilian to military transition. Permission will be sought to collate the outcome of the week-1 and week-9 Royal Marine Fitness Assessment (RMFA). Permission will also be sought to prospectively collate data from the Defence Medical Information Capability Programme (DMICP) system describing the prevalence of injury and illness in study volunteers.

Study Procedures: All potential volunteer recruits to the study will have been initially passed medically and physically fit to undertake RM training. Following an initial brief, those recruits volitionally consenting to participate in the study will complete a Health History Questionnaire and a Smoking Habit and Alcohol Consumption Questionnaire. The Royal Marine Fitness Assessment (RMFA) is completed as part of the Recruit Syllabus (RS10) in weeks 1 and 9 of training; these data (i.e. Multi-Stage Fitness Test performance, number of sit-ups, number of press-ups and number of pull-ups) are collected by the PT Branch at CTC, and will be compiled by the study team to allow fitness comparisons to be made with the recruit sample monitored during SGBHP. Height and body mass will be measured (from which BMI will be calculated), and calf girth/skinfold will be measured, the Smoking Habit and Alcohol Consumption Questionnaire completed, antibiotic exposure determined (i.e. antibiotics use not prescribed by the Medical Centre will be ascertained, where the antibiotics prescribed by Medical Centre will be collected from medical centre notes), occurrence of skin infections treated outside the CTCRM Medical Centre determined (where skin infections diagnosed by Medical Centre will be collected from medical centre notes), and a further blood sample will be drawn every two months during training (i.e. at weeks 8, 16) and at the End of training (week32). The precise timing of measurement sessions will be determined through discussions between the study team and the Commando Training Wing (CTW). All measures will be undertaken in appropriate venues at CTC, and will be accommodated in the recruits' programme where there would be minimum impact upon other training/personal administration activities.

Vitamin D or Placebo Supplement Administration: The INM study team staff will undertake vitamin D or placebo supplement administration during a programmed medical serial in the RM recruit programme. The study team will observe and monitor recruits taking the supplement or placebo tablet, and will further confirm supplement or placebo taking through exit interviews. The pattern of randomisation of the supplement(s) and placebo for the study will be determined and monitored independently by UoS study team members. There will be two study groups - a vitamin D supplement group and a placebo supplement group. The two groups will be matched for age, height, body mass and aerobic fitness. The study plan is to supplement at the Start of Training, and every two months thereafter (i.e. at weeks 8, 16 and 24 of RM training). Preliminary discussions with CTC indicate that - to schedule this within the RM training programme and therefore ensure minimum impact on RM recruit time - supplementation during training may need to take place at weeks 6, 15 and 24. During these programmed serials, the study team will also collate information detailing if a study participant had undertaken military exercises or leave, where they would be exposed to increased sunlight, since the last measurement time point. This will be particularly pertinent where measurement points span CTC block leave (i.e. Christmas, Easter and Summer).

Assessment of Injury/Illness Incidence: The incidence of injury/illness (including SF, SSTI and respiratory infection) in recruits during training will be monitored in association with colleagues from the Medical Centre.