Hello again, Linnie,

In your reply here and your reply to another post I wrote, you talk about blood clotting and anticoagulants; I just happen to know something about what you face, as both my wife and daughter have been hospitalized for DVT, and in both instances, doctors tried to prepare me for the very real possibility that they would die.

(My daughter was pregnant and needed to inject heparin daily; she and her children had to move in with us to be closer to the med center, and I remember waking early every morning in order to be the first to learn whether she survived another night).

In addition to two incidents of DVT, my wife has suffered two pulmonary embolisms and a stroke during surgery (age 34). I know something about the consequences of the disease you face, and about the dangers of anticoagulant therapy; it is a very delicate balance.

I don’t know what blood thinner you use, but I assume its warfarin, and that means you must be constantly monitored even though your dosage has probably been well-established over time. (For others: Warfarin is the active ingredient in mouse and rat killers; their blood stops clotting and they eventually die of internal hemorrhage).

Anything that could affect the warfarin, enhancing or inhibiting its effect, could cost you your life, so you must be extremely careful. The dangers of interactions between this and so many other drugs and foods may be greater than with any other medication.

After reading your reply here, I did a quick keyword search of PubMed and Medscape, and learned of research showing that GSE does enhance the effects of warfarin, and this may someday lead to a combination with fewer risks of bleeding; but not yet. Today, no one knows the proper balance, so it is simply too dangerous to combine the two.

You are justified in fearing GSE with your disorder, and the known consequences of birth control drugs and devices include abnormal clotting, so any woman who has experienced this and is on anticoagulants should avoid GSE, but that is not the case with most of us afflicted with RSD. In fact, anyone who has suffered clotting, but not taking anticoagulants, would most likely benefit from GSE as it appears to reduce the risk of future incidents.

My brief search turned up research showing that GSE is useful in countless disorders: Type “grape seed extract” into PubMed and you will find more than 200 abstracts talking about the benefits GSE in the context of many disorders; it reduces cholesterol, is effective in killing cancer cells in many types of cancer, and even reduces the risks of smoking.

For some reason, a keyword search using “antioxidants” and “anticoagulants” brings up more than 3900 abstracts, but not all involving anticoagulants; this shows that the number of uses for antioxidants has increased nearly exponentially since I first looked nearly ten years ago.

I see that in another post you appear to locate yourself in San Diego; as a neuroscientist there, perhaps you know of Stuart Lipton, M.D., Ph.D.; professor and Scientific Director of the Center for Neuroscience, Stem Cells, and Aging, Burnham Institute for Medical Research, and professor at the Salk Institute; Scripps Center and UCSD. Here is what he had to say about antioxidants.

In a lecture on Alzheimer's Disease (aired on UCTV on 4/01/07), Dr Lipton spent the first half-hour discussing the free radical theory on aging and the benefits of antioxidants. He did not mention GSE specifically, but did talk about resveratol (from red wine). He suggested wine alone will not provide adequate antioxidant protection; joking that one would need to drink "many, many cases of red wine a night" to achieve adequate antioxidant protection.

Later in the lecture he discussed how oxidants (oxygen free radicals - OFRs), damage DNA, and how they specifically misfold proteins, and that "Misfolded proteins are thought to disrupt the normal function of nerve cells, leading to their injury and eventual demise"

Speaking specifically about Alzheimer's disease, he talked about when NMDA (Glutamate) receptors in neural ion pathways are misfolded; they allow glutamate to build up to the point that these ion pathways (specifically calcium + ions) remain open and the cells "excite each other to death"

One of the original researchers into memantine, Lipton talked about how that drug closes these ion channels and then exits quickly, allowing the channel to reopen; but that he doesn't believe that will lead to a cure. In his opinion, the cure will be found in antioxidants that prevent Lewy body-like inclusions to the PDI protein that refolds proteins.

Finding the antioxidant that can cross the blood-brain barrier is a significant part of Dr Lipton’s research.

