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n-6 Fatty acids and cardiovascular health: a review of the evidence for dietary intake recommendations

Published online by Cambridge University Press:  04 June 2010

Sébastien Czernichow*
Affiliation:
Nutritional Epidemiology Research Unit, UMR INSERM U557, INRA U1125, CNAM, UP13, CRNH-IdF, Faculté SMBH, 74 rue Marcel Cachin, 93017Bobigny, France Public Health Department, Hôpital Avicenne (AP-HP) and University Paris 13, Bobigny, France
Daniel Thomas
Affiliation:
Department of Medical Cardiology, Institute of Cardiology, Pitié-Salpêtrière Hospital, 47 Bd de l'Hôpital, 75651Paris Cedex 13, France
Eric Bruckert
Affiliation:
Department of Endocrinology and Metabolism, Pitié-Salpêtrière Hospital, 47, Bd de l'Hôpital, 75013Paris Cedex 13, France
*
*Corresponding author: Associate Professor S. Czernichow, email s.czernichow@uren.smbh.univ-paris13.fr
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Abstract

n-6 PUFA are well known for their critical role in many physiological functions and seem to reduce risks of CHD. However, some argue that excessive consumption of n-6 PUFA may lead to adverse effects on health and therefore recommend reducing dietary n-6 PUFA intake or fixing an upper limit. In this context, the present work aimed to review evidence on the link between n-6 PUFA and risks of CVD. Epidemiological studies show that n-6 PUFA dietary intake significantly lowers blood LDL-cholesterol levels. In addition, n-6 PUFA intake does not increase several CVD risk factors such as blood pressure, inflammatory markers, haemostatic parameters and obesity. Data from prospective cohort and interventional studies converge towards a specific protective role of dietary n-6 PUFA intake, in particular linoleic acid, against CVD. n-6 PUFA benefits are even increased when SFA intake is also reduced. In regards to studies examined in this narrative review, recommendation for n-6 PUFA intake above 5 %, and ideally about 10 %, of total energy appears justified.

Keywords

Type
Review Article
Copyright
Copyright © The Authors 2010

With change in the western human diet over the past 100 years, consumption of food rich in n-6 PUFA has increased(Reference Kris-Etherton, Taylor and Yu-Poth1). n-6 PUFA are needed for many physiological functions of the human system and are well known for their protective effects against CVD. For these reasons, the American Heart Association Nutrition Subcommittee has recently recommended a consumption of at least 5–10 % of energy from n-6 PUFA(Reference Harris, Mozaffarian and Rimm2). However, some researchers recommend to reduce dietary n-6 PUFA intake in order to prevent adverse effects on health, in particular pro-inflammatory response(Reference Simopoulos3Reference Ailhaud5). In parallel, some national recommendations for daily n-6 PUFA intake are already based on low figures (i.e. 4 % of total energy in France), considering the risk of inflammation or obesity linked with significant n-6 PUFA consumption as non-negligible. Fixing an upper limit to n-6 PUFA consumption for healthy populations is a recurrent issue in the international scientific agenda for lipids intake guidelines. To get an in-depth analysis of the benefits/risks balance of n-6 PUFA intake, the present work reviews studies on the link between n-6 PUFA and CVD risks factors: dyslipidaemia, hypertension, thrombosis susceptibility, oxidisability of lipoproteins, obesity and a pro-inflammatory response. Based on this analysis, recommendation and comments regarding minimal v. optimal n-6 PUFA intake, and the need for an upper limit, are discussed.

Dietary n-6 PUFA

A carbon chain that contains two or more cis double bonds with the first double bond located between the sixth and seventh carbon atom from the methyl end of the fatty acid (n-6 position) characterises n-6 PUFA. The main dietary n-6 PUFA is linoleic acid (LA; 18: 2n-6), which can be found in vegetable oils such as soyabean, safflower, maize and rapeseed oils. LA cannot be synthesised by human subjects and other mammals and, as such, is provided by dietary intake only(Reference Holman6, Reference Williard, Nwankwo and Kaduce7). The average LA intake in USA is 14·8 g/d (6·7 % of energy)(Reference Moshfegh, Goldman and Cleveland8). In France, according to the SUpplementation en VItamines et Mineraux AntioXydants study, LA intake is 10·6 g/d in men and 8·1 g/d in women, representing 4·2 % of energy intake(Reference Astorg, Bertrais and Laporte9). These values reflect well the variability of daily LA consumption across countries(Reference Poudel-Tandukar, Nanri and Matsushita10Reference Baylin, Kim and Donovan-Palmer12).

Another n-6 PUFA provided by the diet, but in a lower amount, is the arachidonic acid (AA; 20 : 4n-6) which can be found in meats, poultry and eggs. Dietary AA intake accounts for an average of 0·08 % energy in France with a daily consumption of 0·22 g/d in men and 0·16 g/d in women(Reference Astorg, Bertrais and Laporte13), similar to the world intakes(Reference Calder14Reference Williams, Baylin and Campos16). AA can also be synthesised by the conversion of LA after successive desaturation and elongation reactions occurring in the endoplasmic reticulum of the cell(Reference Sprecher, Luthria and Mohammed17). The δ-6-desaturase enzyme, which catalyses the conversion of LA to γ-linolenic acid (18 : 3n-6), seems to be the rate-limiting step in the n-6 PUFA metabolism(Reference Nakamura and Nara18). Results from human subjects and animal studies report that the rate of this initial conversion is low(Reference Cunnane, Keeling and Thompson19Reference Emken, Adlof and Gulley21). Then, γ-linolenic acid is in turn elongated to dihomo-γ-linolenic acid (20 : 3n-6). In a third step, dihomo-γ-linolenic acid is desaturated to AA by δ-5 desaturase. It is worth mentioning that the overall conversion of LA to AA is extremely low, certainly below 0·5 %(Reference Hussein, Ah-Sing and Wilkinson22). This might explain why variations in dietary n-6 intake, including LA, have little effect on AA levels in serum cholesterol esters, erythrocyte and platelet membranes(Reference Sarkkinen, Agren and Ahola23).

