B12 background information

[rose]

Medical researchers and medical journals have been warning for decades that anyone (regardless of diet) can become B-12 deficient. Occasionally it happens early in life, but it becomes more common by middle age.

If B-12 deficiency is not eliminated while the damage is minor, it is common for the spinal cord to become damaged, and even the brain may, or the patient may be misdiagnosed with Alzheimer's and die of heart failure. This may happen within a few years, or over decades, depending on the extent of malabsorption. And symptoms are often so subtle for quite a while that the problems seem sudden, even though they have been worsening for a quite a while.

Research during recent decades has shown that people who have neurologic damage as a result of B-12 malabsorption are misdiagnosed even more often than thought previously. And people who do not show signs of anemia (which most doctors think must occur in anyone B12 deficient) are even more likely to be damaged neurologically. They are being allowed to worsen unnecessarily for lack of a safe and inexpensive vitamin.

People who have neurological symptoms should be tested and/or treated immediately (not after weeks, months or years of other testing or waiting). If immediate testing is not possible, they should take at least 1000 mcg B-12 per day, while continuing to look at other possibilities. If B-12 deficiency is the cause, they will almost surely stop the damage within weeks and then their bodies will have an opportunity to begin a months-long (years in more serious cases) process of repair. The earlier deficiency is treated, the more likely is complete repair.

It is important to note that sometimes a very long time elapses before it is obvious that the B12 is doing anything. The body can do a lot of work (and even experience temporary worsened symptoms) while working to stop damage and repair.

rose
http://roseannster.googlepages.com/home

[rose]

If the B-12 test result is clearly deficient, B-12 therapy should be given immediately and follow up tests should be scheduled within a month or so. B-12 treatment should be continued, because most people who malabsorb continue to do so for life.

Please obtain copes of your B-12 and other lab results. Hearing "It's normal" or "everything is fine" from most doctors is meaningless, because they don't know how to diagnose deficiency. In addition, it is surprising how often out-of-range results, along with other clues, are ignored.

Many doctors think that a B12 serum result within "normal" range rules out deficiency----it clearly does not, especially in a patient with neurological symptoms.
Many doctors think that ruling out anemia eliminates the possibility of B-12 deficiency--on the contrary, people low in B-12 who do not become anemic are more at risk for severe neurologic damage.

Many patients are damaged, even disabled while testing well into normal. Rare patients are deficient even when blood levels are high, because B-12 does not work in the blood; it works in the tissues. Some people can absorb B-12, but they cannot deliver it from blood to tissues.

If the B-12 result is not clearly deficient, the patient with neurologic symptoms should have follow up tests: methylmalonic acid and homocysteine. The two follow-up tests have a good, but not perfect, record for exposing deficiency. In case you are one of the few who test "normal" all round but still need B12, it is a good idea to take at least 1000 mcg B-12 per day to cover the possibility that you are in that minority. In that case, one can only hope.

If follow-up testing cannot be obtained right away, the patient should consider taking at least 1000 mcg of B-12 per day on the chance that it is needed. If deficiency is causing the damage, sufficient doses of B-12 will stop the damage and eventually allow some degree (sometimes 100%) of recovery over time. If testing is done after B12 has been taken, the results will probably be normal; that does NOT mean that the person was not deficient prior to taking the vitamin or will not become deficient again if it is stopped.

B12 is safe and inexpensive. Too little of it is very dangerous.
A more detailed description of diagnostic procedures for your doctor is available in current medical textbooks, such as Goldman: Cecil Textbook of Medicine, 21st Ed., Copyright © 2000 (or 2004) W. B. Saunders Company.

Once the damage has been stopped, it is time to look for the cause of malabsorption or failure to convert, transport or store B12 normally. Unfortunately, most doctors will not be interested in finding the reason. And worse yet for some people, many assume that if B12 deficiency did the damage, all problems will immediately disappear as soon as the B12 level is up. Good grief.

rose
http://roseannster.googlepages.com/home

[rose]

It will happen, but a lot is going on right now so not able to work on it often or for long.

rose

[Moyvore]

Rose,

There have been an number of recent articles in the medical literature in effect endorsing your years of posts about B12 misdiagnosis:


Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing.

