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

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.

Homocysteine and vitamin B12 status and iron deficiency anemia in female university students from Gaza Strip, Palestine

“…The association between elevated homocysteine levels and reduced free vitamin B 12 was previously reported by Miller et al, who assumed this elevation was an early marker for the development of vitamin B 12 deficiency 31 . The significant inverse correlation between serum homocysteine and vitamin B 12 reported in this study is concomitant to what has been published previously 32, 33, 34…”

Risk Factors for Development of Dementia in a Unique Six-Year Cohort Study. I. An Exploratory, Pilot Study of Involvement of the E4 Allele of Apolipoprotein E, Mutations of the Hemochromatosis-HFE Gene, Type 2 Diabetes, and Stroke

“…There also is no information about whether these HFE gene variants interact with E4, diabetes, or stroke in the development of dementia. In 1997, one of our group (AG) initiated a longitudinal study of elderly volunteers to study the relation between blood markers of cobalamin metabolism and the development of cognitive impairment [70,71]. Because exclusion criteria for this study were quite stringent and the cohort was unique, we reasoned that an exploratory "addon" nested case/control study might shed new light on the involvement of E4 and the hemochromatosisassociated HFE alleles, as well as of diabetes and stroke, in the development of dementia.…”

“…Procedures involving experiments on human subjects were done in accord with the Helsinki Declaration of 1975. Informed signed consent was obtained from all volunteers before entry into the study [70].…”

“…Independently-living volunteers aged 65 years and older were recruited from the Kingston area through the use of flyers and announcements at senior community group meetings and activities. Recruitment was conducted between 1997 and 2001; follow-up continued until mid-2006 [70]. The study began at approximately the time that folic acid fortification of food was made mandatory in Canada [70].…”

Folic acid in older adults

“…An overwhelming proportion of older people aged between 65 and 94 years had elevated levels of total folate in a seven-year cohort (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)). 2 The levels were elevated in 84% of people obtaining folic acid exclusively from their diet (i.e., not taking folic acid supplements) as opposed to 100% in those taking multivitamins. Moreover, total folate levels were found to increase at an annual rate of 234 ng/mL (p < 0.001) since the beginning of fortification in 1998 and had not reached a plateau by 2004.…”