Light rhythmic exercise with dietary milk fat globule membrane improves physical fitness in an elderly Japanese population: a double-blind randomized placebo-controlled trial

Abstract

This study aimed to investigate the efficacy of home-based, light gymnastic exercise plus dietary milk fat globule membrane (MFGM) intake on physical fitness of an elderly Japanese sample in a pilot, double-blind, randomized, placebo-controlled trial. Seventy-one subjects (male, n = 13; female, n = 58) were randomly assigned into two groups: placebo (n = 35 [male, n = 6; female, n = 29]) and MFGM group (n = 36 [male, n = 7; female, n = 29]). The intervention was eight weeks. Subjects ingested either MFGM (1 g/day) or placebo tablets daily and engaged in an exercise program daily. Physical function tests were performed at baseline and after four and 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.

Combination of MFGM intake and light rhythmic gymnastic exercise improved agility in the healthy elderly people. *A significant difference was noted between the two groups in the results of the unpaired t-test (P < 0.05).

Keywords:

• Aging
• gymnastic exercise
• life expectancy
• milk fat globule membrane
• physical fitness

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 insurance 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 problems,” 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 skeletal 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 compliance. 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 gymnastic exercise program that each elderly individual could perform at home and to verify its combined effects with MFGM intake on motor function.

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 supervision of an occupational health physician, in accordance 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 throughout 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 placebo tablets daily throughout the eight-week study period and engaged in gymnastic exercise at home daily. The subjects were instructed to continue their usual exercise habits 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.

Table 1. Characteristics of study subjects.

	Total (n = 71)	Women (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 (kg/m^2)	21.6 ± 2.7	21.6 ± 2.9	21.5 ± 1.9
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).

MFGM

The tablets containing 167 mg MFGM/tablet were produced 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. 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% phospholipids (4.95% phosphatidylcholine, 5.10% phosphatidylethanolamine, 1.62% phosphatidylinositol, 1.90% phosphatidylserine, 3.81% sphingomyelin, and other phospholipids), 4.9% ash, and 4.2% moisture. The composition of the whole milk powder was 26.8% protein, 26.0% fat, 38.3% carbohydrate, 0.322% phospholipids (0.067% phosphatidylcholine, 0.076% phosphatidylethanolamine, 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 exercise daily for eight weeks at home without any supervision 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 stimulate 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 measurements, walking speed, isometric muscle strength, stepping, 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 measured 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 intervention 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 walking. This test was used to measure the time that subjects required to step over six obstacles (height: 20 cm) at 2-m intervals twice. The shorter time value was used for analyses [34].

Isometric muscle strength

Isometric knee extension strength of a dominant leg was measured using the Force Measurement System for One Leg (T.K.K.5715; TAKEI Scientific Instruments Co., Niigata, Japan) equipped with tensiometer D (T.K.K.5710e; TAKEI Scientific Instruments Co., Niigata, Japan) [35–37]. The subjects performed maximal 3-s voluntary contractions at 90° knee flexion.

Foot tapping and open–close stepping tests

Foot tapping and open–close stepping tests were performed as an indicator of coordination ability of nerve and muscle such as agility. In the foot tapping test, subjects were seated and tapped the sole of the foot alternately as quickly as possible, and the maximum frequency of taps was measured in 10 s [38]. In the open–close stepping test, subjects were seated and placed their feet on a simple measurement board (width: 30 cm). The subjects opened their legs and spread the feet as quickly as possible, touching the floor beside the board with the forefoot, and then they quickly returned the feet and legs to their original position [39]. The maximum frequency of open and close was measured in 20 s [40].

Statistical analysis

Data were analyzed using two-way repeated measures analysis of variance, followed by Dunnett’s test to compare within-group baseline values and values obtained after four and eight weeks (Stat View for Windows version 5; SAS Institute, Cary, NC). In a separate analysis, percent changes in values from baseline to the end of the intervention were evaluated using an unpaired t-test for intergroup comparisons. Statistical significance was set at a probability level of p < 0.05. All data are expressed as means ± SD.

