SOD2 A16V homozygous mutation - anyone else?

[Thinktank]

jenbooks, Thanks for the explanation. I will do some reading on it.

P.s. do you know when jarrow will be carrying out the tocotrienol-complex without the glycine you mentioned before?
I always notice remarkable anti-inflammatory effects from the product. I recently read something about tocotrienols inhibiting prostaglandin 2 or offsetting the 3 types of PG favoring 1 and 3.
I have D6D impairment so it might be a good idea to start supplementing with it again.

 

[roxie60]

I know this is a SOD2 thread but anyone have the Rs#'s for these SOD1's


SOD1 G93A

SOD1 A4V

 

[Bluebrid]

I came to the conclusion that the SOD2 snp has been at the heart of all of my health conditions my entire life - from my asthma which started at age 2 to my fibroids which have put me in the hospital with severe anemia to my glaucoma and chronic fatigue. I have also traced this snp as a causative factor in my father's Parkinson's and glaucoma.

SOD2 snp causes oxidative stress on the mitochondrial and then basically everywhere -- as free radicals make more free radicals when they bump into healthy cells. It is a reaction to simply runs unchecked in the body. To find out if any health condition is related to free radicals and could then possibly be related to this SNP, use the health condition and ROS as the keyword in a pubmed search.

Surprisingly, most chronic health conditions are related to ROS (Reactive Oxygen Species) or free radicals.

Please be careful when trying to use manganese to supplement -- there is a high correlation between manganese overload and certain neurological conditions. If you have this SNP, you simply cannot make SOD2 efficiently or perhaps entirely -- and you may end up with too much manganese.

Vegetarian diets can increase SOD levels - but there is still the issue of making SOD2.

The only thing that helped was an SOD mimic that is able to act as SOD1, SOD2, SOD3 and catalase.

My father and I have been taking it for several months. Within a week, my fibroids disappeared - completely. I must have had them my entire life as I never experienced a pain free, low flow, 5-day period in my life.

I began to wonder how my entire life would have been different with this newfound energy -- and how my body will now heal with normal hemoglobin levels and energy.

A skin condition that biopsied as scleroderma disappeared. The skin is soft now. I still have a few small cysts that are healing. I would assume this is probably going on internally as well and my body is now undergoing a healing process.

Also my thinning hair is coming back --- with more color coming through in areas that had previously been all gray. I was never bald – but my hair had been falling out in clumps as my energy levels sagged over the years.

For my Dad, it has been a Godsend.

He is now using a walker -- no more wheelchair. No shakes, no choking - no other symptoms. He is still not the fastest walker and still has balance issues. But he is now independent.

He is still taking antioxidants and supplements according to his detox and methylation report, including weekly glutathione pushes. His doctor felt the SOD mimic would simply level the playing field with respect to free radicals and he still needed the nutrients to help his body heal.

My non-medical opinion is to try this SOD mimic if you have this snp. All the other treatments tried to this point will simply fall into place once the free radicals are handled.

The substance, Tempol, is not currently FDA approved. There are a few human clinical trials or reported clinical use-- one for Parkinson's which I am still trying to get a copy. There is another trial on teenage smokers -- some with a derivative of this substance in an eye drop for macular degeneration -- a few for radiation burns and alopecia from chemotherapy.

It has been used in a topical alopecia product for about 25 years. I get mine for research purposes from TempolResearch@gmail.com. Clinical trial or physician information can be found at info@Tempol.info

I have been told that daily dosing anywhere between 10mg and 100mg for 160 pound adult is average. The key is redox balance, not over reduction or over anti-oxidant. Dosing can be increased or decreased in that range depending on symptoms.

Googgle patent US20120115905 for dosing information and reported clinical use. This patent indicates that it does not build up in the system – and that stopping treatment brought back symptoms within 2 week’s time

Hope this information helps. I stumbled on this completely out of desperation to help my father – knowing that I too have the genetic potential to follow in his footsteps.

 

[boohealth]

Thanks, @Bluebrid. May I ask--who are you, what is your history, and how did you come across this thread? I don't mean to be skeptical--and am always grateful for new info--but when someone registers on a site and shortly thereafter makes one post recommending one FDA unapproved supplement, I am always a little concerned as to who the person recommending the supplement is, and want to be sure they are not affiliated with the company. Please don't take that as offensive. Thanks.

