The induction of human superoxide dismutase and catalase in vivo: A Guide to Cellular Health.

by Philip Kavanaugh M.D.; Peter Rothschild M.D. Ph.D

©2004 Agrigenic Food Corporation Original Artwork – Agrigenic Food Corporation
IsoSproutPlex: A Novel Antoxidant Enzyme Induction Methodology.
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]

1 Ingredients
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.

2 Mechanism 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
4.1 The 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 1989 as 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]

4.2 Unpublished 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.

5 Published Clinical Studies
5.1 Chernobyl 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.

7 Veterinary 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].

8 Competing 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.

8.1 U.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]

8.3 Orally 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.

9 See 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

10 References
^ 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=0543b7a65c9d5985cf5f438b45fe317d#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. PMID 18167310.

^ 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. PMID 12239572.

^ 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. PMID 19568888.

^ 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. PMID 11466310.

^ “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. PMID 18820905.

^ 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. PMID 12816884.

^ 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. PMID 12726915.

^ 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. PMID 15754123.

^ {{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/S0007114508965752. PMID 18503734.

^ Birkhäuser, Basel (September 2006doi=10.1007/s00011-006-5195-y). “Therapeutic potential of superoxide dismutase (SOD) for resolution of inflammation”. Journal Inflammation Research 55: 359–363. doi:10.1007/s00011-006-5195-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.

12 Further 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/nature02583. 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/nature01960. 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/nature02789. 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/BF00421046. 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.

Stress is a relatively new notion that everybody talks about, yet few understand. The dictionary defines stress as “pressure”, force, strain: a state of physical or mental tension inducing it, or affecting something. “This definition, while obviously correct, is not very helpful in understanding the concept of stress. On the other hand, it is important to comprehend the notion, because all of us are continuously exposed to stress. Stress occurs in many forms. The four major categories which concern us are: 1) chemical stress; 2) emotional stress; 3) physical trauma; and 4) infections.

Each of these stress forms can originate from multiple sources. Most of these have appeared as primary threats in our environment as recently as this century. For example, chemical stress can come from pesticides, insecticides, polluted air and water, heavy metals such as mercury or lead, asbestos and, worst of all, radioactive waste. Even jet travel, a welcome commonplace today but unheard of a mere half a century ago, exposes passengers to unhealthy high levels of ozone and random, cosmic radiations. In the light of such widespread physiological insult, it is a miracle that any of us manage to stay healthy at all.

One of the primary reasons why stress is so important to understand, is because it is intricately linked to the functioning of our immune systems. How have many of us gotten a cold when our defenses were impaired by excessive stress? This is another angle from which to view the recent rash of immune disorders unleashed in our culture. Could these problems be partly caused by an overwhelmed immune system? It should be obvious that this is quite possible, and the more we consider the high levels of stress that most of us are exposed to daily, the more relevant the idea becomes. In other words, understanding and compensating for the stress in our liveswill help our immune systems and enhance our abilities to stay well.

This is not to imply that all stress is harmful. Exercise, for example, is a form of stress on the body that is quite healthy. Yet, if we over-exer tourselves during exercise, we can damage the body and create problems. As we have already mentioned, many unavoidable stress factors, such as pollution, and others that cause damage to the body, stem from today’s world of technological progress. In many cases the physical result brought on by several different forms of stress is the same. These unnecessary, but avoidable, results are cellular damage caused by overreactive molecules called free radicals.

Due to their overreactive natur , free radicals can be extremely toxic and are a direct consequence of the primary stress factors that adversely affect the immune system and threaten our health. However, this is not to imply that free radicals are always harmful or dangerous. Minute amounts of free radicals are essential for many important functions of the immune system and other vital cellular activities. For example, the immune system will actually generate free radicals to use in the process of removing a virus or bacteria. Only when high concentrations of free radicals are present, or when the levels of free radicals overwhelm the body’s ability to remove them, does a threat to our health occur. Maintaining the balance between the free radical activity and antioxidant enzyme supply is one of the important functions of the body. (Fig. 1)

Fig. 1 – Balance maintained. Normal levels of toxic free radicals are neutralized by cellular production of antioxidant enzymes.
It is the cell where free radicals are created and do the most damage. In the case of the immune system, this random circulation of unprepaired electrons causes communication breakdown between the immune system cells and the body, thus weakening and frequently wiping out some of their signals. Simply put, excess free radicals create chemical reactions in the wrong place at the wrong time causing confusion and wreaking havoc with the cellular environment. If we consider that most components that eventually increase the free radical release in our bodies are ultimately linked to factors generated by the so-called progress of our civilization, it is easy to understand why such an increasing number of us fall prey to germs and viruses.
©2004 Agrigenic Food Corporation Original Artwork – of Medici Studios Limited

An immune system overwhelmed by the high toxicity of massive free radical assault will react very poorly, if at all, to threats posed by germs, viruses or to abnormal cell formations (like cancer). This is particularly true if such abnormalities are due to cell poisoning to begin with. Our ability to resist and defeat the onslaught of invaders like germs and viruses rests precisely on the reliability of a strong and capable immune system. Again, stress and the resulant free radicals are a primary cause in weakening the immune system.

