The prevalence of osteoporosis among women aged 50 years and older is expected to reach 13.6 million by 2030. Alternative non-pharmaceutical 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 ten studies suggests that in addition to anti-resorptive effects, prunes exert anti-inflammatory and antioxidant effects. Ten preclinical studies have found that prunes and/or their polyphenol extracts decrease malondialdehyde and nitric oxide secretion, increase antioxidant enzyme expression, or suppress NF-κB activation and pro-inflammatory cytokine production. Two clinical trials have investigated the impact of dried plum consumption (50–100g/day for 6–12 months) on bone health in postmenopausal women and demonstrate 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 relationship 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.

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)-1β, 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-1β, 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-1β, 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 ( β =0.078, p =0.028). Plasma IL-6 negatively predicted BMD at the total body ( β =–0.131, p =0.027) and lumbar spine ( β =–0.151, p =0.036), whereas plasma TNF-α negatively predicted total hip BMD ( β =–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.

Prunes have health benefits, particularly in postmenopausal women. It is likely that the gut microbiome mediates some of these effects, but its exact role remains to be elucidated. This study...

The prevalence of osteoporosis among women aged 50 years and older is expected to reach 13.6 million by 2030. Osteoporosis is characterized by compromised bone strength due to reduced bone mineral density (BMD) and bone quality, representing a major public health issue that necessitates effective treatment regimens that are safe, cost‐effective, and associated with fewer adverse effects than pharmaceutical agents. Alternative dietary interventions such as prunes (dried plum) have been extensively studied to mitigate bone loss in preclinical models of osteoporosis. In postmenopausal women, estrogen deficiency triggers an upregulation of inflammatory pathways, which promotes bone loss, thus increasing risk of fractures. Our understanding of the effect of prune consumption on inflammatory markers in humans is limited, warranting further investigation. This study aimed to evaluate the effects of 12 months of prune consumption (two doses) on inflammatory mediators. Postmenopausal women (n=106, 55‐75 years old) with low BMD were randomized to consume 0g prunes/day (control), 50g prunes/day, or 100g prunes/day for 12 months. All participants received 1200mg calcium and 800 IU vitamin D3 as standard of care. We hypothesized that prune consumption at 50g/day and 100g/day will reduce inflammatory markers in postmenopausal women with low BMD compared to control group (0g/day). At baseline and after 12 months of prune consumption, serum and peripheral blood mononuclear cells (PBMCs) were isolated to quantify C‐reactive protein (CRP) using a high‐sensitivity CRP immunoassay, the number of circulating monocytes using flow cytometry, and pro‐inflammatory cytokines [interleukin (IL)‐1β, IL‐6, IL‐8, monocyte chemoattractant protein (MCP)‐1, and tumor necrosis factor (TNF)‐α] from lipopolysaccharide (LPS)‐stimulated PBMCs using a multiplex enzyme‐linked immunosorbent assay. Differences among groups were assessed using one‐way ANOVA or Kruskal‐Wallis test. No significant differences in baseline characteristics were found among the three treatment groups. Prune consumption did not alter serum CRP or the number of monocytes. However, consumption of 100g prunes/day resulted in a significant reduction from baseline in IL‐1β (p=0.013), IL‐6 (p=0.007), and IL‐8 (p=0.049) secretion and consumption of 50g prunes/day resulted in a significant reduction from baseline in TNF‐α (p<0.001) secretion from LPS‐stimulated PBMCs compared to the control group. Our findings demonstrate that 12 months of prune consumption suppresses inflammatory cytokines from LPS‐stimulated PBMCs. Thus, daily consumption of 50g‐100g of prunes may reduce inflammatory mediators that can contribute to bone loss in postmenopausal women.