Solomon LR. Department of Medicine, Yale University Health Services

http://intl.bloodjournal.org/cgi/content/full/105/3/978

(Full text, with link to free pdf file)

Editorial comment on Solomon, same journal:

Unreliability of current assays to detect cobalamin deficiency: "nothing gold can stay"

http://www.bloodjournal.org/cgi/content/full/105/3/910

Responses and rejoinder:

To the editor:
Cobalamin-responsive disorders and unreliability of cobalamin, methylmalonic acid, and homocysteine testing

http://www.bloodjournal.org/cgi/content/full/106/3/1136


To the editor:
Is testing for clinical cobalamin deficiency truly unreliable?

http://www.bloodjournal.org/cgi/content/full/106/3/1136-a


A subsequent UK confirmation:

Haematologica. 2006 Feb;91(2):231-4.

The limited value of methylmalonic acid, homocysteine and holotranscobalamin in the diagnosis of early B12 deficiency.

http://www.haematologica.org/journal/2006/910231.pdf

"The symptomatic effects of high dose B12 therapy
warrant further investigation in larger studies. Our findings
are in keeping with the recent report by Solomon
that the metabolite markers MMA and tHCY cannot be
regarded as the gold standards for assessing B12 deficiency."


There have been reports describing B12 deficiency with high serum B12 levels in immunological or kidney issues.

Eur Neurol. 2006;56(1):62-5.

Chronic renal failure promotes severe variant of vitamin B12 deficiency
(Letter, no abstract provided)

"The vitamin B 12 deficiency in patients with chronic renal insufficiency is however much more difficult to assess and poorly understood. There is evidence that patients with renal dysfunction might develop a vitamin B 12 resistance [10] . Here we report a foudroyant case of SCD [subacute combined degeneration] with severe affection of the white matter of the brain and spinal cord in a patient with chronic renal failure."

"The patient had been on vitamin B 12 supplementation for 2 years (1,000
g/month).


"In conclusion, severe SCD courses combined with epilepsy, cognitive decline and reduced vigilance, and normal levels of vitamin B 12 , homocysteine and MMA
should be considered in the spectrum of cobalamin-deficiency-associated neurological disorders, especially in patients with chronic renal failure. Such fulminant
courses of the disease might be related to a generalized resistance to vitamin B 12 in such patients and may require earlier and much larger therapeutic cobalamin doses than previously considered."

[10] was:

Nephron Clin Pract. 2005;99(2):c42-8. .

Cellular uptake of vitamin B12 in patients with chronic renal failure.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15637428

"...CONCLUSIONS: Our results show that vitamin B12 uptake is impaired in [mononuclear cells] from renal patients, with no evidence that the surface receptor is down-regulated. High serum concentrations of holoTC [holo-transcobalamin] are common in renal patients and might be related to a generalized resistance to this vitamin. Serum concentrations of vitamin B12 within the reference range are not likely to ensure vitamin delivery into the cells. Supraphysiological doses of vitamin B12 may be necessary to deliver a sufficient amount of the vitamins to the cells via mechanisms largely independent of holoTC receptor."


I wonder if you have noted any poster on this List with B12 issues (masked or not) has reported either a diminished sense of thirst (noted camel effect) and or sporatically (or constantly) elevated blood urea nitrogen levels (BUN). It turns out that diminished kidney function (which may be associated with reduced fluid intake) apparently can have a material influence on B12 serum to tissue transfer.


Moyvore

[rose]

In some cases homocysteine remains high even though plenty of B vitamins have been taken, including lots of B12. Definitely should look at kidneys in those cases.

And, to reinforce the kidney/B12 connection, for a very long time elevated methylmalonic acid has been known to indicate either low B12 or kidney problem.

