Superoxide dismutase 2 – my genetic timebomb?

time-running-out[N]early 2 years after receiving my 23andme genetic information, I’m still piecing together the puzzle but… my SOD2 polymorphisms are starting to look more and more like the ticking time bomb. Or, maybe a better metaphor is a bridge that crumbled underneath of me slowly for years and then suddenly washed away.

For those who’ve done either their 23andMe or AncestryDNA test, this is a link to check your results for SOD SNPs. Click “View Report” to get your results.

From my genetics report:

SOD2 rs2758331 A AA +/+
SOD2 rs2855262 T CT +/-
SOD2 A16V rs4880 G GG +/+
The SOD2 gene is a member of the iron/manganese superoxide dismutase family. This protein transforms toxic superoxide, a byproduct of the mitochondrial electron transport chain, into hydrogen peroxide and diatomic oxygen. The more energy your mitochondria produce, the more byproducts (free radicals) get produced. The toxic byproducts tear up cell membranes and walls through a process called oxidative stress.  Mutations in the SOD2 gene diminish your ability to transform these toxic byproducts into harmless (and beneficial) components.

livewello-sod2Not all of my SOD2 genes are defective — I was relatively healthy at 10 years old. A more complete picture of my SOD2 flaws at the right comes from

What probably happened is that heavy metals and possibly other toxins began to interfere with my already limited production of SOD2. Mercury is known to disrupt the functioning of many many enzymes in your body and I did find some evidence that SOD2 maybe one of them (see study 1 and study 2).

Mercury is the most potent enzyme inhibitor that exists; it is in a class of its own and well deserves its title as the most toxic non-radioactive element. Since mercury and lead attach themselves… read more

While mercury can disrupt the functioning of a critical enzyme like SOD2, it also induces additional oxidative stress making my diminishing supply of SOD2 even less adequate.

Here’s where the vicious cycle gets even darker – as my body’s supply of life-giving superoxide dismutase 2 (also known as MnSOD or manganese superoxide dismutase) was diminishing, my body produced less hydrogen peroxide and less oxygen as a consequence, thereby allowing mold and pathogens to proliferate in my gut.

Molds produce mycotoxins and pathogens produce other toxins further increasing oxidative stress.

The end result? My SOD2 levels are  insufficient to cope with the natural oxidative stress caused by walking up a few flights of stairs. That’s chronic fatigue in a nutshell.

As I write this, it’s feeling kind of tragic. But fortunately, not all genetic flaws are irreparable. Remember that I was healthy when I was 10 years old. My physical endurance was probably low (but at the time I still didn’t know it).

Remarkably, I may be in luck because there are some ways of treating SOD deficiency:

  • Extramel – note this is an SOD1 supplement, not SOD2. You can read about it at LEF, who also makes supplements containing Extramel: Endothelial DefenseSODzyme and Liver Efficiency Formula.
  • Fullerene (C60) – Buckminsterfullerene, also known as fullerene C60, is a sphere-like molecule made entirely of carbon atoms. Fullerene C60 is composed of 60 carbon atoms arranged in hexagon formations that combine to form a hollow spherical structure, giving it the nickname “buckyball”. C60 molecules often aggregate into large particles.  As a substance, it is highly stable but also insoluble in water, unless it is in its hydrated form. A derivative of the fullerene C60 molecule (C3) has been shown capable of removing the biologically important superoxide radical with a rate constant (k(C3)) of 2 x 10(6) mol(-1) s(-1), approximately 100-fold slower than the superoxide dismutases (SOD).
  • N-acetylcysteine (NAC) – recommended by Dr. Cutler in the 500 to 4,000 mg range for raising blood glutathione. He says that people who are sensitive to paint fumes exhaust or the preservatives BHT, BHA, and TBHQ and other hydrocarbons are most likely to benefit. NAC is a slightly modified version of the sulfur-containing amino acid cysteine. When taken internally, NAC replenishes intracellular levels of the natural antioxidant glutathione (GSH, often deficient with advancing age and in chronic illness), helping to restore cells’ ability to fight damage from reactive oxygen species (ROS). NAC also regulates expression of scores of genes in the pathways that link oxidative stress to inflammation. These dual effects give NAC a unique role in the prevention and treatment of many common diseases, both acute and chronic. NAC protects tissues from the effects of exercise-induced oxidative stress, adding value and safety to your workout. Has been shown to reduce oxidative stress in workers with lead exposure.
  • Pycnogenol – patented formulation of Pine Bark Extract standardized to 65-75% Procyanidin compounds (chain-like structures consisted of catechins similar to some found in green tea), shown to increase SOD1 and SOD2 and inhibit HIV.
  • Reservatrol – a type of natural phenol, (and thiol) produced naturally by several plants in response to injury or when the plant is under attack by pathogens such as bacteria or fungi (see study listing other SOD2 enhancers)
  • Spirulina – a cyanobacterium that can be consumed by humans and other animals, is often contaminated and has a bad reputation with Dr. Cutler’s chelation fans (see exercise study).
  • Tempola superoxide dismutase mimetic that belongs to a class of non-thiol-containing radiation protectors, and has the ability to permeate the membrane. Read more here, check out the patent or learn the chemistry.

