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Omega-3 Fatty Acids: The “Japanese” Factor?
... Для нормальной жизнедеятельности человека омега 3 ПНЖК должны поступать не только в достаточ ном количестве, но и в сбалансированном соотношении с омега 6 ПНЖК. Идеальное соотношение омега 6 : оме га 3 составляет 4:1 [14,17,21,37]. ...
... Harris W.S. с коллегами [33] изучили 25 метаанализов результатов исследований, в которых оценивали зави симость уровня ПНЖК и степень риска коронарных событий. Исследователи доказали, что количество боль ших коронарных событий обратно коррелирует с уровнем содержания ЭПК и даже больше -с уровнем ДГК в тка нях [24,27,29,33,37]. Этот эффект группа исследователей объяснили антиатерогенной ролью омега 3 ПНЖК. ...
In the article the scientific review of domestic and foreign medical literature devoted to the analysis of the role of omega-3 polyunsaturated fatty acids (PUFAs) — the most important factor of the cell membrane of essential nutrition is presented. The medical effects of omega-3 PUFAs are analyzed. The omega-3 has particular importance in children, first of all for the correct formation and normal functioning of the brain and nervous system as in utero so from the first days of life; during the periods of intense growth and stress coming from learning. A wide range of curative effects, almost universality of omega-3 PUFAs preparations explain its efficacy in various diseases, as well as during the «background» conditions. Therefore, the use of preparation with omega-3 fatty acids in the treatment of vegetative syndromes, autonomic dysfunction in children is an important corrector of cerebro-intestinal and cerebro-cardiac disorders and other interactions. Prospective in this direction is "Reytoil" preparation, which can be used from the age of three years (2–3 base courses during the year), especially at periods of children's adaptative loads.
... The beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) were first noted when researchers identified low rates of cardiovascular disease (CVD) among Greenland Inuit, whose diet consisted of foods high in omega-3 PUFAs, such as whale, fish and seal. [1][2][3][4] This population was also noted to have low levels of serum cholesterol and triglycerides, despite high intake of fat and cholesterol and low intake of fruit and vegetables. Proposed mechanisms for the cardiovascular (CV) protective effects of omega-3 PUFAs include antiarrhythmic effects, improvements in autonomic function, decreased platelet aggregation, decreased blood pressure, improvements in endothelial function, plaque stabilization and reduced atherosclerosis. ...
... The previous identification of lower incidences of CVD among populations that consume large amounts of fish, termed the "Eskimo effect" or "Japanese effect, " is based on epidemiologic data rather than RCTs. [1][2][3] More recent data suggest that the incidence of CV death and coronary heart disease among populations with a high fish diet (Greenland Inuit, Alaskan Native) is comparable to Western or Caucasian populations. 16,17 One explanation is that a gradual shift to a "Westernized" diet high in saturated fats may outweigh the potential benefits of omega-3 PUFAs in these populations. ...
Introduction:
Omega-3 polyunsaturated fatty acids (PUFAs) have purported protective cardiovascular (CV) effects. We sought to assess the evidence available for the use of omega-3 PUFAs for the prevention of cardiovascular disease (CVD).
Methods:
A systematic literature search was conducted using MEDLINE and EMBASE from 1999 to 2015. Placebo-controlled, randomized controlled trials (RCTs) that enrolled over 1000 patients with follow-up greater than 1 year and meta-analyses of RCTs were included.
Results:
Eight RCTs and 2 meta-analyses were included. In patients with preexisting CVD, only 1 of 5 included RCTs demonstrated a reduction in CV events with omega-3 PUFAs; however, the effect size was minimal, and the study was limited by an open-label design and lack of placebo control. Two meta-analyses concluded omega-3 PUFAs do not reduce CV events in addition to standard, evidence-based therapy in patients after myocardial infarction. Of the 3 predominantly primary prevention RCTs, only 1 demonstrated a minor reduction in major coronary events; however, it was also an open-label study. Furthermore, the safety of omega-3 PUFAs should be considered. While data from RCTs have not demonstrated serious safety concerns, omega-3 PUFAs can increase the risk of bleeding and may interact with other medications that affect hemostasis, such as antiplatelet agents and warfarin.
Discussion and conclusion:
There is currently a lack of evidence to support the routine use of omega-3 PUFAs in the primary and secondary prevention of CVD. Pharmacists are ideally situated to engage patients in the discussion of the lack of benefit and possible risk of omega-3 PUFA supplements.
... Overall, the favorable involvement of omega-3 PUFA supplementation is debated, as recently pointed out by a meta-analysis [43]. We must also consider that an increase in consumption of long-chain omega-3 fatty acids through the intake of fish or supplementation could result in different outcomes [44]. First, increasing the consumption of fish would probably result in a diminution of consumption of meat, which is not necessary in the case with the long-chain omega-3 PUFA supplementation. ...
The high-fat diet of North Americans has a major impact on cardiovascular disease occurrence. Notably, fatty acids have been identified as important factors that could modulate such diseases, especially myocardial infarction (MI). Experimentally, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated positive effects on cardiovascular disorders and have also shown cardioprotection by decreasing MI size. Although many animal experiments have clearly established the benefits of omega-3 PUFA, clinical studies have not reached similar conclusions. In fact, the findings of recent clinical investigations indicate that omega-3 PUFA play only a minor role in cardiovascular health. This dichotomy between experimental and clinical studies may be due to different parameters that are not taken into account in animal experiments. We have recently observed that the high consumption of omega-6 PUFA results in significant attenuation of the beneficial effect of omega-3 PUFA on MI. We believe that part of the dichotomy between experimental and clinical research may be related to the quantity of omega-6 PUFA ingested. This review of the data indicates the importance of considering omega-6 PUFA consumption in omega-3 PUFA studies.
... IMT was associated with the plasma concentration of n-3 PUFAs in Japanese men, but a similar association was not observed for coronary artery disease (CAD). Previous reports had found that an extremely high intake of n-3 PUFAs inhibits atherosclerosis [87]. On the other hand, another report showed that DHA prevented chronic intermittent hypoxia-induced atherosclerosis but did not improve atherosclerosis in control apolipoprotein-E deficient mice [88]. ...
