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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 been 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. Deb S says:

    Can you discuss the role of lithium, if any, in the absorption of B12 from blood plasma into cells? I was told that depending on their genetics, some people need more lithium or the B12 does not penetrate the cells and remains at high levels in the blood.

    • Kathleen Kazanjian says:

      For seven years I was experiencing off and on, hands and feet tingling, burning, pain, difficulty walking, extreme fatigue and depression. Countless visits to the ER and Dr. Office,checking for everything but B12. It then started where I had extreme difficulty getting dressed, had trouble feeding myself, could not write or hold a pen. Bending my neck sent electric shocks thru my body. Went to the hospital for MS testing. MRI, spinal tap, brain scan. After more testing, one Dr. checked my B12 level, it was 80. I spent 10 days in the hospital and 10 days in rehab. They were not sure if I would recover. Left untreated, B12 deficiency can cause permanent brain damage. I was lucky, everything reversed. Maybe if B12 METHYLCOBALAMIN were given early on, we might be able to help prevent MS and other brain and nerve related diseases.
      If that one Dr. didn’t check my B12 level,I would have been misdiagnosed with MS, because the symptoms are the same.
      B12 is vital for our health. It helps make DNA & RNA, your red blood cells.
      Helps with Depression,Dementia,Sleep Disorders.
      Helps with sleep-wake rhythm disorders (Circadian)
      Protects &a rebuilds the Myelin sheath covering your nerve fibers.
      Slows brain shrinkage up to 80%.
      Lowers Homocysteine levels associated with heart disease.
      If low levels are left unchecked, brain damage will occur and can become permanent.
      Helps with age related macular degeneration.
      By supplementing with sublingual Methylcobalmin B12 around 40 or 50 years of age, we could help prevent problems before they start.
      Everyone should supplement and maintain blood levels of B12 in the range from 600 to 2000 pg/ml in order to avoid and, if this is the case, help recover from the wide range of problems that result from B12 deficiency or insufficiency. Health care practitioners: this is the first thing you should check for every patient that comes in, independently of their age or condition

      Methylcobalamin: This is the neurologically active form of B12. It is technically a `coenzyme` of vitamin B12 and it is almost never prescribed by doctors despite being effective, readily available and inexpensive. It is also available in an injectable form. Degenerative neurological conditions are where methylcobalamin shows its greatest benefits over other cobalamin preparations. Brilliant news for MS’ers! Not only has Methylcobalamin been shown to work in neurologic diseases, it also helps with the elimination of toxic substances in the body.

  2. Teresa Strong says:

    I have another story of how B12 deficiency can be missed. For a number of years, my doctors saw I had megoblastic anemia, but my b12 and folic acid were very high. It was finally discovered that I have MTHFR C677T genetic defect which can give you both B12 and folic acid deficiency while giving you high B12 and folic acid levels because your body cannot break down synthetic B12 and folic acid into useable forms.

  3. Irene Frederick says:

    Dr. E . . . Your articles are THE best… clearly understandable,
    with all the info needed so a person may incorporate a new plan of action, if they choose. I appreciate the time and energy you put into writing these articles . . . THANK YOU!!!!

  4. sam barbary says:

    Can you have a normal methymalonic acid level result which would indicate normal B-12 levela and still be B-12 deficient? I have heard that if one does not have the cofactors to synthesize B-12, symptoms of B-12 deficiency would still exist. So the real question is how do you know if you have the correct cofactors? Basically, you are deficient if your body cant absorb or sythesize it even though you consume enough B-12.

    Thank you


  5. Beth says:

    Dr. E, is salcaprozate still effective if someone’s intrinsic factor is depleted?

    • Goran says:

      I have 390pg /ml b12 and my doctor says its normal but I’ve been experiencing planty of symptoms despite the normal result, depression, anxiety, disorientation double vision, balance problems, lack of focus, poor concentration, sensitive to light, dizziness if i try to lay down on othet bad numbness, tingling, tremors, hot sweats around my neck, insomnia and etc.. I’m 33 year old male. I desperately want to know how much shoud my b12 lvls be to be symptoms free.. I rly appreciate of some of u give me a proper answer.

  6. Cathy says:

    Can low b12 cause hair loss? I had my colon removed and a jpouch made from the lower third of my small intestine due to ulcerative colitis. I

  7. Davis S. says:

    Teresa Strong, it sounds like I might be in the same boat as you. How are you treating your MTHFR situation…your whole situation in general? Thanks!

