Superoxide Dismutase
Common Name(s): Cu/Zn SOD, Fe SOD, Metalloprotein, Mn Sod, Orgotein, Palosein, SOD
Medically reviewed by Drugs.com. Last updated on Sep 21, 2023.
Clinical Overview
Use
Superoxide dismutase (SOD) enzymes have anti-inflammatory effects, prompting evaluation of use in osteoarthritis, rheumatoid arthritis, and idiopathic pulmonary fibrosis; however, limited clinical trials are available to support these uses. Clinical trials evaluating the use of SOD in cancer, cardiovascular disease, and other conditions in which antioxidant status plays a role are also lacking. No evidence exists regarding long-term use of SOD; therefore, SOD cannot be recommended for any indication.
Dosing
Oral supplementation is limited by the enzyme's inactivation in gastric acid. Plant-derived oral SOD (commercial product) 500 mg taken orally once daily over 6 weeks was used in a clinical study evaluating effects on the balance between oxidants and antioxidants and on inflammatory marker levels in professional rowers.
Daily intravenous (IV) administration of 40 or 80 mg of lecithinized SOD over 28 days was compared with placebo in the treatment of idiopathic pulmonary fibrosis.
Weekly intra-articular injections of orgotein (range, 4 to 32 mg) have been studied in patients with rheumatoid arthritis or osteoarthritis of the knee (treatment duration, 3 to 6 weeks).
Contraindications
Contraindications have not been identified.
Pregnancy/Lactation
Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
Information from large clinical studies is lacking; however, adverse effects appear to be limited. Pain and irritation at injection sites have been reported.
Toxicology
SOD is regarded as nontoxic, based on data from earlier studies. Data from newer formulations are lacking.
Source
SOD enzymes are found in all living cells in several common forms. SOD was initially biochemically extracted from the serum and liver of animals, as well as from plant sources; however, this process was inefficient.Bafana 2011 Induction of oxidative stress in microbes has been the mainstay of SOD production; however, a method in which recombinant copper/zinc SOD is produced in Escherichia coli and bound to lecithin has been developed.Broeyer 2008, Suzuki 2008 Commercial preparations previously relied on bovine-derived SOD (orgotein and palosein), with patents also filed for yeast- and marine-derived SOD.Bafana 2011
History
In 1967, geneticist George J. Brewer described the protein indophenol oxidase, which was later identified as superoxide dismutase, in his work analyzing starch gels.Brewer 1967 The enzymatic activity of SOD was first described in 1968 by biochemists Irwin Fridovich and Joe M. McCord.McCord 1969 In Germany, SOD (as orgotein) has been used in general medicine as an anti-inflammatory agent.Huskisson 1981
Chemistry
SOD enzymes catalyze the conversion of superoxide, a reactive oxygen species (ROS) produced during aerobic respiration, to oxygen and hydrogen peroxide.McCord 1969 SOD has various recognized forms in humans and other mammals. SOD1 and SOD2 (intracellular) contain copper and zinc, and SOD2 (found in mitochondria) relies on manganese for reactivity. The enzymatic forms found in plants also have an iron form.Bafana 2011, McCord 1969 SOD3, or extracellular superoxide dismutase (EC-SOD), is the only SOD in the extracellular space and has unique characteristics and functions in cellular signal transduction.Griess 2017
Uses and Pharmacology
The dual roles of SOD enzymes include controlling ROS damage and regulating ROS signaling enzymes.Wang 2018 Alterations in the activity and expression of the enzymatic antioxidant Cu,Zn‐SOD (SOD1 and SOD3) have been observed in pathological occurrences, including inflammatory bowel disease, obesity, diabetes, hypertension, and chronic obstructive pulmonary disease. In addition, SOD1 and SOD3 gene polymorphisms have been associated with the risk of developing or exacerbating particular types of disease.Lewandowski 2019
One study shows that SOD is a marker of cardiovascular alterations in hypertensive and diabetic patients, as changes in SOD serum levels are correlated with alterations in vascular structure and function.Gómez-Marcos 2016
Overexpression of EC-SOD inhibits tumor growth and metastasis, indicating a role as a tumor suppressor, while low EC-SOD expression has shown reduced cancer patient survival, which further suggests that a loss of extracellular redox regulation promotes a conducive microenvironment that favors cancer progression.Griess 2017 EC-SOD (ie, SOD3) gene transfer to tissue damage results in increased healing, increased cell proliferation, decreased apoptosis, and decreased inflammatory cell infiltration. However, in cancer, SOD3 has been shown to either increase or decrease cell proliferation and survival depending on the model system used, indicating that SOD3-derived growth mechanisms are not completely understood.Laukkanen 2016
