Hepatotoxicity of titanium dioxide nanoparticles.

The food additive E171 (titanium dioxide, TiO2), is widely used in foods, pharmaceuticals and cosmetics. It is a fine white powder, with at least one third of its particles sized in the nanoparticulate (˂100 nm range, TiO2 NPs). The use of E171 is controversial as its relevant risk assessment has never been satisfactorily accomplished. In vitro and in vivo studies have shown dose-dependent toxicity in various organs including the liver. TiO2 NPs have been shown to induce inflammation, cell death and structural and functional changes within the liver. The toxicity of TiO2 NPs in experimental models varies between organs and according to their physiochemical characteristics and parameters such as dosage and route of administration. Among these factors, ingestion is the most significant exposure route, and the liver is a key target organ. The aim of this review is to highlight the reported adverse effects of orally administered TiO2 NPs on the liver and to discuss the controversial state of its toxicity.

The Effects of GreenShell Mussel Powder (Brand-Named PERNAULTRA) on Physical Performance and Subjective Pain, Symptoms, and Function Measures in Knee Osteoarthritis: A 6-Mo Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Osteoarthritis (OA) can cause disability and reduce quality of life (QoL). Objectives: This study aimed to determine whether GreenShell mussel (GSM) powder (PERNAULTRA) consumption was more effective than placebo at improving physical performance and subjective measures of symptoms and function in adults with early signs of knee OA. Methods: The Researching Osteoarthritis and GSM study was a 6-mo randomized, double-blind, placebo-controlled trial in adults aged 55-80 y, screened for signs of OA (n = 120, 65.9 ± 6.43 y, 63% female). Participants consumed either 3 g of powdered whole GSM or placebo (pea protein) daily. Baseline and end data collection included 30-s chair stand, stair test, 40-m fast-paced walk test, Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire categorized into 5 subscales [pain (P), symptoms except pain (S), function in activities of daily living (ADL), function in sports/recreation (SP), and QoL], a measure of Intermittent and Constant Osteoarthritis Pain, and visual analog scale of pain and symptoms. Results: Visual analog scale symptoms showed a significantly greater reduction in percentage change for GSM than that for placebo [-28.1 (-59.2, 43.2) compared with 0.00 (-28.6, 100); P = 0.03]. Further, a trend for improvement in percentage change for GSM compared with placebo was seen in 40m fast-paced walk [2.51 (-3.55, 8.12) compared with 0.20 (-6.58, 4.92); P = 0.09], KOOS-SP [11.4 (-4.48, 27.0) compared with 0.00 (-11.1, 17.7); P = 0.09], and Intermittent and Constant Osteoarthritis Pain intermittent pain scale [-27.7 (-77.3, 0.00) compared with -14.6 (-50.0, 36.4); P = 0.08]. In those with body mass index (BMI; in kg/m2) <25, GSM consumption significantly improved KOOS-S compared with placebo [6.35 (3.49, 12.7) compared with 0.00 (-4.65, 4.49); P = 0.03] and showed a trend for improvement in KOOS-ADL [3.29 (1.01, 8.79) compared with 1.01 (-5.75, 4.30); P = 0.07]. Those with BMI of ≥25, consuming GSM showed a trend for improvement in KOOS-SP [13.6 (-4.76, 33.3) compared with 0.00 (-12.5, 20.0); P = 0.07]. Conclusions: This research suggests consumption of GSM has potential to alleviate symptoms and improve functionality in OA.This trial was registered at Clinical Trial Registry as ACTRN12620001112954p (https://www.anzctr.org.au/ACTRN12620001112954p.aspx).

A comparative intervention trial of deer milk and an oral nutritional supplement efficacy for improving older adults' nutritional status, muscle mass and physical performance.