  8. Dr E says:

    Hi Debra
    The association between B12 and lithium is simply úncertain´at this point. An association is theoretically possible but not clinically evident.

    Hi Teresa
    Yours is a typical MTHFR story. If your doctor suspects B12 or folate deficiencies and the levels come back elevated, ask for an MTHFR test. If positive, you´ll need the methyl forms of both folate and B12 but you´ll need to start with low doses as you´ll be sensitive to the sudden rush as these nutritionals become available to your cells

    Hi Sam
    Basically, see the above note and get MTHFR testing.

    Hi Beth
    According to the published data, the answer to your question is ýes but look at the company´s website and as it is a small company, I suspect they´ll answer your question personally

    Hi Cathy
    The answer is ýes

    Dr E

  9. Cheryl T says:

    If you have MTHFR you need to determine if you are an overmethylator or undermethylator. If you are an undermethylator you would take Methylcobalamin and methylfolate. If you are an overmethylator like I am you cannot take methyls. So I take Hydroxo B12 and folinic acid. I take a prescription called Leucovorin which is folinic acid.

  10. Kathleen pepsnik- good says:

    Thank you for what you do . You really are the healer
    People need. I pray for you – you are the best!!!!!

  11. Karen C says:

    I have been reading a lot about b12 deficiency and wonder if it can can cause hair loss? I had mine tested and it was around 450, but I do have other symptoms along with the hair loss.

  12. Dr E says:

    Hi Karen C
    Although low B-12 can cause hair loss, your level is okay and should not be the culprit. The three commonest causes of hair loss are: stress; underactive thyroid (even minimally underactive thyroid); low iron.
    Have your doctor run appropriate tests if these have not been done

  13. Robert S says:

    I actually have been taking Eligen B12, the product you mentioned, since late March, because of my pernicious anemia, which caused my B12 levels to sink as low as 200 at one point. Since my doctor put me on it in late March my levels have been consistently around 2000pg/ml! I had been taking OTC B12 sublingual 1000mg but because of my condition my doc told me I was not absorbing the B12 and passing most of it, so my levels had not been improving.

  14. Pearl M says:

    I’ve been to 3 major Chicago universities and then Mayo, all in the last 8 months.
    I’m getting sicker and sicker and have lost 26 lbs in the last 7 weeks.
    I’ve now learned my serum B12 is >2000 BUT my transcobalamin or B12 binding capacity is critically low at <88 (normal range 65-1340). Hematologist doesn't know what to do with me. Bone marrow biopsy two weeks ago came back normal

  15. Kathleen Hough says:

    There is a wonderful liquid vegan safe B12 product by Global Healing Center. it has 2500 mcg of B12 as 80% methylcobalamin, 20% adenosylcobalamin. I have been taking this for a couple of months and have seen increased energy, and no more brain fog.

    It is recommended by Anthony William, Medical Medium as one of the most imp. supplements. He has a book coming out this month you might want to consider.

  16. KS says:

    Hi. I had a strange event while driving a few weeks ago where I felt tingling in both hands (pinkies and thumbs), swimming vision (not blurry or fuzzy), weak knees/legs, and a flash of energy in my chest (without racing heart or pulse). For a few weeks before, I’ve had very negative thoughts (highly unusual for me, a very happy person). Symptoms are on-going and easing up (significantly after one session of acupuncture). Went to an integrative health cardiologist; EKG was normal. After researching your excellent site, I thought for sure this could be Vitamin B12 and/or D deficiency. Received blood test results today which are normal — no MTHFR mutation, B12 (623), D (300), TSH (2.05), T4 (5.4), T3 (83), Free T4 (0.98), Free T3 (2.31). Low omegas though (3.8). I have half my thyroid (no supplement) and stage IV endometriosis. Otherwise, “good” health. Ideas on what’s going on? Thank you.

  17. Dr E says:

    Hi KS
    All your numbers are indeed excellent. The abruptness of the symptoms and their quick resolution sounds most like a hypoglycemic episode (low blood sugar). Think about what you ate (or did not eat) that day and see if this is a possibility

    • KS says:

      Thanks, Doc. I appreciate you taking the time to reply. It’s so odd, as the symptoms are intermittent across a few weeks now (although receding), with a burst of finger tingling (10 minute events occurring twice), sometimes accompanied by or followed by very anxious or negative thoughts. Never had a panic attack or reason for it (thankfully), but I wonder if that’s a cause for these symptoms over the past few weeks. I’ll keep a food log to watch the hypoglycemia angle too. Thanks again.