n-6 PUFA and CVD risk factors

n-6 PUFA and blood lipids

Abnormal blood lipid levels such as elevated LDL-cholesterol (LDL-C) are major risk factors for atherosclerosis and CVD(24, Reference Briel, Ferreira-Gonzalez and You25). These risks can be reduced by dietary intervention and, in particular, by change in fat composition of the diet. Indeed, a decrease in dietary SFA can induce a significant lowering of plasma LDL-C levels(Reference Katan, Zock and Mensink26). Diets rich in PUFA are well known for their hypocholesterolaemic action(Reference Nichaman, Sweeley and Olson27, Reference Shepherd, Packard and Grundy28). When the dietary proportion of SFA remains constant and n-6 PUFA replace carbohydrates, a decrease in LDL-C plasma levels is observed(Reference Mensink, Zock and Katan29). A meta-analysis of sixty controlled trials reported that the replacement of carbohydrates with PUFA (largely n-6) was predictive of the largest change in the total cholesterol:HDL-cholesterol (HDL-C) ratio, and in LDL-C concentrations, compared with other types of fatty acids(Reference Mensink, Zock and Kester30). Replacement of 1 % of energy of carbohydrates by saturated fats increases LDL-C serum level by approximately 0·03 mmol/l, whereas replacement by n-6 PUFA decreases this level by 0·02 mmol/l.

Replacing dietary SFA by PUFA, which are mainly n-6 PUFA, is also efficient in decreasing plasma concentration of cholesterol. In a meta-analysis of seventy-two metabolic ward studies of solid food diets in healthy volunteers, Clarke et al. (Reference Clarke, Frost and Collins31) observed that replacement of 5 % energy as SFA by PUFA led to a − 0·39 mmol/l change in total blood cholesterol. In the work of Hodson et al. (Reference Hodson, Skeaff and Chisholm32), replacing 6·4 % energy as SFA by n-6 PUFA while keeping total fat content at 30–33 % of energy led to a 22 % decrease in plasma LDL-C ( − 0·63 mmol/l) and a 14 % decrease in HDL-C. The decrease in HDL-C, although not systematically observed in all n-6 PUFA interventional studies, could be challenged because a low concentration of HDL-C has been associated with a higher risk for CHD(Reference Franceschini33). However, the total cholesterol:HDL-C ratio is considered as a better predictor of CVD than HDL-C alone(Reference Yusuf, Hawken and Ounpuu34). Analysis of the Framingham Heart Study's data by Siguel(Reference Siguel35) reported that a total cholesterol:HDL-C ratio decreased when the percentage of plasma PUFA increased, either in response to a diet enriched in PUFA or across different subjects. To conclude, replacing SFA by n-6 PUFA (or eating a diet enriched with n-6 PUFA) leads to a substantial reduction in total and LDL-C cholesterol, as well as a reduction of the total cholesterol:HDL-C ratio, and may reduce the risk of CVD(Reference Jakobsen, O'Reilly and Heitmann36, Reference Hodson, Skeaff and Chisholm37).

n-6 PUFA and blood pressure

In a cross-sectional study by Salonen et al. (Reference Salonen, Salonen and Ihanainen38), LA intake (average of 10 g/d) assessed by a 4-d dietary recall by household measures in 722 men was not correlated with the mean resting blood pressure. In contrast, Oster et al. (Reference Oster, Arab and Schellenberg39) found a strongly significant negative correlation between LA content of adipose tissue and systolic as well as diastolic blood pressure (Pearson's r − 0·16, P < 0·001 and r − 0·12, P < 0·001, respectively) in a cohort of 650 healthy men. In an other observational study in a large population of 4033 healthy men, a 2-sd increase in plasma levels of LA was associated with a 1·9 (95 % CI 1·0, 2·8) mmHg decrease in systolic blood pressure(Reference Grimsgaard, Bonaa and Jacobsen40). This is in line with the results obtained in control subjects of the multiple risk factor intervention trial, where plasma levels of LA were inversely associated with systolic and diastolic blood pressures ( − 3·02 (95 % CI − 5·26, − 0·77) and − 1·62 (95 % CI − 2·83, − 0·41), respectively)(Reference Simon, Fong and Bernert41). Results of several interventional trials reported by Iacono et al. (Reference Iacono, Dougherty and Puska42) showed that consumption of a diet with PUFA:SFA ratio at about 1·0 led to a significant decrease in blood pressure in normotensive or mildly hypertensive healthy subjects, compared with an usual diet, regardless of the level of fat energy of the intervention diets (25 or 44 % of energy). As highlighted by a recent review of cross-sectional studies, an increase in dietary n-6 PUFA intake is often associated with a decrease in blood pressure, which is in favour of a reduced risk of CVD(Reference Hall43).

n-6 PUFA and thrombus susceptibility

Three decades ago, dietary LA was administered as a natural precursor of PGE1 in order to reduce platelet aggregation, a well-known risk factor for atherogenesis and thrombogenesis. Hornstra et al. (Reference Hornstra, Chait and Karvonen44) reported that a polyunsaturated-rich diet (PUFA:SFA ratio = 1·60) was associated with a significant decrease in platelet aggregation compared with a saturated-rich diet (PUFA:SFA ratio = 0·25) in men. Since then, other interventional studies have investigated the effect of LA on various haemostatic parameters but the results are not consistent(Reference Knapp45). In the recent randomised cross-over controlled trial of Thijssen et al. (Reference Thijssen, Hornstra and Mensink46), forty-five healthy subjects consumed three different diets for 5 weeks each. Diets contained 38 % energy as fat and differed by 7 % of energy from stearic acid, oleic acid or LA. Consumption of LA relative to stearic acid was related to an increase in ex vivo platelet aggregation time in men (P < 0·036) suggesting an antithrombogenic effect of LA. However, the three diets had no effect on in vitro whole-blood platelet aggregation variables, on factor VIIam activity and on fibrinolytic activity. Overall, the results from human studies are not conclusive, and further investigation is needed to clarify the role of n-6 PUFA in susceptibility to thrombus.

