1. Introduction
Good physical performance is central to active and healthy aging. Physical performance relates not only to the musculoskeletal system, but also to other aspects of daily living. Sarcopenia can be defined as low muscle strength, mass, and quality according to the European Working Group on Sarcopenia in Older People 2 group [1]. In addition to the previous characteristics, severe sarcopenia includes poor physical performance. The prevalence of sarcopenia increases with aging, especially in people > 70 years. Loss of muscle mass is associated with malnutrition, low protein intake, low physical activity, inflammation, chronic disease, unintentional weight loss, and low body mass index [1,2,3]. Both sarcopenia and frailty increase the risk of mobility disability, falls, poor physical function, decline in quality of life, institutionalization, and premature death [1,2,3,4]. As the world’s population is aging, it is of utmost importance to find feasible interventions to counteract this harmful cycle leading to these poor outcomes in older people.
Milk fat globule membrane (MFGM) is a complex structure composed primarily of lipids and proteins that surround fat globules in mammal milk. It is a source of multiple bioactive compounds, including phospholipids, glycolipids, and glycoproteins, that have important functional roles within the brain and gut [5]. MFGM is found to be antimicrobial, anti-inflammatory, anti-cholesterolemic, and safe to use as a supplement [6,7,8]. Supplementation of infant formula with MFGM has enhanced cognitive development in infants compared to standard infant formula [9,10], whereas effects of MFGM on cognitive functions in older individuals have not been reported.
Previous studies on physical function and performance have found that MFGM supplementation may stimulate neuromuscular junction development, which is a critical structure of motor units involved in physical movement [11]. Therefore, an increase in active motor units may lead to improvement in physical function and performance. Interventions including MFGM supplements combined with exercise have in fact improved ambulatory activities, leg muscle mass, and muscle fiber velocity in older adults [7]. MFGM supplementation given to middle-aged adults as part of a regular exercise regime enhanced physical agility by promoting fast-type motor unit maintenance compared to a control group [12]. Similarly, MFGM supplementation combined with twice-weekly physical activity improved frail older (>75 years) women’s frailty status compared with exercise and placebo supplementation as well as MFGM supplementation alone [13].
So far, most of the research on MFGM supplementation on physical performance has been published from Japan [12,13,14,15]. There are no data on the effects of MFGM supplementation on other ethnic groups. Moreover, many older people consume less protein than recommended [16]. Hydrolyzed milk protein is absorbed more rapidly than intact protein and increases postprandial amino acid availability; thus, it may augment postprandial muscle protein synthetic response in older people [17]. Therefore, we decided to offer our study participants a snack product high in both MFGM and hydrolyzed protein. Thus, the purpose of this study was to test whether a snack product high both in MFGM and hydrolyzed protein would improve the physical performance of older women with protein intake below the recommended level at baseline.
2. Methods
In 2021, 101 older, home-dwelling women (≥70 years) were recruited to the study mainly via Facebook and a newspaper ad in the major Finnish newspaper Helsingin Sanomat. Sarcopenia was screened with the SARC-F questionnaire [18]. The subjects were excluded from the study if they scored 0 points on the SARC-F questionnaire [18], had a diagnosed memory disorder or poor cognition Mini-Mental State Examination (MMSE) score < 24 [19], or were unable to move independently. All the inclusion and exclusion criteria are presented in more detail in Table 1. Because our study took place during an ongoing pandemic, we only accepted participants who had been vaccinated against COVID-19 due to safety reasons, although this was not an exclusion criterion in our original study plan. Oral and written informed consent was obtained from the participants after they were fully informed about the methods of the study. The ethics committee of the Department of Medicine at Helsinki University Hospital and City of Helsinki approved the study protocol (No. HUS/3022/2020). The trial was registered by the ACTRN, registration No. ACTRN12621001630808.
2.1. Study Protocol
The participants were randomly assigned to the intervention or control group. The intervention group received a daily snack product containing MFGM and protein for 12 weeks. In addition, both groups (intervention and control) were taught and advised on a simple five-movement exercise routine, which they were encouraged to independently perform every day during the study. To monitor their compliance with the advice, the participants filled out a daily track sheet, where they reported whether they had consumed a snack product and/or performed the exercise.
2.2. Advice
A trained dietician gave advice by phone to the participants in the intervention group about the consumption of the snack products provided by the study. In case their BMI was >23 kg/m2, the dietician advised the participants to replace a usually consumed snack (e.g., bread or pastry) in their daily diets with the study product. If their BMI was ≤23 kg/m2, the participants were encouraged to consume the snack product in addition to their usual diet. The participants were also advised to consume the snack within an hour following the exercise routine.
