HEALTH AND NUTRITION NEWSNo. 18December 15, 2006

Table of Contents

PREFATORY NOTE
Future perspectives of nutritional sciences as an academic field………………………..…Yukiko Miura

CURRENT RESEARCH PROJECTS
Project for Shokuiku…………………………..…..…………..……………………….….……....Naomi Aiba

THOUGHTS ON HEALTH AND NUTRITION RESEARCH
Dietary survey should reflect the regional characteristics ……….………………….......... Akemi Morita

RESEARCH FINDINGS
Resistance training and arterial compliance: keeping the benefits while minimizing the stiffening……………………………………..……............ Motohiko Miyachi
Moisture and mineral content of human feces -- high fecal moisture is associated with increase sodium
and decreased potassium content -- …………………………………..………….…...Mamoru Nishimuta
Dietary folate intakes and folate biomarker profiles of pregnant Japanese women……...…….…..Natsuko Mito, Keizo Umegaki, Nobuo Yoshiike
Docosahexaenoic acid-induced lipid peroxidation and urinary excretion of mercapturic acid…………………………….………………………..…..…Morio Saito© National Institute of Health and Nutrition

Prefatory Note
Future perspectives of nutritional sciences as an academic field
Yukiko Miura
Senior researcher,
National Institute of Science and Technology Policy
Ministry of Education, Culture, Sports, Science and Technology
The National Institute of Health and Nutrition(NIHN) has the website of “Information system onsafety and effectiveness for health foods(http://hfnet.nih.go.jp: in Japanese only)”, and the hit
count is currently about five millions. I expect that
the NIHN will continue to enhance the functions of
this website, and also that more people will utilize it.
In Japan, many people tend to be allergic to theterm of “science and technology”, assuming that it
must be incomprehensible. Besides, there are thescientists who do not take it important to facilitate
the general public to understand science andtechnology. Yet, I would request the people whowork on the health science to face fully with these
problems. As the staff at the Ministry of Education,
Culture, Sports, Science and Technology, one of ourduties is to raise awareness of importance that “Thesciences should be understood correctly by
everyone” among both the public and the scientists.
I am grateful to the experts who work for our healthpromotion in the research and clinical field, and now,
I would expect them to advocate, through theirpractices, the importance of explaining to the people
based on scientific evidences as well as making
them understand correctly to the scientists in otheracademic fields. This is why I put the above title tothis prefatory note.

The third Science and Technology Basic Plan
(2006-2010) was formulated in the spring of 2006.
This plan indicates the direction of Japan thatproclaims to establish a nation based on thecreativity of science and technology in the national
strategy. The following three principles are stated in
the chapter of principles and policy goals; 1) todevelop the wisdom of human, 2) to create thesources of national strength, 3) to protect health andsafety of the people. The first two principles may
bring the distant image of science and technology,
as the general public would have, whereas the last
one clearly shows for whom science and technology
are used.
Well, the nutrition science is the academic fieldfrom which everyone can equally enjoy andacknowledge its research outcome. It is therefore
important to obtain the accurate information andunderstand its message correctly. Let me bring an
example here; we can use a mobile phone without
knowing its mechanism, while it could be dangerous
to take a dietary supplement without knowing its
effect properly.
In reality, however, while we are now surroundedby an overflow of information, we hardly know how
to evaluate its reliability. To make the matter worse,
in many cases, we are not aware of our lack ofknowledge. Some people may realize that theywrongly used the health foods, only after the serious
health hazard caused by these health foods arereported in the media.

