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.

Lycopene Does Not Affect Prostate-Specific Antigen in Men with Non-Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Several randomized controlled trials (RCTs) have investigated the effect of lycopene supplementation on serum levels of prostate-specific antigen (PSA) in patients with prostate cancer. However, results have been inconclusive. We systematically searched PubMed, Embase, and Scopus up to January 2020 to find RCTs investigating the effect of lycopene supplementation on serum levels of PSA in patients with non-metastatic prostate cancer. Using a random-effects model, the reported risk estimates were pooled. A total of six trials were included in the final analysis. we found no significant effect of lycopene on circulating PSA (WMD: -0.60, 95% CI: -2.01, 0.81 µg/L). However, we observed a significant reducing effect when the analysis was confined to studies that included patients with higher baseline levels of PSA (≥6.5 µg/L) (WMD: -3.74 µg/L, 95% CI: -5.15, -2.32, P < 0.001). Subgroup analysis based on the duration of intervention did not result in any significant effect. Non-linear dose-response analysis did not show any significant effects of lycopene dosage (Pnon-linearity = 0.50) and duration of the intervention (Pnon-linearity = 0.63) on serum levels of PSA. Although lycopene supplementation did not produce any reduction in PSA levels overall, a significant reducing effect was observed in patients with higher levels of baseline PSA. Due to the heterogeneity of our results, further high-quality clinical trials with long-term duration are required to determine the efficacy of lycopene in patients with non-metastatic prostate cancer.

G1359A Variant of the Cannabinoid Receptor Gene (rs1049353) and Obesity-Related Traits and Related Endophenotypes: A Meta-Analysis.

BACKGROUND: This study aimed to investigate the comparison of G1359A variant of cannabinoid receptor gene (rs1049353) with obesity-related traits including body mass index (BMI), fat mass (FM), fat-free mass (FFM), food-related traits, and leptin among healthy and non-healthy adults. METHODS: We searched PubMed, Cochrane, Scopus, Web of Science, and EMBASE until December 2016 for observational studies assessing each of the anthropometric measurements, food-related traits, and leptin of 1359 G/A polymorphism of CNR1 gene. A total of 22 studies were included in the meta-analysis comparing mean and SD differences of the anthropometric measurements, leptin, and dietary intake between GA/AA and GG genotypes. RESULTS: The results showed that subjects with GA/AA genotype had significantly lower BMI (weighted mean difference = -0.59 kg/m2, p < 0.001) compared to those with the GG genotype. Dietary intake of fat, carbohydrate, and protein as well as serum levels of leptin was not significantly different between GA/AA and GG genotypes. CONCLUSION: It was revealed that subjects with mutant polymorphism (GA/AA) of CNR1, compared to the wild-type group (GG), had lower BMI (although there was unexplained heterogeneity).

Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.

Soy Foods and the Risk of Fracture: A Systematic Review of Prospective Cohort Studies.

OBJECTIVES: The primary objective of our study was to systematically review all available prospective cohort studies which investigated the association of soy food intake and incident fracture risk. METHODS: We searched PubMed, Scopus, and Embase databases for relevant studies up to June 2021. SYNTHESIS: Of 695 records, a total of 5 cohort studies were included in the current systematic review. Two studies that were performed in China evaluated hip fracture while 2 studies that were done in Singapore evaluated any kind of fractures. The other study was conducted in Japan and evaluated osteoporosis fractures. All studies used a face-to-face interview to assess the dietary intake of soy foods. All 5 cohort studies were determined to be of high quality. One study considered soy food as a part of a vegetables-fruit-soy food dietary pattern. Others reported the association of dietary intake of soy foods with the risk of fractures. CONCLUSION: The evidence from prospective cohort studies was suggestive for a protective role of soy foods, alone or within a dietary pattern, in the risk of incident fracture among Asian women, particularly for those in early menopause and those who used fermented soy products. But for men, the association was not significant. However, more cohort studies, including non-Asian populations, are required to confirm this association fully.

A review of fasting effects on the response of cancer to chemotherapy.