 

[ttt]

Ditto boohealth's question/concern, Bluebrid.

And I'm also intrigued. How long did you take this stuff before you felt an effect? And what dosage do you take, and how much does it cost? Thanx!

 

[boohealth]

I am looking on pubmed. There is a lot of research. One thing that concerns me is it reduces cerebral vascular remodelling, and this study too, for instance...although it's beneficial in many ways, it is a mimic...not the same as sod2:

Braz J Med Biol Res. 2014 Feb;47(2):119-27. doi: 10.1590/1414-431X20133193. Epub 2014 Jan 24.
Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis.
Bassi E1, Liberman M1, Martinatti MK1, Bortolotto LA2, Laurindo FR1.
Author information
Abstract
Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.

PMID:
24519127

 

[boohealth]

@ttt She is saying her lifelong fibroids disappeared in one week. This is the kind of statement that makes me a bit skeptical. I doubt that is possible, but it would have to be confirmed by ultrasound anyway.

 

[Bluebrid]

One thing to remember with Tempol is that extrapolations from animal models, which are how human doses are normally calculated, do not apply to Tempol. The explanation is given in patent US20120115905.

As for who I am – I am not a medical doctor. I worked in biotech for years for a federal agency and then moved into another area of law, and then to a private company in a completely different capacity. No one at the alphabet agency where I was employed could figure out my complex medical history.

I cannot tell you how many physicians, grantees and top-notch research hospitals have looked at my case. Rich had corresponded with me and helped me along the way – as had several integrative physicians. I had been reading about Tempol and some other mimics like Ebselen for quite a while – urging my father’s physician to look into the matter.

I have been on it for about 3 months. I noticed a change in my fibroids within 7 days – reduced pain, no PMS symptoms, less bleeding. The next month was even better, as was this last month.

I would also say it was about a week or less for my Dad as well. He really was going down fast – the wheel chair, the choking – Parkinson’s always progresses. We had increased his glutathione pushes, added sodium thiosulfate to his IV treatments and he was still slipping. It was hard to watch….and hard to care for him. The muscle stiffness meant he was dead weight. Even lifting his leg to put on a pair of pants was a major undertaking.

It was maybe 3 days after starting Tempol that he went in to the doctor for his IV push and the sodium thiosulfate. He took a nap when he got home – slept for a long, long time. And when he woke up, he did not need the wheel chair. He has gradually gotten steadier on his feet. He still uses a walker – but on occasion he will leave the walker behind and forget that he left it in the kitchen. I think that is a good sign that he does not feel the need to rely on it. I prefer for safety that he keeps it with him though.

His doctor does not know if he will continue to improve or even if it will keep the Parkinson’s from progressing. This is new territory. But it certainly beats the alternative – and watching him decline in a nursing home.

When I found this substance, I felt so angry that it was not more widely available. I wrote to some of the researchers doing the animal studies asking why this is not yet available – and no one seemed to know. The best answer I found is that although there are utility patents on Tempol for different medical conditions, there is no composition of material patent. It is unlikely that a pharmaceutical company will invest in a substance that does not have complete patent protection. It may also have something to do with the NIH retaining utility patent rights on cancer. I really cannot say.

 

[Bluebrid]

Yes - they did -- fibroids are 100% related to free radicals – gone! Glad my clotting issues prevented me earlier from taking a surgical approach to my fibroids.
Patent US20120115905 mentions fibroids and cites clinical experience with it.

Believe me I too was skeptical when I read the patent and the research. But I acted out of desperation for my father's condition and tried it first so I could asses my own reaction.

 

[boohealth]

@Bluebrid, I am simply saying that though your symptoms may have abated quickly, if that is the case, without ultrasound before and after that is a pretty uncertain statement.

Tempol is apparently owned by Mitos, Inc? A review paper by Christopher Wilcox is available on pubmed, but he notes a conflict of interest (honoraria from Mitos).

It does look like an interesting substance. My big concern is 1) I do not know if other snp's help compensate for my own SOD2 double deletion. Lots we don't know. There is lots of redundancy in nature.

