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-1ß 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.

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.

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

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.

Are menstrual disturbances associated with an energy availability threshold? A critical review of the evidence.

Exercising women have a high prevalence of menstrual disturbances. In 2003, it was suggested that disruption in luteinizing hormone (LH) pulsatility occurs below a threshold of energy availability (EA) of 30 kcal/kg lean body mass (LBM)/day. This paper is a critical review of the evidence regarding the theory that disruptions to the reproductive axis and menstrual disturbances occur below the proposed threshold. Short-term laboratory studies demonstrated that 4-5 days of an EA below 30 kcal/kg LBM/day, induced with or without exercise, decreased serum triiodothyronine and LH pulse frequency, and increased LH pulse amplitude in sedentary, regularly menstruating women. Fewer studies have investigated downstream ovarian effects after long-term exposure to low EA. The Sargent Camp Study was the first randomized trial that induced luteal phase defects, delayed menses, and anovulation by causing weight loss (-4 ± 0.3 kg) with an abrupt increase in exercise volume for two menstrual cycles. The BioEnergetics Study was a randomized controlled trial that induced varying levels of energy deficits by manipulating energy intake and expenditure for three menstrual cycles. LH pulse frequency and triiodothyronine decreased, and 57% of women developed luteal phase defects, anovulation, and/or oligomenorrhea. An EA below 30 kcal/kg fat free mass/day increased the chance of experiencing a menstrual disturbance by 50%. However, menstrual disturbances were observed above and below that EA threshold, and changes in LH pulse frequency predicted only luteal phase defects, not oligomenorrhea or anovulation. The proposed EA threshold is not a cut-off below which menstrual disturbances occur, but represents an increased risk of experiencing menstrual disturbances.

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.

12-months of increased dietary intake does not exacerbate disordered eating-related attitudes, stress, or depressive symptoms in women with exercise-associated menstrual disturbances: The REFUEL randomized controlled trial.

Disordered eating-related attitudes are a leading cause of energy deficiency and menstrual disturbances in exercising women. Although treatment recommendations include psychological counseling with increases in dietary intake, a key concern is whether increased dietary intake may exacerbate negative eating behaviors. OBJECTIVE: To determine the effects of a 12-month nutritional intervention on eating-related attitudes and psychological characteristics in exercising women with oligomenorrhea/amenorrhea (Oligo/Amen). METHODS: Intent-to-treat analysis of the REFUEL randomized controlled trial (#NCT00392873) in 113 exercising women (age [mean±SEM]:] 21.9 ± 0.4 yrs; BMI: 20.9 ± 0.2 kg/m2). Women were randomized to increase energy intake 20-40% above baseline energy needs (Oligo/Amen+Cal, n = 40) or maintain energy intake (Oligo/Amen Control, n = 36) while maintaining their exercise behaviors. A reference group of ovulatory women (OVref, n = 37) maintained diet and exercise behaviors. Body composition, eating attitudes, stress, and depressive symptoms were assessed at baseline and every 3 months. RESULTS: At baseline, the Oligo/Amen groups had higher drive for thinness, cognitive restraint, and eating disorder risk than OVref group (p < 0.001). Increased energy intake led to increases in percent body fat and fat mass (p < 0.010), but not psychobehavioral outcomes, in the Oligo/Amen+Cal compared to Oligo/Amen Control group. Independent of group, cognitive restraint decreased (p < 0.001) and resilient coping increased (p < 0.007) over 12-months, while perceived stress (p = 0.143) and depressive symptoms (p = 0.344) were unchanged. DISCUSSION: Long-term nutritional intervention consisting of modest increases in dietary intake with guidance from a registered dietician and a psychologist increases body and fat mass without increasing disordered eating-related attitudes, stress, or depressive symptoms in exercising women with Oligo/Amen.

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.

Sex differences and indications of metabolic compensation in within-day energy balance in elite Division 1 swimmers.

