HEALTH AND NUTRITION NEWSNo. 9
September 15, 2004 volume 4 number 6

Table of Contents
PREFATORY NOTE
Dietary Life as a Philosophy….…………………………………………………………….Junzoh Hayashi
CURRENT RESEARCH PROJECTSIn the Laboratory Now……………………………………………………………………Tomomi Yamazaki
THOUGHTS ON HEALTH AND NUTRITION RESEARCH
The Falling Birthrate ~ What Can Nutrition Do ~ ?................................Nobuyo Kasaoka-Tsuboyama
RESEARCH FINDINGS
Swimming Works Gene Everyday to Improve Physical Fitness…………………………….Izumi Tabata
Nutritional Status of Pregnant and Lactating Women in Japan………………………..Hidemi Takimoto
Tumor-Suppressive Effect of Connexin 32 in Renal Cell Carcinoma from Maintenance Hemodialysis
Patients…………………………………………………………………………………………Tomohiro Yano
Interactions between Health Foods and Medications ~ Does Overconsumption of Ginkgo Biloba
Extract Lose Effectiveness of Medicines? ~………………………………………………..Keizo Umegaki© National Institute of Health and Nutrition

Prefatory Note
Dietary Life as a Philosophy
Junzoh Hayashi
Principal, Shoeigakuen(Ex principal, Kanto Gakuin Women’s Junior College)variety of knowledge of food and nutrition. But
with extreme difficulty, we finally build it up as“Studies on Dietary Life”. When Dietitian’s Law
was conducted in 1985, “Studies on Dietary Life”
became mandatory in a training course of dietitians
and registered dietitians (currently it is notmandatory). In 1989, I retired, and I was freed
from duties of college administration. At this time,
I had an opportunity to discuss several times with
Dr. Tatsuyuki Sugawara, then professor of Kagawa
Nutrition University (present professor of Seitoku
Univ.) and Mr. Yoshio Tsukushi, president of
Kenpakusha and organized a workshop on“Studies on Dietary Life”. And we named a
meeting of promoters “Dietary Life General
Workshop” and about 20 people got together at theprivate hall in March, 1990. A few people left fromthe workshop in several times for supreme
academic learning. In October 27, 1990, the firstworkshop was conducted at Japan Publishing Club
Conference Room and about 100 people attended.
I gave a lecture of “Focusing on Dietary Habits”.
Also, the concept of Dietary Life General
Workshop was recognized on the day. Someparts are introduced as followed: “It is believed to
be useful in human health maintenance and theirhappiness by expanding the issue of food andnutrition from the viewpoint of dietary life andsystematize the knowledge.” The workshop wasnamed “The Japan Association for the Integrated
Study of Dietary Habits” since 1994, and has been
published 4 times a year. In 1998, it became
science council registered association, andincreased the membership of 700 people or more.
I am expecting the Japan Association for
the Integrated Study of Dietary Habits to contributeto public health and nutrition, and also subjected in
the National Institute of Health and Nutrition.

While diet is an everyday expression, it is
one of the most important things in health andnutrition. In about 1980, this popular term has
become one of the subjects in universities andjunior colleges as“Studies on Dietary Life”. After
the World War Ⅱ, many courses related to dietary
life has come in education of domestic science or
dietary nutrition as follows: “nutritional science”,
derived from biochemistry or physiology, “foodscience” and “food hygiene” from agriculture, “foodeconomics” from economics, and “cookery”.
When the purpose of the education and researchof these courses is fostering of dietitians or
education in domestic science, the area was likely
to be preoccupied with its segmentation. Isn’t italso necessary to look them from total point of view,
although an academic advancement is necessary?
If we succeed in systematizing dietary life
academically, it will become deeply involved inhealth and nutrition.
At such demands, “Studies on DietaryLife” was arisen. “Studies on Dietary Life” was,therefore, dietary life that theorized and practiced
human’s health and nutrition. It was as if Dr.
Tadasu Saeki who created the Institute of Nutritionemphasized on practice of nutrition improvement.
In 1981, “Studies on Dietary Life” was fit in acurriculum of domestic science course of women’scollege where I belonged to, and then I tookcharge of it. At the beginning, it was made of a2

Current Research Projects
In the Laboratory Now
Tomomi Yamazaki
Division of Clinical Nutrition

