研究成果の刊行に関する一覧表
雑誌
発表者氏名

論文タイトル名

発表誌名巻号

Yoh K, Uzawa T, Orito T, Improvement of quality ofJapanese
Tanaka K.
life （QOL） in osteoporotic Clinicalpatients by elcatonin
Medicine
treatment: a trial taking theparticipants’ preference into
account.

ページ

出版年

In press

2012

Saito K, Yokoyama T,
Yoshida H, Kim H,
Shimada H, Yoshida Y,
Iwasa H, Shimizu Y,
Yoshitaka K, Handa S,
Maruyama N, Ishigami A,
Suzuki T.

A Significant Relationshipbetween Plasma Vitamin C
Concentration and Physical
Performance among
Japanese Elderly Women.

J Gerontol A
Biol Sci Med Sci

67

295-3012012

Ogawa A, Naruse Y,
Shigemura Y, Kobayashi
Y, Suzuki I, Wada S,
Hayamizu K, Kuwahata
M, Kido Y.

An evaluation of protein
intake for metabolic
demands and the quality of
dietary protein in rats using
an indicator amino acidoxidation method.

J Nutr Sci
Vitaminol

57

418-425

2011

Ezaki O.

The optimal dietary fat to
J Nutr Sci
carbohydrate ratio to prevent Vitaminol
obesity in Japanese
population: a review of theepidemiological,
physiological and molecularevidence.

57

383-393

2011

木戸康博.

たんぱく質・アミノ酸の必 栄養学雑誌
要量に関する研究．

69285-2932011

坪田（宇津木）恵.

欧米の循環器疾患予防のための食事ガイドライン
の現状.

70

607-6142011

笠岡（坪山）宜代, 桑木 諸外国における栄養士養 日本栄養士会
泰子, 瀧沢あす香, 田 成のための臨地･校外実習 雑誌
中律子，藤生惠子, 斎藤 の現状に関する調査研究.
トシ子，恩田理恵，山岸博之，江田節子，木村祐子，小谷一子，小田光子，
田代晶子，池本真二.

54556-5652011

田中清、桑原晶子.

85608-6092011

日本人の食事摂取基準における目安量は健康人の摂取の中央値でよいの
か？

167

循環器内科

ビタミン

Journal of Gerontology: MEDICAL SCIENCES
Cite journal as: J Gerontol A Biol Sci Med Sci
doi:10.1093/gerona/glr174© The Author 2011. Published by Oxford University Press on behalf of The Gerontological Society of America.
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A Significant Relationship between Plasma Vitamin C
Concentration and Physical Performance among Japanese
Elderly Women
Kyoko Saito,1,2 Tetsuji Yokoyama,2 Hideyo Yoshida,1 Hunkyung Kim,1 Hiroyuki Shimada,3 Yuko Yoshida,1
Hajime Iwasa,4 Yoko Shimizu,1 Kondo Yoshitaka,5 Setsuko Handa,5 Naoki Maruyama,5 Akihito Ishigami,5and Takao Suzuki6
1Research Team for Promoting Independence of the Elderly, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
2Department of Human Resources Development, National Institute of Public Health, Saitama, Japan.

3Section for Health promotion, Department of Health and Medical Care, Center for Development of Advanced Medicine

for Dementia, National Center for Geriatrics and Gerontology, Aichi, Japan.

4Department of Social Gerontology, School of Public Health, Tokyo University, Tokyo, Japan.
5Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
6Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan.

Downloaded from biomedgerontology.oxfordjournals.org by guest on October 11, 2011

Address correspondence to Kyoko Saito, PhD, Research Team for Promoting Independence of the Elderly, Tokyo Metropolitan
Institute of Gerontology, 35-2, Sakaecho, Itabashi, Tokyo, 173-0015, Japan. Email:kyon@tmig.or.jp

Background. Maintenance of physical performance could improve the quality of life in old age. Recent studies suggested a beneficial relationship between antioxidant vitamin (eg, vitamin C) intake and physical performance in elderly
people. The purpose of this study was to examine the relationship between plasma vitamin C concentration and physicalperformance among Japanese community-dwelling elderly women.
Methods. This is a cross-sectional study involving elderly females residing in an urban area in Tokyo, Japan, in
October 2006. We examined anthropometric measurements, physical performance, lifestyles, and plasma vitamin C
concentration of participants.
Results. A total of 655 subjects who did not take supplements were analyzed. The mean age (±standard deviation) of
participants was 75.7 ± 4.1 years in this study. The geometric mean (geometric standard deviation) of plasma vitamin C
concentration was 8.9 (1.5) mg/mL. The plasma vitamin C concentration was positively correlated with handgrip strength,
length of time standing on one leg with eyes open and walking speed, and inversely correlated with body mass index.
After adjusting for the confounding factors, the quartile plasma vitamin C level was significantly correlated with thesubject’s handgrip strength (p for trend = .0004) and ability to stand on one leg with eyes open (p for trend = .049).
Conclusions. In community-dwelling elderly women, the concentration of plasma vitamin C related well to theirmuscle strength and physical performance.
Key Words: Plasma vitamin C—Physical performance—Elderly women—Japanese.
Received January 26, 2011; Accepted August 30, 2011
Decision Editor: Luigi Ferrucci, MD, PhD

P

HYSICAL performance and physical ability are themost important indicators of health status in elderly
people and are also closely related to the quality of life.
Declines in physical performance and physical activity,
whether from specific disease, fall, fracture, poor nutrition,or aging itself, are associated with future disability, morbidity, and death (1,2).
In recent years, many studies have examined the roles of
diet, protein, and vitamins in physical performance andphysical activity(3–5). Several studies have associated low
serum albumin concentration with deteriorated muscle
strength and function (6,7). Some other studies have examined the relationship between serum vitamin D level andphysical performance such as muscle mass, muscle strength,
handgrip, walking speed, and functional capacity (8,9).
Cesari et al. (3) examined the relationship between antioxidant vitamin intake (vitamin C, vitamin E, b-carotene, andretinol) and physical performance in elderly people andshowed significant positive correlations between mostantioxidants, especially vitamin C, and higher skeletal muscular strength in this group of people.
There are a number of mechanistic hypotheses about thepotential beneficial effects of antioxidant vitamins(10–12).
Vitamin C, vitamin E, b-carotene, and retinol are importantantioxidants that are not synthesized by humans and, therefore, are mainly supplied via dietary intake. Vitamin C
1

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SAITO ET AL.

