Influences of Vitamin D and Iron Status on Skeletal Muscle Health: A Narrative Review



1. Introduction

2. Materials and Methods

3. Discussion

3.1. Vitamin D and Skeletal Muscle Health

3.1.1. Vitamin D and Skeletal Muscle Physiology

3.1.2. Vitamin D Status and Skeletal Muscle Health

3.1.3. Vitamin D Interventions and Skeletal Muscle Health

3.2. Iron and Skeletal Muscle Health

3.2.1. Iron and Skeletal Muscle Physiology

3.2.2. Iron and Skeletal Muscle Health

3.2.3. Iron Interventions and Skeletal Muscle Health

3.3. Interrelationship between Vitamin D, Iron, and Chronic Inflammation

3.3.1. Anti-Inflammatory Role of Vitamin D

3.3.2. Connection between Vitamin D and Iron Status

3.4. Animal Food Sources

4. Conclusions

Author Contributions


Institutional Review Board Statement

Informed Consent Statement

Data Availability Statement

Conflicts of Interest


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Author, Year, Country Study Participants

(Mean ± SD)

Measurements Conclusions
Koundourakis et al., 2014, Greece [84] Caucasian male soccer players, mean age: 25.6 ± 6.2 years

n = 67

Serum 25(OH)D concentrations and performance of the squat jump, countermovement jump, sprint performance, and VO2max, Concentrations of serum 25(OH)D were positively associated with an increase in performance during the squat jump, counter movement jump, VO2max (r = 0.394–0.740), and negatively associated with sprint performance at 10 m and 20 m (r = −410–−0.649) before the soccer season (pre) and during the six-week off-season period (post) (p > 0.01)
Fitzgerald et al., 2014, United States [89] Professional male ice hockey players, mean age: 20.1 ± 1.5

n = 52

Serum 25(OH)D concentrations and performance during skate treadmill graded exercise testing Concentration of serum 25(OH)D was not associated with VO2max, max heart rate, peak respiratory exchange ratio, final stage completed, and total exercise time completed during the graded exercise test (p = 0.22–0.71)
Hamilton et al., 2014, Qatar [85] Male soccer players stratified based on 25(OH)D concentration (<10–>30 ng/mL) mean age: 24.4 ± 8.1

n = 342

Serum 25(OH)D concentrations and lower limb isokinetic performance (peak torque) Soccer players with serum 25(OH)D levels >30 ng·mL−1 displayed 17% greater concentric and 13% greater eccentric hamstring peak torque in the non-dominant leg compared to those with 25(OH)D levels of ≤10 ng·mL−1 (p = 0.015–0.021)
Forney et al., 2014, United States [90] Recreationally active college students, mean age: 23.0 ± 0.7 years

n = 39; n = 20 males, n = 19 females

Serum 25(OH)D concentrations and performance during aerobic testing (Bruce Protocol [VO2max]), anaerobic power (Wingate), strength (upright bench press, bicep curl, triceps pushdown, leg curl, leg extension, and upright row [8-repetition max]), and power (maximal vertical and horizontal jump). Concentrations of serum 25(OH)D were associated with VO2max (r = 0.360, p = 0.018), however, there was no association of 25(OH)D with anaerobic power, muscular strength, and muscular power
Ksiazek et al., 2016, Poland [86] Polish premier league soccer players, mean age: 22.7 ± 5.3 years

n = 43

Serum 25(OH)D concentrations and performance during hand grip strength, lower-limb isokinetic strength, and aerobic performance (VO2max) Soccer players with serum 25(OH)D concentrations >20 ng·mL−1 displayed a 12% greaterpeak torque compared to those with 25(OH)D levels of ≤20 ng·mL−1 (p ≤ 0.05)

A significant positive correlation between 25(OH)D levels and concentric leg extension peak torque (r = 0.410, p < 0.040).

