HEALTH AND NUTRITION NEWSNo. 11March 15, 2005

Table of Contents

Prefatory Note
Achievements of National Institute of Health and Nutrition, and future expectations..…Yu Hosokawa
CURRENT RESEARCH PROJECTS
Laboratory of Physical Activity and Health Evaluation…………………………….……Motohiko Miyachi
THOUGHTS ON HEALTH AND NUTRITION RESEARCH
Needs of the new QOL evaluation methods for the disease prevention............................ Osamu Ezaki
LATEST RESEARCH
PCAF and PCAF-B are required for normal estrogen response in the uterus….....………..Erina Inoue
Functions of the new structured lipids containing n-3 fatty acids (EPA or DHA) and medium –chain fatty
acids………………………………………………………….………………………….…...Junichi Nagata
Decreased trends of the trace elements involved in antioxidation with ageing.................Masao Kondo
Resistance training “reduces” central arterial compliance in healthy men..................Motohiko Miyachi© National Institute of Health and Nutrition

Prefatory Note
Achievements of the National Institute of Health andNutrition, and future expectations
Prof. Yu Hosokawa
Faculty of Human Life Sciences, Jissen Women’s University

About Four years has passed since National

graduated from these universities at the national

Institute of Health and Nutrition (NIHN) was

examination for the registered dietitians will betransformed into an independent administrative

demolished after March 2006, and then a newagency in 2001, and now, this is the last year offramework of the examination guideline will be

the midterm plans. In 2006, therefore, the results

introduced. In prior to the revision of Nutritionists

and achievement levels of the midterm goals will

Law, the expected roles and works of registered

be evaluated. Last autumns, as one of the major

dietitians toward 21st century were discussed.

achievements, “Dietary Reference Intakes (DRIs)

In order to prevent the development andfor Japanese, 2005” was officially announced. For

progress of lifestyle related diseases, which isexamples, the estimation of DRIs for energy is

now the major social issues, the most important

based on the research findings at NIHN on

thing is to improve our diets. Therefore, thereference value of Japanese energy expenditure.

registeredThat is, the energy expenditure of general/healthyknowledge/skills to assess the physical andJapanese was actually measured by the doubly

nutritional status or dietary pattern of individuals

labeled water (DLW), and then, Physical Activity

comprehensively, as well as to undertake theLevel (PAL) replaced the existing intensity of daily

appropriate nutrition guidance program, areactivity. In addition, new DG (tentative dietaryrequired.

dietitians

with

the

professional

goal for preventing lifestyle related diseases) was

For which, the educational curriculum at theset up for some nutrients to reduce the risk of

universities for the registered dietitians’ has also

life-style related diseases. In this way, the new

been considerably reviewed. Furthermore, these

DRIs would meet the social needs. Now, theuniversities

nutrition

registeredcurriculums for the nutrition teacher as well. A

dietitians) are supposed to utilize DRIs as thenutritional teacher is responsible for the childrenreference values for nutritional assessment andto gain the appropriate diets, since irregular andplans. Since the roles of NIHN comprise theunbalanced diets among children (e.g. skipping

dissemination of research findings to the public, I

breakfast) become serious issue these days. It is

expect that, in addition to the further development

therefore essential to provide the dietary andof research, the information is more easily

nutrition education, not only for the children

understandable considering the social needs notthemselves, but also for their families. Now, in

only for experts but also for general population.

order that the registered dietitians will acquire

experts(e.g.

dietitians,

also

prepareto

introducethe

In 2006, the universities for the registered

more professional knowledge, the needs ofdietitians will be evaluated on the educational

