Low serum B12 but high Active B12 (HoloTC) - confused!

[fireflymairi]

I just picked up 5 years worth of blood test results (frustrated with being in the dark about results all the time) and checked out my latest results.

For reference, I'm in Australia.

On my most recent test on 16th July 2021 (before any B12 supplementation):

Total B12 is 250 pmol/L

Active B12 (HoloTC) seems high at 113 pmol/L (> 35)

Serum folate is also quite high? >54 nmol/L (8.4 - 55)

Vitamin D is 62 nmol/L (> 49)

Iron is 12 umol/L (10-33)

Ferritin 100 ug/L (25-290)

I can provide any other results on request...

I went to the doctor with the following symptoms:

* General fatigue / tiredness

* Not feeling rested after 8 hours sleep

* Sore muscles, takes days to recover from exercise or exertion

* Hard to concentrate sometimes, easily distracted

* Hard to follow conversations between people sometimes

* Forgetting things/names

* Concentrating for extended periods leaves me feeling exhausted

* Short and medium term memory issues

* Breathlessness, feel need to sigh or breathe deeply

* Racing heartbeat at rest

* Heavy legs

* Pins and needles in legs and more recently in hands/fingers at night or when resting

* Burning feeling in feet/legs

* Tip of tongue feels irritated or like I’ve burnt it on something

* Ringing ears

* Nausea, sore stomach to varying degrees almost constantly

* Constipation (I take Metamucil daily for the last couple of years to prevent this)

* Long periods, up to 10 days, mostly spotting or very light flow

* Sometimes short cycles - vary from 23 to 28 days

* Infertility - have been trying to conceive for last 4 years or so

* Feelings of anxiety / impending doom

* Sometimes mood swings to a bit manic

* General feeling of not being able to do or commit to much or I’ll feel like rubbish!

My diet is high in meat and animal products, my hubby hunts so we eat a lot of venison and smoked slow cooked meat so I would imagine my B12 should be pretty high.

My mum has Pernicious Anemia and struggles with low Iron, also has an autoimmune disease.

The doctor prescribed me monthly shots of B12 for 3 months (I had to push for this), I've had two of these so far and each time nothing has happened for 5 days or so, then I've felt like I've had more energy and can think clearer. The tingling legs and arms also stopped about a week after the first injection. However about 2-3 weeks after the injection both times, most of my symptoms have returned (even a little bit tingly in the feet this time).

I was positive that this all pointed to a B12 deficiency, but the Active B12 has thrown me a curve ball.

My main question: Is is possible to have a B12 deficiency / Pernicious Anemia with Active B12 so high?!

[fireflymairi]

These were the recommendations after the B12 results in the pathology report.

[Gambit62 Administrator in reply to fireflymairi]

fireflymair, unfortunately we have had to remove the image as it contained the name of the reporting physician - you can repost without the name.

[fireflymairi in reply to Gambit62]

Oops sorry about that! Here you go.

pathologist report

[Nackapan]

Yes. With your history .Many on here were testing within range but had deficiency.

If yiu responded to b12 injections there's your answer .

Soundsije you need more as have neurological symptoms.

Other tests can be done.

Homocysteine Mma intrinsic factor antybody test.

Other conditions ruled out

[fireflymairi in reply to Nackapan]

Thank you Nackapan, I definitely felt better after the B12 shots.

[Gambit62 Administrator]

are these result before or after you had your first B12 shot?

[fireflymairi in reply to Gambit62]

They were before any treatment / B12 shot / supplementation.

[Gambit62 Administrator in reply to fireflymairi]

normally active B12 would be about 1/5 of total B12, that fact that yours was 1/2 is a bit unusual and might warrant further investigation. It isn't suggestive of PA or a B12 absorption problem but it might indicate something to do with the way the body is processing B12. Unfortunately that's off topic for this forum but it might be worth asking about DNA testing.

[fireflymairi in reply to Gambit62]

Thanks Gambit62 that’s helpful, I did think it was a pretty weird result. I know this is off topic now but if you could give me any more information about what kind of DNA testing I would be very grateful.

[Gambit62 Administrator in reply to fireflymairi]

really outside my area of expertise. Probably start with a general screening and see if it throws up any variants of interest on genes relating to processes that use B12. You really need to follow up with GP or look for a genetic counsellor.

[fireflymairi in reply to Gambit62]

Okay thank you!

[Sleepybunny]

Hi,

There are some serious health conditions where a patient can have high B12 levels but still have symptoms of B12 deficiency. The articles I read mentioned high serum B12 (total B12) rather than high active B12 (holotranscobalamin).

Have you had liver and kidney function tests recently?

Have a look into causes of Functional B12 deficiency.

Article about Functional B12 deficiency

pubmed.ncbi.nlm.nih.gov/191...

Has your doctor ordered a full panel of iron tests?

