A review of the science and health benefits for GliSODin

Literature review of a cantaloupe melon concentrate naturally rich in superoxide dismutase/wheat gliadin biopolymer and its beneficial health aspects.  

GliSODin : the 1st orally effective form of superoxide dismutase

In the past, oral supplementation with the superoxide dismutase enzyme in order to boost the body’s antioxidant defenses has been ineffective. This is due to the biochemical conditions experienced in the gastrointestinal tract, leading to degradation of the enzyme and subsequently rendering it useless. This technical publication reviews the science related to GliSODin, a trade name for SOD-rich cantaloupe melon combined with wheat gliadin. Science is presented to demonstrate that combination with gliadin protects the SOD during passage through the stomach and enhances absorption once inside the intestine.

pyramid sod

Superoxide dismutase (SOD) a main antioxidant defenses

Superoxide dismutase (SOD) constitutes part of the body’s front line in antioxidant defenses, helping to maintain the physiological oxidant-antioxidant balance. However, this balance can be disturbed by a number of different factors, including aging, smoking, pollution, exposure to sunlight, infection and the subsequent immune response, and high intensity exercise. Under such conditions the body experiences oxidative stress and this is linked with increased risk of chronic disease.

Antioxidant and imuno modulation properties

Results from in vitro, in vivo and human studies which show both the increase in antioxidant status as well as the reduction of markers of oxidative stress. It will also be shown that Glisodin’s bioactivity in humans has been demonstrated with a daily dose of as little as 250 mg over a period of just 14 days.

Anti-inflammatory and immune system modulating effects for the SOD-gliadin combination have also been reported, and these are discussed in this publication, with particular attention paid to the mechanism(s) behind the effects.

Reducing the production of reactive oxygen species associated with oxidative stress has many important health implications. These benefits include improved recovery after strenuous exercise, reduction of inflammation (reddening) in the skin on exposure to sunlight (UV radiation), improvement in heart health, and complications arising from diabetes. Sections in the review are dedicated to each of these areas.

sod gliadin
dna protection
immunity
cardiovascular
allergies
skin health
oxygen species

The theory of free radicals in aging

Production of reactive oxygen species (ROS) is a normal process in oxygen-breathing organisms. Under normal physiological conditions a balance between these species and the body’s anti-oxidant defenses exists. (Figure 1) However, certain conditions, like smoking, pollution, exposure to sunlight (UV radiation), infection and the subsequent immune response, metabolism of sugars related to high intensity exercise, and aging, can increase the production of Reactive Oxygen Species (ROS) such as the superoxide ion (O2-) and the hydroxyl ion (OH-). This can disrupt the natural balance and lead ultimately to oxidative stress [1][2].

The detrimental health effects that can result from prolonged exposure to oxidative stress include: DNA damage that can ultimately produce cancer and atherosclerosis (hardening of the arteries) that leads to cardiovascular disease. Oxidative stress is known to significantly contribute to the process of inflammation, which underpins conditions like rheumatoid arthritis, inflammation, metabolic syndrome and diabetes, as well as to neurodegenerative diseases like Alzheimer’s [3].

SOD, the enzyme of life

Superoxide dismutase (SOD), along with catalase and glutathione peroxidase, form the front line of the body’s antioxidant enzyme defenses [4]. The superoxide anion is the starting point of the cascade of reactions of free radical production.

SOD, dubbed the “enzyme of life” on discovery in 1968, is the first antioxidant mobilized by the cell as defense against oxidative stress. The enzyme reacts with the superoxide ion and turns it into hydrogen peroxide (H2O2). This is then catabolised by catalase and glutathione peroxidase to produce molecular oxygen (O2) and water (H2O).

zoom melon
pills glisodin zoom

An approach entirely different from conventional antioxidants

These antioxidant enzymes have a distinct advantage over the antioxidants consumed from the diet or nutritional supplements, like the vitamins A, C, and E, carotenoids, and thiols since the enzymes are biological catalysts, rapidly and repeatedly reducing reactive oxygen species without being consumed themselves. By reacting early in the process, the antioxidant enzymes can minimize the potentially-harmful oxidation of a range of biological molecules. On the other hand, a non-catalytic or stoichiometric relationship exists for most vitamins, carotenoids and thiols, meaning a defined relationship exists – one vitamin C molecule, for example, quenches just one ROS. As vitamin stores can be readily depleted under extreme free radical burden, more vitamin C must be consumed to replace that which has been lost. Moreover, in this example, as Vitamin C is involved in many other essential activities within the cell, relying on Vitamin C to quench free radicals means that Vitamin C is no longer available to perform its other essential tasks; these tasks include the production of collagen, and synthesis of certain neurotransmitters to name but two.

