A vitamin B-12 supplement of 500 μg/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 status.
What this study found
Oral cyanocobalamin improved vitamin B-12 status biomarkers in a dose-dependent way, but 8 weeks of treatment did not normalize all participants. Plasma vitamin B-12 and serum holoTC increased at all doses versus placebo (both P < 0.0001), and 500 mg/d produced greater increases than 10 or 100 mg/d for both markers (P < 0.0001). Urinary MMA ratio and plasma MMA fell by 14 days and showed smoking-related differences: among never-smokers, 500 mg/d gave the largest 56-day reductions, while ex-smokers responded to all doses, with 100 mg/d borderline versus placebo for the urinary MMA ratio (P =…
- Study & population
- Elderly men and women in the United Kingdom with moderately poor vitamin B-12 status were studied at the Royal Hallamshire Hospital in Sheffield.
- Intervention
- Oral cyanocobalamin capsules were given daily for 8 weeks in three active doses: 10 mg/d, 100 mg/d, or 500 mg/d, with placebo capsules as comparator.
- Key limitation
- The active arms were small (25 participants each) and the intervention lasted only 8 weeks, limiting conclusions about longer-term normalization.
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Open PDFOriginal abstract
Plasma vitamin B-12 is the most commonly used biomarker of vitamin B-12 status, but the predictive value for low vitamin B-12 status is poor. The urinary methylmalonic acid (uMMA) concentration has potential as a functional biomarker of vitamin B-12 status, but the response to supplemental vitamin B-12 is uncertain. A study was conducted to investigate the responsiveness of uMMA to supplemental vitamin B-12 in comparison with other biomarkers of vitamin B-12 status [plasma vitamin B-12, serum holotranscobalamin (holoTC), plasma MMA] in elderly people with moderately poor vitamin B-12 status. A double-blind, placebo-controlled, randomized 8-wk intervention study was carried out using vitamin B-12 supplements (500 μg/d, 100 μg/d, and 10 μg/d cyanocobalamin) in 100 elderly people with a combined plasma vitamin B-12 <250 pmol/L and uMMA ratio (μmol MMA/mmol creatinine) >1.5. All biomarkers had a dose response to supplemental vitamin B-12. Improvements in plasma vitamin B-12 and serum holoTC were achieved at cobalamin supplements of 10 μg/d, but even 500 μg/d for 8 wk did not normalize plasma vitamin B-12 in 8% and serum holoTC in 12% of people. The response in uMMA was comparable with plasma MMA; 15-25% of people still showed evidence of metabolic deficiency after 500 μg/d cobalamin for 8 wk. There was a differential response in urinary and plasma MMA according to smoking behavior; the response was enhanced in ex-smokers compared with never-smokers. uMMA offers an alternative marker of metabolic vitamin-B12 status, obviating the need for blood sampling.