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Clinical Review

Vitamin B12 deficiency

BMJ 2014; 349 doi: (Published 04 September 2014) Cite this as: BMJ 2014;349:g5226

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Hunt, Harrington and Robinson provide a welcome overview of vitamin B12 deficiency and its treatment. A few aspects, however, could be emphasised more.

First, one of the most common and most debilitating symptoms of vitamin B12 deficiency is extreme fatigue, ‘tired all the time’ and in some patients also insomnia. If a patient’s mood is low at the same time, this can easily be interpreted as depression. Vitamin B12 deficiency is then easily missed.

Second, the presence of risk factors should increase the level of clinical suspicion. One important risk factor is the use of nitrous oxide. Nitrous oxide inactivates vitamin B12 [1] but leaves it detectable on serum B12 essay, thereby increasing the risk of a false negative test. It is used in general anaesthesia, as an analgesic in obstetrics and in ambulances and emergency departments. It is increasingly used as a recreational drug, sometimes in large amounts and for prolonged periods of time. In elderly patients who deteriorate after an operation, or patients whose symptoms worsen after delivery, an operation or a painful emergency, vitamin B12 deficiency should be suspected. Some drug-seeking patients repeatedly obtain nitrous oxide in ambulances and emergency departments. Recreational drug use should be part of the history.

The prevalence of vitamin B12 deficiency is increased in the elderly, [2] people with diabetes [3], obesity and in those who have undergone bariatric surgery, [4 5] alcohol abuse, and in eating disorders.

Vitamin B12 deficiency can be easily missed, because its symptoms may be clinically indistinguishable from those of dementia, [6] Parkinson's disease, frailty of old age, diabetic neuropathy, alcoholic central and peripheral neuropathy, and mental illness. It needs to be diligently sought, and treated if there is any clinical suspicion, even if serum B12 levels are within the reference range.

Third, the sensitivity of the serum B12 test is poor. [7] Adding methylmalonic acid and homocysteine improves sensitivity, but may still leave nearly half of patients with B12-responsive symptoms undetected. [8] In patients whose symptoms are consistent with vitamin B12 deficiency but whose serum B12 is within the reference range, a trial of treatment may be used as an adjunct to diagnosis. [6]

1. Sanders RD, Weimann J, Maze M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008;109(4):707-22 doi: 10.1097/ALN.0b013e3181870a17[published Online First: Epub Date]|.
2. Obeid R, Schorr H, Eckert R, et al. Vitamin B12 status in the elderly as judged by available biochemical markers. Clin Chem 2004;50(1):238-41 doi: 10.1373/clinchem.2003.021717[published Online First: Epub Date]|.
3. Kibirige D, Mwebaze R. Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified? Journal of diabetes and metabolic disorders 2013;12(1):17 doi: 10.1186/2251-6581-12-17[published Online First: Epub Date]|.
4. van Rutte PW, Aarts EO, Smulders JF, et al. Nutrient Deficiencies Before and After Sleeve Gastrectomy. Obesity surgery 2014 doi: 10.1007/s11695-014-1225-y[published Online First: Epub Date]|.
5. Stein J, Stier C, Raab H, et al. Review article: the nutritional and pharmacological consequences of obesity surgery. Alimentary pharmacology & therapeutics 2014 doi: 10.1111/apt.12872[published Online First: Epub Date]|.
6. Rietsema WJ. Unexpected Recovery of Moderate Cognitive Impairment on Treatment with Oral Methylcobalamin. Journal of the American Geriatrics Society 2014;62(8):1611-12 doi: 10.1111/jgs.12966[published Online First: Epub Date]|.
7. Carmel R, Agrawal YP. Failures of cobalamin assays in pernicious anemia. N Engl J Med 2012;367(4):385-6 doi: 10.1056/NEJMc1204070[published Online First: Epub Date]|.
8. Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood 2005;105(3):978-85 doi: 10.1182/blood-2004-04-1641[published Online First: Epub Date]|.

Competing interests: No competing interests

09 September 2014
Wilhelmina J. Rietsema
Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, OX2 6GG