Vitamin B12
BMJ 2023; 383 doi: https://doi.org/10.1136/bmj-2022-071725 (Published 20 November 2023) Cite this as: BMJ 2023;383:e071725
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Dear Editor
Whenever Vitamin B12 deficiency is characterised as a disorder typically associated with macrocytosis[1], the caveat that should apply is that the majority of vitamin B12 deficient subjects have a normocytic haematological profile[2]. In the latter retrospective study, which enrolled Indian subjects, serum vitamin B12 levels were measured by an assay in which the normal range for serum vitamin B12 was 239-931 pg/ml. Among 868 subjects who were deemed to be Vitamin B12 deficient, 664 were characterised by a mean corpuscular volume (MCV) in the range 80-100 fl. An MCV >100 fl was documented in 90 subjects, and an MCV < 80 fl in 114 subjects[2].
In a prospective study which enrolled Indian adolescent girls aged 10-18, vitamin B12 deficiency was defined as a serum vitamin B12 level < 200 pmol/l. In that study macrocytosis was prevalent in 10% of 290 subjects with Vitamin B12 deficiency . The sensitivity and specificity of macrocytosis to screen out vitamin B12 deficiency amounted to 10.14%, with a specificity of 92.8%. Positive predictive value amounted to 65.91%, with a negative predictive value of 43.01% [3].
These observations have been replicated in other populations as follows:-
A prospective study which enrolled female Chinese vegetarians utilised both subnormal serum vitamin B12 levels and raised methyl malonic acid (MMA) levels as markers of of vitamin B12 deficiency. Although the lower limit of normal in the assay was a serum vitamin B12 level of 187 pmol/L, a serum vitamin B12 level < 150 pmol/l was the one defined as being indicative of vitamin B12 deficiency. The combination of serum B12 < 150 pnol/L and raised MMA was the defining feature of definite vitamin B12 deficiency in that study. Macrocytosis was documented in only 16% of subjects with definite vitamin B12 deficiency[4].
In a Canadian study macrocytosis was documented in only 12.5% of 96 subjects with vitamin B12 deficiency anaemia[5].
A systematic review of the diagnostic value of macrocytosis (MCV > 100 fl) for vitamin B12 deficiency, both in anaemic and in nonanaemic subjects, generated a 17% prevalence of macrocytosis in vitamin B12 deficient subjects but this increased to 30% prevalence in the anaemic subgroup of vitamin B12 deficient subjects[6].
Microcytosis can also be a feature of vitamin B12 deficiency[2],[6], especially when the underlying cause is autoimmune gastritis[7]. In Hershko et al, among 160 patients with autoimmune gastritis, 29 had macrocytosis (MCV > 100 fl), 48 had a normocytic haematological profile (MCV 80-100 fl), and 83 had microcytosis (MCV < 80 fl). All 29 of the patients with macrocytosis had vitamin B12 deficiency.
Among the 48 with a normocytic profile, 44 (92%) were vitamin B12 deficient.
Among the 83 with microcytic profile 38 (46%) were vitamin B12 deficient[7].
Accordingly, "MCV should not be the only criterion to order vitamin B12[measurement] for anemia under evaluation"[2].
I have no conflict of interest
References
[1] Wolffenbatel B et al. Vitamin B12. BMJ 2023;383: e071725
[2] Jain R., Kapil M., Gupta GN. MCV should not be the only criterion to order vitamin B12 for anemia under evaluation. Open Journal of Gastroenterology 2012;2:187-190
[3] Patel S., Dhupar P., Bjattar A. Diagnostic accuracy of mean corpuscular volume in delineating vitamin B12 deficiency. Annals of Clinical Laboratory Research 2017. ISSN 2386-5180. DOI:10.21767/2386-5180.1000195
[4] Kwok T., Cheng G., Woo J., Lai WK., Pang CP. Independent effect of vitamin B12 deficiency on hematological status in older Chinese vegetarian women. Am J Hematol 2002;70:186-190
[5] Gupta M., Copley K., Keeney M., Chin-Yee I. Does cell size matter? Utilizing mean cell volume as a screen to determine common causes of anemia including iron deficiency anemia, vitamin B12 and folate deficiency
Blood 2016;128:2338
[6] Oosterhuis WP., Niessen RWL., Bossuyt PMM., Sanders GTB., Sturk A. Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency. Scandinavian Journal of Clinical and Laboratory Investigation 2000;60:9-18
[7] Hershko C., Ronson A., Souroujon M et al. Variable hematological presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood 2006;107:1673-1679
Competing interests: No competing interests
Dear Editor
The authors cover the breadth of issues in vitamin B12 deficiency diagnosis and treatment, but do little to address the contradictions.
