Historically, oral administration of SOD has been inefficient due to the fragility of this enzyme, which is immediately destroyed by the gastric acidity. SOD commonly found on the market does not survive gastric activity, giving the body little benefit, and is a waste of money. The makers know this - all commonly available SOD products are ineffective and practically worthless. Moreover, concerns linked to sanitary risks led to giving up the use of bovine SOD, which at the time, was used by intramuscular injection that led to problems and side effects. Two major discoveries resolved these problems:
Identification of a vegetable source of SOD. The objective was reached by selecting a variety of melon (Cucumus melo not genetically modified) that is naturally rich in SOD. As an enzyme, SOD has particular value as an antioxidant that can help to protect against cell destruction. It has the distinct ability to neutralize superoxide, one of the most damaging free radical substances in nature. Like so many other protective compounds which naturally occur in the body, it decreases with age, making cells much more vulnerable to the oxidants which cause aging and disease. It occurs naturally in broccoli, brussel sprouts, wheat grass and in the majority of green plants.
Development of a natural compound capable of protecting the SOD from the gastric degradation. This was possible thanks to the conception of a special wheat protein matrix that protects the SOD from break down by stomach acids, a limitation of many other antioxidants, allowing it to be assimilated by the intestinal cells and also promotes the delivery of the bioactive molecule in the small-intestine mucosa (Patent FR 2 729 296, WO 96 21 462: EP 804 225, US 6 045 809 and JP 520 616).
The unique and beneficial properties of Super GliSODin (reg) allow it to be recommended in all situations where the natural protection system is solicited against free radicals, leading to the weakening of the immune system. Such situations are found among elderly people and also any person subjected to external aggressions: winter, convalescence, stress, sun exposure and intense physical exercise.
A Major Study and Human Trial
Influence of an Orally Effective SOD on Hyperbaric Oxygen-related Cell Damage
Free Radical Research, Volume 38 Number 9 (September 2004), pp. 927–932
In a new study using a dramatic human model, where healthy volunteers are subjected to intense oxidative stress, GliSODin (reg) was shown to protect against cellular DNA damage. These findings coincided with reduced blood isoprostane levels, another marker of oxidative stress. Interestingly, GliSODin (reg) is the first to show this protective benefit in this model. Vitamin E, for example, did not pass this model.
The double-blind randomized study was performed at the University Hospital in Ulm, Germany. It used a hyperbaric model for oxidative stress on nuclear DNA in vivo. The SOD in GliSODin is co-processed with gliadin protein by a patented process. Gliadin has been shown to both protect the melon SOD and increase its effectiveness.
These findings support the body of evidence behind GliSODin (reg) benefits.
GliSODin (reg) ability to promote SOD, Catalase & Glutathione peroxidase, the powerful cellular antioxidants produced by our bodies, clearly make this a desirable dietary supplement, as well as a powerful addition to antioxidant and anti-inflammatory formulations.
From the study:
Influence of an Orally Effective SOD on Hyperbaric Oxygen-related Cell Damage, C. Muth, Y. Glenz, M. Klaus, P. Radermacher, Guenter Speit, X. Leverve. Free Radical Research, Number 9 (2004) 927–932.
"In a prospective, double-blind, randomised placebo controlled study, we tested the hypothesis that a new formulation consisting of wheat gliadin chemically combined with a vegetal (thus orally effective) preparation of superoxide dismutase (SOD) allows to prevent hyperbaric oxygen (HBO)-induced oxidative cell stress. Twenty healthy volunteers were exposed to 100% oxygen breathing at 2.5 ATA for a total of 60 min. DNA strand breaks (tail moments) were determined using the alkaline version of the comet assay. Whole blood concentrations of reduced (GSH) and oxidised (GSSG) glutathione and F2-isoprostanes, SOD, glutathione peroxidase (GPx) and catalase (Cat) activities and red cell malondialdehyde (MDA) content were determined.
After HBO exposure the tail moment (p=.03) and isoprostane levels (p=.049) were significantly lower in the group that received the vegetal formulation. Neither SOD and Cat nor GSH and GSSG were significantly affected by this preparation or HBO exposure. By contrast, blood GPx activity, which tended to be lower in the SOD group already before the HBO exposure (p=.076); was significantly lower afterwards (p=.045).
We conclude that an orally effective SOD–wheat Gliadin mixture is able to protect against DNA damage, which coincided with reduced blood isoprostane levels, and may therefore be used as an antioxidant."
Clinically Supported Applications
· Animal studies have demonstrated that oral administration of GliSODin (reg) induced not only an increase in SOD activity (in plasma and erythrocytes) but also an increase of SOD, Catalase and Glutathione peroxidase in the liver! The entire system gains protection.
· One animal study shows that oral ingestion of GliSODin (reg) results in increased levels of SOD for three weeks after usage ends!
