Mitochondria (from the Greek, meaning "string grain" -- yeah, it's lame, but it sounds good in Greek) are independent little one-celled organisms that live inside your cells and make energy for them. If you ever studied the ATP cycle (also called the Krebbs cycle or the citric acid cycle, depending on where you went to school and how deeply they went into it), then you should know that this is where the ATP cycle takes place.
Without mitochondria, you have no way of converting food into energy.
When you were being conceived, half your cells' genes came from your mother and half from your father. All of the other stuff that goes inside a cell came from your mother. This includes the mitochondria. (This is why mitochondrial DNA is used to track maternal inheritance: it always comes down the female line.) Your mother's cell hosts conception, just as (normally) your mother's body hosts gestation.
Mitochondria have a fairly smooth outer layer and a deeply-rumpled inner layer. Most of the action happens inside the rumpled layer. This is where the ribosomes, most of the fluids and loose protein, and the ATP-making particles hang out.
Cells, including mitochondria, need various proteins to do their work with. Large proteins get carefully handed from the outside world, through the outer layer of the mitochondrion (singular of "mitochondria" -- sorry, it's still Greek), then into the inner layer.
If the smooth outer layer is damaged, this makes this transfer process screw up, and the inner layer gets disrupted, ripping up the cell. Granules and nucleic acids all over the place. Bang goes that ATP production.
This kind of damage happens in response to certain kinds of toxins (including certain medications for AIDS and all psychoactives -- including antidepressants and pain medications, which seems especially mean!), occasionally from genetic disturbance, and occasionally as a consequence of illness -- or nerve injury and its complications.
Mitochondrial dysfunction has been repeatedly and profoundly linked to neurogenerative diseases like Alzheimer's and Parkinson's; cell-metabolism problems like heart disease, insulin resistance and type II diabetes; and several diseases often mistaken for CRPS.
Not surprisingly, symptoms of mitochondrial dysfunction are the worst in tissues that use the most energy and have the largest number of mitochondria per cell: nerves, muscles, brain.
Recently, it has been strongly associated with CRPS. And the cherry on top: it plays a vital role in neuroplasticity, or the way your nerves and brain change -- for better or worse.
Hell-o, "pain-brain." We thought we knew ya!
Knowing why it's so damnably exhausting to walk a mile, when it used to be fun -- fun! -- to run 3, is a bit of a relief. First question that leaps to my mind: How do I fix 'em? How do I give them what they need to get better and protect themselves? The answer seems simple: antioxidants are what's needed to prevent and repair that damage (good explanation of that here) to the walls of the mitochondrial cell. Mitochondria are both the biggest makers of reactive oxygen species and the biggest scavengers of them, so of course it makes sense that that's exactly the kind of help they need when they can't keep up.
Downing antioxidants by the bucketful is one way to get them in. Intriguing for three reasons:
- Taking moderate amounts of the antioxidant Vitamin C after surgery hugely reduces your chances of getting CRPS. (Upper limb and lower limb surgeries were studied.)
- There's some indication that Vitamin K may help combat the progress of CRPS.
- Taking antioxidants is pretty easy: delicious food, accessible pills, not bad.
Kind of depressing for one simple reason: it's iffy whether, once you've got the disease process going, the antioxidants can get where they're needed and save your poor beleaguered mitochondria. ... Having said that, I notice that the writers of that article seem to be trying to sell something, and that makes me very suspicious of their conclusions.
Next, I'll offer suggestions for patients, suggestions for clinicians, and then wind this up with a foray into the question of whether mitochondrial issues have a genetic component, like being X-linked -- the way a cat's fur color is!
For people with CRPS -- So what is a poor, confused CRPSer to do?
Two things that you hardly need reminding of:- Trust your sense of your own body.
- Do what works for you.
Also, eat all the leafy greens you can get: seaweed snacks, Mom's collard greens, kale krunchies, spinach salad, you name it. It's amazing nerve food.
For antioxidant powerhouses, look for dark-red and dark-blue fruits: pomegranates, blueberries, red wine, chocolate (though some CRPS people have to avoid that for its nerve effects), mangosteen (my favorite fruit), cranberries, and so on.
Stay smart. Stay loose. Keep going.
Most treatment standards, particularly for CRPS, are based on science that's over a decade old. They shouldn't be changed blithely but they can certainly be improved. There is plenty of room for that.
The following points are intended as additions to the standards you follow for CRPS, as they are good guidelines for mitochondrial and neurologic support in a system compromised by CRPS.
These ranges are empirical; if you can find the funding to do the science to develop more reliable ranges for this population, so much the better.
Adequate tissue oxygenation and perfusion can return substantial function and significantly reduce pharmacologic burden. Patients can demonstrate this, even where the data have not been published and peer reviewed. Therefore, use antioxidants rigorously and intelligently.
Image credit: http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging. (Article's not bad.)
