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Treatment of hypertriglyceridemia with omega-3 fatty acids: a systematic review
Abstract
To (a) critically appraise available randomized controlled trials (RCTs) addressing the efficacy of long-chain omega-3 fatty acids as secondary agents for prevention of hypertriglyceridemia and (b) make recommendations for clinical practice.
Two independent reviewers examined all RCTs from 1994 to 2003 identified in several databases, extracted data from each study, and used the previously tested Boyack and Lookinland Methodological Quality Index (MQI) to determine study quality.
Ten studies reported long-chain omega-3 fatty acids to be effective in the treatment of hypertriglyceridemia. The average decrease in triglycerides was 29%, total cholesterol 11.6%, very low density lipoprotein (VLDL) 30.2%, and low-density lipoprotein (LDL) 32.5%. One study found LDLs to increase by 25%. The average increase in high-density lipoprotein was 10%. The overall average MQI score was 36% (range = 26% to 54%). Many of the RCTs had serious shortcomings, including short duration, lack of a power analysis, no intention-to-treat analysis, no report of blind assessment of outcome, and lack of dietary control as a confounding variable.
Overall study methodology was weak. Although the evidence supporting use of long-chain omega-3 fatty acids in the secondary prevention of hypertriglyceridemia is reasonably strong, until there are larger RCTs of better methodological quality, it is not recommended that practitioners treat hypertriglyceridemia with omega-3 fatty acid supplementation in lieu of lipid-lowering medications.
... Although the effects of n-3 PUFA on triacylglycerol (TG), total cholesterol (TC), HDL-cholesterol and LDLcholesterol have been reviewed systematically in metaanalyses in patients with [9] and without diabetes [10,11], the only consistent effect reported in patients with type 2 diabetes is a significant reduction in TG concentrations. However, established cardiovascular disease (CVD) risk markers explain only some of the excess risk of CVD in type 2 diabetes [12], which may partly be due to abnormalities in LDL particle size and HDL subfraction concentrations [13], apolipoprotein concentrations [14] and plasma lipase activity [15]. ...
... We have also identified more recently published randomised trials. A fourth systematic review considered the effects of n-3 PUFA on TG, HDL, VLDL and LDL-cholesterol [11] in ten trials including 606 patients with hypertriacylglycerolaemia, but not type 2 diabetes. Three other systematic reviews of effects of n-3 PUFA in the general population [1,15,58] considered mortality as their main endpoint but also reported lipid markers. ...
... After adjusting for HDL, increasing levels of TG have been shown to be an independent risk factor for cardiovascular disease in epidemiological studies [60], so lowering of TG levels may be an important therapeutic effect of n-3 PUFA supplementation in patients with type 2 diabetes. TC levels were non-significantly lowered, similar to results of previous systematic reviews in type 2 diabetes [9,56,57] and in the general population [1], but were reduced in hypertriacylglycerolaemic patients [11]. HDL was non-significantly increased, as shown in previous systematic reviews of type 2 diabetes [9,56,57], in the general population and in type IIa hypercholesterolaemia patients [15]. ...
To determine the effects of marine-derived n-3 polyunsaturated fatty acids (PUFA) on established and emerging lipid and lipoprotein cardiovascular risk markers in patients with type 2 diabetes.
We performed a systematic review and meta-analysis of randomised controlled trials comparing dietary or non-dietary intake of n-3 PUFA with placebo in patients with type 2 diabetes by searching databases from 1966 to December 2006. Changes in the following variables were recorded triacylglycerol; total cholesterol; HDL, LDL and VLDL and their subfractions; lipid ratios; apolipoproteins; and cholesterol particle sizes.
There were 23 trials on non-dietary supplementation, involving 1,075 subjects with a mean treatment duration of 8.9 weeks, with sufficient data to permit pooling. Compared with placebo, n-3 PUFA had a statistically significant effect on four outcomes, reducing levels of (1) triacylglycerol (18 trials, 969 subjects) by 25% (mean 0.45 mmol/l; 95% CI -0.58 to -0.32; p < 0.00001); (2) VLDL-cholesterol (7 trials, 238 subjects) by 36% (0.07 mmol/l; 95% CI -0.13 to 0.00; p = 0.04); and (3) VLDL-triacylglycerol (6 trials, 178 subjects) by 39.7% (0.44 mmol/l; 95% CI -0.83 to -0.05; p = 0.03); while slightly increasing LDL (16 trials, 565 subjects) by 5.7% (0.11 mmol/l; 95% CI 0.00 to 0.22; p = 0.05). There were no significant effects on total cholesterol, apolipoproteins, lipid subfractions or ratios.
In addition to recognised triacylglycerol-lowering effects, n-3 PUFA supplementation decreases VLDL-cholesterol and VLDL-triacylglycerol, but may have an adverse effect on LDL-cholesterol. Larger and longer term clinical trials are required to conclusively establish the effect of n-3 PUFA on cardiovascular risk markers and outcomes in type 2 diabetic patients.
... Numerous epidemiologic and interventional studies have demonstrated beneficial effects of dietary n-3 polyunsaturated fatty acids (PUFA), including eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA), on many cardiovascular disease (CVD) risk factors [1] . However, past studies have documented that there is considerable interindividual variability in the response of plasma lipoprotein/lipid concentrations to alterations in dietary fat [1][2] . ...
... Numerous epidemiologic and interventional studies have demonstrated beneficial effects of dietary n-3 polyunsaturated fatty acids (PUFA), including eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA), on many cardiovascular disease (CVD) risk factors [1] . However, past studies have documented that there is considerable interindividual variability in the response of plasma lipoprotein/lipid concentrations to alterations in dietary fat [1][2] . There is strong evidence that this variability in the response to diet is partly attributable to genetic factors [3] . ...
Dietary n-3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-alpha (PPARalpha) can also modulate CVD risk factors. Since fatty acids, including n-3 PUFAs, are natural ligands of PPARalpha, a gene-diet interaction effect could be observed.
To examine whether n-3 PUFA- induced changes in CVD risk factors are influenced by the PPARalpha L162V polymorphism.
Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks.
Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01).
The PPARalpha L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n-3 PUFAs.
... Several interventional authors have observed the effect of phospholipids in reducing plasma total cholesterol levels, of particular relevance in patients with primary hyperlipidemia and diabetes mellitus [134,135]. Phospholipid supplementation with krill oil significantly reduced total cholesterol, LDL cholesterol, TGs and increased HDL40 cholesterol levels, which did not occur when supplemented with fish oil, as this supplement only decreased blood TGs [136]. ...
Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds on the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of pro-oxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid and antihypertensive activities. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.
... Several interventional authors have observed the effect of phospholipids in reducing plasma total cholesterol levels, of particular relevance in patients with primary hyperlipidemia and diabetes mellitus 132 , 133 . Phospholipid supplementation with krill oil significantly reduced total cholesterol, LDL cholesterol, TGs and increased HDL40 cholesterol levels, which did not occur when supplemented with fish oil, as this supplement only decreased blood TGs 134 . ...
Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds in the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of prooxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid, antihypertensive, etc. activity. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements, and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn, in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.
... The antilipogenic effect of omega-3 has been stated [25]. However, less is known about the exact mechanism of its antihyperlipidemic activity [26]. Omega-3 has been found to increase triglycerides hydrolysis. ...
PurposeMethotrexate (MTX) therapy is widely used in treatment of different types of diseases including inflammatory diseases, autoimmune disorders, and cancer. However, most of patients respond well to MTX, they suffer from multiple side effects including severe anorexia. Omega-3 fatty acid possesses many beneficial biological activities. Therefore, the objective of our study is to explore the effect of the combined modality of omega-3 (400 mg/kg/day) in MTX-induced anorexia in rats.Methods
The effect of MTX alone and in combination with omega-3 on the body weight, ghrelin hormone level, histopathological findings of taste buds and hypothalamus and POMC gene expression were investigated.ResultsInterestingly, the capability of omega-3 to overcome the anorexic effect of MTX could be manifested by controlling weight loss, increasing serum HDL, elevating the ghrelin level as well as reducing both lesions within taste buds and hypothalamus and hypothalamic POMC gene expression.Conclusionsour findings revealed that the omega-3 might be used as a complementary supplement during the MTX therapy to ameliorate its anorexic effect.
... Patients with higher O3-I had higher levels of HDL cholesterol and lower levels of serum triglycerides. The positive influence of the intake of omega-3 fatty acids on dyslipidemia has repeatedly been reported in clinical trials [35]. The decrease in levels of serum triglycerides was significantly correlated with dose-dependent intake of EPA and DHA [36]. ...
Background:
Epidemiologic studies on the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in heart failure are scarce, while one large intervention trial demonstrated a modest benefit.
Methods:
This is a secondary analysis from the Interdisciplinary Network Heart Failure (INH) program. Patients hospitalized for systolic heart failure were enrolled and followed for 36 months. At baseline, whole blood samples from 899 patients were analyzed for fatty acid composition using a standardized analytical procedure (HS-Omega-3 Index®, O3-I). Associations of the O3-I with markers of heart failure severity, clinical characteristics, biomarkers, and mortality were analyzed.
Results:
The mean O3-I was 3.7 ± 1.0%. Patient mean age was 68 ± 12 years (72% male, 43% in New York Heart Association (NYHA) class III or IV, mean LVEF 30 ± 8%). During follow-up 258 patients (28.7%) died. After adjustment for potential confounders, the O3-I showed weak associations with uncured malignancy, end-systolic diameter of the left atrium, left ventricular end-diastolic and end-systolic diameters, and blood lipids and other laboratory parameters (all p < 0.05), but not with NYHA class, left ventricular ejection fraction, and the underlying cause of heart failure. The O3-I did not predict the 3-year mortality risk.
Conclusions:
Our results show a marked depletion of omega-3 fatty acids in patients hospitalized for decompensated heart failure (suggested target range 8-11%). Although the O3-I was associated with a panel of established risk indicators in heart failure, it did not predict mortality risk.
