superoxide dismutase

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superoxide dismutase

Post by gibbledygook » Wed Dec 24, 2008 1:11 am

Once again I believe I have had a bad experience from superoxide dismutase (glisodin). After the most exciting and revolutionary postings on the venous obstructions by Dignan et al I hastily decided to resume superoxide dismutase, despite its consumption being strongly associated with a relapse in February 2008. My thinking was that I had venous sclerosis and superoxide dismutase is good for atherosclerosis so...
Anyway once again this pill seems to have triggered a mini-relapse. For about 4 or 5 days I took 500mg of glisodin in the morning. The following evenings involved champagne and red wine in varying quantities. I started to notice that my walking was much much worse than usual after a few glasses and the pain in my left leg reappeared at night. However I was also taking much lower quantities of salvia, than I have over the last few months. Maybe the combination of reduced quantities of salvia and glisodin is a relapse trigger. I will never again consume glisodin. :(
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

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Post by jimmylegs » Wed Dec 24, 2008 9:23 am

in spite of the typos and the fact that it's in med h, i still think this abstract is notable for it's many deficiency links to ms, the way the deficiencies connect to the excess nutrients also potentially implicated in ms, and in this case, the reference to superoxide dismutase, make it a worthwhile re-read
Med Hypotheses. 2000 Sep;55(3):239-41.
The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis.
Johnson S.

Multiple sclerosis (MS) has a much higher incidence among caucasians that in any other race. Furthermore: females are much more susceptible than males and white females living in colder, wetter areas are much more susceptible than those living in warmer areas. On the other hand, menstruating women have increased copper (Cu) absorption and half-life, so they tend to accumulate more Cu than males. Moreover, rapidly growing girls have an increased demand for zinc (Zn), but their rapidly decreasing production of melatonin results in impaired Zn absorption, which is exacerbated by the high Cu levels. The low Zn levels result in deficient CuZnSuperoxide dismutase (CuZnSOD), which in turn leads to increased levels of superoxide. Menstruating females also often present with low magnesium (Mg) and vitamin B6 levels. Vitamin B6 moderates intracellular nitric oxide (NO) production and extracellular Mg is required for NO release from the cell, so that a deficiency of these nutrients results in increased NO production in the cell and reduced release from the cell. The trapped NO combines with superoxide to form peroxinitrite, an extremely powerful free radical that leads to the myelin damage of MS. Iron (Fe), molybdenum (Mo) and cadmium (Cd) accumulation also increase superoxide production. Which explains MS in males, who tend to accumulate Fe much faster and Cu much less rapidly than females. Since vitamin D is paramount for Mg absorption, the much reduced exposure to sunlight in the higher latitudes may account for the higher incidence in these areas. Moreover, vitamin B2 is a cofactor for xanthine oxidase, and its deficiency exacerbates the low levels of uric acid caused by high Cu levels, resulting in myelin degeneration. Finally Selenium (Se) and vitamin E prevent lipid peroxidation and EPA and DHA upregulate CuZnSOD...
The abstract does start out pretty scattered, but then it makes sense for a bit... finally, it heads off on a total tangent as far as I'm concerned, wrt asserting dosages and age restrictions, but up til this point, i think this abstract makes more sense every time, over the last 2 years, that i go back and read it again
...Therefore, supplementation with 100 mg MG, 25 mg vit B6, 10 mg vit B2, 15 mg Zn and 400 IU vit D and E, 100 microg Se, 180 mg EPA and 120 mg DHA per day between 14 and 16 years of age may prevent MS.

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Post by Jaded » Fri Dec 26, 2008 2:29 pm

Wot about reducing the effects of MS'ers??? I wonder if the same supps would help...


Great article by the way, thanks jimmylegs.


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Post by gibbledygook » Mon Dec 29, 2008 2:11 am

I must admit that I immediately started taking inosine to mop up the byproducts of the superoxide dismutase and almost immediately this mini-relapse calmed down. Here's the wikipedia story on SOD=
The enzyme superoxide dismutase (SOD, EC, 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.

The SOD-catalysed dismutation of superoxide may be written with the following half-reactions :

M(n+1)+ − SOD + O2− → Mn+ − SOD + O2
Mn+ − SOD + O2− + 2H+ → M(n+1)+ − SOD + H2O2.
where M = Cu (n=1) ; Mn (n=2) ; Fe (n=2) ; Ni (n=2).

In this reaction the oxidation state of the metal cation oscillates between n and n+1.

