Urinary α-carboxyethyl hydroxychroman can be used as a predictor of α-tocopherol adequacy, as demonstrated in the Energetics Study

Lebold, Katie M.; Ang, Alfonso; Traber, Maret G.; Arab, Lenore

doi:10.3945/ajcn.112.038620

Cited by 44 publications

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“…In the current study, only healthy women had least-squares mean 6 SEM urinary a-CEHC concentrations (1.26 6 0.11 mmol/g creatinine) that approached this cutoff, whereas healthy men (0.87 6 0.11 mmol/g creatinine), women with MetS (0.77 6 0.11 mmol/g creatinine), and men with MetS (0.48 6 0.11 mmol/g creatinine) excreted less (health status, P ¼ 0.0002; sex, P ¼ 0.003, health status 3 sex, P ¼ 0.64; n ¼ 5/sex in each health status group). Given that the sample set from which we derived the cutoff was predominantly diet-conscious women (20), we expected that our current participants, who were nonusers of dietary supplements, would fall below this cutoff, which is a finding that is consistent with the 92% of men and 98% of women in the United States who fail to meet the Estimated Average Requirement for a-tocopherol (22).…”

Section: Discussionsupporting

confidence: 53%

“…Hypothetically, a-carboxyethyl hydroxychromanol (a-CEHC) is synthesized endogenously when the quantity of hepatic a-tocopherol exceeds the capacity of a-TTP to facilitate a-tocopherol secretion from the liver into the circulation. Indeed, urinary a-CEHC excretion has been correlated with increasing amounts of both dietary and plasma a-tocopherol concentrations in healthy participants (20). However, to our knowledge, it is unknown whether urinary a-CEHC excretion reflects a-tocopherol intake from a single meal or whether its changes reflect long-term vitamin E status.…”

Section: Introductionmentioning

confidence: 86%

“…We previously suggested that a cutoff of excreted urinary a-CEHC .1.39 mmol/g creatinine was associated with morethan-adequate vitamin E intakes (20). In the current study, only healthy women had least-squares mean 6 SEM urinary a-CEHC concentrations (1.26 6 0.11 mmol/g creatinine) that approached this cutoff, whereas healthy men (0.87 6 0.11 mmol/g creatinine), women with MetS (0.77 6 0.11 mmol/g creatinine), and men with MetS (0.48 6 0.11 mmol/g creatinine) excreted less (health status, P ¼ 0.0002; sex, P ¼ 0.003, health status 3 sex, P ¼ 0.64; n ¼ 5/sex in each health status group).…”

Section: Discussionmentioning

confidence: 99%

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Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Traber

Mah

Leonard

et al. 2017

The American Journal of Clinical Nutrition

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Background: Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that a-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements. Objective: We hypothesized that a-tocopherol catabolites a-carboxyethyl hydroxychromanol (a-CEHC) and a-carboxymethylbutyl hydroxychromanol (a-CMBHC) are useful biomarkers of a-tocopherol status. Design: Adults (healthy or with MetS; n = 10/group) completed a double-blind, crossover clinical trial with four 72-h interventions during which they co-ingested 15 mg hexadeuterium-labeled RRR-a-tocopherol (d 6 -a-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured a-CEHC and a-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma a-tocopherol, a-CEHC, and a-CMBHC concentrations at various times #72 h. Results: During the first 24 h, participants with MetS compared with healthy adults excreted 41% less a-CEHC (all values are leastsquares means 6 SEMs: 0.6 6 0.1 compared with 1.0 6 0.1 mmol/g creatinine, respectively; P = 0.002), 63% less hexadeuterium-labeled (d 6 )-a-CEHC (0.04 6 0.02 compared with 0.13 6 0.02 mmol/g creatinine, respectively; P = 0.002), and 58% less d 6 -a-CMBHC (0.017 6 0.004 compared with 0.041 6 0.004 mmol/g creatinine, respectively; P = 0.0009) and had 52% lower plasma d 6 -a-CEHC areas under the concentration curves [area under the curve from 0 to 24 h (AUC 0-24h ): 27.7 6 7.9 compared with 58.4 6 7.9 nmol/L 3 h, respectively; P = 0.01]. d 6 -a-CEHC peaked before d 6 -a-T in 77 of 80 paired plasma concentration curves. Urinary d 6 -a-CEHC 24-h concentrations were associated with the plasma AUC 0-24 h of d 6 -a-T (r = 0.53, P = 0.02) and d 6 -a-CEHC (r = 0.72, P = 0.0003), and with urinary d 6 -a-CMBHC (r = 0.88, P , 0.0001), and inversely with the plasma inflammation biomarkers C-reactive protein (r = 20.70, P = 0.0006), interleukin-10 (r = 20.59, P = 0.007), and interleukin-6 (r = 20.54, P = 0.01). Conclusion: Urinary a-CEHC and a-CMBHC are useful biomarkers to noninvasively assess a-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs a-tocopherol trafficking. This trial was registered at clinicaltrials.gov as NCT01787591.Am J Clin Nutr 2017;105:571-9.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Traber

