Biomarker responses to folic acid intervention in healthy adults: A meta-analysis of randomized controlled trials

American Journal of Clinical Nutrition

Volumn 99, Issue 1, 2014, Pages 96-106

  Duffy, Maresa E ^a   Hoey, Leane ^a   Hughes, Catherine F ^a   Strain, J J ^a   Rankin, Audrey ^a   Souverein, Olga W ^b   Dullemeijer, Carla ^b   Collings, Rachel ^c   Hooper, Lee ^c   McNulty, Helene ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

^b WAGENINGEN UNIVERSITY   (Netherlands)

^c UNIVERSITY OF EAST ANGLIA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; FOLIC ACID; HOMOCYSTEINE;

ARTICLE; DIETARY INTAKE; DOSE RESPONSE; ERYTHROCYTE; FOLIC ACID BLOOD LEVEL; HUMAN; META ANALYSIS; MICROBIOLOGY; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT RESPONSE; VITAMIN SUPPLEMENTATION;

EID: 84891474224     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.113.062752     Document Type: Article

References (62)

1. Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. Folate levels and neural tube defects, implications for prevention. JAMA 1995;274: 1698-702.
2. van Beynum IM, Kapusta L, Bakker MK, den Heijer M, Blom HJ, de Walle HE. Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case-control study in the northern Netherlands. Eur Heart J 2010;31:464-71.
3. Relton CL, Pearce MS, Parker L. The influence of erythrocyte folate and serum vitamin B12 status on birth weight. Br J Nutr 2005;93: 593-9.
4. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA 2005;293:1082-8.
5. Durga J, van Boxtel MPJ, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369:208-16.
6. Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E, the Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke 2009;40:1365-72.
7. Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X. Efficacy of folic acid supplementation in stroke prevention: a metaanalysis. Lancet 2007;369:1876-82.
8. Holmes MV, Newcombe P, Hubacek JA, Sofat R, Ricketts SL, Cooper J, Breteler MM, Bautista LE, Sharma P, Whittaker JC, et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 2011;378:584-94.
9. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354:2764-72.
10. Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297:2351-9.
11. Mason JB. Folate consumption and cancer risk: a confirmation and some reassurance, but we're not out of the woods quite yet. Am J Clin Nutr 2011;94:965-6.
12. Shane B. Folate status assessment history: implications for measurement of biomarkers in NHANES. Am J Clin Nutr 2011;94:337S-42S.
13. Gibson RS. Assessment of folate and vitamin B12 status. In: Principles of nutritional assessment. 2nd ed. New York, NY: Oxford University Press, 2005:595-640.
14. Wu A, Chanarin I, Slavin G, Levi AJ. Folate deficiency in the alcoholic-its relationship to clinical and haematological abnormalities, liver disease and folate stores. Br Haematol 1975;29:469-78.
15. Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, Johnston C, Engbaek F, Schneede J, McPartlin C, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004;50:3-32.
16. McNulty H, Pentieva K. Folate bioavailability. In: Bailey LB, ed. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press, 2010: 25-47.
17. Moher D, Liberati A, Tetzlaff J, Altman DG, Prisma Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006-12.
18. Tighe P, Ward M, McNulty H, Finnegan O, Dunne A, Strain J, Molloy AM, Duffy M, Pentieva K, Scott JM. A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy. Am J Clin Nutr 2011;93:11-8.
19. van Oort FVA, Melse-Boonstra A, Brouwer IA, Clarke R, West CE, Katan MB, Verhoef P. Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. Am J Clin Nutr 2003;77:1318-23.
20. Anderson CAM, Jee SH, Charleston J, Narrett M, Appel LJ. Effects of folic acid supplementation on serum folate and plasma homocysteine concentrations in older adults: a dose-response trial. Am J Epidemiol 2010;172:932-41.
21. Venn BJ, Green TJ. Effect of supplementation with L-5- methyltetrahydrofolate or folic acid on plasma and red blood cell folate, and plasma homocysteine. Proc Nutr Soc New Zeal 2002:62.
22. Venn BJ, Green TJ, Moser R, McKenzie JE, Skeaff CM, Mann J. Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid. J Nutr 2002;132:3353-5.
23. Venn BJ, Green TJ, Moser R, Mann JI. Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study. Am J Clin Nutr 2003;77:658-62.
24. Adank C, Green TJ, Skeaff CM, Briars B. Weekly high-dose folic acid supplementation is effective in lowering serum homocysteine concentrations in women. Ann Nutr Metab 2003;47:55-9.
25. Green TJ, Skeaff CM, Whiting SJ, Gibson RS. Effect of folic acid supplementation on plasma zinc concentrations of young women. Nutrition 2003;19:522-3.
26. Norsworthy B, Skeaff CM, Adank C, Green TJ. Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women. Eur J Clin Nutr 2004;58:548-54.
27. Durga J, van Tits LJ, Schouten EG, Kok FJ, Verhoef P. Effect of lowering of homocysteine levels on inflammatory markers: a randomized controlled trial. Arch Intern Med 2005;165:1388-94.
28. Duthie SJ, Horgan G, de Roos B, Rucklidge G, Reid M, Duncan G, Pirie L, Basten GP, Powers HJ. Blood folate status and expression of proteins involved in immune function, inflammation, and coagulation: biochemical and proteomic changes in the plasma of humans in response to long-term synthetic folic acid supplementation. J Proteome Res 2010;9:1941-50.