* The original Japanese version was translated by Projectfor International Research and Development, NIHN

Summary of The third Science and Technology Basic Plan (2006-2010)• Basic principles •Basic stances
1) Science and technology that are supported by society and people and return the outcomes to society¾ to improve the levels of science constantly Ö creation of intellectual and cultural values¾ to return the research outcomes to society and people through innovation Ö creation of social and economic values2) emphasis on human resource development and competitive environment for researchClarification of policy goals in science and technology
In order to clarify the targets of the government research and development investment, the following concrete
policy goals are set under the three basic principles;(1) breakthrough of significant knowledge (2) breaking the limitation of science and technology(3) simultaneous pursuit of environmental preservation and economic development(4) contribution of Japan as an innovator (5) healthy living throughout one’s life(6) the country that can be proud of secure public security

Government research and development investment
Total amount is about 25 trillion yen (1% of GDP during the 5 year plan, with 3.1 % GDP nominal growth rate)2

Current Research Projects
Project for Shokuiku
Naomi Aiba
Project for Shokuiku

Recently, the opportunities to see and hear of theterm of “Shokuiku” have been gradually increasing.
The Basic Law on Shokuiku was enacted in 2005,
followed by formulation of the Basic Plan for
Promotion of Shokuiku in March 2006. The main
targets set in this Basic Plan are shown in Table 1.
The Basic Law on Shokuiku was enacted due thatvarious social problems had been occurring,
including change of food environment (social andnatural environment) and increase of various
diseases associated with unbalanced diet (e.g.
lifestyle-related diseases). Shokuiku is therefore
promoted as a national movement with the aims thatJapanese people will have healthy livings both
physically and mentally throughout ones’ lives andalso that an environment to foster rich humanity willbe established.
Project for Shokuiku works on the researches
under the slogan of “Health Promotion throughout
our lives”, so as to explore the appropriate
approaches (when, how) to draw attention of people
on diet and to change one’s dietary behaviors.
Besides, the environmental settings necessary to
implement these approaches are also investigated.
The numerical targets of reducing breakfast
skippers and increasing awareness on metabolic
syndrome set in the Basic Plan for Promotion of
Shokuiku eventually aim to reduce the people at riskof metabolic syndrome, especially by changing
one’s dietary behaviors. For which, in addition todissemination of the relevant information, nutrition

The first national convention on Shokuiku promotion (June, 2006)

education should be designed in the way that eachindividual can achieve behavioral change.
In particular, food education for children should not
be enough if it is implemented only within the
educational curriculum at school, as it is crucial to
involve their families/communities too continuously.
In order to eliminate breakfast skipping, it isessential to review the lifestyle resulting in breakfast
skipping, instead of simply encouraging children to
take breakfast. We therefore propose a practicalnutrition education program where the foodeducation can be implemented effectively, with
providing scientific evidences to work out how eachindividual can improve one’s lifestyle, and how
school and family can support it.
In addition, we also propose an education programon “Shokuiku” by incorporating it in the integrated
study class at school.

Table 1. Numerical targets in the Basic Plan for Promotion of Shokuiku
Targets
Having an interest in Shokuiku
Skipping breakfast(elementary school)(20-29 years old)(30-39 years old)
Use of local agricultural products in school lunch menu
Use of the Food Balance Guide, as a guide to pursue appropriate diet
Awareness on metabolic syndrome
Number of volunteers working on Shokuiku promotion
Municipalities with education farm
Having basic knowledge on food safety
Prefectures planning/implementing the Basic Plan for Promotion of Shokuiku

Baseline (2006)
70%
4%
30%
23%
21%
42%
-

by 201090%
0%≤ 15 %
≤ 15%
≥ 30%
≥ 60%
≥ 80%
≥ +20%
60%
≥ 60%
100%

Municipalities planning/implementing the Basic Plan for Promotion of Shokuiku

-

≥ 50%

3

Thoughts on Health and Nutrition Research
Dietary survey should reflect the regional characteristics
Akemi Morita
Project for lifestyle-related diseases prevention
them “sando mame” and “nanba”, respectively.
When I was in the childhood, I always called the
deep-fried tofu mixed with thinly sliced vegetables
as “hirousu”. Thus, when I heard of “ganmodoki” on
TV, I was wondering what it was like, while in fact
they were the same food. When it comes to dishes, I
guess that there are more terms that I used in
Kansai, but people in other areas would notunderstand; for example, boiled egg (“ninuki” in
Kansai vs. “yudetamago” in Tokyo), boiled eel withrice (“mamushi” in Kansai vs. “unadon” in Tokyo)
It is said that the current young generations tend
to use the standard Japanese, rather than local
dialect. Yet, when I conducted the interviews forjunior high school students to obtain the data on
their dietary intake, one of them said “daikon no
taitan” which is the Kansai dialect meaning “daikonno nimono (= boiled radish)”. Since the interviewer
was the dietitian from outside Kansai, she looked
perplexed to understand what it meant. Well, I was
happy to interpret for her, feeling pleasant to seethat the Kansai dialect still commonly used by the
local junior high school students.
Needless to say, the preliminary research should
be undertaken to obtain the relevant information
including the local foods and dishes, and based on
which the questionnaires and detail implementation
plan should be established. In addition, whenever I
carry out a survey, I would emphasize theimportance of local dialect related to diet and local
dishes by working in collaboration with the local
dietitians and people living in the study area.

I have visited various areas in Japan, even not allover the country, for the purpose of surveys andresearches, where there are many occasions tohear dialect and term specific to the area from thelocal people. At a survey in Okinawa undertaken in
the early summer, when I asked the municipality
staff to check the greeting letter for the expectedparticipants, they corrected the term used in theseasonal greeting from the standard “shoka (= earlysummer) ” to Okinawa dialect “urizun”. In Okinawa,“urizun” is used as a term to express the specificseason (around February-March of lunar calendar)
when animals and plants grow well, and the field soil
becomes fertile. I was really impressed to hear thisbeautiful term that reflects the regional
characteristics very well. Next, when I went to arural village in the northern part of Japan (Tohoku
district), I asked the municipality staff whether there
was an area-specific seasonal term. Then, theymentioned “season of sanaburi” which is used toexpress June. “Sanaburi” is the traditional festivity
held after a period of rice planting, in order tocelebrate the god of paddy field. While “sanaburi” isvery old practice, people in some areas still continue
to hold this festivity.
Not surprisingly, the area-specific terms can beobserved at the dietary survey too. For example,
when we call “soba”, it generally means the one
made of buckwheat. However, when people in
Okinawa say “soba”, this mean “Okinawa soba”
made of wheat. Likewise, the food composition of
tofu (shima tofu) in Okinawa is very different fromthe standard hard tofu. In addition, the weight of one
unit of tofu is also different (300-350g in Tokyo vs.
1kg in Okinawa). Recently, some of soba or tofu
shops expand the service to all over Japan, by
utilizing the internet, and thus, there is a possibility
that the answer of “soba” or “tofu” in Okinawa may
be the standard ones and vice versa.
Vegetable names could also vary by region; forexample, pumpkin is “kabocya” in the standard
Japanese, while it is called differently in some areas
like “nanban uri”, “boubura”, “nankin”, “tounatsu” etc.
Likewise, for kidney beans and corn, it is generally
called in the standard Japanese as “ingen mame”
and “toumorokoshi” respectively. On the other hand,in the Kansai area where I was grown up, we called4Latest Research
Resistance training and arterial compliance: keeping the benefits while minimizing
the stiffening.
Motohiko Miyachi (Health Promotion and Exercise Program)
Reduction in central arterial compliance, as represented by carotid arterial
compliance, is an independent risk factor of cardiovascular diseases. It has been
well known that regular aerobic training increases carotid arterial compliance. In
contrast, we have recently demonstrated that high-intensity resistance training is
associated with reduced carotid arterial compliance. Yet, since resistance training
contributes to the prevention of sarcopenia and significantly reduces the risk ofbeing in need of nursing care, it has become an integral component of exercise
guidelines endorsed by a number of national health organizations. It is therefore
meaningful to investigate the type of resistance training that does not induce thereduction in arterial compliance.
In this context, two strategies appear plausible; one is moderate exercise training
and the other is the combined training where regular aerobic exercise andhigh-intensity resistance training are performed simultaneously. Accordingly, theprimary aim of the present study was to longitudinally examine the effects ofmoderate-intensity resistance training as well as the combined strength andendurance training on carotid arterial compliance.
A total of 39 young healthy men were studied. Subjects were randomly assigned
into three groups; 1) the moderate intensity resistance training group (MODE), 2) the
combined high-intensity resistance training and moderate-intensity aerobic exercise training group (COMBO), 3)
sedentary control group (CONTROL). In the first four months of study period (exercise intervention period),
participants in all training groups underwent three supervised resistance training sessions per week. During eachtraining session, participants in the COMBO group completed three sets of 10 exercises at 80% of 1RM andsubjects in the MODE group completed three sets of 16 exercises at 50% of 1 RM in the following order: leg
extension, seated chest press, leg curls, lateral row, squat and sit-ups. In addition, subjects in the COMBO groupperformed a cycle exercise at 60% of the maximal heart rate for 30 min immediately after each resistance training
session. Following the exercise intervention period, detraining was implemented for a period of four months, inorder to confirm that the observed changes in arterial compliance were induced by the prescribed exercise training.
Carotid arterial compliance decreased after four months of MODE interventions (p < 0.05), whereas arterial
compliance did not decrease, but rather tended to increase (p = 0.06), after 4 months of the COMBO intervention(Figure). After the detraining period, arterial compliance values returned to the baseline level in both groups. No
significant changes in carotid arterial compliance were observed in the CONTROL group throughout the eightmonths’ study period. Furthermore, peripheral (femoral) artery compliance did not change in any groups.
In the present study, we demonstrated that simultaneously performed endurance training prevented the reductionin arterial compliance that was accompanied by high-intensity resistance training. One possibility is that the
profound effects of regular aerobic exercise (e.g improved endothelial function, shared stress) may have negatedthe opposing effects of resistance training.
It is therefore important to recommend that aerobic training should be performed simultaneously with resistanttraining, when the exercise guidance is provided for prevention of nursing care and lifestyle-related diseases.

