Supplementation with anti-oxidants Vitamin C and E decreases cyclosporine A trough-levels in renal transplant recipients

Sir, Blackhall et al. [1] recently reported that anti-oxidant supplementation with vitamin C, vitamin E and β-carotene resulted in a 24% decrease in cyclosporine A (CsA) trough-levels in renal transplant recipients. We agree with the authors that this is an important finding requiring confirmation. Supplementation of anti-oxidant vitamins is not uncommon in renal transplant recipients, because there is strong belief that these supplements are of special benefit to subjects with increased oxidative stress [2,3]. However, injudicious use of these vitamins might evoke rejection, if they indeed decrease blood CsA concentrations. We recently finished a 3 month double-blind placebo-controlled trial of combination therapy of vitamin C (1000 mg/day) and vitamin E (300 mg/day) in 56 renal transplant recipients. All patients were on a CsA-based immunosuppressive regimen. Our Institutional Review Board had approved the study and all participants signed informed consent. Serum creatinine and trough-levels of CsA were measured at baseline and at the end of the study by the Jaffé-method (MEGA AU 510; Merck Diagnostics, Darmstadt, Germany) and a fluorescence polarization immunoassay (Abbott Diagnostics; Abbott Park, IL, USA), respectively. Two subjects in the treatment group and one in the placebo group did not complete the study because of hospitalization for cardiovascular events, and were therefore not eligible for analyses. There were no significant differences in baseline characteristics between the two groups (Table 1). Antioxidant supplementation with vitamin C and vitamin E resulted in significant changes in plasma concentrations of vitamin C (40±48 vs −19±33 µmol/l for placebo, P<0.001) as well as vitamin E (25±15 vs 1±10 µmol/l for placebo, P<0.001). CsA trough-levels decreased in the treatment group compared with the placebo group (−14±25 vs 10±30 mg/l, P = 0.003), as did the serum creatinine concentration (resp, −6±17 and 4±15 mmol/l, P = 0.035). Neither changes in vitamin C nor changes in vitamin E concentrations were correlated with changes in CsA trough-levels or changes in serum creatinine concentrations in the treatment group. A borderline significant correlation was found between changes in CsA trough-levels and changes in serum creatinine concentrations (r = 0.36, P = 0.07). Baseline characteristics of the study participants Data are presented as mean (SD). Differences between groups were investigated using Student's t-test for continuous variables and χ-square for proportions. Baseline characteristics of the study participants Data are presented as mean (SD). Differences between groups were investigated using Student's t-test for continuous variables and χ-square for proportions. The results of our study confirm the finding by Blackhall et al. [1] that antioxidant supplementation reduces CsA trough-levels in renal transplant recipients. Injudicious use of vitamin C and E supplementation should therefore be avoided, until it has been documented that the decreased CsA levels associated with their use pose no risk for transplant rejection. Blackhall et al. [1] also found a significant decrease in serum creatinine concentrations. Our results confirm this finding as well. Blackhall et al. [1] supplemented β-carotene in addition to vitamin E and vitamin C, whereas our study only supplemented the latter two anti-oxidants. It is therefore unlikely that β-carotene in the study of Blackhall was responsible for either the changes in CsA trough-levels or the changes in serum creatinine concentrations. In conclusion, we concur with Blackhall et al. [1] that transplant nephrologists should be aware of the CsA trough-level lowering effect of anti-oxidants. The present study was funded by a grant from the Dutch Kidney Foundation (Nierstichting Nederland C00-1877). A.d.V. is sponsored by a Clinical Research Fellowship from the Netherlands Organization of Scientific Research (NWO-AGIKO 920-03-181). Conflict of interest statement. None declared.