Positive effect of selenium on muscle mass: a cross sectional research : The association between minerals, muscle mass, muscle strength and physical performance in older adults

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Positive effect of selenium on muscle mass: a cross

sectional research

The association between minerals, muscle mass, muscle strength and physical performance in older adults.

Beyza Dogan: 500713797 Gulistan Yilmaz: 500713798

Supervising lecturer: Michael Tieland Examiner: Ljiljana Stanic-Jovic

Practice supervisor: Jantine van den Helder and Carliene van Dronkelaar Graduation number: 2018105

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Preface

This thesis is written to complete our Bachelor’s degree in Nutrition and Dietetics at the Amsterdam University of Applied Sciences. In this thesis, we describe the association between calcium,

magnesium, selenium, muscle mass, muscle strength and physical performance in adults. Which is also known as sarcopenia. We sincerely hope to give you more insight into older adults in relation to sarcopenia.

The data we used for this cross sectional study originated from the VITAMINE research. Therefore, we would like to thank all members of the VITAMINE project. Especially, we thank Carliene van Dronkelaar and Jantine van den Helder for the opportunity and guidance. We also want to thank our supervisor Michael Tieland for the great motivation and providing feedback. Finally, we want to thank our examiner Ljiljana Stanic-Jovic for improving our thesis.

We wish you a pleasant reading. Beyza Dogan and Gülistan Yilmaz Amsterdam, January 2017

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Abstract Introduction:

The Dutch population is aging. Aging is associated with low muscle mass, strength and function, also known as sarcopenia. Sarcopenia leads to several problems as falling more often, physical frailty, disability and a higher risk of mortality. Additionally, absorption of many nutrients decreases with aging and sarcopenia. Some studies show that several minerals such as calcium, magnesium and selenium have a role in muscle metabolism and muscle function. Therefore, the aim of this study is to examine the association between calcium, magnesium, selenium, muscle mass, muscle strength and physical performance in older adults.

Method:

The participants in this cross sectional study were older adults aged 55 years. The calcium, magnesium and selenium intake were measured using a 3-day food record. The Dual Energy X-ray Absorptiometry was used to measure the appendicular lean mass. The muscle strength was assessed by the Handgrip strength. The physical performance was assessed by the Short Physical Performance Battery and the 6 Minute Walk Test. The following confounders were included in the statistical analysis: age, gender, body weight, physical activity, energy intake and protein intake. The multivariable linear regression model was used to assess the relation of calcium, magnesium, selenium and muscle mass, muscle strength and physical performance.

Results:

The study population consisted of 158 females (70.5%) and 66 males (29.5%). The multivariable linear regression models showed that there was significant association between selenium and muscle mass (β=0.0023, P=0.002). No significant association was found between calcium, magnesium, selenium and physical performance.

Conclusion:

In conclusion, this cross-sectional study did not find a significant association between dietary intake of calcium and magnesium and muslce mass, muscle strength and physical performance in older adults. However, this study found significant association between selenium and muscle mass. Besides, there was no significant association found between selenium and muscle strength and physical performance.

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According to the World Health Organization we soon will have more older people with an extreme old age compared to children than ever before. In 2010 was the number of people aged 65 or older estimated 524 million and in 2050 is expected 1.5 billion. That is representing 16 percent of the world’s population (1).

The 65 and above population increased between 2000 and 2014 with 4.1 percent. Also, the life expectancy is good (81.8 years in relative to 80.9 for the EU), though not one of the very highest in Europe (2).

Aging is associated with low muscle mass, strength and function, also named sarcopenia (3). Sarcopenia leads to problems as falls, physical frailty, disability and mortality (4). Additionally, absorption of many nutrients decreases with aging and sarcopenia (5). Sarcopenia may be influenced in part by nutritional factors that declare cross-sectional and prospective studies (3). Between 40 and 70 years, healthy adults lose an estimate of 24% muscle leading to sarcopenia, which exacerbated with 15% per decade after age of 70 (4).

Of several minerals such as calcium, magnesium and selenium it is known that they have a role in muscle metabolism and muscle function. Calcium is involved with many physiological processes in the human body such as occupying a role in muscle contraction (6). As shown by De Baaij et al magnesium has an important physiological role especially in the skeletal muscles. Magnesium is shown to have a positive effect on skeletal muscle function, muscle relaxation and displaces muscle cramps and spasms (7). Selenium is shown to have an important role in normal muscle function, selenium protects the muscles against oxidative damage. Selenium deficiency provoke white muscle disease, a situation characterized by muscle weakness and degeneration of skeletal and cardiac muscles(8).

Minerals seem to be important nutrients to prevent sarcopenia. However, there is no strong evidence in the previous studies. Some studies show that there is an association between these minerals and muscle mass, muscle strength and physical performance in older adults and others do not. Therefore, the association and underlying mechanism between calcium, magnesium, selenium and sarcopenia needs further research.

