Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age

Daly, Seán; Mills, James L.; Molloy, Anne M.; Conley, Mary; McPartlin, Joseph; Lee, Y.J.; Young, P. B.; Kirke, Peadar N.; Weir, Donald G.; Scott, John M.

doi:10.1093/qjmed/95.11.733

Cited by 23 publications

(11 citation statements)

References 24 publications

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“…Mean concentrations of tHcy in the present study were similar [ 47 , 48 ] or lower than others in young women [ 49 ] or in a random population sample [ 50 ]. Small doses of folate have been shown to reduce tHcy in a young population [ 49 ] so the high blood folate levels observed in the present study may be protective of hyperhomocysteinaemia, which was found in 2% of women in this study, half of that in previous reports in young women [ 51 ].…”

Section: Discussionsupporting

confidence: 75%

Micronutrient Status in Female University Students: Iron, Zinc, Copper, Selenium, Vitamin B12 and Folate

2014

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Young women are at an increased risk of micronutrient deficiencies, particularly due to higher micronutrient requirements during childbearing years and multiple food group avoidances. The objective of this study was to investigate biomarkers of particular micronutrients in apparently healthy young women. Female students (n = 308; age range 18–35 year; Body Mass Index 21.5 ± 2.8 kg/m2; mean ± SD) were recruited to participate in a cross-sectional study. Blood samples were obtained from participants in the fasted state and analysed for biomarkers of iron status, vitamin B12, folate, homocysteine, selenium, zinc, and copper. The results show iron deficiency anaemia, unspecified anaemia, and hypoferritinemia in 3%, 7% and 33.9% of participants, respectively. Low vitamin B12 concentrations (<120 pmol/L) were found in 11.3% of participants, while 4.7% showed sub-clinical deficiency based on serum methylmalonic acid concentrations >0.34 μmol/L. Folate concentrations below the reference range were observed in 1.7% (serum) or 1% (erythrocytes) of participants, and 99.7% of the participant had erythrocyte-folate concentrations >300 nmol/L. Serum zinc concentrations <10.7 μmol/L were observed in 2% of participants. Serum copper and selenium concentrations were below the reference range in 23% and 11% of participants, respectively. Micronutrient deficiencies including iron and vitamin B12, and apparent excess of folate are present in educated Australian female students of childbearing age, including those studying nutrition. The effects of dietary behaviours and food choices on markers of micronutrient status require further investigation.

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Section: Discussionsupporting

confidence: 75%

Micronutrient Status in Female University Students: Iron, Zinc, Copper, Selenium, Vitamin B12 and Folate

2014

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“…Several studies have investigated the dose-response relationship of folic acid with tHcy in the lowdose range, using either capsules or fortified breakfast cereals. [40][41][42][43] All studies were conducted in populations in which there was no folic acid fortification. These studies indicate that a supplement should contain at least 400 mg/day for maximal tHcy lowering.…”

Section: Folatementioning

confidence: 99%

Dietary Determinants of Plasma Homocysteine Concentrations

Verhoef

Groot

2005

Seminars in Vascular Medicine

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Severe hyperhomocysteinemia is typically caused by rare enzymatic defects or by renal failure. In contrast, mild to moderate hyperhomocysteinemia chiefly results from suboptimal status of nutritional factors involved in homocysteine metabolism. Low dietary intake of folate is the most important nutritional cause of elevated homocysteine (tHcy) concentrations. Folic acid is more effective than dietary folate in lowering tHcy concentrations, and a daily dose of 400 mug of folic acid is the minimum daily dose associated with the maximum tHcy-lowering effect ( approximately 20-25% reduction). Mean fasting tHcy concentrations have dropped substantially in populations with mandatory folic acid fortification, and other B-vitamins, such as vitamin B (12), are important determinants of tHcy levels in this setting. Vitamins B (2) and B (6) have little influence on fasting tHcy concentrations, although the former may be relevant in individuals with the MTHFR 677 TT-genotype, and the latter may improve tHcy catabolism in elderly individuals. Betaine and choline can lower fasting tHcy concentrations to a similar extent as folic acid, particularly in the setting of a high intake of methionine. Consumption of tea and coffee increase tHcy concentrations by up to 20%. A high-protein meal also increases tHcy, but these changes are transient, and levels return to normal after an overnight fast. Serine and cystine also influence the methionine-induced postprandial rise in tHcy concentrations. In conclusion, alteration in dietary intake or use of folic acid supplements can substantially lower tHcy concentrations. However, it is not known whether lowering tHcy levels can reduce the risk of cardiovascular disease or cognitive decline or prevent pregnancy complications or osteoporosis.

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“…This possibility is consistent with the hypothesis that B-vitamins inadequacy per se is a major causal pathway to cognitive decline. Other studies found that doses in the range of 0.2-0.5 mg/day achieve maximum reduction in tHcy levels in healthy populations and that a higher dose of 0.8 mg/day is required for maximal lowering of tHcy in individuals with vascular diseases [52][53][54]. There are several ways by which this could be accomplished: one is by comparing responders to nonresponders within the treatment arm and by analyzing the extent of response to treatment by baseline B-vitamin status and change.…”

mentioning

confidence: 99%

“…In the Framingham heart study, it was shown that the inverse association between plasma tHcy and folate intake plateaus when folate intake exceeds 0.4 mg/day [51]. Other studies found that doses in the range of 0.2-0.5 mg/day achieve maximum reduction in tHcy levels in healthy populations and that a higher dose of 0.8 mg/day is required for maximal lowering of tHcy in individuals with vascular diseases [52][53][54]. Hence, increasing folate intake over 0.8 mg/day would not be expected to have additional benefit and may in fact diminish efficacy.…”

mentioning

confidence: 99%

B‐vitamins for neuroprotection: Narrowing the evidence gap

Nachum‐Biala

Troen

2012

BioFactors

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A compelling and extensive epidemiological literature documents the strong association of inadequate status of folate, vitamin B₁₂, and to a lesser degree vitamin B6, with increased risk of neurodegenerative and cerebrovascular disease. Mildly elevated plasma total homocysteine, which is biochemically related to low status of these B-vitamins, is similarly associated with increased risk for these conditions. This, together with experimental data showing that experimental B-vitamin deficiency and/or hyperhomocysteinemia can cause a variety of neurological and vascular deficits in animals, has provided the evidence base and motivation for a growing number of large randomized, double-blind clinical trials aimed at determining the efficacy and safety of B-vitamin supplementation for preserving cognitive function in older adults. Despite some encouraging trials showing benefit of B-vitamins for slowing brain atrophy and cognitive decline, the majority of these studies have not demonstrated that B-vitamin supplementation has protective or therapeutic cognitive benefit. There are many possible explanations for the inconsistency between the clinical trials and for the discrepancy between their findings and the predictions of the epidemiological evidence. Among these are the possibility of inadequate hypotheses guiding the trials, design limitations of the individual trials, and inherent limitations of nutritional randomized clinical trials. Resolving these issues will be crucial for designing definitive trials and ultimately for guiding nutritional interventions for cognitive protection.

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Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age

Abstract: In this sub-population, low doses of folic acid significantly lower plasma homocysteine. This could be achieved safely by fortification.

Cited by 23 publications

References 24 publications

Micronutrient Status in Female University Students: Iron, Zinc, Copper, Selenium, Vitamin B12 and Folate

Micronutrient Status in Female University Students: Iron, Zinc, Copper, Selenium, Vitamin B12 and Folate

Dietary Determinants of Plasma Homocysteine Concentrations

B‐vitamins for neuroprotection: Narrowing the evidence gap

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