HEALTH AND NUTRITION NEWSNo. 17
September 15, 2006

Table of Contents

PREFATORY NOTE
Our future expectations for the NIHN, with respect to public health nutrition activities……Kayoko Sato

CURRENT RESEARCH PROJECTS
Food Function and Labeling Program…………..…………..……………………….….…..Junichi Nagata

THOUGHTS ON HEALTH AND NUTRITION RESEARCH
A thought on health and nutrition research at a pet shop? ……….…………………....... Takashi Kumae

SEMINAR REPORT
Exercise Guidelines for Health Promotion 2006 ……….………………….......................... Izumi Tabata

RESEARCH FINDINGS
Effects of simultaneous intakes of indigestible dextlin and diacylglycerol on lipid profiles in rats fed
cholesterol diets……………………………………………………………...……………….. Junichi Nagata
Dietary glycemic index and metabolic risk factors: a cross sectional study of Japanese female farmers…………...…….…..Kentaro Murakami, Yoshiko Takahashi, Satoshi Sasaki
Garcinia cambogia, as a dietary supplement for suppressing fat accumulation: Attention to its toxicity
in testis………………………………………………………………………………………..…..…Morio Saito© National Institute of Health and Nutrition

Prefatory Note
Our future expectations for the NIHN, with respect to publichealth nutrition activities
Kayoko Sato
Chief of Public Health Nutrition,
Department of Health Promotion and Research,
National Institute of Public Healththe origin of “public health dietitian”, who worked actively
on the educational activities in the field of public healthnutrition including the “Kitchen car” program to overcome
the malnutrition period. The NIPH was founded in 1938,
though it was merged with the NIHN in 1940 to become
the “Research Institute of Health Sciences (RIHS)”, where
Department of National Nutrition and Department of
Dietitian Training were established. Later, following
separation of the NIPH from the RIHS in 1947,
Department of Nutrition was established in the NIPH,
where the training of dietitian has been continued. The
name of this training course changed in line with social
situations, and it is presently named as “Pubic Health
Nutrition Course”. The NIHN evolved as a specialized
nutrition research institute, and contributed to nutritional
improvement and public health activities; e.g.
establishment of Recommended Dietary Allowances(present “Dietary Reference Intakes), National Nutrition
Survey (present “National Health and Nutrition Survey”).
In this way, the NIHN has been taking the uniqueapproaches that are different from the NIPH.
Recently, it has been reported that one in two Japanesemales aged 40-74 years were at risk of metabolic
syndrome (Report of the National Health and Nutrition
Survey, 2004). This problem concerns not only
themselves, but also their children. Another survey
reported that 10% of under-four children do not takebreakfast everyday, which was likely to be associated with
their mothers’ dietary habits (Children and Infant Growth
Survey, 2005). Similarly, our survey on the infants aged
18 months also revealed that the proportions of infants
and their mothers who did not take breakfast everyday
were 20% and 40%, respectively. No matter whatever thereason is, skipping meals of infants are of responsibility of
their parents. While raising motivation and temporal
behavioral changes may be possible in adults, it is noteasy to start and continue a new lifestyle. It is therefore
obvious that food education from an early age should be
important and promising. For which, health guidance and“Shokuiku” targeting children (with their family) could be
effective and thus, we place our hopes on implementationof the “Basic Plan for Promotion of Shokuiku”.
The NIHN made the organizational reformation in 2006,
with the second mid-term goal of “The NIHN to be open to
the public”. We can see enthusiasm for achieving its goalin the staffs and concerned persons. Field activities basedon the scientific evidences are now required, and thus, we
expect that the NIHN will keep working on the researches
and providing information to support the registereddietitians, dietitians and other nutrition-related specialists.

