Bioscience, Biotechnology, and Biochemistry

ISSN: 0916-8451 (Print) 1347-6947 (Online) Journal homepage: https://www.tandfonline.com/loi/tbbb20

Light rhythmic exercise with dietary milk fat

globule membrane improves physical fitness in
an elderly Japanese population: a double-blind
randomized placebo-controlled trial

Yasuko Yoshinaka, Satoko Soga, Noriyasu Ota, Keiichi Yokoyama, Yosuke

Yamada & Misaka Kimura

To cite this article: Yasuko Yoshinaka, Satoko Soga, Noriyasu Ota, Keiichi Yokoyama,
Yosuke Yamada & Misaka Kimura (2018) Light rhythmic exercise with dietary milk fat globule
membrane improves physical fitness in an elderly Japanese population: a double-blind randomized
placebo-controlled trial, Bioscience, Biotechnology, and Biochemistry, 82:4, 677-682, DOI:
10.1080/09168451.2017.1412248

To link to this article: https://doi.org/10.1080/09168451.2017.1412248

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Bioscience, Biotechnology, and Biochemistry, 2018
VOL. 82, NO. 4, 677–682
https://doi.org/10.1080/09168451.2017.1412248

SPECIAL ISSUE: FUNCTIONAL FOOD SCIENCE

Light rhythmic exercise with dietary milk fat globule membrane improves
physical fitness in an elderly Japanese population: a double-blind randomized
placebo-controlled trial
Yasuko Yoshinakaa, Satoko Sogab, Noriyasu Otab, Keiichi Yokoyamaa, Yosuke Yamadaa and Misaka Kimurac
a
Faculty of Business Administration, Kyoto Gakuen University, Kameoka, Japan; bBiological Science Research, Kao Corporation, Ichikai-machi,
Japan; cFaculty of Health and Medical Sciences, Kyoto Gakuen University, Kameoka, Japan

ABSTRACT ARTICLE HISTORY

This study aimed to investigate the efficacy of home-based, light gymnastic exercise plus dietary Received 17 September 2017
milk fat globule membrane (MFGM) intake on physical fitness of an elderly Japanese sample in Accepted 19 November 2017
a pilot, double-blind, randomized, placebo-controlled trial. Seventy-one subjects (male, n = 13;
KEYWORDS
female, n = 58) were randomly assigned into two groups: placebo (n = 35 [male, n = 6; female, Aging; gymnastic exercise;
n  =  29]) and MFGM group (n  =  36 [male, n  =  7; female, n  =  29]). The intervention was eight life expectancy; milk fat
weeks. Subjects ingested either MFGM (1  g/day) or placebo tablets daily and engaged in an globule membrane; physical
exercise program daily. Physical function tests were performed at baseline and after four and fitness
eight weeks. Foot tapping and open–close stepping scores significantly increased from baseline
to eight weeks in the MFGM group. Study results suggest daily MFGM ingestion might further
enhance the effects of light-intensity exercise in healthy elderly people.

The elderly population in Japan is projected to continue
to increase, while the total population of the country
declines due to increase in longevity and decline in
birth rate. Increasing medical and long-term care insur-
ance expenses are a serious concern in Japan. In such
a society, the extension of life expectancy [1,2] as well
as the extension of healthy life expectancy [3,4], which
is defined as “a period during which an individual can
live daily life without being restricted by health prob-
lems,” is an essential task. The Ministry of Health, Labor
and Welfare established “Health Japan 21,” a national
policy aimed at achieving the extension of healthy life
expectancy [5]. This policy promotes efforts to increase
physical activity and good eating habits. An increase in
daily physical activity has been shown to reduce the risk
of mobility disability, bedridden state, and death [6–9];
and improve mental health and quality of life [10–12].
A decline in motor function and physical activity is
commonly observed in the elderly [13–18]. In some
cases, reduced motor function may cause a decline in
physical activity, and vice versa. Regardless, both are
related to each other and can lead to a negative spiral,
eventually requiring long-term care; this is called the
frailty cycle [19,20]. The core elements of the frailty cycle
include changes in the quality and quantity of skele-
tal muscle mass (i.e. sarcopenia [21–23]: age-related
muscle weakness) [19,24–26]. Avoiding or preventing
the frailty cycle is important in extending the healthy life
expectancy of the elderly. In other words, maintaining
skeletal muscle mass, as well as improving its function,
is important.
The functional unit of muscle contraction is the
motor unit, which is composed of a motor nerve and
muscle fibers. The skeletal muscle fibers contract upon
receiving signals from the motor nerve. The numbers of
motor units decrease dramatically after age 50–60 years
[27,28]. Muscle strength and agility have been found to
improve by regular exercises and consumption of milk
fat globule membrane (MFGM), both of which improve
the motor unit in the healthy middle-aged and elderly,
as well as in the 30–40 years old [29–32]. MFGM seems
to further enhance the effects of exercise. However,
implementing the combination of exercise and MFGM
in routine life seems difficult, because the exercises in
previous studies were supervised by a full-time trainer
at a fitness facility to ensure participant safety and com-
pliance. Developing a simple and light exercise program
that can be performed daily by each individual at home
seems necessary so that more people are able to improve
their motor functions. Thus, the objective of this study
was to develop a simple and light rhythmic gymnas-
tic exercise program that each elderly individual could
perform at home and to verify its combined effects with
MFGM intake on motor function.

