Mechanisms for the prevention of vitamin E excess

Traber, Maret G.

doi:10.1194/jlr.r032946

Cited by 116 publications

(102 citation statements)

References 181 publications

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“…Hepatic a-T can be excreted in bile, but whether this pathway is affected by MetS is unknown. However, data from the current study indicate that MetS limits the hepatic metabolism of a-T to a-CEHC, which can be secreted in bile for fecal excretion or secreted into plasma, transported to the kidney, and excreted in urine, as reviewed by Traber (12). Alternatively, hepatic a-T can be sequestered in steatotic hepatocytes, which is consistent with the observation that MetS patients are frequently afflicted by nonalcoholic fatty liver disease (2).…”

Section: Figuresupporting

confidence: 87%

“…Urine was collected in 8-h intervals during the first 24 h of each milk intervention. Blood samples were collected before (0 h) and at 3,6,9,12,24,36,48, and 72 h after co-ingestion of test beverages and d 6 -a-T. Plasma a-tocopherol (10) and its catabolites a-CEHC and a-CMHBC were assessed from blood that was collected into evacuated tubes containing sodium heparin.…”

Section: Participants and Study Designmentioning

confidence: 99%

“…a-TTP can facilitate a-T's transfer to VLDL, which is enriched with a-T to a lesser extent in MetS (10). Secreted VLDL is metabolized to LDL and HDL in the circulation (31); all mechanisms for lipid delivery to tissues can transport a-T to extrahepatic tissues and facilitate its return to the liver (12). Plasma a-T disappearance is slower, and a-T enrichment in both LDL and HDL occurs to a lesser extent, in adults with MetS (10).…”

Section: Figurementioning

confidence: 99%

“…For a-tocopherol, the term bioavailability (11) is defined as the extent and rate of the incorporation of a-tocopherol into the circulation and is dependent on absorption, lipoprotein incorporation, trafficking, and lipoprotein-mediated tissue uptake as well as liver a-tocopherol catabolism (12). Thus, the time to achieve maximum plasma a-tocopherol concentrations from an oral-labeled dose is fairly long and usually observed at 9-12 h postdosing (10,(13)(14)(15).…”

Section: Introductionmentioning

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: Figuresupporting

confidence: 87%

Section: Participants and Study Designmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

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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“…No specific plasma transport protein for α-TOH has yet been described [43,63] . The transport of vitamin E in blood circulation follows largely that of cholesterol within lipoprotein metabolism [64] .…”

Section: Vascular Transportmentioning

confidence: 99%

Complexity of vitamin E metabolism

Schmölz¹,

Birringer²,

Lorkowski³

et al. 2016

WJBC

175

138

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Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e. , when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their sidechain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a REVIEW

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