Zeitler et al., 2018, Austria [87] Healthy recreational athletes age: 18–65 years; 40.5 ± 9.2 (males), 38.7 ± 9.8 (females)

n = 581; n = 287 males, n = 284 females

Serum 25(OH)D concentrations and performance during maximal and submaximal treadmill running Males with serum 25(OH)D levels <20 ng·mL−1 had significantly lower submaximal performance on the treadmill compared with those with normal 25(OH)D levels (p = 0.045)

Associations between 25(OH)D levels and maximal and submaximal treadmill performance in males and females displayed no significant differences

Most et al., 2021, Germany [88] 88 male handball and 24 male ice hockey players stratified based on 25(OH)D concentration (<30 and >30 ng/mL) mean age: 26.1 ± 5.2 years

n = 112

Serum 25(OH)D concentrations and performance during a maximal cycle ergometer test (W/kg) Athletes with serum 25(OH)D levels <30 ng·mL−1 achieved an 11% higher maximal aerobic power compared to those with insufficient levels (>30 ng·mL−1) (p = 0.030)
Older Adults
Marantes et al., 2011, United States [91] Age-stratified, random sample of males and females ages 21–97 years old, mean age: 57.0 ± 18.0 years.

n = 700; n = 325 males, n = 375 females

Concentrations of serum 25(OH)D and 1,25(OH)2D, fat mass and muscle mass, handgrip strength, isometric leg extension strength Lower serum 25(OH)D levels were inversely associated with greater fat mass, while lower 1,25(OH)2D levels were positively associated with lower muscle mass and muscle strength in males and females
Mastaglia et al., 2011, Argentina [4] Females over age 70 years attending bone health assessments at the Buenos Aires Hospital, mean age: 71.0 ± 4.0 years.

n = 54

Lower limb lean mass, muscle function (walking speed, chair stand, balance), muscle strength (hip flexors and abductors, leg extensors), levels of calcium, phosphorus, serum 25(OH)D concentrations, and urinary calcium and creatinine Older adults with serum 25(OH)D levels ≥20 ng·mL−1 (n = 25) had 11% better scores on muscle function tests, 0.4 s faster walking speed, and were 14% and 13% stronger in tests of leg extension and hip abduction strength, respectively, than those with serum 25(OH)D levels <20 ng·mL−1 (n = 29).
Toffanello et al., 2012, Italy [20] Older adults aged 65–98 years from a large cohort study in Italy (Pro.V.A), mean age: 75.6 ± 7.5.

n = 2694

Physical Performance (balance, chair stand, gait speed, 6 min walking test), handgrip strength, quadriceps strength, levels of PTH andserum 25(OH)D Levels of serum 25(OH)D were positively associated with the chair stand, gait speed, 6 min walking test, and handgrip strength (p < 0.001). Concentrations of 100 nmol·L−1 was determined to be related to greater muscle function
Tieland et al., 2013, The Netherlands [92] Older adults >age 65 years who were considered frail or pre-frail, mean age: 79.0 ± 7.8 years.

n = 127

Serum 25(OH)D, creatinine, glucose, and insulin concentrations, dietary intake, body composition, leg strength (leg press and leg extension), handgrip strength, and physical performance (SPPB) Levels of serum 25(OH)D were associated with appendicular skeletal muscle mass (β = 0.012, p = 0.050). Levels of 25(OH)D and vitamin D intake were positively associated with higher SPPB scores (β = 0.020–0.180, p = 0.020–0.038).
Gumieriro et al., 2015, Brazil [93] Older adults with a hip fracture and older than 65 years admitted to hospital, mean age: 80.0 ± 7.0 years.

n = 100

Serum 25(OH)D concentrations, handgrip strength, mid-upper arm muscle circumference, length of hospital stay, mortality Participants with lower serum 25(OH)D concentrations had 40% lower handgrip strength and 52% higher mortality rate. Levels of serum 25(OH)D predicted handgrip strength when adjusted for age and sex (β = −1.945, p = 0.020).
Iolascon et al., 2015, Italy [94] Post-menopausal females aged 50 years or older, mean age: 65.9 ± 7.7 years.

n = 80; n = 46 with low vitamin D levels, n = 34 with normal vitamin D levels

Handgrip strength, isometric leg extension strength, SPPB, gait speed, serum 25(OH)D concentrations Serum 25(OH)D concentrations were positively associated with handgrip strength (r = 0.234), leg extensor strength (r = 0.234), and inverselyl associated with time to complete physical performance tests such as walking speed (r = −0.457) and chair stand (r = −0.564). Those with serum 25(OH)D levels ≥30 ng·mL−1 had better results for handgrip strength, leg extension strength, and SPPB scores (p = 0.001–0.003)
Verlaan et al., 2017, The Netherlands [6] Subsample of sarcopenic participants from the PROVIDE study, which were ≥65 years old, mean age: 71.0 ± 4.0 years.

