Ginseng and Cancer-Related Fatigue: A Systematic Review of Clinical Trials.

PURPOSE: The data on the effect of ginseng on general fatigue were previously reviewed. However, there is limited data on the effect of various types of ginseng on cancer-related fatigue (CRF). CRF is one of the most pervasive symptoms of cancer and cancer treatment. The primary objective of the current study was to systematically review trials investigating the safety and efficacy of three different types of ginseng separately used in the treatment protocol for patients with CRF. METHODS: We searched the available online databases for relevant publications up to October 2019. Data were independently extracted by two reviewers. We assessed the risk of bias using the Cochrane Collaboration Review Manager (RevMan, version 5.3) and reported the results in a narrative summary. RESULTS: A total of 210 studies were identified by the initial search, from which seven clinical trials and one retrospective study were included in this systematic review. A total of two clinical trials and one retrospective review examined the impact of American ginseng on CRF symptoms, three studies tested Asian ginseng, and two trials were conducted using Korean ginseng. The quality of the selected studies varied greatly. All three types of ginseng were tolerated well with few low-grade adverse events. American ginseng, containing more than 5% ginsenosides, consumed at the dosage of 2000 mg/day for up to eight weeks significantly reduced fatigue. Asian ginseng, containing ≥ 7% ginsenosides, relieved symptoms of fatigue at the dosage of 400 mg/day in the majority of patients with CRF. Korean ginseng, consumed at the dosage of 3000 mg/day for 12 weeks, decreased symptoms of CRF. CONCLUSIONS: Although our findings support the safety and effectiveness of ginseng in the treatment of CRF, the number of high-quality studies is not adequate to adopt ginseng as a standard treatment option for CRF.

Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta-analysis.

The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta-analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF-α, and IL-6 were included. For each outcome, mean differences and SDs were pooled using a random-effects model. Overall, eight RCTs were included in this meta-analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: -0.43 mg/L; 95% confidence interval [CI]: -1.04 to 0.17; p = .16), serum TNF-α (WMD: -1.29 pg/mL; 95% CI: -4.13 to 1.55; p = .37), and IL-6 concentrations (WMD: 0.11 pg/mL; 95% CI: -0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF-α in studies that recruited non-diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non-linear effect of saffron dosage on serum CRP concentrations (pnon-linearity = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high-quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.

The effect of oral curcumin supplementation on health-related quality of life: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: With an aging society, a multitude of physical, mental, and emotional challenges are being faced both in the general population and by those with chronic disorders. An enhanced understanding of 'quality of life' could be considered a major criterion for improved clinical care. We performed a meta-analysis to examine the effect of oral curcumin on improving the health-related quality of life (HRQOL). METHODS: A systematic search was performed through PubMed, Clarivate Web of Science, Scopus, and Embase up to February 2020 using relevant keywords. Trials that met the inclusion criteria were included in this study. We applied the standardized mean difference (SMD) in a random-effects model to analyze the impact of combined trials. Additionally, we used the Cochrane Risk Bias Tool to evaluate any potential risks of bias. RESULTS: A total of 10 studies were considered eligible and included in the meta-analysis. We found an overall significant effect of oral curcumin supplementation on improved HRQOL (SMD: 2.46, 95% CI: 1.30, 3.63; I2=97.4). In the subgroup analysis, curcumin showed significantly favorable effects on HRQOL in trials with a short duration of curcumin intervention (<5 months) and those that used curcumin formulations with high bioavailability. CONCLUSION: Oral curcumin has a strong positive impact on HRQOL. Our analysis supports the use of an improved-bioavailability formulation of curcumin to improve HRQOL. However, given the heterogeneity among the studies included in this review, additional evidence from well-designed, large, and long-term trials is still required.

The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials.

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (- 0.52, 95% CI - 0.80, - 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose-response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.

The effects of green coffee extract supplementation on glycemic indices and lipid profile in adults: a systematic review and dose-response meta-analysis of clinical trials.