  18. Bev Dawn says:

    Hello Dr D.E.
    I really appreciate all your comments here it is very kind of you to take the time most sites ask for payment which I don’t have. I also thank those that pose the Q’s. It has made things a lot clearer. Even though I am still a little confused as to whether or not to have the injections my doc has said is the best and quickest way to bring my level back up or to ask if I could have the Eligin B12. I have read some reviews that patients say themselves…of being very unwell even wks and months after having the injections .. In fact all the same symptoms that I am having due to the lack of B12.. This I find very strange, one would think that these symptoms should / would be much less not worse! ( Or could it be that they are not absorbing the B12 from the injections?). On the other hand I read that the Eligin B12 is not as quick or as effective as the injections.
    I went for a pre op and they found my platelets low – 50 instead of 150. I then told them of all my symptoms which I put down to my poor / loss of appetite and age -62- Yet working and very active – family saying I was overdoing things. They took further blood test and said that everything was fine but for the B12 which was very low but did not give me a reading. Could you suggest … Injections or Oral.
    Kind Regards
    Bev 🙂 🙂

  19. P Marie says:

    Dr Edelberg
    Can you explain why my B12 level is over 2000, but my blood smear shows macrocytes and my MCV is 102 and the B12 binding capacity test is <80, done at Quest.

    My doctor says I'm not deficient because B12 is over 2000!

  20. Dr E says:

    Hi P Marie
    Actually there are several causes of macrocytosis and B-12 deficiency is only one of them. Most macrocytosis is harmless but it might be worthwhile consulting with a hematologist (blood specialist)

    • P Marie says:

      I’ve seen two hematologist: one at Rush and one at Mayo. Mayo only was concerned about ruling out myeloprolific diseases, leukemias, etc.
      No one addressed my elevated MCV and macrocytes. RBCs on the low side.
      Been getting chest pressure. Cardiac ruled out.
      Also positive for the IFBA and MTHFR compound heterozygous.

  21. Jennifer says:

    Hello Dr Edelber,

    I found your article to be very enlightening. Have been suffering from a number if symptoms, but I find the breathlessness to be the most difficult to deal with. Lab results: MCV 98, MCH 32.6, MCHC 33.2, B12 206. Told there isn’t a problem with labs and referred for a sleep study. Have had lipid panel (all good), stress test (great results), but am wondering if I need to find a different doctor or if his advice seems within reason.

  22. STam says:

    My 11 year old son has a history of fevers, infections, night terrors and anxiety. His immunologist ran several tests to rule out immune deficiency; these tests included a B12 binding Capacity test. His serum B12 was normal and his Folic Acid levels were high, the binding test also came back low. What are our next steps here – the immunologist told us to refer to our primary care doctor…..and they also are not sure what to do???!!

  23. Cecilia says:

    HI there, I have had low levels of b12 in the past and even had some neurological symptoms, which after ruling out others things via MRI etc the neurologist pointed to low B12 as the culprit (200s this was about 4 years ago). I have been having issues in my legs again (some burning, muscle cramping etc) and wanted to see if my levels were low again.Recently I have been taking b12 vitamins and wonder if this could somehow mask the blood results if I took a good amount of vitamins in the days leading up to the blood test? I asked about a MMA test and Homosystene test but my doc declined to do those unfortunately. My test last week read normal ( 700s)but I was taking the oral 5000 once daily in the few days leading up to it. I am a strict vegetarian and try to get all my vitamins through food clearly I have a history of running low. Just wondering if those other tests could indicate a deficiency even with a normal B12 serum? My hemoglobin was normal. Any suggestions or thoughts would be welcome. Thank you

  24. Dr E says:

    Hi Cecilia
    There are other causes for your symptoms than low B12. It sounds as if your neurologist is a good diagnostician. Tell him about these and let him choose what tests would be helpful

  25. Som says:

    After my annual exam, my b12 leve was 358, whihc is in range but on lower side. I am veggie, but do take dairy products daily. Doc advised to jsut take 1000mcg sublingual b12 supplement. I started taking it. but with 506 days I started getting weird sensation in my legs… its like sweetish pain/sensation/tingling…while walking its better but can feel more when resting bed. What is this?

