Tocotrienol

From Wikipedia, the free encyclopedia
Jump to: navigation, search
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

Tocotrienols are members of the vitamin E family:[1] four tocotrienols (alpha, beta, gamma, delta) and four tocopherols (alpha, beta, gamma, delta).[2] The critical chemical structura difference between tocotrienols and tocopherols is in that tocopherols have saturated side chains, whereas tocotrienols have unsaturated isoprenoid side chains (farnesyl isoprenoid tails) with three double bonds (see Figure).[3][4]

Tocotrienols are compounds naturally occurring at higher levels in select vegetable oils, including palm oil, rice bran oil wheat germ, barley, saw palmetto, anatto, and certain other types of seeds, nuts, grains, and the oils derived from them.[5][6]

Chemically, different analogues of vitamin E all show some activity as a chemical antioxidant,[7] but do not all have the same vitamin E equivalence. Alpha-Tocopherol is the form of vitamin E that has the highest biological activity and is preferentially absorbed and accumulated in humans.[2] Like tocopherols, individual tocotrienol isomers demonstrate different bioavailability[8] and efficacy depending on the type of antioxidant performance being measured. All tocotrienol and tocopherol isomers 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.[9] A scientific compilation of tocotrienol research, Tocotrienols: Vitamin E Beyond Tocopherols, was published in 2013.[5]

Health effects[edit]

A number of health benefits have been proposed included decreased risk of heart disease and cancer.[10] 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 or Tolerable Upper Intake Level for tocotrienols, only for alpha tocopherol.[11]

Stroke[edit]

There are no human trials of tocotrienols for prevention or treatment of stroke. Use in animal models show promising results.[12]

Cancer[edit]

There is promising early stage research.[10] One trial small trial of women with breast cancer found a non significant trend of outcomes.[10]

Heart disease[edit]

Tocotrienols have been linked to improved markers of heart disease.[13]

Diabetes[edit]

Animal models and observational studies in humans have shown potential benefit.[10] Benefit; however, does not appear to occur from supplementation but only dietary sources.[10]

Radiation countermeasures[edit]

No human trials. 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.[14] 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.[14][15] 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.[16]

Side effects[edit]

Tocotrienols are generally well tolerated and without significant side effects.[10]

History[edit]

The discovery of tocotrienols was first reported by Pennock and Whittle in 1964, describing the isolation of tocotrienols from rubber.[17] 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.[18] During the 1990s, the anti-cancer properties of tocopherols and tocotrienols began to be delineated.[19] The current commercial sources of tocotrienol are rice and palm.[20] Other natural tocotrienol sources include rice bran oil, coconut oil, cocoa butter, barley, and wheat germ.[21] Tocotrienols are safe and human studies show no adverse effects with consumption of 240 mg/day for 48 months.[22] 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. Molecular distillation occurs at lower temperatures and reduces the problem of thermal decomposition. High vacuum also eliminates oxidation that might occur in the presence of air.[23] Annatto tocotrienol has the highest tocotrienol concentration and is tocopherol-free.

Etymology[edit]

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 of tocotrienol and tocopherol[edit]

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 due to tocotrienol's unsaturation at these sites. Tocotrienols extracted from natural sources always consist of the dextrorotatory enantiomers only. These naturally occurring, dextrorotatory stereoisomers are generally abbreviated as the "d-" forms, for example, "d-tocotrienol" or "d-alpha-tocotrienol". In theory, the unnatural "l-tocotrienol" (levorotatory) forms of tocotrienols could exist as well, which would have a 2S (rather than 2R) configuration at the molecules' single chiral center. In practice, however, tocotrienols are only produced in the d-form i.e. from natural sources. The synthetic mixed stereoisomer ("dl-tocotrienol") and its acetate are available as dietary supplements. Tocopherols and tocotrienolss have different antioxidant activities when measured in human plasma [24]

Tocotrienol studies confirm anti-oxidation[25] and suggest anti-cancer effects[26][27] than the common forms of tocopherol due to their chemical structure. The unsaturated side-chain in tocotrienols causes them to penetrate tissues with saturated fatty layers more efficiently.[28]

Lipid ORAC values are highest for δ-tocotrienol.[29] 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." Scientists have suggested tocotrienols are better antioxidants than tocopherols[30][31] at preventing cardiovascular diseases[32] and cancer.[33] From the pharmacological standpoint, current formulation of vitamin E supplements, composed mainly of alpha- tocopherol, seems questionable.[34]

Metabolism and bioavailability[edit]

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.[35]

α-Tocopherol interference[edit]

Various studies have shown that alpha-tocopherol interferes with tocotrienol benefits.[35] High levels of α-tocopherol increase cholesterol production.[36] 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.[37] Finally, α-tocopherol was shown to interfere with tocotrienols by increasing catabolism.[38]

Sources[edit]

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.[39] In anatto however, tocotrienols are relatively abundant (only delta- and gamma-tocotrienol) and it contains no tocopherols.[40]