CONTACT  Noriyasu Ota  ota.noriyasu@kao.co.jp

© 2017 Japan Society for Bioscience, Biotechnology, and Agrochemistry
678   Y. YOSHINAKA ET AL.
Materials and methods
Subjects
Thirteen male and 58 female healthy subjects were
enrolled in this study. Subjects were excluded from the
study if they had coronary heart disease, uncontrolled
hypertension, or severe damage to the locomotive organs.
Written informed consent was obtained from the subjects
after being fully informed about the details and methods
of this study. The study was performed under the super-
vision of an occupational health physician, in accord-
ance with the regulations of the Kyoto-gakuen University
Ethics Committee for Clinical Studies and in conformity
with the Helsinki Declaration (approval number: 28–4).
Study protocol
A double-blind, randomized, controlled design was used.
The randomization procedure was conducted by a person
who was not involved in the study, and the subjects and
test staff remained unaware of the assignments through-
out the study. The subjects were randomly assigned into
one of two groups: one group received placebo tablets
(placebo group, n = 35; 6 male and 29 female), and the
other received MFGM tablets (MFGM group, n = 36; 7
male and 29 female). The baseline characteristics of the
subjects (Table 1) were similar between groups. Subjects
ingested either the MFGM-containing tablets or the pla-
cebo tablets daily throughout the eight-week study period
and engaged in gymnastic exercise at home daily. The sub-
jects were instructed to continue their usual exercise hab-
its and food intake, especially milk and dairy products,
throughout the study period. In addition, ingestion of a
dietary supplement that might affect physical fitness was
prohibited during the study. To monitor their dairy intake,
they were instructed to record the intake of milk and/or
dairy products. Physical function tests were performed at
baseline, four, and eight weeks of the intervention.
MFGM
The tablets containing 167 mg MFGM/tablet were pro-
duced by a direct compression of mixtures. The placebo
tablet was prepared using whole milk powder instead
of MFGM. The placebo tablets had indistinguishably
similar shape, taste, and texture as the MFGM tablets.
Table 1. Characteristics of study subjects.
Women
Total (n = 71) (n = 58) Men (n = 13)
Age (years) 72.3 ± 5.2 71.6 ± 5.1 75.6 ± 4.6
Height (cm) 154.5 ± 7.8 151.9 ± 5.6 166.4 ± 4.5
Body weight (kg) 51.6 ± 7.5 49.8 ± 6.7 59.4 ± 5.5
Body mass index 21.6 ± 2.7 21.6 ± 2.9 21.5 ± 1.9
(kg/m2)
Muscle mass (kg) 35.7± 5.7 33.4 ± 2.6 46.0 ± 3.9
Body fat ratio (%) 26.4 ± 6.9 28.2 ± 6.1 18.1 ± 3.0
Values are means ± SD. Body weight, muscle mass, and body fat ratio were
measured using a bio-impedance body fat analyzer (BC-720; Tanita, Co.,
Tokyo, Japan).
The MFGM and whole milk powder compositions were
analyzed at Japan Food Research Laboratories (Tokyo,
Japan). The MFGM composition was 53.1% protein,
26.5% fat, 11.3% carbohydrate, 16.0% phospholip-
ids (4.95% phosphatidylcholine, 5.10% phosphatidy-
lethanolamine, 1.62% phosphatidylinositol, 1.90%
phosphatidylserine, 3.81% sphingomyelin, and other
phospholipids), 4.9% ash, and 4.2% moisture. The com-
position of the whole milk powder was 26.8% protein,
26.0% fat, 38.3% carbohydrate, 0.322% phospholipids
(0.067% phosphatidylcholine, 0.076% phosphatidy-
lethanolamine, 0.035% phosphatidylinositol, 0.044%
phosphatidylserine, 0.067% sphingomyelin, and other
phospholipids), 5.8% ash, and 3.1% moisture.
Each subject consumed six MFGM (1 g MFGM/day)
or placebo (1 g whole milk powder/day) tablets daily for
eight weeks. The subjects were instructed to consume the
tablets within one hour before the gymnastic exercise or
during daily physical activity.
Light rhythmic gymnastic exercise
Each subject underwent light rhythmic gymnastic exer-
cise daily for eight weeks at home without any supervi-
sion by an expert trainer. A lack of exercise and aging
depress the signal transmission from nerve to muscle.
The present gymnastic exercise was designed to stimu-
late the coordination of nerve and muscle in motor units.
The routine consists of some light intensity movements,
such as raising arms and legs, and multiple body parts
rhythmically in parallel at 120 beats for 1 min [33].
Physical function test
Physical function tests were performed at weeks 0, 4, and
8 at the same time of day. Alcohol ingestion and intense
exercise were prohibited the day before the tests. Physical
function testing consisted of anthropometric measure-
ments, walking speed, isometric muscle strength, step-
ping, and open–close stepping tests.
Anthropometric measurements and daily activity
Height was measured before the intervention. Body
weight, body fat ratio, and muscle mass were meas-
ured using a bio-impedance body fat analyzer (BC-
720; Tanita, Co., Tokyo, Japan). The daily amounts of
activity were measured using an electronic pedometer
(GT-40; ACOS, Co., Nagano, Japan) during the inter-
vention period, and energy expenditure was calculated
through the daily activities.
Walking speed
The 10-m obstacle walking speed test is an indicator of
lower muscle strength and general balance during walk-
ing. This test was used to measure the time that subjects
 BIOSCIENCE, BIOTECHNOLOGY, AND BIOCHEMISTRY   679