Clinical trial registration:
www.controlled-trials.com; ISRCTN23325295.
... However, in the multiple models this was adjusted for (cod liver oil/fish oil capsules use). Consumption of fish oil has been associated with decreased TG [60][61][62][63]as well as increased HDL-C [61,64,65]. N-3 fatty acids are considered a valuable clinical tool in treatment of hypertriglyceridemia [66], and it has been argued that n-3 fatty acids may be more efficacious when consumed in fish rather than when an equivalent amount is provided by fish oil capsules [67]. ...
Background: Fish consumption may have beneficial effects on metabolic syndrome (MetS);
however, limited information of such associations exists. This study investigated possible associations
between fish consumption and changes in MetS components during a 13-year follow-up period.
Methods: The sample included participants (26–69 years) from the Tromsø Study 4 (1994–1995,
n = 23,907) and Tromsø Study 6 (2007–2008, n = 12,981). Data were collected using questionnaires
including food frequency questions, non-fasting blood samples, and physical examinations. MetS
was defined using the Joint Interim Societies (JIS) definition, in which one point was given for each
MetS criteria fulfilled (metabolic score). Longitudinal analyses were performed using Linear mixed
models. Results: For both genders, lean fish consumption once a week or more was significantly
associated with decreased future metabolic score, decreased triglycerides, and increased high-density
lipoprotein (HDL)-cholesterol, whereas decreased waist circumference and blood pressure was
identified only for men (age adjusted models). Fatty fish consumption was significantly associated
with increased waist circumference for both genders and increased HDL-cholesterol levels in men.
Conclusion: The results suggest that fatty and lean fish consumption may influence MetS differently
and that lean fish consumption in particular seems to be associated with beneficial changes in the
MetS components.
... Роль ω-3 ПНЖК в настоящее время широко обсуждается (Nordoy A. et al., 1998; Davidson M.H. et al., 2007 ). Однако многие данные свидетельствуют об отсутствии позитивного влияния этого класса лекарственных средств в отношении твердых клинических конечных точек (Burr M.L. et al., 1989; Lewis A. et al., 2004; Frost L., Vestergaard P., 2005; Mozaffarian D., Rimm E.B., 2006 ), хотя в отдельном рандомизированном клиническом исследовании доказана возможность снижения риска внезапной сердечной смерти (Lee K.W. et al., 2004 ). Таким образом, статины сохраняют свои позиции как основной компонент комбинированной терапии у пациентов со смешанными формами гиперлипидемий , тогда как в отношении фибратов и ω-3 ПНЖК единства мнений пока нет. ...
... Лекарственные средства, содержащие ω-3-ненасыщенные жирные кислоты, обладают доказанной способностью к снижению синтеза ЛПОНП гепатоцитами и повышению активности липопротеинлипазы за счет снижения энзиматической конверсии ацетил-КоА в СЖК (Park Y., Harris W.S., 2003; Lewis A. et al., 2004). Кроме того, ω-3-ненасыщенные жирные кислоты способны стимулировать трансфер ТГ и ТГ-обогащенных липопротеидов, таких как ЛПОНП и хиломикроны, а также способствовать ускорению клиренса ТГ, что приводит к редукции плазменного содержания ТГ (Harris W.S., Bulchandani D., 2006). ...
... Fish oils have been widely reported to be a useful supplement to reduce serum TG levels in individuals with hyperlipidemia; however, effects of fish oils on serum HDL-C remained obscure. Lewis et al reviewed all RCTs from 1994 to 2003 which addressed the efficacy of long-chain omega-3 FA for dyslipidemia, and they found that 10 studies reported longchain omega-3 FA to be effective in the treatment of hypertriglyceridemia (Table 3) [12][13][14][15][16]. According to accumulation of the data obtained from 10 studies, the average increase in HDL-C was 10%. ...
High-density lipoprotein (HDL) is a lipoprotein which has anti-atherogenic property by reversing cholesterol transport from the peripheral tissues to liver. Low HDL-cholesterol (HDL-C) as well as high low-density lipoprotein-cholesterol (LDL-C) is associated with the development of coronary heart diseases (CHD). Various epidemiological studies have suggested that the development of CHD increase in individuals with less than 40 mg/dL of HDL-C. In spite of accumulation of evidences suggesting a significant association between low HDL-C and CHD, effects of dietary factors on HDL metabolism remained largely unknown. We reviewed published articles about effects of dietary fat intake on HDL metabolism. The substitution of fatty acids (FA) for carbohydrates is beneficially associated with HDL metabolism. Monounsaturated FA intake may not affect HDL-C. Trans-FA is significantly associated with reduction of HDL-C, and is also adversely related with total cholesterol/HDL-C. Fish oils consumption, especially docosahexaenoic acid consumption, may be favorably associated with HDL metabolism. Although plant sterols and stanols may not affect HDL-C, policosanol intake is associated with a clinically significant decrease in the LDL/HDL ratio.
... Los estudios que han utilizado el tratamiento de Lapostabil ® (fosfolípidos de soja), en pacientes con enfermedad coronaria han sugerido los efectos beneficiosos en la reducción del colesterol y en la prevención de la agregación plaquetaria 38,39 . Por otra parte la administración de suplementos de fosfolípidos con aceite de krill redujo significativamente el colesterol Total, colesterol LDL, TGs y aumentaron los niveles de colesterol HDL 40 , lo que no ocurrió cuando se suplementó con aceite de pescado, ya que este suplemento solo disminuyó los TGs en sangre 41 . ...
Phospholipids are amphipathic lipids, which are found in all the cell membranes, organized as a lipid bilayer. They belong to the glycerol-derived lipids, showing a similar structure as triglycerides. The current interest of them comes from its effectiveness to incorporate different fatty acids in the cell membrane, as they exhibit better absorption and utilization than triglycerides. In this paper, the bibliographical data published about the benefits of the phospholipids in inflammatory processes, cancer, cardiovascular diseases, neurological disorders, liver disease and as an antioxidants transporter is reviewed.
Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
... Similar observations were made by Taylor et al., where a significant HDL increase could be seen in tumor patients after six weeks of MPL supplementation (Vitalipin ® , see table 2), while total and LDL cholesterol decreased [4]. Since the supplementation with traditional fish oil (FAs bound to TG instead of PL) lowers only blood TG levels [49], but has no effect on LDL and HDL levels [50], PLs must be responsible for the observed beneficial changes of blood lipid profiles. ...
Beneficial effects of dietary phospholipids (PLs) have been mentioned since the early 1900's in relation to different illnesses and symptoms, e.g. coronary heart disease, inflammation or cancer. This article gives a summary of the most common therapeutic uses of dietary PLs to provide an overview of their approved and proposed benefits; and to identify further investigational needs.
From the majority of the studies it became evident that dietary PLs have a positive impact in several diseases, apparently without severe side effects. Furthermore, they were shown to reduce side effects of some drugs. Both effects can partially be explained by the fact that PL are highly effective in delivering their fatty acid (FA) residues for incorporation into the membranes of cells involved in different diseases, e.g. immune or cancer cells. The altered membrane composition is assumed to have effects on the activity of membrane proteins (e.g. receptors) by affecting the microstructure of membranes and, therefore, the characteristics of the cellular membrane, e.g. of lipid rafts, or by influencing the biosynthesis of FA derived lipid second messengers. However, since the FAs originally bound to the applied PLs are increased in the cellular membrane after their consumption or supplementation, the FA composition of the PL and thus the type of PL is crucial for its effect. Here, we have reviewed the effects of PL from soy, egg yolk, milk and marine sources. Most studies have been performed in vitro or in animals and only limited evidence is available for the benefit of PL supplementation in humans. More research is needed to understand the impact of PL supplementation and confirm its health benefits.
... For example, it is well known that hypothyroidism can lead to depression, however, omega-3 fatty acid supplementation has no effect upon thyroid status in an experimental animal model (Morcos and Camilo, 2001;Davis and Tremont, 2007), although human subject studies appear warranted. Furthermore, although there may be an association between depression and obesity and it is established that omega-3 PUFA can effectively reduce circulating triglyceride levels (Lewis et al. 2004), there is no evidence that hypertriglyceridemia per se is a risk factor for the development of depression (Lehto et al. in press). Conversely, although elevated homocysteine levels have been associated with depression (Kim et al. 2008), omega-3 PUFA are reported to either have no effect upon or to slightly increase homocysteine levels (Piolot et al. 2003;Beavers et al. 2008). ...
Omega-3 polyunsaturated fatty acids play important roles in both the structure and communication processes of cells. Dietary deficiences of these fatty acids have been implicated in cardiac dysfunction, cancer and mood disorders. In the latter, clinical trials have strongly suggested that not all types of omega-3 PUFA are equally efficacious. In particular eicosapentaenoic acid (EPA) appears to be the most useful in ameliorating the symptoms of major depressive disorder. The mechanism by which omega-3 PUFA have these effects, and why EPA is apparently more effective in this role than the much more abundant brain lipid docosahexaenoic acid, is unclear. The available data do suggest various biologically plausible mechanisms all of which are amenable to study using straightforward experimental approaches. To progress further, a better understanding of how EPA and other omega-3 PUFA effect neurophysiological and neurosignalling processes is required.
... Moreover, the American College of Cardiology (ACC) in conjunction with the American Heart Association (AHA) recommends the intake of 1 g/day of long chain omega-3 fatty acids for the prevention of cardiovascular disease [7]. These recommendations exist even though several conflicting meta-analyses have failed to agree on the efficacy of taking fish oils for preventing cardiovascular disease or reducing cardiovascular mortality [8] [9] [10] [11] [12] [13] [14] [15]. The previous meta-analyses have varying limitations including selection of non-RCT studies [8], small numbers of studies [9–12], and studies that were conducted for less than 6 months duration [13]. ...
