Journal Articles

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    A blinded, placebo-controlled study on the clinical effects of vitamin E supplementation in dogs with osteoarthritis
    (Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine., 2023-07-31) Gordon CL; Reeves SJ; Burchell RK; Thomson C; Gal A; Lopez-Villalobos N; Webster NSL; Litster KM; Mitchell RAS
    BACKGROUND: Vitamin E has a positive effect in the management of osteoarthritis in humans, and in a previous study of dogs. It has been suggested to decrease C-reactive protein concentrations and liver enzyme activities in humans and animals. OBJECTIVE: To assess the effect of vitamin E supplementation on lameness, pain, pain medication requirement, clinical pathology variables, and quality of life in large-breed dogs with naturally occurring osteoarthritis. ANIMALS: Fifty-seven client-owned dogs with naturally occurring osteoarthritis. METHODS: Dogs received either vitamin E or placebo for 90 days in a randomized, placebo-controlled, double-blinded, prospective clinical trial. Clinical lameness scores, pain medication requirements, and owner questionnaires were used to assess response to treatment every 30 days. Blood samples were collected at enrollment and at the end of the study period. RESULTS: Vitamin E administration did not improve pain, lameness, or quality of life as assessed by owners and veterinarians. Vitamin E supplementation did not decrease the requirement for rescue pain relief. No changes in clinical pathology variables were observed after 90 days of vitamin E supplementation. Body weight was negatively associated with the lameness scores and requirement for rescue pain relief. CONCLUSION: Vitamin E supplementation did not have any observable positive effects in dogs with naturally occurring osteoarthritis.
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    Does chronic oral contraceptive use detrimentally affect C-reactive protein or iron status for endurance-trained women?
    (Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society., 2023-07-24) Badenhorst CE; Govus AD; Mündel T
    PURPOSE: Chronic use of the oral contraceptive pill (OCP) is reported to increase C-reactive protein (CRP) levels and increase the risk of cardiovascular disease in premenopausal females. METHODS: A secondary analysis of data from two research studies in eumenorrheic (n = 8) and OCP (n = 8) female athletes. Basal CRP and iron parameters were included in the analysis. Sample collection occurred following a standardized exercise and nutritional control for 24 h. Eumenorrheic females were tested in the early-follicular and mid-luteal phases, and the OCP users were tested in quasi-follicular and quasi-luteal phases (both active pill periods). RESULTS: A main effect for group (p < 0.01) indicated that average CRP concentration was higher in OCP users compared with eumenorrheic females, regardless of the day of measurement within the cycle. Results demonstrate a degree of iron parameters moderation throughout the menstrual cycle that is influenced by basal CRP levels; however, no linear relationship with CRP, serum iron, and ferritin was observed. CONCLUSIONS: Basal CRP values were consistently higher in the OCP group despite participants being in a rested state. These results may indicate a potential risk of cardiovascular disease in prolonged users of the OCP when compared to eumenorrheic female athletes.
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    The Efficacy of New Zealand Greenshell™ Mussel Powder Supplementation in Supporting Muscle Recovery Following Eccentric Exercise-Induced Muscle Damage in Healthy, Untrained Adult Males
    (MDPI (Basel, Switzerland), 2023-05-15) Lomiwes D; Barnes M; Shaw O; Ngametua N; Sawyer G; Burr N; Hedderley D; Kanon A; Bear T; Carroll A; Bentley_Hewitt K; Tian HS; Miller MR; Nieman DC
    Unaccustomed eccentric exercise results in muscle damage limiting physical performance for several days. This study investigated if Greenshell™ mussel (GSM) powder consumption expedited muscle recovery from eccentric exercise-induced muscle damage (EIMD). Methods: Twenty untrained adult men were recruited into a double-blind, placebo-controlled, cross-over study and were randomly assigned to receive the GSM powder or placebo treatment first. Participants consumed their allocated intervention for four weeks then completed a bench-stepping exercise that induced muscle damage to the eccentrically exercised leg. Muscle function, soreness and biomarkers of muscle damage, oxidative stress and inflammation were measured before exercise, immediately after exercise and 24, 48 and 72 h post exercise. GSM powder promoted muscle function recovery, significantly improving (p < 0.05) isometric and concentric peak torque at 48 h and 72 h post exercise, respectively. Participants on the GSM treatment had faster dissipation of soreness, with significant treatment × time interactions for affective (p = 0.007) and Visual Analogue Scale-assessed pain (p = 0.018). At 72 h, plasma creatine kinase concentrations in the GSM group were lower (p < 0.05) compared with the placebo group. This study provides evidence for GSM powder being effective in supporting muscle recovery from EIMD.
