In July 2013, Health Quality Ontario released recommendations on vitamin B12 testing from the Appropriateness Working Group of the Ontario Health Technology Advisory Committee (OHTAC).(86) The objective of their Appropriateness Initiative is to develop a systematic framework for the ongoing identification, prioritisation, and assessment of health interventions in Ontario for which there is possible misuse, overuse, or underuse. Seven health interventions were examined in the first phase: annual health exams, aspartate aminotransferase testing, ferritin testing, folate testing and vitamin B12 testing. The analysis of vitamin B12 testing was based on a rapid review (see Sections 5.1.2, 5.1.3 and 5.1.6). On the basis of the findings of the review, OHTAC recommended that vitamin B12 testing is removed from the Ontario laboratory requisition form.(86)
4.3 Summary of clinical guidance
No relevant Australian guidelines were identified in the literature search. Four guidelines on diagnosing vitamin B12 deficiency were identified (two from the UK and two from Canada), with limited evidence supporting the recommendations.
One 2012 guideline from the British Columbia Medical Association and Ministry of Health, Canada, concluded that routine screening for vitamin B12 deficiency is not recommended. No other guidelines made recommendations relating to routine screening.
Several guidelines recommend that patients with symptoms or signs of vitamin B12 deficiency anaemia (macrocytic anaemia or macrocytosis) and patients with suspected neuropsychiatric abnormalities should be tested for vitamin B12 deficiency. Other populations where testing could be considered include the elderly, long-term vegans, people on drugs that interfere with vitamin absorption (long-term H2 receptor antagonists or proton pump inhibitors or metformin) and patients with inflammatory bowel disease, gastric or small intestine resection.
The frequency with which patients should be tested was not addressed in the guidelines. However, a 2005 best practice review from the UK stated that there is no obvious merit in repeating vitamin B12 measurements (in patients with macrocytic anaemia, macrocytosis, or patients with specific neuropsychiatric abnormalities) unless lack of compliance is suspected or anaemia recurs.
In July 2013, Health Quality Ontario released recommendations on a variety of common clinical tests, including vitamin B12. On the basis of their rapid review which found that serum vitamin B12 test has low diagnostic accuracy, it was recommended that vitamin B12 testing is removed from the Ontario laboratory requisition form.
5 REVIEW OF THE CLINICAL EVIDENCE FOR VITAMIN B12 TESTING
This Chapter presents the results of the systematic literature review on vitamin B12 testing in relation to the clinical research questions.
5.1 Evidence base
5.1.1 Search results
A literature search was performed on 23rd September 2013, using OVID MEDLINE, EMBASE, and the Cochrane Library, for studies published from January 2006 until September 2013. Abstracts were reviewed and for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. The database search yielded 1,763 citations (with duplicates removed). Articles were excluded based on information in the title and abstract. The full texts of potentially relevant articles were obtained for further assessment.
5.1.2 Existing health technology reports and systematic reviews
The literature search identified a recent Rapid Review on serum vitamin B12 testing(71) published in December 2012 by Health Quality Ontario. The objective of this rapid review was to establish under what circumstances, and how often, serum vitamin B12 tests should be used to assess vitamin B12 deficiency. A systematic literature search was conducted between January 2000 and June 2012 to identify relevant systematic reviews, health technology assessments and meta-analyses. The review’s search was also expanded to include randomised controlled trials (RCTs) and guidelines.
5.2 Appropriate clinical indications for vitamin B12 testing
There were no studies identified that evaluated the clinical indications for vitamin B12 testing. However, several guidelines (described in Chapter 4) recommended the evaluation of vitamin B12 deficiency in the workup for clinical indications (anaemia in CKD, post-gastrectomy patients, elderly with cognitive impairment, neuropathy, as well as patients at risk of vitamin B12 deficiency). In addition, the rapid review by Health Quality Ontario concluded (based on three low-grade guidelines) that patients with symptoms or signs of vitamin B12 deficiency anaemia (macrocytic anaemia) should be tested for vitamin B12 deficiency. However, it stated that it is unclear whether other special populations should be tested for B12 deficiency (e.g. patients with suspect neuropsychiatric abnormalities).(71)
5.3 Evidence that testing for vitamin B12 levels improves health outcomes
No definitive conclusions can be drawn about the effectiveness of vitamin B12 testing since no prospective comparative trials have been conducted to directly assess the impact of testing on health outcomes in healthy populations or in patients with chronic disease associated with vitamin B12 deficiency.
5.4 Risks/harms associated with vitamin B12 testing
No trials designed to directly measure the risks or harms associated with vitamin B12 testing were identified. In terms of harms, vitamin B12 testing relies on a blood draw, which is a safe procedure.
It is likely that the consequences of inaccurate or inappropriately interpreted serum vitamin B12 test results, such as a false positive, are relatively small. Vitamin B12 supplements are generally considered safe when taken in amounts that are not higher than the recommended dietary allowance. Findings from the NORVIT(87) and HOPE 2(88) intervention trials support these claims. In both of these trials, vitamin B12 supplementation (in combination with folic acid and vitamin B6) did not cause any serious adverse events when administered at doses of 0.4 mg for 40 months (NORVIT trial) and 1.0 mg for 5 years (HOPE 2 trial).
