Project description:BACKGROUND:Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood. OBJECTIVES:We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS:A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis. RESULTS:Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets. CONCLUSIONS:In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9. This trial was registered at clinicaltrials.gov as NCT01235832.
Project description:BackgroundThe 2019 Canada's Food Guide (CFG) recommends that foods containing mostly unsaturated fatty acid (UFA) should replace foods that contain mostly SFA to reduce SFA intakes.ObjectivesThe objective of this study was to model the theoretical changes in intake of SFA at the population level if all Canadians adhered to that recommendation.MethodsDietary intakes from 24-h recalls in the nationally representative 2015 Canadian Community Health Survey-Nutrition were used for these analyses. Foods identified as high in SFA based on Health Canada's criteria [≥2 g SFA per reference amount and/or ≥15% of energy (%E) of the food's content as SFA] were replaced by an equal amount (gram per gram) of substitution foods that were lower in SFA and had a higher UFA to SFA ratio. Distributions of SFA and other nutrients before and after substitutions were estimated using the National Cancer Institute (NCI) method based on dietary intakes data from a 24-h recall repeated in 37% of the population.ResultsThe mean (95% CI) dietary SFA intake among Canadians 2 y or older would be theoretically reduced from 10.8%E (10.7, 11.0%E) to 5.8%E (5.7, 5.9%E) if all high-SFA foods consumed were replaced by the corresponding low-SFA/high-UFA foods. Modeled usual intake of SFA after substitution was <10%E in 100% of Canadians, irrespective of sex and age. Almost half (44%) of the modeled reduction in SFA intake was attributed to replacement of SFA-rich foods not recommended in the 2019 CFG.ConclusionsThis food-based substitution modeling analysis suggests that consumption of SFA would be below 10%E in Canada if all Canadians adhered to the 2019 CFG recommendation that foods containing mostly UFA should replace foods that contain mostly SFA.
Project description:BackgroundThe associations between dietary saturated fats and the risk of coronary heart disease (CHD) remain controversial, but few studies have compared saturated with unsaturated fats and sources of carbohydrates in relation to CHD risk.ObjectivesThis study sought to investigate associations of saturated fats compared with unsaturated fats and different sources of carbohydrates in relation to CHD risk.MethodsWe followed 84,628 women (Nurses' Health Study, 1980 to 2010), and 42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years.ResultsDuring 24 to 30 years of follow-up, we documented 7,667 incident cases of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates from whole grains were significantly associated with a lower risk of CHD comparing the highest with lowest quintile for PUFAs (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend = 0.003). In contrast, carbohydrates from refined starches/added sugars were positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p trend = 0.04). Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10).ConclusionsOur findings indicate that unsaturated fats, especially PUFAs, and/or high-quality carbohydrates can be used to replace saturated fats to reduce CHD risk.
Project description:Background and aimsCarbohydrates and fat intake have both been linked to development of atherosclerosis. We examined associations between glycemic index (GI) and fat intake with carotid atherosclerosis.MethodsThe Atherosclerosis Risk in Communities (ARIC) cohort enrolled participants during the period 1987-1989 and the Carotid MRI sub-study occurred between 2004 and 2006 (1672 participants attending both visits). Measures of carbohydrate quality (usual GI), fat intake (total, polyunsaturated and saturated) and overall dietary quality index (DASH Diet Score) were derived from a 66-item food frequency questionnaire administered at baseline. Trained readers measured lipid core presence and maximum wall thickness. Using multivariate logistic regression, we determined the odds of lipid core presence by quintile (Q) of energy-adjusted dietary components. Restricted cubic spline models were used to examine non-linear associations between dietary components and maximum wall thickness.ResultsMean daily polyunsaturated fat intake was 5 g (SD 1.4). GI and polyunsaturated fat intake had a nonlinear relationship with maximum wall thickness. Low (1-4 g) and high (6-12 g) polyunsaturated fat intake were associated with a statistically significant decreased odds of lipid core presence compared to intake in a majority of participants (OR Q5 vs. Q2-4: 0.64, 95% CI 0.42 to 0.98; OR Q1 vs. Q2-4: 0.64, 95% CI 0.42, 0.96), however, the association with lipid core was attenuated by adjustment for maximum wall thickness, hypertension, hyperlipidemia, and diabetes.ConclusionsGI and polyunsaturated fat intake were not associated with high-risk plaque features, such as lipid core presence, independent of traditional vascular risk factors.
Project description:Background/objectivesTo predict the health economic consequences of modest reductions in the daily intake of salt (-1.0?g per day) and replacement of saturated fat (SFA, -1.0 energy percent (E%)) with polyunsaturated fat (PUFA, +1.0 E%) in the Finnish population aged 30-74 years.Subjects/methodsA Markov model with dynamic population structure was constructed to present the natural history of cardiovascular diseases (CVDs) based on the most current information about the age- and sex-specific cardiovascular risk factors, dietary habits and nutrient intake. To predict the undiscounted future health economic consequences of the reduction of dietary salt and SFA, the model results were extrapolated for the years 2010-2030 by replacing the baseline population in the year 2007 with the extrapolated populations from the official Finnish statistics. Finnish costs (€2009, societal perspective) and EQ-5D utilities were obtained from published references.ResultsDuring the next 20 years, a population-wide intervention directed at salt intake and dietary fat quality could potentially lead to 8000-13,000 prevented CVD cases among the Finnish adults compared the situation in year 2007. In addition, the reduced incidence of CVDs could gain 26,000-45,000 quality-adjusted life years and save €150-225 million over the same time period.ConclusionA modest reduction of salt and replacement of SFA with PUFA in food products can significantly reduce the burden of CVD in the adult Finnish population. This impact may be even larger in the near future due to the ageing of Finnish population.
