The effects of probiotic supplementation and exercise training on liver enzymes and cardiometabolic markers in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver ailment worldwide, in which nonpharmacological strategies have a considerable role in the treatment. Probiotic supplementation as well as physical exercise can improve cardiometabolic parameters, but further research is needed to determine the effects of combined treatment versus exercise alone in managing NAFLD-associated biomarkers, primarily liver enzymes, lipid markers, and insulin resistance. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation, combined with exercise versus exercise alone, on liver enzymes and cardiometabolic markers in patients with NAFLD. METHODS: A systematic review and meta-analysis of randomized clinical trials was performed by searching PubMed, Scopus, and Web of Science databases up to April 2024. The search was restricted to articles published in the English language and human studies. Random effects models were used to calculate weighted mean differences (WMD). RESULTS: Pooled estimates (9 studies, 615 patients, intervention durations ranging from 8 to 48 weeks) revealed that probiotics plus exercise decreased aspartate transaminase (AST) [WMD=-5.64 U/L, p = 0.02], gamma-glutamyl transferase (GGT) [WMD=-7.09 U/L, p = 0.004], low-density lipoprotein (LDL) [WMD=-8.98 mg/dL, p = 0.03], total cholesterol (TC) [WMD=-16.97 mg/dL, p = 0.01], and homeostatic model assessment for insulin resistance (HOMA-IR) [WMD=-0.94, p = 0.005] significantly more than exercise only. However, probiotics plus exercise did not significantly change high-density lipoprotein (HDL) [WMD = 0.07 mg/dL, p = 0.9], fasting insulin [WMD=-1.47 µIU/mL, p = 0.4] or fasting blood glucose (FBG) [WMD=-1.57 mg/dL, p = 0.3] compared with exercise only. While not statistically significant, there were clinically relevant reductions in alanine aminotransferase (ALT) [WMD=-6.78 U/L, p = 0.1], triglycerides (TG) [WMD=-21.84 mg/dL, p = 0.1], and body weight (BW) [WMD=-1.45 kg, p = 0.5] for probiotics plus exercise compared with exercise only. The included studies exhibited significant heterogeneity for AST (I2 = 78.99%, p = 0.001), GGT (I2 = 73.87%, p = 0.004), LDL (I2 = 62.78%, p = 0.02), TC (I2 = 72.41%, p = 0.003), HOMA-IR (I2 = 93.86%, p = 0.001), HDL (I2 = 0.00%, p = 0.9), FBG (I2 = 66.30%, p = 0.01), ALT (I2 = 88.08%, p = 0.001), and TG (I2 = 85.46%, p = 0.001). There was no significant heterogeneity among the included studies for BW (I2 = 0.00%, p = 0.9). CONCLUSION: Probiotic supplementation combined with exercise training elicited better results compared to exercise alone on liver enzymes, lipid profile, and insulin resistance in patients with NAFLD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42023424290.

Association between hepcidin levels and inflammatory bowel disease: A systematic review and meta-analysis of observational studies.

Hepcidin has a crucial role in iron homeostasis upon inflammatory conditions such as inflammatory bowel disease (IBD). Thus, we conducted a systematic review and meta-analysis to determine the overall association between serum hepcidin concentrations and IBD. Based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols, an electronic literature search was conducted on PubMed/MEDLINE, Scopus, and Web of Science until June 2020. Studies were deemed eligible for inclusion if they met the following criteria: (1) diagnosis of IBD, (2) observational design, and (3) measured serum hepcidin and prohepcidin concentrations in IBD patients and control group. Overall, 10 studies including 1184 participants were evaluated. Random-effects meta-analysis revealed that subjects with IBD had 7.22 ng/mL (95% CI: 2.10, 12.34; p = .006) higher serum hepcidin concentrations compared to control groups. A nonsignificantly lower serum prohepcidin concentration (0.522 ng/mL, 95% CI: -1.983 to 0.939; p = .484) was found for IBD patients compared to healthy subjects. However, there was significant heterogeneity among the studies regarding both hepcidin (I 2 = 98%, p < .001) and prohepcidin levels (I 2 = 96%, p < .001), respectively. In an age-based subgroup analysis, patients aged ≥18 years with IBD displayed higher serum hepcidin levels when compared to healthy individuals (22.36 ng/mL, 95% CI, 2.12-42.61; p = .030). Hepcidin concentrations are elevated in subjects with IBD; however, the clinical relevance of this finding requires further evaluation in future investigations as the increase is relatively small compared to the wide range of normal hepcidin values.

