Re: Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
Martineau AR, Jolliffe DA, Hopper RL et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. British Medical Journal 2017;356:i6583.
The authors of the study undertook an individual participant data (IPD) meta-analysis based on 25 randomised control trials, in order to determine whether vitamin D supplementation can decrease the risk of acute respiratory tract infections. As acute respiratory tract infections are a major cause of global morbidity and mortality, many studies have reported association between low serum concentrations of 25-hydroxyvitamin D and susceptibility to such infections.
The study included randomized, double-blind, placebo controlled trials of supplementation with vitamin D3 or D2 of any duration. The studies were reanalyzed separately. Random effects model was performed for IPD meta-analysis. The heterogeneity was assessed by calculation of the standard deviation of random effects and using the I2 statistic. Further subgroup analyses was done to explore the cause of heterogeneity and identify modifying factors.
The aim of subgroup analyses was to investigate whether effects of vitamin D supplementation on risk of acute respiratory tract infection differed according to baseline vitamin D status, dosing frequency, dose size, age, body mass index, presence or absence of comrbidity and influenza vaccination status. Race or ethnicity was not investigated as a potential effect modifier, as data for this was missing for 4% of participants.
The researchers found statistically significant protective effects of vitamin D for one step analysis of acute respiratory tract infection. Two step analysis also showed steady effects for the proportion of participants experiencing at least one acute respiratory tract infection. Subgroup analysis revealed a strong protective effect of vitamin D supplementation among those with baseline circulating 25-hydroxyvitamin D levels less than 25 nmol/l and no statiscally significant effect among those with baseline levels of 25 nmol/l. When vitamin D was administered using a daily or weekly regimen the protective effect was seen in comparison to when administered as a bolus dose. Also the protective effects of daily or weekly administration was greater in both groups with baseline levels of 25-hydroxyvitamin D both above or below 25 nmol/l. P values for interaction were more than 0.05 for all other potential effect modifiers investigated. Only two factors modified the influence of vitamin D supplementation on risk of acute respiratory tract infection (i.e. baseline vitamin D status and dosing frequency).
The authors have been successful in reporting that vitamin D supplementation shows a protective effect against acute respiratory tract infections. The main benefit is seen in individuals with deficient serum 25-hydroxyvitamin D and those receiving daily or weekly supplement without any additional bolus dose. The authors state that age did not modify the effect of vitamin D supplementation. In our view, in the study a very wider age range of 0-95yrs is considered. It is proper to consider a subgroup analysis for age and other specific group should be studied separately.
Dr. Sumedha Mohan
MDS (Periodontology and Oral Implantology)
Dr. L Satyanarayana
Scientist 'G' (Epidemiology & Biostatistics)
Dr. Smita Asthana
Scientist 'D' (Epidemiology & Biostatistics)
Competing interests:
No competing interests
03 March 2017
Dr Sumedha Mohan
Research Intern
Dr. L Satyanarayana, Dr. Smita Asthana
ICMR-National Institute Of Cancer Prevention And Research
Rapid Response:
Re: Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
Martineau AR, Jolliffe DA, Hopper RL et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. British Medical Journal 2017;356:i6583.
The authors of the study undertook an individual participant data (IPD) meta-analysis based on 25 randomised control trials, in order to determine whether vitamin D supplementation can decrease the risk of acute respiratory tract infections. As acute respiratory tract infections are a major cause of global morbidity and mortality, many studies have reported association between low serum concentrations of 25-hydroxyvitamin D and susceptibility to such infections.
The study included randomized, double-blind, placebo controlled trials of supplementation with vitamin D3 or D2 of any duration. The studies were reanalyzed separately. Random effects model was performed for IPD meta-analysis. The heterogeneity was assessed by calculation of the standard deviation of random effects and using the I2 statistic. Further subgroup analyses was done to explore the cause of heterogeneity and identify modifying factors.
The aim of subgroup analyses was to investigate whether effects of vitamin D supplementation on risk of acute respiratory tract infection differed according to baseline vitamin D status, dosing frequency, dose size, age, body mass index, presence or absence of comrbidity and influenza vaccination status. Race or ethnicity was not investigated as a potential effect modifier, as data for this was missing for 4% of participants.
The researchers found statistically significant protective effects of vitamin D for one step analysis of acute respiratory tract infection. Two step analysis also showed steady effects for the proportion of participants experiencing at least one acute respiratory tract infection. Subgroup analysis revealed a strong protective effect of vitamin D supplementation among those with baseline circulating 25-hydroxyvitamin D levels less than 25 nmol/l and no statiscally significant effect among those with baseline levels of 25 nmol/l. When vitamin D was administered using a daily or weekly regimen the protective effect was seen in comparison to when administered as a bolus dose. Also the protective effects of daily or weekly administration was greater in both groups with baseline levels of 25-hydroxyvitamin D both above or below 25 nmol/l. P values for interaction were more than 0.05 for all other potential effect modifiers investigated. Only two factors modified the influence of vitamin D supplementation on risk of acute respiratory tract infection (i.e. baseline vitamin D status and dosing frequency).
The authors have been successful in reporting that vitamin D supplementation shows a protective effect against acute respiratory tract infections. The main benefit is seen in individuals with deficient serum 25-hydroxyvitamin D and those receiving daily or weekly supplement without any additional bolus dose. The authors state that age did not modify the effect of vitamin D supplementation. In our view, in the study a very wider age range of 0-95yrs is considered. It is proper to consider a subgroup analysis for age and other specific group should be studied separately.
Dr. Sumedha Mohan
MDS (Periodontology and Oral Implantology)
Dr. L Satyanarayana
Scientist 'G' (Epidemiology & Biostatistics)
Dr. Smita Asthana
Scientist 'D' (Epidemiology & Biostatistics)
Competing interests: No competing interests