Mah

Leonard

et al. 2017

The American Journal of Clinical Nutrition

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“…From a spline curve of median daily urinary α-CEHC excretion according to dietary α-tocopherol, Lebold et al (2012) visually estimated that the median excretion remained at a plateau of about 1.39 µmol/g creatinine until an intake of about 9 mg α-tocopherol/day, then the slope of the curve increased (Section 2.4.3).…”

Section: Conclusion On Indicators Of α-Tocopherol Requirement For Admentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for vitamin E as α‐tocopherol

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2015

EFS2

111

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Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for vitamin E. In this Opinion, the Panel considers vitamin E as α-tocopherol only. The Panel considers that Average Requirements (ARs) and Population Reference Intakes (PRIs) for vitamin E (as α-tocopherol) cannot be derived for adults, infants and children, and therefore defines Adequate Intakes (AIs), based on observed intakes in healthy populations with no apparent α-tocopherol deficiency in the EU. This approach considers the range of average intakes of α-tocopherol and of α-tocopherol equivalents estimated by EFSA from dietary surveys in children and adults in nine countries. The Panel notes the uncertainties in the available food composition and consumption data, the fact that most EU food composition databases contain values for vitamin E as α-tocopherol equivalents, as well as the contribution of average α-tocopherol intakes to average α-tocopherol equivalent intakes in these countries. For adults, an AI for α-tocopherol is set at 13 mg/day for men and 11 mg/day for women. For children aged 1 to < 3 years, an AI for α-tocopherol is set at 6 mg/day for both sexes. For children aged 3 to < 10 years, an AI for α-tocopherol is set at 9 mg/day for both sexes. For children aged 10 to < 18 years, an AI for α-tocopherol is set at 13 mg/day for boys and 11 mg/day for girls. For infants aged 7-11 months, an AI for α-tocopherol of 5 mg/day is derived by extrapolating upwards from the estimated α-tocopherol intake in exclusively breast-fed infants aged 0-6 months and rounding. For pregnant or lactating women, the Panel considers that there is no evidence for an increased dietary α-tocopherol requirement, and the same AI is set as for non-pregnant non-lactating women. Vitamin E is a fat-soluble vitamin. Previously, the term vitamin E was used as the generic term for four tocopherols (α, β, γ, δ) and four tocotrienols (α, β, γ, δ), which are organic compounds that possess antioxidant activity to a different degree. Factors have been used to convert food contents of tocopherols and tocotrienols to α-tocopherol equivalents. In this Opinion, based on the available evidence and in line with other authoritative bodies, the Panel considers vitamin E as being α-tocopherol only. Its naturally occurring form is RRR-α-tocopherol. Commercially available forms of α-tocopherol include RRR-α-tocopherol, a synthetic form that contains in equal proportions the eight stereoisomers of α-tocopherol (RRR-, RRS-, RSR-, RSS-and their enantiomers SSS-, SSR-, SRS-, SRR-) and is called all-rac-α-tocopherol, and their esterified forms. © EuropeanEfficient α-tocopherol absorption requires the presence of fat. The Panel considered that the average α-tocopherol absorption from a usual diet is about 75 %. This is based on the means observed in two balance studies and in a kinetic study using a multi-compartmental model of α-tocopherol metabolism. After its intestinal absorption, α-toc...

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“…Moreover, CYP4F2 activity toward ␣ -tocopherol was limited relative to other forms of vitamin E ( 122 ). An inhibitor of CYP4F , an omega imidazole-containing compound 1,[(R)-2-(9-(1H-imidazol-1-yl)nonyl)-2,5,7,8-tetramethylchroman-6-ol], decreased CEHC production from ␥ -tocopherol in HepG2 cells in culture and increased plasma There appears to be a threshold in ␣ -CEHC excretion that corresponds to ␣ -tocopherol intake; this increase in ␣ -CEHC excretion has been proposed as an indicator to ␣ -tocopherol adequacy ( 165 ). It is important to note that ␣ -CEHC excretion does increase to a greater extent if supplements or foods fortifi ed with all racemic ␣ -tocopherol are consumed ( 162 ), because ␣ -CEHC levels increase to a greater extent in response to 2S-␣ -tocopherols ( 112 ).…”

Section: Phase I Cypmentioning

confidence: 99%

Mechanisms for the prevention of vitamin E excess

Traber

2013

Journal of Lipid Research

120

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Urinary α-carboxyethyl hydroxychroman can be used as a predictor of α-tocopherol adequacy, as demonstrated in the Energetics Study

Abstract: Thus, urinary α-CEHC is a valid biomarker of α-tocopherol status that can be used to set a value for the Estimated Adequate Requirement of vitamin E.

Cited by 44 publications

References 38 publications

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Scientific Opinion on Dietary Reference Values for vitamin E as α‐tocopherol

Mechanisms for the prevention of vitamin E excess

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