About SOD2 and How to Increase It (Including SOD2 Genes/SNPs)

The SOD2 is an important gene the people should check up.

If you want to check what you have, you need to order your 23andme.

If you want to interpret your genes, you can use SelfDecode.

About Superoxide Dismutase 2 (SOD2)

Superoxide dismutases are enzymes that transform the superoxide (O2−) 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 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 the incidence of cancer.

In flies, overproduction of Sod2 has been shown to increase lifespan by 20%.

The Positives and Negatives of Superoxide Dismutase 2



Superoxide has a few very positive functions in the body: clearing infections, cellular communication, creating new mitochondria and destroying tumors.

However, superoxide is damaging, and 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).

SOD2 Genes: Do You Have High or Low SOD2?

The SOD2 gene has a bunch of SNPs from 23andme.

Most important SOD2 SNP:

  1. RS4880 (SOD2) GG

Other SOD2 SNPs:

  1. RS10370 (SOD2) TT
  2. RS2758331 (SOD2) AA
  3. RS2758339 (SOD2) CC
  4. RS2758346 (SOD2) TT

My Experience With SOD2 SNPs

The GG genotype is much more common in my brain fog clients because brain fog is most commonly a result of oxidative stress.

People who have AA tend to have a lot of other bad genes or might have an infection – because having less superoxide in this cause might not be beneficial.

Top Fixes if You Have Low SOD2 Levels

How to Increase SOD




Since studies often don’t distinguish what kind of SOD something increases, I just list them all here.

Most herbal supplements increase SOD, but here’s some that I happened to have references for……

Supplements That Decrease Superoxide

Hormones That Reduce Superoxide

Hormones That Increase Superoxide

You should be aware that the following hormones increase superoxide.  They need to be balanced.


You should make sure your breathing is good.  Sleep apnea or intermittent hypoxia can cause excess superoxide (R).


  1. Maddy

    What about SOD3??? The extracellular component. Is it copper and zinc dependent?
    Can boosting glutathione via liposomal supplement (which boosts serum levels) help compensate for low SOD3? Can glutathione in the extracellular space scavenge superoxide also?

    And on SOD2, presuming I understand this right and this version is intracellular and works at mitochondrial level, does adenoB12 help the SOD2 enzyme? Same thinking on glutathione, as the acetyl-glutathione reportedly raises intra-cellular glutathione.

    Also…SOD3 gene transfer in animals lowers insulin resistance, reduced obesity, increased adiponectin, lowered TNFa and IL6…


  2. Tina Stonely

    Hi there interesting reading but trying to establish how to move forward having identified I have SOD2 rs4880 G/G +|+. I believe this means I need to upregulate or boost SOD metabolism in the mitochondria. Is this correct?


  3. Learner

    Homozygous for SOD2 SNPs here…. Doing HBOT and ozone to kill chronic infections. Good for killing bugs, but is there a problem, given the SOD2 SNPs, or am I asking for a peroxynitrite mito membrane shredding problem?


        • Learner

          It seems not. Thank you for pushing me to find the details.it seems that study only looked at SOD1, not SOD2, so we actually don’t know what happened with SOD2 – it very well have helped but they didn’t measure it.

          However, this study shows that SOD2 was altered in a time dependent manner in Wistar rats with brain injuries.


          From what I’ve learned at conferences for doctors, having the SNPs doesn’t necessarily mean a process doesn’t work at all – many times it’s just bottlenecked, making those of us with them having to work harder.

          Anecdotally, I’ve done about 25 HBOT sessions, and while I felt a little woozy after the first 4 or so, I now am feeling that they’re benefiting me tremendously. (I also take manganese bisglycinate, and have been on a comprehensive antioxidant program including IV glutathione and vitamin C, before and during my HBOT treatments.)

  4. cheri

    Hi, I’m a bit confused. I am GG for SOD2 rs4880. Is PQQ a supplement you should take if you are low and need it to come up, or the opposite? At the top of this article it says PQQ is good for if you have low SOD2 levels, then at the bottom, it has PQQ listed under the category saying it decreases SOD. Thanks!