Fish oils have been widely reported as a useful supplement to reduce fasting blood triglyceride levels in individuals with hyperlipidemia. We performed an updated meta-analysis to quantitatively evaluate all the randomized trials of fish oils in hyperlipidemic subjects.
We conducted a systematic literature search using several electronic databases supplemented by manual searches of published reference lists, review articles and conference abstracts. We included all placebo-controlled randomized trials of parallel design that evaluated any of the main blood lipid outcomes: total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol or triglycerides (TG). Data were pooled using DerSimonian-Laird's random effects model.
The final analysis comprised of 47 studies in otherwise untreated subjects showed that taking fish oils (weighted average daily intake of 3.25 g of EPA and/or DHA) produced a clinically significant reduction of TG (-0.34 mmol/L, 95% CI: -0.41 to -0.27), no change in total cholesterol (-0.01 mmol/L, 95% CI: -0.03 to 0.01) and very slight increases in HDL (0.01 mmol/L, 95% CI: 0.00 to 0.02) and LDL cholesterol (0.06 mmol/L, 95% CI: 0.03 to 0.09). The reduction of TG correlated with both EPA+DHA intake and initial TG level.
Fish oil supplementation produces a clinically significant dose-dependent reduction of fasting blood TG but not total, HDL or LDL cholesterol in hyperlipidemic subjects.
... Two studies of 4 g/d of Omacor demonstrated a 50% reduction in triglycerides and a 44.5% increase in lowdensity lipoprotein (LDL) cholesterol in 84 adults with primary hypertriglyceridemia. 32 A review of 10 trials in 606 subjects with primary hypertriglyceridemia (triglycerides N150 mg/dL and/or total cholesterol N200 mg/dL) supplemented with 3.4 to 4 g/d of fish oil for 4 to 16 weeks was notable for a 16% to 45% reduction in triglycerides in all but one study. 33 Total cholesterol decreased 0% to 9.3%, high-density lipoprotein increased 0% to 13%, and changes in LDL ranged from À11.3% to +32%. Although fish oil may increase total LDL (at doses N1 g/d), the resultant LDL population may have an increased particle size that is potentially less atherogenic than small, dense LDL. ...
Omega-3 fatty acids are a subset of polyunsaturated fatty acids found in marine sources as eicosapentaenoic acid and docosahexaenoic acid and in some leafy vegetables, nuts, and oils as alpha-linolenic acid (ALA). The metabolism of omega-3's may explain the cardioprotective effects observed in epidemiologic and experimental studies. Although most data for cardioprotective effects come from studies of marine sources, vegetable sources of omega-3 fatty acids (alpha-linolenic acid) may have similar effects through in vivo conversion to eicosapentaenoic acid and docosahexaenoic acid. This document will provide an overview of omega-3 fatty acids with a focus on specific sources, metabolism, safety issues, and their potential indication for cardiovascular prevention.
... Many other trials performed in different populations gave rise to conflicting results. In any case, fish oil consumption was associated with a triglyceride-lowering effect [21] and a reduced mortality from heart disease [12]; the effects of n.3 fatty acids on a variety of diseases have recently been reviewed [30,31]. Some of the conflicting results might be related to the ingestion of low amounts of n-3 PUFA or to their malabsorption or to the variable levels of the toxic lipoperoxidation by-products in the administered oils. ...
Numerous changes occur post‐mortem in fish, affecting its chemical composition and nutritional quality. In the present paper we describe the effect of storage on ice or at −30°C or −80°C on 10 species of Mediterranean fish. Water and lipid soluble antioxidants, lipid pattern and products of oxidative attack on lipids, proteins and DNA were quantified for 7 consecutive days on homogenates of fish light muscle. The earliest events were oxidation of ubiquinol and vitamin C, which disappeared almost completely within 48 hours. Ubiquinol oxidation gave rise to an initial increase of ubiquinone, which peaked at the second day: thereafter ubiquinone itslef decreased, more rapidly and to a greater extent than vitamin E. The decrease in antioxidants was accompanied by significant oxidative damage to lipids, proteins and DNA. TBARS significantly increased beginning from the third day of storage in all species and were linked to a significant reduction in the n‐3 PUFA of triglycerides (TG) and phospholipid fractions (PL). A remarkable elevation of protein carbonyls and 8OHdG occurred approximately 24 hours later than PUFA oxidation. For SOD, GPX and GSH significant depletions occurred for all species only at 6th or 7th day, but the final values were always higher than 50% compared to the initial ones.
Deep‐freezing of the same species at −30°C and −80°C for up to 12 months did not significantly affect the levels of enzymatic antioxidants, the redox couple GSH/GS‐SG, n‐3 and n‐6 PUFA of TG and PL fractions of the light muscle.
The only antioxidants, which at −30°C and −80°C appeared to be degraded after 6 and 12 months were ubiquinol and vitamin C. As expected their degradation was higher at −30°C than at −80°C. In fact the average decrease for ubiquinol at −80°C was 42% at 6 and 12 months respectively, whereas at −30°C the decrease was 61% and 87% For vitamin C the average decrease at −80°C was 36% and 67% at 6 and 12 months respectively, and at −30°C it was 61% and 82%.
Vitamin E was considerably more stable than ubiquinol and vitamin C. The relative stability of the antioxidants, with the exceptions of ubiquionols, vitamin C and, to a certain extent, vitamin E, was accompanied by a very limited increase in oxidation products.
In addition no significant hydrolysis of TG and PL fractions were observed throughout the storage time.
The dynamics of lipid, protein and DNA oxidation is discussed in the light of depletion of the various antioxidant systems.
... g/day of long-chain n-3PUFA in the dip matrix for a period of 6 weeks resulted in a 35% reduction in the median plasma triglyceride values. A critical appraisal of 10 available randomized controlled trials addressing the efficacy of long-chain n-3PUFA as secondary agents for the prevention of hypertriglyceridaemia revealed that the average decrease in plasma triglyceride was 29% (Lewis et al., 2004). Mechanisms for the reduction of plasma triglyceride involve a significant decrease in very LDL synthesis in the liver (Harris et al., 1997) and an increased triglyceride clearance as indicated by an increase in fractional catabolic rate (Simopoulos, 1999). ...
Recent developments in micro-emulsification technology have allowed the fortification of foods with long-chain n-3 polyunsaturated fatty acid (PUFA) without the undesirable fish odour/taste and with reasonable shelf life. The effects of supplementing the diets of people with diabetes type II with a hummus-based dip enriched with long-chain n-3PUFA on plasma fatty acid composition and lipid levels were examined.
A pre- and post-intervention study.
This study was conducted at the University of Newcastle, Australia.
Participants were recruited via advertisements on the University of Newcastle notice boards and in the local newspapers. Following initial response to study advertisements, information statements were mailed out to 29 potential participants. Thirteen participants were eligible and consented to participate in the trial. There were no dropouts as all the 13 participants completed 6-week intervention trial.
Free-living male and female subjects with diabetes type II (n=13) consumed the n-3PUFA-enriched dip for a period of 6 weeks. Fasting blood samples were collected pre- and post-intervention for analyses of fatty acids and plasma lipids.
Following 6 weeks of consuming the enriched dip, all the long-chain n-3PUFA (20:5n-3, 22:5n-3 and 22:6n-3) were significantly (P<0.05) elevated in the plasma lipids. This represented an increase in 20:5n-3 content by 117%, an increase in 22:5n-3 content by 15% and an increase in 22:6n-3 content by 80% over the baseline values before dip consumption. A significant reduction (P<0.05) in the plasma triglyceride levels from 1.93 (1.08-2.09) mmol/l at baseline to 1.27 (0.93-2.22) mmol/l after 6 weeks was also apparent following the consumption of the n-3PUFA-enriched dip. Plasma cholesterol was unchanged; however, low-density lipoprotein (LDL)-cholesterol (2.46+/-0.21 versus 2.72+/-0.22 mmol/l, P<0.034) and high-density lipoprotein (HDL)-cholesterol (1.16+/-0.09 versus 1.22+/-0.09 mmol/l, P<0.042) were significantly increased following the dietary intervention.
These results demonstrate that n-3PUFA are readily bioavailable from the fortified dip matrix and alter the plasma lipid profile.
Background
Omega-3 fatty acids (FAs) have been suggested as a beneficial supplement in chronic kidney disease (CKD) patients, but the results of randomized clinical trials (RCTs) are controversial. We conducted a systematic review and meta-analysis to evaluate all the RCTs about the impact of omega-3 FAs supplementation on cardiometabolic outcomes and oxidative stress parameters in patients with CKD.
Methods
We performed a systematic database search in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central, up to May 2020. We included all placebo-controlled randomized trials that assessed the effect of omega-3 FAs supplementation on any cardiometabolic outcomes: blood pressure, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) or triglycerides (TG) and oxidative stress parameters. Data were pooled using DerSimonian–Laird’s random-effects model.
Results
Finally, thirteen articles met the inclusion criteria for this review omega-3 FAs supplementation significantly decrease TC (SMD: -0.26; 95% CI: − 0.51, − 0.02; I² = 52.7%), TG (SMD: -0.22; 95% CI: − 0.43, − 0.02; I² = 36.0%) and Malondialdehyde (MDA) levels (SMD: -0.91; 95% CI: − 1.29, − 0.54; I² = 00.0%) and also significantly increase superoxide dismutase (SOD) (SMD: 0.58; 95% CI: 0.27, 0.90; I² = 00.0%) and Glutathione peroxidase (GPx) (SMD: 0.50; 95% CI: 0.14, 0.86; I² = 00.0%) activities. However our results show that omega-3 FAs supplementation have no significant effects on HDL, LDL and blood pressure.
Conclusion
This systematic review and meta-analysis supports current evidence for the clinical benefit of omega-3 FAs intake to improve cardiometabolic parameters in CKD patients. However, well-designed RCTs still needed to provide a conclusive picture in this field.