29. Basten GP, Hill MH, Duthie SJ, Powers HJ. Effect of folic acid supplementation on the folate status of buccal mucosa and lymphocytes. Cancer Epidemiol Biomarkers Prev 2004;13:1244-9.
30. Souverein OW, Dullemeijer C, van 't Veer P, van der Voet H. Transformations of summary statistics as input in meta-analysis for linear dose-response models on a logarithmic scale: a methodology developed within EURRECA. BMC Med Res Methodol 2012;12:57.
31. Wright AJ, King MJ, Wolfe CA, Powers HJ, Finglas PM. Comparison of (6 S)-5-methyltetrahydrofolic acid v. folic acid as the reference folate in longer-term human dietary intervention studies assessing the relative bioavailability of natural food folates: comparative changes in folate status following a 16-week placebo-controlled study in healthy adults. Br J Nutr 2010;103:724-9.
32. Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
33. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
34. Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test. BMJ 1997;315:629-34.
35. Araki R, Maruyama C, Igarashi S, Yoshida M, Maruyama T, Satoh T, Umegaki K. Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects. Eur J Clin Nutr 2006;60:573-9.
36. Brouwer IA, van Dusseldorp M, Duran M, Thomas CM, Hautvast JG, Eskes TK, Steegers-Theunissen RP. Low-dose folic acid supplementation does not influence plasma methionine concentrations in young non-pregnant women. Br J Nutr 1999;82:85-9.
37. Fohr IP, Prinz-Langenohl R, Bronstrup A, Bohlmann AM, Nau H, Berthold HK, Pietrzik K. 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5- methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr 2002;75:275-82.
38. Lamers Y, Prinz-Langenohl R, Moser R, Pietrzik K. Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am J Clin Nutr 2004;79:473-8.
39. Mangoni AA, Sherwood RA, Swift CG, Jackson SHD. Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial. J Intern Med 2002;252:497-503.
40. Melse-Boonstra A, West CE, Katan MB, Kok FJ, Verhoef P. Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults. Am J Clin Nutr 2004;79:424-9.
41. Pathansali R, Mangoni AA, Creagh-Brown B, Lan ZC, Ngow GL, Yuan XF, Ouldred EL, Sherwood RA, Swift CG, Jackson SH. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr 2006;43: 127-37.
42. Sheu WH, Chin HM, Lee WJ, Wan CJ, Su HY, Lang HF. Prospective evaluation of folic acid supplementation on plasma homocysteine concentrations during weight reduction: a randomized, double-blinded, placebo-controlled study in obese women. Life Sci 2005;76:2137-45.
43. Strandhagen E, Landaas S, Thelle DS. Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study. Eur J Clin Nutr 2003;57:1411-7.
44. Toprak A, Erenus M, Ilhan AH, Haklar G, Fak AS, Oktay A. The effect of postmenopausal hormone therapy with or without folic acid supplementation on serum homocysteine level. Climacteric 2005;8:279-86.
45. Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.
46. Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ 1998;316:894-8.
47. Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a metaanalysis of the randomized trials. Am J Clin Nutr 2005;82:806-12.
48. Wald NJ, Law MR, Morris JK, Wald DS. Quantifying the effect of folic acid. Lancet 2001;358:2069-73.
49. Berti C, Fekete K, Dullemeijer C, Trovato M, Souverein OW, Cavelaars A, Dhonukshe-Rutten R, Massari M, Decsi, T, van't Veer P, Cetin I. Folate intake and markers of folate status in women of reproductive age, pregnant and lactating women: a meta-analysis. J Nutr Metab 2012;2012:13.
50. Mason JB. Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J Nutr 2003;133:941S-7S.
51. Quinlivan EP, Gregory JF. Reassessing folic acid consumption patterns in the United States (1999-2004): potential effect on neural tube defects and overexposure to folate. Am J Clin Nutr 2007;86:1773-9.
52. Yetley EA, Pfeiffer CM, Phinney KW, Fazili Z, Lacher DA, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, et al. Biomarkers of folate status in NHANES: a roundtable summary. Am J Clin Nutr 2011;94:303S-12S.
53. Gunter EW, Bowman BA, Caudill SP, Twite DB, Adams MJ, Sampson EJ. Results of an international round robin for serum and whole-blood folate. Clin Chem 1996;42:1689-94.
54. Pfeiffer CM, Fazili Z, Zhang M. Folate Analytical Methodology. In: Bailey LB, ed. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press, 2010:517-67.
55. Cooperman JM, Pesci-Bourel A, Luhby AL. Urinary excretion of folic acid activity in man. Clin Chem 1970;16:375-81.
56. Park JY, Vollset SE, Melse-Boonstra A, Chajès V, Ueland PM, Slimani N. Dietary intake and biological measurement of folate: a qualitative review of validation studies. Mol Nut Food Res 2013;57:562-81.
57. Pfeiffer CM, Schleicher RL, Johnson CL, Coates PM. Assessing vitamin status in large population surveys by measuring biomarkers and dietary intake-two case studies: folate and vitamin D. Food Nutr Res (Epub ahead of print 2 April 2012).
58. Institute of Medicine. Panel on folate, other B-vitamins and choline. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: The National Academies Press, 1998.
59. Winkels RM, Brouwer IA, Siebelink E, Katan MB, Verhoef P. Bioavailability of food folates is 80% of that of folic acid. Am J Clin Nutr 2007;85:465-73.
60. The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke. JAMA 2002;288:2015-22.
61. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325: 1202-6.
62. McNulty H, Strain JJ, Pentieva K, Ward M. C1 metabolism and CVD outcomes in older adults. Proc Nutr Soc 2012;71:213-21.