2.3. The Snack Product
We offered two types of products to the participants in the intervention group: a chocolate milkshake (a serving of 250 mL) and protein powder (a serving of 30 g). Lactose-free, protein-hydrolyzed buttermilk powder and chocolate-flavored milkshakes were produced from ultrafiltered lactose-free buttermilk concentrate. In ultrafiltration, some of the monosaccharides were removed, and proteins and residual fats were concentrated. After ultrafiltration, part of the proteins was hydrolyzed by enzymatic hydrolysis. The lactose content of the final protein concentrate was <0.01%. Protein hydrolysis was undertaken according to patent EP 2632277B1 [20] and as described previously [21]. The serving size of both products contained the same amount of protein (23 g) and a similar amount of MFGM (powder 3.9 g and milkshake 3.6 g). A more precise nutritional content of the snack products is presented in Table 2. The snack products were manufactured by the study sponsor Valio Ltd.
2.4. Exercise Routine
At the baseline visit, each participant in both groups was taught a short, five-movement exercise routine which they were encouraged to perform daily. The routine was planned to maintain muscle mass and strength of the lower extremities. It was designed by a non-governmental organization, Age Institute, which is an expert organization specialized in enhancing healthy aging (
2.5. Measurements
The participants were followed up for 12 weeks. The primary outcome of the study was the difference in changes in the five-time-sit-to-stand test between the intervention and the control groups. The five-time-sit-to-stand test was measured during baseline and end visits at 12 weeks. The test is an indicator of muscular endurance and agility and is a good predictor of mobility disability and falls in home-dwelling older people [22]. During the test, the participants stood up and sat down five times with their arms folded in front of their chest as quickly as possible on a firm chair [23]. The time required to complete five cycles was measured. The test is also part of the Short Physical Performance Battery (SPPB) test, which also includes walking speed and balance tests [24]. The SPPB test in its entirety was included in the measurements. Grip strength was measured with a dynamometer (Saehan DHD-1 Digital hand dynamometer) “using a standard protocol”.
Cognition was measured using Trail Making Test (TMT) A and B, which test attention and psychomotor speed [25]. TMT B also requires good executive function (Reitan 1958). Health-related quality of life was assessed using the RAND-36 test, which is also validated in the Finnish population [26,27].
Energy and protein intakes were measured using a 3-day food diary before the baseline visit to verify whether potential participants met the inclusion criteria on protein intake (protein intake < 1.2 g/kg body weight (BW)/d). In addition, 3-day food diaries were collected at the end of the trial to see whether the use of snack products increased the protein intake and energy intake of the participants.
The participants received the 3-day food diaries by mail with written instructions on how to fill them in. They were also instructed via phone by the study personnel. The participants returned the food diaries by mail, and the study personnel contacted them by phone if any clarification was needed. The food diaries were analyzed using Fineli, which contains a database of Finnish foods [28].
In addition, a background questionnaire included questions on lifestyle habits, general health, diseases, and the use of medications and dietary supplements. Height, weight, and waist circumference were measured during the baseline visit, and weight and waist circumference were also measured during the end visit. Measurements of weight and height were used to calculate body mass index (BMI kg/m2).
2.6. Sample Size
The sample size was based on the change in time of the five-time-sit-to-stand test. The reference values used to calculate the sample size are based on the Helsinki Businessmen study (unpublished) [29] and on results obtained from a previous study [22]. Clinically meaningful change in the five-time-sit-to-stand test was estimated to be 3 s. As type 1 error is 5% and power is 80%, we estimated that 44 persons per group were needed. We estimated the dropout percentage to be 15%; therefore, we aimed to recruit 102 persons for the study.
The randomization was performed with computer-generated random numbers, which randomly assigned participants to either the intervention or control group.
2.7. Statistical Analysis
Data are presented as means with standard deviation (SD) or as counts with percentages. Statistical comparisons between groups were made using t test for continuous variables and Pearson’s chi-square for categorical variables. Mean changes in primary and secondary outcomes between three months and baseline values were assessed using analysis of covariance (ANCOVA) with baseline values as covariates. Effect size (d) was calculated by using the method of Cohen where an effect size of 0.20 is considered small, 0.50 moderate, and 0.80 large. CIs for the effect sizes were obtained by bias-corrected bootstrapping (10,000 replications). Statistical analyses were performed using statistical software (Stata, release 17.0, Stata Corp., College Station, TX, USA).
3. Results
In total, we recruited 101 instead of the calculated 102 participants of which 94 finalized the trial (44 participants in the intervention group, 50 in the control group). The flowchart of the study is presented in Figure 1. The intervention and the control groups were similar in most of the baseline characteristics. SARC-F score was 2.2 and 2.3 points in the control and intervention groups, respectively. The baseline characteristics of the participants are presented in Table 3.
