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Tocotrienol

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Not to be confused with the more common class of molecules that are also forms of vitamin E, thetocopherols.
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 fourtocotrienols( Alpha, beta, gamma, delta) and fourtocopherols( Alpha, beta, gamma, delta). The critical chemical structural difference between tocotrienols and tocopherols is that tocotrienols have unsaturatedisoprenoidside chains with three carbon-carbondouble bondsversus saturated side chains for tocopherols (see Figure).[1][2]

Tocotrienols are compounds naturally occurring at higher levels in somevegetable oils,includingpalm 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 chemicalantioxidant,[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 thehydroxylgroup on the chromanol ring, tofree radicalandreactive oxygen species.Historically studies of tocotrienols account for less than 1% of all research into vitamin E.[7]

Health effects[edit]

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 theInstitute of Medicineof theUnited States National Academy of Sciencesdoes not define a Recommended Dietary Allowance or Adequate Intake for tocotrienols.[9]

Brain[edit]

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[edit]

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

Skin[edit]

Tocotrienols have been linked to improveatopic eczema.[8][12]

Side effects[edit]

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

History[edit]

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 lowercholesterolwas first reported byAsaf Qureshiand Elson in theJournal 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 andpalm.[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, orannatto,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[edit]

Tocotrienols are named by analogy to tocopherols (from Greek words meaningto bear a pregnancy(seetocopherol); but with this word changed to include the chemical difference that tocotrienols aretrienes,meaning that they share identical structure with the tocopherols except for the addition of the threedouble bondsto theirside chains.

Comparison to tocopherols[edit]

Tocotrienols have only a singlechiral 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 theirsaturatedtail chain, the unsaturated chain of the tocotrienols instead have double-bonds at this sites. Tocotrienols extracted from plants are alwaysdextrorotatorystereoisomers, 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 tocotrienoldietary supplementsare 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[edit]

Absorption and distribution[edit]

Tocotrienols are primarily administered orally and, due to theirlipophilicnature, their absorption is significantly enhanced when taken with a fat-rich diet. These compounds are mainly absorbed in the small intestine, with absorption depending on adequate pancreatic function,bilesecretion, andmicelleformation in the intestines. Upon administration, tocotrienols are distributed throughout the body, with higher concentrations observed in plasma and adipose tissues.[28]

Bioavailability factors[edit]

The short half-lives of tocotrienols are attributed to their low binding affinity forα-TTP,which maintains plasma levels of tocopherols. Specifically, α-tocopherol has a significantly higher binding affinity for α-TTP compared to tocotrienols. Relative to α-tocopherol's affinity, α-tocotrienol has about 9%, δ-tocotrienol 12%, and ɤ-tocotrienol 2% affinity for α-TTP. Consequently, δ-tocotrienol remains in plasma for a longer duration, offering greater bioavailability and slower biotransformation compared to other isomers. Human studies have indicated that δ-tocotrienol has a bioavailability of 28%, while ɤ- and α- isomers exhibit 9%.[28]

Metabolism and excretion[edit]

Tocotrienols are primarily metabolized in the liver, undergoingω-hydroxylationby the enzymesCYP3A4andCYP4F2,followed byβ-oxidation.The final metabolites, carboxyethyl-hydroxychromanols (CEHC) and carboxymethylbutyl hydroxychroman (CMBHC), are readily excreted in urine.[28]

Sources[edit]

In nature, tocotrienols are present in many plants and fruits. The oil palm fruit (Elaeis guineensis) is particularly high in tocotrienols, primarilygamma-tocotrienol,Alpha -tocotrienoland delta-tocotrienol. Other cultivated plants high in tocotrienols includes rice, wheat, barley, rye and oat.[29]

Research[edit]

Radiation countermeasures[edit]

Following exposure togamma radiation,hematopoietic stem cells(HSCs) in thebone marrow,which are important for producing blood cells, rapidly undergoapoptosis(cell death). There are no known treatments for this acute effect of radiation.[30]Two studies conducted by theU.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.[30][31]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.[32]No human trials have yet been completed.

Further reading[edit]

  • Tan B, Watson RR, Preedy VR, eds. (2013). Tocotrienols: Vitamin E Beyond Tocopherols (2nd ed.). Boca Raton: CRC Press. ISBN 9781439884416.

References[edit]

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  2. ^Clarke MW, Burnett JR, Croft KD (2008). "Vitamin E in human health and disease".Critical Reviews in Clinical Laboratory Sciences.45(5): 417–50.doi:10.1080/10408360802118625.PMID18712629.S2CID85991655.
  3. ^Tan B, Watson RR, Preedy VR, eds. (2013).Tocotrienols: Vitamin E Beyond Tocopherols(2nd ed.). Boca Raton: CRC Press.ISBN9781439884416.
  4. ^Sen CK, Rink C, Khanna S (June 2010)."Palm oil-derived natural vitamin E Alpha -tocotrienol in brain health and disease".Journal of the American College of Nutrition.29(3 Suppl): 314S–323S.doi:10.1080/07315724.2010.10719846.PMC3065441.PMID20823491.
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  14. ^Pearce BC, Parker RA, Deason ME, Qureshi AA, Wright JJ (October 1992). "Hypocholesterolemic activity of synthetic and natural tocotrienols".Journal of Medicinal Chemistry.35(20): 3595–606.doi:10.1021/jm00098a002.PMID1433170.
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  17. ^Packer L, Weber SU, Rimbach G (February 2001)."Molecular aspects of Alpha -tocotrienol antioxidant action and cell signalling".The Journal of Nutrition.131(2): 369S–73S.doi:10.1093/jn/131.2.369S.PMID11160563.
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  27. ^Müller L, Theile K, Böhm V (May 2010). "In vitro antioxidant activity of tocopherols and tocotrienols and comparison of vitamin E concentration and lipophilic antioxidant capacity in human plasma".Molecular Nutrition & Food Research.54(5): 731–42.doi:10.1002/mnfr.200900399.PMID20333724.
  28. ^abcSharif M, Khan DA, Farhat K, Mudassar Noor, Mohammad Asghar Khan, Saima Rafique (2023-02-15)."Pharmacokinetics and bioavailability of tocotrienols in healthy human volunteers: a systematic review".Journal of the Pakistan Medical Association.73(3): 603–610.doi:10.47391/JPMA.6008.ISSN0030-9982.PMID36932765.S2CID257423183.
  29. ^Tocopherol and tocotrienol contents of raw and processed fruits and vegetables in the United States dietp.199
  30. ^abLi XH, Fu D, Latif NH, Mullaney CP, Ney PH, Mog SR, et al. (December 2010)."Delta-tocotrienol protects mouse and human hematopoietic progenitors from gamma-irradiation through extracellular signal-regulated kinase/mammalian target of rapamycin signaling".Haematologica.95(12): 1996–2004.doi:10.3324/haematol.2010.026492.PMC2995556.PMID20823133.
  31. ^Kulkarni S, Ghosh SP, Satyamitra M, Mog S, Hieber K, Romanyukha L, et al. (June 2010). "Gamma-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation".Radiation Research.173(6): 738–47.Bibcode:2010RadR..173..738K.doi:10.1667/RR1824.1.PMID20518653.S2CID24874530.
  32. ^Singh VK, Beattie LA, Seed TM (November 2013)."Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures".Journal of Radiation Research.54(6): 973–88.doi:10.1093/jrr/rrt048.PMC3823775.PMID23658414.

External links[edit]

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