establishing the graduate school have also been

efforts and achievements. As the Nutritionists Law

discussed. I personally expect that the National

revised in 2001 was executed from April, 2002,

Institute of Health and Nutrition will play a core

the present partial exemption for the students

role in education program at the graduate schools.
22Current Research Projects
Laboratory of Physical Activity and Health Evaluation
Motohiko Miyachi
Division of Health Promotion and Exercise
research on the exercise with high intensity,
so-called “resistance training” such as weightlifting and so on.
2. “Is the possible side-effect of the exercise is
explored?”
While many studies have explored thelong-lasting impact of exercises on risk factor oflifestyle related diseases, little has been reported
on the unfavorable effects (namely, side-effect)of exercise. Thus, we are investigating thepossible unfavorable effect of exercise.
3. “Is it based not only on the knowledge inEurope, but also on that for Japanese?”
Only a few researches, well-designed andlarge-scaled, have been undertaken forJapanese, There is an obvious difference in the
disease patterns between Japanese andEuropeans, and their genetic background andlifestyle are also very different. Not only working
on the laboratory-based research, we are now
conducting the field research in Okayama
Prefecture entitled “Randomized interventions
for several hundreds of local residents”.
4. “Does it focus on increasing QOL, in additiono the medical effect?”
Generally, the values of exercise have been
examined based on the evidence by medical
model. However, in terms of health among theelderly, it is necessary to evaluate the effect of
exercise, as well as the QOL properly. We are
now organizing the classes for exercise andswimming for the elderly, by which the effects ofexercise can be assessed from various aspects.
Our research works in this laboratory aremostly targeted on humans. I would like toprovide the better quality of research on exercise
for health with the cooperation of the study
subjects and collaborative researchers.

Laboratory of Physical Activity and Health
Evaluation, Division of Health Promotion andExercise, mainly works on the research on healthpromotion and exercise for the human beings. It
has been well acknowledged that the exercise
and physical activity are useful for developing thephysical strength and preventing lifestyle relateddiseases. In addition, with the accelerated aging
in Japan, the positive impacts of exercise andphysical activity are now expected for the elderly
people in need of nursing care as well. Yet, arethere enough scientific evidences on theeffectiveness of exercise and physical activity fordevelopment of physical strength and preventionof lifestyle related diseases as well as of being in
the nursing care? If not, what aspect ofknowledge is insufficient?
Now, the questions can be summarized into
four categories as below;
1. What types and how much of exercise iseffective for the prevention of eachdisease?
2. Is the possible side-effect of the exercise
is explored?
3. Is it based not only on the knowledge inEurope, but also on that for Japanese?
4. Does it focus on improving QOL, in
addition to the medical effect?
We, therefore, have been working on the
researches based on these questions.
1. “What types and how much of exercise iseffective for the prevention of each disease?”
So far, studies have focused on several types of
exercises with low intensity for the whole body,so-called aerobic exercise such as walking,jogging, and swimming. Now, we attempt the

Active life with high QOL
If you spend active midlife
with the regular exercise,
you can maintain yourphysical strength.

Everybody enjoys
good health during
the youth

If you are always
short of exercise,
you will suffer fromthe lifestyle relateddiseases.
Dependent life3

Figure.
For healthy life in your old age….

Thoughts on Health and Nutrition Research
Needs of a new QOL evaluation methods for the disease prevention
Osamu Ezaki
Division of Clinical Nutrition
following data are available.

Recently, QOL (quality of life) is often used as aproxy for the “degree of happiness”. It is expressed
mostly by comparison such as “lower than…” or“better than…”, and is rarely shown as quantity like“my QOL is…%” or “your QOL is…%”. So, it isdifficult to use QOL in the research. In addition,
there are two more features/problems; one is that itis the indicator of psychological well-beings for theindividuals, and the other is that it is the indicator atone (present) point, not that for the future.
Since it is the indicator of psychologicalwell-beings for the individual person, it can not be
estimated unless the questionnaire survey isundertaken. Even though one looks rich and healthy,s/he may have some problems, hence low QOL.
Besides, one’s past experience also greatly
influences his/her present QOL. Assuming that if thepresent living condition is physically same… if one
experienced hard time in the past, s/he may feel
happy with the present condition, whereas if one
experienced better time in the past, s/he may feel
unhappy now. It is therefore quite difficult to assessthe degree of QOL of other persons. However, one’s
QOL can be generally estimated low, when s/he issick or having hard work.
Dietary or exercise therapy for the disease
prevention is incompatible with one’s present QOL.
In some cases, these therapies could worsen one’s
present QOL. For example, one may be forced to
eat what s/he doesn’t like, or restricted from whats/he want to eat. One may be unhappy with forcing
oneself to do exercise. On the other hand, smoking
improves the present QOL of smokers. Nobody
knows what will happen in the future, so it is no
surprise that one prefers to enjoy oneself at thepresent point. Yet, it must be noted that the primaryprevention of diseases is expected to improve one’s
future QOL. Even if you find it hard now, you can
expect the improvement of future QOL, by modifying
the diet, doing exercise, and stopping smoking.
In order to solve the above inconsistency, it isnecessary to develop a new indicator thatcomprises the present and future QOL till one dies,that is, QOL integral value. For example, for dietary
therapy, the new indicator can be introduced, if the

1.
2.
3.

4.

