Effect of Dietary Fiber Supplementation on Metabolic Endotoxemia: A Protocol for Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Introduction: Metabolic endotoxemia (ME) is the main cause of sub-clinical chronic inflammation, which subsequently triggers the onset of several chronic diseases. However, recent reports have indicated that dietary fiber (DF) contributes significantly to ameliorating ME and inflammation. This protocol aims to provide an outline of all procedures in synthesizing the available data on the effect of DF against ME. Methods: Following the PRISMA 2020 guidelines for preparing protocols, this protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) with registration number (CRD42023417833). In this review, we specifically focused on the inclusion of clinical trials that met the following criteria: they were published or available as preprints, employed random, quasi-random, or cross-over designs, and were exclusively documented in the English language. Clinical medical subject headings (MeSH) as search terms were used on prominent databases such as MEDLINE, COCHRANE library, PubMed, World Health Organization International Clinical Trials Registry Platforms, and US National Institutes of Health Ongoing Trials Register Clinicaltrials.gov. Results and discussion: This protocol will guide the exploration of articles that report changes in ME biomarkers in subjects supplemented with DF. The findings of this protocol will ensure a comprehensive evaluation of available evidence, provide a quantitative summary, identify patterns and trends, enhance statistical power, and address heterogeneity, which collectively will clarify the optimal types, doses, and duration of DF interventions for managing ME and low-grade inflammation. Ethics and dissemination: The quantitative data of clinical trials will be collected, and a meta-analysis will be performed using RevMan V.5.3 software. Therefore, no ethical approval is required.

Micronutrient intake and risk of ulcerative colitis: A meta-analysis of observational studies.

BACKGROUND & AIMS: Ulcerative colitis (UC) poses a challenge to patients' health status and lifestyle. Micronutrient intake has been associated with the risk of UC, but the association has been inconsistent. Therefore, we performed a meta-analysis to clarify the overall association between micronutrient intake, as potentially modifiable risk factors, and the risk of UC. METHODS: Based on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocols, systematic searches were conducted in PubMed, Scopus, and Web of Science up to September 2021. Studies were considered eligible for inclusion if they met the following criteria: (1) observational studies that compared dietary intake of zinc, calcium, or magnesium between the UC group and the control group and (2) had means and standard deviations or medians and interquartile ranges of outcome variables. RESULTS: A total of 7 studies with 1197 participants were included in the meta-analysis. The random-effects meta-analysis showed that there was no significant association between the intake of calcium (WMD: -66.25 mg/day, 95% CI: -276.7 to 144.21, P = 0.54), magnesium (WMD: -21.47 mg/day, 95% CI: -95.54 to 52.6, P = 0.57), and zinc (WMD: 0.3 mg/day, 95% CI: -1.5 to 2, P = 0.74) and the risk of UC. However, there was high significant heterogeneity between studies in dietary intake of calcium (I2 = 95.1%, P < 0.001), magnesium (I2 = 96%, P < 0.001), and zinc (I2 = 95.8%, P = <0.001). In a location-based subgroup analysis, calcium intake in non-Asian countries was significantly lower in patients with UC compared to healthy controls. In addition, magnesium intake was negatively associated with the risk of UC in studies with a sample size of less than 190 subjects. However, for the association between zinc intake and UC risk, subgroup analysis failed to find a source of heterogeneity. CONCLUSION: No significant association was found between dietary calcium, magnesium, and zinc intake and risk of UC.

