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A double-blinded, randomized, parallel intervention to evaluate biomarker-based nutrition plans for weight loss: The PREVENTOMICS study.
Aldubayan, MA, Pigsborg, K, Gormsen, SMO, Serra, F, Palou, M, Galmés, S, Palou-March, A, Favari, C, Wetzels, M, Calleja, A, et al
Clinical nutrition (Edinburgh, Scotland). 2022;41(8):1834-1844
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Obesity, and particularly abdominal adiposity, is associated with various metabolic abnormalities. Diet has a vital role in preventing and managing obesity, but evidence from clinical studies demonstrates there is a great interindividual variability in response to the same dietary intervention, which likely indicates that no one diet is superior to another. The aim of this study was to examine the efficacy of the PREVENTOMICS (empowering consumers to PREVENT diet-related diseases through OMICS sciences) platform, incorporated in an e-commerce digital tool, for producing more favourable health outcomes over dietary plans based on general diet recommendations, in subjects with overweight or obesity and elevated waist circumference. This study is a 10-week randomised single-centre, parallel-group, double-blinded intervention study. Participants were allocated in a 1:1 ratio, stratified by cluster to either the intervention group (personalised plan) or the control group (generic recommendations). Results show that there isn’t any additional benefit of personalising dietary plans, over a generic approach, on the change in fat mass and body weight in individuals with overweight or obesity and elevated waist circumference. Accordingly, personalisation of the diet did not significantly improve health parameters beyond the changes induced by the control diet. Participants in both groups lost approximately 3 kg of body weight. Authors conclude that based on their findings evidence to translate personalised nutrition approaches into clinical practice is insufficient.
Abstract
BACKGROUND & AIMS Growing evidence suggests that biomarker-guided dietary interventions can optimize response to treatment. In this study, we evaluated the efficacy of the PREVENTOMCIS platform-which uses metabolomic and genetic information to classify individuals into different 'metabolic clusters' and create personalized dietary plans-for improving health outcomes in subjects with overweight or obesity. METHODS A 10-week parallel, double-blinded, randomized intervention was conducted in 100 adults (82 completers) aged 18-65 years, with body mass index ≥27 but <40 kg/m2, who were allocated into either a personalized diet group (n = 49) or a control diet group (n = 51). About 60% of all food was provided free-of-charge. No specific instruction to restrict energy intake was given. The primary outcome was change in fat mass from baseline, evaluated by dual energy X-ray absorptiometry. Other endpoints included body weight, waist circumference, lipid profile, glucose homeostasis markers, inflammatory markers, blood pressure, physical activity, stress and eating behavior. RESULTS There were significant main effects of time (P < 0.01), but no group main effects, or time-by-group interactions, for the change in fat mass (personalized: -2.1 [95% CI -2.9, -1.4] kg; control: -2.0 [95% CI -2.7, -1.3] kg) and body weight (personalized: -3.1 [95% CI -4.1, -2.1] kg; control: -3.3 [95% CI -4.2, -2.4] kg). The difference between groups in fat mass change was -0.1 kg (95% CI -1.2, 0.9 kg, P = 0.77). Both diets resulted in significant improvements in insulin resistance and lipid profile, but there were no significant differences between groups. CONCLUSION Personalized dietary plans did not result in greater benefits over a generic, but generally healthy diet, in this 10-week clinical trial. Further studies are required to establish the soundness of different precision nutrition approaches, and translate this science into clinically relevant dietary advice to reduce the burden of obesity and its comorbidities. CLINICAL TRIAL REGISTRY ClinicalTrials.gov registry (NCT04590989).
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One-year supplementation with Lactobacillus reuteri ATCC PTA 6475 counteracts a degradation of gut microbiota in older women with low bone mineral density.
