Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease

Nicholas Dudman; David Hunt; Stephen MacMahon; Bruce Neal; Mark Richards; John Simes; Andrew Tonkin; David Wilcken; Judy Murphy; Yvonne Cleverly; Anthony Keech; Takayoshi Ohkubo; Kathy Bos; Hazel Bartram; Derrick Bennett; Joanna Broad; Deanne Douglas; Sheila Fisher; Barry Gray; Amanda Milne; Alan McCulloch; Colleen Ng; Megan Pledger; Adrienne Pryor; Aimee Santos; Alex Slater; Karen Yiu; Alan Brnabic; Mark Woodward; Louise Burrell; Louise Brown; Angas Hamer; Louise Roberts; Ian Jeffery; Pearle Taverner; Alice Kam; Philip Aylward; Fiona Wollaston; Anthony Whitehead; Geoffrey Lane; Gill Tulloch; Nicole Forrest; Jan Garrett; Greg Aroney; Pam Hicks; Jonathan Silberberg; Anne Gordon; Julie Holliday; Liz Hicks; Bhuwan Singh; Carol Singh; Judi Wilken; Bruce Jackson; Gloria Rudge; Malcolm West; Anne Carle; Thomas Marwick; Cindy Hall; David Cross; Daphne Craw; David Hunt; Michelle Sallaberger; John Horowitz; Matthew Worthley; Liz Owen; Dwain Owensby; Bill McKenzie; Julie Kesby-Smith; Suzanne MacKinley; Norman Sharpe; Robert Doughty; Jenne Pomfret; Mark Richards; Rona Buttimore; Lorraine Skelton; Michael Williams; Ralph Stewart; Marguerite McLelland; Richard Luke; Jane Kenyon; Stewart Mann; Anne Cuthbert; Stuart Reubin; Pam Yorke; Douglas Scott; Miles Williams; Renee Coxon; Darryl Fry; Malcolm Clark; Pauline Barclay; Hamish Hart; Carol O'Toole; Philippa Wright; Leigh Nairn; Jeannie Bruning

doi:10.1053/euhj.2002.3161

Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease

Nicholas Dudman, David Hunt, Stephen MacMahon, Bruce Neal, Mark Richards, John Simes, Andrew Tonkin, David Wilcken, Judy Murphy, Yvonne Cleverly, Anthony Keech, Takayoshi Ohkubo, Kathy Bos, Hazel Bartram, Derrick Bennett, Joanna Broad, Deanne Douglas, Sheila Fisher, Barry Gray, Amanda MilneAlan McCulloch, Colleen Ng, Megan Pledger, Adrienne Pryor, Aimee Santos, Alex Slater, Karen Yiu, Alan Brnabic, Mark Woodward, Louise Burrell, Louise Brown, Angas Hamer, Louise Roberts, Ian Jeffery, Pearle Taverner, Alice Kam, Philip Aylward, Fiona Wollaston, Anthony Whitehead, Geoffrey Lane, Gill Tulloch, Nicole Forrest, Jan Garrett, Greg Aroney, Pam Hicks, Jonathan Silberberg, Anne Gordon, Julie Holliday, Liz Hicks, Bhuwan Singh, Carol Singh, Judi Wilken, Bruce Jackson, Gloria Rudge, Malcolm West, Anne Carle, Thomas Marwick, Cindy Hall, David Cross, Daphne Craw, David Hunt, Michelle Sallaberger, John Horowitz, Matthew Worthley, Liz Owen, Dwain Owensby, Bill McKenzie, Julie Kesby-Smith, Suzanne MacKinley, Norman Sharpe, Robert Doughty, Jenne Pomfret, Mark Richards, Rona Buttimore, Lorraine Skelton, Michael Williams, Ralph Stewart, Marguerite McLelland, Richard Luke, Jane Kenyon, Stewart Mann, Anne Cuthbert, Stuart Reubin, Pam Yorke, Douglas Scott, Miles Williams, Renee Coxon, Darryl Fry, Malcolm Clark, Pauline Barclay, Hamish Hart, Carol O'Toole, Philippa Wright, Leigh Nairn, Jeannie Bruning

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Abstract

Aims: To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. Methods and Results: The PACIFIC study was a doubleblind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2·0 mg daily, folic acid 0·2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2·0mg folic acid reduced homocysteine by 1·8 μmol . 1 ^{- 1} [95% confidence interval (CI) 1·3-2·3] and 0·2 mg reduced homocysteine by 1·2 μmol . 1 ^{- 1} (95% CI 0·8-1·7). The higher dose reduced homocysteine significantly more than the lower dose (P=0·01). Conclusions: Both doses of folic acid reduced homocysteine, but the effects of the 2·0 mg dose were about one third greater than the 0·2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.

Original language	English
Pages (from-to)	1509-1515
Number of pages	7
Journal	European Heart Journal
Volume	23
Issue number	19
DOIs	https://doi.org/10.1053/euhj.2002.3161
Publication status	Published - 1 Oct 2002
Externally published	Yes

Keywords

Coronary heart disease
Folic acid
Homocysteine
Randomized trial

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10.1053/euhj.2002.3161Licence: In Copyright

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Dudman, N., Hunt, D., MacMahon, S., Neal, B., Richards, M., Simes, J., Tonkin, A., Wilcken, D., Murphy, J., Cleverly, Y., Keech, A., Ohkubo, T., Bos, K., Bartram, H., Bennett, D., Broad, J., Douglas, D., Fisher, S., Gray, B., ... Bruning, J. (2002). Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease. European Heart Journal, 23(19), 1509-1515. https://doi.org/10.1053/euhj.2002.3161

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title = "Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease",

abstract = "Aims: To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. Methods and Results: The PACIFIC study was a doubleblind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2·0 mg daily, folic acid 0·2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2·0mg folic acid reduced homocysteine by 1·8 μmol . 1 - 1 [95% confidence interval (CI) 1·3-2·3] and 0·2 mg reduced homocysteine by 1·2 μmol . 1 - 1 (95% CI 0·8-1·7). The higher dose reduced homocysteine significantly more than the lower dose (P=0·01). Conclusions: Both doses of folic acid reduced homocysteine, but the effects of the 2·0 mg dose were about one third greater than the 0·2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.",

keywords = "Coronary heart disease, Folic acid, Homocysteine, Randomized trial",

author = "Nicholas Dudman and David Hunt and Stephen MacMahon and Bruce Neal and Mark Richards and John Simes and Andrew Tonkin and David Wilcken and Judy Murphy and Yvonne Cleverly and Anthony Keech and Takayoshi Ohkubo and Kathy Bos and Hazel Bartram and Derrick Bennett and Joanna Broad and Deanne Douglas and Sheila Fisher and Barry Gray and Amanda Milne and Alan McCulloch and Colleen Ng and Megan Pledger and Adrienne Pryor and Aimee Santos and Alex Slater and Karen Yiu and Alan Brnabic and Mark Woodward and Louise Burrell and Louise Brown and Angas Hamer and Louise Roberts and Ian Jeffery and Pearle Taverner and Alice Kam and Philip Aylward and Fiona Wollaston and Anthony Whitehead and Geoffrey Lane and Gill Tulloch and Nicole Forrest and Jan Garrett and Greg Aroney and Pam Hicks and Jonathan Silberberg and Anne Gordon and Julie Holliday and Liz Hicks and Bhuwan Singh and Carol Singh and Judi Wilken and Bruce Jackson and Gloria Rudge and Malcolm West and Anne Carle and Thomas Marwick and Cindy Hall and David Cross and Daphne Craw and David Hunt and Michelle Sallaberger and John Horowitz and Matthew Worthley and Liz Owen and Dwain Owensby and Bill McKenzie and Julie Kesby-Smith and Suzanne MacKinley and Norman Sharpe and Robert Doughty and Jenne Pomfret and Mark Richards and Rona Buttimore and Lorraine Skelton and Michael Williams and Ralph Stewart and Marguerite McLelland and Richard Luke and Jane Kenyon and Stewart Mann and Anne Cuthbert and Stuart Reubin and Pam Yorke and Douglas Scott and Miles Williams and Renee Coxon and Darryl Fry and Malcolm Clark and Pauline Barclay and Hamish Hart and Carol O'Toole and Philippa Wright and Leigh Nairn and Jeannie Bruning",

year = "2002",

month = oct,

day = "1",

doi = "10.1053/euhj.2002.3161",

language = "English",

volume = "23",

pages = "1509--1515",

journal = "European Heart Journal",

issn = "0195-668X",

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Dudman, N, Hunt, D, MacMahon, S, Neal, B, Richards, M, Simes, J, Tonkin, A, Wilcken, D, Murphy, J, Cleverly, Y, Keech, A, Ohkubo, T, Bos, K, Bartram, H, Bennett, D, Broad, J, Douglas, D, Fisher, S, Gray, B, Milne, A, McCulloch, A, Ng, C, Pledger, M, Pryor, A, Santos, A, Slater, A, Yiu, K, Brnabic, A, Woodward, M, Burrell, L, Brown, L, Hamer, A, Roberts, L, Jeffery, I, Taverner, P, Kam, A, Aylward, P, Wollaston, F, Whitehead, A, Lane, G, Tulloch, G, Forrest, N, Garrett, J, Aroney, G, Hicks, P, Silberberg, J, Gordon, A, Holliday, J, Hicks, L, Singh, B, Singh, C, Wilken, J, Jackson, B, Rudge, G, West, M, Carle, A, Marwick, T, Hall, C, Cross, D, Craw, D, Hunt, D, Sallaberger, M, Horowitz, J, Worthley, M, Owen, L, Owensby, D, McKenzie, B, Kesby-Smith, J, MacKinley, S, Sharpe, N, Doughty, R, Pomfret, J, Richards, M, Buttimore, R, Skelton, L, Williams, M, Stewart, R, McLelland, M, Luke, R, Kenyon, J, Mann, S, Cuthbert, A, Reubin, S, Yorke, P, Scott, D, Williams, M, Coxon, R, Fry, D, Clark, M, Barclay, P, Hart, H, O'Toole, C, Wright, P, Nairn, L & Bruning, J 2002, 'Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease', European Heart Journal, vol. 23, no. 19, pp. 1509-1515. https://doi.org/10.1053/euhj.2002.3161