Secondly, the law of unintended consequences. As in, the review paper, anaerobic bacterial infections being stimulated. So it's kinda scary--unless you are desperate--to try something only tested in animals, short term. Thanks much for the info though, and glad you found something helpful. I myself would like to study the gene--and see whether lifestyle and dietary changes own to be safe can help. I've emailed Garth Nicholson and others to see what they think.

 

[Bluebrid]

I too wonder about how my body compensated for the double deletion -- albeit poorly all these years. I mean I survived and was athletic in my youth -- so something was working. I am now looking closer at mitochondrial DNA for answers.

Mitos has a few utility patents – but as near as I can figure, their key investor fell on hard times or had some unrelated legal trouble that affected his ability to fund the trials. Mitos is just one of a handful of start-ups that have tried to take this compound to market. All seem to encounter legal or financial issues completely unrelated to their clinical work.

For the record, there was no change in either my blood pressure or my father’s – but we both tend to be on the low side anyway. I do not know the dosing that Mitos was testing for hypertension.

I do know from discussing this with my father’s physician (who is a fairly famous ACAM redox and chelation lecturer) that dosing between 10 mg and 100mg would not be an issue for anyone. That it is not enough to stop the redox cycling. He looked at the matter closely. And believe me, with all the immune issues I have had in the past, upsetting that balance is the last thing I want to do.

He said that at that dose, it is fine. He also said that the immune system would be improved through increased cell signaling and that is why it works for cancer and autoimmune conditions.

And yes – there are YEARS of sonograms showing the fibroids – and there are pre and post scans. Completely gone – vanished!

 

[boohealth]

Who is your fairly famous ACAM physician, @Bluebrid.
As to the fibroids...you said they disappeared in one week, but I am pointing out that's actually very unlikely, but besides, you'd have had to go in for a sonogram a week after starting the supplement to support that claim.

Do you know what TEMPOL is actually made of?

 

[Bluebrid]

http://www.freepatentsonline.com/y2012/0115905.html

 

[Thinktank]

Interesting because i've been looking for something similar to supplement my +/+ SOD2 mutation.
Do you perhaps know where i can find more user experiences?

 

[boohealth]

http://www.freepatentsonline.com/y2012/0115905.html

Bluebrid, personally, I don't know what to make of somebody who joins mid April, and then posts about a non FDA approved supplement, claiming nigh-miraculous curative powers for it, and quotes a supposedly famous ACAM doctor who says its perfectly safe in certain dosages, but won't give that ACAM doctor's name.

Too many claims for me, none substantiated--and no history of posts so that I can trust you aren't affiliated with the supplement or promoting it.

This may NOT be the case. You may be telling 100% the truth, but the mysterious doctor, and the decades of fibroids cleared up completely in one week--beggar my belief. Sorry.

 

[Bluebrid]

Boo!!!! health - I politely sent you a note about not wanting to reveal the name of the physician -- and had you given me the same courtesy, I would have given you his name in an email.

And for your information, I am an old, almost original member of this site who had not posted in a while so I needed to rejoin. I clearly remember rules from those days and discussions as to whether or not to post physician names on the internet given the current state of some medical boards on alternative treatment.

Shame on you!

I rejoined to investigate more on issues that now may be secondary to SOD2 – and to see if there were any discussions on mitochondrial DNA and to ask questions.

I did not have to post my find – which is so well known in certain research circles, that some physicians who study it gave me and my mystery doctor their personal long-term experience with it.

Some have been taking it for over 20 years and look pretty darn good for their ages.
In my estimation, Tempol is potentially the answer or part of an answer to ALS and mitochondrial disorders which have devastating effects on families and young children. Why has no one stepped up to the plate for these people – let alone those with CFS?

Seriously, look at all the research and patents over the last 30 years, the potential benefit for people suffering from these conditions makes it a crime that it has not been approved. Are treating these conditions with this compound not profitable enough for a company to step in and help?

 

[boohealth]

Now you up the ante and its the cure for als? And more physicians you won't or can't name who are taking it?
From my perspective, all your claims are not validated. Saying your dads doctor is famous...but you can't give his name...whatever. Law of unintended consequences, I don't want to experiment on myself.

