SOD2

The SOD2 gene codes for superoxide dismutase 2 (SOD2). SOD2 is also called MnSOD2. As its name suggests, SOD2 needs the mineral manganese (Mn) to work [R].

SOD enzymes are antioxidants. They help protect against oxidative stress by transforming the toxic molecule superoxide (O2-) into oxygen (O2) and hydrogen peroxide (H2O2) [R, R].

SOD2 variants are linked to [R, R, R, R]:

• Depression

• Higher stress levels

• Cancer

• Parkinson’s disease

• Diabetes

Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.

Read: The Brain Fog Gene: rs4880 or The Main SOD2 SNP.

Superoxide dismutases are enzymes that transform the superoxide (O2ˆ’) radical into either ordinary oxygen (O2) or hydrogen peroxide (H2O2). Superoxide is produced as a by-product of oxygen metabolism and, if not regulated, causes many types of cell damage.

Hydrogen peroxide is also damaging, but less so, and is degraded by other enzymes such as catalase. Thus, SOD is an important antioxidant defense in nearly all living cells exposed to oxygen. This protein plays a protective role against oxidative stress, ionizing radiation, and inflammatory cytokines.

There are a three forms of SOD: SOD1, SOD2 and SOD3. SOD1 is located in the cellular fluid, SOD2 in the mitochondria, and SOD3 outside the cell. Superoxide is one of the main reactive oxygen species in the cell.

As a consequence, SOD serves a key antioxidant role. So SOD2 (also called MnSOD) transforms superoxide produced by your mitochondria into the less toxic hydrogen peroxide and oxygen.

This function allows SOD2 to clear mitochondrial reactive oxygen species (ROS) and confer protection against cell death. Mutations (not variations) in the SOD2 gene have been associated with idiopathic cardiomyopathy (IDC), sporadic motor neuron disease, and cancer.

Mice lacking SOD2 die shortly after birth, amid massive oxidative stress (R). However, mice 50% deficient in SOD2 have a normal lifespan and minimal defects but do suffer increased DNA damage and increased incidence of cancer. In flies, overproduction of SOD2 has been show to increase lifespan by 20%.

Superoxide has a few very positive functions in the body: clearing infections, cellular communication, creating new mitochondria and destroying tumors. However, superoxide is really damaging and pretty much every chronic disease has too much oxidative stress as a contributory cause.

In the modern environment, overall, having a high producing version of SOD2 will be better, so that you have less superoxide.  But there’s a tradeoff. Overproduction of SOD2 has been linked to increased invasiveness of tumor metastasis – presumably because superoxide is needed to kill cancer. (R)

On the other hand, increased superoxide will cause DNA damage and start cancer. SOD inhibits bacterial clearance (R).

     From NCBI Gene: Microvascular complications of diabetes 6From UniProt: Microvascular complications of diabetes 6 (MVCD6): Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [MIM:612634]

     From NCBI Gene: This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016] From UniProt: Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.

Top Fixes if You Have Low SOD2 Levels:

• Vitamin C and E (R)
• PQQ (R)
• Pregnenolone – pregnenolone and downstream hormones are all antioxidants that decrease superoxide.
• Curcumin (R)
• Molecular hydrogen (R)
• Zinc (R)
• Grape Seed Extract (R)