Health Effects of Cows’ Milk
http://www.eps1.comlink.ne.jp/~mayus/eng/index.html

Cows’ Milk is Responsible for Human Reproductive
Disorders
Adopted from:

Ganmaa D, Wang PY, Qin LQ, Hoshi K, Sato A.
Is milk responsible for male reproductive disorders?
Medical Hypotheses 2001;57:510-4.
Summary
The role of environmental compounds with estrogenic activity in the development of male
reproductive disorders has been a source of great concern. Among the routes of human
exposure to estrogens, we are particularly concerned about cows ﾕ milk, which contains
considerable amounts of estrogens. The major sources of animal-derived estrogens in thehuman diet are milk and dairy products, which account for 60-70% of the estrogens consumed.
Humans consume milk obtained from cows in the latter half of pregnancy, when the estrogenlevels in cows are markedly elevated. The milk that we now consume may be quite unlike that
consumed 100 years ago. Modern genetically-improved dairy cows, such as the Holstein areusually fed a combination of grass and concentrates (grain/protein mixes and various
by-products), allowing them to lactate during the latter half of pregnancy, even at 220 days ofgestation. We are certain that milk is responsible, at least in part, for some humanreproductive disorders.

Introduction
In the past 50 years, the incidence of testicular cancer has increased while semen quality has
decreased (1-8). Since this decline in male reproductive health is both recent and appears tohave occurred in many countries, Shape and Skakkebaek (9) presumed that the disorders
reflect adverse effects on men of environmental and lifestyle factors. They listed several
routes of human exposure to estrogens that have changed in the past half-century.
Of these, we are particularly concerned about cows’ milk, which contains
considerable amounts of estrogens (10-16). Estrogens are also contained in animal meat andeggs, but the major sources of animal-derived estrogens in the human diet are milk and dairy
products, according to Hartmann et al. (14), which account for 60-70% of the estrogens. The
high estrogen content is because humans consume milk obtained from cows in the latter halfof pregnancy, when estrogen levels are markedly elevated (11,12,15). We hypothesize that1

milk is responsible, at least in part, for the decreased sperm count and increased incidence ofmale reproductive abnormalities.

Traditional and Modern Milk
Man is the only mammal that consumes milk after weanling. When we name cows’ milk as
one of the important routes of human exposure to estrogens, the general response of Western
people is that "man has been drinking cows’ milk for around 2,000 years without apparent
harm" (17). However, the milk that we consume today may be quite unlike that consumed 100
years ago.
Hurt (18) described how poor the milk production was in the mid-eighteenth
century, stating that "cows that produced a gallon per day were considered good milkers, but aquart per day was most common." Nowadays, however, production levels as high as 24 kg per
day are typical in modern dairy farming (19).
In 1908, Fritz Haber combined nitrogen (N) from the air with hydrogen tosynthesize ammonia (NH4-N), and in 1914, Karl Bosch completed the first large ammonia
manufacturing plant (20). As new technology lowered the price of N fertilizer, farmers began
applying it to raise yields, enabling dairy farmers to use surplus crops as feed grains for cows.
Furthermore, during the1960s and 1970s, when the Green Revolution spread throughout theworld (21), the possibility of year-round milk production was realized worldwide.
Our survey in Mongolia found that cows fed only on pasture do not lactate during
the latter half of pregnancy. Mongolian cows become pregnant as a result of natural mating inJuly or August, and give birth tocalves in April or May. The
Mongolian nomads milk their cows
for 5 months from June to October,obtaining, at best, 5 L milk per day
from a cow (Figure). Pregnant
cows are milked only in the firsttrimester of pregnancy. One of these
nomads told us "Cows produce milk
for the calves of the next generation,
not for humans. If we steal too
much milk from pregnant cows,
they cannot give us good calves."
However, modern genetically-improved dairy cows, such as the Holstein, which are
artificially inseminated three months after calving, are usually kept on a combination of grassand concentrates (grain/protein mixes and various by-products). They continue to lactate foralmost the whole of pregnancy, extending the milk-producing period to 305 days per year (19)2(Figure).