Docosahexaenoic acid (DHA) is present in high concentrations in salmon, herring, and trout. Epidemiologic studies have shown that high dietary consumption of these and other oily fish is associated with reduced rates of myocardial infarction, atherosclerosis, and other ischemic pathologies. Atherosclerosis is induced by inflammation and can lead to acute cardiovascular events and extensive plaque. DHA inhibits the development of inflammation in endothelial cells, alters the function and regulation of vascular biomarkers, and reduces cardiovascular risk. It also affects vascular relaxation and constriction by controlling nitric oxide and endothelin 1 production in endothelial cells. DHA also contributes to the prevention of arteriosclerosis by regulating the expression of oxidized low density lipoprotein receptor 1, plasminogen activator inhibitor 1, thromboxane A2 receptor, and adhesion molecules such as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and intercellular adhesion molecule 1 in endothelial cells. Recent research showed that DHA reduces the increase in adhesion factor expression induced by lipopolysaccharide by suppressing toll-like receptor 4. A new mechanism of action of DHA has been described that is mediated through endothelial free fatty acid receptor 4, associated with heme oxygenase 1 induction by Nrf2. However, the efficacy and mechanisms of action of DHA in cardiovascular disease prevention are not yet completely understood. The aim of this paper was to review the effects of DHA on vascular endothelial cells and recent findings on their potential for the prevention of circulatory diseases.
... [13][14][15][16] Others have demonstrated that omega-3 PUFAs assist in prevention of oxidative damage and regulation of brain-derived neurotrophic factor levels after traumatic brain injury, and counteracting learning disabilities typically associated with traumatic brain injury in rats. 17 Other studies have reported that omega-3 FAs can lower the risk for coronary heart disease, atherosclerosis, sudden cardiac death, and atrial fibrillation, [18][19][20][21][22][23] all of which could serve to benefit members of the armed forces. ...
Increasingly, private and military consumers are becoming aware of the positive benefits of a diet rich in omega-3 fatty acids (FAs) as health claims range from reducing inflammation to improving mood. The number of positive scientific articles supporting these claims is rapidly increasing, leading the military to examine the possibility of omega-3 supplementation for personnel. A variety of menus used either in shipboard or garrison feeding include fatty fishes that are rich in omega-3 FAs. However, omega-3 FAs have shelf-stability issues because of their susceptibility to oxidize; therefore, they create a challenge in terms of incorporation into ration components in nutritionally significant amounts. As a result, the Department of Defense Combat Feeding Directorate is investigating methods, technologies, and emerging products for incorporation of omega-3s into ration components. Based on existing research, fortification of foods with omega-3 FAs would improve nutritional quality as well as provide added benefit to the Warfighters.
... I USA er omega-3-fettsyreinntaket fra EPH/DHA anslått til omkring 200 mg daglig (7). Tilsvarende i Japan er 0,8-1,5 g om dagen (49). ...
... Only a few epidemiological studies and randomized controlled trials have presented results indicative of a lack of effect [54,55,[71][72][73][74] or a direct harmful effect of a high intake of n-3 PUFAs [75,76]. The lack of effect on CAD from a relatively high intake of n-3 PUFAs in Western coastal populations has been suggested to be due to a concomitant high intake of saturated FAs and monounsaturated FAs [77]. The Western coastal populations differ not only from the Japanese with respect to n-3 PUFA levels; they also ingest more of the apparently unhealthy FAs with a possible attenuation of the health effects of n-3 PUFAs. ...
This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists a dose-response relation for n-3 PUFA supplementation is widely discussed. Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.
... Also unclear is how EPA and DHA consumption interacts with other factors, such as physical activity or use of NSAIDs, in affecting inflammatory processes linked to aging. In this regard, epidemiological studies in ethnic groups with life-time exposure to high levels of fatty acids, specifically Japanese, Icelandic and Norwegian cohorts may provide insights into the effectiveness of diet in different genetic populations [195]. ...
Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests that inflammation is a shared mechanism, contributing to both cognitive decline and abnormalities in brain structure and metabolism. Thus, inflammation may provide a target for intervention. Specifically, circulating inflammatory markers have been associated with declines in cognitive function and worsening of brain structural and metabolic characteristics. Additionally, it has been proposed that older brains are characterized by a sensitization to neuroinflammatory responses, even in the absence of overt disease. This increased propensity to central inflammation may contribute to poor brain health and premature brain aging. Still unknown is whether and how peripheral inflammatory factors directly contribute to decline of brain health. Human research is limited by the challenges of directly measuring neuroinflammation in vivo. This review assesses the role that inflammation may play in the brain changes that often accompany aging, focusing on relationships between peripheral inflammatory markers and brain health among well-functioning, community-dwelling adults seventy years and older. We propose that monitoring and maintaining lower levels of systemic and central inflammation among older adults could help preserve brain health and support successful aging. Hence, we also identify plausible ways and novel experimental study designs of maintaining brain health late in age through interventions that target the immune system.
... Intriguing observations have been recently made in Alaska (46). Although some investigators continue to report that Inuit consuming traditional diets have lower CHD rates, others are questioning this dogma. ...
In this article, we compare two strategies for atherosclerosis treatment: drugs and healthy lifestyle. Statins are the principal drugs used for the treatment of atherosclerosis. Several secondary prevention studies have demonstrated that statins can significantly reduce cardiovascular events including coronary death, the need for surgical revascularization, stroke, total mortality, as well as fatal and non-fatal myocardial infarction. These results were observed in both men and women, the elderly, smokers and non-smokers, diabetics and hypertensives. Primary prevention studies yielded similar results, although total mortality was not affected. Statins also induce atheroma regression and do not cause cancer. However, many unresolved issues remain, such as partial risk reduction, costs, several potential side effects, and long-term use by young patients. Statins act mainly as lipid-lowering drugs but pleiotropic actions are also present. Healthy lifestyle, on the other hand, is effective and inexpensive and has no harmful effects. Five items are associated with lower cardiac risk: non-smoking, BMI ≤25, regular exercise (30 min/day), healthy diet (fruits, vegetables, low-saturated fat, and 5-30 g alcohol/day). Nevertheless, there are difficulties in implementing these measures both at the individual and population levels. Changes in behavior require multidisciplinary care, including medical, nutritional, and psychological counseling. Participation of the entire society is required for such implementation, i.e., universities, schools, media, government, and medical societies. Although these efforts represent a major challenge, such a task must be faced in order to halt the atherosclerosis epidemic that threatens the world.
... The amount of fat in the diet and the type of fatty acids consumed can influence the likelihood of CVD and its risk factors [22]. The first recognition of the beneficial effect of fatty acids on CVD came from the observations on the longevity of Eskimos, which was later attributed to the high contents of fish-derived n-3 long chain fatty acids (e.g., EPA and DHA) in their diets198199200201. Since then, the cardioprotective effects of fish oil n-3 PUFAs appear well determined. ...