OBJECTIVES: To compare the effectiveness of deer milk (DM) for improving nutritional status, muscle mass and physical performance with that of a commercially available oral nutritional supplement (ONS) in older women. METHODS: This study was an 11-week randomised, double-blind, parallel group study. Healthy women (N = 120) aged 65-80 years, the majority having a body mass index (BMI) < 25 kg/m2 were recruited. The women were randomly assigned to either 200 ml DM or a commercial ONS for 11 weeks. Data on habitual macronutrient intake, nutritional status (Mini Nutrition Assessment-Short Form, MNA-SF; ≤7 malnourished, 8-11 at risk of malnutrition, ≥12 normal nutrition), anthropometrics/body composition, and physical performance were collected. Blood samples were collected for metabolic markers. RESULTS: 102 women (DM 45, ONS 57) completed the study, of whom 29% had a dietary protein intake of <1 g/kg body weight per day, and 38% at risk of malnutrition. There were no between group differences in percentage change in MNA-SF score and body composition (P > 0.05), but a trend for a difference in handgrip strength (DM 11.7 ± 49.8% vs. ONS -2.42 ± 17.9%, P = 0.06). Further exploratory analysis showed that there was a trend for a between group difference in percentage change in MNA-SF score, favoring DM (DM 7.72 + 13.0% vs. ONS 0.63 + 9.25%, P = 0.06) only in women at risk of malnutrition. There was also a between group difference in percentage change in muscle mass (DM 1.68 ± 2.77% vs. ONS -0.18 ± 2.81%, P = 0.02) in women with BMI ≥25 kg/m2 and in handgrip strength (DM 10.6 ± 23.6% vs. ONS -5.03 ± 18.1%, P < 0.01) in women with BMI<25 kg/m2. Total cholesterol, LDL and LDL:HDL ratio did not change over time (P > 0.05), but there was a between group difference in percentage change in these markers (total cholesterol: DM 3.01 ± 6.97% vs. ONS -2.65 ± 9.92%, P < 0.01; LDL: DM 4.22 ± 14.9% vs. ONS -6.05 ± 17.6%, P < 0.01; LDL:HDL ratio: DM: 2.27 ± 16.4% vs. ONS: -5.78 ± 18.2%, P = 0.02). CONCLUSION: Baseline nutritional status and BMI may modulate nutritional status, muscle mass and physical performance response to DM (as compared with ONS), suggesting DM may improve nutritional status and physical performance in women at risk of malnutrition and/or with lower BMI, and improve muscle mass in women with a higher BMI. The study was registered with the Australian New Zealand Clinical Trial Registry ACTRN12621000650897p.

Associations between dietary patterns and an array of inflammation biomarkers and plasma lipid profile in postmenopausal women.

OBJECTIVE AND DESIGN: In this cross-sectional study, evaluation of the association between four dietary patterns, nutrients and food intakes and an array of systemic inflammation biomarkers and lipid profile among 80 New Zealand postmenopausal women were conducted. MATERIALS: Eighty postmenopausal women participated in the study. A validated food frequency questionnaire was used to collect nutrients and food intake. Four dietary patterns were identified by principal component analysis (PCA) and plasma samples collected for inflammatory biomarkers and lipid profile measures. RESULTS: There were negative correlations between intake of dietary fibre, soluble and insoluble non-starch polysaccharides (NSP), vitamin C and niacin and with almost all the inflammatory markers for the whole group. Vegetables, tea/coffee and especially fruit intake were negatively correlated with the inflammatory biomarkers in the whole group. A high intake of Pattern 1 (potato, bread, and fruit pattern) was associated with a low risk of high interferon (IFN)-α2, IFN-λ, interleukin (IL)-6 and IL-8 levels while a high intake of Pattern 3 (fast-food pattern) was associated high risk of IFN-α2 levels. Multiple linear regression showed a negative correlation between Pattern 2 (soups and vegetables pattern) and levels of C-reactive protein (CRP) as well as ferritin. A positive association was observed between Pattern 3 (fast-food pattern) and CRP levels. Positive correlation was also observed between Pattern 2 and high-density lipoprotein (HDL) and total cholesterol (TC) levels, Pattern 4 (meat and vegetables pattern) was however negatively correlated with TC, low-density lipoprotein (LDL) and TC/HDL ratio. CONCLUSIONS: The result of this study reinforces the contribution and role of diet in modifying inflammation in postmenopausal women.