If the free radical theory on aging proves correct, antioxidants may be the most important discovery of the 20th century. I don’t believe they are the fountain of youth, but they could produce the safest and most effective medications ever known.

The other side-effects you mention are constantly reported with placebos, but whether they are, or aren't placebo effect, they are trivial compared with the benefits of GSE.

While I agree with: So please exercise caution with these supplements. We're all on a lot of meds and sometimes there can be pretty severe interactions!I don’t think this warning is appropriate to antioxidants in general or GSE specifically; it is safe, and even if I’m proved wrong about symptom migration, a wise precaution for nearly everyone…Vic

Hi Ali,

You wrote: I think that the fact sheet by the National Institute for Neurological Disorders and Stroke (NINDS) is accurate, which one?

The 1996 Fact Sheet is clearly a product of the prevalent belief at the time that the sympathetic nervous (SNS) system plays some sort of causal role in RSD, and since the SNS exerts tremendous control over circulation through dilating and constricting arteries, they felt safe in mentioning “cool, blue skin color”. They hoped that someday, someone would find out how the SNS was doing it.

In 2006, following the International Association for the Study of Pain (IASP) rejection of SNS causation, NINDS pretty much abandoned this idea. In addition, the view that this disorder is the result of central sensitization (CS) had taken hold; but CS occurs in the spinal cord and can’t explain a process in which skin is first red and then blue, so they changed those objective signs into non-specific color changes. That may help someone your age, but it doesn’t help clinicians confronted with this disease for the first time.

I have tried many supplements including Grape Seed Extract to try and help reduce swelling but they don't seem to work. There is no reason to expect that GSE would. GSE neutralizes OFRs, which cause inflammation. As NINDS once reported, RSD begins with warm red skin that later becomes cool and bluish; the warm red skin is inflammation, and by stopping it, you stop the RSD process before it becomes cool and cyanotic, and incurable.

It is true that swelling is a part of the inflammatory process, but it appears that other factors are at work here since swelling can continue long after inflammation ends. GSE would not affect those factors.

When I PMd your mother and recommended that you start taking GSE, my thought was that since it delays symptom migration by neutralizing OFRs, it might be effective even after inflammation becomes widespread. My message was based on the hope that it might still help, not that it would be as effective as it appears to be in preventing inflammation from developing.

Even if it does not stop the 2nd (cyanotic) stage from developing, I hope you will continue to take it: Much of your body remains unaffected, and antioxidants are the only protection I know of from further inroads by this disease.

.I am also experiencing horrible colour changes which I didn't have before. I don’t have anything to add to what I’ve said, but my concern for you compels me to ask if you could tell us more about these color changes: What is going on right now?

Your posts have shown you to be both thoughtful and spiritually generous, and all of us hate seeing you go through this…Vic

Vicc,
Just posting a quick reply. The fact sheet that I was on about was the one published in 2006.

My colour changes - the whole of my foot goes blue, yellow and black, is this normal with RSD? I am a bit worried about when my foot goes black.
I also get a 'red' colour around my ankle bone that comes and goes ever so often, this seems to happen when I try to walk on my foot for a short period of time (like 2 minutes)
The colour changes have got worse over the last couple of weeks.

Balance problem - I understand that balance problems can happen with Dystonia, am I right?. I suffer from RSD, Dystonia, and Arthritis. I have spoke to my PM doctor many times about the balance problems and he says that it is a Psychological issue - why would I do that?? I am getting sick of people accusing me of something that isn't true. I only developed the balance problems after a Guanethidine nerve block. Do you think I should see a different PM doctor at a different hospital???

Pain - I am getting a LOT of pain (the pains got worse over the last couple of weeks too, it is a 9 and a half on the pain scale)
I am getting a LOT of burning pain, a sharp shooting pain at the bottom of my foot, and a stabbing pain.