The marine environment represents a relatively untapped source of functional ingredients that can be applied to various aspects of food processing, storage, and fortification. Moreover, numerous marine-based compounds have been identified as having diverse biological activities, with some reported to interfere with the pathogenesis of diseases. Bioactive peptides isolated from fish protein hydrolysates as well as algal fucans, galactans and alginates have been shown to possess anticoagulant, anticancer and hypocholesterolemic activities. Additionally, fish oils and marine bacteria are excellent sources of omega-3 fatty acids, while crustaceans and seaweeds contain powerful antioxidants such as carotenoids and phenolic compounds. On the basis of their bioactive properties, this review focuses on the potential use of marine-derived compounds as functional food ingredients for health maintenance and the prevention of chronic diseases.
... On similar analysis of other ethnic groups, studies of Japanese populations add considerable weight to the findings of Bang and Dyerberg [81]. Here, serum omega-3 PUFA levels were inversely related to objective markers of subclinical CVD. ...
The consumption of long chain omega-3 polyunsaturated acids (PUFA) is considered to protect against cardiovascular disease and promote longevity following a heart attack. Historically, research in this area was fuelled by compelling reports of the cardiovascular benefits of omega-3 PUFA in select populations and cultures. More recent studies, in wider populations, suggest discordant findings: differences that are difficult to reconcile as the mechanism of action of omega-3 PUFA are poorly understood. As such, the use of this 'natural treatment' for cardiovascular disease is increasingly controversial, and potentially one of unfulfilled promise. To what extent does ethnicity influence the impact that omega-3 PUFA have on cardiovascular disease and its associated complications? We were interested to review the benefits of omega-3 PUFA in the management of cardiovascular risk amongst diverse ethnic groups. Using a systematic review of literature relating to omega-3 PUFA and cardiovascular disease, we found ethnicity to be a factor that accounts for inconsistency between studies. Some of the effects of omega-3 PUFA are limited to cultures with a very high omega-3 intake, and in turn, ethnicity moderates the efficiency with which PUFA are derived from the diet. Moreover, omega-3 PUFA are an important health care intervention in the current climate of globalization, where supplementation is likely to give protection to cultural groups undergoing dietary transition. Future epidemiological research into the efficacy of omega-3 PUFA in cardiovascular disease should consider the influence of ethnicity.
... Moreover, in a cross-sectional study, very high levels of marine-derived fatty acids showed antiatherogenic properties in Japanese living in Japan [17]. Furthermore, the usual intake of foods rich in u-3 fatty acids in Japan has been considered the cornerstone for the protection against cardiovascular diseases in this population [18]. ...
We investigated whether lifestyle-induced changes in dietary fat quality are related to improvements on glucose metabolism disturbances in Japanese Brazilians at high risk of type 2 diabetes.
One hundred forty-eight first- and second-generation subjects with impaired glucose tolerance or impaired fasting glycemia who attended a lifestyle intervention program for 12 mo were studied in the city of Bauru, State of São Paulo, Brazil. Dietary fatty acid intakes at baseline and after 12 mo were estimated using three 24-h recalls. The effect of dietary fat intake on glucose metabolism was investigated by multiple logistic regression models.
At baseline, mean +/- standard deviation age and body mass index were 60+/-11 y and 25.5+/-4.2kg/m(2), respectively. After 12 mo, 92 subjects had normal plasma glucose levels and 56 remained in prediabetic conditions. Using logistic regression models adjusted for age, gender, generation, basal intake of explanatory nutrient, energy intake, physical activity, and waist circumference, the odds ratios (95% confidence intervals) for reversion to normoglycemia were 3.14 (1.22-8.10) in the second tertile of total omega-3 fatty acid, 4.26 (1.34-13.57) in the second tertile of eicosapentaenoic acid, and 2.80 (1.10-7.10) in the second tertile of linolenic acid. Similarly, subjects in the highest tertile of omega-3:omega-6 fatty acid ratio showed a higher chance of improving glucose disturbances (2.51, 1.01-6.37).
Our findings support the evidence of an independent protective effect of omega-3 fatty acid and of a higher omega-3:omega-6 fatty acid ratio on the glucose metabolism of high-risk individuals.
... It has been suggested that high doses and a prolonged intake of (n-3) FA are needed to affect atherosclerosis and nonfatal events, as opposed to the antiarrhythmic effects of a lower intake, probably responsible for the reduced risk of death (3,24). It has also been argued that the lack of effect of (n-3) FA on atherosclerosis in the Norwegian population, to some extent, might be related to a concomitant high intake of saturated and monounsaturated fat (27). ...
A reduced risk of fatal coronary artery disease has been associated with a high intake of (n-3) fatty acids (FA) and a direct cardioprotective effect by their incorporation into myocardial cells has been suggested. Based on these observations, the omega-3 index (eicosapentaenoic acid + docosahexaenoic acid in cell membranes of RBC expressed as percent of total FA) has been suggested as a new risk marker for cardiac death. In this study, our aim was to evaluate the omega-3 index as a prognostic risk marker following hospitalization with an acute coronary syndrome (ACS). The omega-3 index was measured at admission in 460 patients with an ACS as defined by Troponin-T (TnT) > or = 0.02 microg/L. During a 2-y follow-up, recurrent myocardial infarctions (MI) (defined as TnT > 0.05 microg/L with a typical MI presentation) and cardiac and all-cause mortality were registered. Cox regression analyses were used to relate the risk of new events to the quartiles of the omega-3 index at inclusion. After correction for age, sex, previous heart disease, hypertension, diabetes, smoking, high-sensitivity C-reactive protein, brain natriuretic peptide, creatinine, total cholesterol, HDL-cholesterol, triacylglycerol, homocysteine, BMI, and medication, there was no significant reduction in risk for all-cause mortality, cardiac death, or MI with increasing values of the index. In conclusion, we could not confirm the omega-3 index as a useful prognostic risk marker following an ACS.
