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Relation Between Serum 25-Hydroxyvitamin D and C-Reactive Protein in Asymptomatic Adults (From the Continuous National Health and Nutrition Examination Survey 2001 to 2006)

Published:October 14, 2011DOI:https://doi.org/10.1016/j.amjcard.2011.08.032
      The inverse relation between vitamin D supplementation and inflammatory biomarkers among asymptomatic adults is not settled. We hypothesized that the inverse relation is present only at lower levels and disappears at higher serum levels of vitamin D. We examined the relation between 25-hydroxyvitamin D [25(OH)D] and C-reactive protein (CRP) using the continuous National Health and Nutrition Examination Survey data from 2001 to 2006. Linear spline [single knot at median serum levels of 25(OH)D] regression models were used. The median serum 25(OH)D and CRP level was 21 ng/ml (interquartile range 15 to 27) and 0.21 mg/dl (interquartile range 0.08 to 0.5), respectively. On univariate linear regression analysis, CRP decreased [geometric mean CRP change 0.285 mg/dl for each 10-ng/ml change in 25(OH)D, 95% confidence interval [CI] −0.33 to −0.23] as 25(OH)D increased ≤21 ng/ml. However, an increase in 25(OH)D to >21 ng/ml was not associated with any significant decrease [geometric mean CRP change 0.05 mg/dl for each 10-ng/ml change in 25(OH)D, 95% CI −0.11 to 0.005) in CRP. The inverse relation between 25(OH)D below its median and CRP remained significant [geometric mean CRP change 0.11 mg/dl for each 10-ng/ml change in 25(OH)D, 95% CI 0.16 to −0.04] on multivariate linear regression analysis. Additionally, we observed a positive relation between 25(OH)D above its median and CRP [geometric mean CRP change 0.06 mg/dl for each 10-ng/ml change in 25(OH)D, 95% CI 0.02 to 0.11) after adjusting for traditional cardiovascular risk factors. In conclusion, from this cohort of asymptomatic adults, independent of traditional cardiovascular risk factors, we observed a statistically significant inverse relation between 25(OH)D at levels <21 ng/ml and CRP. We found that 25(OH)D at a level ≥21 ng/ml is associated with an increase in serum CRP. It is possible that the role of vitamin D supplementation to reduce inflammation is beneficial only among those with a lower serum 25(OH)D.
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          The epidemiologic study suggesting a relation between serum 25-hydroxyvitamin D (25[OH]D) and C-reactive protein (CRP) by Amer and Qayyum1 is timely, given the prominence of 25(OH)D in recent scientific research and the recent increase in vitamin D recommended daily allowances.2 However, the study appears to suffer from deficiencies in internal validity (due to the analysis methods used) and external validity (because vitamin D supplementation by subjects was not included in the analysis). Their findings contradict evidence for a dose-dependent reduction of coronary heart disease mortality with higher serum 25(OH)D,3 and furthermore, CRP has questionable utility in guiding treatment of patients with coronary heart disease.
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