· A double blind human study that showed the use of SOD significantly improved function and reduced pain in patients with active osteoarthritis of the knee. (Lund-Olsen K, Menander-Huber. Intra-articular orgotein therapy in osteoarthritis of the knee. A double-blind, placebo-controlled trial. Arzneimittelforschung 1983; 33(8):1199-1203.)
· A human clinical study demonstrates SOD’s ability to reduce tumor necrosis factor (TNF), additionally, an animal study on GliSODin (reg) also showed reduced TNF.
· New Human clinical study from Japan showing reduction in Lactic Acid build up after exercise. Excellent for use in athletic / recovery products.
On Oxidative Stress Reduction
Oxygen is the most important element for life. During its utilization by the human body, oxygen gives birth to very reactive forms called "free radicals". Free radicals are destroyed by the natural defense systems termed "antioxidants".
The body’s antioxidant mechanisms can be classified into 2 groups:
• Dietary antioxidants (exogenous): certain foods are rich in antioxidant substances like vitamins (Vitamin C, Vitamin E and Vitamin A or its precursor beta-carotene), minerals (Selenium, Zinc, Copper and Manganese) and other substances, including the polyphenols found in grapes and green tea.
Enzymatic antioxidants made by the body (endogenous): the three main enzymes are Super Oxide Dismutase (SOD), Catalase and Glutathi-one Peroxidase.
Free radicals and/or chemical related compounds, when produced in excess, are responsible for cellular toxicity and contribute to the longterm development of most inflammatory-related diseases. In fact, the molecular and cellular activities of free radicals are highly dependent upon the threshold of production of these chemical entities.
Under "normal" conditions the potential excess production of free radicals is buffered by anti-oxidant enzymes and/or quenching molecules.
The disturbance of the delicate equilibrium between oxidant and anti-oxidant molecules is mainly initiated by pathogens (virus, bacteria etc.) and/or antigens (nutritional products, allergens, vaccine etc.) and is regulated positively or negatively by various immune reactions (2,3).
The majority of free radical actions can be divided in seven Immuno-Redox overlapping categories:
1. cytokine, growth factor, hormone and mediator action and secretion,
2. ion transport,
3. alteration of cell signaling,
5. gene activation and/or repression,
6. alteration of mitochondrial functions, and cell death by apoptosis
These observations led to the development of a large number of anti-oxidant products (nutrients and drugs). However, until now the development of these products has not been optimal for two main reasons. Previous products often had poor bioavailability, and the complexity of the dynamic equilibrium between free radicals and the related anti-oxidants has always been underestimated.
In the mid-1950s, the proposed ‘free radical theory of aging’ postulated that the accumulation of damage caused by free radicals was the underlying mechanism by which organisms age. Oxidative stress is the harmful condition that occurs when there is an excess of free radicals, a decrease in antioxidant levels, or both. Strategies aimed at limiting and repairing the damage attributed to oxidative stress may slow the advance of numerous age-related diseases. Today, there are many genes that have been identified in certain insects, which, when manipulated, lead to an increase in lifespan in insects. Of those tested, all provide an increased resistance to oxidative stress as a means of modifying lifespan. In addition, the lifespan can also be extended by the administration of synthetic superoxide dismutase (SOD) as it also appears to provide resistance to oxidative damage. An interesting study in insects demonstrated that when SOD-producing genes were inserted into cells of fruit flies it caused them to produce even more SOD, resulting in a 40% extension of life. In a human study, findings suggested that increased SOD activity in certain populations resulted in better protective mechanisms against aging effects. Research with GliSODin (reg) clearly demonstrates that it can protect the cell from genetic damage caused by oxidative stress while boosting total cellular defense – all critical in diminishing the aging effect in cells. GliSODin (reg) is the first vegetarian SOD that has been shown to be orally bioactive.* Carl Germano, R.D., C.N.S., L.D.N.
Based on the antigenic nature of vegetal SOD, the GliSODin (reg) complex induces adaptive systems of redox regulation and immuno-modulation.
Quality of Life:
GliSODin (reg) complex is being actively investigated to clarify the strong indications that it can help alleviate a wide range of symptoms linked to cellular inflammation. GliSODin (reg) is also being studied to follow up on indications that its consumption may help slow the cellular aging process.
While conventional medicine generally acts to alleviate specific symptoms, the GliSODin (reg) product maintains its general ability to promote tissue health and reduce the damage to certain injured vital organs, notably the liver.
Individuality of Dose:
The dosing of GliSODin (reg) depends on the clinical status of the subject. The base dose is the equivalent of 100 IU SOD per day and may be increases if necessary to 500 IU SOD per day. GliSODin (reg) has a very low toxicity.
GliSODin versus usual anti-oxidant drugs:
As a dietary supplement, GliSODin (reg) is unique in that it is a natural extract that can regulate production of anti-oxidant enzymes and molecules in the body. GliSODin (reg) is a natural detoxifying enzyme that promotes natural defenses of the organism.