A section considering whether the diverse cognitive, mental health and neurological (85% in the graphic) signs and symptoms are due to association or causation would benefit from consideration. To confound readers further the authors critique the subjective laboratory assays (a well recognised issue) without consideration of measurement of uncertainty or as clinical practice requires, how to apply a level of certainty.
The authors state that symptoms may take years to regress, but also that normal levels of vitamin B12 / metabolism is not a way to decide how to revert to "maintenance" dosing. It it truly their intention to advise alternate day parenteral replacement until years have passed, as appears from the combined content of text and graphic? They then recommend maintenance dosing of twice a week to monthly, but clarity on how this is established in contrast to the BNF standard of care is needed. As is whether other interventions may be useful for at least some symptomatic individuals alongside standard, or more frequent, vitamin B12 replacement.
Given the critique of the utility of vitamin B12 assays, we may ponder the advice for those supplemented for inadequate diet to have annual monitoring of vitamin B12 status, to guide dose adjustment.
Their advice to support self-administration of parenteral vitamin B12 replacement for those where oral supplementation is not suitable is welcome,
The article by Wolffenbuttel et al is timely, but perhaps would have been better described as an opinion piece.
Competing interests: No competing interests
Dear Editor
It was refreshing to read Wolffenbuttel et al.’s article on B12 deficiency (1), particularly because it had a patient-centred focus. In my experience, the NHS can be incredibly rigid and myopic with regards to B12 replacement, often leading to patients avoidably suffering due to restricted access to intramuscular injections.
Wolffenbuttel et al. touch upon several related common deficiencies that can co-occur with, or present similarly to, B12 deficiency, such as B6 and folate deficiencies. However, one nutrient that is often forgotten is choline (2). Choline is an essential nutrient, with endogenous production being inadequate for metabolic and other needs. It has many roles in the body, including the synthesis of the neurotransmitter acetylcholine, and being critical for cell structure and proper functioning (3). In addition, choline acts within the same biochemical pathway as B12 and folate, making it essential for methylation (3).
Considering the roles of choline in one-carbon metabolism, in 2011 EFSA approved health claims for choline to reduce homocysteine (4). Inadequate intakes of choline can lead to an increased demand for folate and vice versa, which can have knock-on effects on B12 status (3). As such, it seems prudent for clinicians to establish whether choline deficiency could be contributing to B12 deficiency (or other nutrient/biomarker abnormalities in the same biochemical pathway).
In the general population, research on the optimal intake of choline is limited; as such, adequate intakes (AIs) have been established, typically between ~400-550 mg/d, with an upper tolerable limit of 3-3.5 g/d in adults (2,3). However, some have argued that the AIs may be sufficient but not optimal for health, and propose that higher intakes of 1-2 g/d may be optimal (5). Nonetheless, further research is needed to understand optimal dosage. Choline is found in many foods, but is generally higher in animal products (6); therefore, similar to B12, it seems likely that those who limit animal products may be at higher risk of deficiency.
Further, the lack of choline in total parenteral nutrition (TPN) has been recognised for many years now. Some patients experience liver steatosis (and/or other side effects, such as memory deficits, similar to B12 deficiency) when on TPN, with resolution upon choline administration (5). Healthcare professionals have a duty to do no harm; as such, it seems negligent that this issue has not been addressed. It also raises questions regarding the aetiology of allegedly idiopathic liver problems: could some of these cases be from inadequate dietary choline?
There are currently no validated blood tests on the NHS to assess choline status. In personal discussions, some have argued that blood levels have high variability so having defined cut-offs would be difficult. However, this same argument could be made for tests assessing B12 status—something Wolffenbuttel et al. describe in detail. Therefore, this does not seem like a valid argument to avoid choline measurements. Indeed, just like B12, the information can be useful in making clinical assessments and treatment plans in the context of the full clinical picture. Accordingly, validating a choline assay seems like a reasonable step to take.