Subjects and Methods

Study Subjects
The present cross-sectional study was carried out as part ofa project involving mass health examination of communitydwelling people (“Otasha-kenshin” in Japanese) aged 70 years
and older living in Itabashi-ku, Tokyo. “Otasha-kenshin,”which literally means “health examination for successful
aging,” is a comprehensive health examination program forcommunity-dwelling older adults aimed at preventing geriatric syndromes including falls and fractures, incontinence, mild
cognitive impairment, depression, and undernutrition (16).
The eligible subjects were all female residents, aged between 70 and 84 years, living in the Itabashi area, an urban
part of Itabashi-ku, Tokyo, Japan in October 2006. The population of women belonging to this age range and residingin the Itabashi area was 5937, and they were recruitedby invitation through postal mail. Of them, 1,112 women
applied for admission and 957 women ultimately participatedin this study. The participants who were taking vitamin C

supplements (n = 238) were excluded from the primary
analyses for examination of the relationship between plasma
vitamin C and physical performance because intake of supplements could strongly influence the plasma vitamin C
level. Thus, data from 655 subjects were ultimately used forthe primary analysis. However, data from the 238 supplement users were also used for subanalysis to determine
whether any relationship exists between vitamin C supplementation and physical performance.
All participants were examined at the Tokyo Metropolitan
Institute of Gerontology’s hall. Physical performance, blood
examinations, lifestyle assessments, and anthropometricmeasurements were performed as described below (9).
The present study was approved by the ethics review
committee of the Tokyo Metropolitan Institute of Gerontology. All subjects gave written informed consent.
Anthropometric Measurements
Height and weight of each participant were measured, andbody mass index was defined as weight/height2 (kg/m2). Body
composition measurements (percent body fat) were obtainedby segmental bioelectrical impedance using eight tactile
electrodes according to the manufacturer’s instructions (InBody 3.0; Biospace, Seoul, Korea). Measurements for the triceps surae muscles were taken between the knee and the ankle,
at the level of maximum circumference of the medial and anterior calf of the left leg of each participant at sitting position.
Physical Performance
Physical performance was assessed by muscle strength(handgrip strength), balance capability, and usual and maximal walking speeds, without prior practice before the actual
measurements. These assessments are routinely conducted
for the elderly community as described previously (9). Handgrip strength (kg) was measured once for the dominant handwith the subjects in a standing position using a Smedley’s
Hand Dynamometer (Yagami, Tokyo, Japan). Grip devices
were calibrated with known weights. Subjects held the dynamometer at thigh level and were encouraged to exert thestrongest possible force. Balance capability was measured interms of the length of time standing on one leg, that is, we
asked the subjects to look straight ahead at a dot 1 m in frontof them and to stand on the preferred leg with their eyes open
and hands down alongside the trunk. The time until balance
was lost (or maximum 60 seconds) was recorded. We used
the better of two trials in the analysis. To determine the walking speed, participants were asked to walk on a flat surface attheir “usual and maximum walking speeds.” Two marks
were used to delineate the start and end of a 5-m path. The
start mark was preceded by a 3-m approach to ensure that theparticipants achieved their pace of usual or maximum before
entering the test path. The participants were also instructedto continue walking past the end of the 5-m path for a further
3 m to ensure that their walking pace was maintained

Downloaded from biomedgerontology.oxfordjournals.org by guest on October 11, 2011(ascorbic acid) is a water-soluble antioxidant present in thecytosol and extracellular fluid and can directly react withfree radicals such as superoxide (O2·−) and hydroxyl radicals (·OH) (13,14). Each one of these oxygen-derived intermediates is considered highly reactive because of their
unstable electron configurations, which could attract electrons from other molecules, resulting in another free radicalthat is capable of reacting with yet another molecule. This
chain reaction is thought to contribute to lipid peroxidation,
DNA damage, and protein degradation during oxidative
stress. Oxidative damage is thought to play an importantrole in the age-related decline of functional activity in human skeletal muscle (15). Concentration of plasma vitaminC, which has potent antioxidant activity, is known to increase after exercise (4).
An increase in the amount of blood vitamin C content has
been used as an indicator of increased oxidative reaction (11).
Previous studies have examined the effects of vitamin C supplementation on physical performance and exercise (4,11).
Although findings from some of the previous studies do notsupport any beneficial effect of increased antioxidant intake
on physical performance, other studies have shown improved
recovery from exercise with antioxidant intake and havealso shown a preventive role of antioxidant supplementation
against oxidative damage. These studies were carried out on
athletes after heavy exercise. So far, however, there has been
no study examining the relationship between physical performance and blood levels of vitamin C, which may be a more
direct marker of the antioxidative ability of the human body.
The present study, to the best of our knowledge, is thefirst report that examines the relationship between plasma
vitamin C concentration and physical performance in Japanese community-dwelling elderly women.

3

VITAMIN C AND PHYSICAL PERFORMANCE

throughout the test path. The time taken to complete the 5-m
walk was measured by an investigator and used for analysis.
Walking test at maximum speed was repeated twice, and thefaster speed was recorded for the test.
All physical performance tests were performed between
9 am and 4 pm during the day. We have no data on the reproducibility of the measurements. To reduce interexaminer
variation, each test was conducted by the same staff member specifically trained for this study.

