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Manuscript received 6 January 1998. Initial reviews completed 3 March 1998. Revision accepted 27 March 1998.
, and
Western Human Nutrition Research Center, U.S. Department of Agriculture, Agricultural Research Service, Presidio of San Francisco, CA 94129; * National Center for Toxicological Research, FDA, Division of Nutritional Toxicology, Jefferson, AR 72079; and School of Public Health, University of California, Los Angeles, CA 90024
To determine the human folate requirement on the basis of changes in biochemical pathways, we studied the effect of controlled folate intakes on plasma homocysteine and lymphocyte DNA methylation and deoxynucleotide content in healthy postmenopausal women. Eight women (49-63 y of age) were housed in a metabolic unit and fed a low folate diet containing 56 µg/d of folate for 91 d. Folate intake was varied by supplementing 55-460 µg/d of folic acid (pteroylglutamic acid) to the diet to provide total folate intake periods of 5 wk at 56 µg/d, 4 wk at 111 µg/d and 3 wk at 286-516 µg/d. A subclinical folate deficiency with decreased plasma folate was created during the first two periods. This resulted in significantly elevated plasma homocysteine and urinary malondialdehyde, and lymphocyte DNA hypomethylation. The folate depletion also resulted in an increased ratio of dUTP/dTTP in mitogen-stimulated lymphocyte DNA and decreased lymphocyte NAD, changes suggesting misincorporation of uracil into DNA and increased DNA repair activity. The DNA hypomethylation was reversed with 286-516 µg/d of folate repletion, whereas the elevated homocysteine decreased with 516 but not 286 µg/d of folate. The results indicate that marginal folate deficiency may alter DNA composition and that the current RDA of 180 µg/d may not be sufficient to maintain low plasma homocysteine concentrations of some postmenopausal women.
Key words: folic acid, homocysteine, methylation, DNA, humans.
The Journal of Nutrition Vol. 128 No. 7 July 1998,
pp. 1204-1212
Copyright ©1998 by the American Society for Nutritional Sciences
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 A. Khajuria and D. S. Houston Induction of monocyte tissue factor expression by homocysteine: a possible mechanism for thrombosis Blood, August 1, 2000; 96(3): 966 - 972. [Abstract] [Full Text] [PDF]
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W. D. Rees, S. M. Hay, D. S. Brown, C. Antipatis, and R. M. Palmer Maternal Protein Deficiency Causes Hypermethylation of DNA in the Livers of Rat Fetuses J. Nutr., July 1, 2000; 130(7): 1821 - 1826. [Abstract] [Full Text]
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J.-C. Essama-Tjani, J.-C. Guilland, G. Potier de Courcy, F. Fuchs, and D. Richard Folate Status Worsens in Recently Institutionalized Elderly People without Evidence of Functional Deterioration J. Am. Coll. Nutr., June 1, 2000; 19(3): 392 - 404. [Abstract] [Full Text] [PDF]
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G. P. A. Kauwell, B. L. Lippert, C. E. Wilsky, K. Herrlinger-Garcia, A. D. Hutson, D. W. Theriaque, G. C. Rampersaud, J. J. Cerda, and L. B. Bailey Folate Status of Elderly Women following Moderate Folate Depletion Responds Only to a Higher Folate Intake J. Nutr., June 1, 2000; 130(6): 1584 - 1590. [Abstract] [Full Text]
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 S. Melnyk, M. Pogribna, I. P. Pogribny, P. Yi, and S. J. James Measurement of Plasma and Intracellular S-Adenosylmethionine and S-Adenosylhomocysteine Utilizing Coulometric Electrochemical Detection: Alterations with Plasma Homocysteine and Pyridoxal 5'-Phosphate Concentrations Clin. Chem., February 1, 2000; 46(2): 265 - 272. [Abstract] [Full Text] [PDF]
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S.-W. Choi and J. B. Mason Folate and Carcinogenesis: An Integrated Scheme1-3 J. Nutr., January 1, 2000; 130(2): 129 - 132. [Abstract] [Full Text]
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 C. F. Skibola, M. T. Smith, E. Kane, E. Roman, S. Rollinson, R. A. Cartwright, and G. Morgan Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults PNAS, October 26, 1999; 96(22): 12810 - 12815. [Abstract] [Full Text] [PDF]
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L. B. Bailey and J. F. Gregory III Folate Metabolism and Requirements J. Nutr., April 1, 1999; 129(4): 779 - 782. [Abstract] [Full Text]
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R. A. Jacob, D. J. Jenden, M. A. Allman-Farinelli, and M. E. Swendseid Folate Nutriture Alters Choline Status of Women and Men Fed Low Choline Diets J. Nutr., March 1, 1999; 129(3): 712 - 717. [Abstract] [Full Text]
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J. F. Gregory III, J. Williamson, L. B. Bailey, and J. P. Toth Urinary Excretion of [2H4]Folate by Nonpregnant Women Following a Single Oral Dose of [2H4]Folic Acid Is a Functional Index of Folate Nutritional Status J. Nutr., November 1, 1998; 128(11): 1907 - 1912. [Abstract] [Full Text]
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 P. Yi, S. Melnyk, M. Pogribna, I. P. Pogribny, R. J. Hine, and S. J. James Increase in Plasma Homocysteine Associated with Parallel Increases in Plasma S-Adenosylhomocysteine and Lymphocyte DNA Hypomethylation J. Biol. Chem., September 15, 2000; 275(38): 29318 - 29323. [Abstract] [Full Text] [PDF]
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