Therefore, the aim of this study is to examine the association between calcium, magnesium,

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Method Population

The data from the VITAMINE (VITale AMsterdamse ouderen IN dE stad) project is used to anwser the main question of this study. The research group in the VITAMINE study were older adults aged 55 years and older. Participants were recruited in 2016 through gym classes for the elderly and were divided into three different groups: a control group, a digital supported group and a group that, in addition to the digitally supported motion program, also maintained a protein-rich dietary pattern. The HvA (Amsterdam University of Applied Sciences) research VITAMINE developed a home training program in addition to the National More Movement for Elderly Program. The training was digitally supported and enriched with protein rich food to optimize the effect on physical function. The VITAMINE project was therefore investigating the effectiveness of a tablet computer supported home-based training program and optimal protein intake in community dwelling older adults to improve physical functioning.

Design

This study was a cross sectional research with 240 participants. For this research, various

measurements and measuring instruments is used. Which will be discussed further. This research used the baseline data of the VITAMINE project. Because the baseline data is available and the follow up data is not available yet.

Inclusion and exclusion criteria

To be eligible to participate in the VITAMINE project, a subject must meet all of the following criteria: 55 years or older, willingness that general practitioner will be notified on study

participation, written informed consent, willingness to comply with the protocol, ability to comply with the protocol in the opinion of the study physician(s). A potential subject who meets any of the following criteria will be excluded from participation in this study: inability to understand the Dutch language, current alcohol or drug abuse in the opinion of the investigator, cognitive impairment (MMSE <15), knee or hip surgery in the last 6 months. These were the inclusion and exclusion criteria of VITAMINE. This study had included additional inclusion criteria: minimum 2 day food diary completed, food diaries that were entered plus checked, full dxa scan performed and data that has been entered twice.

Calcium, magnesium and selenium

The calcium, magnesium and selenium intake measured using a 3-day dietary record. The 3-day dietary record included two week days and one weekend day. The time of food, type of food and portion size were filled in. In addition, the food supplements use were asked. This supplement was then written in the medication list. The NEVO table (Dutch nutrient databank version 2013 4.0) of RIVM (Rijksinstituut voor Volksgezondheid en Milieu) and Excel were used to calculate the intake. The cutpoints for the Recommended Dietary Allowance of calcium intake between 51 and 70 years is 1100 mg/day for both gender, magnesium intake is 350 mg/day for men and 280 mg/day for

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years are only different for calcium intake, 1200 mg/day for both gender (14). These cutpoints were used to give recommendations for dietitians, scientists and society.

Energy and protein

The energy and protein intake are also measured using a 3-day dietary record. This data was used as confounders.

Muscle mass

The appendicular lean mass (ALM) assessed by Dual Energy X-ray Absorptiometry (Lunar Prodigy Advance; GE Health Care, Madison, WI, USA). A DXA scan is a non-invasive procedure with very low radiation dose (9). At the beginning of the procedure subjects will be asked to lie down on a scan table and remain still during the measurements. As the scanner moves, a dual energy beam (0.03 mrem) passes through the targeted skeletal muscle section and is measured by a detector. The results were transferred and anlyzed in SPSS.

Muscle strength

The muscle strength is assessed by Handgrip strength (HGS). Handgrip strength is measured using a hydraulic hand dynamometer (Jamar, Jackson, MI, USA). Three consecutive measures of handgrip strength (kg) at both hands will be recorded to the nearest 1 kg with the subjects sitting in an upward position with the arm in a 90º angle. The maximum strength effort was reported (10). Physical performance

The physical performance assessed by Short Physical Performance Battery (SPPB) and 6 Minute Walk Test (6MWT). The SPPB assess lower extremity function using measures of gait speed, standing balance, and lower extremity strength. It comprises three components: standing balance, gait speed and chair stands according to the method outlined by Guralnik et al (11). The fastest time is used in the final SPPB score. Each of the three components was scored on its test-specific scale and on a 0 to 4 point scale. When subjects were unable to perform a test, a score of 0 was allocated. A summary performance score of 0 to 12 were be calculated by summing the scores of the tests. The 6MWT performed as a performance-based measure of functional performance. The 6MWT measured the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. All the data from the measurements were put into a database called Research Manager. The data was entered twice to prevent incorrect entry. Thereafter, the double data analysis was done for a better quality of the study. Finally, baseline data transported to SPSS version 22 (IBM Corp, 2013) for further analysis.

Potential confounders

This research contained few confounding variables that could influence the relation between the independent and dependent variables. The following potential confounders were included in the statistical analysis:

 Age and gender: it is well established that age per se and gender impact the prevalence of sarcopenia (4,12).