As we have discussed earlier, the different forms of stress exert a common free radical insult on many of the body’s vital cellular processes. Understanding the relationship between stress, free radicals and cell damage is very important. By understanding this relationship, we can more effectively ward off the negative effects of stress. The issue becomes even more relevant when we realize that over 30 years of medical research has revealed that intensive free radical activity represents a major cell damaging factor that is implicated in every degenerative disease of our time.

Fortunately this massive amount of medical research, consisting of over 6000 published scientific studies, has also uncovered the primary factors for free radical protection in the body. This free radical protection system is primarily made up of an array of body-produced enzymes called antioxidants. Antioxidant enzymes are the first line of defense against free radicals and must be present in in sufficient amounts to avoid unnecessary cellular and tissue damage.

All enzymes are essentially catalysts, that is, they are complex molecules stimulate chemical reactions without becoming consumed or integrated in the reactions thet trigger. There are literally thousands of enzymesthat occur in nature. Some of these serve to split and break down molecules. These enzymes are able to degrade tissue and compounds into simpler molecules, or in some cases, even to their constituent atoms. Life on this planet would be impossible without enzymes since organic waste and dead tissue could not be disposed of and food could not be digested. Examples of break-down enzymes are the digestive enzymes such as protease or trypsin.

A smaller, but not less important part of all existing enzymes are the types that stimulate the building up – or the synthesizing – of atoms to form molecules. The enzymes that enhance synthesis of atoms and molecules into larger and more complex molecules and tissuesare also essential to life. They are linked to the creation of new tissue, and no organism could ever germinate, or grow without their support. Examples of synthesizing enzymes would be ribonuclease (RNA), and deoxyribonuclease (DNA).

Thus, our body functions are regulated by an elaborate system of enzymes responsible for the unhindered operation of most of the complex interactions between breakdown and synthesis, and whose intricate communication patterns we define as life. Without the assistance of enzymes we could never be conceived, nor could we grow or live and, paradoxically, we coulden’t even die properly.

Antioxidant enzymes in particular, have the all-important role of controlling and regulating free radical activity in the body; and, therefor, allowing for the possible prevention of unnecessary cellular and tissue damage all too common in our society. Fig. 2

©2004 Agrigenic Food Corporation Original Artwork – of Medici Studios Limited

Fig. 2 – Adapted from Healing Aids Naturally, L. Badgley; M.D.
The cells utilize oxygen and nutrients to make ATP, the basic energy molecule. Free radical by-products are generated in this process, and are removed by a system of antioxidant enzymes and nutrients. The free radicals which are deactivated are then recycled by the body again. For example, hydrogen peroxide is converted into oxygen and water. If there is plenty of oxygen, fuel, water, and antioxidant enzymes, cell damage is kept at a minimum. If any of these are missing at any point in the system, cell damage, (aging) follows. The body will employ antioxidant nutrients, such as beta-carotene, vitamin E, and vitamin C, to clean up any free radicals that get by the antioxidant enzymes. The antioxidant enzymes remove free radicals 3 to 10 times faster than the antioxidant nutrients.

Despite hundreds of different medical terms that are used to describe them, many aging processes and most diseased conditions are nothing more than an accumulation of cellular damage. In these situations, more cells are being damaged than the body is able to repair or replace. The understanding of this concept and it’s implications is overwhelming when we realize that much of this cellular damage has it’s begininng or ending in a free radical induced chemical reaction. When the levels of free radicals are higher than the supply of antioxidant enzymes, we speak of free radical pathology which represents a more accurate definition of the cause of most conditions than the current terms being used which tend to denote the result (i.e. cancer, heart disease, etc…). (Fig. 3) Additionally, free radical damage to certain types of cells is irreversable. Three types of cells: heart muscle cells, nerve cells (which include brain cells), and certain sensor cells of the immune system cannot be replaced in the adult human. Damage to these types of cells must be prevented to ensure a long healthy life.

Fig.3 – Excess free radicals from stress create imbalance and free radical pathology.
©2004 Agrigenic Food Corporation Original Artwork – Agrigenic Food Corporation

Once again, this is not to imply that excess free radical activity is the sole cause of aging and disease. Yet, it is true that a large majority of unnecessary cellular damage which leads to aging and disease can be avoided by following two simple guidelines. First, the free radical causing stress in our lives must be reduced or removed. Second, the antioxidant enzyme, or anti-free radical defense system, of the body must be properly supported. If even one of these premises can be implemented effectively, the process of our own individual aging and disease potential will be altered significantly.

