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B12 Deficiency: Still America’s #1 Missed Diagnosis

Over the years of writing Health Tips, I was surprised to discover that one I’d written a few years ago about vitamin B12 deficiency had received the most comments and questions from readers. Since there have been some interesting developments in both the diagnosis and treatment of B12 deficiency, and since B12 deficiency remains so common, this seems like a good opportunity for some updates.

The symptoms of low levels of vitamin B12 can be pretty vague. You’re just not feeling right and you’re tired, maybe a little depressed, a bit achy. Your digestion might somehow feel off and you’re not thinking clearly. Balancing a checkbook becomes an exercise in higher math.

Your doctor’s empathetic, not at all dismissive of your symptoms, but after a physical exam and some apparently appropriate tests with normal results she can’t find anything really wrong. On the surface, this is reassuring. After all, the main reason we go to doctors is to ascertain that nothing serious is going on.

Still, could she be overlooking something?

All about B12
One of the eight B vitamins, B12 is involved in the metabolism of every cell in your body. Years ago B12 was called “maturation factor” because cells need B12 to mature from being young and ineffectual whippersnappers to fully functioning, mature cells. Imagine a child, about seven years old, who’s stuck at that age and can’t grow into adolescence and later adulthood. Now imagine a magical substance that will allow her to grow and mature. That’s vitamin B12.

In fact, B12 is so potent a factor in cell maturation that some of the original studies on it showed that cells in the bone marrow (where blood is manufactured) when deliberately deprived of B12 could mature in just a few hours when B12 was added. This phenomenon explained how B12-deficient patients reported feeling magically rejuvenated within a day or two of their first B12 injection.

Years ago, I read that the late Bruno Bartoletti, conductor of the Lyric Opera orchestra, would not go onstage unless he’d had a B12 injection earlier that day. At the time, I thought it was a placebo effect. Now I think differently.

B12 deficiencies
Three major systems in your body are affected by B12 deficiency: your blood, nervous system, and, less often, gastrointestinal tract. These three are targets because their cells either have a high turnover rate (blood and intestinal lining) or need a lot of B12 to function smoothly (nervous system). The symptoms of low B12 are related to each of these areas.

  • Low B12’s effect on blood is a specific type of anemia called megaloblastic anemia (as distinct from the more common iron deficiency anemia). A megaloblast is an immature, undeveloped red blood cell, large and bulky (megalo=large, blast=immature form). Remember, B12 is needed for this cell to mature, so with insufficient B12, megaloblasts accumulate in your bone marrow and large red cells called macrocytes appear in your blood. Symptoms are the same as for anemia from any cause: fatigue, breathlessness, and lightheadedness. Your skin becomes a pale yellow, most likely because the red cells that do make it to maturity are very fragile and easily broken, releasing their yellow bilirubin pigment.
  • In the nervous system, B12 deficiency causes symptoms affecting the nerves (numbness, tingling, tremors, balance problems) and the mind (depression, brain fog, mood swings, and, in rare cases, hallucinations and psychosis).
  • In the GI tract, deficiency can cause digestive symptoms and weight loss because you’re not absorbing food efficiently.

The irony is that with all these there’s usually just one predominant symptom, and making a connection to low B12 can easily be delayed until other symptoms start to appear. For example, if your only symptom is tingling in your hands, you might undergo all sorts of diagnostic tests before your doctor thinks “Maybe we should check her B12 level.”

But even if you manage to get your doctor to test your B12 level, you’re only halfway there because the blood test is just not very good.

The normal range for B12 in the US is 200 to 800 pg (picograms)/milliliter of blood. But it’s been shown that symptoms can begin as low as 400 pg/ml, so the US “normals” are definitely not OK. In Europe and Japan, anything below 550 pg/ml is considered abnormal. Therefore, if your level is, for example, 350 pg/ml, your doctor reads a printout for you that reports “normal B12” and she doesn’t initiate treatment. I’ve had patients come in with B12 levels of 201 pg/ml with the word “normal” scribbled across it by the doctor.