 Body weight: high fat mass coinciding with sarcopenia poses greater risks for continued and hastened declines in mobility (3).

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 Physical activity: reduced physical activity have been associated with a high risk of sarcopenia (4).

 Energy intake: Slow gait speed was associated with lower total calories (15).

 Protein intake: higher dietary intake of protein has been consistently associated with greater muscle mass in older adults (3).

Body weight was measured with a calibrated digital BodPod (Air Displacement Plethysmography)

scale. Physical activity estimated with a 2 dimensional accelerometer (PAM) and a 3-day record. Participants are requested to wear the accelerometer on the hip for 3 days and fill out their major daily physical activities for these 3 days. The confounders were derived from the literature and analysis level. When the β substantially has changed by 10%, the confounder is included in this study (appendix: confounders).

Statistical analysis

Characteristics of the study population reported as the mean±standard deviation (SD) and as percentage. To make the data visually more clear statistic tables were incorporated. The multivariable linear regression models is used to assess the relation of calcium, magnesium,

selenium and muscle mass, muscle strength and physical performance. The models are adjusted for age, gender, body weight, physical activity (model 2), energy and protein intake (model 3). Baseline levels were compared between men and women. The statistical analysis carried out using SPSS. A P-value <0.05 will be considered as statistically significant.

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Results

General characteristics of the study population are presented in Table 1. The study population consisted of 158 females (70.5%) and 66 males (29.5%). The table shows that the mean of the appendicular lean mass was 21.1 kg. The hand grip strength left had an average of 31.0 kg and hand grip strength right had an average of 31.5 kg. Additionally, the mean score of the short physical performance battery is 11.3 points.

Table 1. Characteristics of the participants

Variable N Mean SD Age (yrs) 224 72.01 6.47 Gender, female 158 1.00 0.00 Gender, male 66 0.00 0.00 Height (m) 224 1.68 0.09 Weight (kg) 224 73.58 13.91

Appendicular Lean Mass (kg) 222 21.06 4.64

HGS Dominant Left (kg) 26 31.04 12.34

HGS Dominant Right (kg) 198 31.50 11.08

SPPB (score) 221 11.26 1.25

Gait Speed fastes (m/s) 224 0.82 0.26

Physical activity level (MET) 206 1.50 0.15

Energy (kcal/day) 196 1870.91 509.35

Protein total (g/day) 196 77.42 21.51

Calcium (mg/day) 196 991.74 377.88

Magnesium (mg/day) 196 335.06 104.06

Selenium (ug/day) 196 47.65 21.75

Table 2 shows the association between the dietary mineral intake of calcium, magnesium and selenium and muscle mass. The relation between calcium and muscle mass was not significant Model 3c _{(β=0.000, P=0.296). There was significant association between magnesium and muscle}

mass when it is not adjusted (β=0.009, P=0.009). There was significant association between selenium and muscle mass for adjusted as well as not adjusted confounders (Model 1a_{β=0.067, P=0.000,}

Model 2b _{β=0.019, P=0.001, Model 3}c_{β=0.0023, P=0.002).}

Abbreviations: SD, standard deviation; HGS, hand grip strength; SPPB, short physical performance battery

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10 Table 2. Association between minerals and muscle mass

Variable β 95% CI P-value n Calcium (mg) Muscle mass (kg) Model 1 Model 2 Model 3 Magnesium (mg) Muscle mass (kg) Model 1 Model 2 Model 3 Selenium (mg) Muscle mass (kg) Model 1 Model 2 Model 3 0.001 0.000 0.000 0.009 0.002 0.002 0.067 0.019 0.023 -0.001-0.003 -0.001-0.001 -0.001-0.000 0.002-0.015 0.000-0.004 -0.002-0.006 0.038-0.096 0.008-0.030 0.009-0.038 0.397 0.828 0.296 0.009 0.078 0.348 0.000 0.001 0.002 184 184 184 184 184 184 184 184 184

Table 3 presents the association between the dietery mineral intake of calcium, magnesium and selenium and muscle strength. The relation between calcium and muscle strength was not significant Model 3e _{(β=0.001, P=0.606). Magnesium and selenium had significant associated with}

muscle strength. However, when they were adjusted for potential confounders, there was no significant association found between these minerals and muscle strength (for magnesium β=0.003,

P=0.673 and for selenium β=0.012, P=0.722).

