Xu M J, Plezia P M, Alberts D S, Emerson S S, Peng Y M, Sayers S M, Liu Y, Ritenbaugh C, Gensler H L
Cancer Prevention and Control Program, Arizona Cancer Center, Tucson 85724.
J Natl Cancer Inst. 1992 Oct 21;84(20):1559-65. doi: 10.1093/jnci/84.20.1559.
Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol.
This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model.
In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha-tocopherol, except for the control mice, which received UV radiation for 27 weeks from week 3 to week 30. Plasma and dorsal skin samples were taken after 40 weeks and were analyzed for alpha-tocopherol and/or beta-carotene by high-performance liquid chromatography.
Long-term dietary beta-carotene administration resulted in statistically significant reductions in levels of alpha-tocopherol in the skin and plasma of UV-irradiated mice. In the human study, the decrease in plasma alpha-tocopherol levels was progressive and significant between 6 and 9 months of beta-carotene dosing in all dosage groups. The greatest decrease was observed during the 9th (last) month of dosing, with a decrease of 40% from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels.
Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta-carotene dose groups.
Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies.
β-胡萝卜素是各类肿瘤疾病化学预防剂临床试验中最常用的化合物之一。包括我们自己的研究在内，动物研究已证明，膳食中的β-胡萝卜素可降低血浆α-生育酚（维生素E）水平，但很少有已发表的研究探讨长期、高剂量β-胡萝卜素方案对其他脂溶性维生素（如α-生育酚）的临床或药代动力学影响。
本研究旨在确定长期补充β-胡萝卜素对正常人类受试者以及实验性C3H/HeN小鼠模型血浆α-生育酚浓度的影响。
在一项双盲研究中，45名正常受试者被随机分配，每天口服0（安慰剂）、15、30、45或60毫克β-胡萝卜素，持续约9个月。每月采集血浆样本。35只C3H/HeN小鼠喂食含或不含β-胡萝卜素的基础饮食，并局部给予或不给予α-生育酚，但对照组小鼠从第3周到第30周接受27周的紫外线辐射。40周后采集血浆和背部皮肤样本，通过高效液相色谱法分析α-生育酚和/或β-胡萝卜素。
长期给予膳食β-胡萝卜素导致紫外线照射小鼠的皮肤和血浆中α-生育酚水平在统计学上显著降低。在人体研究中，所有剂量组在β-胡萝卜素给药6至9个月期间，血浆α-生育酚水平呈进行性且显著下降。在给药的第9个月（最后一个月）下降最为明显，较基线水平下降了40%。然而，所有口服β-胡萝卜素剂量（15 - 60毫克/天）导致α-生育酚稳态血浆水平下降相似，且β-胡萝卜素血浆水平仅存在微小差异。
长期口服β-胡萝卜素会降低α-生育酚的稳态血浆浓度。鉴于四个β-胡萝卜素剂量组中稳态β-胡萝卜素血浆水平差异较小，β-胡萝卜素剂量与α-生育酚血浆水平之间缺乏显著的剂量反应效应并不意外。
需要开展研究以确定长期给予β-胡萝卜素如何影响膳食α-生育酚的组织分布。对这种以及其他潜在有害的营养相互作用进行仔细监测应成为所有长期干预研究的一部分。