BACKGROUND: The role of coffee consumption in the risk of cardiovascular diseases has been debated for many years. The current study aimed to summarize earlier evidence on the effects of green coffee extract (GCE) supplementation on glycemic indices and lipid profile. METHODS: We searched available online databases for relevant clinical trials published up to October 2019. All clinical trials investigating the effect of GCE supplementation, compared with a control group, on fasting blood glucose (FBG), serum insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were included. Overall, 14 clinical trials with a total sample size of 766 participants were included in the current meta-analysis. RESULTS: We found a significant reducing effect of GCE supplementation on FBG (weighted mean difference (WMD): -2.35, 95% CI: - 3.78, - 0.92 mg/dL, P = 0.001) and serum insulin (WMD: -0.63, 95% CI: - 1.11, - 0.15 µU/L, P = 0.01). With regard to lipid profile, we observed a significant reduction only in serum levels of TC following GCE supplementation in the overall meta-analysis (WMD: -4.51, 95% CI: - 8.39, - 0.64, P = 0.02). However, subgroup analysis showed a significant reduction in serum TG in studies enrolled both genders. Also, such a significant reduction was seen in serum levels of LDL and HDL when the analyses confined to studies with intervention duration of ≥8 weeks and those included female subjects. In the non-linear dose-response analyses, we found that the effects of chlorogenic acid (CGA) dosage, the main polyphenol in GCE, on FBG, TG and HDL were in the non-linear fashions. CONCLUSION: In conclusion, we found that GCE supplementation improved FBG and serum levels of insulin and TC. Also, there was a significant improvement in other markers of lipid profile in some subgroups of clinical trials.

The effect of green coffee extract supplementation on anthropometric measures in adults: A comprehensive systematic review and dose-response meta-analysis of randomized clinical trials.

BACKGROUND AND AIM: Two meta-analyses summarized data on the effects of green coffee extract (GCE) supplementation on anthropometric measures. However, the accuracy of those meta-analyses is uncertain due to several methodological limitations. Therefore, we aimed to conduct a comprehensive systematic review and dose-response meta-analysis to summarize all available evidence on the effects of GCE supplementation on anthropometric measures by considering the main limitations in the previous meta-analyses. METHODS: We searched available online databases for relevant publications up to January 2020, using relevant keywords. All randomized clinical trials (RCTs) investigating the effects of GCE supplementation, compared with a control group, on anthropometric measures [including body weight, body mass index (BMI), body fat percentage, waist circumference (WC) and waist-to-hip ratio (WHR)] were included. RESULTS: After identifying 1871 studies from our initial search, 15 RCTs with a total sample size of 897 participants were included in the systematic review and meta-analysis. We found a significant reducing effect of GCE supplementation on body weight (weighted mean difference (WMD): -1.23, 95 % CI: -1.64, -0.82 kg,P < 0.001), BMI (WMD: -0.48, 95 % CI: -0.78, -0.18 kg/m2, P = 0.001), and WC (WMD: -1.00, 95 % CI: -1.70, -0.29 cm, P = 0.006). No significant effect of GCE supplementation on body fat percentage and WHR was seen. In the dose-response analyses, there was no significant association between chlorogenic acid (CGA) dosage, as the main polyphenol in green coffee, and changes in anthropometric measures. CONCLUSION: We found that GCE supplementation had a beneficial effect on body weight, BMI and WC. It provides a cost-effective and safe alternative for the treatment of obesity. Additional well-designed studies are required to further confirm our findings.

Effects of zinc supplementation on lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Findings on the effects of zinc supplementation on the lipid profile in patients with type 2 diabetes mellitus (T2DM) are conflicting. The current comprehensive systematic review and meta-analysis aimed to summarize available evidence in this regard. METHODS AND RESULTS: After a systematic search in the online databases, we included the randomized controlled trials (RCTs) investigating the effect of zinc supplementation on lipid profile [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)] in patients with T2DM. Altogether, 9 studies with a total sample size of 424 patients with T2DM were included in the analysis. Combining 9 effect sizes from 9 RCTs, we found a significant lowering effect of zinc supplementation on serum levels of TG (weighted mean difference (WMD): -17.08, 95% CI: -30.59, -3.58 mg/dL, P = 0.01) and TC (WMD: -26.16, 95% CI: -49.69, -2.62 mg/dL, P = 0.02). Although the overall effect of zinc supplementation on LDL-C levels was not significant, a beneficial effect was seen in studies that administered <100 mg/d zinc. Based on the non-linear dose-response analysis, a greater reduction in serum levels of TC and LDL-C following zinc supplementation was seen at <12 weeks' duration of intervention. Unlike the overall effect size, we found a significant increasing effect of zinc supplementation on serum HDL-C concentrations in most subgroups of RCTs according to the subgroup analyses. CONCLUSION: We found that zinc supplementation may beneficially influence lipid profile in patients with T2DM.