Introduction. Recently, much attention has been paid to the study of medicinal plants’ lipophilic complexes, part of which is fatty acids, which play an important role in the life activities of a human body. The plants of the Asteraceae family — yacon (the Smallanhus sonchifolius (Poepp. and Endl.) H. Robinson), stevia rebaudiana (Bertoni) Hemsley and cat’s paw (Antennaria dioica (L.) Gaertn.) contain the complex of biologically active substances, among which a significant place is given to lipophilic components (fatty acids, carotenoids, chlorophylls, etc.). In the sources of scientific literature, there is not enough information about the studied species’ fatty acid composition. Therefore, the purpose of our research is to study the lipophilic fractions of stevia leaves, yacon root tubers and leaves, cat’s paw herbs, and to determine the content of fatty acids in their composition.Research Methods. Lipophilic fractions of the studied species are obtained by exhaustive extraction of raw materials with chloroform in the Soxhlet apparatus. Determination of qualitative composition and quantitative content of fatty acids in the investigated medicinal plant material is carried out by the gas-liquid chromatographic/mass spectrometric method of fatty acids methyl esters on the gas chromatographic/mass spectrometric system Agilent 6890N/5973inert (Agilent Technologies, USA). The identification of fatty acid methyl esters in the test mixture is carried out by comparing the retention time of fatty acids methyl esters standard mixture (Supelco, USA). The NIST 02 mass spectrum library is used.Results and Discussion. The isolated lipophilic fraction from yacon root tubers – a thick oily homogeneous mass of brown colour with a pleasant specific odor; not soluble in water and ethanol, is readily soluble in chloroform. Lipophilic fractions of stevia leaves are of dark green colour; cat’s paw herbs – light green colour; according to other physical indicators, the obtained substances do not differ. It is established that the yield of lipophilic substances from yacon and stevia leaves are almost the same – (9.55±0.09)% and (9.05±0.07) %, from yacon roots – in 2.4 and 2.2 times smaller than leaves, respectively. The yield of the lipophilic fraction from cat’s paw herbs is (8.25 ± 0.09) %.9 fatty acids are detected in the lipophilic extract of yacon leaves and cat’s paw herbs, 2 of which are polyunsaturated (linoleic and linolenic). 8 fatty acids are detected in the lipophilic extract of stevia leaves, where linolenic acid is present in the largest number. The lipophilic extract of stevia leaves and cat’s paw herbs contains the saturated palmitic acid. The content of unsaturated fatty acids in the studied lipophilic extracts predominates over saturated. Their ratio in yacon leaves is 55.35:8.63; stevia leaves – 3.04:1.87; cat’s paw herbs – 29.09:20.26, respectively. Only the linoleic and linolenic acids are identified in the lipophilic extract of yacon root tubers.Conclusions. 1. The fatty acid composition of the lipophilic fractions of stevia leaves, yacon root tubers and leaves, and cat’s paw herbs is determined by the gas-liquid chromatographic/mass spectrometric method for the first time.2. The content of unsaturated fatty acids in stevia and yacon leaves, and cat’s paw herbs predominates over saturated. Polyunsaturated fatty acids (linoleic and linolenic) are dominant in the investigated objects.3. Only the linoleic and linolenic acids are identified in yacon root tubers.
Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33.0%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA + DHA in erythrocyte equivalents. Regions with high EPA + DHA blood levels (> 8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤ 4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA + DHA and the very low to low range of blood EPA + DHA for most of the world may increase global risk for chronic disease.
Cardiovascular disease (CVD) is the main cause of increased mortality in patients with chronic kidney disease (CKD). Patients with CKD have an accumulation of risk factors for CVD, including mixed dyslipidemia, specifc for the uremic state. Randomized controlled trials (RCTs) in patients with CKD are limited, and existing RCTs with statins have been disappointingly negative. Both epidemiological and interventional data support a cardioprotective effect from dietary intake of fatty fish or supplementation with n-3 fatty acids. Several mechanisms may explain why n-3 fatty acids have a beneficial effect on patients with CVD, and the effects on lipids and triglycerides are especially well described. In patients with CKD, the effect of n-3 fatty acids has not been extensively studied. This review will provide an update on existing data concerning treatment with n-3 fatty acids in patients with CKD, with a special focus on lipids and lipoproteins.
The increased mortality in end-stage renal disease (ESRD) is mainly caused by cardiovascular disease (CVD). Several risk factors for CVD are present in patients with ESRD, including a mixed dyslipidemia, specific for the uremic state. Randomized controlled trials in patients with ESRD are sparse and some cholesterol-lowering randomized controlled trials have had negative results. Both epidemiological and interventional data support a cardioprotective effect of an increased intake of n-3 polyunsaturated fatty acids (n-3 PUFA). Several mechanisms could explain why n-3 PUFA have a beneficial effect on patients with CVD. Thus, the effects on lipids and triglycerides are especially well described. In patients with ESRD the effect of n-3 PUFA has only been sparsely studied. This article will provide an update on existing data concerning treatment with n-3 PUFA in patients with ESRD with a special focus on lipids and lipoproteins.
Blood pressure (BP) is a strong determinant of cardiovascular diseases (CVD). The strength of this association in 2 Japanese communities with different intakes of fish was investigated.
The analysis was carried out in the Japanese cohorts of the Seven Countries Study (Tanushimaru and Ushibuka), which were followed for 40 years. We included 1,006 subjects for whom data on baseline BP and relevant potential confounders were available. Data were analysed using multivariable Cox proportional hazard models. In Tanushimaru men, the systolic BP level was strongly directly related to risk of stroke and CVD mortality, with hazard ratios (HR) of 4.42 (2.02-9.70) for stroke and 3.05 (1.73-3.25) for CVD for BP levels ≥ 140 mmHg compared to <120 mmHg. In Ushibuka, the HR were 1.74 (0.91-3.32) for stroke mortality and 1.66 (1.01-2.75) for CVD mortality for high vs. low systolic BP. With regard to diastolic BP, the associations with stroke and CVD mortality were similar in Tanushimaru and Ushibuka subjects.
This study showed that the well-known relationship of systolic BP with stroke and CVD mortality was more pronounced in the Japanese farming community than in the fishing community. This brings up the hypothesis that the detrimental effect of raised systolic BP could be attenuated by a high intake of fish.
Omega-3 polyunsaturated fatty acid (omega-3 PUFA) therapy continues to show great promise in primary and, particularly in secondary prevention of cardiovascular (CV) diseases. The most compelling evidence for CV benefits of omega-3 PUFA comes from 4 controlled trials of nearly 40,000 participants randomized to receive eicosapentaenoic acid (EPA) with or without docosahexaenoic acid (DHA) in studies of patients in primary prevention, after myocardial infarction, and most recently, with heart failure (HF). We discuss the evidence from retrospective epidemiologic studies and from large randomized controlled trials showing the benefits of omega-3 PUFA, specifically EPA and DHA, in primary and secondary CV prevention and provide insight into potential mechanisms of these observed benefits. The target EPA + DHA consumption should be at least 500 mg/day for individuals without underlying overt CV disease and at least 800 to 1,000 mg/day for individuals with known coronary heart disease and HF. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA omega-3 PUFA that provides maximal cardioprotection in those at risk of CV disease as well in the treatment of atherosclerotic, arrhythmic, and primary myocardial disorders.
Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease. We aimed to test the hypothesis that long-term use of eicosapentaenoic acid (EPA) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish.
18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. The study was registered at ClinicalTrials.gov, number NCT00231738.
At mean follow-up of 4.6 years, we detected the primary endpoint in 262 (2.8%) patients in the EPA group and 324 (3.5%) in controls-a 19% relative reduction in major coronary events (p=0.011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4.7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8.7%] in the EPA group vs 197 [10.7%] in the control group; p=0.048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1.4%] in the EPA group vs 127 [1.7%] in the control group; p=0.132).
EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients.
Unlike arachidonic acid (eicosatetraenoic acid, C20:4omega-6, A.A.), eicosapentaenoic acid (C20:5omega-3, E.P.A.) does not induce platelet aggregation in human platelet-rich plasma (P.R.P.), probably because of the formation of thromboxane A3 (T.X.A3) which does not have platelet aggregating properties. Moreover, E.P.A., like A.A., can be utilised by the vessel wall to make an anti-aggregating substance, probably a delta17-prostacyclin (P.G.I3). This finding suggests that, in vivo, high levels of E.P.A. and low levels of A.A. could lead to an antithrombotic state in which an active P.G.I3 and a non-active T.X.A3 are formed. Eskimos have high levels of E.P.A. and low levels of A.A. and they also have a low incidence of myocardial infarction and a tendency to bleed. It is possible that dietary enrichment with E.P.A. will protect against thrombosis.
: The plasma-lipid pattern, including quantitative lipoprotein electrophoresis, was examined in 130 Eskimos (69 females, 61 males)—hunters and/or fishermen, and their wives—in the northern part of the west coast of Greenland, and consuming a predominantly meat diet rich in polyunsaturated fatty acids. Most types of lipid were decreased, compared with Danish controls and Eskimos living in Denmark. The most remarkable finding was much lower levels of pre-β-lipoprotein and consequently of plasma-triglycerides in Greenlandic Eskimos than in Danish controls. These findings may explain the very low incidence of ischæmic heart-disease and the complete absence of diabetes mellitus in Greenlandic Eskimos.
We examined how supplementation with very-long-chain n-3 fatty acids was reflected in the concentration of these fatty acids in plasma phospholipids of 363 Norwegian men and women. The concentration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma phospholipids was significantly higher among individuals supplemented with n-3 fatty acids after the supplementation period than before. We also examined the relation between dietary intake of fatty acids measured with a 180-item quantitative food-frequency questionnaire and the concentration of the same fatty acids in plasma phospholipids in 579 men and women. Correlation coefficients between plasma phospholipid fatty acids and dietary intake of fatty acids were 0.51 and 0.49 for EPA and DHA, respectively. The correlation between fish intake and n-3 fatty acids in plasma phospholipids was 0.37. These results suggest that dietary intake measured with our food-frequency questionnaire may be used to predict the biological availability of some of the essential n-3 fatty acids.
Since World War II, people in Japan, South Korea, and Taiwan have been exposed to a westernized lifestyle. It is most likely that the post World War II cohorts (1950+) have been more exposed. We hypothesize that there would be an increase in mortality from coronary heart disease (CHD) in men aged 35-44 in these countries.
Mortality from CHD in men aged 35-44 in South Korea and Taiwan has recently increased, and in Japan it has decreased. Mortality from CHD in men aged 35-44 is lower in Japan than in either South Korea or Taiwan, and much lower than in the US. National sample data and several epidemiological studies have shown that risk factors for CHD including hypercholesterolaemia and hypertension in the past decade were not much different between young adult men in Japan and the US. Based upon these risk factors, CHD death rates among post World War II cohorts should be similar in Japan and the US. However, the rates are five times higher in the US for men aged 35-44. The majority of deaths in the category of diseases of the heart were from heart failure in men in this age group in Japan; the mortality from heart failure was about three times higher than the mortality from CHD. Heart failure was rarely used in men aged 35-44 in the US.
The continued low mortality rates from CHD in young men in Japan may be an artifact. It is possible that CHD death rates in post World War II birth cohort in Japan are similar to US rates.
The notion that the incidence of ischemic heart disease (IHD) is low among the Inuit subsisting on a traditional marine diet has attained axiomatic status. The scientific evidence for this is weak and rests on early clinical evidence and uncertain mortality statistics.
We reviewed the literature and performed new analyses of the mortality statistics from Greenland, Canada, and Alaska.
The evidence for a low mortality from IHD among the Inuit is fragile and rests on unreliable mortality statistics. Mortality from stroke, however, is higher among the Inuit than among other western populations. Based on the examination of 15 candidate gene polymorphisms, the Inuit genetic architecture does not obviously explain putative differences in cardiovascular disease prevalence.
The mortality from all cardiovascular diseases combined is not lower among the Inuit than in white comparison populations. If the mortality from IHD is low, it seems not to be associated with a low prevalence of general atherosclerosis. A decreasing trend in mortality from IHD in Inuit populations undergoing rapid westernization supports the need for a critical rethinking of cardiovascular epidemiology among the Inuit and the role of a marine diet in this population.
Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies
We compared fatty acid intake estimated from our 138-item food frequency questionnaire (FFQ) with 28-day weighed dietary records among a subgroup of JPHC Study Cohort 1 (102 men and 113 women), and with the corresponding two serum phospholipid levels (88 men). Spearman rank correlation coeffi- cients between fatty acid intakes estimated from FFQ and intakes estimated from DR were as follows: saturated fatty acid, r=0.61 and r=0.60; monounsaturated fatty acid, r=0.50 and r=0.44; for energy adjusted value and Eicosapentaenoic acid (EPA), r=0.62 and r=0.55; docosahexaenoic acid (DHA), r=0.61 and r=0.50; for percentage of total fatty acid intake in men and women, respectively. Spearman rank correlation coefficients between fatty acid intakes estimated from FFQ and the corresponding serum phospholipid levels (% of total fatty acid) were as follows: EPA, r=0.43 and r=0.59; DHA, r=0.35 and r=0.49; for crude value (g/day) and percentage of total fatty acid intake, respectively. In conclusion, relatively high correlations were observed for SFA, MUFA and marine-origin n-3 polyunsaturated fatty acid, whereas we must take into account the indicator of each fatty acid intake when using the data of fatty acid intake assessed with FFQ for JPHC study.
