Hormonal effects of cows’ milk on human health
Sato A and Ganmaa D
Slide 1
Japan had no dairy culture until theend of World War II. Japanese had
essentially been vegetarians forseveral hundred years. Cereals,
soybeans, vegetables and occasionalseafood consumption met
nutritional needs. Ordinary
Japanese neither drank milk nor ate
dairy products. In contrast toWestern people who have been
drinking milk for several hundredyears, Asians only began drinking
milk 60 years ago. Cows' milk at
one time may have been beneficial
for Western people, but I will show evidence for its ill effects on humans, particularly on
Japanese health. Even for Westerners, today's milk may be harmful because dairy farming
practices have changed significantly since the 1920s or 1930s. Beginning about 80 years ago,
pregnant cows and especially those in the latter half of pregnancy have come to produce agreater proportion of the milk that is consumed. Pregnancy increases the production of female
sex hormones, and these hormones are in the same or much higher range in the milk frompregnant cows than in the blood of pregnant animals. Consumption of dairy products isexcessive in developed countries, a trend that probably started in the 1940s and 1950s.* Ourhypothesis is that the consumption of cow milk and milk products causes various ill effects onhuman health. We sincerely hope that you test this hypothesis.
*Sharpe RM, Skakkebaek NE. Are oestrogens involved in falling sperm counts and disordersof the male reproductive tract? Lancet 341: 1392-95, 1993.

Slide 2
There are two main reasons why wethink today's cows' milk is not
appropriate for humans: First, cows'
milk contains estrogens andprogesterone in large quantities.
Second, cows' milk contains toomuch calcium, amounting to 125
milligrams per 100 milliliters,
which is about 4 times more thanthat of breast milk.

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Slide 3
First, I will describe modern andtraditional milk production
practices, using Mongolia as amodel for traditional milk. Next I
will focus on the hormone
concentrations in these two typesof milk. Then I will trace the link
between the increased hormones inmodern milk and their ill effects onhuman health.

Slide 4
I visited Mongolian Nomads in 1999.
Cattle there behave as wild animals.
They move around freely, grazing at
will. Nomads control their cows bykeeping their calves in an enclosure.
After grazing, mother cows return tothe enclosure to nurse their calves.
The nomad binds the mother cows to
the fence of the enclosure.

Slide 5The nomad lets a calf out to suckle
its mother’s milk. While the calf isnursing, the nomad binds the cow's
hind legs.

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Slide 6
Then, the nomad separates the calffrom the mother and binds the calf
to the fence and begins to milk thecow for human use. Afterward thenomad allows the calf to suckle milk
again until it is satiated. I was toldthat the cow pictured here was 14
years old and had given birth to 10
calves.

Slide 7The volume of milk that wascollected from this cow was 2 or 3
liters at most. The volume of thiscontainer is about 20 liters.

Slide 8
Mongolian cows feed only on grass
and they do not secrete milk during
the latter half of pregnancy. They
get pregnant by natural mating inJuly or August, and give birth tocalves in April or May. The
Mongolian nomads milk their cows
for only 5 or 6 months from May to
October, obtaining, at best, 5 litersof milk per day per cow.

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Slide 9
I do not know whether modern
dairy farming practices in Japan are
the same as in other developed
countries. In Japan, the cow isimpregnated by artificial
insemination 12 to 14 months after
birth. The length of pregnancy is
280 days, the same as in humans.
After giving birth, the cow secrets
colostrum. Soon after birth the calf
is separated from its mother and thecolostrum is milked by machine
and given to the calf with a feeding
bottle for five days.
From the sixth day after delivery, the cow is milked every day for 300 days. Two or threemonths after delivery, the cow is inseminated artificially and gets pregnant while it isproficient in milk secretion. Milking is stopped for 60 days just before the next delivery,
which is referred to as the "dry period or days dry." The cow is slaughtered after giving birth
to 4 or 6 calves.

Slide 10
Cows are milked for 7 or 8 months
while they are pregnant, including
the latter half of pregnancy up to
the dry period. Modern geneticallyimproved dairy cows are usually
fed a combination of grass andconcentrates (grain/protein mixes
and various by-products). They aremilked during the latter half ofpregnancy, even at 220 days ofgestation. One final comment on
Japanese dairy practices, the use ofrecombinant bovine growth
hormone is legal in Japan as it is in
the US. However, it is said that dairy farmers in Japan do not use this hormone. I do not know
why nor whether this is true.

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Slide 11
The most abundant hormone inmilk is estrone sulfate. According
to a 1979 study by Heap andHamon, milk from non-pregnant
cows contains 30 picograms per
milliliter estrone sulfate. The
concentration rises with pregnancy
progression. It is 150 picograms in
the first or second month of
pregnancy, and in the last stage ofpregnancy it rises to as high as
1,000 picograms per milliliter.

