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)-1β, 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-1β, 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-1β, 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 as NCT02822378.

Gut microbes differ in postmenopausal women responding to prunes to maintain hip bone mineral density

Foods high in phenolics such as prunes have been shown to exert protective effects on bone mineral density (BMD), but only certain individuals experience these benefits. This post-hoc analysis of a 12-month randomized controlled trial aimed to identify the relationship among the gut microbiome, immune responses, and bone protective effects of prunes on postmenopausal women. Subjects who consumed 50-100 g prunes daily were divided into responders (n = 20) and non-responders (n = 32) based on percent change in total hip bone mineral density (BMD, ≥1% or ≤-1% change, respectively). DXA scans were used to determine body composition and BMD. Immune markers were measured using immunoassays and flow cytometry. Targeted phenolic metabolites were analyzed using ultra performance liquid chromatography-tandem mass spectrometry. The fecal microbiota was characterized through 16S rRNA gene PCR amplicon sequencing. After 12 months of prune consumption, anti-inflammatory markers showed responders had significantly lower levels of IL-1β and TNF-α. QIIME2 sequence analysis showed that microbiomes of responders and non-responders differed in alpha (Shannon and Faith PD, Kruskal-Wallis p < 0.05) and beta diversity (unweighted Unifrac, PERMANOVA p < 0.04) metrics both before and after prune treatment. Furthermore, responders had a higher abundance of bacterial families Oscillospiraceae and Lachnospiraceae (ANCOM-BC p < 0.05). These findings provide evidence that postmenopausal women with initial low BMD can benefit from prunes if they host certain gut microbes. These insights can guide precision nutrition strategies to improve BMD tailored to diet and microbiome composition.

Prunes preserve cortical density and estimated strength of the tibia in a 12-month randomized controlled trial in postmenopausal women: The Prune Study

Summary: Non-pharmacological therapies, such as whole-food interventions, are gaining interest as potential approaches to prevent and/or treat low bone mineral density (BMD) in postmenopausal women. Previously, prune consumption preserved two-dimensional BMD at the total hip. Here we demonstrate that prune consumption preserved three-dimensional BMD and estimated strength at the tibia. Purpose: Dietary consumption of prunes has favorable impacts on areal bone mineral density (aBMD); however, more research is necessary to understand the influence on volumetric BMD (vBMD), bone geometry, and estimated bone strength. Methods: This investigation was a single center, parallel arm 12-month randomized controlled trial (RCT; NCT02822378) to evaluate the effects of 50 g and 100 g of prunes vs. a Control group on vBMD, bone geometry, and estimated strength of the radius and tibia via peripheral quantitative computed tomography (pQCT) in postmenopausal women. Women (age 62.1 ± 5.0yrs) were randomized into Control (n = 78), 50 g Prune (n = 79), or 100 g Prune (n = 78) groups. General linear mixed effects (LME) modeling was used to assess changes over time and percent change from baseline was compared between groups. Results:_ The most notable effects were observed at the 14% diaphyseal tibia in the Pooled (50 g + 100 g) Prune group, in which group × time interactions were observed for cortical vBMD (p = 0.012) and estimated bone strength (SSI; p = 0.024); all of which decreased in the Control vs. no change in the Pooled Prune group from baseline to 12 months/post. Conclusion: Prune consumption for 12 months preserved cortical bone structure and estimated bone strength at the weight-bearing tibia in postmenopausal women.

The Short-Term Effect of Prunes in Improving Bone in Men.

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between -0.1 and -2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.

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

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.

Effects of 12 Months Consumption of 100 g Dried Plum (Prunes) on Bone Biomarkers, Density, and Strength in Men.

Several male animal studies have demonstrated bone-protective effects of dried plum; however, no human male study has evaluated the effect of dried plum on bone health. We conducted a randomized controlled clinical study to test if daily inclusion of 100 g of dried plum in the diet positively influenced bone mineral density (BMD), bone strength, and bone biomarkers in men. Sixty-six men were randomly assigned to one of two daily treatment groups: (1) control (0 g dried plum) or (2) 100 g dried plum. Blood samples were collected at baseline and after 3, 6, and 12 months to assess bone biomarkers. Bone was measured at baseline and after 6 and 12 months via dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Tartrate-resistant acid phosphatase-5b (TRAP5b) and C-terminal collagen cross-link (CTX) levels decreased significantly in the dried plum group at 3-, 6-, and 12-month intervals compared with baseline. No changes were observed in the control group for TRAP5b and CTX levels. Bone-specific alkaline phosphatase levels decreased significantly after 6 and 12 months in the control and dried plum groups. BMD for total body, spine (L1-L4), hip, and ulna did not change in the control and dried plum groups from baseline to 6 or 12 months. In the proximal tibia, endosteal circumferences increased significantly within the dried plum group during the course of treatment. The results suggest that daily consumption of 100 g dried plum for 12 months has modest bone-protective effects in men. identifier: NCT04720833. DOI: 10.1089/jmf.2021.0080

Dried plum consumption improves bone mineral density in osteopenic postmenopausal woman: A case report.