References[edit]

  1. ^ Whittle KJ, Dunphy PJ, Pennock JF (July 1966). "The isolation and properties of δ-tocotrienol from Hevea latex". The Biochemical Journal. 100 (1): 138–45. PMC 1265104Freely accessible. PMID 5965249. 
  2. ^ Brigelius-Flohé R, Traber MG (July 1999). "Vitamin E: function and metabolism". The FASEB Journal. 13 (10): 1145–55. PMID 10385606. 
  3. ^ Kamal-Eldin A, Appelqvist LA (July 1996). "The chemistry and antioxidant properties of tocopherols and tocotrienols". Lipids. 31 (7): 671–701. PMID 8827691. doi:10.1007/BF02522884. 
  4. ^ Clarke MW, Burnett JR, Croft KD (2008). "Vitamin E in human health and disease". Critical Reviews in Clinical Laboratory Sciences. 45 (5): 417–50. PMID 18712629. doi:10.1080/10408360802118625. 
  5. ^ a b Tan, B; Watson, RR; Preedy, VR (2013), Tocotrienols: Vitamin E Beyond Tocopherols (2nd ed.), Boca Raton: CRC Press, ISBN 9781439884416 
  6. ^ Sen, Chandran (June 2010). "Palm Oil–Derived Natural Vitamin E α-Tocotrienol in Brain Health and Disease". J Am Coll Nutr. 29: 314S–323S. PMC 3065441Freely accessible. PMID 20823491. doi:10.1080/07315724.2010.10719846. 
  7. ^ Cerecetto H, López GV (March 2007). "Antioxidants derived from vitamin E: an overview". Mini Reviews in Medicinal Chemistry. 7 (3): 315–38. PMID 17346221. doi:10.2174/138955707780059871. 
  8. ^ Fu JY, Che HL, Tan DM, Teng KT (2014). "Bioavailability of tocotrienols: evidence in human studies". Nutrition & Metabolism. 11: 5. PMC 3895660Freely accessible. PMID 24410975. doi:10.1186/1743-7075-11-5. 
  9. ^ Sen CK, Khanna S, Roy S (2007). "Tocotrienols in health and disease: the other half of the natural vitamin E family". Molecular Aspects of Medicine. 28 (5–6): 692–728. PMC 2435257Freely accessible. PMID 17507086. doi:10.1016/j.mam.2007.03.001. 
  10. ^ a b c d e f Meganathan, P; Fu, JY (26 October 2016). "Biological Properties of Tocotrienols: Evidence in Human Studies.". International journal of molecular sciences. 17 (11): 1682. PMC 5133770Freely accessible. PMID 27792171. doi:10.3390/ijms17111682. 
  11. ^ Dietary Reference Intakes (DRIs): Recommended Intakes for Individuals, Food and Nutrition Board, Institute of Medicine, National Academies, 2004, retrieved 2009-06-09 
  12. ^ 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. PMC 3065441Freely accessible. PMID 20823491. doi:10.1080/07315724.2010.10719846. 
  13. ^ Prasad, K (2011). "Tocotrienols and cardiovascular health.". Current pharmaceutical design. 17 (21): 2147–54. PMID 21774782. doi:10.2174/138161211796957418. 
  14. ^ a b Li XH, Fu D, Latif NH, et al. (December 2010). "δ-tocotrienol protects mouse and human hematopoietic progenitors from γ-irradiation through extracellular signal-regulated kinase/mammalian target of rapamycin signaling". Haematologica. 95 (12): 1996–2004. PMC 2995556Freely accessible. PMID 20823133. doi:10.3324/haematol.2010.026492. 
  15. ^ Kulkarni S, Ghosh SP, Satyamitra M, et al. (June 2010). "Gamma-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation". Radiat. Res. 173 (6): 738–47. PMID 20518653. doi:10.1667/RR1824.1. 
  16. ^ Singh VK, Beattie LA, Seed TM (Nov 1, 2013). "Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures". Journal of Radiation Research. 54 (6): 973–988. PMID 23658414. doi:10.1093/jrr/rrt048. 
  17. ^ Dunphy, P. J.; Whittle, K. J.; Pennock, J. F.; Morton, R. A. (1965). "Identification and Estimation of Tocotrienols in Hevea Latex". Nature. 207 (4996): 521–522. doi:10.1038/207521a0. 
  18. ^ Pearce BC, Parker RA, Deason ME, Qureshi AA, Wright JJ (October 1992). "Hypocholesterolemic activity of synthetic and natural tocotrienols". J. Med. Chem. 35 (20): 3595–606. PMID 1433170. doi:10.1021/jm00098a002. 
  19. ^ Watson & Preedy 2008, p. 6
  20. ^ Tan, B. and M.H. Saleh, Integrated process for recovery of carotenoids and tocotrienols from oil in USPTO 5,157,132. 1992
  21. ^ 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. PMID 11160563. 
