We read with great interest the recent article by Liguori et al.,1 suggesting an association between short-term nasal continuous positive airway pressure (nCPAP) and improved serum 25-hydroxyvitamin D (25OHD) levels in subjects with obstructive sleep apnea (OSA) syndrome. Interestingly, of the 90 OSA patients in the study, only men (n = 41) demonstrated a significant improvement in 25OHD levels after nCPAP therapy. The lack of a similar response in women was hypothesized to be related to vitamin D regulation by female sex hormones. However, we believe that it is important to acknowledge the interplay between vitamin D status, sex hormones, and systemic inflammation to better understand the potential biological reasons for the difference in men and women regarding 25OHD levels and short-term nCPAP therapy.
Studies suggest a U-shaped relationship between vitamin D status and markers of systemic inflammation, e.g., C-reactive protein (CRP).2 Moreover, acute inflammation is associated with concomitant rapid reductions in circulating 25OHD levels.3 The combination of low vitamin D status and presence of OSA likely resulted in elevated baseline CRP levels in male study participants. We hypothesize that men treated with short-term nCPAP experienced a significant reduction in CRP levels and a concomitant elevation in 25OHD levels. On the other hand, in women, estrogen can strongly influence CRP levels depending on whether the hormone is endogenously produced or exogenously supplemented.4 Therefore, we hypothesize that in women with adequate endogenous estrogen production, baseline CRP levels were likely low at baseline and unlikely to change significantly after nCPAP therapy. In women taking exogenous estrogen, CRP levels were likely high at baseline and unlikely to be altered significantly with short-term nCPAP therapy.
In summary, we hypothesize that a relationship between female sex hormones and inflammation plays a critical role in the observed results of this study. Future studies should account for CRP levels when considering sex differences and micro-nutrient status.
The authors have indicated no financial conflicts of interest.
Eng KJ, Quraishi SA. Changes in vitamin D status after nasal continuous positive airway pressure: could alterations in systemic inflammatory markers explain these observations? J Clin Sleep Med 2015;11(12):1471.
Liguori C, Romigi A, Izzi F, et al., authors. 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. [PubMed]
Mellenthin L, Wallaschofski H, Grotevendt A, Völzke H, Nauck M, Hannemann A, authors. Association between serum vitamin D concentrations and inflammatory markers in the general adult population. Metab Clini Exp. 2014;63:1056–62
Dunca A, Talwar D, McMillan D, Stefanowicz F, O'Reilly D, authors. Quantitative data on the magnitude of the systemic inflammatory response and its effect on micronutrient status based on plasma measurements. Am J Clin Nutr. 2012;95:64–71. [PubMed]
Davison S, Davis S, authors. New markers for cardiovascular disease risk in women: impact of endogenous estrogen status and exogenous postmenopausal hormone therapy. J Clin Endocrinol Metab. 2003;88:2470–8. [PubMed]