IMPORTANT INFORMATION FOR CLINICIANS

PROBLEMS WITH DIAGNOSING B12 DEFICIENCY

• The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin

status since there is no ‘gold standard’ test to define deficiency.

• Serum cobalamin remains the first line test currently, with additional second line plasma methylmalonic acid to

help clarify uncertainties of underlying biochemical/functional deficiencies. Serum holotranscobalamin has the

potential as a first line test, but an indeterminate ‘grey area’ may still exist. Plasma homocysteine may be helpful as

a second line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited.

• Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of

methodologies used and technical issues, and local reference ranges should be established.

• In the presence of discordance between the test result and strong clinical features of deficiency, treatment should

not be delayed to avoid neurological impairment.

Problems with the Current B12 Assay

• There are serious problems with patients receiving an accurate and timely diagnosis of B12 deficiency. A recently

published survey of patients’ experiences showed that one-third of patients experienced symptoms for up to 1 year

before diagnosis; 21% waited over two years, 19% waited over five years and 14% waited for more than 10 years for

a correct explanation for their symptoms1

• Before being diagnosed as having pernicious anaemia 44% of patients surveyed were initially given an incorrect

explanation for their symptoms1

.

• The reason for the above is probably due the current assay used to determine B12 status (the Combined Binding

Luminescence Assay) which gives false high results in between 22-35% of tests3

.

• There is an erroneous belief that B12 deficiency cannot occur without macrocytosis or anaemia. In a study of 70

consecutive patients with pernicious anaemia only 45 (64%) had very low cobalamin levels (i.e. under 100pg/ml).

Anaemia was absent in 13 (19%) and macrocytosis was absent in 23 (33%)4.

• Do not rule out a diagnosis of vitamin B12 deficiency based solely on the absence of either anaemia or

macrocytosis2

.

• Another report showed that among 141 consecutive patients with neuropsychiatric abnormalities due to cobalamin

deficiency 40 (38%) had no anaemia or macrocytosis5

.

SUMMARY

Whilst it is now recognised that there are serious issues with relying on the current assay to determine B12 deficiency

there is no ‘gold standard’ alternative test.

Replacement therapy B12 is extremely safe as well as being cheap. There is

no danger of overdosing on B12 and so you may want to consider a therapeutic trial of injections if the patient’s clinical

picture suggests a deficiency which is not confirmed by the result of the assay.

1. Hooper et al, British Journal of Nursing, 2014, Vol. 23, No. 7

2. NICE Guideline: Vitamin B12 deficiency in over 16s: diagnosis and management March 2024

3. Carmel, R and Agrawal, YP,(2012), Failures of Cobalamin Assays in Pernicious Anemia; New England Journal of Medicine: 367:385-386. See also -

D. T. Yang and R. J. Cook: 2012: Spurious Elevations of Vitamin B12 with Pernicious Anemia; New England Journal of Medicine; 366;18

1. Beck, WS (1991): Neuropsychiatric Consequences of Cobalamin Deficiency; Advanced Internal Medicine; 1991;36:33-56.

2. Lindenbaum et al; Neuropsychiatric Disorders caused by Cobalamin Deficiency in the Absence of Anaemia or Macrocytosis; N Engl J Med 1988;

318:1720-1728

1. Devalia V, Hamilton M, Molloy A; Guidelines for the Diagnosis and Treatment of Cobalamin and Folate Disorders; British Journal of Haematology,

2014,166,496-513

Asking this question since I took it without any requirement and I felt a lot of energy and I was unable to sleep for few days after taking Methylcobalamin Vitamin B12 for few days(I took it in the morning before food).

I have a teenage daughter. She’s been stable on lexapro for over two years now. She was prescribed lexapro for anxiety and it’s helped her so much. She has really done a 180.
Up until last week….
The first thing I noticed was her speech. Talking so fast, I could barely keep up. And if I interjected in any way she would lose her train of thought. She was also complaining up joint pain, and she pretty much had no short term memory.
This was followed by angry outbursts, and eventually a full blow panic attack that landed her in the ER. They suggested it could be an issue with her ssri, which I thought was unlikely since she hasn’t had any issues in over two years.
The ER visit was overall unhelpful. We were told to follow up with primary care, which we did. After explaining all of her symptoms-her doctor immediately thought it was b12 deficiency. We don’t have test results yet, but this doctor was extremely confident.
Is this not something that they can test for in the ER? They didn’t even mention it being a possibility.
I’m glad to have found this community because it looks like there’s tons of great info here!

