Mysterious Undiagnosed Illness-seeking advice, suggestions and stories!

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A tho
Hi @Booksellercate,

I can very enthusiastically recommend a doctor in Orpington that is an absolutely fantastic lead doctor for complex conditions. He is a consultant cardiologist with special interest in OI and POTS, but is also acutely aware of many overlapping issues. After seeing him so much of what I was previously told was 'just ME/CFS' has actually been clarified as individually treatable conditions.

The most encouraging thing (aside from the fact he gives you an hour appointment!) is that he absolutely knows his limitations and will refer onto his select colleagues that understand their specific areas, but still personally takes responsibility for managing you. One of his colleagues, a consultant endocrinologist, is also absolutely fantastic with complex fatigue conditions and fully embraces the significance of B12, MTHFR, EBV, SIBO, MCAS etc. After having seen maybe a dozen run-of-the-mill consultants over 20 years I was gobsmacked to find a 'proper' doctor that appreciates these things and will also champion your cause.

Feel free to message me if you want to know more - thread here has some details too:
http://forums.phoenixrising.me/inde...ll-very-promising-pots-treatment-in-uk.43598/

Hope its helpful,
Ryan
Thank you - that's really useful and encouraging information. Would you be kind enough to message me with the details? Can he organise NHS referrals where applicable?
 

ryan31337

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Sure, will do.

He will recommend other consultants and then your GP will refer you to them, at least that's how it worked for me. It didn't matter that they were all out of my area.

I saw him privately for the first appointment (waiting time of days), he then immediately took me on as an NHS patient. Cardiorespiratory tests on NHS were performed within a couple of months and then I saw him for NHS follow up a few more months later. The initial appointment was £230 but its the best money I ever spent (same goes for his endocrine colleague).
 
Hey-thanks for replying! I agree-I am not ruling severe longterm B12 deficiency out just yet, although I am looking at other things as well. In 2003 a blood test showed I had macrocytosis - this usually appears in the later stages of a B12 deficiency. Unfortunately it wasn't followed up with a B12 test then. I have often felt 'not right' or as if I should feel better as I am reasonably health, active and eat well. I am wondering if I was limping along with B12 deficiency symptoms for many years which I simply dismissed as modern life tiredness and stress.

The cyanocobalamin is actually 3mg (although I think this dose is too high as my urine occasionally has a pinkish hue some hours after). I have to order in bulk but I think that perhaps I will simply stick to hydroxo once my supply of cyano has finished. I have some methyl sublinguals on the way - some earlier messages also convinced me to reinstate them. Same with folate and I have reduced the dose to 1mg folate from today-I'll see how I fare with that.

I am currently suffering with severe gastric symptoms - so my diet is incomplete. I am struggling to eat.

I admit to knowing nothing of my SNPs - I have had no genetic testing done yet. It's something I'd like to have looked at but I've been off work for a year and have to be very careful with how I allocate my very limited funds.

I feel I should learn a little more about the chemical processes involved in B12...
Sounds good.

I don't think genetic testing is really necessary right now. You would have to do experimentation with doses anyway.

I've found it answers more of the "why" questions - for example, why did I get into B12 deficiency when most people doing the same diet don't, and/or why do I need more B12 than most people?

You could also find out that you don't have genetic mutations on the B12 or folate SNPs. In that case, be aware that mercury and lead can inhibit those same enzymes where the SNPs are and produce the same sorts of symptoms. In that case, you would want to do chelation to get the metals out.

You might also want to starting thinking about metals if you still have a lot of symptoms despite high supplementation.

If you go to my signature link, I have a section on Cutler Frequent Dose Chelation, which is the best and safest protocol I've found.

Good luck!
 

kangaSue

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Some suggestions out of the ordinary so low down on a list of possibilities with any doctors..

Quite a high rarity but with all the autonomic issues, consider Autoimmune Autonomic Ganglionopathy or less likely, Paraneoplastic Gastroparesis. There's a crossover with several of the same antibodies in both conditions.

You said you've been tested for Sjogren's Syndrome, did you get a full ENA panel done to rule out other connective tissue disorders, Scleroderma, Lupus, MCTD? Also consider an ANCA blood test for possible vasculitis or IBD issues.
https://labtestsonline.org/understanding/analytes/ena-panel/tab/test
https://labtestsonline.org/understanding/analytes/anca/tab/test

Do a Poor Man's Tilt Table Test (PMTTT) at home to get an idea if you might have POTS.
http://www.oiresource.com/oitest.htm

Consider getting a Doppler Ultrasound done of your mesentery arteries looking for any abdominal vascular compression syndrome which can cause your gut symptoms and other autonomic dysfunction, in particular if you think you have POTS looking for Median Arcuate Ligament Syndrome (MALS) which has popped up on my radar in recent days as something having a strong relationship with POTS.
http://meetings.ssat.com/abstracts/2015/566.cgi
https://gastroenterologen.no/2013/11/the-celiac-ganglion-artery-compression-syndrome-cgcs/

Compression of your left renal vein can cause POTS too as well as Renal Anemia.

Have it ruled out that gastritis and low B12 doesn't involve parietal cell and intrinsic factor antibodies which can lead to Autoimmune Gastritis.
 

Valentijn

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You're having trouble finding injectable methylcobalamin. The information that I have seen is that sublingual B12 is just as effective, if not more effective than injection.
This is extremely unlikely. First of all, "sublingual" methylB12 molecules are too large to be absorbed sublingually, though they might be a bit helpful due to slowly dissolving. The reason this might be helpful is because there's a limit in how much B12 can be absorbed at a time. But even with slowed dissolving, most of the B12 is likely unabsorbed. Whereas B12 injected into the muscle doesn't have any such limitations.
 
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Long term vegetarianism is a risk factor for vitamin B12 deficiency. You have many symptoms of B12 deficiency and have improved somewhat with supplementation.

So it seems to me that tweaking your B12 protocol should be beneficial.

-=-=-=

A couple of observations - you're taking 2 injections of B12 per day - one cyano and one hydroxycobalamin.
I assume each injection is 1000mg.

Then you're taking 4.8mg of folic acid.

Over time, this would cause methyl trapping, which would be counter productive as it would inhibit methylation. The amount of B12 should be somewhat higher than folate to avoid methyl trapping. (Let's say 20%.)

My first suggestion would be to either raise B12 or lower folate, or a little of both, until you get to the right ratio.

-=-=-=-=

Then the forms of these vitamins you're taking may not be ideal. It depends on what your genetic SNPs are. (SNP = Single Nucleotide Polymorphism or a mutation from normal function.)

If you have MTHFR, then folic acid doesn't convert well. Depending on your SNPs there could be a partial block of anywhere from 20% to 80%. It will also leave unmetabolized folic acid which can cause cancer.

4.8mg is also quite a high dose. A normal dose is about 400 - 800mcg. If you're a vegetarian, presumably eating lots of vegetables and thus getting lots of vegetable folate, you actually may not need any supplementation - your test showed high (assuming the kind of test you got was accurate for what's in the cells). It may be that B12 is all you need.

For B12, there are also SNPs that can reduce functioning, but I haven't seen as good of research such as "X SNP produces Y% block in functioning" like there is for folic acid. Anyway, the SNPs that control B12 are MTR (B12 intake) and MTRR (B12 recycling). If you have both (like me), it's like a double whammy. Adding other risk factors like vegetarianism and gut absorption issues makes it even worse.

The easiest form for your body to metabolize regardless of SNPs is methylcobalamin, which is an already converted version, so your body doesn't have to do the conversion.

You're having trouble finding injectable methylcobalamin. The information that I have seen is that sublingual B12 is just as effective, if not more effective than injection.

As you seem to be tolerating the folic acid and B12 well and in high amounts, you probably won't have any trouble with switching forms.

My second suggestion would be to switch to a sublingual methylcobalamin (either a liquid that you hold under your tongue or a lozenge that you let dissolve in your mouth) and methylfolate (just in case you have MTHFR).

As far as adenosylcoblamin - that doesn't affect methylation, but it does affect the mitochondria and thus may increase energy. Hydroxycobalamin is converted in the body to methylcobalamin and adenosylcobalamin.
Hello, Caledonia. I've been doing a lot of reading the past 6 months, mostly on Freddd's old threads. I've now started reading your information on methylation. It's wonderful information. My body has struggled with mb12, however, and I cannot tolerate even 100 mcg of folate without flu like symptoms. I used to take folate without issue, but since starting mb12 (used to do hydroxy and adeno), it seems folate is just too much. The mb12 has calmed my nerve pain at times, but mostly it has intensified my pain for the past 6 months and I've decided I need to change my path a bit.
I've been reading your posts and noticed you take a liquid mb12. I have some and it appears that liquids offer far more flexibility with doing small doses. I've found a Seeking Health liquid folate that I can also do micro doses with. Here's my question for you- Freddd is pretty clear about using sublinguals and dissolving them for 45+ minutes. You're using liquid b12 and holding it under your tongue for 20-30 seconds I believe. Do you believe that you're getting that same absorption as with 45+ minutes of a sublingual? Thank you!
 