The main outcome of the study, the change in the five-time-sit-to-stand test, did not differ between the intervention and control groups at the end of the trial (intervention −2.3 (95% CI −3.9 to −1.6) vs. control −2.2 (95% CI −3.2 to −1.2), p = 0.29). Thus, both groups somewhat improved in the five-time-sit-to-stand test. Of the secondary outcomes, the change in total SPPB score differed significantly (+0.8 points (95% CI +0.5 to +1.1) in the intervention group vs. 0.2 points (95% CI −0.2 to +0.7) in the control group), favoring the intervention group (p < 0.020) (Table 3). The effect size was moderate. The improvement in the intervention group derives mainly from the improved balance test in the intervention compared with the control.
Protein intake increased significantly in the intervention group due to the intervention compared to the control group; +14 g in the intervention group vs. +2 g in the control group (p < 0.001) (Figure 2). There was no significant change in energy intake or in participants’ weights between the baseline and follow-up in either group. Other secondary outcomes (walking speed, hand grip strength, Trail Making Test A and B, health-related quality of life by RAND-36) did not change significantly due to the intervention (Table 4).
The compliance with using the snack products in the intervention group was 92.1%, and self-reported compliance with performing the five-movement exercise routine was 81.8% and 70.7% in the intervention and control groups, respectively (p = 0.015).
4. Discussion
In our study, supplementation with a snack product containing both MFGM and hydrolyzed protein for 12 weeks did not lead to a significant difference in five-time-sit-to-stand test in the intervention group compared to the control group in older women. However, the physical performance-related balance test and the total SPPB score changed significantly, favoring the intervention group.
Some previous studies have explored the effects of MFGM supplementation combined with exercise on leg muscle mass, muscle fiber velocity, physical performance, and frailty status in older adults and physical agility in middle-aged adults [7,12,13,14,15]. Unlike in these studies on MFGM, our primary outcome (five-time-sit-to-stand test) did not change between the intervention and control groups. One of the key differences between our study and these studies was that our study did not include mandatory exercise. Instead, we provided the participants in both groups with an exercise routine with written instructions that they were advised to perform independently at home without further supervision. The intervention group was also advised to consume the snack product after daily physical activity, which could have potentially enhanced the effect of MFGM and protein. Although the participants self-reported whether they had performed the routine daily, the exercise probably was not as effective as a mandatory, regular, progressive, instructor-based type of exercise. Thus, these results suggest that MFGM and protein supplementation may require additional, more structured exercise to improve muscle strength clinically significantly. The aim of this study was to test whether supplementation alone could improve physical performance, and therefore, both groups were instructed to exercise. In addition, we tested whether our snack product could have had cognitive benefits for our participants, since infant formulas supplemented with MFGM have in some studies enhanced infants’ cognitive development compared to standard infant formula [9,10]. However, we did not observe any cognitive benefits in the intervention group.
Our study further differed from previous studies in respect of the study product; instead of giving the participants MFGM tablets, we offered the intervention participants a snack product high both in MFGM and protein. As the participants had lower than recommended protein intake at baseline, increased protein intake could have had further benefits on physical performance-related outcomes. The protein was also hydrolyzed, which has been shown to enhance absorption and augment postprandial amino acid availability, an important regulator of muscle protein synthesis [17]. A third difference in the study design was that our snack products contained more MFGM than previously reported studies [7,12,13] (3.6 to 3.9 g vs. 1 g). MFGM was deemed safe at 6.5 g/day in a previous study [8], and it was generally well tolerated in our study population.
The balance test score of the SPPB changed significantly, as did the SPPB total score, mainly due to the balance and walking speed scores, favoring the intervention group. In fact, the effect size (ES) for the difference between changes in groups (ES 0.42) was quite good, indicating significant improvement. Similarly, in line with our results, MFGM without mandatory exercise also improved balance measured with a one-leg stand test with eyes closed in community-dwelling Japanese adults (n = 113) aged 50–70 years [30]. Although our results seem similar, our study products were also high in protein; thus, additional protein intake could have also played a role in these findings, especially since the participants had lower than recommended protein intake at baseline. Balance is crucial in preventing falls and injury in older people, and it is necessary for performing daily activities and leading an independent life. Maintaining balance is a complex task that requires coordination of vestibular function, visual function, muscle strength, and the sensory nervous system. MFGM with voluntary exercise has enhanced neuromuscular junction development in middle-aged animals [11] and suppressed the progression of age-related neuromuscular junction degeneration in older animals [31]. Moreover, the effect of MFGM intake with exercise was not restricted to neuromuscular junctions but extended also to the structure and function of peripheral nerves [31]. In particular, the function of peripheral nerves could affect the balance of older people due to age-related changes in these physiological systems, as well as in muscle and bone, which may likely contribute to an increased risk of falls in older people [31]. Thus, balance could be an important target for interventions in older people. Improving balance by adding MFGM and protein-rich snacks to the daily diets of older people could, thus, potentially support healthy and active aging.