Of course, I might be barking up the wrong tree… perfect storms are messy and all of these issues are somewhat murky because so little information is available and there’s often contradictory information. For now, though, I feel like I’m on the verge of a big breakthrough!

UPDATE: A reader commented that the way to boost SOD/SOD2 is to supplement manganese. Remembering Dr. Cutler’s discussion of manganese as it relates to mercury toxicity, I decided to have my manganese levels tested and guess what? my levels were so low they were almost not measurable. I’ve been supplementing now (September 8, 2015) for three or four months and they’ve just entered the normal range at the low-end.

Please share if you know of any other ways to treat SOD2 flaws.


61 thoughts to “Superoxide dismutase 2 – my genetic timebomb?”

  1. Where did you get your manganese test and how much do you take. How is your health now since adding the manganese. Thx, have a great day 🙂

    1. It’s a LabCorp test Chad.. Unfortunately it doesn’t change how I feel, most likely because of Candida and possibly mold colonization.

      1. What are you doing now for your health that is working. Do you have your health back yet?


  2. Have you tried just buy superoxide dismutase in pills? I’ve seen such pills on iherb and I’m going to try.

        1. Thanks, I just ordered it Mikhail since it is not too expensive – the first time I looked at it a year ago or so, if I remember correctly, I decided not to buy it because it’s SOD1 not SOD2…

          1. Did you buy this product for your SOD2? If so, have you seen any improvement? Has it had any type of negative impact or affected other minerals? Thank you for any information.

  3. There was a discussion about manganese from Mthfr Support on facebook, interestingly it claimed that people treating themselves with high doses of magnesium were unintentionally depleting their manganese. If you have SOD2 snps that makes it that much worse. It also links to an article that claims the weedkiller glyphosate chelates manganese. All together, the perfect storm.

    By the way, I seem to have the same SOD2 snps as you based on the 23andMe results. I wonder how common this particular variance is?

    1. That is super interesting Julian because I have been taking very very large quantities of magnesium for years and that might explain why my manganese was barely detectable. I’ve been titrating up manganese for four or five months and I’m at 200 mg per day now. I test monthly and hoping to get into the middle of the normal range soon. thanks for sharing that!

      1. I’m taking 200 mg per day and my blood work shows I am just above the low range limit – I’m nervous about taking more so will probably just continue at 200 mg. I think this may have fixed my blood sugar problems as I’m no longer overweight and not gaining in spite of eating as much as I like… Still have tight muscles though.

  4. i read your paragraph on Fullerene but I don’t understand it. :). Does it mean that it helps by removing a bad version of SOD? Thanks!

    1. My recollection is that it’s a mimetic – meaning that it mimics SOD2. so it’s a little like hormone replacement. some people take hormones when their body doesn’t make enough. In the same way some people take Fullerene when their body doesn’t make enough SOD2.

  5. HI Erik,

    I was wondering where you read that Extramel helps with SOD1, but not SOD2 polymorphisms?

    1. Sorry Kelly, this was too long ago… one of the reasons I blog is because my memory is terrible!

  6. I have a chronic exhaustion issue 14 years. Recently tested very high lead and mercury, mould, yeast, lyme, virus, methylation and detox gene mutations, and now I read this article and I notice these following gene mutations;

    SOD2 rs2758331 A AC +/-
    SOD2 rs4880 G AG +/-
    SOD3 rs2855262 C CC +/+

    Do all of these supplements work for everyone or is one unique to the individual. How to choose which one of these supplements? How big a factor is SOD in the greater scheme of things? I sense detox is a big part of the problem for me. I’m doing ozone for a few months now and have improved considerably, but still have a ways to go. I still wake in considerable pain and distress, non-restorative sleep but improved, and I now wonder if that is a detox issue, my body’s inability to detox through the night and the wake pain and discomfort is being overly toxic. When I get up, walk around, have a big glass of water, the pain and discomforts decrease considerably and quickly.