    • Dr. R says:

      Hi Som. There are many possible reasons for your symptoms. Speak with your primary care physician for re-testing of B12 as well as vitamin D, CBC, CMP, and thyroid panel. Hopefully, you’ll be able to uncover some additional clues.

  26. Som says:

    thanks. my vit D is low at 18 and so taking the booster weekly dose. thyroid is good (2.1). RBC WBS all are in range. Blood pressure/urine all are good. I never had these symptoms. Only began once I started with sublingual b12 (cyanocobalamin).

  27. Mary says:

    If you are still around–is Methylmalonic acid level always elevated in B12 deficiency? Diagnosed with B12 neuromyelopathy but my MMA has always been normal (lower end of normal to be exact). Thanks if you see this and answer.

  28. Dr E says:

    Hi Mary
    This may be due to you being in the third of patients who carry a gene called MTHFR. This is an easy test for your doctor to run and if you are ‘positive’ you may be taking the wrong form of B12, cobalamin instead of methylcobalamin. Discuss with your doctor

  29. Mary says:

    Also, does MMA return to normal in B12 shots?

  30. Alina J. says:

    Hi Dr. E,

    If you’re still active on this thread, I would highly appreciate your opinion on this.

    My husband has B12 deficiency, his levels are around 160.
    The doctor recommended B12 injections (50 mcg) once every month, but I wonder if that is the appropriate dosage since there’s been no improvement in his symptoms.
    He still has numbness and tingling in his hands and feet, fatigue, weakness in his legs.

    Also he has constant hip pain.. could this be related to the B12 deficiency? We went to the specialist for this issue and they said everything is fine, they don’t know where the pain could come from.

    Thank you!!

  31. Dr E says:

    His B12 dose is inadequate. He should be on 1,000 mcg injections every week until his blood level is between 900 and 1,000. He should be tested for failure to absorb B-12. The test is called Intrinsic Factor Antibody. If it is positive, once his levels are normal, he will need monthly injections for life.
    The symptoms are most likely B12 deficiency but may take weeks to months to resolve even if blood levels return to normal

  32. Nancy says:

    Hi Dr,
    I had a 313 b-12 serum, but with symptoms. I convinced my Dr to order the MMA and Homosysteine and the MMA was (493) and the Homosysteine was just 1 point over the high limit for the lab. I am still waiting on the IF factor results. Doctor has yet to speal with me, but am I still considered deficient if the homosysteine is just 1 point over high? These symptoms started 3 years ago and more symptoms have come up and gotten worse.

  33. Dr E says:

    You are B12 deficient and you would likely benefit from B12 injections

  34. Hi Dr. Edelberg!
    I’m a new practicing provider (just graduated with my DNP from Rush actually 🙂 and was wondering if you could help me with a new patient case?
    – Pt is 32yo F with extensive PMH who presents with 8 month hx of pain, numbness & tingling in her BLE, and recently has worsened constant sensation of cold feet as well as worsening numbness causing periodic falls during her normal daily activity. Other medical hx includes (not limited to): fatigue, HA, IBS, vertigo, GERD, Back pain, Iron def anemia, constipation, adrenal insufficiency..
    Historically w/her chronic back pain, I ordered lumbar and c spine xrays, both normal besides mild degenerative disc space changes to c5-6.
    I then ordered an EMG- normal, no evidence of radiculopathy ,plexopathy, or mononeuropathy. Motor recruitment and units all normal.

    -Recent (limited) blood work 2/2019 :
    B12 binding capacity-636
    Hct 34.5 ( noticed this is the only CBC value consistently low for pt in past 5-6 yrs)
    All other values for CBC, TSH, Free T4, Iron, and Ferritin normal.
    In 2/2018 Folate- 16.8 & B12-640

    I will seeing this patient again soon for further workup, and the lab tests I’m thinking about around are:
    CMP, Vit D, Folic acid, ESR, Methylmalonic acid, serum homocysteine, IF antibody

    I’d SO appreciate your time and thoughts. Do you have any suggestions or corrections to those labs listed and/or my diagnostic workup-train of thought? (I want to make sure my ordered tests are appropriate and not ‘overboard’) Very curious to hear your input! Thanks Dr. E!

