Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Nutrition Journal
Published in: Nutrition Journal 1/2012

Open Access 01-12-2012 | Research

Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation

Authors: Syed Fairus, Rosnah M Nor, Hwee M Cheng, Kalyana Sundram

Published in: Nutrition Journal | Issue 1/2012

Login to get access

Abstract

Background

Tocotrienols (T3) and tocopherols (T), both members of the natural vitamin E family have unique biological functions in humans. T3 are detected in circulating human plasma and lipoproteins, although at concentrations significantly lower than α-tocopherol (α-T). T3, especially α-T3 is known to be neuropotective at nanomolar concentrations and this study evaluated the postprandial fate of T3 and α-T in plasma and lipoproteins.

Methods

Ten healthy volunteers (5 males and 5 females) were administered a single dose of vitamin E [526 mg palm tocotrienol-rich fraction (TRF) or 537 mg α-T] after 7-d pre-conditioning on a T3-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of T and T3 isomers in plasma, triacylglycerol-rich particles (TRP), LDL, and HDL were measured at each postprandial interval.

Results

After TRF supplementation, plasma α-T3 and γ-T3 peaked at 5 h (α-T3: 4.74 ± 1.69 μM; γ-T3: 2.73 ± 1.27 μM). δ-T3 peaked earlier at 4 h (0.53 ± 0.25 μM). In contrast, α-T peaked at 6 h (30.13 ± 2.91 μM) and 8 h (37.80 ± 3.59 μM) following supplementation with TRF and α-T, respectively. α-T was the major vitamin E isomer detected in plasma, TRP, LDL, and HDL even after supplementation with TRF (composed of 70% T3). No T3 were detected during fasted states. T3 are detected postprandially only after TRF supplementation and concentrations were significantly lower than α-T.

