Young people naturally produce the antioxidant enzymes superoxide dismutase (SOD) and catalase to protect against destructive free radicals. Unfortunately, levels of SOD and catalase decline with age.

Adults can now replenish their stores of these powerful antioxidant enzymes. Emerging research suggests that two novel SOD/catalase-boosting agents help increase antioxidant status, reduce pain, quench free radicals, quell inflammation, and promote longevity.

Over the past 60 years, numerous studies have demonstrated superoxide and other free radicals contribute to aging.1-3 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 are produced within our cells and are far more potent in preventing free radical damage than dietary antioxidants. SOD, for example, may be up to 3500 times more potent than vitamin C in quenching the dangerous superoxide radical.

Regrettably, levels of antioxidant enzymes like SOD decline markedly with advancing age, leading to an accumulation of free radicals and oxidative damage.4,5 In particular, the decline in SOD levels correlate with increased incidences of degenerative and inflammatory problems.

SOD levels in humans vary by as much as 50% due to genetic differences, which may help to explain why some people are more prone to degenerative disorders while others lead long, disease-free lives.6

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.7,8 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.7,8

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.7,8

Interestingly, although pigeons and rats weigh the same, pigeons live about 12 times longer. The difference is that pigeons have high SOD levels and produce about half as many free radicals as rats.9

Blood levels after 2 weeks of SODzyme™ supplementation

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 SODzyme™—derived from the sprouts of corn, soy, and wheat—could boost the body’s endogenous SOD levels.

Since free radicals are thought to contribute to 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 SODzyme™ for two weeks. SODzyme™ boosted serum SOD levels by 30% on average while lowering blood levels of hydrogen peroxide by 47%.10 This is significant, because hydrogen peroxide may contribute to inflammation. While immune cells use bursts of hydrogen peroxide to kill viruses and bacteria, excess hydrogen peroxide may contribute to inflammatory disorders.11,12

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 SODzyme™ supplementation restored their serum and blood levels of SOD to youthful parameters. Furthermore, supplementation with SODzyme™ boosted activity of blood catalase, another crucial antioxidant enzyme, by an impressive 47%.10 If these subjects continue to use SODzyme™ and thus maintain or further boost their blood levels of SOD, they should remain well protected, as suggested by the numerous studies correlating low SOD levels with pain.13-15

A second pilot study (placebo-controlled) conducted by Life Extension examined SODzyme™’s effects on adults diagnosed with inflammatory conditions such as arthritis. This placebo-controlled, three-arm study involving 30 subjects over four weeks tested placebo, probiotic SODzyme™, and non-probiotic SODzyme™. A dramatic 71% response (clinically defined as a meaningful decrease in pain as measured by a validated pain assessment instrument) in the probiotic SODzyme™ 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 SODzyme™.16

Responde rate after 2 weeks of SODzyme™ supplementation

Case Studies Confirm Benefits

Case studies are a valuable means of gauging individual responses to SODzyme™’s beneficial effects. 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 SODzyme™, 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 joint pain.16

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 SODzyme™ 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 SODzyme™ that he had experienced initially.16

Marie R. reported a 90% improvement in her pain symptoms within two weeks of taking 2000 mg of SODzyme™ 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.16

The two Life Extension pilot studies confirm that SODzyme™ supports cartilage and joint function. 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).

Another Powerful SOD Booster: GliSODin®

Elevating serum and blood levels of endogenous antioxidants such as SOD and catalase is a safe, natural way to reduce inflammation and pain. Like SODzyme™, another recently developed natural product called GliSODin® raises serum and tissue levels of SOD. GliSODin® is derived from an extract of cantaloupe bred to produce more SOD than ordinary melons.17,18

In 1980, melon growers noticed that some varieties of cantaloupe had a shelf life of 15 days, or three to four times longer than the shelf life of the average fully ripened melon. Extensive research demonstrated that these non-rotting cantaloupes contained much higher levels of SOD and catalase than did standard melons. Years of additional research involving crushing, filtering, centrifuging, and freeze-drying extracts of the melons produced SOD in a concentrated granule form that, when bonded to wheat protein, made it highly absorbable in and bioavailable to the human body.17,18

GliSODin® is a natural, plant-derived SOD that has been bonded to a wheat protein called gliadin for better absorption. In fact, it has taken 40 years of research to make SOD orally bioavailable, since unbound SOD is broken down rapidly in the stomach into its separate amino acid components. Its high molecular weight of 25,000-40,000 units also makes it difficult or impossible to pass through cell membranes, even if directly injected into the bloodstream.17,18

Most of the early research with SOD was done with bovine SOD that was injected into the joints and bloodstreams of laboratory animals and humans. While the human studies produced some dramatic results, injecting SOD into joints posed a logistical challenge, especially since exogenously derived bovine SOD is rapidly broken down.19