  22. ^ Tomeo AC, Geller M, Watkins TR, Gapor A, Bierenbaum ML (December 1995). "Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis". Lipids. 30 (12): 1179–83. PMID 8614310. doi:10.1007/BF02536621. 
  23. ^ Liu, Donghong; Shi, John; Posada, Luidy Rodriguez; Kakuda, Yukio; Xue, Sophia Jun (2008). "Separating Tocotrienols from Palm Oil by Molecular Distillation". Food Reviews International. 24 (4): 376–391. doi:10.1080/87559120802303840. 
  24. ^ Muller (2010). "Mol Nutr Food Res.". In vitro antioxidant activity of tocopherols and tocotrienols and comparison of vitamin E concentration and lipophilic antioxidant capacity in human plasma. 54: 731–42. PMID 20333724. doi:10.1002/mnfr.200900399. 
  25. ^ Serbinova E, Kagan V, Han D, Packer L (1991). "Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol". Free Radical Biology & Medicine. 10 (5): 263–75. PMID 1649783. doi:10.1016/0891-5849(91)90033-Y. 
  26. ^ Constantinou C, Papas A, Constantinou AI (August 2008). "Vitamin E and cancer: An insight into the anticancer activities of vitamin E isomers and analogs". International Journal of Cancer. 123 (4): 739–52. PMID 18512238. doi:10.1002/ijc.23689. 
  27. ^ Wada S (2009). "Chemoprevention of tocotrienols: the mechanism of antiproliferative effects". Forum of Nutrition. Forum of Nutrition. 61: 204–16. ISBN 978-3-8055-9097-6. PMID 19367124. doi:10.1159/000212752. 
  28. ^ Suzuki YJ, Tsuchiya M, Wassall SR, et al. (October 1993). "Structural and dynamic membrane properties of alpha-tocopherol and alpha-tocotrienol: implication to the molecular mechanism of their antioxidant potency". Biochemistry. 32 (40): 10692–9. PMID 8399214. doi:10.1021/bi00091a020. 
  29. ^ 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". Mol Nutr Food Res. 54 (5): 731–42. PMID 20333724. doi:10.1002/mnfr.200900399. 
  30. ^ Yoshida Y, Niki E, Noguchi N (March 2003). "Comparative study on the action of tocopherols and tocotrienols as antioxidant: chemical and physical effects". Chemistry and Physics of Lipids. 123 (1): 63–75. PMID 12637165. doi:10.1016/S0009-3084(02)00164-0. 
  31. ^ Schaffer S, Müller WE, Eckert GP (February 2005). "Tocotrienols: constitutional effects in aging and disease". The Journal of Nutrition. 135 (2): 151–4. PMID 15671205. 
  32. ^ Pruthi S, Allison TG, Hensrud DD (November 2001). "Vitamin E supplementation in the prevention of coronary heart disease". Mayo Clinic Proceedings. 76 (11): 1131–6. PMID 11702901. doi:10.4065/76.11.1131. 
  33. ^ Inokuchi H, Hirokane H, Tsuzuki T, Nakagawa K, Igarashi M, Miyazawa T (July 2003). "Anti-angiogenic activity of tocotrienol". Bioscience, Biotechnology, and Biochemistry. 67 (7): 1623–7. PMID 12913317. doi:10.1271/bbb.67.1623. 
  34. ^ Theriault A, Chao JT, Wang Q, Gapor A, Adeli K (July 1999). "Tocotrienol: a review of its therapeutic potential". Clinical Biochemistry. 32 (5): 309–19. PMID 10480444. doi:10.1016/S0009-9120(99)00027-2. 
  35. ^ a b Fu, J. Y.; Che, H. L.; Tan, D. M.; Teng, K. T. (2014). "Bioavailability of tocotrienols: Evidence in human studies". Nutrition & Metabolism. 11 (1): 5. PMC 3895660Freely accessible. PMID 24410975. doi:10.1186/1743-7075-11-5. 
  36. ^ Stocker A (December 2004). "Molecular mechanisms of vitamin E transport". Ann. N. Y. Acad. Sci. 1031: 44–59. PMID 15753133. doi:10.1196/annals.1331.005. 
  37. ^ Ikeda S, Tohyama T, Yoshimura H, Hamamura K, Abe K, Yamashita K (February 2003). "Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats". J. Nutr. 133 (2): 428–34. PMID 12566479. 
  38. ^ Sontag TJ, Parker RS (May 2007). "Influence of major structural features of tocopherols and tocotrienols on their omega-oxidation by tocopherol-omega-hydroxylase". J. Lipid Res. 48 (5): 1090–8. PMID 17284776. doi:10.1194/jlr.M600514-JLR200. 
  39. ^ Tocopherol and tocotrienol contents of raw and processed fruits and vegetables in the United States diet p.199
  40. ^ Identification and estimation of tocotrienols in the annatto lipid fraction by gas chromatography-mass spectrometry

External links[edit]