    1. Wish I could answer those questions for you Greg, but I just don’t know. The supplements are so expensive that proper experimentation is really beyond my budget. When I am killing and eliminating biofilm with ozone, I feel like garbage and of course don’t sleep well either.. my impression is there’s no supplement that can compete with the scale of the toxins moving through my digestive system. I’m currently doing 200 mg a day of acetyl-glutathione which is very expensive but well documented. I still feel sick. Just got to clean the pipes out in my opinion.

      1. Thanks for the feedback. I’m also reading up regulating NRf2 with R-lipoic acid is good for detox, especially metals and mercury, and it looks quite cheap. Ozone has made a big big difference for me, but I sense it’s not a cure but more helping my body get back online, the rest is up to me, and the rest is a lot of work, but worth it.

        1. Greg, make sure to read Dr. Cutler’s books before you experiment with lipoic acid – you can do very severe permanent damage to yourself if you’re unlucky… Or, you may get healthy quickly using frequent dose chelation using his methods.

          1. Eric- there is 50mg of alpha lipoic acid in the multivitamin my functional Dr recommended (ONE by pure encapsulations). She said it was an antioxidant. Is is still harmful at that dose??

            1. YES in the right circumstances for the right person, it could be big trouble. 50 mg is a significant dose for anyone with mercury toxicity.

              1. Ok, thank you! Is there a multi you recommend? I don’t have mercury toxicity, and neither does my husband (that I know of).

                1. No, sorry but I don’t like or use multivitamins… the problem for me is that if I react poorly to one there’s no way to know what ingredient is causing a problem.

  7. What are your thoughts on high SOD enzymatic activity? I did the Genova oxidative stress profile and all that came back was low sulphate levels and very high SOD enzyme activity. All other markers were normal, including glutathione, lipid peroxidase, etc. The interpretive guide said this could be from Inflammation or infection,Environmental toxicity,impaired glucose tolerance,Alcoholism,Homocysteinemia. My best guesses are infection/inflammation since I have high EBV titers and possibly Lyme. I don’t drink and my homocysteine is normal. I was just curious if you knew anything about how to counteract this or bring the levels down. Thank you!!

    1. I don’t know what high SOD enzymatic activity means. Kind of sounds like a good thing to me… I’d recommend you read everything I’ve written about ozone therapy for your EBV / Lyme.

  8. I can’t drink coffee anymore as it triggers a bad flare of rosacea but do drink black tea. If you’re wondering whether the coffee enemas affect me the same way as a cup of coffee, no, not at all. I get no buzz, no shakiness the way I would with coffee, also no speedy activity. It’s more like instant endorphins, a feeling of wellness. I can do them in the evening too and I fall asleep no problem. Coffee would keep me awake until 3 am if I had a cup any time after 4 pm. I’m a slow coffee metabolizer.

    I’m waiting for results of a SIBO lactulose breath test and the pre-test diet was very difficult as it required 2 weeks without enemas. I felt sluggish and slow most of those 2 weeks. Feel much better since then 🙂

    Hoping your recovery continues. Thanks for your excellent blog!

  9. I’ve read that coffee enemas stimulate the production of SOD and glutathione in the liver. I benefit a lot from coffee enemas, going from feeling sluggish, moody and tired to feeling cheerful and normal or better than normal. This lasts for 3-5 hours, depending on what I do during those post CE hours. There are very few human studies of coffee enemas however. They’re mostly rodent studies, so unsure how useful.

  10. Hi Eric,
    Obviously, that last comment was meant for the guy who got rashes when he took mB12.

    Regarding increasing SOD and glutathione, nigella sativa has been shown to do these things.

  11. Hi, it’s brad.
    I had a big problem starting mB12. The first time I took it my tongue swelled and split. The second time, I got super blood shot eyes rash (mostly on face and wiener) and cracks at corners of mouth. When we take mB12 we are kick-starting the methylation system which uses B2 in about 3 different places.
    B2 deficiency is almost unheard of but is a real possibility for the chronically ill because of our gut issues.

    “A deficiency can lead to various problems with the skin, such as dry, flaky, cracked skin and seborrheic dermatitis (scaly/flaky skin located on the scalp, face, or body). It could also cause hair to be dull or oily, oily skin, wrinkling of the skin on the arms and face, and splitting of finger and toenails”.

