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Journal of Nutrition Vol. 124 No. 11 November 1994, pp. 2197-2203
Copyright © 1994 by American Society for Nutrition
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Severe Folate Deficiency Causes Secondary Depletion of Choline and Phosphocholine in Rat Liver1,2,3,

Young-In Kim4,5,, Joshua W. Miller, Kerry-Ann da Costa*, Marie Nadeau, Donald Smith, Jacob Selhub, Steven H. Zeisel*,6 and Joel B. Mason

Vitamin Bioavailability Laboratory, U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 * Department of Nutrition, School of Public Health and School of Medicine, The University of North Carolina, Chapel Hill, NC 27599-7400

It has previously been shown that choline deficiency causes depletion of hepatic folate concentration in rats. Two separate experiments were undertaken to investigate the converse phenomenon: whether folate deficiency would lead to depletion of hepatic choline. In Experiment 1, severe folate deficiency was induced in rats by feeding an amino acid-defined diet containing (per kg diet) 1.4 g choline, 0 mg folate and 10 g succinylsulfathiazole. Control rats were fed the same diet containing 8 mg folate/kg. After 4 wk, plasma and hepatic folate concentrations were significantly depleted in the severely folate-deficient rats compared with controls (P < 0.001), and hepatic choline and phosphocholine concentrations were 65 and 80% lower, respectively (P < 0.001). In Experiment 2, moderate folate deficiency was induced in rats by feeding the same diet as described above, but with the succinylsulfathiazole omitted. After 24 wk, significant systemic folate deficiency was present in the moderately folate-deficient rats compared with controls (P < 0.001). A modest reduction (36%, P = 0.087) in hepatic choline concentration was observed in the moderately folate-deficient rats compared with controls. No significant differences in hepatic phosphocholine concentrations were detected between the two groups. These results indicate that severe folate deficiency causes secondary hepatic choline deficiency in rats.


KEY WORDS: • folate • choline • rats

1 Presented in part at the 1994 meeting of the American Association for Cancer Research, April 10–18, 1994, San Francisco, CA [Kim, Y. I., Miller, J. W., da Costa, K-A., Nadeau, M., Smith, D., Selhub, J., Zeisel, S. H. & Mason, J. B. (1994) Secondary depletion of hepatic choline by severe folate deficiency: possible implications for carcinogenesis. Proc. Am. Assoc. Cancer Res. 35: A104 (abs.)].

2 Supported in part by NCI grant 1U01 CA63812-01 and with federal funds from the U.S. Department of Agriculture, Agricultural Research Service Contract 53-3K06-0-1. The contents of this publication do not necessarily reflect the views of the U.S. Department of Agriculture, nor does mention of trade names, commercial products or organizations imply endorsement by the United States government.

3 The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

4 Y-I. Kim is a recipient of a Research Fellowship from the Medical Research Council of Canada.

5 To whom correspondence and reprint requests should be addressed.

6 S. H. Zeisel is supported by grant AG-09525 from the NIH and by a grant from the American Institute for Cancer Research.

Manuscript received 25 February 1994. Revision accepted 17 May 1994.




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