Introduction

Cardiovascular pathology represents in developed countries the first cause of mortality before cancer. Healthcare improvements and their significant effects on infectious diseases, discovery of new efficient treatments in chronic diseases and significant lifespan increase, all have contributed to this ranking. The major cardiovascular diseases such as angina, infarct or heart failure are often associated with risk factors, which belong to three main classes, physiological factors (age, gender, genetic background), pathological factors (hyperlipidemia, hypertension, diabetes, obesity) and life conditions (smoking, exercise, alcohol, dietary behaviour). In this context, hypertension is the cardiovascular risk factor with a very high occurrence. Rare in the developing countries, hypertension is one of the most frequent and worrying disease in western countries. In spite of significant improvements in detection and treatment, blood pressure values remain most often poorly controlled. Like hyperlipidemia, diabetes and obesity, hypertension has become dramatically common in developed countries. Defined on the basis of systolic blood pressure above 140 mmHg and/or a diastolic blood pressure above 90 mmHg, epidemiological studies reveal that approximately 10–15% of European people can be ranked as hypertensive. Due to its insidious characteristics, its high occurrence and its contribution to the development of cardiovascular diseases, hypertension is one of the major problems in public healthcare. Ageing is the main factor in the development of hypertension, partly because of the increasing arterial stiffness whose occurrence increases with age. Moreover, as a pathology related to reduced physical exercise and plethoric food intake, diabetic and obese people are more sensitive to hypertension. Although frequently based on a genetic background, hypertension is often triggered by nutritional factors (or nutritionally induced dysfunctions) including obesity, insulin resistance and excessive consumption of alcohol or salt. Some nutrients have thus been incriminated in spite of a very poor scientific file able to demonstrate the direct link between this specific consumption and the development of hypertension (excess fat intake, saturated fatty acids (SFA); excess carbohydrates, fast sugars, etc.). This is due to the difficulty to demonstrate the direct relationship between a nutrient and the onset of hypertension, mainly because of the heterogeneity of the disease and the variability among population subgroups in the responses to a specific food component.

Blood pressure is controlled by the complex interaction between cardiac output and peripheral arterial resistance. Hypertension results from the imbalance between the various mechanisms contributing to pressure regulation, such as hyperactivity of the sympathetic system or altered Renin–Angiotensine–Aldosterone system as elicited by numerous environmental factors, including nutrients or stress.¹ Per se, hypertension is not really a pathology of the vascular bed, but becomes a significant vascular risk factor when the increased blood pressure interacts with the biology of the vessel wall and triggers its dysfunction. When arterial tension reaches an excessive level, chronic lesions appear in the arteries and related organs (like kidneys, heart, brain and eyes). The target tissue is the arterial and arteriolar wall with significant alterations in compliance and remodelling, and the occurrence of microtrauma, which increase the arterial sensitivity to atherosclerotic plaque installation. Thus, the definition of hypertension is arbitrary and is mainly used to define the high-risk groups.² Hypertension is ranked moderate for constant values above 140/90 mmHg before 50 years and severe for constant values above 160/95 mmHg after 50 years,³ but varies spontaneously with circumstances (day vs night, ambient temperature, exercise, stress). The treatment strategies are based on modifications of life conditions including weaning from smoking, weight control, increased exercise, decreased alcohol and salt consumption and numerous efficient pharmaceutical treatments.⁴ However, as stated in the American Heart Association nutrition report,⁵ most of the factors that contribute to the development of hypertension can be influenced by diet. For these reasons, it has become necessary to try to identify the mechanisms by which a given nutrient may prevent or trigger hypertension and also the possible interactions between different groups of nutrients.⁶

Dietary fatty acids

It is well known that in western countries, the unbalanced diet favours lipid intake, which represents approximately 45% of the daily energy intake (80–100 g for a 2000 kcal daily intake), instead of the 30–35% recommended (approximately 65 g for a 2000 kcal daily intake). However, in addition to this excess in fat consumption, the nature of these fats is a major issue, which is not sufficiently controlled. The SFA often represent 50% of the fatty acid intake, whereas they should only represent 10%. On the contrary, the proportion of the polyunsaturated fatty acids (PUFA) could be significantly increased.⁷