BACKGROUND & AIMS: Studies suggest that fasting before or during chemotherapy may induce differential stress resistance, reducing the adverse effects of chemotherapy and enhancing the efficacy of drugs. In this article, we review the effects of fasting, including intermittent, periodic, water-only short-term fasting, and caloric restriction on the responsiveness of tumor cells to cytotoxic drugs, their protective effect on normal cells, and possible mechanisms of action. METHODS: We could not perform a systematic review due to the wide variation in the study population, design, dependent measures, and outcomes (eg, type of cancer, treatment variation, experimental setting, etc.). However, a systematic approach to search and review literature was used. The electronic databases PubMed (MEDLINE), Scopus, and Embase were searched up to July 2020. RESULTS: Fasting potentially improves the response of tumor cells to chemotherapy by (1) repairing DNA damage in normal tissues (but not tumor cells); (2) upregulating autophagy flux as a protection against damage to organelles and some cancer cells; (3) altering apoptosis and increasing tumor cells' sensitivity to the apoptotic stimuli, and preventing apoptosis-mediated damage to normal cells; (4) depleting regulatory T cells and improving the stimulation of CD8 cells; and (5) accumulating unfolded proteins and protecting cancer cells from immune surveillance. We also discuss how 'fasting-mimicking diet' as a modified form of fasting enables patients to eat a low calorie, low protein, and low sugar diet while achieving similar metabolic outcomes of fasting. CONCLUSION: This review suggests the potential benefits of fasting in combination with chemotherapy to reduce tumor progression and increase the effectiveness of chemotherapy. However, with limited human trials, it is not possible to generalize the findings from animal and in vitro studies. More human studies with adequate sample size and follow-ups are required to confirm these findings.

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 Effects of Probiotic/Synbiotic on Serum Level of Zonulin as a Biomarker of Intestinal Permeability: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis was conducted to obtain a conclusive result on the influence of probiotics/synbiotic on serum levels of zonulin. Data related to serum levels of zonulin were extracted to determine the effects of probiotic/synbiotic on intestinal permeability. METHODS: The literature search was conducted across the Cochrane Central Register of Controlled Trials, Pub-Med, Scopus and ISI Web of Science, Search up to Nov 2018. Clinical trials evaluating the effect of probiotic/synbiotic on serum zonulin levels of all human subjects were included. RESULTS: Nine studies (including 496 intervention and 443 control subjects) met the inclusion criteria for the meta-analysis. According to the meta-analysis, probiotic/synbiotic has a significant effect on serum zonulin reduction (WMD=-10.55 [95% CI: -17.76, -3.34]; P=0.004). However, the high level of heterogeneity was observed among the studies (I2=97.8, P<0.001). The subgroup analysis suggested study quality, blinding, study duration, Participants age, subject's health status and supplement type as sources of heterogeneity. CONCLUSION: Probiotic/synbiotic have favorable effects on serum levels of zonulin as a measure of intestinal permeability. However, the results should be interpreted with caution due to the high heterogeneity and further evidence is required before definitive recommendations can be made.

The Effect of Whole-Grain Intake on Biomarkers of Subclinical Inflammation: A Comprehensive Meta-analysis of Randomized Controlled Trials.

Findings on the effect of whole-grain consumption on inflammatory biomarkers are conflicting. This study aimed to summarize available studies on the effects of whole-grain consumption on inflammatory biomarkers in adults. Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched for relevant studies published up to January 2018, using relevant keywords. We included randomized controlled trials (RCTs) investigating the effect of whole-grain foods or diets high in whole-grain foods on markers of inflammation. Studies were selected if they had a control diet low in whole grains or diets without whole grains, whether calorie restricted or not. We did not include studies that examined the effect of individual grain components, including bran or germ, or fiber-based diets. Overall, 14 RCTs, with 1238 individuals aged ≥18 y, were included. Pooling 13 effect sizes from 11 RCTs on serum C-reactive protein (CRP) concentrations, we found no significant effect of whole-grain consumption on serum CRP concentrations [weighted mean difference (WMD): -0.29 mg/L; 95% CI: -1.10, 0.52 mg/L]. However, the beneficial effects of whole-grain intake on serum CRP concentrations were observed in studies in individuals with elevated serum concentrations of CRP and studies with isocaloric diets. Combining 11 effect sizes from 10 RCTs, we found no significant effect of whole-grain consumption on serum IL-6 concentrations (WMD: -0.08 pg/mL; 95% CI: -0.27, 0.11 pg/mL). Nevertheless, we observed a significant effect of whole-grain consumption on serum IL-6 concentrations in studies in unhealthy individuals. A nonsignificant effect of whole-grain intake on circulating serum TNF-α concentrations was also seen when we summarized effect sizes from 7 RCTs (WMD: -0.06 pg/mL; 95% CI: -0.25, 0.14 pg/mL). Such a nonsignificant effect was observed for serum concentrations of plasminogen activator inhibitor-1 (PAI-1) (WMD: -3.59; 95% CI: -1.25, 8.44 kU/L). Unlike observational studies, we found no significant effect of whole-grain consumption on serum concentrations of inflammatory cytokines, including serum concentrations of CRP, IL-6, TNF-α, and PAI-1. However, beneficial effects of whole grains were found in some subgroups. Given the high between-study heterogeneity, deriving firm conclusions is difficult.

Whole-Grain Consumption Does Not Affect Obesity Measures: An Updated Systematic Review and Meta-analysis of Randomized Clinical Trials.

