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Keywords:

  • blood pressure;
  • cardiovascular disease;
  • diabetes mellitus;
  • dyslipidemia;
  • ethnicity;
  • obesity

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

Summary.  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.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

Long chain omega- 3 polyunsaturated fatty acids (PUFA) are made by plants and marine algae. Omega-3 PUFA pass through the food chain to humans by the consumption of deep, cold-water fish (salmon, mackerel, anchovies and sardines) and their predators (seal). The cardiovascular benefits of consuming omega-3 PUFA were first observed amongst the Greenland Inuit. The subsistence of the Greenland Inuit on these cold water food sources stimulated more than three decades of research into omega-3 PUFA within diverse and varied populations. Today, for many countries, omega-3 PUFA such as docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) have an established role in the treatment of dyslipidemia [1] and the secondary prevention of coronary heart disease (CHD) [2]. However, since the original findings that omega-3 PUFA protect Greenland Inuit against cardiovascular disease (CVD), studies investigating the efficacy of omega-3 PUFA in broader populations have often shown conflicting results. These differences are difficult to reconcile given that the mechanisms by which omega-3 PUFA protect against CVD are unclear. Moreover, the levels of omega-3 PUFA that are required to protect against CVD have not been established within general or ‘select’ populations. Despite its appeal as a natural treatment [3], the use of omega-3 PUFA in CVD is increasingly controversial, and generally regarded as an ‘unfulfilled promise’[4].

Ethnicity and cultural access to deep and cold water fish may influence our interpretation of the efficacy of omega-3 PUFA. The aim of this article was to review research investigating the impact of omega-3 PUFA on disorders associated with CVD, with a particular focus on the contribution of ethnicity. We were interested to investigate the impact of omega-3 PUFA on CVD amongst diverse ethnic groups to determine whether the magnitude of benefit varied by ethnicity.

Search strategy

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

We performed a systematic literature search by using electronic literature databases (i.e. MEDLINE and COCHRANE). For the search, we used the terms ‘ω-3 fatty acids, ethnicity, cardiovascular, dyslipidemia, cholesterol, triglycerides, obesity, diabetes mellitus, hypertension, stroke, peripheral vascular disease and coronary heart disease’. Those articles that included ‘homogenous’ populations (an identifiable ethnic group) and original studies of CVD and omega-3 PUFA were included. Reference lists of all selected articles and review articles were further reviewed for other relevant articles.

Ethnicity and omega-3 polyunsaturated fatty acids

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

The concept of ethnicity encompasses numerous features: shared origins or social backgrounds, shared culture and traditions, identity of a group and a common language or religious tradition [5]. Using this social theory, the Greenland Inuit can be taken as a prime example (‘Inuit’ is the general term used to describe indigenous groups inhabiting the Arctic regions of Canada, Greenland, Russia and Alaska). Despite severe weather conditions, the Greenland Inuit have successfully thrived in an arctic environment (dating back to the 13th century). A cultural tradition of hunting and fishing was a key adaptation to their environment, which conferred a diet low in carbohydrate, high in protein and very high in fat [6]. The effects of omega-3 PUFA within this and other culturally similar groups may not extrapolate to other ethnic groups. The manner with which CVD is manifest amongst the Greenland Inuit may be specific to the antecedents and environmental exposures associated with this group. Moreover, distinct cultures are rapidly becoming ‘diluted’, as populations are increasingly integrated through a global network of communication and trade.

Using a systematic approach, we were able to identify and compare omega-3 PUFA research amongst six distinct ethnic groups: African and African American, Inuit (Canada and Greenland) and Eskimo (Alaska), Italian, South Asian (mostly Indian and Indian migrants), Eastern Asian (Japanese, Korean, Mongolian) and indigenous white populations of Europe, the United States (US) and Australia. From the data available, we were able to compare the effect of ethnic variations of omega-3 PUFA on lipids and other metabolic cardiovascular risk factors, such as obesity, hypertension, stroke and coronary heart disease. Studies were largely observational with longitudinal and cross-sectional designs using varied methods for the assessment of omega-3 PUFA. The effects of omega-3 PUFA on metabolic risk factors, by ethnic group, are summarized in Table 1.

