Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase crossover design.
HDL and LDL
chylomicrons
dual-isotope ratio method
fecal α-T analysis
triglyceride-rich lipoproteins
Journal
The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
29
04
2019
accepted:
05
07
2019
pubmed:
10
9
2019
medline:
3
4
2020
entrez:
10
9
2019
Statut:
ppublish
Résumé
Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed. We hypothesized that the dual-isotope technique, using 2 deuterium-labeled [intravenous (IV) d6- and oral d3-] α-T, would be effective in determining α-T fractional absorption. Further, defined liquid meal (DLM) fat or fasting would modulate α-T fractional absorption and lipoprotein transport. A 3-phase cr ossover design was used. At 0 h, participants received IV d6-α-T and consumed d3-α-T with a 600-kcal DLM (40% or 0% fat) followed by controlled meals or by the 0% fat DLM, a 12-h fast, and then controlled meals. Blood samples and fecal samples were collected at intervals and analyzed by LC-MS. Pharmacokinetic parameters were calculated from plasma tracer concentrations and enrichments. Fractional absorption was calculated from d3- to d6-α-T areas under the curve, from a novel mathematical model, and from the balance method (oral d3-α-T minus fecal d3-α-T excreted). Estimated α-T fractional absorption during the 40% fat intervention was 55% ± 3% (mean ± SEM; n = 10), which was 9% less than during the 0% fat intervention (64% ± 3%, n = 10; P < 0.02). Fasting had no apparent effect (56% ± 3%, n = 7), except it slowed plasma oral d3-α-T appearance. Both balance data and model outcomes confirmed that the DLM fat did not potentiate d3-α-T absorption. During the IV emulsion clearance, HDL rapidly acquired d6-α-T (21 ± 2 nmol/L plasma per minute). During the first 8 h postdosing, triglyceride-rich lipoproteins (TRLs) were preferentially d3-α-T enriched relative to LDL or HDL, showing the TRL precursor role. Quantitatively, α-T absorption is not limited by fat absence or by fasting. However, α-T leaves the intestine by a process that is prolonged during fasting and potentiated by eating, suggesting that α-T absorption is highly dependent on chylomicron assembly processes. This trial was registered at clinicaltrials.gov as NCT00862433.
Sections du résumé
BACKGROUND
Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed.
OBJECTIVE
We hypothesized that the dual-isotope technique, using 2 deuterium-labeled [intravenous (IV) d6- and oral d3-] α-T, would be effective in determining α-T fractional absorption. Further, defined liquid meal (DLM) fat or fasting would modulate α-T fractional absorption and lipoprotein transport.
METHODS
A 3-phase cr ossover design was used. At 0 h, participants received IV d6-α-T and consumed d3-α-T with a 600-kcal DLM (40% or 0% fat) followed by controlled meals or by the 0% fat DLM, a 12-h fast, and then controlled meals. Blood samples and fecal samples were collected at intervals and analyzed by LC-MS. Pharmacokinetic parameters were calculated from plasma tracer concentrations and enrichments. Fractional absorption was calculated from d3- to d6-α-T areas under the curve, from a novel mathematical model, and from the balance method (oral d3-α-T minus fecal d3-α-T excreted).
RESULTS
Estimated α-T fractional absorption during the 40% fat intervention was 55% ± 3% (mean ± SEM; n = 10), which was 9% less than during the 0% fat intervention (64% ± 3%, n = 10; P < 0.02). Fasting had no apparent effect (56% ± 3%, n = 7), except it slowed plasma oral d3-α-T appearance. Both balance data and model outcomes confirmed that the DLM fat did not potentiate d3-α-T absorption. During the IV emulsion clearance, HDL rapidly acquired d6-α-T (21 ± 2 nmol/L plasma per minute). During the first 8 h postdosing, triglyceride-rich lipoproteins (TRLs) were preferentially d3-α-T enriched relative to LDL or HDL, showing the TRL precursor role.
CONCLUSIONS
Quantitatively, α-T absorption is not limited by fat absence or by fasting. However, α-T leaves the intestine by a process that is prolonged during fasting and potentiated by eating, suggesting that α-T absorption is highly dependent on chylomicron assembly processes. This trial was registered at clinicaltrials.gov as NCT00862433.
Identifiants
pubmed: 31495886
pii: S0002-9165(23)01058-4
doi: 10.1093/ajcn/nqz172
pmc: PMC6821549
doi:
Substances chimiques
Dietary Fats
0
Vitamin E
1406-18-4
Deuterium
AR09D82C7G
Banques de données
ClinicalTrials.gov
['NCT00862433']
Types de publication
Clinical Trial, Phase III
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1148-1167Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
Copyright © American Society for Nutrition 2019.