Effect of green-lipped mussel (Perna canaliculus) supplementation on faecal microbiota, body composition and iron status markers in overweight and obese postmenopausal women: a randomised, double-blind, placebo-controlled trial.

The present study aimed to determine the effect of whole meat GSM powder on gut microbiota abundance, body composition and iron status markers in healthy overweight or obese postmenopausal women. This was a 3-months trial involving forty-nine healthy postmenopausal women with body mass index (BMI) between 25 and 35 kg/m2 who were randomly assigned to receive 3 g/d of either GSM powder (n 25) or placebo (n 24). The gut microbe abundance, serum iron status markers and body composition were measured at the baseline and the end of the study. The between-group comparison at the baseline showed a lower abundance of Bacteroides and Clostridium XIVa in the GSM group compared with the placebo (P = 0⋅04). At the baseline, the body fat (BF)% and gynoid fat% were higher in the GSM group compared with the placebo (P < 0⋅05). No significant changes were found in any of the outcome measures, except for ferritin levels that showed a significant reduction over time (time effect P = 0⋅01). Some trend was observed in bacteria including Bacteroides and Bifidobacterium which tended to increase in the GSM group while their abundance decreased or remained at their baseline level in the control group. Supplementation with GSM powder did not result in any significant changes in gut microbe abundance, body composition and iron markers compared with placebo. However, some commensal bacteria such as Bacteroides and Bifidobacteria tended to increase following supplementation with GSM powder. Overall, these findings can expand the knowledge surrounding the effects of whole GSM powder on these outcome measures in healthy postmenopausal women.

Plasma metabolomic response to high-carbohydrate meals of differing glycaemic load in overweight women.

BACKGROUND: Metabolomic dysregulation following a meal in overweight individuals with the Metabolic Syndrome (MetS) involves multiple pathways of nutrient storage and oxidation. OBJECTIVE: The aim of the current study was to perform an acute cross-over intervention to examine the interactive actions of meal glycaemic load (GL) on the dynamic responses of the plasma metabolome in overweight females. METHODS: Postmenopausal women [63 ± 1.23y; Healthy (n = 20) and MetS (n = 20)] ingested two differing high-carbohydrate test meals (73 g carbohydrate; 51% energy) composed of either low glycemic index (LGI) or high (HGI) foods in a randomised sequence. Plasma metabolome was analysed using liquid chromatography-mass spectrometry (LC-MS). RESULTS: In the overweight women with MetS, there were suppressed postprandial responses for several amino acids (AAs), including phenylalanine, leucine, valine, and tryptophan, p < 0.05), irrespective of the meal type. Meal GL exerted a limited impact on the overall metabolomic response, although the postprandial levels of alanine were higher with the low GL meal and uric acid was greater following the high GL meal (p < 0.05). CONCLUSIONS: MetS participants exhibited reduced differences in the concentrations of a small set of AAs and a limited group of metabolites implicated in energy metabolism following the meals. However, the manipulation of meal GL had minimal impact on the postprandial metabolome. This study suggests that the GL of a meal is not a major determinant of postprandial response, with a greater impact exerted by the metabolic health of the individual. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12615001108505 (21/10/2015).

B vitamins and homocysteine as determinants of bone health: A literature review of human studies.

Although there are several factors related to bone diseases such as physical activity, gender (oestrogen), race/ethnicity, smoking and alcohol habits, nutrition is a modifiable risk factor that could be employed to prevent or manage the onset of bone health diseases such as osteoporosis in humans. Aside from calcium and vitamin D, B vitamins are a group of water-soluble vitamins that play a vital role in cell metabolism. In this review, current evidence on B vitamins and bone health is assessed. Clinical trials (interventions) indicate that treatment with B vitamins impact the concentrations of total plasma/serum homocysteine concentrations (tHcy); however, most studies have reported the lack of an effect of low homocysteine concentrations on bone turnover markers, bone mineral density or fracture risks. Current studies have been inconsistent in their reports on the role of B vitamins and homocysteine in bone health. More data are therefore required to show the mechanism and effect of tHcy and B vitamins on bone mineral density, bone metabolism and fracture risk.

