Obese postmenopausal women with elevated fasting glucose, insulin and lipids, have an increased risk of developing cardiovascular disease. Persistent inflammation, secondary to translocation of low levels of lipopolysaccharide (LPS)i across hyperpermeable intestinal barriers, is an additional risk factor. Probiotics have cardioprotective effects and reduce inflammation through several mechanisms. This randomized, placebo-controlled clinical trial evaluated the effects of two different dosages of probiotics on hyperpermeable intestinal barriers (as indicated by LPS levels) as well as on cardiometabolic risk factors in obese postmenopausal women.
Eighty-one obese postmenopausal women were randomly assigned to groups consuming either placeboii, or low dose (LD) probiotic (2.5 X 109 cfu/day) or high dose (HD) probiotic (1X 1010 cfu/day) over a period of 12 weeksiii. Anthropomorphic measurements (e.g. BMI, waist circumference, body fat content (%)) as well as laboratory values (e.g. fasting serum glucose, uric acid, total cholesterol (TC), high-density lipoprotein (HDL), and triglycerides (TG), low density lipoprotein (LDL), serum insulin (INS) and homeostatic model assessment of insulin-resistance (HOMA-IR) were recorded upon enrollment and upon completion of the study.
Reductions in waist circumference, visceral and subcutaneous fat occurred following 12 weeks of consumption of both dosages of probiotics. Moreover, significant reductions in uric acid, glucose, INS, HOMA-IR and LPS were recorded in both groups consuming probiotics compared to placebo. The HD group had greater mean reduction in LPS, uric acid, glucose, INS, HOMA-IR compared to the LD group, suggesting higher doses of probiotics are more likely to repair hyperpermeable epithelial barriers as well as be cardioprotective.
Reduction in uric acid following probiotic usage is of particular interest, considering hyeruricemia not only increases the risk of gout, but also is an independent risk factor for cardiovascular disease1. Moreover, persistently high uric acid levels trigger inflammation as well as contribute to coronary atherosclerosis and adverse outcomes in various population groups including postmenopausal women.2
The strengths of this study include a relatively robust trial design with rigorous inclusion and exclusion criteria, periodic monitoring to ensure compliance, a study period of sufficient length to show effectiveness, testing of gut permeability (indirectly via LPS levels) and the inclusion of different dosages of probiotics for elucidation of any dose-dependent effects.3
Potential weaknesses include relatively low sample sizes (n=24 for each group), no tracking of potentially confounding dietary factors, no microbial analysis of fecal samples (to help estimate associated compositional changes in microbiota), and no measurement of inflammatory markers or markers of gut permeability (to help associate changes in LPS with clinically meaningful outcomes).
This clinical study provides the first evidence that probiotics have a dose-dependent, beneficial effect on the cardiometabolic profile in obese postmenopausal women. Moreover, it supports evidence indicating probiotics could lower cardiometabolic risk factors via a number of different mechanisms including repair of hyperpermeable intestinal barriers. Finally, it suggests probiotics could be a useful adjunctive therapy in the prevention and treatment of cardiovascular disease.
i. Lipopolysaccharide (LPS) is also named endotoxin. The presence of persistent low levels of endotoxin in the blood (i.e. endotoxemia) is a recently recognized trigger of the low-level chronic inflammation associated with many chronic diseases.
ii. Placebo contained only the excipients maize starch and maltodextrins and was considered indistinguishable in color, smell, and taste to the trial probiotic.
iii. Probiotic was Ecological® Barrier (Winclove probiotics, Amsterdam, The Netherlands). It is found in sachets containing 2 grams of freeze-dried powder comprised of equal amounts of nine bacterial strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58. The total amount given to either LD or HD groups was split into equal doses and consumed 2 times per day. The trial participants dissolved the probiotics in room temperature water and consumed one sachet before breakfast and one sachet before going to bed.
References:
1. Ndprepa, G., et al. Clin Chim Acta. 2018; 484:150-163.
2. Prasad, M., et al. Hypertension. 2017;69(2):236-242
3. Szulinśka, M., et al. Nutrients 2018, 10(6). pii: E773.