Our study has several limitations. The most important limitation arises from the failure to produce a change in the primary outcome. Since our study was designed based on the primary outcome including sample size, the interpretation of secondary outcomes and generalization of the results should be cautiously considered, because the failure of the primary outcome may significantly affect the statistical power of secondary outcomes. Our intention was to find participants who experienced some mobility limitations, and we thus carefully screened the participants with the validated SARC-F questionnaire [18]. However, the mean baseline SPPB total score of the participants was >10 points, which generally indicates robustness. This might cause a ceiling effect in physical performance-related outcomes such as muscle strength and walking speed, therefore making it difficult to observe clinically meaningful changes in these outcomes. Despite this, the ES was quite good, showing a meaningful difference between the groups. It is thus possible that a group with a lower physical performance at baseline could have improved more in response to MFGM and protein supplementation. A further limitation of the study derives from the COVID-19 pandemic. The pandemic challenged and delayed carrying out our study and forced us to make some changes in the original study design by limiting intervention and physical contact with the participants due to the vulnerability of the target population. The pandemic might also have changed the typical physical activity patterns of the participants, thus reducing their daily activity. In our study, we had only dropouts in the intervention group. Since we only had two types of products, a few (n = 2) participants did not like the taste of the products or became bored consuming the same products and consequently dropped out of the study. A few others (n = 2) dropped out due to bowel symptoms, one due to weight gain, one due to allergy, and one due to worsening rheumatic arthritis symptoms. Fortunately, the statistical power of the study remained unaffected by the dropouts. For future studies and for practice, it would be beneficial to have more variety of snack products to match the varied tastes of people. Nevertheless, for those who remained in the study, the self-reported compliance with consuming the study snacks was very high. There was a difference in self-reported compliance with performing the exercise routine between the intervention and control groups; the intervention participants reported higher compliance than the control group (81.8% vs. 70.7%). However, the five-time-sit-to-stand test improved similarly in both groups. One limitation was also that the study was not blinded. Since only the intervention group received a snack product, it was not possible to keep the study blinded.
The strengths of the study derive from the study design. The study was a randomized controlled trial. Both intervention and control participants were advised to exercise; therefore, we could evaluate whether the supplement has an effect on physical performance. The participants were a homogeneous group of Caucasian older women of >70 years of age. As previously reported studies on MFGM and physical performance-related outcomes have mainly been carried out in the Japanese population, our study adds to the scientific knowledge of the effects of MFGM supplementation. We carefully selected people with lower than recommended protein intake at baseline, as well as those who reported having some mobility limitations. All the tests performed (e.g., physical performance, muscle strength) and measurements carried out were validated. The study personnel performing the measurements were experienced in assessing physical performance tests and further received unified training. Our study showed similar results to a previous study by Kokai et al., whose study subjects were somewhat younger, healthy Japanese volunteers. Similar to our study, the balance test was also a secondary outcome [30]. If our results would be corroborated in future studies, adding MFGM with or without protein to the diets of older people could be a feasible way to improve their balance and allow them to lead more active and healthy lives. Benefits in balance could possibly be achieved even without increasing exercise [30]. Carefully considered primary outcomes and well-designed study designs are of the essence in future studies.
In conclusion, our study suggests that the combination of MFGM and protein improved physical performance related to balance and total SPPB score in community-dwelling older women. In the future, balance and fall prevention could be considered as primary outcomes in studies with MFGM or MFGM combined with protein, especially in study designs without mandatory exercise. It would also be interesting to see the results of RCTs on diverse groups of older people to learn who would possibly benefit the most from these types of interventions.
Conceptualization, S.K.J., M.H.S. and A.M.T.; data curation, R.T.N.; formal analysis, S.K.J.; investigation, R.T.N., M.M., S.K.J., S.K., K.S. and M.H.S.; methodology, S.K.J., M.H.S., K.H.P. and R.T.N.; project administration, R.T.N., S.K.J. and M.H.S.; product development and quality control, T.S., K.-M.L. and A.M.T.; supervision, S.K.J. and M.H.S.; writing—original draft, S.K.J. and R.T.N., writing—review and editing, all authors. All authors have read and agreed to the published version of the manuscript.
The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Department of Medicine at Helsinki University Hospital and City of Helsinki.
Informed consent was obtained from all subjects involved in the study.
The data are not publicly available due to the signed consent agreements around data sharing, which only allow access for the researchers of the study following the project purposes. Requestors wishing to access the data used in this study can make a request to M.H.S. The request will be subject to approval and formal agreements regarding confidentiality and secure data storage being signed.
T.S., L.-K.M. and A.M.T. are employees of Valio Ltd. Other authors declare no conflict of interest.
Footnotes
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
Enlarge this image.Figure 2. Protein intake total g and g/kg body weight (BW)/d in the control and intervention groups at baseline and at the end of the trial.
