Vitamin E consists of eight isomers: four tocotrienols and four tocopherols. Each isomer has a different molecular weight and a slightly different chemical structure; this imparts distinct properties that influence their biochemical function. Commercial vitamin E supplements are typically rich in tocopherols and may be low or absent in tocotrienols. However, research suggests that tocotrienols may have uniquely beneficial effects on metabolic health and healthy aging.

Cognitive Health

Prospective and case-controlled studies reveal that individuals with increased plasma tocotrienol levels were associated with favorable outcomes for cognitive function, such as improved cellular health. The researchers concluded that tocotrienols may be clinically relevant to those with neurological health concerns.

DNA Health

A randomized clinical trial assigned 64 individuals to receive either a placebo or 160 mg of tocotrienol-rich supplements per day for 6 months. The participants in the intervention group displayed significantly decreased DNA damage compared to the placebo group. Reduced DNA damage appeared to be greater in a subgroup of adults aged 50 years or older, which may support healthy aging.

Bone Health

After receiving annatto seed-derived tocotrienol supplements for 12 weeks with 90% delta- and 10% gamma-tocotrienols at 430 mg per day or 860 mg per day, postmenopausal women with osteopenia (n = 89) in both groups displayed decreased bone resorption and improved bone turnover rates, potentially through reduced oxidative stress. In vitro, benefits on bone health were only observed in the case of tocotrienols.

Healthy Blood Sugar Metabolism

A randomized controlled trial with 110 participants observed the effects of supplementation with delta-tocotrienols (250 mg per day) or a placebo for 24 weeks in patients with type 2 diabetes mellitus. Compared to the placebo, the intervention group displayed many significantly improved indicators, such as glycemic control, microRNA expression, and various inflammatory and oxidative markers, including high-sensitivity C-reactive protein (CRP).

Another randomized controlled trial was conducted with 77 pre-diabetic individuals. This study demonstrated significantly improved blood glucose markers for these individuals after supplementation of 300 mg of delta-tocotrienols per day when compared to a placebo.

Healthy Inflammatory Responses

In human studies, tocotrienols have shown a potential role in the modulation of several signaling and transcriptional pathways that regulate inflammation, including nuclear factor-kappa B, which may support metabolic health and healthy aging. A systematic review and meta-analysis concluded that individuals receiving supplementation with tocotrienols (between 180 mg/day and 600 mg/day) had significantly reduced CRP.

In a pilot study for a randomized controlled trial with 71 participants, decreased inflammatory markers after tocotrienol supplementation were observed in patients with nonalcoholic fatty liver disease (NAFLD). The same results were observed in patients with hypercholesterolemia in an open-label randomized study with a total of 33 participants.

Unlike tocopherols, tocotrienols may be incorporated into the tissues with saturated fatty layers (e.g., brain and liver) more efficiently due to their unsaturated side chain and unique antioxidant properties. Furthermore, human studies have revealed that alpha-tocopherols may attenuate the bioavailability of tocotrienols and interfere with its potential clinical benefits if simultaneously administered. 

Annatto is the richest source of naturally occurring tocotrienols and is free of tocopherols. Tocotrienol supplementation, such as annatto-derived tocotrienols, may be clinically relevant to the general population, and it may support healthy aging and metabolic health.

By Danielle Moyer, MS, CNS, LDN