QOL is shown properly and quantitatively, inthe questionnaire survey,.
QOL value without dietary therapy (A), andwhen one follows the dietary therapy (A’)
Future morbidity of diabetic mellitus or
cerebral infarction without dietary therapy(R), and when one follows the dietary
therapy (R’).
QOL value when one suffered from thediabetic mellitus or cerebral infarction.

QOL integral value without dietary therapy= A ＋RB＋(1−R)A＋・・・.
QOL integral value when one follows the dietary
therapy = A’＋R’B＋(1−R’)A’＋・・・.
By investigating which of the above two QOL
integral values is higher, we can evaluate if thepresent dietary therapy is necessary for him/her.
Value B could vary by the type of diseases. In orderto improve the QOL integral value, more effort isrequires for the disease with lower B to reduce R’.
In terms of public health, however, it isnecessary to improve QOL of the populations,rather than QOL of each individual. Here, smoking
is a typical example. If one’s QOL is quite highwhen s/he smokes, QOL integral value may bealso high, even if the future QOL is estimated lower
due to the increasing morbidity of lung cancer andcardiac infarction etc. So, we can say that smoking
is good for this person. On the other hand, it can be
anticipated that nonsmoker’s QOL could become
lower due to the secondhand smoke and increaseof medical expenses, leading to the lower average
QOL of the population.
As was mentioned earlier, QOL is influenced bymany factors not only diets and health, but also
economic status, educational level, personal
relationships, public security and so on. If all thosefactors can be included in the calculation of QOL
integral value, and if the average QOL integral valueof the population can be obtained, it should be very
useful for the future policy making.

4

Latest Research
PCAF and PCAF-B are required for normal Estrogen response in the uterus
Erina Inoue (Division of Applied Food Research)
Estrogen is the main female hormone, which targets genital grand, bone and brain tissues. The
physiological responses are mediated by the transcriptional regulations of target genes with thenuclear receptors for estrogens. In addition, it is also known that not only estrogen receptor but also
several transcription co-factors are involved, which form complexes for the transcriptional
regulations. Transcription co-factors mediate the basic transcription factors necessary for all thetranscriptions and DNA-binding transcription factors by protein-protein interaction. Of which,transcription co-factors called PCAF and PCAF-B are also known to function as the transcriptional
coactivators of the receptors for various steroid hormones including Estrogens. In this way, thecooperative effects between the nuclear receptors and the protein complexes are known in vitro, though
few studies have been done in vivo. Under this circumstance, this study aimed to explore theendogenous physiological responses in vivo, using the mice with targeted gene disruption of one of thetranscription co-factors for the estrogen receptor, PCAF and PCAF-B. And then, this study confirmedthat PCAF and PCAF-B are required for the normal estrogen responses in the uterus. Recently, it isrecognized as a serious problem that many endocrine disruptors (endocrine disrupting chemicals) likedioxin affect the reproduction and growth of the animals/human beings etc. Even very small amount of
endocrine disruptors could disturb the normal hormone responses, with most serious influence on the
estrogens. Most of the endocrine disruptors are, perhaps unknowingly, taken orally via foods andutensils. We are concerned that the endocrine disruptors can be easily accumulated in the body, andthat the long-termed exposure could cause the serious problems to our health.
* This study was undertaken as a part of Core Research for Evolutional Science and Technology” on theendocrine disrupting chemicals.

Transcriptional Coactivator p300/CBP-Associated Factor and p300/CBP-AssociatedFactor Type B Are Required for Normal Estrogen Response of the Mouse Uterus
Bioscience, Biotechnology, and Biochemistry, Vol. 68 (2004) , No. 10 pp.2209-2211
Erina INOUE1)2), Miho HANAI1)3), Kazuhiko YAMADA1), Takatoshi ESASHI1)3) and Jun YAMAUCHI1)2)
1) Division of Applied Food Research, National Institute of Health and Nutrition
2) Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation
3) Department of Human Life and Culture, Faculty of Humanities, Seitoku University

Abstract:

Mice with targeted gene disruption of one of the estrogen receptor coactivators,
p300/CBP-associated factor (PCAF), and its counterpart, PCAF-B, were used to investigate thepossible involvement of PCAF and PCAF-B in estrogen receptor-mediated actions in vivo. Among
ovariectomized mice that were treated with estrogen, PCAF and PCAF/PCAF-B knockouts showedabnormal growth of the uterus compared with the wild type. The level of c-fos gene expression in
the uterus was not induced by estrogen in the knockouts. These observations suggest that PCAF
and PCAF-B are required for estrogen-dependent normal growth of the uterus via estrogen
receptor-mediated transcriptional regulations.
5Latest Research
Functions of the new structured lipids containing n-3 fatty acids (EPA or DHA) andmedium-chain fatty acids.
Junichi Nagata (Division of Food Science)
Generally, the edible fat/oil exists in the form of triacylglycerol, which consists of three fatty acids
attaching to a glycerol. The fatty acids of triacylglycerol attached to the sn-1,3 positions of the glycerol
are hydrolyzed by digestive enzyme “lipase”, and a 2-monoacylglycerol and two fatty acids are formed.
“Structured lipids (SLs)” can be formed by attaching functional fatty acids to the detached positions(sn-1.3 position) and the sn-2 position of glycerol. SLs are the physiologically advantaged lipid, which
can be absorbed into body effectively. So far, most of the studies focused on the effects of fatty acids
that compose the fat/oil. In Japan, edible fat/oil that maximized the effects of fatty acid, by attaching
optional fatty acids to the glycerol, and processed edible fat/oil designed to improve the absorption by
the change of attaching positions and number of fatty acids are now widely available at the market.
Fat/oil containing lots of diacylglycerol and medium-chain fatty acids fall into these SLs. In this study, we
synthesized new SLs using the enzyme by which the reaction with high specificity positions can be
expected, by combining n-3 fatty acids (EPA or DHA) and medium-chain fatty acids (caprylic acid).
The effect of n-3 fatty acids is known to reduce the obesity as a risk factor of lifestyle related diseases
and serum lipid profiles, and that of medium-chain fatty acids is to reduce the body fat accumulation.
Next, the serum- and liver- lipid profiles were compared between the rats fed SLs and those fed theordinal edible oil, and the differences of the fatty acids and structures were investigated. The findings ofthis study showed that all the synthesized SLs have the effects to improve the serum lipid profiles.
However, it was also explored that the reduced risk factor of the lifestyle related diseases observed inthis study were mainly due to the effects of fatty acids, and the differential effects by the triglyceride
structures were not confirmed. We, therefore, would like to attempt the further study to develop the SLs
which is effective for the prevention of the lifestyle related diseases.

Effects of structured lipids containing eicosapentaenoic or docosahexaenoic acidand caprylic acid on serum and liver lipid profiles in rats.
Biofactors. 2004;22(1-4):157-60.
Nagata J, Kasai M, Negishi S, Saito M.
Division of Food Science, National Institute of Health and Nutrition, Japan

Abstract:
The physiological activity and effect on lipid metabolism of four types of structured lipids (SLs), that
contain caprylic acid (C8) and either eicosapentaenoic (EPA) or docosahesaenoic acid (DHA),
were evaluated in male Wistar rats fed experimental diets containing 7% (wt %) of each SL and 3%(wt %) soybean oil for 28 days. Control rats were fed a diet containing 10% (wt %) soybean oil. The
relative perirenal adipose tissue weights of rats fed D-8-8 and 8-D-8 diets were significantly lower
than those of other groups. We observed significantly lower serum cholesterol concentrations inrats fed SLs than those of control group over experimental period. The serum lipids concentrations
in rats fed diets containing SLs were significantly lower P < 0.05) than those of soybean oil group.
The fatty acid compositions of WAT did not reflect the structural differences in the triglyceride.
These results suggest that the physiological effects of the SLs used in this study were due to thefatty acids rather than the structural specificity. Therefore, further study will be needed to ascertain
the most desirable structural configuration.
6

Latest Research
Decreased trends of the trace elements involved in antioxidation with ageing
Masao Kondo (Division of Applied Nutrition)
Environmental factors associated with the rapid ageing include the stress, ultraviolet, radiation, nutrition,smoking, alcohol. It has been noted that active enzyme like superoxide produced and accumulated inbody through metabolism under these environments for a long time could cause the lipid peroxidation ofcell membrane, degeneration of cytoplasm and membrane protein, as well as interference of enzyme,
subcellular organelle and cell. In order to prevent these peroxide chain of cellular component,
superoxide dismutase and NADPH・GSH system function as an antioxidant, for which the traceelements involved in antioxidation (e.g. Se, Cu, Zn and Ms) are required. This study therefore aimed toinvestigate the changes of the trace elements in the blood that are involved in the antioxodation
mechanism according to age and living environments. One of the interesting findings was the different
trends before and after 50 years old (Figure). The possible reasons include the various stress andchange in the diets. Besides, more obvious variation in the concentration of elements may be related to
the facts that the resistance and immune strength against stress by oxidation is stronger for women thanmen. Another interesting finding was the associations with the subjective symptoms; those who reported
dizzy, palsy, tangled tongue, chest pain, headache, palpitation and insomnia had significantly less Cu,
Se, Zn and Mn in the whole blood. Although the increase of mineral intake is recommended to make up
for the decrease in the blood, the excessive consumption also brings other functional disorders. It is thus
crucial to ensure the intake of appropriate amounts, considering the balance with other nutrients as well.
Male

