SOD, Glisodin and Oxidative Stress in PD

[Mezmerric]

Has anyone had any experience of supplementing with SOD (Superoxide Dismutase) - inn particular by using Glisodin, which makes SOD absorbable and bioavailable?

Potential reasons:

1 . Oxidative stress is considered a major cause of ageing and degradation of DNA and proteins, starting with an Superoxide anion free radical (which has an extra electron).

2. Superoxides are produced in the mitochondria by electrons leaking from the electron transfer chain (ETC), which is located in the inner membrane of mitochondria. These electrons are then captured by molecular oxygen and become Superoxide.

3. SOD enzymes deactivate the Superoxide anion by transforming it into Hydrogen Peroxide, which in turn is then transformed into di-oxygen (O2) and water (H20). So, SOD is considered a critical enzyme in the defence against free radicals and oxidative stress.

4. Research shows that SOD levels decline with age, it also shows that there is a further negative correlation between SOD levels and the progression of Parkinsons.

5 Research also shows that those with PD have a less efficient ETC - causing loss of electrons, and lowering conversion to ATP (which is the key energy currency in the body).

If there is an increased loss of electrons, I’m guessing this increases Superoxide in PD, and also may explain why SOD levels are lower in PD, since more SOD is being used to combat greater amounts of superoxide - creating an increasingly negative cycle.

Would be interested in anyone’s thoughts or experience on this

[Trig27]

Statins greatly increase ecSOD, if you aren't on a statin you could get on one.

Nitric oxide also increases SOD. How to increase NO? Eat raw vegetables, don't put things in your mouth that kill bacteria, so no flouride, no mouthwash. Exercise. Sunlight. UV and IR both increase NO and protect the endothelium.

Also a lot of theories on mitochondrial dysfunction. Maybe thats where the problem is. What helps that? Exercise. Fasting.

[Mezmerric in reply to Trig27]

Nitric oxide (NO) reacts rapidly with superoxide, producing peroxynitrite - which is a very dangerous free radical.

[Trig27 in reply to Mezmerric]

So what?

Maybe spend a bit more than 2 min on Google to figure it out?

[Mezmerric]

Well, not a 2 min search but below is an excellent and detailed 1.5hr lecture that explains, step by step, the movement of electrons to create Reactive Oxygen Species and the impact of free radicals on the cells.

This lecture also covers Reactive Nitrogen Species (RNS) and explains that RNS comes solely from Nitric Oxide and can combine with superoxide to create Peroxynitrates, which are much more damaging.

youtube.com/watch?v=mMl9eHC...(Not working as expected?) (26mins in).

So it seems that Nitric Oxide does reduce SuperOxide, but in a very damaging way - by converting it to Peroxynitrate, which is even worse.

My original question was about supplementing with SuperOxide Dismutase - as a means of reducing levels of SuperOxide in a way which is not damaging.

Hope this is useful.

[Following_closely]

Hello Mezmerric,

The most recent "No silver bullet for PD" episode featured a physician-scientist who spoke about mitochondria and mitochondrial reactive oxygen species (ROS) in the pathogenesis of at least some forms of PD. I don't remember her saying that there was any evidence that inadequate levels of superoxide dismutase were responsible, but maybe I missed it. You can listen for yourself (Dr. Sonia Gandhi; youtube.com/watch?v=DttWHq8...(Not working as expected?). Even if I remembered incorrectly, however, superoxide dismutase is a protein and would most likely be broken down and inactivated in the stomach. If it was provided as an infusion, which would get it into the circulation, it would still have to cross the blood-brain barrier and probably the cell membrane, if not also the mitochondrial membrane, to have any effect on PD. In short, I doubt that a superoxide dismutase supplement would work as a treatment for PD. However, you can hear for yourself what Dr. Gandhi said about potential mitochondrial-based therapies in the Q&A after her talk ended.

[Mezmerric in reply to Following_closely]

Yes, SOD is an enzyme/protein that acts as the first line of defence in reactive oxidative stress.

The abstract linked below indicates that there is s correlation between mutations in SOD gene and neurodegenerative diseases, like Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease (HD), Parkinson’s Disease (PD) and Alzheimer’s Disease (AD)

Apparently Glisodin is a formulation that makes SOD supplementation viable to pass the BBB, which was why I asked if snyone had tried it

Many thanks for the link i think I’ve seen the talk but will review

Thanks again

sciencedirect.com/science/a....

[chartist]

Melatonin increases SOD at the protein and gene levels. Melatonin increases production of other members of the bodies potent antioxidants and activates Nrf2. Melatonin is itself a potent scavenger of reactive nitrogen species (RNS), reactive oxygen species (ROS) and peroxynitrite (ONOO) and melatonin metabolites are also potent antioxidants allowing melatonin to neutralize more free radicals than other common antioxidants such as vitamin C and E which work on a one to one basis.

More importantly, melatonin has shown itself to return elevated oxidative stress levels in people with PD to healthy control levels while helping to maintain homeostasis of mitochondria of same, as discussed here :

onlinelibrary.wiley.com/doi...

Here are three relevant quotes from the human study :

' After three months of treatment with melatonin, the levels of lipoperoxides, nitric oxide metabolites, and carbonyl groups in proteins were lower than in the placebo group and were statistically similar to the levels of healthy controls. '

' At baseline, the activity of mitochondrial complex I and the respiratory control ratio were significantly lower in PD patients than in the healthy control group (Figures 2(a) and 2(b), respectively). Compared with the placebo group, the melatonin group showed significant increases of both parameters after 3 months and reached values similar to the healthy control group. '

' Intervention with daily supplementation of 50 mg of melatonin, for three months, resulted in a significant reduction of oxidative stress markers. These data are according to the reported previously [6] and were paralleled with significant increases of catalase, complex I activity, and respiratory control ratio. In consonance, previous data showed that melatonin increases the levels of reduced glutathione [33], decreases malondialdehyde levels, and stimulates gene expression of important antioxidant enzymes such as superoxide dismutase, complex I, and catalase [34, 35] in rat models of PD. In addition, melatonin prevents cardiolipin loss and oxidation which avoids mitochondrial membrane permeabilization induced by reactive oxygen species and other factors [36]. Reduced glutathione levels are increased by melatonin action, and glutathione also contributes to maintain the correct mitochondrial redox status and the integrity of the mitochondrial membranes [37]. Melatonin also has anti-inflammatory effects by diminishing cyclooxygenase type 2 activity in PD patients [6] and in MPTP-induced PD in mice [38]. Additionally, melatonin lowers the activation of inducible nitric oxide synthase, a well-known pathological marker of neuroinflammation [39, 40], and also decreases protein lipase A2, lipoxygenase, and cytokine activities owing to its antioxidant actions [41]. Therefore, nitrosative stress and inflammation are diminished by the action of melatonin. '

Art

[Mezmerric in reply to chartist]

Hi Art

Many thanks for the info. I’ll resesrch some more. Meanwhile would still love to know if anyone is trying SOD supplementation directly using Glisodin orsimilar.