In the Division of Clinical Nutrition, weare researching on the relationship between
metabolicsyndromesuchasdiabetes,
hyperlipidemia, or obesity that leads to metabolic
syndrome, and nutrition and exercise, by
molecular biology.
Acutely, an exercise bout increases
glucose uptake in skeletal muscles bytranslocating
intracellular
GLUT4,
theinsulin-responsive glucose transporter, to plasma
membrane. Exercise stimulated translocation of
GLUT4 is considered to be mediated by activationof AMP kinase. Chronically, endurance exercise
training decreases the incidence rate of diabetes
mellitus. This might be due to increased GLUT4
and number of mitochondria in skeletal muscle,
respectively. Development of diabetes causedby high fat diet can be prevented byoverexpressing as twice of GLUT4 in muscle andadipose tissue so that new treatment for diabetes
can be expected by increase in GLUT4. We arenow
investigatingthemechanisms
ofexercise-mediated increase of GLUT4 andmitochondria. We found exercise responsive
elements that control the expression of GLUT4,
and are searching the transcription factors thatbind to the elements. We also created transgenic
mice over expressed PGC-1 α , co-factor that
promote mitochondria biosynthesis, in skeletal
muscle. As a result, mitochondrion increased in
the muscle of the transgenic mouse, and changed
to red muscle. We are now analyzing more.
Next, it is nutrition. High fat diet causes
visceral obesity, and it also accumulates fats inthe liver and muscle. High fat diet accumulatesfats in each tissue and insulin resistance andhyperlipemia. However, the mechanism is still
not clear. Now we created the transgenic mousethat over expressed UCPs, thermogenic proteins,in tissue specifically and analyzed. First, wefound improvement of obesity caused by high fat
diet or insulin resistance in the mouse that overexpressed UCP2 in fat tissue specifically. But,
there was no response in the mouse that overexpressed UCP3 in the muscle tissue specifically.
Then we found increasing of heat production of
the fat tissue was effective in prevention of
metabolic syndrome. Currently we create themice that over express UCP2 in the liver tissue
specifically.
On the other hand, high consumption offish has been advanced for low incidence ofarteriosclerosis among Japanese people. Then
we are identifying the suppressive mechanism of
fat synthesis by consuming fish oil. Fish oil
feeding activates PPAR α , the transcription
factor, promotes β -oxidation of fatty acid,decreases an amount of the transcription factor
that controls expression of SREBP-1c, sterol
regulatory element binding protein, decreases
lipogenesis and blood lipid concentration. In thelaboratory, we examined a mechanism ofdecrease in lipogenesis by consuming both highand low concentration of fish oil. As a result, it
became clear that high fish oil diet leads to3

Thoughts on Health and Nutrition Research
The Falling Birthrate ~What Can Nutrition Do? ~Nobuyo Kasaoka-Tsuboyama
Division of Clinical Nutrition

I had a bad dream the other night.
A child plays all alone at the large park,
talking to oneself with no expression.
I shuddered with horror at the thought ofJapan’s future that there are no brothers andsisters, even neighborhood kid.
Many people still remember of “1.29
shock“, Japan’s birth rate (total birth rate) was thelowest in the past.
In fact, a number ofJapanese children are getting smaller and smaller
each year. It is assumed that total population
will be decrease in 2 years of 2006. It isestimated that total population is going to be half
after 100 years.
I’m not going to discuss about
unprecedented problem of the falling birthrate
now in here because it is out of place to do so.
However, measures to the various problems thatworking women face fall far behind. Japan
introduces 3 years of child-care leave. However,
how many mothers can leave their job for 3
years? If they want to keep their job, mostmothers will leave their baby in the day-care
center, and come back to work. Actually, I am
one of them. I took one and half month ofchild-care leave, and came back to work in 3
months when my child’s neck was not stabilized
yet. While it is unusual that a researcher take achild-care leave, I stayed with my child as muchas I can since it was hard to leave after I actually
delivered the baby. But I always felt guilty.
Because it is believed of a legend, called“3-year-old myth,” in Japan that mothers stayclose and have to raise their children until age ofthree. Scientific and theoretical ground of thismyth is weak, but power of mental pressure toworking women is enough. And many of earlychildhood educators say that parents should raise
their children by their side for at least 1 year.
But recently, another research result
reported from different point of view. Many
people may remember that a study group of the
Health and Welfare Ministry reported that whether
children eat meals at home or not influences their
growth while length of stay in the nursery doesn’t.
According to the Prof. Yasuume and others’
survey of night nursery, “children who rarely havechance to eat meals with their family have 70
times more risk of underdeveloped interpersonal
skills and 44 times more risk of underdeveloped