n-6 PUFA and oxidative stress

PUFA are particularly vulnerable substrates to oxidative stress because reactive oxygen species can easily remove hydrogen atom from their numerous double bonds and generate toxic peroxide species(Reference Halliwell and Chirico47). This lipid peroxidation leading to pro-inflammatory oxidised LDL and HDL is highly suspected of contributing to atherosclerosis pathogenesis(Reference Steinberg, Parthasarathy and Carew48, Reference Navab, Ananthramaiah and Reddy49). Interventional studies investigating the link between dietary PUFA intake and atherogenesis produced mixed results. Several works have shown that dietary supplementation rich in n-6 PUFA increases the extent of LDL oxidation in vitro compared with a diet enriched in MUFA(Reference Abbey, Belling and Noakes50Reference Bonanome, Pagnan and Biffanti52). In contrast, markers related to LDL-C oxidation in vitro or LDL levels of malondialdehyde were not correlated with the n-6 PUFA intake in a group of healthy volunteers(Reference Kleemola, Freese and Jauhiainen53). Furthermore, a controlled double-blind 2 × 2-factorial, 8-week intervention in a cohort of healthy men showed that fish oil consumption combined with a high LA intake (21 g/d) did not raise the plasma level of oxidised LDL compared with the same fish oil consumption but combined with a low level of LA(Reference Damsgaard, Frokiaer and Andersen54).

n-6 PUFA and inflammation

n-6 PUFA have long been considered as pro-inflammatory molecules because they are the main precursors of eicosanoids, a family of mediator molecules which are involved in immune and inflammatory response such as Prostaglandin E2, thromboxane A2 and leukotriene B4(Reference Calder and Grimble55). However, both the level and the nature of the prostanoids synthesised from AA change dramatically according to the amplitude of the inflammatory response and the course of this response(Reference Tilley, Coffman and Koller56Reference Serhan58). It is also argued that higher dietary intake of n-6 PUFA may lead to a competition between n-6 and n-3 metabolism resulting in a reduced production of anti-inflammatory molecules from n-3 PUFA(Reference Simopoulos3). In human subjects, higher intakes of n-6 fatty acids do not appear to be associated with elevated levels of inflammatory markers. A study in a large US adult population reported that n-6 fatty acids did not inhibit the anti-inflammatory effects of n-3 fatty acids. In addition, combination of both types of fatty acids (higher percentile of EPA+DHA intake of 1·12 % of energy among men and 0·471 % among women; α-linolenic acid ranging from 0·46 to 0·52 % and LA ranging from 4·3 to 5·4 %) was associated with the lowest levels of inflammation, assessed by C-reactive protein, IL 6 and soluble TNF receptors 1 and 2 plasma levels(Reference Pischon, Hankinson and Hotamisligil59). In the In CHIANTI (Invecchiare in Chianti, ageing in the Chianti area) study, in the context of a mean PUFA intake of 7 g/d, higher plasma levels of n-6 PUFA (mainly AA) and n-3 PUFA (mainly DHA) were independently associated with lower levels of serum pro-inflammatory markers(Reference Ferrucci, Cherubini and Bandinelli60). Nevertheless, Thies et al. (Reference Thies, Miles and Nebe-von-Caron61) reported that a dietary supplementation with moderate amounts of long-chain n-6 or n-3 PUFA did not significantly affect inflammatory cell numbers or neutrophil and monocyte responses.

n-6 PUFA and obesity

Obesity is a cardiovascular risk factor which is linked with substantial increases in incidence of type 2 diabetes mellitus, systemic hypertension and dyslipidaemia, which are all known risk factors for CVD(Reference Lewis, McTigue and Burke62). Normal weight obesity (normal BMI and high body fat content) is also associated with a high prevalence of cardiometabolic abnormalities and CVD risk factors(Reference Romero-Corral, Somers and Sierra-Johnson63). Adipose tissue obesity is thought to depend on both hypertrophy of preexisting adipocytes and hyperplasia due to adipogenesis(Reference DiGirolamo, Fine and Tagra64Reference Tchoukalova, Sarr and Jensen66). It has been proposed that n-6 PUFA may be involved in the differentiation of preadipose cells to adipocytes(Reference Cleary, Phillips and Morton67, Reference Massiera, Saint-Marc and Seydoux68). To date, no firm conclusion can be drawn on AA role in the differentiation of preadipose cells from available in vitro studies(Reference Gaillard, Negrel and Lagarde69Reference Serrero, Lepak and Goodrich72), and animal studies investigating the effect of a diet enriched in n-6 PUFA on adipose tissue have produced conflicting results(Reference Cleary, Phillips and Morton67, Reference Massiera, Saint-Marc and Seydoux68, Reference Matsuo, Takeuchi and Suzuki73, Reference Okuno, Kajiwara and Imai74). There are few interventional studies which have investigated the relationship between a diet enriched in n-6 PUFA and adiposity as well as body weight. A recent work on fatty acids composition of adipose tissues in extremely obese patients (BMI>40 kg/m2) has found significant negative associations between n-6 PUFA and metabolic risk factors such as cholesterol and HDL-C(Reference Hernandez-Morante, Larque and Lujan75). These data suggest that n-6 PUFA from different sources, i.e. plasma as well as subcutaneous and visceral adipose tissues, may protect extreme obese patients against metabolic alterations. Overall, the role of n-6 PUFA in adipogenesis and obesity is still unclear as no firm conclusion can be drawn from available epidemiological or experimental data.