It is difficult to evaluate the PUFA requirement in humans, but some indications are available. In France, the requirements of 6 PUFAs to allow optimised biological functions have been evaluated to be around 6%, supplied as linoleic acid.⁸ For the 3 PUFAs, 1% supplied as linolenic acid and 0.4% supplied as long-chain 3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) are considered as satisfactory. However, the intake in 3 PUFAs, and mainly in long chains, has to be higher in specific physiological circumstances like pregnancy and breast feeding, mainly for vision and nervous development of the neonates. A dietary 3/6 ratio between 1/4 and 1/6 is usually recommended (Table 1).

• Palmitic acid (C16:0) and stearic acid (C18:0) are the main saturated fatty acids in human food and represent 15–20 and 5–10% of total circulating fatty acids, respectively. Palmitic acid (but not stearic acid) was reported to contribute significantly to the increase in blood cholesterol level. For most of the consumers, saturated fat means animal fat. The large majority of the consumers consider that the saturated fatty acid intake results from meat or dairy products consumption, and often does not take into consideration that animal fat may also supply PUFAs, since the p/s (polyunsaturated/saturated ratio) is in the 10–12 range in beef tallow but in the 1–2 range in chicken fat. Similarly, vegetal fat is considered to supply PUFAs, whereas it largely contributes to the total saturated fatty acid intake (polyunsaturated margarines, or food products containing 'vegetable oil', which in fact are cocoa, palm or copra).
• Oleic acid (C18:1 9) is the main monounsaturated fatty acid in food and also the main circulating fatty acid in human blood (30–45% of plasma fatty acids).
• PUFA of the two series (6 and 3) are essential fatty acids that have to be provided by food. The 18-carbon precursors are mainly supplied by vegetable oils as linoleic acid (18:2 6, in corn, peanut, sunflower or soybean oil) or -linolenic acid (18:3 3, in soybean or rapeseed oil). Longer chains are supplied by meat products for the 6 PUFAs (liver, eggs) and sea products for the 3 PUFAs (fish and sea mammals).

Table 1 - 3/6 ratio in various diets.

Full table

Some vegetable organisms contain a 12-desaturase able to create a group of two nonconjugated double bonds in oleic acid to give linoleic acid. Some other organisms can further desaturate to -linolenic acid by a 15-desaturase. Numerous animal cells can convert these 18-carbon precursors in long-chain PUFAs, through a series of successive elongation and desaturation steps (Figure 1), but no transfer between the two series can occur. All mammals including humans possess 6- and 5-desaturases, and can thus produce the biologically active PUFAs arachidonic acid (AA, 20:4 6) and eicosapentaenoic acid (EPA, 20:5 3). In humans, this metabolic activity is highly efficient in the liver and adrenals and much less in the heart, brain and kidney. Conversely, 4-desaturase can be found only in algae and marine animal species. The 4-desaturation step leading to end products like docosahexaenoic (DHA, 22:6 3) involves an additional elongation step and 6-desaturase in a more sophisticated pathway,⁹ which does not take place in several organs like the brain and heart (Figure 1). However, several organs, including the heart and nervous tissue, are unable to realize this 4 desaturation step, which makes the exogenous supply of DHA necessary. This overall conversion process was shown to be influenced by several factors, both physiological (PUFA supply, trans fatty acids, 6 to 3 ratio, insulin, catecholamines and ageing) and pathological (alcohol, malnutrition, inflammatory bowel disease, diabetes and neuropathies). Due to multiplicity of the 6 PUFA sources and the fact that the major biologically active 6 PUFA (AA) is a 5-desaturase product, it is easy to foresee that an increase in 6 PUFA intake will balance biological requirements in the population. On the contrary, the situation is different for 3 PUFAs, whose main biologically active fatty acid (DHA) has to be supplied by food. The satisfactory 3/6 ratio in the biological membrane can reach 1/2 in several tissues, whereas it is only 1/15 in western diet. The heart is a good example, since it is unable to produce any DHA,¹⁰ which is the major 3 PUFA contributing to the membrane structure. The dietary 6/3 ratio appears as a very important factor. Although it is clear that it has to be increased in most populations, it is not a factor easy to handle. One reason for this is because the 6/3 ratio in a given food ingredient can vary with technology or culture conditions. It is known that the 6/3 ratio in eggs can vary from 1/3 in Greece to 1/50 in USA, as well as the meat of beef grown on grass (1/3) differs from the meat of grain-fed beef (1/15). Another reason is because these ratios most often refer to -linolenic acid as 3 PUFA and to the -linolenic/linoleic acid ratio. The important information has also to consider the value of long-chain 3 PUFAs, and mainly DHA, whose supply, until now, depended only on marine products. Evidently, increasing the dietary -linolenic acid intake does not result in a significant DHA increase (unlike in the 6 series where the most important metabolite is the product of the 5 desaturase). Moreover, a relative excess of 6 PUFAs (high 6/3 ratio, even with a high/3 content) counteracts the good metabolic utilization of 3 PUFAs. Due to the concurrence of desaturases, the low available amount of -linolenic acid is poorly transformed in higher metabolites, and hence in DHA. Already considered as efficient in the perinatal period for the development of neonate retina and cognition, the dietary supply in DHA is now viewed as necessary for cardiac and vascular health.