Myocardial infarction associated with atherosclerosis is the leading cause of death globally. Novel therapies are needed to reduce the rates of mortality and morbidity associated with cardiovascular disease (CVD). Previous study findings suggest omega-3 fatty acids (FO) may have a beneficial effect on risk for CVD and its associated morbidity and mortality rates. Both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have demonstrated positive effects on cholesterol levels, inflammatory markers, blood pressure, endothelial dysfunction, resting hear rate, and arrhythmia. Study authors have reported positive effects on low-density lipoprotein cholesterol (LDL), highdensity lipoprotein cholesterol (HDL), triglycerides, and emerging risk factors of LDL particle number and LDL size. Additionally, various study outcomes have demonstrated an effect of n-3 on inflammatory markers such as Interleukin-6 (IL-6), Interleukin-1beta (IL-1β), and Tumor Necrosis Factor-alpha (TNF-α). Many of these same effects have been reported for individuals who regularly engage in aerobic exercise including a decreased heart rate and additional improvements in heart rate variability. The primary inflammatory markers associated with exercise have been improved levels of IL-6, IL-1 β, TNF-α, and C-reactive protein (CRP). Therefore exercise may contribute to the reduction of vascular and inflammatory diseases, more specifically CVD. Recently, studies have emerged attempting to understand the effects of combining exercise and supplementing FO on mortality and morbidity associated with CVD. Findings have ranged from increased performance during exercise to improving heart function or heart rate variability, decreasing resting heart rates, and improving lipid and inflammatory profiles. Most importantly there has been emerging evidence that the combination of exercise and FO supplementation may have a synergistic effect when combined. Though little is known among the general public and health practitioners about this combination of therapy on the reduction in heart disease, a growing body of research has addressed this issue. Therefore the purpose of this chapter will be to explore the literature to address what effects combining exercise and FO supplementation have on CVD. Specifically we will address issues of cholesterol, inflammation, heart rate variability, blood pressure, and general health markers of CVD.
This book is about the fish we eat, fish that not only sustains us but also provides us with pleasure and well-being. Fish is also a valuable source of nutraceuticals and pharmaceuticals. We follow a holistic approach in this book viewing fish in its entirety from the food that fish need in order to grow to the pharmaceutical applications of fish oil.
2014 is a historic year, it is the first year in human history where the amount of fish we consume from aquaculture will surpass that from the wild.
As it seems that aquaculture will play a vital role in the future feeding of mankind, it should be considered imperative that it be done in a responsible and sustainable way.
Food security is both the top political and scientific priority today. With this book, we try to provoke some thoughts as to how fish is produced, how it is valorised and what could be done in the future.
We address within this book the issue of resource management, fish nutritional requirements, aquatic food security, nutritional value of marine oils and fish themselves as well as to how we can further exploit marine oil usage in the production of nutraceuticals and pharmaceuticals. (Imprint: Nova)
https://www.novapublishers.com/catalog/product_info.php?products_id=53103&osCsid=
Non-alcoholic steatohepatitis (NASH) has a relation to obesity. It may lead to hepatocellular carcinoma. To date, the therapeutic options are limited due to complex pathogenesis. This study aimed to investigate the effect of atorvastatin and omega 3 fatty acids on experimentally-induced NASH. Sixty male albino rats were divided into 6 equal groups; control group, high fat emulsion/sucrose (HFE/S) diet, HFE/S+carboxymethyl cellulose, HFE/S +Atorvastatin, HFE/S+Fish oil and HFE/S+Atorvastatin+Fish oil. Serum alanine aminotransferase, total cholesterol (TC), triglycerides (TG), high density lipoproteins, insulin, glucose, C-reactive protein and quantitative insulin sensitivity check index were measured. Also, hepatic TC, TG, malondialdehyde, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor beta 1 (TGF-β1) were determined. Liver sections were examined histopathologically. Atorvastatin improved lipid profile, inflammation and oxidative stress but didn't improve insulin resistance, hepatic TGF-β1 or body weight while fish oil improved lipid profile, decreased inflammation and oxidative stress, improved insulin resistance, hepatic TGF-β1 and body weight compared to HFE/S group. Atorvastatin/fish oil combination produced significant improvement in the lipid profile, inflammation, oxidative stress, insulin resistance, hepatic TGF-β1 and body weight compared to the use of each of these drugs alone. This might be attributed to the effect of fish oil on the lipid profile, inflammatory cytokines, insulin resistance and TGF-β1 which potentiates the effect of atorvastatin on NASH.KeywordsFish oilAtorvastatinCholesterolNASH
ω3-Fettsäuren eignen sich hervorragend in der Therapie von Hypertriglyceridämien. Je nach genetischer Disposition können möglicherweise allein durch die Ernährungsumstellung die Triglyceride in den Normbereich gesenkt und eine medikamentöse Therapie umgangen werden. Daher sollte der diätetische Ansatz immer erste Therapieoption sein. Gegebenenfalls können auch Fischölkapseln zum Einsatz kommen. Bei Hypercholesterinämien können aufgrund widersprüchlicher Daten derzeit noch keine Empfehlung zum Einsatz von Fischöl gegeben werden.
Aim: High serum levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and low levels of high-densitycholesterol (HDL) are associated to elevated incidence of cardiovascular events and to sudden death. This lipidic pattern is often observed in patients with visceral obesity such as patients with Metabolic Syndrome (MS) and Type 2 Diabetes Mellitus (T2DM) which have an increased risk of cardiovascular events. This open-label, cross-over study evaluated the efficacy of n-3 PUFA (3g/die) added to atorvastatin (20 mg) (ATV) on lipidic profile, on haemorherologic and inflammatory parameters in patients with MS without and with T2DM. Methods: All patients enrolled in this study with MS (N=62; M.31/F.31) and MS-T2DM (N=60; M.30/F.30) were submitted to 4 weeks period of isocaloric diet and pharmacological wash-out before study entry. Duration time of the study was 40 weeks. After an 8-week period of atorvastatin treatment, both patients with MS and with T2DM-MS were randomized in two groups: group A switching (24-week) from ATV alone to ATV/PUFA and group B switching (24-week) from ATV/PUFA to ATV alone. Results: Significant (p<0.001) reductions in low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC) and apo-B wereachieved during both treatments as compared with baseline. Moreover significant lowering effects on triglycerides (p<0.01) and significant increasing effects on HDL-C and Apo-A1 (p<0.001) were observed during ATV/PUFA treatment than ATV alone. The ATV/PUFA treatment induced significant improvements in fibrinogen, factor VII (p<0.01), PAI-1 (p<0.001), blood and plasma viscosity (p<0.01) levels compared to ATV alone results. Significant reductions during ATV/PUFA on CRP (p<0.01) were observed. ATV/PUFA treatment was generally well-tolerated, with a safety profile on laboratory parameters. Conclusions: In these patients with MS and T2DM-MS combined treatment with ATV plus n-3 PUFA provided strong reductions on LDL-C and TG and increase of HDL-C with evident improvement of lipidic profile. The improvement of haemorheology and inflammatory parameters together towards an antiatherogenic lipid profile is expected to have favourable effects in reducing cardiovascular risk.
Large doses of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are used to treat several diseases including hypertriglyceridemia in humans. Modest levels of EPA and DHA may be obtained from food, particularly from fatty fish. This review presents the literature examining the differences between omega-3 fatty acid dietary supplementation and prescribed omega-3-acid ethyl esters (P-OM3). Reports published between 1995 and 2007 containing sources, recommended intake, and differences in the various formulations of omega-3 fatty acids were sought in PubMed and the Food and Drug Administration (FDA) Websites. However, lack of head-to-head clinical trials using both P-OM3 and dietary-supplement omega-3 fatty acids is the greatest limitation of this review. Although many kinds of omega-3 fatty acid dietary supplements are available, the efficacy, quality, and safety of these products are questionable because they are beyond any pharmaceutical control. Thus, P-OM3 is the only FDA approved omega-3 fatty acid product which is available in the United States as an adjunct to diet to improve human health.
At present, dyslipidemia is most commonly treated with drug therapy. However, because safety concerns regarding the use of pharmaceutical agents have arisen, a need for alternative nonpharmacological therapies has become increasingly apparent. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) recommends lifestyle therapies, which include a combination of diet and exercise modifications, in place of drug treatment for patients who fall into an intermediate range of coronary heart disease (CHD) risk. This review examined the cholesterol lowering efficacy of the following 2 NCEP-recommended combination therapies: 1) low saturated fat diets combined with exercise, and 2) nutritional supplementation, i.e., fish oil, oat bran, or plant sterol supplementation, combined with exercise, in the treatment of dyslipidemia. Combination therapies are particularly advantageous because diet and exercise elicit complementary effects on lipid profiles. More specifically, diet therapies, with some exceptions, lower total (TC) and LDL cholesterol (LDL-C) concentrations, whereas exercise interventions increase HDL cholesterol (HDL-C) while decreasing triglyceride (TG) levels. With respect to specific interventions, low saturated fat diets combined with exercise lowered TC, LDL-C, and TG concentrations by 7-18, 7-15, and 4-18%, respectively, while increasing HDL-C levels by 5-14%. Alternatively, nutritional supplements combined with exercise, decreased TC, LDL-C, and TG concentrations by 8-26, 8-30, and 12-39%, respectively, while increasing HDL-C levels by 2-8%. These findings suggest that combination lifestyle therapies are an efficacious, preliminary means of improving cholesterol levels in those diagnosed with dyslipidemia, and should be implemented in place of drug therapy when cholesterol levels fall just above the normal range.
Low-carbohydrate diets raise high-density lipoprotein (HDL) cholesterol levels by approximately 10%; soy protein with isoflavones raises HDL by 3% (strength of recommendation [SOR]: C, based on meta-analysis of physiologic parameters). The Dietary Approaches to Stop Hypertension (DASH) diet and multivitamin supplementation raise HDL 21% to 33% (SOR: C, based on single randomized trial each measuring physiologic parameters). No other dietary interventions studied raise HDL (SOR: C, based on meta-analysis of physiologic parameters).