A far better test for early B12 deficiency is measuring your blood levels of methylmalonic acid (MMA) because this will show the very first sign that something’s amiss with B12. You can have a perfectly normal B12 level, but if your MMA is elevated B12 deficiency troubles are on the horizon. The real problem is that you’ll have to ask for an MMA test without sounding like a smartass who’s been spending too much time on the internet

What causes B12 deficiency?
The list of causes is lengthy, but by far the most common is dietary. Vegetarians who aren’t paying attention to the B12 in their food choices will have downward-drifting B12 levels, and virtually all vegans not taking vitamin B12 supplements ultimately develop deficiencies. Even vegan organizations acknowledge it’s not possible to get adequate B12 while following a strictly vegan diet, and that’s because the richest sources are animal products.

Other causes of B12 deficiency include pernicious anemia, an uncommon (and spookily named) autoimmune disease that destroys parietal stomach cells. These cells produce a substance called intrinsic factor, necessary for B12 absorption. Also, since you need stomach acid to absorb B12, long-term use of acid-suppressing proton pump inhibitors (such as Nexium, etc.) can lead to B12 deficiency, as can chronic intestinal conditions such as Crohn’s disease, celiac disease, and intestinal parasites.

The missed diagnosis
The main danger of missing a diagnosis of low B12 is that, while quite rare, the damage to your nerves and even brain can be permanent. Other serious consequences: your anemia can get so severe it causes heart failure and collapse. Or you could be misdiagnosed with a major depressive disorder or even psychosis and take unneeded psychiatric medications for months (or years) before someone notices you look yellowish and you’re finally diagnosed with megaloblastic anemia.

There are three reasons why this diagnosis is missed:

  1. Although it’s not an expensive test, B12 isn’t measured during routine blood tests. Doctors generally don’t order a B12 evaluation if there’s no evidence of anemia (which would be picked up on a routine blood test). However, the fatigue and nervous system and GI symptoms can precede anemia by months.
  1. Doctors rarely ask (and patients rarely volunteer) information about their eating habits. In medical school, we’re taught that the US diet is plenty good enough to prevent any vitamin deficiencies. To which I now respond, “Ha!” I agree most of us eat plenty of food (obesity levels are still on the rise), but it’s often food whose nutritional value has been castrated. Also, all vegetarians and vegans should be regularly tested for possible B12 deficiency, but if your doc doesn’t know your eating habits you won’t be tested.
  1. Taking the B vitamin folic acid (folate) or eating a lot of folate-containing foods without adding B12 can actually mask the symptoms of a developing B12 deficiency. Although folate will keep your blood count normal even if your B12 is falling, the folate will not protect your brain and nervous system. You’ll have no evidence of megaloblastic anemia (because of the folate), but symptoms of numbness, tingling, balance problems, and emotional issues will continue unchecked. By eating so many folate-containing green vegetables, beans, and lentils, vegetarians and vegans inadvertently mask their own slowly developing B12 deficiency.

Treatment is easy
It’s virtually impossible to take too much B12 as any excess of this water-soluble vitamin is eliminated via urine. Nutritional guru Alan Gaby, MD, has commented that the only way too much B12 will kill you is if you fill your bathtub with it and drown.

Foods high in B12 are animal products: meat, poultry, seafood, dairy, and eggs, with eggs having the least. Because all animals store B12 in their livers, eating liver is an excellent, though not particularly popular, treatment for B12 deficiency. Your grandmother or great grandmother likely remembers a time when her doctor told someone in the family to eat more liver.

Although B12 injections have been used for decades as the fastest way to raise B12 levels, the latest research is saying that well chosen forms of oral B12 will probably work just as well. The Integrative Therapeutics product B12 Active is a chewable, cherry-flavored tablet containing 1,000 mcg of methylcobalamin. Taken daily, it generally restores B12 levels to a normal range in one month.

This brings up another confusing point. Most B12 in both injections and pills is called cyanocobalamin, which, yes indeed, does contain a totally nontoxic form of Agatha Christie’s favorite murder weapon, cyanide. But what’s the difference between the two? When it comes to raising your personal B12 levels, both work equally well. To be honest, the main reason for the prevalence of cyanocobalamin is cost. Totally synthetic, cyanocobalamin is cheap to make.