n-6 PUFA and CVD epidemiological studies

Observational studies

Prospective cohort studies on dietary PUFA intake and prevalence of CHD events are listed in Table 1. CHD events taken into account vary between studies, but myocardial infarction, sudden cardiac death and acute coronary syndrome were generally cited. One study found a correlation between dietary PUFA level of the initial examination and coronary deaths observed 19 years later(Reference Shekelle, Shryock and Paul76). Of eleven studies, five examined LA or total n-6 PUFA specifically: a significant negative association between n-6 PUFA and risk of CHD events or mortality was observed in three of them. In the nurse's health study, Hu et al. (Reference Hu, Stampfer and Manson77) found that PUFA intake (no details about n-6 or LA figures) was inversely associated with CHD risk, with the highest quintile corresponding to a daily intake of 6·4 % of energy. The authors concluded that replacing 5 % of energy from SFA with energy from unhydrogenated MUFA and PUFA would reduce CHD risk by 42 %, and would be more effective in preventing CHD than reducing overall fat intake. When extending the follow-up time from 14 to 20 years, Oh et al. (Reference Oh, Hu and Manson78) reported an inverse association between the highest quintile of PUFA intake (7·4 % of energy, no details about n-6 or LA figures) and the risk of CHD, with a stronger association in women under 65 years or overweight. A spline regression analysis showed a linear relationship between the dietary LA intake and the relative risk of CHD, with the highest proportion of LA intake (7·0 % of energy) corresponding to the lowest risk. In the Kuopio IHD risk factor study, men with the highest daily intake of LA (12·9 g/d) were up to 61 % less likely to die of CVD than their counterparts whose intake was in the lower third (6·5 g/d). Dietary PUFA intake was also positively associated with a lower risk of CVD mortality. The associations of serum-esterified fatty acids proportions with CVD mortality were equivalent to those of dietary fatty acids: higher thirds of esterified PUFA proportions (44 % of serum fatty acids), esterified LA (32 % of serum fatty acids) and esterified n-6 fatty acids (38 % of serum fatty acids) were associated with lower CVD mortality compared with lower third proportions (37, 24 and 31 %, respectively). Overall, men with the highest levels of serum LA were up to three times less likely to die of CVD(Reference Laaksonen, Nyyssonen and Niskanen79).

Table 1 Prospective cohort studies on dietary PUFA intake and CHD events and mortality

M, male; F, female; LA, linoleic acid; RR, relative risk.

A meta-analysis of 25 case–control studies was carried out by Harris et al. (Reference Harris, Poston and Haddock80) in 2007 in order to assess the association between n-3 and n-6 tissue content and CHD events. When all studies were combined, LA values were significantly lower in cases relative to controls (effect size: Hedges g = − 0·28, P = 0·02, 95 % CI − 0·04, − 0·53) and were inversely associated with non-fatal coronary events (Hedges g = − 0·21, P < 0·01, 95 % CI − 0·06, − 0·36). When studies were stratified by phospholipid- v. TAG-rich tissues, the AA content of adipose tissue was higher in cases relative to control (Hedges g = 0·47, P = 0·01, 95 % CI 0·83, 0·1) but, overall, the tissue AA content was not associated with CHD events. Similar results were found in the study by Block et al. (Reference Block, Harris and Reid81) investigating the link between acute coronary syndrome and the fatty acid content of whole-blood cell membranes. The authors found that a 1-sd decrease in LA was associated with more than three times the odds for having a acute coronary syndrome (OR 3·23, 95 % CI 2·63, 4·17). Results with AA were more complex to interpret because both very low and very high levels were associated with increased risk of acute coronary syndrome.

Randomised controlled trials

Several small randomised trials have investigated the impact of dietary PUFA on CVD. Most of them were based on the replacement of SFA, and not carbohydrates or protein, in populations of patients presented with CHD. Dietary intervention varied between studies with a PUFA intake ranging from 5·7 % of total energy in the study of Frantz et al. (Reference Frantz, Dawson and Ashman82) to 20·6 % in the study of Leren(Reference Leren83), and included reduction of total fat in some cases (see Table 2). A first major result is that all these dietary interventions resulted in substantial reduction of serum cholesterol (from 11 % in Woodhill et al. (Reference Woodhill, Palmer and Leelarthaepin84) up to 25 % in Rose et al. (Reference Rose, Thomson and Williams85)). The effect of dietary PUFA intake on CVD mortality and incidents differed between studies. Of nine studies listed in Table 2, four showed a decrease in CHD events in both men and women(Reference Frantz, Dawson and Ashman82, Reference Leren83, Reference Turpeinen, Karvonen and Pekkarinen86, Reference Miettinen, Turpeinen and Karvonen87). Miettinen et al. (Reference Miettinen, Turpeinen and Karvonen87) found a lower CHD events' incidence in the test group (25 %) compared with the control (39·4 %) after a diet rich in PUFA (36·8 % of total fat). When data are stratified by age, it seems that this type of diet is more efficient in preventing CHD in younger subjects than in older ones(Reference Leren83, Reference Dayton, Pearce and Goldman88).

Table 2 Interventional studies

NA, not applicable; M, male; LA, linoleic acid; F, female.

Many of the intervention trials that have examined the impact of PUFA on health outcomes have done so by replacing SFA in the diet with PUFA. Furthermore, in many of the epidemiological studies, it is likely that a PUFA-rich diet may be associated with a lower SFA intake. The respective PUFA and SFA weights in terms of CVD benefits/risks balance is therefore a recurrent topic. Interestingly, a recent meta-analysis of twenty-one prospective studies has been concluded on an absence of significant evidence for an association of dietary saturated fat with an increased risk of CHD or CVD(Reference Siri-Tarino, Sun and Hu89). In parallel, the cholesterol-lowering effect of n-6 PUFA and, especially, LA is well established from human trials, as well as observational studies generally suggest a benefit of n-6 PUFA intake on CHD risk. In the nurse health study, the inverse association found between polyunsaturated fat and relative risk of CHD (relative risk 0·62; 95 % CI; for each increase of 5 % of energy) appears stronger compared with the positive association linked to saturated fat (relative risk 1·17; 95 % CI; for each increase of 5 % of energy). Overall, data converge to an SFA-independent benefit of n-6 PUFA intake on CVD risk.

International recommendations for n-6 PUFA intake

Despite large variations across the world, increasing quantities and changing qualities of fat consumed, in particular SFA and trans-fatty acids, give rise to serious concerns in the maintenance of good public health. There is a consensus for an upper limit of saturated fat intake at 10 % of total energy intake, but this is not the case for n-6 PUFA.