    • Brett

      Because SOD supplements like GilSODin and Extramel (French Melon Extract) only produce SOD1 – not the mitochondrial MnSOD2 that is used in the mitochondria, which the SOD2 A16V SNP can cause lower levels of.

      • nicole shipman

        I have all of the SOD snp’s. I take SOD from seeking Health and it seems to help a bit but is not miraculous. I will try the maganese and MitoQ. Any other recommendations?
        SOD2 rs2758331 AA +/+
        SOD2 rs4880 GG +/+
        SOD3 rs2855262 CC +/+

  5. Hello Joseph,

    I have AG alleles on SOD2 gene. My serum zinc blood levels are always high 151 mcg/dL (ref range is 68 – 107) and I know this could be due to SOD2 SNP. Zn/Cu and manganese imbalance, what do you think about it?

    Thanks for all.

  6. Hi Joseph,

    My SOD2 gene is AG… my zinc blood serum levels are out of range (high), can it be related in some way with this gene and with Zn/Cu and manganese disorders?

    Thanks for all.

  7. Matt

    I am confused. Am i looking at minor allele or geno type? My information is : SOD2 rs4880 G AA -/-. Anyone have any input? thanks!

  8. Hey Joseph.

    So I have had this experience today, strangely the same day you chose to write about brain fog and I had to ask you this question, but first the background.

    So I usually take pregnenolone, 25-50 mg and to be honest I have noticed jack-sh*t from it. I take a few other supplements, calcium, magnesium, vitamin C etc but as of now I am trying to keep the amount of supplements I am taking low as I want to be able to differentiate between those that I can feel an effect from and those I cannot.
    So, a strange but lovely thing happens today, actually only a few hours ago.
    I come home from working out and open the fridge to get out some vitamin D, vitamin k2 and krill oil. For some reason I look at my pregnenolone container and without thinking I down an extra 150 mg(mcg?) on top of the 50 I took in the morning. No big deal I think and the vitamin D, vitamin k2 and krill is just standard supplements for me, taking those for a long time.

    A curious thing has happened though – I don’t feel fatigued or cognitively foggy anymore, which I usually do, most of the time during my waking hours. This is horrible and was actually the primary reason why I came to your site, it is such an excellent source for information and I cannot commend you enough for it. Being the citizen scientist I am, I immediately start pondering over this curious incident, because it so so unexpected and profound. As mentioned, I have been taking the krill oil, vitmain K and D along with all the other supplements for months. I mentioned I came home from a work out, nothing new there either. So I apply Occams Razor and deduce that it must be the pregnenolone working. The effect is quite dramatic, I don’t feel wired or spaced out, I just feel really good, a feeling I honestly can’t remember the last time I had. So my question is, have I accidently solved a long-term health issue by ramping up my intake of pregnenolone dramatically and is this something I can keep on doing to keep this very positive improvement?



  9. Brandon Gregg

    I think Life Extension Foundation ( lef.org ) has the best quality supplements, plus their monthly magazine is vastly superior to any other supplement seller. Why don’t you recommend any of their products or their well researched articles? They have an impressive panel of medical advisers, and use some of their proceeds to run clinical trials, as well as having knowledgeable yet free advisers. Check out their website and read some of their articles and you will be impressed.
    P.S. I have been fighting 24/7 major depression for 35 + years, have tired all the meds, do clinical trials as a human guinea pig, have had the vagus nerve simulator implanted ( then ex-planted – – – nice scars ), TMS, etc. Still fighting, still looking for something that works ( am now trying Botox ), and will try your LLLT recommendations when this study is over.
    P.P.S. Thanks for all you do. You are making a difference.

    • Joseph M. Cohen

      LFE is too expensive most of the time – other companies are cheaper for the same product. I try to give people the cheapest supps that aren’t lower in quality.

    • Steve Weiss

      Vastly superior? Any company that uses stearate(s), not so superior — and that leaves me questioning the rest of their supply chain. If I can get a Thorne, Pure Encapsulations, Healthy Origins, Apex, etc, for about the same price, that’s vastly superior.

  10. Niki

    This is right up my alley of interest, SOD and it’s relationship with bioavailable copper and mineral imbalances and how those relate to my chronic illness… now to go through my 23andm2 results!

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