Homocysteine and Cereal: Help the Heart by Eating Right
By Sandra Schaefer, MSN, ARNP, RN-C
Summary-The results of a randomized, double-blind, placebo-controlled, crossover trial in 75 men and women with coronary artery disease showed that eating cereal fortified with folic acid and the recommended dietary allowances of B6 and B12 lowered homocysteine levels. Elevated plasma homocysteine is a recognized risk factor for coronary artery disease, neural tube defects in newborns, and atherosclerotic diseases. On Jan. 1, 1998, responding to recommendations from the Food and Drug Administration, U.S. manufacturers began fortifying cereal with folic acid.
· This study demonstrates that folic acid in the amount approximating that used to fortify cereal (127 mg) is not adequate to significantly decrease homocysteine levels. However, cereal fortified with 499 or 655 mg folic acid decreased plasma homocysteine 11% and 14%, respectively.
· The Centers for Disease Control and Prevention recommends folic acid supplement of 0.04 mg daily for women ages 18-45.
· Advanced practice nurses may want to encourage patients to increase dietary intake of fortified cereal products or supplement daily with folic acid or a B-group vitamin.
In a recent study, the amount of folic acid (127 mg) recommended under the Food and Drug Administra tion's new enrichment policy, combined with recommended daily allowances (RDAs) of B6 and B12, did not significantly reduce homocysteine levels (3.7%).1 The study demonstrates that eating cereal containing 499 and 665 mg of folic acid decreased homocystine levels by 11% and 14%, respectively (P<0.001 and P=0.001).
It would take a die-hard skeptic to deny the value of folic acid supplements in preventing and treating a variety of medical conditions today. Folic acid deficiency plays a part in neural tube defects in newborns2 and is suspect in others, including cervical dysplasia, neoplasia in ulcerative colitis, peripheral neuropathy, myelopathy, and neuropsychiatric diseases.3 It is an acknowledged risk factor for premature cardiovascular disease4 and atherosclerotic disease.5,6
Elevated Homocysteine Correlates with Atherosclerosis
Numerous studies from 1989-1997 showed that 13-47% of patients with arterial occlusive diseases might have elevated levels of plasma homocysteine.
In the department of medicine at New York Univer sity Medical Center, researchers Konecky, Mainow, Tunick, et al6 reported dietary deficiencies of vitamin B6, B12, or folic acid might result in elevated blood homocysteine levels, and patients with hyperhomocysteinemia showed a higher proportion of atherosclerosis. Elevated homocysteine levels are only one variant in the development of plaque formation but appear to be one that is amenable to change. The possibility that a simple dietary change could reduce homocysteine levels warranted investigation.
Beginning Jan. 1, 1998, the U.S. food supply of cereal-grain products was fortified with folic acid to prevent neural-tube defects in newborns as a result of an FDA recommendation. Because numerous prior studies showed that folic acid supplementation reduced homocysteine levels, researchers Malinow, Duell, Hess, et al hypothesized that folic acid-fortified cereal might do the same. Their study, reported in The New England Journal of Medicine, assessed the effects of vitamin-fortified breakfast cereals on plasma folic acid and homocysteine.1
Seventy-five patients diagnosed with coronary artery or ischemic heart disease from cardiology and primary care clinics at Providence St. Vincent Medical Center in Portland, OR, were evaluated to see if adding folic acid to their diet in the form of fortified breakfast cereal would lower their homocysteine levels. General Mills research laboratories in Minneapolis prepared one ounce (30 g) of ready-to-eat wheat-based cereal packets containing 127 mg folate, 499 mg folate, or 665 mg folate. Packets contained RDAs of vitamins and minerals including pyridoxine and cyanocobalamin. Placebo packets contained cereal without folic acid, pyridoxine, or cyanocobalamin.
Each subject consumed one packet daily for five weeks, resumed a regular diet for five weeks, then returned to eating one packet of cereal for another five weeks. Analysis of blood homocysteine levels showed a significant correlation with higher levels of folic acid.
Although a small study, the results were significant. Cereals containing 499 and 665 mg of folic acid decreased homocystine levels by 11% and 14%, respectively (P<0.001 and P=0.001). However, most fortified cereal today provides only 127 mg folic acid, which decreased homocysteine levels less than 4%.
Researchers noted that compliance with daily cereal consumption was high among study participants, but only 49% previously had eaten breakfast cereal five or more times a week. The general population may consume less cereal and derive less benefit. (See information on international studies, at left.)
Practice Implications
The body cannot store large amounts of folic acid, and deficiency can develop within a few months. Vitamin B12 deficiency develops over years. When a macrocytic anemia is present, both serum vitamin B12 and RBC folate levels should be measured. If B12 or folate levels are equivocal, serum methylmalonic acid and homocysteine may be useful. Both are elevated in B12 deficiency; only homocysteine is elevated in folic acid deficiency.7
Concern for clients' nutritional status is important to advanced nursing practice. A survey of 2,000 women of childbearing age found only 32% took daily vitamins with folic acid, another 12% took them but not every day, and 20% took vitamins lacking folic acid.8 Even with enriched cereals, the Centers for Disease Control and Prevention recommends 0.4 mg folic acid daily for women ages 18-45. Patients at risk for folic acid deficiency, such as pregnant women, patients receiving long-term low-dose methotrexate for rheumatoid arthritis and those at risk or diagnosed with coronary artery disease, should be considered for folic acid or B-group vitamin supplementation.
You may want to encourage patients who are reluctant or cannot afford to add another pill to their regimen to increase their dietary intake of fortified cereal and foods rich in folic acid. (See above table.)
References
1. Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. NEJM 1998;338:1009-1015.
2. Copp AJ. Prevention of neural tube defects: Vitamins, enzymes and genes. Current Opinion in Neurology 1998;11:97-102.
3. Kelly GS. Folates: Supplemental forms and therapeutic applications. Alt Med Review 1998;3:208-220.
4. Woodside JV, Yarnell JW, McMaster D, et al. Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial. Am J Clin Nutrition 1998;67:858-866.
5. Kroesen DJ, Pietrzik K. Folic acid and Vitamin B 6 supplementation and plasma homocysteine concentrations in healthy young women. 1998;68:98-103.
6. Konecky N, Mainow MR, Tunick PA, et al. Correlation between plasma homocyst(e)ine and aortic atherosclerosis. Am Heart J 1997;133:534-540.
7. Carey CF, Lee HH, Woeltje KF (Editors). The Washing ton Manual of Medical Therapeutics, 29th Edition. Philadelphia; Lippincott-Raven Publishers. 1998.
8. Centers for Disease Control and Prevention. News release: Women not taking folic acid. Feb. 26, 1998. Atlanta.
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