Muscle spasms - the muscle spasms seem to be worse (they come a lot more often than they did a couple of months ago)
My toes twitch up and down. I also have spasms in my knee, my physiotherapist and PM doctor says that I only have RSD in my foot, so why is my knee and hip shaking??
I twisted my knee a few weeks ago and I am getting pain in it (the pains a 4 and half on the pain scale)

Thanks
Alison

Hi Ali,


I hope you don't mind me answering your question about the colour changes in your foot when you said you were worried when your foot goes black.
If your foot still has the ability to return to a normal pink or red colour after a period of cyanosis this means there is still the ability for blood to well oxygenate your foot and there is probably no permanent damage to the vessels and tissue.
There are many reasons for cyanosis and in CRPS/RSD it is still thought to be due to vasomotor changes of sympathetic dysfunction if it is not being caused by some type of tourniquet effect in which the flow has been temporarily stopped.
Some people have very cyanosed extremeties from a disease called Peripheral Vascular disease where the circulation is poor due to disease in the blood vessels, this is most common in those who smoke heavily.--- I am sure this does not apply to you
When skin is cyanotic all the time this may reflect that the tissue is not being well oxygenated and this is when there is more likely to be trophic changes occuring as a result.
Definitely trying to keep your limb working and moving will encourage blood flow and also reduction of oedema will also encourage blood flow.
I do hope that you are going to move on to a Pain Team who can work with you and help you get better by applying a multidisciplinary approach to your pain management and management of your mobility.
You are way to young to have to be dealing with this but at the same time your youth should radically help you to get healed.
All my good wishes to you
Love Tayla

Vicc-
While I appreciate your understanding of clotting issues, my own personal experience with this problem was not the impetus for my posting. Yes, there are things that can interact with coumadin that can produce deleterious effects. It's definitely a tempramental medication! But my warning was not just for coumadin users, and it was more objective than you make it out to be. Anyone who is on any medication should be cautious when adding anything to their regimen, whether or not it is a prescription drug or a 'natural' supplement. These can be powerful substances, even if they are found in the vitamin section. Too much vitamin A or vitamin E can have toxic effects. You have to be careful when taking such supplements. For instance, you casually mentioned taking DMSO, but DMSO is a very hazardous substance that is a powerful organic solvent. The material hazards page for this chemical advises having no direct contact with DMSO and washing it off immediately if it does touch the skin.

Also, there was a landmark study on antioxidants that came out in the Journal of the American Medical Association (JAMA) that actually implicates them in increasing mortality. It was a systematic review of hundreds of other studies. They included 68 randomized trials with 232 606 participants from 385 publications. The authors found that beta carotene significantly increased mortality. And there have been recent studies that suggest that beta carotene my act as a cocarcinogen. Vitamin A also increased mortality dramatically, as did vitamin E. Vitamin C had no significant effect on mortality, but the sample size of vitamin C takers was much smaller than the sample size of other antioxicant takers. But still, it did not increase mortality. Selenium also had no effect.

The authors acknowledge that the findings directly contradict the findings of observational studies- it is folk knowledge that antioxidants are beneficial, but when the hard science is performed, you can see that they actually have a detrimental effect on health. They suggest that oxidative stress is most likely an effect of disease processes rather than the cause of them. Also, free radicals DO perform essential defense mechanisms in the body. They help in apoptosis (programmed cell death- the body's way of eliminating dying or mutated cells), phagocytosis (a white blood cell's ability to engulf and "eat" foreign invaders or damaged cells) and detoxification.

So in the face of this evidence, maybe people should be cautious about these specific supplements, but one should be cautious about supplements in general. Natural may not equal safe. Also, these are completely unregulated and their purities cannot be ascertained. It is virtually impossible to know what kinds of impurities and toxins are in these supplements, most of which are manufactured in China.

http://jama.ama-assn.org/cgi/content/full/297/8/842

Linnie

We do have Drug Interaction checkers in our useful sticky thread and on our Medications forum.
I think many do include supplements in most of them for checking.

I'm sure we all encourage everyone to use those tools to double check all their meds and talk with their Dr before making changes.