So many interesting and important connections are being explored now. MS and B12 deficiency is another one.

rose

[rose]

I don't remember anyone mentioning diminished sense of thirst in connection with B12 deficiency. But, now that you mention it, I wonder whether there is sometimes a connection between lessened thirst in older people and the higher likelihood of B12 deficiency.

BUN. Looks like the attitude regarding BUN is a setup for missing cases of B12 deficiency. As you say, elevated BUN points to kidney problem, and usually low BUN (which can point to malnutrition) is not taken seriously.

Excellent observations.

rose

[annelb]

Not only does this need to be bumped, I want to add an abstract. It is not a new one but the message still holds true.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed

South Med J. 1991 Dec;84(12):1475-81. Links
Myths about vitamin B12 deficiency.Fine EJ, Soria ED.
Department of Neurology, School of Medicine, State University of New York, Buffalo.

Neurologic manifestations of vitamin B12 deficiency are protean, including neuropathy, depression, and dementia. We present evidence to dispel confounding myths about vitamin B12 deficiency. Hematologic indices are normal in up to 30% of patients with vitamin B12 deficiency, and results of the Schilling test may be normal in patients with symptoms of deficiency. Isolated neuropathy or myelopathy may occur independently, but often appear concurrently. The neuropathy is primarily axonal and predominantly sensory. Myelopathy is caused by demyelinated areas in posterior and lateral columns. After therapy, recovery from neuropathy is incomplete or may extend for several years. Vitamin B12 replacement should not be withheld from patients with borderline vitamin B12 levels, since the consequences of allowing myelopathy, neuropathy, dementia, and mental disorders to worsen clearly outweigh any disadvantage of therapy.

PMID: 1749982 [PubMed - indexed for MEDLINE]

Anne

[BrokenBladder]

Thanks for all of the links posted!!! I'm new to all of this and feel a bit overwhelmed. My B-12 is low, I'm anemic(sp?), and I have low potassiam. I'm making an appointment with my PCP this week, but I don't know how helpful he will be. I seriously need some energy back!!

[Cry Tears]

Rose...can I be your "poster child" for B12 deficiency?!?!!?
Its too bad my very first post from Sept 3, 2004 got lost.
The thread proved how true everything you've written is correct.
Dr's told me all my levels were NORMAL!...yes, but the standards are wrong!
A B 12 level of 232, loss of balance, burning lips, extreme fatigue, mental confusion, Peripheral Neuropathy, severe muscle weakness, muscle twitching and spinal cord pain is NOT normal!
My moderate level sock glove pattern of Peripheral Neuropathy
documented by OHSU teaching hospital.....with that low level of B12 should speak volumes!
NORMAL LEVEL? I think NOT!

I began taking the Methlycobalamin Sept 3, 2004....I was near death then.
Within 10 days I was able to get out of bed after being totally bedridden half a year....
finally I could take my own shower unassisted!

By mid October, I kept the Mayo Clinic appointment made 6 months earlier.
I was doing so well I was able to travel there all by myself!
2 weeks of their thorough testings, they agree'd my symptoms most likely were from B12 deficiency.
I paid how much to learn this? Hhhhhmmmmm! Where's the OMG sticker when you need one?!

My EMG and NC test were then back to NORMAL....B12 level....800+
Most of those horrible symptoms began abating!
My walker sits in my garage....a testament to what's written here on BT
and that Rose is a Godsend to many who are suffering....needlessly!
If only more could find this web site...I pray, pray, pray!

I thank the LORD every single day that I was able to find this web site
and for Rose. She anwered my final plee for help.
God Bless you Rose...and those who support her endeavors!
Cheryl

[rose]

Good idea, Cheryl. We'll have a very large poster made, and many of us will be on it. ;) Thanks again for the support!

Anne. As far as I'm concerned, that cannot be quoted too often. Thanks for bringing it back up.