Inclusion and exclusion criteria.
| Inclusion Criteria: |
| Home-dwelling female ≥ 70 years of age |
| SARC-F > 0 |
| Protein intake < 1.2 g/kg body weight/d according to a 3-day food diary |
| Subjective walking ability 400 m |
| Exclusion Criteria: |
| Poor cognition or neurocognitive disorder, MMSE < 24 |
| SARC = 0 |
| AUDIT ≥ 3 |
| Bed- or wheelchair-bound |
| Self-reported severe kidney malfunction |
| Acute cancer treatment less than a year ago, except for basal cell carcinoma |
| Parkinson’s disease |
| Insulin-dependent diabetes |
| Special diet that prevents use of the snack product provided by the study |
| Spends long time away from the metropolitan area during the study |
| Currently participates in another lifestyle intervention |
| Unintentional weight loss > 3 kg in 3 months |
| Severe obesity (BMI over 35 kg/m2) |
| Evaluation by the researchers that the subject will not be able to finish the study |
Nutritional contents of the research snack products.
| Snack Product | Protein Powder | Milkshake |
|---|---|---|
| Nutritional Content | Serving Size 30 g | Serving Size 250 mL |
| Energy, kcal | 140 | 190 |
| Protein, g | 23 | 23 |
| Fat, g | 4 | 4 |
| Carbohydrates, g | 2 | 16 |
| Lactose, g | 0 | 0 |
| MFGM, g | 3.9 | 3.6 |
| Phospholipids, g | 1.3 | 1.2 |
Baseline characteristics of the participants in the control and intervention groups.
| Group | Control | Intervention |
|---|---|---|
| Characteristics | N = 50 | N = 44 |
| Age, mean (SD) | 76 (4) | 75 (4) |
| Education, n (%) | ||
| elementary school or less | 2 (4) | 3 (6) |
| vocational school | 8 (16) | 7 (14) |
| upper comprehensive school | 7 (14) | 6 (12) |
| upper secondary school | 7 (14) | 11 (22) |
| institute of higher education | 25 (51) | 23 (46) |
| Financial status, n (%) | ||
| good | 23 (48) | 18 (36) |
| moderate | 24 (50) | 30 (60) |
| poor | 1 (2) | 2 (4) |
| Current smoker, n (%) | 2 (4) | 3 (6) |
| AUDIT, mean (SD) | 1.7 (1.1) | 2.1 (1.6) |
| SARC-F score, mean (SD) | 2.3 (0.9) | 2.2 (1.2) |
| MMSE score mean (SD) | 28.8 (1.6) | 28.6 (1.7) |
| Weight, kg, mean (SD) | 75 (11) | 74 (11) |
| BMI, kg/m2, mean (SD) | 28.3 (3.6) | 28.3 (3.6) |
| Waist circumference, cm, mean (SD) | 95.6 (11.1) | 93.0 (10.1) |
| Energy, kcal, mean (SD) | 1559 (275) | 1644 (388) |
| Protein intake g, mean (SD) | 62 (13) | 66 (15) |
| protein g/kg BW/day | 0.85 (0.20) | 0.90 (0.18) |
| Protein intake < 1.0 g/kg BW/day, n (%) | 15 (30) | 16 (30) |
| Diseases during the last 12 months, n (%) | ||
| Diabetes | 4 (8) | 7 (14) |
| Coronary artery disease | 4 (8) | 4 (8) |
| Cardiac failure | 2 (4) | 1 (2) |
| Arterial fibrillation | 4 (8) | 5 (10) |
| Other cardiac disease | 3 (6) | 2 (4) |
| Hypertension | 31 (63) | 25 (51) |
| Other transient ischemic attack | 4 (8) | 4 (8) |
| Foot circulatory disorder | 10 (20) | 5 (10) |
| Asthma | 5 (10) | 8 (16) |
| Osteoarthritis | 31 (63) | 34 (69) |
| Thyroid disease | 15 (30) | 10 (20) |
| Cancer | 16 (32) | 11 (22) |
| Number of medications, n (%) | 4.6 (3.3) | 3.9 (2.7) |
AUDIT = Alcohol Use Disorders Identification Test; SARC-F = sarcopenia–frailty questionnaire; MMSE = Mini-Mental State Examination: BMI = body mass index; BW = body weight.
Primary and secondary physical performance, cognition, and health-related quality of life outcomes of the study at baseline and the change in 12 weeks.
| Baseline | Change from Baseline to 12 Weeks | p-Value * | Effect Size (95% CI) ** | |||
|---|---|---|---|---|---|---|
| Primary and Secondary Outcomes | Control |
Intervention |
Control |
Intervention |
||
| 5-time-chair-stand test, s | 14.9 (4.2) | 13.8 (3.4) | −2.2 (−3.2 to −1.2) | −2.3 (−3.0 to −1.6) | 0.29 | 0.05 (−0.36 to 0.47) |
| Balance test, s | 3.70 (0.58) | 3.82 (0.45) | −0.06 (−0.21 to 0.10) | 0.09 (−0.05 to 0.23) | 0.022 | 0.29 (−0.06 to 0.69) |
| Walking speed, m/s | 1.27 (0.37) | 1.30 (0.33) | 0.03 (−0.03 to 0.09) | 0.06 (−0.01 to 0.13) | 0.36 | 0.15 (−0.25 to 0.55) |
| Total SPPB score | 10.0 (1.5) | 10.3 (1.5) | 0.2 (−0.2 to 0.7) | 0.8 (0.5 to 1.1) | 0.020 | 0.42 (0.04 to 0.74) |
| Hand grip strength, kg | 20.4 (5.1) | 21.4 (5.4) | 0.9 (0.1 to 1.7) | 1.0 (0.0 to 1.9) | 0.51 | 0.03 (−0.38 to 0.43) |
| Trail Making Test, s | ||||||
| A | 42.1(15.2) | 47.8 (17.9) | −5.7 (−9.1 to −2.3) | −6.7 (−10.7 to −2.7) | 0.50 | 0.08 (−0.34 to 0.54) |
| B | 108.2 (41.1) | 112.9 (49.2) | −14.1 (−23.4 to −4.8) | −8.0 (−20.7 to 4.6) | 0.22 | −0.16 (−0.60 to 0.26) |
| RAND-36 | ||||||
| Physical Health Summary | 41.7(9.0) | 42.2 (8.6) | 1.8 (−0.2 to 3.9) | 1.3 (−0.7 to 3.4) | 0.80 | −0.07 (−0.51 to 0.34) |
| Mental Health Summary | 51.8(9.7) | 50.9 (11.1) | −1.2 (−3.5 to 1.1) | −1.5 (−4.1 to 1.1) | 0.75 | −0.04 (−0.45 to 0.37) |
* Baseline adjusted; ** 95% confidence intervals (CIs) were obtained by means of bias-corrected bootstrapping (10,000 replications). − favoring control, favoring intervention.
References
1. Cruz-Jentoft, A.J.; Baeyens, J.P.; Bauer, J.M.; Boirie, Y.; Cederholm, T.; Landi, F.; Martin, F.C.; Michel, J.-P.; Rolland, Y.; Schneider, S.M. et al. European Working Group on Sarcopenia in Older People: Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing; 2010; 39, pp. 412-423. [DOI: https://dx.doi.org/10.1093/ageing/afq034] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20392703]
2. Rolland, Y.; Czerwinski, S.; Abellan Van Kan, G.; Morley, J.E.; Cesari, M.; Onder, G.; Woo, J.; Baumgartner, R.; Pillard, F.; Boirie, Y. et al. Sarcopenia: Its assessment, etiology, pathogenesis, consequences and future perspectives. J. Nutr. Health Aging; 2008; 12, pp. 433-450. [DOI: https://dx.doi.org/10.1007/BF02982704] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18615225]
3. Evans, C.J.; Chiou, C.-F.; Fitzgerald, K.A.; Evans, W.J.; Ferrell, B.R.; Dale, W.; Fried, L.P.; Gandra, S.R.; Dennee-Sommers, B.; Patrick, D.L. Development of a new patient-reported outcome measure in sarcopenia. J. Am. Med. Dir Assoc.; 2011; 12, pp. 226-233. [DOI: https://dx.doi.org/10.1016/j.jamda.2010.09.010] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21333926]
4. Fried, L.P.; Tangen, C.M.; Walston, J.; Newman, A.B.; Hirsch, C.; Gottdiener, J.; Seeman, T.; Tracy, R.; Kop, W.J.; Burke, G. et al. Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: Evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci.; 2001; 56, pp. M146-M156. [DOI: https://dx.doi.org/10.1093/gerona/56.3.M146]
5. Cavaletto, M.; Giuffrida, M.G.; Conti, A. Milk fat globule membrane components-a proteomic approach. Adv. Exp. Med. Biol.; 2008; 606, pp. 129-141.
