Reaven P D, Khouw A, Beltz W F, Parthasarathy S, Witztum J L
Department of Medicine, University of California, San Diego, La Jolla 92093-0682.
Arterioscler Thromb. 1993 Apr;13(4):590-600. doi: 10.1161/01.atv.13.4.590.
Experimental and epidemiological evidence supports the hypothesis that oxidation of low density lipoprotein (LDL) appears to be important in mediating the atherogenicity of LDL. To test this hypothesis in humans, it will be necessary to perform intervention studies in large populations. We performed two studies to assess the effectiveness of supplementation with beta-carotene and vitamin E, used alone and in combination with each other, and with vitamin C, to protect LDL from oxidation. In phase 1, after a placebo period, eight subjects were given beta-carotene (60 mg/day) for 3 months, then beta-carotene plus vitamin E (1,600 mg/day) for another 3 months, and then beta-carotene plus vitamin E plus vitamin C (2 g/day) for 3 months. During phase 2, beta-carotene and vitamin C were discontinued, and subjects took only vitamin E for 5 months. During each period, LDL samples were isolated, and measurements of susceptibility to oxidation were performed. beta-Carotene levels in LDL increased nearly 20-fold, but LDL susceptibility to oxidation did not change. Addition of vitamin E increased LDL vitamin E levels nearly 2.5-fold, and this decreased LDL oxidation 30-40%. During the vitamin C supplementation period, plasma levels of beta-carotene and vitamin E rose, but only beta-carotene increased in LDL. However, the susceptibility of LDL to oxidation in this period was not decreased further. During phase 2, when subjects took only vitamin E, LDL susceptibility to oxidation was decreased by 50% as measured by thiobarbituric acid-reactive substances, conjugated dienes, and lipid peroxide formation as well as by macrophage degradation. Thus, long-term supplementation with large doses of vitamin E alone, but not beta-carotene, conferred increased protection to LDL in in vitro assays of oxidation. These data should be useful in planning therapeutic strategies to test the antioxidant hypothesis in humans.
低密度脂蛋白（LDL）的氧化在介导LDL的致动脉粥样硬化性方面似乎很重要。为了在人体中验证这一假说，有必要在大量人群中开展干预研究。我们进行了两项研究，以评估单独补充β-胡萝卜素和维生素E，以及二者与维生素C联合补充，对保护LDL免受氧化的有效性。在第1阶段，经过一个安慰剂期后，8名受试者服用β-胡萝卜素（60毫克/天）3个月，然后服用β-胡萝卜素加维生素E（1600毫克/天）再3个月，接着服用β-胡萝卜素加维生素E加维生素C（2克/天）3个月。在第2阶段，停用β-胡萝卜素和维生素C，受试者仅服用维生素E 5个月。在每个阶段，分离LDL样本，并进行氧化易感性测量。LDL中的β-胡萝卜素水平增加了近20倍，但LDL的氧化易感性没有变化。添加维生素E使LDL中的维生素E水平增加了近2.5倍，这使LDL氧化减少了30 - 40%。在补充维生素C期间，血浆中的β-胡萝卜素和维生素E水平升高，但LDL中仅β-胡萝卜素增加。然而，在此期间LDL的氧化易感性没有进一步降低。在第2阶段，当受试者仅服用维生素E时，通过硫代巴比妥酸反应性物质、共轭二烯和脂质过氧化物形成以及巨噬细胞降解测量，LDL的氧化易感性降低了50%。因此，在体外氧化试验中，单独长期大剂量补充维生素E而非β-胡萝卜素，能增强对LDL的保护作用。这些数据对于规划在人体中检验抗氧化假说的治疗策略应是有用的。