Figure 1.

Metabolic pathway of the synthesis of biologically active long-chain polyunsaturated fatty acids by successive elongation and desaturation (e=elongase, dSase=desaturase). When available, the last 4-desaturation step includes three steps: 1=elongation, 2=desaturation step by 6 desaturase and 3=peroxysomal -oxidation step.

Full figure and legend (66K)

Hypertension and SFA

Due to their negative effect on cholesterol metabolism, the SFA suffer from a very bad image in the cardiovascular field. Conversely, very few data are available on the specific effect on blood pressure. Several experimental investigations have evidenced the progressive increase in systolic blood pressure due to a highly saturated diet in animals.¹¹ Most of these work in animals, as well as all the investigations in humans, reported in fact the effects of high fat diets making it difficult to distinguish the consequence of lipid excess from the specific effects of SFA. SFA were reported to increase systolic blood pressure in male rats, but not in female or gonadectomized male rats.¹¹ Interestingly, this sensitivity to SFA was restored in castrated male rats given testosterone. On the contrary, feeding a diet rich in lard to pregnant rats also affected systolic blood pressure in adult offspring, even if fed a normal diet, but the female offspring were more sensitive than the male to this foetal nutrition-induced hypertension.¹² These results could be related to the saturated/polyunsaturated fatty acid ratio in endothelium, since it was shown that a saturated diet in rat increases catecholamine sensitivity and decreases endothelium-dependent relaxation mesenteric arteries.¹³ Some epidemiological studies including a 'saturated fat' arm have focused on cholesterol, circulating lipids, atherosclerosis, coronaropathies and stroke, but not on blood pressure. However, the ARIC study (Atherosclerosis Risk in Communities) showed that in hypertensive men, the cholesterol esters are characterized by a significantly higher content in palmitic acid and lower content in linoleic acid,¹⁴ which could be characteristic of a saturated fat diet (Figure 2). The mechanical investigations on SFA are not fully informative, because the p/s ratio is also altered, because the total fat intake is often altered and because the associated insulin resistance is per se a highly significant hypertension factor. However, a gender-related mechanism has been evidenced in several reports but has not yet been understood and remains to be elucidated.

Figure 2.

The ARIC study. Left panel: relationship between hypertension and plasma cholesterol ester fatty acid content. Right panel: blood predictors of vasodilation function (NEFA: nonesterified fatty acids, CHOL: cholesterol, TAG: triacylglycerol, SFA: saturated fatty acids, 18:2 6: linoleic acid, 18:3 3: -linolenic acid).

