RESUMO
OBJECTIVE: Recommended dietary patterns improve cardiovascular disease (CVD) risk factors such as blood pressure and LDL-C, as well as emerging markers that confer residual risk. Strawberry consumption has been shown to improve CVD risk factors, but further research is needed to better understand these effects using a dose-response model that evaluates a standard serving and a higher (but still achievable) dose. METHODS: A randomized, placebo-controlled, double-blinded crossover trial was conducted in middle-aged adults with overweight or obesity (n = 40; mean BMI = 29.4 ± 0.2 kg/m2; mean age = 50 ± 1.0 years) and moderately elevated LDL-C (mean LDL-C: 140 ± 3 mg/dL) to investigate the effect of two doses of strawberry supplementation on LDL-C and other CVD risk factors. Study interventions were: 0 g/d (control), 13 g/d (low-dose), and 40 g/d (high-dose) of freeze-dried strawberry powder (4-week supplementation periods separated by a 2-week compliance break). RESULTS: There was a significant main effect of treatment for the primary outcome of LDL-C, with a 4.9% reduction following the low-dose strawberry supplement compared to the high-dose (P = 0.01), but not compared to the control. There was also a significant effect on total cholesterol (TC), with a 2.8% and 2.4% reduction following the low-dose compared to the control and high-dose, respectively (P ≤ 0.05 in post-hoc analyses). There was a near significant effect for direct LDL-C (P = 0.07). There were no significant treatment effects for other atherogenic lipoprotein characteristics, indices of vascular function, measures of inflammation, or HDL efflux. CONCLUSION: Low-dose supplementation with freeze-dried strawberry powder, equivalent to â¼1 serving/day of fresh strawberries, improved cholesterol in adults with overweight or obesity, compared to both the high-dose (â¼3 servings/day of fresh strawberries) and control, but did not alter other markers of CVD.Supplemental data for this article is available online at.
Assuntos
Aterosclerose , Fragaria , Hipercolesterolemia , Sobrepeso , Pós , LDL-Colesterol , Obesidade , Colesterol , Suplementos NutricionaisRESUMO
There are limited studies on neuroprotection from repeated subconcussive head impacts (RSHI) following docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) supplementation in contact sports athletes. We performed a randomized, placebo-controlled, double-blinded, parallel-group design trial to determine the impact of 26 weeks of DHA+EPA supplementation (n = 12) vs. placebo (high-oleic safflower oil) (n = 17) on serum concentrations of neurofilament light (NfL), a biomarker of axonal injury, and inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a)) in National Collegiate Athletic Association Division I American football athletes. DHA+EPA supplementation increased (p < 0.01) plasma DHA and EPA concentrations throughout the treatment period. NfL concentrations increased from baseline to week 26 in both groups (treatment (<0.001); placebo (p < 0.05)), with starting players (vs. non-starters) showing significant higher circulating concentrations at week 26 (p < 0.01). Fish oil (DHA+EPA) supplementation did not mitigate the adverse effects of RSHI, as measured by NfL levels; however, participants with the highest plasma DHA+EPA concentrations tended to have lower NfL levels. DHA+EPA supplementation had no effects on inflammatory cytokine levels at any of the timepoints tested. These findings emphasize the need for effective strategies to protect American football participants from the effects of RSHI.
