COPD: 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: Vitamin D Supplementation for Serum 25(OH)D Levels 10ng/ml or Lower
If an adult with COPD has baseline serum 25(OH)D levels ≤10ng per ml, the RDN should advise vitamin D supplementation to optimize serum 25(OH)D status. Evidence from adults with COPD with baseline serum 25(OH)D levels ≤10ng per ml, showed that vitamin D supplementation decreased exacerbations.
COPD: Vitamin D Supplementation for Serum 25(OH)D Levels 11-29ng/ml
If an adult with COPD has baseline serum 25(OH)D levels 11ng to 29ng per ml, the RDN should consider vitamin D supplementation to optimize serum 25(OH)D status. While vitamin D is important for health, evidence indicates that vitamin D supplementation may or may not improve lung function or reduce exacerbations in adults with COPD who have baseline serum levels within this range. Evidence related to the effect of vitamin D supplementation on lung function and exacerbation outcomes yielded mixed findings and depended upon on dosing, dosing frequency and delivery routes, length of intervention and baseline serum 25(OH)D levels.
Risks/Harms of Implementing This Recommendation
There are no potential risks or harms associated with the application of this recommendation.
Conditions of Application
- The recommendation COPD: Vitamin D Supplementation for Serum 25(OH)D Levels 10ng per ml or Lower applies to those with baseline serum 25(OH)D levels ≤10ng per ml
- The recommendation COPD: Vitamin D Supplementation for Serum 25(OH)D Levels 11ng to 29ng per ml applies to those with baseline serum 25(OH)D levels that are insufficient (21ng to 29ng per ml) or deficient (less than 20ng per ml)
- Comorbidities should be considered before starting vitamin D supplementation (Marra and Bailey 2018; Pludowski et al, 2018)
- Vitamin D dosage is based on age, body weight, and baseline 25(OH)D level and should be administered according to local protocol or national clinical guidelines (Pludowski et al, 2018) and clinical expertise (Marra and Bailey 2018; Thompson et al, 2002)
- Coordination with the prescribing provider may be required for vitamin D supplement orders
- 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).
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.
A total of eight studies were included in the evidence analysis supporting the recommendations:
- 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 statements supporting the recommendations are Grade II, Fair
- Synthesis of the 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.
Jolliffe DA, Greenberg L, Hooper RL, Mathyssen C, Rafiq R, deJongh RT, Camargo C, Griffiths CJ, Janssens W, Martineau AR. Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax. Published Online First: 10 January 2019. doi: 10.1136/thoraxjnl-2018-212092.
Marra MV, Bailey RL. Position of the Academy of Nutrition and Dietetics: Micronutrient Supplementation. J Acad Nutr Diet. 2018 Nov;118(11): 2, 162-2, 173. doi: 10.1016/j.jand.2018.07.022. Erratum in: J Acad Nutr Diet. 2019 Feb; 119(2): 344. PMID: 30366569.
Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A, Povoroznyuk V, Balatska N, Barbosa AP, Karonova T, Rudenka E, Misiorowski W, Zakharova I, Rudenka A, Lukaszkiewicz J, Marcinowska-Suchowierska E, Laszcz N, Abramowicz P, Bhattoa HP, Wimalawansa SJ. Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol. 2018 Jan; 175: 125-135. doi: 10.1016/j.jsbmb.2017.01.021. Epub 2017 Feb 12. PMID: 28216084.
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: 2990437.
Thomson C, Diekman C, Fragakis AS, Meerschaert C, Holler H, Devlin C; American Dietetic Association. Guidelines regarding the recommendation and sale of dietary supplements. J Am Diet Assoc. 2002 Aug; 102(8): 1, 158-1, 164. No abstract available. PMID: 12171465.