The reform of the medical care system aims to shift thecurrent system into a structure more stressing disease
prevention. It is a big reform in the health, medical andwelfare sectors, where the target issues extend acrosshealth promotion, treatment and home care. In order tocontrol lifestyle-related diseases, the measures involving
the concept of metabolic syndrome are enhanced. The
national health insurance associations will be obligated toprovide the health check/guidance, by which effectivenessof health guidance can be well secured. Besides, it isimportant to ensure harmonization of three schemes;
health promotion, medical and nursing care insurance.
A control program of lifestyle-related diseases starts
from 2008, focusing on prevention of lifestyle-relateddiseases (obesity, diabetes, hypertension, hyperlipidemiaetc.) derived from metabolic syndrome, cardiovasculardiseases (ischemic heart disease, cerebral stroke) anddiabetes complications, through the lifestyle modificationon unbalanced diet, lack of exercise, stress, alcohol
drinking, smoking etc. This program combines high-risk
approach and population one, considering prevention of
impaired vital functions and being in need of nursing care.
The health services will greatly change, and the publichealth nurses and the registered dietitians are expected totake more important roles to implement the new healthservices. The National Institute of Public Health (NIPH),
therefore, starts the human resource development
program in the field of health services from 2007.
NIPH provides various courses; long-term training
courses to develop the highly-specialized professionals in
the field of health, medicine and environmental health inlocal public authorities (Doctor of Public Health Course,
Master of Public Health Course, Diploma in Public Health
Course: 3 months - 3 years), short-term special course forcontinuing education in public health (about one month),
pinpoint seminars for the latest and urgent public healthissues (a few days), and distant learning course using theInternet. For which, we receive supports from the experts
in the National Institute of Health and Nutrition (NIHN).
Talking about “dietitian”, I heard that Dr. Tadasu Saiki(the founding Director-General of NIHN), who established
the base of nutritional sciences and started the training of
dietitians in 1920, stated that “Dietitians should voluntarily
advocate the importance of nutrition and appropriate dietto as many people as possible, instead of waiting for theirvisits”. The Japanese term of “dietitian” therefore contains
the meaning of “serve” (instead of “teach”, which istypically included in the health-related qualifications).
Following promulgation of the Public Health Center Law,
the public health centers were established across thecountry, where the dietitians were also assigned. This was* The original Japanese version was translated by Projectfor International Research and Development, NIHN

2

Current Research Projects
Food Function and Labeling Program
Junichi Nagata
Food Function and Labeling Program

factors, inflammation and the inhibitory factors ofendothelial cell injury.
In addition to these administrative affairs related tofood component analyses of “Food for Special
Dietary Use” and labeling, our program collects theinformation on the foods taken for the sake of fitness,
and attempts the advanced uses of functional
components, through the basic researches on thefunctionality of food components and health effects.
As a member of Project for Food Component
Analysis, my main duties are the analyses of “Foodfor Special Dietary Uses” and “Food for SpecifiedHealth Uses”, and the technical supports for the
food and health administration. In addition, I havebeen working on the examination of the functionalityof lipid and nutritive composition of foods.
Despite that lipid is an essential nutrient for living
body working as energy source, component of cell
membrane, prohormone and carrier of lipid-solublecomponent, this is the typical nutrient that has anegative image as a food component worsening
lifestyle-related diseases. Yet, the past studies have
explored the lipid-soluble components with various
physiological functions, and thus some of them are
utilized as functional food materials; phytosterol, fishoil (EPA, DHA), middle-chain fatty acids, structured
lipid and conjugated linoleic acid (CLA).
Since excess lipid intake would increase the risk ofdeveloping lifestyle-related diseases, lipid isregarded as the food component that we should becautious about its quality and quantity taken.
Besides, it is reported that excess intake of fat/oil
widely used for cooking/processing foods (e.g. theone with high proportion of trans fatty acids) is
associated with the increased risk of developing
lifestyle-related diseases. Under this circumstance,
more attention has been paid to the researches onfood materials, where fat/oil with less absorption into
the body, low calorie fat/oil and alternative fat/oil aredeveloped. While there remain many problems with
its application in cooking and taste, it is expectedthat this type of fat/oil with various functionality will
be widely used. Now, I am trying to develop edible
fat/oil effective to prevent lifestyle-related diseases,
through evaluation of new functional fat/oil for its
design, physiological functions, nutrition and safety.