The unfortunate truth is that many forms of free radical forming stress that originate in our so-called civilized environment and society are completely avoidable. For example, while it is true that it is entirely up to you to give up smoking, drinking and eating junkfood, you’ll find it very difficult to avoid inhaling polluted air – especially if you live in the city. Pesticide residues on food and in water are also difficult to avoid completely. Radioactive wastes and nuclear experiments, as well as increased cosmic radiation due to a weakened ozone layer, are also potentially harmful. Additionally, hundreds of other force fields generated by computers, microwaves, and power lines compound the problem. Unless you are prepared to to become a hermit – in which case it would be a different set of stresses you would have to adjust to – there is nothing you can do to eliminate all of these free radical causing stress factors.

Fortunately, there are many things you can do to support the antioxidant enzyme defense system. Even before many of these stress factors were present, the ancient Essene medical practitioners proposed that ingesting certain types of wheat sprouts would be helpful to the body in it’s quest to maintain health and balance. Today, confirming ancient Essene experiences, modern scientific analysis has shown that certain types of wheat sprouts will actually enhance the body’s production of antioxidant enzymes. This is a paramount in our search for methods of counteracting unavoidable stress. Though adding specially prepared, whole, sprouted foodconcentrates to our diet and supplement programs, we can ensure that excessive free radicals from any source are removed from the body by literally enhancing the body’s production of antioxidant enzymes.

Even though the production of antioxidant enzymes in the body is a complex process that is not yet totally understood, there are several processes that we are aware of and which seem to constitute a large part of the finished system.

The antioxidant enzyme defense system consists of hundreds of different substances and mechanisms. This is why only an adequate combination of whole foods, such as sprouted food concentrates, will contain all of the known and unknown nutritional factors that the body requires to enhance it’s antioxidant enzyme supply.

We are a species that cannot live without breathing. As a result of this circumstance oxygen has turned into a synonym for life. A fact much less known is that not all oxygen atoms are life supporting. Some are actually quite destructive for our cells.

These unhealthy oxygen atoms are unbalanced and constitute the most common free radical known. Characterized by having an unpaired electron in it’s molecular structure, this oxygen free radical, called superoxide , is quite capable of causing cell damage.

The first line of defense the body has against superoxide free radicals is the enzyme known as superoxide dismutase, or SOD, which is considered the most effective antioxidant. The importance of SOD is so paramount for the protection of our cells, that it represents a substantial proportion of the proteins manufactured by the body. In brief, SOD keeps oxygen under control.

In the process of removing superoxide free radicals, SOD rarely operates alone. It requires the enzyme catalase to remove hydrogen peroxide molecules which are byproducts of the reactions created by SOD. Similar to SOD, catalase is abundant in the body. Integrated in all red blood cells, catalase removes hydrogen peroxide from our tissues, preventing both cell damage and, more importantly, the formation of other, more toxic, free radicals. In nature, and in the body, SOD and catalase always coexist. The natural interaction – synergy – between these two antioxidant enzymes constitute the most effective system of free radical control in our bodies.

Superoxide free radicals initiate the the breakdown of synovial fluid – the lubricating element – in the joints, causing friction and, eventually inflammation. For this reason, the attention of clinical SOD research has been focused primarily on inflammatory processes triggered by superoxide free radicals such as arthritis, bursitis and gout. Deficiency in SOD/catalase is the most notorious nutritional factor in most inflammatory processes. Recent applications of SOD/catalase enhancing foods have also proven to be extremely useful as a pre- and postoperative supplement which stimulates recovery and reduces convalescence periods remarkably.

Considering the powerful link between free radicals and many health problems, supplements that enhance SOD and catalase activity in the body offer tremendous potential in the field of preventive nutrition.

Glutathione peroxidase is another of the body’s major protectors against free radicals. This antioxidant enzyme consists of the amino acid glutathione and trace mineral selenium. These two nutrients team up to combat a specific class of free radicals called peroxides. The main biological function of selenium in mammals is a component of the glutathione peroxidase enzyme. Many of the attributes of selenium and glutathione are actually attributes of glutathione peroxidase.Cell membranes consist primarily of lipids (fats). These lipid membranes are very susceptible to damage by free radicals, especially peroxide free radicals. This is why rancid fats (lipid peroxides) have been proven to be highly toxic. Glutathione peroxidase prevents destruction of cell membranes by removing several classes of these lipid peroxides.The main symptoms of excess peroxide free radicals include heart disease, liver disease, premature aging, and skin diseases such as skin cancer, eczema, wrinkling, age spots, dermatitis and psoriasis. Peroxide free radicals mediate much damage to the body by impairing liver functions. Consisting of nearly 50% fatty tissue, the liver is very susceptable to lipid peroxidative damage.Although used primarily for skin related problems, many environmentally sensitive and chemically poisoned people report that glutathione peroxidase helps them control their allergies and build resistance to the side effects of pollution. Generally speaking, all of the antioxidant enzymes are important to where pollution is a concern due to their abilityto remove free radicals generated by toxic substances. The list of protective effects of glutathione peroxidase is growing and is in no way limited to any single symptom such as age spots. The effects of excess peroxidation in our cells is diverse and dangerous and must be limited to maintain cellular health.