To determine whether mismatched energy intake and expenditure across the day and associated sex differences may be related with metabolic compensation and/or negative health outcomes, we assessed total-day and hourly energy balance (TDEB and EB), total-day and hourly energy intake (TDEI and EI), total-day and hourly energy expenditure (TDEE and EE) and within-day energy balance (WDEB) in elite male and female swimmers (n = 25; 18-22 years). Total triiodothyronine (TT3), resting metabolic rate (RMR), and the ratio of actual-to-predicted RMR were determined. Males exhibited higher TDEB (+758 ± 702 kcal vs +52 ± 505 kcal, t-test; p = 0.007) than females. Males exhibited a more positive hourly EB, driven by greater hourly EI at 11:00, 13:00, 16:00, and 19:00 h (ANOVA, p < 0.05), while EE did not differ. TT3 was negatively correlated with consecutive hours of negative EB (R = -0.604, p = 0.049) and positively correlated to hours in EB (R = 0.740, p = 0.009) in those exhibiting metabolic suppression (n = 12). In individuals in TDEB (n = 21), "backloaders" (consumption of ≥50% daily kcals at or after 1700 h) had lower TT3 (79.3 ng/dL vs 92.9 ng/dL, p = 0.009) than "nonbackloaders" (n = 12). WDEB analyses indicate a greater risk of energy deficiency in females and may capture indices of metabolic compensation not evident with EB analyses alone.

Prune supplementation for 12 months alters the gut microbiome in postmenopausal women.

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 aims to characterize the effect of prune supplementation on the gut microbiome of postmenopausal women. The fecal microbiome of 143 postmenopausal women ages 55-75 who met the compliance criteria in a randomized controlled trial of a 12-month dietary intervention in one of three treatment groups - no prunes (n = 52), 50 g prunes per day (n = 54), or 100 g prunes per day (n = 37) - was characterized at baseline and at the 12-month endpoint using 16S rRNA gene sequencing and QIIME2. Additional outcomes included assessment of select urinary phenolic metabolites and inflammatory markers. After 12 months, microbiomes of women consuming 50 g prunes had decreased evenness in bacteria taxa (Pielou's Evenness, Kruskal-Wallis p = 0.026). Beta diversity comparisons indicated significant differences in microbiomes among prune treatments (Bray-Curtis PERMANOVA, p = 0.005), and the effect was different at each prune dose (p = 0.057). Prunes enriched some bacterial taxa such as the family Lachnospiraceae (LEfSe LDA = 4.5). Some taxa correlated with urinary phenolic metabolites and inflammatory markers. Blautia negatively correlated with total urinary phenolics (r = -0.25, p = 0.035) and Lachnospiraceae UCG-001 negatively correlated with plasma concentrations of IL-1ß (r = -0.29, p = 0.002). Differing gut microbiomes and correlation of some taxa with select phenolic metabolites and inflammatory markers, particularly Lachnospiraceae, after prune consumption suggest a potential mechanism mediating health effects. The microbiome differences at each dose may have implications for the use of prunes as a non-pharmacological whole food intervention for gut health.

Association of diet quality and hormonal status in exercising women with menstrual disturbances.

Diet plays a role in the pathophysiology and treatment of women with hyperandrogenic menstrual disturbances; however, limited research exists examining components of dietary intake in women with subclinical menstrual disturbances. The aim of this investigation was to evaluate the relationship between diet quality and hormonal status in exercising women with menstrual disturbances. Eighty exercising women with ovulatory menstrual cycles (OV; n = 32), women with oligo/amenorrhea without evidence of hyperandrogenism (Oligo/Amen-LowFAI; n = 28), and women with oligo/amenorrhea and evidence of subclinical hyperandrogenism (Oligo/Amen-HighFAI; n = 32) participated in the cross-sectional observational study (Clinical Trial Number: NCT00392873). Self-reported menstrual history, resting energy expenditure, body composition, hormonal and metabolic hormone concentrations determined reproductive and metabolic status. Serum androgens and calculated free androgen index (FAI) determined androgen status. The Diet Quality Index International (DQI-I) and the Dietary Inflammatory Index (DII) evaluated quality of diet. Oligo/Amen-HighFAI group had the highest androgen concentrations (P < 0.05) and lower DQI-I score compared to OV group and Oligo/Amen-LowFAI (P < 0.05). The Oligo/Amen-HighFAI group consumed less of vitamin A, B2, B6, B12, magnesium, and potassium compared to the Oligo/Amen-LowFAI group (all P < 0.05). In the women with menstrual disturbances with subclinically elevated androgens, poor diet quality is related to altered hormonal parameters which may have implications for future nutritional treatment strategies.

Prunes preserve hip bone mineral density in a 12-month randomized controlled trial in postmenopausal women: the Prune Study.