Slide 12
Estrone sulfate has a high oral,
estrogenic activity. Once in the
body it is converted to estrone or
estradiol. That estrone sulfate has ahigh oral activity can be understoodby the fact that Premarin, which ismarketed for hormone replacement
therapy contains naturally occurring
conjugated estrogens derived frompregnant mares.

Slide 13
We measured by high performanceliquid chromatography the estrone
levels in Japanese commercial milk
and traditional Mongolian milk.
Holstein milk was sterilized at 130
degrees Centigrade for 2 seconds
and Jersey milk at 125 degrees
Centigrade for 2 seconds. The
samples brought back from
Mongolia were of raw milk.
Considerable amounts of estrone
sulfate were found in both Holsteinand Jersey milk. The concentrationin the commercial milk wassignificantly higher than that in Mongolian raw milk. This finding clearly shows that estrone
sulfate is not destroyed by sterilization at 125 or 130 degrees Centigrade.

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Slide 14
Milk contains another female sex
hormone, progesterone. The
concentration is known to range
from 10,000 picograms per
milliliter in whole milk to 300,000
picograms per gram in butter.* Thatis, the concentration ofprogesterone in milk is higher by afactor of 10-3 than that of estrone
sulfate. We measured theconcentration in the commercial
milk in Japan and the raw
Mongolian milk. The commercial
whole milk had a much higher
concentration of progesterone than Mongolian milk. It is said that when a dairy cow ispregnant, the progesterone concentration in whole milk exceeds 8 nanograms or 8,000
picograms per milliliter. I can therefore positively state that the commercial milk in Japan isderived predominantly from pregnant cows and that the Mongolian milk is derived
predominantly from non-pregnant cows. Please note that the progesterone level in milk fat ismuch higher than that in whole milk. Therefore butter and cream contain abundant female sex
hormones. Also, the ratio of the concentration of estrogens to progesterone in the milk frompregnant cows resembles the ratio of estrogens to progesterone in oral contraceptive pills.
However, the absolute amounts of these hormones are much lower in milk.
*Hartmann S, Lacorn M, Steinhart H. Natural occurrence of steroid hormones in food. Food
Chemistry 62: 7-20, 1998.

Slide 15
The question is whether the sex
hormones in milk have biologicalsignificance in humans. In
answering this question, we
performed two series ofuterotrophic tests, one with young
ovariectomized rats and the otherwith sexually immature rats.

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Slide 16
The estrogen levels in the milk usedin this study are listed on this slide.
The total estrogen content was 700
picograms per milliliter, of which
estrone conjugates, at 380
picograms per milliliter, comprised
more than half. In each experiment,
36 rats were divided equally among
three groups. Each group of 12 rats
was kept on powder chow for 7days, and given one of threedifferent liquids: commercial lowfat milk, artificial milk, or artificial
milk containing estrone sulfate at 100 nanograms per milliliter. The artificial milk contained
the same amount of protein, fat, and carbohydrates as the low-fat milk.
Slide 17
At autopsy, the uterine weights
were measured. This table shows
the body weight, uterine weight,
and the ratio of uterine weight tobody weight in theseovariectomized rats. The uterine
weight of rats treated with low-fat
milk was significantly greater thanthat of rats treated with artificial
milk. The ratio of the uterine
weight to the body weight was alsosignificantly higher in thecommercial milk-treated rats than
the artificial milk-treated rats.
Both the absolute and relative values of the uterine weights were higher in the estrone sulfate
group than those in the milk groups. But the difference between the two groups was notstatistically significant.
Slide 18
This table shows the results insexually immature rats. Estrone
sulfate at a concentration of 100
nanograms per milliliter had a moremarked uterotrophic activity thanthe low-fat milk. The uterine weightin the commercial milk group was
significantly higher than that of theartificial milk group. It can be said
that the uteri of immature rats aremuch more sensitive to estrone
sulfate than the uteri of sexually7mature rats. From this study, we conclude that commercially available milk in Japan has
uterotrophic activity in both young ovariectomized rats and sexually immature rats.
Slide 19
I would like to draw your attention
now to the recent decline infertility in Japan.
Japan has experienced dramatic
lifestyle changes since World War
II. In 1954 a law was enacted
making it compulsory for children
to drink 200 milliliters of milk at
every school lunch. School
children are not allowed to go out
until they finish their milk. Since
the enactment of The School
Lunch Law, consumption of milk
and dairy products increased 20fold over the past 50 years.
Slide 20
As a natural consequence of the
School Lunch Law, theconsumption of milk and dairy
products by prepubertal boys andgirls is quite high in Japan. The
average dairy consumption in thisage group reaches 320 grams perday (approximately 11 ounces or
325 milliliters).