Recommendations on PUFA intake in healthy adults are listed in Table 3. PUFA intake values range from 3·6(Reference Kris-Etherton, Innis and Ammerican90) to 12 % of total energy(Reference Trumbo, Schlicker and Yates91). The same disparity holds true for dietary n-6 PUFA amounts which vary from 3(Reference Kris-Etherton, Innis and Ammerican90) to 10 % of total energy(92, Reference Sasaki93). Beyond these recommendations, controversial issues exist on the relevance of setting an upper limit for n-6 consumption and recommending an optimal n-6:n-3 ratio(Reference Simopoulos3Reference Ailhaud5).

Table 3 Recommendations for intake of PUFA in healthy adults

FA, fatty acid; LA, linoleic acid.

Currently, there is no mention of an upper n-6 PUFA value in the Eurodiet core report(92, 94, 95). The 2005 advisory committee on dietary guidelines for America documents the upper limit of LA intake assimilated to n-6 PUFA intake on three lines of evidence: the actual dietary intake of North American populations, absence of epidemiological data on health consequences of a greater intake, and finally the pro-oxidant state produced by high intakes of LA that could promote CHD and cancer(95). In contrast, in the nutrient reference values report for Australia and New Zealand, no upper level of intake for either linoleic or α-linolenic acids is set because ‘there is no known level at which adverse effects may occur’(92, 95). These different positions reflect the current worldwide debate on the relevance of an upper limit in dietary n-6 PUFA intake and highlight the need for further in vivo investigations. The n-6:n-3 ratio issue has been debated in detail by Stanley et al. (Reference Stanley, Elsom and Calder96) and Harris(Reference Harris97), which concludes that using this ratio is not relevant when setting up recommendations.

Conclusion

n-6 PUFA are critical to many physiological functions of the organism, and their derivatives are involved in complex molecular pathways. Dietary n-6 PUFA intake from 5 to 20 % of the energy intake lowers LDL-C blood levels, and this may explain why n-6 PUFA (in particular LA) consumption is associated with a decreased risk of CHD(Reference Jakobsen, O'Reilly and Heitmann36, Reference Katan98). No adverse effect of n-6 PUFA intake on blood pressure, inflammatory markers or haemostatic parameters has been observed, even with intake up to 15 % of total energy. In addition, there is no evidence for a causal link between n-6 PUFA intake and obesity in human subjects. From all available investigations, the most effective replacement of saturated fat in regards to CHD outcome are PUFA, especially LA(Reference Harris, Mozaffarian and Rimm2, Reference Tunstall-Pedoe99). The body of data supports the recommendation for n-6 PUFA intake above 5 %, and ideally about 10 % of total energy. The cardiovascular benefit could be even stronger when combined with a recommendation on reducing SFA intake. Finally, whatever the objective might be (i.e. to limit the risk of developing inflammatory or obesity diseases), recommending n-6 PUFA consumption below the current lowest values (i.e. 4 % of total energy in France) is not supported.

Acknowledgements

S. C. has received honoraria from Lesieur, E. B. has received honoraria from Danone and Unilever, and D. T. has received honoraria from Unilever.