Lifestyle Assessment
Information regarding the participants’ general health (suchas medical history, smoking habits, alcohol drinking habits,
regular exercise habits, vegetable intake, fruit intake and use ofvitamin C supplement) was collected by interview, and historyof medical conditions including hypertension, stroke, heart attack, diabetes mellitus, and hyperlipidemia was self-reported.
Alcohol drinking habits of the subjects were classified as
nondrinker, current drinker, or ex-drinker. Smoking habitsof the subjects were classified using three categories: neversmokers, current smokers, and ex-smokers. The frequency
of vegetable and fruit intake was asked using four categories: almost every day, once every two days, once or twice
per week, and almost never. Subsequently, for analysis, thecategories were summarized as almost every day and others.
Statistical Analysis
Data were summarized as mean and standard deviation or
percentage values. The data of plasma vitamin C concentration was logarithmically transformed to approximate a normal distribution and was summarized as the geometricmean and geometric standard deviation.

Characteristic

Mean (SD)Age (y)Height (cm)Weight (kg)Body mass index (kg/m2)
Triceps surae muscle (cm)
Plasma vitamin C (mg/ml)*
Serum albumin (mg/dL)
Body composition
Percent body fat (%)
Physical performance tests
Handgrip strength (kg)
One leg standing with eyes open (s)Usual walking speed (m/s)
Maximal walking speed (m/s)

75.7 (4.1)
149.1 (5.7)
51.0 (8.3)
22.9 (3.4)
33.1 (2.8)
8.9 (1.5)
4.3 (0.2)
32.2 (7.0)
18.7 (4.4)
35.2 (23.5)
1.2 (0.3)
1.8 (0.4)%

Medical history
Hypertension
StrokeHeart attack
Diabetes mellitus
Hyperlipidemia
Alcohol drinking habit
Current
FormerNever
Smoking habit
Current
FormerNeverRegular exercise habit
Yes
No
Vegetable intake
Everyday
Others†Fruit intake
Everyday
Others†

50.7
6.6
21.2
9.0
34.7
25.3
5.0
69.6
3.7
5.7
90.7
69.2
30.8
84.2
15.8
81.8
18.2

Notes: Data of vitamin C supplement users were excluded.
* The geometric mean and geometric SD.
† Including participants taking vegetables/fruits not everyday or almost never.

The age-adjusted Pearson’s correlation coefficient between
the plasma vitamin C concentration and other factors were
calculated. The least square means and SEs adjusted forpotential confounders were calculated and compared between
categories by analysis of covariance. To examine the relationship between plasma vitamin C concentration and physicalperformance, statistical adjustment was done by analysis ofcovariance for variables (except for other physical performance variables) that were correlated to plasma vitamin C
concentration with p < .20. The same analyses were repeated
for the 238 users of vitamin C supplement. All statistical analyses were performed using the SAS (version 9.0; SAS Institute Inc., NC).
Results
Table 1 summarizes the basic characteristics of the subjects. As shown, the mean age (±standard deviation) of the

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Blood Examinations
Blood samples (nonfasting) were collected from the subjects
between 9 am and 4 pm during the day. There was no difference in mean plasma vitamin C concentration with regard to
the time of collection (data not shown). Venous blood samples
were drawn into Ethylene diamine tetraacetic acid tubes.
Plasma was then obtained by centrifugation at 3,000 rpm
for 15 min at 4°C and subsequently used for biochemical
assays. Plasma was treated with Ethylene diamine tetraacetic
acid to prevent the spontaneous vitamin C degradation. Next,
100 ml of the plasma was dispensed into storage tubes, towhich 450 ml of 3% metaphosphoric acid solution was added,
and the mixture was stored at −80°C until further use. Vitamin
C concentration was determined by an High performance liquid chromatography-electrochemical detection–based method(17). The analysis was carried out centrally in our laboratory.
Serum albumin concentration was measured by the Bromocresol Green method (Special Reference Laboratories Inc.,Tokyo, Japan). The coefficient of variation for serum albuminfound using this method was less than 1% (9).

Table 1. Characteristics of Study Subjects (N = 655)

4

SAITO ET AL.

Table 2. Correlation between Plasma Vitamin C Concentration and
Selected Factors (N = 655)
Correlation*
FactorAge
HeightWeightBody mass index
Triceps surae muscle
Serum albumin
Percent body fat
Handgrip strength
One leg standing with eyes open
Usual walking speed
Maximal walking speedrp−0.004
0.04
−0.05
−0.08
0.001
−0.04
−0.12
0.16
0.15
0.14
0.09

.91
.27
.19
.054
.98
.33
.002
<.001
<.001
<.001
.036

Notes: Number of subjects is slightly different for the selected factors becauseof missing values.
* Age-adjusted Pearson’s correlation coefficient between logarithm of vitamin C concentration and each factor.

Discussion
A previous study has shown an association between
higher daily dietary intake of vitamin C and skeletal muscle
strength in elderly people (3). Results described in the present study indicated that plasma vitamin C concentration was
positively related with muscle and physical performance incommunity-dwelling elderly women. To the best of ourknowledge, this is the first study showing a significant

Table 3. Relationship between Plasma Vitamin C Concentration and Physical Performance Adjusted for Potential Confounder
Quartile of plasma vitamin C level
Q1

Q2

Q3

Q4

Physical performance

Mean ± SE

Mean ± SE

Mean ± SE

Mean ± SE

Handgrip strength (kg), N
Age adjusted
Multivariate adjusted*
One leg standing with eyes open† (s), N
Age adjusted
Multivariate adjusted*
Usual walking speed (m/s), N
Age adjusted
Multivariate adjusted*
Maximal walking speed (m/s), N
Age adjusted
Multivariate adjusted*

154
17.70 ± 0.34
17.83 ± 0.34
162
31.44 ± 1.71
33.39 ± 1.74
146
1.13 ± 0.02
1.18 ± 0.02
146
1.70 ± 0.03
1.76 ± 0.03

159
18.75 ± 0.33
18.83 ± 0.32
163
33.98 ± 1.70
34.08 ± 1.67
154
1.19 ± 0.02
1.19 ± 0.02
154
1.76 ± 0.03
1.77 ± 0.03

154
18.75 ± 0.34
18.89 ± 0.33
16437.70 ± 1.70
37.63 ± 1.67
145
1.23 ± 0.02
1.22 ± 0.02
154
1.82 ± 0.03
1.80 ± 0.03

152
19.60 ± 0.34
19.60 ± 0.33
161
37.83 ± 1.71
37.50 ± 1.70
147
1.21 ± 0.02
1.21 ± 0.02
147
1.76 ± 0.03
1.75 ± 0.03

p for trend
.0001
.0004
.003
.049
.008
.23
.15
.94

Notes: Values are least squares mean and SE adjusted for the factors by analysis of covariance. Q1–Q4: first to fourth quartile groups of plasma vitamin C concentration, respectively.
* Adjusted for age, body mass index, percent body fat, hypertension, diabetes mellitus and fruit intake.
† Length of time standing on one leg with eyes open.