Slide 21
A boy who drinks 300 milliliters ofmilk a day is calculated to take 100
nanograms estrone sulfate into his
body everyday. Some children
actually drink 1 liter of milk a day
because their parents encouragethem to quench their thirst withmilk instead of water. One liter ofmilk contains 370 nanograms of
estrone sulfate alone. According toAndersson and Skakkebaek ofDenmark,* the daily production of
estradiol in prepubertal boys is in8the range of 40 to 100 nanograms. The question that naturally arises is whether the several
hundred nanograms of estrone sulfate in commercial milk has any adverse effects on thesexual maturity of prepubertal boys. No clear answer to this question is available at present.
*Andersson AM, Skakkebaek NE. Exposure to exogenous estrogens in food: possible impact
on human development and health. European Journal of Endocrinology 140: 477-85, 1999.

Slide 22
The population size of Japan isshrinking. The total fertility rate,that is, the average number ofchildren born to each woman in her
lifetime was 2.16 in 1970. It started
declining in 1974, and has
continued to decline, recording thelowest level, 1.25 in 2005.
According to economists andsociologists, this decline is
attributable to non-marriage andlate marriage, which now prevails
among the younger generation in
Japan. In principle I agree with thisview.

Slide 23
However, in Japan one in sevencouples are infertile and about
460,000 couples now receive
infertility treatment. In 1973, 2.8
million pregnancies occurred. But
30 years later in 2004, the numberof pregnancies declined by one half
to 1.4 million. Use of oral
contraceptives was not approved by
The Japan Ministry of Health andWelfare until 1999. As in the
United States, access to oral
contraceptives in Japan is restricted
to prescription by a gynecologist or
obstetrician. I am therefore inclined to consider that the decline in fertility in Japan is partly
caused by a decrease in male reproductive ability.
Semen quality has so far been said to be the lowest in Denmark. However, according to a
recent study performed in Japan, semen quality of Japanese men in Kawasaki and Yokohama
was worse than Danish men in Copenhagen.

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Slide 24
It is of importance to note that in
the past 50 years, the incidence oftestis cancer has increased while
semen quality has decreased
worldwide. Dr. Skakkebaek ofDenmark has proposed thetesticular dysgenesis syndrome
hypothesis that suggests that theincidences of hypospadia,
cryptorchidism, impaired
spermatogenesis, and testis cancer
are related to perinatal exposures toenvironmental endocrine disruptors.

Slide 25
To further investigate the recent
increase in testicular cancer, we
examined the relationship between
food consumption and testis cancer
incidence in 42 countries.* In
almost all countries, the highest
incidence of testis cancer was foundbetween ages 20 to 39 years. Hence,
the incidence in 1990 was
correlated with food consumption
between 1961 and 1970. Amongfood items, cheese was most closely
correlated with testis cancer
incidence, followed by milk andanimal fats.
*Ganmaa D, Li XM, Wang J, Qin LQ, Wang PY, Sato A. Incidence and mortality of
testicular and prostatic cancers in relation to world dietary practices. International Journal ofCancer 98: 262-267, 2002..

Slide 26
Stepwise-multiple regression
analysis identified the combinationof cheese and milk as the factor
contributing most to the incidenceof testis cancer. We hypothesizethat sex hormones or some otheringredients in cheese or someparticular processes in cheese
production may have adverse
effects on testicular development.

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Slide 27
The association of testis cancer
incidence with cheese consumption
shows a distinct difference between
the two Scandinavian countries,
Denmark and Finland. Both testis
cancer incidence and cheese
consumption are high in Denmark,but both are low in Finland. We
were eager to know why the
opposite occurs in these two dairy
consuming countries.

Slide 28This figure shows the yearly
consumption of cheese in Denmarkand Finland from 1961 to 1990. In
the 1960s and 1970s, theconsumption of cheese was muchhigher in Denmark than in Finland.
However, the consumption in
Finland increased rapidly in the
1980s and is reaching almost thesame level as that in Denmark inmore recent years. We suspect that
testis cancer incidence in Finland isincreasing now as well, and willcatch up to the incidence inDenmark in 20 or 30 years.

Slide 29
I will now address the topic ofhormone-dependent cancers,
prostate cancer in men and breast
cancer in women.

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Slide 30
Prostate cancer incidence is much
lower in Japan than in Westerncountries. Nevertheless, prostatecancer mortality increased almost
linearly, about 25-fold over the last
50 years.

Slide 31
Our ecological study found thatboth incidence and mortality of
prostate cancer are most closely
correlated with the consumption of
milk.

Slide 32
Multiple-regression analysis
identified the consumption of milk
and cheese as the factor mostcontributing to both the incidence
and mortality of prostate cancer.

