Cardiovascular Disease
Regulation of Cholesterol Synthesis in Animal and Clinical Studies
Recently, animal studies supported results found in earlier cell line studies. Animals whose diet was supplemented with gamma- and delta-tocotrienols showed the greatest decrease in cholesterol levels (32% total and 66% LDL cholesterol), whereas alpha- tocopherol had no effect on cholesterol-lowering. In this study, HDL/LDL cholesterol ratios were improved by 123-150% on chickens, which more closely reflect the lipogenic activity and cholesterol levels of humans. The safe dose of various tocotrienols for human consumption is estimated to be 200-1,000mg/day13.
In two open clinical studies60 fasting blood lipids were measured before and after 2 months of annatto tocotrienol (75mg/day) supplementation. In both groups, total cholesterol levels dropped 13%, whereas LDL cholesterol dropped 9-15% and HDL cholesterol increased by 4-7%.
The LDL/HDL ratio was reduced by 12-21%. An additional benefit of delta-tocotrienol was found to promote metabolic health, where triglyceride levels dropped 20-30%.
Another study conducted by Bristol-Myers Squibb found that after 4-week supplementation with gamma- and delta-tocotrienol (100mg/day) total cholesterol was reduced by 15-22%, and LDL cholesterol was decreased by 10-20% 4.
Tocotrienol in the Prevention of Monocyte-Endothelial Cell Adhesion and Platelet Aggregation
One of the first steps of atherogenesis is fatty streak formation in arteries, which begins with the adherence of circulating monocytes to the endothelium. Tocotrienols have been shown to reduce cellular adhesion molecule expression and monocytic cell adherence15.
In particular, delta-tocotrienol showed the most profound inhibitory effect on monocytic cell adherence as compared to tocopherols and other tocotrienol isomers6 It has been suggested that this phenomenon occurs via inhibition of VCAM-1 expression by delta- tocotrienol7.
In a human double-blind cross over study, delta-tocotrienol was shown to be significantly more potent in the inhibition of platelet aggregation than the other tocotrienol isomers, giving an overall inhibition of 71%, as compared to 5-37% with other tocotrienols8.
Tocotrienol’s Antioxidant Properties
The antioxidant efficiency of tocotrienols was evaluated as the ability of the compounds to inhibit lipid peroxidation, reactive oxygen species (ROS) production, and heat shock protein expression. Delta-tocotrienol was found to have the greatest antioxidant properties among the tocotrienol isomers4, which is due to the decreased methylation of the chromanol ring that allows the molecule to be more easily incorporated into cell membranes5. A comparative in vitro study showed that gamma- and delta-tocotrienol was 4-fold more efficient as scavenger of peroxyl radicals than other tocotrienol isomers6.
Tocotrienols and Hypertension
Recent animal studies showed tocotrienols to lower blood pressure. When hypertensive rats were treated with gamma-tocotrienol for three months, plasma and blood vessel lipid peroxides were reduced, and total antioxidant status was improved9. Gamma-tocotrienol was shown to reduce systolic blood pressure significantly, and improved nitric oxide synthase activity (NOS), both of which play a critical role in the pathogenesis of essential hypertension20.
Protection from Atheroma Formation
The effects of tocotrienols on atheroma formation have been compared in vivo. Mice fed an atherogenic diet and given desmethyl tocotrienols had 60% lower plasma cholesterol than the control group on the same diet without supplementation, and the size of atherosclerotic lesions was reduced 10-fold. Alpha-tocopherol, on the other hand, had no effect. This finding was further corroborated in a similar independent study, where desmethyl tocotrienols inhibited atherosclerotic lesions in hyperlipidemic mice. Atherosclerotic lesion size in mice supplemented with desmethyl tocotrienols was decreased by 42%, whereas with alpha-tocopherol, lesion size was only decreased by 11%2. Fully methylated tocotrienols and tocopherols do not have the cardiovascular benefits characteristic of desmethyl tocotrienols22.
Effect of Tocotrienols on Carotid Arteriosclerosis
A 4-year study on patients with carotid artery arteriosclerosis showed that tocotrienol supplementation caused regression of carotid atherosclerosis. In 88% of patients that took the supplement carotid artery stenosis was regressed or stabilized. Of the control group receiving a placebo, 60% deteriorated, and only 8% improved23,24. Interestingly, total cholesterol decreased 14% and LDL cholesterol fell 21% in the third and fourth year of the study25.
