Literature Briefs-Analysis by Cydney E. McQueen, PharmD

Tocotrienol Effects on Serum Lipids and Platelet Aggregation

Source: Mensink RP, et al. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr 1999;69:213-219.

Objective: To examine effects of tocotrienols on serum lipoproteins and platelet function in men with mildly elevated serum total cholesterol or lipoprotein(a) [Lp(a)] concentrations.

Design and Setting: A randomized, double-blind, controlled trial (RDBCT) conducted at the Human Biology Department of Maastricht University in Maastricht, Netherlands.

Subjects: Forty males with total cholesterol levels between 251 and 309 mg/dL, no history of cardiovascular disease, and on no medications known to interfere with lipids or platelet function.

Treatment: Capsules containing 40 mg tocotrienols with 240 mg palm olein (40% palmitic acid, 4% stearic acid, 43% oleic acid, 11% linoleic acid) and 20 mg (22 IU) dL-a-tocopherol vs. placebo capsules of 280 mg palm olein and 20 mg dL-a-tocopherol.

Dose/Duration: 160 mg/day toco-trienols or placebo for six weeks.

Outcome Measures: Changes in total cholesterol, LDL, HDL, triacylglycerol, and Lp(a) concentrations, and in vitro platelet function measures of aggregation velocity, maximum aggregation, TxB2 production, and ATP release, as well as urinary thromboxane metabolites.

Results: No significant differences between groups were found for changes in total cholesterol, LDL, HDL, triacylglycerol, or Lp(a) concentrations (P values = 0.9, 0.33, 0.5, 0.16, and 0.81, respectively). After adjusting statistically for baseline differences in platelet aggregation velocity and maximum aggregation, no significant difference between groups was found for these or for TxB2 formation. ATP release rate and maximum ATP release were significantly decreased in the treatment group (P = 0.042 and 0.024, respectively). Urinary thromboxane metabolites in-creased and decreased slightly in treatment and placebo groups respectively, but changes were not significantly different between groups.

Strengths/Limitations: Differences be-tween groups after randomization were found for baseline platelet aggregation velocity and maximum aggregation as well as caloric (but not nutrient) intake. It is unclear whether an a priori power calculation was actually performed. The dose of tocotrienols was low compared to other studies demonstrating positive results. Although the authors concluded that tocotrienol supplementation is not beneficial to "subjects at risk of cardiovascular disease," no information was provided about the study population in regard to any CVD risk factors other than the range of total serum cholesterol.

Level of Evidence: Level II, several major limitations.

Comments: Although the "placebo" and treatment capsules both contained other components (linoleic acid, palmitic acid) known to affect lipids and thromboxane synthesis, differences observed should be attributable to the tocotrienol. Sample size needed to meet power was unclear; because no differences were found between groups for most outcomes, there is a possibility of a Type II statistical error—not detecting a difference when one exists. Despite the negative results, due to dose and power limitations, a larger study is needed to confirm lack of benefit before a firm conclusion can be reached. This is especially important in light of the observed increase in ATP release rate and maximum release, which entertains possibilities of benefit at higher doses.

Clinical Impact: Because tocotrienol-enriched vitamin E is more expensive and does not appear to provide additional beneficial effects, it is recommended that patients wishing to supplement use plain vitamin E until more data are available.