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Slide 33
Although Japan now has the most
rapidly increasing rate of prostatecancer incidence in the world, theincidence in Japan is less than onetenth that in the United States. Whatcauses this big difference?

Slide 34
I am sure that this difference can be
explained by the difference in milk
consumption between the twocountries. This graph compares
daily milk and dairy productconsumption, excluding butter.
Americans consume more than
1,000 grams of milk and dairy
products a day, while Japanese
consume about 300 grams a day.
The consumption in the UnitedStates is about 4 times higher thanthat in Japan.

Slide 35
With respect to breast cancer, ourecological study revealed that the
food that is most highly associatedwith the incidence and mortality of
the cancer is milk and dairy
products.

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Slide 36
Multiple-regression analysis
revealed that the most significant
contributor to breast cancer
incidence is meat, while the mostsignificant contributor to breast
cancer mortality is milk and cheese
consumption.

Slide 37
Breast cancer incidence in the US ismuch higher than that in Japan.

Slide 38
I am sure that, as in the case of
prostate cancer, this big difference
can be explained by the differencein milk consumption between Japanand the U.S. Epidemiologicalfindings have not always evidenced
this association between incidenceof breast cancer and consumption ofmilk and dairy products. However,in nutritional epidemiology precise
evaluations of individual
consumption of dairy products isvery difficult because dairy
products are used in a variety ofWestern foods, including bread, ice cream, chocolate, cake, and some cookies. In Westerncountries dairy consumption is a life long dietary habit of most people. It may be difficult to14

find a group of women who completely avoid dairy consumption, except for vegans. The
problem would easily be solved if epidemiologists compare the breast cancer incidence
between strict vegans and lacto-ovo vegetarians.

Slide 39
We assessed the effects ofcommercial low-fat milk on thedevelopment of DMBA-induced
mammary tumors in rats. The
details have been described in theInternational Journal of Cancer.

Slide 40
DMBA or 7,12dimethylbenzanthracene is achemical carcinogen. When given
to rats, it causes mammary tumors.
The development of mammary
tumors is hormone-dependent andhas frequently been used as a modelfor human breast cancer.

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Slide 41
I will outline the experimental
design. Rats of six weeks of age
were given a single oral dose of
DMBA. The animals were thendivided into four groups and kept
on different dietary regimens. Lowfat milk was the experimentalgroup; artificial milk served as thecontrol group; estrone sulfate as the
positive control group; and water as
the negative control group. Rats
were palpated weekly to monitor
tumor development. 20 weeks after
DMBA administration, rats were
autopsied.

Slide 42
As you can see from this slide, there
was no significant difference inbody weight between thecommercial milk group and theartificial milk group.

Slide 43
This slide shows the cumulative
incidence of mammary tumors.
Please note the difference between
the commercial milk and theartificial milk groups. The incidence
was significantly higher in thecommercial milk group than in theartificial milk group.

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Slide 44
This slide shows the cumulative
number of mammary tumors. The
number of tumors was also greaterin the commercial milk group thanin the artificial milk group. Estrone
sulfate, too, significantly promoted
the development of tumors.

Slide 45
Finally, the size of the tumors thatdeveloped in the commercial milkgroup was greater than those in theartificial milk group.

Slide 46
This table shows the serum levels of
estrone and IGF-1 at the end of theexperiment. Commercial low-fat
milk increased the level of IGF-1 inaddition to the estrone level.
Although estrone sulfate given
orally increased the serum level of
estrone, this hormone alone did notaffect the level of IGF-1.

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Slide 47
We conclude that commerciallyavailable low-fat milk promotes thedevelopment of DMBA-induced
mammary tumors in rats. The
degree of the promotion is almost
comparable to that of 100
nanograms per milliliter of estrone
sulfate. The high estrogen content
in milk may be responsible for thepromotional effects, acting inconcert with other hormones suchas IGF-1.

Slide 48
Before I conclude my talk, I will
briefly update you on the problem
of Bovine Spongiform
Encephalopathy, or BSE in Japan.

Slide 49
By September 28th of this year
(2006), 29 cattle had been
diagnosed with BSE. Of them, 28
were Holstein dairy cows. It is
certain that the BSE outbreak inJapan is related to today’s dairy
farming practices, but the details
remain unknown.

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Slide 50
We have a proposal for dairy
farmers all over the world.
Consumers have demonstrated their
willingness to pay higher prices fororganic milk. We feel that milk from
non-pregnant cows would also bemarketable at premium prices.

Slide 51
In conclusion, you may feelskeptical that milk is harmful tohuman health. You may say thatyou have been drinking milk andeating dairy products for several
hundred years without any apparent
harm. I would like you tounderstand that today's milk isvastly different from the milk yourancestors consumed 80 years ago.

Acknowledgement
We thank Ms. Kris Demko for revising our manuscript.

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