Long-Term Effects of Folic Acid Fortification and B-Vitamin Supplementation on Total Folate, Homocysteine, Methylmalonic Acid and Cobalamin in Older Adults

By Garcia, Angeles A. Md, PhD, Frcpc; Day, Andrew G. MSc et al. | Canadian Journal of Public Health, September/October 2008 | Go to article overview

Long-Term Effects of Folic Acid Fortification and B-Vitamin Supplementation on Total Folate, Homocysteine, Methylmalonic Acid and Cobalamin in Older Adults


Garcia, Angeles A. Md, PhD, Frcpc, Day, Andrew G. MSc, Zanibbi, Katherine BSc, Zunzunegui, Maria Victoria PhD, Canadian Journal of Public Health


ABSTRACT

Objective: To investigate the long-term effects of the Canadian folic acid fortification program in older adults' whole blood cell folate (folate) and cobalamin (Cbl) status, including homocysteine (tHcy) and methylmalonic acid (MMA), with and without voluntary B-vitamin intake, from 1997 to 2004.

Methods: Cohort of community-dwelling volunteer older adults. Clinical and biochemical data, including intake of B-vitamin supplements, were obtained at 2- to 2.5-year intervals and divided in 4 periods. Random coefficients (mixed effects) models were used to estimate the linear trend in folate and to compare levels of biochemical parameters between periods. All models were estimated by restricted maximum likelihood as implemented in PROC MIXED of SAS V8.2.

Results: Folate levels increased continuously at a yearly rate of 234 ng/mL (95% CI 213-254; p<0.001) and had not plateaued by the last period when 84% of subjects without B-vitamins had elevated folate. Homocysteine did not remain suppressed. Elevated tHcy was as prevalent in the last study period as in the first. No significant deficits of Cbl or increases of MMA were observed, but MMA levels tended to increase with time in subjects without B-vitamins. B-vitamin supplements significantly affected all results, reducing tHcy and MMA levels.

Conclusion: In this population, fortification with folic acid has resulted in cumulative increases of folate with no long-term reduction in tHcy or changes in Cbl or MMA. Possible deleterious effects of cumulative increases of folate, and beneficial effects of B-vitamin supplements in reducing tHcy and MMA, should be investigated.

Key words: Folate; cobalamin; homocysteine; methylmalonic acid; aged; fortification

RÉSUMÉ

Objectif : Étudier les effets à long terme du programme canadien d'enrichissement en acide folique sur la concentration de folates et de cobalamine (Cbl) dans le sang total des personnes âgées, y compris l'homocystéine (tHcy) et l'acide méthylmalonique (MMA), avec et sans apport volontaire en vitamine B, entre 1997 et 2004.

Méthode : Cohorte bénévole de personnes âgées résidant dans la communauté. Les données cliniques et biochimiques, y compris les apports en vitamine B, ont été obtenues à 2 ans ou 2,5 ans d'intervalle et divisées en 4 périodes. Des modèles à coefficients aléatoires (effets mixtes) ont servi à estimer la tendance linéaire pour les folates et à comparer les niveaux des paramètres biochimiques d'une période à l'autre. Tous les modèles ont été estimés par le maximum de vraisemblance restreint tel que mis en oeuvre avec PROC MIXED de SAS, version 8.2.

Résultats : Les niveaux de folates ont régulièrement augmenté de 234 ng/mL par année (IC de 95 % = 213-254; p<0,001) et ne s'étaient pas encore stabilisés durant la dernière période, où 84 % des sujets sans apport supplémentaire en vitamine B affichaient des niveaux élevés. La suppression de l'homocystéine n'a pas persisté. Une tHcy élevée était aussi courante pendant la dernière période d'étude que pendant la première. On n'a observé aucun déficit significatif en Cbl ni augmentation du MMA, mais les niveaux de MMA ont eu tendance à s'accroÎtre avec le temps chez les sujets sans apport supplémentaire en vitamine B. Les suppléments de vitamine B ont eu un effet significatif sur tous les résultats, en réduisant les niveaux de tHcy et de MMA.

Conclusion : Dans la population à l'étude, l'enrichissement en acide folique a entraÎné des augmentations cumulatives de folates sans diminution à long terme de la tHcy ni changements dans les niveaux de Cbl ou de MMA. Les effets néfastes éventuels des hausses cumulatives de folates, et les effets bénéfiques des apports supplémentaires en vitamine B pour réduire la tHcy et le MMA, méritent d'être examinés.

Mots clés : folates; cobalamine; homocystéine; acide méthylmalonique; personnes âgées; enrichissement

The folic acid fortification of grain products was mandated in Canada in 1998, although it began earlier and was nearly complete by mid-1998. …

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