Mutations in SOD1 can lead to the accumulation of highly toxic hydroxyl radicals. Accumulation of these free radicals causes degradation of both nuclear and mitochondrial DNA and protein misfolding, features that can be used as pathological indicators associated with amyotrophic lateral sclerosis (ALS).Kaur 2016 SOD1 mutations are the first mutation reported to contribute to the development of ALS and account for 15% to 20% of all familial ALS and 3% of sporadic ALS cases.Nowicka 2019
Overall, SOD activity is increased in patients with vitiligo, although in serum, plasma, and whole blood, results are inconclusive.Speeckaert 2018 This was supported by a meta-analysis showing an association between vitiligo and high levels of both SOD and malondialdehyde (MDA).Shi 2017 Decreased SOD activity but no change in catalase, glutathione peroxidase, nonprotein thiols level, and total antioxidant activity in erythrocytes suggests the presence of a compensatory mechanism for SOD dysfunction in red blood cells of patients with androgenetic alopecia.Prie 2016
The role of SOD as a dietary supplement is examined in the following sections; for information on SOD deficiency states, see standard medical references.Bafana 2011
Anti-inflammatory effects
The use of SOD as an anti-inflammatory agent has been postulated because increased production of ROS is recognized to cause tissue damage associated with inflammation.Afonso 2007, Carillon 2013, Uthman 2003 Associated effects of decreased peroxynitrite production, decreased influx of neutrophils, and release of proinflammatory cytokines have been discussed.Afonso 2007
Animal data
Anti-inflammatory effects of SOD have been demonstrated in animal models.Afonso 2007, Carillon 2013 Parenteral SOD has been used in the treatment of soft tissue inflammation in horses and dogs; however, in an exercise trial in mares comparing placebo with oral SOD supplementation, biomarkers of inflammation were unaffected by SOD.Lamprecht 2012 In a study of oral SOD in horses undergoing a 60-day training regimen, creatine kinase activity, a marker of hemolysis, was steady in the SOD group compared with an increase in the placebo group.Notin 2010
Clinical data
Limited, older clinical trials evaluating intra-articular or bovine-derived SOD were conducted in patients with osteoarthritis.Afonso 2007 In a placebo-controlled study of 139 patients with osteoarthritis of the knee, intra-articular injections of orgotein 8 to 32 mg/week for 3 weeks was effective in reducing symptoms of osteoarthritis; superiority to placebo for up to 3 months was demonstrated.McIlwain 1989 In a double-blind trial in 30 patients with active rheumatoid arthritis of the knee, treatment with intra-articular injections of orgotein 4 mg/week for 6 weeks was superior to aspirin on biochemical assessments.Goebel 1981 A single trial evaluated the effectiveness of intramuscular bovine-derived orgotein in rheumatoid arthritis; though demonstrating efficacy, orgotein was less potent than gold for treatment of rheumatoid arthritis.Walravens 1976
In a double-blind, randomized, multicenter study in idiopathic pulmonary fibrosis (N=55), daily IV administration of 40 or 80 mg of lecithinized SOD was compared with placebo over 28 days. Forced vital capacity did not improve in the treatment arm; however, lactate dehydrogenase and surfactant protein-A makers were improved.Kamio 2014
Oral supplementation with plant-derived SOD 500 mg once daily for 6 weeks improved SOD activity and reduced C-reactive protein in a study of 19 professional rowers; however, no effect on oxidative damage from exhaustive exercise was demonstrated.Skarpanska-Stejnborn 2011
Antioxidant effects
Animal data
Antioxidant effects, such as in reperfusion injury, have been studied in rodents.Romao 2015
Cancer
In a study evaluating the relationship between serum SOD levels and the risk of cancer mortality, elevated serum SOD levels were associated with an increased risk of death from all cancers combined; this result may indicate an increased response to stress.Pham 2009
The relationship between ROS and cancer has been studied extensively, and the role of SOD expression in cancer cells has been evaluated, with most attention given to mitochondrial manganese SOD3.Dhar 2012, Holley 2012, Robbins 2014