    I had a hard time figuring this out because I was supplementing B2. I needed to take large amounts in the early weeks of my methylation protocol.
    So, this is what you can do. Take a B vitamin and see if your urine turns bright “vitamin B” yellow. If it does then you are spilling B2 into the urine and that means that you have extra and are absorbing it. If you don’t have this response then you are not absorbing B2 and may be on my path.
    I had Bipolar which morphed into CFS. Bipolar is gone. CFS is 90+% gone. I had to chelate mercury, fix methylation and treat chronic infections.

  12. All those symptoms sound like environmental health issues, of which certainly mercury is suspect along with other metals. But what is even more suspect is that it sounds a lot like the type of gene SNP in people with CFS and amalgam illness who tend to over produce ammonia and sulfur. I’m one of these people who does have these signs and symptoms but I don’t seem to have noticeable reactions to methyl b12 or methyl folate or folic of folinic. But the foam urine thing is a dead give away. I think CBS and NOX and SOD and SOUX SNP seem to overlap and confuse the symptoms of each with one another.

    1. It is maddening trying to tease apart how the symptoms of one problem are subtly different from the symptoms of another – that’s why people like me can stay sick for decades… Even more difficult is when you’ve got for five or six different causes all blending symptoms together!

  13. I haven’t tried it, but Gynostemma pentaphyllum (Jiaogulan) also increases SOD. It’s available on iherb.

    Protective Role of Polysaccharides from Gynostemma pentaphyllum Makino Supplementation against Exhaustive Swimming Exercise-Induced Oxidative Stress in Liver and Skeletal Muscle of Mice

    The objective of this study was to investigate the protective role of polysaccharide from Gynostemma pentaphyllum Makino (PGP) supplementation against exhaustive swimming exercise-induced oxidative stress. A total of 48 mice were randomly divided into four groups: control, low-dose, medium-dose, and high-dose PGP supplementation groups. The control group received distilled water and the supplementation groups received different doses of PGP (50, 100 and 200 mg/kg body weight) by gavage once a day for 28 consecutive days. After 28 days, the mice performed an exhaustive swimming exercise, and some biochemical parameters related to oxidative stress, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and malondialdehyde (MDA), were measured. The results showed that PGP supplementation could increase SOD, GPx and CAT contents, as well as decrease MDA contents in the liver and skeletal muscle of mice, which suggests that PGP supplementation has a protective role against exhaustive swimming exercise-induced oxidative stress.

    You’ll have to pay to read the whole article and find out exactly how much it increased SOD. The good news is that gynostemma is cheap.

  14. I have the the same mutations as you and I suffer from chronic fatigue my whole lifeas well. When I run I gt shin splints… my feet burn. It’s insane how much they hurt!

    I’ve taken 15mg of chelated manganese for a week now and my bursitis in my shoulder is gone. I had it for 2 years after an injury. Going to megadose and try 3x15mg a day now.

    1. so interesting Jean, congratulations!!! I asked my doctor for her and got every copper and manganese test in the Lab Corp. catalog and as soon as I have the results will also start supplementing manganese probably at 60 mg per day for a week, and then evaluate dosage…

    1. After reading your fascinating comment I did many hours of research and believe there’s a possibility that I’ve had a manganese deficiency for as long as I’ve been ill. It’s fascinating because some of my earliest symptoms could be attributable to manganese deficiency. It’s also frustrating because it’s not a clear picture – I don’t have hypertension for example. Even if I did not have manganese deficiency 13 years ago when I first got seriously ill, it’s possible that I acquired it when I started chelating and discovered my high copper. When I look at the list of manganese antagonists, I’m taking a great many of them including high doses of zinc to reduce copper. It also turns out that manganese is used to reduce copper so potentially very useful for me. I did do a very minimal test with manganese taking only 11 mg once a week, which I now see was probably like taking nothing at all. I was so careful because of the warnings given by Dr. Cutler. Anyway, I’m going to test it out more fully soon – thank you so much for writing!! I’d love to read your blog, but it looks like you pulled the plug on it…

  15. Eric,

    I really appreciate your blog posts wholeheartedly. Even though I am much younger than you are, I am facing similar problems that you’ve dealt with in the past. I was wondering if there’s a better way to communicate what might be beneficial for me treatment wise. I have gone through four major surgeries with general anesthesia, severe weight loss, and physical/mental trauma, which damaged my health quite a bit. I believe you are miles ahead of me in terms of supplements/treatments, and was wondering if you could share your email or even facebook. I would truly appreciate your response.

    PS: have you tried GliSODin? I will post link, but feel free to remove it if you find it inappropriate.