Project description:ObjectiveTo create a database of long-term randomised controlled trials (RCTs) comparing higher with lower omega-3, omega-6 or total polyunsaturated fatty acid (PUFA), regardless of reported outcomes, and to develop methods to assess effects of increasing omega-6, alpha-linolenic acid (ALA), long-chain omega-3 (LCn3) and total PUFA on health outcomes.DesignSystematic review search, methodology and meta-analyses.Data sourcesMedline, Embase, CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov and trials in relevant systematic reviews.Eligibility criteriaRCTs of ≥24 weeks' duration assessing effects of increasing ALA, LCn3, omega-6 or total PUFAs, regardless of outcomes reported.Data synthesisMethods included random-effects meta-analyses and sensitivity analyses. Funnel plots were examined, and subgrouping assessed effects of intervention type, replacement, baseline diabetes risk and use of diabetic medications, trial duration and dose. Quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsElectronic searches generated 37 810 hits, de-duplicated to 19 772 titles and abstracts. We assessed 2155 full-text papers, conference abstracts and trials registry entries independently in duplicate. Included studies were grouped into 363 RCTs comparing higher with lower omega-3, omega-6 and/or total PUFA intake of at least 6 months' duration-the Database.Of these 363 included RCTs, 216 RCTs were included in at least one of our reviews of health outcomes, data extracted and risk of bias assessed in duplicate. Ninety five RCTs were included in the Database but not included in our current reviews. Of these 311 completed trials, 27 altered ALA intake, 221 altered LCn3 intake and 16 trials altered omega-3 intake without specifying whether ALA or LCn3. Forty one trials altered omega-6 and 59 total PUFA.The remaining 52 trials are ongoing though 13 (25%) appear to be outstanding, or constitute missing data.ConclusionsThis extensive database of trials is available to allow assessment of further health outcomes.
Project description:Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response. In contrast to cis-unsaturated fatty acids, trans-unsaturated fatty acids failed to stimulate signs of autophagy including the formation of GFP-LC3B-positive puncta, production of phosphatidylinositol-3-phosphate, and activation of the transcription factor TFEB. When combined effects were assessed, several trans-unsaturated fatty acids including elaidic acid (the trans-isomer of oleate), linoelaidic acid, trans-vaccenic acid and palmitelaidic acid, were highly efficient in suppressing autophagy and endoplasmic reticulum stress induced by palmitic, but not by oleic acid. Elaidic acid also inhibited autophagy induction by palmitic acid in vivo, in mouse livers and hearts. We conclude that the well-established, though mechanistically enigmatic toxicity of trans-unsaturated fatty acids may reside in their capacity to abolish cytoprotective stress responses induced by saturated fatty acids.
Project description:Various health-related effects of long-chain (LC) ω-3 PUFAs, EPA, and DHA have been suggested. LC ω-3 PUFAs reduce TG concentrations and have anti-inflammatory, immunomodulatory, antiplatelet, and vascular protective effects. Controversially, they might help in restoring glucose homeostasis via the gut microbiota. However, previous studies have not shown the clear benefits of LC ω-3 PUFAs for CVDs. REDUCE-IT and STRENGTH-representative randomized controlled trials (RCTs) that examined whether LC ω-3 PUFAs would prevent major adverse cardiovascular (CV) events (MACE)-showed conflicting results with differences in the types, doses, or comparators of LC ω-3 PUFAs and study populations. Therefore, we performed a meta-analysis using major RCTs to address this inconsistency and assess the clinical and biological effects of LC ω-3 PUFAs. We included RCTs that involved ≥500 participants with ≥1 y follow-up. Of 17 studies involving 143,410 people, LC ω-3 PUFA supplementation showed beneficial effects on CV death (RR: 0.94; 95% CI: 0.88, 0.99; P = 0.029) and fatal or nonfatal MI (RR: 0.83; 95% CI: 0.72, 0.95; P = 0.010). RCTs on EPA alone showed better results for 3-point MACE, CV death, and fatal or nonfatal MI. However, the benefits were not found for fatal or nonfatal stroke, all-cause mortality, and hospitalization for heart failure. Of note, studies of both the EPA/DHA combination and EPA alone showed a significant increase in risk of new-onset atrial fibrillation. Thus, well-designed studies are needed to investigate the underlying mechanisms involved in the distinct effects of EPA compared with DHA on cardiometabolic diseases. This review discusses the potential benefits and safety of LC ω-3 PUFAs from a cardiometabolic perspective focusing on recent updates and controversies.
Project description:Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) have important signalling roles in the hypothalamus, a region of the brain that regulates whole-body energy homeostasis. While evidence suggests that high PUFA intake can impact hypothalamic activity, the underlying molecular mechanisms regulated by essential dietary PUFA (i.e., linoleic acid and alpha-linolenic acid) remain poorly described in this brain region. To differentiate the roles of essential dietary PUFA on hypothalamic function, we fed male rats high-fat diets (35% kcal/d) containing either safflower (linoleic acid) or flaxseed (alpha-linolenic acid) oil for 2 months. Control rats were fed a low-fat (16% kcal/d) diet containing soybean oil. Hypothalmic gene expression was investigated by microrray.
Project description:Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65-79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.