The effect of vitamin d-calcium co-supplementation on inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials.

Data on the effect of vitamin d-calcium co-supplementation on inflammatory biomarkers, compared to placebo or intake of calcium and vitamin D supplements alone, are conflicting. The current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize available findings on the effect of vitamin d-calcium co-supplementation on inflammatory biomarkers in adults. Online databases including PubMed, Scopus, ISI Web of Science and Google Scholar were searched using relevant keywords up to June 2019. We included RCTs investigating the effect of vitamin d-calcium co-supplementation, compared to placebo or intake of calcium and vitamin D supplements alone, on inflammatory biomarkers. In total, 8 RCTs that enrolled 706 participants, aged ≥18 years, were included. Pooling 9 effect sizes from 8 RCTs on C-reactive protein (CRP) levels revealed a significant reducing effect of vitamin d-calcium co-supplementation on serum CRP concentrations compared to placebo intake (WMD: -0.82, 95% CI: -1.56, -0.07 mg/L, P = 0.03). However, this beneficial effect became non-significant when compared to the intake of calcium and vitamin D supplements alone. Also, we found that the associations of vitamin d-calcium dosages and duration of intervention with the reduction in CRP concentrations were in a non-linear fashion. Combining 5 effect sizes for IL-6 and 3 effect sizes for TNF-α, we found no significant effect of joint calcium and vitamin D supplementation on serum concentrations of IL-6 (WMD: -1.45, 95% CI: -5.31, 2.41 pg/mL, P = 0.46) and TNF-α (WMD: -0.79, 95% CI: -2.19, 0.61 pg/mL, P = 0.26). We found a beneficial effect of vitamin d-calcium co-supplementation on serum CRP concentrations. However, such a beneficial effect was not seen for IL-6 and TNF-α concentrations.

Oral Magnesium Supplementation Improved Lipid Profile but Increased Insulin Resistance in Patients with Diabetic Nephropathy: a Double-Blind Randomized Controlled Clinical Trial.

Low serum magnesium concentrations were associated with development of renal failure. We aimed to determine whether magnesium supplementation improves renal function, insulin resistance, and metabolic profiles in patients with diabetic nephropathy. A total of 80 hypomagnesemic patients diagnosed with type 2 diabetes and early-stage nephropathy were recruited. Subjects received either daily magnesium oxide or placebo for 12 weeks. Biochemical and anthropometric variables were measured. Physical activity and dietary intakes were also recorded. This study was approved by the ethics committee of Isfahan University of Medical Sciences and was registered on the Iranian Registry of Clinical Trials website (IRCT registration no. IRCT201404271485N12). Serum magnesium levels were not changed significantly. Although the supplementation did not influence glycemic indices, patients in the magnesium group had greater insulin resistance compared with the placebo group after intervention (0.3 ± 2.3 µIU/mL vs. - 0.04 ± 2.05, P = 0.04). No significant changes were observed in serum total cholesterol, triglycerides, HDL, LDL, and total cholesterol/HDL cholesterol ratio. Furthermore, magnesium did not affect inflammation, serum levels of creatinine, and blood urine nitrogen. However, a marginal decrease in microalbuminuria (- 3.1 ± 2.2 mg/L vs. - 14 ± 9.9, P = 0.09) was observed. Oral magnesium supplementation slightly improved microalbuminuria but resulted in increased insulin resistance in patients with diabetic nephropathy.