Methionine reductase is a unique enzyme that has demonstrated an ability to remove an extremely toxic free radical called the hydroxyl radical. The hydroxyl radical is commonly formed through reactions involving heavy metals and other less toxic free radicals, such as mercury reacting with hydrogen peroxide. The hydroxyl radical has the ability to damage any type of organic cellular tissue and is considered to be the most dangerous free radical. Hydroxyl radicals are also the main toxins generated by exposure to excessive radiation. With their ability to any type of tissue, symptoms directly related to hydroxyl radical-induced tissue damage are difficult to identify.

One effective detoxifying application for methionine reductase is in the removal of free radical toxins generated by the mercury found in dental fillings. Another interesting application of methionine reductase is for the modern day athlete. It seems that hydroxyl radicals are also formed during exercise. This is especially true if we are exercising in oxygen starved closed rooms or in car exhaust filled polluted environments. It is amazing to see joggers running along the road during rush hour traffic. Quite possibly, they are doing more harm than good.

Most avid exercisers are aware of the need to obtain extra nutrition to fuel their activities. What many miss, is the importance of cleaning out the extra metabolic wastes that are direct results of this exercise. Hydroxyl radicals can be created when we burn fat molecules to produce energy as in strenuous exercise or dieting. This is due to lack of evacuation of chemicals and toxins stored in the fatty tissue which are released when these tissues are used for fuel. These toxins, when not properly evacuated, generate the formation of hydroxyl radicals. People using methionine reductase have reported greater resistance to the ill effects of pollution as well as greater endurance, stamina, flexibility, and ability to recover from extensive exercise. Although it is generally important to exercise, our modern civilized environments force us to compensate for free radical by-products if we wish to gain health or longetivity from our workout programs.


Today, many people are aware of the nutritional power of “live” foods and try to incorporate raw and/or sprouted foods into their diet. As mentioned earlier, the ancient Essene medical practitioners prescribed sprouted foods to treat and prevent many illnesses. One of the ways that science has demonstrated the revelance of sprouts as a superior source of nutrition, is through the use of certain types of specially developed organically grown sprouts that actually increase the antioxidant enzyme supply of the body. More importantly, these special types of organically grown sprouts seem to carry out this very important task by literally enhancing the body’s own production of antioxidant enzymes.

Although it is not totally understood how certain sprouts are able to have this effect on antioxidant enzyme production in the body (i.e, in-vivo), certain characteristics observed during the growth stage of sprouts reveal some important clues. Grains, such as wheat, go through four primary stages of growth – 1) from seed to sprout: 2) from sprout to grass: 3) from grass to grain: and 4) from grain back to seed. At each stage of growth the needs of the plant as well as the nutritional structure and content change dramatically. For example, the sprout contains little or no chlorophyll, whereas the grass, through it’s contact with light, contains large amounts of chlorophyll. Another important example is in the protein gluten, the sprout and grass do not. This is why people who are allergic to wheat are able to tolerate wheat sprouts or wheat grass. The fiber content and type changes significantly during the Growth Cycle of the wheat plant as well. The sprout contains higher amounts of soluble fiber than the grass from predominately insoluble fiber.

Sprouts are the vegetable equivalent to the fetal stage development in humans and animals. This is probably the most important clue in understanding the sprouts ability to affect antioxidant enzyme production in mammals. The sprouts’ cells are nondifferentiated, meaning they have not totally taken the structured form yet of the complete plant. At this stage of development, just as in the fetus, the sprout is quite vulnerable to random free radical activity. It must not only contain a large supply of antioxidant enzymes, but also be able to produce more if the need arises. These antioxidant enzymes preserve vital components ensuring the proper growth and development of the plant. It has also been shown that young children or infants contain much higher levels of antioxidant enzymes, superoxide dismutase and catalase, than their adult counterparts.

As the sprout matures, breaks through the ground, and gains access to light, it’s antioxidant enzyme content reduces while it’s chlorophyll, vitamin A, and other nutrients related to photosynthesis increase. Thus, at the earliest stages of development, the sprout has a naturally built-in capacity to produce antioxidant enzymes in whatever amounts that may be necessary to preserve it’s development.