Downloaded from biomedgerontology.oxfordjournals.org by guest on October 11, 2011subjects was 75.7 ± 4.1 years. The geometric mean (geometric standard deviation) of plasma vitamin C concentration was 8.9 (1.5) mg/mL. The prevalence of women eating
vegetables everyday was 84.2% and those eating fruits
everyday was 81.8%.
The age-adjusted geometric mean of plasma vitamin C
concentration was significantly lower in subjects who had a
medical history of hypertension (8.53 vs 9.22, p = .0015)
and diabetes mellitus (7.59 vs 9.00, p = .002) as comparedwith those who did not. A history of stroke, heart attack, or
hyperlipidemia was not associated with plasma vitamin C
concentration. Subjects who took fruits every day had a significantly higher concentration of vitamin C than those who
did not (9.14 vs 7.78, p < .0001). Vegetable intake, alcohol
drinking habit and smoking habit were not related to plasma
vitamin C concentration (not shown in table).
Table 2 shows the age-adjusted correlations between theplasma vitamin C concentration and selected factors. As

shown, the plasma vitamin C concentration was positively
but modestly correlated with handgrip strength, length oftime standing on one leg with eyes open, as well as usual
walking speed and maximal walking speed, and modestly
inversely correlated with body mass index and percent bodyfat of the subjects.
Table 3 shows the relationship between plasma vitamin C
concentration and each physical performance after adjustingfor confounding factors. Results obtained after the adjustment for potential confounders confirmed that the plasma
vitamin C concentration was correlated with the handgrip
strength independently from the other factors (eg, p fortrend = .0004 after adjusting for age, body mass index,
percent body fat, hypertension, diabetes mellitus, and fruit
intake; Table 3). There was also a significant relationshipbetween the plasma vitamin C level and the subject’s lengthof time standing on one leg with eyes open after adjustments
for age, body mass index, percent body fat, hypertension,
diabetes mellitus, and fruit intake (Table 3; p for trend =.049). We did not observe any significant association between the plasma vitamin C level and the usual or the maximal walking speed of the subjects.
A subanalysis using data from the 238 vitamin C supplement users showed almost null relationship between handgrip strength and plasma vitamin C concentration (data notshown).

VITAMIN C AND PHYSICAL PERFORMANCE

habitual exercise reduces systemic inflammation and oxidative stress as the production of endogenous antioxidants areenhanced, acute exercise increases the generation of oxygen-free radicals and lipid peroxidation (4,25). Strenuous
physical performance can increase oxygen consumption by
10- to 15-folds over the resting state to meet the energy
demands and results in muscle injury (26). Prolonged submaximal exercise was shown to increase the amount ofboth whole-body and skeletal muscle lipid peroxidation
by-products; in the case of the former, the increase wasindicated by greater exhalation of pentane but not of ethane(4,27,28). Supplementation with vitamin C was shown todecrease the exercise-induced increase in the rate of lipid
peroxidation (27,28). Several studies suggested that oxidative damage may play a crucial role in the decline of functional activity in human skeletal muscle with normal aging(15). Consistent with this idea, several studies showed significantly lower plasma vitamin C level in the elderly population than in the younger adult population (29–31). Because
the plasma vitamin C levels in these apparently healthyelderly persons rose markedly after an oral dose of vitamin C,
their initially low plasma levels can be attributed to the low
intake rather than to an age-related physiological defect.
In fact, the relationship between handgrip strength andplasma vitamin C concentration was significantly different
between supplement users and nonusers, that is, an almost
null relationship in the former and a positive relationship in
the latter (data not shown). This finding suggested that vitamin C supplementation did not have any beneficial effect on
the physical performance and muscle strength despite the increased plasma level of vitamin C. A number of studies
reported that vitamin C supplement users had significantly
higher blood vitamin C concentration than non-users (29, 32,
33). Several studies have examined the effects of exercise onchanges in the serum vitamin C concentration (34–36).
Some other experimental studies have shown that vitamin C
supplementation can reduce symptoms or indicators of exercise-induced oxidative stress (37–40). However, the results
regarding vitamin C supplementation are equivocal, andmost well-controlled intervention studies report no beneficial
effect of vitamin C supplementation on either endurance orstrength performance (41,42). Likewise, vitamin C restriction studies showed that a marginal vitamin C deficiency did
not affect the physical performance (43). Although evidence
from a number of studies show that vitamin C is a powerfulantioxidant in biological systems in vitro, its antioxidant rolein humans has not been supported by currently available
clinical studies.
Vitamin C is especially plentiful in fresh fruits and vegetables. Plasma vitamin C concentration may be merely amarker for intake of other nutrients that are abundant infruits and vegetables. However, the statistical adjustment
for fruit intake did not attenuate the relationship between
plasma vitamin C and physical performance (Table 3),
suggesting that vitamin C did have some beneficial effects