The effect of 17ß-estradiol plus norethisterone acetate treatment on the lipid profile in women: a dose-response meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The impact of 17ß-estradiol plus norethisterone acetate administration on serum lipids in women is controversial as previously published studies have produced conflicting results. Thus, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of 17ß-estradiol plus norethisterone acetate therapy on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in females. METHODS: We searched the PubMed/MEDLINE, Scopus, Embase, and Web of Science databases for relevant trials published in English until 15 July 2021. The weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using a random-effects model (the DerSimonian and Laird methods). RESULTS: A total of 32 RCTs were included in the final analysis. Treatment with 17ß-estradiol plus norethisterone acetate significantly decreased LDL-C (WMD: -13.49 mg/dL, 95% CI: -16.46 to -10.52; P < 0.001), HDL-C (WMD: -3.57 mg/dL, 95% CI: -5.56 to -1.58; P < 0.001), TC (WMD: -19.33 mg/dL, 95% CI: -24.14 to -14.52; P < 0.001), and TG (WMD: -10.86 mg/dL, 95% CI: -16.06 to -5.13; P < 0.001) levels in females. The non-linear dose-response meta-analysis revealed a negative correlation between HDL-C levels and increased treatment periods (P ˂ 0.001). CONCLUSION: Evidence to date suggests that the administration of 17ß-estradiol plus norethisterone acetate in females reduces LDL-C, HDL-C, TC, and TG concentrations. Future investigations should clarify whether the reduction in HDL-C following the administration of 17ß-estradiol plus norethisterone acetate is clinically significant and poses any risks to the subjects who receive this treatment.

Modulation of Bone and Joint Biomarkers, Gut Microbiota, and Inflammation Status by Synbiotic Supplementation and Weight-Bearing Exercise: Human Study Protocol for a Randomized Controlled Trial.

BACKGROUND: There is strong evidence suggesting that prebiotics and probiotics regulate gut microbiota, reducing inflammation and thereby potentially improving bone health status. Similarly, mechanistic evidence suggests that either low-impact or high-impact weight-bearing exercises improve body composition and consequently increase bone mineral density in individuals with osteoporosis and osteoarthritis. OBJECTIVE: This study aims to investigate the effects of a synbiotic (probiotic+prebiotic) supplementation, an exercise intervention, or a combination of both on gut microbiota, inflammation, and bone biomarkers in postmenopausal women. METHODS: A total of 160 postmenopausal women from New Zealand will be recruited and randomized to one of four interventions or treatments for 12 weeks: control, synbiotic supplementation, exercise intervention, or synbiotic supplementation and exercise. The primary outcome measure is the bone and joint biomarkers at baseline and week 12, whereas the gut microbiota profile and inflammatory cytokine measurements will serve as the secondary outcome measures at baseline and week 12. Baseline data and exercise history will be used to assess, allocate, and stratify participants into treatment measures. RESULTS: Recruitment of participants will begin in September 2021, and the anticipated completion date is June 2022. CONCLUSIONS: To the best of our knowledge, this will be the first randomized controlled trial to analyze the effects of both a synbiotic supplement and an exercise intervention in postmenopausal women. On the basis of the results obtained, a combination of synbiotic supplements and exercise might serve as a noninvasive approach to manage and/or improve body composition and bone health in postmenopausal women. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000998943p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380336&isClinicalTrial=False.

Potential modulatory mechanisms of action by long-chain polyunsaturated fatty acids on bone cell and chondrocyte metabolism.

Long-chain polyunsaturated fatty acids (LCPUFAs) and their metabolites are considered essential factors to support bone and joint health. The n-6 PUFAs suppress the osteoblasts differentiation via increasing peroxisome proliferator-activated receptor gamma (PPARγ) expression and promoting adipogenesis while n-3 PUFAs promote osteoblastogenesis by down-regulating PPARγ and enhancing osteoblastic activity. Arachidonic acid (AA) and its metabolite prostaglandin E2 (PGE2) are key regulators of osteoclast differentiation via induction of the receptor activator of nuclear factor kappa-Β ligand (RANKL) pathway. Marine-derived n-3 LCPUFAs have been shown to inhibit osteoclastogenesis by decreasing the osteoprotegerin (OPG)/RANKL signalling pathway mediated by a reduction of pro-inflammatory PGE2 derived from AA. Omega-3 PUFAs reduce the expression of cartilage degrading enzyme matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloprotease with thrombospondin motifs-5 (ADAMTS-5) protein, oxidative stress and thereby apoptosis via nuclear factor kappa-betta (NF-kß) and inducible nitric oxide synthase (iNOS) pathways. In this review, a diverse range of important effects of LCPUFAs on bone cells and chondrocyte was highlighted through different mechanisms of action established by cell cultures and animal studies. This review allows a better understanding of the possible role of LCPUFAs in bone and chondrocyte metabolism as potential therapeutics in combating the pathological complications such as osteoporosis and osteoarthritis.