Effects of Greenshell™ mussel intervention on biomarkers of cartilage metabolism, inflammatory markers and joint symptoms in overweight/obese postmenopausal women: A randomized, double-blind, and placebo-controlled trial.

Objective: To investigate the effect of whole greenshell mussel (GSM) powder on biomarkers of cartilage metabolism, inflammatory cytokines, and joint symptoms in postmenopausal women with overweight/obesity and joint discomfort. Design: Fifty-five postmenopausal women with overweight/obesity were randomly assigned to receive 3 g/day whole GSM powder or placebo for 12 weeks. Cartilage turnover biomarkers urinary C-telopeptide of type II collagen (CTX-II) and serum cartilage oligomeric matrix protein (COMP) were measured at baseline, week 6 and 12. Plasma cytokines were measured at baseline and week 12. Joint pain and knee-related problems were assessed at baseline and week 12 using a 100 mm Visual Analogue Scale (VAS) and the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, respectively. Results: Forty-nine participants completed the study (GSM n = 25, placebo n = 24). After 12 weeks, urinary CTX-II showed no significant change over time or between the groups (interaction effect P = 0.1). However, in women with symptomatic knees, a significant difference was noted between the group (treatment effect P = 0.04), as it was lower in the GSM group compared to placebo group at week 6 (P = 0.04) and week 12 (P = 0.03). Serum COMP and plasma cytokines were not affected. GSM supplementation showed greater reduction in the VAS pain score than placebo (-13.2 ± 20.3 vs. -2.9 ± 15.9; P = 0.04). No significant change in KOOS domains between the two groups was observed. Conclusion: Oral supplementation of whole GSM powder at 3 g/day may slow down the degradation of type II collagen in postmenopausal women with symptomatic knees. GSM treatment conferred clinical benefit on overall joint pain. No significant effect was noted for inflammatory cytokines, suggesting that GSM may act within the joint microenvironment rather than at the systemic level. Clinical trial registration: [www.australianclinicaltrials.gov.au/clinical-trialregistries], identifier [ACTRN12620000413921p].

Effects of early postnatal life nutritional interventions on immune-microbiome interactions in the gastrointestinal tract and implications for brain development and function.

The gastrointestinal (GI) microbiota has co-evolved with the host in an intricate relationship for mutual benefit, however, inappropriate development of this relationship can have detrimental effects. The developing GI microbiota plays a vital role during the first 1,000 days of postnatal life, during which occurs parallel development and maturation of the GI tract, immune system, and brain. Several factors such as mode of delivery, gestational age at birth, exposure to antibiotics, host genetics, and nutrition affect the establishment and resultant composition of the GI microbiota, and therefore play a role in shaping host development. Nutrition during the first 1,000 days is considered to have the most potential in shaping microbiota structure and function, influencing its interactions with the immune system in the GI tract and consequent impact on brain development. The importance of the microbiota-GI-brain (MGB) axis is also increasingly recognized for its importance in these developmental changes. This narrative review focuses on the importance of the GI microbiota and the impact of nutrition on MGB axis during the immune system and brain developmental period in early postnatal life of infants.

Dissecting the relationship between plasma and tissue metabolome in a cohort of women with obesity: Analysis of subcutaneous and visceral adipose, muscle, and liver.

Untargeted metabolomics of blood samples has become widely applied to study metabolic alterations underpinning disease and to identify biomarkers. However, understanding the relevance of a blood metabolite marker can be challenging if it is unknown whether it reflects the concentration in relevant tissues. To explore this field, metabolomic and lipidomic profiles of plasma, four sites of adipose tissues (ATs) from peripheral or central depot, two sites of muscle tissue, and liver tissue from a group of nondiabetic women with obesity who were scheduled to undergo bariatric surgery (n = 21) or other upper GI surgery (n = 5), were measured by liquid chromatography coupled with mass spectrometry. Relationships between plasma and tissue profiles were examined using Pearson correlation analysis subject to Benjamini-Hochberg correction. Plasma metabolites and lipids showed the highest number of significantly positive correlations with their corresponding concentrations in liver tissue, including lipid species of ceramide, mono- and di-hexosylceramide, sphingomyelin, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine, dimethyl phosphatidylethanolamine, ether-linked PC, ether-linked PE, free fatty acid, cholesteryl ester, diacylglycerol and triacylglycerol, and polar metabolites linked to several metabolic functions and gut microbial metabolism. Plasma also showed significantly positive correlations with muscle for several phospholipid species and polar metabolites linked to metabolic functions and gut microbial metabolism, and with AT for several triacylglycerol species. In conclusion, plasma metabolomic and lipidomic profiles were reflective more of the liver profile than any of the muscle or AT sites examined in the present study. Our findings highlighted the importance of taking into consideration the metabolomic relationship of various tissues with plasma when postulating plasma metabolites marker to underlying mechanisms occurring in a specific tissue.

