METHODS: This study followed a scoping review framework. Peer-reviewed journal articles were included if they reported the effect of d-limonene or its derivatives on breast cancer in human subjects. Articles were retrieved from academic databases - PubMed, EMBASE, CINAHL, Web of Science, and Cochrane reviews - and iteratively through review of bibliographies of relevant manuscripts. Titles and abstracts were appraised against the aforementioned inclusion criteria in a first round of screening. Through consensus meetings and full article review by authors, a final set of studies were selected. Results were reported according to the PRISMA extension for scoping reviews.
RESULTS: Our search strategy yielded 367 records. Following screening and adjudication, five articles reporting on phase 1(n = 2), phase 2 (n = 2) and both trial phases (n = 1) were included as the final dataset for this review. Trials evaluating the effect of d-limonene (n = 2) showed it was well tolerated in subjects. One study (n = 43 participants) showed d-limonene concentrated in breast tissue (mean 41.3 μg/g tissue) and reduction in tumor cyclin D1 expression, which is associated with tumor proliferation arrest. This study did not show meaningful change in serum biomarkers associated with breast cancer, except for a statistically significant increase in insulin-like growth factor-1 (IGF-I) levels. While elevation of IGF-I is associated with increased cancer risk, the clinical implication of this study remains uncertain given its short duration. Trials with perillyl alcohol (n = 3) showed low tolerance and no effect on breast cancer.
CONCLUSIONS: This review demonstrated a dearth of clinical studies exploring the effect of d-limonene and its derivatives on breast cancer. Limited literature suggests d-limonene is safe and tolerable in human subjects compared to its derivative, perillyl alcohol. Our review demonstrates the need for additional well-powered placebo-controlled trials that assess d-limonene\'s efficacy on breast cancer compared to other therapies.
方法:本研究遵循范围审查框架。如果同行评审的期刊文章报道了d-柠檬烯或其衍生物对人类受试者乳腺癌的影响,则包括在内。文章从学术数据库中检索-PubMed,EMBASE,CINAHL,WebofScience,和Cochrane评论-并反复审查相关手稿的参考书目。在第一轮筛选中,对照上述纳入标准对标题和摘要进行了评估。通过共识会议和作者的全文审查,我们选择了最后一组研究.根据PRISMA扩展范围审查报告结果。
结果:我们的搜索策略产生了367条记录。经过筛选和裁决,五篇报告第一阶段的文章(n=2),2期(n=2)和两个试验阶段(n=1)作为本综述的最终数据集.评价d-柠檬烯(n=2)的作用的试验显示其在受试者中具有良好的耐受性。一项研究(n=43名参与者)显示d-柠檬烯集中在乳腺组织(平均41.3μg/g组织)和肿瘤细胞周期蛋白D1表达减少,这与肿瘤增殖停滞有关。这项研究没有显示与乳腺癌相关的血清生物标志物有意义的变化,除了胰岛素样生长因子-1(IGF-I)水平的统计学显着增加。虽然IGF-I的升高与癌症风险增加有关,由于研究持续时间短,本研究的临床意义仍不确定.紫苏醇(n=3)的试验显示耐受性低,对乳腺癌没有影响。
结论:这篇综述表明缺乏探索d-柠檬烯及其衍生物对乳腺癌影响的临床研究。有限的文献表明d-柠檬烯与其衍生物相比在人类受试者中是安全和可耐受的。紫苏醇。我们的综述表明,与其他疗法相比,需要更多有效的安慰剂对照试验来评估d-柠檬烯对乳腺癌的疗效。