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Old 03-09-2009, 07:06 PM #1
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Default Looking for articles linking B12 deficiency and Nitrous Oxide

I apologize in advance for the long and convoluted story that gets to my subject question ....

I am a 45 year old female who was first diagnosed with Peripheral Neuropathy as the result of a Vitamin B-12 deficiency at age 33. I was under a maintenance plan of monthly B-12 injections and 400 mg daily of Neurontin for years, after the initial treatment. Every couple of years, I would have flares, and would have to increase both meds for a couple of months to get things under control - but then back to maintenance mode.

That all changed a year ago when my body basically spiraled out of control on me. From my thighs to my toes, elbows to fingers, scalp, face, mouth - my body was in constant pain, although it changed between burning, tingling, stabbing (all the typical PN symptoms) - the really fun part being different body parts might experience different things at the same time. The change came upon suddenly, like flipping a light switch. And, at the same time, my vertigo spiraled out of control with the 2nd worst bought I had ever had. I never had the pleasure of having both spike at the same time. My body basically shut me down.

It took 5 months and a dozen doctors to finally get to the bottom of things. Along the way, I went from one diagnosis to the next, being told I might have M.S., Raynaud's Syndrome, Sjogren's Syndrome, Celiac's Disease, and a variety of other less interesting things.

In the end (thanks to Dr. Latov and a really great Gastro doctor at Weill-Cornell) the puzzle fits together like this:
- I have a condition called Achlorhydria, whereby my stomach does not produce acid. As a result, my body doesn't break down nutrients properly.
- The Achlorhydria causes the Vitamin B-12 deficiency (which previously couldn't be explained). I had never tested positive for Pernicious Anemia, since I don't have the intrinsic factor problem. But, basically have the same thing because of my inability to absorb B-12 as a result of the Achlorhydria.
- The B-12 deficiency is responsible for the Peripheral Neuropathy. Skin biopsies showed that the disease had indeed progressed (vs. biopsies taken 4 years prior)
- The vertigo was even related to the PN.

Now - for the kicker. My teeth have always been extremely sensitive (because of the nerves) and over the previous couple of years, my dentist had resorted giving me Nitrous Oxide just to clean them! My last cleaning was right before my body spiraled out of control. Dr. Latov explained to me that Nitrous Oxide is linked to B-12 depletion, and was most likely the key to what had suddenly happened. Up until then, although I obviously had a problem with the B-12, my body was managing to protect itself as best it could, but the Nitrous Oxide depleted the levels and 'flipped the switch', and the PN went out of control. As I looked back on the documented history of those 'flares' that I had over the years, most could also be tied to a visit to the dentist.

I'm managing the illness with a cocktail of medications, and moved from New York to North Carolina in December in order to get to a more temperate climate and to simplify my life. I am happy to say, there is definite improvement since the move.

The hardest thing has been establishing with all new doctors, and today, I went to a dentist for the first time. She was not aware of the link between B-12 depletion and Nitrous Oxide (Dr. Latov told me many aren't or don't see the direct effects) so I want to help educate her, and am looking for articles that I can give her when I go back in a couple of weeks. I've searched the web, but mostly have found personal websites, forums, and wikipedia sources - I want to have something more "medically" sound. If anybody can point me in the right direction, I'd appreciate it. And, the more the merrier.

Sorry for the long story ....

Patti
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Old 03-09-2009, 08:44 PM #2
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There are many reports of B12/nitrous problems like this:

Quote:
Rev Neurol (Paris). 2007 Mar;163(3):362-4.Click here to read Links
[Nitric-oxide triggered neurological disorders in subjects with vitamin B12 deficiency]
[Article in French]

Cohen Aubart F, Sedel F, Vicart S, Lyon-Caen O, Fontaine B.

Assistance Publique-Hôpitaux de Paris, Fédération des maladies du Système Nerveux, et Université Pierre et Marie Curie, Groupe Hospitalier Pitié Salpêtrière 47-83 boulevard de l'hôpital 75013 Paris, France.

INTRODUCTION: Nitrous oxide is frequently used for anesthesia. It may cause spinal cord toxicity. CASE REPORTS: We report two patients who presented gait disorders after nitrous oxide anesthesia. Physical examination revealed arms and legs pyramidal syndrome and abnormal proprioception, consistent with subacute combined degeneration of the spinal cord. Serum vitamin B12 level was extremely low. The patients improved with parenteral treatment with hydroxycobalamin. CONCLUSIONS: The inactivation of methionine synthase and L methylmalonylcoA mutase by nitrous oxide has been previously demonstrated. Anesthesia-related exposure to nitrous oxide may induce neurologic disorders even in patients with no preliminary vitamin B12 deficiency.