Biodisponibility of oral supplementation

Oral administration of SOD and the other antioxidant enzymes present in many plant extracts is, under normal conditions, not effective. During passage through the gastrointestinal pathway the enzyme is denatured (deactivated) rendering it ineffective as an antioxidant. However, studies have shown that combining a melon concentrate naturally rich in SOD with a wheat gliadin biopolymer system temporarily protects the SOD during its passage through the gastro-intestinal tract. One explanation of this efficiency was presented by Clemente et al. who showed that gliadin increases the permeability of the intestinal wall by promoting the release of a zonulin, thereby allowing the transport of the macromolecule SOD across the intestinal barrier [6].

The combination of a cantaloupe melon (Cucumis melo L.C.) concentrate naturally rich in SOD with the wheat gliadin biopolymer (Glisodin) significantly improves the delayed release of SOD as evidenced in vitro by the progressive increase of its activity in a medium mimicking the digestive conditions (Figure 3)[7].

melon

GliSODin activates the body’s own internal  antioxidant defense system, including superoxide dismutase (SOD), glutathione peroxidase and catalase: the 3 essential primary internal antioxidants

An in vivo study performed on a mouse model showed a significant increase in endogenous antioxidant levels SOD, CAT and GPx in mice supplemented with the SOD + gliadin complex, GliSODin®.After 28 days of supplementation, the SOD-gliadin group showed erythrocyte antioxidant activity four times higher than the group with SOD alone [8].

In 2006, a Japanese university published a study on the mouse model in the British Journal of Cancer highlighting the preventive role of GliSODin® in inflammation. Inducing tumour tissue in mice causes the formation of cytotoxic ROS leading to strong inflammation that can turn a benign tumour into a malignant one. The mice were divided into four groups: control (saline solution), gliadin alone, SOD alone, and GliSODin®, with two administration routes under study: oral and intraperitoneal. Results showed that only oral GliSODin® stimulated the enzymatic defense systems in mice, reducing inflammation induced by tumour formation and significantly decreasing tumour progression [5].

Overall results of in vivo research showed the bio-activity of GliSODin® taken orally and important improvements in the antioxidant status of the organism.

SOD

  • GliSODin
  • Placebo

GPx

  • GliSODin
  • Placebo

Catalase

  • GliSODin
  • Placebo

The role of Glisodin in suppressing inflammation

An in vivo study by Vouldoukis et al.[7] submitted C57BL/6 mice groups to various supplements for 28 days: placebo, gliadin only (1 mg), SOD only (5 IU), the SOD-gliadin combination (5 mg equivalent to 5 IU of SOD, Glisodin), or heat-inactivated SOD-gliadin combination (5 mg) for 28 days and then given an intra-peritoneal INF- injection (300 IU). Peritoneal macrophages were harvested 24 hours later and challenged with IgGl/anti-IgG1 immunocomplexes to amplify the inflammatory response. Only Glisodin reduced the production of the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α) and promoted production of the anti-inflammatory cytokine interleukin-10 (IL-10), compared to the other treatments.

This result also showed that it is necessary to preserve the enzymatic activity of the administered-SOD to retain the anti-inflammatory effect of Glisodin® since IL-10 production was not observed when Glisodin was previously heat inactivated.

The anti-inflammatory effects of Glisodin are significant since chronic inflammation is associated with the onset and progression of many chronic diseases.

Effect of per os mice supplementation by CME, gliadin, CME/gliadin, or HI-CME/gliadin on TNF-α  and IL-10 production

pg/ml

TNF-α (induces an inflammatory response)

  • Placebo
  • SOD only
  • Gliadin
  • GliSODin

IL-10 (induces an anti-inflammatory response)

  • Placebo
  • SOD only
  • Gliadin
  • GliSODin
glisodin inflammation

Conclusion

Production of reactive oxygen species (ROS) is a normal process in oxygen-breathing organisms. Under normal physiological conditions a balance between these species and the body’s anti-oxidant defenses exists, but certain conditions can increase the production of ROS like the superoxide ion (O2-) and disrupt the natural balance and lead ultimately to oxidative stress.