Estrogens in Milk and Dairy Products
There is about 30 pg/mL estrone sulfate in the whey fraction of milk from non-pregnant cows
(15). During pregnancy, however, this level becomes elevated to 151pg/mL from day 41 today 60, and to maximum levels of about 1,000 pg/mL from 220 to 240 days of gestation.
According to Gyawu and Pope (12), peak levels of circulating estrogens in cows of latepregnancy are several hundred fold higher than those in non-pregnant cows during ovulation,
which suggests that milk from cows in late pregnancy contains much larger amounts ofestrogens than does milk from non-pregnant cows.
The oral bioactivity of estradiol and estrone may be relatively low. According toAndersson and Skakkebaek (22), however, estrone sulfate has a high oral activity, and once
inside the body it can be converted to estrone and estradiol.
In addition to estrogens, milk contains a large amount of another female hormone,progesterone, at concentrations ranging from 1,400 pg/mL in skim milk to 10,000 pg/mL inwhole milk and 300,000 pg/g in butter (14).
Batra et al. (10) measured the levels of estradiol-17β in plasma and whole milk of
Murrah buffaloes by radioimmuno assay, and found a very close correlation between levels inplasma and milk; the estradioI concentration in milk was approximately twice that in plasma.
Thus, hormone concentrations in whole milk can exceed those in plasma, probably because ofsynthesis in the mammary gland (11). This phenomenon has been used to diagnose pregnancy
in cattle by analyzing the progesterone, estrone, or estradiol-17β content of milk (15,23).
It might be argued that the increased volume of milk per cow per day in modern
dairy farming would dilute the estrogens transferred from the circulation of a cow to the milk.
However, modern milk contains almost the same amounts of protein, fat, calcium, etc., as
traditional milk; it is unlikely that the mammary gland of a high-producing dairy cow secretes
nutrients selectively, leaving estrogens alone in the circulation.
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Estrogens and Male Reproductive Organs
Endogenous estradiol-17β secreted by the ovaries in the female, exerts negative feedback
effects on the secretion of gonadotropins FSH and LH, affecting the hypothalamo-pituitarysystem (9,24-26). FSH regulates the multiplication of Sertoli cells, which, in turn, areresponsible for orchestrating and regulating spermatogenesis. Estrogens can not only impair
the development of the male reproductive tract via physiological pathways, but also alter themultiplication of Sertoli cells. In humans, significant qualitative and quantitative changes in
the Sertoli cell population take place even after birth, especially during the prepubertal period(27).
Animal studies have shown that alteration of the Serto1i cell number in early life
determines testicular size and sperm output in adulthood (28). In rats, the oral dose ofexogenous estradioI sufficient to induce sterility was reported to be high (29). However, in themale rat, intraperitoneal doses as low as 10 ng estradiol/rat were reported to induce
morphological lesions and spermatogenic arrest without affecting gonadotropin release, after
21 dai1y exposures (30). This suggests that estradiol has a direct effect on developing
spermatids.
The dose of 10 ng used for rats (30) can be extrapolated to humans by using bodysurface area, on the assumption that the two species have the same sensitivity to exogenous
estrogens. Assuming that body surface area is proportional to body weight (kg) to the powerof 0.7 (31), i.e., (body weight)*0.7, then 10 ng of estradiol in a rat (0.1 kg) corresponds to 410
or 540 ng of estradiol in a child weighing 20 or 30 kg, respectively.
This extrapolation certainly cannot be applied directly to the estrogens in milk,
since the bioavailability of estrogens taken orally may differ from that of intraperitoneallyadministered estrogens (14). However, since no data are available on the species difference insusceptibility to exogenous estrogens, and since susceptibility is expected to differ greatly
among children, it is not unreasonable to suggest that several hundred nanograms of estrogens
from foods might be enough to affect spermatogenesis in particularly susceptible boys.

Adverse Effects of Milk on Male Reproductive Organs
The adverse effects of milk on male reproductive organs are only sparsely discussed in theliterature. One reason may be that precise evaluation of individual milk intake is difficult,because milk and its products (cheese, cream, butter, fermented milk, powdered milk, etc.) areused in a variety of foods, including cakes, candies, ice cream, and chocolates.
Davies et al. (32) tested the hypothesis that milk and dairy products are risk factors
for testicular cancer in a case-control study undertaken in East Anglia, UK. All the cases weremen with testicular cancer, and for each of the 200 cases, there were four controls: two cancer
controls and two population controls. All the responding subjects completed a dietary4questionnaire that included questions on their current and adolescent consumption of milk,
dairy products, fruits, and vegetables. Cases had consumed significantly more milk inadolescence than controls.
In a case-control study conducted in Northern Italy on 96 histologically confirmed
cases and 292 controls with acute, non-neoplastic or genital tract disease, milk was identified
as a risk factor for prostate cancer (33). There was a significant increase in risk withfrequency of milk consumption: compared with nondrinkers or occasional milk drinkers, therelative risk was 5.0 (95% confidence interval 1.5-16.6) for two or more glasses per day.