PMID: 17404524 [PubMed - indexed for MEDLINE]
from http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

If you click on the PubMed link at the top right of the page here, and then type into the keyword search:
vitamin B12 nitrous oxide

you'll find many more papers.
From what I saw tonight, this effect is more pronounced in people who are marginally low in B12.

I suspect your once a month injection was not enough for you in the first place. Do you know what your level was then?
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Old 03-10-2009, 08:21 AM #3
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Default B12 levels

Thank you Mrs. D for your help.

You're correct on the frequency of shots. It seems that during the 'flares', we'd increase the shots to get the levels up, and then they'd gradually fall.

When I 'collapsed' last year the level was in the 200 range. We've been monitoring it very closely ever since, in an effort to keep it above 500 which is the minimum Dr. Latov told me he wanted it to be. It took months with shots every 2 weeks, at a double dosage (2ml). Oral dosages never worked, due to the fact my stomach couldn't process/absorb it. However, I recently began taking a liquid sub-lingual version which seems to be helping, and for the first time in years, got it above 1000!
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Old 03-10-2009, 09:37 AM #4
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Oral does not depend on the stomach at all.

Oral is absorbed "passively" in the small intestine.

When oral fails, it is most likely being done wrong.
You must take it alone, on an empty stomach 1 or 2 hours before any food. Presence of food with it will prevent absorption.

I'd suggest you invest in 5mg oral methylcobalamin and use it daily on an empty stomach, and for 3-4 months and then get a new test to compare.
examples of online types:
http://www.iherb.com/Search.aspx?kw=methylcobalamin

And next time you see Dr. Latov, tell him I am very disappointed in his book...there are TWO recommendations for B12 for 500mg in two places in his book !!! Now I assume this is a typo, and was not proofread. If he meant 500 mcg...that is NOT enough IMO to bring up serum levels.

I have seen so many doctors who order weird amounts of B12 oral. In nursing homes a common one is 1000mcg MONTHLY orally...just like the shots. This is just nervewracking to me.
They don't understand how the B12 works by passive absorption, or anything! Passive absorption is very low if stomach acid is poor for any reason, or intrinsic factor not working anymore. One needs daily high doses to make up for these facts. Most is never even absorbed into the body at all.
And if food is present including fiber...NOTHING may get into the blood stream! (This has been shown to be the case with drugs used in microgram amounts-- levothyroxine and digoxin.)
Those drugs have to be taken on an empty stomach too.
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Old 03-10-2009, 10:43 AM #5
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Default B12 Levels

MrsD-
I had a resection 20 years ago for Chroyns removing some large intestine and ileum. I have tried 5mg of methylcobalamin, but my PN seems stable versus improving. B12 level hovers between 250 and 400. Decades ago I also played with nitrous oxide recreationaly. I would appreciate any thoughts you might share.
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Old 03-10-2009, 11:48 AM #6
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Quote:
Originally Posted by Vern View Post
MrsD-
I had a resection 20 years ago for Chroyns removing some large intestine and ileum. I have tried 5mg of methylcobalamin, but my PN seems stable versus improving. B12 level hovers between 250 and 400. Decades ago I also played with nitrous oxide recreationaly. I would appreciate any thoughts you might share.
If all the ileum is gone? Most of the textbooks say the ileum is where B12 is absorbed...but this is when it is hooked up to
intrinsic factor. I cannot find adequate information about passive absorption in other areas of the small intestine other than the ileum:
Quote:
Int J Vitam Nutr Res. 1999 May;69(3):228-33.Links
Studies on vitamin B12 status in the elderly--prophylactic and therapeutic consequences.
Loew D, Wanitschke R, Schroedter A.

Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Frankfurt, Germany.

Because of the large liver stores (about 5 mg), low turnover rate (0.143%) and small daily requirement (3 micrograms), vitamin B12 deficiency does not occur under normal circumstances. This is not the case in individuals with chronic inflammatory or trophic changes at vitamin B12 absorption sites. Without supplementation, vitamin B12 deficiency can be expected within 5 years of gastrectomy. Characteristic features of type A gastritis are hyposecretion and mucosal atrophy in the fundus and body of the stomach, with absent intrinsic factor.In the small intestine, active and/or passive absorption is impaired by extensive ileal resection, exocrine pancreatic insufficiency and chronic inflammatory disorders such as Crohn's disease.
Definitive plasma concentrations cannot be quoted for vitamin B12 deficiency. Dietary habits, subjective symptoms, hematological laboratory results, function tests and gastrointestinal endoscopic and histological findings must all be taken into account in the diagnosis. Modern diagnostic parameters, such as methylmalonic acid and homocysteine serum assays, are useful for achieving early diagnosis and hence optimal treatment. With their assured availability, parenteral vitamin B12 preparations remain the treatment of choice. Results from vitamin B12 bioavailability studies in healthy subjects suggest that > 300 micrograms probably suffices as an oral maintenance dose after parenteral loading. Further well-documented cases are needed in order to establish whether these doses are adequate in malabsorption syndromes and gastrointestinal diseases. Various case reports indicate the value of prophylactic and therapeutic oral vitamin B12 administration, especially in disorders of homocysteine metabolism, a substance postulated as a further important risk factor for atherosclerosis.

