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Blood Determinations of S-Adenosylmethionine, S-Adenosylhomocysteine, and Homocysteine

Correlations with Diet¹

Division of Molecular Epidemiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079 [L. A. P., C. K. W., R. R. D.], and Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland 20892 [R. S.]

An increasing number of both clinical and experimental studies have shown an association between deficiencies of the dietary sources of physiological methyl groups and cancer formation. The critical metabolic intermediate in a determination of methylation status is S-adenosylmethionine (SAM), the body’s chief physiological methyl donor. The present study examined the erythrocyte levels of SAM and of its demethylated metabolite S-adenosylhomocysteine (SAH) in 66 normal subjects (33 men and 33 women), whose blood had been drawn at days 0, 7 and 14 of an experimental period during which they were fed a fixed diet. The plasma levels of homocysteine (HCys) were also determined in the same individuals at the same time points. In addition, the subjects had completed a food frequency questionnaire (FFQ) describing their usual dietary habits before being placed on the dietary regimen. The blood levels of SAM, SAH, and HCys were compared with the dietary intakes of folate, vitamin B₆, fats, and calories, both prior to using the FFQ and during the experimental period. The results indicated that the intraindividual differences were very low, but the interindividual differences were large for the values of SAM, SAH, SAM:SAH ratios, and HCys. Interestingly, the blood levels of SAM and HCys were higher in men than in women and generally showed the expected correlations with folate intake i.e., positive for SAM and negative for HCys. The intakes of folate (276 µg/days) and B₆ (1.87 mg/days) during the 2-week experimental period were relatively low compared with the usual intakes of these vitamins (375 and 2.06 mg/day for folate and B₆, respectively) but correlated well with each other during both periods of the study. Surprisingly, both men and women showed a significant rise in erythrocyte SAM:SAH ratios as a function of age. In addition, the combined results from men and women, even adjusted for gender, showed significant correlations between HCys and both weight and body mass index. On the other hand, during the experimental period of the study, blood SAM levels were inversely correlated with the intakes of both fat and calories when the data for both men and women were combined and adjusted for gender. The blood determinations of SAM and related compounds showed a high degree of reproducibility over time and thus appear to provide a practical marker of methylation status for the assessment of cancer risk from dietary, environmental, and genetic factors.

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