Analysis of Multiple Metabolites of Tocopherols and Tocotrienols in Mice and Humans

Abstract

Tocopherols and tocotrienols, collectively known as vitamin E, are essential antioxidant nutrients. The biological fates and metabolite profiles of the different forms are not clearly understood. The objective of this study is to simultaneously analyze the metabolites of different tocopherols and tocotrienols in mouse and human samples. Using HPLC/electrochemical detection and mass spectrometry, 18 tocopherol-derived and 24 tocotrienol-derived side-chain degradation metabolites were identified in fecal samples. Short-chain degradation metabolites, in particular γ-and δ-carboxyethyl hydroxychromans (CEHCs) and carboxymethylbutyl hydroxychromans (CMBHCs) were detected in urine, serum and liver samples, with tocopherols additionally detected in serum and liver samples. The metabolite profiles of tocotrienols and tocopherols were similar, but new tocotrienol metabolites with double bonds were identified. This is the first comprehensive report describing simultaneous analysis of different side-chain metabolites of tocopherols and tocotrienols in mice and humans. Urinary metabolites may serve as useful biomarkers for nutritional assessment of vitamin E.

Metabolism of tocotrienols in animals and synergistic inhibitory actions of tocotrienols with atorvastatin in cancer cells

“…These metabolites are similar to those reported in HepG2 cells (Birringer et al 2002). Importantly, we also identified three additional groups of T3 metabolites: major peaks of CMBenHCs with one double bond in the side chain, minor peaks of carboxydimethyloctadienyl hydroxychromans (CDMO(en) 2 HCs) with two double bonds, and carboxyl tocotrienols (Zhao et al 2010). Based on these results, we proposed the degradation pathway of T3s as shown in Fig.…”

“…We first used this sensitive HPLC/ECD coupled with LC-MS to identify and characterize different side chain metabolites of T3s in mouse fecal and urine samples (Zhao et al 2010). In fecal samples from the mice fed with diets supplemented with mixed T3s (20.2% a-T3, 4.0% b-T3, 16.1% c-T3, 9.9% d-T3, 14.8% a-tocopherol, and 3.1% c-tocopherol), d-, c-, and a-CEHCs and CMBHCs, as well as some new metabolites, were observed in HPLC chromatogram.…”

“…In fecal samples from the mice fed with diets supplemented with mixed T3s (20.2% a-T3, 4.0% b-T3, 16.1% c-T3, 9.9% d-T3, 14.8% a-tocopherol, and 3.1% c-tocopherol), d-, c-, and a-CEHCs and CMBHCs, as well as some new metabolites, were observed in HPLC chromatogram. A new metabolite was identified as c-carboxymethylbutenyl hydroxychroman (CMBenHC) (Zhao et al 2010). It is worth noting that more short-chain metabolites of T3s were present than long-chain metabolites.…”

Extraction, purification and nuclear magnetic resonance (NMR) assignment of garcinoic acid from Garcinia kola (bitter kola) fruit

“…The vitamin E family comprises of a mixture of eight chromanols, compounds 1 to 4 (Figure 1) differing both by the extent and position of methylation on the aromatic ring and the degree of unsaturation in the prenyl-based side-chain (DellaPenna, 2005;Gerald, 2007;Zhao et al, 2010). Their lipid soluble antioxidant behaviour has been appreciated for many years and both naturally occurring and synthetically derived samples are widely used in the food industry (Zhao et al, 2010;Rein et al, 2007;Gerald, 2007).…”

“…Their lipid soluble antioxidant behaviour has been appreciated for many years and both naturally occurring and synthetically derived samples are widely used in the food industry (Zhao et al, 2010;Rein et al, 2007;Gerald, 2007). Plants represent the main natural source of vitamin E, where biosynthetically they are derived/ originate from the plastoquinone pathway (DellaPenna, 2005;Sontag and Parker, 2002).…”