Randomized Trial of Folic Acid Supplementation and Serum Homocysteine Levels

Wald, David S; Bishop, Lucy; Wald, Nicholas; Law, Malcolm; Hennessy, Enid; Weir, Donald G.; McPartlin, Joe; Scott, John M.

doi:10.1001/archinte.161.5.695

Cited by 174 publications

(106 citation statements)

References 21 publications

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“…The fact that both filtered and unfiltered coffee are associated in a dose-response manner with tHcy makes diterpenes (which are occurring at higher concentrations in unfiltered coffee, Bak, 1990) a less likely causal factor. These consistent findings also raised the question whether it is possible to reduce the coffee-induced tHcy increase by agents known to reduce homocysteine such as folic acid or pyridoxine (Mansoor et al, 1999;Wald et al, 2001).…”

Section: Introductionmentioning

confidence: 78%

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Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

2003

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Objective: Elevated levels of plasma total homocysteine (tHcy) are identified as independent risk factors for coronary heart disease and for fetal neural tube defects. tHcy levels are negatively associated with folic acid, pyridoxine and cobalamine, and positively associated with coffee consumption and smoking. A total of 600 ml of filtered coffee results in a tHcy increase that 200 mg of folic acid or 40 mg of pyridoxine supplementation might eliminate. Design: Randomised, blinded study with two consecutive trial periods. Setting: Free living population. Volunteers. Subjects: A total of 121 healthy, nonsmoking men and women (78%) aged 29-65 y. Interventions: (1) A coffee-free period of 3 weeks, (2) 600 ml coffee/day and a supplement of 200 mg folic acid/day or placebo for 4 weeks, (3) 3-week coffee-free period, (4) 600 ml coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks. Main outcome measures:The difference between the change in tHcy in the supplement group and the change in tHcy in the placebo group during the 4-week trial period. Results: Coffee abstention resulted in a tHcy decrease of 1.04 mmol/l for the whole group. In the subsequent coffee period, a further decrease of 0.17 mmol/l was observed in the folic acid group whereas an increase of 1.26 mmol/l was observed in the placebo group, the difference was 1.43 mmol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no impact on tHcy levels. Conclusions: Supplementation of 200 mg folic acid/day eliminates the tHcy increasing effect of 600 ml filtered coffee in subjects not already on folic acid supplements. A supplement of 40 mg pyridoxine/day does not have the same effect. Sponsorship: None.

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Section: Introductionmentioning

confidence: 78%

“…The dosage of folic acid supplement was set to 200 mg/day, which corresponds to a change in homocysteine levels of 0.1-2.5 mmol dependent on initial tHcy levels (Wald et al, 2001). The current recommendation of folic acid in Sweden is 300 mg/day for the general population, and 400 mg for pregnant women (Swedish Recommended Allowances, 1997).…”

Section: Methodsmentioning

confidence: 99%

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

2003

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“…While this appears to be the most likely explanation of the differences in response of tHcy between the study by Malinow et al (1998) and our own study, it should also be noted that participants in the Malinow study were older individuals with ischaemic heart disease while those in the Ward et al (1997) study and our own study were younger and free of clinical disease. Indeed, Wald et al (2001) found that patients with ischemic heart disease required daily doses of folic acid of up to 800 mg to optimally lower tHcy.…”

Section: Discussionmentioning

confidence: 99%

Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial

et al. 2002

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Objective: To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine (tHcy). Design: Double-blind, randomised placebo-controlled intervention trial. Setting: Community-based project in a New Zealand city. Subjects: Seventy free living men and women with tHcy ! 10 mmol=l. Mean age (range) was 58 (29 -90) y. Interventions: Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified (placebo) or fortified with 100, 200 or 300 mg folic acid. Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided. Main outcome measures: Plasma tHcy and serum folate concentrations. Results: Average serum folate concentrations (95% CI) increased significantly in the treatment groups relative to the control group by 28(9 -51)%, 60(37 -87)% and 79(51 -114)% for supplementation with 100, 200 and 300 mg folic acid, respectively. A reduction in tHcy was observed, being 16(8 -22)%, 12(4 -18)% and 17(9 -24)% in the three treatment groups, respectively. Conclusions: A regular intake of as little as 100 mg folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy. Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that, when aggregated from all sources, the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women. Funding: The breakfast cereals were supplied and the study partially funded by Kellogg Company.

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“…24 Such a reduction in homocysteine would be achievable by folic acid supplementation of 0.8 mg day À1 . 25 Other studies, however, have suggested that folic acid intervention, in the presence and absence of vitamin B 6 , does not lower the risk of recurrent cardiovascular disease or death after acute myocardial infarction. 26 This finding is mirrored in studies in which patients with vascular disease showed no decrease in the risk of major cardiovascular events after supplementation with folic acid and vitamin B 6 and B 12 .…”

Section: Cardiovascular Diseasementioning

confidence: 99%

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

2009

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Randomized Trial of Folic Acid Supplementation and Serum Homocysteine Levels

Abstract: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.

Cited by 174 publications

References 21 publications

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

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