  35. Dr E says:

    Hi Molly
    Did you actually send that at 2AM?!
    For a female in that age group with”unexplained” neuro symptoms, MS needs to be considered. I suggest consulting with a neurologist. Over at Rush, you’ve got the best MSspecialists in the Midwest

  36. Tom says:

    Hi Dr. E… if you are still answering I would love to hear your thoughts. I have been experiencing some recent issues that I thought might be B12 deficiency. Numbness in left leg and foot and left arm. Exhaustion and complete loss of energy. Depression. I have had some health issue the last few months and had lost 30ish pounds and was eating a lot less mostly due to GERD concerns. I was put on high dosage of Omeprazole (40mg twice a day) about 2 months back by primary care and GI. I suspected b12 for a few reasons with the meds and the fact that I know my sister has MTHFR mutation. I started taking 5000mcg of methol b12 daily about a week ago and had a blood test come back as 623 today. Is there a chance that the supplement spiked my b12 and may be hiding the deficiency? I am curious what could happen to my numbers if I am carrier of MTHFR that started taking such a high dose of methyl b12 in just a few days.

    Also, for reference my d3 came back low (20) so I am starting to take that. Also for reference I am a fairly healthy 50 year old male who has never had issue with mood or depression before these last few months.

    Thank you in advance and for all your help!

  37. Dr E says:

    Have your doc give you weekly methylcobalamin injections at least for a month PLUS a prescription for Vit D3 50,000 IU weekly for 8 weeks. Then see if you feel better. Both treatments are harmless

  38. Dino says:

    Dear Dr E.,

    You’re advise and help with the medical community is greatly appreciated from us all. I wanted to see if you perhaps had any advice for me here. I’ve been suffering severe neurological symptoms for the last 6-7 months – tingling, cramping, burning, muscle weakness, fatigue, pain particularly in legs and FEET. I was taking a multivitamin which had about 15 times RDA of B6, which I’m aware is linked to peripheral neuropathy through B6 toxicity. My blood level for B6 shows 65.3 on a scale of 2-21.7. Simultaneously, I am pretty much a vegetarian eater for years with small quantities of fish only, up until about 2 months ago when I started eating chicken and turkey again. My B12 blood level came back normal but high at 1050. I read about homocysteine and methylmalonic acid being the more trusted markers of B12 deficiency as B12 plasma can sometimes yield false positive normal or high results do to malabsorption or genetic mutation? My homocysteine is elevated normal at 10.8 (scale supposed to be less than 11.4) and methylmalonic acid is also elevated normal 317 (scale 87-318).

    At what point would you decide a patient like myself might be B12 deficient and advise supplementing with injection or pill. If malabsorption due to low stomach acid, etc is a factor, then would tongue dissolvable B12 supplements be a better suggestion? Is it safe for me to try supplementing daily even though my level is 1050 currently? If so, at what point would you advise retesting either MMA or homocysteine to see if those levels are dropping?

    Thanks for your advice in advance.



  39. Dr E says:

    Hi Dino
    I think the B6 excess is the villain here. Your symptoms are common in patient who arrive with levels such as yours. Stop all supplement sources of B6 for 3 months and see how things go. Also get tested for MTHFR gener

  40. Elise Phipps says:

    Great article! I received test results back with very very low B12 binding capacity, extremely high circulating b12, but lymphocyte levels of b12 in the deficiency status. Low RDW, and transferin saturation over 84%. It seems all the b12 I am taking- both oral hydrocobalamin and methyl are not actually getting absorbed in the cell. Do you have experience treating the binding capacity issue? I cannot find any articles or Doctors that reference treatment. Thank you in advance!

    • cliffmaurer says:

      Hi Elise – When you refer to binding capacity is this for B12 or for iron? Typically when we talk about binding capacity in this context is is for iron. But in any case, if your B12 levels are not improving on oral supplementation, sometimes physicians at WHC will recommend periodic B12 injections instead.
      Hope this helps,
      Dr M.