Li, P, Ji, B, Luo, H, Sundh, D, Lorentzon, M, Nielsen, J
NPJ biofilms and microbiomes. 2022;8(1):84
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Osteoporosis is a highly prevalent bone disease in the elderly population and is characterised by decreased bone mineral density, deteriorated bone microarchitecture, reduced bone strength and increased susceptibility to fragility fractures. Due to the lack of awareness about osteoporosis, there is the need to develop a novel and effective intervention for its prevention and treatment. The aim of this study was to gain mechanistic insight into the effect of Lactobacillus reuteri ATCC PTA 6475 on bone metabolism and identify factors important for a good response to the probiotic. This study was based on a placebo-controlled cohort trial where 68 elderly women had been randomised to supplementation with the probiotic strain L. reuteri ATCC PTA 6475 or placebo. For this secondary analysis, 20 out of the 68 elderly women with bone loss who supplemented with probiotic L. reuteri ATCC PTA 6475 were selected. Results showed that after one-year probiotic supplementation, there was decreased inflammation and significantly increased gene richness of the gut microbiota in the good responders, whereas there was altered microbial composition and function, including enrichment of E. coli and its biofilm formation in the poor responders. Authors conclude that L. reuteri ATCC PTA 6475 supplementation might promote bone formation by modulating the gut microbiota composition and function, which could be crucial for the development of novel osteoporosis treatments.
Abstract
Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher (P < 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved (P < 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P < 0.05 by DESeq2) and its biofilm formation (P < 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.
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Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.
Toups, K, Hathaway, A, Gordon, D, Chung, H, Raji, C, Boyd, A, Hill, BD, Hausman-Cohen, S, Attarha, M, Chwa, WJ, et al
Journal of Alzheimer's disease : JAD. 2022;88(4):1411-1421
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Neurodegenerative diseases such as Alzheimer’s disease are without effective therapeutics. The aim of this study was to compare the effects of a precision medicine approach to historical controls in patients with mild cognitive impairment or early dementia. This study is a proof-of-concept study which recruited twenty-five patients with Alzheimer’s disease or mild cognitive impairment, aged between 50–76 years. Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors. Results show that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time. Authors conclude that their findings indicate that it is possible to reverse cognitive decline in mild cognitive impairment and early dementia with a personalised, precision medicine (/systems medicine) protocol. This is a small study that requires larger scale initiatives, including examining the practicalities of integrating this approach into healthcare systems.
Abstract
BACKGROUND Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. OBJECTIVE To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. METHODS Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months. RESULTS All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. CONCLUSION Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.
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A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.
Basak, SK, Bera, A, Yoon, AJ, Morselli, M, Jeong, C, Tosevska, A, Dong, TS, Eklund, M, Russ, E, Nasser, H, et al
Cancer. 2020;126(8):1668-1682
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APG-157 is a botanical drug containing multiple polyphenols that delivers the active components to oromucosal tissues near the tumour target. APG-157 slowly disintegrates in the oral cavity over 15 to 20 minutes to release the drug substance. The drug substance is a precise, rational combination of multiple molecules derived from Curcuma longa wherein curcumin is the principal component. The main aim of this study was to determine the pharmacokinetics and safety of the orally delivered pastille (APG-157) when used by normal subjects and patients with cancer. This study is a randomised, double-blind, placebo-controlled trial. A total of 32 subjects were enrolled, and 25 completed the study (13 normal individuals and 12 patients with oral cancer). Results demonstrated that transoral APG-157 treatment leads to systemic absorption of curcumin and its analogs. There was a statistically significant concentration reduction in inflammatory cytokines and Bacteroides species noted in the salivary cells. Pre-treatment and post-treatment tumour samples from patients with cancer demonstrated T-cell recruitment to the tumour microenvironment. Authors conclude that APG-157 is absorbed well, reduces inflammation, and attracts T-cells to the tumour thus, it can be potentially used in combination with immunotherapy drugs. Furthermore, a long-term evaluation of immune checkpoint blockade with and without APG-157 could provide a clear understanding of the usefulness of APG-157 as either an adjuvant or neoadjuvant therapeutic agent for patients with advanced or recurrent head and neck cancer.