Simply stated, SOD outcompetes damaging reactions of superoxide, thus protecting the cell from superoxide toxicity. The reaction of superoxide with non-radicals is spin forbidden. In biological systems, this means its main reactions are with itself (dismutation) or with another biological radical such as nitric oxide (NO). The superoxide anion radical (O2-) spontaneously dismutes to O2 and hydrogen peroxide (H2O2) quite rapidly (~105 M-1 s-1 at pH 7). SOD is biologically necessary because superoxide reacts even faster with certain targets such as NO radical, which makes peroxynitrite. Similarly, the dismutation rate is second order with respect to initial superoxide concentration. Thus, the half-life of superoxide, although very short at high concentrations (e.g. 0.05 seconds at 0.1mM) is actually quite long at low concentrations (e.g. 14 hours at 0.1 nM). In contrast, the reaction of superoxide with SOD is first order with respect to superoxide concentration. Moreover, superoxide dismutase has the fastest turnover number (reaction rate with its substrate) of any known enzyme (~7 x 109 M-1 s-1)[3], this reaction being only limited by the frequency of collision between itself and superoxide. That is, the reaction rate is "diffusion limited".

Superoxide is one of the main reactive oxygen species in the cell and as such, SOD serves a key antioxidant role. The physiological importance of SODs is illustrated by the severe pathologies evident in mice genetically engineered to lack these enzymes. Mice lacking SOD2 die several days after birth, amidst massive oxidative stress.[4] Mice lacking SOD1 develop a wide range of pathologies, including hepatocellular carcinoma,[5] an acceleration of age-related muscle mass loss,[6] an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3 do not show any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic injury.[7] Knockout mice of any SOD enzyme are more sensitive to the lethal effects of superoxide generating drugs, such as paraquat and diquat.

Drosophila lacking Sod1 have a dramatically shortned lifespan while flies lacking Sod2 die before birth. SOD knockdowns in C. elegans do not cause major physiological disruptions. Knockout or null mutations in Sod1 are highly detrimental to aerobic growth in the yeast Sacchormyces cerevisiae and result in a dramatic reduction in post-diauxic lifespan. Sod2 knockout or null mutations cause growth inhibition on respiratory carbon sources in addition to decreased post-diauxic lifespan.

Several prokaryotic SOD null mutants have been generated, including E. Coli. The loss of periplasmic CuZnSOD causes loss of virulence and might be an atractive target for new antibiotics.

Mutations in the first SOD enzyme (SOD1) can cause familial amyotrophic lateral sclerosis (ALS, a form of motor neuron disease).[8][9] The most common mutation in the U.S. is A4V while the most intensely studied is G93A. The other two types have not been linked to any human diseases, however, in mice inactivation of SOD2 causes perinatal lethality[4] and inactivation of SOD1 causes hepatocellular carcinoma.[5] Mutations in SOD1 can cause familial ALS, by a mechanism that is presently not understood, but not due to loss of enzymatic activity or a decrease in the conformational stability of the SOD1 protein. Overexpression of SOD1 has been linked to Down's syndrome.[10] The veterinary antiinflammatory drug "Orgotein" is purified bovine liver superoxide dismutase.[citation needed]

SOD has proved to be highly effective in treatment of colonic inflammation in experimental colitis. Treatment with SOD decreases reactive oxygen species generation and oxidative stress and thus, inhibits endothelial activation and indicate that modulation of factors that govern adhesion molecule expression and leukocyte-endothelial interactions, such as antioxidants, may be important, new tools for the treatment of inflammatory bowel disease. [11]
this may be a clearer picture of dismutation by superoxide dismutase
The dismutation of superoxide free radical to hydrogen peroxide and oxygen, catalysed in living systems by superoxide dismutase:
2O2− + 2H+ → H2O2 + O2
Ultimately the superoxide free radical ends up as peroxynitrite via the reaction of h202 and no2:

Peroxynitrite (sometimes called peroxonitrite) is the anion with the formula ONOO−. It is an unstable "valence isomer" of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution.[1] It is prepared by the reaction of hydrogen peroxide with nitrite:

H2O2 + NO2− → ONOO− + H2O
Peroxynitrite is an oxidant and nitrating agent. Because of its oxidizing properties, peroxynitrite can damage a wide array of molecules in cells, including DNA and proteins. Formation of peroxynitrite in vivo has been ascribed to the reaction of the free radical superoxide with the free radical nitric oxide[2]:

·O2− + ·NO → ONO2−
The resultant paring of these two free radicals results in peroxynitrite, a molecule which is itself not a free radical, but which is a powerful oxidant.
and finally here's the way to mop up the peroxynitrite:
1: Ther Umsch. 2004 Sep;61(9):553-5.Links
[Uric acid and multiple sclerosis][Article in German]

Mattle HP, Lienert C, Greeve I.
Neurologische Klinik und Poliklinik, Universitätsspital Bern, Inselspital, Bern.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.

PMID: 15493114 [PubMed - indexed for MEDLINE]

Related ArticlesUric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. [FASEB J. 2000] Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. [Proc Natl Acad Sci U S A. 2002] The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity. [J Immunol. 2000] ReviewUric acid in multiple sclerosis. [Neurol Res. 2006] ReviewRole of uric acid in multiple sclerosis. [Curr Top Microbiol Immunol. 2008] » See Reviews... | » See All...

From my negative experiences with superoxide dismutase I would think that this antioxidant simply increases peroxynitrite levels to relapse inducing levels and is a harmful compound in MS.
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

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