A Simple, Robust, and Convenient HPLC Assay for Urinary Lactulose and Mannitol in the Dual Sugar Absorption Test.

BACKGROUND: Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing. METHODS: We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using a series of dilutions from standard stock solutions of lactulose and mannitol 'spiked' into urine samples. The utility to quantify urinary excretion during the dual sugar absorption test over 6 h was also determined. RESULTS: Lactulose and mannitol were eluted isocratically at 5.7 and 10.1 min, respectively, with water as a mobile phase at a flow rate of 0.3 mL min-1, 858 psi, 60 °C. The calibration curves for both sugars were linear up to 500 µg mL-1 with a limit of detection in standard solutions at 4 µg mL-1 and in 'spiked' urine samples at 15 µg mL-1. The intra-assay and inter-assay CVs were between 2.0-5.1% and 2.0-5.1% for lactulose and 2.5-4.4% and 2.8-3.9% for mannitol. The urinary profiles of the 6 h absorption of lactulose and mannitol showed similar peak-retention times to standard solutions and were well-resolved at 5.9 and 10.4 min, respectively. CONCLUSIONS: The assay was easy to automate, using commonly available equipment and convenient requiring no prior laborious sample derivatization. The simplicity, reproducibility, and robustness of this assay facilitates its use in routine clinical settings for the quantification of intestinal permeability.

The Influence of Obesity, Ovariectomy, and Greenshell Mussel Supplementation on Bone Mineral Density in Rats.

Obesity is considered to impair long-term health by disturbing multiple physiological functions. However, it remains a controversial issue as to whether obesity has beneficial or detrimental effects on bone health in postmenopausal women. The aims of this study were to investigate the relationships between obesity and bone mineral density (BMD) under conditions of ovarian hormone deficiency in an animal model and to evaluate the potential health benefits of Greenshell mussel (GSM) on bone health. A total of 144 adult female Sprague-Dawley rats were fed from age 12 weeks on one of four diets (normal [ND]; ND + GSM; high fat/high sugar [HF/HS]; HF/HS + GSM; n = 36 per diet). At age 20 weeks, after a dual-energy X-ray absorptiometry (DXA) scan, 12 of the rats on each diet underwent ovariectomy (OVX) and the remaining rats were left intact. Twelve of the intact rats in each diet group were culled at age 26 weeks (short-term cohort). The remaining rats were culled at age 48 weeks (long-term cohort). Rats were DXA scanned before cull, then various fat pads were dissected. The results revealed that HF/HS rats and OVX rats dramatically increased body weight and fat deposition in correlation with leptin. In the long-term cohort, vertebral spine BMD rapidly declined after OVX. At termination, the OVX rats had decreased plasma bone turnover markers of CTX-1 and TRAP when compared with sham rats. Significantly higher BMD was found in OVX rats fed the HF/HS diet compared with ND, but this difference was not recapitulated in intact rats. BMD of right femur was significantly increased 5% to 10% by GSM in the short-term cohort. The data demonstrated that obesity can be beneficial by increasing BMD in OVX rats, and this may extrapolate to postmenopausal women as adipocyte-produced estrogen may slightly compensate for the reduction in ovarian hormones. Finally, the data showed that GSM may be beneficial to bone health by increasing BMD accrual. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Mass Spectrometry-Based Metabolomic and Lipidomic Analysis of the Effect of High Fat/High Sugar Diet and GreenshellTM Mussel Feeding on Plasma of Ovariectomized Rats.