Resistance training and arterial compliance: keeping the benefits while minimizing
the stiffening.
Journal of Hypertension. 2006; 24(9): 1753-59.
Kawano H1),2),3), Tanaka H4), Miyachi M1)
1) Division of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan
2) Graduate School of Human Sciences, Waseda University, Saitama, Japan
3) Department of Health and Sports Sciences, Kawasaki University of Medical Welfare, Okayama, Japan
4) Department of Kinesiology and Health Education, University of Texas, Austin, Texas, USA

Abstract:
OBJECTIVES: This study aimed to determine the effects of moderate resistance training as well as
the combined resistance and aerobic training intervention on carotid arterial compliance. BACKGROUND:
Resistance training has become a popular mode of exercise, but intense weight training is shown to stiffen carotid
arteries. METHODS: Thirty-nine young healthy men were assigned either to the moderate-intensity resistancetraining (MODE), the combined resistance training and endurance training (COMBO) or the sedentary control(CONTROL) groups. Participants in the training groups underwent three training sessions per week for 4 months
followed by four additional months of detraining. RESULTS: All training groups increased maximal strength in all
the muscle groups tested (P < 0.05). Carotid arterial compliance (via simultaneous carotid ultrasound andapplanation tonometry) decreased approximately 20% after MODE training (from 0.20 +/- 0.01 to 0.16 +/- 0.01
mm2/mmHg, P < 0.01). No significant changes in carotid arterial compliance were observed in the COMBO (0.20+/- 0.01 to 0.23 +/- 0.01 mm2/mmHg) and CONTROL (0.20 +/- 0.01 to 0.20 +/- 0.01 mm2/mmHg) groups. Following
the detraining period, carotid arterial compliance returned to the baseline level. Peripheral (femoral) arterycompliance did not change in any groups. CONCLUSIONS: We concluded that simultaneously performed aerobic
exercise training could prevent the stiffening of carotid arteries caused by resistance training in young healthy men.
5

