OBJECTIVES: Tocotrienols, unsaturated forms of vitamin E, had gained global attention due to their distinctive physiological properties, including hypocholesterolemic, anti-cancer, and anti-inflammatory properties, and neuroprotective. However, evidence related to their beneficial effects remains unclear. This systematic review aimed to summarize the lipid-lowering effects of tocotrienols in human.

METHODS: Comprehensive search using 10 electronic databases were conducted for publications from inception through October 2017. Randomized controlled trials (RCTs) investigating any intervention containing any type of tocotrienols, either alone or in combination were included. Data from all eligible articles were extracted.

RESULTS: Twenty RCTs were included, involving 637 subjects in intervention group and 452 subjects in control group. Participants included healthy individuals, patients with dyslipidemia, diabetes, chronic hemodialysis, and metabolic syndrome. Interventions investigated were tocotrienol-rich fraction (TRF) (n=12) and combined nutraceutical (n=8). Treatment duration ranged from 14 days to 12 months. Lipid was the most common outcome measured. When TRF intervention (≤200mg) was used alone, limited data indicated significant lipid-lowering effects of tocotrienols over various range of doses and treatment durations. In 3 studies that demonstrated significant lipid improvement with TRF alone, an inconsistent trend of this effect was noted due to the different patient populations. Compared to placebo, 3 out of 8 studies revealed that the daily intake of combined nutraceuticals containing 30mg tocotrienols for 8-12 weeks in dyslipidemic patients was associated with significant decline in total cholesterol [mean difference (MD) -0.66mmol/L (95%CI -0.94, -0.38), p<0.001; -0.49 (-1.59, -0.24), p<0.001; -2.24 (-2.53, -1.92), p≤0.05), low density lipoprotein-cholesterol [-0.54 (-0.82, -0.26), p<0.001; -0.39 (-1.17, -0.07), p<0.001; -1.42 (-1.71, -1.14), p≤0.05], and triglycerides [-0.40 (-0.55, -0.26), p<0.001; -0.24 (-0.72, -0.01), p<0.001; -0.36 (-0.45, -0.28), p≤0.05]. All tocotrienols-containing interventions were well-tolerated.

CONCLUSIONS: Current evidence suggests that the lipid-lowering properties of tocotrienols are lacking. Further study quality assessment and subgroup analysis will be conducted to confirm the effect.