Table 3. Association between minerals and muscle strength

Variable β 95% CI P-value n Calcium (mg) Muscle strength (kg) Model 1 Model 2 Model 3 Magnesium (mg) Muscle strength (kg) Model 1 Model 2 Model 3 Selenium (mg) Muscle strength (kg) Model 1 Model 2 Model 3 0.003 0.002 0.001 0.021 0.007 0.003 0.088 0.019 0.012 -0.001-0.008 -0.001-0.004 -0.003-0.004 0.006-0.036 -0.002-0.017 -0.012-0.019 0.013-0.162 -0.030-0.063 -0.052-0.075 0.116 0.233 0.606 0.007 0.134 0.673 0.021 0.445 0.722 184 184 184 184 184 184 184 184 184

Abbreviations: CI, confidence interval. Model 1: unadjusted model. Model 2: adjusted for age, gender and weight. Model 3: adjusted for age, gender, weight, protein and energy.

Abbreviations: CI, confidence interval. Model 1: unadjusted model.

Model 2: adjusted for age, gender, physical activity level and weight. Model 3: adjusted for age, gender, physical activity level, weight, protein and energy.

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Table 4,5 and 6 show the association between the dietary mineral intake of calcium, magnesium and selenium and physical performance. There was no significant association found between calcium, magnesium, selenium and physical performance.

Table 4. Association between calcium and physical performance

Variable β 95% CI P-value n Calcium (mg) Physical performance: gait speed (m/s) Model 1 Model 2a Model 3a 0.000 0.000 0.000 0.000-0.000 0.000-0.000 0.000-0.000 0.698 0.612 0.706 184 184 184 Calcium (mg) Physical performance: balance test (sec)

Model 1 Model 2b Model 3b 0.000 0.000 0.000 0.000-0.000 0.000-0.000 0.000-0.000 0.202 0.258 0.935 184 184 184 Calcium (mg) Physical performance: repeated chair rise test (sec) Model 1 Model 2c Model 3c 0.000 0.000 0.000 0.000-0.000 0.000-0.000 -0.001-0.000 0.572 0.802 0.633 184 184 184 Calcium (mg)

Physical performance: total score SPPB Model 1 Model 2c Model 3c 0.000 0.000 0.000 0.000-0.000 -0.001-0.000 -0.001-0.001 0.963 0.838 0.805 184 184 184 Calcium (mg) Physical performance: 6MWT (m/sec) Model 1 Model 2c Model 3c 0.000 0.000 0.000 0.000-0.000 0.000-0.000 0.000-0.000 0.866 0.367 0.397 184 184 184

Model 2a_{: adjusted for gender and physical activity level.}

Model 2b_:_{adjusted for age and weight.}

Model 2c_:_{adjusted for age, gender, physical activity level and weight.}

Model 3a_{: adjusted for gender, physical activity level, protein and energy.}

Model 3b_{: adjusted for age, weight, protein and energy.}

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12 Table 5. Association between magnesium and physical performance

Variable β 95% CI P-value n Magnesium (mg) Physical performance: gait speed (m/s) Model 1 Model 2a Model 3a 0.000 0.000 0.000 -0.001-0.000 0.000-0.000 -0.001-0.000 0.332 0.892 0.206 184 184 184 Magnesium (mg) Physical performance: balance test (sec)

Model 1 Model 2b Model 3b -0.001 -0.001 0.000 -0.001-0.000 -0.001-0.000 -0.002-0.001 0.109 0.064 0.634 184 184 184 Magnesium (mg) Physical performance: repeated chair rise test (sec) Model 1 Model 2c Model 3c 0.001 0.001 0.000 0.000-0.002 -0.001-0.002 -0.001-0.002 0.126 0.316 0.597 184 184 184 Magnesium (mg)

Physical performance: total score SPPB Model 1 Model 2c Model 3c 0.000 0.000 0.000 -0.002-0.002 -0.002-0.001 -0.002-0.003 0.876 0.668 0.758 184 184 184 Magnesium (mg) Physical performance: 6MWT (m/sec) Model 1 Model 2c Model 3c 0.000 0.000 0.000 0.000-0.001 0.000-0.000 0.000-0.001 0.118 0.620 0.401 184 184 184

Model 2c_{: adjusted for age, gender, physical activity level and weight.}

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13 Table 6. Association between selenium and physical performance

Variable β 95% CI P-value n Selenium (mcg) Physical performance: gait speed (m/s) Model 1 Model 2a Model 3a -0.001 0.000 -0.002 -0.003-0.001 -0.002-0.001 -0.004-0.000 0.363 0.736 0.099 184 184 184 Selenium (mcg) Physical performance: balance test (sec)

Model 1 Model 2b Model 3b -0.001 -0.001 0.002 -0.004-0.003 -0.004-0.003 -0.003-0.007 0.783 0.682 0.433 184 184 184 Selenium (mcg) Physical performance: repeated chair rise test (sec) Model 1 Model 2c Model 3c 0.004 0.005 0.005 -0.002-0.010 -0.001-0.011 -0.002-0.013 0.183 0.077 0.157 184 184 184 Selenium (mcg)