BACKGROUND: Dietary consumption of prunes has favorable impacts on bone health, but more research is necessary to improve upon study designs and refine our understandings. OBJECTIVES: We evaluated the effects of prunes (50 g or 100 g/d) on bone mineral density (BMD) in postmenopausal women during a 12-mo dietary intervention. Secondary outcomes include effects on bone biomarkers. METHODS: The single-center, parallel-arm 12-mo randomized controlled trial tested the effects of 50 g and 100 g prunes compared with a control group on BMD (every 6 mo) and bone biomarkers in postmenopausal women. RESULTS: In total, 235 women (age 62.1 ± 5.0 y) were randomly allocated into control (n = 78), 50-g prune (n = 79), or 100-g prune (n = 78) groups. Compliance was 90.2 ± 1.8% and 87.1 ± 2.1% in the 50-g and 100-g prune groups. Dropout was 22%; however, the dropout rate was 41% for the 100-g prune group (compared with other groups: 10%, control; 15%, 50 g prune; P < 0.001). A group × time interaction for total hip BMD was observed in control compared with 50-g prune groups (P < 0.05) but not in control compared with 100-g prune groups (P > 0.05). Total hip BMD decreased -1.1 ± 0.2% in the control group at 12 mo, whereas the 50-g prune group preserved BMD (-0.3 ± 0.2%) at 12 mo (P < 0.05). Although hip fracture risk (FRAX) worsened in the control group at 6 mo compared with baseline (10.3 ± 0.5% compared with 9.8 ± 0.5%, P < 0.05), FRAX score was maintained in the pooled (50 g + 100 g) prune groups. CONCLUSIONS: A 50-g daily dose of prunes can prevent loss of total hip BMD in postmenopausal women after 6 mo, which persisted for 12 mo. Given that there was high compliance and retention at the 50-g dosage over 12 mo, we propose that the 50-g dose represents a valuable nonpharmacologic treatment strategy that can be used to preserve hip BMD in postmenopausal women and possibly reduce hip fracture risk. This trial was registered at clinicaltrials.gov as NCT02822378.

Moderate Weight Loss is associated with Reductions in LH Pulse Frequency and Increases in 24-hour Cortisol with no change in Perceived Stress in Young Ovulatory Women.

OBJECTIVE: Determine the potential role of cortisol as an indicator of both metabolic and psychosocial stress and its relation to LH pulse dynamics during a three-month diet and exercise intervention causing moderate weight loss. METHODS: Secondary analysis of a randomized controlled trial that demonstrated the causal role of low energy availability in the disruption of the menstrual cycle. Twenty-one women aged 18-24 yrs (BMI 21.7± 1.9 kg·m-2), completed a baseline menstrual cycle and three intervention menstrual cycles of a controlled diet and supervised exercise program. Twenty-four-hour LH pulse dynamics (q10 min) and diurnal patterns of cortisol (q60 min) as well as Perceived Stress Scale scores were determined in the early follicular phase prior to the intervention and in the post intervention cycle. Pre to post comparisons were determined with paired t-tests, and Pearson bivariate correlations assessed associations. RESULTS: Subjects lost weight (-2.8±1.97 kg) and LH pulse frequency declined pre=0.79±0.23 pulses·hr-1 to post=0.60±0.29 pulses·hr-1 (p=0.014). Weight loss was associated with an increase in cortisol AUC R= -0.473, (p=0.03) and the decline in LH pulse frequency R= 0.523; (p=0.026). Increases in cortisol AUC were associated with declines in LH pulse frequency R= -0.472; (p=0.048). The morning cortisol rise AUC increased from pre=2140±878 µg·dL-1 · day to post=2556±1067 µg·dL-1 · day (p=0.034). Changes in PSS were not associated with changes in LH or cortisol. CONCLUSION: The initial perturbation of LH pulsatility with moderate diet and exercise is associated with metabolically driven increases in cortisol AUC with no influence of psychological stress.

Rationale and study design of Randomized Controlled Trial of Dietary Supplementation with prune (dried plums) on bone density, geometry, and estimated bone strength in postmenopausal women: The Prune study.

