February 5, 2014

Vitamin D and Risk of Acute Respiratory Tract Infection

In those who were deficient, vitamin D significantly decreased respiratory tract infections
It seems clear from this study that even when vitamin D dosing may not be optimal it can still have a large impact on the health of children.

Reference                                              

Camargo CA Jr, Ganmaa D, Frazier AL, et al. Randomized trial of vitamin D supplementation and risk of acute respiratory tract infection in Mongolia. Pediatrics. 2012;130(3):e561-567.
 
Design
Randomized, controlled double-blind
 

Participants

744 Mongolian schoolchildren in the 3rd and 4th grades
 

Outcome Measures

Reported acute respiratory infections (ARIs) by participants’ parents in the past 3 months (January–March)
 

Key Findings

In those who were deficient, vitamin D supplementation decreased ARIs during the winter months by approximately 50% compared to controls. Over 7 weeks of supplementation with 300 IU vitamin D/day, there was significant increase of 25-hydroxycholicalciferol in the intervention versus the control group (7 vs 19 mg/mL, P<0.001), although levels were still in the range of deficiency.
 

Practice Implications

Mongolians are at particularly high risk of vitamin D deficiency due to the lack of fortification of their food sources, as well as the cold weather—and therefore decreased skin exposure to sunlight. Several studies speak to the fact that lower levels of vitamin D lead to an increased risk or acute respiratory infections, including influenza infection, especially during seasons when most people experience a drop in those levels.1 Supplementation can help prevent these infections; a dosage of 2,000 IU of vitamin D3 per day drastically decreased occurrence of colds and flu.2
 
The 2 groups in this study were randomized to consume either cow’s milk with no fortification or milk fortified with vitamin D3. The daily dose was 300 IU of vitamin D3 for 7 weeks. It is not surprising that this supplementation failed to raise 25-OH vitamin D levels above 20 ng/mL in the participants, as the daily pediatric intake standards of the United States and Canada are 400 and 1,000 IU of vitamin D3. In addition, the duration of the study was only 7 weeks, and in many clinical cases it takes longer than this to raise serum vitamin D to adequate levels. It is important to note that the cutoff for Labcorp’s 25-OH vitamin D level is 30 ng/mL, and deficiency is determined to be <20 ng/mL.3,4 It is not clear why the researchers didn’t use the dose The American Academy of Pediatrics recommends for infants (400 IU/day).5 The Canadian Pediatric Society recommends 400–800 IU vitamin D3/day for children up to 1 year of age, depending on the time of year.6 This may be due to an increased willingness to use more realistic vitamin supplementation, or to the fact that Canada experiences a colder climate, and therefore its children have less opportunity for sun exposure, similar to Mongolia. 
 
Previous studies have shown that vitamin D supplementation can enhance immune function. Low serum vitamin D is correlated with multiple sclerosis diagnosis,7 and low cord blood of 25-OH vitamin D has a strong inverse correlation of number of acute respiratory infections in the first 3 months of life, as well as RSV infections in the first year.8 The latter is most likely explained by the fact that activated vitamin D increases the endogenous antimicrobial peptide, cathelicidin, in bronchial epithelial cells.9
 
It seems clear from this study that even when vitamin D dosing may not be optimal it can still have a large impact on the health of children.
 
 
This study is of particular importance. The dairy industry purports that consuming dairy products will provide significant amounts of vitamin D. However, despite widespread dairy consumption in this country, 20% of US children still have vitamin D levels below 20ng/mL,10  and this number may be even higher among those children with darker skin, such as Hispanics and African Americans. Furthermore, this does not account for children with levels of vitamin D within the reference range of most labs (>32.0 ng/mL), which is still deemed suboptimal by some physicians, most notably Dr. Cannell of the Vitamin D Council.11 It seems clear from this study that even when vitamin D dosing is not optimal, it can still have a large impact on the health of children. I am therefore of the opinion that it is of utmost importance that physicians test all children for vitamin D levels at 1 year of age, along with serum lead. I also like to do a complete blood count and comprehensive metabolic panel while the patient is already getting his blood drawn. Vitamin D3 supplementation at levels between 400 and 800 IU/day should certainly occur in the first year, regardless of breastfeeding status. It should be safe to supplement shortly after birth.

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References

1. Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006;134(6):1129-1140. 2. Aloia JF, Talwar SA, Pollack S, Yeh J. A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med. 2005;165(14):1618-1623.
3. Institute of Medicine. Dietary reference intakes for calcium and D. Washington DC:  The National Academies Press. 4. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930. 5. Wagner CL, Greer FR, American Academy of Pediatrics Section on Breastfeeding, American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142-1152. 6. Canadian Paediatric Society, First Nations and Inuit Health Committee. Vitamin D supplementation in northern Native communities. Paediatr Child Health. 2002;7:459-463. 7. Décard BF, von Ahsen N, Grunwald T, et al. Low vitamin D and elevated immunoreactivity against Epstein–Barr virus before first clinical manifestation of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012 Aug 11. 8. Belderbos ME, et al. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011;127(6)e1513-1520. 9. Yim S, Dhawan P, Ragunath C, Christakos S, Diamond G. Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3). J Cyst Fibros. 2007;6(6):403-410. 10. Mansbach JM, Ginde AA, Camargo CA Jr. Serum 25-hydroxyvitamin D levels among US children aged 1 to 11 years: do children need more vitamin D? Pediatrics. 2009;124(5):1404-1410. 11. Vitamin D Council. Vitamin D deficiency: A global epidemic. Vitamin D Council. July 9, 2012. Available at http://www.vitamindcouncil.org/about-vitamin-d/vitamin-d-deficiency/#ref663. Accessed November 6, 2012.