Abstract
BACKGROUND Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
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Gut microbiota alterations associated with reduced bone mineral density in older adults.
Das, M, Cronin, O, Keohane, DM, Cormac, EM, Nugent, H, Nugent, M, Molloy, C, O'Toole, PW, Shanahan, F, Molloy, MG, et al
Rheumatology (Oxford, England). 2019;58(12):2295-2304
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Osteoporosis, characterised by reduced bone density or ‘brittle bones’ affects a significant number of individuals over the age of 50 worldwide. Contributing factors include calcium and vitamin D deficiency and the presence of other inflammatory conditions. The composition of gut bacteria, the gut microbiome, plays an important role in immune activity and changes in composition have been associated with other inflammatory conditions. This cohort study of 181 individuals at high risk of reduced bone density and fractures, aimed to determine whether different gut microbiota composition is associated with bone density. Dexa scans and faecal samples were used as part of the assessment and confounding factors of diet, BMI, supplementation and medication were included in the analysis. The authors of the study found 6 species of gut bacteria that were significantly altered in numbers in the groups with osteoporosis and osteopenia, after controlling for confounding factors, and suggest that they could be used as markers of disease risk or progression and as a therapeutic target. Nutrition Practitioners working with bone density can focus on supporting the gut microbiome as part of their nutrition protocols.
Abstract
OBJECTIVE To investigate compositional differences in the gut microbiota associated with bone homeostasis and fractures in a cohort of older adults. METHODS Faecal microbiota profiles were determined from 181 individuals with osteopenia (n = 61) or osteoporosis (n = 60), and an age- and gender-matched group with normal BMD (n = 60). Analysis of the 16S (V3-V4 region) amplicon dataset classified to the genus level was used to identify significantly differentially abundant taxa. Adjustments were made for potential confounding variables identified from the literature using several statistical models. RESULTS We identified six genera that were significantly altered in abundance in the osteoporosis or osteopenic groups compared with age- and gender-matched controls. A detailed study of microbiota associations with meta-data variables that included BMI, health status, diet and medication revealed that these meta-data explained 15-17% of the variance within the microbiota dataset. BMD measurements were significantly associated with alterations in the microbiota. After controlling for known biological confounders, five of the six taxa remained significant. Overall microbiota alpha diversity did not correlate to BMD in this study. CONCLUSION Reduced BMD in osteopenia and osteoporosis is associated with an altered microbiota. These alterations may be useful as biomarkers or therapeutic targets in individuals at high risk of reductions in BMD. These observations will lead to a better understanding of the relationship between the microbiota and bone homeostasis.
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A Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients With Nonalcoholic Fatty Liver Disease (NAFLD): A Randomized Clinical Trial.
Dinu, M, Whittaker, A, Pagliai, G, Giangrandi, I, Colombini, B, Gori, AM, Fiorillo, C, Becatti, M, Casini, A, Benedettelli, S, et al
Journal of the American College of Nutrition. 2018;37(6):508-514
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Non-alcoholic fatty liver disease (NAFLD) is prevalent, however early intervention with lifestyle modifications such as weight loss, dietary therapy and physical activity may reverse it. Previous studies have shown that the Mediterranean diet, which includes a large proportion of grains, may reduce NAFLD. However no prior studies have assessed grains in isolation on these individuals. This randomised double blind parallel arm study aimed to assess the effects of a replacement diet with ancient khorasan wheat products on patients with NAFLD. 40 people with mild- moderate NAFLD were assigned to either khorasan wheat diet or a modern wheat grain diet for three months. This comparatively small study found that a khorasan wheat based diet improved liver function and inflammation. However regardless of the diet, measures of oxidative stress, which assesses the imbalance of free radicals and antioxidants in the body, was significantly reduced and some individuals were shown to regress from moderate to mild NAFLD. Nutrition practitioners who have clients with mild-moderate NAFLD may recommend a khorasan wheat based diet in the short term to improve biochemical and inflammatory markers and to potentially reverse disease development.
