Elsevier

The Lancet

Volume 350, Issue 9070, 5 July 1997, Pages 23-27
The Lancet

Early Report
Exposure of infants to phyto-oestrogens from soy-based infant formula

https://doi.org/10.1016/S0140-6736(96)09480-9Get rights and content

Summary

Background

The isoflavones genistein, daidzein, and thier glycosides, found in high concentrations in soybeans and soy-protein foods, may have beneficial effects in the prevention or treatment of many hormone-dependent diseases. Because these bioactive phyto-oestrogens possess a wide range of hormonal and non-hormonal activities, it has been suggested that adverse effects may occur in infants fed soy-based formulas.

Methods

To evaluate the extent of infant exposure to phyto-oestrogens from soy formula, the isoflavone composition of 25 randomly selected samples from five major brands of commercially available soy-based infant formulas were analysed, and the plasma concentrations of genistein and daidzein, and the intestinally derived metabolite, equol, were compared in 4-month-old infants fed exclusively soy-based infant formula (n=7), cow-milk formula (n=7), or human breast-milk (n=7).

Findings

All of the soy formulas contained mainly glycosides of genistein and daidzein, and the total isoflavone content was similar among the five formulas analysed and was related to the proportion of soy isolate used in their manufacture. From the concentrations of isoflavones in these formulas (means 32–47 μg/mL), the typical daily volume of milk consumed, and average body-weight, a 4-month-old infant fed soy formula would be exposed to 28–47 per day, or about 4·5–8·0 mg/kg body-weight per day, of total isoflavones. Mean (SD) plasma concentrations of genistein and daidzein in the seven infants fed soy-based formulas were 684 (443) ng/mL and 295 (60) ng/mL, respectively, which was significantly greater (p<0·05) than in the infants fed either cow-milk formulas (2·2 [0·7] and 2·1 [0·3] ng/mL), or human breast-milk (2·8 [0·7] and 1·4 [0·1] ng/mL), and an order of magnitude higher per bodyweight than typical plasma concentrations of adults consuming soy foods.

Interpretation

The daily exposure of infants to isoflavones in soy infant-formulas is 6–11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods. Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13 000–22 000 times higher than plasma oestradiol concentrations in early life, and may be sufficient to exert biological effects, whereas the contribution of isoflavones from breast-milk and cow-milk is negligible.

Introduction

More than a decade after attention was first drawn to the levels of phyto-oestrogens in soy infant-formulas,1, 2 concerns are being expressed about the possibility of hormonal effects from exposure of infants to phyto-oestrogens from soy-based infant formulas.3 These concerns have prompted at least one government agency to issue statements and recommendations about the use of soy-based infant formulas in early life.4

The phyto-oestrogens in all soy-protein foods belong to the isoflavone class.1 With few exceptions all soy-protein products and soybeans are rich in isoflavones.5, 6 Variation in amount of isoflavones in different soy foods is accounted for mainly by the differences in industrial processing of the soybean, and the type and extent of incorporation of the soy protein into the food matrix.5 Isoflavones when ingested are metabolised extensively in the intestinal tract, absorbed, transported to the liver, and undergo enterohepatic recycling.1, 7, 8 Intestinal bacterial glucosidases cleave the sugar moieties and release the biologically active isoflavones, daidzein and genistein, and in the adult these can be further biotransformed by bacteria to the specific metabolites, equol,9 desmethylangolensin, and p-ethylphenol.10 All of these phyto-oestrogens are then eliminated, mainly by the kidney, and therefore share the physiological features and behaviour of endogenous oestrogens.7

In addition to acting as oestrogen mimics,7, 8 isoflavones have important non-hormonal activities. Genistein, for example, is a potent inhibitor of tyrosine kinases11 and interferes with cell signal-transduction pathways.12 The ingestion of high concentrations of phyto-oestrogens has adversely affected reproduction in several animal species,13, 14 and in premenopausal women daily ingestion of soy protein lengthens the menstrual cycle and suppresses the usual midcycle surge in pituitary gonadotropins,15 effects that epidemiological evidence suggests are beneficial in decreasing risk of breast cancer. The hypocholesterolaemic action of soy protein is well established and anticancer actions of soy isoflavones have been shown in in-vitro studies and in several classic animal models of chemically-induced breast cancer.7, 8

Although urinary analyses have indicated that isoflavones are absorbed by the infant fed soy-based infant formula, data on the composition of phyto-oestrogens in infant formulas are scant and the level of exposure of the infant fed soy-based formula to phyto-oestrogens is uncertain. We now describe a comprehensive analysis of the isoflavone composition of randomly selected samples of five different brands of commercially available soy-based infant formulas and a comparison of the plasma concentrations of isoflavones in 4-month-old infants fed soy infant-formula, cow-milk formula, and human breast-milk.

Section snippets

Phyto-oestrogen analysis of soy-based infant formulas

Five samples each of five of the major commercial brands of soy-based infant formulas were purchased from three stores in the Cincinnati area. The brands were: Nursoy powdered formula (Wyeth Laboratories, Philadelphia, Pennsylvania), Isomil powdered formula (Ross Products Division Abbott Laboratories, Columbus, Ohio), Isomil “Ready to Feed” liquid formula (Ross Products Division Abbott Laboratories, Columbus, Ohio), Alsoy liquid formula concentrate (Carnation Nutritional Products Division,

Isoflavone composition of soy-based infant formulas

A typical HPLC profile of the phenolic fraction of soy-based infant formula consists of a complex pattern of peaks with absorbance at 260 nm that were identified on the basis of retention index and mass spectrometry to be conjugated and unconjugated isoflavones.5 The predominant isoflavones identified in all of the soy-based formulas were the β-glycosides, genistin and daidzin, and the 6-“O”-malonyglycosides and 6-“O”-acetylglycosides of genistein and daidzein. Glycitin was also found in

Discussion

Since most brands of soy infant-formulas are prepared from soy isolates, the total isoflavone content should be similar among formulas, and related to the proportion of soy isolate incorporated. All five soy-based formulas analysed contained considerable amounts of isoflavones, and these were mostly glycosidic conjugates of daidzein and especially of genistein. Unconjugated isoflavones accounted for only 3–6% of the total. This composition is consistent with the reported findings for soy

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