Why all that anti-oxidation when the medical literature is not definitive? 2 reasons, which you ought to know for yourselves:
Keep in mind that doctors are not the only scientists interested in the human body. Be prepared to look into other disciplines for leads when your own offers no good options.
Try Nursing, PT, Nutrition, Therapeutic Massage -- you'll realize that nobody knows more about soft tissue's functional physiology in vivo than therapeutic massage science, and if nothing else, the exercise in intellectual flexibility might do you good.
The accepted style is very different, but the info they have is tremendous.
Forward-looking thoughts:
We know that women have two X chromosomes. The Y chromosome is a stubby little object with hardly any data to use, unless you're into color-blindness or hemophilia; this means women have quantities of extra data, which can have even more devastating effects (as in, Down syndrome.) So how to handle the extra genes?
Pick one. Simple as that.
Shortly after conception, when the cells are just dividing like mad and haven't decided what to be yet, every single cell turns off one of its two X chromosomes; each of that cell's daughter cells inactivates the same X chromosome. As the cells continue to multiply, then fill out, fold, bend around, and specialize, to become a whole, separate being, it means that X-linked traits appear in a mottled pattern throughout the body, as the two sets of daughter cells continue reproducing and passing on their particular X-activations. Isn't that curious?
As an especially decorative instance, cats' hair color is an X-linked trait:
Cool, huh? Love her accent, too.
But this fact brings me to a serious question about mitochondrial disease. If mitochondria are sex-linked, is there a relationship between the X chromosome and mitochondrial expression? It seems improbable that there wouldn't be, because mitochondria reside inside the cell, and the cell's action is determined by the genes within it. The mitochondria had to have developed a special relationship with the X's in the 23rd chromosomal pair, after all those millenia.
It's generally accepted that mitochondrial diseases are due to toxification or to complex, multigenetic issues. Ok, fine. But what about mitochondrial vulnerabilities that don't become pathologic until they are damaged in some other way? To what degree is toxification an issue related to X-activation? In other words, is mitochnodrial vulnerability related to vulnerabilities in the active X chromosome?
Is there a patchy characteristic to the early stages of mitochondrial destruction? -- You know, the early stages of rare disorders, the time when it's impossible to get a diagnosis because the doctors are all so busy chasing their own tails around your irrational symptoms and their own ignorance.
Is that initial "mottled" activity one reason why these diseases are so damn weird?
For antioxidant powerhouses, look for dark-red and dark-blue fruits: pomegranates, blueberries, red wine, chocolate (though some CRPS people have to avoid that for its nerve effects), mangosteen (my favorite fruit), cranberries, and so on.
Stay smart. Stay loose. Keep going.
For medical people -- clinical takeaways:
Most treatment standards, particularly for CRPS, are based on science that's over a decade old. They shouldn't be changed blithely but they can certainly be improved. There is plenty of room for that.
The following points are intended as additions to the standards you follow for CRPS, as they are good guidelines for mitochondrial and neurologic support in a system compromised by CRPS.
- After any limb surgery, give Vitamin C 500 mg, QD or BID, for a couple weeks beforehand and 30-50 days after -- or to metabolic tolerance, if that's too much. Use a food-associated form for best uptake. This one intervention will reduce the risk of developing CRPS by 80%, according to the best current data.
- We assume your patients are taking an adequate multivitamin and are eating plenty of greens, dark fruits, and wholesome proteins. So make sure they are. Direct them to food bank, food stamps or other food assistance as needed. Give recipes. (No kidding.) 2 benefits: better antioxidant uptake if taken with antioxidant-rich food, and increasing the patient's own sense of agency/participation improves pain and affect. (If you don't believe in multivitamins, then get out of the supermarket/pharmacy and get some real ones.)
- Stress the antioxidant vitamins. In acute CRPS, give water-soluble antioxidant vitamins in 1-3x the doses you'd give a healthy person. Give fat-soluble antioxidants (A, D, E) up to 2x normal, testing levels as indicated. Consider vitamin K inj.
- In cold/chronic CRPS, give water-soluble antioxidant vitamins in 3-5x the doses you'd give a healthy person (start at 2x and work up). Give fat-soluble antioxidants (A, D, E) up to 2-4x normal, testing levels as indicated; consider weekly mega-dose D (as used in AIDS.) Give vitamin K inj. Check serum or urine levels as indicated, especially as we develop absorption disorders.
- Give "uber-antioxidants" like ubiquinone (co-Q 10), N-acetylcysteine, or glutathione. There are indications that these can provide substantial benefit -- though again, not normally curative of chronic CRPS. They are impressive, especially for mitochondrial-dysfunction issues.
These ranges are empirical; if you can find the funding to do the science to develop more reliable ranges for this population, so much the better.
Adequate tissue oxygenation and perfusion can return substantial function and significantly reduce pharmacologic burden. Patients can demonstrate this, even where the data have not been published and peer reviewed. Therefore, use antioxidants rigorously and intelligently.
