Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis
Vitamin D supplementation reduced the risk of acute respiratory infections, with very vitamin D deficient people and those receiving daily or weekly doses experiencing the most benefit.
Health Technology Assessment Vol: 23, Issue: 2, January 2019, https://doi.org/10.3310/hta23020
Martineau A R, Jolliffe D A, Greenberg L, Aloia J F, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde A A, Goodall E C, Grant C C, Janssens W, Jensen M E, Kerley C P, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch D R, Neale R, Rees J R, Simpson S, Stelmach I, Trilok Kumar G, Urashima M, Camargo C A, Griffiths C J & Hooper R L.
- Those with Asthma or COPD had half the response to Vitamin D – March 2020
- Lower Respiratory Tract Infection in Infants reduced 5.9 X by daily 600 IU of vitamin D (China) - March 2020
- Hay Fever treated by Vitamin D (50,000 IU weekly) – RCT July 2019
- COPD trial to use 80,000 IU of vitamin D weekly – RCT 2021
- Allergic Rhinitis in infants treated by 1,000 IU vitamin D daily – June 2019
- Childhood colds reduced 25 percent by 14,000 IU of Vitamin D (need larger dose) – RCT Jan 2019
- All asthma problems reduced after 1 year of Vitamin D – Nov 2017
- Asthma treated by daily 50,000 IU of Vitamin D – April 2018
- Childhood Respiratory Health hardly improved with 600 IU of vitamin D (need much more) – May 2018
- Allergic rhinitis in children reduced somewhat during pollen season by just 1,000 IU of vitamin D – RCT Jan 2018
- Influenza risk reduced 2X by 2,000 IU of Vitamin D (vs 400), RTI reduced 3X by 400 or more IU – July 2017
- Influenza -A infections half as often in children getting 1200 IU of vitamin D – RCT Jan 2018
- Risk of infant Asthma cut in half if mother supplemented Vitamin D to get more than 30 ng – RCT Oct 2017
- Childhood asthma problems eliminated for months by 600,000 IU of Vitamin D – June 2017
- Reduction of infant asthma may require good vitamin D when lung development starts (4 weeks) – March 2017
- Monthly 100,000 IU of vitamin D decreased respiratory infection but increased falls – Nov 2016
- RTI – Feel much better if increase vitamin D level above 40 ng (4000 IU) – RCT Sept 2015
- Five times less mite allergy when vitamin D added in mid pregnancy and to infant – RCT April 2016
- Childhood asthma still reduced 4 months after 800 IU of Vitamin D daily - RCT Feb 2016
- Asthma exacerbations with colds reduced by 40 percent with vitamin D supplementation – Nov 2015
- Allergic Rhinitis (hay fever) reduced by just 1,000 IU of vitamin D for 30 days – RCT Sept 2015
- Vitamin D loading dose then weekly 50,000 IU not help (COPD) if very deficient – Oct 2015
- Respiratory tract infection eliminated in 36 percent of people by 4000 IU of Vitamin D – RCT Sept 2015
- COPD reduced by 40 percent with monthly 100,000 IU of vitamin D – RCT Jan 2015
- 500,000 IU of vitamin D cut in half the hospital days following a lung failure – RCT 2015
- Respiratory infections cut in half by 20,000 IU weekly vitamin D if initially deficient – RCT March 2015
- Wheezing reduced 35 percent if vitamin D added during pregnancy – April 2015
- Loading dose of 500,000 IU vitamin D increased hemoglobin in critical illness – RCT April 2015
- Respiratory diseases helped by vitamin D if initially have low level – RCT review Jan 2015
- COPD reduced by vitamin D taken once every 60 days – RCT Dec 2014
- Asthma reduced 60 percent with vitamin D supplementation – meta-analysis 2014, 2015
- Respiratory Tract visits 2.5 less likely with vitamin D: Pregnancy 2000 IU, Infant 800 IU – RCT Oct 2014
- Allergy to House dust mite greatly reduced by adding just 600 IU of vitamin D – RCT Nov 2014
- Asthma reduced by weekly 50,000 IU of vitamin D – RCT Aug 2014