Methylcobalamin, the natural B12 form that your body actually prefers because it doesn’t have to detoxify the cyano part, is simply more expensive to manufacture. However, there is one completely new cyanocobalamin product worth mentioning. Eligen B12 (available by prescription) contains B12 combined with a carrier called salcaprozate that enhances B12 absorption into the stomach. B12 levels go up as quickly as they do with injections so you can avoid your doctor’s needles. However, I suspect Eligen B12 is not superior to the Integrative Therapeutics product mentioned above.

I think this all answers most of the questions and comments that followed my previous B12 article, but if you have more send them along.

Be well,
David Edelberg, MD

Leave a Comment

  1. Lina says:

    David, I love you, truly!!! Thank you. This information is so much needed. If you remember my first previous comment earlier about that I couldn’t find the good doctor … My previous doctor are stupid as it can be… When I told her my heart palpitations and numbness she did not even took proper blood test for iron as I asked her to but just want to give me right in my hand without even prescription antidepressants (2 pils to try) like a narcotic by any street drug dealer… Is it doctor? No it’s killer and not a doctor. So I told her she can take them her self and left. Finally I went to naturopathic and she checked my blood test and I have anemia. By prescription I am taking an iron which cause my stomach problems… If it’s any form of iron that doesn’t hurt stomach that much?
    Also I will ask her to check my B12 by blood test or MMA as you recommend. Numbness it’s what I have most in my shoulders and arms and legs, feet and toes ..
    I will have her to read this post of yours. Why all the doctors cannot be so smart and caring?:)
    And why you are not in WA state?:)
    … any way thank you for the post. So much light and answers I got!!!:)

  2. Katharine Hathaway says:

    Dr. E
    Would you address the methylation problem with Vitamin B’s?

  3. Kem says:

    What form of B12 do vitamin injections use? Do they contain methylcobalamin?

    I ask because I’m in the unlucky minority who experiences side effects from methylcobalamin. Despite trying multiple brands and dosages, I get a headache every time I use it. I haven’t experienced side effects with cyanocobalamin. I’m concerned that a B12 injection will lead to the mother of all headaches.

    I want to stress to readers that plenty of people take methylcobalamin without incident, so don’t let my comment discourage you from trying it.

  4. Dr E says:

    Hi Lina
    Thanks for your kind words about our blog. Lots os people have trouble with iron. Your naturopath can guide you about an iron tonic she can likely order for you made completely of herbs. Eating iron rich foods such as liver, figs, seafood, molasses, beets, brown rice, whole grains, poultry, eggs, grapes, raisons, yams, and beans can help. Avoid drinking coffee, tea, beer, or cola with meals as these drinks inhibit the absorption of iron. Manganese rich foods including whole grains, greens, legumes, nuts, pineapple, and eggs help increase iron uptake into the system.

  5. jeff Lupetin says:

    Thanks David.

    Great info!!

  6. Beth says:

    Dr E,
    Will the oral forms of B12 you mention work for people who lack intrinsic factor?

    Thank you.

  7. Gina Pera says:

    Fantastic update. Thank you, Dr. Edelberg!

  8. Mary says:

    My vitamin B level is at 1500 which is very high. Could that be problematic? A quick search on the web shows it could be a sign of cancer or liver disease.

  9. G says:

    Pernicious anemia/B12 deficiency whether autoimmune or acquired because of procedures(gastric) or meds (numerous) or diet is prevalent, injections are easley self administered after haveing the first one at your Dr’s to see if you have any sensitivity/ alergic reaction.and they are inexpensive.

  10. Leigh Ann Barnett says:

    great article. I pump myself with B12 (and other vitamins) throughout the day, per genetic defects, but can only seem to handle Hydroxy and Adeno forms. I haven’t tried cyno I don’t believe, but am happy with the 2 that I’m taking. I take some molyb as well, which helps combat the numbness / tingling, headaches, and eye / face twitches. I can tell when I’m not getting enough, as those symptoms all start creeping back. Scary stuff, and sad to think that my regular doctors were never able to figure out the cause. Thank goodness for Alternative docs like yourself!

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