So far, vitamin D is known for its benefits for bone health. However, this vitamin also plays a vital role in the immune system. Therefore, vitamin D supplementation is thought to prevent respiratory infections by bacteria and viruses, such as the common cold, influenza, and pneumonia.

The main metabolite of vitamin D related to immunity is 25-hydroxyvitamin D. Low levels of 25-hydroxyvitamin D in plasma can make a person susceptible to respiratory infections. This is then studied further by studies from various countries because respiratory tract infection is a disease with high global morbidity and mortality.


Vitamin D - Immune System - Respiratory Tract Infections

Vitamin D supports the induction of antimicrobial peptides in the body and helps strengthen mucosal defenses. Also, vitamin D metabolites induce autophagy processes, synthesize reactive nitrogen intermediates, and synthesize reactive oxygen intermediates. This whole process has an antimicrobial effect on the human body.

Although the current average for vitamin D studies has considerable heterogeneity due to the variation in participant characteristics, study methodology, and vitamin D supplementation regimens used, most studies suggest that supplementation with vitamin D reduces the risk of respiratory tract infections.


Efficacy of Vitamin D Supplementation in Preventing Airway Infections

Previous Studies 

Bergman et al.'s meta-analysis of 11 studies with 5660 patients showed that vitamin D decreased the risk of respiratory tract infections. The protective effect was also reported to be more significant at daily doses of 300–2000 IU / day than at doses of 100 000 IU or 200000 IU per month or three months.

Research in New Zealand in 2012 also showed that vitamin D supplementation of 200,000 IU per month did not provide a significant difference in benefits between the intervention group and the control group.

Lower doses are reported to be more effective. The results of research in Sweden in 2012 stated that vitamin D supplementation of 4000 IU / day for one year could help prevent respiratory infections in adults.

A study on children with vitamin D deficiency in Mongolia in 2012 also showed that the group that received 300 IU / day of vitamin D supplementation for three months had a lower risk of respiratory tract infections than the control group.

Recent Studies 

Martineau et al.'s meta-analysis involved 25 randomized clinical trials with a total of 11321 participants (from ages 0–95 years). It showed that vitamin D supplementation could reduce the risk of respiratory tract infections, especially in patients with vitamin D deficiency. Patients with normal vitamin D levels also receive a protective benefit, but the benefit appears to be more significant in patients with deficiency.

The results of the study also showed that daily or weekly vitamin D supplementation (dose <800 IU / day to ≥2000 IU / day) provided a greater protective effect than high-dose vitamin D bolus (≥30000 IU) given once per month or one time every three months. Allegedly, this is because of high doses of vitamin D bolus cause:
  • fluctuations in the concentration of 25-hydroxyvitamin D in plasma 
  • dysregulation of the enzymes that metabolize it.

This study is supported by strong quality evidence. This study also studied double-blinded and placebo-controlled randomized clinical trials at the individual participant data level, thus providing more accurate outcome estimates than other meta-analyzes that are more generalized and have many heterogeneous variables.


Side Effects of Vitamin D Supplementation

In the studies mentioned above, most vitamin D supplementation was not reported to cause significant users' significant side effects. However, high doses of vitamin D bolus were reported to increase the risk of pneumonia, suppress the proliferative response of peripheral blood monocytes, and suppress the inflammatory response.

High vitamin D levels in the blood can also cause fatigue, nausea, vomiting, abdominal pain, constipation, diarrhea, and decreased appetite.

In addition, excess vitamin D can reduce vitamin K2, which plays a role in keeping calcium in the bones. This decrease in vitamin K2 can cause bone loss. Meanwhile, increased calcium levels in the blood (hypercalcemia) can cause indigestion, dizziness, excessive thirst, and frequent urination.



Conclusion
Vitamin D supplementation has been reported to reduce the risk of respiratory tract infections. This protective effect was particularly significant in patients with vitamin D deficiency. Lower daily or weekly doses were reported to be more effective than high-dose boluses (≥30000 IU) once every month or once every three months.

The use of low doses of vitamin D supplementation did not cause significant side effects. However, consuming too high a dose of vitamin D has been reported to increase the risk of pneumonia and cause side effects, such as indigestion, hypercalcemia, and bone loss.


References
1. Bergman P, Lindh AU, Björkhem-Bergman L, Lindh JD. Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS One. 2013 Jun 19;8(6):e65835. doi:10.1371/journal.pone.0065835
2. Bergman P, Norlin AC, Hansen S, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomized and double-blind intervention study. BMJ Open. 2012 Dec 13;2(6):e001663. doi:10.1136/bmjopen-2012-001663
3. Camargo CA Jr, Ganmaa D, Frazier AL, et al. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. Pediatrics. 2012 Sep;130(3):e561-7. doi:10.1542/peds.2011-3029
4. Marshall B, Bennett N, Smith A, Oh R, Burket J. PURL: Can vitamin D prevent acute respiratory infections?. J Fam Pract. 2019;68(4):230-231.
5. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi: 10.1136/bmj.i6583
6. Masterjohn C. Vitamin D toxicity redefined: vitamin K and the molecular mechanism. Med Hypotheses. 2007;68(5):1026-34.
7. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012 Oct 3;308(13):1333-9. doi:10.1001/jama.2012.12505
8. WHO. Vitamin D for the prevention of respiratory tract infections. 2017. https://www.who.int/elena/titles/commentary/vitamind_pneumonia_children/en/