To determine the baseline arachidonic acid:eicosapentaenoic acid (AA:EPA) ratio in patients with coronary artery disease and healthy subjects, and whether supplementation of omega-3 fatty acids, administered as fish oil capsules, affects this ratio.
Prospective, open-label trial.
University-affiliated cardiology clinic.
Thirty patients with stable coronary artery disease (CAD) and 30 healthy subjects.
All participants received omega-3 fatty acids 1.5 g/day for 4 weeks, followed by 3 g/day for an additional 4 weeks.
For each participant, a lipid profile was determined at baseline and after 4 weeks of treatment with each dose. Other laboratory results analyzed were serum AA:EPA ratios, high-sensitivity C-reactive protein (hs-CRP) levels, and blood glucose levels. Mean +/- SD baseline AA:EPA ratios were 39.6 +/- 19.0 in healthy subjects and 23.7 +/- 12.5 in patients with CAD. These ratios decreased significantly in both groups after treatment with 1.5 g/day of omega-3 fatty acids: 9.0 +/- 4.2 in healthy subjects and 10.3 +/- 8.8 in patients with CAD. After treatment with 3 g/day, the ratios were further reduced: 5.1 +/- 3.2 in healthy subjects and 4.9 +/- 2.6 in patients with CAD. Supplementation with omega-3 fatty acids did not significantly affect hs-CRP, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or blood glucose levels. Triglyceride levels were not reduced in patients with CAD but were significantly decreased in healthy subjects (by 20% decrease with omega-3 fatty acids 1.5 g/day and by 32% decrease with 3 g/day).
Treatment with omega-3 fatty acids significantly reduced AA:EPA ratios in both healthy subjects and in patients with stable CAD. The treatment had no effect on hs-CRP levels in either group, and it reduced triglyceride levels in healthy subjects but not in patients with CAD.
A reliable means of treating hyper-triglyceridemia is the use of large doses of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Modest levels of EPA and DHA may be obtained from food, particularly fatty fish.
This article is intended to review clinically relevant differences between dietary-supplement omega-3 fatty acids and prescription omega-3-acid ethyl esters (P-OM3).
PubMed and the Food and Drug Administration (FDA) Website were searched for articles published between 1995 and 2007 that contained the terms fish oil, fatty acids, n-3 fatty acids, omega fatty acids, docosahexaenoic acid, or eicosapentaenoic acid. Articles discussing sources, recommended intake, and differences among various formulations of omega-3 fatty acids were selected for review. A limitation to this review is the lack of head-to-head clinical trials using P-OM3 and dietary-supplement omega-3 fatty acids.
Many types of nonprescription dietary supplements of omega-3 fatty acids are available; however, the efficacy, quality, and safety of these products are open to question because they are not regulated by the same standards as pharmaceutical agents. P-OM3 is the only omega-3 fatty acid product (Omacor capsules) approved by the US FDA available in the United States as an adjunct to diet to reduce very high (> or = 500 mg/dL) triglyceride levels in adult patients.
P-OM3 can be used with confidence by practitioners who want to provide therapeutic doses of omega-3 fatty acids in a preparation that has been documented to be both safe and effective.
Both HIV and its treatment, particularly protease inhibitors, can cause lipidemia similar to that seen with the metabolic syndrome. The most notable effects are elevated triglyceride levels and decreased high-density lipoprotein cholesterol levels, with or without elevated low-density lipoprotein cholesterol (LDL-C) levels. Current recommendations by the National Cholesterol Education Program for HIV-infected persons focus on LDL-C as the primary target of therapy: after lifestyle modifications, statins should be used to lower LDL-C levels. Therapy with fibrates is recommended to lower triglyceride levels. However, omega-3 fatty acids can be an effective means of lowering triglyceride levels as well, particularly in patients with markedly elevated triglyceride levels.
Hypertriglyceridemia is a risk factor for atherosclerotic coronary heart disease. Very high triglyceride (TG) levels (> or =500 mg/dl [5.65 mmol/l]) increase the risk of pancreatitis. One therapeutic option to lower TG levels is omega-3 fatty acids, which are derived from the oil of fish and other seafood. The American Heart Association has acknowledged that fish oils may decrease dysrhythmias, decrease sudden death, decrease the rate of atherosclerosis and slightly lower blood pressure, and has recommended fish consumption or fish oil supplementation as a therapeutic strategy to reduce cardiovascular disease. A prescription omega-3-acid ethyl esters (P-OM3) preparation has been available in many European nations for at least a decade, and was approved by the US FDA in 2004 to reduce very high TG levels (> or =500 mg/dl [5.65 mmol/l]). Mechanistically, most evidence suggests that omega-3 fatty acids reduce the synthesis and secretion of very-low-density lipoprotein (VLDL) particles, and increase TG removal from VLDL and chylomicron particles through the upregulation of enzymes, such as lipoprotein lipase. Omega-3 fatty acids differ mechanistically from other lipid-altering drugs, which helps to explain why therapies such as P-OM3 have complementary mechanisms of action and, thus, complementary lipid benefits when administered with statins. Additional human studies are needed to define more clearly the cellular and molecular basis for the TG-lowering effects of omega-3 fatty acids and their favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.
The effect of a fish oil preparation, K-85, in which the omega-3 fatty acid content was concentrated to 92% of total fat, on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia.
The study was a randomized, double-blind, placebo-controlled study.
Seven centres participated in the study, five secondary referral centres and two general practices.
Men and women aged 18-70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied. Patients with diabetes mellitus, hypothyroidism, serious illness in the previous 3 months or severe concurrent illness were excluded from the study, as were drug or alcohol abusers and pregnant and lactating women. Ninety-five subjects entered the study, 79 completed the study.
Patients were randomized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks.
The serum concentrations of triglycerides and cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein (a). Fasting blood glucose and blood pressure.
Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6, 10 and 14 weeks (all P < 0.01) and there was a decrease in the serum triglyceride concentration from 3.99 (2.94-9.47) to 2.87 (1.2-9.93) mmol/l (P < 0.001) and in VLDL-cholesterol from 1.47 (0.77-3.63) to 1.12 (0.21-3.67) mmol/l (P < 0.01) in patients receiving K-85. Serum HDL-cholesterol increased from 0.98 (0.95-1.01) to 1.11 (1.07-1.15) mmol/l (P < 0.01) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb. Serum LDL-cholesterol, lipoprotein (a) and fasting blood glucose were unaffected by K-85. Diastolic blood pressure decreased from 86 +/- 11 to 80 +/- 12 mmHg (P < 0.02) and was also lower than in the placebo group (P < 0.05). The corn oil placebo did not affect any of the parameters.
K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent.
To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum lipids, apolipoproteins, and serum phospholipid fatty acids in humans, we conducted a double-blind, placebo-controlled, parallel design intervention study. Healthy nonsmoking men (n = 234) aged 36-56 y were randomly assigned to dietary supplementation with 3.8 g EPA/d, 3.6 g DHA/d, or 4.0 g corn oil/d (placebo) for 7 wk. Serum triacylglycerols decreased 26% (P < 0.0001) in the DHA group and 21% (P = 0.0001) in the EPA group compared with the corn oil group. Although not significant, net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations. Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L (P = 0.0002) in the DHA group. In the EPA group, serum total cholesterol decreased 0.15 mmol/L (P = 0.02) and apolipoprotein A-I decreased 0.04 g/L (P = 0.0003). In the DHA group, serum phospholipid DHA increased by 69% and EPA increased by 29%, indicating retroconversion of DHA to EPA. In the EPA group, serum phospholipid EPA increased by 297% whereas DHA decreased by 15%, suggesting that EPA is not elongated to DHA in humans. The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups, whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group. We conclude that both DHA and EPA decrease serum triacylglycerols, but have differential effects on lipoprotein and fatty acid metabolism in humans.
Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk.
This study aimed to determine whether eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have differential effects on serum lipids and lipoproteins, glucose, and insulin in humans.
In a double-blind, placebo-controlled trial of parallel design, 59 overweight, nonsmoking, mildly hyperlipidemic men were randomly assigned to receive 4 g purified EPA, DHA, or olive oil (placebo) daily while continuing their usual diets for 6 wk.
Fifty-six men aged 48.8 +/- 1.1 y completed the study. Relative to those in the olive oil group, triacylglycerols fell by 0.45 +/- 0.15 mmol/L ( approximately 20%; P = 0.003) in the DHA group and by 0.37 +/- 0.14 mmol/L ( approximately 18%; P = 0.012) in the EPA group. Neither EPA nor DHA had any effect on total cholesterol. LDL, HDL, and HDL(2) cholesterol were not affected significantly by EPA, but HDL(3) cholesterol decreased significantly (6.7%; P = 0.032). Although HDL cholesterol was not significantly increased by DHA (3. 1%), HDL(2) cholesterol increased by approximately 29% (P = 0.004). DHA increased LDL cholesterol by 8% (P = 0.019). Adjusted LDL particle size increased by 0.25 +/- 0.08 nm (P = 0.002) with DHA but not with EPA. EPA supplementation increased plasma and platelet phospholipid EPA but reduced DHA. DHA supplementation increased DHA and EPA in plasma and platelet phospholipids. Both EPA and DHA increased fasting insulin significantly. EPA, but not DHA, tended to increase fasting glucose, but not significantly so.
EPA and DHA had differential effects on lipids, fatty acids, and glucose metabolism in overweight men with mild hyperlipidemia.
