Amanda MacFarlane
Adjunct Research Professor
| Degrees: | B.Sc. (Carleton), Ph.D. (Ottawa) |
| Phone: | 613-558-7802 |
| Email: | amanda.macfarlane@canada.ca |
| Office: | Health Canada, E337-AL2203E, Sir Frederick Banting Research Centre, 251 Sir Frederick Banting Drive, Ottawa, ON, K1A 0K9 |
Current Research
My lab studies folate-mediated one-carbon (1C) metabolism in health and disease. Folic acid (folate), along with the other essential B vitamins, is required for DNA synthesis and cellular methylation reactions. Folate-mediated 1C metabolism provides 1C groups for the de novo synthesis of purines, thymidylate, and methionine. Nucleotide pool imbalances (too much or too little of one nucleotide) can result in cytotoxicity, DNA mutagenesis, genome instability and changes in gene expression. Methionine is used to form S-adenosylmethionine (AdoMet) the major methyl donor in the cell required for DNA, RNA and histone methylation, which impacts genome stability and the expression of epigenetically regulated genes. Using in vitro and in vivo models, my lab examines the biochemical, genetic and epigenetic mechanisms underpinning folate-dependent diseases with a particular interest in the effect of maternal and paternal nutrition on fertility, and its effect on the health of their offspring. Using nationally-representative population health data, we also assess the folate and B vitamin status of Canadians, and identify socioeconomic, dietary and genetic determinants of status in the Canadian population. I am also actively involved in policy work related to food fortification and supplement use, and international standard setting including the Dietary Reference Intakes.
Selected Publications
Page, R., A. Wong, T. Arbuckle, and A.J. MacFarlane. The MTHFR 677C>T polymorphism is associated with unmetabolized folic acid in breast milk in a cohort of Canadian women. Accepted in the American Journal of Clinical Nutrition.
Rahimi, S., J. Martel, G. Karahan, D. Chan, C. Angle, N.A. Behan, A.J. MacFarlane, J.M. Trasler. Impact of maternal folic acid supplementation in assisted reproduction on embryonic outcomes and epigenetic patterning. Accepted in Human Reproduction.
Liu, S., J. Evans, A.J. MacFarlane, C.V. Ananth, J. Little, M.S. Kramer, K.S. Joseph for the Canadian Perinatal Surveillance System. Association of maternal risk factors with the recent rise of neural tube defects in Canada. Paediatr Perinat Epidemiol 33(2): 145-153. 2019.
Chaudhry, S.H., M. Taljaard, A.J. MacFarlane, L.M. Gaudet, G.N. Smith, M. Rodger, R. Rennicks White, M.C. Walker, S.W. Wen. The role of maternal homocysteine concentration in placenta-mediated complications: findings from the Ottawa and Kingston birth cohort. BMC Pregnancy Childbirth 19(1):75. 2019.
MacFarlane, A.J., M.E. Cogswell, J. de Jesus, L. Greene-Finestone, D.M. Klurfeld, C.J. Lynch, K. Regan, S. Yamini. A report of activities related to the Dietary Reference Intakes from the Joint Canada-US Dietary Reference Intakes Working Group. Am J Clin Nutr 109: 1-9. 2019.
Lowry, R.B., T. Bedard, A.J. MacFarlane, S. Crawford, B. Sibbald, B.C. Agborsangaya. Prevalence rates of Spina Bifida in Alberta, Canada: 2001-2015. Why can’t we do better with prevention? Birth Defects Research 111(3): 151-158. 2019.
Lamers, Y., A.J. MacFarlane, D.L. O’Connor, B. Fontaine-Bisson. Periconceptional intake of folic acid among low-risk women: summary of a workshop aiming to align prenatal folic acid supplement composition with current expert guidelines. Am J Clin Nutr 108(6):1357-1368. 2018.
LeBlanc, D., N. Behan, J.M. O’Brien, F. Marchetti, A.J. MacFarlane. Folate deficiency increases chromosomal damage and mutations in hematopoietic cells in the transgenic MutaMouse model. Environ Mol Mutagen. 59(5):366-374. 2018.
Ly, L., D. Chan, M. Aarabi, M. Landry, N. Behan, A.J. MacFarlane, J. Trasler. Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation. Mol Hum Reprod 23(7):461-477. 2017.
Page, R., A. Robichaud, T. Arbuckle, W. Fraser and A.J. MacFarlane. Total folate and unmetabolized folic acid in the breast milk of a cross-section of Canadian women. Am J Clin Nutr 105(5):1101-1109. 2017.
Yetley E.A., A.J. MacFarlane, L.S. Green-Finestone, B.G. Garza, et al. Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: Report from a Joint US/Canadian-sponsored working group. Am J Clin Nutr 105(1): 249S-285S. 2017.
MacFarlane, A.J. The elephant in the room: Using nutritional biomarker cut-offs to assess status. Am J Clin Nutr 104(6): 1493-1494. 2016.
Shen M., S.H. Chaudhry, A.J. MacFarlane, L. Gaudet, G.N. Smith, M. Rodger, R.R. White, M.C. Walker, S.W. Wen. Serum and red-blood-cell folate demonstrate differential associations with BMI in pregnant women. Public Health Nutr 18:1-8. 2016.
Chan Y.-M., A.J. MacFarlane, D.L. O’Connor. Modeling demonstrates that folic acid fortification of whole wheat flour could reduce the prevalence of folate inadequacy in Canadian whole-wheat consumers. J Nutr 145(11):2622-9. 2015.
Moussa, C., N. Ross, P. Jolette, A.J. MacFarlane. Altered folate metabolism modifies cell proliferation and progesterone secretion in human placental choriocarcinoma JEG-3 cells. Br J Nutr 114(6): 844-52. 2015.
Aarabi, M., M.C. San Gabriel, D. Chan, N.A. Behan, M. Caron, T. Pastinen, G. Bourque, A.J. MacFarlane, A. Zini, J. Trasler. High dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Hum Mol Genet 24(22): 6301-13. 2015.
MacFarlane, A.J., N.A. Behan, M.S. Field, A. Williams, P.J. Stover, C.L. Yauk. Dietary folic acid protects against genotoxicity in the red blood cells of mice. Mutat Res 779: 105–111. 2015.
Stover P.J., A.J. MacFarlane, M.S. Field. Bringing clarity to the role of MTHFR variants in neural tube defect prevention. Am J Clin Nutr 101: 1111-1112. 2015.
Zinck, J.W.R., M. de Groh, A.J. MacFarlane. Genetic modifiers of folate, vitamin B-12, and homocysteine status in a cross-sectional study of the Canadian population. Am J Clin Nutr 101: 1295-1304. 2015.
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