Results

Subjects’ compliance and anthropometric values

The subjects tolerated the intervention protocol well, and no adverse effects were reported from the MFGM or placebo tablets. Nine subjects (placebo = 5, MFGM = 4) were unable to complete the study after randomization because of personal reasons. Energy expenditures through daily activities calculated using an electronic pedometer during the intervention were 1669 ± 192 and 1634 ± 126 kcal/day in the placebo and MFGM groups, respectively. No significant intergroup difference was noted in energy expenditure by daily activities. In addition, there was no significant change in their usual exercise habits (data not shown). The average daily intake of milk and dairy products, such as milk beverages, yogurt, and cheese, at baseline and 8 weeks in the MFGM group were 218 ± 123 and 207 ± 114 g/day; in the placebo group, they were 179 ± 102, and 191 ± 94 g/day, respectively. No significant inter- or intragroup differences were noted in dairy intake. No overall changes in body weight, whole body muscle mass, and body fat ratio were observed during the intervention (Table 2).

Table 2. Changes in anthropometric variables before and after the intervention.

		Placebo	MFGM
Body weight (kg)	Baseline	52.1 ± 8.1	51.4 ± 7.1
	4 weeks	51.9 ± 7.8	51.3 ± 6.9
	8 weeks	51.9 ± 7.9	51.2 ± 6.8
Body mass index (kg/m^2)	Baseline	21.8 ± 2.5	21.6 ± 3.1
	4 weeks	21.7 ± 2.4	21.6 ± 3.1
	8 weeks	21.7 ± 2.4	21.5 ± 3.0
Muscle mass (kg)	Baseline	36.0 ± 6.5	35.3 ± 4.9
	4 weeks	35.6 ± 6.4	35.6 ± 5.0
	8 weeks	35.5 ± 6.4	35.4 ± 5.0
Body fat ratio (%)	Baseline	26.7 ± 6.9	26.8 ± 7.5
	4 weeks	27.1 ± 7.5	26.1 ± 7.7
	8 weeks	27.4 ± 7.5	26.3 ± 7.4

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, n = 27; men, n = 5).

No significant inter- or intragroup differences were noted in the measurements.

MFGM, milk fat globule membrane.

Effect on physical fitness

After an eight-week intervention, no significant group-by-time interaction was observed. Significant inter- or intragroup differences were not noted in the 10-m obstacle walking speed and the isometric knee extension strength (Table 3). Significant time effects were found for the foot tapping and open–close stepping tests. The foot tapping and open–close stepping scores were measured as indicators of coordination ability such as agility, and they significantly increased from baseline to eight weeks in the MFGM group; no significant change was noted for these parameters in the placebo group. In addition, the change from baseline of the open–close stepping score was significantly higher in the MFGM group than in the placebo group at eight weeks (Table 3).

Table 3. Changes in physical fitness scores before and after the intervention.

		Placebo	MFGM
10-m obstacle walking speed (s)	Baseline	8.27 ± 1.17	8.11 ± 1.27
	4 weeks	8.09 ± 1.28	7.96 ± 1.22
	8 weeks	8.14 ± 1.17	7.91 ± 1.25
	Δ 8 weeks (%)^a	98.6 ± 7.6	97.6 ± 7.0
Isometric knee extension strength (kg)	Baseline	28.8 ± 9.4	28.6 ± 9.2
	4 weeks	28.9 ± 10.0	27.6 ± 8.4
	8 weeks	29.0 ± 8.3	27.1 ± 7.8
	Δ 8 weeks (%)^a	102.6 ± 14.0	97.0 ± 17.3
Foot tapping (times)	Baseline	79.2 ± 14.8	78.7 ± 16.2
	4 weeks	77.9 ± 16.0	81.0 ± 14.6
	8 weeks	84.9 ± 11.7	87.1 ± 7.9^b
	Δ 8 weeks (%)^a	109.9 ± 21.9	117.5 ± 39.0
Open–close stepping (times)	Baseline	31.9 ± 7.2	29.5 ± 9.9
	4 weeks	30.9 ± 6.9	32.3 ± 8.3
	8 weeks	35.4 ± 4.1	37.1 ± 5.2^b
	Δ 8 weeks (%)^a	116.0 ± 26.6	145.7 ± 71.3^c

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, n = 27; men, n = 5).

MFGM, milk fat globule membrane.

^a The value is the percentage change from the baseline to 8 weeks.

^b A significant difference was observed from the baseline during the interventional period. Data were analyzed using two-way repeated measures analysis of variance, followed by Dunnett’s test (p < 0.05).