6. Rosqvist, F.; Smedman, A.; Lindmark-Månsson, H.; Paulsson, M.; Petrus, P.; Straniero, S.; Rudling, M.; Dahlman, I.; Risérus, U. Potential role of milk fat globule membrane in modulating plasma lipoproteins, gene expression, and cholesterol metabolism in humans: A randomized study. Am. J. Clin. Nutr.; 2015; 102, pp. 20-30. [DOI: https://dx.doi.org/10.3945/ajcn.115.107045]
7. Raza, G.S.; Herzig, K.-H.; Leppäluoto, J. Invited review: Milk fat globule membrane-A possible panacea for neurodevelopment, infections, cardiometabolic diseases, and frailty. J. Dairy Sci.; 2021; 104, pp. 7345-7363. [DOI: https://dx.doi.org/10.3168/jds.2020-19649]
8. Hari, S.; Ochiai, R.; Shioya, Y.; Katsuragi, Y. Safety evaluation of the consumption of high dose milk fat globule membrane in healthy adults: A double-blind, randomized controlled trial with parallel group design. Biosci. Biotechnol. Biochem.; 2015; 79, pp. 1172-1177. [DOI: https://dx.doi.org/10.1080/09168451.2015.1012150]
9. Timby, N.; Domellöf, E.; Hernell, O.; Lönnerdal, B.; Domellöf, M. Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: A randomized controlled trial. Am. J. Clin. Nutr.; 2014; 99, pp. 860-868. [DOI: https://dx.doi.org/10.3945/ajcn.113.064295]
10. Li, F.; Wu, S.S.; Berseth, C.L.; Harris, C.L.; Richards, J.D.; Wampler, J.L.; Zhuang, W.; Cleghorn, G.; Rudolph, C.D.; Liu, B. et al. Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial. J. Pediatr.; 2019; 215, pp. 24-31.e8. [DOI: https://dx.doi.org/10.1016/j.jpeds.2019.08.030]
11. Haramizu, S.; Mori, T.; Yano, M.; Ota, N.; Hashizume, K.; Otsuka, A.; Hase, T.; Shimotoyodome, A. Habitual exercise plus dietary supplementation with milk fat globule membrane improves muscle function deficits via neuromuscular development in senescence-accelerated mice. Springerplus; 2014; 3, 339. [DOI: https://dx.doi.org/10.1186/2193-1801-3-339]
12. Ota, N.; Soga, S.; Hase, T.; Shimotoyodome, A. Daily consumption of milk fat globule membrane plus habitual exercise improves physical performance in healthy middle-aged adults. Springerplus; 2015; 4, 120. [DOI: https://dx.doi.org/10.1186/s40064-015-0896-8] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25810952]
13. Kim, H.; Suzuki, T.; Kim, M.; Kojima, N.; Ota, N.; Shimotoyodome, A.; Hase, T.; Hosoi, E.; Yoshida, H. Effects of exercise and milk fat globule membrane (MFGM) supplementation on body composition, physical function, and hematological parameters in community-dwelling frail Japanese women: A randomized double blind, placebo-controlled, follow-up trial. PLoS ONE; 2015; 10, e0116256. [DOI: https://dx.doi.org/10.1371/journal.pone.0116256]
14. Soga, S.; Ota, N.; Shimotoyodome, A. Dietary milk fat globule membrane supplementation combined with regular exercise improves skeletal muscle strength in healthy adults: A randomized double-blind, placebo-controlled, crossover trial. Nutr. J.; 2015; 14, 85. [DOI: https://dx.doi.org/10.1186/s12937-015-0073-5] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26303780]
15. Minegishi, Y.; Ota, N.; Soga, S.; Shimotoyodome, A. Effects of Nutritional Supplementation with Milk Fat Globule Membrane on Physical and Muscle Function in Healthy Adults Aged 60 and Over with Semiweekly Light Exercise: A Randomized Double-Blind, Placebo-Controlled Pilot Trial. J. Nutr. Sci. Vitaminol.; 2016; 62, pp. 409-415. [DOI: https://dx.doi.org/10.3177/jnsv.62.409]
16. Jyväkorpi, S.K.; Pitkälä, K.H.; Puranen, T.M.; Björkman, M.P.; Kautiainen, H.; Strandberg, T.E.; Soini, H.; Suominen, M.H. Low protein and micronutrient intakes in heterogeneous older population samples. Arch. Gerontol. Geriatr.; 2015; 61, pp. 464-471. [DOI: https://dx.doi.org/10.1016/j.archger.2015.06.022] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26298429]
17. Koopman, R.; Walrand, S.; Beelen, M.; Gijsen, A.P.; Kies, A.K.; Boirie, Y.; Saris, W.H.M.; van Loon, L.J.C. Dietary protein digestion and absorption rates and the subsequent postprandial muscle protein synthetic response do not differ between young and elderly men. J. Nutr.; 2009; 139, pp. 1707-1713. [DOI: https://dx.doi.org/10.3945/jn.109.109173] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19625697]
18. Malmstrom, T.K.; Miller, D.K.; Simonsick, E.M.; Ferrucci, L.; Morley, J.E. SARC-F: A symptom score to predict persons with sarcopenia at risk for poor functional outcomes. J. Cachexia Sarcopenia Muscle; 2016; 7, pp. 28-36. [DOI: https://dx.doi.org/10.1002/jcsm.12048] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27066316]
19. Folstein, M.F.; Folstein, S.E.; McHugh, P.R. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res.; 1975; 12, pp. 189-198. [DOI: https://dx.doi.org/10.1016/0022-3956(75)90026-6]
