L E T T E R S TO T H E E D I TO R
pii: jc-00280-15 http://dx.doi.org/10.5664/jcsm.5208
Association between 25-Hydroxyvitamin D and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis Sikarin Upala, MD, MS1,2; Anawin Sanguankeo, MD1,2
1 Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, 2Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand
W
e read an article written by Liguori et al.1 with interest. The authors evaluated the effect of continuous positive airway pressure (CPAP) therapy on serum vitamin D in patients with severe obstructive sleep apnea (OSA). They found that serum vitamin D increased in men after the use of CPAP and concluded that this finding confirmed that patients with OSA suffer from low vitamin D. However, it is unclear whether association between vitamin D deficiency and OSA is due to a pathophysiologic pathway or due to confounders. We completed a systematic review and meta-analysis of published observational studies evaluating 25-hydroxyvitamin D or 25(OH)D level in patients with OSA compared with patients without OSA. Reviews, case reports, letters, commentaries, abstracts, and unpublished studies were excluded. OSA was diagnosed by having polysomnography measured. Vitamin D deficiency was defined as a 25(OH)D level less than 20 ng/ mL (50 nmol/L)2, while optimal or vitamin D sufficiency was defined as a 25(OH)D concentration greater than 30 ng/mL (75 nmol/L). We performed a systematic search from the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE, and EMBASE databases until June 2015. We estimated the pooled mean difference (MD) of 25(OH)D comparing between OSA and non-OSA groups using a random effects model in the Comprehensive Meta-Analysis version 3 software. The heterogeneity of effect size estimates across these studies was quantified using the I2 statistic and Q statistic. A total of 11 articles underwent full-length review. Data from four cross-sectional studies1,3,4,5 involving 506 participants were extracted and included in the meta-analysis. Participants with obstructive sleep apnea had lower 25(OH)D compared with controls with MD of −5.81 (95% confidence interval [CI]: −10.09 to −1.53, p = 0.008). The statistical between-study heterogeneity was high, with an I2 of 83%, Pheterogeneity < 0.001. There were not enough studies to perform subgroup analysis or meta-regression analysis. Previous studies had demonstrated that moderate or severe OSA was associated with low vitamin D level. Our analysis confirmed that association. We believe OSA might cause low vitamin D level by hypoxia-induced mechanism as in chronic obstructive pulmonary disease.6 It is not possible to assess whether this association is confounded by any factors due to 1347
too few included studies from current evidence. Another limitation of our study was that the results analyzed were from cross-sectional studies, which could not determine causal relationship between these two conditions. In conclusion, this is the first systematic review and metaanalysis of published observational studies to evaluate the association between obstructive sleep apnea and low vitamin D level. Still, further randomized controlled studies with adjusted effects for age, sex, or BMI are needed to accurately investigate the efficacy of OSA treatment and improvement in vitamin D level.
CITATION Upala S, Sanguankeo A. Association between 25-hydroxyvitamin D and obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med 2015;11(11):1347.
REFERENCES 1. Liguori C, Romigi A, Izzi F, et al. Continuous positive airway pressure treatment increases serum vitamin D levels in male patients with obstructive sleep apnea. J Clin Sleep Med 2015;11:603–7. 2. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81. 3. Mete T, Yalcin Y, Berker D, et al. Obstructive sleep apnea syndrome and its association with vitamin D deficiency. J Endocrinol Invest 2013;36:681–5. 4. Bozkurt NC, Cakal E, Sahin M, Ozkaya EC, Firat H, Delibasi T. The relation of serum 25-hydroxyvitamin-D levels with severity of obstructive sleep apnea and glucose metabolism abnormalities. Endocrine 2012;41:518–25. 5. Erden ES, Genc S, Motor S, et al. Investigation of serum bisphenol A, vitamin D, and parathyroid hormone levels in patients with obstructive sleep apnea syndrome. Endocrine 2014;45:311–8. 6. Persson LJ, Aanerud M, Hiemstra PS, Hardie JA, Bakke PS, Eagan TM. Chronic obstructive pulmonary disease is associated with low levels of vitamin D. PLoS One 2012;7:e38934.
SUBMISSION & CORRESPONDENCE INFORMATION Submitted for publication July, 2015 Accepted for publication July, 2015 Address correspondence to: Anawin Sanguankeo, MD, Department of Internal Medicine, Bassett Medical Center, 1 Atwell Road, Cooperstown, NY 13326; Tel: (607) 547-4805; Fax: (607) 547-6612; Email: [email protected]
DISCLOSURE STATEMENT The authors have indicated no financial conflicts of interest.
Journal of Clinical Sleep Medicine, Vol. 11, No. 11, 2015
pii: jc-00280-15 http://dx.doi.org/10.5664/jcsm.5208
Association between 25-Hydroxyvitamin D and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis Sikarin Upala, MD, MS1,2; Anawin Sanguankeo, MD1,2
1 Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, 2Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand
W
e read an article written by Liguori et al.1 with interest. The authors evaluated the effect of continuous positive airway pressure (CPAP) therapy on serum vitamin D in patients with severe obstructive sleep apnea (OSA). They found that serum vitamin D increased in men after the use of CPAP and concluded that this finding confirmed that patients with OSA suffer from low vitamin D. However, it is unclear whether association between vitamin D deficiency and OSA is due to a pathophysiologic pathway or due to confounders. We completed a systematic review and meta-analysis of published observational studies evaluating 25-hydroxyvitamin D or 25(OH)D level in patients with OSA compared with patients without OSA. Reviews, case reports, letters, commentaries, abstracts, and unpublished studies were excluded. OSA was diagnosed by having polysomnography measured. Vitamin D deficiency was defined as a 25(OH)D level less than 20 ng/ mL (50 nmol/L)2, while optimal or vitamin D sufficiency was defined as a 25(OH)D concentration greater than 30 ng/mL (75 nmol/L). We performed a systematic search from the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE, and EMBASE databases until June 2015. We estimated the pooled mean difference (MD) of 25(OH)D comparing between OSA and non-OSA groups using a random effects model in the Comprehensive Meta-Analysis version 3 software. The heterogeneity of effect size estimates across these studies was quantified using the I2 statistic and Q statistic. A total of 11 articles underwent full-length review. Data from four cross-sectional studies1,3,4,5 involving 506 participants were extracted and included in the meta-analysis. Participants with obstructive sleep apnea had lower 25(OH)D compared with controls with MD of −5.81 (95% confidence interval [CI]: −10.09 to −1.53, p = 0.008). The statistical between-study heterogeneity was high, with an I2 of 83%, Pheterogeneity < 0.001. There were not enough studies to perform subgroup analysis or meta-regression analysis. Previous studies had demonstrated that moderate or severe OSA was associated with low vitamin D level. Our analysis confirmed that association. We believe OSA might cause low vitamin D level by hypoxia-induced mechanism as in chronic obstructive pulmonary disease.6 It is not possible to assess whether this association is confounded by any factors due to 1347
too few included studies from current evidence. Another limitation of our study was that the results analyzed were from cross-sectional studies, which could not determine causal relationship between these two conditions. In conclusion, this is the first systematic review and metaanalysis of published observational studies to evaluate the association between obstructive sleep apnea and low vitamin D level. Still, further randomized controlled studies with adjusted effects for age, sex, or BMI are needed to accurately investigate the efficacy of OSA treatment and improvement in vitamin D level.
CITATION Upala S, Sanguankeo A. Association between 25-hydroxyvitamin D and obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med 2015;11(11):1347.
REFERENCES 1. Liguori C, Romigi A, Izzi F, et al. Continuous positive airway pressure treatment increases serum vitamin D levels in male patients with obstructive sleep apnea. J Clin Sleep Med 2015;11:603–7. 2. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81. 3. Mete T, Yalcin Y, Berker D, et al. Obstructive sleep apnea syndrome and its association with vitamin D deficiency. J Endocrinol Invest 2013;36:681–5. 4. Bozkurt NC, Cakal E, Sahin M, Ozkaya EC, Firat H, Delibasi T. The relation of serum 25-hydroxyvitamin-D levels with severity of obstructive sleep apnea and glucose metabolism abnormalities. Endocrine 2012;41:518–25. 5. Erden ES, Genc S, Motor S, et al. Investigation of serum bisphenol A, vitamin D, and parathyroid hormone levels in patients with obstructive sleep apnea syndrome. Endocrine 2014;45:311–8. 6. Persson LJ, Aanerud M, Hiemstra PS, Hardie JA, Bakke PS, Eagan TM. Chronic obstructive pulmonary disease is associated with low levels of vitamin D. PLoS One 2012;7:e38934.
SUBMISSION & CORRESPONDENCE INFORMATION Submitted for publication July, 2015 Accepted for publication July, 2015 Address correspondence to: Anawin Sanguankeo, MD, Department of Internal Medicine, Bassett Medical Center, 1 Atwell Road, Cooperstown, NY 13326; Tel: (607) 547-4805; Fax: (607) 547-6612; Email: [email protected]
DISCLOSURE STATEMENT The authors have indicated no financial conflicts of interest.
Journal of Clinical Sleep Medicine, Vol. 11, No. 11, 2015
