Glutathione peroxidase 1 (GPX1) is a peroxidase enzyme, encoded for by the GPX1 gene which has a strong antioxidant activity. GPX1 is expressed in almost all tissue of the body as it plays a major role in protecting cells from oxidative stress. It’s major function is to detoxify hydrogen peroxide, produced by many reactions within a cell into water which can then be excreted. It can also detoxify lipid peroxides as well 1. As its name suggests GPX1 uses glutathione in order to detoxify hydrogen peroxide and other oxidative agents 1.
Interestingly the GPX1 enzyme is one of the few proteins in humans which contain the non-standard amino acid selenocysteine, which replaces the standard cysteine This replacement is a major contributor to the potent antioxidant activity of GPX1 2.
There is one SNP in GPX1 associated with poor health outcomes, rs1050450 or C559T.
|rsID Number||Major Allele||Minor Allele||Minor Allele Frequency (%)||Major Amino Acid||Minor Amino Acid|
The SNP rs1050450 or C599T is associated with several distinct health risks, arising from alterations in antioxidant activity.
The risk ‘T’ allele of C599T is associated with an increased risk of developing breast cancer, potentially through an increase in oxidative stress, and also possibly a poorer response to anticancer therapies 3. Interestingly the authors report that although lipid peroxides (which increase oxidative stress) are increased, counter intuitively so is GPX1 activity.
An additional paper hypothesises that the risk ‘T’ allele may interfere with the incorporation of the non-standard amino acid selenocysteine into the GPX1 enzyme, which provides its potent antioxidant activity. Therefore, GPX1 function may be increased, but its actual effective activity may be reduced 4.
Additional studies have associated the risk ‘T’ allele of C599T with an increased risk of cancer in general 5, and an increased cardiovascular risk 6. In both instances the populations studied are of East Asian descent so it is unknown if this is a global risk marker.
Glutathione is an important antioxidant in its own right, but is also used by GPX1 as a cofactor. In those carrying the risk ‘T’ allele of C599T which is associated with impaired antioxidant capacity supplementation with glutathione may improve outcomes in two ways 1,7.
Firstly, by being present in sufficient quantities to allow GPX1 to function correctly. Secondly, gluathione functions as a potent antioxidant independently of GPX1 activity. Supplementation may therefore help bypass an limitations associated with the risk ‘T’ allele.
|Vitamin C||Ascorbic acid|
Vitamin C is one of the most potent antioxidants, which can protect against oxidative stress induced by free radicals 8.
Those carrying the ‘T’ allele of C599T, which is associated with reduced antioxidant capacity, may benefit from vitamin C supplementation to maintain antioxidant defence.
Vitamin E is a potent antioxidant, especially for lipid derived free radicals 9.
Supplementation with vitamin E may benefit those carrying the risk ‘T’ allele of C599T, which is associated with reduced antioxidant capacity.
Vitamin A is a strong antioxidant, especially for targeting lipid derived free radicals 10.
In those carrying the risk ‘T’ allele of C599T, associated with reduced antioxidant capacity, vitamin A supplementation may prove beneficial.
|Turmeric Root Extract||Curcumin|
Curcumin which is commonly extracted from turmeric roots demonstrates a beneficial antioxidant effect by increasing SOD2 expression 11.
In those carrying the risk ‘T’ allele of C599T, which is associated with reduced GPX1 antioxidant capacity, curcumin supplementation may prove beneficial by increasing the overall antioxidative capacity of the body.
In those carrying the ‘C’ allele of C599T, selenium supplementation provided a beneficial effect decreasing DNA damage. However, in those carrying the risk ‘T’ allele DNA damage was increased in those with higher dietary selenium intakes 12.
Therefore, assuming a normal dietary intake of selenium, those carrying the risk ‘T’ allele of C599T may wish to avoid supplementation, or consider a simple blood test to determine their risk.
Discuss this information with your doctor before taking any course of action.