8 Agricultural Research/January 2004

mother and father have so many decisions to makefor their newborn baby—decisions that can pro-foundly influence their boy’s or girl’s development.The first decision they make might concern how tofeed their baby. After gathering facts on all the avail-able options, different parents reach different con-clusions about what’s best for their child.

ARS nutrition researchers in Little Rock,Arkansas, hope to uncover more information to help parentsmake this important decision. They’re investigating the long-term effects of soy infant formula—an increasingly popularfeeding choice.

A 2000 Surgeon General’s report found that 64 percent ofAmerican women breast-feed during their infants’ first weeksof life. But after 6 months, that figure drops to 29 percent formany reasons.

Once a parent has chosen formula feeding, most pediatricianswill recommend cow’s milk-based formula over soy-basedformula for most babies. But doctors will recommend soyformula if they believe an infant should avoid cow’s milk proteinand/or lactose (milk sugar) or if the baby simply doesn’t toleratemilk-based formula. There are lactose-free milk-based formulasavailable now, but some parents, including vegetarians, stillprefer soy-based formulas.

Although soy infant formulas are now consumed by 20-25percent of formula-fed infants in America, there is little re-search on the immediate and long-term health and cognitiveeffects of this diet in humans.

A 1998 report from the American Academy of Pediatricsmaintains that “isolated soy protein-based formulas are safe

and effective alternatives to provide appropriate nutrition fornormal growth and development” in term infants not being fedbreast milk or cow’s milk-based formulas. But some child-advocacy groups claim that consuming soy-based formula couldaccelerate puberty and cause developmental and reproductiveabnormalities and thyroid disorders later in life.

Previous studies at ARS’s Arkansas Children’s NutritionCenter (ACNC) in Little Rock and elsewhere found no apparentlong-term positive or negative effects of feeding infants soyversus cow’s milk formula. But there are no long-term,systematic studies of the effects of soy formula on development,growth, and central nervous system function. To help clarifythe issue, Thomas M. Badger, ACNC director and a professorin the College of Medicine at the University of Arkansas forMedical Sciences (UAMS) in Little Rock, is leading a 6-yearstudy—begun in September 2002—to compare the effects ofsoy infant formula with those of breast milk and cow’s milkformula.

Isolating Soy Protein for StudySoy-based infant formulas contain soy protein isolate (SPI).

Isoflavones are bound to soy proteins in high amounts. They’rea class of phytoestrogens, which are plant derived and pre-sumably healthful. One controversial aspect of soy-basedformula involves isoflavones because they’re believed to actsimilarly to the female hormone estrogen. Critics suggest thatisoflavones in soy formula might disrupt or impair development

Research assistant Lisa Witcher places a neural net on an 8-month-old study participant while explaining the data collection process tothe child’s mother. The neural net records brain wave activity.

ST

EP

HE

N A

US

MU

S (

K10

901-

1)

STEPHEN AUSMUS (K10898-1)

Neuroendocrinologist Thomas Badger inserts a sample into a mass-spectroscopy unit to measure soy isoflavones in mammary glandepithelial cells. Studies at ACNC have shown that animals fed dietshigh in soy have a lower incidence of breast cancer. Epithelial cellsare studied because they are the cells that develop into breast cancer.

Study Examines Long-Term HealthEffects of Soy Infant Formula

345490 12/19/03, 1:58 AM8

9Agricultural Research/January 2004

Dual energy X-ray absorptiometry (DXA) is used to measure bonedensity and body composition. Nutritionist Janet Gilchrist analyzesa DXA scan completed on a 6-month-old boy.

STEPHEN AUSMUS (K10903-1)

Psychological examiner Mindy Lester (left) uses the Bayley Scales ofInfant Development Assessment to conduct a developmentalassessment on a 1-year-old girl. The child’s mother is pleased to seeher daughter’s progress since the previous study visit.

STEPHEN AUSMUS (K10900-1)

in infants. But taking into account previous ACNC findings,Badger suspects that soy isoflavones are not acting like femalehormones in infants.

In studies of several generations of ratsfed high levels of soy protein, Badger andhis team found they grew and developednormally, except for very minor differenc-es that have not been found in humans.There were no harmful effects, but therewere many beneficial health effects.

Still, ACNC researchers have foundsome reason to be concerned about pos-sible drawbacks of soy proteins: Theycould affect a body system involved in drugmetabolism.

The scientists found that SPI-contain-ing diets fed to young rats increase activi-ties of phase I and II detoxificationsystems, which are involved with metabo-lizing toxins in the body. These beneficialsystems can actually remove substancesthat cause diseases such as cancer. Butstudies also showed that soy consumptionaltered certain phase I enzymes found inthe liver, gut, and other organs. These en-zymes—in the CYP3A family—are responsible for metabo-lism of about 80 percent of all clinical medications taken byhumans and other animals.

Martin J.J. Ronis, a toxicologist at ACNC and a professor atUAMS, is conducting studies to see whether increased CYP3Acould reduce drug levels faster than normal and consequently

Nutritionist Pat Wiggins weighs a 1-year-old boy while his mother watches.

