Exposure of infants to phyto-oestrogens from soy-based infant
formula
Setchell
KD, Zimmer-Nechemias L, Cai J, Heubi JE. Lancet 1997 Jul 5
350:9070 23-7.
Abstract
BACKGROUND:
The isoflavones genistein, daidzein, and their 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 micrograms/mL), the typical daily volume of milk
consumed, and average bodyweight, a 4-month-old infant fed soy formula
would be exposed to 28-47 per day, or about 4.5-8.0 mg/kg bodyweight
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 (3.2 [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 13000-22000
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.
Isoflavone
content of infant formulas and the metabolic fate of these
phytoestrogens in early life.
Setchell
KD, Zimmer-Nechemias L, Cai J, Heubi JE. Am J Clin Nutr 1998
Dec 68:6 Suppl 1453S-1461S.
Abstract
Soy-based
infant formulas have been in use for >30 y. These formulas are
manufactured from soy protein isolates and contain significant amounts
of phytoestrogens of the isoflavone class.
As
determined by HPLC, the isoflavone compositions of commercially
available formulas are similar qualitatively and quantitatively and are
consistent with the isoflavone composition of soy protein isolates.
Genistein, found predominantly in the form of glycosidic conjugates,
accounts for >65% of the isoflavones in soy-based formulas.
Total
isoflavone concentrations of soy-based formulas prepared for infant
feeding range from 32 to 47 mg/L, whereas isoflavone concentrations in
human breast milk are only 5.6 +/- 4.4 microg/L (mean +/- SD, n = 9).
Infants fed soy-based formulas are therefore exposed to 22-45 mg
isoflavones/d (6-11 mg x kg body wt(-1) x d(-1)), whereas the intake of
these phytoestrogens from human milk is negligible (<0.01 mg/d).
The
metabolic fate of isoflavones from soy-based infant formula is
described. Plasma isoflavone concentrations reported previously for
4-mo-old infants fed soy-based formula were 654-1775 microg/L (mean:
979.7 microg/L: Lancet 1997:350;23-7), significantly higher than plasma
concentrations of infants fed either cow-milk formula (mean +/- SD: 9.4
+/- 1.2 microg/L) or human breast milk (4.7 +/- 1.3 microg/L).
The high
steady state plasma concentration of isoflavones in infants fed
soy-based formula is explained by reduced intestinal biotransformation,
as evidenced by low or undetectable concentrations of equol and other
metabolites, and is maintained by constant daily exposure from frequent
feeding.
Isoflavones
circulate at concentrations that are 13,000-22,000-fold higher than
plasma estradiol concentrations in early life. Exposure to these
phytoestrogens early in life may have long-term health benefits for
hormone-dependent diseases.
Author
Address
Clinical
Mass Spectrometry Center, Children's Hospital Medical Center,
Cincinnati, OH 45229, USA.
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