The superoxide ion is the starting point of the cascade of reactions of free radical production. Superoxide dismutase (SOD), dubbed the “enzyme of life” on discovery in 1968, is the first antioxidant mobilized by the cell as defense against oxidative stress.

Oral delivery of the pure enzyme to boost the body’s natural antioxidant defenses has been limited by the harsh conditions experienced in the gastrointestinal (GI) passage. However, combination of SOD-rich cantaloupe melon (Cucumis melo L.C.) with the wheat gliadin biopolymer (Glisodin) can significantly and progressively increase SOD stability and delivery during passage through the GI tract, as shown by results from in vitro, in vivo and human studies.

Production of reactive oxygen species (ROS) is a normal process in oxygen-breathing organisms. Under normal physiological conditions a balance between these species and the body’s anti-oxidant defenses exists, but certain conditions can increase the production of ROS like the superoxide ion (O2-) and disrupt the natural balance and lead ultimately to oxidative stress.

The superoxide ion is the starting point of the cascade of reactions of free radical production. Superoxide dismutase (SOD), dubbed the “enzyme of life” on discovery in 1968, is the first antioxidant mobilized by the cell as defense against oxidative stress.

Oral delivery of the pure enzyme to boost the body’s natural antioxidant defenses has been limited by the harsh conditions experienced in the gastrointestinal (GI) passage. However, combination of SOD-rich cantaloupe melon (Cucumis melo L.C.) with the wheat gliadin biopolymer (Glisodin) can significantly and progressively increase SOD stability and delivery during passage through the GI tract, as shown by results from in vitro, in vivo and human studies.

hand wheat

References

(1)  Halliwell B., Gutteridge J.M.C., Cross C.E., “Free radicals, antioxidants, and human disease: where are we now?” J. Lab Clin Med (1992) Volume 119, Pages 598-620

(2)  Rahman I., Biswas S.K., Kode A., “Oxidant and antioxidant balance in the airways and airway diseases” European Journal of Pharmacology, 2006, Volume 533, Pages 222-239

(3)  Ding Q., Dimayuga E., Keller J.N., “Oxidative damage, protein synthesis, and protein degradation in Alzheimer’s disease” Current Alzheimer Research. 2007, Volume 4, Pages 73-79

(4)  McCord J.M., Fridovich I., “Superoxide dismutase: an enzymatic function for erythrocuprein (hemocuprein)” J. Biol. Chem., (1969) Volume 224, Pages 6049-6055

(5)  Di Massimo C., Scarpelli P., Di Lorenzo N., Caimi G. di Orio F., Ciancarelli M.G.,  “Impaired plasma nitric oxide availability and extracellular superoxide dismutase activity in healthy humans with advancing age” Life Sciences. 2006, Volume 78, Pages 1163-1167

(6)  Clemente M.G., De Virgiliis S., Kang J.S., Macatagney R., Musu M.P., Di Pierro M.R., Drago S., Congia M., Fasano A., “Early effects of gliadin on enterocyte intracellular signaling involved in intestinal barrier function” Gut 2003, Volume 52, Pages 218-223

(7)  Vouldoukis I., Conti M., Krauss P., Kamaté C., Blazquez S., Tefit M., Mazier D., Calenda A., Dugas B., “Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress” Phytotherapy Research 2004, Volume 18, Pages 957-962

(8)  Vouldoukis I., Lacan D., Kamate C., Coste P., Calenda A., Mazier D., Conti M., Dugas B., “Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity” Journal of Ethnopharmacology 2004, Volume 94, Pages 67-75

(9)  Kick J., Hauser B., Bracht H., Albicini M., Öter M., Simon F., Ehrmann U., Garrel C., Sträter J., Brückner U.B., Leverve X.M., Schelzig H., Speit G., Radermacher P., Muth C.-M., “Effects of a cantaloupe melon extract/wheat gliadin biopolymer during aortic cross-clamping” Intensive Care Medicine 2007, doi:10.1007/s00134-006-0518-6

(10)  Muth C.M., Glenz Y., Klaus M., Radermacher P., Speit G., Leverve X., “Influence of an orally effective SOD on hyperbaric oxygen-related cell damage” Free Radical Research, 2004, Volume 38, Number 9, Pages 927-932

(11)  Chenal H., Davit-Spraul A., Brevet J., Legrand A., Demouzon J., Cosson C., Dugas B., Montagnier L., Conti M., “Restored antioxidant circulating capacities in AIDS west african patients receiving an antioxidant nutraceutical Cucumis melon extract rich in superoxide dismutase activity,” Abstract included at the XVI International AIDS Conference Aug 2006

(12)  Rahman H., Rocco R., Latorre J., Tabassum V., “The effects of a specialized superoxide dismutase nutritional supplement for HIV patients on HAART” Millenium Biotechnologies.

(13)  Rahman H., Rocco R., Latorre J., Tabassum V., “The effects of a specialized superoxide dismutase nutritional supplement for HIV patients on HAART” Millenium Biotechnologies

(14)  Marzatico F., Pansarasa O., Bertorelli L., Somenzini L., Della Valle G., “Blood free radical antioxidant enzymes and lipid peroxides following long-distance and lactacidemic performances in highly trained aerobic and sprint athletes” Journal of Sports Medicine and Physical Fitness, 1997, Volume 37, Issue 4, Pages 235-239

(15)  Arent S.M., DiFabio D., Greenwood J., Pellegrino J., Williams C.A., “Nutritional supplementation in male college soccer players: effects on performance and oxidative stress” Rutgers University. 2004

(16)  Shawn M. Arent, PhD, “Nutritional Supplementation (Glisodin® Containing Resurgex® Formula) In Male College Football Players: Effects On Strength, Body Composition  And Oxidative Stress,” Human Performance Lab, Rutgers University, New Brunswick, NJ. 2007.

(17)  Hong Y., Hong S., Chang Y.H., Cho S.H., “Influence of an orally effective superoxide dismutase (glisodin) on strenuous exercise induced changes of blood antioxidant enzymes and plasma lactate,” presented at the American Association for Clinical Chemistry (AACC) National Meeting, July 2004

(18)  Cloarec M., Caillard P., Provost J.-C., Dever J.-M., Elbeze Y., Zamaria N., “Glisodin, a vegetal SOD with gliadin, a preventative agents vs. athersclerosis, as confirmed with carotid ultrasound-B imaging” European Annals of Allergy & Clinical Immunology, 2007, Volume 39, Number 2, Pages 2-7

(19)  Mac-Mary M., Sainthillier J., Creidi P., Series J.P., Vix F., Humbert Ph., “Could a photobiological test be a suitable method to assess the anti-oxidant effect of a nutritional supplement (Glisodin®)?” European Journal of Dermatology, 2007, Volume 17, Number 2

(20)  Laverdet C., Pomarede N., Oliveres-Ghouti C., “Glisodin and Exposure to the Sun,” an open study conducted in France on 150 patients by 40 dermatologists. Sponsored by ISOCELL Nutra, France.  March 2005

(21)  Laverdet C., “Glisodin Sun pilot Trial,” an open study conducted in France on 15 patients presenting fragile skin, hypersensitivity to the sun or even problems of sun disease; Attachee de Consultation des Hopitaux de, Paris. July-September 2003

(19)  DermExpert Trial, “Evaluation Of Glisodin’s Effect On Erythema Induced By UV Radiations,” Intermediate Reports, February 2006

(22)  Okada F., Shionoya H., Kobayashi M. Kobayashi T., Tazaxa H., Onuma K., Iuchi Y., Matsubara N., Ijichi T., Dugas B., Hosokawa M., “Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcina cells by administration of an orally available superoxide dismutase” British Journal of Cancer 2006, Volume 94, Pages 854-862

(23)  Naito Y., Akagiri S., Uchiyama K., Kokura S., Yoshida N., Hasegawa G., Nakamura N., Ichikawa H., Toyokuni S., Ijichi T., Yoshikawa T., “Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice” BioFactors 2005, Volume 23, Pages 85-95

(24)  Ha H., Kim C., Son Y., Chung M.H., Kim K.H., “DNA damage in the kidneys of diabetic rats exhibiting microalbuminuria” Free Radis. Biol Med., 1994, Volume 16, Pages 271-274