SOD/CAT, developed in 1983, was the first antioxidant enzyme inducer available for sale in the United States. It is a proprietary dietary supplement ingredient that is alleged to increase the body’s antioxidant defenses by increasing Superoxide dismutase (as CuMn SOD, a.k.a. SOD2), Catalase, Glutathione peroxidase, (GPx), and Methionine Reductase,[1]. The product is manufactured by Biotec Foods, a division of Agrigenic Food Company. USPTO Registration Number 2933330[1]; Patent [60864798]. According to the company’s website, information about the product has not been reviewed by the Food and Drug Administration, and the product should not be used to cure, prevent or mitigate disease.[2]
SOD/CAT is manufactured from glycine max, T. durum and zea mays sprouts, and includes naturally occurring prebiotic oligosaccharides, as well as probiotic bifidobacteria and lactic acid bacteria, cyanocobalamin, methylcobalamin, and organically bound selenium.
According to its manufacturer, the preparation does not function directly as an antioxidant, but like other plant-based phytoestrogens, including Resveratrol.[3][4] The preparation is claimed to induce a signaling cascade, ultimately activating the genes for a family of protective antioxidant enzymes, including Superoxide dismutase (SOD), Catalase (CAT).[5][6][7]The preparation’s organically bound selenium separately promotes glutathione peroxidase activity,[8] and its specialized form of vitamin B-12 promotes Methionine (synthase) Reductase activitation.[9] Thus, the preparation reduces oxidative stress by increasing endogenous antioxidant enzyme capacity.
According to the manufacturer, it is formulated and designed to convert weaker phytoestrogens, which are found in many conventional foods and supplements, into stronger, higher affinity ER-beta phytoestrogens. The manufacturer believes that a high degree of timing and synergy is necessary to produce the desired intermediary compounds endogenously. The interaction of the prebiotics, probiotics, existing gut micro-flora, and the compound’s daidzein and other antioxidant polyphenols and phytoestrogens in the preparation are likely converted to S-Equol, O-desmethylangolensin and their analogues endogenously.[10] The compound is granulated rather than pulverized into a fine powder, and then compressed into coated tablets. Granulation and coating are significant factors because the critical interaction of the ingredients must occur within the small intestine, after the preparation safely passes through the stomach acids. The compounds genistein and the resulting phytoestrogens act as selective estrogen receptor site modulators (SERMs) which up-regulate SOD and catalase expression by acting as signaling molecules.[11][12][13]
Chemical structures of the most common phytoestrogens found in plants (top and middle) compared with estrogen (bottom) found in animals.
The exact mechanism of gene activation, the precise number and identities of the genes activated, and the primordial or evolutionary purpose behind these genes, remains unclear. However, renewed interest and research into life extension through calorie restriction, as well as extensive research into similar polyphenols and phytoestrogen compounds—though lacking scientific consensus–suggests that these genes evolved to prolong life during periods of near starvation,[14] and that these genes may also be activated directly by dietary stimuli. However, without a scientific consensus, this theory remains highly speculative.
The first formal research on human subjects was the The Smith-Kline Over Sixty-five Study of a small number of people aged 65 to 78, begun in 1989 as a manufacturer-sponsored double-blind placebo controlled study conducted in Honolulu, Hawaii by Smith-Kline, Accupath. [15]. The results suggested that the beneficial, anecdotal observations of health benefit were related to increases in erythrocyte superoxide dismutase and catalase, observed after three weeks of supplementation. Participants outside the control group demonstrated an average increase in erythrocyte superoxide dismutase of 230%. A control group using a placebo consisting of the inactivated (sterilized) version of the ingredients, had significantly smaller increases in erythrocyte superoxide dismutase and catalase after the same three-weeks of supplementation. Catalase activity was measured as a function of decreasing plasma hydrogen peroxide, consisted of measurement of TBARS levels, erythrocyte superoxide dismutase (SOD), and catalase levels, before and after administration of the supplement in 17 healthy adults. The substances measured are markers for oxidative stress.[16]
In 1991, Biotec Foods-Hawaii, Ltd., Agrigenic’s predecessor, funded a study entitled “Health Effects of Cell Guard on Byelorussian children and adolescents exposed to radiation as consequence of the Chernobyl AES accident.” The principal investigators N.A. Gres and T.I. Poliakova published their findings in a Russian language journal. A translation of the study is published on Agrigenic’s website. The company’s website video promanently features interviews with the principal investigators.