Latest Research
Moisture and mineral content of human feces -- high fecal moisture is associatedwith increase sodium and decreased potassium content -Mamoru Nishimuta (Nutritional Epidemiology Program)

Na (mmol/1000g moisture)

K (mmol/1000g moisture)

Na (mmol/1000g moisture)

K (mg/g wet weight)

Na (mg/g wet weight)

K (mg/g dry weight)

Na (mg/g dry weight)

The origin of moisture in diarrhea feces is unknown,
but may come from the unabsorbed part of dermal
contents or body fluids excreted into the digestive
canal. If body fluids do contribute to the moisture
content of feces, it is possible that active transportof water (H20) associated with ion exchange
channels may be involved in this process. In order
to investigate this possibility, we measured
moisture and mineral content (sodium [Na],potassium [K], calcium [Ca], magnesium [Mg],phosphorus [P], zinc [Zn], iron [Fe], copper [Cu],manganese [Mn]) in feces during a 12-d metabolic
study on 11 young Japanese female students.
The study was carried out as part of a humanmineral balance study. The same quantity of foodwas supplied to each of the subjects throughout the
study without consideration of body weight. Fecal
specimens were collected throughout the study andwere separated into those originating from the diet
Moisture (%)
Moisture (%)
during the balance period (12 d) based on the
Fig 1. Relationships between moistureappearance of the ingested colored marker in the feces.
and Na and K contents in feces
The relationship between moisture and the Na and K content are
shown in Figure 1. The moisture content of the feces ranged between
53 and 92%. Na content in the feces was low and stable when the
moisture content was below 80%, whereas it increased up to serum
levels when the moisture content increased above 80%.In contrast, K
content increased when compared to dry matter base, withconcentration/g moisture increasing when moisture was below 70% anddecreasing when moisture was above 70%.Accordingly, in the moisture
K (mmol/1000g moisture)
range above 80%, there was a negative correlation between fecal Na
Fig 2. Relationships between concentrations
and K content (Figure 2).
of fecal Na and K (fecal moisture > 80%)

Moisture and mineral content of human feces -- high fecal moisture is associatedwith increase sodium and decreased potassium content -Journal of Nutritional Science and Vitaminology. 2006; 52: 121-126.
Nishimuta M1), Inoue N1), Kodama N1), Morikuni E1),2), Yoshioka YH1), Matsuzaki N1), Shimada M1), 3),Sato N1),4), Iwamoto T1),5), Ohki K1),6), Takeyama H1),7), Nishimuta H8).
1) Laboratory of Mineral Nutrition, Division of Human Nutrition, National Institute of Health and Nutrition, Tokyo, Japan2) Medical University of Yamanashi, Yamanashi, Japan
3) Chiba College of Health Science, Chiba, Japan4)Seitoku University, Chiba, Japan
5) Prefectural University of Hiroshima, Hiroshima, Japan
6) Showa Women’s University, Tokyo, Japan
7) Nagoya City University Graduate School of Medical Science, Nagoya, Japan
8) Third Department of Surgery, Toho University Ohashi Hospital, Tokyo, Japan

Abstract:
BACKGROUND: The origin of moisture in diarrhea feces is unknown but may represent theunabsorbed part of intestinal contents or alternatively, body fluid excreted into the digestive canal. If the lattermechanism contributes to moisture in the feces, active transport of water (H2O) associated with ion exchange
channels may be involved. OBJECTIVE: To investigate this possibility we measured the content of moistureand minerals (sodium [Na], potassium [K], calcium [Ca], magnesium [Mg], phosphorus [P], zinc [Zn], iron [Fe],copper [Cu] and manganese [Mn]) in feces collected during a 12-d metabolic study on 11 young Japanese
female students. DESIGN: The study was carried out as part of a human mineral balance study. The same
quantity of food was supplied to each of the subjects throughout the study without consideration of bodyweight. Fecal specimens were collected throughout the study and were separated into those originating fromthe diet during the balance period based on the appearance of the ingested colored marker in the feces.
RESULTS: The moisture content of the feces ranged between 53 and 92%. Na content in the feces was low
and stable when the moisture content was below 80%, whereas it increased up to serum levels when the
moisture content increased above 80%. On the other hand, K content increased when compared to dry
matter base. However, when comparing concentration/g moisture, K content increased when moisture was
below 70%, but decreased when this rose above 70%.
6

