Biomarkers of vitamin B-12 status in NHANES: a roundtable summary

Abstract

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.

Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain

“…While the value of these tests are acknowledged mainly in the research setting, in the routine clinical setting definite biomarker(s) of vitamin B12 status remain(s) to be established [32,59] . Thus, an expert opinion report indicates that, as a screening test, total Hcy measurements are less expensive, widely available, and reflect both cobalamin and folate status [32] .…”

“…Thus, an expert opinion report indicates that, as a screening test, total Hcy measurements are less expensive, widely available, and reflect both cobalamin and folate status [32] . Also, a roundtable to discuss the measurement of vitamin B12 status biomarkers in NHANES, stressed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B12 (serum vitamin B12 or holoTC) and one functional biomarker (MMA or total Hcy) [59] . In our study, vitamin B12 and total Hcy were used according to our facilities.…”

Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12

“…A marked interest in monitoring the vitamin B-12 status of the US population was triggered by the 1996 implementation of the national folic acid fortification of cereal grains because of concerns that an improved folate status could adversely affect persons at risk of vitamin B-12 insufficiency, particularly the elderly, for whom a relatively high prevalence has been reported (1,2). NHANES has measured 3 biomarkers of vitamin B-12 status over the past 3 decades: serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy) (3). Serum vitamin B-12 directly reflects the range of circulating vitamin B-12 concentrations in individuals, although not necessarily tissue concentrations.…”

“…This limitation is particularly critical for identifying individuals with subclinical vitamin B-12 deficiency who lack clinically relevant endpoints and often depend on other biomarkers for comparison and validation (3,5). For serum vitamin B-12 and MMA, commonly used cutoffs often come from statistical distributions of different populations.…”

Comparison of two methods for measuring methylmalonic acid as a marker for vitamin B12 deficiency

“…Table 1 shows the concentrations of vitamin B12 markers and the percentage of samples with elevated or lowered concentrations. Several cut-off values have been employed in epidemiological studies for lowered total B12 and holoTC or elevated MMA [18,19]. We considered the following cut-off values: low holoTC < 35 pmol/L; low total vitamin B12 ≤ 148 pmol/L; elevated MMA > 300 nmol/L; elevated tHcy > 12 μmol/L.…”