n = 132; sarcopenic participants (n = 66) and non-sarcopenic controls (n = 66)

Body composition (appendicular muscle mass and fat mass), muscle strength and function (handgrip strength, SPPB), ADLs, frailty status, nutritional status, and levels of serum 25(OH)D, vitamin B12, and folate Serum 25(OH)D levels were not different between groups; however, there was a greater prevalence of vitamin B12 deficiency in sarcopenic individuals
Aspell et al., 2019, Ireland [95] Older adults aged 60 years or older from the English Longitudinal Study of Aging, mean age: 69.8 ± 6.9 years.

n = 4157

Serum 25(OH)D concentrations, handgrip strength, SPPB A greater number of older adults had low handgrip strength and SPPB score in the lowest serum 25(OH)D concentration quintile compared to the others quintiles (p < 0.0001–0.01). After adjusting for confounding factors, vitamin D deficiency was positively associated with low SPPB score [OR 1.65, p < 0.01) and positively predicted low handgrip strength (OR 1.44, p < 0.001).
Conzade et al., 2019, Germany [96] Older adults aged 65 years or older, mean age: 75.7 ± 6.6 years.

n = 702

Muscle mass, handgrip strength, gait speed, TUG, Serum 25(OH)D levels Low levels of serum 25(OH)D (<25 nmol·L−1) were had a 0.94% greater loss in muscle mass and 3.06% increase in time to complete TUG compared to higher levels (≥50 nmol·L−1) but was not related to change in handgrip strength or gait speed.
Vaes et al., 2019, The Netherlands [97] Older adults 65 years or older that attended the screening visit of two clinical trials (D-DOSE and D-FIT), mean age: 74.0 ± 6.0 years.

n = 756

Serum 25(OH)D levels, handgrip strength, gait speed, TUG, isometric leg extension strength Older adults with lower serum 25(OH)D levels (<50 nmol·L−1 and 50–75 nmol·L−1) had inverse relationships for time to complete TUG (β = 0.73–0.83, p = 0.01–0.05) and lower scores for gait speed (β = −0.04, p < 0.05), but there no relationships observed with handgrip or leg extension strength. Those with lower 25(OH)D levels were also more likely to be categorized as frail.
Dong et al., 2010, United States [98] Adolescents aged 14–18 years old, mean age: 16.2 ± 1.2 years.

n = 599

Levels of serum 25(OH)D, time spent in physical activity, cardiovascular fitness determined from oxygen consumption during a treadmill test Positive associations were found between serum 25(OH)D levels and unadjusted and adjusted vigorous physical activity (r = 0.132–0.139, p = 0.002–0.01) and maximal oxygen consumption (r = 0.100–0.212, p < 0.01–0.025).
Gracia-Marco et al., 2012, Europe (Sweden, Greece, Italy, Spain, Hungary, Belgium, France, Germany, Austria) [99] Adolescents aged 12.5–17.5 years old across Europe that completed the blood sample analysis as part of the HELENA-CSS study, mean age: 15.0 ± 1.2 years.

n = 1089; males, n = 509, females, n = 580

Standing long jump, 20 m shuttle run to estimate VO2max, red blood cell parameters, biomarkers of iron status (sTfR and ferritin), other micronutrients (vitamins A, E, C, B6, and B12, folate, and serum 25(OH)D) concentrations Concentrations of serum25(OH)D were positively correlated with estimated VO2max (from 20 m shuttle run) (β = 0.091, p = 0.030) and standing broad jump (β = 0.125, p = 0.010) in female adolescents.
Valtueña et al., 2013, Europe (Sweden, Greece, Italy, Spain, Hungary, Belgium, France, Germany, Austria) [100] European adolescents ages 12.5–17.5 years, mean age: 14.9 ± 1.2 years.

n = 3000, n = 1006 had samples for 25(OH)D and included in the analysis

Serum 25(OH)D concentrtions, BMI, fat mass, fat-free mass, fat mass index, fat-free mass index, 20 m shuttle run to estimate VO2max, handgrip strength, standing long jump In males, VO2max had a positive correlation with serum 25(OH)D concentrations (r = 0.108, p = 0.022). Linear regression demonstrated a positive association between VO2max and serum 25(OH)D concentrations (β = 0.189, p = 0.002) and a negative associaton between BMI and serum 25(OH)D concentrations (β = −0.125, p = 0.023). In females, handgrip strength was positively associated with serum 25(OH)D concentrations (β = 0.168, p = 0.002). Greater long jump performance was a positively ssociated with higher serum 25(OH)D levels in males.
Carson et al., 2015, Ireland [101] Males and females ages 12 and 15 years from Northern Ireland.