required to step over six obstacles (height: 20  cm) at usual exercise habits (data not shown). The average daily
2-m intervals twice. The shorter time value was used intake of milk and dairy products, such as milk bever-
for analyses [34]. ages, yogurt, and cheese, at baseline and 8 weeks in the
MFGM group were 218 ± 123 and 207 ± 114 g/day; in the
Isometric muscle strength placebo group, they were 179 ± 102, and 191 ± 94 g/day,
respectively. No significant inter- or intragroup differ-
Isometric knee extension strength of a dominant leg ences were noted in dairy intake. No overall changes
was measured using the Force Measurement System in body weight, whole body muscle mass, and body fat
for One Leg (T.K.K.5715; TAKEI Scientific Instruments ratio were observed during the intervention (Table 2).
Co., Niigata, Japan) equipped with tensiometer D
(T.K.K.5710e; TAKEI Scientific Instruments Co.,
Effect on physical fitness
Niigata, Japan) [35–37]. The subjects performed maxi-
mal 3-s voluntary contractions at 90° knee flexion. After an eight-week intervention, no significant group-
by-time interaction was observed. Significant inter-
Foot tapping and open–close stepping tests or intragroup differences were not noted in the 10-m
obstacle walking speed and the isometric knee extension
Foot tapping and open–close stepping tests were per- strength (Table 3). Significant time effects were found for
formed as an indicator of coordination ability of nerve the foot tapping and open–close stepping tests. The foot
and muscle such as agility. In the foot tapping test, tapping and open–close stepping scores were measured
subjects were seated and tapped the sole of the foot as indicators of coordination ability such as agility, and
alternately as quickly as possible, and the maximum fre- they significantly increased from baseline to eight weeks
quency of taps was measured in 10 s [38]. In the open– in the MFGM group; no significant change was noted for
close stepping test, subjects were seated and placed their these parameters in the placebo group. In addition, the
feet on a simple measurement board (width: 30 cm). The change from baseline of the open–close stepping score
subjects opened their legs and spread the feet as quickly was significantly higher in the MFGM group than in the
as possible, touching the floor beside the board with the placebo group at eight weeks (Table 3).
forefoot, and then they quickly returned the feet and legs
to their original position [39]. The maximum frequency
Discussion
of open and close was measured in 20 s [40].
We have shown the combination of MFGM intake and
Statistical analysis exercise habits improves muscle function in healthy
middle-aged and elderly people [30–32] through
Data were analyzed using two-way repeated measures improvement of neuromuscular junction (NMJ) forma-
analysis of variance, followed by Dunnett’s test to com- tion [41]. In other words, MFGM can further enhance
pare within-group baseline values and values obtained the effects of exercise. In our previous studies [30–32],
after four and eight weeks (Stat View for Windows ver- each subject underwent exercise training (i.e. treadmill
sion 5; SAS Institute, Cary, NC). In a separate analysis, and bicycle exercises) for 30 min/day, twice weekly under
percent changes in values from baseline to the end of the the guidance of a fitness trainer at a gym to ensure safe
intervention were evaluated using an unpaired t-test for performance of certain levels of exercise. In addition, the
intergroup comparisons. Statistical significance was set subject’s compliance with the MFGM or placebo tablets
at a probability level of p < 0.05. All data are expressed
as means ± SD. Table 2. Changes in anthropometric variables before and after
the intervention.
Results Placebo MFGM
Body weight (kg) Baseline 52.1 ± 8.1 51.4 ± 7.1
Subjects’ compliance and anthropometric values 4 weeks 51.9 ± 7.8 51.3 ± 6.9
8 weeks 51.9 ± 7.9 51.2 ± 6.8
The subjects tolerated the intervention protocol well, and Body mass index (kg/m2) Baseline 21.8 ± 2.5 21.6 ± 3.1
4 weeks 21.7 ± 2.4 21.6 ± 3.1
no adverse effects were reported from the MFGM or 8 weeks 21.7 ± 2.4 21.5 ± 3.0
placebo tablets. Nine subjects (placebo = 5, MFGM = 4) Muscle mass (kg) Baseline 36.0 ± 6.5 35.3 ± 4.9
were unable to complete the study after randomiza- 4 weeks 35.6 ± 6.4 35.6 ± 5.0
8 weeks 35.5 ± 6.4 35.4 ± 5.0
tion because of personal reasons. Energy expenditures Body fat ratio (%) Baseline 26.7 ± 6.9 26.8 ± 7.5
through daily activities calculated using an electronic 4 weeks 27.1 ± 7.5 26.1 ± 7.7
8 weeks 27.4 ± 7.5 26.3 ± 7.4
pedometer during the intervention were 1669  ±  192
Values are means ± SD of 30 subjects from the placebo group (women,
and 1634  ±  126  kcal/day in the placebo and MFGM n = 25; men, n = 5) and 32 subjects from the MFGM group (women,
groups, respectively. No significant intergroup differ- n = 27; men, n = 5).
No significant inter- or intragroup differences were noted in the measure-
ence was noted in energy expenditure by daily activi- ments.
ties. In addition, there was no significant change in their MFGM, milk fat globule membrane.
680   Y. YOSHINAKA ET AL.

