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A systematic review and meta-analysis of randomized controlled trials to evaluate plant-based omega-3 polyunsaturated fatty acids in nonalcoholic fatty liver disease patient biomarkers and parameters.
Moore, E, Patanwala, I, Jafari, A, Davies, IG, Kirwan, RP, Newson, L, Mazidi, M, Lane, KE
Nutrition reviews. 2024;(2):143-165
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Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is prevalent in 25-30% of British and European populations, representing a potential global public health crisis. Marine omega-3 (n-3) polyunsaturated fatty acids offer well-evidenced benefits to NAFLD biomarkers; however, the effect of plant-based n-3 has not been evaluated with a systematic review and meta-analysis. OBJECTIVE The review aimed to systematically evaluate the effect of plant-based n-3 supplementation on NAFLD surrogate biomarkers and parameters. DATA SOURCES Medline (EBSCO), PubMed, CINAHL (EBSCO), Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and Google Scholar databases were searched to identify randomized controlled trials published between January 1970 and March 2022 evaluating the impact of plant-based n-3 interventions on diagnosed NAFLD. The review followed the PRISMA checklist and is PROSPERO registered (CRD42021251980). DATA EXTRACTION A random-effects model and generic inverse variance methods synthesized quantitative data, followed by a leave-one-out method for sensitivity analysis. We identified 986 articles; after the application of selection criteria, six studies remained with 362 patients with NAFLD. RESULTS The meta-analysis showed that plant-based n-3 fatty acid supplementation significantly reduced alanine aminotransferase (ALT) (mean difference: 8.04 IU/L; 95% confidence interval: 14.70, 1.38; I2 = 48.61%) and plasma/serum triglycerides (44.51 mg/dL; 95% confidence interval: -76.93, -12.08; I2 = 69.93%), alongside body-composition markers in patients with NAFLD (P < 0.05). CONCLUSION Plant-based n-3 fatty acid supplementation improves ALT enzyme biomarkers, triglycerides, body mass index, waist circumference, and weight loss when combined with lifestyle interventions to increase physical activity and a calorie-controlled diet. Further research is needed to identify the most effective plant-based n-3 sources in larger numbers of patients with NAFLD over longer study durations. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42021251980.
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The Effect of Carbohydrate Restriction on Lipids, Lipoproteins, and Nuclear Magnetic Resonance-Based Metabolites: CALIBER, a Randomised Parallel Trial.
McCullough, D, Harrison, T, Enright, KJ, Amirabdollahian, F, Mazidi, M, Lane, KE, Stewart, CE, Davies, IG
Nutrients. 2023;(13)
Abstract
Low-carbohydrate high-fat (LCHF) diets can be just as effective as high-carbohydrate, lower-fat (HCLF) diets for improving cardiovascular disease risk markers. Few studies have compared the effects of the UK HCLF dietary guidelines with an LCHF diet on lipids and lipoprotein metabolism using high-throughput NMR spectroscopy. This study aimed to explore the effect of an ad libitum 8-week LCHF diet compared to an HCLF diet on lipids and lipoprotein metabolism and CVD risk factors. For 8 weeks, n = 16 adults were randomly assigned to follow either an LCHF (n = 8, <50 g CHO p/day) or an HCLF diet (n = 8). Fasted blood samples at weeks 0, 4, and 8 were collected and analysed for lipids, lipoprotein subclasses, and energy-related metabolism markers via NMR spectroscopy. The LCHF diet increased (p < 0.05) very small VLDL, IDL, and large HDL cholesterol levels, whereas the HCLF diet increased (p < 0.05) IDL and large LDL cholesterol levels. Following the LCHF diet alone, triglycerides in VLDL and HDL lipoproteins significantly (p < 0.05) decreased, and HDL phospholipids significantly (p < 0.05) increased. Furthermore, the LCHF diet significantly (p < 0.05) increased the large and small HDL particle concentrations compared to the HCLF diet. In conclusion, the LCHF diet may reduce CVD risk factors by reducing triglyceride-rich lipoproteins and improving HDL functionality.
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Dietary inflammatory index and elevated serum C-reactive protein: A systematic review and meta-analysis.
