April 18, 2000 -- Research in recent years has shown that heavy doses of certain bioflavonoids -- chemicals found in some foods and supplements that are often considered beneficial -- may be linked with leukemia in infants and children.
Now, University of Chicago genetics researchers have found the mechanism by which bioflavonoids may damage genetic machinery and trigger leukemia, or blood cancer, in children.
These researchers and other experts urge caution about reading too much into the results, especially concerning bioflavonoids that naturally occur in foods. But questions are being raised about supplements that deliver megadoses of the substances, and experts say pregnant women should avoid these supplements.
"The public health message from this study is not yet clear," Janet Rowley, MD, the University of Chicago molecular geneticist who directed the study, tells WebMD. "The health benefits of a diet high in foods containing bioflavonoids, such as soybeans, citrus fruits and, root vegetables, are unquestioned."
Bioflavonoids are chemical compounds derived from plants. They are not vitamins and are not known to be essential for human nutrition.
Infant leukemias are rare, affecting 37 in 1 million American children. Some researchers have contended infections cause the cancers. But studies have suggested that mothers who consume large amounts of bioflavonoids may have children who are at increased risk of infant and childhood leukemia. A study in several major Asian cities, where soy consumption is at least twice that of the United States, found their rate of infant leukemia is twice as high as in this country.
Rowley is a pioneer in linking cancers to genetic defects, such as when chromosomes are swapped between genes, resulting in cancers. She is credited with discovering the first of these DNA switches in the early 1970s.
In a test-tube study reported in the Proceedings of the National Academy of Sciences, her team found that 10 of 20 bioflavonoids they tested caused breaks in a small area of a gene known as MLL (short for myeloid-lymphoid leukemia). Most adult leukemias involve a different part of the gene.
Rowley in 1992 discovered the MLL gene, which plays a role in eight of 10 infant leukemias. Some bioflavonoids were as potent in causing MLL damage as etoposide, an anticancer agent that has caused some "secondary" bone marrow cancers following therapy.
"This strongly supports the notion that bioflavonoids could be a causative agent for infant and possibly childhood leukemias," Rowley says. Mothers' intake of bioflavonoids during pregnancy may cause MLL damage in the fetuses, leading to leukemia in infants and young children, she says.
Using blood and bone-marrow cells from healthy newborns and adults, as well as leukemia cells, researchers uncovered the mechanism of DNA damage. Once the MLL gene is broken, it can reconnect with more than 40 other genes. In extreme cases, this can cause cell death. These so-called "translocations" of genetic material also can cause uncontrolled cell growth, such as in leukemia.
Manuel Diaz, MD, a molecular geneticist at the Cardinal Bernadin Cancer Center at Loyola University Medical Center in Maywood, Ill., calls for caution in interpreting the study's results.
"It is a big jump from an in vitro study for possible effects in a complete organism," he says. "I wouldn't change my diet because of this study. This paper will help in the design of other studies."
Still, he agrees with Rowley that pregnant women should not take supplements containing bioflavonoids. Linda Van Horn, PhD, RD, professor of preventive medicine and a nutritionist at Northwestern University Medical School, says several recent studies have called supplement use into question.
"Foods, not supplements, are the best source of nutrients for a human body," she says. "When you supplement the body with megadoses of nutrients, you are taking those nutrients out of the context of the food and may be left with a potential toxic effect."
- Researchers have found that chemicals known as bioflavonoids can cause genetic damage, which may explain the suspected link between bioflavonoids and leukemia among infants and children.
- Pregnant women should not take megadoses of bioflavonoids in supplements, researchers say.
- When they are consumed in foods in which they naturally occur, such as soybeans, citrus fruits, and root vegetables, bioflavonoids have many health benefits.