Effect of supplementation with folic-acid on relation between plasma homocysteine, folate, and vitamin B12.

Abstract

E P Quinlivan and colleagues (Jan 19, p 227)1Quinlivan EP McPartlin J McNulty H et al.Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease.Lancet. 2002; 359: 227-228Summary Full Text Full Text PDF PubMed Scopus (194) Google Scholar report a relation between total plasma homocysteine (tHcy) and vitamin B12 in folate-supplemented individuals. There are two B12 carrier proteins in serum. Haptocorrin binds most serum B12 but does not deliver the vitamin to metabolically active cells; this function is done by transcobalamin. Only 5–20% of serum B12 is bound to transcobalamin as holotranscobalamin. Current laboratory assays measure total serum B12 and are relatively poor indicators of the ability of serum to deliver the vitamin to tissues.2Wickramasinghe SN Fida S Correlations between holo-transcobalamin II, holo-haptocorrin, and total B12 in serum samples from healthy subjects and patients.J Clin Pathol. 1993; 46: 537-539Crossref PubMed Scopus (49) Google ScholarWe measured tHcy, folate, total serum B12, and holotranscobalamin concentrations in 111 elderly individuals (51 patients with dementia and 60 controls) with a mean age of 77 years (SD 9·5) recruited to a continuing study of vitamin B12 status and cognitive function. tHcy was measured by an automated high-performance liquid chromatography system, and folate and total serum B12 by an automated chemiluminescence analyser.We used generalised linear models to investigate the relation between known tHcy determinants (age, sex, creatinine, smoking history, and serum folate) and B12 status, assessed by total serum B12 or holotranscobalamin concentrations. Diagnosis was included as an additional independent variable. Individuals receiving B vitamin supplements were excluded.There was a significant and independent relation between tHcy and B12 status assessed by holotranscobalamin concentrations, but not by total serum B12 (table). Current laboratory assays lack sensitivity to measure biologically available B12. We suggest this might be an additional explanation as to why the effects of B12 on tHcy concentrations are frequently masked by folate status.TableGeneralised linear models (GLMs) of potential tHcy determinants showing estimates and strengths of their respective effectsVariableGLM including total serum B12GLM including holotranscobalaminEstimate (95% CI)pEstimate (95% CI)pDementia−0·86 (−1·48 to −0·23)0·007−0·57 (−1·2 to 0·02)0·06Sex−0·10 (−0·82 to 0·62)0·78−0·20 (−0·93 to 0·52)0·57Smoker−0·26 (−1·12 to 0·58)0·54−0·23 (−1·07 to 0·61)0·59Age−0·01 (−0·09 to 0·08)0·870·01 (−0·07 to 0·08)0·89Creatinine (μmol/L)0·09 (0·07 to 0·12)<0·00010·08 (0·06 to 0·10)<0·0001Folate (μg/L)−0·23 (−0·36 to −0·10)0·001−0·15 (−0·28 to −0·03)0·02B12 (ng/L)−0·003 (−0·01 to 0·001)0·12....Holotranscobalamin (pmol/L)....−0·04 (−0·06 to −0·02)0·001 Open table in a new tab E P Quinlivan and colleagues (Jan 19, p 227)1Quinlivan EP McPartlin J McNulty H et al.Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease.Lancet. 2002; 359: 227-228Summary Full Text Full Text PDF PubMed Scopus (194) Google Scholar report a relation between total plasma homocysteine (tHcy) and vitamin B12 in folate-supplemented individuals. There are two B12 carrier proteins in serum. Haptocorrin binds most serum B12 but does not deliver the vitamin to metabolically active cells; this function is done by transcobalamin. Only 5–20% of serum B12 is bound to transcobalamin as holotranscobalamin. Current laboratory assays measure total serum B12 and are relatively poor indicators of the ability of serum to deliver the vitamin to tissues.2Wickramasinghe SN Fida S Correlations between holo-transcobalamin II, holo-haptocorrin, and total B12 in serum samples from healthy subjects and patients.J Clin Pathol. 1993; 46: 537-539Crossref PubMed Scopus (49) Google Scholar We measured tHcy, folate, total serum B12, and holotranscobalamin concentrations in 111 elderly individuals (51 patients with dementia and 60 controls) with a mean age of 77 years (SD 9·5) recruited to a continuing study of vitamin B12 status and cognitive function. tHcy was measured by an automated high-performance liquid chromatography system, and folate and total serum B12 by an automated chemiluminescence analyser. We used generalised linear models to investigate the relation between known tHcy determinants (age, sex, creatinine, smoking history, and serum folate) and B12 status, assessed by total serum B12 or holotranscobalamin concentrations. Diagnosis was included as an additional independent variable. Individuals receiving B vitamin supplements were excluded. There was a significant and independent relation between tHcy and B12 status assessed by holotranscobalamin concentrations, but not by total serum B12 (table). Current laboratory assays lack sensitivity to measure biologically available B12. We suggest this might be an additional explanation as to why the effects of B12 on tHcy concentrations are frequently masked by folate status.