Table 1.   Effects of omega-3 polyunsaturated fatty acids on metabolic risk factors by ethnic group
Effects of omega-3 polyunsaturated fatty acidsInuit and EskimoSouth AsianJapaneseItalianWhite population of the UKAfrican
Triglyceride reductionBang et al. 1971 [7] Lopez-Alvarenga et al. 2010 [12] Dewailly et al. 2001 [13] Bjerregaard P et al. 2000 [14] Kaladottir et al. 1995 [15]Lovegrove et al. 2004 [20]Motoyama et al. 2009 [16] Okuda et al. 2005 [17] Nogi et al. 2007 [18]GISSI investigators 1999 [2] Sirtori et al. 1997 [40]Durrington et al. [28]Marcovina et al. 1999 [26]
Increase high density lipoprotein cholesterolAs aboveAs aboveNogi et al. 2007 [18]Sirtori et al. 1997 [40]As above 
Total/low density lipoprotein cholesterol reductionEskimo – Ebbesson et al. 2005 [34]  As above Marcovina et al. 1999 [26]
Improve glycemic controlEskimo – Ebbesson et al. 2005 [34] Alder et al. 1994 [35]  As abovePatel et al. 2009 [39]Wanjihia et al. 2009 [38]
No change in glycemic control Brady et al. 2004 [37]Nogi et al. 2007 [18]   
HyperglycemicInuit - Dewailly et al. 2001 [13]     

Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

The lipid lowering effects of omega-3 were first reported from cross-sectional research comparing Inuit people with Danish cohorts [7]. Ethnic differences in lipids (low triglycerides, and raised high density lipoprotein (HDL) cholesterol) were attributed to a lower risk of CVD in the Inuit, which was the result of greater dietary omega-3 PUFA intake. Raised triglycerides are an important and independent risk factor for CVD [8], contributing to an increased risk of thrombosis [9] and platelet activation [10]. Similarly, HDL cholesterol is a well-established protective risk factor for CHD independently of other lipid and non-lipid risk factors [11]. Amongst Alaskan Eskimos, Canadian Inuit and other Icelandic groups, serum levels of omega-3 PUFA show a negative association with triglycerides and a positive relationship with HDL cholesterol, as seen in the Greenland Inuit [12] [13–15].

In a study of Japanese people living in Japan, Japanese migrants in the US and the indigenous white people of the US, Motoyama et al. [16] reported ethnic differences in the association between omega-3 PUFA and lipids in men. The intake of omega-3 PUFA was 2-fold higher amongst the Japanese compared with white people, and an association between marine omega-3 intake and low density lipoprotein (LDL) cholesterol was only seen in the former. Amongst all groups, there was a negative association between marine omega-3 PUFA intakes with serum triglycerides, but a positive association with HDL cholesterol was only seen in white people. In a larger study, Okuda et al. [17] reported a similar lack of association between dietary omega-3 PUFA intake and HDL cholesterol amongst Japanese people. Of four centres in Japan, a positive association between HDL cholesterol and omega-3 PUFA intake was only seen amongst men from Toyama (P = 0.05), and no association was seen amongst women. However, estimates of omega-3 PUFA composition of ‘plasma’ fatty acids suggest contrary findings, where amongst Japanese and Mongolian workers, a positive association was observed with HDL cholesterol (as well as a negative association with triglycerides) [18]. The magnitude of the association between HDL and plasma omega-3 PUFA amongst the Japanese was considerably weaker than that observed for Mongolians, which may explain the lack of association seen in the aforementioned dietary studies. Interestingly, robust positive associations between omega-3 and HDL have been observed amongst US white and Mongolian people, who have a relatively low omega-3 PUFA and fish oil intake.