Downloaded from biomedgerontology.oxfordjournals.org by guest on October 11, 2011

correlation between plasma vitamin C concentration andhandgrip strength and ability to stand on one leg with eyes
open. We, however, were unable to find any relationshipbetween skeletal muscle mass and plasma vitamin C concentration. Handgrip strength has been found to correlate wellwith the strength of other muscle groups and is thus a good
indicator of overall strength (18). Consistent with this idea,
handgrip strength was found to be a strong and consistentpredictor of all-cause mortality and morbidity of Activities
of Daily Living in middle-aged people (19). The handgrip
test is considered an easy and inexpensive screening tool
to identify elderly people at risk of disability. Handgrip
strength, an indicator of overall muscle strength, is thought
to predict mortality through mechanisms other than underlying disease that could cause muscle impairment (18,19). The
one leg standing test is one of the balance tests (20). The test
is a clinical tool to assess postural steadiness in a static position by quantitative measurement. Many studies have shownthat the decreased one leg standing time is associated withdeclines in Activities of Daily Living and increases in othermorbidities including osteoporosis and fall (20).
Our findings suggest that vitamin C may play an important role in maintaining physical performance and thereby
may help to improve healthy life expectancy in the elderly.
However, the usual and maximal walking speeds did not
relate to plasma vitamin C concentration. Walking speed
test may be an efficient tool in screening older persons withhigher risk of mortality and may easily identify highrisk groups in the community (21). Walking is a rhythmic,
dynamic, and aerobic activity of the large skeletal muscles
that confers multifarious benefits with minimal adverse
effects. Muscles of the legs, limbs, and lower trunk arestrengthened, and the flexibility of their joints are preserved(22). One of the reasons why walking speed was not related
to vitamin C concentration may be because walking
requires coordinated movements of arms, legs, and many
parts of the body rather than a simple muscle and balance
function. Previous reports showed that walking balance
function did not correlate with standing balance function(23). Although we did not find any clear association
between walking and plasma vitamin C concentration inthis study, vitamin C may still have effects on relatively
simple strength and balance functions.
One of the possible explanations for the observed relationship between vitamin C and physical performance, especially handgrip strength and the ability to stand on one
leg with eyes open, may be the potential protective effectsof the antioxidant vitamins against muscle damage (4,11).
Vitamin C is a six-carbon lactone that is synthesized fromglucose in the liver of most mammalian species, but not inhumans (12). Vitamin C is an antioxidant because, by donating its electrons, it prevents other compounds from being
oxidized (12). Thus, vitamin C readily scavenges reactive
oxygen and nitrogen species, thereby effectively protects
other substrates from oxidative damage (10,24). Although

5

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SAITO ET AL.

Funding
Ministry of Education, Culture, Sports, Science and Technology, Japan(grant-in-aid 16390187 for Scientific Research [B] and grant-in-aid[21790591] for Young Scientists [B]).
Acknowledgment
We offer special thanks to Dr. Satoshi Sasaki for his suggestions anduseful comments to this paper; we are indebted to Dr. Shoji Sinkai, Dr.
Yoshinori Fujiwara, Mr Toshiro Tango, Mrs Sachiko Imai, Mrs Turuko
Maekawa, Miss Erika Hosoi and the staff of the Otasha-kenshin who participated in this study.
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free radical. Ann N Y Acad Sci. 1975;258:231–237.
15. Pansarasa O, Castagna L, Colombi B, Vecchiet J, Felzani G,
Marzatico F. Age and sex differences in human skeletal muscle: role ofreactive oxygen species. Free Radic Res. 2000;33:287–293.
16. Suzuki T, Iwasa H, Yoshida H, et al. [Comprehensive health examination (“Otasha-Kenshin”) for the prevention of geriatric syndromes anda bed-ridden state in the community elderly. 1. Differences in characteristics between participants and non-participants]. Nippon Koshu
Eisei Zasshi. 2003;50:39–48.
17. Sato Y, Uchiki T, Iwama M, Kishimoto Y, Takahashi R, Ishigami A.
Determination of dehydroascorbic acid in mouse tissues and plasma
by using Tris(2-carboxyethyl)phosphine hydrochloride as reductant in
metaphosphoric acid/ethylenediaminetetraacetic acid solution. Biol
Pharm Bull. 2010;33:364–369.
18. Rantanen T, Guralnik JM, Foley D, et al. Midlife hand grip strength asa predictor of old age disability. JAMA. 1999;281:558–560.

Downloaded from biomedgerontology.oxfordjournals.org by guest on October 11, 2011

independently of other nutrients. A number of biochemical, clinical, and observational epidemiologic studies haveindicated that diets rich in fruits, vegetables, and vitamin C
may be of benefit for the prevention of chronic diseases
such as cardiovascular disease and cancer (44,45). Several
cohort studies have examined associations between plasma
vitamin C concentration and mortality from stroke or coronary heart disease (30,46,47). The effects of vitamin C
supplementation are, however, still unclear. A pooled study
suggested reduced incidences of coronary heart disease
events with higher intake of vitamin C supplement (48),while another study showed that a high intake of vitamin C
supplement is associated with an increased risk of mortality due to cardiovascular diseases in postmenopausal
women with diabetes (49). A randomized placebo controlled 5-year trial, however, did not show any significant
reduction in the mortality from, or incidence of, any typeof vascular disease or cancer (50). These studies, in fact,
have failed to demonstrate any benefit from such supplementation.
There are a number of potential weaknesses in our study
that should be mentioned here. The subjects used in thisstudy were not selected randomly from the study population, and they may be relatively healthy elderly women who
were able to come to the health examination hall from theirhomes. A previous study assessed the correlation of antioxidants with physical performance and muscular strength(3) and demonstrated that a higher daily intake of vitamin C
and carotene associated with skeletal muscle strength.
However, we have no data regarding the presence of otherdietary antioxidants in blood such as vitamin E, retinol, andcarotene. In our questionnaire, participants were asked torespond “Yes” or “No” to whether they took supplements,
and not about the frequency and quantity of intake of the
supplements. Thus, we were unable to examine the reason
why plasma vitamin C was not related to the handgrip
strength in the supplement users by considering the dose ofvitamin C they took.
This study was a cross-sectional study and, therefore,
does not provide cause/effect relationships, although wedemonstrated a significant correlation between physicalperformance and concentration of plasma vitamin C. Therefore, longitudinal follow-up studies and controlled clinical
trials are necessary to confirm the role of plasma vitamin C
and physical performance of the elderly women. These limitations should be considered in future studies.
In conclusion, we found a strong correlation of a higher
plasma vitamin C concentration with handgrip strength andone leg standing time in community-dwelling elderly
women. Although the elderly are prone to vitamin C deficiency, and they appear to have a higher dietary requirement for vitamin C, the beneficial effects of vitamin C
supplementation to maintain physical performance in elderly people are equivocal and thus, need further in-depth
studies.

