Table 1.
Randomized controlled trials of probiotics in postmenopausal women
| References | Design | Subjects | Probiotics strains (amount) | Probiotic form and dose | Duration | Outcomes | Main findings |
|---|---|---|---|---|---|---|---|
| Lambert et al. [74] | Randomized, double-blind, placebo-controlled trial | 78 postmenopausal women with osteopenia (40 probiotic; 38 placebo) | Heterogeneous culture (proprietary) of probiotic lactic acid bacteria | Powder twice daily | 12 months | Primary: effect of red clover extracts rich in isoflavone aglycones and probiotics against bone mass density loss. Secondary: effects of red clover extract on bone turnover markers, estrogen metabolites, plasma isoflavone concentration, equol-producer status, plasma lipid concentrations, and blood pressure | Red clover extracts significantly attenuated bone mineral density loss at the L2–L4 lumbar spine vertebra, femoral neck, and trochanter compared with the control group. Plasma concentrations of collagen type 1 cross-linked C-telopeptide were significantly decreased in the red clover extract group compared with the control group. Red clover extracts significantly elevated plasma isoflavone concentration, urinary 2-hydroxyestrone (2-OH) to 16a-ydroxyestrone (16a-OH) ratio, and equol-producer status compared with the control group |
| Nettleton et al. [82] | Randomized, crossover trial | 40 postmenopausal women (20 with no cancer history; 20 breast cancer survivors) | Lactobacillus acidophilus DDS1 and Bifidobacterium longum (109 CFU) | Capsules once daily | 6 weeks | Effect of probiotic consumption together with soy protein on the bioavailability and plasma concentrations of phytoestrogens, particularly the isoflavone metabolite equol | Plasma phytoestrogen concentrations and the number of equol-producers did not differ between the soy and soy plus probiotics diets |
| Narva et al. [87] | Randomized, double-blind, crossover trial | 20 postmenopausal women | Lactobacillus helveticus (not reported) | Fermented milk (220 ml) or peptide orange juice (400 ml) once daily | 22 days | Effect of milk fermented with L. helveticus and small peptides formed by the bacterium on acute changes in calcium metabolism and bone resorption in postmenopausal women | L. helveticus-fermented milk reduced serum parathormone and increased serum calcium compared to the control milk. L. helveticus-derived peptides had no significant acute effect on calcium metabolism; in fact, ionized calcium was lower and parathormone higher after the juice containing peptides compared to the control juice |
| Nilsson et al.[88] | Randomized, double-blind, placebo-controlled trial | 70 postmenopausal women with low bone mass density (34 probiotic; 36 placebo) | Lactobacillus reuteri ATCCPTA 6475 (5 × 109 CFU) | Stick packs (freeze-dried probiotics mixed with maltodextrin powder) twice daily | 12 months | Primary: changes after 12 months in tibia total volumetric bone mass density. Secondary: relative changes after 12 months in areal bone mass density measured at the hip and spine; trabecular bone volume fraction; cortical volumetric bone mass density; cortical thickness; serum markers for bone turnover; serum markers for inflammation; serum glycated hemoglobin; and body composition | L. reuteri 6475 reduced loss of total volumetric bone mass density compared to placebo both in the intention-to-treat analysis and per protocol analysis |
| Morato-Martínez et al. [89] | Randomized, double-blind, placebo-controlled trial | 65 postmenopausal women at risk of osteoporosis or untreated osteopenia (33 probiotic; 32 placebo) | Lactobacillus plantarum 3547 (1010 CFU) | Mix packs with water (120 ml) and lyophilized product (30 g) separated by a membrane once daily | 24 weeks | Effect of regular consumption of a dairy product enriched with bioactive nutrients (calcium, vitamin D, vitamin K, vitamin C, zinc, magnesium, L-leucine, and L. plantarum 3547) on bone metabolism markers of postmenopausal women at risk of osteoporosis | The intervention group showed a significantly increased bone mass compared to the control group. The intervention group maintained bone mass density compared to the control group, whose bone mass density significantly decreased at the end of the study. For biochemical markers, the intervention group significantly increased serum levels of the N-terminal propeptide of type I collagen bone formation marker and decreased the carbo-terminal telopeptide of type I collagen bone resorption marker compared to the control group |
