General chemical structure of tocotrienols. alpha(α)-Tocotrienol: R1 = Me, R2 = Me, R3 = Me; beta(β)-Tocotrienol: R1 = Me, R2 = H, R3= Me; gamma(γ)-Tocotrienol: R1 = H, R2 = Me, R3= Me; delta(δ)-Tocotrienol: R1 = H, R2 = H, R3= Me
The vitamin E family comprise four tocotrienols (alpha, beta, gamma, delta) and four tocopherols
(alpha, beta, gamma, delta). The critical chemical structural
difference between tocotrienols and tocopherols is that tocotrienols
have unsaturated isoprenoid side chains with three carbon-carbon double bonds versus saturated side chains for tocopherols (see Figure).
Tocotrienols are compounds naturally occurring at higher levels in some vegetable oils, including palm oil, rice bran oil, wheat germ, barley, saw palmetto, annatto, and certain other types of seeds, nuts and grains, and the oils derived from them.
Chemically, different analogues of vitamin E all show some activity as a chemical antioxidant,
but do not all have the same vitamin E equivalence. Tocotrienols
demonstrate activity depending on the type of antioxidant performance
being measured.
All tocotrienols have some physical antioxidant activity due to an
ability to donate a hydrogen atom (a proton plus electron) from the hydroxyl group on the chromanol ring, to free radical and reactive oxygen species. Historically studies of tocotrienols account for less than 1% of all research into vitamin E. A scientific compilation of tocotrienol research, Tocotrienols: Vitamin E Beyond Tocopherols, was published in 2013.
Health effects
A number of health benefits of tocotrienols have been proposed, included decreased risk of heart disease and cancer. The Food and Nutrition Board of the Institute of Medicine of the United States National Academy of Sciences does not define a Recommended Dietary Allowance or Adequate Intake for tocotrienols.
Brain
A review of
human studies in middle-aged and elderly stated "Evidence from
prospective and case-control studies suggested that increased blood
levels of tocotrienols were associated with favorable cognitive function
outcomes." The review qualified this statement by noting that
randomized, controlled clinical trials were needed to evaluate these
observations.
Heart disease
Tocotrienols have been linked to improved markers of heart disease.
Diabetes
Animal models and observational studies in humans have shown potential benefit.
Side effects
Tocotrienols are generally well tolerated and without significant side effects.
History
The
discovery of tocotrienols was first reported by Pennock and Whittle in
1964, describing the isolation of tocotrienols from rubber. The biological significance of tocotrienols was clearly delineated in the early 1980s, when its ability to lower cholesterol was first reported by Qureshi and Elson in the Journal of Medicinal Chemistry. During the 1990s, the anti-cancer properties of tocopherols and tocotrienols began to be delineated. The current commercial sources of tocotrienol are rice and palm. Other natural tocotrienol sources include rice bran oil, coconut oil, cocoa butter, barley, and wheat germ. Tocotrienols are safe and human studies show no adverse effects with consumption of 240 mg/day for 48 months. Tocotrienol rich fractions from rice, palm, or annatto,
used in nutritional supplements, functional foods, and anti-aging
cosmetics, are available in the market at 20%, 35%, 50%, and 70% total
vitamin E content.
Etymology
Tocotrienols are named by analogy to tocopherols (from Greek words meaning to bear a pregnancy; but with this word changed to include the chemical difference that tocotrienols are trienes, meaning that they share identical structure with the tocopherols except for the addition of the three double bonds to their side chains.
Comparison of tocotrienols and tocopherols
Tocotrienols have only a single chiral center,
which exists at the 2' chromanol ring carbon, at the point where the
isoprenoid tail joins the ring. The other two corresponding centers in
the phytyl tail of the corresponding tocopherols do not exist as chiral
centers for tocotrienols due to unsaturation (C-C double bonds) at these
sites. Tocotrienols extracted from plants are always dextrorotatory stereoisomers, signified as d-tocotrienols. In theory, (levorotatory;
l-tocotrienol) forms of tocotrienols could exist as well, which would
have a 2S rather than 2R configuration at the molecules' single chiral
center, but unlike synthetic, dl-alpha-tocopherol, the marketed
tocotrienol dietary supplements are all d-tocotrienol extracts from palm or annatto oils.
Tocotrienol studies confirm anti-oxidation, anti-inflammatory potentials and suggest anti-cancer effects
better than the common forms of tocopherol due to their chemical
structure. Scientists have suggested tocotrienols are better
antioxidants than tocopherols.
It has been proposed that the unsaturated side-chain in tocotrienols
causes them to penetrate tissues with saturated fatty layers more
efficiently than tocopherol. Lipid ORAC values are highest for δ-tocotrienol.
However that study also says: "Regarding α-tocopherol equivalent
antioxidant capacity, no significant differences in the antioxidant
activity of all vitamin E isoforms were found."
Metabolism and bioavailability
The metabolism and thus the bioavailability
of tocotrienols are not well understood and simply increasing the
intake of tocotrienols might not increase tocotrienol levels in the
body.
α-Tocopherol interference
Various studies have shown that alpha-tocopherol interferes with tocotrienol benefits. High levels of α-tocopherol increase cholesterol production.
α-Tocopherol interference with tocotrienol absorption was described
previously by Ikeda, who showed that α-tococopherol interfered with
absorption of α-tocotrienol, but not γ-tocotrienol. Finally, α-tocopherol was shown to interfere with tocotrienols by increasing catabolism.
Sources
In nature, tocotrienols are present in many plants and fruits. The palm fruit (Elaeis guineensis) is particularly high in tocotrienols, primarily gamma-tocotrienol, alpha-tocotrienol and delta-tocotrienol. Other cultivated plants high in tocotrienols includes rice, wheat, barley, rye and oat. In annatto, tocotrienols are relatively abundant (only delta- and gamma-tocotrienol however) and it contains no tocopherols.
Research
Radiation countermeasures
Following exposure to gamma radiation, hematopoietic stem cells (HSCs) in the bone marrow, which are important for producing blood cells, rapidly undergo apoptosis (cell death). There are no known treatments for this acute effect of radiation. Two studies conducted by the U.S. Armed Forces Radiobiology Research Institute
(AFRRI) found that treatment with γ-tocotrienol or δ-tocotrienol
enhanced survival of hematopoietic stem cells, which are essential for
renewing the body's supply of blood cells.
Based on these successful results of studies in mice, γ-tocotrienol is
being studied for its safety and efficacy as a radioprotective measure
in nonhuman primates.