Full figure and legend (17K)

Hypertension, monounsaturated and trans fatty acids

Transcultural investigations like the Seven Country Study¹⁵ reported an inverse relationship between monounsaturated fatty acid consumption and cardiovascular mortality. These results have been confirmed by epidemiological studies like the Ireland–Boston Diet Heart Study¹⁶ or the Lyon Heart Study.¹⁷ The Nurse Study¹⁸ showed that in women, a 5% increase in monounsaturated fatty acid and PUFAs decreases the cardiovascular risk by 19 and 38%, respectively. These studies demonstrated that monounsaturated fat contributes to the reduction of LDL cholesterol and the increase of HDL cholesterol (in part via the reduction in SFA), but they brought no experimental information on blood pressure and the influence of monounsaturated fatty acids on blood pressure remains largely unknown.

Dietary trans fatty acids are mainly produced by hydrogenation of unsaturated fatty acids in the rumen of ruminants (which leads essentially to trans vaccenic acid 11 trans-C18:1) or by technology-based partial hydrogenation of vegetable oils (which leads essentially to elaidic acid, 9 trans-18:1) or by high-temperature cooking of highly polyunsaturated oils. In the last two decades, nutritionists have been very suspicious of the health effects of trans fatty acids. Several authors reported the deleterious effect of high trans fatty acid intake on serum lipid profile (cholesterol), a result that deserves consideration by the cardiologist. However, no experimental evidence could be reported on the influence of trans fatty acids on blood pressure in spontaneously hypertensive rats,¹⁹ and epidemiological investigations did not confirm the relationship between trans fatty acids intake and cardiovascular diseases.²⁰ In addition, the multicentric Transfair study concluded that trans fatty acids are not associated with an unfavourable serum lipid profile at the current European intake levels.²¹ Conformational studies suggest that trans-monounsaturated fatty acids are viewed as SFA in the cell and thus display the biological behaviour of a saturated fatty acid (they are incorporated in a phospholipid structure in place of a saturated fatty acid). This is partly explained by steric features showing large similarities between trans-monounsaturated fatty acids and unsaturated fatty acids and between trans-PUFA and monounsaturated fatty acids (Figure 3).

Figure 3.

Conformation of the cis vs trans double bonds in unsaturated fatty acids.

Full figure and legend (16K)

Hypertension and PUFA

The decrease in blood pressure in moderate hypertensive patients by an increased 6 PUFA supply, mainly linoleic acid from vegetable oils, is now well accepted in the scientific community.⁵ This supplement allows a significant increase in p/s and linoleic acid and supports the conclusions of the ARIC Study showing the relationship between hypertension and high plasma p/s and linoleic acid.¹⁴ However, a greater part of the investigations focuses on 3 PUFAs. Everybody knows the beneficial effects on cardiovascular disease prevention associated with the consumption of the long-chain 3 PUFAs (EPA, DPA and DHA) provided by marine oils. Numerous studies reported outstanding results with a significant decrease (20–50%) in cardiac events and mortality. Some of these studies involved diets containing marine oils rich in these long-chain 3 PUFAs like in the DART Study²² and the GISSI-prevenzione Study,²³ and some other studies involved diets rich in the precursor -linoleic acid as in the Lyon Heart Study¹⁷ or the Indo-Mediterranean Diet Heart Study.²⁴ Unfortunately, only some of these studies investigated blood pressure and most of them increased both 3 PUFAs and p/s, making it hypothetic to discuss the very effect of 3 PUFAs on blood pressure. More recently, some investigators suggested that long-chain 3 PUFAs can affect the pressure level and focused on the chain length specificity. Forsyth et al²⁵ reported that breast-fed infants and infants fed a DHA+AA enriched formula display at the age of 6 years a mean blood pressure significantly lower than that of the children previously fed an 18-carbon-PUFAs enriched formula. This arouses interest to investigate which 3 PUFA can influence blood pressure and the associated mechanism.