Abstract
OBJECTIVE KAMUT khorasan is an ancient grain with widely acclaimed health benefits. The aim of this study was to investigate the effects of a replacement diet with ancient khorasan wheat products in patients with NAFLD, in comparison to a similar replacement diet with control products made from organic semi-whole-grain modern wheat. METHODS Forty NAFLD patients (12 M/28 F; age 55.2 ± 10.4 years) with mild to moderate liver steatosis were included. The experimental design was a randomized, double-blind, parallel-arm study with 20 participants assigned to consume either KAMUT khorasan or control wheat products (pasta, bread, crackers, biscuits) over a 3-month period. Anthropometric measurements, blood analyses, and ultrasonography examination were performed at both the beginning and end of each dietary intervention. RESULTS After the implementation of a general linear model for repeated measurements adjusted for baseline demographic details, risk factors, and medication, alanine aminotransferase (ALT) was significantly reduced by 12%, aspartate aminotransferase (AST) by 14%, alkaline phosphatase (ALP) by 8%, and cholesterol by 6% only in the khorasan group (p < 0.05 for all). Similarly, significant reductions in circulating proinflammatory tumor necrosis factor-alpha by 50%, interleukin l-receptor antagonist-alpha by 37%, interleukin-8 by 24%, and interferon gamma by 24% were evident only in participants who consumed the khorasan products (p < 0.05 for all). Finally, significant improvements in the liver steatosis grading, Doppler perfusion index values, and reactive oxygen species (ROS) production were evident after consumption of both the khorasan and control products. CONCLUSIONS This study suggests that a short-term replacement diet with ancient KAMUT khorasan products is most effective in reducing metabolic risk factors and ameliorating the liver profile in patients with NAFLD.
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Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative.
Stout, AC, Barbe, MF, Eaton, CB, Amin, M, Al-Eid, F, Price, LL, Lu, B, Lo, GH, Zhang, M, Pang, J, et al
BMC musculoskeletal disorders. 2018;19(1):1
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Individuals with osteoarthritis (OA) typically present with greater systemic inflammation and impaired glucose homeostasis. Currently it is unclear whether these factors are associated with early-stage OA, namely bone marrow lesions and swelling. The purpose of this cross-sectional study was to investigate the role of inflammation and glucose homeostasis in early-stage OA. Using baseline data from the Osteoarthritis Initiative, 343 participants were enrolled and tested for markers of inflammation and impaired glucose homeostasis. Bone marrow lesions and swelling were also assessed through imaging results. Results indicate that among individuals without OA, those with greater systemic inflammation were more likely to have bone marrow lesions and knee swelling. According to these results, the authors conclude that systemic inflammation and glucose homeostasis are related to structural features of osteoarthritis. Future studies should explore whether these factors are predictive of OA in order to identify therapeutic targets to prevent or delay the onset of knee OA.
