Benefits
Liver ultrasound appearance: one trial, imaging endpoint only
In one 1-year randomized placebo-controlled trial in 87 adults with mildly raised cholesterol and ultrasound-diagnosed fatty liver, 400 mg a day of mixed palm tocotrienols normalised the liver's ultrasound appearance in 34.9 percent of the treated group versus 18.2 percent on placebo (odds ratio 2.4, 95 percent confidence interval 0.9 to 6.5, which crosses 1). That is an imaging appearance, not a measure of liver function: ALT fell by 5.9 IU/L on tocotrienols against 0.6 IU/L on placebo (p = 0.118) and AST fell by 4.8 against 3.4 (p = 0.207), and the authors state tocotrienols did not significantly affect liver function versus placebo. The liver result was a secondary outcome of a larger registered study, NCT00753532, whose registered primary outcome was brain white-matter lesion volume. Almost a third of the tocotrienol group dropped out. Fatty liver is a medical diagnosis that needs a doctor's assessment and follow-up, not self-treatment with a supplement.
Cholesterol: no reduction in pooled trials
A 2020 meta-analysis of 15 randomized trials, 20 treatment arms, found tocotrienol supplementation did not lower total cholesterol, LDL cholesterol or triglycerides. HDL cholesterol rose by 0.146 mmol/L on average, but the trials disagreed strongly with each other (I2 = 85.9 percent). In the fatty liver trial on this page, total cholesterol, LDL and triglycerides in the tocotrienol group were no different from placebo after a year, and the triglyceride fall the tocotrienol group did show was matched by an equal fall on placebo.
Oxidative-damage markers in blood
In a 6-month randomized study in 62 healthy adults, 160 mg a day of a palm tocotrienol-rich fraction lowered protein carbonyls, a blood marker of oxidative damage to proteins, and lowered advanced glycation end-products in participants over 50. Those are laboratory markers, not health outcomes, and the study used a generic palm tocotrienol fraction rather than EVNol. Two trials have looked at tissue: a 2-year trial in 121 people found less growth in brain white-matter lesions on MRI, and a 2-month trial in 36 healthy men found improved arterial stiffness readings. Both used a self-emulsifying tocotrienol preparation, both measured an image or a reading rather than a health outcome, and neither has been repeated by an independent group.
Mechanism of action
Tocotrienol antioxidant action
In laboratory systems the unsaturated tail of a tocotrienol lets it move more freely within cell membranes than a tocopherol, and it quenches free radicals there. Whether that translates into a health outcome in people, as opposed to a change in a blood marker or a scan, has not been shown.
Cholesterol pathway in the laboratory, blunted by tocopherol
In cell and animal work, gamma and delta tocotrienol speed the breakdown of HMG-CoA reductase, the enzyme that makes cholesterol. Alpha-tocopherol blunts this. In chickens, adding alpha-tocopherol to a tocotrienol blend attenuated the effect on HMG-CoA reductase activity (p < 0.001), and blends containing 30 percent or more alpha-tocopherol worked less well than blends with 15 to 20 percent. EVNol is sold as a tocotrienol plus tocopherol complex, and the trial capsule on this page carried 61.1 mg of alpha-tocopherol against 200 mg of tocotrienols. In humans this mechanism has not produced lower LDL or total cholesterol in pooled trials.
Clinical trials
Randomised, double-blind, placebo-controlled, 1 year, 87 adults at a single Malaysian centre. This liver report comes from a larger registered study, NCT00753532, which enrolled 241 people and whose registered primary outcome was brain white-matter lesion volume, with liver echogenicity listed as a secondary outcome. The study material was Tocovid Suprabio, a self-emulsifying softgel purchased from Hovid (Ipoh, Malaysia), given as 200 mg mixed tocotrienols twice daily. Two of the nine authors work for Hovid Research Sdn Bhd, four of them own shares in Hovid, and the corresponding author holds the patent on the self-emulsifying delivery system used. The research grant came from the Malaysian Palm Oil Board. (Magosso et al. 2013, Nutrition Journal)
87 untreated Malaysian adults with mildly raised cholesterol (total cholesterol 5.2 to 6.2 mmol/L) and ultrasound-proven fatty liver, mean age 51. Around three quarters had mild steatosis, the mildest of the three ultrasound grades, and mean ALT and AST were between 35 and 39 IU/L, close to the top of the normal range.
The liver's ultrasound echogenic response normalised in 34.9 percent on tocotrienols versus 18.2 percent on placebo in the intention to treat analysis (p = 0.039; odds ratio 2.411, 95 percent confidence interval 0.896 to 6.488, which crosses 1; number needed to treat 6). Nothing else moved: the authors write that tocotrienols did not significantly affect lipid profile and liver function compared with placebo. Mean 1-year falls on tocotrienols versus placebo were ALT 5.9 versus 0.6 IU/L (p = 0.118), AST 4.8 versus 3.4 (p = 0.207), total cholesterol 0.3 versus 0.2 mmol/L (p = 0.055) and triglycerides 0.2 versus 0.2 mmol/L (p = 0.814). 13 of 43 on tocotrienols and 10 of 44 on placebo dropped out and were counted as unchanged. Two people on placebo and none on tocotrienols worsened by a grade. No adverse events were reported in either group.