VITAMIN C AND PHYSICAL PERFORMANCE

36. Duthie GG, Robertson JD, Maughan RJ, Morrice PC. Blood antioxidant status and erythrocyte lipid peroxidation following distance running. Arch Biochem Biophys. 1990;282:78–83.
37. Maxwell SR, Jakeman P, Thomason H, Leguen C, Thorpe GH.
Changes in plasma antioxidant status during eccentric exercise and theeffect of vitamin supplementation. Free Radic Res Commun. 1993;19:
191–202.
38. Jakeman P, Maxwell S. Effect of antioxidant vitamin supplementation
on muscle function after eccentric exercise. Eur J Appl Physiol Occup
Physiol. 1993;67:426–430.
39. Kaminski M, Boal R. An effect of ascorbic acid on delayed-onset
muscle soreness. Pain. 1992;50:317–321.
40. Bryer SC, Goldfarb AH. Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stressto eccentric exercise. Int J Sport Nutr Exerc Metab. 2006;16:
270–280.
41. Thompson D, Williams C, Kingsley M, et al. Muscle soreness anddamage parameters after prolonged intermittent shuttle-runningfollowing acute vitamin C supplementation. Int J Sports Med. 2001;
22:68–75.
42. Gey GO, Cooper KH, Bottenberg RA. Effect of ascorbic acid on
endurance performance and athletic injury. Jama. 1970;211:105.
43. van der Beek EJ, van Dokkum W, Schrijver J, Wesstra A, Kistemaker C,
Hermus RJ. Controlled vitamin C restriction and physical performance in volunteers. J Am Coll Nutr. 1990;9:332–339.
44. Ness AR, Powles JW. Fruit and vegetables, and cardiovascular disease:a review. Int J Epidemiol. 1997;26:1–13.
45. Genkinger JM, Platz EA, Hoffman SC, Comstock GW, Helzlsouer KJ.
Fruit, vegetable, and antioxidant intake and all-cause, cancer, and cardiovascular disease mortality in a community-dwelling populationin Washington County, Maryland. Am J Epidemiol. 2004;160:1223–
1233.
46. Yokoyama T, Date C, Kokubo Y, Yoshiike N, Matsumura Y, Tanaka H.
Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a Japanese rural community. The
Shibata study. Stroke. 2000;31:2287–2294.
47. Gale CR, Martyn CN, Winter PD, Cooper C. Vitamin C and risk ofdeath from stroke and coronary heart disease in cohort of elderly people. BMJ. 1995;310:1563–1566.
48. Knekt P, Ritz J, Pereira MA, et al. Antioxidant vitamins and coronary
heart disease risk: a pooled analysis of 9 cohorts. Am J Clin Nutr.
2004;80:1508–1520.
49. Lee DH, Folsom AR, Harnack L, Halliwell B, Jacobs DR Jr. Does
supplemental vitamin C increase cardiovascular disease risk in womenwith diabetes? Am J Clin Nutr. 2004;80:1194–1200.
50. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection
Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23–33.

Downloaded from biomedgerontology.oxfordjournals.org by guest on October 11, 2011

19. Rantanen T, Volpato S, Ferrucci L, Heikkinen E, Fried LP,
Guralnik JM. Handgrip strength and cause-specific and total mortality
in older disabled women: exploring the mechanism. J Am Geriatr Soc.
2003;51:636–641.
20. Michikawa T, Nishiwaki Y, Takebayashi T, Toyama Y. One-leg standing
test for elderly populations. J Orthop Sci. 2009;14:675–685.
21. Rolland Y, Lauwers-Cances V, Cesari M, Vellas B, Pahor M,
Grandjean H. Physical performance measures as predictors of mortality in a cohort of community-dwelling older French women. Eur J
Epidemiol. 2006;21:113–122.
22. Morris JN, Hardman AE. Walking to health. Sports Med. 1997;23:
306–332.
23. Shimada H, Obuchi S, Kamide N, Shiba Y, Okamoto M, Kakurai S.
Relationship with dynamic balance function during standing andwalking. Am J Phys Med Rehabil. 2003;82:511–516.
24. Halliwell B. Vitamin C: antioxidant or pro-oxidant in vivo? Free Radic
Res. 1996;25:439–454.
25. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise.
J Appl Physiol. 2005;98:1154–1162.
26. Clarkson PM. Antioxidants and physical performance. Crit Rev FoodSci Nutr. 1995;35:131–141.
27. Gee DL, Tappel AL. The effect of exhaustive exercise on expired
pentane as a measure of in vivo lipid peroxidation in the rat. Life Sci.
1981;28:2425–2429.
28. Davies KJ, Quintanilha AT, Brooks GA, Packer L. Free radicals andtissue damage produced by exercise. Biochem Biophys Res Commun.
1982;107:1198–1205.
29. Blanchard J, Conrad KA, Mead RA, Garry PJ. Vitamin C disposition
in young and elderly men. Am J Clin Nutr. 1990;51:837–845.
30. Fletcher AE, Breeze E, Shetty PS. Antioxidant vitamins and mortality
in older persons: findings from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older
People in the Community. Am J Clin Nutr. 2003;78:999–1010.
31. Jacob RA, Otradovec CL, Russell RM, et al. Vitamin C status andnutrient interactions in a healthy elderly population. Am J Clin Nutr.
1988;48:1436–1442.
32. Sinha R, Block G, Taylor PR. Determinants of plasma ascorbic acid ina healthy male population. Cancer Epidemiol Biomarkers Prev.
1992;1:297–302.
33. Newton HM, Schorah CJ, Habibzadeh N, Morgan DB, Hullin RP. The
cause and correction of low blood vitamin C concentrations in the elderly. Am J Clin Nutr. 1985;42:656–659.
34. Gleeson M, Robertson JD, Maughan RJ. Influence of exercise on
ascorbic acid status in man. Clin Sci (Lond). 1987;73:501–505.
35. Camus G, Felekidis A, Pincemail J, et al. Blood levels of reduced/oxidized glutathione and plasma concentration of ascorbic acid during
eccentric and concentric exercises of similar energy cost. Arch Int
Physiol Biochim Biophys. 1994;102:67–70.