Effects of intermittent fasting combined with exercise on serum leptin and adiponectin in adults with or without obesity: a systematic review and meta-analysis of randomized clinical trials.

Context: Intermittent fasting (IF) and exercise training (Exe) have been evaluated in several studies for improving cardiometabolic biomarkers related to weight loss. However, further investigation is required to understand the potential effects on leptin and adiponectin concentrations. IF protocols have been shown to be efficient in improving adipokines, but further research is required to determine whether or not IF regimens combined with Exe are superior to Exe alone. Objective: The aim of this study was to determine whether or not interventions combining IF plus Exe are more effective than Exe only for improving serum leptin and adiponectin in adults with and without obesity. Data extraction: A systematic review and meta-analysis was performed by searching PubMed, Scopus, and Web of Science databases up to August 2023 for randomized clinical trials that determined the effects of IF plus Exe vs. Exe alone (control) on body weight, serum leptin, and serum adiponectin. Analyses were conducted for IF plus Exe vs. Exe alone to calculate weighted mean differences (WMD) and standardized mean differences (SMD). Analysis: The current meta-analysis included 6 studies with a total sample of 153 participants, with intervention durations ranging from three days to 52 weeks. IF plus Exe elicited significantly larger decreases in leptin levels [SMD = -0.47, p = 0.03], which were accompanied by weight loss [WMD = -1.25 kg, p = 0.05], as compared with exercise-only interventions, but adiponectin did not differ between the two [SMD = 0.02, p = 0.9]. Conclusion: IF combined with Exe reduced leptin significantly, but did not change adiponectin levels, when compared to exercise only. Perhaps these reductions in leptin levels may have been associated with weight loss; however, due to the small number of included studies and the high heterogeneity in the weight loss outcomes, this result is uncertain. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023460735.

The effects of melatonin and magnesium in a novel supplement delivery system on sleep scores, body composition and metabolism in otherwise healthy individuals with sleep disturbances.

The purpose of this study was to investigate the effects of a novel dietary supplement, including melatonin and magnesium, delivered via coffee pods on sleep quality, resting metabolic rate (RMR), and body composition in individuals with poor sleep quality disturbances. Using a double-blinded, randomized, crossover trial, we recruited 35 participants to a 4-week intervention with both supplements (1.9 mg melatonin + 200 mg elemental magnesium before sleep) and placebo conditions, considering a 7d washout period between treatments. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was applied, RMR (kcal) was measured using indirect calorimetry (canopy ventilated open-circuit system) and body composition was assessed using dual-energy X-ray absorptiometry. Decreases in PSQI and anger - hostility scores, as well as in energy intake and fat mass, were observed (p < 0.05) for both conditions, from baseline to the end of each 4-week intervention. Differences between conditions were also observed for these parameters along with energy spent in activity, number of sedentary breaks, sleep efficiency, latency time, time in bed, total sleep time, awakening time, and movement index (p < 0.05) favouring the supplement condition. However, the final PSQI questionnaire scores still indicated poor sleep quality on average (PSQI > 5), in both conditions, with no changes regarding RMR. A melatonin-magnesium supplement, in a coffee pod format, showed improvements in sleep quality in otherwise healthy individuals with sleep disturbances, however PSQI questionnaire scores still indicated poor quality on average (PSQI > 5).

Effects of low-carbohydrate diets, with and without caloric restriction, on inflammatory markers in adults: a systematic review and meta-analysis of randomized clinical trials.

Low-carbohydrate diets (LCDs) have gained interest due to their favorable effects on health outcomes, such as inflammation. However, further research is needed to ascertain the overall effects of LCDs on inflammatory parameters, but at the same time considering weight loss and calorie intake. Thus, a systematic review and meta-analysis of randomized clinical trials was performed to investigate the effects of LCDs compared with low-fat diets (LFDs), with and without caloric restriction, on inflammatory markers in adults. PubMed, Scopus, and Web of Science were searched through March 2022 to select intervention studies addressing LCDs vs. LFDs, in which the following circulating inflammatory markers were used: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin (IL-6). Analyses were conducted comparing LCDs vs. LFDs through weighted mean differences (WMD) or standardized mean differences (SMD) and 95% confidence intervals (95% CIs) using random effects models. The systematic review and meta-analysis included a total of 51 studies with a total sample of 4,164 adults, with or without other chronic diseases. Intervention durations ranged from 2-144 weeks. LCDs, compared with LFDs, significantly decreased body weight [WMD = -1.35%, p = 0.001], CRP [SMD = -0.1, p = 0.03], and IL-6 [SMD = -0.15, p = 0.09]. However, LCDs did not significantly decrease TNF-α [SMD = -0.02, p = 0.7] compared to LFDs. In conclusion, LCDs have a beneficial effect on markers of inflammation by decreasing CRP and IL-6; this effect has an association with weight loss. However, LCDs were not more effective than LFDs in decreasing TNF-α.