This study aimed to examine the changes in lipid and metabolite profiles of ovariectomized (OVX) rats with diet-induced metabolic syndrome-associated osteoarthritis (MetOA) after supplementation with greenshell mussel (GSM) using an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach. Ninety-six rats were fed with one of four diets: control, control supplemented with GSM + GSM, high fat/high sugar (HFHS), or high fat/high sugar enriched with GSM (HFHS + GSM). After 8 weeks on experimental diets, half of the rats in each group underwent OVX and the other half were sham operated. After being fed for an additional 28 weeks, blood samples were collected for the metabolomics analysis. Lipid and polar metabolites were extracted from plasma and analysed by LC-MS. We identified 29 lipid species from four lipid subclasses (phosphatidylcholine, lysophosphatidylcholine, diacylglycerol, and triacylglycerol) and a set of eight metabolites involved in amino acid metabolism (serine, threonine, lysine, valine, histidine, pipecolic acid, 3-methylcytidine, and cholic acid) as potential biomarkers for the effect of HFHS diet and GSM supplementation. GSM incorporation more specifically in the control diet generated significant alterations in the levels of several lipids and metabolites. Further studies are required to validate these findings that identify potential biomarkers to follow OA progression and to monitor the impact of GSM supplementation.

Non-polar lipid from greenshell mussel (Perna canaliculus) inhibits osteoclast differentiation.

The osteoclast-dependent bone resorption process is a crucial part of the bone regulatory system. The excessive function of osteoclasts can cause diseases of bone, joint, and other tissues such as osteoporosis and osteoarthritis. Greenshell mussel oil (GSM), a good source of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs), was fractionated into total lipid, polar lipid, and non-polar lipid components and their anti-osteoclastogenic activity tested in RAW 264.7 cell cultures. Osteoclast differentiation process was achieved after 5 days of incubation with RANKL in 24-well culture plates. Introducing the non-polar lipid fraction into the culture caused a lack of cell differentiation, and a reduction in tartrate-resistant acid phosphatase (TRAP) activity and TRAP cell numbers in a dose-dependent manner (50% reduction at the concentration of 20 µg/mL, p < 0.001). Moreover, actin ring formation was significantly diminished by non-polar lipids at 10-20 µg/mL. The bone digestive enzymes released by osteoclasts into the pit formation were also compromised by downregulating gene expression of cathepsin K, carbonic anhydrase II (CA II), matrix metalloproteinase 9 (MMP-9), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). This study revealed that the non-polar lipid fraction of GSM oil contains bioactive substances which possess potent anti-osteoclastogenic activity.

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.

Factors Associated with Bone Mineral Density and Bone Resorption Markers in Postmenopausal HIV-Infected Women on Antiretroviral Therapy: A Prospective Cohort Study.

The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged > 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV.

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.

Effect of GreenshellTM mussel on osteoarthritis biomarkers and inflammation in healthy postmenopausal women: a study protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: New Zealand Greenshell™ mussels (GSM; Perna canaliculus) have recently been shown to decrease cartilage degradation in a rat model of induced metabolic osteoarthritis (MetOA). However, this effect has not been investigated in human subjects. This study aims to determine the effect of GSM powder on biomarkers of cartilage metabolism, bone resorption, and inflammation in New Zealand healthy overweight/obese postmenopausal women who are at early stage or at high risk of OA. METHOD: Fifty overweight or obese (BMI 25-35 kg/m2) postmenopausal women (aged 55-75 years) will be recruited by advertisement. Participants will be randomized based on a double-blind randomization schedule and stratified randomization based on BMI and age distribution. The participant will be assigned with a 1:1 allocation ratio to receive 3 g/d whole meat GSM powder or placebo (sunflower seed protein) for 12 weeks. Data on socio-demographics, physical activity, and dietary intake will be collected for each subject. Cartilage turnover biomarkers [(C-telopeptide of type II collagen (CTX-II), C-propeptide of type II procollagen (CPII), Cartilage oligomeric matrix protein (COMP)], and bone resorption marker (CTX-I) will be measured in blood and urine samples. Inflammatory status (hs-CRP and cytokine panel) will be assessed and iron status will be measured. Body composition including fat mass (FM), lean mass (LM), and fat percentage will be measured using dual-energy X-ray absorptiometry (DXA). Joint pain and knee function will be assessed using a 100-mm visual analog scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, respectively. DISCUSSION: This trial will be the first to explore the effects of whole meat GSM powder on cartilage turnover, bone resorption, and inflammation biomarkers in overweight/obese postmenopausal women. The results from this trial will provide evidence on the efficacy of GSM in the prevention of OA. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000413921p . Registration on 27 March 2020.