Physical performance: total score SPPB Model 1 Model 2c Model 3c 0.002 0.003 0.007 -0.006-0.011 -0.005-0.011 -0.003-0.018 0.587 0.410 0.171 184 184 184 Selenium (mcg) Physical performance: 6MWT (m/sec) Model 1 Model 2c Model 3c 0.001 0.000 0.001 -0.001-0.002 -0.001-0.002 -0.001-0.003 0.564 0.676 0.228 184 184 184

Model 2c_:_{adjusted for age, gender, physical activity level and weight.}

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Discussion

The purpose of this study is to research the association between minerals such as magnesium, calcium and selenium and muscle mass, muscle strength and physical performance in older adults. Our study found that calcium and magnesium are not associated with muscle mass. In contrast, selenium is positive associated with muscle mass. In addition, none of these minerals are significant associated with strength or physical performance. Muscle strength is not associated with these minerals. For as well as gait speed, balance test, repeated chair rise test, total score SPPB and 6MWT there is no association found.

This research is one of the first cross-sectional studies that investigate the relation between minerals and sarcopenia outcomes. Minerals are estimated by a three-day dietary record. Three-day dietary record is the most commonly and valid method to assess dietary intake in in older adults (16,17). Bossola et al did not included any weekend days, whereby the micronutrients were not estimated accurately (18). Therefore to asses mineral intake, three-day dietary records may not be valid

method and seven-day dietary record are suggested. In contrary to Bossola et al we did included two weekdays and one weekend day for better estimation.

The three-day dietary record was self reported by the older adults at home. A common problem herewith is underreporting or overreporting the food consumption, which may lead to a less specific estimation (17). Payette et al compared a three-day dietary record with a seven-day dietary record. The seven-day dietary record is more sufficient and accurate for the intake of all nutrients (16). However, seven-day dietary record is difficult to maintain for older adults. Therefore, we have chosen for a three-day dietary record. It is more practical applicable for the older adults. In conclusion, for older adults, a three-day dietary record represent valid means to assess dietary intake and also mineral intake. Therefore we consider the three-day dietary records as a valid mean to assess the minerals in our study.

The major strength of this study is using the DXA to assess appendicular lean mass. The appendicular lean mass is derived from appendicular skeleton. Appendicular skeleton includes the bones of the shoulder girdle, the upper limbs, the pelvic girdle, and lower limbs (19). Many professionals use the DXA, because it determines accurate diagnosis (20). Besides the DXA is considered as a Golden Standard to measure body composition (21). Because, reference values for ALM were developed as the DXA is a good indicator of skeletal muscle mass and it is commonly used in defining sarcopenia (22).

Another strength of this study is using the 6MWT. The 6MWT is a useful measurement for physical activity in older adults. Because the results in our study of this measurement provide a wide spread in the scatterplot. That means there is a clear difference in physical performance in our study population. The 6MWT is also the most popular assessment in past ten years. Besides the 6MWT is a valid, safe, simple and inexpensive measurement (23).

Further we use the SPPB for the physical performance. Because the SPPB is also a valid, safe, simple and inexpensive measurement. The SPPB is a good measurement for evaluating the functional exercise capacity of the individual to perform activities of daily living (24). Because the SPPB consists of the components balance test, repeated chair rise test and gait speed test (3m walking). However,

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our study shows that the SPPB is not a good reflection of the total population. Because the

population of this study consist of healthy older adults and barely frail elderly. The outcome of the results shows that there is limited variation among the study population. Because the SPPB has a maximum score of 12 points (11). The most older adults in our study scored 11 and 12 points. Only one participant scored 5 points. Therefore, for our study population we need a higher maximum score of the SPPB. The SPPB is only useful for frailty older adults to report who can walk and climbing stairs without help and who need help with activities of daily living (11).

Calcium is a key nutrient in the human body. More than 99% (1.2-1.4 kg) is stored in the bones and teeth. Less than 1% is found in the extracellular tissue (25). The calcium in the extracellular tissue has a role in the muscle contraction and for general proper functioning of the muscles (6). In this study, we did not find a significant association between calcium and muscle mass, muscle stength and physical performance. This study may did not find a significant association, because older adults are at risk for dietary calcium deficiency. There are multiple reasons for this, including low calcium intake over time, malabsorption, medication interactions that may decrease calcium, and the underlying chronic disease osteoporosis which changes bone formation and strength (25). There is only one study of Seo et al that shows there is significant association between muscle mass and calcium by a daily intake of >444.5 mg per day. While the mean intake of our study population is 991.74 mg calcium per day. The main difference is that Seo et al used the 24 hour recall which is not representative (26). That means that there could be a difference in mineral estimation when the 24 hour recall is used. Besides, Dronkelaar et al suggest in a systematic review that a high calcium intake did not show a significant effect in comparison with studies that had a low calcium intake (27). That could be the reason why Seo et al found a significant association and this study did not. We did not find any other study who prove that high calcium intake (above the Recommended Dietary Allowance) has a positive effect on sarcopenia. It is not clear that calcium intake above the Recommended Dietary Allowance reduce sarcopenia, therefore to give advice more research is needed. Dronkelaar et al confirms there is more research needed in the future (27).

