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SOD2 A16V homozygous mutation - anyone else?

Discussion in 'Genetic Testing and SNPs' started by Thinktank, May 11, 2013.

  1. Hip

    Hip Senior Member

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    Looking at my 23andme results, I found that I also have the GG risk alleles for SOD2 A16V rs4880.

    Click HERE to see your SOD2 A16V rs4880 result on 23andme.

    However, it says here in dbSNP that the GG risk alleles (reported as CC in dbSNP) are found in 14.8% of the European population, so this SOD2 deficiency is not exactly a rare condition to have. (@Valentijn have I read that percentage data correctly?)
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  2. Valentijn

    Valentijn Activity Level: 3

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    Actually it's a fairly small sample showing 14.8%. The bigger European sample says 22.1%, and the huge multi-ethnic sample says 20.7%. So it's probably 20-22% of people with CC.

    Regarding the research, http://www.ncbi.nlm.nih.gov/pubmed/15864132?dopt=Abstract says that the C allele (Alanine) results in 40% more enzyme activity. But http://www.ncbi.nlm.nih.gov/pubmed/16538174?dopt=Abstract says the opposite, that the T allele results in a 33% increase of enzyme activity compared to people with CC.

    This might indicate that the bigger factor in enzyme activity is due to something other than this SNP, and the alleles are just random background noise. For example, one study mentions that gender results in a 15% difference in enzyme activity.

    At any rate, any version only confers a pretty small risk of problems. 20% of the population certainly does not seem to be dropping dead or suffering from chronic or other illness related to it!

    And just for fun, the comparison of 12 ME patients with 12 controls I have rs4880 data for:
    GG: 2 ME patients, 3 controls
    AG: 6 ME patients, 5 controls
    AA: 4 ME patients, 4 controls
    Last edited: Apr 29, 2014
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  3. Hip

    Hip Senior Member

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    So from your data, @Valentijn, there is no indication of a link between rs4880 and ME/CFS.

    Looking at this study, there is no link between rs4880 and Parkinson's either.


    Though this study found that the rs4880 C allele is associated with increased longevity. Presumably on 23andme this translates to the rs4880 G allele being linked to increased longevity. Is that right Valentijn? My foggy brain still has trouble understanding these positive and negative strand reporting conventions.


    By the way, the herb Gynostemma pentaphyllum has been shown to increase SOD2 in the mitochondria, and this herb is considered a longevity herb. Gynostemma pentaphyllum doses are around 300 mg.
    Last edited: Apr 29, 2014
  4. boohealth

    boohealth

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    Correlation is not causality. To say a disease is caused by ROS is a gross oversimpification that is ultimately false. Redox has to be a continual cycle. Fire is life, and too much fire can burn, but without fire, you have nothing. Many activities that increase oxidative stress stimulate production of antioxidants by the host. ROS in and of themselves are not bad. A mouse study does not equal a human trial. As you know, many substances tested in cell lines and mice failed in clinical trials. That doesn't mean one shouldn't research, or take a calculated risk on a nonapproved supplement or drug, but YMMV.
  5. lansbergen

    lansbergen Senior Member

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    Right and too much superoxide can kill. A superoxide scavenger saved my life and I still need it every day. Superoxide causes the symptoms but the infectious pathogen I suspect is the cause. That infection is associated with SOD2 impairment.
  6. Hip

    Hip Senior Member

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    Not really. In some mitochondrial complex deficiency diseases, although these diseases result in a reduction of ATP production, they also generate high levels of superoxide at the mitochondria, and this superoxide creates a chain of reactive oxygen species (ROS) which appear to cause a lot of damage.

    In this paper the authors created a mouse model for mitochondrial complex III and complex IV deficiencies. They found that the complex III model manifested severe reactive oxygen species damage:

    And this study found that complex I deficiency leads to increased production of cellular reactive oxygen species, pointing to a major role that ROS may play in this condition.

    Parkinson's involves a complex I deficiency, so from that alone you might expect ROS to play a big role in this disease. And indeed, this paper says that in Parkinson's, not only does the increase in ROS from mitochondrial dysfunction trigger a sequence of events that leads to cell demise, but also, the brain inflammation activated microglia in this Parkinson's produce further reactive oxygen and reactive nitrogen species: namely nitric oxide and superoxide. The paper concludes that reducing oxidative stress can provide a therapeutic strategy in Parkinson's.

    In summary: the use of the potent, mitochondrially targeted antioxidant tempol in Parkinson's disease would seem very appropriate.
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  7. boohealth

    boohealth

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    @Iansbergen, what is your supplement?

    Mitochondrial diseases are rare...generally speaking, ROS are not the cause--they are simply part of redox cycling, and balance is key. Too many antioxidants can kill, too.

    A mouse model for a mitochondrial disorder says nothing about most human beings imo.