understanding than children who does havemeals with their family. Of course, we shouldn’t
believe everything of this result. But even theconcept of hospitalism which was often quoted to“3-year-old myth” - “infants who spent long time inthe orphanage for children or infants, or pediatrichospitals, may develop psychosomatic disorder”
that Spitz advocated reported that nurse can
improve the disorder by caring with maternity. It
leads to the result that meals with full of maternity
is the most important factor to the way of raising
the quality of child-care.
I am researching the function of nutrient
on a genetic level and I must confess that I was
surprised with this result. Meals may haveimmeasurable power that can not be explainedwith just nutrient. For example, isn’t it possiblethat “atmosphere” or “with whom” of eating may
make a difference in taking the same nutrient?
Isn’t eating of “tasty” or “fan” influence on
regulation of nutrient on a genetic level? My
work willingness fills up.
In addition, well utilization of meals as acommunication tool, it may lead to realization offamily ties, lower anxiety of child care, and halt of
the declining birth rate. Since I at least tried tohave dinner with my child in a relaxed mood, guilt
toward child-care outside home reduced. This
lower guilt may lead to the next birth. And I can’t
help expecting a possibility of meals.
From now on, we may add an option of adeclining birth rate by approaching from nutrition.

4

Research Findings
Swimming Works Gene Everyday to Improve Physical Fitness
Izumi Tabata
Division of Health Promotion and Exercise

According to the recent survey,
swimming always ranks in the top of the exercisethat people want to do from now. This time, I’m
going to explain a little further about a trick ofgaining physical fitness by swimming and trainingthat everyone want to do.
Swimming
graduallybuildsup
endurance. This means that exercise increases
mitochondria in everyone’s meat (indicatesskeletal muscle.
It doesn’t mean fat.)
Mitochondrion is a subcellular organelle which
produces a lot of energy by utilizing oxygen taken
up from lung. It doesn’t produce lactic acid,substance of fatigue, and it is a fundamentalbuilding block for endurance.
Increase in mitochondria by exercise
was already reported 40 years ago. Although
how the mitochondria increase by exercise, inother words, its’ mechanism was not clear,recently it’s getting reveal.
Mitochondrion is a soul of protein. To
increase protein, it is necessary to work with thecorresponding gene.
Gene exists in DNA,mRNA is produced from DNA, and protein, which
is an amino acid chain, is synthesized from RNA.
Recently, we are focusing on PGC-1 α, genetranscription
coactivator.
Transcription
coactivator is needed when making mRNA from
DNA (It is called transcription because DNA
sequence (template) transfers precisely to mRNA
sequence). It is like a printer cable that connects
a printer which copies mRNA from DNA and gene,in other words, it is like a line that connects a
computer which everyone use and printer (basic
transcription factor). If this cable increases, it
receives the information fast (like a broadband),produces lots of mRNA, and increases productsof protein, mitochondria. We found on rats that
this printer cable like substance increases only on
muscle (epitrochlearis muscle) used by swimming(Figure).
Therefore, either building up endurance,or increase in mitochondria by exercise meansthat everyone’s gene are activated by swimming.
Although gene, DNA, and mRNA are not very
familiar words, actually those are the words thatare related to inside of everyone’s body,especially the muscle taken place in swimming.
Currently, it is reported that brain genecan be worked by exercise and training. Let’sswim, we want to do the most, everyone! Your
muscle and brain gene can be activated.

PGC-1α protein

PGC-1α protein

Effects of swimming on PGC-1αin rat skeletal muscle

at restafter exercise

6 hrs

18 hrsat restSwimming on Epitrochlearis Muscle

after exercise 6 hrs

18 hrsNon-Swimming on Soleus Muscle* Contents: 2 sets of 3 hr.-swimming exercise with 45-min. rest in between