J Epidemiol 2003;13(Suppl):S64-S81.
The thirty-year-old hypothesis that omega-3 fatty acid (FA) may "reduce the development of thrombosis and atherosclerosis in the Western World" still needs to be tested. Dyerberg-Bang based their supposition on casual observations that coronary atherosclerosis in Greenlandic Inuit was 'almost unknown' and that they consumed large amounts of omega-3 FAs. However, no association was demonstrated with data.
Cross-sectional study.
454 Alaskan Eskimos were screened for coronary heart disease (CHD), using a protocol that included ECG, medical history, Rose questionnaire, blood chemistries, including plasma FA concentrations, and a 24-hour recall and a food frequency questionnaire assessment of omega-3 FA consumption.
CHD was found in 6% of the cohort under 55 years of age and in 26% of those > or = 55 years of age. Eskimos with CHD consume as much omega-3 FAs as those without CHD, and the plasma concentrations confirm that dietary assessment.
Average daily consumption of omega-3 FAs among Eskimos was high, with about 3-4 g/d reported, compared with 1-2 g/d used in intervention studies and the average consumption of 0.2 g/d by the American population. There was no association between current omega-3 FA consumption/blood concentrations and the presence of CHD.
Fish intake, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and in some cases alpha-linolenic acid (ALA) have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and the progression of coronary artery atherosclerosis was assessed among women with established coronary artery disease (CAD). A prospective cohort study involved postmenopausal women (n = 228) participating in the Estrogen Replacement and Atherosclerosis Trial. Quantitative coronary angiography was performed at baseline and after 3.2 +/- 0.6 (mean +/- SD) years. Women with plasma phospholipid (PL) DHA levels above the median, compared with below, exhibited less atherosclerosis progression, as expressed by decline in minimum coronary artery diameter (-0.04 +/- 0.02 and -0.10 +/- 0.02 mm, respectively; P = 0.007) or increase in percentage stenosis (1.34 +/- 0.76% and 3.75 +/- 0.74%, respectively; P = 0.006), and had fewer new lesions [2.0% (0.5-3.5%) of measured segments (95% confidence interval) and 4.2% (2.8-5.6%), respectively; P = 0.009] after adjustments for cardiovascular risk factors. Similar results were observed for DHA in the triglycerides (TGs). EPA and ALA in plasma lipids were not significantly associated with atherosclerosis progression. Consistent with higher reported fish intake, higher levels of plasma TG and PL DHA are associated with less progression of coronary atherosclerosis in postmenopausal women with CAD.
Coronary heart disease incidence and mortality remain very low in Japan despite major dietary changes and increases in risk
factors that should have resulted in a substantial increase in coronary heart disease rates (Japanese paradox). Primary genetic
effects are unlikely, given the substantial increase in coronary heart disease in Japanese migrating to the United States.
For men aged 40–49 years, levels of total cholesterol and blood pressure have been similar in Japan and the United States
throughout their lifetimes. The authors tested the hypothesis that levels of subclinical atherosclerosis, coronary artery
calcification, and intima-media thickness of the carotid artery in men aged 40–49 years are similar in Japan and the United
States. They conducted a population-based study of 493 randomly selected men: 250 in Kusatsu City, Shiga, Japan, and 243 White
men in Allegheny County, Pennsylvania, in 2002–2005. Compared with the Whites, the Japanese had a less favorable profile regarding
many risk factors. The prevalence ratio for the presence of a coronary calcium score of ≥10 for the Japanese compared with
the Whites was 0.52 (95% confidence interval: 0.35, 0.76). Mean intima-media thickness was significantly lower in the Japanese
(0.616 mm (standard error, 0.005) vs. 0.672 (standard error, 0.005) mm, p < 0.01). Both associations remained significant after adjusting for risk factors. The findings warrant further investigations.
Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies
Background-Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction. Methods and Results-In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths. Conclusions-The early effect of low-dose ( I g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.
An epidemiological survey of several chronic diseases in the Upernavik district, Northwest Greeland, is reported. The study population (ap-prox. 1 800 inhabitants) is one of the remaining whaling and sealing populations in Greenland. It was observed over the 25-year period 1950–74 as to the incidence of the diseases, which was based on all cases diagnosed in hospital during this period. The disease pattern of the Greenlanders differs from that of West-European populations, having a higher frequency of apoplexy and epilepsy but a lower frequency or absence of acute myocardial infarction, diabetes mellitus, thyrotoxicosis, bronchial asthma, multiple sclerosis and psoriasis. The distribution of cancer types differs from that of the Danish population, but the total incidence of cancer is of the same magnitude. Further comparable studies should be performed in Greenlandic districts that are characterized by more profound changes in life style, in order to elucidate the effect of these changes on the disease pattern.
Acta Med Scand 208: 401, 1980.
We sought to examine whether marine-derived n-3 fatty acids are associated with less atherosclerosis in Japanese versus white populations in the U.S.
Marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic effect.
A population-based cross-sectional study in 281 Japanese (defined as born and living in Japan), 306 white (defined as white men born and living in the U.S.), and 281 Japanese-American men (defined as Japanese men born and living in the U.S.) ages 40 to 49 years was conducted to assess intima-media thickness (IMT) of the carotid artery, coronary artery calcification (CAC), and serum fatty acids.
Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar levels. Japanese had 2-fold higher levels of marine-derived n-3 fatty acids than whites and Japanese Americans in the U.S. Japanese had significant and nonsignificant inverse associations of marine-derived n-3 fatty acids with IMT and CAC prevalence, respectively. The significant inverse association with IMT remained after adjusting for traditional cardiovascular risk factors. Neither whites nor Japanese Americans had such associations. Significant differences between Japanese and whites in multivariable-adjusted IMT (mean difference 39 mum, 95% confidence interval [CI]: 21 to 57mum, p < 0.001) and CAC prevalence (mean difference 10.7%, 95% CI: 2.9% to 18.4%, p = 0.007) became nonsignificant after we adjusted further for marine-derived n-3 fatty acids (22 mum, 95% CI: -1 to 46 mum, p = 0.065 and 5.0%, 95% CI: -5.3% to 15.4%, p = 0.341, respectively).