Epidemiological and clinical trial evidence suggests that omega-3 polyunsaturated fatty acids (PUFAs) might have a significant role in the prevention of coronary heart disease. Dietary sources of omega-3 PUFA include fish oils rich in eicosapentaenoic acid and docosahexaenoic acid along with plants rich in alpha-linolenic acid. Randomized clinical trials with fish oils (eicosapentaenoic acid and docosahexaenoic acid) and alpha-linolenic acid have demonstrated reductions in risk that compare favorably with those seen in landmark secondary prevention trials with lipid-lowering drugs. Several mechanisms explaining the cardioprotective effect of omega-3 PUFAs have been suggested, including antiarrhythmic, hypolipidemic, and antithrombotic roles. Although official US guidelines for the dietary intake of omega-3 PUFAs are not available, several international guidelines have been published. Fish is an important source of omega-3 PUFAs in the US diet; however, vegetable sources, including grains and oils, offer an alternative source for those who are unable to regularly consume fish.
Lipid abnormalities may contribute to the increased risk of atherosclerosis and coronary disease in visceral obesity. Fish oils lower plasma triacylglycerols, but the underlying mechanisms are not fully understood.
We studied the effect of fish oils on the metabolism of apolipoprotein B-100 (apo B) and chylomicron remnants in obese men.
Twenty-four dyslipidemic, viscerally obese men were randomly assigned to receive either fish oil capsules (4 g/d, consisting of 45% eicosapentaenoic acid and 39% docosahexaenoic acid as ethyl esters) or matching placebo (corn oil, 4 g/d) for 6 wk. VLDL, intermediate-density lipoprotein (IDL), and LDL apo B kinetics were assessed by following apo B isotopic enrichment with the use of gas chromatography-mass spectrometry after an intravenous bolus injection of trideuterated leucine. Chylomicron remnant catabolism was measured with the use of an intravenous injection of a chylomicron remnant-like emulsion containing cholesteryl [(13)C]oleate, and isotopic enrichment of (13)CO(2) in breath was measured with isotope ratio mass spectrometry. Kinetic values were derived with multicompartmental models.
Fish oil supplementation significantly (P < 0.05) lowered plasma concentrations of triacylglycerols (-18%) and VLDL apo B (-20%) and the hepatic secretion of VLDL apo B (-29%) compared with placebo. The percentage of conversions of VLDL apo B to IDL apo B, VLDL apo B to LDL apo B, and IDL apo B to LDL apo B also increased significantly (P < 0.05): 71%, 93%, and 11%, respectively. Fish oils did not significantly alter the fractional catabolic rates of apo B in VLDL, IDL, or LDL or alter the catabolism of the chylomicron remnant-like emulsion.
Fish oils effectively lower the plasma concentration of triacylglycerols, chiefly by decreasing VLDL apo B production but not by altering the catabolism of apo B-containing lipoprotein or chylomicron remnants.
To comprehend the results of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis and interpretation. That goal can only be achieved through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement.
The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results and Discussion. The revised checklist includes 22-items selected because empirical evidence indicates that not reporting the information is associated with biasedestimates of treatment effect or the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of a trial (enrolment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, for each intervention group, included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis.
In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
This report summarizes our current understanding of how monounsaturated fatty acids (MUFAs) affect risk for cardiovascular disease (CVD). This is a topic that has attracted considerable scientific interest,1 2 3 in large part because of uncertainty regarding whether MUFA or carbohydrate should be substituted for saturated fatty acids (SFAs) and the desirable quantity of MUFA to include in the diet.
MUFAs are distinguished from the other fatty acid classes on the basis of having only 1 double bond. In contrast, polyunsaturated fatty acids (PUFAs) have 2 or more double bonds, and SFAs have none. The position of the hydrogen atoms around the double bond determines the geometric configuration of the MUFA and hence whether it is a cis or trans isomer. In a cis MUFA, the hydrogen atoms are present on the same side of the double bond, whereas in the trans configuration, they are on opposite sides. The American Heart Association Nutrition Committee recently published a scientific statement regarding the relationship of trans MUFA to CVD risk,4 and the present statement, therefore, will be limited to a discussion of dietary cis MUFAs, of which oleic acid ( cis C18:1) comprises ≈92% of cis MUFAs. In the United States, average total MUFA intake is 13% to 14% of total energy intake, an amount that is comparable to (or slightly greater than) SFA intake. In contrast, PUFAs contribute less (ie, 7% of energy).
The major emphasis of current dietary guidelines involves replacing SFAs with complex carbohydrates to achieve a total fat intake of ≤30% of calories. There is evidence suggesting that the substitution of MUFA instead of carbohydrate for SFA calories may favorably affect CVD risk.5 6 7 The American Heart Association dietary guidelines for healthy American adults recommend a diet that provides <10% of calories from SFA, up …
Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (SD) proportion of -linolenic acid was 0.77% (0.19) of fatty acids in cases and 0.80% (0.19) of fatty acids in controls (P0.01). The relative risk for the highest quintile of -linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trend0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trend0.38). The mean proportion of docosahexaenoic acid was 0.24% (0.13) of fatty acids in cases and 0.25% (0.13) of fatty acids in controls (P0.14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of -linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research. (Arterioscler Thromb Vasc Biol. 1999;19:1111-1118.) Key Words: myocardial infarction -linolenic acid docosahexaenoic acid case-control studies adipose tissue.
To 1) conduct a thorough search of the literature for randomized controlled trials (RCTs) addressing the efficacy of garlic as an antihy-perlipidemic agent, 2) critically appraise those studies, and 3) make a recommendation for practicing health care professionals.
Two independent reviewers extracted data from the articles identified from several data bases, using the previously tested Boyack and Lookinland Methodological Quality Index (MQI) as the standard.
Six of ten studies found garlic to be effective. The average drop in total cholesterol was 24.8 mg/dL (9.9%), LDL 15.3 mg/dL (11.4%), and triglycerides 38 mg/dL (9.9%). The over-all average MQI score was 39.6% (18%-70%). Major shortcomings of many of the RCTs included short duration, lack of power analysis and intention to treat analysis, as well as lack of control of diet as a confoundingvariable.
The low methodological quality of the studies make it difficult to recommend garlic as an antihyperlipidemic agent. Until larger RCTs of longer duration, which correct the existing methodological flaws, are designed and carried out, it is best not to recommend garlic be used to treat mild to moderate hyperlipidemia.
In 753 patients with acute myocardial infarction, use of fish oils (FO, n = 242) before onset of infarction seemed to reduce infarct size as estimated from peak creatine kinase (CKmax) and lactate dehydrogenase (LDmax) activities. The study had an observational exposed/nonexposed design, and both crude and adjusted effects were looked for. CRUDE EFFECTS: In the restricted cohort of patients not receiving thrombolytic treatment (n = 411), FO reduced CKmax from 879 to 759 U/l (2 p = 0.030) and LDmax from 870 to 768 U/l (2 p = 0.011), respectively. More of these patients in the lowest enzyme quartiles used FO, p for linear trend was for CKmax 0.008 and for LDmax 0.06, respectively. ADJUSTED EFFECTS: In patients not receiving thrombolytic treatment, FO reduced CKmax (2 p = 0.007) and LDmax (2 p = 0.005), but in patients receiving such treatment, CKmax and LDmax values increased, 2 p being 0.036 and 0.097, respectively. In patients not receiving thrombolysis, FO increased the incidence of small infarcts (the 25% quartile), odds ratio for CKmax was 1.82 (2 p = 0.018) and for LDmax 1.66 (2 p = 0.048), respectively. The results indicate that FO may reduce infarct size and the incidence of large infarcts. In addition, FO seems to enhance the effect of thrombolysis.
To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest.
Population-based case-control study.
Seattle and suburban King County, Washington.
A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements. MEASURES OF EXPOSURE: Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake.
Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6).
Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest.
The impact of n-3 fatty acids (FA) on blood lipoprotein levels has been examined in many studies over the last 15 yr in both animals and humans. Studies in humans first demonstrated the potent triglyceride-lowering effect of n-3 FA, and these were followed up with animal studies to unravel the mechanism of action. This paper reviews the reported effects of n-3 FA on blood lipoproteins in 72 placebo-controlled human trials, at least 2 wk in length and providing 7 or less g of n-3 FA/day. Trials in normolipidemic subjects (triglycerides < 2.0 mM; 177 mg/dL) were compared to those in hypertriglyceridemic patients (triglycerides > or = 2.0 mM). In the healthy subjects, mean triglyceride levels decreased by 25% (P < 0.0001), and total cholesterol (C) levels increased by 2% (P < 0.009) due to the combined increases in low density lipoprotein (LDL)-C (4%, P < 0.02) and high density lipoprotein (HDL)-C (3%, P < 0.008). In the patients, triglyceride levels decreased by 28% (P < 0.0001), LDL-C rose by 7% (P < 0.0001), but neither total C nor HDL-C changed significantly. Although the effect on triglyceride levels is also observed in rats and swine, it is rarely seen in mice, rabbits, monkeys, dogs, and hamsters. Whereas n-3 FA have only a minor impact on lipoprotein C levels in humans, they often markedly lower both total C and HDL-C levels in animals, especially monkeys. These differences are not widely appreciated and must be taken into account when studying the effects of n-3 FA on lipoprotein metabolism.
We investigated the efficacy of fish oils in Portuguese patients with hypertriglyceridaemia and mixed hyperlipidaemia, and the influence of fish consumption on the triglyceride lowering capacity of fish oils. Forty patients participated in this double-blind study, consisting of a 4-week dietary or wash-out baseline period after which patients were randomly assigned to receive either 12 fish oil capsules (3.6 g/day of omega 3) or similar 12 soya oil capsules per day for a period of 2 months. There were no statistically significant changes of total, HDL or LDL-cholesterol, and triglycerides. Nevertheless, triglycerides increased 19.9% with soya oil and decreased 27.8% with fish oils. Also, there was an inverse relationship (rho = -0.352) between fish consumption and fish oils effect on triglycerides, and the triglyceride lowering with fish oils increased (from 27.8% to 44.4%), reaching borderline significance, if we excluded patients consuming one or more meals with fish per day. Glucose increased 11% (P = 0.0047) with fish oils. These findings suggest that the triglyceride lowering effect of fish oils is affected by fish consumption, and confirm that fish oils increase blood glucose levels in diabetics and non-diabetics.
