The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine

Hvas, Anne‐Mette; Juul, Svend; Gerdes, Lars Ulrik; Nexø, Ebba

doi:10.1046/j.1365-2796.2000.00632.x

Cited by 42 publications

(28 citation statements)

References 29 publications

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“…After vitamin treatment, single subjects with higher serum creatinine concentrations had metabolite concentrations above the reference limits of the laboratory. Somewhat unexpectedly (Norlund et al, 1998;Bostom et al, 1999;Brattström & Wilcken, 2000;Hvas et al, 2000), metabolite concentrations did not correlate to serum creatinine. This might call for a better marker for renal function in this elderly population.…”

Section: Discussionmentioning

confidence: 90%

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Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial

et al. 2003

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Objectives: To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B 12 /folate deficiency on the basis of different decision limits. Design: Double-blind placebo-controlled intervention study. Setting: Outpatient clinic. Subjects: A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y. Intervention: Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B 6 . Results: High P-tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B 12 deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (Po0.001) and S-MMA (P ¼ 0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B 12 and age. Conclusions: Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA. Sponsorship: SupportFRecip AB.

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Section: Discussionmentioning

confidence: 90%

“…Certain lifestyle factors may also contribute (Nygård et al, 1998;Stolzenberg-Solomon et al, 1999;de Bree et al, 2001). Elevated concentrations of serum methylmalonate (S-MMA) is seen in vitamin B 12 deficiency, impaired renal function (Hvas et al, 2000) and dehydration , low values after antibiotic therapy (Lindenbaum et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial

et al. 2003

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“…Table 3 of the present study indicate that some elderly respondents with raised MMA levels also have abnormal plasma urea and creatinine concentration, and therefore impaired kidney function. Many other studies have also detected a link between raised blood MMA levels and impaired kidney function (Stabler et al, 1986;Rasmussen et al, 1990a, b;Joosten et al, 1993;Lindenbaum et al, 1994;Koehler et al, 1996;Norman, 1998Norman, , 1999van Asselt et al, 1998;Herrmann et al, 2000;Hvas et al, 2000). According to Whitehead et al (1994), the 97.5th centile of plasma creatinine in adults aged 25 -55 y is approximately 122 mmol=l (males) and 100 mmol=l (females), and for plasma urea it is 7.6 mmol=l (males) and 6.8 mmol=l (females).…”

Section: Discussionmentioning

confidence: 97%

Relationship between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the British National Diet and Nutrition Survey of people aged 65 y and over

et al. 2003

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Objective: Assessment of functional vitamin B 12 status in a subset of the respondents in the British National Diet and Nutrition Survey of people aged 65 y and over. Setting: National Diet and Nutrition Survey: a British nationwide cross-sectional sample of people aged 65 y and over, living either in the community or in institutions such as nursing homes, during one calendar year spanning 1994 -1995. Methods: Methylmalonic acid (MMA) concentrations were measured in plasma samples from 313 subjects (ca 14% of those originally enrolled in the survey). The results were compared with those for serum vitamin B 12 , vitamin B 12 intakes and other status and intake estimates and with socio-demographic indices. Results: Of the NDNS participants overall, 20% had serum vitamin B 12 concentrations < 150 pmol=l. In the subset studied here, 24% of free-living and 46% of institution-living participants had MMA >0.5 mmol=l. Geometric mean MMA increased with age, from 0.25 mmol=l in people aged 65 -74 y to 0.38 mmol=l in people aged 85 þ y. There was little evidence for any gender difference in MMA. It was inversely correlated with serum vitamin B 12 and with red blood cell folate; it was positively correlated directly with total homocysteine, but not significantly with serum folate or with vitamin B 12 intake. Among respondents with high MMA, a subgroup had normal serum vitamin B 12 but higher-than-average plasma urea and creatinine. Socio-demographic co-variates of MMA included receipt of State income benefits, social class of head of household, and educational attainment. These indices were not correlated with serum vitamin B 12 . Conclusions: The progressive increase in MMA with age is metabolic evidence for increasing risk of functional vitamin B 12 deficiency with increasing age in older people. There is evidence that renal function is linked to high MMA in some older people. Age and renal function are thus both important when establishing upper reference limits for MMA. The socio-demographic observations suggest a link between poverty and poor functional vitamin B 12 status in older British people.

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“…MMA concentrations are highly dependent on kidney function and serum creatinine (9), even within the normal range (45). We excluded those with high serum creatinine concentrations, which are indicative of serious renal impairment, but also recognized that some residual effect on MMA concentrations might occur in persons with milder renal impairment.…”

Section: Discussionmentioning

confidence: 99%

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

Bailey¹,

Carmel²,

Green³

et al. 2011

The American Journal of Clinical Nutrition

136

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Background: Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects. Objective: The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency. Design: Data from NHANES, a nationally representative crosssectional survey, were examined for adults aged .19 y (mean 6 SD age: 45 6 1 y) from 1999 to 2004 (n = 12,612). Results: Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of .148 pmol/L for vitamin B-12 and of 210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency. Conclusions: These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal.Am J Clin Nutr 2011;94:552-61.

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The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine

Abstract: Abstract. Hvas AM,

Cited by 42 publications

References 29 publications

Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial

Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial

Relationship between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the British National Diet and Nutrition Survey of people aged 65 y and over

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

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