Vitamin D Insufficiency in Young Finnish Men

Associations with bone stress fracture and respiratory tract infections
Acta Universitatis Tamperensis No. 1736

By Ilkka Laaksi
July 2012
Tampere University Press
ISBN: 9789514488191
82 pages
$87.50 Paper original

Vitamin D is not an actual vitamin but a secosteroid hormone produced in the skin from 7-dehydrocholesterol after exposure to sunlight’s ultraviolet B radiation. Vitamin D needs to be hydroxylated twice to reach an active form that is able to regulate gene expression through binding with vitamin D receptors (VDRs) and further to vitamin-D-responsive elements (VDREs) in vitamin-D-responsive genes. The level of the major circulating form of the hormone, serum 25OHD, is used for determination of vitamin D status. Vitamin D insufficiency can be regarded as a global issue with substantial implications for health. On account of inadequate sun exposure in wintertime, vitamin D insufficiency is commonplace among all age groups in Finland. As sunlight exposure is inadequate for vitamin D production in the skin, nutrition and supplements are the main sources of vitamin D in northern countries during winter months. Upon the recommendation of the Ministry of Social Affairs and Health, vitamin D has been added to commercial milk products and margarines since February 2003 in Finland.

In the first study, we determined the effects of national policy on vitamin D fortification in young Finnish men. The study population consisted of 196 young Finnish men (18–28 yrs) whose serum 25OHD concentrations were determined with Octeia® enzyme immunoassay by IDS in January 2003 (n = 96) or in January 2004, one year after national vitamin D fortification started. We found a 50% increase in mean serum 25OHD3 concentrations after implementation of the vitamin D fortification of dairy products. In addition, the prevalence of vitamin D insufficiency (<40 nmol/l) had decreased by 50% (from 78% in January 2003 to 35% in January 2004). The study showed that national vitamin D fortification substantially improved the vitamin D status of young Finnish men. However, 35% remained vitamin D insufficient.

The most commonly known function of vitamin D is the effect on bone mineralisation. Bone stress fractures are one of the most frequently seen types of overuse injuries in athletes and military recruits. An association was recently shown between vitamin D and bone mineral content, with a correlation between low femoral bone density and stress fractures. In the second study, we measured the serum 25OHD concentration in a population sample of military recruits to determine whether vitamin D is a predisposing factor for bone stress fractures. In this prospective study, 800 healthy Finnish military recruits with a mean age of 19 years were followed up for development of stress fractures in homogenous circumstances. Serum 25OHD concentrations were measured with enzyme immunoassay at entry into military service, and the weight, height, body mass index (BMI), physical fitness score, and result of a 12 minute running test were measured for all subjects. In all, 756 subjects had completed the study at the end of 90-day follow-up, and subjects without a fracture constituted controls. The study found 22 recruits with a stress fracture (2.9%), the incidence being 11.6 (95% CI: 6.8–16.5) per 100 person-years. In the final multivariate analysis, the statistically significant risk factor for stress fracture in conscripts was below-median serum 25OHD level (75.8 nmol/l) OR being 3.6 (95% CI: 1.1–11.1). No statistically significant associations between BMI, age, physical fitness score, 12-minute running test or smoking and bone stress fractures were found in this study population. In conclusion, a lower serum 25OHD concentration may be a generally predisposing factor for bone stress fractures.

Vitamin D has a role in innate immunity activation; the production of antimicrobial peptides following toll-like receptor (TLR) stimulation by pathogen lipopeptides is dependent on a high enough level of 25OHD. Recent evidence suggest that differences in the ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection. In the third study, we explored whether an association exists between vitamin D insufficiency and acute respiratory tract infection in young Finnish men. For this prospective study, young Finnish men (n = 800) serving at a military base in Finland were enrolled. Serum 25OHD concentrations were measured in July 2002 and the subjects were followed up for six months, and the number of days of absence from duty due to respiratory infection was calculated. The mean serum 25OHD concentration was 80 nmol/l in July 2002 (n = 756). The subjects with serum 25OHD concentrations <40 nmol/l, indicating vitamin D insufficiency, had statistically significantly more days of absence from duty due to respiratory infection. Also, a statistically significant positive association between serum 25OHD concentrations and the amount of physical exercise before induction into military service was found. In addition, smoking was statistically significantly associated with lower serum 25OHD concentrations. In conclusion, the study showed that a low vitamin D level increases the risk of acute respiratory tract infections.

There is clinical evidence of an association between vitamin D insufficiency and respiratory tract infections. There is also some evidence of prevention of infections by vitamin D supplementation. In the fourth study, we determined the effect of vitamin D supplementation on the incidence of acute respiratory tract infections in young Finnish men. For this RCT, 164 healthy conscripts were enrolled. From October to March, half of them received 10 µg of vitamin D daily and half received a placebo. Smoking was adjusted for in the study’s analysis. The mean serum 25OHD concentrations were 79 nmol/l in October 2005 and 72 nmol/l in March 2006 in the vitamin D group. The corresponding concentrations in the placebo group were 74 and 51 nmol/l. There was no statistically significant difference in the number of days of absence from duty (the main outcome variable) between the vitamin D and placebo group. However, the proportion of men remaining healthy throughout the six-month study period was greater in the vitamin D group (51%) than in the placebo group (36%), p = 0.045. Further, in a Cox regression analysis with adjustment for smoking, the adjusted hazard ratio (HR) for absence from duty due to a respiratory tract infection was lower in the vitamin D group (HR 0.71; 95% CI: 0.43–1.15). The RCT showed some evidence of a preventive effect of vitamin D supplementation against respiratory tract infection. Larger randomised controlled trials are warranted to explore this preventive effect.

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