In their analysis of the relationship between carotid plaque area and vitamin B12 status,1 Julie Robertson and colleagues define vitamin B12 deficiency as a serum concentration of less than 258 pmol/L, with a plasma homocysteine concentration of 14 μmol/L or more or a plasma methylmalonic acid (MMA) level of 271 nmol/L or more. We question the use of these thresholds and the conclusions that are based on them.
Their threshold for vitamin B12 deficiency of 258 pmol/L is almost the same as the sample median value of 253 pmol/L . This value is exceedingly high and probably inappropriately labeled many study patients as having a vitamin B12 deficiency. Among 11 000 elderly women in Ontario and British Columbia, the mean and fifth centile serum vitamin B12concentrations were 300 and 118 pmol/L, respectively, after folic acid food fortification.2 Similar values were found among Ontario women of reproductive age.3
We previously showed that plasma total homocysteine levels can be relatively insensitive for detecting vitamin B12 deficiency.4 A homocysteine concentration at or above 15 μmol/L has positive and negative predictive values of 7.4% and 97.2%, respectively, for the detection of a serum vitamin B12 concentration below 120 pmol/L. For vitamin B12 levels between 120 and 150 pmol/L, the corresponding predictive values are just 6.3% and 94.0%.4 In Fig. 1 of the article by Robertson and colleagues the mean homocysteine concentration was just 12 μmol/L even in the quartile of patients with the lowest serum vitamin B12 concentrations (below 203 pmol/L). Thus, it is unlikely that vitamin B12 deficiency could be efficiently detected on the basis of a homocysteine measurement equal to or greater than 15 μmol/L.
Their lack of use of a comprehensive and suitable definition of vitamin B12 leads us to question the authors' conclusions that “vitamin B12 deficiency is surprisingly common among patients with vascular disease” and that “low serum vitamin B12 levels are a major determinant of elevated homocysteine levels and increased carotid plaque area.”1 With nearly 50% of patients omitted from their major analysis, could not age and serum creatinine alone have explained some of their findings?
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