Table 3. Changes in physical fitness scores before and after the proteins, among other biomolecules. According to Kim
intervention. et al. [44], the combination of amino acid intake (6 g/
Placebo MFGM day) and regular exercises improves muscle strength and
10-m obstacle walk- Baseline 8.27 ± 1.17 8.11 ± 1.27 mass in female participants with sarcopenia. MFGM-
ing speed (s) 4 weeks 8.09 ± 1.28 7.96 ± 1.22
8 weeks 8.14 ± 1.17 7.91 ± 1.25
derived amino acid intake in our interventional study
Δ 8 weeks (%)a 98.6 ± 7.6 97.6 ± 7.0 was several hundred milligrams per day, which indicates
Isometric knee Baseline 28.8 ± 9.4 28.6 ± 9.2 possible negligible effects of amino acid intake on the
extension strength 4 weeks 28.9 ± 10.0 27.6 ± 8.4
(kg) 8 weeks 29.0 ± 8.3 27.1 ± 7.8 improvement of physical function. In our previous study
Δ 8 weeks (%)a 102.6 ± 14.0 97.0 ± 17.3 with mice, sphingomyelin in phospholipids is at least
Foot tapping (times) Baseline 79.2 ± 14.8 78.7 ± 16.2
4 weeks 77.9 ± 16.0 81.0 ± 14.6 one of the components that promotes nerve and muscle
8 weeks 84.9 ± 11.7 87.1 ± 7.9b fiber development [41]. In addition, because sphingo-
Δ 8 weeks (%)a 109.9 ± 21.9 117.5 ± 39.0
Open–close stepping Baseline 31.9 ± 7.2 29.5 ± 9.9 myelin is a constituent of myelin sheaths, we infer that
(times) 4 weeks 30.9 ± 6.9 32.3 ± 8.3 this component in MFGM promotes the formation of
8 weeks 35.4 ± 4.1 37.1 ± 5.2b
Δ 8 weeks (%)a 116.0 ± 26.6 145.7 ± 71.3c
myelin sheath and NMJs and enhances contractile motor
nerve impulse transmission to the muscle.
Values are means ± SD of 30 subjects from the placebo group (women,
n = 25; men, n = 5) and 32 subjects from the MFGM group (women, The present study has several limitations. First, the
n = 27; men, n = 5). sample size, especially with regard to males, was small,
MFGM, milk fat globule membrane.
a
The value is the percentage change from the baseline to 8 weeks. and we could not take into account the sex difference
b
A significant difference was observed from the baseline during the inter- such as body composition. In addition, participants were
ventional period. Data were analyzed using two-way repeated measures
analysis of variance, followed by Dunnett’s test (p < 0.05). limited to healthy individuals. Future studies require
c
A significant difference was noted between the two groups in the results of larger sample sizes and should include people with low
the unpaired t-test (p < 0.05).
physical activity levels or low participation in the sports.
Second, because we did not include a group subjected to
intake was checked periodically throughout the study by
MFGM intake without gymnastic exercise, we could not
the trainer or test staff at the gym. However, applying a
show the effects of MFGM intake alone on the physical
strictly managed intervention program with the elderly
fitness. However, the intensity of gymnastic exercise was
in their daily life as described in the earlier studies is
light, and the subjects in the placebo group performed