Experimental investigations: the importance of aetiology

In experimental hypertension, it is easy to decide the aetiology of hypertension and to investigate the animal before and after the onset of the mechanism leading to hypertension. Experimental hypertension results either from pressure overload (systolic overload) induced by systemic hypertension or aortic coarctation, or from volume overload (diastolic overload) induced by cardiac output increase. Numerous animal models of hypertension have been developed, particularly in the rat, including secondary renovascular hypertension (Glodblatt model), hyperaldosteronism by desoxycorticosterone overload (DOCA rat), essential hypertension (the Spontaneously Hypertensive Rat displaying hypertension of central origin, or the NEDH rat developing spontaneous catecholamine-secreting pheochromocytom), salt-sensitive models (Dahl rat) and mineralocorticoïd intoxication or glucocorticoïd administration (model of the Cushing syndrome). Moreover, in these models, cardiac hypertrophy is associated with the development of hypertension. The comparison of these various models allows a fine interpretation of the mechanisms involved, and several have been used in the investigations on the effect of 3 PUFAs. Investigations on hypertension resulting from psychosocial stress in rats showed that EPA and DHA can delay the onset of hypertension, improve associated cardiac function impairments and increase spontaneous heart rate.²⁶ Other studies reported a limitation by fish oil of the systolic blood pressure increase in essential hypertension,²⁷ reno-vascular hypertension²⁸ and insulin resistance.²⁹

Clinical studies

The Tromso Study revealed that the blood pressure lowering effect of 3 PUFAs is correlated to the composition of the plasma 3 PUFA rich phospholipids.³⁰ A high dose supplement with long-chain 3 PUFAs (3–9 g/day) reduces significantly both systolic and diastolic pressure in patients with a moderate hypertension. Similarly, in an intervention study on a group declaring not to consume any fish and displaying a moderate hypertension (systolic<180, diastolic<110), a fish oil supplement (6 g/day, representing 5 g of EPA+DHA) reduced significantly both systolic and diastolic blood pressure.³¹ Interestingly, the same fish oil supplement failed to elicit any hypotensive effect in the group declaring three or more fish meals per week, and in patients displaying a plasma content in phospholipid 3 PUFA above 175 mg/l. Other studies with very low doses reported (150 mg DHA and 30 mg EPA) a positive effect on systolic pressure but no effect on diastolic blood pressure.³² The clinical investigations in humans tend to confirm the hypothesis that 3 PUFAs display antihypertensive properties,^{25, 30, 32, 33, 34} in spite of some discrepancies.^{35, 36} In a meta-analysis, Morris et al³¹ outlined the variability of experimental factors (dose, group size, duration of the experiment and patient selection) as a major cause of discrepancy. The biochemical and physiological effects of 3 PUFAs are evidently dose dependent, and most of the significant results in humans have been obtained with high doses.³⁷

The mechanisms involved

Deeper investigations on 3 PUFAs specific effects reveal that their effect on blood pressure is correlated to the plasma phospholipid composition in long chains EPA and DHA. These hypotensive properties appear not only related to the modification of membrane fluidity but also to their capacity to influence prostanoid balance, which affects constriction and dilation of the arterial wall.³⁸ The replacement of AA by either EPA or DHA in various structural phospholipids (platelets, endothelium, heart) alters the functional prostacycline/thromboxane balance towards vasodilatation. In spite of the fact that -linolenic acid is easier to increase in the general diet, the effect of this precursor on blood pressure is poorly documented and the beneficial effects of 3 PUFAs on blood pressure are attributed to the higher metabolites EPA and DHA. However, this known effect on prostanoids is not the single mechanism proposed. The incorporation of DHA in cardiac membrane phospholipids was shown to affect adrenergic function in vitro³⁹ and in vivo. In rats with metabolic syndrome (mild hypertension, hyperinsulinaemia and hypertriglyceridaemia), a pure DHA supplement (200 mg/kg per day) significantly affected the increase in blood pressure in vivo. Additionally, this supplement significantly lowered heart rate and reduced the QT interval length.²⁹ Conversely, a pure EPA supplement also lowered blood pressure but failed to affect heart rate and QT interval. DHA readily enters cardiac membrane phospholipids, but not EPA, suggesting that unlike EPA, the mechanism of action of DHA may involve the regulation of adrenergic function, like -blockers. This model of hypertension is complex and involves several mechanisms including a contribution of catecholamines, which explains why DHA and EPA may act on different components of the pathology. A similar study was realized in patients displaying a mild hypertension and a mild dyslipidemia (Figure 4).⁴⁰ Ambulatory pressure was recorded during either DHA or EPA supplementation. DHA (4 g/day) was found to lower systolic blood pressure and heart rate, like in rats. In these conditions, EPA did not elicit any significant effect. In a model of essential hypertension in the rat (spontaneously hypertensive rat) with a high catecholamine contribution, DHA prevented the development of hypertension, but not EPA, unlike in metabolic syndrome hypertension.⁴¹ Each long-chain 3 PUFA has thus a specific mechanism of action, and displays variable antihypertensive properties depending on aetiology. The mechanism of DHA involves the adrenergic function and adrenergic signalling, as discussed above, and outlined by the synergic effects of fish oil and -blockers on hypertension in humans.⁴²

Figure 4.