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日本人の食事摂取基準における目安量は健康人の摂取の中央値 でよいのか ?
Adequate intakeは D fOr宙 tamin D;how is it to be determined?

本稿 は トビックスの原稿 として書 い た ものであ るが最近 の話題 を取 り上 げて概説 す るとい う本来 の トピ ック
スではない 著者 らがふだん疑 間に感 じてい る点を述 べ

D不 足の意義が考慮 されるようになつて きた と思 われる
例 えば,第 六次改訂 日本人の栄養所要量 にお い ては,「 20〜 46歳 の 人で 1 7μ g(681U)ノ 日以下の ビタミン D摂 取て, ビタ ミン学会会員諸先 生の ご意見 を承 りた い とい う
意図で書 い た ものであ り,い わば著者 らの個人的見解 を述べ たもので あ ることを,最 初 にお ことわ りしてお くを数 年間続 けると骨軟化症が認 め られるようにな り,25
μg(1001U)/日 では発生 はみ られなかつた との報告があるので,2 5μ g(1001U)/日 とした」と述べ られてお り, この記述 はクル病 骨軟化症防止 を念頭 にお い た,欠 乏症
対策 と理解 される しか し,現行 の 2010年 版 におい ては「成 人, と くに高齢者 にお いて, ビタミン D欠 乏 とはい,

ビタミンの欠乏 によ り,古 典的欠乏症が起 こる

ビタ

ミン Bl欠 乏による脚気 ウェルニ ッケ脳症,ナ イアシン欠乏 によるペ ラグラ, ビタミン C欠 乏 による壊血病, ビ
タミン K欠 乏 による出血傾向な ど 多数 の有名な例がある 少な くともわが国にお い ては, これ らの 多 くはほぼ克服 された といって よいが,近 年 ビタミンの新たな意義が注 目されてい る
古典的な欠乏症 を起 こす ほ どの ビ タミン欠乏 (dendc̲
り軽 度 の ビ タ ミ ン不足 (insumcicncy)で あ って も,")よ
疾患 の リス クが増加す る
ビタミン Dを 例 に述 べ る と,骨 は タ ンパ ク質 (主 に コ
ラーゲ ン)の 枠組み の上 に, リン酸 カルシウムが 沈着 して(石 灰化)形 成 される ビタミン Dの 最 も基本的な作用は,

腸管か らの カルシウム リン吸J又 促進 なので, ビタミンD欠 乏の結果 ,石 灰 化障害が起 こるのが クル病 骨軟化症である
一方, よ り軽度の不足 の場合,石 灰化障害 は起 こ らないが,骨 粗豚症 骨折 の リス ク増加が起 こる 副甲1大 腺ホル
モ ン (PIH)と ビ タミン Dは 血清 カルシウム濃度 を維持するのが重要 な役割であ り,PTHは ビタ ミン Dの 活性化 を促進 し,活 性型 ビ タミンDは PrH分 泌 を抑制す るとい う
形で,両 者 は協調 して,血 清 カルシウム濃度を維持するのに作用す るが,作 用が過剰 となって,高 カルシウム血症を起 こさない ように, フイー ドバ ック調節 を受けている し
たが って, ビ タミ ン D不 足状態 にお い ては,PrH分 泌 が克進 し,そ れによって骨吸収が尤進 して,骨 粗穆症 をきた
す なお, ビ タミン D栄 養状態 の最 もよい指標 は:血 中
25ヒ ドロキシ ビタミン D(250HD)濃 度 であ る
わが 国にお い て,残 念 なが らまだまだ ビタミ ン不足の重要性が十分認識 され て い るとは言 いがた い状況 で あるが,そ の重要性が わか りに くいの も事実である 脚気
クル病 壊 血病 と列挙す れば明 らかなよ うに,古 典的欠乏症 は外 見上 の異常 を伴 うので,個 々の人 ごとにその有無が判定 で きる しか し, ビタミ ン D不 足 の場合 ,外 見
上 は何 の異常 もな く,疫 学調査 によ り初 めて疾患 リスク
が1曽 加 してい ることが 明 らかになる
食事摂取基準 にお いて も,改 訂 の度 に徐 々 に ビタミン,

えな い ものの ビタミン D不 足の状態が長期 にわたって続くと,血 中副 甲状腺 ホルモ ン濃度が上昇 し,骨 密度が低下する したが って,正 常なカルシウム利用能が保持 され血中副甲状腺 ホルモ ン濃度が上昇 しない血中 25‑ヒ ドロキ
シビタミン D濃 度を維持す るのに必要 な量の ビ タミン D,を摂 取す ることが.骨 折や骨粗修症 などの予防の観点か
ら重要 と考 え られる しか し,そ の血 中濃度 を与 える ビ
タミン D摂 取量 に関す る根拠 は乏 しいため,そ の血 中濃度 を維持 してい る と考 えられる集 団 のビタミン D摂 取量の中央値 を目安量 と したJと の記述が み られ, これは明 ら
かに, ビタ ミン D不 足 による骨折 リス ク増加対策 をも意識 した ものである この ように,不 足 をも考慮す る時代になる と, 目安量の策定 にお い て,欠 乏対策だけを考 え
てい た 時代 にはなかった,新 た な問題点 を生 じて きたのではないか とい うのが ,著 者 らが最近考 えてい ることである
目安量の策定理論 に関 して,2010年 版 の記述 を引用す
ると,「 特定 の集団にお いて,生 体指標等 を用 い た健 康状
態 の確認 と当該栄養素摂取量 の調査 を同時 に行 い。そ の
結果か ら不足状態 を示す者力ヽまとん ど存在 しない摂取量を推測 し,そ の値 を用 い る 対象集団 で不足状態 を示 す
者が ほ とん ど存在 しない場合 には栄養素摂取量 の 中央値を用 い る 」とされてい るビ タミン Dに 関す る具体的な数字 として,「 成人にお いて血 中副 甲状腺 ホルモ ン濃度 の上 昇 を抑制 し,骨 密度 の低下 を予防す るのに最低 限必要 な血中 25‐ ヒ ドロキシ ビタ
ミン D濃 度 は 50 nmol几 前後であると考えられる」と書かれてい る
表 1は ,食 事摂取基準 2010年 版 の ビ タ ミン Dの 項 に示 されて い る表 を改変引用 した ものであ る 確 かにここで 引用 されて い る論文 にお い て,50〜 69歳 の 集団 における平均 250HD濃 度 は 50 nmo1/L(20 ng/mL)を 越 えて いるが,平 均値が 50 nlnol圧 (20nノ mL)を 越 えてい るか らとい って,「 特定 の集団において不足状態 を示 す人 がほ とんH号 (11月 )2011〕

