N-6 Linoleic acid and n-9 Oleic acid

Epidemiological studies have revealed that a significant inverse correlation between the consumption of linoleic acid and mortality from coronary heart disease (CHD). Furthermore, an increase in consumption of polyunsaturated fats is the most consistent dietary change noted in countries that have experienced a decline in CHD mortality over the past 20-30 years.

Populations that have a high consumption of monounsaturated fats from olive oil (e.g. Greece, Italy) tend to have low rates of CHD. It is tempting to conclude that monounsaturated fats may therefore protect against CHD. It must be emphasised, however, that the Mediterranean diet contains much more than olive oil and that olive oil contains more than oleic acid. It is possible that a low rate of CHD in these countries relates to other constituents such as vegetables, fruits and cereals that are rich in antioxidants.

Following the early studies by Keys (Lancet 1957; 2: 959-66) and Hegsted (AJCN 1965; 14: 776-87) it became accepted that polyunsaturated fats reduced blood cholesterol and monounsaturated fats had a neutral effect, relative to carbohydrate. A 1985 report by Mattson and Grundy (J Lipid Res 1985; 26: 194-202) which showed monounsaturated fats could lower plasma cholesterol as much as polyunsaturated fat, stimulated a reconsideration of the potential role of monounsaturated fats. Other studies since have resulted in the general consensus that both polyunsaturated and monounsaturated fats reduce blood LDL cholesterol when they replace saturated fats in the diet, but the polyunsaturates have a larger impact (Gardner & Kraemer Arterioscler Throm Vasc Biol 1995; 15: 1917-27). The effects on HDL cholesterol are similar, although some studies have shown that n-6 fat can lower HDL cholesterol whereas monounsaturated fats tend to raise HDL (Mensink et al. Arterioscler Thromb 1992; 12: 911-9).

There is growing evidence suggesting oxidation of LDL plays an important part in atherosclerosis (Steinberg Circulation 1991; 84: 1420-25). The process of LDL oxidation may be enhanced by polyunsaturated fats from plants and fish. These are susceptible to oxidation but this may be inhibited by the presence of vitamin E, an antioxidant carried in LDL (Esterbauer et al. AJCN 1991; 53: 314-321). Vitamin E requirement is believed to be related to dietary intakes of polyunsaturated fats. Some authorities suggest that there should be at least 1mg of vitamin E for each gram of linoleic acid (Australians consume 0.6mg vitamin E for every gram of linoleic acid) and several times that for each gram of  eicosapentaenoic acid (EPA),  docosahexaenoic acid (DHA) or linolenic acid. Monounsaturated fats do not require an increased intake of vitamin E (Nestel Food Australia 1995; 47 (3): 28-29).

Omega-9 fat in plasma (e.g. in LDL) and cell membranes are less susceptible to oxidation in animal and human models – the reverse was found for omega-6 fats. In bench top studies, plasma LDL and cell membranes enriched in monounsaturated fat clearly resist oxidation compared to polyunsaturates(Abbey et al. AJCN 1993; 57: 391-8; Reaven AJCN 1991; 54: 701-6; J Clin Invest 1993; 91: 668-76). If the oxidation theory of atherosclerosis is correct, this should lead to less atherosclerosis on a monounsaturated fat enriched diet. However, animal studies do not support this hypothesis and unfortunately oleic acid levels in lipoproteins are not related to dietary intake of oleic acid. In the Seven Countries Study, monounsaturated fat intake was inversely related to mortality from CHD, but it is difficult to conclude that monounsaturated fat itself is protective.

Although evidence is still lacking that a reduction in the oxidisability of LDL will translate into a reduction in coronary events, there is suggestion of benefit. For example, high intakes of the antioxidant vitamin E which is carried in LDL, is associated with less deaths from CHD (Rimm et al. NEJM 1993; 328: 1450-6).

One argument offered in favour of monounsaturated fats is based on the hypothesis that n-6 fats are pro-inflammatory. Linoleic acid might promote coronary thrombosis, arrhythmia and inflammation by competing with n-3 fatty acids. This favours the production of arachiodonic acid and its metabolites that increase platelet aggregation, arteriolar vasoconstriction, pro-inflammatory leukotrienes and other pro-arrhythmia metabolites.  There is now some human evidence to support this. A study at RMIT by Professor Sinclair found that vegetarians who had high N-6 intakes (e.g. from sunflower oil) had blood more prone to clotting than non-vegetarians. More evidence is needed to substantiate these findings.

It is suggested the use of monounsaturated fats in preference to n-6 polyunsaturated fats would result in a lower ratio of n-6 to n-3 polyunsaturates in the diet and a less inflammatory state. Certainly the long chain n-3 fats found in fish suppress some inflammatory mediators and some selected inflammatory conditions. A very good case can be made for increasing the intake of n-3 fats from its current low level in most industrialised societies. Whether a concomitant reduction in n-6 polyunsaturated fats would be benefit is unclear. Whether there is any benefit relating to inflammation from lowering the linoleic acid intake from current levels of about 15g per day to 5-10g per day is unknown.

There is a large body of literature that shows n-6 polyunsaturated fats enhance the number of metastases and the growth of chemically-induced breast cancer in animals. A large prospective trial from Sweden examined the relationship between diet and the risk of developing breast cancer in 61,471 women aged 40 to 76.  During the 4 year follow-up period 674 cases of invasive breast cancer occurred. Women in the highest quartile of polyunsaturated fat intake had a significantly 20% higher risk of breast cancer than those in the lowest quartile (relative risk 1.2). The opposite  was true for monounsaturated fat. The amount of saturated fat in the diet did not influence risk (Modern Medicine 1998). Other studies that have suggested a protective effect of monounsaturated fat against breast cancer have come from Mediterranean countries where olive oil is the main source of monounsaturated fat. It was not clear whether other components of olive oil (such as phytoestrogens) were responsible for the effect. Because the Swedish diet is very low in olive oil, this study suggests that monounsaturated fat itself is protective. The Swedish study also raises questions about the safe upper limit of n-6 polyunsaturated fat in the diet.

Summary

The optimal amount of polyunsaturated fat in the diet remains uncertain. When the effects of polyunsaturated fat on blood lipids (lower LDL cholesterol, but may also lower HDL cholesterol) are the primary consideration it appears that intakes should be maximised (e.g. 10% energy intake). When its other effects are considered, especially its ability to decrease the conversion of n-3 linolenic acid to the cardio-protective metabolites, some researchers argue that intakes should be either decreased from our current intake of 6% to about 3%, whilst other experts argue that our intakes should remain unchanged, but not increased.

The n-6 fat content of oils is about 70% for safflower, grapeseed, sunflower; 50% for corn and soy oils and 35% for peanut oil, 20% for canola and 10% for olive oil.  If you restrict your intake of oils to either canola or olive oil (or margarine), 1-2 tbs/day of these oils would provide enough n-6 linoleic.

Last Updated: March 28, 2001