Food Function and Labeling Program is composedof three projects; Project for Food Component
Analysis, Project for Complementary Factors, andProject for Food Functionality. Here, I would like tointroduce the outlines of researches at each project,
together with the latest research issues on lipid as afunctional component.
Project for Food Component Analysis is in chargeof technical aspects of the food and healthadministration, which is implemented by the Ministryof Health, Labour and Welfare. In particular, thisproject undertakes the analytical tests of the foods
labeled as "Food for Special Dietary Uses", and of
those with nutritional labeling, using the foodsamples collected by the Ministry of Health, Labourand Welfare, in order to assess if the nutrients andfood components are labeled correctly. We also
examine the submitted application forms for “Foodfor Specified Health Use”, and work on the properlabeling on foods. Furthermore, in order to respondtechnically to new food components of "Food forSpecified Health Uses", the standardization is madefor the analytical technique and the standard goodsof these food components. A great effort is made to
improve the environment for correct and effective
implementation of the above food analyses.
Project for Complementary Factors works to
explore the complementary factors that havepositive effects on prevention and treatment ofchronic diseases (e.g. lifestyle-related diseases).
These complementary factors are screened fromthe food-derived components that possibly havephysiological functions, and their effectiveness isscientifically evaluated by cell or animal models. In
this way, this project investigates the possibilities ofdeveloping a new method to prevent and treat
chronic diseases, using the complementary factors.
Project for Food Functionality aims to develop
tailor-made functional foods, focusing on thefunctional food components with inhibitory effects
against atherosclerosis. The functional foodcomponents mainly studied are docosahexaenoic
acid (DHA) (n-3 fatty acid), Sesamin derived fromsesame seeds, antioxidants etc. In order to develop
antiatherosclerotic functional foods, this project
undertakes screening for the food components, byinvestigating the effects on atherosclerosis risk

3

Thoughts on Health and Nutrition Research
A thought on health and nutrition research at a pet shop?
Takashi Kumae
Health Promotion and Exercise Program
Do you know that the number of pet dogs is
growing beyond the number of children? In 2005,
the number of new born babies in Japan was 1.06
million, and the number of registered pet dogs
was 6.26 million (2003). A survey conducted by
the pet food industry association in 2005
estimated the number of pet dogs to be 130.6
million. When I go to work or take a walk, I often
see people with their dogs. Most supermarkets
have the pet section, where dog foods etc. areavailable. The pet-related market has about one
trillion yen business in 2005. In my childhood, it
was common to give the leftovers to dogs and werarely bought any special foods for dogs. At thattime, the average lifetime of dogs was shorter
than now, for about four or five years. Nowadays,
special food for older dogs is also available. The
average lifetime of dog is now 12-14 years,
though it varies by its kind to some degree.
Seeing-eye dogs even work up to 10 years old.
Whilst there is no statistical data, it is obvious that
their lifetime has been increasing dramatically.
One of the reasons seems to be the widespreaduse of dog food. Looking at the prolonged lifetimeby change of diet, we can say that dogs haveshown the importance of nutrition on their health.
I started this article with a topic on pet dogs.
Why? Well, let me move to the topic of nutrition
for human now. It was not until I came to thisinstitute that I joined in human metabolic studies. I
am grateful to Dr. Nishimuta (Project for Bio-index,
Nutritional Epidemiology Program) for giving me
an opportunity to participate in a 21 day study on
nonspecific immune function. I dare not tomention its results here, as the published articleof this study is now available on the web. Since I
had never been involved in this type of humanstudy, everything was new and surprising to me. I
was impressed with the cooperative attitudes of
11 female college students as the participants. In
this study, both food intake and excretion werechecked. Collecting the excretory substances
should be quite tough, though it was found thatmeasuring food intake was even more laborious. I
was impressed with the study team who cooked,
served and measured those foods, and also withthe study participants who had to eat up all theprovided food, while the same menu was served
every four days. I saw the contents of miso soupby chance, where tofu was cut into so tiny dicesize. This effort was to make sure that all theparticipants take the same amount of foods andingredients. If I were the study participant, I would
run away on the fifth day.
Since dogs are given same food once or twice a
day regularly, experiments on dogs could be easy.
One dog food promo says “In order to build theanti-aging and strong body, this dog food is
supplemented with anti-oxidant bio-factor and thenutrients that are likely to decrease with age”. We,
human, also might need such food in this aging
society, though it must be practically difficult toundertake the experimental studies on the elderly.
Even if we develop well-balanced dried food likedog food, it is not feasible to recommend people
to take it all the time to have healthier and longer
lives, as it would decrease one’s quality of life
(QOL). Now, let’s think how can the health andnutrition researches intervene for capricious
humans who have various demands?