Effects of intermittent fasting regimens on glycemic, hepatic, anthropometric, and clinical markers in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Intermittent fasting (IF) regimens have been hypothesized to influence several markers of cardiometabolic and liver function. The objective of our meta-analysis was to investigate the impact of IF regimens on cardiometabolic and liver markers in subjects diagnosed with non-alcoholic fatty liver disease (NAFLD). METHODS: We searched several online databases (PubMed/Medline, Web of Science, Scopus and Embase) in order to identify suitable publications for inclusion in the meta-analysis. Results were expressed as weighted mean differences (WMD). RESULTS: From 12343 articles identified in different databases, a total of 7 RCT arms were entered into the quantitative synthesis. The manuscripts were published between 2019 and 2023. IF regimens (the 5:2 diet, 16/8 time-restricting feeding, and alternate day fasting) varied from 2 months to 3 months. IF regimens reduced steatosis scores (WMD: -33.22 CAP dB/m, 95 % CI: -50.72 to -15.72), anthropometric characteristics of obesity (WMD: -0.77 kg/m2, 95 % CI: -1.38 to -0.17 for body mass index; WMD: -3.16 kg, 95 % CI: -4.71 to -1.61 for body weight; WMD: -1.90 kg, 95 % CI: -3.51 to -0.29 for waist circumference), as well as ALT (WMD: -9.10 U/L, 95 % CI: -12.45 to -5.75), triglyceride (WMD: -20.83 mg/dl, 95 % CI: -39.01 to -2.66), total cholesterol (WMD: -7.80 mg/dl, 95 % CI: -15.18), HbA1c (WMD: -0.14 %, 95 % CI: -0.20 to -0.08) and HOMA-IR (WMD: -1.21, 95 % CI: -2.08 to -0.34) levels versus controls. Nevertheless, no between-group differences were detected for other biomarkers, e.g., fasting blood glucose, insulin, AST, HDL-C or LDL-C values, and fibrosis scores. CONCLUSION: IF regimens can improve some markers of cardiometabolic and liver function in patients with NAFLD. However, the available evidence to support the benefits of IF regimens is limited and derived from a small number of studies, thus further research is needed to clarify the impact of IF on the cardiometabolic health of NAFLD patients.

Effects of intermittent fasting combined with physical exercise on cardiometabolic outcomes: systematic review and meta-analysis of clinical studies.

CONTEXT: Different intermittent fasting (IF) protocols have been proven to be efficient in improving cardiometabolic markers, but further research is needed to examine whether or not combining IF regimens plus physical exercise is superior to control diets (ie, nonfasting eating) plus physical exercise in this setting. OBJECTIVE: The aim of this study was to determine whether or not combining IF plus exercise interventions is more favorable than a control diet plus exercise for improving cardiometabolic health outcomes. DATA SOURCE: PubMed, Scopus, and Web of Science were comprehensively searched until April 2023. DATA EXTRACTION: Electronic databases were searched for clinical trials that determined the effect of IF plus exercise vs a control diet plus exercise on body weight, lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol), and systolic and diastolic blood pressure (SBP and DBP, respectively). Analyses were conducted for IF plus exercise vs a nonfasting diet plus exercise to calculate weighted mean differences (WMDs). DATA ANALYSIS: The meta-analysis included a total of 14 studies, with a total sample of 360 adults with or without obesity. The duration ranged from 4 to 52 weeks. IF plus exercise decreased body weight (WMD = -1.83 kg; P = 0.001), LDL (WMD = -5.35 mg/dL; P = 0.03), and SBP (WMD = -2.99 mm Hg; P = 0.003) significantly more than a control diet plus exercise. HDL (WMD = 1.57 mg/dL; P = 0.4) and total cholesterol (WMD = -2.24 mg/dL; P = 0.3) did not change significantly for IF plus exercise vs a control diet plus exercise, but there was a trend for reducing triglycerides (WMD = -13.13 mg/dL; P = 0.07) and DBP (WMD = 2.13 mm Hg; P = 0.05), which shows clinical magnitude. CONCLUSION: IF plus exercise improved some cardiometabolic outcomes (body weight, blood pressure, and lipid profile) compared with a control diet plus exercise. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023423878.