Journal Name:
Current Topics in Nutraceutical Research

Article Title:
Effects of controlled diets enriched with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on soluble adhesion molecules and endothelin-1 concentrations in healthy volunteers

Date Written:
2007

Volume:
5

Number:
4

Page:
189

Author(s):
Egert, S.; Rassoul, F.; Boesch-Saadatmandi, C.; Richter, V.; Rimbach, G.; Erbersdobler, H. F.

Article:
The oxidative modification of low-density lipoprotein (LDL) particles in the arterial wall (LDL oxidation) is believed to play a role in atherogenesis. Lipid peroxidation is catalyzed by free radical attack on double bonds of unsaturated fatty acids in the LDL. Ex vivo susceptibility of LDL to oxidation can be influenced by the content of 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. This study was designed to assess whether the n-3 fatty acids -linolenic acid (C18:3; ALA), eicosapentaenoic acid (C20:5; EPA) and docosahexaenoic acid (C22:6; DHA) would lead to an even higher susceptibility to LDL oxidation than linoleic acid.

Forty-one healthy subjects (13 males, 35 females, aged between 18 and 45 years) met the following inclusion criteria: a body mass index of less than 28 kg/m2, serum total cholesterol values below 7.76 mmol/l (300 mg/dl) and serum triglycerides below 2.26 mmol/l (<200 mg/dl). The study was conducted in a parallel design and consisted of a 2-week wash-in period followed by an experimental period of 3 weeks. During the wash-in period, all subjects received a diet rich in MUFAs. Thereafter, the subjects were randomly divided into three diet groups: One group (n=15) received a low linolenic acid canola oil diet fortified with ALA (3.7% ALA group), for the second group (n=17), the canola oil diet was fortified with EPA (EPA group) and for the third group (n=16) with DHA (DHA group). The mean daily intake of ALA in the ALA group was 6.0 ± 1.1 g (range 5.0–8.4 g/day), the mean daily intake of EPA in the EPA group was 2.8 g ± 0.6 g (range 2.1–4.5 g/day) and the intake of DHA in the DHA group was 2.9 ± 0.5 g (range 2.2–3.8 g/day). The ratio of n-6 to n-3 PUFA in all experimental diets was 2.8:1. Natural mixed tocopherols were added to the study oils.

All three experimental diets (ALA, EPA, and DHA diet) significantly decreased the lag time. Ex vivo oxidative susceptibility of LDL was highest after the DHA diet (-16%) and an increase in the maximum amount of conjugated dienes (+7%, P<0.001). 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%).The mean reductions in the EPA (mean difference: -9.64min (-16.4%), and DHA diet group (mean difference: -9.51min (-15.9%) were significantly higher than in the ALA group (mean difference: -3.19min (-5.1%). The EPA diet led to a decrease in propagation rate (mean difference: -0.37nmol CD/min/mg LDL cholesterol (-11.3%), whereas the DHA diet increased the maximum amount of CDs (mean difference: +7.85nmol CD/ mg LDL cholesterol (+7.1%).

ALA, EPA and DHA differ in their effects on the different LDL oxidation parameters. The EPA diet showed a reduction in lag time, indicating an enhanced oxidative susceptibility. However, a simultaneous reduction in propagation rate that indicates a decreased susceptibility to oxidation was observed. The slow propagation rate appears paradoxical and may support the hypothesis that LDL rich in highly unsaturated fatty acids is not necessarily oxidized more rapidly in biological systems than particles containing fatty acids with fewer double bonds. Further studies are needed to investigate whether and how EPA influences LDL susceptibility in vitro and in vivo and, in addition, to determine the biological relevance of a reduced propagation rate and concomitant decreased lag time in atherogenesis. 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 incorporated. On the ALA diet, a significant increase in the LDL ALA content, and an increase in LDL content of EPA was found, indicating that ALA might have been converted to EPA through a series of elongation and desaturation reactions.

In summary, 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 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 via canola oil, ALA enrichment did not enhance LDL oxidizability, whereas the effects of EPA and DHA on the ex vivo LDL oxidation were conflicting, possibly in part due to their complex metabolic pathways with a variety of possible conversion and retroconversion reactions. The authors suggest that more studies investigating the omega 3 fatty acids individually are needed to obtain knowledge of their specific metabolic actions.

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