Effects of interaction of RRR-alpha-tocopheryl acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy

Abstract

We evaluated the effects of RRR-alpha-tocpheryl acetate (alpha-tocopheryl acetate) and hormone-replacement therapy (HRT) on the oxidative susceptibility of low-density lipoprotein (LDL) in postmenopausal women consuming a fish oil supplement. The independent effect of fish oil was also assessed. Forty-eight women, equally divided between women using and not using HRT, participated in a double-blind crossover trial. Each of the four periods lasted 5 wk and was followed by a 4-wk washout interval. During each period all subjects were given a 15-g supplement of fish oil and either 0 (placebo), 100, 200, or 400 mg alpha-tocopheryl acetate daily. LDL resistance to oxidative modification was assessed by calculating lag time, propagation rate, and maximum production of conjugated dienes. Supplementation with fish oil and placebo shortened lag time and slowed propagation rate in women both using and not using HRT. After subjects consumed fish oil, supplementation with alpha-tocopheryl acetate increased plasma and LDL alpha-tocopherol contents significantly and lengthened lag time (at even the lowest concentration) but had no significant effect on propagation rate or maximum production compared with values measured after consumption of fish oil alone. Women not using HRT had faster propagation rates and higher maximum production than women using HRT; after supplementation with fish oil and alpha-tocopheryl acetate these differences prevailed. Supplements as low as 100 mg alpha-tocopheryl acetate/d increase the resistance of LDL to oxidation when fish oil supplements are used. HRT and fish oil supplements may independently affect LDL oxidative susceptibility.

Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes

“…We found a shorter lag time and a slower propagation rate after fish oil supplement, which have also been reported by others (Suzukawa et al, 1995;Wander et al, 1996;Sørensen et al, 1998;Foulon et al, 1999). The finding of a shorter lag time and concomitant reduced propagation rate after fish oil supplement may seem paradoxical: a shortened lag time is believed to reflect enhanced LDL oxidizability, while a lower propagation rate is commonly considered an indicator of decreased oxidation.…”

“…This marked decrease in both lag time and propagation rate and the increase in LDL-MDA suggests a pronounced effect of a moderate fish oil dose on LDL susceptibility to oxidation in type 2 diabetes. Earlier studies of nondiabetic subjects also found fish oil consumption to be associated with shortened LDL lag time and lowered propagation rate (Suzukawa et al, 1995;Tsai & Lu, 1997;Sørensen et al, 1998;Wander et al, 1996;Foulon et al, 1999). As the only exception, Brude et al (1997), observed neither lag time nor propagation rate changes, possibly due to insufficient statistical power (n ¼ 10).…”

Effects of enhanced consumption of fruit and vegetables on plasma antioxidant status and oxidative resistance of LDL in smokers supplemented with fish oil

“…Fish oil supplementation also produced a 15% reduction in LDL lag phase between weeks 0 and 3. This potentially adverse effect is a measure of the increased susceptibility of LDL to oxidation because of the incorporation of highly unsaturated n-3 PUFA into the phospholipids of the LDL particles, as observed in previous studies (Wander et al, 1996;Sorensen et al, 1998;Foulon et al, 1999). One of the effects of the increased consumption of fruits and vegetables was a 9.7% reduction in caloric intake, with a significant reduction in percent energy from fat from 34.9 to 30.0%.…”

Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction

“…The vast majority of studies investigating the oxidative potential of n-3 PUFAs include short-term supplementation periods (Harats et al, 1991;Nenseter et al, 1992;Bonanome et al, 1996;Wander et al, 1996;Hansen et al, 1998;Higdon et al, 2000). Long-term effects in vivo after 9 months of intervention were studied by Eritsland et al (1995), and susceptibility to lipid peroxidation induced in vitro was evaluated after 180 days of n-3 PUFAs treatment in the study by Palozza (Palozza et al, 1996).…”

“…However, the impact of n-3 PUFAs supplementation on lipid peroxidation is controversial (Nenseter & Drevon, 1996). Several clinical studies have reported no significant change in the lipid peroxidation following increased consumption of n-3 PUFAs (Nenseter et al, 1992;Bittolo-Bon et al, 1993;Frankel et al, 1994;Eritsland et al, 1995;Bonanome et al, 1996;Wander et al, 1996;Brude et al, 1997;Hansen et al, 1998). No enhancement of the lipid peroxidation was noted after 9 months supplementation with 4 g n-3 PUFA concentrate in the shunt occlusion trial (Eritsland et al, 1995).…”