One of the difficulties of utilizing sprouts to enhance antioxidant enzyme levels in the body that the amounts required to have an effect are quite large – usually much more than even sprout fanatics are willing, or able, to eat in a day. Fortunately there are products available today, developed from specially developed organically grown wheat sprouts, that contain amounts of antioxidant enzyme nutrition large enough to increase antioxidant enzyme levels in the body.

Using special growing and drying techniques, these antioxidant enzyme products contain over a quart of sprouts to each tablet. The technique employed to produce the finished product guarantees that most of the original active ingrediants of the living sprout are preserved in the tablet form. Grown in totally controlled environmenta, gently dried at room temperature, and tableted without fillers or binders, these whole sprout concentrates are the most powerful food supplement available today. Most importantly, being whole food products, they contain balanced amounts of hundreds of different nutritional factors, instead of just vitamins or minerals in isolated forms. While nutritional imbalances may be created with isolated vitamins and minerals, such imbalances are virtually impossible with unprocessed whole food products. Whole food supersprout concentrates are Nature’s Way of providing antioxidant enzyme nutrition to the body.

The importance of the special techniques utilized in the production of whole food supersprout concentrates is illustrated in one of the double blind studies that was performed with the products. Being a whole food product, creating a placebo that looked identical to the real product, was a difficult task. Yet, realizing that enzymes and co-enzymes are degraded when exposed to excessive heat, the placebo was then created by overheating the original product. While the original product created a dramatic increase in the antioxidant enzyme activity in the test group, the cooked product had no effect on the antioxidant enzyme activity in the placebo group. (fig. 4) How many of us eat primarily cooked foods in our diets? It is easy to see that eating primarily cooked foods, coupled with excessive free radical causing stress could contribute to create the problem of poor levels of health that afflict people in civilized cultures.

©2004 Agrigenic Food Corporation Original Artwork – of Medici Studios Limited

Fig. 4 – Results of serum superoxide dismutase (SOD) and catalase (CAT) from absorbtion. Study with STRESS RELEASE (SOD/CAT)tm by Agrigenic Food Corporation, Ordonez, L., Rothchild, P., Academia de Medicina, Francisco Villa 18, Las Palmas, Matamoros, Tamaulipas, Mexico, 1988. Testing procedures involved Fluorescence Fading Time and are described in detail by Rigo, A., Rotillo, G., Determination of Superoxide Dismutase and Catalase in Biological Materials by Polargraphy, Anal. Biochem., 81 (1) 157-661/ 1977 Jul/1MD

The absorbtion of enzymes and other complex proteins (i.e. peptides) is easily the most controversial issue when regarding supplementation designed to increase antioxidant enzyme enzyme activity in the body. It is generally believed that all complex proteins are completely broken down by the acids in the stomach and, therefor, supplementation of either enzymes or peptides is supposedly worthless at best. These ideas are based on research mostly performed over 50 years ago and – despite a large volume of recent scientific studies, including the one mentioned above, which demonstrate that some active peptides and compounds do effectively bypass stomach acids and are being absorbed into the intestines – the established scientific community has been reluctant to change it’s mind. Recently published articles have taken this issue to task and , “…..there is irrefutable evidence that small amounts of of intact peptides and proteins do enter the circulation under normal circumstances.” (See reference 3)

While biological results of increased enzyme activity, such as the study mentioned above, do not necessarily prove absorbtion of enzymes or peptides in the intestines, the fact that the active or unheated product did create an increase in enzyme activity, while the heated product – used as a placebo – did not , demonstrates that some complex enzyme(s) or peptide(s) within the product was indeed responsible for the result.

Physicians and veterinarians utilizing whole food supersprout concentrates to improve the nutritional ststus of their patients, report a long list of positive benefits that can only be related to an improved nutritional standard. These benefits include deminished joint pains and inflammation, more energy, better circulation, and, most importantly, significantly reduced recovery time after surgery and other types of convalescence after severe stress conditions such as physical trauma. Clearly, the degree to which a patient is well nourished does affect their ability to cope with stress. Apparently, whole food sprout concentrates supply the right nutrition for these circumstances. Due to the growing understanding of antioxidant enzymes, pharmaceutical companies are also persuing the development of new compounds includind SOD. These products, unlike whole foods, contain isolated enzymes and could potentially create imbalances. Such new products will, of course, be regulated as drugs and require prescriptions. Fortunately, we have whole food ‘supersprout’ concentrates at our disposal to naturally assist our body’s maintenance of adequate antioxidant enzymes.