Références
Clin Chem. 1985 Feb;31(2):217-22
pubmed: 2578337
Br J Anaesth. 2003 Feb;90(2):148-54
pubmed: 12538369
Atherosclerosis. 2019 May;284:75-82
pubmed: 30875496
J Clin Invest. 1995 Dec;96(6):2932-46
pubmed: 8675665
Lipids. 1992 Sep;27(9):657-63
pubmed: 1487963
Am J Clin Nutr. 2015 Apr;101(4):752-9
pubmed: 25739929
J Nutr. 2012 Dec;142(12):2105-11
pubmed: 23077194
J Lipid Res. 1993 Feb;34(2):201-10
pubmed: 8429255
Am J Cardiol. 1990 Sep 4;66(6):20A-23A
pubmed: 2203246
Am J Clin Nutr. 2004 Jan;79(1):86-92
pubmed: 14684402
Arch Biochem Biophys. 1998 Feb 15;350(2):183-92
pubmed: 9473291
J Nutr. 2011 Aug;141(8):1482-8
pubmed: 21715470
Free Radic Biol Med. 2004 Feb 15;36(4):456-63
pubmed: 14975448
BBA Clin. 2015 Jan 31;3:175-88
pubmed: 26674734
J Lipid Res. 2013 Sep;54(9):2295-306
pubmed: 23505319
J Lipid Res. 1993 Feb;34(2):167-79
pubmed: 8381452
Antioxidants (Basel). 2017 Nov 22;6(4):null
pubmed: 29165370
Biochimie. 2014 Jan;96:48-55
pubmed: 23871915
Am J Clin Nutr. 1985 Jan;41(1):66-72
pubmed: 3966426
J Clin Invest. 1990 Feb;85(2):397-407
pubmed: 2298915
Free Radic Biol Med. 1995 Nov;19(5):591-8
pubmed: 8529918
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10005-8
pubmed: 7937827
Free Radic Biol Med. 2005 Apr 1;38(7):857-66
pubmed: 15749381
Science. 2013 May 31;340(6136):1106-10
pubmed: 23599266
Lipids. 2006 Jun;41(6):615-22
pubmed: 16981439
J Biol Chem. 2001 Oct 26;276(43):39898-902
pubmed: 11546785
Clin Nutr. 2005 Aug;24(4):492-501
pubmed: 16054521
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3704-9
pubmed: 8623000
JCI Insight. 2016 Nov 3;1(18):e87418
pubmed: 27812539
Anal Biochem. 1975 May 12;65(1-2):42-9
pubmed: 165752
J Clin Invest. 1985 May;75(5):1729-34
pubmed: 3998153
Am J Clin Nutr. 2006 Feb;83(2):299-304
pubmed: 16469987
Am J Clin Nutr. 2015 Nov;102(5):1070-80
pubmed: 26447154
Traffic. 2015 Jan;16(1):19-34
pubmed: 25262571
J Lipid Res. 1999 Jan;40(1):1-16
pubmed: 9869645
Am J Clin Nutr. 1956 Jul-Aug;4(4):408-19
pubmed: 13339713
Am J Clin Nutr. 2006 Dec;84(6):1430-41
pubmed: 17158427
Am J Clin Nutr. 2005 Jan;81(1):95-103
pubmed: 15640466
Scand J Gastroenterol. 2003 Jul;38(7):712-8
pubmed: 12889556
J Biol Chem. 2016 May 13;291(20):10659-76
pubmed: 27013658
Bull Math Biol. 2010 Nov;72(8):2019-46
pubmed: 20195911
J Nutr Biochem. 2010 May;21(5):451-6
pubmed: 19427182
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9842-6
pubmed: 11504949
Am J Clin Nutr. 1998 Apr;67(4):669-84
pubmed: 9537614
Nutr Metab (Lond). 2016 Jul 28;13:48
pubmed: 27478484
Free Radic Biol Med. 2006 Feb 15;40(4):689-97
pubmed: 16458200
Clin Chem. 1984 Nov;30(11):1784-8
pubmed: 6207956
Clin Nutr. 2004 Dec;23(6):1360-70
pubmed: 15556258
Biochem J. 1995 Jan 15;305 ( Pt 2):659-67
pubmed: 7832785
Lipids. 2008 Jul;43(7):663-71
pubmed: 18509690
Gastroenterology. 1983 Nov;85(5):1172-82
pubmed: 6618108
Br J Nutr. 2004 Oct;92(4):575-9
pubmed: 15522126
Clin Biochem. 2000 Nov;33(8):619-25
pubmed: 11166008
J Nutr. 2013 Oct;143(10):1565-72
pubmed: 23946344
J Biol Chem. 2016 Aug 12;291(33):17028-39
pubmed: 27307040
Int J Vitam Nutr Res. 2018 Jun;88(3-4):151-157
pubmed: 30747603
Biochim Biophys Acta. 1987 Sep 25;921(2):175-81
pubmed: 3651482
Lipids. 2008 Oct;43(10):925-36
pubmed: 18751751
Mol Nutr Food Res. 2013 Jul;57(7):1237-45
pubmed: 23520193
Am J Clin Nutr. 2001 May;73(5):870-7
pubmed: 11333839
Chemistry. 2014 Sep 15;20(38):12051-5
pubmed: 25088810
J Lipid Res. 1986 Jan;27(1):40-8
pubmed: 3958613