Animal and in vitro data
Animal model studies of supplemental SOD for chemoprevention are limited.Robbins 2014 A study evaluating effects of recombinant manganese SOD (rMnSOD) on survival signaling in pediatric high-risk T-cell acute lymphoblastic leukemia found increased apoptotic death in leukemic cells, with no effect on healthy lymphocytes at low and moderate concentrations.Pica 2015
Clinical data
Clinical studies of supplemental SOD in cancer treatment are limited. SOD has been evaluated for its protective effects against irradiation-induced toxicities, with some reduction in late toxicity noted in one study of patients receiving pelvic radiation.Carillon 2013, Esco 2004 Lecithinized human recombinant SOD was not protective against the cardiotoxic effects of anthracycline treatment in breast cancer patients.Broeyer 2014
Cardiovascular disease
Animal data
A rodent study reported benefit in angiotensin II–dependent hypertension with use of Cu,Zn-SOD nanozyme (nanomedicine-based delivery system); however, significance of results is limited due to limitations of the intracerebroventricular route of administration.Savalia 2014
CNS effects
Clinical data
Limited clinical studies report equivocal results in psychometric scale measures and depression with oral administration of gliadin-combined plant SOD supplements compared with placebo.Carillon 2014, Houghton 2011
Dermatologic activity
Dermatological applications have been evaluated, and a role for SOD3 supplementation has been theorized.Hellstrom 2009, Kwon 2012
Kidney injury
Animal data
Pretreatment with rMnSOD greatly reduced contrast-induced nephropathy in rats, including both intratubular cysts and tubular necrosis.Pisani 2014
Preterm infants
Clinical data
Following a multicenter trial evaluating intratracheal recombinant human Cu,ZN-SOD for prevention of bronchopulmonary dysplasia in preterm infants, post hoc analysis of a subgroup of newborns (born at less than 26 weeks) suggested a reduction in the risk of retinopathy of prematurity.Parad 2012
A Cochrane Collaboration meta-analysis of 2 trials concluded that SOD administration provided limited benefit to preterm infants on ventilators for prevention of chronic lung conditions.Suresh 2001
Dosing
Orally administered SOD alone (including that occurring naturally in food) is rapidly degraded by gastric acids when ingested, even if enteric coated; however, newer formulations may overcome this limitation.Giri 1984, Zidenberg-Cherr 1983 Methods such as liposomal encapsulation and coating with wheat-derived gliadin have been used to overcome poor oral bioavailability.Romao 2015
Plant-derived oral SOD (commercial product) 500 mg taken orally once daily over 6 weeks was used in a clinical study evaluating effects on the balance between oxidants and antioxidants and on inflammatory marker levels in professional rowers.Skarpanska-Stejnborn 2011
Lecithinized SOD 40 or 80 mg/day IV over 28 days was used in a study of patients with idiopathic pulmonary fibrosis.Kamio 2014
Weekly intra-articular injections of orgotein (range, 4 to 32 mg) have been studied in patients with rheumatoid arthritis or osteoarthritis of the knee (treatment duration, 3 to 6 weeks).Goebel 1981, McIlwain 1989
No evidence exists regarding the long-term use of SOD.
Pharmacokinetic studies of recombinant-derived SOD have evaluated IV doses of up to 160 mg and report a mean terminal half-life of 25 hours (standard deviation [SD]=4 hours) for an 80 mg dose and 31 hours (SD=15 hours) for a single 160 mg dose.Broeyer 2008, Suzuki 2008
Pregnancy / Lactation
Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
Information from large clinical studies is lacking; however, adverse effects appear to be limited.Romao 2015 Pain and irritation at injection sites have been reported.Afonso 2007, Uthman 2003
Toxicology
SOD is regarded as nontoxic, based on data from earlier studies. Data on newer formulations are lacking.Batinić-Haberle 2010 The safety of SOD has been investigated in numerous older studies of animal models using doses 5 to 2,500 times the average human clinical dose of 0.04 mg/kg/day. Abnormalities were noted rarely following acute or long-term parenteral administration in mice, rats, guinea pigs, rabbits, and monkeys. SOD did not induce embryonic or teratogenic changes in rats or rabbits.Carson 1973
References
Disclaimer
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This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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