Author's response: Pandolfo M (2008) Author response to “Reply to Drug Insight: antioxidant therapy in inherited ataxias”. Nat Clin Pract Neurol 4: E2 doi:10.1038/ncpneuro0834
We read with great interest and curiosity the recent Review entitled Drug Insight: antioxidant therapy in inherited ataxias.1 We acknowledge that the review criteria included the search terms “vitamin E” and “oxidative stress”, and on the basis of these criteria, are inclined to overlook Professor Pandolfo's assertion that vitamin E is an antioxidant (page 90). We are, however, very concerned that the Review ignores scientific literature that questions the antioxidant role of vitamin E.2,3,4
More importantly, recent studies suggest that chronic vitamin E deficiency in a mouse model of ataxia with vitamin E deficiency (AVED) decreases superoxide production from mitochondria and decreases oxidative stress in the brain.5 The lungs6 and heart7 of the AVED mouse also show a lack of oxidative stress. To the best of our knowledge, there is not a single study in AVED humans that has assayed markers of oxidative stress in the affected tissue. Vitamin E deficiency should, therefore, not be equated with increased oxidative stress.
References
Pandolfo M (2008) Drug Insight: antioxidant therapy in inherited ataxias. Nat Clin Pract Neurol 4: 86–96
Azzi A and Stocker A (2000) Vitamin E: non-antioxidant roles. Prog Lipid Res 39: 231–255
Ricciarelli R et al. (2002) The 80th anniversary of vitamin E: beyond its antioxidant properties. Biol Chem 383: 457–465
Azzi A (2007) Molecular mechanism of α-tocopherol action. Free Radic Biol Med 43: 16–21
Cuddihy SL et al. (2008) Prolonged α-tocopherol deficiency decreases oxidative stress and unmasks α-tocopherol-dependent regulation of mitochondrial function in brain. J Biol Chem 283: 6915–6924
Gohil KS et al. (2007) Tocopherol transfer protein deficiency modifies nuclear receptor transcriptional networks in lungs: modulation by cigarette smoke in vivo. Mol Aspects Med 28: 453–480
Vasu VT et al. (2007) Genome-wide screening of alpha-tocopherol sensitive genes in heart tissue from alpha-tocopherol transfer protein null mice (ATTP−/−). FEBS Lett 581: 1572–1578
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Gohil, K., Azzi, A. Reply to Drug Insight: antioxidant therapy in inherited ataxias. Nat Rev Neurol 4, E1 (2008). https://doi.org/10.1038/ncpneuro0833
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DOI: https://doi.org/10.1038/ncpneuro0833
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