Objectives Osteoporosis is characterized by decreased bone strength and increased risk for fracture and is estimated to affect over 200 million women worldwide, causing approximately 9 million fractures annually. Current pharmacological therapies include antiresorptive and anabolic agents to treat low bone mineral density (BMD) but are associated with high cost, poor compliance, and adverse effects, contributing to their declining use and popularity. There is increasing interest in the potential of whole food dietary interventions to mitigate postmenopausal bone loss. Prunes (dried plums) are an abundant source of bioactive phenolic compounds that can target inflammatory pathways, which are upregulated in a hypoestrogenic environment and consequently promote bone loss. However, few studies have evaluated the effect of prunes on inflammatory mediators in postmenopausal women. This study aimed to evaluate the effect of 12 months of prune consumption (two doses, 50 and 100 g) on pro-inflammatory cytokine secretion in postmenopausal women. Methods Postmenopausal women (n = 87, 55–75 years old) were recruited for a single-center, parallel-arm, 12-month randomized controlled trial to test the effects of 50 g and 100 g prunes/day compared to a control group on inflammatory mediators. All participants received 1200 m g calcium and 800 IU vitamin D3 as standard of care. Blood was collected at baseline and after 12 months of prune consumption. Peripheral blood mononuclear cells (PBMCs) were isolated at each time point and stimulated with lipopolysaccharide (LPS). Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, MCP-1) were quantified by ELISA in the supernatants from LPS-stimulated PBMCs and in plasma. Results Prune consumption did not alter plasma pro-inflammatory cytokine concentrations. However, in supernatants from LPS-stimulated PBMCs, there were reductions in IL-1β (P = 0.013), IL-6 (P = 0.007), and IL-8 (P = 0.049) secretion in the 100 g prunes/day group and in TNF-α (P &lt; 0.001) secretion in the 50 g prunes/day group compared to the control group. Conclusions Consumption of 50g-100g/day of prunes for 12 months attenuated TNF-α, IL-1β, IL-6, and IL-8 production from LPS-stimulated PBMCs in postmenopausal women, suggesting a potential anti-inflammatory effect secondary to prune consumption. Funding Sources California Prune Board.

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OBJECTIVES/GOALS: Obesity is associated with gut dysbiosis, inflammation, and increased intestinal permeability. Probiotic consumption may reverse these outcomes. The goal of this study is to evaluate the evidence linking probiotic consumption to changes in intestinal permeability in subjects with overweight or obesity. METHODS/STUDY POPULATION: Articles were searched in Pubmed, Web of Science, and CAB Direct through February 2022 using search terms: intestinal permeability, overweight or obesity, and probiotic supplementation. 694 articles were exported, and 289 duplicates were identified. Titles and abstract were screened in the 405 remaining references by two investigators to determine eligibility. Eligible studies had data extracted on study participant characteristics, probiotic strain used, probiotic dosage, length of intervention, and intestinal barrier outcomes. Results were summarized in tabular form based on intestinal permeability response to probiotics. Quality of the studies was assessed based on Cochrane–Risk of Bias’ tool (RoB2). RESULTS/ANTICIPATED RESULTS: Thirteen eligible studies were identified. Probiotic genera included Akkermansia, Bifidobacterium, Lactobacillus, Streptococcus, Lactococcus, and Bacillus. Single strain probiotics were used in 3 studies, while the other 10 used multi-strain formulas. Dosage and length of probiotic supplementation ranged from 2.4 x 10^7 to 5 x 10^10 CFU/person/day and 3 to 26 weeks, respectively. The most widely used gut permeability outcomes were serum lipopolysaccharide (LPS) (n=10) and mixed sugar solution consumption with urine analysis (n=6). Five of the 10 studies reported decreases in serum LPS following probiotic consumption, while the other 5 showed no effect. Urinary lactulose/mannitol ratio decreased in 1 of the 4 studies, and urinary lactulose percent decreased in 2 studies. DISCUSSION/SIGNIFICANCE: Probiotic supplementation may be remediating an obesity-induced increase in intestinal permeability as evidenced from the effect on serum LPS and mixed sugar solution assays. However, additional studies are needed to further clarify which strain of probiotic bacteria is most effective and the optimal intervention length in subjects with obesity.