Abstract
BACKGROUND Greater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features. We examined if serum concentrations of glucose homeostasis (glucose, glycated serum protein [GSP]) or inflammation (C-reactive protein [CRP]) were associated with prevalent knee bone marrow lesions (BMLs) or effusion among adults without knee OA. METHODS We conducted a cross-sectional study using baseline data from the Osteoarthritis Initiative. We selected participants who had no radiographic knee OA but were at high risk for knee OA. Blinded staff conducted assays for CRP, GSP, and glucose. Readers segmented BML volume and effusion using semi-automated programs. Our outcomes were prevalent BML (knee with a BML volume > 1 cm3) and effusion (knee with an effusion volume > 7.5 cm3). We used logistic regression models with CRP, GSP, or glucose concentrations as the predictors. We adjusted for age, sex, body mass index (BMI), and Physical Activity Scale for the Elderly (PASE) scores. RESULTS We included 343 participants: mean age = 59 ± 9 years, BMI = 27.9 ± 4.5 kg/m2, PASE score = 171 ± 82, and 64% female. Only CRP was associated with BML prevalence (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09 to 1.87). For effusion, we found an interaction between BMI and CRP: only among adults with a BMI <25 kg/m2 was there a significant trend towards a positive association between CRP and effusion (OR = 1.40, 95% CI = 1.00 to 1.97). We detected a U-shaped relationship between GSP and effusion prevalence. Fasting glucose levels were not significantly associated with the presence of baseline effusion or BML. CONCLUSIONS Among individuals without knee OA, CRP may be related to the presence of BMLs and effusion among normal weight individuals. Abnormal GSP may be associated with effusion. Future studies should explore whether inflammation and glucose homeostasis are predictive of symptomatic knee OA.
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Association of dietary patterns, anthropometric measurements, and metabolic parameters with C-reactive protein and neutrophil-to-lymphocyte ratio in middle-aged and older adults with metabolic syndrome in Taiwan: a cross-sectional study.
Syauqy, A, Hsu, CY, Rau, HH, Chao, JC
Nutrition journal. 2018;17(1):106
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Metabolic syndrome, which is classified as having high blood pressure, obesity, high blood glucose and high cholesterol, is believed to be a consequence of the Westernised diet and lifestyle, which has become increasingly common place in several countries worldwide. The Westernised diet comprises of a high intake of saturated fats, meats, processed foods, sweets, salt and food additives, all of which can add to the burden of inflammatory processes. The objective of this cross-sectional study was to investigate associations evident between diet, body composition and metabolic measurements (such as BMI and blood pressure) with inflammatory markers; C-reactive protein and neutrophil-to-lymphocyte ratio (inflammatory markers that increase in response to inflammation), in adults diagnosed with metabolic syndrome. Researchers found that regardless of gender or age, there was a direct association with C-reactive protein and neutrophil-to-lymphocyte ratio and metabolic syndrome. The subjects who consumed a higher amount of ‘Westernised foods’ showed higher levels of inflammatory markers when compared to those who a consumed a more healthful diet.
Abstract
BACKGROUND Metabolic syndrome is commonly associated with inflammation. The underlying factors of inflammation in metabolic syndrome are not fully understood. The objective of the study was to determine the association of dietary patterns, anthropometric measurements, and metabolic parameters with inflammatory markers in middle-aged and older adults with metabolic syndrome in Taiwan. METHODS A total of 26,016 subjects aged ≥35 y with metabolic syndrome were recruited from Mei Jau institution between 2004 and 2013 for a cross sectional study. Metabolic syndrome was defined by the International Diabetes Federation. Multivariate logistic regression was performed to evaluate the association of dietary patterns, anthropometric measurements, and metabolic parameters with C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in men and women with metabolic syndrome. Crude and adjusted models were analyzed by gender. RESULTS The western dietary pattern, obesity, high body fat, high waist or hip circumference, and high waist-to-hip ratio were significantly associated with increased odds ratios of high CRP and NLR in both genders. High systolic or diastolic blood pressure (BP), low high-density lipoprotein-cholesterol (HDL-C), high low-density lipoprotein-cholesterol (LDL-C), high total cholesterol (TC), high serum triglycerides (TG), and high fasting blood glucose (FBG) were significantly correlated with increased odds ratios of high CRP in both genders. Low HDL-C, high LDL-C, high serum TG, and high FBG were significantly associated with increased odds ratios of high NLR in both genders. However, high systolic (OR = 1.124, 95% CI 1.047-1.206, P < 0.01) or diastolic BP (OR = 1.176, 95% CI 1.087-1.273, P < 0.001) and high TC (OR = 1.138, 95% CI 1.062-1.220, P < 0.001) were significantly correlated with increased odds ratios of high NLR only in men. CONCLUSIONS The western dietary pattern, obese-related anthropometric parameters, and most components of metabolic syndrome are positively associated with CRP levels and NLR in men and women with metabolic syndrome.