Female

20’

30’

40’

50’

60’

30’

70’ (Age)

40’

50’

60’

70’ (Age)

Figure Changes of trace elements in the whole blood with ageing

Changes due to ageing in the concentrations of trace elements in the whole bloodthat assist with the process of antioxidation
Biomedical Research on Trace Elements, Vol. 15 (2004) , No. 4 342-344
Masao Kondo1), Naomi Aiba1), Emi Higashi1), Jun Oka2) and Masatoshi Kajimoto3
1) Department of Applied Nutrition, National Institute of Health and Nutrition, 2) Tokyo Kasei University
3) Sagami Women's University

Abstract:
Seven elements, Co, Cr, Cu, Mn, Ni, Se, and Zn, in the whole blood of a total of 94 healthy
individuals (36 males and 58 females), ranging from 30 to 79 years of age, were measured by the
coupled plasma-mass spectrometer (ICP-MS) method. Gender differences were found only in Cu (p<0.05). By age bracket, low values were measured for Cu in the 70s, Co in the 60-70s, Cr, Ni and
Se in the 60s, Zn in the 40s, and Mn in the 30s and 60s. These results reveal that there is a trend
for many elements that are involved in antioxidation, except for Zn, to decrease with ageing.
7

Latest Research
Resistance training "reduces" central arterial compliance in healthy men
Motohiko Miyachi (Division of Health Promotion and Exercise)
Regular exercise is one of the essential parts for the prevention and treatment of the cardiovasculardisease. It is known that the regular aerobic exercises like walking could prevent the Increase of
stiffness of the central artery by ageing, which is an independent risk factor for the cardiovasculardisease, and also improve the arterial stiffness among middle- and old-aged people with no habits ofregular exercise. Now, it can be questioned if another type of exercise “resistance training” could havethe beneficial effect on the arterial stiffness. This study was therefore undertaken under the hypotheses
that the resistance training for 4 months
could increase the arterial stiffness. In
Intervention
order to investigate the validity of theControl
P <0.05 vs. before
hypotheses, the detraining period was set
intervention
P< 0.05, 4th monthup after the interventions, assuming thatthe increased stiffness would returns tothe baseline levels. The findings of thisstudy suggest that it must be cautious toapply the resistance training, especially tothose at risk of cardiovascular disease.

Unfavorable effects of resistance training on central arterial compliance: arandomized intervention study.
Circulation. 2004 Nov 2;110(18):2858-63.
Miyachi M, Kawano H, Sugawara J, Takahashi K, Hayashi K, Yamazaki K, Tabata I, Tanaka H.
Division of Health Promotion and Exercise, National Institute of Health and Nutrition, Japan.

BACKGROUND: Reductions in the compliance of central arteries exert a number of adverse
effects on cardiovascular function and disease risk. Endurance training is efficacious in increasingarterial compliance in healthy adults. We determined the effects of resistance training on carotid
arterial compliance using the intervention study design.
METHODS AND RESULTS: Twenty-eight healthy men 20 to 38 years old were randomly assigned
to the intervention group (n=14) and the control group (n=14). Control subjects were instructed not
to alter their normal activity levels throughout the study period. Intervention subjects underwent 3
supervised resistance training sessions per week for 4 months and detraining for a subsequent 4
months. The resistance training increased maximal strength in all muscle groups tested (P<0.001).
There were no significant differences in baseline arterial compliance and beta-stiffness index
between the intervention and control groups. In the intervention group, carotid arterial compliancedecreased 19% (P<0.05), and beta-stiffness index increased 21% (P<0.01) after resistancetraining. These values returned completely to the baseline levels during the detraining period.
Arterial compliance did not change in the control group. In both groups, there were no significant
changes in brachial and carotid blood pressure, carotid intima-media thickness, lumen diameter,and femoral arterial compliance. Changes in carotid artery compliance were significantly andnegatively related to corresponding changes in left ventricular mass index (r=-0.56, P<0.001) andleft ventricular hypertrophy index (r=-0.68, P<0.001).
CONCLUSIONS: In marked contrast to the beneficial effect of regular aerobic exercise, several
months of resistance training "reduces" central arterial compliance in healthy men.
8