In 2005, Life Extension Foundation conducted several independent studies. In the first open-label study, 12 middle-aged volunteers of both sexes took 2000 mg daily of the product for two weeks. It boosted serum SOD levels by 30% on average while lowering blood levels of hydrogen peroxide by 47%. This is significant, because hydrogen peroxide may contribute to the inflammation of arthritis. While immune cells use bursts of hydrogen peroxide to kill viruses and bacteria, excess hydrogen peroxide may contribute to inflammation and arthritis. The 12 subjects in this study, whose average age was 58, did not suffer from arthritis but were beginning to experience normal age-related decline in their SOD levels. Two weeks of oral supplementation restored their serum and blood levels of SOD to youthful parameters. Furthermore, supplementation boosted activity of blood catalase, another antioxidant enzyme, by 47%. A second pilot study (placebo-controlled) published by Life Extension [3] examined its effects on adults diagnosed with inflammatory conditions such as arthritis. This placebo-controlled, 3-arm study involving 30 subjects over 4 weeks tested placebo, probiotic SOD/CAT and non-probiotic SOD/CAT (placebo). A dramatic 71% response (clinically defined as a meaningful decrease in pain as measured by a validated pain assessment instrument) in the probiotic SOD/CAT group vs. a 30% response in the non-probiotic group was observed. No differences were observed in the placebo group. Those who were suffering the most pain at the study’s onset experienced the greatest pain relief benefit from the product. [4]
SOD/CAT is synonymous with the following dietary supplements and trademarks: Cell Guard, Synovalex, AOX/PLX, Anti-Stess Enzymes, Ageless Beauty, Extra-Energy Enzymes, SODZyme, Biovet Dismutase, and IsoSproutPlex. In Japan, the supplement is branded as V-Pet.
As a veterinary supplement, it is marketed as AOX/PLX, Biovet Dismutase, Canine Support and Feline Support, and has been used as a feed supplement to help reduce inflammation.[17]. Some homeopathic veterinary practitioners have documented their successful use of antioxidant enzyme agonists in place of the traditional corticosteroid drugs, which can have major side effects.. [3], [4].
Antioxidant enzyme inducers, including SOD/CAT, Protandim, Resveratrol and Wolfberry, as well as other oral forms of S.O.D., including GliSODin and bovine liver extracts, are marketed as dietary supplements rather than as drugs.
While still policed by the U.S. Food and Drug Administration, dietary supplements are regulated in accordance with the Dietary Supplement Health and Education Act of 1994DSHEA[5]. DSHEA does not require the rigorous scientific proof required for FDA approval of new drug applications, (NDA). As a consequence, dietary supplements must limit their commercial speech when promoting product efficacy to so called, structure function claims, which must be disclosed in writing to the FDA and disclaimed as follows: This information has not been reviewed by the Food and Drug Administration. This product should not be used to cure, prevent or mitigate disease.
An injectible form of superoxide dismutase (Orgotein), obtained from bovine liver, is an approved drug, and has been promoted as an anti-aging agent and an effective treatment forscleroderma, radiation-induced cystitis, osteo-arthritis, inflammation, and urinary tract disorders. The Food and Drug Administration (FDA) has classified the parenteral formulation of the agent as an orphan drug used for familial forms of amyotrophic lateral sclerosis (ALS) and (FALS). [18]
Orgotein is the CuZn form of superoxide dismutase, or extra-cellular SOD1. Recent medical research suggests that FALS occurs when the SOD1 gene inexplicably begins to produce misfolded, ineffective SOD1 proteins, thereby exposing motor neurons to superoxide free radicals. More research is necessary to understand the underlying cause.[19]
Several dietary supplement manufacters promote bovine extracts as an oral form of S.O.D. However, the efficacy of orally ingested SOD from bovine extracts has been largely discounted.[20] Bovine extracts of SOD are rapidly degraded by gastric acids when ingested. It is essentially unabsorbed after oral administration even when enteric coated, and confers no pharmacologic activity when taken orally. While many foods (red meats, vegetables) are rich in SOD, their SOD is degraded when ingested and is rendered enzymatically inactive.
Robert Kavanaugh is an accomplished researcher whose primary focus over the past twenty years has been free radical biology and medicine.
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