I was diagnosed with vulvodynia yesterday. Dr confirmed it's most likely due to neuropathic pain.
Fully believed me about vitamin, iron deficiencies.
I was prescribed 10% lidocaine + 40% vaseline + other stuff in a custom made cream.
Anyone else has vulvodynia and wants to share their experience ?

Sometimes you get help where you the least expect it. She told me my PCP did a "medical error" and said "that's wild" that he didn't test me for b12 deficiency despite 2 years of limb neuro symptoms.

Was diagnosed with 94 pg/ml B12 deficiency in February.

​

Hi everyone! I'm looking for some insight from people who have experience with B12 deficiency, particularly anyone who has dealt with figuring out the underlying cause.

I'm in my 30s and recently had bloodwork after experiencing worsening fatigue and other symptoms. My results were:

Vitamin B12: 74 pmol/L

Ferritin: 17 µg/L

Hemoglobin: 135 g/L (normal)

MCV: 92 fL (normal)

My symptoms

I've been feeling increasingly exhausted for months, but things became noticeably worse when I returned to work as a teacher in September. I'm tired even after sleeping, have very little energy, and feel mentally drained and foggy by the end of the workday. I've also noticed that I sometimes mix up words or call students by the wrong names, which isn't typical for me.

Other symptoms have included dizziness, feeling weak and generally unwell, occasional shortness of breath/chest tightness, and a resting heart rate around 100 bpm. I had a chest X-ray, which didn't show anything concerning. My symptoms were getting to the point that I was really struggling with working as a grade 1 teacher full time and wondering if I needed to take time off.

I've also had intermittent digestive issues for years, including episodes of cramping and diarrhea, sometimes during or shortly after meals. Coffee alone can trigger diarrhea, and occasionally the diarrhea wakes me from sleep. Recently, I've also noticed that my clothes seem looser around my hips and backside, although I haven't confirmed any weight loss on a scale.

Treatment so far

My doctor started me on B12 injections: daily injections for 7 days, followed by monthly injections for 6 months. I've completed the initial 7-day loading course. I'm also taking 300 mg ferrous fumarate daily for my low ferritin.

I've noticed some improvement in my energy since starting the B12 injections.

Investigations into the cause

My doctor ordered several additional tests, including:

Tissue transglutaminase IgA (celiac screen): negative, less than 0.5. I was eating gluten regularly at the time.

Parietal cell antibodies: negative.

Intrinsic factor antibodies: ordered, but apparently it was unavailable and not performed by the lab, so I don't have a result.

Helicobacter pylori IgG: negative.

Smooth muscle antibodies and mitochondrial antibodies: negative.

My sister was also recently diagnosed with celiac disease, so that has been on my mind. I know a negative celiac screen doesn't necessarily answer every question about why someone might have low B12 or iron.

My doctor doesn't seem particularly concerned about malabsorption and has said he doesn't think that's the issue. The current plan seems to be to repeat my bloodwork in three months.

What I'm concerned about

I'm worried that my B12 will look normal after several months of injections, but that won't necessarily tell us why it was so low in the first place. If the underlying issue isn't addressed, could my levels simply drop again if treatment is reduced or stopped?

I'm also wondering whether having both low B12 and low ferritin, despite normal hemoglobin and MCV, should prompt further investigation. I'm not sure whether my longstanding digestive symptoms are relevant or a separate issue.

I'd really appreciate hearing from anyone who has experienced something similar, especially:

Did you find out what caused your deficiency?

Were intrinsic factor antibodies, parietal cell antibodies, or other tests helpful in identifying the cause?

If your intrinsic factor antibody test was negative, did you need further testing for pernicious anemia or other causes of malabsorption?

Did anyone have negative celiac bloodwork but eventually discover another gastrointestinal issue?

Would you push for further investigation now, or is monitoring blood levels after treatment a reasonable first step?

For those on injections, how was your long-term treatment plan determined?