The use of non-pharmacological alternatives to pharmacological interventions, e.g., nutritional therapy, to improve or maintain bone mineral density (BMD) in postmenopausal women has gained traction over the past decade, but limited data exist regarding its efficacy. The purpose of this case report was to compare changes in BMD of an osteopenic postmenopausal woman over the course of 28 months, including an abrupt change in diet. For the first 12 months, a participant assigned to the control arm of a randomized controlled trial (RCT) only took calcium and vitamin D3 supplements, but in the following 16 months after completing the RCT, she introduced and maintained daily consumption of 50 g of dried plums in addition to calcium and vitamin D3 supplements. This case report provides a unique opportunity to follow the trajectory of distinct changes in bone in response to one dietary modification.

Effects of Short-Term Dried Plum (Prune) Intake on Markers of Bone Resorption and Vascular Function in Healthy Postmenopausal Women: A Randomized Crossover Trial.

Osteoporosis and cardiovascular disease are global health burdens, with postmenopausal women being at great risk. Dried plums/prunes (DPs) have been reported to provide bone health benefits in animal models, which is consistent with in vitro models. Data from human studies suggest that DP intake can enhance lipid metabolism, anti-inflammatory, and oxidant defense systems, which can impact cardiovascular health. We tested the hypothesis that short-term consumption of low and reasonable levels of DPs augments bone resorption and vascular function. Twenty-seven healthy, postmenopausal women were randomly assigned to consume six DPs (∼42 g) or two DPs (∼14 g) per day for 2 weeks, then a 2-week washout period and then crossed over. Serum C-telopeptide, beta-crosslinked (CTX) was used as a measure of bone resorption. Peripheral artery tonometry (PAT) was used to assess microvascular function. The pattern of changes in CTX in the second 2-week period (no change or decline) differed significantly from the pattern in the first 2 weeks (increases in both groups; F = 9.26, P = .006), suggesting a trend in CTX reduction (i.e., a decrease in bone resorption) in those consuming six DPs per day in the second phase. No effects on vascular function were noted. A significant interaction was observed for the augmentation index, a measure of arterial stiffness, between treatment and years after menopause (P = .045). The results suggest a potentially favorable impact of DPs on bone health when assessed with a short-term, crossover study design in postmenopausal women. Given the novel assessments used in this study, follow-up studies are warranted.

A Mediterranean Diet Enriched with Olive Oil Is Associated with Higher Serum Total Osteocalcin Levels in Elderly Men at High Cardiovascular Risk.

Background:The intake of olive oil has been related to the prevention of osteoporosis in experimental and in in vitro models. Very few prospective studies have evaluated the effects of olive oil intake on circulating osteocalcin (OC) in humans.Objective:The objective of the study was to examine the longitudinal effects of a low-fat control diet (n = 34), a Mediterranean diet enriched with nuts (MedDiet+nuts, n = 51), or a Mediterranean diet enriched with virgin olive oil (MedDiet+VOO, n = 42) on circulating forms of OC and bone formation markers in elderly men at high cardiovascular risk.Design:Longitudinal associations between baseline and follow-up (2 yr) measurements of total OC, undercarboxylated osteocalcin, C-telopeptide of type I collagen, and procollagen I N-terminal propeptide (P1NP) concentrations were examined in 127 elderly men randomized to three healthy dietary interventions.Results:Baseline characteristics (age, body mass index, waist circumference, lipid profile, fasting insulin levels, and bone formation and resorption markers) were similar in all intervention groups. The total osteocalcin concentration increased robustly in the MedDiet+VOO group (P = 0.007) in parallel to increased P1NP levels (P = 0.01) and homeostasis model assessment-β-cell function (P = 0.01) but not in subjects on the MedDiet+nuts (P = 0.32) or after the control diet (P = 0.74). Interestingly, the consumption of olives was associated positively with both baseline total osteocalcin (r = 0.23, P = 0.02) and the 2-yr osteocalcin concentrations (r = 0.21, P = 0.04) in the total cohort.Conclusions:Consumption of a Mediterranean diet enriched with virgin olive oil for 2 years is associated with increased serum osteocalcin and P1NP concentrations, suggesting protective effects on bone.