INTERVENTION STUDIES IN HUMANS WITH BIOCHEMICAL ENDPOINTS
A number of studies have evaluated the effects of vitamin E on copper-catalyzed LDL oxidation in healthy volunteers. In one study, men supplemented with 268, 537, or 805 mg vitamin E per day for 8 wk showed a decreased susceptibility of LDL to oxidation. There WlU no significant effect of daily supplementation with 40 or 1.34 mg. In a study of the effects 0: low-dose vitamin E supplementation (100 mg/d for 1 wk, then 200 mg/d for 3 wk), there WlU a significant increase in lag time before the onset ofLDL oxidation and a significant decrease in the propagation rate. Princen and associates have evaluated the minimal supplementary dose of vitamin E necessary to protect LDL against oxidation in vitro in healthy young adults
Resistance of LDL to oxidation increased in a dose-dependent manner with resistance time differing significantly from baseline even after ingestion of only 17 mg/d of vitamin E. However. the progression of lipid peroxidation in LDL was only reduced after intake of 268 and 536 mg/d. In a study of 200 mg a-tocopherol supplementation over a 2-mo period in smoking men lag time was increased in LDL + VLDL after both copper induction and heminlhydroger: peroxide induction. Plasma a-tocopherol, VLDL + LDL a-tocopherol, and LDL total antioxidan capacity were all increased in the intervention group. Vitamin E supplementation appears tc promote a clear reduction in the susceptibility of LDL to oxidation. The case for (3-carotenE and vitamin C, however, is less clear cut. The effect of high-dose vitamin C supplementation (1000 mg/d) on LDL oxidation was evaluated in a study of 19 smokers.
The vitamin C-supplemented group had a significant reduction in the susceptibility of LDL to oxidation after 4 wk. two months of vitamin C supplementation with freshly squeezed orange juice (estimated 500 mg/d) also produced a significant increase in lag time in 36 healthy male consuming a diet high in saturated fatty acids. Jialal and associates found that supplementation with B-carotene (1-2 J.l.mol) inhibited the oxidative modification of LDL in healthy subjects. By contrast, Lin and colleagues reported that a natural-food diet containing 0.93 (micro mol B-carotene per day was insufficient to alter either plasma or LDL (3-carotene or carbonyl groups in LDL.
A higher dose of 6.2 J.l.mol B-carotene per day did increase both plasma and LDL B-carotene and reduce LDL carbonyl production. When the effectiveness of B-carotene, vitamin C, and vitamin E supplements were compared by Reaven and associates, susceptibility of LDL to oxidation did not change during B-carotene supplementation (60 mg/d) but decreased 30-40% with the addition of a vitamin E supplement (1600 mg/d). Addition of vitamin C supplementation (2 g/d) did not further reduce the susceptibility to oxidation. In another study, a combined supplement B-carotene (30 mg/d), vitamin C (1 g/d), and vitamin E (530 mg/d)-was given to men for 3 mo. It produced a twofold prolongation of the lag phase of LDL oxidation and a 40% reduction in the oxidation rate.
The effects of combined antioxidant supplementation were not significantly different from the effects of vitamin E supplementation alone. Finally, we have recently shown that a combination of low-dose antioxidant vitamins (150 mg ascorbic acid, 67 mg a-tocopherol, 9 mg B-carotene daily) over a period of 8 wk significantly prolonged the lag time to oxidation. The effects of antioxidant supplementation on LDL oxidation may depend on smoking status. In a group of smokers and nonsmokers, resistance of LDL to oxidation increased significantly and the rate of LDL oxidation decreased significantly after vitamin E supplementation (671 mg/d for 7 d). There was some indication of a small increase in the resistance of LDL to oxidation in smokers after supplementation with B-carotene (20 mg/d for 2 wk, then 40 mg/d for 12wk). In Summary, therefore, experimental evidence suggests that antioxidants vitamins can reduce the susceptibility of LDL to oxdation in vitro.
Vitamin E would appear to be the most effective antioxidant; both B-carotene and vitamin have produced extensions in lag time to oxidation only in a minority of studies, although it remains possible that they may have a beneficial effect in individuals with poor baseline status.