Assuntos
Óleos de Peixe , Futebol Americano , Biomarcadores , Citocinas , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Método Duplo-Cego , Ácido Eicosapentaenoico , Humanos , InflamaçãoRESUMO
Emerging cardiovascular disease (CVD) risk factors, including central vascular function and HDL efflux, may be modifiable with food-based interventions such as cranberry juice. A randomized, placebo-controlled, crossover trial was conducted in middle-aged adults with overweight/obesity (n = 40; mean BMI: 28.7 ± 0.8 kg/m2; mean age: 47 ± 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 ± 2/81 ± 1 mm Hg). Study participants consumed 500 mL/d of cranberry juice (~16 fl oz; 27% cranberry juice) or a matched placebo juice in a randomized order (8-week supplementation periods; 8-week compliance break), with blood samples and vascular measurements obtained at study entry and following each supplementation period. There was no significant treatment effect of cranberry juice supplementation on the primary endpoint of central systolic blood pressure or central or brachial diastolic pressure. Cranberry juice significantly reduced 24-h diastolic ambulatory BP by ~2 mm Hg compared to the placebo (p = 0.05) during daytime hours. Cranberry juice supplementation did not alter LDL-C but significantly changed the composition of the lipoprotein profile compared to the placebo, increasing the concentration of large LDL-C particles (+29.5 vs. -6.7 nmol/L; p = 0.02) and LDL size (+0.073 vs. -0.068 nm; p = 0.001). There was no effect of treatment on ex vivo HDL efflux in the total population, but exploratory subgroup analyses identified an interaction between BMI and global HDL efflux (p = 0.02), with greater effect of cranberry juice in participants who were overweight. Exploratory analyses indicate that baseline C-reactive protein (CRP) values may moderate treatment effects. In this population of adults with elevated blood pressure, cranberry juice supplementation had no significant effect on central systolic blood pressure but did have modest effects on 24-h diastolic ambulatory BP and the lipoprotein profile. Future studies are needed to verify these findings and the results of our exploratory analyses related to baseline health moderators.
Assuntos
Doenças Cardiovasculares/dietoterapia , Suplementos Nutricionais , Sucos de Frutas e Vegetais , Hipertensão/dietoterapia , Vaccinium macrocarpon , Adulto , Idoso , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Colesterol/sangue , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Obesidade , Sobrepeso , Fatores de Risco , Rigidez VascularRESUMO
Although there are many recognized health benefits for the consumption of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA), intake in the United States remains below recommended amounts. This analysis was designed to provide an updated assessment of fish and n-3 LCPUFA intake (eicosapentaenoic (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States adult population, based on education, income, and race/ethnicity, using data from the 2003-2014 National Health and Nutrition Examination Survey (NHANES) (n = 44,585). Over this survey period, participants with less education and lower income had significantly lower n-3 LCPUFA intakes and fish intakes (p < 0.001 for all between group comparisons). N-3 LCPUFA intake differed significantly according to ethnicity (p < 0.001), with the highest intake of n-3 LCPUFA and fish in individuals in the "Other" category (including Asian Americans). Supplement use increased EPA + DHA intake, but only 7.4% of individuals consistently took supplements. Overall, n-3 LCPUFA intake in this study population was low, but our findings indicate that individuals with lower educational attainment and income are at even higher risk of lower n-3 LCPUFA and fish intake.
Assuntos
Escolaridade , Etnicidade , Ácidos Graxos Ômega-3/administração & dosagem , Renda , Adulto , Animais , Dieta , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Peixes , Humanos , Masculino , Inquéritos Nutricionais , Alimentos Marinhos , Estados UnidosRESUMO
