Superoxide Dismutase supplement pill SOD  benefit and risk, by Ray Sahelian, M.D.
March 17 2017

Superoxide dismutase has been found in almost all organisms living in the presence of oxygen, including some anaerobic bacteria, supporting the notion that superoxide is a key and general component of oxidative stress.
   In aerobic cells, free radicals are constantly produced mostly as reactive oxygen species. Once produced, free radicals are removed by antioxidant defenses including the enzymes catalase, glutathione peroxidase, and superoxide dismutase. Reactive oxygen species, including nitric oxide and related species, commonly exert a series of useful physiological effects. However, imbalance between prooxidant and antioxidant defenses in favor of prooxidants results in oxidative stress. This results in damage to lipids, proteins, and nucleic acids. Alone or in combination with primary factors, free radicals are involved in the cause of hundreds of diseases.

Superoxide Dismutase supplements - do they work? Are they worth buying?
There are vitamin companies selling supplements that they claim to have superoxide dismutase. I am aware of few human studies regarding the ingestion of a superoxide dismutase supplement and its effect on health. Does this enzyme get absorbed intact from the gastrointestinal system? If it does, does it then make its way to the cells in the body and function similar to the intrinsic superoxide dismutase within our cells? Are there side effects to its use? Is it safe? There is little research to know whether taking a SOD supplement is useful in the long run. Hopefully some organization will do additional research and we can have a better idea as to whether taking such a supplement is beneficial.
  A. I have also seen supplements promoted to increase superoxide dismutase levels in the body. Again, I have not come across any human research that these superoxide dismutase enhancing supplements are effective, and if they are, which medical conditions they would be appropriate to prescribe. Also, we have no idea what dosages would be appropriate. Is it possible that taking too much of these SD pills would cause harm or damage to the body and cause side effects? We currently don't know.

Naturally increase through food, spices, herbs, teas, etc
There are many herbs that increase levels, here is just one example of one:

Int J Food Sci Nutr. 2013. Consumption of polyphenol-rich juar tea increases endothelium-bound extracellular superoxide dismutase levels in men with metabolic syndrome: link with LDL oxidizability. Endothelium-bound extracellular superoxide dismutase (eEC-SOD), a major antioxidative enzyme in the vasculature, is involved in anti-atherogenesis by inhibiting low-density lipoprotein (LDL) oxidation. The objective was to investigate whether the polyphenol-rich juar tea had beneficial effects on LDL oxidation and eEC-SOD levels in patients with metabolic syndrome (MetS). A total of 20 men with MetS participated in a randomized cross-over trial, comparing consumption of five cups/day of juar tea with that of a polyphenol-poor tea, barley tea, for 4 weeks. Although there was no change in LDL oxidizability after consumption of either tea, juar tea significantly increased eEC-SOD levels by 16%, whereas barley tea significantly decreased levels by 15%. It is noteworthy that the changes in eEC-SOD were positively associated with those in LDL oxidizability after tea consumption. Tea polyphenols may provide anti-atherosclerotic effects by inhibiting LDL oxidation through EC-SOD bound to the endothelium.

Different types of SOD in the body
Three forms of superoxide dismutase are found in humans. SOD1 is located in the cytoplasm, SOD2 in the mitochondria and SOD3 is outside of the cell. SOD1 and SOD3 contain copper and zinc, while SOD2 has manganese.

Superoxide Dismutase outside of the cell
Extra cellular superoxide dismutase ( EC-SOD ) catalyzes the dismutation of superoxide radical to hydrogen peroxide and oxygen in the interstitial spaces of tissues and in extracellular fluids (plasma, lymph, and synovial fluid). It eliminates superoxide radicals from the cell environment and prevents the formation of reactive oxygen species and their derivatives. EC-SOD is a secretory, tetrameric glycoprotein containing copper and zinc, with a high affinity to certain glycosaminoglycans, such as heparin and heparan sulfate. It plays an important role in maintaining vascular tone, lung function, and the metabolism of NO, and in the pathology of such diseases as atherosclerosis, diabetes, and arthritis.

