Maret G Traber1,2, Scott W Leonard1, Ifechukwude Ebenuwa3, Pierre-Christian Violet3, Yu Wang3, Mahtab Niyyati3, Sebastian Padayatty3, Hongbin Tu3, Amber Courville4, Shanna Bernstein4, Jaewoo Choi1, Robert Shamburek5, Sheila Smith3, Brian Head1, Gerd Bobe1, Rajasekhar Ramakrishnan6, Mark Levine3. 1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA. 2. School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA. 3. Molecular and Clinical Nutrition Section, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. 4. Clinical Center Nutrition Department, Oregon State University, Corvallis, OR, USA. 5. Cardiovascular Branch, Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 6. Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Abstract
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.
RCT Entities:
BACKGROUND: Determining the humanvitamin 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.
Authors: S G Young; C M Cham; R E Pitas; B J Burri; A Connolly; L Flynn; A S Pappu; J S Wong; R L Hamilton; R V Farese Journal: J Clin Invest Date: 1995-12 Impact factor: 14.808
Authors: Maret G Traber; Scott W Leonard; Gerd Bobe; Xueyan Fu; Edward Saltzman; Michael A Grusak; Sarah L Booth Journal: Am J Clin Nutr Date: 2015-03-04 Impact factor: 7.045
Authors: Pierre-Christian Violet; Ifechukwude C Ebenuwa; Yu Wang; Mahtab Niyyati; Sebastian J Padayatty; Brian Head; Kenneth Wilkins; Stacey Chung; Varsha Thakur; Lynn Ulatowski; Jeffrey Atkinson; Mikel Ghelfi; Sheila Smith; Hongbin Tu; Gerd Bobe; Chia-Ying Liu; David W Herion; Robert D Shamburek; Danny Manor; Maret G Traber; Mark Levine Journal: JCI Insight Date: 2020-01-16
Authors: Julie Hviid Klaebel; Mia Skjødt; Josephine Skat-Rørdam; Günaj Rakipovski; David H Ipsen; Anne Marie V Schou-Pedersen; Jens Lykkesfeldt; Pernille Tveden-Nyborg Journal: Nutrients Date: 2019-11-19 Impact factor: 5.717