PMID: 10389032 [PubMed - indexed for MEDLINE]
from http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

I don't agree about 300mcg daily..after loading. I don't understand why doctor's are so stingy with oral B12. There is no reason not to use higher doses and get better results!
No side effects not expensive...<shrugs>

This book link claims 1-2 % of B12 is passively absorbed throughout the small intestine:
http://books.google.com/books?id=HMF...ErSlsjIZ3LsbFk
The keyword here is PASSIVE.
1% of 5mg is alot of B12...so it should work for you.
I would make sure you use the methylcobalamin form, which is already activated.

But if it doesn't work for you then injection is what is left.
I'd go with hydroxycobalamin form in this case, since cyano is synthetic. I'd get that level up...near 1000 if possible. When serum levels are low, then the spinal fluid levels fall. You want to get those up too and a dose gradient helps with that issue.
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Old 03-10-2009, 04:17 PM #7
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Quote:
Originally Posted by mrsD View Post
Oral does not depend on the stomach at all.

Oral is absorbed "passively" in the small intestine.

When oral fails, it is most likely being done wrong.
You must take it alone, on an empty stomach 1 or 2 hours before any food. Presence of food with it will prevent absorption.

I'd suggest you invest in 5mg oral methylcobalamin and use it daily on an empty stomach, and for 3-4 months and then get a new test to compare.
Hi mrsD: I have seen the above bold text debated back and forth somewhere, maybe this forum or others. What leads you to take this side of the debate?

I've been on SLs for 6 months for PN and other neurological symptoms, have seen some improvement but want to make sure I'm doing everything the best I can. My doctors, not surprisingly, are pretty clueless. My story is in the intro section, titled "Hi, I need some advice . . ." (sorry I can't link yet til I get more posts)
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Old 03-10-2009, 05:21 PM #8
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Here's the link that you mentioned Bruce.
http://neurotalk.psychcentral.com/sh...310#post472310
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Old 03-10-2009, 06:13 PM #9
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Quote:
Originally Posted by Bruce 01 View Post
Hi mrsD: I have seen the above bold text debated back and forth somewhere, maybe this forum or others. What leads you to take this side of the debate?

I've been on SLs for 6 months for PN and other neurological symptoms, have seen some improvement but want to make sure I'm doing everything the best I can. My doctors, not surprisingly, are pretty clueless. My story is in the intro section, titled "Hi, I need some advice . . ." (sorry I can't link yet til I get more posts)

I am sorry, I don't understand this question.

I don't think the sublinguals are absorbed much sublingually.
This argument goes back YEARS. I think the old sublingual bit is a just a gimmick.

I think that the B12 dissolves in your saliva and is swallowed.
The molecule is huge. The surface area under the tongue is small. And there are just no studies showing that the rest is not swallowed.

Since early 2000, there have been studies on ORAL showing equivalence to injectable if doses are used correctly.

Taking with food is based on studies done with levothyroxine...showing food prevented thyroid absorption.
This has generalized to other drugs that are given in microgram quantities. Levothyroxine failures have been traced to taking with food. If you get an RX filled today for it, there will be a sticker on it explaining that.
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Old 03-14-2009, 08:39 AM #10
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Default No Stomach Acid

Sorry for the delay in responding. Mrs D. - you make a key statement about passive absorption, which agrees with what the specialists told me. You may have not caught this point in my post, but I produce NO stomach acid. Thus, I don't / can't passively absorb the B-12 to the levels that I need. I was told that it obviously couldn't hurt to take oral, just in case a very small amount gets through. I have tried the oral it in all different ways in the last 12 years, at all different doses and varieties, and it has absolutely no impact on my levels. When it comes to the sublingual - I was told that I should try the liquid - not the pill format. That the pill dissolves, as you say, and is simply swallowed. But, that the liquid form, gets partially absorbed directly into the blood. My blood is tested regularly (monthly if not more often) to make sure my levels are up, or we will adjust the shots .... and starting the liquid oral has made a huge and obvious difference. I could barely get it to 500 after 9 months .... and then once I started the oral, it jumped to 800 in 2 weeks, and then over 1000 2 weeks later. Maybe it's just my body - but I'm glad to have found a good combination that seems to work and I'm going to stick with it.
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