Journal Name:
Eur. J. Clin. Nutr.

Article Title:
Influence of three rapeseed oil-rich diets, fortified with a-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers.

Date Written:
2007

Volume:
61

Number:
0

Page:
314

Author(s):
Egert, S.; Somoza, V.; Kannenberg, F.; Fobker, M.; Krome, K.; Erbersdobler, H.F.; Wahrburg, U.

Article:
Oxidative modifications of low-density lipoprotein (LDL) particles in the arterial wall (LDL oxidation) are believed to play a crucial role in atherogenesis. The oxidation is triggered by an attack of free radicals on double bonds of unsaturated fatty acids in the LDL, leading to lipid peroxidation and degradation of the fatty acids. The oxidized LDL particles promote a variety of atherogenic processes, such as formation of foam cells and endothelial dysfunction. It has been shown that the ex vivo susceptibility of LDL to oxidation is largely dependent on dietary factors, especially antioxidants and the fatty acid composition of the diet. A diet rich in monounsaturated fatty acids (MUFAs) leads to an enrichment of MUFAs in the LDL particle and thereby to a higher resistance to the oxidative processes as compared to diets rich in omega-6 (n-6) polyunsaturated fatty acids (PUFAs), especially linoleic acid (C18:2).
It might be assumed that the intake of fatty acids with more than two double bonds, such as a-linolenic acid (C18:3; ALA), eicosapentae¬noic acid (C20:5; EPA) and docosahexaenoic acid (C22:6; DHA) would lead to an even higher susceptibility to LDL oxidation than linoleic acid. The main objective of this study was to investigate the influence of dietary intakes of ALA, EPA and DHA on LDL fatty acid composition and ex vivo oxidizability. An evaluation of the additional tocopherol requirement was also conducted through a strictly controlled dietary study in healthy volunteers with conventional food diets enriched with either ALA, EPA or DHA.
This strictly controlled dietary study was designed to investigate the independent effects of ALA, EPA and DHA on the ex vivo susceptibility of LDL to oxidation, the fatty acid composition of LDL particles and the tocopherol concentrations in LDL and plasma. The n-3 fatty acids were provided as ethyl esters, added to naturally low-linolenic rapeseed oil. The study oils were incorporated into diets with normal foodstuffs. The study was a randomized strictly controlled dietary pattern with three groups and a parallel design, consisting of two consecutive periods. Sixty-one healthy young volunteers included forty-eight subjects (13 males, 35 females). Subjects received a 2-week wash-in diet rich in monounsaturated fatty acids (21% energy) followed by experimental diets enriched with about 1% of energy of ALA, EPA or DHA for 3 weeks. The omega-3 (n-3) fatty acids were provided with special canola oils and margarines. The wash-in diet and the experimental diets were identical, apart from the n-3 fatty acid composition and the tocopherol content, which was adjusted to the content of dienoic acid equivalents.
Ex vivo oxidative susceptibility of LDL was highest after the DHA diet, indicated by a decrease in lag time (16%) and an increase in the maximum amount of conjugated dienes (7%). The EPA diet decreased the lag time (16%) and the propagation rate (12%). Tocopherol concentrations in LDL decreased in the ALA group (13.5%) and DHA group (7.3%). Plasma contents of tocopherol equivalents significantly decreased in all three experimental groups (ALA group: 5.0%, EPA group: 5.7%, DHA group: 12.8%). The content of the three n-3 polyunsaturated fatty acid differently increased in the LDL. On the ALA diet, the ALA content increased by 89%, on the EPA diet the EPA content increased by 809% and on the DHA diet, the DHA content increased by 200%. In addition, the EPA content also enhanced (without dietary intake) in the ALA group (35%) and in the DHA group (284%).
This study shows that ALA, EPA and DHA differ in their effects on the different LDL oxidation parameters. The three n-3 PUFA ALA, EPA and DHA were provided in the context of diets rich in MUFA. This led to LDL particles with a relatively high content of MUFA from canola oil (about 21.3% of LDL fatty acids). It can be argued that the changes in LDL oxidizability might have been more pronounced if the MUFA content of the diets, and, subse¬quently, the LDL had been lower because MUFA are thought to have antioxidant properties. This may explain why only a minor decrease in lag time and no changes in propagation rate or maximum amount of conjugated dienes was noted on the ALA diet. These data suggest that a dietary intake of ALA of up to 2.5% of energy does not exert adverse affects with regard to LDL oxidation when provided in the context of a diet rich in MUFA. This finding is of high practical relevance and supports current dietary guidelines that recommend MUFA as main source of dietary fat, primarily provided by canola oil, which is also rich in ALA.
The enrichment of the diets with ALA, EPA or DHA changed the n-3 fatty acid profiles in the LDL particles confirming that the ingested fatty acids are effectively incorporated. An increased dietary intake of ALA, EPA or DHA led to a significant enrichment of the respective fatty acid in the LDL particles. In addition, dietary ALA also caused an EPA enrichment. Dietary EPA seemed to be preferentially incorporated in the LDL particles, and, simultaneously increased their DHA content. In the context of a MUFA-rich diet, ALA enrichment did not enhance LDL oxidizability, whereas the effects of EPA and DHA on the ex vivo LDL oxidation were somewhat conflicting, possibly in part due to their complex metabolic pathways with a variety of possible conversion and retro¬conversion reactions. Especially with regard to the numerous cardioprotective effects of n-3 fatty acids more studies investigating them individually are needed to obtain more detailed knowledge of their specific metabolic actions as an essential prerequisite for general and special dietary recommendations.

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