A. Yes, most do, just in significantly smaller quantities. For example,
miso is a good source, but who eats a 1/2 cup of miso, since it is used as an
ingredient? Soy hot dogs, soy burgers, soy cheeses, soy yogurts and soy
isolate powder do contain isoflavones, but competition with other ingredients
and processing all affect amounts of isoflavones. The best way to know is to
call the consumer line on the package of food and ask them if they have
analyzed for isoflavones. Soy oil doesn't contain isoflavones.
A. Isoflavones are fairly stable, so under normal home or institutional
cooking methods they are not destroyed.
A. Optimal isoflavone intake to prevent or treat specific diseases is not
known. At this time, overall health benefits of isoflavones as well as other
phytochemicals are best met by eating a varied diet from all food groups,
built upon a foundation of one serving of soyfood with plenty of whole grains,
fruits, vegetables and other legumes each day.
(Anne Patterson is president of Nutrition Advantage, a food and nutrition
consulting company specializing in food and nutrition communications,
marketing, recipe development and project management. She is a soy nutrition
specialist, a nationally known speaker, a media spokesperson, and one of the
presenters at Soy Connection seminars held throughout the country. Her e-mail
address is: agprd@aol.com)
Absorption and Metabolism of Isoflavones
By Kenneth D. R. Setchell, Ph.D.
Isoflavones represent one of the classes of the so-called "phytoestrogens."
These bioactive non-nutrients are strikingly similar in chemical structure to
estradiol, the main female hormone (1). Indeed, one can superimpose almost
exactly the structures of estradiol and isoflavones so they become
indistinguishable, and therefore they fit beautifully into the pocket
representing the binding domain of the estrogen receptor. It is therefore not
surprising that isoflavones share many of the properties of endogenous
estrogens. Isoflavones have the ability to behave as estrogen mimics, but also
have other important non-hormonal properties that have attracted the attention
of many investigators.
The chemical form in which isoflavones occur is an important consideration
since it can dramatically influence the biological activity, the
bioavailability, and therefore the physiological effects of these dietary
constituents. We showed almost two decades ago that intestinal microflora play
a key role in the metabolism and bioavailability of phytoestrogens (2).
After ingestion, soybean isoflavones are hydrolyzed by intestinal
glucosidases, which releases the aglycones, daidzein, genistein and glycitein.
These may be absorbed or further metabolized to many specific metabolites,
including equol and p-ethylphenol (3,4). The extent of this metabolism appears
to be highly variable among individuals and is influenced by other components
of the diet. A high carbohydrate milieu, which causes increased intestinal
fermentation, results in more extensive biotransformation of phytoestrogens,
with greatly increased formation of equol, a mammalian isoflavone metabolite.
This metabolic pathway may be clinically relevant to the efficacy of
soybean isoflavones, because the estrogenic potency of equol is an order of
magnitude higher than that of its plant precursor, daidzein. The importance of
the microflora in the metabolic handling of isoflavones is well illustrated
from observations that antibiotic administration blocks metabolism, germfree
animals do not excrete the metabolites, and infants fed soy infant formulas in
the first four months of life cannot form appreciable amounts of equol (5,6).
Like endogenous estrogens (7), isoflavones undergo an enterohepatic
circulation; they are secreted in bile. This has been shown in rats (6,8,9),
and our pharmacokinetic studies in humans (unpublished) indicate that
absorption takes place along the entire length of the intestine, presumably by
nonionic passive diffusion. There is no evidence, to my knowledge, that the
glycoside conjugates, can be absorbed, and this would be consistent with
observations for flavonoids. Conjugation of isoflavones to glucuronic acid, a
reaction catalyzed by one of the UDP-glucuronyltransferase isozymes, occurs on
first-pass. Whether this takes place exclusively in the liver, or in the
intestine is uncertain. Studies in rats suggest glucuronidation takes place
during transport across the intestinal wall (6,9). Isoflavone glucuronide
concentrations in portal venous blood of rats are high, and older studies of
sheep showed that intestinal epithelia had a higher capacity for
glucuronidation of equol than hepatocytes. Like estradiol, isoflavones are
found in plasma mostly in the form of glucuronide conjugates, and to a lesser
extent as sulfates (10); there also occur double conjugates.
Estrogens are strongly bound to the serum proteins, albimin and sex hormone
binding globulin, so that <5 percent is circulating unbound, or free. The
extent of protein binding is a major factor in governing the availability of
estrogen for occupancy of nuclear receptor sites. Interestingly,
phytoestrogens are less avidly bound to serum proteins; equol for example
shows 10-fold less affinity for serum proteins that estradiol, and therefore a
greater proportion will be available to occupy the estrogen receptor, which
hypothetically may bolster the effectiveness of isoflavones.