  41. Nicky says:

    Hi , do you know how long you have to be off a b12 supplement to check ur levels , to see if ur high b12 is coming from supplement or natural . Also what does a slightly low mma test mean if ur b12 ranged from normal to super high . ( also have mthfr ) but i have rediculous symptoms of zero energy neurological etc

    • cliffmaurer says:

      Hi Nicky – A lot of this depends on how deficient you were and why you had the deficiency. Often times, B12 supplementation needs to be maintained. This is definitely a question suited for whomever recommended the B12 for you so that you get a response tailored to your situation.
      Dr M

  42. Tomas says:

    Hello, I hope someone is able to help me with advice. After getting sudden panic attacks, anxiety, difficulty breathing and tingling sensations in my back, arms and fingers out of the blue and for 2 months I recently got tested and had the following lab results:

    b12 236
    VitD 44.34
    Hemoglobin 14.2
    MCV 89.4
    MCH 27.9
    MCHC 31.2

    (Everything else was well within range, including Thyroid markers.)

    Also a bunch of parasites including Giardia, Tenia Soleum, Blastocystis Hominis, Endolimax Nana and Campylobacter.

    The parasites have been eliminated and the panic attacks and anxiety are 95% gone, however Dr ordered daily sublingual 5000 mcg B12-lozenges for a month and I’ve been taking them for a couple of days but tingling and breathing symptoms seem to stay the same although intermittently (feel somewhat better after I have a large meal).

    Am I missing other tests/ doing something wrong or is it simply way too early to tell?

    Thank you!

  43. Dr E says:

    B12 of 236 is very low. Ask your doctor to test to see if you have the MTHFR gene which, if present, would mean you must use methylcobalamin instead of the usual cyanocobalamin. You need additional testing to see if you have a defect in absorbing B12 and you need your B12 administered by injection. The ‘nerve’ B12 symptoms may tale weeks to months to improve

  44. Nikki says:

    Hi, I have low B12, 266, so my regular dr. ordered me to take 500mcg daily. But, I’ve also had pins & needles for 14 years & bad OCD symptoms lately. At first, I was ordered to take 1000 of folic acid in the hospital, iron supplement, & then my regular Dr. after the hospital noticed my low B12 and ordered a supplement. So, my Dr. said she’ll recheck B12 in 3 months. Do I need any other tests now or just wait to retest in 3 months my B12?

    • cliffmaurer says:

      Hi Nikki

      Your symptoms could be arising from a number of places but it makes sense to do a trial of B12 then retest before going down other diagnostic roads. If you’re in the area and would like a second opinion, I recommend our integrative nurse practitioner Wendy Ploegstra as someone who might be able to help.

      Take good care, and best wishes!
      -Dr M

  45. Marta says:

    Dear Drs,
    I hope it is not too late to write here asking for advice.
    In November 2018 I started experiencing fatigue, weakness, shortness of breath and irritability. For the following few months the symptoms were worsening to the point where couldn’t walk for 200m without muscle cramps and falling over my own legs. I was experiencing depressive and anxiety episodes, my arms and legs were shaking whenever at rest, my memory was gone and eyesight slightly deteriorating. I was honestly fearing an early onset of MS (I am 24 yo female) but then found online information about B12 and got tested. The results came back at 107, way below the norm, however my GP was deflecting my requests for help for two months until referring me to my endocrinologist because “either that is the cause or I need to go to a psychiatrist”.
    I have Hashimoto disease but my thyroid levels are all good (TSH oscillating 1.5-1.7, other markers good too). Thankfully the endocrinologist took me seriously and advised 1000mcg of methylocobalamin sublingually every day for a month, then every other day and after 2-3 months new tests to see whether it works. After a few weeks of supplementation I was feeling better but still not great, set my tests and appointment for two months later, just before I was set to move abroad. Unfortunately the office cancelled the appointment and tried to reschedule for the time I would be abroad already. Since then I’ve been trying to get help from local health services with no avail.
    I ended up taking the 1000mcg dose every day since April 2019 and over the summer months I was feeling acceptable. However now for the last couple of months I’ve been getting worse with the depression and anxiety returning, balance issues, shaking and weak legs, bad memory, shortness of breath, heart palpitations. I seem to forget what I was talking about in the middle of the sentence.
    On 9 Oct I was tested for serum B12 and basic blood – result B12 (231) in a test taken 24h after the last sublingual pill and blood tests all within range (MCV 87 so normal). The doctor says my level is “perfect” and that I can try taking two pills per day but it’s not the reason of my symptoms. She offered me a mix of SSRIs, muscle relaxants and beta blockers, saying that prescribing B12 shots to a person who doesn’t need them would be “unethical”.
    My question is, do you think my B12 is normal or could the symptoms be linked to that? I’ve been taking 2000mcg of methylocobalamin for the last 10 days and the heart palpitations have basically stopped as well as balance issues, but others remain.
    I guess I’m hoping for reassurance that I’m not crazy and for some direction about what to do next. As a poor student in a foreign country I only have access to that one student health services office.

