Effects of Folic Acid Supplementation on Serum Folate and Plasma Homocysteine Concentrations in Older Adults: A Dose-Response Trial

Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
American journal of epidemiology (Impact Factor: 5.23). 10/2010; 172(8):932-41. DOI: 10.1093/aje/kwq197
Source: PubMed


The authors' objective in this study was to estimate the changes in serum folate and homocysteine concentration that resulted from 6 weeks of supplementation with folic acid. A randomized, double-blind, placebo-controlled, dose-response trial with a parallel-group design was conducted. A total of 133 participants aged 60-90 years (70% female, 19% nonwhite) were assigned to receive 0, 100, 400, 1,000, or 2,000 μg/day of folic acid for 6 weeks. Data were collected in the United States between June and September 1996. At baseline, median serum folate and plasma homocysteine concentrations were 5.7 ng/mL (interquartile range (25th-75th percentiles), 4.1-7.8) and 8.3 μmol/L (interquartile range, 7.1-10.0), respectively. As the folic acid dose increased, serum folate levels increased (P-trend < 0.001). There was no dose-response relation with homocysteine level among all participants. In analyses restricted to persons with the lowest serum folate concentration (<4.5 ng/mL) at baseline, there was a trend (P = 0.06) toward decreased homocysteine levels with increasing folic acid dose. In healthy, older adults with adequate folate status, folic acid supplementation is not beneficial for homocysteine reduction. However, for older adults with low serum folate levels, supplementation will improve folate status and may be beneficial for lowering homocysteine concentrations.

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Available from: Jeanne Charleston, Dec 23, 2013
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    • "In addition to serum homocysteine level, folate status may be affected. There is a report that in healthy older adults with normal serum folate level, folic acid supplementation cannot reduce homocysteine level while in those with low serum folate supplementation it may lower homocysteine concentration [21]. It should be noted that in our study and most of other studies, blood samples were taken in the fasting state while a study indicated that about 50% of participants show hyperhomocysteinemia after methionine load [22]. "
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    ABSTRACT: Background In spite of several studies, the impact of homocysteine level and folic acid supplementation on bone metabolism is yet to be recognized. In this registered clinical trial (IRCT2014042217385N1), we aimed to find out the power of 6-month folic acid supplementation on homocysteine level and bone metabolism.Methods Forty postmenopausal osteoporotic women (50 to 87 years) were enrolled in the study. All participants were randomized to receive folic acid 1 mg (n¿=¿17) or placebo (n¿=¿14). At baseline, 3 months, and finally 6 months post intervention, the level of homocysteine, vitamin B12, and bone biomarkers were measured.ResultsBoth groups were similar at baseline. The homocysteine decreased in both groups but statistically non-significant (P¿>¿0.05). The changes of the serum level of vitamin B12, osteocalcin, and ß cross laps were significant between groups after 6 months (P¿¿¿0.05).Conclusion The trend of changes of bone biomarkers after 6 months folic acid supplementation shows that homocysteine concentration and/or folic acid supplementation have impact on the rate of bone metabolism. However, further investigations by larger sample size and differentiating age and gender are still needed to clarify the exact role of folate, homocysteine and vitamin B12.
    DARU Journal of Pharmaceutical Sciences 09/2014; 22(1):62. DOI:10.1186/s40199-014-0062-9 · 1.64 Impact Factor
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    • "Both a previous dose-finding trial [10] and a dose-response trial [11] have discussed the relationship between homocysteine-lowering efficacy and optimal dose of FA supplementation, but without considering the possible modifying effect of MTHFR C677T polymorphism. A more recent study [12] evaluated the effect of MTHFR C677T polymorphism on the response to different doses of FA supplementation (0.1 mg/d, 0.4 mg/d, 4 mg/d and 4 mg/week) in northern Chinese women of childbearing age and reported that the MTHFR 677 TT genotype was an independent predictor of plasma homocysteine concentrations, irrespective of FA dose, which was consistent with our results. "
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    ABSTRACT: This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d) of folic acid (FA) can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T and/or methionine synthase (MTR) A2756G polymorphisms in hypertensive Chinese adults. A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1) enalapril only (10 mg, control group); 2) enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8 mg, high FA group), once daily for 8 weeks. After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (P < 0.05 for either of these genotypes) and TT genotype in the high FA group (P < 0.05). Furthermore, subjects with TT genotype showed a greater homocysteine-lowering response than did subjects with CC genotype in the high FA group (mean percent reduction of homocysteine at week 8: CC 10.8% vs. TT: 22.0%, P = 0.005), but not in the low FA group (CC 9.9% vs. TT 11.2%, P = 0.989). This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation.
    Nutrition Journal 10/2012; 11(1):2. DOI:10.1186/1475-2891-11-2 · 2.60 Impact Factor
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    • "Thus, depending on their grain consumption, many people likely consume more than 200% of the 400 μg recommended allowance. In fact, up to 2000 μg folate/day is used in humans for clinical trials (Anderson et al. 2010). Just as folate deficiency can be harmful, especially to vulnerable populations such as the elderly (Selhub et al. 1993 "
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    ABSTRACT: Cognitive and memory deficits can be caused or exacerbated by dietary folate deficiency, which has been combatted by the addition of folate to grains and dietary supplements. The recommended dose of the B9 vitamin folate is 400 µg/day for adolescents and non-pregnant adults, and consumption above the recommended daily allowance is not considered to be detrimental. However, the effects of excess folate have not been tested in adolescence when neuro and endocrine development suggest possible vulnerability to long-term cognitive effects. We administered folate-supplemented (8.0 mg folic acid/kg diet) or control lab chow (2.7 mg folic acid/kg diet) to rats ad libitum from 30 to 60 days of age, and subsequently tested their motivation and learning and memory in the Morris water maze. We found that folate-supplemented animals had deficits in motivation and spatial memory, but they showed no changes of the learning- and memory-related molecules growth-associated protein-43 or Gs-α subunit protein in the hippocampus. They had decreased levels of thyroxine (T4) and triiodothyronine (T3) in the periphery and decreased protein levels of thyroid receptor-α1 and -α2 (TRα1 and TRα2) in the hippocampus. The latter may have been due to an observed increase of cytosine-phosphate-guanosine island methylation within the putative thyroid hormone receptor-α promoter, which we have mapped for the first time in the rat. Overall, folate supplementation in adolescence led to motivational and spatial memory deficits that may have been mediated by suppressed thyroid hormone function in the periphery and hippocampus.
    Genes Brain and Behavior 11/2011; 11(2):193-200. DOI:10.1111/j.1601-183X.2011.00749.x · 3.66 Impact Factor
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