    Also, reducing oxidative stress in a chronic degenerative illness still doesn't prove ROS cause all diseases, or most of them.
  8. lansbergen

    lansbergen Senior Member

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    I do not take any supplements.
  9. boohealth

    boohealth

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    @Iansbergen, what is the superoxide scavenger that saved your life?
  10. lansbergen

    lansbergen Senior Member

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    Levamisole
  11. Hip

    Hip Senior Member

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    Hereditary mitochondrial diseases may be comparatively rare; however, mitochondrial dysfunction has been implicated in many common diseases. To quote this website:
    Mitochondrial dysfunction may also be part of the ME/CFS picture. See this stusy:

    Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways.
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  12. boohealth

    boohealth

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    @Hip, it isn't scientifically sound to draw a long bow between mitochondrial disorders in mice in studies, and mitochondrial "dysfunction" or function which is a slowly emerging science.
  13. boohealth

    boohealth

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    @Iansbergen, I must be missing something.

    https://en.wikipedia.org/wiki/Levamisole

    Did you take it as an anticancer drug or a dewormer? It certainly sounds toxic, having been pulled from the market in many places because of its risk profile. Really, it's none of my business why you took it, but I don't see how this applies to the SOD mutation that was the subject of this thread...
  14. Hip

    Hip Senior Member

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    What mice studies are you referring to?
  15. lansbergen

    lansbergen Senior Member

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    I used it as a dewormer in animals for many years.

    When I was dying I started taking it myself because it was known as an immunemodulator.

    Later I found it decreases superoxide production. In one paper I read it stops superoxide production.

    In high dosis it can kill. For me it was a lifesaver.


  16. lansbergen

    lansbergen Senior Member

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    I understand the mutation influences the antioxidant activity of MnSOD. With the infectious pathogen I supect SOD2 is impaired.
  17. boohealth

    boohealth

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    @Iansbergen, glad you were able to save your life. What do you mean, "with the infectious pathogen"?
    This drug sounds wayyyyyy scarier than tempol...omg. I have asked some smart people about tempol, but haven't heard back.
  18. Violeta

    Violeta Senior Member

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    I've been rereading about Lyme since last night when a lot of people who have histamine issues said their issues started with Lyme. I found this article today, https://www.whoi.edu/oceanus/featur...rising-lyme-disease-bacteria-has-quirky-needs and I found this thread by searching for manganese. The first post I read was by Bluebird saying that too much manganese can cause neurological problems, and this article says Lyme thrive in a high manganese environment. Lyme can cause neurological problems.

    But I would like to ask if someone else can figure out if there is a tie in between the Borrelia using manganese and making SOD and the benefits of the Tempol that was spoken about here.

    Thanks
  19. Bluebrid

    Bluebrid

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    Interesting article on iron and Borrelia.

    I agree with the article that superoxide radicals are an important for the immune system. This is why oxidative therapies are so effective.

    However, excess free radicals are extremely damaging. Getting the redox cycle to work in balance is the key -- and cell signaling is an important part. Physicians who use oxidation to fight infection or cancer do so in a pulsed fashion. Even standard chemotherapy functions through an oxidative process.

    Some pathogens are more sensitive to oxidation. Some pathogens, like Tularemia which can be airborne or tick-borne are anaerobic. Tularemia is commonly seen with the mix of pathogens that are often termed Lyme Disease.

    I would say malaria is extremely oxidant sensitive, its cousin babesia slightly less so – and borrelia even less as it is pleomorphic and can change forms rather rapidly to evade the immune system. That does not mean that a pulsed oxidative therapy would not be effective with borrelia, just that it is unlikely to completely eradicate the infection without using other therapies in conjunction with the oxidation.

    Any time I have ever used or been given an oxidative treatment to treat an infection, I was told to limit my antioxidants the day of the treatment, undergo the therapy and, after a few hours, to take an antioxidant to mop up the excess free radicals.

    Even when you are undergoing an oxidative treatment, your body is never completely in an oxidative state. It simply means that the balance it tipped toward or more favorable to oxidation so that the immune system can utilize the extra oxygen where it is needed. If reduction were not also occurring simultaneously – even adjacent to the oxidative processes, we would surely die. The body is a complex, intelligent machine that utilizes what it is given to our advantage.

    To starve the body of essential nutrients to fight an infection or cancer is simply not wise. Limiting excess sugars or excess nutrients that would feed a pathogen is wise. When starving the host to fight the pathogen, the pathogen will always win as the body simply gets weaker and weaker.

    Iron is one of those essential, tricky elements where too much can wreak havoc – mostly through oxidative stress. I have read studies where Tempol or similar cellular antioxidants like Ebselen have curbed the potential oxidative issues with iron supplementation.

    When someone is iron deficient, it presents a vicious cycle. If the iron deficiency is due to excess bleeding from fibroids or stomach cancer or ulcerations in the digestive tract, the blood vessels at the site of the blood loss are unable to contract without ferritin or “usable-iron” in the hemoglobin. IV or supplemental iron takes weeks to transform into ferritin and potentially increases free radicals that exacerbate the condition that caused the blood loss in the beginning – like fibroids or inflammation in the digestive tract etc. It is a real Catch 22 and hard to get out of that sort of hole once you start slipping in.