5Research Findings
Nutritional Status of Pregnant and Lactating Women in Japan
Hidemi Takimoto
Center for Collaborative Research
Duration of the pregnancy and thelactation is the most important period of nutrition
intake for women. All nutrition that fetus needs
to develop is delivered from mother body via theplacenta.
And breast milk is the important
nutrient supply source for unweaned infant. But
nutritional status of women during pregnancy orlactation at national level is rarely reported in ourcountry. So we utilized data of the National
Nutrition Survey which represent Japanese, andexamined epidemiologically about nutrient andfood intake and hemoglobin (Hb) level during
pregnancy or lactation in our country.
Object is 330 pregnant and 388 lactating
women from data of the National Nutrition Survey
in 1995-99, and non-pregnant and non-lactating
women (controls) which match one-on-on to eachgroup on age, survey year, region, and with orwithout blood test. Average age of pregnant
group and lactating group were 29.2 and 32.1
respectively.
Proportion of smokers, drinkers, anddrivers in a pregnant and a lactating group was
significantly low, compared to each control group(p<0.01).
Compared with nutritional status
between pregnant women and non-pregnant
controls (Table1), no significant differences wereshown in energy intake. Lactating women weresignificantly low in energy intake compared tocontrols (p<0.01).
Each woman in bothpregnant and lactating were significantly high incarbohydrates, calcium, and vitamin B2 intake
compared to each control (p<0.05), milk and daily
Table 1. Nutritional Status

products intake were significantly high (p<0.05),
and alcohol intake were resulted low (p<0.01).
Average intake of iron from meals in pregnant
women was as low as 11.0mg/day.
22.9% of pregnant women were anemia(if less than 11g/dl of Hb level was anemia).
Proportion of anemia in lactating women andnon-pregnant/non-lactating women (if less than
12g/dl of Hb level was anemia) were 11.1% and15.7% respectively. Ratio of women, whose Hblevel were less than 10g/dl, were 5.7% in
pregnant, 2.0% in lactating, 1.7% in non-pregnant
controls, and 3.3% in non-lactating controls.
Comparing nutritional status between women
who were anemia and non-anemia in each group,no differences were shown in iron intake.
It was revealed that pregnant andlactating women in Japan concerned about theirlifestyle and meals by refraining from drinking andsmoking, and taking more daily products
compared to non-pregnant/non-lactating women.
Contrary to our existing expectations, pregnant
women didn’t consume much energy compared
to controls. In the National Nutritional Survey,
pregnant women are classified either less than 19
weeks or more than 19 weeks pregnant. It’s
interesting to get these results despite 223 out of
330 objects at this time were more than 19 weeks
pregnant, and about 2/3 passed morning
sickness. In addition, while rate of anemia in
pregnant are high, it was mostly mild anemia that
was associated with physiological increase inblood circulation during pregnancy.

Pregnant

Non-Pregnant

Lactating

Non-Lactating

N=330

N=330

N=388

N=388

Average±S.D.

Allowances† Average±S.D

Allowances†

Average±S.D

Allowances† Average±S.D

Allowances†

Energy (kcal)

1869±498

2153

1813±536

1919

2072±558**

2589

1893±511

1917

Protein (g)73.7±22.876.9

72.6±25.160.7

80.4±25.1**

80.3

73.8±23.4

60.8

Fat (g)60.4±22.7

58.9±27.565.7±25.9**61.2±23.9

Carbohydrate (g)254.7±73.5*

241.7±73.3

282.6±81.7**

253.8±71.7

Calcium (mg)597.7±296.8**

923.3

499.6±250.4

600

609.4±308.8**

1100

499.1±249.9600

Fe(mg)

11.0±4.6

18.4

10.6±4.51211.5±4.6**

2010.3±3.9

12

VitaminA(IU)

3442±6593*

1935

2431±2550

1800

3200±4443**

3200

2643±4297

1800

VitaminB1(mg)1.20±0.47

0.90

1.08±0.50

0.80

1.20±0.50**

1.10

1.07±0.42

0.80

VitaminB2(mg)1.42±0.6**1.2

1.26±0.6

1.1

1.5±0.6**

1.5

1.3±0.6

1.1**p<0.01,*p<0.05：Significant differences in a comparisonwithcontrols†： Average allowances ofobjects ineachgroup6

Research Findings
Tumor-Suppressive Effect of Connexin 32 in Renal Cell Carcinoma from
Maintenance Hemodialysis Patients
Tomohiro Yano
Laboratory of Nutrient Research for Labeling

