Vitamin B-12

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 feel off and you’re not thinking clearly. Balancing a checkbook becomes an exercise in higher math.

When your B-12 numbers are low, any of the following can occur:

  • extreme tiredness,
  • a lack of energy,
  • pins and needles (paraesthesia),
  • ringing in ears (tinnitus),
  • a sore and red tongue,
  • mouth ulcers,
  • muscle weakness,
  • disturbed vision,
  • psychological problems, which may include depression and confusion,
  • problems with memory, understanding and judgment.

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 your eight B vitamins, B12 is involved in the metabolism of every cell in your body. Years ago B12 was called “maturation factor” because your 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 to adult forms 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 your nerves (numbness, tingling, tremors, balance problems and the ringing in your ears called tinnitus) 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.

Most recently, with the COVID pandemic, low B-12 was associated with increased susceptibility to the virus and is now included in most regimens for victims of “long COVID”.

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 U.S. 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 here in the US such “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 will read a printout for you that reports “normal B12”, and she won’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 to combine serum B-12 level with 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. Also, if your doctor notes that you have a megaloblastic anemia, she’ll also order a folate level. Deficiencies of both are similar but if folate alone is treated, your anemia will improve but the nerve damage from low B-12 will continue unchecked.

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. Up until the 1950’s, Jewish grandmothers making gefilte fish would taste the partially cooked pike and carp which contained fish tapeworm (often growing to several feet long) which blocked B12 absorption. Fish inspection and thorough cooking ended this unusual source of B-12 deficiency.

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. (We order B12/folate routinely at WholeHealth Chicago)
  2. 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 very much on the rise), but it’s 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. (You know our intake questionnaires ask about what you’re eating!)
  3. 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 (and we review your supplements).

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 Quicksilver Spray is a fast oral spray containing 500 mcg of methylcobalamin per pump. Taken daily, it generally restores B12 levels to a normal range in one month. However, we do have many patients with absorption difficulties and prescribe B-12 self-administration by injection, usually weekly.

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.

Our most popular B-12 products:

Quicksilver Methylcobalamin Oral Spray 90 day supply

Perque Activated B-12 Guard 100 day supply

Integrative Therapeutics Chewable 30 day supply

If you have any questions or problems, send them along, and be sure to schedule with a WholeHealth provider to check your levels.

Be well,
David Edelberg, MD


    As someone who recovered from a severe deficiency to the point of permanent nerve and brain damage (thankfully not to a devastating degree), I must add that after my recovery plateaued to what I was calling my new normal, I began consuming lion’s mane mushrooms and noticed a dramatic effect in my mental functioning. It supports nerve growth factor, which helps neurons repair. A game changer for me. Actually a life changer.

    Your info on folate was interesting and helpful in understanding what happened to me, since I consume a lot of foods high in folate.

    Jessica Ferraro
    Posted November 1, 2023 at 12:18 pm

      Hi Jessica,

      We are glad you are recovered and experiencing full cognition.

      WholeHealth Chicago
      Posted December 23, 2023 at 12:52 pm

    Hello, Dr. Edelberg. Thank you very much for educating us. I have pernicious anemia and am taking 2500mg oral dissolvable b12 every other day. My folate level is very high although I’m talking only multivitamin and no additional b complex. What b12 supplement would you recommend for me and is there a way to bring folate level down closer to normal. Thank you very much!

    Posted October 31, 2023 at 7:21 pm

      Hi Tatiana,

      There are several reasons why you may be experiencing your imbalance. Feel free to call our office at 773-296-6700. Any one of our providers can recommend an appropriate B12 supplement and help reduce your folate levels.

      WholeHealth Chicago
      Posted December 23, 2023 at 12:54 pm

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