Dietary fish intake has been associated with a reduced risk of fatal cardiac end points, but not with nonfatal end points. Dietary fish intake may have a selective benefit on fatal arrhythmias and therefore sudden cardiac death.
To investigate prospectively the association between fish consumption and the risk of sudden cardiac death.
Prospective cohort study.
The US Physicians' Health Study.
A total of 20 551 US male physicians 40 to 84 years of age and free of myocardial infarction, cerebrovascular disease, and cancer at baseline who completed an abbreviated, semiquantitative food frequency questionnaire on fish consumption and were then followed up to 11 years.
Incidence of sudden cardiac death (death within 1 hour of symptom onset) as ascertained by hospital records and reports of next of kin.
There were 133 sudden deaths over the course of the study. After controlling for age, randomized aspirin and beta carotene assignment, and coronary risk factors, dietary fish intake was associated with a reduced risk of sudden death, with an apparent threshold effect at a consumption level of 1 fish meal per week (P for trend=.03). For men who consumed fish at least once per week, the multivariate relative risk of sudden death was 0.48 (95% confidence interval, 0.24-0.96; P=.04) compared with men who consumed fish less than monthly. Estimated dietary n-3 fatty acid intake from seafood also was associated with a reduced risk of sudden death but without a significant trend across increasing categories of intake. Neither dietary fish consumption nor n-3 fatty acid intake was associated with a reduced risk of total myocardial infarction, nonsudden cardiac death, or total cardiovascular mortality. However, fish consumption was associated with a significantly reduced risk of total mortality.
These prospective data suggest that consumption of fish at least once per week may reduce the risk of sudden cardiac death in men.
To determine whether cardiovascular disease can be predicted from plasma triglyceride levels independent of high density lipoprotein (HDL) cholesterol levels.
Seventeen prospective population-based studies, ranging in publication date from 1965 to 1994, were selected based on uniform criteria. Among the studies, 16 were conducted in men, comprising data for more than 46,000 men, with an average follow-up period of more than eight years. The data from women came from five studies, including nearly 11,000 women with an 11-year average follow-up.
The meta-analysis protocol comprised the following steps: estimating the relative risk of triglyceride for each individual study; standardizing the relative risks to a 1 mmol/l increase; estimating the variance and weighting relative risks by the inverse of the variance, and estimating the summary relative risk by averaging the weighted relative risks.
Among studies of men, relative risks ranged from 1.1 to 2.0, and the summary relative risk was 1.32 (P < 0.05). All five studies of women were statistically significant, with relative risks ranging from 1.7 to 2.0. The summary relative risk was 1.76, higher than that for men, indicating a 76% increase in risk for women. For the studies among men in which HDL cholesterol data were available, multivariate adjusted relative risk was attenuated to 1.14 but was still statistically significant. Although only two studies of women included HDL cholesterol adjustments, the summary relative risk for triglyceride remained statistically significant, with a value of 1.37.
When all available data are taken into account, increased triglyceride level is a risk factor for cardiovascular disease, independent of HDL cholesterol level. Clinical trials are urgently needed to determine whether lowering plasma triglyceride levels reduces subsequent risk of cardiovascular disease.
Severe hypertriglyceridemia is a risk factor for acute pancreatitis, therefore decreasing serum triglyceride concentrations is an important component of risk management. Omega-3 fatty acids are well known hypotriglyceridemic agents, but their efficacy in severe forms of the disorder is not well documented. Our objective was to examine the effects of Omacor, a drug composed of 85% omega-3 fatty acid ethyl esters.
Forty-two patients with triglyceride concentrations between 5.65 and 22.60 mmol/l (500 and 2000 mg/dl) were studied in a prospective, double-blind, placebo-controlled trial of Omacor (4 g/day for 4 months).
Compared with baseline values, Omacor significantly reduced mean triglyceride concentrations by 45% (P<0.00001), cholesterol by 15% (P< 0.001), very-low-density lipoprotein cholesterol by 32% (P< 0.0001) and cholesterol:high density lipoprotein (HDL) cholesterol ratio by 20% (P=0.0013), and increased HDL cholesterol by 13% (P=0.014) and low-density lipoprotein cholesterol by 31% (P=0.0014). The placebo had no effect on these parameters. Omacor was well tolerated and no patient discontinued medication because of side effects.
Four capsules of Omacor per day markedly decreased triglyceride concentrations in patients with severe hypertriglyceridemia. The availability of a potent and safe omega-3 fatty acid preparation for this patient population should diminish the risk for acute pancreatitis, and may also reduce the long-term risk for cardiovascular disease.
Elevations of plasma cholesterol and/or triglycerides, and the prevalence of small, dense LDL particles remarkably increase coronary risk in patients with familial combined hyperlipidemia (FCHL). A total of 14 FCHL patients were studied, to investigate the ability of Omacor, a drug containing the n-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA and DHA), to favorably correct plasma lipid/lipoprotein levels and LDL particle distribution. The patients received four capsules daily of Omacor (providing 3.4 g EPA+DHA per day) or placebo for 8 weeks in a randomized, double-blind, cross-over study. Omacor significantly lowered plasma triglycerides and VLDL-cholesterol levels, by 27 and 18%, respectively. Total cholesterol did not change but LDL-cholesterol and apolipoprotein B (apoB) concentrations increased by 21 and 6%. As expected, LDL particles were small (diameter=24.9+/-0.3 nm) and apoB-rich (LDL-cholesterol/apoB ratio=1.27+/-0.26) in the selected subjects. After Omacor treatment LDL became enriched in cholesterol (LDL-cholesterol/apoB ratio=1.40+/-0.17), mainly cholesteryl esters, indicating accumulation in plasma of more buoyant and core enriched LDL particles. Indeed, the separation of LDL subclasses by rate zonal ultracentrifugation showed an increase of the plasma concentration of IDL and of the more buoyant, fast floating LDL-1 and LDL-2 subclasses after Omacor, with a parallel decrease in the concentration of the denser, slow floating LDL-3 subclass. However, the average LDL size did not change after Omacor (25.0+/-0.3 nm). The resistance of the small LDL pattern to drug-induced modifications implies that a maximal lipid-lowering effect must be achieved to reduce coronary risk in FCHL patients.
This work was undertaken to determine whether dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia.
Marine omega-3 fatty acids improve vascular function, but the underlying mechanism(s) are unclear. We studied the effects of marine omega-3 fatty acids on large artery endothelial function in subjects with hypercholesterolemia.
Hypercholesterolemic subjects with no other known cause for endothelial dysfunction were recruited to a prospective, placebo-controlled, randomized, double-blind, parallel-group study. Treatment with omega-3 fatty acids at a dose of 4 g/day (n = 15/group) was compared with placebo, at the beginning (day 0) and end (day 120) of a four-month treatment period. Endothelial function was assessed pre- and posttreatment by noninvasive ultrasonic vessel wall tracking of brachial artery flow-mediated dilation (FMD).
Treatment with marine omega-3 fatty acids resulted in a significant improvement in FMD (0.05 +/- 0.12 to 0.12 +/- 0.07 mm, p < 0.05) and a significant reduction in triglycerides (2.07 +/- 1.13 to 1.73 +/- 0.95 mmol/liter, p < 0.05), whereas treatment with placebo resulted in no change in FMD (0.03 +/- 0.10 to 0.04 +/- 0.10 mm) or triglycerides (2.29 +/- 2.09 to 2.05 +/- 1.36 mmol/liter) (both p < 0.05 treated compared with control). Responses to sublingual glyceryl trinitrate were unchanged.
Marine omega-3 fatty acids improve large artery endothelium-dependent dilation in subjects with hypercholesterolemia without affecting endothelium-independent dilation.
Epidemiologic studies suggest that a higher consumption of eicosapentaenoic acid and docosahexaenoic acid is associated with a reduced risk of cardiovascular disease. Studies in humans and animals also reported an inverse association between alpha-linolenic acid and cardiovascular disease morbidity and mortality.
We examined the relation between dietary linolenic acid and prevalent coronary artery disease (CAD).
We studied 4584 participants with a mean (+/-SD) age of 52.1 +/- 13.7 y in the National Heart, Lung, and Blood Institute Family Heart Study in a cross-sectional design. Participants' diets were assessed with a semiquantitative food-frequency questionnaire. For each sex, we created age- and energy-adjusted quintiles of linolenic acid, and we used logistic regression to estimate prevalent odds ratios for CAD.
From the lowest to the highest quintile of linolenic acid, the prevalence odds ratios of CAD were 1.0, 0.77, 0.61, 0.58, and 0.60 for the men (P for trend = 0.012) and 1.0, 0.57, 0.52, 0.30, and 0.42 for the women (P for trend = 0.014) after adjustment for age, linoleic acid, and anthropometric, lifestyle, and metabolic factors. Linoleic acid was also inversely related to the prevalence odds ratios of CAD in the multivariate model (0.60 and 0.61 in the second and third tertiles, respectively) after adjustment for linolenic acid. The combined effect of linoleic and linolenic acids was stronger than the individual effects of either fatty acid.
A higher intake of either linolenic or linoleic acid was inversely related to the prevalence odds ratio of CAD. The 2 fatty acids had synergistic effects on the prevalence odds ratio of CAD.
Experimental data suggest that long-chain n-3 polyunsaturated fatty acids found in fish have antiarrhythmic properties, and a randomized trial suggested that dietary supplements of n-3 fatty acids may reduce the risk of sudden death among survivors of myocardial infarction. Whether long-chain n-3 fatty acids are also associated with the risk of sudden death in those without a history of cardiovascular disease is unknown.
We conducted a prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study. The fatty-acid composition of previously collected blood was analyzed by gas-liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status.
Base-line blood levels of long-chain n-3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71).
