Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Integrative Oncology and Quality of Life Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Pharmacol Res. 2020 Jun;156:104767. doi: 10.1016/j.phrs.2020.104767. Epub 2020 Mar 20.
The aim of this systematic review and dose-response meta-analysis was to determine the effect of Nigella sativa (N.S) supplementation on liver and kidney parameters. We searched PubMed, Scopus, ISI Web of Science, Cochrane central register for controlled trials and Google Scholar from database inception to April 2019 for relevant controlled trials. Mean differences and standard deviations for each outcome were pooled using a random-effects model and a dose-response analysis was performed using a fractional polynomial model. Quality of evidence was evaluated using Cochrane Collaboration Risk of Bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Nineteen trials (n = 1295 participants) were included in the meta-analysis. We observed that N.S supplements had significant reducing effects on alkaline-phosphatase (ALP) [9 trials, n = 710 participants, weighted mean difference (WMD)= -10.825; 95 %CI: -19.658, -1.992 U/L; P = 0.016; I = 75.7 %; P-heterogeneity = 0.000) and blood urea nitrogen (BUN) (12 trials, n = 821 participants, WMD= -1.016; 95 % CI: -1.760, -0.273 U/L; P = 0.007; I = 87.7 %; P-heterogeneity = 0.000) concentrations. Subgroup analysis showed that, an intervention of more than 12 weeks was found to have a reducing effect on aspartate- aminotransferase (AST) measures (2 trials, n = 201 participants, WMD= -11.317; 95 % CI: -15.007, -7.626; P = 0.000; I = 0.0 %; P-heterogeneity = 0.977). Creatinine levels increased significantly in studies that considered adjusted analysis based on covariates (3 trials, n = 152 participants, WMD = 0.070; 95 % CI: 0.027, 0.112 U/L; P = 0.001; I = 0.0 %; P-heterogeneity = 0.788). A daily dose of 1100-1500 mg of N.S supplements was observed to have a substantial reducing effect on ALP levels (5 trials, n = 340 participants, WMD= -11.323; 95 % CI: -21.418, -1.229 U/L; P = 0.028; I = 0.00 %; P-heterogeneity = 0.686), while a dosage of more than 2000 mg per day led to a significant increase in BUN concentrations (2 trials, n = 101 participants, WMD= -1.016; 95 % CI: -1.760, -0.273 U/L; P = 0.007; I = 87.7 %; P-heterogeneity = 0.000). Our data suggested that N.S supplementation had significant impacts on liver and kidney parameters leading to a decrease in ALP and BUN levels. Longer duration of intervention and normal daily dosages of N.S supplements led to significant reductions in ALP and AST concentrations, respectively, while higher daily dosages increased BUN levels. Hence, in spite of favorable impacts of N.S supplements on liver and kidney parameters, due to the herbal nature of N.S, more studies with high-quality, large-scale, long-term intervention and precise baseline characteristics are needed to assess the exact effective dose, duration and efficacy of N.S supplementation on kidney and liver parameters.
本系统评价和剂量反应荟萃分析的目的是确定黑种草（N.S）补充剂对肝脏和肾脏参数的影响。我们检索了 PubMed、Scopus、ISI Web of Science、Cochrane 对照试验中心注册库和 Google Scholar，从数据库建立到 2019 年 4 月，以检索相关对照试验。使用随机效应模型汇总每个结局的均数差异和标准差，并使用分数多项式模型进行剂量反应分析。使用 Cochrane 协作风险偏倚工具和 Grading of Recommendations Assessment, Development and Evaluation (GRADE) 方法评估证据质量。纳入了 19 项试验（n = 1295 名参与者）进行荟萃分析。我们观察到，N.S 补充剂对碱性磷酸酶（ALP）[9 项试验，n = 710 名参与者，加权均数差异（WMD）= -10.825; 95 %CI：-19.658，-1.992 U/L; P = 0.016; I = 75.7 %; P 异质性 = 0.000]和血尿素氮（BUN）[12 项试验，n = 821 名参与者，WMD= -1.016; 95 %CI：-1.760，-0.273 U/L; P = 0.007; I = 87.7 %; P 异质性 = 0.000]浓度有显著的降低作用。亚组分析显示，干预时间超过 12 周对天冬氨酸氨基转移酶（AST）指标有降低作用（2 项试验，n = 201 名参与者，WMD= -11.317; 95 %CI：-15.007，-7.626; P = 0.000; I = 0.0 %; P 异质性 = 0.977）。考虑到根据协变量进行调整分析的研究中，肌酐水平显著升高（3 项试验，n = 152 名参与者，WMD = 0.070; 95 %CI：0.027，0.112 U/L; P = 0.001; I = 0.0 %; P 异质性 = 0.788）。观察到每天 1100-1500 mg 的 N.S 补充剂对 ALP 水平有显著的降低作用（5 项试验，n = 340 名参与者，WMD= -11.323; 95 %CI：-21.418，-1.229 U/L; P = 0.028; I = 0.00 %; P 异质性 = 0.686），而每天超过 2000 mg 的剂量导致 BUN 浓度显著升高（2 项试验，n = 101 名参与者，WMD= -1.016; 95 %CI：-1.760，-0.273 U/L; P = 0.007; I = 87.7 %; P 异质性 = 0.000）。我们的数据表明，N.S 补充剂对肝脏和肾脏参数有显著影响，导致 ALP 和 BUN 水平降低。干预时间更长和 N.S 补充剂的正常日剂量导致 ALP 和 AST 浓度分别显著降低，而更高的日剂量增加了 BUN 水平。因此，尽管 N.S 补充剂对肝脏和肾脏参数有有利影响，但由于 N.S 的草药性质，需要更多高质量、大规模、长期干预和精确基线特征的研究来评估 N.S 补充剂对肾脏和肝脏参数的确切有效剂量、持续时间和疗效。