4

Seminar Report
Exercise Guideline for Health Promotion 2006
Let’s target 23 Ex (METs・hour) per week by physical activity, of which 4 Ex by active exercise!
Izumi Tabata
Health Promotion and Exercise Program
Following establishment of “Exercise andIf we practice on average 3 Ex per day byPhysical Activity Reference Quantity for Healthincorporating these activities actively in everyday
Promotion (EPARQ2006): Physical Activity,
life, we can meet the references in the
Exercise and Physical Fitness” (as introduced in
EPARQ2006. By which, it is expected that
Health and Nutrition News No. 15) thatlifestyle-related diseases (e.g. diabetes) can be
determined the references of physical activity,
prevented.
exercise and physical fitness, and reported the
Likewise, regular exercise can reduce waist
scientific evidences, the Ministry of Health,circumference, eventually relieving metabolic
Labour and Welfare issued the “Exercise
syndrome.
Guidelines for Health Promotion
Exercise Guideline for Health Promotion
2006 (Exercise Guidelines 2006)”.
(Exercise Guidelines 2006 )While EPARQ2006 was prepared for1. For people who want to increase physical activity for health promotion
the experts on exercise, the Exercise
 Health promotion by physical activity
Guidelines 2006 was developed toLet’s walk to achieve the following goals in everyday life.
encourage the nation to increase theCorrespond to..
Walking60
min
4 Km
amounts of physical activity andper day
exercise for health promotion.
Under the slogan written on the top
7 hour 28 Km
per dayof this page (with title), the Exercise
Guidelines 2006 were established for¾ When one uses a pedometer…
The goal should be set as 10,000 steps per day (70,000 per week),
the nation to understand theincluding 2,000~4,000 steps unconsciously taken in everyday life.
EPARQ2006 very well. In addition,
 Health promotion by exercises
the Exercise Guidelines 2006
Let’s practice more exercises, in addition to physical activity inintroduces how to relieve metabolic
everyday life, according to your lifestyle and physical fitness. For
example, the following goals can be set (*).
syndrome, which was not included in
the EPARQ2006.
per week
60 min Correspond to..
6 Km
The unit for the quantity of physicalBrisk walking
activity and exercise was set as“exercise (Ex)”. For physical activity,
per week
35 min 4 Km
Jogging
1 Ex corresponds to walking/child*In this case, the goal of walking should be 50 minutes per day (350 minutes per week)
care/car washing/house cleaning for2. For people who are conscious about visceral fat
20 minutes, brisk walking/bicycling/
Let’s try to achieve the following goals, so as to reduce visceral fat andshow shovel for 15 minutes, andimprove the metabolic syndrome. People with no exercise habit could
start with one fifth of these goals, and then increase the amount ofcarrying heavy loads for 7 minutes.
exercise gradually.
As for exercise, 1 Ex corresponds toCorrespond to..
bowling/volley ball for 20 minutes,
150 min 15 Km
per weekwater exercise/jazz dance/badminton Brisk walking
for 15 minutes, and aerobics/jogging
per week
90 min 11 Km
for 9 minutes.
Jogging5Latest Research
Effects of simultaneous intakes of indigestible dextrin and diacylglycerol on lipid
profiles in rats fed cholesterol diets.
Jun-ichi Nagata (Food Function and Labeling Program)
Now, in Japan, there are many types of health foods that claim physiologic benefits in the market. Although
the functionalities are scientifically proven for some foods (food with health claims), there are also “so-called”
health foods which do not necessarily have adequate scientific support. Regardless of the proof of scientificevidences, there is a strong trend that these health foods are taken simply based on the images from theirpromo words. It is therefore possible that some of the consumers may take health foods inappropriately (e.g.
those who take too much health food with expectation of physiologic functions, those who take various healthfoods with similar effects simultaneously). Whilst the past food science studies have investigated theeffectiveness of each particular health food or food component in details, little has been studied on thephysiologic effects and safety of simultaneous intake of several functional foods so far yet.
Under this circumstance, we investigated whether simultaneous intake of health foods or food constituents,
which are scientifically claimed to decrease risk factors for lifestyle-related diseases (such as obesity andhyperlipidemia), produce any physiological advantage with respect to lipid profiles and body fat accumulation.
In the present study, we focused on the effects of a combination of diacylglycerol (DG) which is recognized topossess physiologic effects, such as prevention of obesity and reduction of serum lipid levels and indigestible
dextrin (IDex) which modulates intestinal functions and also possibly decreases serum lipid level. For which,five-week-old male Wistar rats were fed a cholesterol-containing diet with DG and IDex for 28 days.
IDex significantly decreased serum triacylglycerol concentration and increased the length of small intestinal
villi, which indicates that IDex acts as a dietary fiber. On the other hand, DG produced significant decrease inserum high-density lipoprotein (HDL) cholesterol concentration and significant increases in liver cholesterol
and triacylglycerol concentration. The physiological effects of DG, however, were not clearly detected under
the present experimental conditions.
In conclusion, IDex intake characteristically decreased serum triacylglycerol concentrations in rats fed acholesterol-containing diet, no additive or synergistic interactions were observed during feeding with the
combined DG and IDex diet. These results indicate thatsimultaneous intake of food components with similar
physiologic functions does not necessarily produce
additive or synergistic physiologic benefits.
In order to utilize widely available functional foods
appropriately and safely for prevention/improvement oflifestyle-related diseases, further studies will be needed to
examine various dietary conditions and the combinationsof functional foods with different physiologic functions.