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表 1 日本人女性 を対象 として血清 25‐ ヒ ドロキシビタミンD濃 度を測定 した報告
文献

人数

7

117

調査地域

m清 25ヒ ドロ キ シ ビ タ ミ ン D濃 度

50 nmo1/L(nll101 L)

未 満 者 の 割合

新潟 (9月 )83■ 2267%

新潟 (2月 )547± 94309%

長野 (限 定 せ ず )501± 136

新潟 (9月 )80± 16新潟 (9月 )フ86± 182

497%
30%
58%

新潟 (2月 )597± 171新潟 (2月 )599± 170

新潟 (2月 )591± 161

285%
280%
286%

新潟 (11月 )556± 146351%

対応す る年齢 階級 の ビタ ミン D
摂取量 中央値 (μ ゾ 日)

日本人の食事摂取基準 2010年 版 1よ り改変引用 した「50 nmo1/L未 満者の割合」は 正規分布するものと仮定して,平 均値 標準偏差に基づ き 著者らが計算 したものである

仮 に 250HD濃の度が正規分布す るもの として,摂 取基準 表 に示 されてい る平均 ±標準偏差 の値 に基 づ き,50 nlnol厄 を下 回る
対象者 の 割合 を概算 した結果 を,「 50 nlllol几 未満者 の 割
合 Jと して加筆 した 一見 して明 らかに,多 くの文献 におい て,50 nmol几 未満者 の割合 はかな り高 い値 で あ った
す るとこれ らの集団 は ビタミン Dが 充足 してい る集団でど観 察 されない」と言 えるのであろうか

あるか ら,そ れに対応す る性 年齢階級 におけるlI取 の中央値 をもって 目安量 として もよいのだろ うか とい う疑間が生 じて くる
そうする と, ビタミン Dの 摂取基準策定 にどうい う方
法論 を用 い ることがで きるので あ ろ うか 2010年 カルシ
ウム ビ タミン Dに つい て,ア メ リカ カナダの食事摂取基準が全面改訂 された 方法論 か らみ ると, 目安量で
はな く,推 定平均必要量 (E思 )推 奨量 (RDA)に 変 わったのが大 きな変化である これ らは欠乏 充足実験 によって定 め られるの力'原 則 であ り,EARは 当該集団にお い て50%の 人が必要量 を満 たす量 ,RDAは ほ とん どの人 (97〜 98%)が 満 たす量 として定 め られる このアメリカ カ
ナダの食事摂取基 準 にお い ては,骨 の健康 を維持す るための血 中 250HD濃 度 (50 nmol L)を 基 に, ビ タ ミン Dの摂取量が算定 されてお り,RDAは ,血 中 250HD濃 度 と摂取量 の容量依存性試験 の結果か ら定め られてい る ア
メリカ カナダの食事摂取基準 における RDAは ,1歳 から 70歳 まで 6001U/日 となってい る カ ー方 わが 国の平成のでは な く,従 来 の 目安量の概念 に従 って策定す るな らば,現 行 の摂取基準 の よ うな定 め方 にな らざるを得 ないであろう しか し,栄 養素 の不足 をも考慮 した場合の摂取基準策定 にお い て,そ の摂取 の 中央値 をもって 目安量とす ることがで きるような健常 人 とい うものはそ もそ も存在す るので あ ろ うか 一 見 して外見上 の異常 を伴 わ ない対象者であ って も,不 足 の リスクの低 い 人か ら高 い 人
まで連続 的 に分布する と考 える方が よ り摂取基準 の精神に合致す るように思 われてな らない
ビタミン不足 をも考慮 しなけれ ば な らない時代 にお いては, 目安量策定 の方法論 に関 して,再 検討 の時期 が 来
てい るのではない だろ うかκ″ Zο ras:Dtta″ rcfcrcncc llltakcs,adcquatc intakc,宙 ta‐

mln D,mcdian,ostcopOrosis
lDcpartlllcnt ofFood and Nu血

Univcrsi″

KiyOshi Tanakal Akiko Kun abara2

1京都女子大学家政学部食物栄養学科

2大 阪樟蔭女子大学学芸学部人間栄養学科

田中

清 1,乗 原晶子 219年 国民健康栄養調査 の結果 を見ると,成 人で 6001U日
摂取で きてい るのは,集 団 の上 位 10%に 限 られて い るのが実際であ り', この数字 を日本 に適用で きるのか どうかについ ては,多 くの議論が必要 で あ るが , ビタ ミン不足をも考慮 した場合, この策定 の方法論 は注 目す べ きものと思われる
誤解 の ない よ うに一言述べ てお くと,著 者 らは 2010年
版 に定め られた 目安量 の値 が 不適切 であると述 べ ているК,oto WOmen'sU面 verslサ2Dcpartmcnt of Hcalth and Nutrition,Osakàon
Shoinヽ、mcn s

参考文献
1)第 一 出 版 編 集 部 編 :厚 生 労働 省 策 定 日本 人 の 食事 摂 取 基 準(2010年 版 )第 一 出版

東京 20092)Ins● ●lte of Medicin 201l Dieta,reFerence intakes for calcitl n andvitamin D WashingtOn,DC:Tlle National Academies Press3)健 康

栄 養情報研 究会 :国 民健康

生労働省 国民健康

栄 養 の現状― 平成 19年 厚栄養調査 報告― ,第 一 出版

東京 2009