Differences between EPA and DHA in mild hypertension. (a) Ambulatory blood pressure recorded during 24 h in overweight mildly hyperlipidaemic men (data from Mori et al⁴⁰). (b) Effect of DHA or EPA alone on systolic and diastolic blood pressure in mild hypertension reported in various studies.

Full figure and legend (38K)

These data all confirm the relationship between 3 PUFAs and hypertension, although animal and human investigations are in fact different in scope. The clinical studies were made with a dietary supplement given to patients with an established hypertension, in order to attribute to the dietary supplement a 'therapeutic value'. In this context, such a dietary treatment should be considered as additive to the hypotensive strategy. And this observation allows a flashback to the GISSI-prevenzione study,²³ which reported that long-chain 3 PUFAs did not lower blood pressure in post-infarct patients. However, the number of patients receiving -blockers was probably very high and the effect of DHA involving adrenergic function may be difficult if the patients under -blockers are not excluded. On the contrary, preclinical investigations in animals were conducted with a dietary supplement given before the development of hypertensive pathology, in order to attribute to the dietary supplement a 'preventive value'. This 'preventive value' is difficult to assess in humans and was thus not thoroughly investigated. The results of a cross-sectional analysis on 9758 men, aged 50–59 years, without coronary heart disease were published recently, and they demonstrated that fish oil consumers display, as compared with non-fish consumers, a lower heart rate and lower systolic and diastolic blood pressure.⁴³ Another concern is the specificity of EPA and DHA in this context, which questions the efficiency of the precursor -linolenic acid. The conversion of -linolenic acid to EPA is limited in men (and more generally in mammals) and further transformation to DHA acid is very low.⁴⁴ This 3 PUFA may thus contribute to influence the prostanoid balance, but does not significantly affect the cardiac membrane DHA status. Moreover, the meta-analysis of the various randomised control trials did not evidence a significant effect of -linolenic acid intake (for a few weeks) on systolic or diastolic blood pressure,⁴⁵ and the relationship between -linolenic acid intake and blood pressure remains a question of debate. Some discussions on possible dietary strategies to help control blood pressure are ongoing, merely at the beginning of the pressure rise, when a pharmaceutical prescription is not yet necessary. Moreover, more data are required to evaluate the interaction with existing treatments, the importance of aetiology in humans and the specific mechanism in order to optimise the dietary intake.

Dietary fatty acids: research and development

Epidemiological studies have evidenced a protective effect of fish oils rich in long-chain 3 PUFAs on the cardiovascular system, which was confirmed by secondary intervention studies.^{22, 23} However, the mechanism of this effect remains to be a matter of debate and more specifically in the field of hypertension, which remains an important object of experimental research. These fatty acids, as a membrane component, influence the biological and functional efficiency of membranes through the regulation of membrane-bound proteins. They contribute to the signalling processes through their metabolites (leukotrienes and prostaglandins). Moreover, these two actions can be complementary like for the platelet antiaggregating effect of EPA. The mechanisms involved in hypertension are also complex because they depend on the aetiology of the disease. However, the preventive effect of EPA and DHA appears as a constant throughout the literature and increasing their availability remains an objective in public health. The recommended intakes in western countries outline some important features. (i) There is no bad fatty acid but only bad intake levels, and this also concerns the relative intake. This statement deals with the p/s ratio and the requirements for a balanced value, which avoid the excessively low p/s (as observed in eastern EC countries) as well as the excessively high p/s (as observed in Israel for instance). (ii) The -linolenic/linoleic ratio should be close to 1/5. The ratio is considered as representative of the ingested 3/6 ratio and this value is acceptable among the different country recommendations. This highlights the importance of the balance between the two series, necessary to avoid some antagonistic effects as observed in haemostasis, platelet aggregation and inflammation. Conversely, these recommendations consider only the precursors and not the biologically active metabolites such as EPA and DHA, whose availability must be increased. The objective is difficult to reach and research and development has investigated different routes:

