Korean J Nutr.  2009 Jul;42(5):423-433. 10.4163/kjn.2009.42.5.423.

A Critical Evaluation of the Correlation Between Biomarkers of Folate and Vitamin B12 in Nutritional Homocysteinemia

• Min H
• Kim M

• KMID: 2267324
• DOI: http://doi.org/10.4163/kjn.2009.42.5.423

Abstract

Folate and vitamin B12 are essential cofactors for homocysteine (Hcy) metabolism. Homocysteinemia has been related with cardiovascular and neurodegenerative disease. We examined the effect of folate and/or vitamin B12 deficiency on biomarkers of one carbon metabolism in blood, liver and brain, and analyzed the correlation between vitamin biomarkers in mild and moderate homocysteinemia. In this study, Sprague-Dawley male rats (5 groups, n = 10) were fed folate-sufficient diet (FS), folate-deficient diet (FD) with 0 or 3 g homocystine (FSH and FDH), and folate-/vitamin B12-deficient diet with 3 g homocystine (FDHCD) for 8 weeks. The FDH diet induced mild homocysteinemia (plasma Hcy 17.41 +/- 1.94 nmol/mL) and the FDHCD diet induced moderate homocysteinemia (plasma Hcy 44.13 +/- 2.65 nmol/mL), respectively. Although liver and brain folate levels were significantly lower compared with those values of rats fed FS or FSH (p < 0.001, p < 0.01 respectively), there were no significant differences in folate levels in liver and brain among the rats fed FD, FDH and FDHCD diet. However, rats fed FDHCD showed higher plasma folate levels (126.5 +/- 9.6 nmol/L) compared with rats fed FD and FDH (21.1 +/- 1.4 nmol/L, 22.0 +/- 2.2 nmol/L)(p < 0.001), which is the feature of "ethyl-folate trap"by vitamin B12 deficiency. Plasma Hcy was correlated with hepatic folate (r = -0.641, p < 0.01) but not with plasma folate or brain folate in this experimental condition. However, as we eliminated FDHCD group during correlation test, plasma Hcy was correlated with plasma folate (r = -0.581, p < 0.01), hepatic folate (r = -0.684, p < 0.01) and brain folate (r = -0.321, p < 0.05). Hepatic S-adenosylmethionine (SAM) level was lower in rats fed FD, FDH and FDHCD than in rats fed FS and FSH (p < 0.001, p < 0.001 respectively) and hepatic S-adenosylhomocysteine (SAH) level was significantly higher in those groups. The SAH level in brain was also significantly increased in rats fed FDHCD (p < 0.05). However, brain SAM level was not affected by folate and/or vitamin B12 deficiency. This result suggests that dietary folate- and vitamin B12-deficiency may inhibit methylation in brain by increasing SAH rather than decreasing SAM level, which may be closely associated with impaired cognitive function in nutritional homocysteinemia.

Keyword

homocyteine; S-adenosylmethionine; S-adenosylhomocysteine; DNA methylation; cognitive function

MeSH Terms

Animals
Biomarkers
Brain
Carbon
Diet
DNA Methylation
Folic Acid
Homocysteine
Homocystine
Humans
Hyperhomocysteinemia
Liver
Male
Methylation
Neurodegenerative Diseases
Plasma
Rats
S-Adenosylhomocysteine
S-Adenosylmethionine
Vitamin B 12
Vitamin B 12 Deficiency
Vitamins
Carbon
Folic Acid
Homocysteine
Homocystine
Hyperhomocysteinemia
S-Adenosylhomocysteine
S-Adenosylmethionine
Vitamin B 12
Vitamins

Figure

• 

  Fig. 1 The effects of folate- and vitamin B12-deficient diet combined with homocystine feeding on plasma homocysteine. Mean ± S.E (n = 10). Bars with different superscript letter are significantly different among groups (p < 0.05). Folate-deficient diets (FD, FDH) elevated plasma homocysteine significantly (p < 0.001), whereas homocystine feeding alone did not affect plasma Hcy in rats. Mild homocysteinemia was induced by FD or FDH and moderate homocysteinemia was induced by FDHCD. FS: folate-sufficient diet, FSH: folate-sufficient/0.3% homocystine diet, FD: folate-deficient diet, FDH: folate-deficient/0.3% homocystine diet, FDHCD: folate-deficient/vitamin B12-deficient/0.3% homocystine diet.

• 

  Fig. 2 The correlation between concentrations of plasma homocysteine and tissue folate. A: Data of biomarkers of FS, FSH, FD, FDH and FDCDH (5 groups) were analyzed for correlation test. Correlation coefficients between plasma homocysteine and plasma folate, a: liver folate, b: and brain folate, c. B: Data of biomarkers of FS, FSH, FD and FDH (4 groups) were analyzed for correlation test. NS: not significant.

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