As for our newer B12 recruit ;) , you may be lucky to be anemic. Unfortunately, people who do not become anemic, even with severe longstanding damage, are much less likely to be diagnosed.

rose

[edg]

Hi, all. I was Dx with low B12 about a year and a half ago. My symptoms were sleepiness, recurrent vertigo and increased clumsiness. I have been taking 1000mcg of B12 IM since then. I started at once a month but found that I developed mild symptoms three weeks after a shot and started taking one every 3 weeks. I recently had a B12 level about three weeks after my last shot and was surprised to find it to be in the low 300's, not much higher than when I started therapy.

Does anyone know if there is a mechanism for low blood levels, such as sequestration of B12 or antibodies to B12? I know that with decreased renal function utilization of B12 by cells is decreased, but that would give normal levels of serum B12.

I haven't been able to find any info on low levels while on IM injections.

Thanks for any help.

Ed

[annelb]

I know many people who take 1000mcg (or more) per day of methylcobalamin. There is evidence that taking that much orally will raise B12 levels.

Arch Intern Med. 2005 May 23;165(10):1167-72.
Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial.Eussen SJ, de Groot LC, Clarke R, Schneede J, Ueland PM, Hoefnagels WH, van Staveren WA.
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

BACKGROUND: Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B(12) deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain. METHODS: We conducted a randomized, parallel-group, double-blind, dose-finding trial to determine the lowest oral dose of cyanocobalamin required to normalize biochemical markers of vitamin B(12) deficiency in older people with mild vitamin B(12) deficiency, defined as a serum vitamin B(12) level of 100 to 300 pmol/L (135-406 pg/mL) and a methylmalonic acid level of 0.26 mumol/L or greater. We assessed the effects of daily oral doses of 2.5, 100, 250, 500, and 1000 mug of cyanocobalamin administered for 16 weeks on biochemical markers of vitamin B(12) deficiency in 120 people. The main outcome measure was the dose of oral cyanocobalamin that produced 80% to 90% of the estimated maximal reduction in the plasma methylmalonic acid concentration. RESULTS: Supplementation with cyanocobalamin in daily oral doses of 2.5, 100, 250, 500, and 1000 mug was associated with mean reductions in plasma methylmalonic acid concentrations of 16%, 16%, 23%, 33%, and 33%, respectively. Daily doses of 647 to 1032 mug of cyanocobalamin were associated with 80% to 90% of the estimated maximum reduction in the plasma methylmalonic acid concentration. CONCLUSION: The lowest dose of oral cyanocobalamin required to normalize mild vitamin B(12) deficiency is more than 200 times greater than the recommended dietary allowance, which is approximately 3 mug daily.

PMID: 15911731 [PubMed - indexed for MEDLINE]



I mention methylcobalamin as that does not have to be converted as does cyanocoblalmin. Not everyone does a good job of doing this conversion.
Anne

[rose]

In addition to what Anne replied :) , there has been lab confirmation that some rare people who do not accumulate usable B12 from cyanocobalamin shots do build stores well with oral methylcobalamin.

There are some uncommon reasons for this. In order to store and appropriately use B12, it must be a usable type (converted as Anne said, or the usable type taken in the first place---methylcobalamin). Also, the body must be able to transport the B12 and store it.

You may not be able to convert cyanocobalamin. Or, you may need it very frequently because you store it very badly (is your liver ok?). Or, you may need large quantitied of usable B12 (methylcobalamin) for some reason or reasons.

Any one of these things, or a combination of them, or other very rare conditions can cause what you describe. The absorption and use of B12 is very complex and much can go wrong.

I would take 5000 mcg methylcobalamin daily for a long while. 1000 mcg would probably be fine, but I wouldn't want to take the chance in your situation. Then, once it is established that the B12 evel is very high, I might cut back to a couple of times a week to keep it that way.

rose

[mrsdoubtfyre]

There is a new DNA test over the counter provided by Solgar now (just being introduced) that measures genetic failures in vitamin utilization by the body.

They then taylor supplements to match your weaknesses.