 

[Bluebrid]

Open your mind and do some basic research. 20% of all ALS is caused by a genetic issue with SOD1. The remainder have mixed causality -- some of which is attributed to toxins that effect the SOD pathway.

And yes, depending on when in the disease process that Tempol is introduced and what other stressors are involved in the case, Tempol or another equivalent SOD mimic would be effective.

There is lots of research to support this – including the latest paper - http://www.ncbi.nlm.nih.gov/pubmed/23405225
“Tempol moderately extends survival in a hSOD1(G93A) ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A) forms.”

hSOD1(G93A) ALS rats do not have functioning SOD1 pathways. Moderate extension in their survival on plain rat chow and a low dose of Tempol is extremely promising.

If I had ALS, I would be reaching for this and exploring reducing other stressors – perhaps metals, eliminating glutamate and adding IV glutathione and a host of antioxidants.

And yes. ALS is a condition caused by ROS.

 

[Sea]

Thank you for this interesting info @Bluebrid

 

[Hip]

@Bluebrid
Thanks for posting this information about the superoxide dismutase (SOD) mimetic tempol (also called 4-hydroxy tempo), which is very interesting.

Tempol seems to have worked well for you.

Tempol has had a potent effect on your fibroid symptoms — you noted reduced pain, no PMS symptoms, and less bleeding within a week of starting tempol, and later a complete disappearance of the fibroids (no longer seen on your ultrasound scan). How long had you been taking tempol when you had the ultrasound scan in which you saw that the fibroids had shrunk down to nothing, by the way, Bluebrid?

Tempol also seems to have put your scleroderma into remission, and promoted new hair growth.

Plus tempol seems to have worked very well for your father's Parkinson's disease.



Looking at studies on tempol, and on these various diseases, the following would seem to support what you observed:

• This report by Peter Proctor and Donna Rolling-Proctor (who is should be mentioned have intellectual property claims to tempol) documented that when 10 mg of tempol a day was given to one patient with fibrocystic breast disease (which are like uterine fibroids, but located in the breast), within 1 or 2 weeks there was significant symptomatic relief and regression of palpable cysts, which was confirmed by mammography and ultrasonography. What did your doctor say about the sudden disappearance of your fibroids, by the way?

• This study found that scleroderma patients have autoantibodies to CuZn-SOD (SOD1) that inhibited SOD activity, and the study authors suggest that this autoimmune inhibition of SOD1 activity may play a role in the development of scleroderma fibrosis. So if low SOD1 is indeed playing a role in scleroderma, then this might explain why the SOD1, SOD2 and SOD3 mimetic tempol helped with your scleroderma.

• This study found that tempol restored the hair growth cycle in psychological stress induced hair loss.

• This study demonstrated that tempol is neuroprotective in models of Parkinson's disease.



The website detailing tempol is found here: http://tempol.info You can subscribe to the newsletter on the home page. The links do not seem to be working properly on this website, but the following three pages of the website are of interest:

• Information on Tempol
• Sources for Tempol
• Information on Superoxide Dismutase (SOD)

Note that there are three types of SOD:

CuZn-SOD (SOD1) found almost exclusively within cells (in the cytoplasm).
Mn-SOD (SOD2) found exclusively to the mitochondria.
EC-SOD (SOD3) found exclusively to extracellular spaces outside cells.



By the way, are you aware of the supplement Glisodin, which comprises the enzyme superoxide dismutase (SOD) linked to the gliadin protein from wheat, which allows the SOD to survive transit through the acid environment of the stomach. SOD is deactivated by stomach acid, so orally taken SOD supplements are normally ineffective; however, the gliadin protects the SOD from the acid.

GliSODin raised blood levels of SOD by 89% and increased catalase levels by 171%.†

Glisodin has been shown to be neuroprotective.†

However, I don't think Glisodin is able to protect mitochondria, as I don't think the SOD from Glisodin can get to the mitochondria like SOD2 can. Thus Tempol, which mimics SOD1, SOD2 and SOD3, would be superior to Glisodin in this respect.

I tried Glisodin myself a few years ago, but did not notice any benefits for my ME/CFS.​