Authors

Study participants

Objective

Design and Methodology

 Results and Conclusions

Li-hong Gao, et al. 2015 [12]

Community-dwelling postmenopausal women, capable of independently completing the tests involved in the study and with normal blood counts, normal results on liver and kidney function tests and normal serum levels of calcium, phosphorus, alkaline phosphatase (ALP), and parathyroid hormone (PTH) (n = 461)

To investigate the effects of calcium and vitamin D supplementation on bone turnover marker levels, muscle strength and quality of life in postmenopausal Chinese women.

Open-label trial.

The participants were divided into group A, B, C, which were treated with calcium (600 mg/d) alone, calcium (600 mg/d) and cholecalciferol (800 IU/d) or calcium (600 mg/d) and calcitriol (0.25 μg/d), respectively, for 2 years.

The participants in group C (calcium (600 mg/d) and calcitriol (0.25 μg/d)) maintained the grip strength, while those in groups A (calcium (600 mg/d) alone) and B (calcium (600 mg/d) and cholecalciferol (800 IU/d)) exhibited decreased grip strength at 24-month follow-up.

Pirotta S, Kidgell DJ, Daly RM. 2015 [13]

Older adults (≥ 60 years) recruited from the local community in Melbourne, Australia and with 25(OH)D concentrations between 25-60 nmol/L (n = 26)

To examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults.

Double-blinded, placebo-controlled randomized trial.

The participants were randomized to receive 2,000 IU/day of vitamin D3 or matched placebo for 10 weeks.

There was no effect of vitamin D on muscle power and function (Muscle strength, stair climbing power, TUG/Dynamic balance)

Bauer, et al. 2015 [14]

Participants (≥ 65 anos) were recruited from 18 study centers in 6 European countries. They were diagnosed with sarcopenic

according to the following criteria: SPPB scores between 4 and 9, and low skeletal muscle index muscle mass index (≤ 37% for men and  ≤ 28% for women) (n = 380)

To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia.

Randomized, Double-Blind, Placebo-Controlled Trial

The active group received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group received an iso-caloric control product to consume twice daily for the same period.

This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in appendicular muscle mass  and in the chair-stand test. However handgrip strength and SPPB improved in both groups without significant between-group differences.

Bischoff-Ferrari, et al. 2016 [15]

Home-dwelling men and women 70 years and older with a low-trauma fall in the previous 12 months

To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline.

Randomized, double-blind, clinical trial. The participants were randomized in three groups: low-dose control group receiving 24,000 IU of vitamin D3; a group receiving 60,000 IU of vitamin D3 and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol. All participants were treated monthly

Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function (SPPB) and were associated with increased risk of falls compared with 24,000 IU.

Rosendahl-Riise H, et al. 2017 [16]

Community-dwelling older subjects with 65 years old or more (n = 2866, 15 clinical trials)

To investigate the effects of vitamin D supplementation (with or without calcium) in community-dwelling older subjects on muscle strength and mobility

Systematic review

A systematic search of the literature (PubMed, Embase, Medline, Web of Science e Cochrane) was performed in April of 2016. The systematic review includes studies that used vitamin D with or without calcium supplementation as the exposure variable and various measurements of muscle strength and mobility.

In the majority of studies, no improvement in muscle strength and mobility was observed after administration of vitamin D with or without calcium supplements. In the meta-analysis, it was observed a small, significant increase in the TUG test after vitamin D supplementation

Levis S, Gómez-Marín O. 2017 [17]

 Sedentary men (n = 130) with baseline 25(OH)D levels of less than 30 ng/mL and SPPB scores of 9 or less.

To determine the effectiveness of vitamin D supplementation in preventing decline in physical function in older men.

Randomized, double-blind, placebo-controlled clinical trial. Participants were daily supplemented with 4,000 IU of cholecalciferol or placebo for 9 months

Daily supplementation resulted in significant increases in 25(OH)D concentrations, but achieving these higher levels did not result in improvements in SPPB score or gait speed.