Linnie,

I’m sorry you took my reference to your posts discussing your experiences with a blood disorder as some sort of editorial about your motives in your previous post: But my warning was not just for coumadin users, and it was more objective than you make it out to be. You specifically discussed blood thinners and I felt an explanation of them was necessary and related my experiences to show I fully understood the import of what you said. (For the reader: Coumadin is a brand name for warfarin).

As to your statements here, I will try to reply briefly and directly to the points you make.

For instance, you casually mentioned taking DMSO, but DMSO is a very hazardous substance that is a powerful organic solvent. I also wrote: That much DMSO made me feel pretty sick, but sick is better than possible full-body RSD.

I have written posts about DMSO in the past, including abstracts demonstrating the efficacy of that drug in the acute (inflammatory) stage of RSD, and; that the Government of the Netherlands has mandated that physicians there make DMSO available to their RSD patients.

DMSO is topical and I believe we need a systemic antioxidant. I don't recommend its use, if for no other reason than daily application to one's extremities would be messy and could make you feel sick.

I have written numerous posts and don’t fault anyone for not reading all of them, but I want to make it clear that there is scientific support for the use of this volatile chemical. As in many things, we constantly make decisions involving balancing risks and benefits, and in this instance, I felt the circumstances justified the temporary discomfort I experienced.

Also, there was a landmark study on antioxidants that came out in the Journal of the American Medical Association (JAMA) that actually implicates them in increasing mortality…..The authors found that beta carotene significantly increased mortality. I did a quick Yahoo search of beta carotene and found a link to the University of California, Berkeley Wellness Newsletter (which I assume to be a reliable source), which included this passage:

Beta carotene is one of several carotenoids, natural plant pigmentsfound in deeply colored fruits and vegetables. Others include alpha carotene, lutein, lycopene, and zeaxanthin. Beta carotene and some other carotenoids are “provitamin A carotenoids,” meaning that the body can convert them into vitamin A. Beta carotene is also an antioxidant; thus it may help deactivate free radicals, unstable molecules that are by-products of cells “burning” oxygen for energy. Free radicals can damage the basic structure of cells and thus lead to chronicdiseases (notably cancer and heart disease) and accelerate the aging process. There is no daily recommended intake, or safe upper level. (emphasis added)

Beta carotene is not an antioxidant; it has antioxidant properties. The same is true of vitamins E and C. They have other functions besides neutralizing free radicals, and I’m perfectly willing to concede that those functions could be harmful, especially when consumed in large quantities.

Antioxidants appear to have a single function: They surrender an electron to a free radical molecule, allowing it to return to its normal state. Without antioxidants, they would steal an electron from another molecule, which would restore them, but turn the victim into a free radical.

These electron thefts are chain reactions in which the cells loses energy with each theft, and when they involve DNA, they enhance the risk of mutation.

I do not recommend any of these things as useful in delaying the onset of symptom migration. I recommend antioxidants and specifically GSE because of its low cost and widespread availability,

it is folk knowledge that antioxidants are beneficial… I refer you, and everyone else, to my statement that I found more than 3900 abstracts discussing antioxidants in my brief PubMed search, and suggest that this is more than “folk knowledge”. When in doubt, forget Jimmy Buffett: Research it for yourself.

ADDED LATER: Using "antioxidants" as the single keyword, I found 65,235 documents listed in MedScape and 242,148 in Pubmed; this suggests that science takes this subject very seriously. Not all of the documents found at these sources represent actual research, but scienctists don't waste a lot of time on "folk knowledge", urban myths, etc).

Also, free radicals DO perform essential defense mechanisms in the body. They do indeed: In fact, they have been identified as neurotransmitters too.

They have also been identified as damaging nearly everything they touch. The roles you mention are destructive (sometimes beneficial for the body), but to put to rest fears that antioxidant supplements could impair the body's ability to perform these functions: Our mitochondria produce one OFR for every ATP, with some cells containing more than 100 mitochondria, and estimates of 50 to 100 trillion cells in our body, I don’t think an additional 300mg of GSE daily will reduce OFR levels to a point that the body suffers.