Estrogens in Milk and Prepubertal Children
Exposure to exogenous sex steroids is a greater risk for prepubertal children, since theirendogenous levels are extremely low (22). Hartmann et al. (14) estimated the average daily
intake of animal-derived estrogens (estradiol-17β and estrone) for prepubertal boys to be 80
ng, with milk and dairy products accounting for 60-70% of this. Nonetheless, Hartmann et al.
concluded that no hormonal effects could be expected from naturally occurring sex steroids infood, because this value is far exceeded by steroid production in prepubertal boys.
However, the value 6,500 ng/day given by JECFA-WHO (34) for the daily
production rate (PR) of estradiol in prepubertal boys is a significant overestimate, according
to Andersson and Skakkebaek (22), JECFA-WHO used the metabolic clearance rate for adultwomen and serum estradiol levels higher than realistic, when calculating the PR in
prepubertal boys. Therefore, prepubertal boys ﾕ average intake of 80 ng/day of food-derived
estrogens (14) may not be negligible.

Milk Consumption in Japan
Sharpe and Skakkebaek (9) stated that consumption of dairy products is too excessive indeveloped countries, a trend that probably started in the1940s and 1950s.
This holds true in Japan, where a no-meat/no-milk culture essentially prevailed until
the end of World War Two. In the past 50 years, Western dishes using more animal products
as ingredients have become popular in Japan (35) (Figure).
Each Japanese child is given 200 mL of milk daily at lunch in school. For thisreason, the average daily milk consumption of this age group reaches 322 g (36), a
remarkable quantity in Japan, where the population's average milk consumption is as low as
135 g/day (Figure). Pregnant women in Japan are also encouraged to consume milk and dairy
products, to meet their calcium requirements during pregnancy.
Commercial milk in Japan contained estrone 21.8-26.0 pg/mL, estradiol-17β25.1-33.6 pg/mL, and estriol 31.4-98.6 pg/mL (authors’ unpublished data). By drinking 300
mL of milk per day, a child’s intake of estradiol-17β alone, the most potent estrogenic

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hormone, is approximately 10 ng per day. This is 4,000 times the intake of environmental
hormones of xenoestrogens, in terms of hormone activity (37).
Between 1950 and 1997,
milk consumption per person per
day increased almost 20-fold, fromless than 7 g to 135 g (Figure). Thissudden increase in consumption of
estrogenic milk might have affected
the reproductive organs of Japanesemales. For example, the incidence
rate of prostate cancer in Japan isincreasing at the fastest rate in theworld (38), and the associatedage-adjusted death rate has risen
almost 13-fold during the last 45
years, from 0.45/100,000 in 1950 to
5.93/100,000 in 1995 (Figure).
Reproductive health should
be monitored carefully in Japan,
where milk consumption started toincrease only 40 years ago, andwhere prepubertal children are themajor consumers. Epidemiologicalstudies into reproductive outcomesin Japan will certainly shed light on
the relationship between milk andmale reproductive health.

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Conclusion
The increased incidence of male reproductive disorders over the last 50 years has attracted
much attention. Although great concern has been raised over the role of environmental
compounds with estrogenic activity in the development of hormone-related diseases, exposure
to exogenous sex steroids from food has not been widely discussed. Humans consume milk
from cows in the latter half of pregnancy, when estrogen levels are markedly elevated.
Estradiol-17β is about 10,000-fold more biopotent than most identified environmental
xenoestrogens (22). For prepubertal boys in the critical period of sexual development excess
consumption of milk and dairy products might interfere with the physiological developmentof the reproductive system and result in decreased semen quality in adulthood.
Epidemiological or experimental studies should be undertaken to test our hypothesisthat milk is responsible, at least in part, for male reproductive disorders.

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