B12/ neuropathy/Transcobalamin II

[Lessing]

After complaining of peripheral neuropathy, memory problems, I was diagnosed with low "Vit B12 Binding Capacity, Unsat (Transcobalamin)."  That is the name of the test, given by Quest Diagnostics.  My serum B12 levels were normal, I had been orally supplementing for a long time.  My doctor said the treatment is B12 injections, and began me on a standard regimen.  Upon my insistance, she allowed me to take the weekly shots for three months, as the improvement was quite notable, in terms of cognitive function, and neuropathy symptoms.  While my Transcobalamin II levels (I believe that is what the test shows) have risen somewhat, from ~200 pg/ml to 360 pg/mL, the normal rage is 650-1340.  As soon as she cut me back to 1 shot a month, my neuropathy symptoms worsened, and my cognitive function stopped improving.  I know that the T II is what gets the B12 into the cells themselves.  Why do the shots work, and not oral Sup? Is there any medical reason why I couldn't continue to take the B12 shots weekly?  My serum levels are high, out of range.  Since it was never my serum level which was a problem: Isn't it wrong to cut back on the shots when my symptoms worsen as a result?  I have hypogammaglobulinemia, which I treat with IVIG infusions.  It never notably improved my neuropathy, and my cognitive function continued to decline, until the B12 shots.  Please tell me as much as you can about the T II, any B12 toxicity, and the above questions.  These problems run in my family but we haven't gotten answers on this.  Thanks in advance for your help.

[CCF-Neuro-M.D.-SH]

First of all, keep in mind that I am unable to diagnose you because I am unable to examine you, this forum is for educational purposes.      
   B12 is a vitamin found in animal products (not in vegetables) that is absorbed through a complex mechanism of co-factors in the gut.  B12 is water soluble like the other B vitamins, but unlike the others that are absorbed immediately, B12 take 3 hours to be absorbed under normal conditions due to the co-factor binding.  First B12 binds to Haptocortin in the stomach.  The stomach (parietal cells) also produces intrinsic factor, which binds to B12 in the duodenum (first section of small bowel).   The intrinic factor-B12 complex is internalized  (at the ileum) and then B12 binds to Transcobalamin II, which distributes it from the blood to the cells.  A deficiency in B12 can cause anemia and demyelination of peripheral nerves, spinal cord and even the brain (which causes numbness/tingling, weakness and stiffness, and mental confusion).  There are multiple ways to become deficient in B12.  One way is decreased intake (vegetarian diet, malnutrition).  Another way is to have decreased absorbtion due to the lack of intrinsic factor (an autoimmune condition called pernious anemia due to antibodies against intrinsic factor and/or parietal cells).  Decreased stomach acid can also interfere with the binding of B12 to its co-factors (due to proton pump inhibitors, antacids).  Another common cause is short gut syndrome due to surgery/gastric bypass surgery (no ileum).  Finally if the transcobalamin II does not bind B12 efficently, this can lead to a B12 deficient state in the cells (with normal levels in the blood).  Transcobalamin II deficiency is diagnosed by measuring the amount of transcobalamin II that has B12 bound to it (holo-transcobalamin II) was compared to unbound transcobalamin II (apo-transcobalamin II).  Some people have defects in their transcobalamin II (that does not efficiently bind B12).  From the story and symptoms that you describe, it is unclear why you only respond to very high serum levels of B12.  It could be due to a transcobalamin II defect, or that your peripheral neuropathy and cognitive changes are unrelated to your B12 level.  I would suggest a methylmalonic acid (MMA), a CBC with MCV (test for anemia), homocysteine level, and intrinsic factor/parietal cell antibodies.  I would also recommend an EMG and MRI of the brain to evaluate your peripheral neuropathy, cognitive problems further.  There is no known toxicity to B12, but this is not well studied.
I hope this has been helpful.

[Annie62]

Regarding B12 shots vs. oral supplements, it is true that pills won't bring B12 levels up when it is a problem of absorption, but a low B12 level due to a strict vegetarian/vegan diet (no meat and no or little dairy) can be replenished by just B12 tablets.

[lcy]

I also am having memory problems and went to get some blood work done.  It was discovered that my b12 levels were low (258).  I asked the doctor whether or not i can take a suppliment to bring it up and she said no.  She said that the reason why my b12 level is low is because my stomach isn't absorbing b12 from the normal food i eat and the only way to bring the level up is through an injection.  She said if i were to take a suppliment, i'd essentially just be swallowing pills.  Hope this was helpful and i hope everyone feels better!

[ahoskrn]

I don't have anything to offer you as far as answers, but I was wondering if you could answer a question for me. What was your serum B-12 level initial when you started having neurosymptoms? My B-12 level is 300 (normal 211-990) and I started having paresthesia (tingling, prickling, burning sensations)3 weeks ago all this following severe abuse of tagamet and prilosec on my part for stress induced gastritis. When I offered up the idea of B-12 defficiency my Dr. said "you level is normal". Is the other test you had called something specific and is it ordered separatly from the B-12 test. What kind of body symptoms specifically did you have? I am having an MRI Wednesday and see a Neuro next week. I have been taking 2000mg B-12 daily for a week, symptoms still there but diminishing a little. How quickly did the shots help? I think you should persue this with your doctor because I have been reading alot on B-12 levels in the US not measuring up to the standards in the UK ( they measure normal more like 500 and up) and I am wondering how many other people are misdiagnosed because of this. I hope you are feeling better, thank you in advance if you can answer any of my questions!http://roseannster.googlepages.com/home This is a good link for B-12 info!