In addition, research should investigate the utility of more widespread clinical genetic testing, such as MTHFR, COMT, and PEMT (7,8), in order to help identify whether different supplement forms (e.g. oral methylcobalamin, phosphatidylcholine) could be more beneficial for certain patients, consequently providing a rationale for their prescription on the NHS.
Until healthcare professionals can screen properly for choline deficiency, at the very least, dietary intake should be assessed to help determine whether choline supplementation could be warranted, thereby reducing demands on B12 and other nutrients in patients presenting with deficiency.
References
1. Wolffenbuttel BH, Owen PJ, Ward M, Green R. Vitamin B12. BMJ. 2023 Nov 20;383:e071725.
2. Derbyshire E. Could we be overlooking a potential choline crisis in the United Kingdom? BMJ Nutrition, Prevention & Health. 2019 Aug 29;bmjnph.
3. Sanders LM, Zeisel SH. Choline. Nutr Today. 2007;42(4):181–6.
4. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of health claims related to choline and contribution to normal lipid metabolism (ID 3186), maintenance of normal liver function (ID 1501), contribution to normal homocysteine metabolism (ID 3090), maintenance of normal neurological function (ID 1502), contribution to normal cognitive function (ID 1502), and brain and neurological development (ID 1503) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal. 2011;9(4):2056.
5. Buchman AL. The Addition of Choline to Parenteral Nutrition. Gastroenterology. 2009 Nov 1;137(5):S119–28.
6. USDA. Choline [Internet]. 2018. Available from: https://www.nal.usda.gov/sites/default/files/page-files/choline.pdf
7. Silver MJ, Corbin KD, Hellenthal G, Costa KA da, Dominguez-Salas P, Moore SE, et al. Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort. The FASEB Journal. 2015;29(8):3426–35.
8. Surendran S, Adaikalakoteswari A, Saravanan P, Shatwaan IA, Lovegrove JA, Vimaleswaran KS. An update on vitamin B12-related gene polymorphisms and B12 status. Genes & Nutrition. 2018 Feb 6;13(1):2.
Competing interests: No competing interests
Dear Editor
Sadly, I disagree with most of the highlighted statements in the box. My comments on the statements are shown below each.
1. The clinical picture is the most important factor in assessing the significance of results of blood tests assessing cobalamin (B12) status because there is no “gold standard” test to define deficiency.
Comment: B12 deficiency takes a long time to develop; it is a mistake to wait until there are symptoms before treating it. In high-risk patients, such as patients at risk of stroke, it is important to detect and treat B12 deficiency and hyperhomocysteinemia to prevent stroke, not wait for symptoms such as stroke to occur. [1]
2. Neurological symptoms resulting from B12 deficiency may take several months or even years to resolve completely
Comment: Agreed.
3. Measuring serum biomarkers such as B12 or methylmalonic acid is neither helpful nor indicated in assessing or monitoring clinical improvement, neither is titration of injection frequency based on biomarker assessment.
Comment: No, but they are crucial for the diagnosis of metabolic B12 deficiency, which is more common than “biochemical” B12 deficiency, and can cause stroke, neuropathy, dementia, and myelopathy.[2]
4. Self-administration of intramuscular B12 injections can lead to greater patient satisfaction and better health outcomes.
Comment: Most patients with B12 deficiency can take high-dose oral B12; those with severe B12 deficiency may need injections at first to restore the intestinal villi. (Villous atrophy results from impaired synthesis of DNA; the intestinal villi turn over about every 5 days, so they atrophy much faster than the changes in leukocytes appear.) [3-6]
Finally, there was no discussion of the important issue of toxicity of cyanocobalamin in patients with impaired renal function, probably due to cyanide. In the early clinical trials of B vitamins to lower homocysteine in stroke prevention, that phenomenon obscured the substantial reduction of stroke risk with B vitamins. Patients with impaired renal function, including the elderly, should take methylcobalamin or hydroxocobalamin, not cyanocobalamin.[1]
1. Spence JD, Hankey GJ. Problem in the Recent American Heart Association Guideline on Secondary Stroke Prevention: B Vitamins to Lower Homocysteine Do Prevent Stroke. Stroke. 2022;53(8):2702-8.
2. Spence JD. Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res. 2016;36(2):109-16.
3. Arvantakis C, Lyford CL, Folscroft J. Intestinal absorptive and digestive function in pernicious anemia. Am J Med. 1977;63(6):859-64.