    • cliffmaurer says:

      Hi Marta –

      This is quite a complex history, especially involving the Hashimotos diagnosis. It’s great news that you started feeling better after the sublingual treatment, but if you feel you have symptoms that have not been addressed and/or would just like a second opinion, I recommend discussing your complete health picture with a qualified functional medicine practitioner. If you’re in the Chicago, any of our physicians or nurse practitioners would be happy to see you for a thorough overview. These symptoms and conditions can overlap and become complex; your health certainly deserves a thorough work-up and conversation.

      Hope this helps,
      Dr M

      • Kelly Schlunegger says:

        As a patient with APS ( antiphospholipid syndrome) it might be worth checking antibodies.

        Hashimotos, low b12, balance issues, vision issues, often are hallmarks of APS . ( before it leads to clotting)

        Quite often patients are sent to neurologists for a work up to rule our MS befor arriving at a diagnosis of APS.

  46. Goran says:

    My result of b12 is 390 pg and i still have symptoms like depression, brain fog, low energy, shortness of breath, anxiety poor concentration, and more.. Can someone give me a answer what should my lvls be to be symptoms free? Pls..

    • cliffmaurer says:

      Hi Goran –

      390 is quite low for B12, and we often see patients with similar symptoms who are in this range. I highly suggest working with your healthcare provider to improve this value, and also discuss other reasons you might be experiencing these symptoms. If you’re in the Chicago area, any of our physicians or nurse practitioners can see you for these issues for an outside opinion.

      Hope this helps,
      Dr M

  47. Hillary says:

    Hi, I am a disabled chronic pain patient due to radiculopathy, myofascial pain syndrome, and degenerative disc disease. I also have chronic proctitis which I am currently working with my GI doctor to determine if it has progressed to another form of UC. In doing so, he ordered a series of tests one of which is B12; my result being 412. That is coming back as normal and within range, however, I came across your website and wanted to get your opinion to see if it is perhaps a possible deficiency. I have many of the symptoms similar to those indicated in your article: pain, numbness/tingling in extremities, hand tremors, unexplained falls, fatigue/painsomnia, brain fog, cold limbs, nausea, loss of appetite, poor digestion, and recently blurry vision (not sure if that might be related). I already take a daily vitamin that has B12 in it too (albeit only 6 mcg). I know this is probably a stretch, I’ve been desperately searching for something that could help with my various symptoms for years but, even if it could just help alleviate some of my symptoms I’d be extremely grateful. Thank you in advance for your time.

    ~ Hillary

    • cliffmaurer says:

      Hi Hillary –
      Your B12 level is low enough to be concerning that it might be playing a role here. I recommend discussing different ways to supplement B12 with your primary care provider. If you’re in or around Chicago, feel free to schedule a consultation with one of our primary care providers at the Center. If you’re outside of the area, this is a good tool to help find a functional medicine provider: https://www.ifm.org/find-a-practitioner/

      I hope this helps, and wish you sincere luck.


  48. Jill says:

    I am not sure if you are still responding on this thread or not but I would love an opinion from you as this article has some of the best information I have found!

    And this may be long winded!
    I am a 31 year old female, 5’5″ 140lb, I have been a vegetarian for 13 years, and about 10 years ago my doctor at the time told me I had low B12 (145pg) after I complained about being tired all of the time and to take a supplement and check it again in a few months – the next time I checked it it was somewhere around 500pg and he said it looks like I can absorb it from a supplement so I moved on and sort of forgot about it and just made sure I was always eating lots of eggs and taking a b12 supplement off and on.

    In the last 4 years I have had two ekg’s from two other doctors for heart pain and fluttering, and also told them I am extremely short of breath all of the time and both told me my heart looked fine and that I just have anxiety(I know how I feel when I have anxiety and this is not it), no bloodwork was ordered for this.