References

1 Kris-Etherton, PM, Taylor, DS, Yu-Poth, S, et al. (2000) Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 71, 179S188S.Google ScholarPubMed
2 Harris, WS, Mozaffarian, D, Rimm, E, et al. (2009) Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation 119, 902907.CrossRefGoogle Scholar
3 Simopoulos, AP (2008) The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood) 233, 674688.CrossRefGoogle ScholarPubMed
4 Hamazaki, T & Okuyama, H (2003) The Japan Society for Lipid Nutrition recommends to reduce the intake of linoleic acid. A review and critique of the scientific evidence. World Rev Nutr Diet 92, 109132.CrossRefGoogle ScholarPubMed
5 Ailhaud, G (2008) Omega-6 fatty acids and excessive adipose tissue development. World Rev Nutr Diet 98, 5161.CrossRefGoogle ScholarPubMed
6 Holman, RT (1961) How essential are fatty acids? JAMA 178, 930933.CrossRefGoogle ScholarPubMed
7 Williard, DE, Nwankwo, JO, Kaduce, TL, et al. (2001) Identification of a fatty acid delta6-desaturase deficiency in human skin fibroblasts. J Lipid Res 42, 501508.Google ScholarPubMed
8 Moshfegh, A, Goldman, J & Cleveland, L (2005) What we Eat in America: NHANES 2001–2002: Usual Nutrient Intakes from Food Compared to Dietary Reference Intakes. Beltsville, MD: US Department of Agriculture, Agricultural Research Service.Google Scholar
9 Astorg, P, Bertrais, S, Laporte, F, et al. (2008) Plasma n-6 and n-3 polyunsaturated fatty acids as biomarkers of their dietary intakes: a cross-sectional study within a cohort of middle-aged French men and women. Eur J Clin Nutr 62, 11551161.CrossRefGoogle ScholarPubMed
10 Poudel-Tandukar, K, Nanri, A, Matsushita, Y, et al. (2009) Dietary intakes of alpha-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men. Nutr Res 29, 363370.CrossRefGoogle ScholarPubMed
11 Rosell, MS, Lloyd-Wright, Z, Appleby, PN, et al. (2005) Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men. Am J Clin Nutr 82, 327334.Google ScholarPubMed
12 Baylin, A, Kim, MK, Donovan-Palmer, A, et al. (2005) Fasting whole blood as a biomarker of essential fatty acid intake in epidemiologic studies: comparison with adipose tissue and plasma. Am J Epidemiol 162, 373381.CrossRefGoogle ScholarPubMed
13 Astorg, P, Bertrais, S, Laporte, F, et al. (2008) Plasma n-6 and n-3 polyunsaturated fatty acids as biomarkers of their dietary intakes: a cross-sectional study within a cohort of middle-aged French men and women. Eur J Clin Nutr 62, 11551161.CrossRefGoogle ScholarPubMed
14 Calder, PC (2007) Dietary arachidonic acid: harmful, harmless or helpful? Br J Nutr 98, 451453.CrossRefGoogle ScholarPubMed
15 Kusumoto, A, Ishikura, Y, Kawashima, H, et al. (2007) Effects of arachidonate-enriched triacylglycerol supplementation on serum fatty acids and platelet aggregation in healthy male subjects with a fish diet. Br J Nutr 98, 626635.CrossRefGoogle ScholarPubMed
16 Williams, ES, Baylin, A & Campos, H (2007) Adipose tissue arachidonic acid and the metabolic syndrome in Costa Rican adults. Clin Nutr 26, 474482.CrossRefGoogle ScholarPubMed
17 Sprecher, H, Luthria, DL, Mohammed, BS, et al. (1995) Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J Lipid Res 36, 24712477.Google ScholarPubMed
18 Nakamura, MT & Nara, TY (2004) Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr 24, 345376.CrossRefGoogle ScholarPubMed
19 Cunnane, SC, Keeling, PW, Thompson, RP, et al. (1984) Linoleic acid and arachidonic acid metabolism in human peripheral blood leucocytes: comparison with the rat. Br J Nutr 51, 209217.CrossRefGoogle ScholarPubMed
20 Demmelmair, H, Iser, B, Rauh-Pfeiffer, A, et al. (1999) Comparison of bolus versus fractionated oral applications of [13C]-linoleic acid in humans. Eur J Clin Invest 29, 603609.CrossRefGoogle ScholarPubMed
21 Emken, EA, Adlof, RO & Gulley, RM (1994) Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1213, 277288.CrossRefGoogle ScholarPubMed
22 Hussein, N, Ah-Sing, E, Wilkinson, P, et al. (2005) Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men. J Lipid Res 46, 269280.CrossRefGoogle Scholar
23 Sarkkinen, ES, Agren, JJ, Ahola, I, et al. (1994) Fatty acid composition of serum cholesterol esters, and erythrocyte and platelet membranes as indicators of long-term adherence to fat-modified diets. Am J Clin Nutr 59, 364370.Google ScholarPubMed
24 NCEP NCaEP (2001) Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).Google Scholar
25 Briel, M, Ferreira-Gonzalez, I, You, JJ, et al. (2009) Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ 338, b92.CrossRefGoogle ScholarPubMed
26 Katan, MB, Zock, PL & Mensink, RP (1994) Effects of fats and fatty acids on blood lipids in humans: an overview. Am J Clin Nutr 60, 1017S1022S.Google ScholarPubMed
27 Nichaman, MZ, Sweeley, CC & Olson, RE (1967) Plasma fatty acids in normolipemic and hyperlipemic subjects during fasting and after linoleate feeding. Am J Clin Nutr 20, 10571069.Google ScholarPubMed
28 Shepherd, J, Packard, CJ, Grundy, SM, et al. (1980) Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res 21, 9199.Google ScholarPubMed
29 Mensink, RP, Zock, PL, Katan, MB, et al. (1992) Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans. J Lipid Res 33, 14931501.Google ScholarPubMed
30 Mensink, RP, Zock, PL, Kester, AD, et al. (2003) Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr 77, 11461155.Google ScholarPubMed
31 Clarke, R, Frost, C, Collins, R, et al. (1997) Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ 314, 112117.CrossRefGoogle ScholarPubMed
32 Hodson, L, Skeaff, CM & Chisholm, WA (2001) The effect of replacing dietary saturated fat with polyunsaturated or monounsaturated fat on plasma lipids in free-living young adults. Eur J Clin Nutr 55, 908915.CrossRefGoogle ScholarPubMed
33 Franceschini, G (2001) Epidemiologic evidence for high-density lipoprotein cholesterol as a risk factor for coronary artery disease. Am J Cardiol 88, 9N13N.CrossRefGoogle ScholarPubMed
34 Yusuf, S, Hawken, S, Ounpuu, S, et al. (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet 364, 937952.CrossRefGoogle ScholarPubMed
35 Siguel, E (1996) A new relationship between total/high density lipoprotein cholesterol and polyunsaturated fatty acids. Lipids 31, S51S56.CrossRefGoogle ScholarPubMed
36 Jakobsen, MU, O'Reilly, EJ, Heitmann, BL, et al. (2009) Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr 89, 14251432.CrossRefGoogle ScholarPubMed