So in the face of this evidence, maybe people should be cautious about these specific supplements, You haven’t provided any evidence that antioxidants in general, or GSE specifically, poses any danger whatsoever (except with the concurrent use of anticoagulants).

It is virtually impossible to know what kinds of impurities and toxins are in these supplements, most of which are manufactured in China.

I suggest you’re suggesting that we avoid putting anything into our bodies that we don’t know for sure was made or grown in the U.S. In that case, one must still be very careful: Witness the recent reports involving E-coli in spinach, lettuce and ground beef.

Nothing you have written persuades me that grape seed extract poses a greater threat to my health than the widespread inflammation that resulted when I stopped taking it. I hope it doesn’t persuade anyone else, either…Vic


NOTE: Ali, I will reply to your post, but I got so angry at the way you are being treated and your obvious signs of RSD ignored, that I decided to follow my 24 hour rule: Take a day to calm down…Vic

Hi again Ali,

The reason for this delayed response is that I have written many drafts but none of them were adequate. You are 13, and I expect to be criticized for being blunt in my honesty in light of your age, but I couldn’t lie to my kids about Santa Claus, and I can’t lie to you (even by silence), in response to issues you addressed specifically to me. I’m not going to talk gloom and doom, but I am going to tell you what I believe is true.

I’ll begin with a simple question: Do you think I should see a different PM doctor at a different hospital??? Before asking that question, you said: I am getting sick of people accusing me of something that isn't true. Should you find a doctor you can trust, and who will believe you; and the evidence right in front of him? Absolutely.

Although I talk with an air of certainty when I’m sure I know what I’m talking about, but I also admit that there is much I don’t know about the RSD process. I’m pretty sure that children (yup, you’re still a kid), have a much better chance for remission than adults. I’m still hopeful your youth will see you through this ordeal, but that is a hope, not a promise. You must prepare yourself for a lengthy battle against RSD, and that means sometimes accommodating to the disease.

My RSD is mild, but I have a lot of experience fighting the consequences of disabling injuries, and my experience contradicts much of what you’ve been told; both by medical professionals and people here at NT. You will have to judge for yourself whether my experience is relevant here.

After two badly botched back surgeries in 1979, I could not walk 100 feet while using a cane before pain made further effort impossible. I fought back by forcing myself to walk until I simply couldn’t take another step, and after 13 years I was able to manage as many as 400 feet. I refused to surrender to a wheelchair, and I think I regret that decision most.

I was a truck driver before my injury, and some of the most enjoyable aspects of that job included seeing more of this country than most people ever will; meeting all kinds of people, and visiting countless art galleries, museums and amusement parks.

Travel became out of the question, but during those 13 years I visited only one art gallery and went to Disneyland once (using a rented wheel chair). I denied my self the enormous pleasure of doing things with my kids (before my injury they also went to museums, and to beaches and parks with the best playgrounds, because I was afraid of becoming dependent upon a chair. My wife still took them, but I didn't get to see them laugh and have fun.

Well, after completing college I had to use a wheelchair in order to work, and I can tell you that if I were given the opportunity to walk again I would show my gratitude to that chair for the opportunities it allowed me, by abandoning it without a backward glance. Wheelchairs are inconvenient, and in all but a few large cities facing a curb may as well be facing a mountain.

Nobody would choose rolling over riding: Ever. I hope you won’t listen to anyone who tells you that using a wheelchair when two minutes of walking hurts so much, is surrendering. It’s an accommodation to a fact you can’t control. And it’s not a matter of one or the other: You can, and you will, continue to walk as much as possible.

You may learn that the rest afforded by the chair will allow you to walk more when you want to do something that requires walking; pain and the tissue damage it represents is cumulative, it reduces your ability to walk when walking is most important.