Very high levels of marine-derived n-3 fatty acids have antiatherogenic properties that are independent of traditional cardiovascular risk factors and may contribute to lower the burden of atherosclerosis in Japanese, a lower burden that is unlikely the result of genetic factors.
A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.
An epidemiological survey of several chronic diseases in the Upernavik district, Northwest Greenland, is reported. The study population (approx. 1800 inhabitants) is one of the remaining whaling and sealing populations in Greenland. It was observed over the 25-year period 1950-74 as to the incidence of the diseases, which was based on all cases diagnosed in hospital during this period. The disease pattern of the Greenlanders differs from that of West-European populations, having a higher frequency of apoplexy and epilepsy but a lower frequency or absence of acute myocardial infarction, diabetes mellitus, thyrotoxicosis, bronchial asthma, multiple sclerosis and psoriasis. The distribution of cancer types differs from that of the Danish population, but the total incidence of cancer is of the same magnitude. Further comparable studies should be performed in Greenlandic districts that are characterized by more profound changes in life style, in order to elucidate the effect of these changes on the disease pattern.
This randomized clinical trial tested whether fish oil supplements can improve human coronary atherosclerosis.
Epidemiologic studies of populations whose intake of oily fish is high, as well as laboratory studies of the effects of the polyunsaturated fatty acids in fish oil, support the hypothesis that fish oil is antiatherogenic.
Patients with angiographically documented coronary heart disease and normal plasma lipid levels were randomized to receive either fish oil capsules (n = 31), containing 6 g of n-3 fatty acids, or olive oil capsules (n = 28) for an average duration of 28 months. Coronary atherosclerosis on angiography was quantified by computer-assisted image analysis.
Mean (+/- SD) baseline characteristics were age 62 +/- 7 years, plasma total cholesterol concentration 187 +/- 31 mg/dl (4.83 +/- 0.80 mmol/liter) and triglyceride levels 132 +/- 70 mg/dl (1.51 +/- 0.80 mmol/liter). Fish oil lowered triglyceride levels by 30% (p = 0.007) but had no significant effects on other plasma lipoprotein levels. At the end of the trial, eicosapentaenoic acid in adipose tissue samples was 0.91% in the fish oil group compared with 0.20% in the control group (p < 0.0001). At baseline, the minimal lumen diameter of coronary artery lesions (n = 305) was 1.64 +/- 0.76 mm, and percent narrowing was 48 +/- 14%. Mean minimal diameter of atherosclerotic coronary arteries decreased by 0.104 and 0.138 mm in the fish oil and control groups, respectively (p = 0.6 between groups), and percent stenosis increased by 2.4% and 2.6%, respectively (p = 0.8). Confidence intervals exclude improvement by fish oil treatment of > 0.17 mm, or > 2.6%.
Fish oil treatment for 2 years does not promote major favorable changes in the diameter of atherosclerotic coronary arteries.
Cardiac disease mortality in Alaska, from both ischaemic and rheumatic heart disease, is of interest given the high consumption of fish and high streptococcal disease rates in the indigenous population. Uniformly coded underlying cause-of-death data for the period 1979-1988, compared with that from 1955-1965, indicated that deaths from all cardiac diseases combined, have been increasing in Alaska Natives over the past 30 years. Recent mortality from all cardiac, ischaemic, and rheumatic heart diseases in Alaska Natives were 80%, 61%, and 202% of those corresponding levels in Alaskan whites, whose cardiac mortality closely profiles US whites. Alaska Native men aged 30-45 years had higher overall mortality rates for cardiac diseases than did whites because of higher mortality rates of rheumatic heart disease and cardiomyopathy. Elderly Alaska Native men had lower rates than whites, reflecting less ischaemic heart disease mortality. The lowest levels of ischaemic heart disease mortality, less than one-third that of US whites, occurred in Alaskan Eskimos who lived in an area with documented patterns of high salmon consumption by individuals with high blood concentrations of omega-3 fatty acids. Elevated mortality from non-ischaemic heart disease and previously documented genetic markers suggest associations deserving further study.
Atherosclerosis begins early in life and is the major underlying cause of cardiovascular morbidity and death. Yet, population-based information on age and sex differences in the extent and morphology of atherosclerosis throughout life is scarce. Carotid atherosclerosis can be visualized with B-mode ultrasound and is a marker of atherosclerosis elsewhere in the circulation. We assessed both the prevalence and the morphology of carotid atherosclerosis by B-mode ultrasound in 3016 men and 3404 women, 25 to 84 years old, who participated in a population health survey. The participation rate was 88%. Plaque morphology was graded according to whether a plaque was predominantly soft (echolucent) or hard (echogenic). Atherosclerotic plaques were found in 55.4% of the men and 45.8% of the women. In men, there was a linear increase with age in the prevalence of carotid atherosclerosis, whereas in women, there was a curvilinear age trend, with an inflection in the prevalence rate of women at approximately 50 years of age. The male predominance in atherosclerosis declined after the age of 50 years, the plaque prevalence being similar in elderly men and women. Men had softer plaques than women; this sex difference in plaque morphology increased significantly (P=0.005) with age. The sex difference in the prevalence of atherosclerosis and the female age trend in atherosclerosis show significant changes at the age of approximately 50 years, suggesting an adverse effect of menopause on atherosclerosis. The higher proportion of soft plaques in men compared with women increases with age and may partly account for the prevailing male excess risk of coronary heart disease in the elderly despite a similar prevalence of atherosclerosis in elderly men and women.
Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease.
Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada.
The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition.
Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin.
Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.
Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction.
In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths.
The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.
Essential polyunsaturated fatty acids (PUFA) of the omega-3 family are believed to protect against cardiovascular disease. A rich source of omega-3 PUFA is found in fish and marine mammals (seal, walrus, whale), which are a large part of the traditional diet of Alaska Natives (Eskimo, American Indians, Aleuts), a group that has been reported to have a lower mortality rate from cardiovascular disease than non-Natives. An autopsy study using standardized methods to evaluate the extent of atherosclerosis and its risk factors, and analyses of stored triglyceride fatty acids was conducted in a sample of Alaska Native subjects and non-Native subjects living in Alaska. Findings indicate that Alaska Natives had less advanced atherosclerosis in coronary arteries, along with higher proportions of omega-3 and lower proportions of omega-6 PUFA in adipose tissue, than did non-Natives. We conclude that high dietary intake of omega-3 PUFA may account for the lower extent of coronary artery atherosclerosis, contributing to the reported lower heart disease mortality among Alaska Natives.