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Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
Jernerén, F, Elshorbagy, AK, Oulhaj, A, Smith, SM, Refsum, H, Smith, AD
The American journal of clinical nutrition. 2015;102(1):215-21
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Mild cognitive impairment (MCI) is a characterised by a decline in cognitive function between normal aging and the development of dementia. While brain atrophy occurs in normal aging, patients with MCI or dementia exhibit much higher rates of atrophy. Results from a recent trial demonstrated that homocysteine-lowering B vitamins resulted in a significant reduction in brain atrophy rates, and links between omega-3 fatty acids and homocysteine have been suggested. The purpose of this study was to investigate whether plasma omega-3 fatty acid concentrations modify the treatment effect of B vitamins on brain atrophy rates among 168 elderly adults with MCI. Participants were randomly assigned to receive placebo or high-dose vitamin B supplementation and both brain scans and plasma concentrations were done at baseline and 2 years. The findings of this study demonstrated that, in patients with high omega-3 plasma concentrations, B vitamin supplementation slowed brain atrophy by 40% compared with those in the placebo group. This indicates that the effect of B vitamin supplementation on brain atrophy rates depend on plasma omega-3 fatty acid concentrations.
Abstract
BACKGROUND Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. OBJECTIVE We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). DESIGN This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. RESULTS There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. CONCLUSIONS The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.
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Intake of red wine in different meals modulates oxidized LDL level, oxidative and inflammatory gene expression in healthy people: a randomized crossover trial.
Di Renzo, L, Carraro, A, Valente, R, Iacopino, L, Colica, C, De Lorenzo, A
Oxidative medicine and cellular longevity. 2014;2014:681318
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The traditional Mediterranean diet is known to reduce the risk of developing several chronic diseases including cardiovascular disease (CVD). The major underlying factors of CVD are oxidative stress and chronic inflammation, and oxidised low-density lipoprotein (ox-LDL) particles have been associated with increased CVD risk. The aim of this crossover trial was to evaluate the impact of various meal combinations on ox-LDL status and genetic expression of oxidative stress and inflammation. A total of 24 participants were analysed after consumption of four different meal combinations with washout periods in between: Mediterranean meal, McDonald’s meal, both with and without red wine. The findings of this study showed a significant reduction of ox-LDL depending on the quality of meal consumed, and found red wine to have a protective effect. The results of this study indicate that the antioxidant potential of nutrients found in the Mediterranean diet and red wine may be important for reducing inflammation and oxidative stress in chronic disease.
Abstract
Several studies have found that adherence to the Mediterranean Diet, including consumption of red wine, is associated with beneficial effects on oxidative and inflammatory conditions. We evaluate the outcome of consumption of a McDonald's Meal (McD) and a Mediterranean Meal (MM), with and without the additive effect of red wine, in order to ascertain whether the addition of the latter has a positive impact on oxidized (ox-) LDL and on expression of oxidative and inflammatory genes. A total of 24 subjects were analyzed for ox-LDL, CAT, GPX1, SOD2, SIRT2, and CCL5 gene expression levels, before and after consumption of the 4 different meal combinations with washout intervals between each meal. When red wine is associated with McD or MM, values of ox-LDL are lowered (P < 0.05) and expression of antioxidant genes is increased, while CCL5 expression is decreased (P < 0.05). SIRT2 expression after MM and fasting with red wine is significantly correlated with downregulation of CCL5 and upregulation of CAT (P < 0.001). GPX1 increased significantly in the comparison between baseline and all conditions with red wine. We highlighted for the first time the positive effect of red wine intake combined with different but widely consumed meal types on ox-LDL and gene expression. Trial Registration. This trial is registered with ClinicalTrials.gov NCT01890070.