The Journal of Nutrition Vol. 127 No. 8 August 1997, pp. 1534-1535
Copyright ©1997 by the American Society for Nutritional Sciences

LETTER TO THE EDITOR:
Some Vitamin Sources Relating to Plasma Homocysteine Provide not only Folate but also Vitamins B-12 and B-6

Dear Dr. Visek:

We read with interest the report of Tucker et al. (1996), "Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study," and wish to comment on this timely and important topic. Tucker and colleagues (1996) delineated the major sources of folate intake in elderly men and women and showed that these related not only to plasma folate but also to plasma homocysteine, a newly recognized risk factor for vascular disease. In the New Mexico Aging Process Study, we reported that ready-to-eat breakfast cereal contributed 25.6% of population folate intake from food, orange juice 14.9%, total vegetables 23.2% and total fruits 20.8% (Koehler et al. 1997). Interestingly, there were noticeable similarities between the top-ranking food sources of folate in the two studies, showing some commonalities in food patterns of elderly people in two geographic regions, measured using different food frequency instruments (Koehler et al. 1997, Tucker et al. 1996).

We previously reported in the New Mexico Aging Process Study that elderly men and women taking self-selected vitamin supplements had higher mean serum folate and lower mean serum homocysteine concentrations than those not taking supplements (Koehler et al. 1996), consistent with the report of Tucker et al. (1996). In addition to considering the role of supplements, Tucker et al. (1996) moreover related plasma folate and homocysteine to major food sources of folate: ready-to-eat breakfast cereals, orange juice, leafy green vegetables and total fruits and vegetables. Statistically significant relationships with plasma homocysteine were found for supplements and for the food sources mentioned, except for orange juice. This important result lends weight to the role of food selection by the elderly as well as the role of supplement use in determining plasma homocysteine, a risk factor for vascular disease.

In their article, Tucker et al. (1996) pointed out that vitamin B-12 deficiency is a common condition in the elderly, and they noted the concern that excessive folate intake by the elderly might mask the hematologic manifestations of vitamin B-12 deficiency, delaying its diagnosis and treatment. However, we would like to comment that, additionally, vitamin B-12 status should be considered as a factor relating to plasma homocysteine concentration. The demonstrated association of vitamin supplements (Koehler et al. 1996, Tucker et al. 1996) and ready-to-eat cereal (Tucker et al. 1996) with serum/plasma homocysteine is likely due not only to the folate but also to the crystalline vitamin B-12 in these sources. The metabolite homocysteine may be elevated in plasma in deficiency of either folate or vitamin B-12; the metabolite methylmalonic acid is elevated only when vitamin B-12 is deficient. In a previous report from the Framingham Study cohort, 12% of the elderly subjects had vitamin B-12 deficiency based on elevated metabolites and low or low-normal serum vitamin B-12 (Lindenbaum et al. 1994). In a subset of subjects from the New Mexico Aging Process Study, 7% were deficient in vitamin B-12 using similar criteria (Koehler et al. 1996). In our study, a stepwise regression model explained 64% of the variance in serum homocysteine (Koehler et al. 1996).

Using this model, vitamin B-12 status (represented by serum methylmalonic acid) explained 13.8% of the variance in serum homocysteine, more than the 9.3% of variance accounted for by serum folate. Both multivitamin supplements and ready-to-eat breakfast cereals (which are generally fortified) contain crystalline vitamin B-12. These amounts of crystalline vitamin B-12 are probably better absorbed than food-bound vitamin B-12 by elderly people with atrophic gastritis (although they would not be effective for those with pernicious anemia, who lack the intrinsic factor protein).

In addition to its relation to folate and vitamin B-12 status, plasma/serum homocysteine may also be related to vitamin B-6 status. In our regression model for serum homocysteine, measurements of vitamin B-6 status were not available. However, we studied serum samples from fasting subjects, and it has been suggested that vitamin B-6 status is not an important determinant of fasting homocysteine concentrations (Miller et al. 1992). The plasma samples in the 20th cycle examination of the Framingham Study were from non-fasting subjects, and a relationship between homocysteine concentration and vitamin B-6 status in this cohort was reported previously (Selhub et al. 1993). Both multivitamins and ready-to-eat cereal are sources of crystalline vitamin B-6, as well as of folate and vitamin B-12. In the New Mexico Aging Process Study, population food sources of vitamin B-6 included ready-to-eat cereal 21.3%, total fruit 20.2%, total vegetables 17.7%, leafy green vegetables 4.1% and orange juice 2.5% (leafy greens provided 12.9% of food folate) (K. M. Koehler and S. L. Pareo-Tubbeh, unpublished data).

In conclusion, the article by Tucker et al. (1996) makes an important contribution by relating plasma homocysteine not only to supplement intake but also to major food sources. We would simply comment that in the case of supplements and of ready-to-eat cereal, the association with homocysteine can likely be attributed to both vitamins, folate and vitamin B-12, and possibly to vitamin B-6. In the case of fruits and vegetables, the association may also be due to vitamin B-6 as well as to folate. Additionally, considering the irreversible neurologic damage of vitamin B-12 deficiency, screening and treatment of the elderly for this condition deserves increased attention. Health professionals should be active on this issue and aware of modern approaches to screening using serum metabolites (Stabler 1995).

Kathleen M. Koehler
Shirley L. Pareo-Tubbeh
Hwa Chi Liang
Linda J. Romero
Richard N. Baumgartner
Philip J. Garry
School of Medicine University of New Mexico Albuquerque, NM 87131

FOOTNOTES

Manuscript received 24 February 1997. Revision accepted 5 May 1997.

LITERATURE CITED

• Koehler K. M., Pareo-Tubbeh S. L., Romero L. J., Baumgartner R. N., Garry P. J. Folate nutrition and older adults: challenges and opportunities. J. Am. Diet. Assoc. 1997; 97:167-173 [Medline]
• Koehler K. M., Romero L. J., Stauber P. M., Pareo-Tubbeh S. L., Liang H. C., Baumgartner R. N., Garry P. J., Allen R. H., Stabler S. P. Vitamin supplementation and other variables affecting serum homocysteine and methylmalonic acid in elderly men and women. J. Am. Coll. Nutr. 1996; 15:364-376 [Abstract]
• Lindenbaum J., Rosenberg I. H., Wilson P.W.F., Stabler S. P., Allen R. H. Prevalence of cobalamin deficiency in the Framingham elderly population. Am. J. Clin. Nutr. 1994; 60:2-11 [Abstract/Free Full Text]
• Miller J. W., Ribaya-Mercado J. D., Russell R. M., Shepard D. C., Morrow F. D., Cochary E. F., Sadowski J. A., Gershoff S. N., Selhub J. Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations. Am. J. Clin. Nutr. 1992; 55:1154-1160 [Abstract/Free Full Text]
• Selhub J., Jacques P. F., Wilson P.W.F., Rush D., Rosenberg I. H. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. J. Am. Med. Assoc. 1993; 270:2693-2698 [Abstract/Free Full Text]
• Stabler S. P. Screening the older population for cobalamin (vitamin B12) deficiency. J. Am. Geriatr. Soc. 1995; 43:1290-1297 [Medline]
• Tucker K. L., Selhub J., Wilson P.W.F., Rosenberg I. H. Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study. J. Nutr. 1996; 126:3025-3031

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