Mohammadi, S, Hosseinikia, M, Ghaffarian-Bahraman, A, Clark, CCT, Davies, IG, Yousefi Rad, E, Saboori, S
Food science & nutrition. 2023;(10):5786-5798
Abstract
Diet can affect the inflammatory state of the body. Accordingly, the dietary inflammatory index (DII) has been developed to quantify the inflammatory properties of food items. This study sought to investigate the association between dietary inflammation index (DII) and the odds ratio of elevated CRP (E-CRP) through a systematic review and meta-analysis study. The International electronic databases of PubMed, Web of Science (ISI), and Scopus were searched until May 2023 to find related articles. From 719 studies found in the initial search, 14 studies, with a total sample size of 59,941 individuals, were included in the meta-analysis. The calculated pooled odds ratio (OR) of E-CRP in the highest DII category was 1.39 (95% CI: 1.06, 1.14, test for heterogeneity: p = .63, and I 2 = .0%) in comparison with the lowest DII category. Also, the results of this study showed that each unit increase in DII as a continuous variable generally elicited a 10% increase in the odds of E-CRP (OR 1.10, 95% CI 1.06, 1.14, test for heterogeneity: p = .63, and I 2 = .0%). Subgroup meta-analyses showed that there is a higher E-CRP odds ratio for the articles that reported energy-adjusted DII (E-DII) instead of DII, the studies that measured CRP instead of hs-CRP, and the studies that used 24-h recall instead of FFQ as the instrument of dietary intake data collection. Individuals with a higher DII were estimated to have higher chances of developing elevated serum CRP. This value was influenced by factors such as the participants' nationality, instruments of data collection, methods used to measure inflammatory biomarkers, study design, and data adjustments. However, future well-designed studies can help provide a more comprehensive understanding of the inflammatory properties of diet and inflammatory serum biomarkers.
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The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial.
McCullough, D, Harrison, T, Boddy, LM, Enright, KJ, Amirabdollahian, F, Schmidt, MA, Doenges, K, Quinn, K, Reisdorph, N, Mazidi, M, et al
Nutrients. 2022;14(18)
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Insulin resistance is a complex metabolic disorder that increases the risk of type 2 diabetes (T2D) and is integral to cardiometabolic disease. The aim of this study was to investigate the impact of an ad libitum 8-week low-carbohydrate high fat (LCHF) diet compared with a high-carbohydrate low-fat (HCLF) diet (current UK guidelines) on cardiometabolic risk factors, the plasma metabolome, and markers of glucose and insulin metabolism in adults with a slightly elevated cardiometabolic risk. This is a parallel randomised design study where participants were randomly assigned to either a HCLF (n = 8), or a LCHF (n = 8) diet for 8 weeks. Results show that both the LCHF and HCLF diets exerted benefits on markers of insulin resistance and metabolic risk. Both diets had no effect on fasting glucose levels, but insulin concentrations significantly decreased comparably with both diets. Authors conclude that following either a LCHF or HCLF diet may reduce the risk of developing T2D by reducing markers of insulin resistance.
Abstract
High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.
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Bioavailability and conversion of plant based sources of omega-3 fatty acids - a scoping review to update supplementation options for vegetarians and vegans.
Lane, KE, Wilson, M, Hellon, TG, Davies, IG
Critical reviews in food science and nutrition. 2022;(18):4982-4997
Abstract
Omega-3 (n-3) fatty acids offer a plethora of health benefits with the majority of evidence showing beneficial effects from marine sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Emerging research examines the effects of n-3 dietary intakes on blood markers of vegetarians and vegans, but official guidance for plant based marine alternatives is yet to reach consensus. This scoping review provides an overview of trials investigating bioavailability of plant n-3 oils including EPA and DHA conversion. Searches of MEDLINE, PubMed, CINAHL and clinical trial registers identified randomized controlled trials from January 2010 to September 2020. The 'Omega-3 index' (EPA + DHA (O3I)), was used to compare n-3 status, metabolic conversion and bioavailability. Two reviewers independently screened articles and extracted data on outcomes. From 639 identified articles, screening and eligibility checks gave 13 articles. High dose flaxseed or echium seed oil supplements, provided no increases to O3I and some studies showed reductions. However, microalgal oil supplementation increased O3I levels for all studies. Findings indicate preliminary advice for vegetarians and vegans is regular consumption of preformed EPA and DHA supplements may help maintain optimal O3I. Further studies should establish optimum EPA and DHA ratios and dosages in vegetarian and vegan populations.
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Relationship between lipoproteins, thrombosis, and atrial fibrillation.
Ding, WY, Protty, MB, Davies, IG, Lip, GYH
Cardiovascular research. 2022;(3):716-731
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The prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow's triad of hypercoagulability, structural abnormalities, and blood stasis. More recently, there is emerging evidence that lipoproteins are implicated in this process, beyond their traditional role in atherosclerosis. In this review, we provide an overview of the various lipoproteins and explore the association between lipoproteins and AF, the effects of lipoproteins on haemostasis, and the potential contribution of lipoproteins to thrombogenesis in AF. There are several types of lipoproteins based on size, lipid composition, and apolipoprotein category, namely: chylomicrons, very low-density lipoprotein, low-density lipoprotein (LDL), intermediate-density lipoprotein, and high-density lipoprotein. Each of these lipoproteins may contain numerous lipid species and proteins with a variety of different functions. Furthermore, the lipoprotein particles may be oxidized causing an alteration in their structure and content. Of note, there is a paradoxical inverse relationship between total cholesterol and LDL cholesterol (LDL-C) levels, and incident AF. The mechanism by which this occurs may be related to the stabilizing effect of cholesterol on myocardial membranes, along with its role in inflammation. Overall, specific lipoproteins may interact with haemostatic pathways to promote excess platelet activation and thrombin generation, as well as inhibiting fibrinolysis. In this regard, LDL-C has been shown to be an independent risk factor for thromboembolic events in AF. The complex relationship between lipoproteins, thrombosis and AF warrants further research with an aim to improve our knowledge base and contribute to our overall understanding of lipoprotein-mediated thrombosis.
