Table of contents
- Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials - March 2021
- VitaminDWiki comment and other studies
- Breathing Meta-analysis
- 20 studies in Breathing with non-daily Intervention
- Breathing items with ACUTE in title
Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials - March 2021
www.thelancet.com/diabetes-endocrinology DOI:https://doi.org/10.1016/S2213-8587(21)00051-6
David A Jolliffe, PhD; Prof Carlos A Camargo Jr, MD; John D Sluyter, PhD; Mary Aglipay, MSc
Prof John F Aloia, MD; Davaasambuu Ganmaa, PhD
Background
A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis.
Methods
For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0–49·9 nmol/L vs 50·0–74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400–1000 IU vs 1001–2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00–15·99 years vs 16·00–64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633.
Findings
We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0–95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86–0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65–0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400–1000 IU (0·70 [0·55–0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72–0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00–15·99 years at enrolment (0·71 [0·57–0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86–1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials.
Interpretation
Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400–1000 IU for up to 12 months, and age at enrolment of 1·00–15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation.
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VitaminDWiki comment and other studies
Of the 1500 trials to chose from,
most of the trials selected by this meta-analysis used <2,000 IU
about 20% of the trials were too short (<3 months) to expect any response to non-bolus doses
- Respiratory infections (RTI) cut in half by 20,000 IU weekly vitamin D if initially deficient – RCT March 2015
- Infectious Disease typically not treated if use less than 4000 IU vitamin D daily– review Oct 2014
- Asthma treated by monthly 100,000 IU of Vitamin D if person had very low levels – RCT Feb 2021
- Acute respiratory tract infections not reduced by Vitamin D if already have a good level – Jan 2021
- Those with Asthma or COPD had half the response to Vitamin D – March 2020
- Wonder if those prone to RTI have less response as well
- All asthma problems reduced after 1 year of Vitamin D – Nov 2017
- 100,000 IU injection followed by 5,000 IU weekly
- RTI – Feel much better if increase vitamin D level above 40 ng (4000 IU) – RCT Sept 2015
- Respiratory Infection associated with vitamin D less than 40 ng – March 2015 which has the following chart
Breathing Meta-analysis
This list is automatically updated
- Small doses of Vitamin D do not reduce childhood breathing allergies – meta-analysis Oct 2022
- Asthma treated by Vitamin D - 13th Meta-analysis – July 2022
- COPD treated by Vitamin D – meta-analysis March 2022
- Small amounts of Vitamin D reduce Influenza risk by 22 percent (loading dose is far better) – meta-analysis Jan 2022
- Asthma reduced by Vitamin D, even for those using corticosteroids - meta-analysis 2021
- Small vitamin D doses provide small benefits for acute respiratory infections – Meta-analysis March 2021
- Respiratory Tract Infection risk reduced 2X by Vitamin D loading doses – meta-analysis Jan 2021
- Small vitamin D doses given during pregnancy do not reduce childhood asthma – meta-analysis Dec 2020
- Acute viral respiratory infections (RTI) reduced by Vitamin D - 20 reviews - Aug 2020
- 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
- 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
20 studies in Breathing with non-daily Intervention
This list is automatically updated
- Chronic tonsillitis virtually eliminated in children by Vitamin D (50,000 IU weekly) – RCT May 2023
- Several smoking problems treated by Vitamin D (bi-weekly, 50,000 IU) - RCT Dec 2021
- Asthma and COPD in a few seniors greatly decreased by monthly 100,000 IU Vitamin D – RCT Feb 2021
- Acute respiratory tract infections not reduced by Vitamin D if already have a good level – Jan 2021
- Those with Asthma or COPD had half the response to Vitamin D – 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
- Childhood colds reduced 25 percent by weekly Vitamin D – RCT Jan 2019
- All asthma problems reduced after 1 year of Vitamin D – Nov 2017
- Vitamin D loading dose then weekly 50,000 IU not help (COPD) if very deficient – Oct 2015
- Respiratory infections (RTI) cut in half by 20,000 IU weekly vitamin D if initially deficient – RCT March 2015
- Asthma reduced by weekly 50,000 IU of vitamin D – RCT Aug 2014
- COPD fought by Vitamin D - many studies
Breathing items with ACUTE in title
This list is automatically updated