| Marschalek et al.[101] | Randomized, double-blind, placebo-controlled pilot trial | 22 postmenopausal women with breast cancer undergoing chemotherapy (11 probiotic; 11 placebo) | Lactobacillus crispatus LbV 88, Lactobacillus rhamnosus LbV 96, Lactobacillus jensenii LbV 116, Lactobacillus gasseri LbV 150N (2.5 × 109 CFU for each one) | Capsules twice daily | 2 weeks | Effect of an orally administered preparation of 4 L. spp. on the vaginal microbiota of postmenopausal women with breast cancer undergoing chemotherapy | There was a positive influence on the vaginal microbiota in 7/11 (63%) women in the intervention group and 4/11 (36%) women in the control group. There was a shift in the Nugent score towards normal microbiota levels in the intervention group and a significant deterioration of the Nugent score in the control group |
| Colacurci et al. [106] | Randomized, placebo-controlled trial | 124 healthy postmenopausal women suffering from menopausal symptoms (62 probiotic; 62 placebo) | Lactobacillus sporogenes (1 bilion spores) | Tablets once daily | 12 months | Effect of a nutraceutical compound containing isoflavones and L. sporogenes compared to calcium and vitamin D alone on endometrium, breast, and liver function | After 12 months of treatment mammographic density, endometrial thickness and hepatic function did not show significant differences between groups, while menopausal symptoms were progressively and significantly reduced in severity and frequency during treatment with soy isoflavones plus L. sporogenes vs calcium plus vitamin D3 |
| Szulińska et al.[125] | Randomized, placebo-controlled trial | 81 postmenopausal women with obesity (23 high probiotic dose; 24 low probiotic dose; 24 placebo) | 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 (2.5 × 109 CFU for low-dose group; 1010 CFU for high-dose group) | Powder twice daily | 12 weeks | Primary: effects of different doses of supplemented multispecies probiotics on the functional parameters of endothelial and vascular dysfunction. Secondary: effects of different doses of supplemented multispecies probiotics on the biochemical parameters of endothelial and vascular dysfunction | High doses of probiotic supplementation decreased systolic blood pressure, vascular endothelial growth factor, pulse wave analysis systolic pressure, pulse wave analysis pulse pressure, pulse wave analysis augmentation index, pulse wave velocity, interleukin-6, tumor necrosis factor alpha, and thrombomodulin. Low doses of probiotic supplementation decreased systolic blood pressure and interleukin-6 levels. The mean changes in the estimated parameters, compared among the three groups, revealed significant differences in vascular endothelial growth factor, pulse wave analysis systolic pressure, pulse wave analysis augmentation index, pulse wave velocity, tumor necrosis factor alpha, and thrombomodulin |
| Szulińska et al. [126] | Randomized, placebo-controlled trial | 81 postmenopausal women with obesity (23 high probiotic dose; 24 low probiotic dose; 24 placebo) | 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 (2.5 × 109 CFU for low-dose group; 1010 CFU for high-dose group) | Powder twice daily | 12 weeks | Primary: effects of different doses of supplemented multispecies probiotics on the lipopolysaccharide level. Secondary: effects of different doses of supplemented multispecies probiotics on cardiometabolic parameters | There were significant favorable changes (mostly large or medium effects) in evaluated parameters in both the high- and low-dose groups but not in the placebo group. In the high-dose group, lipopolysaccharide, waist, fat mass, subcutaneous fat, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, and insulin-resistant index were improved. Similar changes were observed in the low-dose group, except for lipopolysaccharide, uric acid, triglycerides, and glucose levels. Additionally, significant differences were observed in both groups in terms of fat percentage and visceral fat. When the mean changes were compared between the three groups, statistically significant differences in lipopolysaccharide levels, uric acid, glucose, insulin, and insulin-resistant index were found |
CFU colony-forming unit