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Total Dietary Fat Intake, Fat Quality, and Health Outcomes: A Scoping Review of Systematic Reviews of Prospective Studies.
Schwingshackl, L, Zähringer, J, Beyerbach, J, Werner, SS, Heseker, H, Koletzko, B, Meerpohl, JJ
Annals of nutrition & metabolism. 2021;(1):4-15
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INTRODUCTION We conducted a scoping review of systematic reviews (SRs) on dietary fat intake and health outcomes in human adults within the context of a position paper by the "International Union of Nutritional Sciences Task force on Dietary Fat Quality" tasked to summarize the available evidence and provide dietary recommendations. METHODS We systematically searched several databases for relevant SRs of randomized controlled trials (RCTs) and/or prospective cohort studies published between 2015 and 2019 assessing the association between dietary fat and health outcomes. RESULTS Fifty-nine SRs were included. The findings from SRs of prospective cohort studies, which frequently compare the highest versus lowest intake categories, found mainly no association of total fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) with risk of chronic diseases. SRs of RCTs applying substitution analyses indicate that SFA replacement with PUFA and/or MUFA improves blood lipids and glycemic control, with the effect of PUFA being more pronounced. A higher intake of total trans-fatty acid (TFA), but not ruminant TFA, was probably associated with an increased risk of mortality and cardiovascular disease based on existing SRs. CONCLUSION Overall, the available published evidence deems it reasonable to recommend replacement of SFA with MUFA and PUFA and avoidance of consumption of industrial TFA.
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Fluvastatin for lowering lipids.
Adams, SP, Sekhon, SS, Tsang, M, Wright, JM
The Cochrane database of systematic reviews. 2018;(3):CD012282
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BACKGROUND Fluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known. OBJECTIVES Primary objectiveTo quantify the effects of various doses of fluvastatin on blood total cholesterol, low-density lipoprotein (LDL cholesterol), high-density lipoprotein (HDL cholesterol), and triglycerides in participants with and without evidence of cardiovascular disease.Secondary objectivesTo quantify the variability of the effect of various doses of fluvastatin.To quantify withdrawals due to adverse effects (WDAEs) in randomised placebo-controlled trials. SEARCH METHODS The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to February Week 2 2017), MEDLINE In-Process, MEDLINE Epub Ahead of Print, Embase (1974 to February Week 2 2017), the World Health Organization International Clinical Trials Registry Platform, CDSR, DARE, Epistemonikos and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. No language restrictions were applied. SELECTION CRITERIA Randomised placebo-controlled and uncontrolled before and after trials evaluating the dose response of different fixed doses of fluvastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from placebo-controlled and uncontrolled before and after trials into Review Manager 5 as continuous and generic inverse variance data, respectively. WDAEs information was collected from the placebo-controlled trials. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases. MAIN RESULTS One-hundred and forty-five trials (36 placebo controlled and 109 before and after) evaluated the dose-related efficacy of fluvastatin in 18,846 participants. The participants were of any age with and without evidence of cardiovascular disease, and fluvastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of fluvastatin on blood HDL cholesterol. Fluvastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 15% to 33%, total cholesterol by 11% to 25% and triglycerides by 3% to 17.5%. For every two-fold dose increase there was a 6.0% (95% CI 5.4 to 6.6) decrease in blood LDL cholesterol, a 4.2% (95% CI 3.7 to 4.8) decrease in blood total cholesterol and a 4.2% (95% CI 2.0 to 6.3) decrease in blood triglycerides. The quality of evidence for these effects was judged to be high. When compared to atorvastatin and rosuvastatin, fluvastatin was about 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin at reducing LDL cholesterol. Very low quality of evidence showed no difference in WDAEs between fluvastatin and placebo in 16 of 36 of these short-term trials (risk ratio 1.52 (95% CI 0.94 to 2.45). AUTHORS' CONCLUSIONS Fluvastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, fluvastatin is 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin. This review did not provide a good estimate of the incidence of harms associated with fluvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 56% of the placebo-controlled trials.
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The role of Omega-3 and Omega-9 fatty acids for the treatment of neuropathic pain after neurotrauma.
Galán-Arriero, I, Serrano-Muñoz, D, Gómez-Soriano, J, Goicoechea, C, Taylor, J, Velasco, A, Ávila-Martín, G
Biochimica et biophysica acta. Biomembranes. 2017;(9 Pt B):1629-1635
Abstract
Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA) and eicosapentaenoic acid (EPA), mediate neuroactive effects in experimental models of traumatic peripheral nerve and spinal cord injury. Cellular mechanisms of PUFAs include reduced neuroinflammation and oxidative stress, enhanced neurotrophic support, and activation of cell survival pathways. Bioactive Omega-9 monounsaturated fatty acids, such as oleic acid (OA) and 2-hydroxy oleic acid (2-OHOA), also show therapeutic effects in neurotrauma models. These FAs reduces noxious hyperreflexia and pain-related anxiety behavior following peripheral nerve injury and improves sensorimotor function following spinal cord injury (SCI), including facilitation of descending inhibitory antinociception. The relative safe profile of neuroactive fatty acids (FAs) holds promise for the future clinical development of these molecules as analgesic agents. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
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Effects of Saturated Fat, Polyunsaturated Fat, Monounsaturated Fat, and Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and Meta-analysis of Randomised Controlled Feeding Trials.
Imamura, F, Micha, R, Wu, JH, de Oliveira Otto, MC, Otite, FO, Abioye, AI, Mozaffarian, D
PLoS medicine. 2016;(7):e1002087
Abstract
BACKGROUND Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis. METHODS AND FINDINGS We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias. CONCLUSIONS This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.
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Dietary Fatty Acids: Is it Time to Change the Recommendations?
Nettleton, JA, Lovegrove, JA, Mensink, RP, Schwab, U
Annals of nutrition & metabolism. 2016;(4):249-57
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Limiting the saturated fatty acid (SAFA) consumption forms the basis of dietary fat recommendations for heart health, despite several meta-analyses demonstrating no link between dietary SAFA and the risk of cardiovascular disease (CVD). Three experts on dietary fat and health discussed the evidence of reducing SAFA intake at a symposium of the Federation of European Nutrition Societies in Berlin, Germany, October 23, 2015. Ronald P. Mensink, Maastricht University, the Netherlands, discussed the evidence linking dietary fatty acids and CVD risk. He emphasized the importance of the replacement nutrient(s) when SAFA intake is reduced. Julie Lovegrove, University of Reading, UK, addressed the question of whether higher intakes of unsaturated fatty acids are beneficial. She discussed the replacement of SAFA by polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA), noting the reduction in CVD risk with PUFA replacement and in CVD risk markers with MUFA replacement of SAFA. Ursula Schwab, University of Eastern Finland, Kuopio, Finland, discussed the importance of dietary patterns in achieving reduced risk of CVD, observing that several dietary patterns following the principles of a health-promoting diet and adapted to local customs, food preferences and seasonality are effective in reducing the risk of CVD, type 2 diabetes and other chronic diseases. This paper summarizes the symposium presentations.
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Metabolic Effects of Monounsaturated Fatty Acid-Enriched Diets Compared With Carbohydrate or Polyunsaturated Fatty Acid-Enriched Diets in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Qian, F, Korat, AA, Malik, V, Hu, FB
Diabetes care. 2016;(8):1448-57
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OBJECTIVE Dietary interventions in patients with type 2 diabetes (T2D) are important for preventing long-term complications. Although a healthy diet is crucial, there is still uncertainty about the optimal macronutrient composition. We performed a meta-analysis comparing diets high in cis-monounsaturated fatty acids (MUFA) to diets high in carbohydrates (CHO) or in polyunsaturated fatty acids (PUFA) on metabolic risk factors in patients with T2D. RESEARCH DESIGN AND METHODS We systematically reviewed PubMed, MEDLINE, and Cochrane databases and prior systematic reviews and meta-analyses to identify interventions assessing HbA1c, fasting plasma glucose and insulin, LDL and HDL cholesterol, triglycerides, body weight, or systolic/diastolic blood pressure. Meta-analyses were conducted using both fixed- and random-effects models to calculate the weighted mean difference (WMD) and 95% CI. RESULTS We identified 24 studies totaling 1,460 participants comparing high-MUFA to high-CHO diets and 4 studies totaling 44 participants comparing high-MUFA to high-PUFA diets. When comparing high-MUFA to high-CHO diets, there were significant reductions in fasting plasma glucose (WMD -0.57 mmol/L [95% CI -0.76, -0.39]), triglycerides (-0.31 mmol/L [-0.44, -0.18]), body weight (-1.56 kg [-2.89, -0.23]), and systolic blood pressure (-2.31 mmHg [-4.13, -0.49]) along with significant increases in HDL cholesterol (0.06 mmol/L [0.02, 0.10]). When high-MUFA diets were compared with high-PUFA diets, there was a significant reduction in fasting plasma glucose (-0.87 mmol/L [-1.67, -0.07]). All of the outcomes had low to medium levels of heterogeneity, ranging from 0.0 to 69.5% for diastolic blood pressure (Phet = 0.011). CONCLUSIONS Our meta-analysis provides evidence that consuming diets high in MUFA can improve metabolic risk factors among patients with T2D.
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Effect of dietary Fatty acids on human lipoprotein metabolism: a comprehensive update.
Ooi, EM, Watts, GF, Ng, TW, Barrett, PH
Nutrients. 2015;(6):4416-25
Abstract
Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA) consumption diminished hepatic triglyceride-rich lipoprotein (TRL) secretion and enhanced TRL to low-density lipoprotein (LDL) conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL) cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids.
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Effects of monounsaturated fatty acids on cardiovascular risk factors: a systematic review and meta-analysis.