n = 1015; (12-year-old males, n = 266; 12-year-old females, n = 260; 15-year-old males, n = 239; 15-year-old girls, n = 250)

Serum 25(OH)D concentrations, BMI, fat mass, fat-free mass, fat-free mass index, handgrip strength, jump height, jump power, 20 m shuttle run to estimate VO2max Serum 25(OH)D concentrations in the highest tertile (>51 nmol·L−1) were positively associated with greater muscle strength in the 15-year-old males (β = 3.90, p < 0.001), but this relationship was not present in any other group categorized by age or sex. There were no associations between serum 25(OH)D concentrations and muscle mass, muscle power or VO2max
Bezrati et al., 2016, Tunisia [102] Physically active males aged 7–15 years, mean age: 11.4 ± 2.0, 11.8 ± 2.2, and 11.0 ± 1.9 years for vitamin D deficient, insufficient, and sufficient, respectively.

n = 125

Serum 25(OH)D concentrations, body fat percentage, vertical jump, broad jump, triple hop, sprint agility, and trunk force Serum 25(OH)D levels were positively associated with trunk force, vertical jump, and broad jump (β = 0.165–0.552, p < 0.001) and inversely related to 10 m sprint, 20 m sprint, and shuttle run (β = −4.330–06.436, p < 0.001).
Blakeley et al., 2018, United States [103] Children in fourth through eighth grades in Boston area, mean age: 11.2 ± 1.3 years.

n = 350

Handgrip strength, levels of HDL cholesterol, triglycerides, and serum 25(OH)D concentrations, BMI There were no associations between handgrip strength and serum 25(OH)D concentrations.
Wakayo et al., 2018, Ethiopia [104] Ethiopian school-age children 11–18 years old, median age: 15 years.

n = 174

Serum 25(OH)D concentrations, handgrip strength There was no association between handgrip strength and serum 25(OH)D levels
Author, Year, Country Study Participants Supplemental Treatment Duration Measurements Conclusions
Shanely et al., 2014, USA [111] Professional football, tennis, lacrosse, baseball players, and professional wrestlers. n = 33 mean age: 16.3 ± 0.25 years. 600 IU·d−1 (Portobello mushroom powder) vs. Placebo 6-weeks Serum 25(OH)D concentrations, isometric deadlift strength and vertical jump performance No associations between serum 25(OH)D concentrations with isometric muscle strength or vertical jump performance. Isometric strength and vertical jump performance was not different between supplement and placebo group.
Close et al., 2013, UK [112] Professional rugby, soccer, flat jockeys and national hunt jockeys. n = 61 5000 IU·month−1 vs. placebo 6-weeks Serum 25(OH)D concentrations, isometric strength, 10 m sprint performance and vertical jump performance There was approximately a 3-inch increase in vertical jump height (p = 0.008) and 0.04-s time improvement in 10 m sprint performance (p = 0.008) in the supplementation group with no change in the placebo.
Close et al., 2013, UK [113] Professional rugby and soccer players. n = 30 20,000 or 40,000 IU·week−1 vs. placebo 6 or 12-weeks Serum 25(OH)D concentrations, dynamic strength (1-RM bench press, 1-RM leg press) and vertical jump performance Serum 25(OH)D concentrations increased in both 6-week and 12 week periods (p < 0.0005) with concentrations higher after 6-weeks of 40,000 IUs compared to 20,000 IUs (p = 0.016). However, serum 25(OH)D concentrationswere not associated with improvements in 1-RM bench press, 1-RM leg press and vertical jump performance following 6 or 12-week of supplementation.
Jastzebska et al., 2016, Poland [114] Well trained soccer players.