Antoniak AE, Greig CA. 2017 [18]

 Men and women aged ≥ 65 years or mean age ≥ 65 years (n = 792) from the  community or nursing homes (only one study with 113 women)

To evaluate the effectiveness of combined resistance exercise training and vitamin D3  supplementation on musculoskeletal health in older adults

Systematic review

A systematic search of the literature (Science Direct, Medline, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials) was conducted. Eligible studies were randomized controlled trials published until March 2016

 that evaluated resistance exercise training and vitamin D3 supplementation

Muscle strength of the lower limb was significantly improved within the intervention group (vitamin D and  resistance exercise training group). Nevertheless for other functional variables, such as SPPB and TUG, no additional benefit beyond exercise was shown.

Vaes, et al. 2018 [19]

Prefrail or frail (according to the Fried criteria), community-dwelling older adults (n = 78) aged ≥ 65 years, with a baseline 25(OH)D concentration between 20 and 50 nmol/L.

To investigate the effect of daily supplementation with 25(OH)D3 or cholecalciferol on muscle strength and physical performance in older adults.

Randomized, double-blind, placebo-controlled clinical trial. Participants were supplemented daily with 10 µg 25(OH)D3, 20 µg cholecalciferol, or a placebo capsule.

Increasing the serum 25(OH)D concentration over a period of 6 months did not significantly change muscle strength and physical performance in pre frail and frail older adults

Bislev, et al. 2018 [20]

Healthy community-dwelling postmenopausal women (n = 81) with plasma levels of 25(OH)D < 50 nmol/l and high parathyroid hormone (PTH) levels

To investigate effects of vitamin D3 supplementation on muscle strength, physical performance, postural stability, well-being, and quality of life in healthy community-dwelling postmenopausal women

Randomized Placebo-Controlled Trial. Participants were 1:1 treated with vitamin D3, 70 µg (2800 IU)/day or identical placebo for three months during wintertime

Compared with placebo, a daily supplement with a relatively high dose of vitamin D3 had no beneficial effects on muscle strength and TUG. In some measures of muscle strength and physical performance, it was observed a small unfavorable effect

Bray NW, Doherty TJ, Montero-Odasso M. 2018 [21]

Older adults 75 years of age or more with frail or pre-frail (according to the modified Frailty Phenotype), able to ambulate 10 meters with or without a mobility aid and proficiency in English (n = 40)

To determine if 4000 IU per day of vitamin D3 is safe for frail older adults, and to establish the efficacy of this dose to improve physical performance outcomes in this population.

Open-label, feasibility study

Intervention: 4000 IU of vitamin D3 and 1200 mcg of calcium carbonate daily for four months

Vitamin D supplementation using 4000 IU/daily is safe and has a modest beneficial effect on physical performance (SPPB, grip strength and gait speed)  for frail individuals and those with insufficient vitamin D levels. Participants with vitamin D insufficiency (≤ 75 nmol/L) showed greater benefits.

Verlaan, et al. 2018 [22]

Community-dwelling adults over 65 years were recruited from 18 study centers in Europe. Participants were eligible when presenting mild to moderate limitations in physical function (SPPB score 4-9) and low skeletal muscle mass (37% men and 28% women) (n = 380)

To test if baseline serum 25(OH)D concentrations and dietary protein intake influenced changes in muscle mass and function in older adults who received nutritional intervention.

Randomized, double-blind, placebo-controlled clinical trial.

Participants were randomized to receive either the intervention or an iso-caloric control product twice daily during 13 weeks. The intervention product contained per serving 20 g whey protein, 3 g total leucine, 9 g carbohydrates, 3 g fat, 800 IU vitamin D and a mixture of vitamins, minerals and fibers, and the iso-caloric control drink contained only carbohydrates, fat and some trace elements.