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. This paper describes the design of the Prune Study, a randomized controlled trial (RCT) that explored the effectiveness of a 12-month intervention of daily prune consumption on bone density, bone structure and strength estimates, bone turnover, various biomarkers of immune function, inflammation, and cardiovascular health, as well as phenolic and gut microbiota analyses. Postmenopausal women between the ages of 55-75 years were randomized into either control group (no prune consumption; n = 78), 50g prune (50g prune/day; n = 79), or 100g prune (100g prune/day; n = 78). All participants received 1200 mg calcium +800 IU vitamin D3 daily as standard of care. The Prune Study is the largest and most comprehensive investigation of a dose response of prune consumption on bone health, biomarkers of immune function, inflammation, and cardiovascular health, as well as detailed phenolic and gut microbiota analyses in postmenopausal women. 235 women were randomized and 183 women completed the entire study. The findings of this study will help expand our current understanding of clinical implications and mechanisms underlying the resultant health effects of prune as a functional food therapy.

Bone mineral density in response to increased energy intake in exercising women with oligomenorrhea/amenorrhea: the REFUEL randomized controlled trial.

BACKGROUND: Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad. OBJECTIVES: The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances. METHODS: Exercising women with oligomenorrhea/amenorrhea (Oligo/Amen) were randomly assigned to an intervention group (Oligo/Amen + Cal, n = 40, mean ± SEM age: 21.3 ± 0.5 y; weight: 55.0 ± 1.0 kg; BMI: 20.4 ± 0.3 kg/m2) who increased energy intake 20%-40% above baseline energy needs for 12 mo or a control group (Oligo/Amen Control, n = 36; mean ± SEM age: 20.7 ± 0.5 y; weight: 59.1 ± 1.3 kg; BMI: 21.3 ± 0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed. RESULTS: Oligo/Amen + Cal improved energy status [increased body mass (2.6 ± 0.4 kg), BMI (0.9 ± 0.2 kg/m2), fat mass (2.0 ± 0.3 kg), body fat percentage (2.7% ± 0.4%), and insulin-like growth factor 1 (37.4 ± 14.6 ng/mL)] compared with Oligo/Amen Control and experienced a greater likelihood of menses (P < 0.05). Total body and spine aBMD remained unchanged (P > 0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (-0.006 g/cm2; 95% CI: -0.011, -0.0002 g/cm2 ; time main effect P = 0.043) and month 12 (-0.011 g/cm2; 95% CI: -0.021, -0.001 g/cm2; time main effect P = 0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006 g/cm2; 95% CI: -0.011, -0.002 g/cm2; time main effect P = 0.004). CONCLUSIONS: Although higher dietary energy intake increased weight, body fat, and menstrual frequency, bone mineral density was not improved, compared with the control group. The 12-mo intervention may have been too short and the increase in energy intake (∼352 kcal/d), although sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological interventions for the recovery of bone health in athletes and exercising women with Oligo/Amen.This trial was registered at clinicaltrials.gov as NCT00392873.

The Path Towards Progress: A Critical Review to Advance the Science of the Female and Male Athlete Triad and Relative Energy Deficiency in Sport.

Energy status plays a key role in the health of athletes and exercising individuals. Energy deficiency/low energy availability (EA), referring to a state in which insufficient energy intake and/or excessive exercise energy expenditure has resulted in compensatory metabolic adaptations to conserve fuel, can affect numerous physiological systems in women and men. The Female Athlete Triad, Male Athlete Triad, and Relative Energy Deficiency in Sport (RED-S) models conceptualize the effects of energy deficiency in athletes, and each model has strengths and limitations. For instance, the Female Athlete Triad model depicts relationships between low EA, reproductive, and bone health, underpinning decades of experimental evidence, but may be perceived as limited in scope, while the more recent RED-S model proposes a wider range of potential health effects of low EA, though many model components require more robust scientific justification. This critical review summarizes current evidence regarding the effects of energy deficiency on athlete health by addressing the quality of the underlying science, the strengths and limitations of each model, and highlighting areas where future research is needed to advance the field. With the health and wellness of athletes and exercising individuals as the overarching priority, we conclude with specific steps that will help focus future research on the Female and Male Athlete Triad and RED-S, and encourage all researchers, clinicians, and practitioners to collaborate to support the common goal of promoting the highest quality science and evidence-based medicine in pursuit of the advancement of athletes' health, well-being, and performance.

The Ocean Carbon Response to COVID-Related Emissions Reductions.