n = 36

5000 IU·d−1 vs. placebo 8-weeks Serum 25(OH)D concentrations, 30-s Wingate test for peak power, sprint tests for 5, 10, 20, and 30 m, squat jump, countermovement jump Supplementation group displayed an increase in all power tests except for 30 m sprint time (p < 0.001); however, mean change scores were not different between supplementation and placebo groups.
Todd et al., 2016, Ireland [115] Gaelic football players. n = 42 3000 IU·d−1 vs. placebo 12-weeks Serum 25(OH)D concentrations and VO2max Serum 25(OH)D concentrations increased following supplementation, however, supplementation had no effect on VO2max.
Wyon et al., 2016, UK [109] Judo athletes. n = 22 150,000 IU once vs. placebo 8 days Serum 25(OH)D concentrations, maximal isokinetic leg extension and leg curls Supplement group displayed a 13% increase in muscle strength following 8 days of supplementation (p ≤ 0.001).
Fairbairn et al., 2017, New Zealand [110] Professional rugby players. n = 57 50,000 IU once every 2 weeks 11–12 weeks Serum 25(OH)D concentrations, 30 m sprint performance and maximal dynamic strength (weighted chin-up 1-RM, bench pull 1-RM, and bench press 1-RM) No difference in 30 m sprint performance; however, there was a 5.5 kg increase in dynamic strength (weighted chin-up 1-RM), (p = 0.002).
* Lips et al., 2010, USA, Mexico, The Netherlands, Germany, Canada [116] Older adults aged 70 years or older who were ambulatory and had 25(OH)D levels between 6 and 20 ng·ml−1, mean age: 77.6 ± 6.6 and 78.5 ± 62.0 years in the placebo and experimental groups, respectively.

n = 226 randomized, 202 completed the study.

8400 IU vitamin D3 weekly (n = 105) or placebo (n = 97) 16 weeks Serum 25(OH)D concentrations, postural sway, SPPB, and levels PTH 25(OH)D levels increased from approximately 14 to 26 ng·mL−1 (p < 0.001) in the supplementation group; however, there were no changes in postural sway or SPPB scores for either group
** Ceglia et al., 2013, USA [82] Older females aged 65 years or older who were ambulatory, community-dwelling, and postmenopausal, mean age: 78.0 ± 5.0 years.

n = 24 randomized, 21 included in analysis

4000 IU vitamin D3 (n = 11) or placebo (n = 13) 4 months Serum 25(OH)D concentrations, leg extension strength, muscle fiber type and intramyonuclear VDR from biopsies of the vastus lateralis The supplementation group had a much greater increase in 25(OH)D levels after 4 months (36.4 vs. 4.2 nmol·L−1 increase, p < 0.001), as well as a 10.6% increase in total muscle fiber cross-sectional area (p = 0.048) and 29.7% increase in VDR concentration (p = 0.025) compared to changes of −7.4% and 7.8%, respectively, in the placebo group.
Lagari et al., 2013, USA [117] Older adults aged 65–95 years who were ambulatory, and community dwelling, mean age: 73.4 ± 6.4 years.

n = 105 randomized, n = 86 participated in sub-study

400 IU or 2000 IU vitamin D3 daily 6 months Physical performance (gait speed, timed sit-to-stand, single leg balance, gallon jug test, handgrip), body composition, levels of serum 25(OH)D, calcium, creatinine, and spot urine calcium There was no improvement in physical performance for either group; however, supplementation was more effective in those with low baseline 25(OH)D levels (<30 ng·dL−1. The relative change in serum 25(OH)D (%) was positively associated to change in chair stand test score (5.1%, p = 0.033) and inversely associated with an increase in fat mass (p = 0.027).
Bauer et al., 2015, The Netherlands [118] Older adults aged 65 years or older with mild to moderate physical limitations and low skeletal muscle index, mean age: 77.3 ± 6.7 and 78.1 ± 7.0 years for the experimental and placebo group, respectively.

n = 380 were randomized, 302 completed all three study visits

Active control product (20 g whey protein, 3 g leucine, 9 g carbohydrate, 3 g fat, 800 IU vitamin D) n = 184, or isocaloric control, n = 196 consumed twice daily 13 weeks Handgrip strength, SPPB, appendicular muscle mass, serum 25(OH)D concentrations Handgrip strength increased by 0.79 kg in 13 weeks in the active group (p = 0.005), with no significant increase in the control. The SPPB scores increased in both groups (p < 0.001), with chair stand time improving more in the active group (p = 0.018). An estimated mean difference of 0.17 kg of appendicular muscle mass showed a significant increase over the placebo (p < 0.001).
Cangussu et al., 2015, Brazil [119] Post-menopausal females aged 50–65 years, mean age: 55.6 ± 6.6 years.

