Discussion
The primary finding of these two studies was that vitamin D sufficiency reduced the burden of URTI in healthy young adults completing arduous military training. In study 1, vitamin D–sufficient men and women were 40% less likely to suffer a physician-diagnosed URTI during training than those with serum 25(OH)D <50 nmol·L−1 (Figure 2). Given this finding, and that only 21% of participants were vitamin D sufficient during winter, study 2 examined the effect of winter vitamin D supplementation on URTI. Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (Figure 5). Study 2 is the first to demonstrate the benefits of vitamin D supplementation, in line with IOM and EFSA guidelines, on URTI in an active population. These findings are timely as the nutrition and athletic performance position stands from the International Olympic Committee and American College of Sports Medicine highlight that vitamin D insufficiency is widespread in athletes.[9,41]
In study 1, vitamin D–sufficient men and women were less likely to suffer a physician-diagnosed URTI during training than those with serum 25(OH)D of <50 nmol·L−1 (Figure 2). This finding can be considered robust as it was observed after accounting for sex and smoking, which is a strength of this study when compared with previous research that has not controlled for factors known to independently influence URTI.[17–19] In study 1, the association between baseline vitamin D status and URTI was stronger during the first 3 wk of the 12-wk training program, which might be expected given the high incidence of URTI at this time, and that 25(OH)D has approximately a 3-wk half-life.[35,36] Study 1 extends our understanding of the relationship between vitamin D and URTI in active populations as data were collected in a large sample, across all seasons, and with a large range of serum 25(OH)D concentrations. The burden of URTI was evident as each URTI resulted in an average of 3 d missed training.
In study 2, vitamin D supplementation by simulated sunlight and oral vitamin D3 was similarly effective to achieve IOM- and EFSA-recommended vitamin D sufficiency in the majority of individuals (≥95%; Figure 4). Vitamin D supplementation did not reduce self-reported URTI prevalence or benefit mucosal immunity compared with placebo (Table 2). However, vitamin D supplementation reduced URTI burden compared with placebo: participants receiving vitamin D reported 15% lower peak URTI severity and 36% fewer days with URTI compared with placebo (Figure 5). The magnitude of the reduction in URTI burden in study 2 can be considered meaningful as effect sizes were medium to large. These findings also broadly agree with the previous research in this area,[20,22] i.e., vitamin D supplementation reduced URTI symptoms[22] and absence from duty due to respiratory infection.[20]
The different methods used to assess URTI in the studies may explain the difference between study 1 and study 2 prevalence findings. The lower URTI prevalence in study 1 than study 2 (7% vs 69%) indicates that physician diagnosis of URTI compared with daily self-report likely missed more minor illnesses that did not warrant a medical visit. Further, study 2 physician-diagnosed URTI prevalence was 8%, which was the same as study 1, when controlling for season. Self-reported URTI data were not reported back to the military and therefore did not influence physician diagnosis of URTI or lost training days due to URTI. When considered carefully in the context of these different methods, the findings of studies 1 and 2 are complementary. In study 2, lower peak URTI severity and fewer days with URTI with vitamin D supplementation, compared with placebo, would be expected to translate to vitamin D–sufficient individuals reporting less to medical services, and consequently having fewer physician-diagnosed URTI than those individuals with 25(OH)D <50 nmol·L−1. This is entirely consistent with the main finding of study 1: URTI prevalence was lower in vitamin D–sufficient individuals than those with 25(OH)D <50 nmol·L−1 (Figure 2).
Study 2 findings are notable as they highlight that vitamin D supplementation may reduce URTI burden rather than prevent URTI. Vitamin D supplementation did not influence the innate mucosal antimicrobial proteins SIgA and cathelicidin that form an important part of the first line of defense against URTI. Based on these findings, it is speculated that the tolerogenic effects of vitamin D may reduce URTI burden by limiting inflammation in response to an infection (i.e., controlling infection at a nondamaging level),[3,14,42] which subsequently leads to a reduction in self-reported URTI severity and duration.[14] Future research is warranted to investigate the effect of vitamin D supplementation on URTI and circulating anti-inflammatory cytokines.[3] To better understand the influence of vitamin D supplementation on the immune pathway, these studies should examine serum 1,25(OH)2D, the biologically active form, as well as 25(OH)D. It is also worth noting that women were not included in study 2, and therefore future work should determine the influence of vitamin D supplementation on URTI burden in women.
The pathological determination of URTI using nasopharyngeal throat swabs would have provided assurance that the URTI reported in studies 1 and 2 was infection by origin rather than due to some other cause, e.g., allergy. Nonetheless, previous research has shown that infectious pathogens of URTI identified by self-reported questionnaire methods were confirmed in 82% of recreationally active men and women[31] and in 75% of Winter Olympic Games athletes.[43] Furthermore, study 2 was completed during winter when common cold and flu are prevalent and symptoms caused by summer allergies are rare. Rejecting self-reported URTI for pathogen recognition is not advocated; rather, future research is advised to use a blended approach incorporating the infectious etiology with real-world URTI symptomology. Study 2 findings highlight the importance of the daily assessment of URTI symptoms to monitor URTI duration and severity as well as prevalence, regardless of whether pathogen recognition is available. The assessment of URTI duration and severity will be important in future studies wishing to further examine potential tolerogenic effects of vitamin D on immune health. Future research should also adopt the blended approach to more fully understand the effectiveness of other potential treatments for URTI.
Currently, there is no consensus for the optimal vitamin D threshold or dose for immune health.[13] Participants beginning supplementation with serum 25(OH)D <50 nmol·L−1 reported shorter URTI duration when receiving vitamin D compared with placebo supplementation. Further evidence that participants with serum 25(OH)D <50 nmol·L−1 benefitted more from vitamin D supplementation than the entire sample is clear when examining the effect sizes between vitamin D and placebo for URTI outcomes: small–medium effect sizes for the entire sample, compared with medium and large effect sizes for participants with serum 25(OH)D <50 nmol·L−1 (Figure 5). Compared with the IOM- and the EFSA-recommended vitamin D sufficiency, no additional protection from URTI of higher vitamin D status, including a previously proposed optimal threshold (serum 25(OH)D > 75 nmol·L−1,[44] was revealed. These findings alongside other findings from this research program that show benefits of vitamin D sufficiency on in vivo immunity[45] support 25(OH)D ≥50 nmol·L−1 for immune health. Further, the current studies highlight that exercise performance may indirectly benefit from maintaining vitamin D sufficiency by reducing lost training days to URTI.
No additional benefit of SSR compared with oral vitamin D3 supplementation was shown on URTI, immune function (this study and),[45] or exercise performance.[10] Consequently, active people are advised to take the 400-IU·d−1 oral vitamin D3 dose, from the maintenance phase of study 2, to maintain vitamin D sufficiency when exposure to ambient UVB is inadequate: between early autumn and late winter, and for those that live and/or exercise indoors for the majority of sunlight hours or cover-up from the sun. When accounting for typical dietary vitamin D intake, this oral vitamin D3 supplementation approach corresponds with current IOM and EFSA recommendations (600 IU·d−1 for bone and general health, and unlike simulated sunlight, there is no time burden for an individual, no requirement for bulky irradiation cabinets, and oral vitamin D3 supplementation is effective regardless of sun-reactive skin type. Nevertheless, low-level sunlight may provide benefits to human health, additional to vitamin D synthesis, and this remains an area of active research.[24]
Med Sci Sports Exerc. 2021;53(7):1505-1516. © 2021 American College of Sports Medicine