There are other iron tests besides the two below.

Iron is 12 umol/L (10-33)

Ferritin 100 ug/L (25-290)

Iron Studies

labtestsonline.org.uk/tests...

Both MMA and Homocysteine test results may be affected by recent B12 supplementation.

Article about MMA

stichtingb12tekort.nl/engli...

Link about Homocysteine

labtestsonline.org.uk/tests...

I am not medically trained but if I had symptoms consistent with B12 deficiency with a family history of PA then I would be trying to find out if I had PA.

PA tests

Intrinsic Factor Antibody (IFA) test

labtestsonline.org/tests/in...

Parietal Cell Antibody (PCA) test

labtestsonline.org/tests/pa...

PCA is not recommended as a diagnostic test for PA in UK.

It is still possible to have PA with a negative result in IFA or PCA test.

Have you ever had gastrin levels checked?

labtestsonline.org.uk/tests...

[fireflymairi in reply to Sleepybunny]

Thanks Sleepybunny.

The doctor said my liver and kidney function were fine, but I'm not sure what to refer to on the blood tests that would indicate that?

The rest of the Iron results were:

Iron 12 umol/L (10-33)

TIBC 46 umol/L (45-70)

Saturation 26% (16-50)

Ferritin 100 ug/L (25-290)

I wished she'd ordered the tests recommended here before starting me on B12 injections because yes, they're going to be affected by them now.

She has agreed to the intrinsic factor antibody test but not until 4 weeks after my third injection. I am hoping to push this sooner though.

Unless I decide to just start self injecting (I have everything I need to do this). But I'd probably prefer to get a diagnosis first.

[Sleepybunny in reply to fireflymairi]

"She has agreed to the intrinsic factor antibody test but not until 4 weeks after my third injection. I am hoping to push this sooner though."

It could be that she wants to make absolutely sure there is no effect from B12 injection on results of IFA test.

See section on Test Preparation in UK link below which suggests waiting at least 48 hours after a B12 injection and up to two weeks after before taking blood for Intrinsic Factor Antibody test.

labtestsonline.org/tests/in...

[fireflymairi in reply to Sleepybunny]

Yup that's fine but just not sure why I need to have 3 injections, halfway through my second injection now - it would be good to find out in 2 weeks time rather than 6 weeks time!

[Sleepybunny in reply to fireflymairi]

Liver Function tests

labtestsonline.org.uk/tests...

Kidney Function tests

labtestsonline.org.uk/tests...

[Sleepybunny]

Iron 12 umol/L (10-33) at lower end of normal range

TIBC 46 umol/L (45-70) at lower end of normal range

Saturation 26% (16-50) normal range

Ferritin 100 ug/L (25-290) normal range

Have a look at the "What the test result means" section in Iron Studies link below.

labtestsonline.org.uk/tests...

[fireflymairi in reply to Sleepybunny]

I have a history of low Iron and so does my mum. My ferritin was low in 2017 and I had an iron infusion.

According to this table, the closest interpretation is Chronic Illness.

Iron table

[ClareP5]

In answer to your question - why not? No one tested you when you felt well, so goodness knows what a healthy level is for you! The injections are making you feel better you say and then you deteriorate before the next one - this would suggest you need a greater frequency of injection. Maybe you don't recycle B12 well - some folks reuse up to 90% according to Dr Chandy's book, but some as little as 20% - findings are on small numbers, so wide confidence range. Your iron, ferritin and Vit D are all below optimal, which could cause fatigue and breathlessness. Pulsatile tinnitus is associated with B12 tinnitus - not sure about "ringining" in the ears, but some find their tinnitus improves with thyroid supplementation. Again maybe worth investigating. See thyroid forum for information.

[fireflymairi in reply to ClareP5]

Thanks for your reply ClareP5!

Yes I think it’s important to treat the symptoms, who know what goes on in the individual, we’re all different I guess.

I’ve had ringing in my ears for years, maybe it’s unrelated. My thyroid is fine apparently.

I saw my doctor again today and I think I’m getting somewhere, she’s agreed to test for pernicious anemia and also my iron again.

Now I’m having possible gallbladder pain though so off for an ultrasound about that next!

[Ghound]

Hi, My B12 was higher end of normal, but also I had a long history of iron deficiency anaemia with very low ferritin. My GP kept saying " This is NOT B12 deficiency " , but after fighting for a consultant appointment and treatment , it's evident that I do have B12 deficiency.

I had quite severe anaemia and neurological symptoms, but after intensive loading treatment with Hydroxocobalamin injections I have more or less got my life back !

Best wishes and hope you feel better soon x

[fireflymairi in reply to Ghound]

Thank you for sharing your story Ghound!

I’m glad you were able to persist in seeking treatment and that it was successful for you. That’s very encouraging!

Thank you x

[Ghound in reply to fireflymairi]

You're very welcome xx