4. Arvanitakis C. Functional and morphological abnormalities of the small intestinal mucosa in pernicious anemia--a prospective study. Acta Hepatogastroenterol (Stuttg). 1978;25(4):313-8.
5. Carmel R, Herbert V. Correctable intestinal defect of vitamin B12 absorption in pernicious anemia. Ann Intern Med. 1967;67(6):1201-7.
6. Foroozan P, Trier JS. Mucosa of the small intestine in pernicious anemia. N Engl J Med. 1967;277(11):553-9.
Competing interests: No competing interests
Dear Editor
It is great to see research on B12 that highlights the issues that many face. I did manage to get some loading doses on the NHS by asking for a second opinion, and luckily ended up with a locum GP from an area that had delivered training on the NICE guidelines so was aware of them. Rather than keep arguing for treatment in line with the guidelines while I was feeling so terrible, I opted for self treatment which I am fortunate to be able to afford.
As per another comment these symptoms are generalised across many vitamin and mineral deficiencies as well as other illnesses. It is a shame that basic vitamin and mineral supplements are not widely recognised by GPs as a valid form of treatment or even considered as first line testing over and above psychiatric medication.
I often wonder if my iron and B12 deficiencies had been treated when the signs were first there on my blood tests back in 2013, whether many years of severe depression, numerous doctors' appointments, various antidepressants, CBT and time off work could have been avoided. Of course we will never know but now that I am taking the amount of iron and B12 I need I am gradually on the road to recovery and hope to reduce antidepressants in the new year.
There are many patient forums online where people are taking their treatment into their own hands and making their lives better. It would be wonderful to see this more widely available for all patients, not just those with the ability to find their own answers.
Competing interests: No competing interests
Dear Editor,
The areas of testing for cobalamin (vitamin B12) deficiency, as well as the differentiation of diseases due to cobalamin-deficiency, from conditions or symptoms, associated with cobalamin-deficiency, and otherwise asymptomatic low cobalamin levels are controversial. These areas require a balanced and objective assessment, including acknowledgment of the uncertainties. The usefulness of the recent paper by Wolffenbuttel et al (1) is severely hampered by the authors’ overwhelming agenda. Whilst they clearly wish injectable B12 to be available as often as required to anyone that feels they need it, their use of the literature to support their agenda has failed to provide an impartial position.
The literature they use to support their assumption that neither methylmalonic acid nor homocysteine are useful biomarkers either for the diagnosis, or prognosis, of cobalamin deficiency includes a single case report (2) and a systematic review (3) that does not include any data on methylmalonic acid or homocysteine. In contrast, the authors have failed to discuss (the arguably more convincing) data from Savage et al showing that of 434 patients with cobalamin deficiency 433 had significant elevation of either homocysteine (95.9% sensitivity for cobalamin-deficiency) or methylmalonic acid (98.4%) (4). When looking specifically at neuropsychiatric manifestations (which do indeed commonly occur with haematological changes) 100% of 37 patients had a significant (at least 3 standard deviations above the normal) elevation of either methylmalonic acid or homocysteine, all patients demonstrated a clinical response to cobalamin-replacement, and this was associated with a corresponding reduction in methylmalonic acid and homocysteine (5). This does suggest that these can be useful biomarkers.
The authors also cite “expert opinion,” as a reason to treat with B12 in the absence of objective biomarker evidence. Whilst expert-opinion panels have their own important issues, does a single-author retrospective case-series (6), count as “expert opinion?”
When considering the merits of oral versus parenteral replacement, the authors have been equally over-selective in their appraisal; they cite the most negative comment from the Cochrane review (which did include 3 randomized trials and 4 prospective trials)(7) and place much more weight on an online survey, where even authors quote the major limitations (“…potential bias of the sample. Respondents were members of support groups that advocate for the issues being examined here and who, rightly or wrongly, believe in the observed outcomes”) (8). The authors have also not included a more recent updated systemic review and a further randomized controlled trial that support the effectiveness, safety, and non-inferiority of oral cobalamin (1000 microgrammes daily)(9,10). Sanz-Cuesta et al reported a strong preference for the oral route (83.4% preference) (10).
More clarity is needed on optimal diagnosis and management of cobalamin-deficiency, this needs more research and open discourse. Wolffenbuttel et al seem to have allowed their agenda to over-influence objective presentation of the rational therapeutics.