difficult; therefore, the workable program with a mild
the same exercise. Therefore, MFGM has the potential
gymnastic exercise that elderly people can safely perform
to enhance physical fitness without additional exercise.
at home was developed for the present study, and its
Nevertheless, further studies are required to clarify
combined effects with MFGM were verified.
the effects of dietary MFGM alone. Third, we did not
The study evaluation found improved performance of
directly investigate the functional mechanism of MFGM
subjects in the foot tapping and open–close stepping tests
on NMJ. Performing detailed electromyogram and other
after eight weeks of gymnastic exercise and MFGM intake
analyses is necessary in future studies to clarify the pos-
at home. Performance in the foot tapping and open–close
sible mechanism of MFGM in influencing NMJ.
stepping tests is an indicator of agility (i.e. the ability to
In the present study, we showed that the combination
quickly and accurately alter an ongoing series of motor
of MFGM intake and mild gymnastic exercise that can
pattern movements). Changes in the speed and agility of
be performed at home improved agility in healthy elderly
muscle contraction due to aging have been reported to be
people. Although further investigation is required to clar-
highly associated with motor nerve and/or muscle fiber
ify the effects and the functional mechanism of MFGM,
conduction velocity (MFCV) [28]. In addition, age-re-
MFGM may be a useful addition to a healthy, active life.
lated NMJ failure causes muscle dysfunction [42]. NMJ
fragmentation and concomitant muscle denervation can
occur more likely in fast than slow muscle fibers [43]. Authors’ contributions
In our previous study, MFGM intake improved MFCV YY1 (Yoshinaka), KY, YY2 (Yamada), and MK were
[31]. As mentioned above, MFGM intake combined with involved in the study conception. YY1, SS, and KY per-
regular exercises promotes the formation of NMJ [41]. formed the experiments. YY1 and KY analyzed the data.
Thus, the combination of regular mild exercises with SS and NO contributed the materials and the analysis
MFGM intake seems to promote the formation of fast- tools. YY1, NO, and YY2 drafted the manuscript. All
type NMJ to improve agility. In the present study, the authors contributed to the study design and critical revi-
gymnastic exercise was designed to stimulate the coor- sion of the manuscript.
dination of nerve and muscle, although the intensity and
the duration were light and short. Therefore, the gymnas-
tic movements have the potential for activating the NMJ Acknowledgments
function, and MFGM might have augmented the effect. The sponsor had no control over this interventional study.
MFGM is a covering component of milk fat globules; it We thank the NPO corporate Health up AGE project for
is a complex component that contains phospholipids and their technical assistance.

Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by Kao Corporation.
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