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Superoxide dismutase 2, mitochondrial (SOD2) is a potent antioxidant enzyme which is encoded for by the SOD2 gene. SOD2 is one of three SOD enzymes found in humans, and as its name suggests SOD2 is expressed specifically in the mitochondria where it functions to clear superoxide 1. Superoxide is a by-product of the energy generating process which is constantly occurring in occurring in our mitochondria and is biologically very toxic 2. Indeed, it is often used by cells of the immune system to target and kill invading pathogens 3.

SOD2 plays a key role by processing superoxide into less harmful products which can then be processed or cleared outside of the mitochondria, allowing continued mitochondrial function and preventing damage.

There is one SNP in the SOD2 gene which is associated with poor health outcomes, rs4880 sometimes called T47C or A16V.

T47C, A16V

Science Grade
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs4880 c t 50 Ala Val

Risk Description

There has been much confusion about which allele of T47C presents the risk. It has been shown that the ‘C’ (GCT) allele produces an alanine amino acid in the SOD2 protein, whereas the ‘T’ (GTT) allele produces a valine amino acid.

The (C) alanine containing SOD2 has been shown to move into the mitochondria more readily than the (T) valine containing form. The reduced amount of SOD2 in the mitochondria associated with the (T) valine form of SOD2 was then shown to lead to reduced superoxide processing leading to its accumulation and mitochondrial damage. It is therefore now widely accepted that the ‘T’ allele is the risk allele for T47C in SOD2 46.

The risk ‘T’ allele has been associated with several poor outcomes including increased risk of diabetes 7, cardiovascular disease 8 and cancer 9.

Direct Nutrients:*

Ingredient Active Ingredient Effect

SOD2 is sometimes known as manganese-dependent superoxide dismutase as it requires manganese as a cofactor in order to function.

Supplementation with manganese has been shown to increase SOD2 activity in two lab models, but it is unclear if there will be a direct benefit to humans 11,12.

Indirect Nutrients:*

Ingredient Active Ingredient Effect
Vitamin C Ascorbic acid

Vitamin C is one of the most potent antioxidants, which can protect against oxidative stress induced by free radicals 13.

Those carrying the ‘T’ allele of T47C, who display reduced SOD2 activity may benefit from vitamin C supplementation to maintain antioxidant defence.

Vitamin E α-tocopherol

Vitamin E is a potent antioxidant, especially for lipid derived free radicals 14.

Supplementation may help preserve antioxidant defence in those carrying the risk ‘T’ allele of T47C, which displays reduced SOD2 activity.

Vitamin A Retinol

Vitamin A is a strong antioxidant, especially for targeting lipid derived free radicals 15.

Supplementation with vitamin A may prove beneficial to those with a reduced antioxidant capacity, as is associated with the risk ‘T’ allele of T47C.

Tumeric Root Extract Curcumin

Curcumin is a bright yellow chemical produced by many plants, although it is typically extracted from tumeric roots which are an especially rich source.

Numerous health benefits have been ascribed to curcumin including a reduction in oxidative damage mediated through increased expression of SOD2 16. Therefore, in those carrying the risk ‘T’ allele of T47C supplementation with curcumin may restore, or improve antioxidant function.


Zeaxanthin is one of the most common naturally occurring compounds known as carotenoids. These natural plant pigments absorb energy from light for use in photosynthesis, whilst also protecting the plant from oxidative damage arising from excessive light 17.

Animals cannot synthesize zeaxanthin and so must acquire it from their diet, with reddy vegetables and spices such as paprika or saffron being rich sources.

In those carrying the ‘T’ allele of T47C, who display reduced SOD2 antioxidant activity, zeaxanthin supplementation may assist in preventing oxidative damage.


Lutein is one of over 600 naturally occurring compounds known as carotenoids. These natural pigments are produced by plants to absorb energy from light for use in photosynthesis, whilst also protecting the plant from oxidative damage from excessive light 18.

Animals are incapable of synthesizing lutein and so must acquire it from their diet, with dark green plants such as spinach or kale being particularly rich sources. Therefore supplementation with luetin may prove beneficial to those with impaired antioxidant activity, as is associated with the risk ‘T’ allele of T47C.


Glutathione is an important antioxidant in its own right, but is also used by the glutathione peroxidase family of antioxidant enzymes. There is no direct interaction with SOD2; however, in those carrying the risk ‘T’ allele of T47C which is associated with reduced SOD2 antioxidant capacity, glutathione may supplement for this reduced activity.

Discuss this information with your doctor before taking any course of action.


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