COPD: Monitor and Evaluate Effect of Vitamin D Supplementation 2019
Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.
COPD: Monitor and Evaluate Effect of Vitamin D Supplementation
In adults with COPD who are receiving vitamin D supplementation, the RDN should monitor and evaluate the effect of the supplementation regimen on serum 25(OH)D levels. If baseline (BL) serum 25(OH)D levels were ≤10ng per ml, the RDN should also evaluate the frequency of exacerbations to measure the effectiveness of supplementation. Evidence from adults with COPD with BL serum 25(OH)D levels ≤10ng per ml, showed that vitamin D supplementation decreased exacerbations. While vitamin D is important for general health, vitamin D supplementation in those with BL serum 25(OH)D levels 11ng to 29ng per ml may or may not improve lung function or reduce exacerbations in adults with COPD.
Risks/Harms of Implementing This Recommendation
There are no potential risks or harms associated with the application of the recommendation.
Conditions of Application
- The recommendation applies to adults with COPD with baseline (BL) serum 25(OH)D levels less than 29ng per ml and in whom vitamin D supplements have been initiated, and in COPD patients with BL serum 25(OH)D levels ≤10ng per ml who may also have frequent exacerbations. Frequent exacerbations are defined as two or more exacerbations per year (Hurst et al, 2010; Le Rouzic et al, 2018).
- Coordination with the prescribing provider may be required for recommended changes to vitamin D supplementation and physician orders
- Exacerbations are clinically defined as episodes of increasing respiratory symptoms, particularly dyspnea, cough and sputum production and increased sputum purulence (Wedzicha et al, 2017). The patient perception of an exacerbation is seeking treatment for symptoms; the research criteria is treatment with antibiotics or addition of increased inhaled or systemic steroids.
- Achievement of normal serum 25(OH)D levels may not be possible in all instances. Therefore, optimizing serum 25(OH)D levels is the goal (Rusinska et al, 2018).
- Frequency of monitoring serum 25(OH)D levels post-supplementation should be at three-month intervals (Rusinska et al, 2018).
Potential Costs Associated with Application
- Costs may include expenses related to medical nutrition therapy (MNT) visits from an RDN
- Costs may be incurred related to the purchase of over-the-counter vitamin D supplements or co-pays
- Costs may be incurred due to lab testing to evaluate serum 25(OH)D levels.
A total of eight studies were included in the evidence analysis supporting the recommendation:
- Six randomized controlled trials (RCTs) [four positive-quality (Lehouck et al, 2012; Martineau et al, 2015; Rafiq et al, 2017; Sanjari et al, 2016), one neutral-quality (Khan et al, 2017) and one negative-quality (Zendendel et al, 2015)]
- Two before-after studies [both neutral-quality (Rezk et al, 2015; Said and Abd-Elnaeem, 2015)].
Seven studies tested oral vitamin D3 (cholecalciferol) ranging from 1, 200 IU daily for six months; subjects and controls could also take 400 IU vitamin D3 daily (Rafiq et al, 2017) to 120, 000 IU every two months for 12 months (Martineau et al, 2015).
- One study administered 200, 000 IU cholecalciferol intramuscularly (IM) every four weeks for six months (Said and Abd-Elnaeem, 2015)
- All papers either cited the Endocrine Society Clinical Practice Guideline (ESG) (Holick et al, 2011) for serum 25(OH)D classifications or did not define classifications. In addition to the ESG reference, one study (Lehouck et al, 2012) defined “severe” vitamin D deficiency as serum 25(OH)D levels under 10ng per ml.
Seven studies evaluated lung function (LF) outcomes (Lehouck et al, 2012; Martineau et al, 2015; Rafiq et al, 2017; Rezk et al, 2015; Sanjari et al, 2016; Said and Abd-Elnaeem, 2015; Zendedel et al, 2015). Six studies evaluated acute exacerbation (AE) outcomes (Khan et al, 2017; Lehouck et al, 2012; Martineau et al, 2015; Rafiq et al, 2017; Rezk et al, 2015; Zendedel et al, 2015).
Five studies of vitamin D supplementation included subjects’ pre- and post-supplementation levels, allowing changes in vitamin D status due to supplementation to be assessed. Results according to baseline (BL) and post-supplementation improvements in vitamin D status (ESG categories) are as follows:
- Deficient to sufficient 25(OH)D: Supplementation with 1, 200 IU D3 daily for six months (plus 400 IU daily, if desired) resulted in no impact on LF or AE outcomes (Rafiq et al, 2012). Supplementation with 100, 000 IU D3 every four weeks over 12 months resulted in a decrease in AE rate in a sub-group of subjects with “severe deficiency” [25(OH)D under 10ng per ml] (Lehouck et al, 2012).
- Insufficient to sufficient 25(OH)D: Supplementation with 100, 000 IU D3 every four weeks over 12 months resulted in no impact on AE or LF outcomes (Lehouck et al, 2012). Supplementation with either 5, 000 IU D3 or 0.25mcg calcitriol every four weeks over 12 months resulted in no impact on LF outcomes (Sanjari et al, 2016).
- Deficient to insufficient 25(OH)D: Supplementation with 50, 000 IU D3 per week for eight weeks, then 800 IU daily for 12 months resulted in a decrease in number of AEs and an improvement in MVV, but no impact on other LF outcomes in subjects with 25(OH)D under 10ng per ml at BL (Rezk et al, 2015). Supplementation with 120, 000 IU D3 every two months over 12 months resulted in improvement in AE severity and symptoms, but had no impact on other AE or LF outcomes (Martineau et al, 2015).
