A Metabolomic Investigation of the Effects of Vitamin E Supplementation in Humans

Max Wong; John K Lodge


Nutr Metab. 2012;9(110) 

In This Article


It is well established that nutrients interact with metabolic pathways at various levels and have multiple targets. With the increasing use of '-omic' technologies in nutritional research[1] it is now becoming possible to further explore the influence of single nutrients or dietary change on physiological processes.

Vitamin E has been widely researched owing to its antioxidant[2] and non-antioxidant functions[3] and its potential as a cardioprotective agent. Vitamin E appears to have wide ranging effects on cellular systems with the ability to inhibit protein kinase C, activating diacylglycerol kinase (decreasing diacylglycerol availability) and protein phosphatase 2A,[4] regulating specific gene expression;[5,6] in this way vitamin E can influence a number of biological functions and metabolism. Interestingly, α-TTP knock out mice (model of vitamin E deficiency) had lower glucose levels, improved glucose tolerance and increased insulin excretion[7] indicating a role for α-tocopherol regulation in glucose control. Vitamin E supplementation has been shown to influence platelet[8] and mononuclear cell functions,[8,9] and reduce indices of oxidative stress and inflammation[10] in humans. However vitamin E may also have potential detrimental actions as high dose (>400 mg/d) supplementation was found to increase mortality in a meta-analysis[11] and high dose supplementation has been proposed to potentially interfere with drug metabolism.[12] As nutrients generally have multiple targets and interactions, it is likely that vitamin E has alternate functions and can further influence metabolic pathways.

Metabolomics offers the opportunity to investigate global changes to metabolites in biological samples and there is much interest in this technology for nutritional studies.[1,13] Potential opportunities include a further understanding of the interactions of whole diet or individual nutrients on metabolic pathways, the metabolic interactions between diet and disease, and developing biomarkers for dietary exposure and/or disease.[14,15] Metabolomic technology has been applied to a number of nutritional studies (reviewed in[1,16]), allowing investigators to compare the influence of dietary patterns on metabolite profiles,[17] monitor nutrient metabolism or identify novel metabolic pathways influenced by the nutrient.[18] Interestingly metabolomics has previously been used in animal models to investigate vitamin E metabolism. Following pregnane X receptor activation in knockout mice there was an attenuation of α-tocopherol metabolism but production of a novel γ-tocopherol metabolite.[19] Novel vitamin E metabolites were also found by Johnson et al. in human and mouse models by LC/MS.[20] In a mouse model of neuronal ceroid lipofuscinosis, vitamin E supplementation reversed metabolic abnormalities associated with the phenotype.[21] In a rat liver model of vitamin E deficiency, the authors found metabolic changes associated with amino acids, glucose and purines that suggested shifts in energy metabolism with deficiency.[22] In the only human metabolic study involving vitamin E, metabolomics was successfully used to determine 'predictors of response' to vitamin E treatment in subjects with Non-Alcoholic Steatohepatitis.[23] These studies demonstrate that vitamin E can influence metabolic pathways and so it is of interest to investigate other potential interactions in a human supplementation study.

We have previously highlighted that metabolomics can be used to provide insights into how vitamin E can influence the metabolome[16] and in the present study we have expanded on these observations to identify subtle but distinct changes to human plasma metabolome following vitamin E supplementation, the main effects of which include significant increases in the intensities of a number of lysophospholipid species.