^c A significant difference was noted between the two groups in the results of the unpaired t-test (p < 0.05).

Discussion

We have shown the combination of MFGM intake and exercise habits improves muscle function in healthy middle-aged and elderly people [30–32] through improvement of neuromuscular junction (NMJ) formation [41]. In other words, MFGM can further enhance the effects of exercise. In our previous studies [30–32], each subject underwent exercise training (i.e. treadmill and bicycle exercises) for 30 min/day, twice weekly under the guidance of a fitness trainer at a gym to ensure safe performance of certain levels of exercise. In addition, the subject’s compliance with the MFGM or placebo tablets intake was checked periodically throughout the study by the trainer or test staff at the gym. However, applying a strictly managed intervention program with the elderly in their daily life as described in the earlier studies is difficult; therefore, the workable program with a mild gymnastic exercise that elderly people can safely perform at home was developed for the present study, and its combined effects with MFGM were verified.

The study evaluation found improved performance of subjects in the foot tapping and open–close stepping tests after eight weeks of gymnastic exercise and MFGM intake at home. Performance in the foot tapping and open–close stepping tests is an indicator of agility (i.e. the ability to quickly and accurately alter an ongoing series of motor pattern movements). Changes in the speed and agility of muscle contraction due to aging have been reported to be highly associated with motor nerve and/or muscle fiber conduction velocity (MFCV) [28]. In addition, age-related NMJ failure causes muscle dysfunction [42]. NMJ fragmentation and concomitant muscle denervation can occur more likely in fast than slow muscle fibers [43]. In our previous study, MFGM intake improved MFCV [31]. As mentioned above, MFGM intake combined with regular exercises promotes the formation of NMJ [41]. Thus, the combination of regular mild exercises with MFGM intake seems to promote the formation of fast-type NMJ to improve agility. In the present study, the gymnastic exercise was designed to stimulate the coordination of nerve and muscle, although the intensity and the duration were light and short. Therefore, the gymnastic movements have the potential for activating the NMJ function, and MFGM might have augmented the effect.

MFGM is a covering component of milk fat globules; it is a complex component that contains phospholipids and proteins, among other biomolecules. According to Kim et al. [44], the combination of amino acid intake (6 g/day) and regular exercises improves muscle strength and mass in female participants with sarcopenia. MFGM-derived amino acid intake in our interventional study was several hundred milligrams per day, which indicates possible negligible effects of amino acid intake on the improvement of physical function. In our previous study with mice, sphingomyelin in phospholipids is at least one of the components that promotes nerve and muscle fiber development [41]. In addition, because sphingomyelin is a constituent of myelin sheaths, we infer that this component in MFGM promotes the formation of myelin sheath and NMJs and enhances contractile motor nerve impulse transmission to the muscle.

The present study has several limitations. First, the sample size, especially with regard to males, was small, and we could not take into account the sex difference such as body composition. In addition, participants were limited to healthy individuals. Future studies require larger sample sizes and should include people with low physical activity levels or low participation in the sports. Second, because we did not include a group subjected to MFGM intake without gymnastic exercise, we could not show the effects of MFGM intake alone on the physical fitness. However, the intensity of gymnastic exercise was light, and the subjects in the placebo group performed the same exercise. Therefore, MFGM has the potential to enhance physical fitness without additional exercise. Nevertheless, further studies are required to clarify the effects of dietary MFGM alone. Third, we did not directly investigate the functional mechanism of MFGM on NMJ. Performing detailed electromyogram and other analyses is necessary in future studies to clarify the possible mechanism of MFGM in influencing NMJ.

In the present study, we showed that the combination of MFGM intake and mild gymnastic exercise that can be performed at home improved agility in healthy elderly people. Although further investigation is required to clarify the effects and the functional mechanism of MFGM, MFGM may be a useful addition to a healthy, active life.

Authors’ contributions

YY1 (Yoshinaka), KY, YY2 (Yamada), and MK were involved in the study conception. YY1, SS, and KY performed the experiments. YY1 and KY analyzed the data. SS and NO contributed the materials and the analysis tools. YY1, NO, and YY2 drafted the manuscript. All authors contributed to the study design and critical revision of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported by Kao Corporation.

Acknowledgments

The sponsor had no control over this interventional study. We thank the NPO corporate Health up AGE project for their technical assistance.