, Volume 42, Issue 5, pp 437-459
Date: 30 Sep 2012

Clinical Pharmacokinetics of Antioxidants and Their Impact on Systemic Oxidative Stress

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Dietary antioxidants play a major role in maintaining the homeostasis of the oxidative balance. They are believed to protect humans from disease and aging. Vitamin C (ascorbic acid), vitamin E (tocopherol), β-carotene and other micronutrients such as carotenoids, polyphenols and selenium have been evaluated as antioxidant constituents in the human diet. This article addresses data provided from clinical trials, highlighting the clinical pharmacokinetics of vitamin C, vitamin E, β-carotene, lycopene, lutein, quercetin, rutin, catechins and selenium.

The bioavailability of vitamin C is dose-dependent. Saturation of transport occurs with dosages of 200–400) mg/day. Vitamin C is not protein-bound and is eliminated with an elimination half-life (t½) of 10 hours. In Western populations plasma vitamin C concentrations range from 54–91 µmol/L. Serum α- and γ-tocopherol range from 21 µmol/L (North America) to 27 µmol/L (Europe) and from 3.1 µmol/L to 1.5 µmol/L, respectively. α-Tocopherol is the most abundant tocopherol in human tissue. The bioavailability of all-rac-α-tocopherol is estimated to be 50% of R,R,R-α-tocopherol. The hepatic α-tocopherol transfer protein (α-TTP) together with the tocopherol-associated proteins (TAP) are responsbile for the endogenous accumulation of natural α-tocopherol. Elimination of α-tocopherol takes several days with a t½ of 81 and 73 hours for R,R,R-α-tocopherol and all-rac-α-tocopherol, respectively. The t½ of tocotrienols is short, ranging from 3.8–4.4 hours for γ- and α-tocotrienol, respectively. γ-Tocopherol is degraded to 2, 7, 8-trimethyl-2-(β-carboxyl)-6-hyrdoxychroman by the liver prior to renal elimination. Blood serum carotenoids in Western populations range from 0.28–0.52 p,mol/L for β-carotene, from 0.2–0.28 for lutein, and from 0.29–0.60 for lycopene. All-trans-carotenoids have a better bioavailability than the 9-cis-forms. Elimination of carotenoids takes several days with a t½ of 5-7 and 2–3 days for β-carotene and lycopene, respectively. The bioconversion of β-carotene to retinal is dose-dependent, and ranges between 27% and 2% for a 6 and 126mg dose, respectively. Several oxidised metabolites of carotenoids are known. Flavonols such as quercetin glycosides and rutin are predominantly absorbed as aglycones, bound to plasma proteins and subsequently conjugated to glucuronide, sulfate, and methyl moieties. The t½ ranges from 12–19 hours. The bioavailabillity of catechins is low and they are eliminated with a t½ of 2–4 hours. Catechins are degraded to several γ-valerolactone derivatives and phase II conjugates have also been identified. Only limited clinical pharmacokinetic data for other polyphenols such as resveratrol have been reported to date.