Individuals utilizing whole food ‘supersprout concentrates in their supplement programs report more energy, better mental clarity, reduced allergic reactions to environmental pollution, diminished joint pains and inflammation, more stamina for extended exercise, and, of course, significantly reduced recovery time when injured or subjected to excessive stress such as a hard workout. Many individuals even report that they effectively feel younger.

All these effects can be easily attributed to the reduction of unnecessary tissue damage caused by excess free radicals and can be afforded by all who intelegently choose whole food supersprout concentrates in their diet and supplement programs.

The all-important balance between free radical activity and antioxidant enzyme supply can be effectively maintained with whole food supersprout concentrates. (Fig. 5)

Fig. 5 – Balance restored, whole food antioxidant enzymes neutralize excess free radicals from stress conditions.
©2004 Agrigenic Food Corporation Original Artwork – of Medici Studios Limited

Radiation Protection Manual. Lita Lee, PhD, 2061 Hampton, Redwood City, CA 94061. 415-369-2554.
Antioxidant Adaption: It’s Role in Free Radical Pathology. Stephen Levine, PhD, 400 Preda St., San Leandro, CA 94557.
Gastrointestional Absorbtion of Intact Protein., Michael L.G. Gardnre, Ann. Rev. Nutr. 8:329-50, 1988.
Absorbtion Study With SOD/CAT tm. Rothchild, P.R., Ordoniz, L., University Labs Press, 1215 Center St., Honolulu, HI 96828.
Free Radicals in Medicine, I , Chemical Nature and Biological Reactions. P.A. Southorn and G. Powis, Mayo Clin Proc, 63:381- 389, 1988.
Free Radicals in Medicine, II, Invlovement in Human Disease. P.A. Southorn and G. Powis, Mayo Clin Proc, 63:390- 408, 1988.
Oxygen-Derived Free Radicals: Pathophsiology and Implications. Mark E. Hitt, DVM, Compendium Small Animal, Vol. 10, No. 8 Pg. 939-946. August, 1988.
Aspects of the Structure, Function, and Applications of Superoxide Dismutase. J.V. Bannister, W.H. Bannister, G. Rotilio, Critical Reviews in Biochemistry. Vol. 22, No. 2 Pg. 111-180, 1987.
Superoxide Dismutase and Glutathione Peroxidase Activities in Erythrocytes as Indices of Oxygen Loading Disease: A survey of One Hundred Cases. L.L. Tho and J.K. Candlish, Biochemical Medicine and Metabolic Biology, 38, 74-80, 1987.
Chemical Reactivity and Biological Effects of Superoxide Radicals. C.A. Chuaqui and A. Petkau, Radiat., Phys., chem. Vol. 30. No.5/6 Pg. 365-373, 1987.
The Essene Way of Biogenic Living. E.B. Szekely, Internation al Biogenic Society, Apartado 372. Cartago, Costa Rica, Central America. 1978.
Free Radical Pathology in Age-Associated Diseases: Treatment With EDTA Chelation, Nutrition, and Antioxidants. Elmer Cranton, MD, James Frackelton, MD, Journal of Holistic Medicine. Vol. 6 No. 1 Spring/Summer 1984.
The information contained on this website has not been evaluated by the Food and Drug Administration (FDA). The Information found on this website should not be used to diagnose, cure, prevent or mitigate disease. This website is provided for educational purposes only. Statements contained herein are presented in an effort to share information about free radical biology , medicinal foods and advances in nutrition only. Content may change frequently and may be incomplete; consequently, information presented herein may not be accurate until finalized. Dietary supplement research and information expressed herein should be considered anecdotal in nature or opinions and hypotheses rather than generally accepted science. Unless otherwise noted, the studies presented herein may not have adhered to the strict regulatory controls required for approval of applied nutritional claims. Except where otherwise noted, some unpublished studies referenced herein have not been subjected to peer review in independent scientific journals. None of the information published herein may be used to suggest that any dietary supplement is a generally accepted treatment, preventative, cure or mitigation for any disease, except where approved as a permissible health claim pursuant to current regulation. See the FDA’s Center for Food Safety and Applied Nutrition Website for more information about approved health claims for dietary supplements.


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Superoxide Dismutase (SOD)
Boosting your body’s store of the enzyme SOD provides powerful protection against oxidative stress.
While everyone needs oxygen to stay alive, the same oxygen that sustains life also contributes to the generation of dangerous free radicals. Thousands of published studies implicate free radicals in the development of degenerative disease and accelerated aging.1 Young people naturally produce the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase to help protect against free radicals produced during normal physiological processes.

