Department of Nutrition Science, Purdue University, West Lafayette, IN, United States.
Adv Nutr. 2024 Jul;15(7):100240. doi: 10.1016/j.advnut.2024.100240. Epub 2024 May 10.
The vitamin E family contains α-tocopherol (αT), βT, γT, and δT and α-tocotrienol (TE), βTE, γTE, and δTE. Research has revealed distinct roles of these vitamin E forms in prostate cancer (PCa). The ATBC trial showed that αT at a modest dose significantly decreased PCa mortality among heavy smokers. However, other randomized controlled trials including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicate that supplementation of high-dose αT (≥400 IU) does not prevent PCa among nonsmokers. Preclinical cell and animal studies also do not support chemopreventive roles of high-dose αT and offer explanations for increased incidence of early-stage PCa reported in the SELECT. In contrast, accumulating animal studies have demonstrated that γT, δT, γTE, and δTE appear to be effective for preventing early-stage PCa from progression to adenocarcinoma in various PCa models. Existing evidence also support therapeutic roles of γTE and its related combinations against advanced PCa. Mechanistic and cell-based studies show that different forms of vitamin E display varied efficacy, that is, δTE ≥ γTE > δT ≥ γT >> αT, in inhibiting cancer hallmarks and enabling characteristics, including uncontrolled cell proliferation, angiogenesis, and inflammation possibly via blocking 5-lipoxygenase, nuclear factor κB, hypoxia-inducible factor-1α, modulating sphingolipids, and targeting PCa stem cells. Overall, existing evidence suggests that modest αT supplement may be beneficial to smokers and γT, δT, γTE, and δTE are promising agents for PCa prevention for modest-risk to relatively high-risk population. Despite encouraging preclinical evidence, clinical research testing γT, δT, γTE, and δTE for PCa prevention is sparse and should be considered.
维生素 E 家族包含 α-生育酚（αT）、βT、γT 和 δT 以及 α-生育三烯酚（TE）、βTE、γTE 和 δTE。研究揭示了这些维生素 E 形式在前列腺癌（PCa）中的不同作用。ATBC 试验表明，适度剂量的 αT 可显著降低重度吸烟者的 PCa 死亡率。然而，其他包括硒和维生素 E 癌症预防试验（SELECT）在内的随机对照试验表明，补充高剂量 αT（≥400IU）并不能预防非吸烟者的 PCa。临床前细胞和动物研究也不支持高剂量 αT 的化学预防作用，并解释了 SELECT 中报告的早期 PCa 发病率增加的原因。相比之下，越来越多的动物研究表明，γT、δT、γTE 和 δTE 似乎可有效预防各种 PCa 模型中的早期 PCa 进展为腺癌。现有证据也支持 γTE 及其相关组合对晚期 PCa 的治疗作用。机制和基于细胞的研究表明，不同形式的维生素 E 显示出不同的疗效，即 δTE≥γTE＞δT≥γT＞＞αT，可通过抑制癌症标志物和使特征（包括不受控制的细胞增殖、血管生成和炎症）得以实现，这可能是通过阻断 5-脂氧合酶、核因子 κB、缺氧诱导因子-1α、调节神经鞘脂和针对 PCa 干细胞来实现的。总的来说，现有证据表明，适度的 αT 补充可能对吸烟者有益，而 γT、δT、γTE 和 δTE 是针对中低风险至高风险人群的 PCa 预防的有前途的药物。尽管有令人鼓舞的临床前证据，但针对 γT、δT、γTE 和 δTE 预防 PCa 的临床研究仍很稀缺，应予以考虑。