Once- or twice-weekly consumption of fish (or a small amount of fish intake) reduces the risk of coronary heart disease and sudden cardiac death in Western countries. It is uncertain whether a high frequency or large amount of fish intake, as is the case in Japan, further reduces the risk.
To examine an association between high intake of fish and n3 polyunsaturated fatty acids and the risk of coronary heart disease, a total of 41,578 Japanese men and women aged 40 to 59 years who were free of prior diagnosis of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed up from 1990-1992 to 2001. After 477,325 person-years of follow-up, 258 incident cases of coronary heart disease (198 definite and 23 probable myocardial infarctions and 37 sudden cardiac deaths) were documented, comprising 196 nonfatal and 62 fatal coronary events. The multivariable hazard ratios (HRs) and 95% confidence intervals in the highest (8 times per week, or median intake=180 g/d) versus lowest (once a week, or median intake=23 g/d) quintiles of fish intake were 0.63 (0.38 to 1.04) for total coronary heart disease, 0.44 (0.24 to 0.81) for definite myocardial infarction, and 1.14 (0.36 to 3.63) for sudden cardiac death. The reduced risk was primarily observed for nonfatal coronary events (HR=0.43 [0.23 to 0.81]) but not for fatal coronary events (HR=1.08 [0.42 to 2.76]). Strong inverse associations existed between dietary intake of n3 fatty acids and risk of definite myocardial infarction (HR=0.35 [0.18 to 0.66]) and nonfatal coronary events (HR=0.33 [0.17 to 0.63]).
Compared with a modest fish intake of once a week or &20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons.
This randomized study targeted a comparison of the effect of 3-year diet counselling or omega-3 polyunsaturated fatty acid (PUFA) supplementation (2.4 g/day) on the progression of atherosclerosis in carotid arteries and on finger pulse wave propagation.
Measurements were assessed by high-resolution B-mode ultrasound and a photopletysmographic finger pulse-sensor, respectively. Altogether, 563 elderly men with long-standing hyperlipidaemia were randomized into four groups: controls (no dietary counselling and placebo); dietary counselling (and placebo); omega-3 PUFA supplementation (no dietary counselling); dietary counselling and omega-3 PUFA supplementation.
In the diet only group, the carotid intima-media thickness increase (0.929 to 0.967 mm) was significantly less than in the control group (0.909 to 0.977 mm), (P = 0.018). Significant increase in carotid plaques score and plaques area were observed in all four groups, but without between group differences. Changes in carotid intima-media thickness and in high-density lipoprotein-cholesterol were negatively correlated (adjusted P < 0.001). Pulse wave propagation time decreased significantly in the control group (206 to 198 ms; P = 0.002), reflecting reduced arterial elasticity. In the group receiving omega-3 PUFA only, pulse wave propagation time increased significantly when compared with the control group (P = 0.013).
Reduced progression in carotid intima-media thickness was observed after dietary counselling, whereas omega-3 PUFA supplementation imposed a favourable effect on arterial elasticity.
As an appreciation of the cardioprotective properties of the long-chain, fish-oil-derived omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) has grown, so too have official dietary guidelines. Health organizations and government agencies are typically recommending intakes that either maintain the status quo (about 100-200 mg/day in most western countries) or are intended to actively reduce risk for cardiovascular disease. The latter are around usually 400-600 mg/day, an amount likely to stimulate commercial interests to fortify foods with omega-3 fatty acids. Fortification is perhaps the best long-term solution to the chronically-low intake of omega-3 fatty acids that plagues western cultures.
This study was designed to evaluate the relation between omega-3 fatty acid (FA) consumption and atherosclerosis.
The hypothesis that omega-3 FAs protect against atherosclerosis has not been tested with objective measures of atherosclerosis.
A population-based sample of 1131 Alaskan Eskimos of age >or=18 underwent ultrasound assessment of carotid atherosclerosis. Those of age >35 (N=686) were included in the analysis. Diet was assessed by a food frequency questionnaire. Intimal-medial thickness (IMT) of the far wall of the distal common carotid arteries and plaque score (number of segments containing plaque) were assessed.
Mean consumption of total omega-3 FAs was 4.76 g/day in those without and 5.07 g/day in those with plaque. In models adjusting for relevant risk factors, presence and extent of plaque were unrelated to intake of C20-22 omega-3 FAs or total omega-3 FAs. In contrast, the odds of plaque rose significantly with quartiles of palmitic (p=0.02) and stearic acid intake (p=0.04). The extent of plaque (or plaque score) was also associated with a higher percentage intake of palmitic acid (p=0.01). IMT was negatively associated with grams of C20-22 omega-3 FAs (p=0.05), total omega-3 (p=0.05), palmitate (p=0.03), and stearate (p=0.03) consumed.
Dietary intake of omega-3 FAs in a moderate-to-high range does not appear to be associated with reduced plaque, but is negatively associated with IMT. The presence and extent of carotid atherosclerosis among Eskimos is higher with increasing consumption of saturated FAs.
The recent increase in clinical cardiovascular disease in Alaska Eskimos suggests that changes in traditional lifestyle may have adverse public health consequences. This study examines the prevalence of subclinical vascular disease and its relation to risk factors in Alaska Eskimos.
Participants in the population-based Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study underwent evaluation of cardiovascular disease risk factors and carotid ultrasound. Outcome variables were carotid intimal-medial thickness and presence and extent of atherosclerosis.
In multivariate analyses, intimal-medial thickness and presence and extent of atherosclerosis were all associated with traditional cardiovascular disease risk factors but not dietary intake of omega-3 fatty acids. Rates of carotid atherosclerosis were higher than those reported in 2 large population-based US studies.
Alaska Eskimos have similar traditional risk factors for carotid atherosclerosis as other ethnic and racial populations but have higher prevalences of atherosclerosis, possibly attributable to higher rates of smoking.
Risk Factor Assessment Among Japa-nese and U.S. Men in the Post-World War II Birth Cohort) Study Group. Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study
- A Sekikawa
- Curb Jd
- H Ueshima
Sekikawa A, Curb JD, Ueshima H, et al., for the ERA JUMP (Electron-Beam Tomography, Risk Factor Assessment Among Japa-nese and U.S. Men in the Post-World War II Birth Cohort) Study Group. Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study. J Am Coll Cardiol 2008;52:417–24.
Plasma lipid and lipoprotein pattern in Greenlandic West-Coast Eskimos
- Bang