As for magnesium, as shown by De Baaij et al magnesium has an important physiological role especially in the skeletal muscles. Magnesium is shown to have a positive effect on skeletal muscle function, muscle relaxation and displaces muscle cramps and spasms (7).

However, in our study there is no significant association found between magnesium and muscle mass, muscle strength and physical performance. Our study finds similar results as Scott et al, that magnesium did not have a significant association with muscle strength (28).

The Food and Nutrition Board shows that the effect of magnesium on physical performance is more evident in the population with a magnesium intake below the RDA (29). Our study population have a magnesium intake above the RDA. That could be the reason why we did not find a significant

association. Dronkelaar et al also suggests this hypothesis (27).

Selenium is shown to have an important role in normal muscle function, selenium protects the muscles against oxidative damage. We found in our study a significant association between selenium and muscle mass. Dronkelaar et al also suggests the same result (27). Besides, Rayman confirms that high intake above the Recommended Dietary Allowance has a negative association with muscle mass (30). Our population have also a intake below the

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Recommended Dietary Allowance. The hypothesis of this association could be that a low intake of selenium has a positive effect on muscle mass.

In conclusion, calcium, magnesium and selenium concentrations may not be sensitive to small differences in intake, but is to larger differences in calcium, magnesium and selenium intake. This could be explained by the strict regulation of serum calcium, magnesium and selenium by urinary excretion, bone stores and gastro-intestinal tract (31).

The limitation of this study is that we did not include the intake of multivitamin/mineral supplements as these data were not available.

However, it is remarkable that our results show that, when your mineral intake is much higher, the effect is yet minimal. We interpreted this from the fact that the béta is between 0.088 and -0.002 (table 2,3,4,5,6). That means there is no visible effect on the muscle mass, muscle and physical performance. Unfortunately, we cannot prove this.

There is no study that did research for only calcium supplementation in older adults. However, there are studies who researched the effect of calcium and vitamin D together. Janssen et al shows that 500 mg calcium and 400 IU vitamin D supplementation does not significantly lead to improve muscle strength. But this study did research in female geriatric patients (32). Besides it is known that

calcium and vitamin D have a postive influence on each other (33). Therefore, more research is needed for only calcium supplementation in the general elderly population. Because, calcium seem to be the most promising mineral to prevent and/or treat sarcopenia (27).

For magnesium, only one study was found that researched magnesium supplementation in older adults. Veronese et al shows that 300 mg magnesium supplementation has a positive effect at the physical performance(34). However, the treatment group also attended a mild fitness twice a week. Shortly, it is unknown whether the positive effect is caused by magnesium supplementation or the extra gym activities.Therefore more researched for only magnesium supplementation is needed. The findings of Moslehi et al confirms our study results, that there is no significant visible effect when the population supplemented extra magnesium. Because Moslehi et al indicate that 250 mg magnesium supplementation, for 8 weeks did not lead to a significant gain in muscle strength and physical performance (35).

Finally for selenium supplementation, one study showed a small but significant increase of the mean diameter of muscle fiber. This are results after 4 months of 200 mcg selenium supplementation. However, this population was aged between 25 and 65 years (36). The study of Rannem et al confirms our result that there is a significant association between selenium intake and muscle mass. According to the RIVM 58% of the Dutch women and 30% of the Dutch men (>51 years) use

supplements (37). The human body generally absorbs minerals from supplements more easily than minerals from dietary products (38). It is important to continue using mineral supplements as prophylactic treatment. However, our study shows that a higher intake has a minimal positive effect on the muscle function. In conlusion, extra mineral supplementation is not usefull to improve the physical function, but it is usefull for the maintenance.

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Public relevance

Sarcopenia is a geriatric syndrome that is increasing in the super aged society and is an important risk factor for the outcomes such as disability, falls and fractures (39). Therefore, dietary guidance is extremely important in older adults. Of several minerals such as calcium, magnesium and selenium it is known that they have a positive effect on muscle mass, muscle strength and physical performance (6,7,8). However, there are a few studies that researched this effect in older adults. The power of our study is, that we are the first study that has: a large- scaled population; involved all aspects of sarcopenia; examined the confounders and included this in our study. The outcome of our results is meaningful for scientists, paramedics and society. Because the Dutch elderly population is

increasing, it is necessary to have insight in the relation between minerals and sarcopenia. As well as energy, protein, minerals and vitamins must be examined. Because they may contribute to the development of sarcopenia. It is important for the scientists to have insight, because they researched to advice the paramedici. For the paramedici it is important, because they have recommendations for the society.