Since the release of a previous meta-analysis on the effect of whole-grain intake on obesity measures, several clinical trials have been published. Therefore, we aimed to update the previous meta-analysis on the effect of whole-grain intake on obesity measures by including recently published studies, as well as considering the main limitations in that analysis. We searched the online databases of PubMed, Scopus, Clarivate Web of Science, EmBase, and Google Scholar for relevant studies published up to February 2019, using relevant keywords. Randomized clinical trials investigating the effect of whole-grain products or diets high in whole-grain foods, compared with a control diet, on anthropometric measures [including body weight, BMI, waist circumference, and fat mass (FM)] were included. In total, 21 studies with a total sample of 1798 participants, aged ≥18 years, were considered. Based on 22 effect sizes from 19 studies on body weight, with a total sample of 1698 adults, we found no significant effect of whole-grain consumption on body weight. The same findings were obtained for BMIs, such that using 10 effect sizes from 10 clinical trials with a total sample of 769 individuals we did not find any significant effect. With regards to body fat percentage [weighted mean difference (WMD): 0.27; 95% CI: -0.05 to 0.58%; P = 0.09], FM (WMD: 0.45; 95% CI: -0.12 to 1.02 kg; P = 0.12), fat-free mass (WMD: 0.31; 95% CI: -0.67 to 0.06 kg; P = 0.10), and waist circumference (WMD: 0.06; 95% CI: -0.50 to 0.63 cm; P = 0.82), we failed to find any significant effect of whole-grain consumption. In conclusion, our findings did not support current recommendations of whole-grain intake in attempts to control obesity measures. Given the beneficial effects of whole-grain intake on other measures of human health, additional well-designed studies are required to further investigate the effect on obesity. The protocol has been registered with PROSPERO (registration number CRD42019125320).

Circulating vitamin D and the risk of gestational diabetes: a systematic review and dose-response meta-analysis.

PURPOSE: Several meta-analyses of observational studies revealed a modest increase in the risk of gestational diabetes (GDM) among pregnant women with low levels of serum vitamin D. However, no study examined a dose-response meta-analysis as well as a high versus low analysis in this regard. METHODS: We systematically searched PubMed, Embase, ISI Web of Science, and Scopus up to August 2019 to find prospective observational studies investigating the association of serum 25(OH)D with the risk of developing GDM. Using a random-effects model, the reported risk estimates were pooled. RESULTS: Nine cohort studies and six nested case-control studies were included in the final analysis (40,788 participants and 1848 cases). Considering linear analysis, each 10 nmol/L increase in circulating 25(OH)D was associated with a 2% lower risk of GDM (effect size (ES): 0.98; 95% CI: 0.98, 0.99; I2 = 85.0%, P < 0.001). highest compared with the lowest category of circulating 25(OH)D was associated with a 29% lower risk of GDM, with low evidence of heterogeneity (I2 = 45.0%, P = 0.079). CONCLUSIONS: In conclusion, lower levels of serum 25(OH)D were associated with a higher chance of GDM. Differential results existed between the overall and subgroup analysis, either based on vitamin D detection methods or based on maternal age, although these subgroups partially lowered the heterogeneity.

Effects of curcuminoids on inflammatory status in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: Nonalcoholic fatty liver diseases (NAFLD) is a highly prevalent disease that is closely associated with several cardiometabolic complications. The potential anti-inflammatory role of curcuminoids that have already been reported to reduce hepatic steatosis, in patients with NAFLD was explored in this study. METHODS: This double-blind, randomized placebo-controlled trial was conducted for a period of 8 weeks in patients with NAFLD. Subjects (n = 55) were randomly allocated to receive either curcuminoids or placebo. The curcuminoids group received one capsule containing 500 mg curcuminoids (plus 5 mg piperine to increase intestinal absorption) per day for 8 weeks and the control group received matched placebo capsules for the same period. Liver ultrasonography was performed to assess the severity of hepatic steatosis at baseline and the study end. Serum levels of cytokines including interleukin-1α, interleukin-1ß, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon γ, vascular endothelial growth factor and epidermal growth factor were measured before and after the intervention. RESULTS: The two groups were comparable in demographic features at baseline. The results showed that supplementation with curcuminoids could decrease weight compared to the placebo group (p = 0.016) in patients with NAFLD. Curcuminoids supplementation improved the severity of NAFLD according to the ultrasound results (p = 0.002). Moreover, serum concentrations of TNF-α (p = 0.024), MCP-1 (p = 0.008) and EGF (p = 0.0001) were improved by curcuminoids in NAFLD patients. CONCLUSIONS: The results of our study showed that curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD and this might be at least partly responsible for the anti-steatotic effects of curcuminoids.

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.