Schwingshackl, L, Strasser, B, Hoffmann, G
Annals of nutrition & metabolism. 2011;(2-4):176-86
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The appropriate pattern of macronutrient distribution for dietary protocols aimed at treating or preventing obesity and its associated cardiovascular diseases is still a controversial topic of discussion. Recommendations considering a specific percentage or range for monounsaturated fatty acids (MUFA) are rare. It was the aim of this study to analyze long-term, randomized, controlled dietary intervention trials and to investigate the effects of MUFA on the biomarkers of obesity and cardiovascular risk factors. Dietary regimens with a high amount of MUFA (>12%) were compared to those with ≤12%. The biomarkers taken into account were weight, waist circumference, fat mass, total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, systolic and diastolic blood pressure, as well as C-reactive protein. A total of 12 studies met the inclusion criteria. Data analysis was performed using the Review Manager 5.0.25 software. Significant differences between high- and low-MUFA protocols could be observed with respect to fat mass [-1.94 kg (confidence interval -3.72, -0.17), p = 0.03], systolic blood pressure [-2.26 mm Hg (confidence interval -4.28, -0.25), p = 0.03] and diastolic blood pressure [-1.15 mm Hg (confidence interval -1.96, -0.34), p = 0.005] favoring the dietary protocols with >12% MUFA. Therefore, MUFA might represent a useful tool in the design of dietary regimens for obesity and cardiovascular disease.
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Effects of monounsaturated fatty acids on glycaemic control in patients with abnormal glucose metabolism: a systematic review and meta-analysis.
Schwingshackl, L, Strasser, B, Hoffmann, G
Annals of nutrition & metabolism. 2011;(4):290-6
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BACKGROUND/AIMS: In 2008, the American Diabetes Association recommended low-carbohydrate or low-fat diets for weight management in patients with established type 2 diabetes (T2D), while the amount of monounsaturated fatty acids (MUFA) was not specified. This systematic review focused on the effects of diets high in MUFA versus diets low in MUFA on important risk factors of T2D (i.e. plasma glucose, insulin, homeostasis model assessment of insulin resistance and glycosylated haemoglobin, HbA1c). METHODS Nine randomized controlled intervention trials with a total of 1,547 participants and a running time of at least 6 months, comparing diets high versus low in MUFA among adults with abnormal glucose metabolism (T2D, impaired glucose tolerance and insulin resistant), being overweight or obese, have been included in the meta-analysis. We performed a random effects meta-analysis to determine the weighted mean differences with 95% confidence intervals using the software package Review Manager 5.0.25 of the Cochrane Collaboration. RESULTS Significant differences in HbA1c were found (weighted mean difference -0.21%, 95% CI -0.40 to -0.02; p = 0.03), favouring the high MUFA groups. In contrast, fasting plasma glucose, fasting plasma insulin as well as the homeostasis model assessment of insulin resistance were not affected by the amounts of MUFA in the dietary protocols. CONCLUSIONS In summary, this systematic review found that high MUFA diets appear to be effective in reducing HbA1c, and therefore, should be recommended in the dietary regimes of T2D.
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The effect of fluvastatin on cardiac outcomes in patients with moderate to severe renal insufficiency: a pooled analysis of double-blind, randomized trials.
Holdaas, H, Wanner, C, Abletshauser, C, Gimpelewicz, C, Isaacsohn, J
International journal of cardiology. 2007;(1):64-74
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BACKGROUND Individuals with chronic kidney disease are at high risk for cardiovascular disease and have a high prevalence of hyperlipidemia. Lipid-lowering therapy may help patients with renal disease reduce their risk for cardiovascular events. METHODS A pooled analysis of 30 completed clinical trials compared the efficacy and safety profiles of fluvastatin in subgroups of patients with moderate to severe renal insufficiency (creatinine clearance < 50 ml/min) and patients with normal renal function or mild renal insufficiency (creatinine clearance > or = 50 ml/min). RESULTS Changes in lipid parameters with fluvastatin treatment were similar for the compared patient subgroups. Fluvastatin treatment reduced combined cardiac death and myocardial infarction by 41% compared with placebo among patients with moderate to severe renal insufficiency (hazard ratio, 0.59; p=0.007) and by 30% among patients with normal renal function or mild renal insufficiency (hazard ratio, 0.70; p=0.009). The relative reduction in the risk of major adverse cardiac events, a composite endpoint comprising cardiac death, nonfatal myocardial infarction, and coronary intervention procedures, with fluvastatin treatment was not significant for patients with moderate to severe renal insufficiency (hazard ratio, 0.83; p=0.18); in this patient subgroup, the incidence of coronary intervention procedures was similar between treatment groups. The safety profiles were similar for fluvastatin- and placebo-treated patients. CONCLUSIONS The results of this pooled analysis indicate that fluvastatin is safe and effective for reducing cardiac death and nonfatal myocardial infarction in patients with moderate to severe renal insufficiency. Fluvastatin did not reduce the rate of coronary intervention procedures.