Superoxide Dismutase and amyotrophic lateral sclerosis
In the mid 1990s, the linkage between mutations in the gene coding for the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) and the neurodegenerative disease known as familial amyotrophic lateral sclerosis was established.

Herbs that influence Superoxide
There are herbs and nutrients that influence antioxidant levels. With time I will mention others, for the time being I wanted to present one example:
Extract of Andrographis paniculata inhibits formation of oxygen derived free radicals such as superoxide and hydroxyl radicals.

Superoxide Dismutase study
Vascular protection: superoxide dismutase isoforms in the vessel wall.
Arteriosclerosis Thromb Vasc Biol. 2004. Faraci FM, Didion SP. Department of Internal Medicine, Cardiovascular Center, University of Iowa, Carver College of Medicine, Iowa City, IA
Blood vessels express 3 isoforms of superoxide dismutase : cytosolic or copper-zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD) localized in mitochondria, and an extracellular form of CuZn- superoxide dismutase (EC-SOD). Because there are no selective pharmacological inhibitors of individual superoxide dismutase isoforms, the functional importance of the different SODs has been difficult to define. Recent molecular approaches, primarily the use of genetically-altered mice and viral-mediated gene transfer, have allowed investigators to begin to define the role of specific superoxide dismutase isoforms in vascular biology. This review will focus mainly on the role of individual superoxide dismutase in relation to endothelium under normal conditions and in disease states. This area is important because reactive oxygen species and superoxide anion are thought to play major roles in changes in vascular structure and function in pathophysiology.

Superoxide Dismutase supplement questions
Q. I get a Puritan's Pride catalog and they have listed SOD 250 mg tablets (superoxide dismutase) equivalent to 2000 units of activity. The say that SOD (superoxide dismutase) is an enzyme that can be found in human cells. Does this product work?
     A. I can't say for sure since I have not come across any studies evaluating the role of a superoxide dismutase supplement in human health. I would be surprised if the SOD in this product were absorbed and transported into cells where it could do its work. At this time I personally would not buy this product since there is no evidence that it would be effective. And I have no idea what they mean by 2000 units of activity. Activity where? It is not clear to me how the activity of this enzyme is determined and how do we know the 2000 unit activity will influence our cellular metabolism. Perhaps you could contact the research department at Puritan's Pride and ask them to explain how this superoxide dismutase supplement is supposed to work and perhaps they have some research papers that I am not familiar with. If any researchers out there know more about this topic, please contact me, I am very interested.
   I have also seen a Source Naturals superoxide dismutase product that has 2000 units of this antioxidant.

Q. I see no information on Glicosin on your site, or its original brand name form France, SOD. I am using Glicosin with great success for depression and Chronic Fatigue Syndrome. The French one works better.
   A. We are not familiar with Glicosin. By SOD we think you mean superoxide dismutase.
      Q. Thanks for your reply. I actually meant Glisodin, not glicosin. Glisodin is the brand name for SOD, with the abbreviation for superoxide dismutase. They claim it is the first orally active vegetarian form of superoxide dismutase supplement.
         A. Here are the studies we found with Glisodin.

Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress.
Phytother Res. 2004. Vouldoukis I, Conti M, Krauss P, Kamaté C, Blazquez S, Tefit M, Mazier D, Calenda A, Dugas B. ISOCELL Nutra SAS, 53 bd du Général Martial Valin, 75015, Paris, France.
The development of dietary delivery systems using wheat gliadin biopolymers as a natural carrier represents a new alternative. Combination of antioxidant enzymes with this natural carrier not only delayed their degradation (i.e. the superoxide dismutase, SOD) during the gastrointestinal digestive process, but also promoted, in vivo, the cellular defences by strengthening the antioxidant status. The effects of supplementation for 28 days with a standardized melon SOD extract either combined (Glisodin) or not with gliadin, were evaluated on various oxidative-stress biomarkers. As already described there was no change either in superoxide dismutase, catalase or glutathione peroxidase activities in blood circulation or in the liver following non-protected SOD supplementation. However, animals supplemented with Glisodin showed a significant elevation in circulated antioxidant enzymes activities, correlated with an increased resistance of red blood cells to oxidative stress-induced hemolysis. Liver cells isolated from animals supplemented with Glisodin presented a delayed depolarization response and an enhanced resistance to oxidative stress-induced apoptosis. It is concluded that supplementation with gliadin-combined standardized melon superoxide dismutase extract (Glisodin) promoted the cellular antioxidant status and protected against oxidative stress-induced cell death.

