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<!-- Add categories and interwikis to the /doc subpage, not here! → RGK (talk) 00: 31, 28 July 2012(UTC) '''IsoSproutPlex: A Novel Antioxidant Enzyme Induction Ingredient. ''' IsoSproutPlex, developed In 1983, was the first antioxidant enzyme inducer available for sale In the United States. It is a proprietary dietary supplement ingredient that strengthens the body’S antioxidant defenses by increasing Superoxide dismutase (SOD) [1], and Catalase(CAT), Glutathione peroxidase, (GPx), and Methionine Reductase, [2]. 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. [3] Contents 1Ingredients

2Mechanism of action

3Relationship to Calorie Restriction

4History of Product Development

4. 1The Smith-Kline Over Sixty-five Study

4. 2Unpublished Animal Study

4. 3 Twelve Years of Litigation

5Published Clinical Studies

5. 1Chernobyl Study

5. 2Life Extension Foundation Studies

6Other Trade names

7Veterinary use

8Competing Technologies

8. 1U. S. Dietary Supplement Regulation

8. 2 Approved Drug: Orgotein: Injectible S.O.D.

8. 3Orally Ingested Bovine Extracts: Ineffective

9See also

10References

11 External links

12Further reading

1Ingredients IsoSproutPlex 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.

2Mechanism of action According to its manufacturer, the preparation does not function directly As an antioxidant, [4] but like other plant-based phytoestrogens, including Resveratrol. [5][6] The preparation is claimed to induce a signaling cascade, ultimately activating the genes for a family of protective antioxidant enzymes, including Superoxide dismutase (SOD), [7][8][9] Catalase(CAT). [10][11][12] The preparation'S organically bound selenium separately promotes glutathione peroxidase activity, [13][14] and its specialized form of vitamin B−12 promotes Methionine (synthase) Reductase activation. [15] 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-β phytoestrogens. [16] By using a unique delivery system, [17] which navigates the majority of the preparation through the gastric acids In the stomach, to the small intestine. The improved timing increases the synergy and interaction of the preparations prebiotics, probiotics, existing gut micro-flora, and the compound'S daidzein which is likely converted to S−Equol, O−desmethylangolensin other estrogenic analogues endogenously. [18][19][20] 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. [21][22][23] Other unidentified antioxidant polyphenols and phytoestrogens may Be produced endogenously As a result of this compounds delivery system, which may account for the preparation'S advantage As an antioxidant enzyme inducer over other fractionated phytoestrogens and soy isoflavone concentrates. [24]

3 Relationship to Calorie Restriction 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, [25] and that these genes may also Be activated directly by dietary stimuli. However, without a scientific consensus, this theory remains highly speculative.

4 History of Product Development 4. 1The Smith-Kline Over Sixty-five Study 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 1989As a manufacturer-sponsored double−blind placebo controlled study conducted In Honolulu, Hawaii by Smith-Kline, Accupath. [12]. 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. [26]

4. 2Unpublished Animal Study In April 1989, Agrigenic'S predecessor, Biotec Foods-Hawaii, Ltd., conducted their first clinical animal studies. Entitled: The Effects of Oral Enzyme Supplementation Upon Musculoskeletal Inflammation: A Summary of Veterinary Clinical Research, its principal investigator was David Randall, DVM. The purpose of the study was to document the outcome of 387 dogs that presented to veterinary clinics with nonspecific musculoskeletal, inflammatory diagnosis. Veterinarian used standard techniques, including radio-graphic evaluation, pin-prick tests and palpitation, As well As owner reports, to make an initial diagnosis. Thereafter, participating clinicians/veterinarian enrolled each dog In the supplement'S clinical trial program. The study documented significant improvements In joint mobility and range of motion, As well As a reduced swelling In 340/387 cases (88%). Although 63 of the 340 patients did not show significant improvement until the fourth week, the average response time of the entire group was 8 days. All 340 cases which demonstrated improvement also reported increased levels of mobility As treatment time extended past initial response point. In most cases, a minimum of 1 tablet for each 20 pounds of body weight per day were necessary to achieve a measurable response. The data provided by that first clinical trial was, of course, anecdotal; however, the observations supported the hypothesis that orally induced antioxidant enzymes might Be used As effective anti-inflammatory In mammals.

