Vitamin D and Health

difference was not significant (RR=0.41; 95% CI, 0.16-1.09; p=0.06). A full-scale trial by these
investigators is ongoing and due to complete in 2019 75 .
Observational studies
6.293 Several studies have shown a seasonal pattern associated with TB incidence, peaking in spring and
being lowest in autumn. For example, a study assessing patterns of TB seasonality in New York City
(Parrinello et al., 2012) reported that incidence was highest in March-May (27%) and lowest in
September-November (22%). Although lower serum 25(OH)D concentration during winter was
proposed as a possible cause of this seasonal pattern, another possible cause was increased crowding
in winter.
6.294 A number of observational studies in different populations have reported an association between low
serum 25(OH)D concentration and increased risk of TB. A systematic review and meta-analysis of 7
observational studies (3 prospective, 4 case-control; n=531) comparing serum 25(OH)D concentration
in tuberculosis patients (not yet commenced any treatment) and healthy controls (Nnoaham & Clarke,
2008) reported a 70% probability that a healthy individual without TB would have a higher serum
25(OH)D concentration than an individual with TB. The authors concluded that low serum 25(OH)D
concentration increased the risk of active TB, however serum 25(OH)D concentrations in individuals
with TB ranged from a median (IQR) of 16 (2.25-74.25) to 65.8 (43.8-130.5) nmol/L. A problem with
case-control studies is that the association between low serum 25(OH)D concentration and TB could
be due to reverse causality (i.e., low serum 25(OH)D concentrations are caused by the TB).
6.295 A prospective cohort study in Spain examined the relationship between serum 25(OH)D concentration
and incidence of TB among contacts of TB patients (n=572) who were followed up for 1.6 years
(Arnedo-Pena et al., 2015a). Mean serum 25(OH)D concentration was 34 nmol/L for cases and
64 nmol/L for non-cases. An inverse association was found between serum 25(OH)D concentration
and TB incidence (adjusted HR=0.88; 95% CI, 0.80-0.97).
6.296 Fewer studies have investigated LTBI. A prospective cohort study (Talat et al., 2010) examined serum
25(OH)D concentrations in household contacts (n=109) of patients with recently diagnosed TB. Blood
samples were collected at baseline, and at 6, 12 and 24 months follow-up. Eight percent progressed
to active disease during 4 years of follow-up. TB progression was significantly associated with serum
25(OH)D concentrations < 17.5 nmol/L compared to concentrations >17.5 nmol/L (p=0.02). Arnedo-
Pena et al. (2011) examined the association between serum 25(OH)D concentration and LTBI
prevalence and TST conversion in contacts of TB patients (n=202). After 2 months, 11 out of 93
negative LTBI participants, presented with TST conversions. Serum 25(OH)D concentration
> 75 nmol/L was associated with a protective effect against TST conversion (OR of < 50 vs
> 75 nmol/L=0.10; 95% CI, 0.00-0.76); however, the size of the study in relation to TST conversion is
small and TST has low specificity with the possibility of false results (Mancuso et al., 2008). Another
prospective cohort study (Arnedo-Pena et al., 2015b) examined the association between serum
25(OH)D concentration and TB infection conversion (TBIC) in contacts of pulmonary TB patients
(n=198) in Spain. After 8-10 weeks, 18 presented with TBIC. The mean serum 25(OH)D concentration
in the TIBC cases (51.7 nmol/L) was significantly lower (p=0.03) than that of non-cases (67.9 nmol/L)
and an increase of 2.5 nmol/L decreased TBIC incidence by 6% (RR=0.94; 95% CI, 0.90-0.99; p=0.015).
However, serum 25(OH)D concentrations were only measured on one occasion so seasonal variation
75 NCT02276755: The goal of this clinical trial is to investigate the preventive role of vitamin D supplementation in school age children in a high
transmission setting.
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