Three recent clinical trials have demonstrated the benefits of marine omega-3 fatty acids on cardiovascular disease end points. In the Vitamin D and Omega-3 Trial (VITAL), 840 mg/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) resulted in a 28% reduced risk for heart attacks, 50% reduced risk for fatal heart attacks, and 17% reduced risk for total coronary heart disease events. In the ASCEND trial (A Study of Cardiovascular Events in Diabetes), cardiovascular disease death was significantly reduced by 19% with 840 mg/d of EPA and DHA. However, the primary composite end points were not significantly reduced in either study. In REDUCE-IT (the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), there was a 25% decrease in the primary end point of major cardiovascular events with 4 g/d EPA (icosapent ethyl) in patients with elevated triglycerides (135-499 mg/dL) who also were taking a statin drug. For clinical practice, we now have compelling evidence of the cardiovascular benefits of omega-3 fatty acids. The findings of REDUCE-IT provide a strong rationale for prescribing icosapent ethyl for patients with hypertriglyceridemia who are on a statin. For primary prevention, the goal is to increase the population intake of omega-3 fatty acids to levels currently recommended, which translates to consuming at least one to two servings of fish/seafood per week. For individuals who prefer taking omega-3 fatty acid supplements, recent findings from clinical trials support the benefits for primary prevention.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Dislipidemias/diagnóstico , Dislipidemias/mortalidade , Medicina Baseada em Evidências , Ácidos Graxos Ômega-3/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prevenção Primária , Fatores de Risco , Prevenção Secundária , Resultado do TratamentoRESUMO
BACKGROUND: Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear. OBJECTIVE: The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I. METHODS: Deidentified data from 1422 individuals from 14 published n-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion. RESULTS: Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P < 0.0001). The final model included dose, baseline O3I, and chemical formulation type (EE or TG), and these explained 62% of the variance in response (P < 0.0001). The model predicted that the final O3I (and 95% CI) for a population like this, with a baseline concentration of 4.9%, given 850 mg/d of EPA + DHA EE would be â¼6.5% (95% CI: 6.3%, 6.7%). Gram for gram, TG-based supplements increased the O3I by about 1 percentage point more than EE products. CONCLUSIONS: Of the factors tested, only baseline O3I, dose, and chemical formulation were significant predictors of O3I response to supplementation. The model developed here can be used by researchers to help estimate the O3I response to a given EPA + DHA dose and chemical form.
Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Eritrócitos/química , Modelos Biológicos , Teorema de Bayes , Suplementos Nutricionais , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.
Assuntos
Aterosclerose/diagnóstico , Doenças Cardiovasculares/diagnóstico , Ácidos Graxos Ômega-3/uso terapêutico , Hipertrigliceridemia/diagnóstico , American Heart Association , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Ensaios Clínicos como Assunto , Humanos , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/terapia , Risco , Triglicerídeos/sangue , Estados Unidos/epidemiologiaRESUMO
Background Walnuts have beneficial effects on cardiovascular risk factors, but it is unclear whether these effects are attributable to the fatty acid ( FA ) content, including α-linolenic acid ( ALA ), and/or bioactives. Methods and Results A randomized, controlled, 3-period, crossover, feeding trial was conducted in individuals at risk for cardiovascular disease (n=45). Following a 2-week standard Western diet run-in (12% saturated FAs [ SFA ], 7% polyunsaturated FAs, 12% monounsaturated FAs), participants consumed 3 isocaloric weight-maintenance diets for 6 weeks each: a walnut diet ( WD ; 7% SFA , 16% polyunsaturated FAs, 3% ALA , 9% monounsaturated FAs); a walnut FA -matched diet; and an oleic acid-replaced- ALA diet (7% SFA , 14% polyunsaturated FAs, 0.5% ALA , 12% monounsaturated FAs), which substituted the amount of ALA from walnuts in the WD with oleic acid. This design enabled evaluation of the effects of whole walnuts versus constituent components. The primary end point, central systolic blood pressure, was unchanged, and there were no significant changes in arterial stiffness. There was a treatment effect ( P=0.04) for central diastolic blood pressure; there was a greater change following the WD versus the oleic acid-replaced-ALA diet (-1.78±1.0 versus 0.15±0.7 mm Hg, P=0.04). There were no differences between the WD and the walnut fatty acid-matched diet (-0.22±0.8 mm Hg, P=0.20) or the walnut FA-matched and oleic acid-replaced-ALA diets ( P=0.74). The WD significantly lowered brachial and central mean arterial pressure. All diets lowered total cholesterol, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, and non- HDL cholesterol. Conclusions Cardiovascular benefits occurred with all moderate-fat, high-unsaturated-fat diets. As part of a low- SFA diet, the greater improvement in central diastolic blood pressure following the WD versus the oleic acid-replaced-ALA diet indicates benefits of walnuts as a whole-food replacement for SFA . Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT02210767.
Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/prevenção & controle , Dieta com Restrição de Gorduras , Dieta Saudável , Gorduras Insaturadas na Dieta/administração & dosagem , Dislipidemias/prevenção & controle , Juglans , Valor Nutritivo , Óleos de Plantas/administração & dosagem , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Estudos Cross-Over , Gorduras Insaturadas na Dieta/efeitos adversos , Dislipidemias/sangue , Dislipidemias/etiologia , Dislipidemias/fisiopatologia , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Recomendações Nutricionais , Fatores de Risco , Comportamento de Redução do Risco , Fatores de TempoRESUMO
The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250-500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long-chain n-3 fatty acid intake and impart unique benefits. We used NHANES 2003-2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20-55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (ß = 138.5; p < 0.001) and DHA (ß = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (ß = 13.15; p = 0.001 and ß = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long-chain n-3 fatty acids dietary recommendations.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/administração & dosagem , Adolescente , Adulto , Criança , Estudos Transversais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Insaturados/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Masculino , Estados Unidos , Adulto JovemRESUMO
Despite the importance of n-3 fatty acids for health, intakes remain below recommended levels. The objective of this study was to provide an updated assessment of fish and n-3 fatty acid intake (i.e., eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States using the 2003â»2014 National Health and Nutrition Examination Survey (NHANES) data (n = 45,347)). Over this survey period, toddlers, children, and adolescents (aged 1â»19) had significantly lower n-3 fatty acid intake (p < 0.001) compared to adults and seniors, which remained significant after adjusting for caloric intake. Females demonstrated lower n-3 fatty acid intake than males (p < 0.001), with adult and senior women having significantly lower intakes compared to men in the same age categories (p < 0.001) after adjustment for energy intake. Women also consumed less fish than men (5.8 versus 6.1 servings/month, p < 0.001). The estimated intakes of n-3 fatty acids in pregnant women did not differ from non-pregnant women (p = 0.6 for EPA+DHA), although pregnant women reported consuming less high n-3 fatty acid-containing fish than non-pregnant women (1.8 versus 2.6 servings/month, p < 0.001). Our findings indicate that subgroups of the population may be at higher risk of n-3 fatty acid intakes below recommended levels.
Assuntos
Dieta , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/análogos & derivados , Avaliação Nutricional , Gravidez , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Necessidades Nutricionais , Alimentos Marinhos , Estados Unidos , Adulto JovemRESUMO
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake is well below the amount recommended by the 2015-2020 Dietary Guidelines for Americans (0.25 g/day), supporting the need for alternative dietary sources. Stearidonic acid (SDA)-enriched soybeans were bioengineered to endogenously synthesize SDA, which can be readily metabolized to EPA in humans; thus, incorporating the derived SDA-enriched soybean oil into the food supply is a potential strategy to increase EPA. We performed a dietary modeling exercise using National Health and Nutrition Examination Survey 2003-2008 repeat 24-h dietary recall data (n = 24,621) to estimate the potential contribution of SDA-enriched oils to total long-chain n-3 fatty acid intake (defined as EPA + DHA + EPA-equivalents) following two hypothetical scenarios: (1) replacement of regular soybean oil with SDA soybean oil and (2) replacement of four common vegetable oils (corn, canola, cottonseed, and soybean) with respective SDA-modified varieties. Estimated median daily intakes increased from 0.11 to 0.16 g/day post-replacement of regular soybean oil with SDA-modified soybean oil, and to 0.21 g/day post-replacement of four oils with SDA-modified oil; the corresponding mean intakes were 0.17, 0.27, and 0.44 g/day, respectively. The percent of the population who met the 0.25 g/day recommendation increased from at least 10% to at least 30% and 40% in scenarios 1 and 2, respectively. Additional strategies are needed to ensure the majority of the US population achieve EPA and DHA recommendations, and should be assessed using methods designed to estimate the distribution of usual intake of these episodically consumed nutrients.