5Published Clinical Studies 5. 1Chernobyl Study In 1991, Biotec Foods-Hawaii, Ltd., Agrigenic'S predecessor, funded a study entitled "Health Effects of Cell Guard on Belorussian 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 prominently features interviews with the principal investigators.

5.2 Life Extension Foundation Studies 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 IsoSproutPlex and non-probiotic IsoSproutPlex (placebo). A dramatic 71% response (clinically defined As a meaningful decrease In pain As measured by a validated pain assessment instrument) In the probiotic IsoSproutPlex 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]

6 Other Trade names IsoSproutPlex is synonymous with the following dietary supplements and trademarks: Cell Guard, Synovalex, AOX/PLX, Anti-Stress Enzymes, Ageless Beauty, Extra-Energy Enzymes, SODZyme, Biovet Dismutase, and IsoSproutPlex. In Japan, the supplement is branded As V−Pet.

7Veterinary use As a veterinary supplement, it is marketed As AOX/PLX, Biovet Dismutase, Canine Support, Feline Support, and the Biovet Antioxidant Petwafer. This antioxidant enzyme technology is primarily used to help reduce inflammation. [29]. Some homeopathic veterinary practitioners have documented their successful use of this antioxidant enzyme induction technology In place of the traditional corticosteroid drugs, which can have major side effects. [3], [4].

8Competing Technologies Antioxidant enzyme inducers, including IsoSproutPlex, 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.

8. 1U. S. Dietary Supplement Regulation 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 1994 DSHEA[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.

8. 2 Approved Drug: Orgotein: Injectible S.O.D. 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 for scleroderma, 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). [30]

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. [31]

8. 3Orally Ingested Bovine Extracts: Ineffective Several dietary supplement manufacturers 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. [32] 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 pharmacological 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.

9See also Index of Related Topics

Free Radical Biology and Medicine

Superoxide Dismutase and Catalase

Antioxidant Enzymes

SERMs, Estrogen Receptor Site Beta and S−Equol

Calorie Restriction As life extension

10References ^ See also CuZnSOD a.K.a extra-cellular (EcSOD) or SOD1; See also mitocondrial SOD a.K.a. CuMnSOD or SOD2); and extracellular SOD a.K.a. SOD3.

^ [EC 1. 18. 1.]

^LEF Articles [1]

^ References, .; To View References, Further Reading may Be Available for This Article; Must, Further Reading you; Williams, Robert J.; Spencer, Jeremy P. E.; Rice−Evans, Catherine; Wolfson Centre For Age−related Diseases, G.K.T. School of Biomedical Sciences; Rt, U.K. (December 2004). "Serial Review: Flavonoids and Isoflavones (Phytoestrogens: Absorption, Metabolism, and Bioactivity)". January 12(9): 31. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4BKGCGP−2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=C&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&Md5=0543 B7a65 C9d5985Cf5f438 B45Fe317d#m4. 1. Retrieved on 2009–08–10.

^ Robb EL, Page MM, Wiens BE, Stuart JA (March 2008). "Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD". Biochem Biophys Res Commun. 367(2): 406 – 12. doi: 10. 1016/j.bbrc. 2007. 12. 138..

^ Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (September 2002). "Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress". Nature 419(6904): 316 – 21. doi: 10. 1038/nature01036. .

^ Xu, Zhong; Zhong, Wenwen; Ghavideldarestani, Maryam; Saurabh, Rahul; Lindow, Steve W.; Atkin, Stephen L. (2009). "Multiple mechanisms of soy isoflavones against oxidative stress-induced endothelium injury". Free Radical Biology and Medicine 47(2): 167 – 175. doi: 10. 1016/j. freeradbiomed. 2009. 04. 021.