Right now you are trying to walk and only getting worse. I hope you will limit trying to force your body to do something it can’t do, and focus on increasing distance and duration to that which is tolerable. I especially hope that you won’t needlessly limit you experiences by staying at home when a wheel chair can take you places.

Now, about your color changes: You doctor knows that the hypoxia they represent will not kill you – even the black skin color that would otherwise be considered an emergency. In every other instance I know of, that color would mean gangrene is imminent, but for some reason in RSD it doesn’t.

It does mean, however, that tissue damage is accelerated. Some of that damage is only temporary, the body does heal itself whenever it can, but permanent damage is also taking place.

Several years ago I spoke with the mother of a 14 year old girl with RSD. Her daughter was unable to do anything because of the pain, and the skin on her back and the back of her shoulder was black. The mother told me she couldn’t watch this happen to her child any more. She had decided to kill herself, even though she knew the damage it would do to her child. The last time I talked to that woman, Jen wasn’t available to come to the phone; she was outside rollerblading. She had permanently lost some function in her arm and shoulder, but she was rollerblading.

I will be accused of shamelessly using this situation to promote my hypothesis, and I am. Jen underwent HBO and she got better; should I keep that secret from you? Or from anyone else? I think of them a lot, and wonder whether Jen later relapsed; but I know she improved for a while, and that the improvement was the direct result of HBO.

(I have learned a great deal in the intervening years. I learned that that the regimen Jen underwent could have left her worse rather than better, and I discuss the reasons why in some of my posts on the thread Vascular Issues, but my point here is that something had to be done to mitigate the damage from the severe hypoxia represented by her skin color).

You and your parents don’t have to decide whether my hypothesis will lead to remission from RSD, you only need to know that HBO is the treatment of choice for tissue hypoxia and mandated when skin color is black, and that if left untreated, some permanent damage will result. Anyone who tells you that this black skin color won’t cause permanent damage is absolutely wrong.

I don’t know how things are done in G.B., but in this country anyone who wants to present for HBO can get it (if they have the money). Chamber operators may tell someone with RSD that they need multiple hours, but they will sell one hour because they know if they don’t, someone else will.

Your doctor should not be willing to tolerate this color. He should be fighting to find you a space in a chamber. If he won’t, I hope you and your parents will find a way.

I’m not suggesting a series of HBO interventions, especially the way it’s delivered today: The risk of catastrophic relapse and even coming out worse is too great. I’m urging one hour in order to limit the permanent damage that always results from severe tissue hypoxia. It may take more than one hour. I don’t know how much permanent damage can occur, but I know that some of it is preventable.

I’m not speaking without scientific support: Except for RSD, where they know gangrene hasn’t been reported (to my knowledge), black skin color would result in an immediate test for microvascular oxygenation, followed by an immediate trip into the nearest HBO chamber.

Get rid of that black skin color, and then take your time studying and discussing my hypothesis…Vic

Vicc,
Many thanks for the reply. I will talk to my Physotherapist about the black colour changes and see whether she can arrange for me to try HBO. I am hoping to try HBO after Christmas if my mom and dad can afford the treatment. In England, you can get the HBO treatment if you want it, as long as you can afford it (so it is the same as America)

My moms emailed the National Pain Society and they have arranged for me to see a new PM doctor (he is the top specalist for RSD in England) I don't know when I will be going to see him. Apparently my PM doctor is supposed to be making us an appointment to see the new doctor.

I am getting a LOT more pain in my foot (especially near my big toe). The pain I am experiencing is a shooting pain that comes and goes

Thanks again
Alison
PS: I am 12

Hi again Ali,

Since we're both online at the moment we may as well use this as a sort of instant messenger.

I hope your parents will talk with me before beginning HBO; I think the delievery I suggested in Vascular Issuess, based upon what I've learned about RSD; IRI; the healing process and other issues, offer a greater chance for a successful, or at the least, longer lasting remission period. In addition, it is far less expensive than the usual protocols.

I will have more to say about your pain in another post, but right now I'm just not up to typing...Vic