The decline in global emissions of carbon dioxide due to the COVID-19 pandemic provides a unique opportunity to investigate the sensitivity of the global carbon cycle and climate system to emissions reductions. Recent efforts to study the response to these emissions declines has not addressed their impact on the ocean, yet ocean carbon absorption is particularly susceptible to changing atmospheric carbon concentrations. Here, we use ensembles of simulations conducted with an Earth system model to explore the potential detection of COVID-related emissions reductions in the partial pressure difference in carbon dioxide between the surface ocean and overlying atmosphere (ΔpCO2), a quantity that is regularly measured. We find a unique fingerprint in global-scale ΔpCO2 that is attributable to COVID, though the fingerprint is difficult to detect in individual model realizations unless we force the model with a scenario that has four times the observed emissions reduction.

Randomised controlled trial of the effects of increased energy intake on menstrual recovery in exercising women with menstrual disturbances: the 'REFUEL' study.

STUDY QUESTION: Does increased daily energy intake lead to menstrual recovery in exercising women with oligomenorrhoea (Oligo) or amenorrhoea (Amen)? SUMMARY ANSWER: A modest increase in daily energy intake (330 ± 65 kcal/day; 18 ± 4%) is sufficient to induce menstrual recovery in exercising women with Oligo/Amen. WHAT IS KNOWN ALREADY: Optimal energy availability is critical for normal reproductive function, but the magnitude of increased energy intake necessary for menstrual recovery in exercising women, along with the associated metabolic changes, is not known. STUDY DESIGN, SIZE, DURATION: The REFUEL study (trial # NCT00392873) is the first randomised controlled trial to assess the effectiveness of 12 months of increased energy intake on menstrual function in 76 exercising women with menstrual disturbances. Participants were randomised (block method) to increase energy intake 20-40% above baseline energy needs (Oligo/Amen + Cal, n = 40) or maintain energy intake (Oligo/Amen Control, n = 36). The study was performed from 2006 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were Amen and Oligo exercising women (age = 21.0 ± 0.3 years, BMI = 20.8 ± 0.2 kg/m2, body fat = 24.7 ± 0.6%) recruited from two universities. Detailed assessment of menstrual function was performed using logs and measures of daily urinary ovarian steroids. Body composition and metabolic outcomes were assessed every 3 months. MAIN RESULTS AND THE ROLE OF CHANCE: Using an intent-to-treat analysis, the Oligo/Amen + Cal group was more likely to experience menses during the intervention than the Oligo/Amen Control group (P = 0.002; hazard ratio [CI] = 1.91 [1.27, 2.89]). In the intent-to-treat analysis, the Oligo/Amen + Cal group demonstrated a greater increase in energy intake, body weight, percent body fat and total triiodothyronine (TT3) compared to the Oligo/Amen Control group (P < 0.05). In a subgroup analysis where n = 22 participants were excluded (ambiguous baseline menstrual cycle, insufficient time in intervention for menstrual recovery classification), 64% of the Oligo/Amen + Cal group exhibited improved menstrual function compared with 19% in the Oligo/Amen Control group (χ2, P = 0.001). LIMITATIONS, REASONS FOR CAUTION: While we had a greater than expected dropout rate for the 12-month intervention, it was comparable to other shorter interventions of 3-6 months in duration. Menstrual recovery defined herein does not account for quality of recovery. WIDER IMPLICATIONS OF THE FINDINGS: Expanding upon findings in shorter, non-randomised studies, a modest increase in daily energy intake (330 ± 65 kcal/day; 18 ± 4%) is sufficient to induce menstrual recovery in exercising women with Oligo/Amen. Improved metabolism, as demonstrated by a modest increase in body weight (4.9%), percent body fat (13%) and TT3 (16%), was associated with menstrual recovery. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the U.S. Department of Defense: U.S. Army Medical Research and Material Command (Grant PR054531). Additional research assistance provided by the Penn State Clinical Research Center was supported by the National Center for Advancing Translation Sciences, National Institutes of Health, through Grant UL1 TR002014. M.P.O. was supported in part by the Loretta Anne Rogers Chair in Eating Disorders at University of Toronto and University Health Network. All authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NCT00392873. TRIAL REGISTRATION DATE: October 2006. DATE OF FIRST PATIENT'S ENROLMENT: September 2006.

The Male Athlete Triad-A Consensus Statement From the Female and Male Athlete Triad Coalition Part 1: Definition and Scientific Basis.

