Background & aims: Carboxyethyl-hydroxychromans (CEHC) are hydrosoluble vitamin E metabolites excreted through the renal filter. In this study we investigated the effect of the kidney damage on the blood levels of CEHC.


Methods: Plasma levels of a-CEHC, g-CEHC and their precursors (namely, α-tocopherol and γ-tocopherol) were measured by HPLC with electrochemical detection in chronic (CRF) and end-stage renal failure patients on regular hemodialysis (HD) before and after dialysis. CRF patients (n=26) were divided into three subgroups with different extent of kidney damage as measured by the intervals of creatinine clearance (CrCl, in ml/min): (a) 2–10, (b) 10–20, and (c) 20–45. HD patients (n=8) did not show residual renal function. In all the subjects the intake of vitamin E

(as α-tocopherol) was assessed using a food frequency questionnaire. In the HD group, the plasma concentrations of ascorbic and uric acid (AA and UA, respectively), total thiols, the total antioxidant status (TAS) and reactive carbonyls were also measured.


Results: The progressive deterioration of the kidney function in the different groups of patients produced an exponential increase of both α-CEHC and γ-CEHC in plasma. Compared with healthy controls (α-CEHC¼20.1713.4 and γ-CEHC=230.6±83.0 nmol/l) the levels of CEHC approximately doubled in patients with CrCl<20 ml/min (42.4±20.2 and 424.5.5±174.4; P<0:05 or higher in both) and reached a 3-fold maximum increase in HD patients (77.3±45.7 and 636.6±219.3). The hemodialysis provided a significant, but only a transient, correction of CEHC accumulation (44.8±23.5, 364.2±189.9). The HD patients showed lower intake and levels of vitamin E (α-tocopherol=5.17=±1.0 and γ-tocopherol=0.32±0.11 mmol/mmol cholesterol; P<0:05) compared to healthy controls (5.8±0.8 and 0.43±0.14), but in the CRF patients tocopherol levels were normal or only slightly decreased even though approximately half of the subject had lowered vitamin E intake. When the entire patient population was considered, the blood concentrations of parental tocopherols and CEHC did not correlate. The HD patients before dialysis showed a marked decrease of TAS/UA, AA and thiols levels, while UA and free carbonyls significantly increased. After dialysis, the depletion of AA and thiols further worsened and also UA and TAS/UA decreased, but free carbonyls slightly increased.

Plasma C-reactive protein concentrations in active and passive smokers: Influence of antioxidant supplementation

Gladys Block, PhD, Christopher Jensen, PhD, Marion Dietrich, PhD, Edward P. Norkus, PhD, Mark Hudes, PhD, and Lester Packer, PhD

J Am Coll Nutr. 2004 Apr;23(2):141-7.

Objective: C-reactive protein (CRP) may directly affect the progression of atherosclerosis, and therefore, may be a target for reducing disease risk. The objective was to determine whether antioxidant supplementation reduces plasma CRP in active and passive smokers.

Design: Randomized, double-blind, placebo-controlled, parallel group trial with 2 months exposure to study supplements.

Setting: Berkeley and Oakland, California.

Subjects: Healthy adult men and women, consuming <4 daily servings of fruits and vegetables, and who were actively or passively exposed to cigarette smoke. Analysis was limited to participants with detectable baseline CRP concentrations and no evidence of inflammation associated with acute illness at baseline or follow-up as reflected in CRP elevations (≥10.0 mg/L). A total of 1393 individuals were screened, 216 randomized, 203 completed the study, and 160 were included in the analysis.

Interventions: Participants were randomized to receive a placebo or vitamin C (515 mg/day) or antioxidant mixture (per day: 515 mg vitamin C, 371 mg α-tocopherol, 171 mg  γ-tocopherol, 252 mg  mixed tocotrienols, and 95 mg α-lipoic acid).

Measures of Outcome: Change in plasma CRP concentration.

Results: Vitamin C supplementation yielded a 24.0% reduction (95% confidence interval, -38.9% to-5.5%, p =0.036 compared to control) in plasma CRP, whereas the antioxidant mixture and placebo produced a nonsignificant 4.7% reduction (-23.9% to 19.3%) and 4.3% increase (-15.1% to 28.2%), respectively. Results were adjusted for baseline body mass index and CRP concentrations.

Conclusions: Plasma CRP itself may serve as a potential target for reducing the risk of atherosclerosis, and antioxidants, including vitamin C, should be investigated further to confirm their CRP-lowering and anti-inflammatory effects.