Effects of simultaneous intakes of indigestible dextrin and diacylglycerol on lipid
profiles in rats fed cholesterol diets.
Nutrition. 2006; 22: 395-400.
Nagata J, Saito M
Division of Food Science, National Institute of Health and Nutrition, Tokyo, Japan

Abstract:

OBJECTIVE: Indigestible dextrin (IDex) and diacylglycerol (DG) are food components withphysiologic effects on lipid metabolism. Because simultaneous intake of dietary components with similar
physiologic functions may produce a beneficial decrease in risk factors for lifestyle-related diseases, weinvestigated the physiologic effects of simultaneous IDex and DG intake. METHODS: Five-week-old male
Wistar rats were fed a cholesterol-containing diet with IDex and DG (separately and combined) for 28 d.
RESULTS: IDex significantly decreased serum triacylglycerol concentration and increased the length of small
intestinal villi, whereas DG produced significant decreases in serum high-density lipoprotein cholesterol
concentration and significant increases in liver cholesterol and triacylglycerol concentrations.
CONCLUSIONS: IDex intake characteristically decreased serum triacylglycerol concentrations, although noadditive or synergistic interaction between DG and IDex was observed. These results indicate thatsimultaneous intake of food components with similar physiologic functions do not necessarily produce
additive or synergistic physiologic benefits.