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    The Leptospermum scoparium (Mānuka)-Specific Nectar and Honey Compound 3,6,7-Trimethyllumazine (LepteridineTM) That Inhibits Matrix Metalloproteinase 9 (MMP-9) Activity
    (MDPI (Basel, Switzerland), 2023-11-09) Lin B; Nair S; Fellner DMJ; Nasef NA; Singh H; Negron L; Goldstone DC; Brimble MA; Gerrard JA; Domigan L; Evans JC; Stephens JM; Merry TL; Loomes KM
    3,6,7-trimethyllumazine (Lepteridine™) is a newly discovered natural pteridine derivative unique to Mānuka (Leptospermum scoparium) nectar and honey, with no previously reported biological activity. Pteridine derivative-based medicines, such as methotrexate, are used to treat auto-immune and inflammatory diseases, and Mānuka honey reportedly possesses anti-inflammatory properties and is used topically as a wound dressing. MMP-9 is a potential candidate protein target as it is upregulated in recalcitrant wounds and intestinal inflammation. Using gelatin zymography, 40 μg/mL LepteridineTM inhibited the gelatinase activities of both pro- (22%, p < 0.0001) and activated (59%, p < 0.01) MMP-9 forms. By comparison, LepteridineTM exerted modest (~10%) inhibition against a chromogenic peptide substrate and no effect against a fluorogenic peptide substrate. These findings suggest that LepteridineTM may not interact within the catalytic domain of MMP-9 and exerts a negligible effect on the active site hydrolysis of small soluble peptide substrates. Instead, the findings implicate fibronectin II domain interactions by LepteridineTM which impair gelatinase activity, possibly through perturbed tethering of MMP-9 to the gelatin matrix. Molecular modelling analyses were equivocal over interactions at the S1' pocket versus the fibronectin II domain, while molecular dynamic calculations indicated rapid exchange kinetics. No significant degradation of synthetic or natural LepteridineTM in Mānuka honey occurred during simulated gastrointestinal digestion. MMP-9 regulates skin and gastrointestinal inflammatory responses and extracellular matrix remodelling. These results potentially implicate LepteridineTM bioactivity in Mānuka honey's reported beneficial effects on wound healing via topical application and anti-inflammatory actions in gastrointestinal disorder models via oral consumption.
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    Inflammation and the Association of Vitamin D and Depressive Symptomatology.
    (MDPI (Basel, Switzerland), 2021-06) Dogan-Sander E; Mergl R; Willenberg A; Baber R; Wirkner K; Riedel-Heller SG; Röhr S; Schmidt FM; Schomerus G; Sander C
    Depression and vitamin D deficiency are major public health problems. The existing literature indicates the complex relationship between depression and vitamin D. The purpose of this study was to examine whether this relationship is moderated or mediated by inflammation. A community sample (n = 7162) from the LIFE-Adult-Study was investigated, for whom depressive symptoms were assessed via the German version of CES-D scale and serum 25-hydroxyvitamin D (25(OH)D) levels and inflammatory markers (IL-6 and CRP levels, WBC count) were quantified. Mediation analyses were performed using Hayes’ PROCESS macro and regression analyses were conducted to test moderation effects. There was a significant negative correlation between CES-D and 25(OH)D, and positive associations between inflammatory markers and CES-D scores. Only WBC partially mediated the association between 25(OH)D levels and depressive symptoms both in a simple mediation model (ab: −0.0042) and a model including covariates (ab: −0.0011). None of the inflammatory markers showed a moderation effect on the association between 25(OH)D levels and depressive symptoms. This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation. Future studies are needed to examine the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment.
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    Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2
    (Frontiers Media SA, 2022) dos Santos AAC; Rodrigues LE; Alecrim-Zeza AL; de Araújo Ferreira L; Trettel CDS; Gimenes GM; da Silva AF; Sousa-Filho CPB; Serdan TDA; Levada-Pires AC; Hatanaka E; Borges FT; de Barros MP; Cury-Boaventura MF; Bertolini GL; Cassolla P; Marzuca-Nassr GN; Vitzel KF; Pithon-Curi TC; Masi LN; Curi R; Gorjao R; Hirabara SM
    Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1β, INF-α and INF-β, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.
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    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
    (Frontiers Media S A, 2022-12-05) Abshirini M; Coad J; Wolber FM; von Hurst P; Miller MR; Tian HS; Kruger MC; Pozzuoli, A
    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].
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    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
    (JMIR Publications, 2021-10-26) Ilesanmi-Oyelere BL; Roy NC; Kruger MC; Eysenbach G
    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.
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    Bioactive Yoghurt Containing Curcumin and Chlorogenic Acid Reduces Inflammation in Postmenopausal Women
    (MDPI (Basel, Switzerland), 2022-11-02) Ahmed Nasef N; Thota RN; Mutukumira AN; Rutherfurd-Markwick K; Dickens M; Gopal P; Singh H; Garg ML; Bordoni A
    Menopause is marked by a gradual and permanent decrease of estrogen from the ovaries, leading to metabolic and physiological changes in the body. Combined with increased body mass index, postmenopausal women have elevated systemic inflammation and metabolic disturbances leading to increased risk of developing chronic diseases. A bioactive coconut yoghurt containing curcumin and chlorogenic acid was developed with the potential to target inflammatory processes. In this randomized crossover study, healthy postmenopausal women with a BMI of 25-40 were recruited to consume 125 g of either the bioactive or placebo yoghurt. Blood samples were collected at baseline, 30 min, and 1, 2, 3 and 4 h postprandially. Plasma inflammatory markers (TNFα and IL6) and metabolic markers (triglycerides, insulin and glucose) were measured. Participants had significantly lower plasma TNFα Cmax after consumption of the bioactive yoghurt compared to placebo (mean difference = 0.3 pg/mL; p = 0.04). Additionally, plasma TNFα was significantly lower postprandially compared to baseline after consumption of the bioactive yogurt but not the placebo. No differences were observed in the metabolic markers measured. Conclusions: The bioactive yoghurt fortified with curcumin and chlorogenic acid has the potential to reduce inflammatory mediators; however, a larger and longer-term study is required to confirm these findings.