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Protein interventions augment the effect of resistance exercise on appendicular lean mass and handgrip strength in older adults: a systematic review and meta-analysis of randomized controlled trials.
Kirwan, RP, Mazidi, M, Rodríguez García, C, Lane, KE, Jafari, A, Butler, T, Perez de Heredia, F, Davies, IG
The American journal of clinical nutrition. 2022;(3):897-913
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BACKGROUND Increased protein intake is suggested as a strategy to slow or reverse the loss of muscle mass and strength observed in sarcopenia, but results from studies that directly tested this possibility have been inconsistent. OBJECTIVES We assessed the evidence on the effects of whole protein supplementation or higher-protein diets, without the use of amino acids or supplements known to stimulate hypertrophy, alone or in combination with resistance exercise (RE) interventions, on lean body mass (LBM) and strength in older adults. METHODS A systematic search was conducted using PubMed, Medline, Web of Science, and Cochrane CENTRAL databases from January 1990 to July 2021. Randomized controlled trials that assessed the effects of protein supplementation and/or higher-protein dietary interventions in older adults (mean age ≥50 y) on total LBM, appendicular lean mass (ALM), and handgrip (HG) and knee extension (KE) strength were included. RESULTS Twenty-eight studies were identified. In pooled analysis, compared with lower protein controls, protein supplementation did not have a significant positive effect on total LBM [weighted mean difference in change (WMD): 0.34; 95% CI: -0.21, 0.89; I2 = 90.01%], ALM (WMD: 0.4; 95% CI: -0.01, 0.81; I2 = 90.38%), HG strength (WMD: 0.69; 95% CI: -0.69, 2.06; I2 = 94.52%), or KE strength (WMD: 1.88; 95% CI: -0.6, 4.35; I2 = 95.35%). However, in interventions that used also RE, statistically significant positive effects of protein were observed for ALM (WMD: 0.54; 95% CI: 0.03, 1.05; I2 = 89.76%) and HG (WMD: 1.71; 95% CI: 0.12, 3.30; I2 = 88.71%). Meta-regression revealed no significant association between age, per-meal protein dose, duration, and baseline protein intake with change in any outcome. Subgroup analysis revealed the statistically significant effects on ALM occurred only in sarcopenic/frail populations (WMD: 0.88; 95% CI: 0.51, 1.25; I2 = 79.0%). Most studies (n = 22) had some risk of bias. CONCLUSIONS In older adults performing RE, increased protein intake leads to greater ALM and HG strength compared with lower protein controls. Without RE, protein has no additional benefit on changes in total LBM, ALM, or HG strength.
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Feasibility of a high-PRotein Mediterranean-style diet and resistance Exercise in cardiac Rehabilitation patients with sarcopenic obesity (PRiMER): Study protocol for a randomised control trial.