Low levels of omega-3 PUFA have been reported in South Asian populations [19–21].Globally, the burden of CVD is greatest on the Indian subcontinent, and resident and migrant populations have an earlier onset of CVD [22]. Low levels of HDL cholesterol and raised triglycerides are thought to contribute to their increased CVD risk [23]. Using a randomized, placebo-controlled trial, moderate intervention with fish oils (4 g) was found to increase plasma omega-3 PUFA and reverse the atherogenic lipid profile of a South Asian cohort [20]. Here the short-term administration of EPA and DHA resulted in significantly higher levels of HDL cholesterol and lower serum triglycerides. South Asians may also benefit from other cardio-protective effects of omega-3 PUFA on their lipid profiles. Lipoprotein (a) (Lp(a)) is a cholesterol-rich lipoprotein with structural similarities to low density lipoprotein (LDL), an independent risk factor for CVD [24], which is known to be raised in South Asians [25]. A study of the African Bantu Fishermen (Tanzania) was the first to highlight a negative relationship between plasma omega-3 PUFA and Lp(a) levels [26].

Omega-3 polyunsaturated fatty acids are well known for their effects on dyslipidemia amongst patients with low HDL cholesterol and hypertriglyceridemia [1,27]. The beneficial effects of omega-3 PUFA on lipid profiles do not appear to differ by ethnic group but habitual fish oil/omega-3 PUFA intake is likely to moderate the magnitude of effect between omega-3 PUFA and HDL cholesterol. Clinically, omega-3 PUFA are established as a treatment for hypertriglyceridemia. In a blinded, placebo-control trial, Durrington et al. [28] investigated the benefits of omega-3 PUFA (2 g twice daily) in the treatment of hypertriglyceridemia amongst white European patients, and reported a significant and sustained reduction of triglycerides of between 20% and 30% with PUFA use.

Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

Glucose tolerance

Raised triglycerides and low HDL cholesterol commonly manifest as part of a cluster of co-morbidities such as obesity, hypertension, insulin resistance and abnormal glucose tolerance, the so-called metabolic syndrome [29]. One group that appears to be susceptible to diabetes and cardio-metabolic risk are the Inuit and Eskimo groups [30]. The reasons for this are likely to relate to a dietary transition that is increasingly influenced by our current climate of globalization, which promotes a Western lifestyle and a greater intake of carbohydrate [31]. Importantly, it is considered that a divergence from a traditional diet high in omega-3 PUFA explains the increased cardio-metabolic risk observed amongst Alaskan Eskimos [32,33]. Indeed, a 4-year intervention involving the promotion of a high omega-3 intake successfully resulted in the reduction of cardio-metabolic risk and blood glucose in this group [34]. The findings were supported by a smaller intervention study involving daily seal oil/salmon intake [35]. However, for the Inuit of Canada and Greenland, a marine diet high in omega-3 PUFA was adversely associated with higher blood sugar levels [14]. The differences between these ethnically similar groups may be explained by the fact that the research in Alaskan Eskimos was interventional, whereas that for the Inuit was cross-sectional. Nonetheless, omega-3 PUFA supplementation is known to influence and promote gluconeogenesis. Specifically, omega-3 PUFA promote glucose production associated with triglyceride metabolism (gluconeogenesis from glycerol), without worsening glycemic control or hepatic glucose production [36].

South Asians are another population afflicted by a high risk of diabetes and cardio-metabolic risk, likely to be a result of hyperinsulinemia or a lack of sensitivity to insulin [23]. However, there doesn’t appear to be a relationship between omega-3 PUFA and insulin action in this group [20,37]. Aside from its beneficial action amongst the Alaskan Eskimo, there are very few studies reporting the efficacious action of omega-3 PUFA on glycemic control. Data amongst East Africans suggest that a high omega-3 PUFA intake is protective against glucose intolerance [38]. Results from the European prospective investigation of cancer (EPIC) study [39] suggest that the type of fish is important for reduction of diabetes risk. Here, a greater intake of shellfish was associated with an increased risk of diabetes compared with fish (white, oily and fried) intake, which reduced the risk of diabetes. Amongst Italian diabetics randomized in a large multi-centre clinical trial, there were no changes in fasting glucose, HbA1c, insulinemia or oral glucose tolerance associated with 2–3 g omega-3 PUFA intervention [40]. Woodman et al. [41] administered 4 g of purified omega-3 fish oils to diabetic patients and found that omega-3 fatty acids had no effect on insulin action. Overall, the majority of studies in this area of research suggest that there is no significant improvement or change in glycemic control caused by omega-3 PUFA [42,43].

Obesity

Abdominal or centripetal fat accumulation has been proposed as the etiological driver for cardio-metabolic risk factor clustering [44]. Omega-3 PUFA have a potential role in modulating this risk as they promote the mobilization of triglycerides from adipose sources. Using a nutrigenomic approach, the impact of genetic mutations that promote the abdominal obesity was found to be favourably modulated by plasma omega-3 PUFA [45]. Pathophysiologically, aberrant adipose tissue function is known to be mediated by a group of metabolically active hormones produced by adipocytes, termed ‘adipocytokines’. Adiponectin, leptin and tumor necrosis factor (TNF)-α are all adipocytokines that are related to omega-3 PUFA in European whites [46–48]. Similarly, amongst the Japanese, hormones such as adiponectin are associated with plasma levels of omega-3 PUFA, a relationship that may be explained by fluctuations of body weight [49]. For example, weight loss due to calorie restriction amongst obese subjects results in an alteration in the profiles of serum fatty acids, namely greater omega-3 PUFA. Also, omega-3 PUFA such as DHA levels are low in obese subjects and are normalized with weight loss [50].

Hypertension hemostasis and thrombogenesis

The INTERLIPID study was a cross-sectional epidemiological study that was designed to understand differences in CVD risk and diet between Japanese people living in Japan and third and fourth generation migrants living in Hawaii. Mean blood pressures were significantly higher in men in Japan than in Hawaii, despite lower body weight and a greater intake of omega-3 PUFA in Japan. Elsewhere, amongst different ethnic groups, there are very few studies that report an adverse impact of omega-3 PUFA on blood pressure. The antihypertensive effects of omega-3 PUFA have been analyzed in a series of trials and meta analyses of mixed ethnic groups and cultures [51–53]. These studies suggest that omega-3 PUFA have a small but significant blood pressure lowering effect, which appears to be more effective in old age or in populations with hypertension.

The complications of hypertension are commonly thrombotic in nature [54]. The antithrombotic effects of omega-3 PUFA were first reported amongst Greenland Inuit in 1979 [55]. Here, the Greenland Inuit were observed to have reduced platelet reactivity as a result of high EPA. However, objective evidence of the antithrombotic effects of omega-3 PUFA in other ethnic groups is limited. In a meta-analysis of type 2 diabetes patients participating in small randomized control trials (median n = 40), the efficacy of omega-3 was associated with a reduction of blood pressure but not a protective effect on thrombosis or hemostasis [56]. Similarly amongst European white CHD patients, omega-3 PUFA intervention made no significant changes to circulating markers of thrombosis [57]. The relationship between omega-3 PUFA and their thrombotic and hemostatic effects may be dose dependent, where levels < 2–3 g day−1 (1 g day−1 is the dose prescribed for CHD patients) are unlikely to reflect the effects first observed amongst Greenland Inuit [58]. The mechanism by which omega-3 PUFA improve blood pressure and thrombotic complications may relate to a vasodilatory effect. In a small randomized study of dyslipidemic South Asians, omega-3 PUFA improved both endothelial-dependent and endothelial-independent vasodilatation [59]. Alternatively, thrombotic and hemostatic abnormalities are commonly manifest during hypertriglyceridemia, and independently add to this proposed ‘cardio-metabolic risk’[60]. A reduction in triglycerides and body weight and an improvement in HDL are thought to promote a reduction in factor VII coagulant and fibrinolytic activity [61].

Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

Stroke

Dietary fish intake (at least one portion a week) has been established to reduce the incidence of thrombo-embolic stroke [62] (Table 2). However, evidence from large-scale population studies is conflicting [63–65]. In particular, ethnicity appears to modulate the beneficial effects of fish intake for stroke risk reduction, especially amongst black (African Americans) and Asian groups [64,66]. In the Japan eicosapentaenoic acid (EPA) lipid intervention study (JELIS), a randomized control trial, omega-3 PUFA supplementation was found to be efficacious in the secondary prevention of stroke [67]. However, similar studies do not concur that increased ‘fish intake’ in Japan has the same effect. The inconsistencies may be explained by the assumption that dietary fish intake is a good marker of omega-3 PUFA intake, which is not always the case, especially when one considers ‘shellfish consumption’ [68]. This may also explain a lack of association between stroke risk and omega-3 PUFA amongst Caucasian men in the US [64,65]. In the Nurses’ Health Study (with white Caucasian subjects free of CVD at baseline) there was a reduced risk of thromboembolic and total stroke among women in the highest quintile of intake of omega-3 PUFA [69]. In a meta-analysis of eight of the studies shown in Table 1 (which included 200 575 people and 3491 stroke events [70]) the pooled relative risk of ischemic stroke was 0.65 (0.46–0.93) for those consuming fish ≥ 5 times a week vs. < once a month. For hemorrhagic stroke, there was no benefit from fish intake. Women consistently appear to have a reduced stroke risk with respect to fish intake.

Table 2.   Dietary fish or omega-3 PUFA intake and the risk of stroke in diverse populations
ReferenceAssessment of dietary fish or omega-3 PUFA intakeFollow-up periodPopulationMultivariate adjusted hazard ratio (HR) or relative risk (RR), 95% CIType of stroke
  1. *Placebo controlled clinical trial.

Keri et al. 1994 [62]. Zutphen StudyDiet diary15 years552 men (50–69 years). NetherlandsHR = 0.49, 0.24–0.99%. For those consuming > 20 g of fish a day vs. those consuming lessAll types of stroke
Morris et al. 1995 [63]. Physicians Health StudyDiet diary4 years21 185 men (40–84 years). USRR = 0.7, 0.3–1.5% For those consuming ≥ 5 fish meals a day vs. < 1All types of stroke
Ornecia et al. 1996 [65]. Chicago Western Electric StudyFood frequency questionnaire30 years1847 men (40–55 years). USHR = 1.34, 0.53–3.41%. For those consuming ≥ 35 g day−1 of fish vs. 0 g day−1All types of stroke
Gillium et al. 1996 [64]. National Health and Nutrition Examination Survey 1Food frequency questionnaire12 years2059 men and 2351 women (45–74 years). USRR = 0.85, 0.49–1.46% in men. RR = 0.55, 0.32–0.93% in women. For those consuming 1 fish meal a week vs. noneThrombo-embolic stroke
Yuan et al. 2001 [66].Food frequency questionnaire12 years18 244 men (45–64 years). Shanghai, China.RR = 1.11, 0.83–1.47%. For those consuming ≥ 200 g week−1 of fish or shellfish vs. < 50 g week−1All types of stroke
Iso et al. 2001 [69]. Nurses Healthy Study CohortFood frequency questionnaire14 years79 839 women (34–54 years). USRR = 0.49, 0.26–0.93%. For those consuming fish > 2 times a week vs. < 2Thrombo-embolic stroke
He et al. 2002 [70]. Healthy Professional Follow Up StudyFood frequency questionnaire12 years43 671 men (40–75 years). USRR = 0.57, 0.35–0.95%. For those consuming 1–3 fish meals a month vs. < 1Thrombo-embolic stroke
Mozaffarian et al. 2005 [97]. Cardiovascular Health StudyFood frequency questionnaire12 years4775 men and women (65–98 years). USHR = 0.73, 0.55–0.98. For those consuming fish 1–4 times a week vs. < once a monthThrombo-embolic stroke
Myint et al. 2006 [98]. European Prospective Investigation into CancerFood frequency questionnaire8.5 years24 312 men and women (40–79 years). UKRR = 0.88, 0.65–1.19% in men. RR = 0.69, 0.51–0.94% in women. For those consuming oily fish vs. noneAll types of stroke
Tanaka et al. 2008 [67]*. Japan Eicosapentaenoic acid (EPA) lipid intervention studySupplementation of EPA5 years942 hyper-cholesterolemic stroke patients (30% men, 40–75 years). JapanHR = 0.86, 0.64–0.997%. For those on 1.8 g day−1 EPA vs. placeboAll types of stroke
Yamagishi et al. 2008 [68]. Japan Collaborative Cohort Study for Evaluation of Cancer RiskFood frequency questionnaire12.7 years57 972 men. JapanHR = 0.91, 0.74–1.13%. For those in the 5th quintile for fish intake vs. 1stAll types of stroke