Nutrient and Dietary Patterns in Relation to the Pathogenesis of Postmenopausal Osteoporosis-A Literature Review.

Postmenopausal women tend to be susceptible to primary osteoporosis due to its association with oestrogen deficiency. There is emerging evidence that an unhealthy dietary pattern drives an increase in the risk of postmenopausal osteoporosis (PO), whereas a healthy dietary pattern may decrease its occurrence. In this narrative literature review, we sought to review the role of nutrient and dietary patterns in the pathogenesis of PO. Therefore, we searched and reported all research articles from 2001 to May 2020 in Web of Science, Cinahl and Scopus that have researched a relationship between nutrient and/or dietary patterns and postmenopausal osteoporosis. Nutrients such as calcium, phosphorus, magnesium and vitamin D have been proven to be beneficial for bone health. Meanwhile, for the dietary patterns, foods such as dairy products especially milk, fibre and protein-rich foods, e.g., meat were directly linked to a positive association with bone mineral density (BMD). Likewise, fruits, vegetables and probiotic and prebiotic foods were reported for its positive relationship with BMD. Therefore, aside from physical activity, nutrition and diet in adequate proportions are suggested to be an important tool for ameliorating osteoporosis and bone health issues in older age.

Associations between Self-Reported Physical Activity, Heel Ultrasound Parameters and Bone Health Measures in Post-Menopausal Women.

Physical activity plays an important role in the maintenance of bone health from childhood through adulthood. This study aimed to explore the associations between self-reported physical activity (PA), activity energy expenditure (AEE), heel ultrasound parameters and bone health measures among older adult women. The AEE was estimated from the responses of questionnaires for 125 older adult women aged 54-81 years. The bone parameters were measured by dual energy x-ray absorptiometry (DXA) and heel ultrasound parameters by the heel quantitative ultrasound (QUS). This study showed that AEE and the metabolic equivalent task (MET) were positively correlated with the bone and heel ultrasound parameters. However, fat mass (FM) and fat percentage were negatively correlated with AEE and MET. In addition, the regression analysis showed that higher AEE was a strong predictor of a higher spine T-score (ß = 0.212, p = 0.015), QUS T-score (ß = 0.239, p = 0.011) and stiffness index (ß = 0.240, p = 0.010) after adjusting for age, fat mass, lean mass, height and calcium intake. These results contribute to our understanding of the importance of physical activity in postmenopausal women by reiterating the benefits of physical activity for older adult women. Physical activity is an important tool for the prevention and management of osteoporosis.

Inflammatory markers and bone health in postmenopausal women: a cross-sectional overview.