Conclusions

Bio-discrimination between vitamin E isomers in humans reduces the rate of T3 absorption and affects their incorporation into lipoproteins. Although low absorption of T3 into circulation may impact some of their physiological functions in humans, T3 have biological functions well below concentration noted in this study.
Appendix
Available only for authorised users
Literature
1.
Serbinova EA, Kagan V, Han D, Packer L: Free radical recycling and intramembrane mobility in the antioxidant properties of α-tocopherol and α-tocotrienol. Free Radic Biol Med. 1991, 10: 263-275. 10.1016/0891-5849(91)90033-Y.CrossRefPubMed
2.
Suarna C, Hood RL, Dean RT, Stocker R: Comparative antioxidant activity of tocotrienols and other natural lipid soluble antioxidants in homogenous system, and in rat and human lipoproteins. Biochim Biophys Acta. 1993, 1166: 163-170.CrossRefPubMed
3.
Theriault A, Jun-Tzu C, Wang Q, Gapor A, Adeli K: Tocotrienol: a review of its therapeutic potential. Clin Biochem. 1999, 32: 309-319. 10.1016/S0009-9120(99)00027-2.CrossRefPubMed
4.
Packer L, Weber SU, Rimbach G: Molecular aspects of α-tocotrienol antioxidant action and cell signaling. J Nutr. 2001, 131 (Suppl): 369-373.
5.
Sylvester PW, Theriault A: Role of tocotrienols in the preventive of cardiovascular disease and breast cancer. Curr Top Nutraceutical Res. 2003, 1: 121-136.
6.
Kerckhofts DAJM, Brouns F, Honstra G, Mensink RP: Effects on the human serum lipoprotein profile of β-glucan, soy protein and isoflavones, plant sterols and stanols, garlic and tocotrienols. J Nutr. 2002, 132: 2494-2505.
7.
Schaffer S, Müller WE, Eckert GP: Tocotrienols: constitutional effects in aging and disease. J Nutr. 2005, 135: 151-154.PubMed
8.
9.
Mensink RP, van Houwelingen AC, Kromhout D, Honstra G: A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr. 1999, 69: 213-219.PubMed
10.
O'Byrne D, Grundy S, Packer L, Devaraj S, Baldenius K, Hoppe PP, Kramer K, Jialal I, Traber MG: Studies of LDL oxidation following α-, γ-, or δ-tocotrienyl acetate supplementation of hypercholesterolemic humans. Free Radic Biol Med. 2000, 29: 834-845. 10.1016/S0891-5849(00)00371-3.CrossRefPubMed
11.
Mustad VA, Smith CA, Ruey PP, Edens NK, DeMichele SJ: Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia. Am J Clin Nutr. 2002, 76: 1237-1243.PubMed
12.
Radhakrishnan AK, Lee AL, Wong PK, Kaur J, Aung H, Nesaretnam K: Daily supplementation of tocotrienol-rich fraction or α-tocopherol did not induce immunomodulatory changes in healthy human volunteers. Br J Nutr. 2009, 101: 810-815. 10.1017/S0007114508039998.CrossRefPubMed
13.
Hayes KC, Pronczuk A, Liang JS: Difference in the plasma transport and tissue concentration of tocopherols and tocotrienols: observations in humans and hamsters. Proc Soc Exp Biol Med. 1993, 202: 353-359.CrossRefPubMed
14.
Wahlqvist ML, Krivokuca-Bogetic Z, Sam Lo C: Differential serum responses of tocopherols and tocotrienols during vitamin supplementation in hypercholesterolaemic individuals without change in coronary risk factors. Nutr Res. 1992, 12 (Suppl): 181-201.CrossRef
15.
Qureshi AA, Bradlow BA, Salser WA, Brace LD: Novel tocotrienols of rice bran modulate cardiovascular disease risk parameters of hypercholesterolemic humans. J Nutr Biochem. 1997, 8: 290-298. 10.1016/S0955-2863(97)89667-2.CrossRef
16.
Yap SP, Yuen KH, Wong JW: Pharmacokinetics and bioavailability of α-, γ- and δ-tocotrienols under different food status. J Pharm Pharmacol. 2001, 53: 67-71.CrossRefPubMed
17.
Yap SP, Yuen KH: Influence of lipolysis and droplet size on tocotrienol absorption from self-emulsifying formulations. Int J Pharm. 2004, 281: 67-78. 10.1016/j.ijpharm.2004.05.015.CrossRefPubMed
18.
Rasool AHG, Yuen KH, Yusoff K, Wong AR, Rahman ARA: Dose dependent elevation of plasma tocotrienol level and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E. J Nutr Sci Vitaminol. 2006, 52: 473-478. 10.3177/jnsv.52.473.CrossRefPubMed
19.
Fairus S, Nor RM, Cheng HM, Sundram K: Postprandial metabolic fate of tocotrienol-rich vitamin E differs significantly from that of α-tocopherol. Am J Clin Nutr. 2006, 84: 835-842.PubMed
20.
Khosla P, Patel V, Whinter JM, Khanna S, Rakhkovskaya M, Roy S, Sen CK: Postprandial levels of the natural vitamin E tocotrienol in human circulation. Antioxid Redox Signal. 2006, 8: 1059-1068. 10.1089/ars.2006.8.1059.CrossRefPubMed
21.
Rasool AHG, Rahman ARA, Yuen KH, Wong AR: Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E. Arch Pharm Res. 2008, 31: ;1212-1217. 10.1007/s12272-001-1291-5.CrossRefPubMed
22.
Food and Nutrition Board, Institute of Medicine: Dietary reference intakes for vitamin C, vitamin E, selenium and carotenoids. 2000, Washington DC: National Academy Press
23.
Sundram K, Hayes KC, Siru OH: Dietary palmitic acid results in lower serum cholesterol than does a lauric-myristic acid combination in normolipemic humans. Am J Clin Nutr. 1994, 59: 841-846.PubMed
24.
Sundram K, Nor RM: From analysis of tocotrienols in different sample matrixes by HPLC. Methods in Molecular Biology, Oxidative Stress Biomarkers and Antioxidant Protocols. Edited by: Armstrong D. 2002, Totowa, New Jersey: Humana Press Inc, 186: 221-232.CrossRef
25.