Benefits from using the GliSODin (reg) product:
Chronic, infectious, inflammatory, degenerative and cancer tax the body energy stores and immune capacities. GliSODin (reg) replenishes the energy needed to enhance the natural defense system and alleviate symptoms of cellular stress.
The daily pressures of life, noise and environmental pollution, and other stresses pose a cumulative harmful health threat that may contribute to the onset of disease. GliSODin (reg) has been reported to reduce the effects of stress-induced free radical production.
Influence Of An Orally Effective SOD On Hyperbaric, Oxygen Related Cell Damage
Free Radical Research 38:9 (2004) pp. 927-932
Extreme exercise is another model for induced oxidative stress. Several markers of this stress are serum total antioxidant status and plasma lactic acid. In a compelling study, healthy volunteers supplemented their diets with 1500 mcg of GliSODin (reg) for four weeks. Prior to GliSODin (reg) use, the volunteers participated in strenuous exercise and baseline measurements of serum total antioxidant status, plasma lactate accumulation and several other markers were measured for each participant. After supplementation, the extreme exercise was repeated and the oxidative stress markers where measured once again. GliSODin (reg) supplementation resulted in a significant change in oxidative status and a significant decrease in exercise-induced lactate release, suggesting the damage caused oxidative stress was significantly inhibited.
GliSODin (reg) works by promoting our own, innate cellular protection. Our internal antioxidant defense system differs from "antioxidants" that are obtained from dietary sources.
The body’s antioxidant supply can be classified into two groups:
Dietary antioxidants, which are externally provided: certain foods are rich in antioxidant substances like vitamins (Vitamin C, Vitamin E and Vitamin A), minerals (Selenium, Zinc, Copper and Manganese) and other substances, including the polyphenols found in grapes and green tea. These external antioxidants contribute to the antioxidant reserve yet play a secondary role to the body’s own antioxidants
Enzymatic antioxidants, which are made by the body, thus internally provided: the internal antioxidant defense system includes Super Oxide Dismutase (SOD), Catalase and Glutathione Peroxidase, which are the first, and most powerful, line of defense against oxidative stress.
Among these enzymes, SOD plays the primary role. SOD transforms the most reactive, and therefore the most dangerous, free radicals– the Super Oxide radicals – into ions that are less reactive; these less reactive ions are then transformed by the two other enzymes. This transformation is called dismutation, thus its name Super Oxide Dismutase. SOD also "signals" other cells to produce more SOD, thus preparing the antioxidant defense system against free radical attack.
The Electrostatic Field Around the SOD Enzyme
This image illustrates the electrostatic field (yellow) around an active site (red) of the enzyme superoxide dismutase, which controls oxygen toxicity by converting the superoxide radical to less dangerous forms. Michael Potter of Andrew McCammon's group at the University of California, San Diego, studied the influence of the electrostatic field on the reaction with superoxide using Brownian Dynamics simulations and the UHBD software package on SDSC's CRAY C90. The results were visualized with GRASP software, by A. Nicholls and B. Honig of Columbia University, and resources in SDSC's VisLab.
Technical Data on Forms of SOD
The enzyme superoxide dismutase , or SOD (EC 188.8.131.52 catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. As such it is an important antioxidant defense in nearly all cells exposed to oxygen. One of the exceedingly rare exceptions is Lactobacillus plantarum and related lactobacilli. A dismutation is a reaction in which a single substrate is alternately oxidized and reduced.
A typical reaction of an SOD protein containing copper (and zinc) looks like this:
Cu+2-SOD + O2- → Cu+1-SOD + O2Cu+1-SOD + O2- + 2H+ → Cu+2-SOD + H2O2.In this reaction the oxidation state of the copper changes between +1 and +2.
Several common forms of SOD exist: they are proteins cofactored with copper and zinc, or manganese, or iron. The cytosols of virtually all eukaryotic cells contain an SOD enzyme with copper and zinc (Cu-Zn-SOD). (For example, Cu-Zn-SOD available commercially is normally that found in the bovine erythrocyte: The Cu-Zn enzyme is a homodimer of molecular weight 32,500. The two subunits are joined by a disulfide bond. Chicken liver (and nearly all other) mitochondria, and many bacteria (such as E. coli) contain a form with manganese (Mn-SOD). The Mn-SOD is found in a human mitochondrion. E. coli and many other bacteria also contain a form of the enzyme with iron (Fe-SOD); some bacteria contain Fe-SOD, others Mn-SOD, and some contain both. The superoxide anion radical (O2-) spontaneously dismutes to O2 and H2O2 quite rapidly. However, SOD has the fastest turnover number (reaction rate with its substrate) of any known enzyme. In fact, its rate is diffusion-limited. Thus under real-world intracellular conditions SOD greatly reduces the ambient level of the dangerous superoxide radical.
The presence of SOD has been shown to help protect many types of cells from the free radical damage that is important in aging, senescence, and ischemic tissue damage. SOD also helps protect cells from DNA damage, lipid peroxidation, ionizing radiation damage, protein denaturation, and many other forms of progressive cell degradation.
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