The n-3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease.
To critically appraise recent randomized controlled trials (RCT) of raloxifene and its effects on the long-term consequences of menopause.
All RCTs of greater than six months duration in post-menopausal women found in MEDLINE through July 2000.
Raloxifene lowered lipids, but estrogen had a more beneficial effect on HDL and fibrinolytic markers. Raloxifene had a more beneficial effect on triglycerides, inflammatory and thrombogenic markers. Compared to placebo, raloxifene reduced vertebral fractures but had a similar although lesser effect on bone mineral density and markers of bone turnover than estrogen. Estrogen receptor positive breast cancer was reduced by 90% with no increase in the incidence of endometrial cancer with raloxifene. The most serious side effect of raloxifene was an increased incidence of deep vein thromboses and pulmonary emboli.
Raloxifene has been shown to be beneficial using cardiovascular and osteoporosis end-points in studies of short duration. More RCTs of longer duration with comparisons to other traditional treatments are needed before raloxifene becomes the treatment of choice.
Epidemiological studies have shown that plasma HDL-cholesterol is inversely related to coronary artery disease and that there is an inverse relationship between HDL-cholesterol and triglyceride levels, but it is now demonstrated that hypertriglyceridemia is an independent risk factor for coronary heart disease (CHD). The goal of this review is to discuss if triglycerides and HDL-cholesterol could be therapeutic targets to reduce cardiovascular risk.
Triglyceride measurement is not informative on the specificity of the triglyceride-rich lipoproteins present in the plasma because some of these are not atherogenic (chylomicrons, large VLDLs) while others are highly atherogenic (small VLDLs, remnants, IDL...). Statins, in addition to reducing LDL-cholesterol, significantly reduced atherogenic remnant lipoprotein cholesterol levels. 4S, CARE+LIPID, and AFCAPS/TexCAPS studies, suggested enhanced therapeutic potential of statins for improving triglyceride and HDL-cholesterol levels in patients with CHD. A fibrate (gemfibrozil) was shown to reduce death from CHD and non-fatal myocardial infarction in secondary prevention of CHD in men with low levels of HDL-cholesterol (VA-HIT); during the treatment these levels predicted the magnitude of reduction in risk for CHD events.
ATP III recommendations state, on triglycerides and HDL-cholesterol as targets to reduce cardiovascular risk: (1) that lowering LDL-cholesterol levels is the primary target of therapy, (2) a secondary target is to achieve a triglyceride level < 150 mg/dL and (3) clinical trial data are considered to be insufficient to support recommended a specific HDL-cholesterol goal even if HDL-cholesterol < 40 mg/dL is considered to be a major risk factor of CHD.
To review available literature regarding the cardiovascular effects of marine-derived Omega-3 fatty acids and evaluate the benefit of these fatty acids in the prevention of coronary heart disease.
Biomedical literature accessed through a MEDLINE search (1966-April 2002). Search terms included fish oil, omega-3 fatty acid, sudden death, hypertriglyceridemia, myocardial infarction, and mortality.
Following an early 1970's observational investigation that Omega-3 fatty acids may reduce the occurrence of myocardial infarction-related deaths in Greenland Eskimos, additional trials have been conducted that support this finding. Epidemiologic and clinical trial data suggest that Omega-3 fatty acids may reduce the risk of cardiovascular-related death by 29-52%. In addition, the risk of sudden cardiac death was found to be reduced by 45-81%. Possible mechanisms for these beneficial effects include antiarrhythmic properties, improved endothelial function, antiinflammatory action, and reductions in serum triglyceride concentrations. Omega-3 Fatty acids are fairly well tolerated; potential adverse effects include bloating and gastrointestinal distress, "fishy taste" in the mouth, hyperglycemia, increased risk of bleeding, and a slight increase in low-density-lipoprotein cholesterol.
Omega-3 Fatty acids may be beneficial and should be considered in patients with documented coronary heart disease. They may be particularly beneficial for patients with risk factors for sudden cardiac death.
Epidemiologic and clinical trials show that elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C) are independent risk factors for coronary heart disease (CHD). However, adjustment for covariates frequently weakens or abolishes the predictive significance of triglycerides, whereas the evidence for HDL-C is more consistently strong. Data indicate that there is a 2% to 3% decrease in coronary risk for each 1 mg/dL increase in HDL-C, whereas the benefit of triglyceride lowering appears to occur largely in patients with the highest baseline levels. The 2001 National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines for detecting and treating high blood cholesterol reflect our improved understanding of triglycerides and HDL as CHD risk factors. However, the guidelines place more emphasis on lowering triglycerides than on raising HDL-C by identifying non-HDL-C (ie, low-density lipoprotein cholesterol [LDL-C] + very-low-density lipoprotein cholesterol [VLDL-C]) as a secondary target of therapy. In clinical practice, VLDL-C is the most readily available measure of atherogenic triglyceride-rich remnant lipoproteins. On the basis of the available epidemiologic and clinical evidence, refinement of the NCEP guidelines to include more emphasis on raising HDL-C levels should be considered. Novel drugs are being developed that have the potential to increase HDL-C concentrations and/or improve the functionality of HDL.
Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and gamma-linolenic acid (GLA) have lipid-modifying and antiinflammatory properties. The effects of supplement mixtures of these fatty acids on plasma lipids and the fatty acid compositions of serum phospholipids have received little attention.
The objective was to determine the effects of different levels of GLA supplementation together with a constant intake of EPA plus DHA on the triacylglycerol-lowering effect of EPA plus DHA alone and on the fatty acid patterns (eicosanoid precursors) of serum phospholipids.
Thirty-one women were assigned to 1 of 4 groups, equalized on the basis of their fasting triacylglycerol concentrations. They received supplements providing 4 g EPA+DHA (4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g GLA (4:1), 2 g GLA (4:2), or 4 g GLA (4:4) daily for 28 d. Plasma lipids and fatty acids of serum phospholipids were measured on days 0 and 28.
Plasma triacylglycerol concentrations were significantly lower on day 28 than on day 0 in the 4:0, 4:1, and 4:2 groups. LDL cholesterol decreased significantly (by 11.3%) in the 4:2 group. Dihomo-gamma-linolenic acid increased significantly in serum phospholipids only in the 4:2 and 4:4 groups; however, total n-3 fatty acids increased in all 4 groups.
A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood lipid and fatty acid profiles in healthy women. On the basis of calculated PROCAM values, the 4:2 group was estimated to have a 43% reduction in the 10-y risk of myocardial infarction.
Omega-3 fatty acids have been shown in epidemiological and clinical trials to reduce the incidence of CVD. Large-scale epidemiological studies suggest that individuals at risk for CHD benefit from the consumption of plant- and marine-derived omega-3 fatty acids, although the ideal intakes presently are unclear. Evidence from prospective secondary prevention studies suggests that EPA+DHA supplementation ranging from 0.5 to 1.8 g/d (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality. For α-linolenic acid, total intakes of ≈1.5 to 3 g/d seem to be beneficial. Collectively, these data are supportive of the recommendation made by the AHA Dietary Guidelines to include at least two servings of fish per week (particularly fatty fish). In addition, the data support inclusion of vegetable oils (eg, soybean, canola, walnut, flaxseed) and food sources (eg, walnuts, flaxseeds) high in α-linolenic acid in a healthy diet for the general population (Table 5). The fish recommendation must be balanced with concerns about environmental pollutants, in particular PCB and methylmercury, described in state and federal advisories. Consumption of a variety of fish is recommended to minimize any potentially adverse effects due to environmental pollutants and, at the same time, achieve desired CVD health outcomes. RCTs have demonstrated that omega-3 fatty acid supplements can reduce cardiac events (eg, death, nonfatal MI, nonfatal stroke) and decrease progression of atherosclerosis in coronary patients. However, additional studies are needed to confirm and further define the health benefits of omega-3 fatty acid supplements for both primary and secondary prevention. For example, placebo-controlled, double-blind RCTs are needed to document both the safety and efficacy of omega-3 fatty acid supplements in both high-risk patients (eg, patients with type 2 diabetes, dyslipidemia, and hypertension, and smokers) and coronary patients on drug therapy. Mechanistic studies on their apparent effects on sudden death are also needed. A dietary (ie, food-based) approach to increasing omega-3 fatty acid intake is preferable. Still, for patients with coronary artery disease, the dose of omega-3 (≈1 g/d) may be greater than what can readily be achieved through diet alone (Table 5). These individuals, in consultation with their physician, could consider supplements for CHD risk reduction. Supplements also could be a component of the medical management of hypertriglyceridemia, a setting in which even larger doses (2 to 4 g/d) are required (Table 5). The availability of high-quality omega-3 fatty acid supplements, free of contaminants, is an important prerequisite to their extensive use.
The objective of this study was to investigate the effects and tolerability of an omega-3 ethyl ester concentrate (Omacor™ ) on serum lipid concentrations in patients with hyperlipidaemia. A multicentre, double-blind, randomised, placebo-controlled trial was performed in the hospital and general practice setting. 84 patients with hyperlipidaemia were given a therapeutic lipid-lowering diet for 10 weeks. Of these, 55 patients were randomised to a 12-week treatment period. 47 patients completed the study and two patients withdrew because of adverse events. Randomised patients received omega-3 ethyl ester concentrate or corn oil (placebo), both administered at a dose of 2g twice daily in soft gelatin capsules. Main outcome measures included changes in eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) content of serum phospholipids, total serum triglycerides, total serum cholesterol, and high density lipoprotein (HDL) cholesterol between baseline (week 10) and the end of treatment (week 22). After 12 weeks of treatment, patients receiving the omega-3 ethyl ester concentrate showed a significant increase in the EPA/DHA content of serum phospholipids (p In conclusion, omega-3 ethyl ester concentrate, 4 g/day, produced a significant reduction in mean serum triglyceride concentration in patients with hyperlipidaemia and was well tolerated.
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