Peripheral vascular disease

Peripheral vascular disease (PVD) is a common manifestation of atherosclerosis and is associated with significant morbidity and mortality from CHD and stroke. There is very little research across ethnic groups in this area. Overall cross-sectional studies show that the incidence of PVD is negatively associated with omega-3 PUFA intake [71,72]. However, there is little objective evidence that this temporal relationship can be exploited for clinical care. In a review of randomized controlled trials in symptomatic PVD (of 313 participants with intermittent claudication), supplementation with omega-3 PUFA did not improve ankle brachial pressure index or walking distance amongst patients [73].

Coronary heart disease

Bang and Dyerberg’s landmark studies in the 1970s suggested that the high consumption of omega-3 by the Greenland Inuit protected them from CVD (relative to Danish populations). However, these original data have been difficult to replicate in this group, underlining the importance of cultural traditions. For example, in our current decade, the CHD risk profile of the Greenland Inuit appears to improve on migration from Greenland to Denmark [74]. More recently, Jørgensen et al. [75] have reported that CHD morbidity among the Greenland Inuit is equivalent to American and European populations.

Elsewhere, other culturally similar groups such as the Alaskan Eskimo show a lack of association between omega-3 PUFA and CHD. This is despite an average daily consumption of omega-3 PUFA among Alaskan Eskimos that is nearly twice the concentration used in most intervention studies [76]. Objective evidence of subclinical atherosclerosis amongst the Alaskan Eskimo was not associated with omega-3 PUFA in this group [77,78]. However, by way of an autopsy study, McLaughlin et al. [79] reported that Alaskan natives (Eskimo, American Indians and Aleuts combined) had less advanced atheroma and greater concentrations of omega-3 in their adipose tissue than non-native Alaskans. Another autopsy study also supported the evidence that Alaskan natives had less advanced atherosclerotic disease than non-natives [80].

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. Both carotid artery intima-media thickness and coronary artery calcification were higher amongst Japanese men (born and living in Japan), as compared with white (men born and living in the USA) and Japanese-American men [82]. The negative association between omega-3 PUFA and CVD amongst the Japanese remained after controlling for HDL cholesterol and triglycerides, which were significantly better in this group compared with American cohorts. Studies in other populations have limited information on ethnicity, but the majority of studies concur that CHD events are reduced in those with high tissue levels of omega-3 PUFA [83].

Randomized controlled trials in coronary heart disease

The major clinical trial that has provided the evidence for the efficacy of omega-3 PUFA in the setting of CHD is the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico Prevenzione (GISSI-Prevenzione) trial [2]. The implication of the findings from GISSI was that the benefit of omega-3 PUFA therapy amongst patients surviving a heart attack was over and above that of other commonly used secondary prevention drugs for CHD. Elsewhere in Europe, Burr et al. [84] reported an increased CVD risk for CHD patients randomized onto omega-3 PUFA in the UK. Restenosis after percutaneous transluminal coronary angioplasty (PTCA) has an important impact on mortality amongst patients with CHD, and it is also an important model of the atherosclerotic disease process. PCTA studies investigating the efficacy of omega-3 PUFA are very conflicting, to the extent where studies suggest the reduction [85] and the promotion of restenosis risk with omega-3 intervention [86]. While a lack of effect has been reported in Caucasian [87] and South Asian groups [88], omega-3 PUFA appear more efficacious in Italians. In the Esapent for Prevention of Restenosis ITalian Study (ESPRIT), omega-3 were shown to be beneficial in the prevention of restenosis [89]. This study highlighted that the timing of intervention with omega-3 PUFA before PCTA was a key factor moderating the benefits of omega-3 PUFA.

