Effects of Prune (Dried Plum) Supplementation on Cardiometabolic Health in Postmenopausal Women: An Ancillary Analysis of a 12-Month Randomized Controlled Trial, The Prune Study.

BACKGROUND: Estrogen withdrawal during menopause is associated with an unfavorable cardiometabolic profile. Prunes (dried plums) represent an emerging functional food and have been previously demonstrated to improve bone health. However, our understanding of the effects of daily prune intake on cardiometabolic risk factors in postmenopausal women is limited. OBJECTIVES: We conducted an ancillary investigation of a randomized controlled trial (RCT), The Prune Study, to evaluate the effect of 12-mo prune supplementation on cardiometabolic health markers in postmenopausal women. METHODS: The Prune Study was a single-center, parallel-design, 12-mo RCT in which postmenopausal women were allocated to no-prune control, 50 g/d prune, or 100 g/d prune groups. Blood was collected at baseline, 6 mo, and 12 mo/post to measure markers of glycemic control and blood lipids. Body composition was assessed at baseline, 6 mo, and 12 mo/post using dual-energy X-ray absorptiometry. Linear mixed-effects models were used to evaluate the effect of time, treatment, and their interaction on cardiometabolic health markers, all quantified as exploratory outcomes. RESULTS: A total of 183 postmenopausal women (mean age, 62.1 ± 4.9 y) completed the entire 12-mo RCT: control (n = 70), 50 g/d prune (n = 67), and 100 g/d prune (n = 46). Prune supplementation at 50 g/d or 100 g/d did not alter markers of glycemic control and blood lipids after 12 mo compared with the control group (all P > 0.05). Furthermore, gynoid percent fat and visceral adipose tissue (VAT) indices did not significantly differ in women consuming 50 g/d or 100 g/d prunes compared with the control group after 12 mo of intervention. However, android total mass increased by 3.19% ± 5.5% from baseline in the control group, whereas the 100 g/d prune group experienced 0.02% ± 5.6% decrease in android total mass from baseline (P < 0.01). CONCLUSIONS: Prune supplementation at 50 g/d or 100 g/d for 12 mo does not improve glycemic control and may prevent adverse changes in central adiposity in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02822378.

Prune Consumption Attenuates Proinflammatory Cytokine Secretion and Alters Monocyte Activation in Postmenopausal Women: Secondary Outcome Analysis of a 12-Mo Randomized Controlled Trial: The Prune Study.

BACKGROUND: Proinflammatory cytokines are implicated in the pathophysiology of postmenopausal bone loss. Clinical studies demonstrate that prunes prevent bone mineral density loss; however, the mechanism underlying this effect is unknown. OBJECTIVE: We investigated the effect of prune supplementation on immune, inflammatory, and oxidative stress markers. METHODS: A secondary analysis was conducted in the Prune Study, a single-center, parallel-arm, 12-mo randomized controlled trial of postmenopausal women (55-75 y old; n = 235 recruited; n = 183 completed) who were assigned to 1 of 3 groups: "no-prune" control, 50 g prune/d and 100 g prune/d groups. At baseline and after 12 mo of intervention, blood samples were collected to measure serum high-sensitivity C-reactive protein (hs-CRP), serum total antioxidant capacity (TAC), plasma 8-isoprostane, proinflammatory cytokines [interleukin (IL)-1ß, IL-6, IL-8, monocyte chemoattractant protein-1, and tumor necrosis factor (TNF)-α] concentrations in plasma and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) culture supernatants, and the percentage and activation of circulating monocytes, as secondary outcomes. RESULTS: Prune supplementation did not alter hs-CRP, TAC, 8-isoprostane, and plasma cytokine concentrations. However, percent change from baseline in circulating activated monocytes was lower in the 100 g prune/d group compared with the control group (mean ± SD, -1.8% ± 4.0% in 100 g prune/d compared with 0.1% ± 2.9% in control; P < 0.01). Furthermore, in LPS-stimulated PBMC supernatants, the percent change from baseline in TNF-α secretion was lower in the 50 g prune/d group compared with the control group (-4.4% ± 43.0% in 50 g prune/d compared with 24.3% ± 70.7% in control; P < 0.01), and the percent change from baseline in IL-1ß, IL-6, and IL-8 secretion was lower in the 100 g prune/d group compared with the control group (-8.9% ± 61.6%, -4.3% ± 75.3%, -14.3% ± 60.8% in 100 g prune/d compared with 46.9% ± 107.4%, 16.9% ± 70.6%, 39.8% ± 90.8% in control for IL-1ß, IL-6, and IL-8, respectively; all P < 0.05). CONCLUSIONS: Dietary supplementation with 50-100 g prunes for 12 mo reduced proinflammatory cytokine secretion from PBMCs and suppressed the circulating levels of activated monocytes in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02822378.

Effect of Probiotic Supplementation on Intestinal Permeability in Overweight and Obesity: A Systematic Review of Randomized Controlled Trials and Animal Studies.

