Relationship between methylmalonic acid and cobalamin in uremia

Moelby, L.; Rasmussen, Karsten; Ring, Troels; Nielsen, Gert

doi:10.1046/j.1523-1755.2000.00831.x

Cited by 19 publications

(13 citation statements)

References 45 publications

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“…In our investigation, we found a distinctly increased HCY level in patients with hemodialysis (41). A major reason for the high prevalence of hyperhomocysteinemia in dialysis patients is the strongly disturbed renal remethylation of HCY to methionine which is only partly reversible by vitamin supplementation (42,43). A major reason for the high prevalence of hyperhomocysteinemia in dialysis patients is the strongly disturbed renal remethylation of HCY to methionine which is only partly reversible by vitamin supplementation (42,43).…”

Section: Hyperhomocysteinemia In Renal Patientssupporting

confidence: 46%

The Importance of Hyperhomocysteinemia as a Risk Factor for Diseases: An Overview

Herrmann¹

2001

Clinical Chemistry and Laboratory Medicine

116

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Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological studies have proven, that hyperhomocysteinemia is a risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Conflicting results come from prospective studies. Trials which are now in progress may clarify the "causality" of high homocysteine concentrations and will assess the value of homocysteine-lowering therapy. The induction of the atherogenic process by hyperhomocysteinemia seems to be associated with an alteration of endothelial and smooth muscle cell function leading to an accelerated formation of reactive oxygen species. An increased endothelial expression of adhesion molecules will then lead to an enhanced deposition of oxidized LDL in the vessel wall with the formation of foam cells. Additionally, hyperhomocysteinemia interferes with the coagulation system and thus also has prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a sign of a vitamin deficiency in elderly subjects which strongly increases with age. Elderly people have a high frequency of vitamin B12 deficiency which can be diagnosed more reliably by the measurement of serum methylmalonic acid (MMA) level than by serum vitamin B12. Subjects following a strict vegetarian diet also have a high prevalence of hyperhomocysteinemia caused by functional vitamin B12 deficiency (increased MMA level). Last but not least, hyperhomocysteinemia is a factor in the pathogenesis of neural tube defects and pre-eclampsia. An early diagnosis of vitamin B12 deficiency is important for the prevention of neurological damages. Homocysteine should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in obese subjects, in elderly people, in postmenopausal women, and in early pregnancy. A specific diagnosis of an underlying vitamin deficiency is important for adequate treatment. Individuals with homocysteine level >12 micromol/l should increase and/or supplement their dietary intake of vitamins.

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Section: Hyperhomocysteinemia In Renal Patientssupporting

confidence: 46%

The Importance of Hyperhomocysteinemia as a Risk Factor for Diseases: An Overview

Herrmann¹

2001

Clinical Chemistry and Laboratory Medicine

116

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“…Therefore, a substantial proportion of the high MMA concentrations in the present study are unlikely to be attributable to impaired kidney function, and are thus more likely to be due to poor vitamin B 12 status. An MMA elevation above 0.70 mmol=l is unlikely to be explained by moderately impaired renal function alone (Rasmussen et al, 1990a,b;Moelby et al, 2000). More work is clearly needed to establish reasonable MMA reference limits in older people with partially impaired renal function.…”

Section: Discussionmentioning

confidence: 99%

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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“…A very recent publication by Moelby et al showed the relationship between MMA level and vitamin B 12 concentration in patients on chronic hemodialysis treated with intramuscular cobalamin injections (1mg every third month) (40). Using within-patient comparisons, the authors found that even if MMA levels were high, the patients responded quickly to changes in vitamin B 12 concentrations.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine, Cystathionine, Methylmalonic Acid and B-Vitamins in Patients with Renal Disease

Herrmann

Schorr²,

Geisel³

et al. 2001

Clinical Chemistry and Laboratory Medicine

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Moderate hyperhomocysteinemia is very frequent in renal patients. Aside from homocysteine (HCY) itself, the metabolites methylmalonic acid (MMA) and cystathionine (CYS) supply further information about disturbances in HCY metabolism. In two groups of renal patients, transplant and hemodialysis patients, we measured HCY, MMA and CYS and evaluated their diagnostic value for impaired HCY metabolism due to vitamin deficiency and renal insufficiency. We investigated serum samples from 63 transplant patients and 38 patients undergoing hemodialysis. HCY, MMA and CYS were assayed by gas chromatography-mass spectrometry, vitamin B6 by HPLC, B12 and folate by chemiluminescence immunoassay. The determination of HCY, MMA, and CYS in renal patients provides specific information about intracellular disturbances of HCY metabolism. The frequency of increased metabolite levels in renal patients was much higher than the frequency of lowered vitamin concentrations in serum. Furthermore, the metabolite levels in transplant patients were only moderately increased, whereas they were strongly increased in patients on hemodialysis (HCY 19.2 vs. 28.8 micromol/l, MMA 292 vs. 1025 nmol/l, CYS 733 vs. 2711 nmol/l). Our findings may support the use of MMA determination in the diagnosis of vitamin B12 deficiency in renal patients. Compared to vitamin B12 deficiency, renal dysfunction itself appears to cause only a modest elevation in serum MMA. Regression analysis revealed that the moderate elevation of HCY and CYS in transplant patients is mainly a consequence of impaired remethylation of HCY to methionine with activated transsulfuration, whereas the mildly elevated MMA level is attributable to renal dysfunction. In patients on hemodialysis, all three metabolites were markedly elevated, indicating a strongly disturbed HCY metabolism. Based on a backward regression, we discovered that the HCY metabolism was strongly disturbed by renal insufficiency and vitamin deficiency. The markedly elevated HCY level was mainly attributable to functional vitamin B12 deficiency indicated by high MMA, and the strong CYS elevation was due to renal dysfunction and inhibition of this pathway by low levels of vitamin B6. In conclusion, besides HCY, the determination of MMA and CYS levels supports an early diagnosis of B-vitamin deficiency in renal patients. MMA is a more sensitive indicator of intracellular vitamin B12 deficiency than vitamin B12 in serum.

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Relationship between methylmalonic acid and cobalamin in uremia

Cited by 19 publications

References 45 publications

The Importance of Hyperhomocysteinemia as a Risk Factor for Diseases: An Overview

The Importance of Hyperhomocysteinemia as a Risk Factor for Diseases: An Overview

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

Homocysteine, Cystathionine, Methylmalonic Acid and B-Vitamins in Patients with Renal Disease

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