BACKGROUND: Cytokines, chemokines, C-reactive proteins (CRP) and ferritin are known inflammatory markers. However, cytokines such as interleukin (IL-1ß), (IL-6) and tumour necrosis factor (TNF-α) have been reported to interfere with both the bone resorption and bone formation processes. Similarly, immune cell cytokines are known to contribute to inflammation of the adipose tissue especially with obesity. IL-10 but not IL-33 has been linked to lower ferritin levels and anemia. In this study, we hypothesized that specific cytokine levels in the plasma of women with low bone mineral density (BMD) would be higher than those in the plasma of healthy women due to the actions of elevated levels of pro-inflammatory cytokines in inducing osteoclast formation and differentiation during senescence. RESULTS: Levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in the plasma of the osteoporotic group compared to the osteopenic and/or healthy groups. Meanwhile CRP levels were significantly lower in women with osteoporosis (P = 0.040) than the osteopenic and healthy groups. Hip BMD values were significantly lower in women with high/detectable values of IL-1ß (P = 0.020) and IL-6 (P = 0.030) compared to women where these were not detected. Similarly, women with high/detectable values of IL-1ß had significantly lower spine BMD than those where IL-1ß was not detected (P = 0.030). Participants' CRP levels were significantly positively correlated with BMI, fat mass and fat percentage (P < 0.001). In addition, ferritin levels of women with high/detectable values of anti-osteoclastogenic IL-10 (P = 0.012) and IL-33 (P = 0.017) were significantly lower than those where these were not detected. There was no statistically significant association between TNF-α and BMD of the hip and lumbar spine. CONCLUSIONS: High levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and MCP-1 in apparently healthy postmenopausal women are associated with bone health issues. In addition, an increase in levels of IL-10 and IL-33 may be associated with low ferritin levels in this age group. TRIAL REGISTRATION: ANZCTR, ACTRN12617000802303. Registered May 31st, 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373020.

The Relationship between Nutrient Patterns and Bone Mineral Density in Postmenopausal Women.

In women, the menopausal transition is characterized by acid-base imbalance, estrogen deficiency and rapid bone loss. Research into nutritional factors that influence bone health is therefore necessary. In this study, the relationship between nutrient patterns and nutrients important for bone health with bone mineral density (BMD) was explored. In this cross-sectional analysis, 101 participants aged between 54 and 81 years were eligible. Body composition and BMD analyses were performed using dual-energy X-ray absorptiometry (DXA). Nutrient data were extracted from a 3-day diet diary (3-DDD) using Foodworks 9 and metabolic equivalent (MET-minutes) was calculated from a self-reported New Zealand physical activity questionnaire (NZPAQ). Significant positive correlations were found between intakes of calcium (p = 0.003, r = 0.294), protein (p = 0.013, r = 0.246), riboflavin (p = 0.020, r = 0.232), niacin equivalent (p = 0.010, r = 0.256) and spine BMD. A nutrient pattern high in riboflavin, phosphorus and calcium was significantly positively correlated with spine (p < 0.05, r = 0.197) and femoral neck BMD (p < 0.05, r = 0.213), while the nutrient pattern high in vitamin E, α-tocopherol, ß-carotene and omega 6 fatty acids was negatively correlated with hip (p < 0.05, r = -0.215) and trochanter BMD (p < 0.05, r = -0.251). These findings support the hypothesis that a nutrient pattern high in the intake of vitamin E, α-tocopherol and omega 6 fatty acids appears to be detrimental for bone health in postmenopausal women.

Lean Body Mass in the Prediction of Bone Mineral Density in Postmenopausal Women.

Owing to conflicting results of the association between body composition and bone mineral density (BMD), we investigated the relationship between fat mass (FM), lean mass (LM), and BMD in New Zealand postmenopausal women. We hypothesized that increased LM will indicate a higher BMD. A cross-sectional study was performed examining the associations between body composition, anthropometric measures, activity energy expenditure, and bone health status (using dual-energy X-ray absorptiometry [DXA]). A total of 127 healthy postmenopausal women aged between 54 and 81 years. Both FM and LM were significantly associated with BMD at all sites. However, LM, not FM, was the strongest predictor of femoral neck (FN) BMD (ß = 0.497, p < 0.001), hip BMD (ß = 0.495, p < 0.001), spine BMD (ß = 0.449, p < 0.001), and whole body BMD (ß = 0.406, p < 0.001). Age was negatively associated with FN and hip BMD. LM was positively associated with FN, spine, hip, and whole body BMD. Our findings suggest the need to increase LM rather than FM highlighting the importance of physical activity for this age group.