GliSODin, a vegetal sod with gliadin, as preventative agent vs. atherosclerosis, as confirmed with carotid ultrasound-B imaging.
Eur Ann Allergy Clin Immunol. 2007. Cloarec M, Caillard P, Provost JC, Dever JM, Elbeze Y, Zamaria N. Association Nationale de Prevention Médicale, Paris.
We selected active adults aged 30-60 and investigated these risk factors, in order to recommend preventive measures. Another interesting variable is the preclinical status or atheroma of the arterial (carotid) wall or lumen. We also investigated the presence of oxidative stress in, and the anti-oxidant status of these subjects. We studied the anti-oxidative efficacy of superoxide dismutase (SOD) and variations of malondialdehyde (MDA). Supplementation with GliSODin, a vegetal SOD associated with gliadin, was effective in controlling the thickness of the carotid artery intima and media layers as measured by ultrasonography-B. We could demonstrate the preventive efficacy of GliSODin at a preclinical stage in subjects with risk factors of cardiovascular disease.

I found your website today and will be signing up for your newsletter! Thank you. I have a question re: superoxide dismustate. Your recommendation was not to buy this product as you are not aware of any studies: " I can't say for sure since I have not come across any studies evaluating the role of a superoxide dismutase supplement in human health. I would be surprised if the SOD in this product were absorbed and transported into cells where it could do its work. At this time I personally would not buy this product since there is no evidence that it would be effective." Further in the article, a reader asked about a product called Glisodin. Your response was to post the studies on this product. So, I'm confused. You post the 'studies' yet say you've not read 'any studies". Or, after doing a search, you found 2 studies.. will you be revising your input on the subject? Would you please clarify your 'position/belief' of the efficacy of Glisodin? Would you buy it, yay or nay?
   The product Glisodin is a combination of gliadin and superoxide dismutase. It is not superoxide dismutase by itself. Therefore, we are not aware of human studies with a superoxide dismutase supplement by itself in humans.

I've had DVT. Hence take warfarin daily. Does SOD - superoxide dismutase interact with warfarin or Coumadin? My concern is that warfarin is producing oxygen free radicals. I'm being damaged from it and want to take SOD for repairing tissues. Does the blood thinner warfarin conflict with superoxide dismutase supplement?
    We have not seen any studies with the combination of warfarin and superoxide dismutase supplement use so we don't know if they would interfere when used together.

I just read your article on SOD. If you google "Oral Superoxide Dismutase" you'll see that the top two hits are research articles on Pubmed which both indicate that it is absorbable when ingested, and may reduce markers of inflammation and increase markers of anti-oxidant activity in humans and... cats. From the first study:" In conclusion, supplementation with an extract rich in SOD activity promoted antioxidant status and protected against increased inflammation in the serum of professional rowers ..."From the second study:"... supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats."

Do you know where I can purchase liquid superoxide dismutase?
   A. I have not looked into the liquid version and do not yet know which companies have a reliable formulation.

I have been taking Superoxide Dismuzyme supplement on/off for over 1 yr. with good results for HP virus, but recently I am feeling very dizzy and wondering if this could be aside effect, also wondering if I am taking too much?
   We are not familiar with Dismuzyme product so we don't know exactly what's in it and the quality of the ingredients.