6

Latest Research
Dietary glycemic index and metabolic risk factors: a cross sectional study of Japanese
female farmers.

Fasting glucose
Hb A1cBMI% of mean values relative tothe group with lowest GL

(This
study
was
undertaken as a joint
research with Professor
Fujio Kayama in the
Division of Environmental
Medicine,
Centerfor
Community
Medicine,
Jichi Medical University)% of mean values relative tothe group with lowest GI

Kentaro Murakami, Yoshiko Takahashi, Satoshi Sasaki (Nutritional Epidemiology Program)
Dietary carbohydrate raises blood glucose, but the blood glucose response varies substantially among different
carbohydrate-containing foods. This varied glycemic response is quantified according to the glycemic index (GI).
The GI of a food is defined as the 2-h incremental area under the blood glucose response curve after
consumption of a food portion containing 50 g of available carbohydrate, divided by the corresponding area after
consumption of 50 g glucose, and multiplied by 100 to be expressed as a percentage (GI of glucose = 100).
Glycemic load (GL) is calculated by GI multiplied by available carbohydrate content.
Recent results from observational studies have suggested that diets with a low GI, a low GL, or both have abeneficial effect on several metabolic risk factors. However, almost all studies of dietary GI or GL and metabolicrisk factors have been conducted in Western countries, whereas, to our knowledge, only one small study was
carried out in Asian countries, including Japan. For Japanese people, rice is the food that contributes most to
total carbohydrate, which is a characteristic seldom observed in Western people. Therefore, a different
association of dietary GI or GL and metabolic risk factors may exist between Western and Japanese
populations. Consequently, we examined the cross-sectional associations between dietary GI and GL andseveral metabolic risk factors in a group of apparently healthy Japanese women with traditional dietary habits.
The subjects were 1345 Japanese female farmers aged 20-78 y from 5 regions of Japan. Dietary habits during
the past one month were assessed with a self-administered diet-history questionnaire (DHQ), from which dietary
GI and GL were calculated. Height and weight were measured and fasting blood samples were collected.
White rice was the major contributor to dietary GI and GL (59%) in the present study, whereas in Western
populations, dietary GI and GL are determined by a variety of food including potatoes, breakfast cereals, bread,and rice (4-8%). Figure 1 shows the associations between dietary GI and metabolic risk factors. Dietary GI was
positively associated with body mass index, fasting serum triacylglycerol, fasting plasma glucose and Hb A1c.
Figure 2 shows the associations between dietary GL and metabolic risk factors. Dietary GL was positively
associated with fasting serum triacylglycerol and fasting plasma glucose and negatively associated with serum
HDL cholesterol.
Although the major contributor to dietary GI and GL of Japanese women is very different from that of Western
populations, the results showed that dietary GI and GL were associated with several metabolic risk factors.
Whilst the increase of metabolic syndrome and Type 2 diabetes might be associated with dietary GI and GL (orwhite rice), further studies
Fasting
Fasting
are needed to examine
triacylglycerol
triacylglycerol
the associations in details.
Fasting
glucose

HDL-cholesterol

Median GI of each group (GI of glucose =100)

Median GL of each group (GI of glucose =100)

Fig. 1 Association between GI and metabolic risk factors

Fig. 2 Association between GL and metabolic risk factors

Dietary glycemic index and load in relation to metabolic risk factors in Japanese female
farmers with traditional dietary habits.
American Journal of Clinical Nutrition. 2006 May;83(5):1161-9
Murakami K 1), Sasaki S 1), Takahashi Y 1), Okubo H2), Hosoi Y 1), Horiguchi H4), Oguma E3,4) and Kayama F3,4)
1) National Institute of Health and Nutrition, Tokyo, Japan
2) Department of Nutrition Sciences, Kagawa Nutrition University, Saitama, Japan
3) Division of Environmental Medicine, Center for Community Medicine, Jichi Medical University, Tochigi, Japan
4) Core Research for Evolutional Science and Technology, Japan Science and Technology Cooperation, Kawaguchi City, Japan