37 Hodson, L, Skeaff, CM & Chisholm, WA (2001) The effect of replacing dietary saturated fat with polyunsaturated or monounsaturated fat on plasma lipids in free-living young adults. Eur J Clin Nutr 55, 908915.CrossRefGoogle ScholarPubMed
38 Salonen, JT, Salonen, R, Ihanainen, M, et al. (1988) Blood pressure, dietary fats, and antioxidants. Am J Clin Nutr 48, 12261232.Google ScholarPubMed
39 Oster, P, Arab, L, Schellenberg, B, et al. (1980) Linoleic acid and blood pressure. Prog Food Nutr Sci 4, 3940.Google ScholarPubMed
40 Grimsgaard, S, Bonaa, KH, Jacobsen, BK, et al. (1999) Plasma saturated and linoleic fatty acids are independently associated with blood pressure. Hypertension 34, 478483.CrossRefGoogle ScholarPubMed
41 Simon, JA, Fong, J & Bernert, JT Jr (1996) Serum fatty acids and blood pressure. Hypertension 27, 303307.CrossRefGoogle ScholarPubMed
42 Iacono, JM, Dougherty, RM & Puska, P (1982) Reduction of blood pressure associated with dietary polyunsaturated fat. Hypertension 4, III34III42.CrossRefGoogle ScholarPubMed
43 Hall, WL (2009) Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function. Nutr Res Rev 22, 1838.CrossRefGoogle ScholarPubMed
44 Hornstra, G, Chait, A, Karvonen, MJ, et al. (1973) Influence of dietary fat on platelet function in men. Lancet 1, 11551157.CrossRefGoogle ScholarPubMed
45 Knapp, HR (1997) Dietary fatty acids in human thrombosis and hemostasis. Am J Clin Nutr 65, 1687S1698S.Google ScholarPubMed
46 Thijssen, MA, Hornstra, G & Mensink, RP (2005) Stearic, oleic, and linoleic acids have comparable effects on markers of thrombotic tendency in healthy human subjects. J Nutr 135, 28052811.Google ScholarPubMed
47 Halliwell, B & Chirico, S (1993) Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr 57, 715S724S.Google ScholarPubMed
48 Steinberg, D, Parthasarathy, S, Carew, TE, et al. (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915924.Google ScholarPubMed
49 Navab, M, Ananthramaiah, GM, Reddy, ST, et al. (2004) The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 45, 9931007.CrossRefGoogle ScholarPubMed
50 Abbey, M, Belling, GB, Noakes, M, et al. (1993) Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation. Am J Clin Nutr 57, 391398.Google ScholarPubMed
51 Berry, EM, Eisenberg, S, Haratz, D, et al. (1991) Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins – the Jerusalem Nutrition Study: high MUFAs vs high PUFAs. Am J Clin Nutr 53, 899907.Google Scholar
52 Bonanome, A, Pagnan, A, Biffanti, S, et al. (1992) Effect of dietary monounsaturated and polyunsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification. Arterioscler Thromb 12, 529533.CrossRefGoogle ScholarPubMed
53 Kleemola, P, Freese, R, Jauhiainen, M, et al. (2002) Dietary determinants of serum paraoxonase activity in healthy humans. Atherosclerosis 160, 425432.CrossRefGoogle ScholarPubMed
54 Damsgaard, CT, Frokiaer, H, Andersen, AD, et al. (2008) Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. J Nutr 138, 10611066.Google Scholar
55 Calder, PC & Grimble, RF (2002) Polyunsaturated fatty acids, inflammation and immunity. Eur J Clin Nutr 56, Suppl. 3, S14S19.CrossRefGoogle ScholarPubMed
56 Tilley, SL, Coffman, TM & Koller, BH (2001) Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 108, 1523.CrossRefGoogle ScholarPubMed
57 De Caterina, R, Liao, JK & Libby, P (2000) Fatty acid modulation of endothelial activation. Am J Clin Nutr 71, 213S223S.Google ScholarPubMed
58 Serhan, CN (2005) Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fatty Acids 73, 141162.CrossRefGoogle Scholar
59 Pischon, T, Hankinson, SE, Hotamisligil, GS, et al. (2003) Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 108, 155160.CrossRefGoogle ScholarPubMed
60 Ferrucci, L, Cherubini, A, Bandinelli, S, et al. (2006) Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab 91, 439446.CrossRefGoogle ScholarPubMed
61 Thies, F, Miles, EA, Nebe-von-Caron, G, et al. (2001) Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 36, 11831193.CrossRefGoogle ScholarPubMed
62 Lewis, CE, McTigue, KM, Burke, LE, et al. (2009) Mortality, health outcomes, and body mass index in the overweight range: a science advisory from the American Heart Association. Circulation 119, 32633271.CrossRefGoogle ScholarPubMed
63 Romero-Corral, A, Somers, VK & Sierra-Johnson, J (2009) Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J 31, 737746.CrossRefGoogle ScholarPubMed
64 DiGirolamo, M, Fine, JB, Tagra, K, et al. (1998) Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum. Am J Physiol 274, R1460R1467.Google ScholarPubMed
65 Hausman, DB, DiGirolamo, M, Bartness, TJ, et al. (2001) The biology of white adipocyte proliferation. Obes Rev 2, 239254.CrossRefGoogle ScholarPubMed
66 Tchoukalova, YD, Sarr, MG & Jensen, MD (2004) Measuring committed preadipocytes in human adipose tissue from severely obese patients by using adipocyte fatty acid binding protein. Am J Physiol Regul Integr Comp Physiol 287, R1132R1140.CrossRefGoogle ScholarPubMed
67 Cleary, MP, Phillips, FC & Morton, RA (1999) Genotype and diet effects in lean and obese Zucker rats fed either safflower or coconut oil diets. Proc Soc Exp Biol Med 220, 153161.CrossRefGoogle ScholarPubMed
68 Massiera, F, Saint-Marc, P, Seydoux, J, et al. (2003) Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res 44, 271279.CrossRefGoogle ScholarPubMed
69 Gaillard, D, Negrel, R, Lagarde, M, et al. (1989) Requirement and role of arachidonic acid in the differentiation of pre-adipose cells. Biochem J 257, 389397.CrossRefGoogle ScholarPubMed
70 Miller, CW, Casimir, DA & Ntambi, JM (1996) The mechanism of inhibition of 3T3-L1 preadipocyte differentiation by prostaglandin F2alpha. Endocrinology 137, 56415650.CrossRefGoogle ScholarPubMed
71 Serrero, G, Lepak, NM & Goodrich, SP (1992) Paracrine regulation of adipose differentiation by arachidonate metabolites: prostaglandin F2 alpha inhibits early and late markers of differentiation in the adipogenic cell line 1246. Endocrinology 131, 25452551.CrossRefGoogle ScholarPubMed
72 Serrero, G, Lepak, NM & Goodrich, SP (1992) Prostaglandin F2 alpha inhibits the differentiation of adipocyte precursors in primary culture. Biochem Biophys Res Commun 183, 438442.CrossRefGoogle ScholarPubMed
73 Matsuo, T, Takeuchi, H, Suzuki, H, et al. (2002) Body fat accumulation is greater in rats fed a beef tallow diet than in rats fed a safflower or soybean oil diet. Asia Pac J Clin Nutr 11, 302308.CrossRefGoogle ScholarPubMed
74 Okuno, M, Kajiwara, K, Imai, S, et al. (1997) Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation. J Nutr 127, 17521757.Google ScholarPubMed
