[plf1]

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

[mrsD]

There are many reports of B12/nitrous problems like this:

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?

[plf1]

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!

[mrsD]

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.

[Bruce 01]

Originally Posted by mrsD

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)

[Koala77]

Here's the link that you mentioned Bruce.
http://neurotalk.psychcentral.com/sh...310#post472310

[mrsD]

Originally Posted by Bruce 01

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.

[plf1]

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.

[mrsD]

1 to 2 % of an oral dose of B12 is passively absorbed in the small intestine. So if you take 1000mcg you get maybe 10-20 mcg.

If you take 5mg orally you can possibly get 50-100 mcg that way.
The RDA if you ate food and could break it out of food properly
is 2.4 mcg a day for adults.

Sublingual absorption has not shown up in studies as very useful.

Many doctors do not know about this study however:

Clin Lab Haematol. 2003 Jun;25(3):161-6.Click here to read Links
Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients.
Andrès E, Kaltenbach G, Noel E, Noblet-**** M, Perrin AE, Vogel T, Schlienger JL, Berthel M, Blicklé JF.

Department of Internal Medicine, Diabetes and Metabolic Disorders, Hôpitaux Universitaires de Strasbourg, France. emmanuel.andres@chru-strasbourg.fr

BACKGROUND: It has been suggested that oral cobalamin (vitamin (B12)) therapy may be an effective therapy for treating cobalamin deficiencies related to food-cobalamin malabsorption. However, the duration of this treatment was not determined. PATIENTS AND METHOD: In an open-label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food-cobalamin malabsorption, who received between 250 and 1000 microg of oral crystalline cyanocobalamin per day for at least 1 month. ENDPOINTS: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment. RESULTS: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 x 10(6)/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05). CONCLUSION: Our findings suggest that crystalline cyanocobalamin, 250-1000 microg/day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.

PMID: 12755792 [PubMed - indexed for MEDLINE]

from http://www.ncbi.nlm.nih.gov/pubmed/12755792?ordinalpos=1&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.P ubmed_Discovery_RA&linkpos=4&log$=relatedarticles& logdbfrom=pubmed

We have seen posters here who did not respond quickly to 1000mcg (1mg) doses as in this study. So that is why I recommend 5mg to start. I think if people have depleted the liver, some of the supplement goes there partially, so blood levels may not come up as quickly because of that priority.

Whatever works for you, do it! You are right, everyone is different!

[Vern]

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.