Influence of Vitamin D Supplementation by Simulated Sunlight or Oral D3 on Respiratory Infection During Military Training

Sophie E. Harrison; Samuel J. Oliver; Daniel S. Kashi; Alexander T. Carswell; Jason P. Edwards; Laurel M. Wentz; Ross Roberts; Jonathan C. Y. Tang; Rachel M. Izard; Sarah Jackson; Donald Allan; Lesley E. Rhodes; William D. Fraser; Julie P. Greeves; Neil P. Walsh

Disclosures

Med Sci Sports Exerc. 2021;53(7):1505-1516. 

In This Article

Abstract and Introduction

ABSTRACT

Purpose: This study aimed to determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1) and then to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L−1 by a unique comparison of safe, simulated sunlight or oral D3 supplementation in winter (study 2).

Methods: In study 1, 1644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received placebo, simulated sunlight (1.3× standard erythemal dose, three times per week for 4 wk and then once per week for 8 wk), or oral vitamin D3 (1000 IU·d−1 for 4 wk and then 400 IU·d−1 for 8 wk). URTI was diagnosed by a physician (study 1) and by using the Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA), and cathelicidin were assessed by liquid chromatography–mass spectrometry LC-MS/MS and enzyme-linked immunosorbent assay.

Results: In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D–sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D <50 nmol·L−1 (OR = 0.6, 95% confidence interval = 0.4–0.9), an association that remained after accounting for sex and smoking. Each URTI caused, on average, three missed training days. In study 2, vitamin D supplementation strategies were similarly effective to achieve vitamin D sufficiency in almost all (≥95%). Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (P < 0.05). These reductions were similar with both vitamin D strategies (P > 0.05). Supplementation did not affect salivary secretory immunoglobulin A or cathelicidin.

Conclusion: Vitamin D sufficiency reduced the URTI burden during military training.

Introduction

Athletes and military personnel experience arduous training and nutritional inadequacy that may compromise host defense and increase their susceptibility to respiratory illness such as the common cold, particularly during the autumn-winter.[1,2] The immunomodulatory effects of vitamin D are considered to play a role in the seasonal stimulus for upper respiratory tract infection (URTI).[3,4] This has fueled considerable interest in potential prophylactic benefits of vitamin D supplementation on URTI. Vitamin D can be obtained from diet but is primarily synthesized by skin exposure to sunlight ultraviolet B (UVB) radiation. As dietary vitamin D intakes in the United States and Europe (112–330 IU·d−1)[5–7] are typically less than recommended (600 IU·d−1),[7,8] people who live at latitudes >35° or live indoors for the majority of sunlight hours and cover-up from the sun are at higher risk of vitamin D insufficiency. Indeed, epidemiological studies report vitamin D sufficiency (serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol·L−1 in only 40%–65% of athletes and military personnel during the winter, when skin exposure to UVB radiation is negligible.[9–11]

Vitamin D is widely accepted to influence both innate and adaptive immunity with implications for host defense.[12,13] 25(OH)D is converted in the kidney to the biologically active form 1,25-dihydroxyvitamin D (1,25(OH)2D), which enhances the innate immune response by the induction of antimicrobial proteins like cathelicidin.[13] Antimicrobial proteins help to prevent URTI as part of the first line of defense. The actions of vitamin D on adaptive immunity may also be anti-inflammatory or "tolerogenic".[3] Immune tolerance has been described as the ability to dampen defense yet control infection at a nondamaging level,[14] prompting the search for tolerogenic nutritional supplements to reduce URTI burden.[3] URTI burden can be assessed by URTI prevalence, or the duration or severity of URTI. As such, maintaining or achieving vitamin D sufficiency may reduce URTI burden by preventing URTI symptoms but also by reducing the duration and/or severity of URTI.[3,9,11]

Large cross-sectional and randomized placebo-controlled supplementation studies in the general population highlight that vitamin D reduces the burden of URTI.[4,15,16] However, cross-sectional studies in young healthy and athletic populations present conflicting findings,[17–19] which might be explained by small samples with few URTI, a limited range of vitamin D concentrations due to single-season data collections, and a lack of control for factors known to independently influence URTI (e.g., sex and smoking). Randomized controlled trials investigating the effect of vitamin D supplementation on URTI and immunity in military recruits and athletes are extremely limited and present a mixed picture.[20–23] These studies show reduced URTI symptoms,[22] improved mucosal immunity (i.e., salivary cathelicidin and IgA),[21,23] and fewer missed training days due to URTI,[20] as well as no effect on URTI symptoms[20] or mucosal immunity.[22,23] The significant heterogeneity reported in these trials may stem from variations in participant baseline vitamin D status and dosing regimens; these factors are considered to modify the effect of vitamin D on immunity to respiratory pathogens.[15] The participants in these studies were vitamin D sufficient at baseline,[20,21] which likely limited the need and potential benefit of vitamin D supplementation.[11] Also participants were administered higher oral vitamin D doses than recommended by the Institute of Medicine (IOM) and European Food Safety Authority (EFSA),[21,22] increasing the risk of adverse outcomes (tolerable upper intake 4000 IU·d−1.[7,8] Although vitamin D is derived from skin exposure to sunlight, the effect of safe skin sunlight exposure on URTI burden and mucosal immunity has yet to be studied. Ultraviolet radiation has a range of vitamin D–dependent and vitamin D–independent effects on immunity;[24] however, whether there are additional benefits of safe sunlight exposure, compared with oral vitamin D supplementation, is unknown. Given the negative effect of URTI on training and performance, it is important to determine whether vitamin D supplementation has measurable and meaningful effects on URTI in physically active populations.[2,9,11]

First, the relationship between vitamin D status and URTI prevalence was determined in a large, prospective cohort study of young men and women commencing military training across all seasons (study 1). It was hypothesized that vitamin D–sufficient recruits would be less likely to suffer URTI, compared with those who had serum 25(OH)D <50 nmol·L−1. Then, in a randomized placebo-controlled trial (study 2), the effects on overall URTI burden (prevalence, duration, and severity) and mucosal immunity of achieving vitamin D sufficiency by either simulated sunlight, following recommendations on safe, low-level sunlight exposure,[25] or oral D3 supplementation in wintertime was investigated. Vitamin D sufficiency was targeted because maintaining serum 25(OH)D concentration ≥50 nmol·L−1 has been recommended for health by the IOM and EFSA and is achievable using safe doses of oral vitamin D3 and simulated sunlight.[7,8] It was hypothesized that achieving vitamin D sufficiency during winter by vitamin D supplementation would reduce URTI burden and improve mucosal immunity compared with placebo supplementation.

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