Latest Research
Dietary folate intakes and folate biomarker profiles of pregnant Japanese women.
Natsuko Mito (Food Function and Labeling Program), Keizo Umegaki (Information Center),
Nobuo Yoshiike (Center for Collaboration and Partnership)

Number of the subject

Number of the subject

Folate is a water-soluble vitamin B, which is involved in DNA synthesis relevant to cell proliferation. Recent studies haveshown that an adequate intake of folic acid significantly reduces the risk of neural tube defects (NTDs). NTD is a congenitalabnormality that occurs in the neural tubes such as brain and spinal cord of babies. Since the neural tubes are formed inearly pregnancy, the periconceptional use of folic acid is very important for primary prevention of NTD. Leaf vegetables,
fruits, beans and liver are rich sources of folate. The bioavailability of dietary folate is not so high, and some people may not
be able to take sufficient folate from diet only. The Ministry of Health Labour, and Welfare (MHLW), Japan recommends that
all women planning a pregnancy should consume an additional 400μg/day of folate from supplemental folic acid.
So far, many studies on dietary folate intake and serum folate concentration have been undertaken in Western countries,
but there is no sufficient data on Japanese. Accordingly, we conducted this study to investigate the association between
dietary folate intake and serum folate concentrations of Japanese women in early pregnancy.
A total of 70 healthy pregnant women in the first trimester were included in this study. Weighted dietary records wereobtained from each subject for three nonconsecutive days within a week, from which the mean daily consumption of nutrientsand foods was estimated. In addition, fasting blood samples were drawn for the measurement of hematological parameters(hemoglobin, hematocrit, RBC count) and folate-related biomarkers.
Mean folate intake in all subjects was 289μg/day in the present study, which is lower than the recommended dietary
allowance (RDA) of folate in early pregnancy (440μg), according to the Dietary References Intakes for Japanese 2005. On
the other hand, the mean serum folate concentration was remarkably higher than the one reported in other countries. When
we analyzed the consumption of nutrients and foods in the two groups defined by serum folate concentration, the intakes ofcalcium, fiber, spinach and fruits were significantly greater in the high folate (serum folate ≥ 9ng/ml) group than in the low
folate group. Serum folate levels were positively correlated with other blood markers (plasma vitamin B12, albumin, hematcrit)
It is known that the bioavailability of folate varies widely with different foods and cooking style, and our findings suggest thatthe eating pattern in Japanese may have a unique factor, by which serum folate concentration can be maintained high.
It is reported that insufficient
folate intake may increase
the risk of not only NTD, butalso atherosclerosis andcardiac diseases. Further
study is needed on other age
groups of Japanese as well.
This study was undertakenwith the research grant by
the MHLW Japan (Principal
Figure 2. Distribution of serum folate concentration
investigator: Nobuo Yoshiike). Figure 1. Distribution of dietary folate intake