References
1. Wolffenbuttel BH, Owen PJ, Ward M, et al. Vitamin B(12). BMJ (Clinical research ed) 2023;383:e071725. doi: 10.1136/bmj-2022-071725
2. Graber JJ, Sherman FT, Kaufmann H, et al. Vitamin B12-responsive severe leukoencephalopathy and autonomic dysfunction in a patient with "normal" serum B12 levels. Journal of neurology, neurosurgery, and psychiatry 2010;81(12):1369-71. doi: 10.1136/jnnp.2009.178657
3. Julian T, Syeed R, Glascow N, et al. B12 as a Treatment for Peripheral Neuropathic Pain: A Systematic Review. Nutrients 2020;12(8) doi: 10.3390/nu12082221
4. Savage DG, Lindenbaum J, Stabler SP, et al. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. The American journal of medicine 1994;96(3):239-46. doi: 10.1016/0002-9343(94)90149-x
5. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis. New England Journal of Medicine 1988;318(26):1720-28. doi: 10.1056/NEJM198806303182604
6. Solomon LR. Vitamin B12-responsive neuropathies: A case series. Nutritional neuroscience 2016;19(4):162-8. doi: 10.1179/1476830515y.0000000006
7. Wang H, Li L, Qin LL, et al. Oral vitamin B(12) versus intramuscular vitamin B(12) for vitamin B(12) deficiency. The Cochrane database of systematic reviews 2018;3(3):Cd004655. doi: 10.1002/14651858.CD004655.pub3
8. Kornic P, Harty M, Grant J. Influence of Treatment Parameters on Symptom Relief in Individuals with Vitamin B12 Deficiency. Annual research & review in biology 2016;11:1-8.
9. Andrès E, Zulfiqar AA, Vogel T. State of the art review: oral and nasal vitamin B12 therapy in the elderly. QJM : monthly journal of the Association of Physicians 2020;113(1):5-15. doi: 10.1093/qjmed/hcz046
10. Sanz-Cuesta T, Escortell-Mayor E, Cura-Gonzalez I, et al. Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12). BMJ open 2020;10(8):e033687. doi: 10.1136/bmjopen-2019-033687
Competing interests: No competing interests
Dear Editor
I am writing on behalf of The Pernicious Anaemia/B12 Deficiency Support Group, which has over 40,000 members worldwide. As one of the UK representatives I have a particular interest in the diagnosis and treatment of sufferers in the UK and I have also recently represented the group in the process of the formation of the new NICE guidelines. Having personally suffered a severe deficiency with neurological damage due to initial misdiagnosis I also speak from experience, certainly one that I would never wish anyone else to encounter.
I would like to respond to the comments by Dr Ansari who rightly states that primary care is responsible for initial diagnosis and treatment and that is exactly where the problems start for many sufferers. In general, there appears to be a lack of understanding as to the serious consequence to the patient of an undiagnosed, misdiagnosed or incorrectly treated deficiency. Is it a trait of GPs to smell and see oranges but decide to go looking for lemons instead? With the current lack of available GP appointments in General Practice there is a trend in the UK that GP appointments are only 10 minutes in duration and only one ailment can be discussed at each appointment. When presented with a long list of symptoms the patient is told, well we can only discuss one of these today. It would seem that there is not the time nor the inclination to fully investigate a root cause of symptoms.
He is concerned that the article does nothing to empower Doctors. The new NICE guidelines when published may well help with objectivity but with the lack of accurate diagnostic testing there is little that will give “certainty”! The article might however help to empower patients to encourage their doctors to fully and properly explore every avenue in order to provide the correct diagnoses.
I believe we are currently suffering a pandemic of increased B12 deficiency so I can understand the pressures that this puts on overstretched primary care services. Causes of deficiency are too numerous to mention but modern diets, prescription medicines, and a greater ageing population are all culprits. I agree that there should be more research into what he sees as a phenomenon, such as environmental factors in an effort to understand the causes and identify possible ways of prevention.
Should Dr Ansari be worrying about straying into the realms of wellness rather than health, surely one follows the other, especially in the case of B12 deficiency, sort out the wellness at an early stage and the serious health issues don’t follow along! You can get help from a GP to give up smoking, lose weight or eat a healthier diet, those are wellness services provided in an attempt to stave off potentially serious life changing/threatening future chronic illnesses. Surely Pernicious Anaemia and B12 deficiency should be treated with the same respect. There has recently been a successful medical negligence case and others are now pursuing this route.