Why all that anti-oxidation when the medical literature is not definitive? 2 reasons, which you ought to know for yourselves:
- Between the cortisol and systemic oxidative stresses, it can't hurt and it will help something. You'll see a distinct improvement in affect, activity, motivation and well-being when the dose is optimized, even if it can't be expected to be curative. Making your patient's life more bearable is an essential part of your job.
- Let's say this together, everyone: statistics mean nothing in the case of the individual. Accepted, standardized medicine is what you start with, but, when your case is taking you out to the margins, you go to the margins, because that's where your success is most likely to await.
Keep in mind that doctors are not the only scientists interested in the human body. Be prepared to look into other disciplines for leads when your own offers no good options.
Try Nursing, PT, Nutrition, Therapeutic Massage -- you'll realize that nobody knows more about soft tissue's functional physiology in vivo than therapeutic massage science, and if nothing else, the exercise in intellectual flexibility might do you good.
The accepted style is very different, but the info they have is tremendous.
Forward-looking thoughts:
- Consider infusing vitamin K into CRPS-damaged tissues. I would love to see studies on that.
- Figure out how to deliver antioxidants in a targeted way. (Now! Please!) This would be a good way to save a lot of lives and end tons of misery.
... And for all curious people ...
Let's go back to mitochondria in reproduction. Kind of in an X-rated way, figuratively speaking.We know that women have two X chromosomes. The Y chromosome is a stubby little object with hardly any data to use, unless you're into color-blindness or hemophilia; this means women have quantities of extra data, which can have even more devastating effects (as in, Down syndrome.) So how to handle the extra genes?
Pick one. Simple as that.
Shortly after conception, when the cells are just dividing like mad and haven't decided what to be yet, every single cell turns off one of its two X chromosomes; each of that cell's daughter cells inactivates the same X chromosome. As the cells continue to multiply, then fill out, fold, bend around, and specialize, to become a whole, separate being, it means that X-linked traits appear in a mottled pattern throughout the body, as the two sets of daughter cells continue reproducing and passing on their particular X-activations. Isn't that curious?
As an especially decorative instance, cats' hair color is an X-linked trait:
Cool, huh? Love her accent, too.
But this fact brings me to a serious question about mitochondrial disease. If mitochondria are sex-linked, is there a relationship between the X chromosome and mitochondrial expression? It seems improbable that there wouldn't be, because mitochondria reside inside the cell, and the cell's action is determined by the genes within it. The mitochondria had to have developed a special relationship with the X's in the 23rd chromosomal pair, after all those millenia.
It's generally accepted that mitochondrial diseases are due to toxification or to complex, multigenetic issues. Ok, fine. But what about mitochondrial vulnerabilities that don't become pathologic until they are damaged in some other way? To what degree is toxification an issue related to X-activation? In other words, is mitochnodrial vulnerability related to vulnerabilities in the active X chromosome?
Is there a patchy characteristic to the early stages of mitochondrial destruction? -- You know, the early stages of rare disorders, the time when it's impossible to get a diagnosis because the doctors are all so busy chasing their own tails around your irrational symptoms and their own ignorance.
Is that initial "mottled" activity one reason why these diseases are so damn weird?
Link list:
Wikipedia's entry on mitochondria is pretty good:
http://en.wikipedia.org/wiki/Mitochondria
On mitochondria and AIDS meds:
http://www.ncbi.nlm.nih.gov/pubmed/20818734
On mitochondria and pyschoactives:
http://www.ncbi.nlm.nih.gov/pubmed/18626887
Alzheimer's Foundation:
http://www.alzfdn.org
Michael J. Fox's Parkinson's foundation:
http://www.michaeljfox.org/
United Mitochondrial Disease Foundation, listing diseases which are often mistaken for CRPS:
http://www.umdf.org/
Mitochondria and neuroplasticity:
http://www.ncbi.nlm.nih.gov/pubmed/20957078
A good rundown (so to speak) of antioxidants' function:
http://www.ionizedwateronline.com/Antioxidants.html
Vitamin C around surgery.
Upper limb:
http://www.ncbi.nlm.nih.gov/pubmed/17606778
http://www.ncbi.nlm.nih.gov/pubmed/20224742
Lower limb:
http://www.ncbi.nlm.nih.gov/pubmed/19840748
Vitamin K and CRPS progression:
http://www.ncbi.nlm.nih.gov/pubmed/20378261
Getting antioxidants where they're most needed. Ignore the shystering towards the end:
http://www.ncbi.nlm.nih.gov/pubmed/21422516
ALA and regeneration of Vitamin E:
http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging
Ha! I'd recognize your voice anywhere! Read the excerpt on RSD/CRPS Research and Development and thought "I know that writer for sure!" And what a writer, and researcher, you are! Absolutely awesome article! Now, I know I'm using an awful pile of exclamation marks, but there was no way around it... Awesome article! Thank you!
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