Folate intakes and folate biomarker profiles of pregnant Japanese women in the first trimester.
European Journal of Clinical Nutrition. 2007; 61:83-90
Mito N1), Takimoto H2), Umegaki K1), Ishiwaki A3), Kusama K4), Fukuoka H5), Ohta S6), Abe S7), Yamawaki M8),
Ishida H9), Yoshiike N3).
1) Division of Applied Food Research, National Institute of Health and Nutrition, Tokyo, Japan
2) Section of Maternal and Child Health, Dept. of Health Promotion and Research, National Institute of Public Health, Japan
3) Division of Health and Nutrition Monitoring, National Institute of Health and Nutrition, Tokyo, Japan
4) Dept. of Health Science, Faculty of Human Life and Environmental Science, Kochi Women’s University, Kochi, Japan
5) Dept. of Developmental Medical Science, Graduate School of International Health, University of Tokyo, Tokyo, Japan
6) Obstetrics and Gynecology Unit, Ohta Hospital, Tokyo, Japan
7) Dept. of Obstetrics and Gynecology, Metropolitan Otsuka Hospital, Tokyo, Japan
8) Matsushima Women’s and Children’s Hospital, Tokyo, Japan
9) Laboratory of Administrative Dietetics, Kagawa Nutrition University, Saitama, Japan

Abstract: Objective: To assess the status of dietary folate intake, serum and red blood cell (RBC) folate,and related nutritional biomarkers in healthy Japanese women in early pregnancy. Design: A cross-sectional,
observational study. Subjects: Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were
not consuming any folate supplements or folate fortified foods.Methods:Three-day dietary records were obtained
from each subject to assess dietary folate intake. Blood samples were collected for measurement of biomarkers.
Biomarkers and nutrient intake were analyzed in two groups defined by their serum folate concentrations: thelow folate group (serum folate < 9 ng/ml) and the high folate group (serum folate ≥ 9 ng/ml). Result: Mean serum
and RBC folate concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These levels wereremarkably higher than the reported values from many other countries despite our subjects receiving no folic
acids supplements. However, mean folate intake by our subjects from natural foods was 289 ug/day, which isthought to be low according to the Japanese dietary recommendation specified for pregnant women. The intakeof spinach and fruits was significantly greater in the high folate group than in the low folate group. Conclusion:
Folate intake was thought to be adequate to maintain a desirable level of serum folate concentration in
Japanese pregnant women in the first trimester, although the intake of folate from natural food was not highenough to meet the recommended daily intake. Sponsorship: This study was funded by a Ministry of Health
Labour and Welfare, Health and Labour Research Grant, for Research on Children and Families.
7