    I also went to the emergency department about 5 years ago due to numbness in one side of my face and I was concerned of a stroke(it lasted about a month – numbness with slight nerve pain), I had a CT scan and since it appeared fine I was told that I probably just had a virus on my trigeminal nerve and it was not investigated further.

    I have only had blood work a couple of times in the last 10 years and my doctor never mentioned anything looking off. I recently have been doing research because I know that something is not right with me, so I ordered an at home basic vitamin blood test and received my results last week and my b12 was 395pg – which I am aware that based on Canadian standards this is not considered “low”, but some people may still experience symptoms.

    So after this, I had my doctors receptionist send me my blood work from last November as this was the last time I had blood work done, just so I could begin to keep an eye on it myself, and at that time my B12 was 414pg – so again, no cause for concern on paper but I would still consider that marginally low especially where I try so hard to make sure I consume tons of eggs and take supplements..

    What concerned me when I received that blood work however were the other lines that showed up in red:

    Red blood count – 3.99
    Mean Corpuscular Hemoglobin – 31.3
    Platelets – 454

    Which again, are not severely out of the standards but I would think it would be something that we should be keeping an eye on? I know I was feeling better than usual at the time of that blood work as well.

    Other numbers within the standards were:
    Ferritin 17.04 ug/L
    Hemoglobin 125 g/L
    Hematocrit 37%

    I am aware that a higher consumption of folate can mask a B12 deficiency and I am wondering if this may be my problem that I have been having and how I should go about investigating this further(or whether you feel that I should try to investigate this further)

    A few other symptoms that I have always had (many of which from before I was a vegetarian):

    -Cognitive issues (extreme brain fog, feeling like I’m in a dream sometimes)

    -Memory loss(forgetting very basic things, memories don’t feel real and more like I dreamed the things that I did last month)

    -Extreme fatigue(Cannot wake up ever, and need naps often. I have slept through alarms and have been late for work – the last time it happened, just last week, I only woke up after 10am and I hadn’t even stayed up late the night before)

    -Numbness mostly in hands and feet

    -Migraines with aura, and regular headaches

    -Vision issues (sometimes a slight eye twitch that will last months on end, sometimes lettering on the tv will appear to be vibrating despite having 20/20 vision)

    -I have fainted on multiple occasions ( half of the times prior to being vegetarian)

    -I can hear myself blink from inside my head if that makes any sense!

    -People often tell me I look pale or tired

    -My resting heart rate is often high, like 90bmp, and if I stand up quickly it will shoot up to 130bmp – even when I was a kid if I stood up quickly my vision would sometimes go black.

    So, I feel like I am always complaining or making excuses for how I feel, and I’m sure I probably sound like a hypochondriac – but I just need to find some sort of answers for how I am feeling because I feel like this cant be normal!

    Based on all of this, do you feel like this is related to my b12? Or is there some sort of other test I should be asking for? I have been taking 2500mcg of b12 twice a day for the last two weeks but I am not feeling any better yet – I know this takes time though.

    I know I put a lot of info in there, and if I don’t get a response I totally understand but I figured it was worth a shot!



    • cliffmaurer says:

      Hi Jill,
      This is certainly a complex history and deserving of much more than an email or post. Please consider scheduling a telemedicine visit with one of our functional medicine practitioners. They can go through your history and symptoms with you, recommend testing, and help you get to the bottom of this. You can schedule a telemedicine consultation by calling our scheduling staff at 773-296-6700.
      Hope this helps!
      -Dr M

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Far and away, the commonest phone call/e mail I receive asks about COVID-19 diagnosis.
Just print this out, tape it on your refrigerator door, and stay calm.


• Runny nose
• Sneezing
• Red, swollen eyes
• Itchy eyes and nose
• Tickly throat
• No fever

• Runny nose
• Sneezing
• Sore throat
• Mild muscle aches
• Mild dry cough
• Rarely a low fever

• Painful sore throat
• Hurts to swallow
• Swollen glands in neck
• Fever

FLU (Standard seasonal flu)
• Fever
• Dry cough (no mucus)
• Sudden onset over few hours
• Headache
• Sore throat
• Fatigue, sometimes quite severe
• Muscle aches, sometimes quite severe
• Rarely, diarrhea

• Shortness of breath
• Fever (usually above 100 degrees)
• Dry cough (no mucus)
• Slow onset (2-14 days)
• Mild muscle aches
• Mild fatigue
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