High Methylmalonic Acid Research Articles

Methylmalonic Acid and Homocysteine in Plasma as Indicators of Functional Cobalamin Deficiency in Infants on Macrobiotic Diets

Methylmalonic acid and total homocysteine in plasma and serum have previously been used as indicators of intracellular cobalamin function in adults. To assess the usefulness of quantitation of these metabolites in the diagnosis of dietary cobalamin deficiency in infants, they were determined in plasma from 41 infants (aged 10-20 mo) on a macrobiotic diet and in 50 healthy group-matched omnivorous controls. In the macrobiotic infants, both methylmalonic acid and total homocysteine were markedly increased compared with controls (8-fold and 2-fold, respectively). Both metabolites showed an inverse relation to the plasma cobalamin level. The very low cobalamin content of the macrobiotic diet and low plasma cobalamin in macrobiotic infants makes an impaired cobalamin function likely in these infants. We therefore used dietary group as an independent indicator of cobalamin status. Different test parameters for cobalamin status were evaluated by comparing their ability to discriminate between the two dietary groups. Logistic regression analysis showed that methylmalonic acid followed by total homocysteine and cobalamin, in that order, were the strongest predictors of dietary group. Mean corpuscular volume and Hb had low discriminative power. We conclude that the determination of methylmalonic acid and total homocysteine represents a sensitive and specific test for the diagnosis and follow-up of nutritional cobalamin deficiency in infants. Furthermore, the finding of high methylmalonic acid and total homocysteine in plasma of most macrobiotic infants demonstrates a functional cobalamin deficiency in these subjects.

Nutritional concerns of lactating women consuming vegetarian diets

Nutritional inadequacies during lactation may affect the well-being of the mother, infant, or both. Vitamin D and calcium status in vegetarian women may be low, resulting in maternal bone demineralization. Vitamin B-12 deficiency resulting in neurologic damage has been reported in infants of vegetarian women. A review of several studies completed on women in the northeastern United States who were consuming a macrobiotic diet is presented. Supplemental vitamin D does not appear to be necessary given sufficient sun exposure. Calcium intake in vegetarian mothers was low and differences in calcium-regulating hormones were apparent. However, it is not clear whether these hormonal changes resulted in adequate adaptation whether these hormonal changes resulted in adequate adaptation and prevented bone demineralization. The low calcium intake in the vegetarian women did not result in lower milk calcium concentrations. Elevated methylmalonic acid excretion, which is often seen in vitamin B-12 deficiency, was noted in the vegetarian mothers and their infants. Infants with high methylmalonic acid excretion were consuming milk low in vitamin B-12.

Vitamin B-12 status in a macrobiotic community

Vitamin B-12 status was assessed in a group of 110 adults and 42 children from a macrobiotic community in New England. Dietary and anthropometric information also was obtained. Fifty-one percent of the adults had low concentrations of serum vitamin B-12, which inversely correlated with duration of macrobiotic diet practice. Urinary methylmalonic acid (MMA) excretion was inversely correlated with serum vitamin B-12, and 30% of adults sampled had high urinary MMA. Fifty-five percent of children had high urinary MMA, and MMA was higher in the group that consumed a macrobiotic diet during their entire lifetime. Children were relatively short in stature and weight, and decreased stature was associated with high urinary MMA. In both adults and children vitamin B-12 status was better with more consumption of dairy products or with higher tertile of reported frequencies of vitamin B-12 consumption of various animal products. Vitamin B-12 status appeared to be unrelated to consumption of several vegetarian foods.

Ovine White-Liver Disease (OWLD). Vitamin B12 and Methyl Malonic Acid (MMA) Estimations in Blood

At pasture outlet, mean plasma vitamin B12 varied between 210 and 1,200 pmol/l in 1 month old lambs, 19% of them had values below 250 pmol/l. In those put on OWLD pastures, mean values dropped after 2-4 weeks, and mostly stayed below 150 pmol/l throughout grazing. Plasma methylmalonic acid (MMA) rose above 5 mumol/l 2-8 weeks after outlet, and above 15 mumol/l 4 weeks later. Reduced growth occurred 3-8 weeks after plasma B12 dropped below 150 pmol/l, and 4-6 weeks after MMA rose above 5 mumol/l. Clinical OWLD was most often associated with plasma B12 less than 150 pmol/l and MMA greater than 15 mumol/l. Cobalt fertilization of pastures induced satisfactory plasma B12/MMA values for 3 succeeding years. Elevated plasma B12 was found 3 weeks after Co pellet dosing. The use of Co lick resulted in large individual variations in plasma B12/MMA. The control lambs, which were healthy and grew well on pastures which some years contained marginal/deficient cobalt, had plasma B12/MMA values which varied considerably. One year values indicated functional Co deficiency, but none developed OWLD, and growth was satisfactory, but less than other years. In these lambs, high MMA was not always associated with low B12, or depressed growth. OWLD occurred in Co/B12 deficient lambs, but Co/B12 deficient lambs on other pastures did not develop OWLD.

Dietary Pectin Shortens the Biologic Half-Life of Vitamin B-12 in Rats by Increasing Fecal and Urinary Losses

As little as 5% of pectin added to a fiber-free diet elevates urinary methylmalonic acid (MMA) severalfold in vitamin B-12--deprived rats. The present study examines whether increased urinary MMA reflects lower vitamin B-12 status or occurs only because of fermentation of pectin by intestinal bacteria and increased production of propionate, a precursor of MMA. By monitoring urinary and fecal excretion of 57Co after a tracer dose of [57Co]vitamin B-12, we found the biologic half-life of vitamin B-12 to be 59 d for rats fed a fiber-free diet and only 19 d for rats fed a 5% pectin diet. Also, pectin-fed rats oxidized only 12% of a 1-mmol dose of [14C]propionate to 14CO2 in 2 h, whereas rats fed the fiber-free diet expired 33% of the dose. Finally, high urinary MMA persisted even after the removal of pectin from the diet. We conclude that dietary pectin accelerates vitamin B-12 depletion in rats, possibly by interfering with enterohepatic recycling of vitamin B-12. By stimulating microbial propionate production, pectin and other fermentable fibers may also contribute to increased urinary MMA in vitamin B-12 deficiency, but a larger propionate pool does not account for the other effects of pectin on vitamin B-12 status.