I'm not looking for a diagnosis from Reddit, but I'd really value hearing about other people's experiences and whether there are any questions or investigations I should discuss with my doctor.

Thank you!

DIAGNOSING AND TREATING PERNICIOUS ANAEMIA

For Medical Professionals

The British Committee for Standards in Haematology issued their Guidelines for the Diagnosis and Treatment of Cobalamin and Folate Disorders in June 2014.

This factsheet has been produced for primary healthcare professionals. It also includes findings of the survey of members of the PA Society, published in April 2014 .

Diagnosing Cobalamin Deficiency.

The Serum B12 Test is not a good indicator of the patient’s B12 Status:

“The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no ‘gold standard’ test to define deficiency”.

“Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established”

“In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment”.

“IFAB is positive in 40–60% of cases i.e., low sensitivity, and the finding of a negative IFAB assay does not therefore rule out Pernicious Anaemia (hereafter referred to as AbNegPA)”.

“Patients suspected of having Pernicious Anaemia should be tested for IFAB. Patients found to be positive should have lifelong therapy with cobalamin. Patients negative for IFAB, with no other causes of deficiency, may still have Pernicious Anaemia and should be treated as anti-IFAB-negative Pernicious Anaemia. Lifelong therapy should be continued in the presence of an objective clinical response”

“All patients with anaemia, neuropathy or glossitis, and suspected of having Pernicious Anaemia, should be tested for anti-IFAB regardless of cobalamin levels”

DIAGNOSING AND TREATING PERNICIOUS ANAEMIA

For Medical Professionals

The British Committee for Standards in Haematology issued their Guidelines for the Diagnosis and Treatment of Cobalamin and Folate Disorders in June 2014.

This factsheet has been produced for primary healthcare professionals. It also includes findings of the survey of members of the PA Society, published in April 2014 .

Diagnosing Cobalamin Deficiency:

The Serum B12 Test is not a good indicator of the patient’s B12 Status:

Macrocytosis is not always present in cobalamin deficiency:

“an elevated mean cell volume (MCV) is not a specific indicator of cobalamin deficiency”

“The absence of a raised MCV cannot be used to exclude the need for cobalamin testing because neurological impairment occurs with a normal MCV in 25% of cases”

Children:

“Reduced serum cobalamin levels in infancy in the presence of clinical features should be treated promptly to prevent long term neurological sequelae”

Diagnosing Pernicious Anaemia

Intrinsic Factor Antibody Test:

Treating Pernicious Anaemia

Parenteral treatment is preferred:

“the efficacy and cost–effectiveness of oral treatment in wider population-based settings has yet to be established. There are arguments against the use of oral cobalamin in initiation of cobalamin therapy in severely deficient individuals who have poor absorption, especially due to pernicious anaemia”.

“In patients presenting with anaemia, a reticulocyte response should be evident by 7–10 days provided the patient has adequate levels of iron and folate”

Treatment of Pernicious Anaemia with Neurological Involvement:

“Standard initial therapy for patients without neurological involvement is 1000 µg intramuscularly (i.m.) three times a week for 2 weeks. The BNF advises that patients presenting with neurological symptoms should receive 1000 µg (i.m.) on alternate days until there is no further improvement”.

Folate:

“In the presence of strong clinical suspicion of folate deficiency, despite a normal serum level, a red cell folate assay may be undertaken, having ruled out cobalamin deficiency”

Prevalence:

Vitamin B12 Deficiency is widespread, maybe as many as 1:10 of the population may be deficient caused by inadequate diet, medicines (PPI’s, Antacids and Contraceptive Pill etc.) or Atrophic Gastritis.

Autoimmune Metaplastic Atrophic Gastritis (PA) is considered to be the main cause of B12 Deficiency in the developed world.

Treatment:

48% of patients considered their treatment to be ‘very poor, poor or inadequate’

Once treatment of Pernicious Anaemia has started no further testing for cobalamin levels is required.

Ref:

1. Devalia V, Hamilton M, Molloy A; Guidelines for the Diagnosis and Treatment of Cobalamin and Folate Disorders; British

Journal of Haematology, 2014, 166, 496-513

1. Hooper M, Hudson P, Porter F, McCaddon A; Patients Journeys; the diagnosis and treatment of Pernicious Anaemia;

British Journal of Nursing 2014; 23;7;16-21.