Extensive Research on GliSODin®

Numerous scientific studies have examined the effects of GliSODin®. In one landmark study, 20 volunteers in a hyperbaric chamber breathed pure oxygen at 2.5 atmospheres of pressure for one hour. Hyperbaric oxygen treatment serves as an in vivo model of oxidative stress in humans. Subjects exposed to oxygen in a high-pressure chamber typically demonstrate increased levels of free radicals and DNA damage in their white blood cells that cannot be prevented by oral antioxidants such as vitamin E or N-acetylcysteine.20

Isoprostane increase after 1 hour in a hyperbaric oxyegen chamber

In this study, the group supplemented with GliSODin® capsules had less DNA damage than subjects who did not supplement. The scientists concluded that GliSODin® helped prevent breaks in DNA strands that are associated with exposure to high-pressure oxygen. The results also suggest GliSODin® is readily absorbed in the gastrointestinal tract and makes its way into the cells themselves, something that even injectable bovine SOD failed to do in previous studies.20

An emerging marker of oxidative stress in humans is isoprostanes, which are generated by the peroxidation of fatty acids in cell membranes or lipoproteins. Clinical data indicate that an increased level of isoprostane biosynthesis is correlated with certain states related to oxidative stress.21 Two groups of humans were studied to evaluate the effects of GliSODin®.20 After one hour in a hyperbaric oxygen chamber, isoprostane levels in the control group rose to 22.3 pg/ml, while the GliSODin®-supplemented group experienced no change in isoprostanes, demonstrating a sustained baseline level of 14 pg/ml. Thus, GliSODin® appears to protect against cell membrane damage that occurs in high-pressure oxygen environments. This study illustrates GliSODin®’s ability to limit free radical damage associated with conditions of oxidative stress.20

Another study found that small amounts of orally administered GliSODin® raised circulating blood levels of SOD by 89% in mice.17 Blood levels of catalase, another antioxidant enzyme, also increased to almost three times the level seen in a control group.17 Catalase is the enzyme that converts hydrogen peroxide to water, and high levels of hydrogen peroxide may contribute to inflammation.18 The liver cells of the mice also demonstrated greatly increased levels of SOD and catalase, indicating that GliSODin® stimulates production of these critical antioxidants inside the major organs and deep tissues.17

The potent antioxidant properties of GliSODin® were also studied in mouse macrophages taken from live, normal mice. Macrophages are a type of immune responder cell that is activated in inflammatory processes. When treated with GliSODin®, macrophage cells produced fewer of the free radicals superoxide, nitrites, and peroxynitrite, than did macrophages taken from untreated animals.18

SOD and Catalase increase in response to GliSODin®

Researchers studied the interaction of GliSODin® with cytokines that play a role in inflammation. They found that untreated immune responder cells produced high levels of the inflammatory cytokine, tumor necrosis factor-alpha (TNF-a), and normal levels of an anti-inflammatory cytokine, interleukin-10 (IL-10). When treated with GliSODin®, however, the immune responder cells produced very low levels of inflammatory TNF-a in combination with very high levels of anti-inflammatory IL-10. Previous studies have suggested that people who live to 90 or 100 years of age have high blood levels of IL-10, which may keep their inflammatory reactions in check during aging. GliSODin® may thus promote a protective anti-inflammatory profile similar to that of people who live to extreme old age.18,22

Lactic acid is a metabolic by-product generated during strenuous exercise. In some joint-related problems, the lactic acid content of joints is increased.23 Interventions that lower lactic acid levels in the blood and in joint fluids have been suggested to help modulate muscle and joint pain. Human studies demonstrated that four weeks of GliSODin® supplementation reduced lactic acid levels during strenuous cycling or treadmill exercise. The most strenuous exercise activity generated the highest levels of lactic acid. GliSODin® therapy exerted the most potent lactic acid-reducing effects in extreme cases of exercise-induced stress. GliSODin® may thus be indicated in reducing lactic acid levels related to exercise and certain pain-related conditions.24

Conclusion

Free radicals and oxidative stress are associated with accelerated aging and the onset of degenerative diseases. Internally generated antioxidants provide far greater protection against the effects of oxidative stress than antioxidant nutrients.

One of the most important antioxidant enzymes in humans is superoxide dismutase (SOD). Numerous studies correlate diminished SOD levels with health problems, suggesting that abundant SOD promotes longer life. Two supplements in particular—SODzyme™ and GliSODin®—have been shown to boost levels of SOD and other antioxidant enzymes. SODzyme™ and GliSODin® offer promise in slowing aging, promoting longevity, relieving pain, modulating inflammation, and quenching free radicals. These powerful compounds may thus help promote good health and protect against many of the conditions associated with aging.

Editor’s note: People who are allergic to wheat, soy, corn, or gluten should consult their physician before using products containing SODzyme™ or GliSODin®.