McCullough, D, Kirwan, R, Butler, T, Perez de Heredia, F, Thijssen, D, Lip, GYH, Mills, J, Davies, IG
Clinical nutrition ESPEN. 2021;:492-498
Abstract
BACKGROUND Cardiac rehabilitation (CR) is an essential component of long-term recovery following a cardiac event. Typical CR may not be optimal for patients presenting with sarcopenic obesity (SO) who present with reduced muscle mass and elevated adipose tissue, and may indicate greater cardiovascular disease (CVD) risk. Resistance exercise and high-protein diets are known to increase muscle mass, while Mediterranean-style diets have been shown to reduce CVD risk. A high-protein Mediterranean-style diet combined with resistance exercise intervention is yet to be trialled in cardiac rehabilitation populations. OBJECTIVES Primary outcome: to determine the feasibility of such an intervention by investigating the perceptions, acceptance and adherence to a resistance exercise protocol and high-protein Mediterranean style diet in a UK cardiac rehabilitation population with SO. Secondary outcome: to trial this protocol ahead of a fully powered clinical study. METHODS Eligible cardiac rehabilitation patients will be randomised to one of the following: 1) a control group (standard CR), 2) high-protein Mediterranean-style diet, 3) resistance exercise group, or 4) both high-protein Mediterranean-style diet and resistance exercise group. The pilot study will last 12 weeks. Measures of body composition (dual energy x-ray absorptiometry) grip strength, CVD risk (e.g., fasting triglycerides, glucose, cholesterol) and dietary adherence will be assessed at baseline and after 12 weeks. To compare groups, a mixed model ANOVA (time x intervention) will be performed. Patient participant involvement throughout the development of this project will be used to determine the feasibility of a future, fully powered, randomised control trial. A feasibility questionnaire will help establish the proportion of eligible participants, their willingness to be randomised, response rates, and ethical considerations. Furthermore, focus groups, food tasting and telephone interviews will be conducted to assess the acceptability of recipes and exercise protocols provided. DISCUSSION This pilot trial will determine whether a fully powered, multi-centred randomised control trial in CR patients with SO can be implemented. The information received from patient involvement will be invaluable for identifying possible barriers to participation and tailoring interventions to participant needs, helping to increase the likelihood of long-term compliance to health-promoting lifestyle changes. REGISTRATION This study is registered at clinicaltrials.gov (NCT04272073), registered on 17/02/2020, https://clinicaltrials.gov/ct2/show/NCT04272073. DATE AND VERSION 28/12/20 version 3.0.
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How the love of muscle can break a heart: Impact of anabolic androgenic steroids on skeletal muscle hypertrophy, metabolic and cardiovascular health.
McCullough, D, Webb, R, Enright, KJ, Lane, KE, McVeigh, J, Stewart, CE, Davies, IG
Reviews in endocrine & metabolic disorders. 2021;(2):389-405
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It is estimated 6.4% of males and 1.6% of females globally use anabolic-androgenic steroids (AAS), mostly for appearance and performance enhancing reasons. In combination with resistance exercise, AAS use increases muscle protein synthesis resulting in skeletal muscle hypertrophy and increased performance. Primarily through binding to the androgen receptor, AAS exert their hypertrophic effects via genomic, non-genomic and anti-catabolic mechanisms. However, chronic AAS use also has a detrimental effect on metabolism ultimately increasing the risk of cardiovascular disease (CVD). Much research has focused on AAS effects on blood lipids and lipoproteins, with abnormal concentrations of these associated with insulin resistance, hypertension and increased visceral adipose tissue (VAT). This clustering of interconnected abnormalities is often referred as metabolic syndrome (MetS). Therefore, the aim of this review is to explore the impact of AAS use on mechanisms of muscle hypertrophy and markers of MetS. AAS use markedly decreases high-density lipoprotein cholesterol (HDL-C) and increases low-density lipoprotein cholesterol (LDL-C). Chronic AAS use also appears to cause higher fasting insulin levels and impaired glucose tolerance and possibly higher levels of VAT; however, research is currently lacking on the effects of AAS use on glucose metabolism. While cessation of AAS use can restore normal lipid levels, it may lead to withdrawal symptoms such as depression and hypogonadism that can increase CVD risk. Research is currently lacking on effective treatments for withdrawal symptoms and further long-term research is warranted on the effects of AAS use on metabolic health in males and females.
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Sarcopenia during COVID-19 lockdown restrictions: long-term health effects of short-term muscle loss.
Kirwan, R, McCullough, D, Butler, T, Perez de Heredia, F, Davies, IG, Stewart, C
GeroScience. 2020;(6):1547-1578
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The COVID-19 pandemic is an extraordinary global emergency that has led to the implementation of unprecedented measures in order to stem the spread of the infection. Internationally, governments are enforcing measures such as travel bans, quarantine, isolation, and social distancing leading to an extended period of time at home. This has resulted in reductions in physical activity and changes in dietary intakes that have the potential to accelerate sarcopenia, a deterioration of muscle mass and function (more likely in older populations), as well as increases in body fat. These changes in body composition are associated with a number of chronic, lifestyle diseases including cardiovascular disease (CVD), diabetes, osteoporosis, frailty, cognitive decline, and depression. Furthermore, CVD, diabetes, and elevated body fat are associated with greater risk of COVID-19 infection and more severe symptomology, underscoring the importance of avoiding the development of such morbidities. Here we review mechanisms of sarcopenia and their relation to the current data on the effects of COVID-19 confinement on physical activity, dietary habits, sleep, and stress as well as extended bed rest due to COVID-19 hospitalization. The potential of these factors to lead to an increased likelihood of muscle loss and chronic disease will be discussed. By offering a number of home-based strategies including resistance exercise, higher protein intakes and supplementation, we can potentially guide public health authorities to avoid a lifestyle disease and rehabilitation crisis post-COVID-19. Such strategies may also serve as useful preventative measures for reducing the likelihood of sarcopenia in general and in the event of future periods of isolation.