Levels of SOD and other critical antioxidant enzymes decline with age, contributing to the scourge of age-related disease and decline. Fortunately, recent advances in nutritional science now allow adults to replenish their stores of these powerful antioxidant enzymes. Emerging research suggests that a novel SOD agonist— IsoSproutPlex® helps boost antioxidant enzyme production endogenously. IsoSproutPlex® is a registered trademark used to identify a novel dietary supplement ingredient which acts on a novel pathway to increase superoxide dismutase (SOD) and catalase, as well as the selenium based enzyme glutathione peroxidase. Increasing endogenous antioxidant enzyme levels is has garnered interest from medical researcher as an alternative to steroid based anti-inflammatory drugs for reducing pain related to inflammation by reducing reactive oxygen species (ROS) and thereby promoting longevity.

Dangers of Oxygen Toxicity
Oxygen toxicity was first described in 1878, when laboratory animals were exposed to pure oxygen, and these deleterious effects were further established in 1899.1 During the Battle of Britain in World War II, pilots breathing pure oxygen for several hours daily developed emphysema, scarred lungs, and the effects of greatly accelerated aging. In some cases, the pilots looked and acted like men who were more than three times their age. One of the most tragic episodes of oxygen toxicity occurred later in the 1940s, when newborn infants were placed in oxygen-rich incubators. Some of the newborns went blind because their eye tissue had not yet accumulated dietary antioxidant carotenoids to protect against the toxic effects of higher-than-normal oxygen concentrations.2

When placed in hyperbaric chambers of pure oxygen with several atmospheres of pressure, laboratory animals die within a matter of minutes. By contrast, when the atmospheric pressure is slowly increased over a period of days, the animals manage to survive, because their bodies have time to produce higher-than-normal levels of the antioxidant enzymes that protect against oxygen toxicity. The lungs of animals exposed to higher-than-normal oxygen concentrations reveal massive tissue damage caused by too much oxygen, a condition known as hyperoxia. Thus, at higher-than-normal concentrations, oxygen is a toxic element. Oxygen utilization by aerobic (that is, oxygen-requiring) organisms such as humans is associated with the generation of potent free radicals.1,3

The Oxygen Paradox: Oxygen and Accelerated Aging
Numerous studies conducted over the last 60 years demonstrate that the by-products of normal oxygen utilization, including superoxide radicals and reactive oxygen species, may contribute to aging and degenerative diseases.4-6 Antioxidant enzymes that naturally occur in the body—including SOD, catalase, and glutathione peroxidase—act to minimize this oxidative stress, thus protecting cell membranes, essential proteins, and DNA from damage. These endogenous (internally generated) antioxidants produced within our cells are more potent in preventing free radical damage than are dietary antioxidants. SOD, for example, may be up to 3,500 times more potent than vitamin C in quenching the dangerous superoxide radical.

As noted earlier, however, levels of these antioxidant enzymes decline with advancing age in humans and animals alike, leading to an accumulation of free radicals and oxidative damage.7,8 In particular, SOD levels decline, correlating with an increased incidence of degenerative and inflammatory diseases.

Rheumatoid arthritis sufferers demonstrate lower SOD levels in their cartilage cells than do arthritis-free individuals. These lower levels of SOD may contribute to the destruction of cartilage in this inflammatory disease state.9,10 Low SOD levels in humans have also been associated with a host of degenerative diseases, including fibromyalgia,11 diabetes,12 cancer,13-15 multiple sclerosis,16 Alzheimer’s,17 and Parkinson’s disease.17,18

SOD levels in humans vary by as much as 50% owing to genetic differences, which may help to explain why some people are more prone to degenerative diseases while others lead long, disease-free lives.19

How SOD Promotes Longevity
In research conducted in the early 1980s by Richard Cutler at the Gerontology Research Center at the National Institutes of Health, mammals that produced higher tissue and serum levels of SOD lived longer than those with lower SOD levels.20,21 Cutler’s research demonstrated that mice and rodents have the lowest SOD levels among mammals, and that SOD levels are highest among more highly evolved mammals, with humans displaying the highest relative SOD levels.20,21

Humans produce an average of 90 micrograms per milliliter (mcg/ml) of SOD and live an average of nearly 80 years. Our closest primate relatives, chimpanzees, produce 40 mcg/ml of SOD and live an average of only 40 years. Fruit flies that have been bred to produce twice as much SOD as normal live twice as long as ordinary fruit flies. Cutler’s cross-species investigations strongly suggest that SOD is a primary determinant of longevity in mammals, and that increased SOD production played a key role in the higher order of mammals’ evolution from shorter to longer life spans.20,21

Levels of vitamin E and glutathione transferases similarly increase at the higher rungs of the mammalian evolutionary ladder. Data on antioxidant levels in mammals have been compiled from zoo, veterinary, and medical records from around the world.20,21

Two Studies, Striking Results
Although SOD’s benefits are well established, an orally ingested supplement that can boost SOD levels has eluded scientists for decades. After initial research revealed impressive results, however, Life Extension conducted two pilot studies (one open-label trial, one placebo-controlled trial) to help determine whether a novel plant-based extract called IsoSproutPlex®—derived from the sprouts of corn, soy, and wheat—could boost the body’s endogenous SOD levels and reduce chronic pain in aging adults.