- Asthma attacks reduced in half if Vitamin D level higher than 42 nanograms – RCT May 2014
- 2000 IU of vitamin D should improve toddlers health in winter – RCT almost completed Feb 2014
- Bronchial Asthma reduced with 60,000 IU monthly vitamin D – RCT Nov 2013
- COPD Overview
- Respiratory infections reduced by 63 percent with 4000 IU vitamin D daily - RCT Dec 2012
- Just 300 IU daily of vitamin D reduced respiratory infections by 50% – RCT Aug 2012
- Recurrence of child pneumonia delayed by 100000 IU of vitamin D – RCT Oct 2010
- 100000 IU vitamin D monthly helps COPD patients – 3 RCT
- Asthmatics less able to breathe if low vitamin D – meta-analysis Nov 2019
- Asthma is 20 percent more likely with a poor Vitamin D Receptor gene – meta-analysis Oct 2019
- Pneumonia 6X more likely if very low vitamin D – meta-analysis Sept 2019
- Asthma supplementation by Vitamin D (any amount) reduced attacks by 25 percent – meta-analysis April 2019
- Respiratory infections reduced only 20 percent by Vitamin D (ignored dose size, duration, type, etc) – meta-analysis Jan 2019
- Breath better if higher level of Vitamin D – meta-analysis March 2018
- Asthma risk reduced by 67 percent with Vitamin D supplementation if level was initially low– meta-analysis Nov 2017
- Pneumonia patients 3 X more likely to die if low vitamin D – meta-analysis Sept 2017
- Acute respiratory tract infections prevented by vitamin D (even when ignoring the dose size – Meta-analysis Feb 2017
- Asthma exacerbations in children decrease by 60 percent with vitamin D supplementation – meta-analysis – 2015
- Vitamin D during pregnancy reduces risk of childhood asthma by 13 percent – meta-analysis Dec 2016
- Childhood asthma about 1.3 times more likely if poor Vitamin D Receptor – meta-analysis Aug 2016
- COPD 2.8 times more likely to be severe if low vitamin D – meta-analysis Oct 2016
- Lower respiratory tract infections in children associated with Low Vitamin D – meta-analysis May 2016
- Asthma medicines not helped by vitamin D (if only a small amount of D is taken) – meta-analysis Dec 2015
- Asthma not helped by less than 2,000 IU of vitamin D - meta-analysis Aug 2015
- COPD strongly associated with Vitamin D Binding Protein problems – meta-analysis Aug 2015
- COPD severity is associated with Vitamin D deficiency – meta-analyses 2015, 2019
- Infant wheezing 40 percent less likely if mother supplemented with vitamin D, vitamin E, or Zinc – meta-analysis Aug 2015
- Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014
- Asthma reduced 60 percent with vitamin D supplementation – meta-analysis 2014, 2015
- Infectious Disease typically not treated if use less than 4000 IU vitamin D daily– review Oct 2014
- Acute Lower Respiratory Infections in Children - associated with low vitamin D – meta-analysis Dec 2014
- Asthma is strongly associated with low vitamin D (but not COPD) – meta-analysis Feb 2014
- Vitamin D and Respiratory Tract Infections – meta-analysis with charts June 2013
- Vitamin D reduces respiratory tract infections by 40 percent– meta-analysis Dec 2012
- Acute respiratory infection treated by vitamin D in 6 of 12 clinical trials – review Nov 2012
Note: 4,000 IU is where benefits of Vitamin D are noticed in adults
Background: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity.
Objectives: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect.
Data sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry.
Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected.
Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity.
We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality.
Limitations: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately.
Conclusions: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes.
Study registration: This study is registered as PROSPERO CRD42014013953.