    1. hi, I haven’t tried GliSODin, have you? I started Tempol a little over a week ago. I am feeling better since starting but have so many things going on, I really couldn’t say whether it’s the Tempol! Sorry to say but this really is the best way to communicate with me because I will never lose your messages this way. I receive about 100 emails a day so it’s just not a good option…

      1. Eric,

        I just got my GliSODin today and will be trying it from tomorrow. I believe your condition is pretty similar to mine, the more and more I read your blog posts! I am very sensitive to sulfur/thiol supplements like MSM, taurine, cysteine, B6 (including P5P), coq10, ALA, and most amino acids. I get flare ups whenever I consume foods that are high in sulfur like broccoli, brussel sprouts, and spinach. I am also sensitive to methyl b12, but not so much for methylfolate. Methyl b12 gives me rashes all over the body at even 1,000 mcg.

        In addition, I am histamine intolerant and cannot consume fermented foods easily. All these symptons align with the fac that I have Asian flush; lack of body’s ability produce enzyme aldehyde dehydrogenase 2 to break down histamine. I get acne, rashes, eczema, and seborrheic dermititis very easily and I have been battling them for past 8 years.

        I am not sure what’s causing all these issues, besides genetic mutation. I’ve ordered 23andme kit and the result would be back in 2-3 weeks. Meanwhile, I would like to figure out what’s the missing piece in the puzzle among all the conditions I’ve mentioned. It is important to mention that I’ve been feeling fatigued and my adrenaline hasn’t been functioning properly for about 8-9 years. Do you think heavy metal toxicity, particularly mercury would cause all conditions I’ve mentioned? Have you noticed any improvement from chelation? I am ready to go through the grueling battle if I found mercury to be the connection.

        Lastly, I am a bit worried about my liver and kidney. My kidney and bladder were always strange, ever since I was a child. My urine would always smell and have a lot of foams. I think my body cannot break down ammonia easily… Do you have any recommendation for liver and kidney support? I would truly appreciate your response. Thanks.

        1. It sounds to me like you’re on the right track having already figured out a lot of your issues and getting your genetics tested. That’s a great start. I’d also get a hair test to check for heavy metals. Yes I think mercury can cause just about any chronic illness because it interferes with enzymes and so many more processes.

          Before starting chelation you really do want to cleanse your liver and kidneys – starting with kidneys first. I use Dr. Christopher’s kidney supplement and have also used hydrangea. I’m going to add those to my supplement page… and milk thistle for the liver. I’d read Andreas Moritz book too.

          1. Eric,

            Thanks for the response. I’ve ordered hair test to see if heavy metal is a real issue for me. If it is, I will start Cutler’s chelation protocol in two weeks. Meanwhile, I am taking GliSODin and glutathione to boost my antioxidant reserve. I realize that oral glutathione cannot be absorbed easily and it’s better to take glutathione precursors. Unfortunately, my body cannot handle sulfur supplements right now for some reason, and I hope it’s not due to heavy metal toxicity.

            Also, I have been taking Dr. Christopher’s Kidney Cleanse right before you gave me that response. What a coincidence! I would like to take milk thistle, but it’s not only high in thiol, but also salicylinate, so I get severe negative reaction from it. I will post an update when I notice any change. Thanks.

            1. glad you’ve ordered the hair test! Make sure to check out acetyl glutathione – seems it can be as effective as an IV. I’ve started taking it recently in place of liposomal. Unfortunately it’s very expensive…

      2. I was thinking about giving tempol a try. How did it go, are you still using it?

        Can I ask your source for it?

        1. It went well, I was feeling good while using it but it’s pricey. I stopped when I discovered how low I was in Manganese. Seemed like a much cheaper and more natural place to start. I’m still working on getting my manganese to normal…

          1. That would be great! I’d love to try tempol.

            I developed MCS/chronic fatigue 5 years ago and ever since my diagnostics indicated low glutathione and oxidative stress.

            One thing I’m doing lately is taking high doses of acetyl glutathione (3-5 grams daily). I found the lab that supplies Allergy Research Group and imported it for a fraction of the cost. This is way cheaper than IVs and seems to be working.

  16. Look up mitochondrially locked antioxidants. MitoQ, MitoTempo, C60-oo, SKQ1 and so on. Some of these can be bought online if you are willing to risk it.

  17. thank you for another informative article. For those who’ve done either their 23andMe or AncestryDNA test, this is a link to check your results for SOD SNPs. Click “View Report” to get your results. The notes/info are pretty good too:

    This Gene Report and hundreds of others are stored in the Gene Library. In the Gene Library, you can install and run as many of Gene Reports as you’d like:

    The Gene Library and all its contents are free to LiveWello Gene App users. The library is just one of the 11 other features that are free with the App. The rest are:

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