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Conclusion

In conclusion, this cross-sectional study did not find a significant association between dietary intake of calcium and magnesium and muscle mass, muscle strength and physical performance in older adults. However, this study did find significant association between selenium and muscle mass. Besides, there is no significant association found between selenium and muscle strength and physical performance.

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Recommendation

In our study we did find a significant association between selenium dietary intake and muscle mass. For the dietitian and society it is important to know which selenium-based dietary products has positive effect on the muscle mass. According to the Dutch Health Council (Gezondheidsraad), the Dutch elderly population does not meet the Recommended Dietary Allowance of selenium (40). Our recommendations for the dietitians are as followed: cereals and cereal products are richer in selenium than vegetables (41), such as oatmeal, wholemeal pasta and multi-grain rice. On the other hand cereal products such as dark rye bread and white pasta do not contain selenium. These

vegetables, brussel sprouts, mushroom and sun-dried tomato contains a lot of selenium. In contrast, broccoli, raw tomatoes and spinach do not contain selenium. Both lean and fat fish contain the same amount of selenium. All sort shellfish contains an high amount of selenium. Brazil nuts are very rich in selenium. Almonds and hazelnuts contain a very low amount of selenium. Other dietary products such as eggs, chicken filet and seeds contain much selenium (42). In conclusion, the dietitians should pay attention to the intake of these products to keep selenium intake sufficient to prevent

sarcopenia.

Secondly, in our study there is no association found between calcium dietary intake and muscle mass, muscle strength and physical performance. However, Seo et al did find a significant association between calcium and muscle mass (26). According to the Dutch Health Council, the Dutch elderly population also does not meet the Recommended Dietary Allowance of calcium (40). For these reasons we have a few recommendations for the dietitians. These are as followed: dairy products such as skimmed milk, semi-skimmed milk, spread cheese 20+ and cheese 30+. Also all sort of bread, for example multigrain, wholemeal and brown baguette contain a lot of calcium.

Vegetables that contain a lot of calcium are raw spinach, fennel and French beans. Boiled

mushrooms and sweet red pepper cointain a small amount of calcium. Dried goji berries, dried figs and dried pear contain a high amount of calcium. Other fruits also contain calcium. Legumes like red kidney beans, brown beans and lentils contain much calcium. Splitpeas and mung beans cointain less calcium. Potatoes, several nuts and seeds also contain calcium (42). In conclusion, the dietitians should pay attention to the intake of these products as a prophylactic treatment.

Finally, in our study we did not find a significant association between magnesium dietary intake and muscle mass, muscle strength and physical performance. However, one study shows a positive association between magnesium and physical performance (34). According to the Dutch Health Council the Dutch elderly population does meet the Reccomended Dietary Allowance of magnesium (40). Because the magnesium intake is sufficient in general older adults, we do have

recommendations for those who have a magnesium deficit. Therefore, the effect on the muscle function is positive in older adults with magnesium deficit, when they have an increased dietary intake (29). The recommendations are as followed: dairy product such as cheese 30+, yoghurt low fat and skimmed milk. Vegetables who contain much magnesium are, boiled spinach, long yard beans and purslane. Celery, swede and radish do not contain a lot of magnesium. Besides all wholemeal bread contain a lot of magnesium. We also recommend legumes like red kiney beans, lentils and marrowfat peas. Black olives, dried apricots and dried figs cointain the most magnesium. Other dietary products that contain magnesium are, shellfish, shrimps, eggs, soybeans, nuts and

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water(42). In conclusion, the dietitians should pay attention to the intake of these products as a prophylactic treatment.

Several reasons are known why older adults have problems with absorbing minerals out of dietary products (25). When the Recommended Dietary Allowance of calcium, magnesium and selenium can not be achieved by dietary intake, we recommend supplementation. Previous studies have shown that supplementation can be an effective alternative to reach the Recommended Dietary Allowance of these minerals (34). The general maintenance dose for calcium is 200-600 mg (43), for magnesium 200-600 mg and for selenium 100 mcg per day (44).

Currently there are a few studies that investigated the effect of minerals on muscle mass, muscle strength and physical performance. Therefore, certainly more research is needed. There is also a lack of randomized controlled trials (RCT’s). RCT’s establish causalities, that means RCT’s show reliable evidence. Hereby, there is a ability to ascertain actions and recommondations for the paramedics and society. In contrary, our study had a cross sectional design. Which means that our study is an observational study. Observatinal studies show merely associations (45). Hence, we recommend RCT’s for future studies. This is how we would set up further research: 3-day dietary record; DXA; MPPT; 6MWT; subdivide the study population in elderly with mineral deficit and elderly with no mineral deficit; distinguish between only dietary intake and mineral supplementation; diversity in elderly population; same amount of gender.