Untargeted metabolomics reveals plasma metabolites predictive of ectopic fat in pancreas and liver as assessed by magnetic resonance imaging: the TOFI_Asia study.

BACKGROUND: Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking. METHODS: Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S). Plasma metabolites were measured with untargeted liquid chromatography-mass spectroscopy (LC-MS). Multivariate partial least squares (PLS) regression identified metabolites predictive of VAT/SAT and ectopic fat; univariate linear regression adjusting for potential covariates identified individual metabolites associated with VAT/SAT and ectopic fat; linear regression adjusted for ethnicity identified clinical and anthropometric correlates for each fat depot. RESULTS: PLS identified 56, 64 and 31 metabolites which jointly predicted pancreatic fat (R2Y = 0.81, Q2 = 0.69), liver fat (RY2 = 0.8, Q2 = 0.66) and VAT/SAT ((R2Y = 0.7, Q2 = 0.62)) respectively. Among the PLS-identified metabolites, none of them remained significantly associated with pancreatic fat after adjusting for all covariates. Dihydrosphingomyelin (dhSM(d36:0)), 3 phosphatidylethanolamines, 5 diacylglycerols (DG) and 40 triacylglycerols (TG) were associated with liver fat independent of covariates. Three DGs and 12 TGs were associated with VAT/SAT independent of covariates. Notably, comparison with clinical correlates showed better predictivity of ectopic fat by these PLS-identified plasma metabolite markers. CONCLUSIONS: Untargeted metabolomics identified candidate markers of visceral and ectopic fat that improved fat level prediction over clinical markers. Several plasma metabolites were associated with level of liver fat and VAT/SAT ratio independent of age, total and visceral adiposity, whereas pancreatic fat deposition was only associated with increased sulfolithocholic acid independent of adiposity-related parameters, but not age.

The Gut Microbiome Is Altered in Postmenopausal Women With Osteoporosis and Osteopenia.

Osteoporosis and its precursor osteopenia are common metabolic bone diseases in postmenopausal women. A growing body of evidence suggests that the gut microbiota is involved in the regulation of bone metabolism; however, there are few studies examining how gut microbiomes in osteoporosis and osteopenia may differ from those in healthy individuals. The aim of this study was to characterize the diversity, composition, and functional gene potential of the gut microbiota of healthy, osteopenic, and osteoporotic women. Body composition, bone density, and fecal metagenomes were analyzed in 86 postmenopausal women. The women were classified as healthy, osteopenic, or osteoporotic based on T-scores. The taxonomic and functional gene compositions of the microbiome were analyzed using shotgun metagenomic sequencing. Both osteoporotic and osteopenic taxonomic compositions were found to be significantly different from healthy participants. Linear discriminant-analysis effect-size analyses identified that healthy participants had more unclassified Clostridia and methanogenic archaea (Methanobacteriaceae) than in both osteoporotic and osteopenic participants. Bacteroides was found to be more abundant in osteoporosis and osteopenia groups. Some KEGG pathways, including carbohydrate metabolism, biosynthesis of secondary metabolites, and cyanoamino acid metabolism, were found to be more abundant in both osteoporosis and osteopenia. These results show that osteoporosis and osteopenia alter the gut microbiome of postmenopausal women and identify potential microbial taxonomic and functional pathways that may be involved in this disease. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.