Today in Japan, 200,000 patients are
newly forced to be undergone kidney dialysis byincrease in diabetic renal failure or others eachyear, and kidney transplantation which is the only
treatment of renal failure has not been going wellbecause of donor problems and so forth. As aresult, patients of renal failure are forced toundergo kidney dialysis for long term. As amatter of fact, hemodialysis patients whose
dialytic history is more than 10 years account for
more than 20% of a whole. Recently, several
complications associated with these hemodialysis
patients become an issue. A particular problemof those is associating with acquired cystic
disease of kidney as a result of hemodialysis, andassociating with renal cell carcinoma by mixing inmany cysts of all sizes. Recent survey reported
that incidence rate of renal cell carcinoma on
88,534 hemodialysis patients in Japan was 41
times more than normal healthy subjects. Thus,
it is thought to be important in both prevention
and treatment for renal cell carcinoma by
analyzing development processes of this renal
cancer from maintenance hemodialysis patients,
identifying tumor-suppressive gene that involves
in preventing outbreak, and finding out its’mechanism.
Renal cell carcinoma from hemodialysis
patients is most often associated with acquired
cystic disease of kidney which is thought of as
precancerous change in more than 3-4 years of
hemodialysis.
And longer a period of
hemodialysis, more of cancerous catabolic cyst
will be recognized. Thus, we suspected thatgene involved in suppression of this catabolic cyst
outbreak, works as tumor-suppressive effect inrenal cell carcinoma.
We analyzed renal
cancerous tissue of hemodialysis patients thatsurgically removed in detail by gaining
cooperation of Tokyo Women’s Medical University.
As a result, connexin (Cx) 32 were identified ascancer inhibition gene specifically suppressive inearly stages of cancer.
In addition, weestablished and examined cancer cell line thatdeveloped expression vector in which implanting
human Cx 32 into cancer cell line acquired fromhuman renal cell carcinoma to verify
tumor-suppressive effect of Cx 32 in renal cell
carcinoma. As a result, Cx 32 was verified astumor- suppressive gene in human renal cell
carcinoma by significantly controlling cell growth,
oncogenesis ability, and cellular infiltrate ability invitro, and oncogenesis ability, angiogenesis ability,and examined all parameter related tooncogenesis ability in vivo.
This gene is known in forming gap
junction (GJ), and less than 1200 molecularweight of hydrophilic molecule are exchanged
among cells through this GJ as an importantsignal, and maintain a relative constancy of
intracellular circumstances nearby. It is reported
that Cx induces cytodifferentiation through thisfunction, and works as tumor-suppressive gene.
Therefore, from now, identifying an inhibition
mechanism of Cx 32 manifestation in early stagesof renal cell carcinoma from hemodialysis patients
will reduce the risk of developing renal cell
carcinoma.

7Research FindingsInteractions between Health Foods and Medications~ Does Overconsumption of Ginkgo Biloba Extract Lose Effectiveness of
Medicines? ~Keizo Umegaki
Laboratory of Nutrient Research for Labeling

While consumption of so-called healthfoods is increasing worldwide, safety issues orcomplaints are reported increasingly. Many ofhealth foods consumers are on medication withworry about health, and influences on treatment
or unexpected side effect may be expressed bytaking both medicines and health foods. Since
most of medicines are decomposed bydrug-metabolizing enzyme mainly in liver,changes of drug-metabolizing enzyme directly
influence on medical effect.
Thus, we are
examining effects of health foods materials on
drug-metabolizing enzyme to predict interactions
between health foods and medications. In thepast
animaltesting,
weverifiedthat
overconsumption of ginkgo biloba extract induced
hepatic drug metabolizing enzymes, andincreased its activity. As just described, taking
medicines under circumstances where increasing
activity of drug-metabolizing enzyme hastens
metabolism (decomposition) of medicines, andloses effectiveness of medicines. So, long-term
overconsumption of ginkgo biloba extract may bepossibly discourage medical treatment.
Then, how should one do if one intake
ginkgo biloba extract for long term? We tested

in an animal study whether enzyme activity
recovers in a normal level after excessive
ingestion of ginkgo biloba extract and increase in
drug-metabolizing enzyme. When rats were fed
excessive amount of ginkgo biloba extract,
hepatic drug metabolizing enzymes increased
four times of normal amount. Next, we stopped
giving them ginkgo biloba extract, fed themnormal food, and measured metabolizing active
enzyme.
Then, enzyme activity was
immediately restored to a normal level, in otherwords, recovered as same as before ingestion of
ginkgo biloba extract. This result indicated thatstop taking ginkgo biloba extract when medical
treatment was necessary would be able to avoid
interactions between them.
While induction of drug-metabolizing
enzyme for human has never been reported when
taking recommended amount of ginkgo biloba
extract, it may have a possibility of interactions
with medicines if one intake it more than needed.
If you take health food, you need to avoid taking
more than you needed. While you are on
medication, you may need to consult your doctor,
not by solving all by yourself, and care about your
medical condition.

8