Abstract: BACKGROUND: Little is known about the relation of dietary glycemic index (GI) and glycemic
load (GL) to metabolic risk factors, particularly in non-Western populations. OBJECTIVE: We examined thecross-sectional associations between dietary GI and GL and several metabolic risk factors in healthy Japanesewomen with traditional dietary habits. DESIGN: The subjects were 1354 Japanese female farmers aged 20-78 yfrom 5 regions of Japan. Dietary GI and GL were assessed with a self-administered diet-history questionnaire.
Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m). Fasting blood
samples were collected for biochemical measurements. RESULTS: The mean dietary GI was 67, and the mean
dietary GL (/1000 kcal) was 88 (GI for glucose = 100). White rice (GI = 77) was the major contributor to dietary
GI and GL (58.5%). After adjustment for potential dietary and nondietary confounding factors, dietary GI was
positively correlated with BMI (n = 1354; P for trend = 0.017), fasting triacylglycerol (n = 1349; P for trend =0.001), fasting glucose (n = 764; P for trend = 0.022), and glycated hemoglobin (n = 845; P for trend = 0.038).
Dietary GL was independently negatively correlated with HDL cholesterol (n = 1354; P for trend = 0.004) andpositively correlated with fasting triacylglycerol (P for trend = 0.047) and fasting glucose (P for trend = 0.012).
CONCLUSIONS: Both dietary GI and GL are independently correlated with several metabolic risk factors insubjects whose dietary GI and GL were primarily determined on the basis of the GI of white rice.
7