75 Hernandez-Morante, JJ, Larque, E, Lujan, JA, et al. (2009) N-6 from different sources protect from metabolic alterations to obese patients: a factor analysis. Obesity (Silver Spring) 17, 452459.CrossRefGoogle ScholarPubMed
76 Shekelle, RB, Shryock, AM, Paul, O, et al. (1981) Diet, serum cholesterol, and death from coronary heart disease. The Western Electric study. N Engl J Med 304, 6570.CrossRefGoogle ScholarPubMed
77 Hu, FB, Stampfer, MJ, Manson, JE, et al. (1997) Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 337, 14911499.CrossRefGoogle ScholarPubMed
78 Oh, K, Hu, FB, Manson, JE, et al. (2005) Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the nurses' health study. Am J Epidemiol 161, 672679.CrossRefGoogle ScholarPubMed
79 Laaksonen, DE, Nyyssonen, K, Niskanen, L, et al. (2005) Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. Arch Intern Med 165, 193199.CrossRefGoogle Scholar
80 Harris, WS, Poston, WC & Haddock, CK (2007) Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 193, 110.CrossRefGoogle ScholarPubMed
81 Block, RC, Harris, WS, Reid, KJ, et al. (2008) Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes? Am Heart J 156, 11171123.CrossRefGoogle ScholarPubMed
82 Frantz, ID Jr, Dawson, EA, Ashman, PL, et al. (1989) Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis 9, 129135.CrossRefGoogle ScholarPubMed
83 Leren, P (1966) The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Acta Med Scand Suppl 466, 192.Google ScholarPubMed
84 Woodhill, JM, Palmer, AJ, Leelarthaepin, B, et al. (1978) Low fat, low cholesterol diet in secondary prevention of coronary heart disease. Adv Exp Med Biol 109, 317330.CrossRefGoogle ScholarPubMed
85 Rose, GA, Thomson, WB & Williams, RT (1965) Corn oil in treatment of ischaemic heart disease. Br Med J 1, 15311533.CrossRefGoogle ScholarPubMed
86 Turpeinen, O, Karvonen, MJ, Pekkarinen, M, et al. (1979) Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. Int J Epidemiol 8, 99118.CrossRefGoogle ScholarPubMed
87 Miettinen, M, Turpeinen, O, Karvonen, MJ, et al. (1983) Dietary prevention of coronary heart disease in women: the Finnish Mental Hospital Study. Int J Epidemiol 12, 1725.CrossRefGoogle ScholarPubMed
88 Dayton, S, Pearce, ML, Goldman, H, et al. (1968) Controlled trial of a diet high in unsaturated fat for prevention of atherosclerotic complications. Lancet 2, 10601062.CrossRefGoogle ScholarPubMed
89 Siri-Tarino, PW, Sun, Q, Hu, FB, et al. (2010) Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr 91, 535546.CrossRefGoogle ScholarPubMed
90 Kris-Etherton, PM, Innis, S, Ammerican, DA, et al. (2007) Position of the American Dietetic Association and Dietitians of Canada: dietary fatty acids. J Am Diet Assoc 107, 15991611.Google ScholarPubMed
91 Trumbo, P, Schlicker, S, Yates, AA, et al. (2002) Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc 102, 16211630.CrossRefGoogle ScholarPubMed
92 National Health and Medical Research Council (2006) Nutrient Reference Values for Australia and New Zealand Including Recommended Dietary Intakes. Canberra: ISBN Print.Google Scholar
93 Sasaki, S (2008) Dietary Reference Intakes (DRIs) in Japan. Asia Pac J Clin Nutr 17, Suppl. 2, 420444.Google Scholar
94 Eurodiet Project (2001) Eurodiet Core Report.Google Scholar
95 U.S. Department of Health and Human Services & U.S. Department of Agriculture (2005) Dietary Guidelines for Americans, 6th ed. Washington, DC: U.S. Government Printing Office.Google ScholarPubMed
96 Stanley, JC, Elsom, RL, Calder, PC, et al. (2007) UK Food Standards Agency Workshop Report: the effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. Br J Nutr 98, 13051310.CrossRefGoogle ScholarPubMed
97 Harris, WS (2006) The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep 8, 453459.CrossRefGoogle ScholarPubMed
98 Katan, MB (2009) Omega-6 polyunsaturated fatty acids and coronary heart disease. Am J Clin Nutr 89, 12831284.CrossRefGoogle ScholarPubMed
99 Tunstall-Pedoe, H (2006) Preventing Chronic Diseases. A Vital Investment: WHO Global Report. Geneva: World Health Organization pp. 200. CHF 30·00. ISBN 92 4 1563001. Also published on http://www.who.int/chp/chronic_disease_report/en/. Int J Epidemiol.Google Scholar
100 McGee, DL, Reed, DM, Yano, K, et al. (1984) Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to nutrient intake. Am J Epidemiol 119, 667676.CrossRefGoogle ScholarPubMed
101 Kushi, LH, Lew, RA, Stare, FJ, et al. (1985) Diet and 20-year mortality from coronary heart disease. The Ireland-Boston Diet-Heart Study. N Engl J Med 312, 811818.CrossRefGoogle ScholarPubMed
102 Posner, BM, Cobb, JL, Belanger, AJ, et al. (1991) Dietary lipid predictors of coronary heart disease in men. The Framingham Study. Arch Intern Med 151, 11811187.CrossRefGoogle ScholarPubMed
103 Dolecek, TA (1992) Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med 200, 177182.CrossRefGoogle ScholarPubMed
104 Esrey, KL, Joseph, L & Grover, SA (1996) Relationship between dietary intake and coronary heart disease mortality: lipid research clinics prevalence follow-up study. J Clin Epidemiol 49, 211216.CrossRefGoogle ScholarPubMed
105 Ascherio, A, Rimm, EB, Giovannucci, EL, et al. (1996) Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ 313, 8490.CrossRefGoogle ScholarPubMed
106 Pietinen, P, Ascherio, A, Korhonen, P, et al. (1997) Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol 145, 876887.CrossRefGoogle Scholar
107 Medical Research Council (1968) Controlled trial of soya-bean oil in myocardial infarction: report of a research committee to the Medical Research Council. Lancet 292, 693700.CrossRefGoogle Scholar
108 Watts, GF, Lewis, B, Brunt, JN, et al. (1992) Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS). Lancet 339, 563569.CrossRefGoogle Scholar
109 Agence Française de Sécurité Sanitaire des Aliments (2003) Acides gras de la famille oméga 3 et système cardiovasculaire: intérêt nutritionnel et allégations. (Fatty acids, omega 3 family and the cardiovascular system: nutritional interest and allegations).Google Scholar
110 British Nutrition Foundation (2004) Nutrient Requirements and Recommendations.Google Scholar
Figure 0

Table 1 Prospective cohort studies on dietary PUFA intake and CHD events and mortality

Figure 1

Table 2 Interventional studies

Figure 2

Table 3 Recommendations for intake of PUFA in healthy adults

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