SOD3

Protein:

Superoxide Dismutase 3, Extracellular

SNP ID:

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Superoxide dismutase 3, extracellular (SOD3) is a potent antioxidant enzyme which is encoded for by the SOD3 gene. There are three SOD enzymes found in humans, and as its name suggests SOD3 is secreted outside of cells 1. Functioning to breakdown the harmful superoxide into less harmful products which can then be cleared from the body, SOD3 is expressed in areas particularly at risk of oxidative stress such as the brain or the lungs 2.

Secreted by cells SOD3 binds to the outside of cell membranes and connective tissue and is therefore thought to act as a first line of defense against reactive oxygen species 3. By breaking down superoxide outside the cell it prevents any accumulation within the cell which could lead to protein or DNA damage and in extreme cases cell death.

There is one SNP in the SOD3 gene which is associated with poor health outcomes, rs1799895 or C691G.

C691G

Science Grade
A-
Longevity
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs1799895 c g 11ArgGly

Risk Description

The risk ‘G’ allele of the SNP rs1799895 or C691G in the SOD3 gene is associated with an increased cardiovascular risk 4. Interestingly the same ‘G’ allele is associated with a decreased risk of developing certain fibrotic lung disorders 5.

It is thought that this dual effect arises from changes in the secretion of SOD3 associated with the risk ‘G’ allele. Typically SOD3 is secreted from cells and then binds to the outside of the cell membrane, or to surrounding connective tissues. However, the ‘G’ allele alters this with secreted SOD3 being more likely to float freely. In the circulatory system this means it is rapidly removed exposing the delicate endothelial cells which line the blood vessels and heart to oxidative damage. Whereas in the lung, which contains a natural thin layer of liquid between its epithelial cells, and the air which is inhaled, this altered localisation improves SOD3 efficacy 6.

Direct Nutrients:*

IngredientActive IngredientEffect
Copper

Copper is one of two metal co-enzymes required by SOD3 to function along with zinc 7. Whilst there is no evidence that copper supplementation directly improves SOD3 function it has been shown to increase the amount of SOD3 secreted by cells, with a beneficial effect 8. Therefore those carrying the risk ‘G’ allele of C691G, which is associated with cardiovascular risk, may benefit from supplementation.

Zinc

Zinc, along with copper, is one of two metal co-enzymes required by SOD3 to function 7. There is no evidence demonstrating a beneficial effect on SOD3 activity following zinc supplementation. However, zinc has been shown to demonstrate an antioxidant capacity through unknown means 9, therefore supplementation may benefit those carrying the risk ‘G’ allele of C691G.

Indirect Nutrients:*

IngredientActive IngredientEffect
Vitamin C Ascorbic acid

Vitamin C is one of the most powerful antioxidants which can protect against oxidative stress induced by free radicals 10.

Those carrying the ‘G’ allele of C691G, who display reduced SOD3 activity may therefore benefit from vitamin C supplementation to maintain antioxidant defence.

Vitamin E α-tocopherol

Vitamin E is another potent antioxidant, especially good at processing lipid derived free radicals commonly associated with an increased cardiovascular risk 11.

Supplementation with vitamin E may help preserve antioxidant defence in those carrying the risk ‘G’ allele of C691G, which displays reduced SOD3 activity and an increased cardiovascular risk.

Vitamin A Retinol

Vitamin A is a strong antioxidant, targeting lipid derived free radicals in particular 12.

Supplementation with vitamin A may improve antioxidant defence in those carrying the risk ‘G’ allele of C691G, which displays reduced SOD3 activity.

Tumeric Root Extract Curcumin

Curcumin, often derived from the root of the tumeric plant is a bright yellow chemical with a strong antioxidant capacity. Curcumin has not been shown to influence SOD3 although it can induce SOD2 expression 13. Therefore, supplementation with curcumin may abrogate the loss of SOD3 activity associated with the risk ‘G’ allele, by increasing SOD2 activity.

Zeaxanthin

Zeaxanthin is one of the most common naturally occurring natural plant pigments known as carotenoids. Functioning to absorb energy from light for use in photosynthesis, zeaxanthin also protects the plant from oxidative damage 14.

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 ‘G’ allele of C691G, who display reduced SOD2 antioxidant activity, zeaxanthin supplementation may assist in preventing oxidative damage, through an alternative pathway.

Lutein

Lutein, a natural carotenoid pigment is produced by plants to absorb energy from light for use in photosynthesis, whilst also protecting the plant from damage from oxidative damage associated with excessive light 15.

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.

Supplementation with luetin may prove beneficial to those with impaired antioxidant activity, as is associated with the risk ‘G’ allele of C691G, by providing an alternative antioxidant pathway.

Glutathione

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 SOD3; however, in those carrying the risk ‘G’ allele of C691G which is associated with reduced SOD3 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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