• Incorporation in industrial food of fish oil or purified EPA or DHA supplements (bakery, processed food, etc.), which is now accepted in various countries in spite of the elevated cost.
• Enrichment of processes food with -linolenic using rich oils (soybean, rapeseed), or the direct use of extruded linseed (bakery) with the hope of increasing with time the long chain availability. The results are not fully positive and research is going on.
• The third route, in constant growth, is the increase of -linolenic acid throughout the whole food chain (animal feeding) to increase the 3 PUFA content in human food (eggs, dairy products, meat). These improvements in the fatty acid profile of the products are often associated with a decrease in saturated fatty resulting in the improvement of both the 3/6 ratio and the p/s ratio in food. A study on healthy volunteers, with eggs, meat and dairy products only derived from linseed fed animals showed a significant improvement of blood lipid parameters without significant alteration of dietary habits.⁴⁶ The 3/6 and p/s ratios were increased in plasma and erythrocytes, as well as EPA, but not DHA as expected.
• Another route is oriented to the genetic modification of plants already rich in 15 desaturase (linseed, rapeseed, soybean) to introduce the genes encoding for the other desaturase. The objective is to produce a variety able to synthesize the higher metabolites of -linolenic acid and give oil rich in long-chain 3 PUFAs. This route is currently investigated in several biotechnology industries.

Conclusion

Hypertension has gained a panel of therapeutic treatments more diversified and efficient than many other diseases, as shown by the reduction of hypertension-related morbidity and mortality over the past 25 years.³ However, in spite of these significant therapeutic breakthroughs, recent studies have revealed that the incidence of hypertension (and some complications) has increased again.³ The lifespan has increased in western countries, although the age of the onset of hypertension has not followed this progression and has tended on the contrary to decrease. This is one of the reasons why a nutritional prevention in medical practice has been favourably considered by the NIH and WHO.^{2, 3} In 2001, the AHA nutrition committee considered that 3 PUFAs can reduce blood pressure, but large quantities are needed to see only a modest effect in hypertensive individuals. The committee considered that this is not a practical treatment for lowering blood pressure. The rationale for using 3 PUFAs in the treatment of established hypertension can be criticized by comparison with the efficiency of the available drugs, but the constant use of an adapted diet should be regarded as a powerful tool to prevent or delay the onset of hypertension. Regarding the fatty acid intake, hypertension follows the same rules as other cardiovascular diseases or risk markers and requires a decrease in saturated fatty acid intake and an increase in 3 PUFA intake, mainly the long chains. The research tendencies indicate that both EPA and DHA could be efficient to prevent hypertension associated with metabolic syndrome or reno-vascular disease, whereas DHA alone may affect essential hypertension. Increasing the consumption of marine products in the whole population is not realistic and the efficiency of increasing the consumption of -linolenic acid remains to be demonstrated. To clarify this debate, it is necessary to develop investigations in the direction of the 'preventive value', in contrast with the actual situation, mainly oriented towards the 'therapeutic value'. A meal is a complex thing, which contains a lot of nutrients beside lipids. Dairy products, for instance, are potentially able to prevent hypertension through the effects of calcium, but also through the bioactive peptides resulting from casein hydrolysis. The preventive effect of a given diet may thus be far beyond the fatty acid ratio and this diet should be considered for its 'overall preventive value' in hypertension. The nutritional prevention of chronic pathologies requires more research efforts and investments in research.

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Acknowledgements

This work was commissioned by the Factors Affecting Hypertension Task Force of the European branch of the International Life Sciences Institute (ILSI Europe). At the time of the workshop, industry members of this task force were Frito Lay, Kellog, RHM Technology, Unilever and Valio. Further information about ILSI Europe can be obtained through info@ilsieurope.be or tel. +32 (0) 2 771 0014.