^ "Modulation of Antioxidant Enzyme Expression and Function by Estrogen". Christian 6(5): 6. 2003. doi: 10. 1161/01.RES. 0000082334. 17947. 11 (inactive 2009–08–11).

^ Nrf, Role of N.O. In; Expression, -Mediated Antioxidant Gene; Mann, Giovanni E.; David J. Rowlands, Francois Y.L. Li; Nh, U.K. (February 2007). "Activation of endothelial nitric oxide synthase by dietary isoflavones: ". Stamford Street, London SE 1(9).

^ Colman, J (2005). "Changes In serum levels of superoxide dismutase and catalase In humans after dietary SODzyme supplementation". Life Extension Foundation.

^ Colman, J (4 2005). "Effects of oral SODzyme administration on pain scores In human subjects with arthritis". Life Extension Foundation.

^ a B Rothschild, Peter, Et. Al (1988). "Absorption of oral enzymes and enzyme therapy In immune complex and free radical contingent diseases. ". University Labs Press, Honolulu, Hawaii. http://www.biotecfoods.com/pdf/IsoSproutPlex%20Distribution.pdf.

^ Mitochondria, Insights Into T.H.E. Interaction O.F. Ebselen With; Publication, February; Form, April; Published, J.B.C. Papers In Press; .; Kelso, Geoffrey F.; Smith, Robin A. J.; Unit, Wellcome Trust; Et al. (2005). "Synthesis and Characterization of a Triphenylphosphoniumconjugated". New Zealand 2(56): 9001. doi: 10. 1074/jbc. M501148200(inactive 2009–08–11).

^ Tinggi U (March 2008). "Selenium: its role As antioxidant In human health". Environ Health Prev Med 13(2): 102 – 8. doi: 10. 1007/S12199−007-0019-4. .

^ Olteanu H, Banerjee R (September 2001). "Human methionine synthase reductase, a soluble P−450 reductase−like dual flavoprotein, is sufficient for NADPH−dependent methionine synthase activation". J. Biol. Chem. 276(38): 35558 – 63. doi: 10. 1074/jbc. M103707200. .

^ "Estrogenicity of the Isoflavone Metabolite Equol on Reproductive and Non-Reproductive Organs In Mice. Biology of Reproduction 71, 966 – 972". Published online before print 19 966(972): 19. 2004. doi: 10. 1095/biolreprod. 104. 029512] (inactive 2009–08–11).

^ The compound is low-temperature dried, and granulated rather than pulverized into a fine powder. Thereafter, the compound is compressed into enteric coated tablets. The granules' particle size and pharmaceutical coating methodology are trade secrets.

^ Nutr, Am J. Clin (2009). "Is equol the key to the efficacy of soy foods?". Ajcn 26736(1): 26736.

^ Raimondi S, Roncaglia L, De Lucia M, Amaretti A, Leonardi A, Pagnoni UM, Rossi M (January 2009). "Bio-conversion of soy isoflavones daidzin and daidzein by Bifidobacterium strains". Appl. Microbiol. Biotechnol. 81(5): 943 – 50. doi: 10. 1007/S00253−008-1719-4. .

^ Heinonen, S (2003). "Metabolism of the soy isoflavones daidzein, genistein and glycitein In human subjects. Identification of new metabolites having an intact isoflavonoid skeleton The Journal of Steroid Biochemistry and Molecular Biology 87, !PAGESMARKER!, 285-299, !YEARMARKER!". The Journal of Steroid Biochemistry and Molecular Biology 87: 4 – 5. doi: 10. 1016/j. jsbmb. 2003. 09. 003.

