Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.i6583 (Published 15 February 2017)
Plot of data by GrassrootsHeatlh
- This meta-analysis, like almost all others, ignores the vitamin D dose size
- Thus the same importance was given as 400 IU daily as 4,000 IU daily
- 40% reduction for ages 1-11 - average for all dose sizes
- Vitamin D must be very powerful if benefits are found even when dose size is ignored
- Imagine if Aspirin had a similar meta-analysis, with dose sizes ranging from 40 mg to 400 mg
- Most of the loading-dose (Bolus) trials examined used only a single 120,000 IU dose of vitamin D
- Most successful adult loading-dose/Bolus treatments use dose sizes of 300,000 IU to 1,500,000 IU of vitamin D
- COVID ARDS deaths 2X more likely if less than 10 ng of Vitamin D – Aug 8, 2020
- Acute respiratory infection worsened by too infrequent vitamin D supplementation – RCT June 2015
- Acute respiratory distress – 100 percent of patients were vitamin D deficient– April 2015
- Acute Lower Respiratory Infections in Children - associated with low vitamin D – meta-analysis Dec 2014
VitaminDWiki RTI studies 28 as of Sept 2021
Loading Dose of Vitamin D contains the following studies
- 600,000 vitamin D loading doses – good response to both oral and muscular – Oct 2015
- 500,000 IU of vitamin D cut in half the hospital days following a lung failure – RCT 2015
- ICU survival increased with vitamin D single 540K IU loading dose - JAMA Sept 2014 540,000 IU
- Children in Intensive Care need Vitamin D loading dose of 10000 IU per kg (nearing a consensus) - Oct 2016
which would be 200,000 for a 20 kg child
- 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
Breathing category starts with the following
Adrian R Martineau, professor of respiratory infection and immunity1 2, David A Jolliffe, postdoctoral research fellow1, Richard L Hooper, reader in medical statistics1, Lauren Greenberg, medical statistician1, John F Aloia, professor of medicine3, Peter Bergman, associate professor4, Gal Dubnov-Raz, consultant paediatrician5, Susanna Esposito, professor of paediatrics6, Davaasambuu Ganmaa, assistant professor7, Adit A Ginde, professor of emergency medicine8, Emma C Goodall, assistant professor9, Cameron C Grant, associate professor10, Christopher J Griffiths, professor of primary care1 2 11, Wim Janssens, professor of pneumonology12, Ilkka Laaksi, chief administrative medical officer13, Semira Manaseki-Holland, senior clinical lecturer14, David Mauger, professor of public health sciences and statistics15, David R Murdoch, professor of pathology16, Rachel Neale, associate professor17, Judy R Rees, assistant professor18, Steve Simpson Jr, postdoctoral research fellow19, Iwona Stelmach, professor of paediatric allergy20, Geeta Trilok Kumar, associate professor21, Mitsuyoshi Urashima, professor of molecular epidemiology22, Carlos A Camargo Jr, professor of emergency medicine, medicine, and epidemiology23
Correspondence to: A R Martineau a.martineau at qmul.ac.uk
Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.
Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.
Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.
Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.
Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants.
Vitamin D supplementation [ ignoring dose size] reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05).
Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.
Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.
Systematic review registration PROSPERO CRD42014013953.
Review of the above study: Vitamin D supplementation to prevent acute respiratory tract infections - July 2017
Journal of Paediatics and Child Health, DOI: 10.1111/jpc.13624, First published: 2 July 2017
Professor Craig Mellis, craig.mellis at sydney.edu.au
Vitamin D deficiency, and the role of vitamin D supplementation, is controversial. However, it is hard to ignore the recent systematic review suggesting that, at last, we may have a magic bullet for reducing the rate of respiratory tract infections in children. This systematic review was unusual in that the authors obtained the individual data from all 10 933 participants in the 25 randomised trials included in their review. Such non-aggregated data enable a far more reliable assessment of response in pre-specified subgroups. The quality of the evidence was rated as high, and the overall result was protective, with an adjusted odds ratio (OR) of 0.88; 95% confidence interval (CI) 0.81, 0.96; P = 0.001; number needed to treat (NNT) = 33 (to prevent one respiratory tract infection).
- Twelve randomised controlled trials were in children <16 years;
- four in infants <1 year (n = 5571) and
- eight in 1.1–15.9 years (n = 1079).
No significant benefit was seen in infants; adjusted OR = 0.94 (95% CI 0.83, 1.06; P = 0.33).
However, in the 1.1–15.9 year age group, the adjusted OR was 0.60 (95% CI 0.46, 0.77; P < 0.001), with an NNT of 8. Subgroup analysis found, unsurprisingly, a better response in those with low baseline vitamin D levels (i.e. 25-hydroxyvitamin D < 25 nmol/L). Surprisingly, daily or weekly supplementation was more effective than bolus injections. Influenza vaccine status had no significant effect on response. The generalisability of these findings is unclear.
"Reduce acute respiratory tract infections in those with significant vitamin D deficiency (circulating 25-hydroxyvitamin D levels < 10 ng/mL) with daily or weekly vitamin D supplementation—not bolus vitamin D treatment."
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