Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials

Abstract

Background Vitamin D deficiency has been associated with a number of diseases, including influenza. Whether or not this reflects a causal relationship is unknown. We therefore wanted to examine if supplementation with vitamin D would affect the incidence and severity of influenza-like disease. Methods Questionnaires on influenza were sent to subjects participating in ongoing placebo-controlled intervention studies with vitamin D supplementation, up until the end of April 2010. Results Five hundred and sixty-nine subjects from 10 different clinical trials were included in the study, of whom 289 were randomized to receive vitamin D (1111–6800 IU/day) and 280 to receive placebo. Influenza-like disease during the previous fall/winter was reported in 38 subjects in the vitamin D group and 42 in the placebo group (non-significant), of whom 25 and 26 subjects, respectively, fulfilled our clinical criteria for influenza. In these latter subjects, the duration of illness was significantly longer among those in the vitamin D group than among those in the placebo group (median 7 (range 2–60) days vs median 4 (range 2–18) days; p = 0.007). However, this difference was not statistically significant if all 38 (vitamin D) and 42 (placebo) subjects who reported symptoms were included. Conclusion Our results do not support the hypothesis that high doses of vitamin D supplementation will have a pronounced effect on influenza-like disease in populations not targeted for high influenza risk.

Impact of Vitamin D on Infectious Disease

“…Of the remaining trials ( Table 4 ), 3 evaluated infection rates and antibiotic use in adults [88-90] and single trials studied populations with: hepatitis C virus (HCV) [91] , heart transplants [92] , HIV [93] , schistosomiasis [94] , and infection in pregnancy [95] . Of these manuscripts, 2 combined multiple randomized, controlled data sets [86, 95] and 8 provided a secondary analysis of previously published data [64, 73, 78, 84, 86, 89, 90, 95] . All studies were double blinded except for 2 that used a single blind model [85, 94] and 6 that were non-blinded [58, 61, 65, 71, 87, 91] .…”

“…Two positive studies found fewer RTI [79] and decreased cold and influenza incidences [84] with daily vitamin D 3 doses between 400 IU and 2000 IU for 6 months and 36 months, respectively. However, the remaining trials found no change in the incidence or severity of RTI or influenza symptoms following doses of vitamin D 3 given daily (2,000 IU doses for 4 months [80] or 1,111-6,800 IU doses for 3 months during influenza season [86] ) or monthly (100,000 IU doses for 18 months) [77] .…”

“…For one, vitamin D was administered at intervals ranging from days to months. Although vitamin D administered daily, weekly, or monthly can sustain the same circulating concentrations of 25(OH)D over an equivalent period of time [97] , the high number of trials with daily dosing (more than 50% of studies)[58, 59, 65, 67, 69, 75, 76, 78-81, 83, 84, 86, 88, 89, 91, 92, 94, 95] raises concerns over compliance; several large clinical trials have reported low adherence to daily doses of vitamin D [98, 99] . The doses of vitamin D 3 also varied (300 [78] to 10,000 IU [59] for daily doses, 1,400 [87] to 60,000 IU [61, 87] for weekly doses and 30,000 [90] to 600,000 IU [63] for single or monthly doses), as did the formulation.…”

“…While many physiologic characteristics impact response to vitamin D, including body composition [104] and genetic variations of the vitamin D binding protein [105] , the factors most relevant to these studies are: baseline 25(OH)D concentration [106] and VDR polymorphisms [107] . Though many studies did not measure baseline 25(OH)D [59, 66, 69-71, 75, 82, 83, 86, 87, 89, 92, 94] , multiple studies observed results dependent on the baseline 25(OH)D concentration of participants. Improvements in severe COPD [74] and increases in IFN- γ production in TB patients [63] were only observed in subsets that were vitamin D deficient at baseline, and the greatest reduction in influenza A incidence was observed in children naïve to vitamin D supplements [83] .…”

Relationship Between Serum Vitamin D Levels and Childhood Recurrent Tonsillitis

“…11 Moreover, vitamin D-induced antiviral peptides were shown to be effective against the herpes simplex type 1, adenovirus, human immunodeficiency virus, and chickenpox virus as has been implicated in the previous studies. 26 Furthermore, Science et al 27 demonstrated that a higher risk for viral URTIs which was confirmed by polymerase chain reaction (PCR) was associated with low vitamin D levels. The authors revealed that the risk for URTIs increased by 50%, when vitamin D levels were below 70 nmol/L, whereas the risk increased by 70%, when vitamin D levels were below 50 nmol/L.…”