Hi Jeffrey,

Thanks for the reference.

I have that paper in front of me and I'd like to point out that it's
based on a review of what people actually do, rather than an appraisal
of what they should be doing. As such it is not very informative as to
the best approach to the diagnosis of B12 and folate deficiencies. It
appears that the significant lab decisions these days are taken by
accountants rather than scientists!

And I meant to mention the Haemostasis & Thrombosis and The Human
Nutristasis Unit,St. Thomas’ Hospital, London SE1 7EH, whose head is
Dr. Dominic Harrington, who have developed the approach of measuring
holoTC followed by plasma MMA for B12 deficiency.

Nick Miller
London


On 06/12/2012, Jeffrey Barron <[log in to unmask]> wrote:
> Serum or RBC folate:
> There are many opinions but only a small evidence base for clinical use of
> serum or RBC folate:
> Red cell or serum folate? Results from the National Pathology Alliance
> benchmarking review M Galloway, L Rushworth J Clin Pathol 2003;56:924-926
> Smellie, W S A. Wilson, D. McNulty, C A M. Galloway, M J. Spickett, G A.
> Finnigan, D I. Bareford, D A. Greig, M A. Richards, J. Best practice in
> primary care pathology: review Journal of Clinical Pathology.
> 58(10):1016-24, 2005
>
>
>
> Vitamin B12:
> It is impractical in current clinical practice to use MMA to diagnose B12
> deficiency.
> Due to IF Ab interference, we need to get the kit manufacturers to stop
> using IF in the assay and to use an antibody instead.
> The evidence base for HoloTC so far is not compelling to change from B12.
> I await the next paper from R Carmel.
>
> Hope that the mail base will provide more references for an evidence base.
>
> Jeff
> Auckland
> From: Clinical biochemistry discussion list
> [mailto:[log in to unmask]] On Behalf Of Nick Miller
> Sent: Friday, 7 December 2012 8:24 a.m.
> To: [log in to unmask]
> Subject: Re: Vitamin B12 testing in vegans
>
> Hello Sutirtha,
>
> The approach (developed by St. Thomas' Hospital Haematinics lab) is to
> measure HoloTC and then plasma MMA if there is any ambiguity (which avoids
> an excessive plasma MMA workload). This is the ideal diagnostic approach - a
> quantitative measurement, followed by a functional measurement which
> reflects the action of the analyte.
>
> The problem is that people are confused about the haematological changes
> consequent on B12 and folate deficiencies/depletion. Contrary to what we
> learnt (or previously taught), these are changes that occur late in the
> development of these deficiencies - so there is no point in looking for
> haematological changes early in the deficiency, or if there is marginal
> intake of B12 and folate.
>
> Re: folate measurement -  it is red cell folate, rather than serum folate,
> which reflects intracellular depletion of folic acid. Mike (in Norwich) -
> why not save your lab even more money by dropping the analysis altogether
> (wait until the haematology changes and the patient is really ill)? So stick
> to red cell folate analysis is my advice.
>
> A functional test for folate deficiency is FIGLU (N-Formimino-L-glutamic
> acid), an intermediate of histidine catabolism which is normally degraded to
> L-glutamic acid by a folic acid-dependent enzymatic reaction controlled by
> FIGLU transferase. I used to measure it in urine until Sigma stopped
> supplying the enzyme (which is required for the urine measurement). Maybe
> some bright spark out there has an MS method for FIGLU?
>
> Nick Miller
> London
>
>
> From: sutirtha chakraborty [mailto:[log in to unmask]]
> Sent: 06 December 2012 09:55
> To: Nick Miller
> Cc: [log in to unmask]
> Subject: Re: Vitamin B12 testing in vegans
>
> Dear Nick,
> I agree with you, Vit B 12 between 200- 300 is a big grey zone with majority
> being actually deficient.But I would prefer a Holotranscobalamin assay
> rather than MMA.
> As because the patient has been evaluated for hematological etiology, a good
> CNS examination especially for any mild cognitive impairment is very
> necessary.
> I would also like to know the Folate status in this patient.
> In such cases I usually have a close look at the RDW indices. Anisocytosis
> is occasionally a clue for further testing.
> Regards,
> Sutirtha
> Thanks and Regards,
> Dr Sutirtha Chakraborty, MD,FACB
> Consultant & Chief, Dept of Biochemistry
> Peerless Hospital&B.K Roy Research Center
> Kolkata 700094,India
>
>
> On Thu, Dec 6, 2012 at 2:37 PM, Nick Miller
> <[log in to unmask]<mailto:[log in to unmask]>> wrote:
> Agreed.
>
> Forget the old  total B12 assays now, measure holotranscobalamin and plasma
> MMA. It gives completely different and much more informative results.
>
> A substantial number of our patients are vegetarians or vegans and they turn
> out to be B12 deficient unless they are receiving methyl B12 injections.
> Remember the B12 in supplements in cyano-cobalamin (it's more stable) and in
> many cases seems to result in a raised serum B12 (sometimes quite high)
> without correcting intracellular B12 deficiencies. It can also give you a
> spectacularly high urine cobalt output, but that's another story.
>
> Nick Miller
> London
>
> From: Clinical biochemistry discussion list
> [mailto:[log in to unmask]<mailto:[log in to unmask]>]
> On Behalf Of Jonathan Kay
> Sent: 05 December 2012 12:03
> To:
> [log in to unmask]<mailto:[log in to unmask]>
> Subject: Re: Vitamin B12 testing in vegans
>
> 1 All vegans should take B12 supplements.
>
> 2 What's the clinical question here? Does the patient have anything
> suggesting B12 deficiency, or is she just generally worried or interested?
>
> 3 I think we'll all be doing a lot more methylmalonic acid assays in the
> future as the limitations and non transferability of current B12 assays and
> the clinical effects of B12 deficiency both become more widely known.
>
> Jonathan
>
>
> On 5 Dec 2012, at 11:46, Sally Brady wrote:
>
> Dear collective brain,
>
> I have had a GP write to me asking for some help as one of his vegan
> patients presented him with the following information from the Vegan
> Society. Was anyone else aware of this and how did you deal with it?
>
> Testing B12 status
> A blood B12 level measurement is a very unreliable test for vegans,
> particularly for vegans using any form of algae. Algae and some other plant
> foods contain B12-analogues (false B12) that can imitate true B12 in blood
> tests while actually interfering with B12 metabolism. Blood counts are also
> unreliable as high folate intakes suppress the anaemia symptoms of B12
> deficiency that can be detected by blood counts. Blood homocysteine testing
> is more reliable, with levels less than 10 micromol/litre being desirable.
> The most specific test for B12 status is methylmalonic acid (MMA) testing.
> If this is in the normal range in blood (<370 nmol/L) or urine (less than 4
> mcg /mg creatinine) then your body has enough B12. Many doctors still rely
> on blood B12 levels and blood counts. These are not adequate, especially in
> vegans.
> http://www.vegansociety.com/lifestyle/nutrition/b12.aspx
>
> Thanks,
>
> Sally
>
>
>
> Dr Sally Brady
> Senior Clinical Scientist
> Blood Sciences
> The Hillingdon Hospital
> 01895 279924
>
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> biochemistry. Please note, archived messages are public and can be viewed
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> --
> Thanks and Regards,
> Dr Sutirtha Chakraborty, MD
> Consultant,Dept of Biochemistry
> Peerless Hospital&B.K Roy Research Center
> Kolkata 700094,India
> Mobile: +91 9874787638
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