STEPHEN AUSMUS (K10899-1)

reduce their beneficial effects. High levels of these enzymeswere found in rats fed large amounts of soy, and even higher

amounts were found after they were giv-en medications.

“We found that SPI-fed rats had an in-creased phase I metabolism,” Badger says.“This has two implications. First, these en-zymes are responsible for activation anddeactivation of toxic materials, includingprocarcinogens and carcinogens. This maybe one mechanism by which SPI reducesthe incidence and number of mammaryand colon cancers.

“Second, since medications are alsometabolized by these enzymes, it’spossible that drug efficacy is affected.We’re currently studying this effect ininfants who are fed soy formula andcomparing it to breast-fed and milkformula-fed babies.”

Bringing in BabyPat Wiggins and Jill Brackenbury, nu-

tritionists at ACNC, are co-leading theclinical portion of the ARS-supported in-

fant study, which is building on previous research at the centeron the effects of soy in animals.

“Soy-based formula has been commercially available sincethe sixties,” Wiggins says, “but few studies have examined thelong-term consequences of exposure to high concentrations ofestrogenic compounds during infancy. No one consumes more

345490 12/19/03, 1:58 AM9

10 Agricultural Research/January 2004

soy per kilogram of body weight than infants who are fed soy-based formula. Infants should consume about 115 calories perkilogram to maintain normal growth.”

Three hundred eighty full-term, healthy infants will partici-pate in the study at Arkansas Chil-dren’s Hospital in Little Rock.Ninety-five babies will be recruitedin each of four groups. One groupwill be exclusively breast-fed bytheir mothers; another group will begiven milk-based formula supple-mented with docosahexaenoic acid(DHA), a fatty acid recently madeavailable in U.S. infant formulas; athird group will be given soy-basedformula with DHA; and a fourthgroup, soy formula without DHA.

DHA and another fatty acid,arachidonic acid, are found in smallconcentrations in breast milk. Theywere not available in U.S. infant for-mulas until 2002. It’s believed thatDHA improves infant visual functionand that both compounds improvecognitive development, but more ev-idence is needed to prove this.

ACNC conducted an extensiverecruiting campaign throughout Lit-tle Rock and the surrounding com-munity. Some babies were enrolledas newborns. Babies were selectedon the basis of what their parents hadalready decided to feed them. Therewere no efforts to persuade parentsto feed their babies a certain way.

The researchers start monitoringinfants when they’re about 1 monthold, checking for certain develop-mental milestones and collectinginformation on diet, growth variables, medical history, and brainfunction.

Babies receive four brief health checks at 1, 2, 4, and 5months of age. They receive extensive checkups at 3, 6, and 9months and 1 year, then yearly until they are 6 years old. Theselonger evaluations include a dual energy X-ray absorptiometry(DXA) scan to measure the children’s bone density and bodycomposition. Badger says they expect to find that early expo-sure to soy supports normal bone mineralization and improvesbody composition.

Also during the longer checkups, Terry Pivik and RoscoeDykman, ACNC psychologists and UAMS professors, study

the effects of the diets on brain function and on measures knownto be predictive of later physical and mental development, in-cluding school achievement. They do this by recording brainwave activity from 128 different sites on each child’s head as

the child performs various tasks.The dense array of recording sitesmakes it possible to localize behav-ior to specific brain areas.

The researchers also gather infor-mation on sleep patterns, aspects ofthe home environment and parentalgenetic influences, measures of IQ,and motor and mental development,because these variables are also pre-dictive of later mental developmentand academic performance.

As they wean to regular food, thechildren undergo periodic exami-nations to measure brain develop-ment and function. Says Badger,“We hope to determine how variousdietary factors affect cognitivefunction, learning ability, and at-tention span.”

Perks of participating in the studyinclude tests more thorough than theones most babies would ordinarilyreceive. Parents receive free for-mula—or diapers if nursing. After1 year, they receive $100 compen-sation for each yearly examination.Most importantly, they receivedetailed periodic reports on thehealth of their babies.

Kim Jones of Conway, Arkansas,enrolled her daughter, Kaleigh, whois being breast-fed, in the study inSeptember 2002 when she was just3 months old. Jones believes taking

part in the study will benefit Kaleigh a great deal. “It’s nice to have steady feedback on her growth,” Jones

says. “We’ll see how she is progressing and reaching her de-velopmental milestones.”—By Jim Core, ARS.

This research is part of Human Nutrition, an ARS NationalProgram (#107) described on the World Wide Web at www.nps.ars.usda.gov.

Thomas M. Badger is with the USDA-ARS ArkansasChildren’s Nutrition Center, 1212 Marshall St., Little Rock, AR72202; phone (501) 364-2785, fax (501) 364-2818, e-mailbadgerthomasm@uams.edu. ★

STEPHEN AUSMUS (K10902-1)

Known as the “soy twins” in the study comparinghealth effects of soy-based formula, cow’s milk-basedformula, and human breast milk, these 8-month-oldboys take time out from a busy study schedule to enjoya bottle of formula.

345490 12/17/03, 2:28 AM10