Traber MG: Vitamin E regulatory mechanisms. Annu Rev Nutr. 2007, 27: 347-362. 10.1146/annurev.nutr.27.061406.093819.CrossRefPubMed
26.
Traber MG, Kayden HJ: Preferential incorporation of alpha-tocopherol vs gamma-tocopherol in human lipoproteins. Am J Clin Nutr. 1989, 49: 517-526.PubMed
27.
Schwenke DC: Vitamin E to prevent cardiovascular disease: pill or dietary package?. Curr Opin Lipidol. 2007, 18: 467-469. 10.1097/MOL.0b013e32825fea3a.CrossRefPubMed
28.
Ikeda I, Sasaki E, Sugano M: Lymphatic transport of α-, γ- and δ-tocotrienols and α-tocopherol in rats. Int J Vit Nutr Res. 1996, 66: 217-221.
29.
Yap SP, Yuen KH, Lim AB: Influence of route of administration on the absorption and disposition of α-, γ- and δ-tocotrienols in rats. J Pharm Pharmacol. 2003, 55: 53-58.CrossRefPubMed
30.
Hosomi A, Arita M, Sato Y, Kiyose C, Ueda T, Igarashi O, Arai H, Inoue K: Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogues. FEBS Letters. 1997, 409: 105-108. 10.1016/S0014-5793(97)00499-7.CrossRefPubMed
31.
Anwar K, Iqbal J, Hussain MM: Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption. J Lipid Res. 2007, 48: 2028-2038. 10.1194/jlr.M700207-JLR200.CrossRefPubMed
32.
Lodge JK, Ridllington J, Leonard S, Vaule H, Traber MG: α- and γ-tocotrienols are metabolized to carboxyethyl-hydroxychroman derivatives and excreted in human urine. Lipids. 2001, 36: 43-48. 10.1007/s11745-001-0666-z.CrossRefPubMed
33.
Traber MG, Burton GW, Hughes L, Ingold KU, Hidaka H, Malloy M, Kane J, Hyams J, Kayden HJ: Discrimination between forms of vitamin E by humans with and without genetic abnormalities of lipoprotein metabolism. J Lipid Res. 1992, 33: 1171-1182.PubMed
34.
Kayden HJ, Traber MG: Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res. 1993, 34: 343-358.PubMed
35.
Kiyose C, Muramatsu R, Kameyama Y, Ueda T, Igarashi O: Biodiscrimination of α-tocopherol stereoisomers in humans after oral administration. Am J Clin Nutr. 1997, 65: 785-789.PubMed
36.
Jeanes YM, Hall WL, Ellard S, Lee E, Lodge JK: The absorption of vitamin E is influenced by the amount of fat in a meal and the food matrix. Br J Nutr. 2004, 92: 575-579. 10.1079/BJN20041249.CrossRefPubMed
37.
Abuasal A, Sylvester PW, Kaddoumi A: Intestinal absorption of γ-tocotrienol is mediated by Niemann-Pick C1-Like 1: in situ rat intestinal perfusion studies. Drug Metab Dipos. 2010, 38: 939-945. 10.1124/dmd.109.031567.CrossRef
38.
Abe C, Uchida T, Ohta M, Ichikawa T, Yamashita K, Ikeda S: Cytochrome P450-dependent metabolism of vitamin E isoforms is a critical determinant of their tissue concentration in rats. Lipids. 2007, 42: 637-645. 10.1007/s11745-007-3064-2.CrossRefPubMed
39.
Traber MG, Rader D, Acuff RV, Ramakrishnan R, Brewer HB, Kayden HJ: Vitamin E dose-response studies in humans with use of deuterated RRR-α-tocopherol. Am J Clin Nutr. 1998, 68: 847-853.PubMed
40.
Meydani M, Cohn JS, Macauley JB, McNamara JR, Blumberg JB, Schaefer EJ: Postprandial changes in the plasma concentration of α- and γ-tocopherol in human subjects fed a fat-rich meal supplemented with fat-soluble vitamins. J Nutr. 1989, 119: 1252-1258.PubMed
41.
Borel P, Mekki N, Boirie Y, Partier A, Grolier P, Alexandre-Gouabau MC, Beaufrere B, Armand M, Lairon D, Azais-Braesco V: Postprandial chylomicron and plasma vitamin E responses in healthy older subjects compared with younger ones. Eur J Clin Invest. 1997, 27: 812-821. 10.1046/j.1365-2362.1997.1960744.x.CrossRefPubMed
42.
Baliarsingh S, Beg ZH, Ahmad J: The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis. 2005, 182: 367-374. 10.1016/j.atherosclerosis.2005.02.020.CrossRefPubMed
43.
Qureshi AA, Sami SA, Salser WA: Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans. Atherosclerosis. 2002, 161: 199-207. 10.1016/S0021-9150(01)00619-0.CrossRefPubMed
44.
Qureshi AA, Bradlow BA, Brace L, Manganello J, Peterson DM, Pearce BC, Wright JJK, Gapor A, Elson CE: Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids. 1995, 30: 1171-1177. 10.1007/BF02536620.CrossRefPubMed
45.
Yu SG, Thomas AM, Gapor A, Tan B, Qureshi N, Qureshi AA: Dose-response impact of various tocotrienols on serum lipid parameters in 5-week-old female chickens. Lipids. 2006, 41: 453-461. 10.1007/s11745-006-5119-1.CrossRefPubMed
46.
Metadata
Title
Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation
Authors
Syed Fairus
Rosnah M Nor
Hwee M Cheng
Kalyana Sundram
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Nutrition Journal / Issue 1/2012
Electronic ISSN: 1475-2891
DOI
https://doi.org/10.1186/1475-2891-11-5

Other articles of this Issue 1/2012

Nutrition Journal 1/2012 Go to the issue

Research

Variation in vitamin D supplementation among adults in a multi-race/ethnic health plan population, 2008

Research

Micronutrient deficiency in obese subjects undergoing low calorie diet

Review

Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review

Research

Effect of the yellow passion fruit peel flour (Passiflora edulis f. flavicarpa deg.) in insulin sensitivity in type 2 diabetes mellitus patients

Research

Validity and reproducibility of folate and vitamin B12 intakes estimated from a self-administered diet history questionnaire in Japanese pregnant women

Research

A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits