. 2018 Mar 15;3(3):CD004655.

doi: 10.1002/14651858.CD004655.pub3.

Oral vitamin B₁₂ versus intramuscular vitamin B₁₂ for vitamin B₁₂ deficiency

Haiyan Wang¹, Linyi Li, Ling Ling Qin, Yanan Song, Josep Vidal-Alaball, Tong Hua Liu

Affiliations

Affiliation

¹ Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, School range, ChaoYang District, Beijing, Beijing, China, 100029.

PMID: 29543316
PMCID: PMC6494183
DOI: 10.1002/14651858.CD004655.pub3

Oral vitamin B₁₂ versus intramuscular vitamin B₁₂ for vitamin B₁₂ deficiency

Haiyan Wang et al. Cochrane Database Syst Rev. 2018.

. 2018 Mar 15;3(3):CD004655.

doi: 10.1002/14651858.CD004655.pub3.

Authors

Haiyan Wang¹, Linyi Li, Ling Ling Qin, Yanan Song, Josep Vidal-Alaball, Tong Hua Liu

Affiliation

¹ Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, School range, ChaoYang District, Beijing, Beijing, China, 100029.

PMID: 29543316
PMCID: PMC6494183
DOI: 10.1002/14651858.CD004655.pub3

Abstract

Background: Vitamin B₁₂ deficiency is common, and the incidence increases with age. Most people with vitamin B₁₂ deficiency are treated in primary care with intramuscular (IM) vitamin B₁₂. Doctors may not be prescribing oral vitamin B₁₂ formulations because they may be unaware of this option or have concerns regarding its effectiveness.

Objectives: To assess the effects of oral vitamin B₁₂ versus intramuscular vitamin B₁₂ for vitamin B₁₂ deficiency.

Search methods: We searched CENTRAL, MEDLINE, Embase, and LILACS, as well as the WHO ICTRP and ClinicalTrials.gov. The latest search date was 17 July 2017. We applied no language restrictions. We also contacted authors of relevant trials to enquire about other published or unpublished studies and ongoing trials.

Selection criteria: Randomised controlled trials (RCTs) comparing the effect of oral versus IM vitamin B₁₂ for vitamin B₁₂ deficiency.

Data collection and analysis: We used standard methodological procedures expected by Cochrane. Our primary outcomes were serum vitamin B₁₂ levels, clinical signs and symptoms of vitamin B₁₂ deficiency, and adverse events. Secondary outcomes were health-related quality of life, acceptability to patients, haemoglobin and mean corpuscular volume, total homocysteine and serum methylmalonic acid levels, and socioeconomic effects. We used GRADE to assess the quality of the evidence for important outcomes. We did not perform meta-analyses due to the small number of included trials and substantial clinical heterogeneity.

Main results: Three RCTs met our inclusion criteria. The trials randomised 153 participants (74 participants to oral vitamin B₁₂ and 79 participants to IM vitamin B₁₂). Treatment duration and follow-up ranged between three and four months. The mean age of participants ranged from 38.6 to 72 years. The treatment frequency and daily dose of vitamin B₁₂ in the oral and IM groups varied among trials. Only one trial had low or unclear risk of bias across all domains and outcome measures. Two trials reported data for serum vitamin B₁₂ levels. The overall quality of evidence for this outcome was low due to serious imprecision (low number of trials and participants). In two trials employing 1000 μg/day oral vitamin B₁₂, there was no clinically relevant difference in vitamin B₁₂ levels when compared with IM vitamin B₁₂. One trial used 2000 μg/day vitamin B₁₂ and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B₁₂. Two trials reported data on adverse events (very low-quality evidence due to risk of performance bias, detection bias, and serious imprecision). One trial stated that no treatment-related adverse events were seen in both the oral and IM vitamin B₁₂ groups. One trial reported that 2 of 30 participants (6.7%) in the oral vitamin B₁₂ group left the trial early due to adverse events. Orally taken vitamin B₁₂ showed lower treatment-associated costs than IM vitamin B₁₂ in one trial (low-quality evidence due to serious imprecision). No trial reported on clinical signs and symptoms of vitamin B₁₂ deficiency, health-related quality of life, or acceptability of the treatment scheme.

Authors' conclusions: Low quality evidence shows oral and IM vitamin B₁₂ having similar effects in terms of normalising serum vitamin B₁₂ levels, but oral treatment costs less. We found very low-quality evidence that oral vitamin B₁₂ appears as safe as IM vitamin B₁₂. Further trials should conduct better randomisation and blinding procedures, recruit more participants, and provide adequate reporting. Future trials should also measure important outcomes such as the clinical signs and symptoms of vitamin B₁₂ deficiency, health related-quality of life, socioeconomic effects, and report adverse events adequately, preferably in a primary care setting.

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Conflict of interest statement

HYW: none known

LYL: none known.

LLQ: none known.

YNS: none known.

JVA: none known.

THL: none known.

Figures

2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies (blank cells indicate that the particular outcome was not measured in some studies).

3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study (blank cells indicate that the study did not measure that particular outcome).

**1.1. Analysis**
Comparison 1 Oral versus intramuscular vitamin B₁₂, Outcome 1 Serum vitamin B₁₂ levels.

**1.2. Analysis**
Comparison 1 Oral versus intramuscular vitamin B₁₂, Outcome 2 Number of participants with normalisation of serum vitamin B₁₂ deficiency.

**1.3. Analysis**
Comparison 1 Oral versus intramuscular vitamin B₁₂, Outcome 3 Adverse events.

**1.4. Analysis**
Comparison 1 Oral versus intramuscular vitamin B₁₂, Outcome 4 Haemoglobin.

**1.5. Analysis**
Comparison 1 Oral versus intramuscular vitamin B₁₂, Outcome 5 Mean corpuscular volume.

**1.6. Analysis**
Comparison 1 Oral versus intramuscular vitamin B₁₂, Outcome 6 Total homocysteine.

**1.7. Analysis**
Comparison 1 Oral versus intramuscular vitamin B₁₂, Outcome 7 Serum methylmalonic acid.

See this image and copyright information in PMC

Update of

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.
Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A, Hood K, McCaddon A, McDowell I, Papaioannou A. Vidal-Alaball J, et al. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004655. doi: 10.1002/14651858.CD004655.pub2. Cochrane Database Syst Rev. 2005. Update in: Cochrane Database Syst Rev. 2018 Mar 15;3:CD004655. doi: 10.1002/14651858.CD004655.pub3. PMID: 16034940 Free PMC article. Updated.

Comment in

Update on the evidence for oral B₁₂ supplements to treat deficiency.
[No authors listed] [No authors listed] Drug Ther Bull. 2019 Jan;57(1):9. doi: 10.1136/dtb.2018.000057. Drug Ther Bull. 2019. PMID: 30567852 No abstract available.

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