© The Pernicious Anaemia Society 2016. Charity No. 1147839

B12 was 180 in July. Month of weekly injections. Felt significantly better. Now I’m on once a month injections. I feel great after the shot, then slowly feel worse after. Not vegetarian. Would actually say I have a high b12 diet.

Pernicious anemia blood tests were negative. Celiac blood tests negative. Iron panel was all normal. Thyroid numbers normal. I just had a follow up with my gastroenterologist and she basically was like “we can schedule an endoscopy to see if there’s an absorption issue if you want but I’m not worried.” I scheduled it since it’s almost the end of the year and I want to make sure if I get it I can get it towards this years deductible (love dealing with insurance), but if I’m not having any major upper GI symptoms and PA and celiac tests were negative is it worth it to try and keep searching for a cause? I do deal with ibs, but limited heart burn issues

Hi,
I have dealt with major mood swings, low energy, anxiety issue and lately have had major hair fall.
My hair has become very dry and sticky and are always tangled. Tried everything and nothing really worked.

Have been reading a lot of posts where people have shared positive results of B12 and Magnesium supplements

Currently I am taking Autrin ( Iron Supplement) and Uprise D3 (Vit D Supplement)

I am also attaching my report for B12, can you guys please suggest what will be accurate supplement for me BECAUSE I am also seeing posts where supplements have messed up with peoples hormones and skin and hair.

i feel easily fatigued, tiredness and low energy , difficulty climbing stairs , brain fog ,high anxiety , palpitations , high sweating, sometimes dizziness on suddenly standing up , nerve pain , light and sound sensitivity......my mcv is 59 and mch is 19 and my mcv and mch are constantly reducing like mcv 65 to 59 and mch 21 to 19 in just 5 months , i also had b12 def of level 160 for 5 years which was restored to 757 , 7 months ago , pls guide me what are possible reasons of my symptoms my hb is 12.3 and rbc count is 6.5 , pls reply if i need ferritin test or not, i am 17 yr old male I talked to a few haematologists and doctors and they said no need to worry as hb is normal , they simply ignored the details of mcv and mch.....

Doc suggested I could use B12 nasal sprays so I don't need an injection every time. Any feedback on this method over injections?

Hey everyone. I am not asking for diagnosis but rather an suggestion to what could’ve gone wrong with me after an viral infection in February.

If someone has had a similar experience, please let me know, every information is useful.

I had a viral illness in February with razor- sharp sore throat and high fever, fatigue, vertigo attack, etc..
Suspected COVID, although not sure.

After 1-2 weeks after I felt better from the acute symptoms of sore throat, fever, etc.. my body started acting weird, nothing like I ever felt before and from there on until this day everything snowballed and now I am pausing my career, to see what is wrong with me.

My symptoms best match DPDR/Brain fog, without me feeling unreal or in a dream, but just utterly strange and overstimulated by lights etc, my vision is strange, when I walk sometimes I experience “weightless body” is what I call it.

I’ve done numerous blood works and MRI, tests etc..

But I wanted to ask in this community what is the best way to check your levels with most certainty?

My normal B12 levels were at 500-600 last I checked, my folate though was only 1 point above deficiency zone.

Hi all. Not asking for a diagnosis, just wondering if expensive private tests should be a priority for me. I have a direct family history of pernicious anemia and similar symptoms.

I'm 26M and diagnosed with a bunch of other issues, but almost all of the self help has pretty much failed so far. I recently got diagnosed with MCAS on top of everything else.

A recent total B12 test showed my numbers are off the scale high, which I'm guessing is down to the fact I have to drink a crazy amount of monster to function. No other energy drink helps me in the same way at all, and I've been drinking the same ones for over a decade. Any drink with just caffeine and no B12 doesn't do anything.

I've also read that extremely high B12 levels can be caused by intrinsic factor antibodies, so I'm planning to get those tested for. I'm planning to get Active B12 tested alongside MMA too. My other levels are fine (iron, folate etc.) and only my Vitamin D is low but the first supplements I took made me unwell and I'm waiting on a different prescription.