ABSTRACT: The Male Athlete Triad is a syndrome of 3 interrelated conditions most common in adolescent and young adult male endurance and weight-class athletes and includes the clinically relevant outcomes of (1) energy deficiency/low energy availability (EA) with or without disordered eating/eating disorders, (2) functional hypothalamic hypogonadism, and (3) osteoporosis or low bone mineral density with or without bone stress injury (BSI). The causal role of low EA in the modulation of reproductive function and skeletal health in the male athlete reinforces the notion that skeletal health and reproductive outcomes are the primary clinical concerns. At present, the specific intermediate subclinical outcomes are less clearly defined in male athletes than those in female athletes and are represented as subtle alterations in the hypothalamic-pituitary-gonadal axis and increased risk for BSI. The degree of energy deficiency/low EA associated with such alterations remains unclear. However, available data suggest a more severe energy deficiency/low EA state is needed to affect reproductive and skeletal health in the Male Athlete Triad than in the Female Athlete Triad. Additional research is needed to further clarify and quantify this association. The Female and Male Athlete Triad Coalition Consensus Statements include evidence statements developed after a roundtable of experts held in conjunction with the American College of Sports Medicine 64th Annual Meeting in Denver, Colorado, in 2017 and are in 2 parts-Part I: Definition and Scientific Basis and Part 2: The Male Athlete Triad: Diagnosis, Treatment, and Return-to-Play. In this first article, we discuss the scientific evidence to support the Male Athlete Triad model.

The Male Athlete Triad-A Consensus Statement From the Female and Male Athlete Triad Coalition Part II: Diagnosis, Treatment, and Return-To-Play.

ABSTRACT: The Male Athlete Triad is a medical syndrome most common in adolescent and young adult male athletes in sports that emphasize a lean physique, especially endurance and weight-class athletes. The 3 interrelated conditions of the Male Athlete Triad occur on spectrums of energy deficiency/low energy availability (EA), suppression of the hypothalamic-pituitary-gonadal axis, and impaired bone health, ranging from optimal health to clinically relevant outcomes of energy deficiency/low EA with or without disordered eating or eating disorder, functional hypogonadotropic hypogonadism, and osteoporosis or low bone mineral density with or without bone stress injury (BSI). Because of the importance of bone mass acquisition and health concerns in adolescence, screening is recommended during this time period in the at-risk male athlete. Diagnosis of the Male Athlete Triad is best accomplished by a multidisciplinary medical team. Clearance and return-to-play guidelines are recommended to optimize prevention and treatment. Evidence-based risk assessment protocols for the male athlete at risk for the Male Athlete Triad have been shown to be predictive for BSI and impaired bone health and should be encouraged. Improving energetic status through optimal fueling is the mainstay of treatment. A Roundtable on the Male Athlete Triad was convened by the Female and Male Athlete Triad Coalition in conjunction with the 64th Annual Meeting of the American College of Sports Medicine in Denver, Colorado, in May of 2017. In this second article, the latest clinical research to support current models of screening, diagnosis, and management for at-risk male athlete is reviewed with evidence-based recommendations.

A dementia-friendly church: How can the African American church support families affected by dementia?

Dementia, including Alzheimer's disease, is affecting the African American community at alarming rates, as African Americans have a greater risk of dementia than other races. The African American church has traditionally been a safe haven where families go for support and healing. However, many churches are not equipped to support families living with dementia. The purpose of this study was to explore ways African American churches can be dementia-friendly to support families affected by dementia. A qualitative descriptive design was used to collect data from 12 African American community stakeholders. Participants were inclusive of caregivers, church leaders, community members, and service providers. During the semi-structured interviews, participants were asked to share characteristics of a dementia-friendly church. Thematic analysis was performed using data from interviews, researcher's journal, and field notes. Responses described a dementia-friendly church as (a) resourceful; (b) welcoming and friendly; (c) inclusive and comfortable; (d) understanding and accepting; and (e) concerned about personal well-being. This study has wide implications not only for African American churches and families, but also for families living with dementia outside of African American faith communities. These findings allow for faith leaders and churches to begin the process of becoming dementia-friendly, thus enabling congregations, communities, and persons with dementia to continue living in meaningful ways. In conclusion, churches are a source of religious support and provide access to resources for families in difficult times. Thus, it is imperative for African American churches to explore ways to best support and meet the needs of families living with dementia.