Because free radicals are thought to contribute to chronic pain, it thus follows that antioxidants may offer pain relief. SOD activity in the blood lowers levels of the superoxide radical, which in turn diminishes levels of the inflammatory agent, hydrogen peroxide.

In the first open-label Life Extension study, 12 middle-aged volunteers of both sexes took 2000 mg daily of IsoSproutPlex® for two weeks. IsoSproutPlex® boosted serum SOD levels by 30% on average while lowering blood levels of hydrogen peroxide by 47%.22 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.23,24

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 IsoSproutPlex® supplementation restored their serum and blood levels of SOD to youthful parameters. Furthermore, supplementation with IsoSproutPlex® boosted activity of blood catalase, another crucial antioxidant enzyme, by an impressive 47%.22 If these subjects continue to use IsoSproutPlex® and thus maintain or further boost their blood levels of SOD, they should remain well protected against arthritic diseases, as suggested by the numerous studies correlating low SOD levels with pain and arthritis.9-11

A second pilot study (placebo-controlled) conducted by Life Extension examined IsoSproutPlex®’s 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®. 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. One of the study’s most remarkable findings was that those who were suffering the most pain at the study’s onset experienced the greatest pain relief benefit from IsoSproutPlex®.25

Case Studies Confirm Benefits
Case studies are a valuable means of gauging individual responses to the beneficial effects of IsoSproutPlex®.

Thomas H., a 72-year-old man, had pain in both knees, as well as stiffness and arthritis in both hands. Within a week of beginning the recommended daily 2000-mg dose of IsoSproutPlex®, he reported no noticeable pain in his knees or hands. A month after beginning supplementation, he reported no pain in his knees or hands, and had to be reminded that he had originally experienced pain in both knees. After three months of taking IsoSproutPlex®, he had no return of any pain, nor did the effects diminish over the three-month course of use.25

Ursula A. was diagnosed with pain in both feet that prevented her from standing for more than 20 minutes at a time. After one week of supplementing with IsoSproutPlex®, she reported that not only could she stand for long periods, but she was able to stand in the kitchen for six to eight hours each day for three days in a row doing her holiday baking. After three months, she reported no return of pain in her feet or elsewhere. Despite numerous X-rays, her doctor had previously not been able to pinpoint the exact location of her arthritis.25

Thomas S., a 29-year-old man who had recently had surgery in both knees, re-injured one knee in a fall, further damaging the joint. He was in constant pain and had given up all sports, including rollerblading. After taking IsoSproutPlex® for two weeks, he noticed a dramatic reduction in pain and inflammation in his knees. He has since returned to walking for exercise. During the three-month follow-up interview, he reported the same ongoing relief taking IsoSproutPlex® that he had experienced initially.25

Marie R. reported a 90% improvement in her pain symptoms within two weeks of taking 2000 mg of IsoSproutPlex® daily. She had developed severe inflammation in her right knee and had used crutches for two weeks at work and home. Within a week, she was able to discard the crutches, and at a three-month follow-up interview, she reported that she continued to experience a 90% reduction in pain.25

The two Life Extension pilot studies confirm that IsoSproutPlex® helps to alleviate the discomfort and stiffness associated with arthritis and other painful conditions. As noted in the accompanying sidebar, this natural approach to pain relief utilizes a mechanism of action that differs from conventional therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs).

Conventional pain medications such as aspirin and ibuprofen target the cyclooxygenase-1 (COX-1) and cylooxygenase-2 (COX-2) enzymes, thus decreasing levels of inflammation and pain.26 However, these nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with stomach and gastrointestinal problems. This is because the COX-1 enzyme is required for production of the protective mucosa lining the stomach and intestine. Chronic use or misuse of these products for inflammation and pain can lead to gastrointestinal irritation, ulcerations, and erosion of the digestive tract.26-29

Newer prescription NSAIDs like Celebrex® inhibit only the COX-2 inflammatory enzyme and spare the stomach-protective COX-1 enzyme. While these drugs are associated with fewer gastrointestinal side effects than are medications that inhibit both COX-1 and COX-2,28 these selective COX-2 inhibitors have been associated with increased incidence of heart attack and stroke. They may increase cardiovascular risk by upsetting the balance of vasoactive prostaglandins.30 Two selective COX-2 inhibitors were recently taken off the market, and the last selective COX-2 inhibitor still on the market, Celebrex®, is currently under intense scrutiny.31,32