Has anyone here inherited PA from their parents or been diagnosed in their 20s? I'm struggling to find resources and my family member wasn't diagnosed until around 40 after declining for many years before.

My brain fog and fatigue has been bad for well over a decade, and I'm getting a lot more nerve pains and weird sensations each year. My sleep specialist also pointed out I have some oral markers for B12 deficiency, and I have a constant fizzing sensation in my hands/feet irrespective of having any kind of POTS symptoms or not.

A lot of the time I feel totally 'phased out' and sort of describe it as though comprehending my direct surroundings feels like trying to imagine yourself inside a 2D photograph.

Any information is useful! Thanks for reading.

My B12 levels were a little low(around 300) so my doctor suggested me to take 500mcg daily at night before bed. I've been taking it for just about a week now...I had sudden episodes of lot of sadness randomly and now from past 3 days I'm waking up daily at 3am with horrible nightmares and fast HR.

Can this be caused by B12 supplements? Is there any solution to stop this? I'm taking methylcobalamin orally right now.

My situation: 20sM, I have SIBO after a food poisoning (can’t take antibiotics because of prior history). Main digestive symptoms are diarrhea, gas all over my GI tract, fat/fiber intolerance, gastritis and silent reflux.

I am trying to get proper B12 deficiency diagnosis as I have started to feel the symptoms. I got labs and I am already having early signs of megaloblastic anemia, but its not anemia yet. I will try pushing for MMA and homocysteine to get injections (need prescription to buy and inject B12 in my country) before an endoscopy that will rule out gastritis type.

Anyhow, I want to supplement some things before starting, but I wonder, is it necessary that I supplement Iron as part of my specific cofactor needs?

Inflammation markers (hs-CRP, ESR, Calprotectin) are all so low they are practically nonexistent. So I don’t feel Iron is high due to inflammation.

My ferritin is literally mid range, better than many people here, and I know it will decrease when it begins to be used up by the B vitamins.

but I am weary of trying Iron (considering how many people complain of taking it). So I am unsure if I should take supplemental Iron at all.

My last labs look like this:

Vit B12 - 406 pg/mL

Folate - 3.2 ng/mL (pretty obvious B12 deficiency sign)

D 25-OH - 38.2 ng/mL (dont go out often)

Serum Iron - 156 μg/dL

Ferritin - 227 ng/ML

Vit A - 0.6 mg/L

Vit C - 0.6 mg/L (will definitely supp now)

Sodium (Na+) - 136 mmol/L (low, I rarely eat with salt).

Potassium (K+) - 5.1 mmol/L

Chloride (Cl-) - 104 mmol/L

Magnesium - 2.2 mg/dL

Zinc - 98 ug/dL

Haven’t tested Copper, Selenium, Molybdenum.

Hey everyone I’m glad I saw this community it’s really helped me find people that are going to the same thing. I really didn’t realize how much b12 affected your body.

I’ve been struggling with b12 deficiency for a year now and it’s just getting worse and I’m worried my doctors just aren’t listening to me. Here’s some of my labs I’m curious on what y’all think since b12 deficiency people learn a lot about labs 😭.

2025
March - mono

May b12 - 273
Iron serum - 44
Fertin - 17
Vitamin D - 17

Treatments - Vitamin d prescription
And over the counter b12

2026
March b12- 444
Vitamin D - 31
Iron - 164
Ferttin - 20

March
Mono reactivation

Treatments - vitamin d and b12 over the counter

July 2026
B12 - 175
Iron serum - 175
Ferritin - 23
Vitamin D - 31

July
Celiac panel negative
Pernicious anemia negative
Colonoscopy and endoscopy nothing found and no inflammation

Treatments - b12 injections and vitamin d and iron supplements

My symptoms are fatigue, chronic diarrhea multiple times a day, brain fog and I’m starting to experience some of the pins and needles sensation in my hands. I’ve been to hematologist, GI , and general doctor but if it’s not celiac, pernicious anemia or Crohn’s I’m not sure what else it could be and my doctors just keep trying to treat the b12 but from my labs and symptoms I feel like it might be something else. I also noted the mono and reactiveation because my mom has two primary immune deficiencies and I was wondering if that was related. I’m curious is anyone else is having any of the same symptoms or lab issues or recommend anything test to suggest to my doctor.

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