Valentijn

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Here's my question for you- Freddd is pretty clear about using sublinguals and dissolving them for 45+ minutes. You're using liquid b12 and holding it under your tongue for 20-30 seconds I believe. Do you believe that you're getting that same absorption as with 45+ minutes of a sublingual?
B12 doesn't get absorbed under the tongue. So the absorption would technically be the same :p If you want good absorption of B12, injections are most effective.
 
Hello, Caledonia. I've been doing a lot of reading the past 6 months, mostly on Freddd's old threads. I've now started reading your information on methylation. It's wonderful information. My body has struggled with mb12, however, and I cannot tolerate even 100 mcg of folate without flu like symptoms. I used to take folate without issue, but since starting mb12 (used to do hydroxy and adeno), it seems folate is just too much. The mb12 has calmed my nerve pain at times, but mostly it has intensified my pain for the past 6 months and I've decided I need to change my path a bit.
I've been reading your posts and noticed you take a liquid mb12. I have some and it appears that liquids offer far more flexibility with doing small doses. I've found a Seeking Health liquid folate that I can also do micro doses with. Here's my question for you- Freddd is pretty clear about using sublinguals and dissolving them for 45+ minutes. You're using liquid b12 and holding it under your tongue for 20-30 seconds I believe. Do you believe that you're getting that same absorption as with 45+ minutes of a sublingual? Thank you!
Yes, it seems to work well for me. Like you, if I get even 1 mcg more than my tiny amount, I start to crash and get flu like symptoms. So I know it's doing something.

ps. nice find on the Seeking Health liquid folate. I didn't know anybody had one.
 
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B12 doesn't get absorbed under the tongue. So the absorption would technically be the same :p If you want good absorption of B12, injections are most effective.
Thanks, Valentijn. So, those whole idea of sublinguals for 45+ minutes is incorrect and unfounded? I can say that there's some absorption going on (not necessarily for than just swallowing- I don't know) because my nerves react very strongly to mb12 at even 1-2 mg. I took hydroxy and adeno for more than a year without any noticeable reaction. In other words, I had very strong "start-up effects" with mb12. Even 1/4 or 1/2 mg in the beginning intensified my nerve pain in my feet. But if liquid is going to give me the same absorption, it's way easier to control small doses and more convenient than sucking on sublinguals for extended times.
 
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Yes, it seems to work well for me. Like you, if I get even 1 mcg more than my tiny amount, I start to crash and get flu like symptoms. So I know it's doing something.

ps. nice find on the Seeking Health liquid folate. I didn't know anybody had one.
Thanks, Caledonia :)
 

Valentijn

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Thanks, Valentijn. So, those whole idea of sublinguals for 45+ minutes is incorrect and unfounded?
Well, the sublingual B12 dissolves and goes down the throat to the stomach, where it is then absorbed. It's very limited in how much can be absorbed via the GI system at one time. So slowly dissolving it in the mouth is probably a bit more effective due to slow delivery to the stomach, compared to swallowing all of it at once.
 

Alvin2

The good news is patients don't die the bad news..
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Thank you. I requested seeing an endocrinologist but was declined. The system here works very differently and is not in favour of complex illnesses. I cannot really change my doctor - they are not employed by me or an insurance company. I will find out how much traction others get from writing letters of requests/complaints. I currently cannot get around without a wheelchair due to weakness and lightheadedness/balance issues-so I am severely affected enough to speak loudly, so to speak which might work in my favour.
I know nothing about how your system works but if there is a way you need to find it, whether its complaints, changing physicians, "moving", etc.

The mold/fungus issue is also something I've thought about - especially with chronic sinusitis- but not sure how to test. An organic acids test showed high levels of arabinose, but all other bacterial/yeast markers were relatively low-I don't know if this is enough to suggest a mold/fungus issue is unlikely. Sinus issues do run in my family...
Its tricky when your dealing with outside mainstream medicine possibilities, but at this point i don't personally think you have exhausted traditional diseases, you've barely scratched the surface

I've managed to get some methylcobalamin sublinguals, I'll figure out how to test this. I admit to being quite reluctant to stop injections when I am still unsure how much a part B12 deficiency is (was) playing. Most people report a regression during the healing process if B12 is stopped.
I really think the B12 is not a likely candidate, but the methyl B12 sublingual will do the trick if its B12 deficiency. If its not B12 deficiency then stopping it won't have any effect, if it is your going to be taking it sublingually. So either way you should be okay. I really think you need to lie, cheat, bribe, whatever your way into better professionals to figure this out.