    In the US, the current standard of care is to give transfusions only to the point that you are not fainting and then to use supplementation and IV iron over months and months to get the hemoglobin and ferritin levels back to normal -- very hard to do when you are still losing blood. It is a dangerous teeter-tauter ride; the fatigue can be debilitating – as is the damage to the heart and all the organs that need iron-rich hemoglobin to carry oxygen and function.

    As for the concern that Tempol may prevent free radicals from being utilized by my immune system, I think that is a valid consideration. We are all striving for redox balance. I think my medical history and that of my father shows enough conditions due to oxidative stress and our SNP at SOD2 indicate that something is out of sync.

    My experience thus far and from what I have read and been told by medical doctors is that between 10 mg and 100 mg of Tempol is not enough to upset the redox balance for fighting infections. Also the improved cell signaling from Tempol will help my immune system. I believe that is why Tempol is effective with cancer and with autoimmune conditions -- which are essentially an imbalance between the TH1 and TH2.

    Now if I did not have this genetic profile or these conditions, I would not be bothering with Tempol – or probably very many supplements at all. My health is what forced me to look at these issues to find answers. That is probably why we are all reading and posting on this site. Probably very few of us would ever have questioned what we ate or how he care for ourselves because we would have the energy to have other life pursuits.

    As for manganese, it is vital to the body in the right amount. Overexposure may lead to a neurodegenerative disorder known as manganism. Unfortunately, some people diagnosed with Parkinson’s may actually have mangansim which can easly be corrected with proper supervised chelation therapy. Medical journals are filled with case reports – and sadly, some neurologists still do not check for it.

    There can also be over or under abundance of other minerals that can play a part in neurological conditions. It just felt it was important to warn people not to use supplemental manganese without a doctor’s supervision. If your body is not able to properly make SOD2, supplementation with manganese has the potential to build up and cause other, possibly neurological issues.

    Below are just some of the many articles on manganese toxicity.

    Quantitative neuropathology associated with chronic manganese exposure in South African mine workers. Gonzalez-Cuyar LF, Nelson G, Criswell SR, Ho P, Lonzanida JA, Checkoway H, Seixas N, Gelman BB, Evanoff BA, Murray J, Zhang J, Racette BA. Neurotoxicology. 2013 Dec 26. pii: S0161-813X(13)00189-7. doi: 10.1016/j.neuro.2013.12.008. [Epub ahead of print]

    Vulnerability of welders to manganese exposure - A neuroimaging study. Long Z, Jiang YM, Li XR, Fadel W, Xu J, Yeh CL, Long LL, Luo HL, Harezlak J, Murdoch JB, Zheng W, Dydak U. Neurotoxicology. 2014 Mar 27. pii: S0161-813X(14)00051-5. doi: 10.1016/j.neuro.2014.03.007. [Epub ahead of print]

    Commentary to Krishna et al. (2014): Brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water. Kumasaka MY, Yajima I, Ohgami N, Naito H, Omata Y, Kato M. Arch Toxicol. 2014 May;88(5):1185-6. doi: 10.1007/s00204-014-1221-y. Epub 2014 Mar 11.

    Neurobehavioural effects of developmental toxicity. Grandjean P, Landrigan PJ. Lancet Neurol. 2014 Mar;13(3):330-8. doi: 10.1016/S1474-4422(13)70278-3. Epub 2014 Feb 17. Review.

    Manganese in health and disease. Avila DS, Puntel RL, Aschner M. Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7.

    Elevated airborne manganese and low executive function in school-aged children in Brazil. Carvalho CF, Menezes-Filho JA, Matos VP, Bessa JR, Coelho-Santos J, Viana GF, Argollo N, Abreu N. Neurotoxicology. 2013 Dec 3. pii: S0161-813X(13)00178-2. doi: 10.1016/j.neuro.2013.11.006. [Epub ahead of print]

    Manganese and the brain. Tuschl K, Mills PB, Clayton PT. Int Rev Neurobiol. 2013;110:277-312. doi: 10.1016/B978-0-12-410502-7.00013-2.

    Manganese in human parenteral nutrition: Considerations for toxicity and biomonitoring. Santos D, Batoreu C, Mateus L, Marreilha Dos Santos AP, Aschner M. Neurotoxicology. 2013 Nov 1. pii: S0161-813X(13)00158-7. doi: 10.1016/j.neuro.2013.10.003. [Epub ahead of print]

    Manganism in the 21st century: The Hanninen lecture. Racette BA. Neurotoxicology. 2013 Oct 19. pii: S0161-813X(13)00157-5. doi: 10.1016/j.neuro.2013.09.007. [Epub ahead of print]

    Teaching neuroimages: manganese neurotoxicity of the basal ganglia and thalamus. Lakhan SE, Abboud H. Neurology. 2013 Oct 1;81(14):e111. doi: 10.1212/WNL.0b013e3182a6cb86. No abstract available.

    Manganese neurotoxicity: new perspectives from behavioral, neuroimaging, and neuropathological studies in humans and non-human primates. Guilarte TR. Front Aging Neurosci. 2013 Jun 24;5:23. doi: 10.3389/fnagi.2013.00023. eCollection 2013.
    Last edited: May 6, 2014
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  20. cigana

    cigana Senior Member

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    I am also homozygous for SOD2.

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