The remaining three studies did not report subjects’ post-supplementation vitamin D status. One study (Said and Abd-Elnaeem, 2015) reported BL vitamin D status according to ESG categories, but did not report post-supplementation status. The second study (Khan et al, 2017) reported BL vitamin D status of subjects and controls combined and did not report pre- and post-supplementation status of subjects only. Finally, the last study (Zendedel et al, 2015) did not report either BL or post-supplementation vitamin D status.
- Insufficient 25(OH)D (subjects + controls): Supplementation with 2, 000 IU D3 per day for six months resulted in reduced AEs (Kahn et al, 2017). Supplementation with 200, 000 IU D3 IM every four weeks for six months resulted in no impact in LF outcomes (Said and Abd-Elnaeem, 2015).
- Unknown 25(OHD): Supplementation with 100, 000 IU D3 every month for six months resulted in improvement in LF outcomes and a reduction in AEs (Zendedel et al, 2015).
Recommendation Strength Rationale
- Conclusion statement supporting the recommendation is Grade II, Fair
- Synthesis of results was challenging due to lack of consistency in vitamin D dosing, dosing frequency and delivery routes, length of intervention and baseline serum 25(OH)D levels.
- Risks/Harms of Implementing This Recommendation
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
Khan D,Ullah A,Randhawa F,Iqtadar S,Butt N,Waheed K. Role of Vitamin D in reducing number of acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) patients. Pakistan journal of medical sciences 2017; 33:610-614
Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J, Decallonne B, Bouillon R, Decramer M, Janssens W. High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Annals of Internal Medicine 2012; 156:105-14
Martineau A, James W, Hooper R, Barnes N, Jolliffe D, Greiller C, Islam K, McLaughlin D, Bhowmik A, Timms P, Rajakulasingam R, Rowe M, Venton T, Choudhury A, Simcock D, Wilks M, Degun A, Sadique Z, Monteiro W, Corrigan C, Hawrylowicz C, Griffiths C. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. The Lancet. Respiratory Medicine 2015; 3:120-130
Rafiq R, Prins H, Boersma W, Daniels J, den Heijer M, Lips P, de Jongh R. Effects of daily vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients: a pilot trial. International Journal of Chronic Obstructive Pulmonary Disease 2017; 12:2583-2592
Rezk NA, Yehia AA, Hewidy, AA. Effect of vitamin D replacement in chronic obstructive pulmonary disease patients with vitamin D deficiency. Egyptian Journal of Chest Diseases and Tuberculosos 2015; 64:353-357
Said AF and Abd-Elnaeem EA. Vitamin D and chronic obstructive pulmonary disease. Egyptian Journal of Chest Diseases and Tuberculosis 2015; 64:67-73
Sanjari M, Soltani A, Habibi Khorasani A, Zareinejad M. The effect of vitamin D on COPD exacerbation: a double blind randomized placebo-controlled parallel clinical trial. Journal of Diabetes and Metabolic Disorders 2016; 15:33
Zendedel A, Gholami M, Anbari K, Ghanadi K, Bachari E, Azargon A. Effects of Vitamin D Intake on FEV1 and COPD Exacerbation: A Randomized Clinical Trial Study. Global Journal of Health Science 2015; 7:243-8
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul; 96 (7): 1, 911-1, 930. doi: 10.1210/jc.2011-0385. Epub 2011 Jun 6. Erratum in: J Clin Endocrinol Metab. 2011 Dec; 96 (12): 3, 908. PMID: 21646368.
Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16; 363 (12): 1, 128-1, 138. doi: 10.1056/NEJMoa0909883. PMID: 20843247.
Le Rouzic O, Roche N, Cortot AB, Tillie-Leblond I, Masure F, Perez T, Boucot I, Hamouti L, Ostinelli J, Pribil C, Poutchnine C, Schück S, Pouriel M, Housset B. Defining the "Frequent Exacerbator" Phenotype in COPD: A Hypothesis-Free Approach. Chest. 2018 May; 153 (5): 1, 106-1, 115. doi: 10.1016/j.chest.2017.10.009. Epub 2017 Oct 17. PMID: 29054347.
Rusinska A, Pludowski P, Walczak M, Borszewska-Kornacka MK, Bossowski A, Chlebna-Sokól D, Czech-Kowalska J, Dobrzanska A, Franek E, Helwich E, Jackowska T, Kalina MA, Konstantynowicz J, Ksiazyk J, Lewinski A, Lukaszkiewicz J, Marcinowska-Suchowierska E, Mazur A, Michalus I, Peregud-Pogorzelski J, Romanowska H, Ruchala M, Socha P, Szalecki M, Wielgos M, Zwolinska D, Zygmunt A. Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland - Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies - 2018 Update. Front Endocrinol (Lausanne). 2018 May 31; 9: 246. doi: 10.3389/fendo.2018.00246. eCollection 2018. Review. PMID: 29904370.
Wedzicha JA, Miravitlles M, Hurst JR, Calverley PM, Albert RK, Anzueto A, Criner GJ, Papi A, Rabe KF, Rigau D, Sliwinski P, Tonia T, Vestbo J, Wilson KC, Krishnan JA. Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2017 Mar 15; 49 (3). pii: 1600791. doi: 10.1183/13993003.00791-2016. Print 2017 Mar. PMID: 28298398.