Latest Research
Docosahexaenoic acid-induced lipid peroxidation and urinary excretion of mercapturicacid.
Morio Saito (Food Function and Labeling Program)
The preventive effects of n-3 polyunsaturated fatty acid (PUFA) on cardiovascular diseases are well acknowledged. In
particular, docosahexaenoic acid (DHA) is the predominant n-3 PUFA with distinctive physiological functions. Recently, therelationship between DHA and anti-inflammatory action in inhibitory effects on atherosclerosis becomes a hot issue.
However, n-3 PUFAs are very prone to lipid peroxidation because of its unstable chemical structure, and thus there is aconcern that a high level of DHA intake would enhance the susceptibility to in vivo lipid peroxidation. Focusing on the mosthighly unsaturated DHA, we have undertaken the animal studies using rats as a model animal, with a hypothesis that “There
are primarily two suppressive mechanisms against PUFA-induced lipid peroxidation in healthy body; one is an antioxidative
mechanism that suppresses generation of lipid peroxides, and the other is a detoxification and/or excretion mechanism”. It
was, then, found that tissue lipid peroxides increased in a DHA dose-dependent manner, though it reached a plateau and did
not increase to the extent as calculated by Peroxidizability index (a parameter that indicates the maximal rate ofperoxidation). In addition, even with a very high dose of DHA, neither the end products of lipid peroxidation (e.g. lipofuscin)nor tissue damages were observed. We therefore confirmed that the above hypothesis was feasible and thus further
investigations have been carried out.
So far, we have revealed and published the following antioxidative mechanisms; 1) the uptake of DHA is different by tissues
and the unsaturation level of membrane fatty acids is important to produce lipid peroxides, 2) the uptake of DHA in
phospholipid species is different by tissues, and the resistance to oxidation increases when DHA is ingested into
phosphatidylethanolamine, 3) a very high level of DHA intake transiently increases the uptake of DHA in tissue triglyceride,by which DHA can be protected from oxidation, 4) induction of antioxidative enzymes is not observed, 5) the increased
generation of ascorbic acid (AsA) and glutathione (GSH) induced by DHA intake, which also increases the antioxidative
potency of Vit. E, 6) it is impossible to suppress lipid peroxidation completely even with a high-dose of Vit. E, AsA and GSH.
Yet, since no adverse effect has been initiated, we have investigated the mechanisms of suppressing accumulation anddetoxication and/or excretion of lipid peroxides. Of which, a part of the findings is reported in this paper.
We have previously observed that lipid peroxidation-derived degradation products, particularly reactive aldehydic
compounds, did not form the Schiff base by reacting with macromolecules, hence the end products of lipid peroxidation(lipofuscin) were not detected. In this study, therefore, we hypothesized that detoxification and/or excretion mechanisms ofaldehydic compounds would occur in the course of formation of the end products of lipid peroxidation. Then, our findings
showed a possible pathway as follows; the aldehydic compounds induced after a high level of DHA intake would form
conjugates with GSH in the liver, which is transferred to the kidney through the blood stream, metabolized and converted tothe mercapturic acid, and eventually excreted into urine (1). We also explored for the first time that the excretion process ofthe conjugates in the liver may be mediated by MRP3 (ABCC3), one of the ABC transporter families (2). Besides, aldose
reductase and aldehyde dehydrogenase may be involved in the metabolism of the aldehydic compounds (1). Further studies
are underway.
It is very important to reveal the dynamics of PUFA-induced lipid peroxidation for
their effective utilization. We believe that our findings demonstrated some ingenious
detoxication and/or excretion mechanisms.
<Reference>(1)(2)

Sekine S, Kubo K, Tadokoro T, Saito M. Docosahexaenoic acid-induced lipid peroxidation
and urinary excretion of mercapturic acid in rats. J Clin Biochem Nutr 2006; 39: 40−45.
Kubo K, Sekine S, Saito M. Induction of multidrug resistance-associated protein MRP3 inliver of rats fed docosahexaenoic acid. Biosci Biotech Biochem 2006; 70: 1672−1680.

Docosahexaenoic acid-induced lipid peroxidation and urinary excretion of mercapturic acid in
rats
Journal of Clinical Biochemistry and Nutrition. 2006; 39: 40-45
Sekine S1,2), Kubo K1,3), Tadokoro T2), Saito M1),
1) Division of Food Science, National Institute of Health and Nutrition, Tokyo, Japan
2) Laboratory of Nourishment Biochemistry, Dept. of Applied Biology and Chemistry, Tokyo University of Agriculture, Tokyo, Japan
3) Nursing Course, Narabunka Women’s College, Incorporated Educational Institution, Nara Gakuen, Nara, Japan

Abstract: We hypothesized a suppressive mechanism for dietary docosahexaenoic acid (DHA)-induced tissue
lipid peroxidation in which the degradation products, especially aldehydic compounds, are conjugated withglutathione (GSH) through catalysis by glutathione S-transferases (GSTs), and then excreted into urine as
mercapturic acids. Sprague-Dawley rats were fed a diet containing DHA (8.4 % of total energy) for 31 days. Lipid
peroxides in the liver and kidney, liver GST and urinary excretion of mercapturic acid were measured. The lipid
peroxide levels in the liver and kidney except the liver aldehydic compounds were higher, and the urinary
excretion of mercapturic acid also tended to be higher in the DHA-fed rats although the activity of GST was notincreased after DHA intake. We presume from our results that a proportion of the lipid peroxidation-derived
aldehydic degradation products might be excreted into urine as mercapturic acid after intake of DHA, thus
suppressing the accumulation of aldehydic products in tissues, particularly in the liver.

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