The Effect of Probiotics and Synbiotics on Risk Factors Associated with Cardiometabolic Diseases in Healthy People-A Systematic Review and Meta-Analysis with Meta-Regression of Randomized Controlled Trials.

We aimed to systematically review the effectiveness of probiotic/synbiotic formulations to counteract cardiometabolic risk (CMR) in healthy people not receiving adjunctive medication. The systematic search (PubMed/MEDLINE/Embase) until 1 August 2019 was performed for randomized controlled trials in >20 adult patients. Random-effect meta-analysis subgroup and meta-regression analysis of co-primary (haemoglobin A1c (HbA1C), glucose, insulin, body weight, waist circumference (WC), body mass index (BMI), cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and blood pressure) and secondary outcomes (uric acid, plasminogen activator inhibitor-1-PAI-1, fibrinogen, and any variable related to inflammation/endothelial dysfunction). We included 61 trials (5422 persons). The mean time of probiotic administration was 67.01 ± 38.72 days. Most of probiotic strains were of and genera. The other strains were , , and . The daily probiotic dose varied between 10 and 10 colony-forming units (CFU)/gram. Probiotics/synbiotics counteracted CMR factors (endpoint data on BMI: standardized mean difference (SMD) = -0.156, = 0.006 and difference in means (DM) = -0.45, = 0.00 and on WC: SMD = -0.147, = 0.05 and DM = -1.21, = 0.02; change scores on WC: SMD = -0.166, = 0.04 and DM = -1.35, = 0.03) in healthy persons. Overweight/obese healthy people might additionally benefit from reducing total cholesterol concentration (change scores on WC in overweight/obese: SMD: -0.178, = 0.049). Poor quality of probiotic-related trials make systematic reviews and meta-analyses difficult to conduct and draw definite conclusions. "Gold standard" methodology in probiotic studies awaits further development.