Marjorie G. Garrod

Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate

BACKGROUND An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid and higher odds ratios for cognitive impairment and anemia than the combination of low vitamin B-12 and nonelevated folate. These findings await confirmation in other populations. OBJECTIVE The purpose was to compare metabolic indicators of vitamin B-12 status, cognitive function, and depressive symptoms among elderly Latinos with elevated and nonelevated plasma folate. DESIGN Cross-sectional data were analyzed for 1535 subjects (age: >or=60 y) from the Sacramento Area Latino Study on Aging. Subjects were divided into 4 groups on the basis of plasma vitamin B-12 (< or >or=148 pmol/L) and folate (<or= or >45.3 nmol/L). Homocysteine, methylmalonic acid, holotranscobalamin, ratio of holotranscobalamin to vitamin B-12, Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were compared between the groups. RESULTS Individuals with low vitamin B-12 and elevated folate (n = 22) had the highest concentrations of homocysteine and methylmalonic acid and the lowest concentration of holotranscobalamin and ratio of holotranscobalamin to vitamin B-12 when compared with all other groups (P <or= 0.003). No differences in Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were observed between the low vitamin B-12 and elevated-folate group compared with other groups. CONCLUSIONS Low vitamin B-12 is associated with more pronounced metabolic evidence of vitamin B-12 deficiency when folate is elevated than when folate is not elevated. These data should be considered when assessing the potential costs, risks, and benefits of folic acid and vitamin B-12 fortification programs.

Fraction of Total Plasma Vitamin B12 Bound to Transcobalamin Correlates with Cognitive Function in Elderly Latinos with Depressive Symptoms

BACKGROUND The fraction of total plasma vitamin B(12) bound to transcobalamin (holoTC/B12 ratio) may reflect tissue levels of the vitamin, but its clinical relevance is unclear. METHODS We assessed associations between cognitive function and total B12, holoTC, and holoTC/B12 ratio in a cohort of elderly Latinos (n = 1089, age 60-101 years). We assessed cognitive function using the Modified Mini-Mental State Examination (3MSE) and a delayed recall test; we diagnosed clinical cognitive impairment by neuropsychological and clinical exam with expert adjudication; and we assessed depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). We measured total B12 and holoTC using radioassays. RESULTS HoloTC/B12 ratio was directly associated with 3MSE score (P = 0.026) but not delayed recall score. Interactions between holoTC/B12 and CES-D score were observed for 3MSE (P = 0.026) and delayed recall scores (P = 0.013) such that associations between the ratio and cognitive function scores were confined to individuals with CES-D >/=16. For individuals with CES-D > or = 16, the odds ratio for clinical cognitive impairment for the lowest holoTC/B12 tertile was 3.6 (95% CI 1.2-11.2) compared with the highest tertile (P = 0.03). We observed no associations between cognitive function and total B12 or holoTC alone, except between holoTC and 3MSE score (P = 0.021), and no interactions between holoTC or total B12 and CES-D score on cognitive function. CONCLUSIONS HoloTC/B12 ratio is associated with cognitive function in elderly Latinos with depressive symptoms and may better reflect the adequacy of B12 for nervous system function than either holoTC or total B12 alone.

Transcobalamin C776G Genotype Modifies the Association between Vitamin B12 and Homocysteine in Older Hispanics

Background/Objectives:A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/Methods:TC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60–93 years) from the Sacramento Area Latino Study on Aging (SALSA).Results:The distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P⩽0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 μmol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low.Conclusions:This population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia.