Treatment with n-3 polyunsaturated fatty acids overcomes the inverse association of vitamin D deficiency with inflammation in severely obese patients: a randomized controlled trial

Bianca K Itariu, Maximilian Zeyda, Lukas Leitner, Rodrig Marculescu, Thomas M Stulnig, Bianca K Itariu, Maximilian Zeyda, Lukas Leitner, Rodrig Marculescu, Thomas M Stulnig

Abstract

Obesity affects the vitamin D status in humans. Vitamin D and long-chain n-3 polyunsaturated fatty acids (PUFA) provide benefit for the prevention of fractures and cardiovascular events, respectively, and both are involved in controlling inflammatory and immune responses. However, published epidemiological data suggest a potential interference of n-3 PUFA supplementation with vitamin D status. Therefore, we aimed to investigate in a randomized controlled clinical trial whether treatment with long chain n-3 PUFA affects vitamin D status in severely obese patients and potential interrelations of vitamin D and PUFA treatment with inflammatory parameters. Fifty-four severely obese (BMI ≥ 40 kg/m2) non-diabetic patients were treated for eight weeks with either 3.36 g/d EPA and DHA or the same amount of butter fat as control. Changes in serum 25-hydroxy-vitamin D [25(OH)D] concentrations, plasma fatty acid profiles and circulating inflammatory marker concentrations from baseline to end of treatment were assessed. At baseline 43/54 patients were vitamin D deficient (serum 25(OH)D concentration <50 nmol/l). Treatment with n-3 PUFA did not affect vitamin D status (P = 0.91). Serum 25(OH)D concentration correlated negatively with both IL-6 (P = 0.02) and hsCRP serum concentration (P = 0.03) at baseline. Strikingly, the negative correlations of 25(OH)D with IL-6 and hsCRP were lost after n-3 PUFA treatment. In conclusion, vitamin D status of severely obese patients remained unaffected by n-3 PUFA treatment. However, abrogation of the inverse association of 25(OH)D concentration with inflammatory markers indicated that n-3 PUFA treatment could compensate for some detrimental consequences of vitamin D deficiency.

Trial registration: ClinicalTrials.gov NCT00760760.

Conflict of interest statement

Competing Interests: The authors declare Solvay Pharma, Austria, as a commercial funder. The corresponding author had a consultancy agreement with a company that purchased Solvay Pharma. No other authors have any relevant declarations relating to employment, consultancy, patents, products in development or marketed products, etc.. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. CONSORT flowchart, adapted from .
Figure 1. CONSORT flowchart, adapted from .
Figure 2. Vitamin D, n-3 PUFA and…
Figure 2. Vitamin D, n-3 PUFA and inflammation.
A, B. Correlations of serum 25(OH)D concentrations with IL-6 and EPA in severely obese patients at baseline. Serum 25(OH)D concentrations of obese patients (n = 54), plotted against (A) plasma IL-6 concentration and (B) eicosapentaenoic acid (EPA) in plasma phospholipids at baseline. Statistical analysis was performed by Spearman's rank correlation test. C. The effect of long chain n-3 PUFA treatment on serum 25(OH)D concentrations. The difference (Δ) between serum 25(OH)D concentration at the end of treatment vs. its baseline value in both n-3 PUFA treated patients (n = 26) and controls (n = 28) was not statistically significant (P = 0.58 in ANOVA). D, E. Correlation of serum 25(OH)D concentrations with IL-6 in severely obese n-3 PUFA and control treated patients at study end. Serum 25(OH)D concentration of (D) n-3 PUFA treated patients (n = 26) and (E) controls (n = 28) plotted against plasma IL-6 concentration at the end of the intervention. Statistical analysis was performed by Spearman's rank correlation.

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