You can call them to find a store that is trained in this testing, and also
selling the supplements suggested by the test results.

It is called Nutragenomx
Firms Roll Out Retail Nutrigenomics

Consumer genomics firm GeneLink (Jersey City, N.J.) announced an exclusive, multi-year retail licensing and distribution agreement with Solgar Vitamin and Herb (Leona, N.J.) to market a nutrigenomic line of nutritional supplements. Under the agreement, Solgar will market a brand of nutritional supplements called Nutrigenomx that are tailored to individual consumers’ genes based on the results of a GeneLink DNA collection kit and Genetic Compass reporting system. The collection kits and supplements will be available at health food and specialty natural food retailers in North America.

“By combining Solgar’s leadership in nutritional sciences with GeneLink’s ten-plus years of research and advancements in consumer genomics and SNP testing, we have created an ideal marketing relationship for each of our companies,” said GeneLink CEO Monte Taylor. “A personalized approach to wellness has become an important trend in healthcare.”

from http://www.aacc.org/publications/cln/2008/feb/Pages/Industry_0208.aspx

I know one of the tests is the MTHFR (folate methylation) gene.
I haven't seen the test yet as only one store in my state has it now.
As they train people, more stores will carry the line.
It costs $125.00 OTC (no insurance allowed), for the DNA test which is a cheek swab.

I have been told that methylfolate will be sold as a stand alone product by Solgar beginning in late June or so. It is already included in the Nutrigenomx
line. If you Google Solgar, you can find their toll free # and they will tell you
more.

This is pretty exciting since now we just "guess" and suggest people use activated B12 and folate. Now you can PROVE if you need them. They are typically so inexpensive however, that it is not an issue to use the better forms anyway.

[Naominjw]

My daughter is one of the people with B12 blood level >2000 (2000 was highest the measurement went up to) with normal range up to 911. The doctor said that would only be if her cells somewhow were not getting enough B12 so her kidneys were hanging on to as much as it could.

They have never tested her homocysteine, etc levels.

It explains why getting on a supplement helped her childhood-onset "mental illness" (and yes, she had neurological problems, ataxia, migraines, seizure-like episodes, fatigue).

I keep seeing folate discussed when B12 is discussed, and wonder why? Also, what would testing the MTHFR gene for folate metabolism have to do with B12?

Lastly, I cannot find the genetic test for cobalamin (B12) metabolic variants. Where? I would like to get my daughter tested for both.

I have read that not all MTHFR (folate) problems are fixable with extra folate. :(

Thaks,
"Naomi"

[mrsdoubtfyre]

Chemistry is complex. I don't understand all of it myself.

The MTHFR polymorphism is bypassed by the TYPE of folate used.

By using methylfolate instead of folic acid, the error no longer is an issue.

You can go to Solgar's website and call their toll free number (their email does not work) They will tell you where near you the DNA test is being offered. It is still being worked on, and requires training at the store level, so they will not sell the special Nutrigenomx line without training the store staff first. There is only one store so far in my state, for example.
It costs about $125.00 and does not need a doctor's order.

B12 given as cyanocobalamin has to be activated as well, thru 4 steps.
This may fail as well. The activated form is methylcobalamin and is OTC.
We typically buy it from iherb.com

Solgar makes specific nutrient mixtures based on the DNA test showing
what you specifically need.

[annelb]

I am glad to hear that Solgar will be making methylfolate available. Thanks for this info.

I found this about the conversion of folate to mathylfolate. According to this the majority cannot do this very well. http://www.metanx.com/UnaffectedByTheCTPolymorphism
Anne

[heldo18]

rose,

Dont knowif youy remember me from a couple of years back.. I am worried about having ms as I am getting b12 jabs, my brain and spine scan were normal but I still get lots of mysymptoms. My left arm doenst seem to twist as much as my right and I dont know if this is just something I have and have sterted obsessing over. I am also a very anxious person so some docs say my symptoms are anxiety. Thanks for all you do on this site

x