Assuntos
Ingestão de Alimentos , Ácidos Graxos Ômega-3/metabolismo , Óleos de Plantas/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Adulto JovemRESUMO
Specialized pro-resolving mediator(s) (SPMs) are produced from the endogenous ω-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and accelerate resolution of acute inflammation. We identified specific clusters of SPM in human plasma and serum using LC-MS/MS based lipid mediator (LM) metabololipidomics in two separate laboratories for inter-laboratory validation. The human plasma cluster consisted of resolvin (Rv)E1, RvD1, lipoxin (LX)B4, 18-HEPE, and 17-HDHA, and the human serum cluster consisted of RvE1, RvD1, AT-LXA4, 18-HEPE, and 17-HDHA. Human plasma and serum SPM clusters were increased after ω-3 supplementation (triglyceride dietary supplements or prescription ethyl esters) and low dose intravenous lipopolysaccharide (LPS) challenge. These results were corroborated by parallel determinations with the same coded samples in a second, separate laboratory using essentially identical metabololipidomic operational parameters. In these healthy subjects, two ω-3 supplementation protocols (Study A and Study B) temporally increased the SPM cluster throughout the endotoxin-challenge time course. Study A and Study B were randomized and Study B also had a crossover design with placebo and endotoxin challenge. Endotoxin challenge temporally regulated lipid mediator production in human serum, where pro-inflammatory eicosanoid (prostaglandins and thromboxane) concentrations peaked by 8 hours post-endotoxin and SPMs such as resolvins and lipoxins initially decreased by 2 h and were then elevated at 24 hours. In healthy adults given ω-3 supplementation, the plasma concentration of the SPM cluster (RvE1, RvD1, LXB4, 18-HEPE, and 17-HDHA) peaked at two hours post endotoxin challenge. These results from two separate laboratories with the same samples provide evidence for temporal production of specific pro-resolving mediators with ω-3 supplementation that together support the role of SPM in vivo in inflammation-resolution in humans.
Assuntos
Endotoxinas/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Administração Intravenosa , Adulto , Cromatografia Líquida , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Relação Dose-Resposta a Droga , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/análogos & derivados , Endotoxinas/efeitos adversos , Feminino , Voluntários Saudáveis , Humanos , Inflamação/induzido quimicamente , Inflamação/dietoterapia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Projetos de Pesquisa/normas , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
The American Heart Association recommends consuming fish (particularly oily fish) at least two times per week, which would provide ≈ 0.5 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) for cardiovascular disease risk reduction. Previous analyses indicate that this recommendation is not being met; however, few studies have assessed different ethnicities, subpopulations requiring additional n-3 fatty acid intake (i.e., children and pregnant and/or lactating women), or deciles of intake. Data from the National Health and Nutrition Examination Survey 2003-2008 was used to assess n-3 fatty acid intake from foods and supplements in the US population, according to age, sex, and ethnicity. A unique "EPA equivalents" factor, which accounts for potential conversion of shorter-chain n-3 fatty acids, was used to calculate total long-chain n-3 fatty acid intake. Data are reported for 24,621 individuals. More than 90% consumed less than the recommended 0.5 g/day from food sources (median = 0.11 g/day; mean = 0.17 g/day). Among the top 15% of n-3 fatty acid consumers, fish was the largest dietary contributor (71.2%). Intake was highest in men aged 20 years or more, and lowest in children and women who are or may become pregnant and/or are lactating. Among ethnicities, intake was lowest in Mexican-Americans. Only 6.2% of the total population reported n-3 fatty acid supplement use, and this did not alter median daily intake. Additional strategies are needed to increase awareness of health benefits (particularly among Mexican-Americans and women of childbearing age) and promote consumption of oily fish or alternative dietary sources to meet current recommendations.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Dieta , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Recomendações Nutricionais , Alimentos Marinhos , Estados Unidos , Adulto JovemRESUMO
The role of the long-chain omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3) and inflammation and triglycerides (TG). We evaluated whether n-3 DPA content of red blood cells (RBC) was associated with markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 20-44 years, body mass index (BMI) 20-30 kg/m2, TG = 34-176 mg/dL; Study 2: n = 28, aged 22-65 years, BMI 24-37 kg/m2, TG = 141-339 mg/dL). We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA) and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA). In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001) and with fasting TG (r = -0.30, p = 0.001). The latter finding was replicated in Study 2 (r = -0.33, p = 0.04). In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%-61% vs. 14%-26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study.