This is extremely unlikely. First of all, "sublingual" methylB12 molecules are too large to be absorbed sublingually, though they might be a bit helpful due to slowly dissolving. The reason this might be helpful is because there's a limit in how much B12 can be absorbed at a time. But even with slowed dissolving, most of the B12 is likely unabsorbed. Whereas B12 injected into the muscle doesn't have any such limitations.
Yet studies have found that sublingual B12 is absorbed, at rates that rival injection, though most is done in the intestines through diffusion.
OP keep in mind the body keeps several years of B12 stores, so if the injections have worked your already fully loaded, if not then your loading yourself up with methylcobalamin.
 

Valentijn

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when i can concentrate i'll look it up but i recall reading a study that found 2000mcg daily was equivalent to injection, you can test your google-fu
Not up to it, so we can leave it as an unsupported statement for now.
 
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I know nothing about how your system works but if there is a way you need to find it, whether its complaints, changing physicians, "moving", etc.


Its tricky when your dealing with outside mainstream medicine possibilities, but at this point i don't personally think you have exhausted traditional diseases, you've barely scratched the surface


I really think the B12 is not a likely candidate, but the methyl B12 sublingual will do the trick if its B12 deficiency. If its not B12 deficiency then stopping it won't have any effect, if it is your going to be taking it sublingually. So either way you should be okay. I really think you need to lie, cheat, bribe, whatever your way into better professionals to figure this out.



Yet studies have found that sublingual B12 is absorbed, at rates that rival injection, though most is done in the intestines through diffusion.
OP keep in mind the body keeps several years of B12 stores, so if the injections have worked your already fully loaded, if not then your loading yourself up with methylcobalamin.

Persistence might be key.


I feel the same. My GP referred me for psychiatric assessment as he says "nothing is wrong". I've had one MRI (without contrast), a nerve conduction test. and tests for ANA, coeliac, arthritis. I also had blood work to rule out dysplasia (for ongoing mild macrocytosis). I'm pulling together a comprehensive prioritised list of things to investigate and test but it's a mountain of a job..there seems an almost endless number of things which could go wrong...


It seems inevitable I am going to have to get tough and pushy at least
 

Alvin2

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Persistence might be key.


I feel the same. My GP referred me for psychiatric assessment as he says "nothing is wrong". I've had one MRI (without contrast), a nerve conduction test. and tests for ANA, coeliac, arthritis. I also had blood work to rule out dysplasia (for ongoing mild macrocytosis). I'm pulling together a comprehensive prioritised list of things to investigate and test but it's a mountain of a job..there seems an almost endless number of things which could go wrong...


It seems inevitable I am going to have to get tough and pushy at least
I don't disagree that you need to be active in figuring out ideas but specialists who know what they are doing can also be the key, especially if what you have is rare and it needs a specific test to find that you may not have heard of. Also many doctors feel threatened by patients that ask for tests and have ideas, they like to feel like they are the boss and sometimes react negatively when patients don't act submissive. Its ridiculous but you can be dealing with ego over intelligence.

That said at this point you really need to find a way to get to the right professional, i wish i could advise but your system is different then ours so i don't know how to help you there.
 
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Thanks for the link - letters of complaint are usually treated patronisingly or with derision...but it shows that a carefully, focussed, evidence-backed campaign with many voices can have real power. I'll share this with the pernicious anemia patients who I know suffer dreadfully (along with many others)
 

PinkPanda

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@Booksellercate how are you doing?
Are you still getting cyanocobalamin injections?
I was thinking on the issue of cyanocobalamin, I would really try to avoid it. Cyanocobalamin needs to be metabolized by glutathione so that your body can even use it as B12. CyanoB12 produces cobalamin and cyanide and cyanide is toxic and needs to be detoxed. Low glutathione can impact vitamin C and E status etc.

Cases of cyanide poisoning usually occur at much higher doses, but in chronic illness where detox capacity is bad the body might be more sensitive. Also, if you eat fortified foods they might contain cyanocobalamin, so I would check for that too.

Hydroxycobalamin is used to treat cyanide poisoning and I think the injections 2 times a week might not be enough with all the other supplements you are taking. So I would consider sublingual hydroxocobalamin.
I also feel you are taking a lot of other supplements with very unclear effect. I know that's difficult to figure out, but I would try to reduce to a few basic supplements and see how you react to them.

First of all, "sublingual" methylB12 molecules are too large to be absorbed sublingually, though they might be a bit helpful due to slowly dissolving.
Do you have any citations on that?
 
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