^ Strehlow K, Rotter S, Wassmann S, Adam O, Grohé C, Laufs K, Böhm M, Nickenig G (July 2003). "Modulation of antioxidant enzyme expression and function by estrogen". Circ. Res. 93(2): 170 – 7. doi: 10. 1161/01.RES. 0000082334. 17947. 11..

^ Hwang J, Wang J, Morazzoni P, Hodis HN, Sevanian A (May 2003). "The phytoestrogen equol increases nitric oxide availability by inhibiting superoxide production: an antioxidant mechanism for cell-mediated LDL modification". Free Radic. Biol. Med. 34(10): 1271 – 82. doi: 10. 1016/S0891−5849(03)00104−7. .

^ DiSilvestro RA, Goodman J, Dy E, Lavalle G (February 2005). "Soy isoflavone supplementation elevates erythrocyte superoxide dismutase, but not plasma ceruloplasmin In postmenopausal breast cancer survivors". Breast Cancer Res. Treat. 89(3): 251 – 5. doi: 10. 1007/S10549−004-2227-6. .

^ {{Citation | title = Casts Doubt On Soy'S Health Benefits | url = http://www.consumeraffairs.com/news04/2005/soy_study.html | author = Date=, Study Casts Doubt On Soy'S Health Benefits | journal =. Consumer Affairs. pp. 2005 – 08.

^ Koubova J, Guarente L (February 2003). "How does calorie restriction work?". Genes Dev. 17(3): 313 – 21. doi: 10. 1101/gad. 1052903. {{PMID|12569120}}. Lay summary – New York Times.

^ Knasmüller S, Nersesyan A, MisíK M, Gerner C, Mikulits W, Ehrlich V, Hoelzl C, Szakmary A, Wagner KH (May 2008). "Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview". Br. J. Nutr. 99 E Suppl 1: ES3 – 52. doi: 10. 1017/S{{sub|0007114508965752}}. {{PMID|18503734}}.

^ Birkhäuser, Basel (September 2006doi=10. 1007/S{{sup|00011−}}006-5195-Y). "Therapeutic potential of superoxide dismutase (SOD) for resolution of inflammation". Journal Inflammation Research 55: 359 – 363. doi: 10. 1007/S{{sup|00011−}}006-5195-Y. ISSN 1023-3830.

^ Medical dictionary

^ Amyotrophic_lateral_sclerosis#SOD1

^ Zidenberg-Cherr, S; Et al. (1983). "Dietary superoxide dismutase does not affect tissue levels. ". Am J Clin Nutrit 37: 5..

11 External links "Agrigenic Food Company". http://www.agrigenic.com.

"SFRBM − Society for Free Radical Biology and Medicine". http://www.sfrbm.org.

12Further reading Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (July 2004). "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase". Science 305(5682): 390 – 2. doi: 10. 1126/science. 1099196. {{PMID|15205477}}.

Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L (June 2004). "Sirt1 promotes fat mobilization In white adipocytes by repressing PPAR-gamma". Nature 429(6993): 771 – 6. doi: 10. 1038/nature{{sub|02583}}. {{PMID|15175761}}.

Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (September 2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". Nature 425(6954): 191 – 6. doi: 10. 1038/nature{{sub|01960}}. {{PMID|12939617}}.

Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (August 2004). "Sirtuin activators mimic caloric restriction and delay ageing In metazoans". Nature 430(7000): 686 – 9. doi: 10. 1038/nature{{sub|02789}}. {{PMID|15254550}}.

Flohé L (December 1988). "Superoxide dismutase for therapeutic use: clinical experience, dead ends and hopes". Mol. Cell. Biochem. 84(2): 123 – 31. doi: 10. 1007/BF{{sub|00421046}}. {{PMID|3068519}}.

Muth CM, Glenz Y, Klaus M, Radermacher P, Speit G, Leverve X (September 2004). "Influence of an orally effective SOD on hyperbaric oxygen-related cell damage". Free Radic. Res. 38(9): 927 – 32. doi: 10. 1080/10715760412331273197. {{PMID|15621710}}.