Assuntos
Proteína C-Reativa/metabolismo , Eritrócitos/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Triglicerídeos/sangue , Adulto , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Estudos Cross-Over , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Óleos de Peixe/administração & dosagem , Humanos , Interleucina-6/sangue , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
BACKGROUND: Apolipoprotein (apo) distribution and lipoprotein (Lp)-associated markers of inflammation, such as lipoprotein-associated phospholipase A2 (Lp-PLA2), influence the atherogenicity of circulating lipids and lipoproteins. Little evidence exists regarding the dose-response effects of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on apos, apo-defined Lps, and Lp-PLA2. OBJECTIVE: The purpose of this study was to compare the effects of 0, 0.85, and 3.4 g/d of EPA + DHA on Lp-PLA2 mass and activity in individuals with moderate hypertriglyceridemia. We also measured effects on concentrations of apoAI, apoAII, apoB, apoC, apoD, and apoE-defined Lp subclasses. METHODS: The study was a randomized, doubleblind, crossover design with 8-week treatment periods and 6-week washout periods. During the 3 treatment periods, subjects (n = 25) received 0 g/d EPA + DHA, 0.85 g/d EPA + DHA (low dose), and 3.4 g/d EPA + DHA (high dose) in random order. RESULTS: apoB and apoC-III were significantly decreased by the high dose relative to placebo and low dose (P < .01), as was very low-density lipoprotein cholesterol (P < .005). The low dose had no effect on Lp outcomes compared with placebo. The high- and low-dose effects differed significantly for heparin-precipitated apoC-III, LpB, LpA-I, and apoB/apoA-I ratio (P < .05). There was a trend for a decreased Lp-PLA2 mass with the high dose (P = .1). CONCLUSION: The effects of 3.4 g/d EPA + DHA on apoB and apoC-III may reduce atherosclerotic plaque progression in individuals with elevated triglycerides.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Apolipoproteína A-I/sangue , Apolipoproteína C-III/sangue , Apolipoproteínas B/sangue , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Chronic inflammation is a common underpinning of many diseases. There is a strong pre-clinical evidence base demonstrating the efficacy of omega-3 fatty acids for ameliorating inflammation and thereby reducing disease burden. Clinically, C-reactive protein (CRP) serves as both a reliable marker for monitoring inflammation and a modifiable endpoint for studies of anti-inflammatory pharmaceuticals. However, clinical omega-3 fatty acid supplementation trials have not replicated pre-clinical findings in terms of consistent CRP reductions. Methodological differences present numerous challenges in translating pre-clinical evidence to clinical results. It is crucial that future clinical nutrition research clearly distinguish between the reversal of established inflammation and preventing the development of inflammation. Future clinical studies evaluating the ability of omega-3 fatty acids to attenuate an excessive inflammatory response, may be advanced by employing new statistical approaches and utilizing models of induced inflammation, such as low-dose human endotoxemia.
Assuntos
Endotoxemia/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Animais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Ensaios Clínicos como Assunto , Endotoxemia/sangue , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológicoRESUMO
Despite the popularity of dietary nitrate supplementation and the growing evidence base of its potential ergogenic and vascular health benefits, there is no direct information about its effects on exercising limb blood flow in humans. We hypothesized that acute dietary nitrate supplementation from beetroot juice would augment the increases in forearm blood flow, as well as the progressive dilation of the brachial artery, during graded handgrip exercise in healthy young men. In a randomized, double-blind, placebo-controlled crossover study, 12 young (22 ± 2 years) healthy men consumed a beetroot juice (140 mL Beet-It Sport, James White Juice Company) that provided 12.9 mmol (0.8 g) of nitrate or placebo (nitrate-depleted Beet-It Sport) on 2 study visits. At 3 h postconsumption, brachial artery diameter, flow, and blood velocity were measured (Doppler ultrasound) at rest and during 6 exercise intensities. Nitrate supplementation raised plasma nitrate (19.5-fold) and nitrite (1.6-fold) concentrations, and lowered resting arterial pulse wave velocity (PWV) versus placebo (all p < 0.05), indicating absorption, conversion, and a biological effect of this supplement. The supplement-associated lowering of PWV was also negatively correlated with plasma nitrite (r = -0.72, p = 0.0127). Despite these systemic effects, nitrate supplementation had no effect on brachial artery diameter, flow, or shear rates at rest (all p ≥ 0.28) or during any exercise workload (all p ≥ 0.18). These findings suggest that acute dietary nitrate supplementation favorably modifies arterial PWV, but does not augment blood flow or brachial artery vasodilation during nonfatiguing forearm exercise in healthy young men.
Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Força da Mão/fisiologia , Hiperemia/sangue , Nitratos/farmacologia , Adulto , Beta vulgaris , Bebidas , Estudos Cross-Over , Método Duplo-Cego , Antebraço/fisiologia , Humanos , Masculino , Nitratos/sangue , Extratos Vegetais , Raízes de Plantas , Valores de Referência , Adulto JovemRESUMO
The long-chain omega-3 polyunsaturated (n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), may have anti-inflammatory effects. We evaluated the dose-response effect of EPA+DHA supplementation on circulating TNF-α, IL-6, and CRP and explored associations between red blood cell (RBC) membrane PUFA content and TNF-α, IL-6, and CRP. Young adults with low fish intake (n=116) received one of five doses (0, 300, 600, 900, or 1,800 mg/d EPA+DHA) for 5 months. There were no significant effects of supplemental EPA+DHA on IL-6 or CRP; however, there was a marginal treatment effect for TNF-α (p<0.08). At baseline, higher quartiles of RBC DHA were associated with lower TNF-α (p=0.001); higher quartiles of arachidonic acid were associated with higher TNF-α (p=0.005). EPA+DHA supplementation had no dose-response effect on TNF-α, IL-6, or CRP in healthy young adults; however, associations between inflammatory markers and RBC PUFA warrant further investigation.
Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos/metabolismo , Adulto , Proteína C-Reativa/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Humanos , Interleucina-6/sangue , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangueRESUMO
The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6% (+2 mm) and basal blood flow volume by 22%. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.
Assuntos
Cacau/química , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Flavonoides/farmacologia , Obesidade/fisiopatologia , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/patologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Estudos Cross-Over , Método Duplo-Cego , Endotélio Vascular/fisiopatologia , Jejum , Feminino , Flavonoides/uso terapêutico , Humanos , Hiperemia , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/tratamento farmacológico , Fitoterapia , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Fatores SexuaisRESUMO
BACKGROUND: The erythrocyte membrane content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which constitutes the omega-3 index (O3I), predicts cardiovascular disease mortality. The amount of EPA+DHA needed to achieve a target O3I is poorly defined, as are the determinants of the O3I response to a change in EPA+DHA intake. The objective of this study was to develop a predictive model of the O3I response to EPA+DHA supplementation in healthy adults, specifically identifying factors that determine the response. METHODS AND RESULTS: A randomized, placebo-controlled, double-blind, parallel-group study was conducted in 115 healthy men and women. One of 5 doses (0, 300, 600, 900, 1800 mg) of EPA+DHA was given daily as placebo or fish oil supplements for ≈5 months. The O3I was measured at baseline and at the end of the study. There were no significant differences in the clinical characteristics between the groups at baseline. The O3I increased in a dose-dependent manner (P<0.0001), with the dose of EPA+DHA alone accounting for 68% (quadratic, P<0.0001) of the variability in the O3I response. Dose adjusted per unit body weight (g/kg) accounted for 70% (linear, P<0.0001). Additional factors that improved prediction of treatment response were baseline O3I, age, sex, and physical activity. Collectively, these explained 78% of the response variability (P<0.0001). CONCLUSIONS: Our findings validate the O3I as a biomarker of EPA+DHA consumption and identify additional factors, particularly body weight, that can be used to tailor EPA+DHA recommendations to achieve a target O3I.