We have determined the plasma half-life of daidzein and genistein, measured
from their plasma appearance and disappearance curves to be 7.9 hours in
adults; peak concentrations occur 6-8 hours after ingestion. Consequently,
adherence to a soy-containing diet will ultimately lead to high steady-state
plasma concentrations. Plasma concentrations of 50-800 ng/mL are achieved for
daidzein, genistein and equol in adults consuming modest quantities of
soy-foods containing in the region of 50 mg/day of total isoflavones. These
values are similar to those of Japanese consuming their traditional diet (11).
In infants fed soy formulas plasma concentrations are even higher (5).
Overall, when soy is consumed on a regular basis, levels far exceed normal
plasma estradiol concentrations which in men and women generally range between
40-80 pg/mL. It was this early observation that led us to the hypothesis that
with such disproportional levels one could anticipate hormonal effects from
phytoestrogens (2).
Elimination of isoflavones from the body occurs via the kidneys. In urine,
isoflavones are found mainly as glucuronide conjugates (3). Studies in animals
and humans have indicated that the urinary output of isoflavones accounts for
no more than 50 percent of the ingested dose, and since fecal excretion is
minimal, there is currently an unaccounted balance. It is probable that this
is explained by intestinal biotransformation to metabolites which are not
presently being measured by investigators, and therefore it leads to questions
regarding the reliability of using urinary isoflavone excretion as an
indicator of dietary intake. p-Ethyl phenol, a metabolite formed by a cleavage
of the isoflavone molecule, is not being quantified by most investigators.
There is also a significant proportion of the population that lack the
capacity to biotransform isoflavones (3), and a very high variability in
quantitative excretion among individuals. Clinical efficacy of isoflavones is
almost certainly related to the plasma circulating concentration and it is
this endpoint that is likely to be the most reliable one to measure in
clinical studies.
In summary, considerable knowledge of the metabolism and absorption of
phytoestrogens was gained during the course of their discovery, however there
are still gaps in our knowledge. The optimal dose of isoflavone required to
have clinical effects remains to be established. In general we believe that 50
mg per day of aglycones is sufficient to have a clinical/biological effect.
This would be consistent with intakes in countries consuming soy as a staple,
and is the level at which demonstrable endocrine effects occur in
premenopausal women (12). Dose response relationships remain to be established
and factors governing their absorption and metabolism, which will govern
efficacy will no doubt be understood in the near future.
References
(1) Setchell KDR, Adlercreutz H. Mammalian lignans and phyto-oestrogens.
Recent Studies on their formation, metabolism and biological role in health
and disease. In: Rowland IA, ed. The Role of Gut Microflora in Toxicity and
Cancer. New York: Academic Press 1988:315-345.
(2) Setchell KDR, Borriello SP, Hulme P, Axelson M. Non-steroidal estrogens
of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr
1984;40:569-578.
(3) Axelson M, Sjovall J, Gustafsson B, Setchell KDR. Soya- A dietary
source of the non-steroidal oestrogen equol in humans and animals. J Endocrin
1984;102:49-56.
(4) Joannou GE, Kelly GE, Reeder AY, Waring MA, Nelson C. A urinary profile
study of dietary phytoestrogens. The identification and mode of metabolism of
new isoflavonoids. J Steroid Biochem Molec Biol 1995;54:167-184.
(5) Setchell KDR. Nechemias-Zimmer LZ, Cai J, Heubi JE. Exposure of infants
to phytoestrogens from soy infant formulas. The Lancet 1997; 350:23-27.
(6) Axelson M, Setchell KDR. The excretion of lignans in rats - Evidence
for an intestinal bacterial source for this new group of compounds. FEBS Lett
1981;123:337-342.
(7) Adlercreutz H, Martin F. Biliary excretion and intestinal metabolism of
progesterone and estrogens in man. J Steroid Biochem 1980;13:231-244.
(8) King RA, Broadbent JL, Head RJ. Absorption and excretion of the soy
isoflavone genistein in rats. J Nutr 1996;126:176-182.
(9) Sfakianos J, Coward L, Kirk M, Barnes S. Intestinal uptake and biliary
secretion of the isoflavone genistein in the rat. J. Nutr 1997;127:1260-1268.
(10) Adlercreutz H, Fotsis T, Lampe J, Wahala K, Makela T, Brunow G, Hase
T. Quantitative determination of lignans and isoflavones in plasma of
omnivorous and vegetarian women by isotope-dilution gas chromatography-mass
spectrometry. Scand J Clin Lab Invest 1993;53:5-18.
(11) Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-
oestrogens in Japanese men. Lancet 1993;342:1209-1210.
(12) Cassidy A, Bingham S, Setchell KDR. Biological effects of soy protein
rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin
Nutr 1994;60:333-340.
About the author
Kenneth D.R. Setchell, Ph.D. is a professor in the Department of
Pediatrics, College of Medicine, University of Cincinnati. He obtained his
doctorate in steroid biochemistry from the University of London. Formerly, he
was a fellow at the Royal Society for post-doctoral studies at the Karolinska
Institute in Stockholm, Sweden.