Latest Research
Garcinia cambogia, as a dietary supplement for suppressing fat accumulation: Attention to its
toxicity in testis!
Morio Saito (Food Function and Labeling Program)
Garcinia cambogia, a kind of herb, is an evergreen tree native to India and Southeast Asia, whichbears orange-size fruits between May and September. The fruit or rind has a strong acid taste. Ripen
ones can be eaten raw, and the dried fruit/rind has been used for centuries for flavoring curry orpreservation of salted fish. The rind contains (−)-Hydroxycitric acid (HCA), which is popularly used as
an ingredient of dietary supplements for weight loss.
HCA is a competitive inhibitor of ATP citrate lyase with citric acid. This inhibitory action of HCA
reduces the acetyl-CoA pool, resulting in the suppression of fat synthesis from glucose and body fat
accumulation.
HCA has been shown to be active in reducing body weight and suppressing body fat accumulation in experimental animals.
Similarly, several human studies reported that HCA suppressed the body fat accumulation, though there are many studies
that rejected its effect. Therefore, no consensus has been made yet on the effectiveness of HCA in humans due to various
influencing factors (e.g. characteristics of study subjects, dietary patterns, amount of HCA intake).
As for the safety of Garcinia, it has been considered safe, due to the long dietary history in Southeast Asia and also basedon the result of an acute toxicity test using rats (LD50 5,000mg/kg BW or higher). In our study 1), however, when Zuker obese
rats were fed diets containing HCA, high dose of Gercinia (154 mmol HCA/kg diet) showed significant suppression of
epididymal fat accumulation, but 102 mmol/kg diet or higher (778 mg HCA/kg BW/day) caused testicular toxicity (testicularatrophy and impairment of spermatogenesis). Another study also observed similar findings, and the Ministry of Health,Labour and Welfare of Japan officially reported the testicular toxicity of Garcinia. It has also been presumed that the testicular
toxicity could be caused by HCA itself.
For commercially available dietary supplements containing Garcinia cambogia in Japan, the recommended intake range is
750-1500mg of HCA/d per person. For example, the recommended intake range for a subject with body weight 50kg is 15-30
mg HCA/kg Bw/d, which is one-twentysixth to one-thirteenth of no observed adverse effect level (NOAEL)(The NOAEL of
51mmol HCA/kg diet corresponds to 389 mg HCA/kg Bw/d). Therefore, safety for human consumption is not essentially ruledout. However, a variety of Garcinia cambogia-containing so-called health foods are sold on the market, and the tablet- andcapsule-type dietary supplements are easily taken in excess. Besides, the sensitivity to HCA may vary considerably fromperson to person. Moreover, acetyl-CoA production from glucose in humans has been reported to be approximately
one-fortieth of that in rats because of low activity of ATP-citrate lyase in humans. It is therefore unlikely that obese people
would experience a suppression of body fat accumulation by HCA except in the setting of an unphysiologicalhigh-carbohydrate and low-fat diet containing very high level of HCA.
This is the first published report of the testicular toxicity of HCA-containing Garcinia cambogia, and we do not currently
know which constituent is responsible for the toxicity. Its intake therefore should be restricted, until its safety can be
confirmed. We also investigated the mechanism of the testicular toxicity of Garcinia2), and its effect on female rats3), and nodeleterious influence was observed in the female rats. And we hypothesized from our results2) that HCA-mediated inhibitionof ATP citrate lyase in rats fed GA leads to diminished accumulation of MAS substances, thus resulting in impairment ofspermatogenesis. This study was conducted as one of the prioritized researches titled “Evaluation of physiologicaleffectiveness and health effects of foods and food components” during the period of the First Mid-term Plan (2001-2006).
<Reference>
1) Saito M, Ueno M, Ogino S, Kubo K, Nagata J, Takeuchi M. High dose of Garcinia cambogia is effective in suppressing fat accumulation in developing male
Zucker obese rats, but highly toxic to the testis. Food Chem Toxicol 2005; 43: 411-419.
2) Kiyose C, Ogino S, Kubo K, Takeuchi M, Saito M. Relationship between Garcinia cambogia-induced impairment of spermatogenesis and meiosis-activating
sterol production in rat testis. J Clin Biochem Nutr 2006; 38: 180-187.
3) Kiyose C, Kubo K, Saito M. Effect of Garcinia cambogia administration on female reproductive organs in rats. J Clin Biochem Nutr 2006; 38: 188-194.
4) Saito M．Effectiveness and health effects of so-called health foods: Part 1 Garcinia (in Japanese)．Rinsho-Eiyo 2006; 108: 60-64.

High dose of Garcinia cambogia is effective in suppressing fat accumulation in developing
male Zucker obese rats, but highly toxic to the testis.
Food and Chemical Toxicology. 2005; 43: 411-419
Saito M1), Ueno M1), Ogino S1), Kubo K1), Nagata J1) and Takeuchi M2)
1. Division of Food Sciences, National Institute of Health and Nutrition, Tokyo, Japan
2. Sapporo General Pathology Laboratory Co., Ltd., Hokkaido, Japan

Abstract:

We investigated the ability of Garcinia cambogia extract containing (-)-hydroxycitric acid (HCA) to suppress
body fat accumulation in developing male Zucker obese (fa/fa) rats. We also examined histopathologically the safety of its
high doses. Diets containing different levels of HCA (0, 10, 51, 102 and 154 mmol/kg diet) were fed to 6-week-old rats for 92
or 93 days. Each diet group was pair-fed to the 154 mmol HCA/kg diet group. Epididymal fat accumulation andhistopathological changes in tissues were observed. The highest dose of HCA-containing Garcinia cambogia (154 mmol
HCA/kg diet) showed significant suppression of epididymal fat accumulation in developing male Zucker obese rats,
compared with the other groups. However, the diets containing 102 mmol HCA/kg diet and higher (778 and 1244 mg HCA/kg
BW/d, respectively) caused potent testicular atrophy and toxicity, whereas diets containing 51 mmol HCA/kg diet (389 mg
HCA/kg BW/d) or less did not. Accordingly, 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) was deemed to be the no observed
adverse effect level (NOAEL).

8