Overweight and obesity are associated with increased intestinal permeability, characterized by loss of gut epithelial integrity, resulting in unregulated passage of lipopolysaccharide (LPS) and other inflammatory triggers into circulation, i.e., metabolic endotoxemia. In obesity, shifts in the gut microbiome negatively impact intestinal permeability. Probiotics are an intervention that can target the gut microbiome by introducing beneficial microbial species, potentially restoring gut barrier integrity. Currently, the role of probiotic supplementation in ameliorating obesity- and overweight-associated increases in gut permeability has not been reviewed. This systematic review aimed to summarize findings from both animal and clinical studies that evaluated the effect of probiotic supplementation on obesity-induced impairment in intestinal permeability (International Prospective Register of Systematic Reviews, CRD42022363538). A literature search was conducted using PubMed (Medline), Web of Science, and CAB Direct from origin until August 2023 using keywords of intestinal permeability, overweight or obesity, and probiotic supplementation. Of 920 records, 26 eligible records were included, comprising 12 animal and 14 clinical studies. Clinical trials ranged from 3 to 26 wk and were mostly parallel-arm (n = 13) or crossover (n = 1) design. In both animal and clinical studies, plasma/serum LPS was the most common measure of intestinal permeability. Eleven of 12 animal studies reported a positive effect of probiotic supplementation in reducing intestinal permeability. However, results from clinical trials were inconsistent, with half reporting reductions in serum LPS and half reporting no differences after probiotic supplementation. Bifidobacterium, Lactobacillus, and Akkermansia emerged as the most common genera in probiotic formulations among the animal and clinical studies that yielded positive results, suggesting that specific bacteria may be more effective at reducing intestinal permeability and improving gut barrier function. However, better standardization of strain use, dosage, duration, and the delivery matrix is needed to fully understand the probiotic impact on intestinal permeability in individuals with overweight and obesity.

Associations Between Inflammatory Mediators and Bone Outcomes in Postmenopausal Women: A Cross-Sectional Analysis of Baseline Data from the Prune Study.

Purpose: Hypoestrogenism triggers increased production of inflammatory mediators, which contribute to bone loss during postmenopausal osteoporosis. This study aimed to investigate the association between circulating inflammatory markers and bone outcomes in postmenopausal women. Materials and methods: We conducted a cross-sectional, secondary analysis of baseline data from participants who completed a 12-month randomized controlled trial, The Prune Study (NCT02822378), which included healthy postmenopausal women (n=183, 55-75 years old) with bone mineral density (BMD) T-score between 0.0 and -3.0 at any site. BMD was measured using dual-energy X-ray absorptiometry, and bone geometry and strength were measured using peripheral quantitative computed tomography. Blood was collected at baseline to measure (1) serum biomarkers of bone turnover, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide and (2) inflammatory markers, including serum high-sensitivity C-reactive protein (hs-CRP) and plasma pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1, using enzyme-linked immunosorbent assay. The associations between bone and inflammatory outcomes at baseline were analyzed using correlation and regression analyses. Results: Serum hs-CRP negatively correlated with P1NP (r=-0.197, p=0.042). Plasma IL-1ß, IL-6, IL-8, and TNF-α negatively correlated with trabecular bone score at the lumbar spine (all p<0.05). In normal-weight women, plasma IL-1ß, IL-6, and IL-8 negatively correlated (p<0.05) with trabecular and cortical bone area, content, and density at various sites in the tibia and radius. Serum hs-CRP positively predicted lumbar spine BMD (ß=0.078, p=0.028). Plasma IL-6 negatively predicted BMD at the total body (ß=-0.131, p=0.027) and lumbar spine (ß=-0.151, p=0.036), whereas plasma TNF-α negatively predicted total hip BMD (ß=-0.114, p=0.028). Conclusion: At baseline, inflammatory markers were inversely associated with various estimates of bone density, geometry, and strength in postmenopausal women. These findings suggest that inflammatory markers may be an important mediator for postmenopausal bone loss.

The Role of Prunes in Modulating Inflammatory Pathways to Improve Bone Health in Postmenopausal Women.

The prevalence of osteoporosis among women aged 50 y and older is expected to reach 13.6 million by 2030. Alternative nonpharmaceutical agents for osteoporosis, including nutritional interventions, are becoming increasingly popular. Prunes (dried plums; Prunus domestica L.) have been studied as a potential whole-food dietary intervention to mitigate bone loss in preclinical models of osteoporosis and in osteopenic postmenopausal women. Sixteen preclinical studies using in vivo rodent models of osteopenia or osteoporosis have established that dietary supplementation with prunes confers osteoprotective effects both by preventing and reversing bone loss. Increasing evidence from 10 studies suggests that, in addition to antiresorptive effects, prunes exert anti-inflammatory and antioxidant effects. Ten preclinical studies have found that prunes and/or their polyphenol extracts decrease malondialdehyde and NO secretion, increase antioxidant enzyme expression, or suppress NF-κB activation and proinflammatory cytokine production. Two clinical trials have investigated the impact of dried plum consumption (50-100 g/d for 6-12 mo) on bone health in postmenopausal women and demonstrated promising effects on bone mineral density and bone biomarkers. However, less is known about the impact of prune consumption on oxidative stress and inflammatory mediators in humans and their possible role in modulating bone outcomes. In this review, the current state of knowledge on the relation between inflammation and bone health is outlined. Findings from preclinical and clinical studies that have assessed the effect of prunes on oxidative stress, inflammatory mediators, and bone outcomes are summarized, and evidence supporting a potential role of prunes in modulating inflammatory and immune pathways is highlighted. Key future directions to bridge the knowledge gap in the field are proposed.