Participants with higher baseline 25(OH)D concentrations and dietary protein intake had, independent of other determinants, greater gain in appendicular muscle mass, skeletal muscle index, and relative appendicular muscle mass in response to the nutritional intervention. There was no effect modification of baseline 25(OH)D status or protein intake on change in chair-stand test.

Seino S, et al. 2018 [23]

Community-dwelling older adults (n = 82) who were aged 65 to 80 years and did not exercise regularly

To investigate whether supplementation with low-dose dairy protein plus micronutrients augments the effects of resistance exercise (RE) on muscle mass and physical performance compared with RE alone among older adults.

Randomized, controlled trial

The RE plus supplementation group participants ingested supplements with dairy protein (10.5 g/day) and micronutrients (8.0 mg zinc, 12 μg vitamin B12, 200 μg folic acid, 200 IU vitamin D, and others/day). Both groups performed the same twice-weekly RE program for 12 weeks.

Low-dose dairy protein plus micronutrient supplementation during resistance exercise significantly increased muscle mass in older adults but did not further improve physical performance.

Aoki K, Sakuma M, Endo N. 2018 [24]

Community-dwelling elderly individuals (aged ≥ 60 years) who were not taking osteoporosis medications (n = 130)

To investigate the impact of exercise and vitamin D supplementation on physical function and locomotor dysfunction in community-dwelling elderly individuals

Randomized trial.

The participants were randomly divided into an exercise group, vitamin D group, and exercise and vitamin D group. Exercise comprised three daily sets each of single-leg standing and squatting and vitamin D supplementation was 1000 IU/day. 

Both exercise and vitamin D supplementation independently improved physical function and increased muscle mass in community-dwelling elderly individuals.

Ranathunga, et al. 2019 [25]

Community dwelling men and women (≥ 70 years) (n = 379)

To determine the effect of monthly supplemental vitamin D3 on muscle function in older adults

Randomized double-blind interventional trial.

Participants were randomized to receive one of these three doses of vitamind D3: 12,000 IU, 24,000 IU or 48,000 IU, monthly for one year.

Baseline plasma 25(OH)D concentration < 25 nmol/L was associated with lower Hand Grip Strength. Although, after supplementation the change in Hand Grip Strength and TUG was not different between treatment groups, suggesting no effect of the intervention.

Koning, et al. 2019 [26]

Community-dwelling persons aged 60-80 years who had clinically relevant depressive symptoms, ≥ 1 functional limitations, and serum 25(OH)D concentrations of 15-50/70 nmol/L (n = 155)

To investigate the effect of vitamin D supplementation on depressive symptoms, functional limitations, and physical performance in a high-risk older population with low vitamin D status

Randomized placebo-controlled trial

Participants received 1200 IU/day vitamin D3 or placebo tablets for 12 months

No relevant differences between the treatment groups were observed regarding depressive symptoms, functional limitations, physical performance, or any of the secondary outcomes.

Lee Y, Sohng K. 2019 [27]

Community-dwelling individuals living alone and with vitamin D levels < 20 ng/mL  (n = 94)

To examine the effects of vitamin D on depression, cognitive function, and physical function in elderly individuals

Nonequivalent control group and pre-test–post-test design

In the experimental group exercise programs were prescribed and participants received 1,000 IU  vitamin D daily. In the control group only exercise programs were prescribed. Treatment duration was 12 weeks.

Vitamin D supplementation was associated with improved vitamin D levels, muscle mass, and time to walk a standard course

Hangelbroek, et al. 2019 [28]

Frail older adults according to the Fried criteria aged above 65 years and blood 25(OH)D concentrations between 20 and 50 nmol/L  (n = 22)  

To investigate the effect of calcifediol on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults.

Double-blind placebo-controlled trial

Subjects were randomized across the placebo group and the calcifediol group (10 μg per day). Muscle biopsies were obtained before and after 6 months

No significant difference between treatment groups was observed on strength outcomes.

Grimnes G, Kubiak J, Jorde R. 2019 [29]

Men and women with low serum vitamin D status (< 42 nmol/L) aged 40 years and older (n = 417)

To study whether vitamin D supplementation improves muscle strength in men and women with low serum vitamin D status

Randomized, double-blind, placebo-controlled clinical trial.

All participants were randomized to receive a loading dose of 100,000 IU vitamin D3 followed by 20,000 IU/week, or placebo. Muscle strength was tested by dynamometers at baseline and after four months.

Muscle strength (hip flexion, biceps flexion, pectorals and handgrip strength) did not change in any of the groups. The results were the same in analyses stratified on sex, 25(OH)D above/below 25 nmol/L (10 ng/ml), smoking status and BMI above/below 27 kg/m²

Shea MK, Roger AF, Dawson-Hughes B. 2019 [30]

Healthy community-dwelling men and postmenopausal women ≥ 60 years old who had serum 25(OH)D ≤ 20 ng/mL at screening (n = 100)

To to test the effect of 12 months of vitamin D supplementation on lower-extremity power and function in older community-dwelling adults

Double-blind, randomized, placebo-controlled trial. Participants were randomly assigned to 800 IU vitamin D3/day or placebo. Those in the intervention group whose serum 25(OH)D was < 28 ng/mL after 4 months were given an additional 800 IU vitamin D3/d, whereas all other participants received placebo as an additional pill.

Increasing serum 25(OH)D to > 32 ng/mL (on average) over 12 months did not affect lower-extremity power, strength, or lean mass in older community-dwelling adults.

Bischoff-Ferrari HA, et al. 2020 [31]

Adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status (Mini-Mental State Examination score of at least 24) (n = 2157)

To test whether vitamin D, omega-3 and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults

Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial.

Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/day of vitamin D3, 1 g/day of omega-3s, and a strength-training exercise program; vitamin D3 and omega-3s; vitamin D3 and exercise; vitamin D3 alone; omega-3s and exercise; omega-3s alone; exercise alone; or placebo

Treatment with vitamin D3, omega-3s or a strength- training exercise program did not result in statistically significant differences in physical performance (SPPB). Thus, the results do not support the effectiveness of these three interventions in improving physical performance.

Nilsson MI, et al. 2020 [32]

Male cohort (≥ 65 years) representative of the North American aging community in general: individuals with low physical activity

 levels (sedentary), normal-to-high BMIs, and varying degrees of age-related muscle loss (n = 32) 

To test the utility of a five-ingredient protein-based (Muscle5) in combination with low-intensity training for maintenance of skeletal muscle mass, strength, performance and muscle quality  in sedentary, free-living elderly

Double-blind, randomized, placebo-controlled trial.

Participants underwent twelve weeks of home-based resistance band training (3 d/week), in combination with daily intake of a five-nutrient supplement containing whey, micellar casein, creatine, vitamin D and omega-3 fatty acids or an isocaloric/isonitrogenous placebo containing collagen and sunflower oil

In the intervention group appendicular and total lean mass, lean mass to fat ratios, maximal strength (handgrip and leg press), function (5-Times Sit-to-Stand time) and fast-twitch muscle fiber cross-sectional areas of the quadriceps muscle were significantly improved.

Rathmacher JA, et al. 2020 [33]

Older adults (n = 117) over 60 years of age with insufficient circulating 25(OH)D levels (15-30  ng/mL)

To determine whether supplementation with calcium, HMB and vitamin D3 would enhance muscle function and strength in older adults

Double-blind, randomized, placebo-controlled trial. Participants were randomly assigned to treatments consisting of: (a) control + no exercise, (b) HMB+ Vitamin D3 + no exercise, (c) Control + exercise, and (d) HMB+Vitamin D3+ exercise. The study evaluated the participants via multiple measurements over the 12 months that included body composition, strength, functionality, and questionnaires.

At 3, 6 and 12 months after the intervention, the group who received only the supplementation with HMB and vitamin D3 had a significant increase in the functional index compared to the control group without exercise. Supplementation with HMB+Vitamin D3 did not further improve the functional index within the exercising group.