Because the 3-day dietary record is more practically for the elderly population. The DXA is a gold-standard for body composition. We do not recommend the SPPB for healthy elderly, because the SPPB has a maximum score of 12 points. We would rather recommend the MPPT, because there is a distinction between not frail, mild frailty, moderate frailty and unlikely to able to function in the community. Therefore there is better spread in the scatterplot (46). Besides, we recommend to separate elderly with mineral deficit and elderly with no mineral deficit. Because there are studies that state that the effect on the muscle function is positive in older adults with mineral deficit, when they have an increased dietary intake (29). We recommend distinguish between only dietary intake and mineral supplementation. Because that can change the results of the study. Also we recommend a diversity in elderly population, because scientists have better insight in general elderly population. Finally, we recommend the same quantity of gender. Because the body composition of men and women are different (4,12).

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Appendix: Confounders

Confounders ALM + calcium Beta difference Include yes or no

Age 15% yes

Gender 81% yes

Mean physical activity level over 3 days 7% no Weight 54% yes Protein 480% yes Energy 316% yes Confounders ALM + magnesium

Beta difference Include yes or no

Age 5% yes

Gender 57% yes

Mean physical activity level over 3 days

2% no

Weight 42% yes

Protein 155% yes

Energy 142% yes

Confounders ALM + selenium Beta difference Include yes or no

Age 0.4% yes

Gender 40% yes

0.9% no

Weight 57% yes

Protein 52% yes

Energy 27% yes

Confounders HGS + calcium Beta difference Include yes or no

Age 16% yes

Gender 44% yes

Mean physical activity level over 3 days 20% yes Weight 10% yes Protein 134% yes Energy 39% yes Confounders HGS + magnesium

Age 6% yes

Gender 46% yes

11% yes

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Protein 53% yes

Energy 130% yes

Confounders HGS + selenium Beta difference Include yes or no

Age 0.3% yes

Gender 71% yes

6% yes

Weight 47% yes

Protein 90% yes

Energy 78% yes

Confounders Gait speed + calcium

Age 53% no

Gender 73% yes

16% yes

Weight 7% no

Protein 20% yes

Energy 253% yes

Confounders Gait speed + magnesium

Age 9,87% no

Gender 29% yes

84% yes

Weight 9% no

Protein 130% yes

Energy 14% yes

Confounders Gait speed + selenium

Age 0,4% no

Gender 49% yes

32% yes

Weight 33% no

Protein 120% yes

Energy 26% yes

Confounders balance test + calcium

Age 15% yes

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7% no

Weight 2% yes

Protein 43% yes

Energy 54% yes

Confounders balance test + magnesium

Age 9% yes

Gender 9% no

7% no

Weight 8% yes

Protein 18% yes

Energy 43% yes

Confounders balance test + selenium

Age 14% yes

Gender 53% no

2% no

Weight 105% yes

Protein 75% yes

Energy 320% yes

Confounders chair rise test + calcium

Age 309% yes

Gender 191% yes

110% yes

Weight 127% yes

Protein 736% yes

Energy 1436% yes

Confounders chair rise test + magnesium

Age 9% yes

Gender 14% yes

46% yes

Weight 16% yes

Protein 53% yes

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Confounders chair rise test + selenium

Age 0,5% yes

Gender 28% yes

19% yes

Weight 68% yes

Protein 15% yes

Energy 50% yes

Confounders total score SPPB + calcium

Beta verschil Meenemen ja of nee

Age 27% yes

Gender 19% yes

920% yes

Weight 6% yes

Protein 3% yes

Energy 54% yes

Confounders total score SPPB + magnesium

Age 54% yes

Gender 99% yes

159% yes

Weight 55% yes

Protein 357% yes

Energy 31% yes

Confounders total score SPPB + selenium

Age 12% yes

Gender 94% yes

Mean physical activity level over 3 days 31% yes Weight 109% yes Protein 260% yes Energy 1,2% yes Confounders 6MWT m/sec + calcium

Age 40% yes

Gender 33% yes

500% yes

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Protein 5% yes

Energy 200% yes

Confounders 6MWT m/sec + magnesium

Age 15% yes

Gender 30% yes

Mean physical activity level over 3 days 62% yes Weight 9,2% yes Protein 146% yes Energy 59% yes Confounders 6MWT m/sec + selenium

Beta differnce Include yes or no

Age 6% yes

Gender 455% yes

60% yes

Weight 234% yes

Protein 396% yes

Positive effect of selenium on muscle mass: a cross sectional research : The association between minerals, muscle mass, muscle strength and physical performance in older adults

Positive effect of selenium on muscle mass: a cross

sectional research

TABLE OF CONTENTS