TY - JOUR

T1 - Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease

AU - Dudman, Nicholas

AU - Hunt, David

AU - MacMahon, Stephen

AU - Neal, Bruce

AU - Richards, Mark

AU - Simes, John

AU - Tonkin, Andrew

AU - Wilcken, David

AU - Murphy, Judy

AU - Cleverly, Yvonne

AU - Keech, Anthony

AU - Ohkubo, Takayoshi

AU - Bos, Kathy

AU - Bartram, Hazel

AU - Bennett, Derrick

AU - Broad, Joanna

AU - Douglas, Deanne

AU - Fisher, Sheila

AU - Gray, Barry

AU - Milne, Amanda

AU - McCulloch, Alan

AU - Ng, Colleen

AU - Pledger, Megan

AU - Pryor, Adrienne

AU - Santos, Aimee

AU - Slater, Alex

AU - Yiu, Karen

AU - Brnabic, Alan

AU - Woodward, Mark

AU - Burrell, Louise

AU - Brown, Louise

AU - Hamer, Angas

AU - Roberts, Louise

AU - Jeffery, Ian

AU - Taverner, Pearle

AU - Kam, Alice

AU - Aylward, Philip

AU - Wollaston, Fiona

AU - Whitehead, Anthony

AU - Lane, Geoffrey

AU - Tulloch, Gill

AU - Forrest, Nicole

AU - Garrett, Jan

AU - Aroney, Greg

AU - Hicks, Pam

AU - Silberberg, Jonathan

AU - Gordon, Anne

AU - Holliday, Julie

AU - Hicks, Liz

AU - Singh, Bhuwan

AU - Singh, Carol

AU - Wilken, Judi

AU - Jackson, Bruce

AU - Rudge, Gloria

AU - West, Malcolm

AU - Carle, Anne

AU - Marwick, Thomas

AU - Hall, Cindy

AU - Cross, David

AU - Craw, Daphne

AU - Hunt, David

AU - Sallaberger, Michelle

AU - Horowitz, John

AU - Worthley, Matthew

AU - Owen, Liz

AU - Owensby, Dwain

AU - McKenzie, Bill

AU - Kesby-Smith, Julie

AU - MacKinley, Suzanne

AU - Sharpe, Norman

AU - Doughty, Robert

AU - Pomfret, Jenne

AU - Richards, Mark

AU - Buttimore, Rona

AU - Skelton, Lorraine

AU - Williams, Michael

AU - Stewart, Ralph

AU - McLelland, Marguerite

AU - Luke, Richard

AU - Kenyon, Jane

AU - Mann, Stewart

AU - Cuthbert, Anne

AU - Reubin, Stuart

AU - Yorke, Pam

AU - Scott, Douglas

AU - Williams, Miles

AU - Coxon, Renee

AU - Fry, Darryl

AU - Clark, Malcolm

AU - Barclay, Pauline

AU - Hart, Hamish

AU - O'Toole, Carol

AU - Wright, Philippa

AU - Nairn, Leigh

AU - Bruning, Jeannie

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Aims: To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. Methods and Results: The PACIFIC study was a doubleblind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2·0 mg daily, folic acid 0·2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2·0mg folic acid reduced homocysteine by 1·8 μmol . 1 - 1 [95% confidence interval (CI) 1·3-2·3] and 0·2 mg reduced homocysteine by 1·2 μmol . 1 - 1 (95% CI 0·8-1·7). The higher dose reduced homocysteine significantly more than the lower dose (P=0·01). Conclusions: Both doses of folic acid reduced homocysteine, but the effects of the 2·0 mg dose were about one third greater than the 0·2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.

AB - Aims: To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. Methods and Results: The PACIFIC study was a doubleblind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2·0 mg daily, folic acid 0·2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2·0mg folic acid reduced homocysteine by 1·8 μmol . 1 - 1 [95% confidence interval (CI) 1·3-2·3] and 0·2 mg reduced homocysteine by 1·2 μmol . 1 - 1 (95% CI 0·8-1·7). The higher dose reduced homocysteine significantly more than the lower dose (P=0·01). Conclusions: Both doses of folic acid reduced homocysteine, but the effects of the 2·0 mg dose were about one third greater than the 0·2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.

KW - Coronary heart disease

KW - Folic acid

KW - Homocysteine

KW - Randomized trial

UR - http://www.scopus.com/inward/record.url?scp=0036798802&partnerID=8YFLogxK

U2 - 10.1053/euhj.2002.3161

DO - 10.1053/euhj.2002.3161

M3 - Article

C2 - 12395803

AN - SCOPUS:0036798802

SN - 0195-668X

VL - 23

SP - 1509

EP - 1515

JO - European Heart Journal

JF - European Heart Journal

IS - 19

ER -

Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease

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