Dr Ansari mentions stories of patients becoming incredibly symptomatic through late administration of their B12 injections. Perhaps he should consider why this might be rather than choosing to believe that this is a psychosomatic response. Very few can go 12 weeks without symptom return.
I find it disturbing that a GP working within the NHS seems to think that B12d is only a wellness issue that patients should have to deal with or pay for privately. This is fundamentally against the established guiding principles of the NHS which is supposed to provide a service to all, based on clinical need not on the ability to pay.
Competing interests: No competing interests
Dear Editor
In this day and age, no account of Vitamin B12 deficiency would be complete without mention of nitrous oxide abuse as a cause of poor bioavailability of Vitamin B12.
The toxicity of nitrous oxide is mediated by oxidation and, hence, inactivation of vitamin B12. The result is an impairment of conversion of homocysteine to methionine, the latter a necessary step in myelin production, both in the central and in the peripheral nervous system[1].
As a consequence, nitrous oxide-related myeloneuropathy simulates myeloneuropathy attributable to vitamin B12 deficiency, both by causing symptoms such as those typically associated with subacute combined degeneration of the spinal cord, and by causing symptoms attributable to peripheral neuropathy.
Nitrous oxide abuse can also cause symptoms simulating those attributable to Guillain-Barre syndrome[2].
The neurological symptoms of nitrous oxide abuse resolve after a regime consisting of vitamin B12 injections coupled with discontinuation(albeit sometimes transient) of nitrous oxide abuse.
I have no conflict of interest.
References
[1]Xiang Y., Ma X., Li S
Recreational nitrous oxide abuse: prevalence, neurotoxicity, and treatment
Neurotox Res 2021;39:975-978
[2] Jolobe OMP
Nitrous oxide myeloneuropathy as the differential diagnosis of Guillain Barre syndrome
American Journal of Emergency Medicne
Article in Press
doi.org/10.1016/j.ajem.2023.11.016
Competing interests: No competing interests
Dear Editor,
I was interested to read this article on B12 deficiency, which I noted had no GP in the author list, even though this is an almost exclusively General Practice diagnosis with all treatment being delivered through Primary Care.
There is an omission, from my perspective, for the need to critique and specifically analyse the presenting symptoms associated with B12 deficiency, the other potential underlying causes for such symptoms such as perimenopause, CFS/ME, chronic poor mental health and other nutritional deficiencies.
The neurological symptoms are so vague that they basically support supplementation in all psychiatric patients and about 50% of all GP presentations. Both sets of these patients, depending on the area, are more likely to be nutritionally compromised)
We risk veering into the realms of 'wellness' rather than 'health' if we start offering injectable B12 supplementation to all with a B12 less than 300 who are feeling fatigued or have brain fog.
Most, if not all, GPs will be able to recount stories of people who have been prescribed lifetime B12 supplementation for borderline results leading to situations where they become incredibly symptomatic through administration of B12 injection that is 2-3 days late. There is also the mistaken diagnostic issue of B12 deficiency = pernicious anaemia (a much more significant diagnosis).
This article has been written to support access for patients to receive B12 supplementation when they need it, which is a helpful addition to the literature, but does nothing to empower doctors who actually encounter this presentation to be able to bring some objectivity or certainty to the diagnosis. Further research is certainly indicated into this phenomenon with a hope that B12 deficiency as a medical problem can be fully separated from the syndrome of someone who feels B12 deficient. The former should be treated medically and the offer can have treatment undertaken privately as they would for other vitamin treatments.
Kind regards
Competing interests: No competing interests
Re: Vitamin B12 and correction of the relevance of a reference
Dear Editor
In my recent Rapid Response there is a sentence which reads as follows:-
Microcytosis can also be a feature of vitamin B12 deficiency[2],[6], especially when the underlying cause is autoimmune gastritis[7]"
The correct version should be the following:-
"Microcytosis can also be a feature of vitamin B12 deficiency[2],[7], especially when the underlying cause is autoimmune gastritis[7]"
I would also like to take this opportunity to add that, in the context of autoimmune gastritis the association of vitamin B12 deficiency and microcytosis is attributable to coexistence of iron deficiency. Even in other instances of the association of vitamin B12 deficiency and microcytosis it is highly likely that the association is attributable to coexistence of iron deficiency and vitamin B12 deficiency.
Competing interests: No competing interests