Effects of Dietary ALA Compared with Long Chain n3 Fatty Acid Derivatives on Physiologic Indexes

Several clinical and epidemiologic studies have been conducted to determine the effects of long-chain n-3 PUFAs on various physiologic indexes. Whereas the earlier studies were conducted with large doses of fish or fish oil concentrates, more recent studies have used lower doses. ALA, the precursor of n-3 fatty acids, can be converted to long-chain n-3 PUFAs and can therefore be substituted for fish oils. The minimum intake of long-chain n-3 PUFAs needed for beneficial effects depends on the intake of other fatty acids. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to long-chain n-3 PUFAs. While keeping the amount of dietary LA constant (3.7g) ALA appears to have biological effects similar to those of 0.3 g long-chain n-3 PUFAs with conversion of 11 g ALA to 1 g long-chain n-3 PUFAs. Thus, a ratio of 4 (15gLA:3.7 gALA) is appropriate for conversion. In human studies, the conversion of deuterated ALA to longer chain metabolites was reduced by ffi50% when dietary intake of LA was increased from 4.7% to 9.3% of energy as a result of the known competition between n-6 and n-3 fatty acids for desaturation. After ALA supplementation there is an increase in long-chain n-3 PUFAs in plasma and platelet phospholipids and a decrease in platelet aggregation. ALA supplementation does not alter triacylglycerol concentrations. Only long-chain n-3 PUFA have triacylglycerol-lowering effects. Supplementation with ALA to lower the n-6:n-3 ratio from 13:1 to 1:1 led to a 50% reduction in C-reactive protein (CRP), a risk factor for coronary heart disease.

Hunter-gatherer I Agricultural I Industrial 40 Vitamin C 600













Figure 3 Hypothetical scheme of fat, fatty acid (n-6, n-3, trans and total) intake (as per cent of calories from fat) and intake of vitamins E and C (mgday~1). Data were extrapolated from cross-sectional analyses of contemporary hunter-gatherer populations and from longitudinal observations and their putative changes during the preceding 100 years. Trans-fatty acids, the result of the hydrogenation process, have increased dramatically in the food supply during this century. (Reproduced with permission from Simopoulos AP (1999) Genetic variation and evolutionary aspects of diet. In: Papas A (ed.) Antioxidants in Nutrition and Health, pp. 65-88. Boca Raton: CRC Press.)

Table 5 n-6:n-3 ratios in various populations Population n-6:n-3


Greece prior to 1960

Current Japan

Current India, rural

Current UK and northern Europe

Current US

Current India, urban

Reproduced with permission from Simopoulos AP (2003) Importance of the ratio of omega-6/omega-3 essential fatty acids: Evolutionary aspects. World Review of Nutrition and Diet 92:1-22.

Table 6 Ethnic differences in fatty acid concentrations in thrombocyte phospholipids and percentage of all deaths from cardiovascular disease

Europe and US


Greenland Eskimos

Arachidonic acid









acid (20:5n-3)

Ratio of n-6:n-3




Mortality from






Modified from Weber PC (1989) Are we what we eat? Fatty acids in nutrition and in cell membranes: cell functions and disorders induced by dietary conditions. In: Fish, Fats and your Health, Report no. 4, pp. 9-18. Norway: Svanoybukt Foundation.

50 45 40

s id lipi 35 5 30

25 20 15 10

Urban high income

Urban middle income

Urban low income

^ Rural

2 3 4 5 6 Diabetes prevalence Figure 4 Relation between the ratio of n-6 to n-3 fatty acids in dietary lipids in the Indian diet and the prevalence of type 2 diabetes. (Reproduced with permission from Raheja BS, Sadikot SM, Phatak RB, and Rao MB (1993) Significance of the n-6/n-3 ratio for insulin action in diabetes. Annals of the NewYork Academy of Science 683: 258-271.)

In Australian studies, ventricular fibrillation in rats was reduced with canola oil as much or even more efficiently than with fish oil, an effect attributable to ALA. Further studies should be able to show whether this result is a direct effect of ALA per se or whether it occurs as a result of its desaturation and elongation to EPA and possibly DHA.

The diets of Western countries have contained increasingly larger amounts of LA, which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low-density lipoprotein (LDL) cholesterol, increases platelet response to aggregation, and suppresses the immune system. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of AA metabolism. In clinical studies, ALA contributed to lowering of blood pressure. In a prospective study, ALA was inversely related to the risk of coronary heart disease in men.

ALA is not equivalent in its biological effects to the long-chain n-3 fatty acids found in fish oils. EPA and DHA are more rapidly incorporated into plasma and membrane lipids and produce more rapid effects than does ALA. Relatively large reserves of LA in body fat, as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain n-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term


(^Thromboxan^) TXA2 Prostacyclin pge2


Prostacyclin ) PG|


Tissue phospholipids


Phospholipase Diet

Arachidonic acid

Eicosapentaenoic acid t


5-Lipoxygenase t


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