20. Sibakov, T.; Tossavainen, O. Milk Product and Preparation Method. EP Patent; 2632277B1, 4 September 2013.
21. Laatikainen, R.; Salmenkari, H.; Sibakov, T.; Vapaatalo, H.; Turpeinen, A. Randomised Controlled Trial: Partial Hydrolysation of Casein Protein in Milk Decreases Gastrointestinal Symptoms in Subjects with Functional Gastrointestinal Disorders. Nutrients; 2020; 12, 2140. [DOI: https://dx.doi.org/10.3390/nu12072140]
22. Makizako, H.; Shimada, H.; Doi, T.; Tsutsumimoto, K.; Nakakubo, S.; Hotta, R.; Suzuki, T. Predictive cutoff values of the Five-Times Sit-to-Stand Test and the Timed “Up & Go” Test for disability incidence in older people dwelling in the community. Phys. Ther.; 2017; 97, pp. 417-424. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28371914]
23. Jones, S.E.; Kon, S.S.C.; Canavan, J.L.; Patel, M.S.; Clark, A.L.; Nolan, C.M.; Polkey, M.I.; Man, W.D.-C. The five-repetition sit-to-stand test as a functional outcome measure in COPD. Thorax; 2013; 68, pp. 1015-1020. [DOI: https://dx.doi.org/10.1136/thoraxjnl-2013-203576] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23783372]
24. Guralnik, J.M.; Simonsick, E.M.; Ferrucci, L.; Glynn, R.J.; Berkman, L.F.; Blazer, D.G.; Scherr, P.A.; Wallace, R.B. A short physical performance battery assessing lower extremity function: Association with self-reported disability and prediction of mortality and nursing home admission. J. Gerontol.; 1994; 49, pp. M85-M94. [DOI: https://dx.doi.org/10.1093/geronj/49.2.M85] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8126356]
25. Reitan, R.M. Validity of the Trail Making Test as an Indicator of Organic Brain Damage. Percep. Motor Skills; 1958; 3, pp. 271-276. [DOI: https://dx.doi.org/10.2466/pms.1958.8.3.271]
26. Brazier, J.; Jones, N.; Kind, P. Testing the validity of the Euroqol and comparing it with the SF-36 health survey questionnaire. Qual. Life Res.; 1993; 2, pp. 169-180. [DOI: https://dx.doi.org/10.1007/BF00435221]
27. Aalto, A.M.; Teperi, J.; Aro, A.R. RAND-36 item health survey (RAND-36): Yleinen terveyteen liittyvän elämänlaadun mittari. Suom. Lääkärilehti; 1997; 52, 1065.
28. The National Institute for Health and Welfare. Fineli: The National Food Composition Database in Finland. Available online: https://fineli.fi/fineli/en/Index (accessed on 28 May 2023).
29. Strandberg, E.T.; Salomaa, V.; Strandberg, A.Y.; Vanhanen, H.; Sarna, S.; Pitkälä, K.; Rantanen, K.; Savela, S.; Pienimäki, T.; Huohvanainen, E. et al. Cohort Profile: The Helsinki Businessmen Study (HBS). Int. J. Epidemiol.; 2016; 45, 1074. [DOI: https://dx.doi.org/10.1093/ije/dyv310]
30. Kokai, Y.; Mikami, N.; Tada, M.; Tomonobu, K.; Ochiai, R.; Osaki, N.; Katsuragi, Y.; Sohma, H.; Ito, Y.M. Effects of dietary supplementation with milk fat globule membrane on the physical performance of community-dwelling Japanese adults: A randomised, double-blind, placebo-controlled trial. J. Nutr. Sci.; 2018; 7, e18. [DOI: https://dx.doi.org/10.1017/jns.2018.8]
31. Sugita, S.; Tamura, K.; Yano, M.; Minegishi, Y.; Ota, N. The Impact of Milk Fat Globule Membrane with Exercise on Age-Related Degeneration of Neuromuscular Junctions. Nutrients; 2021; 13, 2310. [DOI: https://dx.doi.org/10.3390/nu13072310]
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Details
; Sibakov, Timo 3 ; Kaity-Marin Lehtonen 3 ; Kunvik, Susanna 4
; Pitkala, Kaisu H 1 ; Turpeinen, Anu M 3 ; Suominen, Merja H 5 1 Unit of Primary Health Care, Department of General Practice and Primary Health Care, Faculty of Medicine, Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland;
2 Department of Food and Nutrition, University of Helsinki, 00014 Helsinki, Finland;
3 Valio Ltd., R&D, 00370 Helsinki, Finland;
4 Faculty of Health and Welfare, Satakunta University of Applied Sciences, 28101 Pori, Finland;
5 Unit of Primary Health Care, Department of General Practice and Primary Health Care, Faculty of Medicine, Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland;