Tocotrienol

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General chemical structure of tocotrienols. alpha(a)-Tocotrienol: R1 = Me, R2 = Me, R3 = Me; beta(b)-Tocotrienol: R1 = Me, R2 = H, R3= Me; gamma(g)-Tocotrienol: R1 = H, R2 = Me, R3= Me; delta(d)-Tocotrienol: R1 = H, R2 = H, R3= Me Tocotrienols.svg
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 comprises 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). [1] [2]

Contents

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. [3] [4]

Chemically, different analogues of vitamin E all show some activity as a chemical antioxidant, [5] but do not all have the same vitamin E equivalence. Tocotrienols demonstrate activity depending on the type of antioxidant performance being measured. [6] 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. [7]

Health effects

A number of health benefits of tocotrienols have been proposed, included decreased risk of heart disease and cancer. [8] 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. [9]

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. [10]

Heart disease

Tocotrienols have been linked to improved markers of heart disease. [8] [11]

Skin

Tocotrienols have been linked to improve atopic eczema. [8] [12]

Side effects

Tocotrienols are generally well tolerated and without significant side effects. [8]

History

The discovery of tocotrienols was first reported by Pennock and Whittle in 1964, describing the isolation of tocotrienols from rubber. [13] The biological significance of tocotrienols was clearly delineated in the early 1980s, when its ability to lower cholesterol was first reported by Asaf Qureshi and Elson in the Journal of Medicinal Chemistry. [14] During the 1990s, the anti-cancer properties of tocopherols and tocotrienols began to be delineated. [15] The current commercial sources of tocotrienol are rice and palm. [16] Other natural tocotrienol sources include rice bran oil, coconut oil, cocoa butter, barley, and wheat germ. [17] Tocotrienols are safe and human studies show no adverse effects with consumption of 240 mg/day for 48 months. [18] 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 (see tocopherol); 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 to tocopherols

Tocotrienols have only a single chiral center—the 2' carbon on the chromanol ring, which is where the isoprenoid tail is attached. Unlike the tocopherols, which have additional chiral centers along their saturated tail chain, the unsaturated chain of the tocotrienols instead have double-bonds at this 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.[ citation needed ]

Tocotrienol studies confirm anti-oxidation, [19] anti-inflammatory potentials and suggest anti-cancer effects [20] [21] better than the common forms of tocopherol due to their chemical structure. Scientists have suggested tocotrienols are better antioxidants than tocopherols. [22] [23] [24] [25] It has been proposed that the unsaturated side-chain in tocotrienols causes them to penetrate tissues with saturated fatty layers more efficiently than tocopherol. [26] Lipid ORAC values are highest for δ-tocotrienol. [27] 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. [6]

α-Tocopherol interference

Various studies have shown that alpha-tocopherol interferes with tocotrienol benefits. [6] High levels of α-tocopherol increase cholesterol production. [28] α-Tocopherol interference with tocotrienol absorption was described previously by scientists, who showed that α-tocopherol interfered with absorption of α-tocotrienol, but not γ-tocotrienol. [29] Finally, α-tocopherol was shown to interfere with tocotrienols by increasing catabolism. [30]

Sources

In nature, tocotrienols are present in many plants and fruits. The oil 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. [31]

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. [32] 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. [32] [33] 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. [34] No human trials have yet been completed.

Further reading

Related Research Articles

Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.

<span class="mw-page-title-main">Carotene</span> Class of compounds

The term carotene (also carotin, from the Latin carota, "carrot") is used for many related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but in general cannot be made by animals (with the exception of some aphids and spider mites which acquired the synthesizing genes from fungi). Carotenes are photosynthetic pigments important for photosynthesis. Carotenes contain no oxygen atoms. They absorb ultraviolet, violet, and blue light and scatter orange or red light, and (in low concentrations) yellow light.

Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitamin E, can cause nerve problems. Vitamin E is a fat-soluble antioxidant which may help protect cell membranes from reactive oxygen species. Worldwide, government organizations recommend adults consume in the range of 3 to 15 mg per day. As of 2016, consumption was below recommendations according to a worldwide summary of more than one hundred studies that reported a median dietary intake of 6.2 mg per day for alpha-tocopherol.

Tocopherols are a class of organic compounds comprising various methylated phenols, many of which have vitamin E activity. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rats, it was named tocopherol, from Greek τόκοςtókos 'birth' and φέρεινphérein 'to bear or carry', that is 'to carry a pregnancy', with the ending -ol signifying its status as a chemical alcohol.

Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health, but cannot synthesize them.

Rancidification is the process of complete or incomplete autoxidation or hydrolysis of fats and oils when exposed to air, light, moisture, or bacterial action, producing short-chain aldehydes, ketones and free fatty acids.

<span class="mw-page-title-main">Bran</span> Hard outer layers of cereal grain

Bran, also known as miller's bran, is the hard layers of cereal grain surrounding the endosperm. It consists of the combined aleurone and pericarp. Corn (maize) bran also includes the pedicel. Along with the germ, it is an integral part of whole grains, and is often produced as a byproduct of milling in the production of refined grains.

β-Carotene Red-orange pigment of the terpenoids class

β-Carotene (beta-carotene) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons.

<span class="mw-page-title-main">Stanol ester</span> Class of chemical compounds

Stanol esters is a heterogeneous group of chemical compounds known to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested, though to a much lesser degree than prescription drugs such as statins. The starting material is phytosterols from plants. These are first hydrogenated to give a plant stanol which is then esterified with a mixture of fatty acids also derived from plants. Plant stanol esters are found naturally occurring in small quantities in fruits, vegetables, nuts, seeds, cereals, legumes, and vegetable oils.

<span class="mw-page-title-main">4-Hydroxynonenal</span> Chemical compound

4-Hydroxynonenal, or 4-hydroxy-2E-nonenal or 4-hydroxy-2-nonenal or 4-HNE or HNE,, is an α,β-unsaturated hydroxyalkenal that is produced by lipid peroxidation in cells. 4-HNE is the primary α,β-unsaturated hydroxyalkenal formed in this process. It is a colorless oil. It is found throughout animal tissues, and in higher quantities during oxidative stress due to the increase in the lipid peroxidation chain reaction, due to the increase in stress events. 4-HNE has been hypothesized to play a key role in cell signal transduction, in a variety of pathways from cell cycle events to cellular adhesion.

Fatty acid desaturases are a family of enzymes that convert saturated fatty acids into unsaturated fatty acids and polyunsaturated fatty acids. For the common fatty acids of the C18 variety, desaturases convert stearic acid into oleic acid. Other desaturases convert oleic acid into linolenic acid, which is the precursor to alpha-linolenic acid, gamma-linolenic acid, and eicosatrienoic acid.

<span class="mw-page-title-main">Essential fatty acid interactions</span>

There are many fatty acids found in nature. Two types of fatty acids considered essential for human health are the omega-3 and omega-6 types. These two essential fatty acids are necessary for some cellular signalling pathways and are involved in mediating inflammation, protein synthesis, and metabolic pathways in the human body.

α-Tocopherol Chemical compound

α-Tocopherol (alpha-tocopherol) is a type of vitamin E. Its E number is "E307". Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. All feature a chromane ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain which allows for penetration into biological membranes. Compared to the others, α-tocopherol is preferentially absorbed and accumulated in humans.

Rose hip seed oil is a pressed seed oil, extracted from the seeds of the wild rose bush Rosa rubiginosa in the southern Andes. Rosehip seed oil can also be extracted from Rosa canina, a wild rose species native to Europe, northwest Africa, and western Asia. The fruits of the rosehip have been used in folk medicine for a long time. Rosehips have prophylactic and therapeutic actions against the common cold, infectious diseases, gastrointestinal disorders, urinary tract diseases, and inflammatory diseases.

<span class="mw-page-title-main">Sea buckthorn oil</span> Vegetable oil

Sea buckthorn oil is a red-orange oil derived from sea buckthorn plants. The most commonly used species for this purpose is Hippophae rhamnoides. Species belonging to this genus accumulate lipids in the mesocarp, so the oil can be extracted from either the seeds or the pulp.

<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.

Vitamins occur in a variety of related forms known as vitamers. A vitamer of a particular vitamin is one of several related compounds that performs the functions of said vitamin and prevents the symptoms of deficiency of said vitamin.

γ-Tocotrienol is one of the four types of tocotrienol, a type of vitamin E.

<span class="mw-page-title-main">Cooking oil</span> Oil consumed by humans, of vegetable or animal origin

Cooking oil is a plant or animal liquid fat used in frying, baking, and other types of cooking. Oil allows higher cooking temperatures than water, making cooking faster and more flavorful, while likewise distributing heat, reducing burning and uneven cooking. It sometimes imparts its own flavor. Cooking oil is also used in food preparation and flavoring not involving heat, such as salad dressings and bread dips.

References

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