DMSO: Summary of Studies

I will try to proof all pieces of the DMSO theory, by quoting from Medical Studies.
Studies confirm the following:
Iron / H2O2 / O(-2) / Fenton Reaction

Striking Resemblances :

Read the details below :

  The Inflammation Mechanism :  
During infection, the body makes considerable metabolic adjustment in order to make iron unavailable to microorganisms.
As a result of infection, there is:
1. decreased intestinal absorption of iron from the diet;
2. a decrease of iron in the plasma and an increase in iron in storage as ferritin;
3. increased synthesis of the human iron-binding proteins (iron chelators) lactoferrin and transferrin which trap iron for use by human cells while making it unavailable to most microbes;
4. coupled with the febrile response, decreased ability of bacteria to synthesize their own iron chelators called siderophores;
5. prior stationing of lactoferrin at common sites of microbial invasion such as in the mucous of mucous membranes, and the entry of transferrin into the tissue during inflammation.
This lack of iron, which is needed for the bacterial electron transport chain, can inhibit the growth of many bacteria.

However, this doesn't help when the inflammation is IN the intestines.
IN the intestines the iron level is elevated and the Haber Weiss reaction is very active.


  The Haber Weiss Reaction :  
  Iron is a catalyzer in The Haber-Weiss (aka Fenton) reaction :

"free" iron can catalyze the formation of very injurious compounds, such as the hydroxyl radical (.OH) from compounds such as hydrogen peroxide, which are normal metabolic byproducts (Fenton reaction).
The hydroxyl radical is highly reactive, and attacks lipids, proteins and DNA.
The initial reaction with each of these molecules is the formation of peroxides (e.g., lipid peroxides) that can interact with other molecules to form cross links. These cross-linked molecules perform their normal functions either poorly or not at all.

Iron supplementation may aggravate inflammatory status of colitis in a rat model.
Iron supplementation is one of the principal therapies in inflammatory bowel disease.
Iron is a major prooxidative agent; therefore therapeutic iron as well as heme iron from chronic mucosal bleeding can increase the iron-mediated oxidative stress in colitis by facilitating the Fenton reaction, namely production of hydroxyl radicals.
It was concluded that iron supplementation can amplify the inflammatory response and enhance the subsequent mucosal damage in a rat model of colitis. We suggest that the resultant oxidative stress generated by iron supplementation leads to the extension and propagation of crypt abscesses.

Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn's disease.

During inflammation, the superoxide anion (O-2) and hydrogen peroxide (H2O2) are produced by stimulated polymorphonuclear leukocytes and macrophages. The toxic effects of these reactive oxygen intermediates increase when traces of iron are present, because iron catalyzes the formation of the hydroxyl radical (OH.).
Iron release from ferritin depends on O-2 because it can be prevented by the addition of superoxide dismutase. Catalase and dimethylsulfoxide have no inhibitory effect on iron mobilization.

This is very interesting...
It seems like DMSO can scavenge the H2O2 Hydrogen Peroxide molecules.
It can't scavenge the SuperOxide Anion (O-2), however.

Summary :
1. Inflammation
2. Superoxide anion (O-2) and Hydrogen Peroxide (H2O2) are produced.
3. The O-2 will release even more iron from the ferritin. Iron overdose in the intestines !
4. H2O2 and Iron will form Hydrogen free radicals (Fenton Reaction).

DMSO will remove most of the H2O2 and will increase the the iron export by stimulating the transferrin receptors.
The SuperOxide Anion is still there, however.
When the O-2 can release more iron than the transferrin receptors can export, the vicious cycle is still not broken.

Perhaps DMSO can stop the damage mechanism in the intestines, but maybe it needs some help from an O-2 scavenger also.

  DMSO can decrease the amount of free iron:  
The ability of Friend erythroleukemic cells to bind transferrin and take up its iron increases substantially as a result of dimethyl sulfoxide-stimulated differentiation.

Dimethylsulfoxide (DMSO) induces hemoglobin synthesis and erythroid differentiation of Friend erythroleukemia cells in vitro. Induction is accompanied by increased transferrin-binding activity which is necessary for the cellular acquisition of iron from transferrin for hemoglobin synthesis.
  Hydroxyl radical scavengers inhibit TNF-alpha production  
dimethylsulfoxide (DMSO) and deferoxamine (DFX), the latter being an iron chelator which prevents HO* formation by blocking the Fenton reaction, were found to inhibit TNF-alpha production in LPS-stimulated human PBMC
  A Parallel : Desferroxamine and Copper/Zinc Superoxide Dismutase:  
DMSO does two things to stop the Fenton Reaction :
  • It neutralizes the H2O2 Hydrogen Peroxide molecules, which are a neccessary compound for the Fenton Reaction.
  • It activates the transferrin receptors, so the free iron is removed, which is also a neccessary compound for the Fenton Reaction.
The parallel with Desferroxamine
  • Desferroxamine is also an antioxidant.
  • Desferroxamine binds the free iron to its molecule, so the Fenton Reaction can't work
Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn's disease.

The parallel with Copper/Zinc Superoxide Dismutase
  • Copper/Zinc Superoxide Dismutase is also an H2O2 Hydrogen Peroxide scavenger.
  • 82% is very close to the 80-90% success rate on David Gregg's Site.
  • Besides this, C/Z Sup.Ox.Dism. is also an O-2 (Superoxide) scavenger !
Bovine CuZnSOD was used during an 8-year period as an anti-inflammatory drug in 26 patients with severe Crohn's disease, usually after failure of corticotherapy, or when this drug was avoided because of side-effects or abscesses.
We obtained 19/26 very good short term responses, and 82% good results on long term evolution.

These results indicate that the anti-inflammatory effects of CuZnSOD were mainly the removal of oxygen free radicals and indirectly the prevention of lipid peroxidation. This study suggests that CuZnSOD may be beneficial in the treatment of patients with ulcerative colitis.

The parallel with 5-ASA (5-aminosalicylic acid)
  • 5-ASA is also an antioxidant (hydroxyl free radical scavenger).
  • 5-ASA stops the flow of iron into the intestines by removing O(-2)
(5-ASA), when used in therapy, exhibit superoxide and hydroxyl-radical scavenger properties.
How does this work:
When tissue is inflammated, two things are created :
  • Hydrogen Peroxide
  • The SuperOxide O(-2)

  • Hydrogen peroxide is one of the elements on the left side of the Fenton Reaction.
    ( H2O2 + Fe(+2) --> Fe(+3) + OH + Hydroxyl Free Radical )

    O(-2) removes the iron from specific iron-carrying cells in the intestine walls.
    Fe(+2) (Iron) is the second element on the left side of the Fenton reaction.

    So, in fact, 5-ASA does two things :

    1. It removes the Hydrogen Peroxide
    2. It stops the flow of iron into the intestines by removing O(-2)

    The parallel with steroids (like Prednisolon)
    Steroids inhibit the secretion of free radicals by Polymorphonuclear neutrophils

    5-ASA (aka Asacol) and Prednisolon are the most effective conventional medicine used for treating Crohn's and UC !