The Italian cohorts from ESPIRIT and GISSI are known to subscribe to a Mediterranean diet, which could be a cultural factor that moderates the effects of omega-3 PUFA. In the Melbourne Collaborative Cohort Study, Hodge et al. [90] looked at ethnic differences in plasma phospholipid proportions of omega-3 PUFA in response to dietary intake of PUFA. Both gender and country of birth were found to influence omega-3 phospholipid composition. Moreover, compared with Greek, UK and Australian populations, for any given level of dietary EPA, plasma phospholipid PUFA was highest amongst the Italians.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References

Evidence from the research reviewed here would suggest that ethnicity and culture have an impact on the effects of omega-3 PUFA, and supplementation to protect against CVD may be more efficacious in certain groups (Table 1). Specifically, ethnicity appears to influence the efficiency with which omega-3 PUFA are accessed from dietary sources.

There is particular discordance between findings relating to omega-3 PUFA benefits amongst Inuit and Eskimo populations. Indeed many of the ‘historical’ findings of omega-3 PUFA amongst the Greenland Inuit have been difficult to replicate in this and similar cultural groups. A key reason for this is that these groups are experiencing lifestyle change due to the progressive effects of globalization. Omega-3 intake for these groups remains an important protective intervention against their increasing risk of CVD. Indeed, the high concentrations of omega-3 PUFA consumed by the Greenland Inuit have extended the efficacious reach of omega-3 PUFA to areas not seen in other ethnic groups.

The Japanese are clearly a population who benefit from omega-3 PUFA. Interestingly, despite the high concentrations of omega-3 PUFA intake in this group, the lipid lowering effects are limited compared with other ethnic groups with a lower omega-3 PUFA intake. Habitual intake of omega-3 PUFA has an important influence on the effects of omega-3 PUFA, and ethnicity appears to moderate this. For example, amongst European groups, Italians are more efficient in their incorporation of omega-3 PUFA from the diet. Ethnic differences in the cardiovascular efficacy of omega-3 PUFA are difficult to reconcile as the mechanism of action of fish oils remains unknown. Cell culture and animal models would suggest there are a number of enzymatic mechanisms by which omega-3 PUFA induce cardiovascular effects [91]. For example, there is increasing evidence that the enzyme desaturase 5 (Delta5), which is involved in long chain PUFA synthesis, has an important role in both the impact of omega-3 PUFA and CVD risk [92]. A reduction in the activity of Delta5 is associated with an increased CVD risk, and its genetic expression occurs in response to omega-3 PUFA intake [93]. In South Asians, mutations of Delta5 are believed to have a dramatic affect on the action of omega-3 PUFA [94].

With respect to global diversity in the morbidity and mortality from CVD, dietary recommendations for omega-3 PUFA for 38 countries have been suggested to achieve plasma levels that prevent and treat country-specific rates of CVD [95]. From the evidence in this review, one would anticipate that ethnicity is also a factor that is likely to influence the efficacy of ‘optimal’ plasma omega-3 PUFA. For the UK to achieve a comparable percentage plasma concentration of long chain PUFA to the Japanese (60%), some 1.6 g day−1 are needed [96]. These amounts are potentially inadequate for South Asians in the UK, in whom omega-3 PUFA appear particularly effective, but their CVD risk is some 50% higher than that for the general UK population [23].

In summary, studies have not shown consistency in the effects of omega-3 PUFA on CVD risk. Ethnicity is a factor that can account for some of this variation. Some of the effects of omega-3 PUFA are limited to cultures with a high omega-3 intake, and ethnicity also moderates the uptake of omega-3 PUFA from the diet.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Search strategy
  5. Ethnicity and omega-3 polyunsaturated fatty acids
  6. Ethnic differences in the action of omega -3 polyunsaturated fatty acids on lipids
  7. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardio-metabolic risk factors
  8. Ethnic differences in the relationship between omega-3 polyunsaturated fatty acids and cardiovascular outcomes
  9. Discussion
  10. Disclosure of Conflict of Interests
  11. References
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