n = 160 randomized and included as intention to treat, n = 140 analyzed per protocol

1000 IU Vitamin D3 (n = 80) or identical placebo (n = 80) 9 months Handgrip strength, Chair stand, lean body mass and fat mass assessed by DXA, serum 25(OH)D concentrations, creatinine, calcium, and parathyroid hormone levels The supplementation group had a 45.4% increase in serum 25(OH)D levels at 9 months compared to the 18.5% decrease seen in the placebo group. Lean mass decreased 6.8% over 9 months only in the placebo group (p = 0.030). The supplementation group had a 25.3% increase in chair stand performance, whereas there were no changes in the placebo (p < 0.0001). Neither group had a change in handgrip strength.
* Apaydin et al., 2018, Turkey [120] Postmenopausal females ages 50–68 years with vitamin D levels <20 ng·mL−1., mean age: 51.6 ± 5.8 and 51.58 ± 5.54 years in the daily and single dose groups, respectively.

n = 60

800 IU daily (n = 32) or a single bolus of 300,000 IU (n = 28) of vitamin D3 3 months Serum 25(OH)D concentrations, muscle strength of the quadriceps and hamstrings There were no differences in muscle strength between groups; however, the daily dose group showed greater non-significant increases over time. Serum 25(OH)D levels increased in both groups but were higher in the single dose compared to the daily dose group.
** Vaes et al., 2018, The Netherlands [121] Older adults aged 65 years or older with 25(OH)D levels between 20 and 50 nmol·L−1 and were considered frail or prefrail, mean age: 74.0 ± 6.0 years.

n = 78

Daily supplements of 10 μg 25(OH)D3 (n = 26), 20 μg vitamin D3 (n = 24), or a placebo (n = 25) 6 months Muscle strength (leg extension and flexion, handgrip strength), Physical performance (TUG, SPPB, postural sway), serum 25(OH)D concentrations, muscle fiber type from biopsies of the vastus lateralis, Body composition (appendicular lean mass, BMI) The two supplementation groups had an increase in serum 25(OH)D levels over time, with the 10 μg 25(OH)D3 showing the greatest increase (p < 0.01). There were no differences between groups for muscle strength or performance
* Hajj et al., 2019, Lebanon [122] Older adults who were pre-sarcopenic and vitamin D deficient, mean age: 73.3 ± 2.1 years.

n = 128

vitamin D supplementation of 10,000 IU of vitamin D3 (n = 64) or a placebo (n = 64) 6 months Handgrip strength, appendicular skeletal muscle mass, serum 25(OH)D concentrations The supplement group had a greater change in serum 25(OH)D levels (10.13 to 27.98 ng·mL−1, p < 0.001) compared to the placebo (10.56 to 15.71 ng·mL−1, p < 0.001). Handgrip strength increased approximately 0.85 kg (p = 0.007), and appendicular skeletal muscle mass increased 0.65 kg (p = 0.001) at 6 months, whereas the placebo group had no differences over time.
Molmen et al., 2021, Norway [123] Older adults with healthy lung function or diagnosed with COPD, ages 65–77, mean age: 68.0 ± 5.0 years.

n = 95 enrolled, 78 completed

Vitamin D3 supplementation of 10,000 IU per day for two weeks and 2000 IU per day for the remainder (n = 34) or the study or a placebo (n = 44) 12 weeks of vitamin D supplementation only, followed by 13 weeks of supplementation + resistance training One repetition maximum (1 RM) of leg extension and leg press, number of repetitions at 50% of 1 RM, isokinetic peak torque, VO2max, Wmax, sit-to-stand, 6 min step test, muscle thickness, leg lean mass, blood analysis for total testosterone, cortisol, growth hormone, IGF-1, SHBG, androstenedione, serum 25(OH)D concentrations, PTH, calcium, albumin, creatinine, creatine kinase AST, CRP, triglycerides, LDL, HDL, thyroid hormones, and iron status variables, and muscle fiber cross-sectional area and nuclei number from biopsies. Overall, supplementation resulted in a 42 nmol·L−1 increase in serum 25(OH)D concentrations (p < 0.001) but did not lead to any additional improvement in training-related effects.
** Ward et al., 2010, UK [124] Post-menarchal females ages 12–14 years, mean age: 13.8 ± 0.6 years.

n = 73, n = 72 completed intervention

4 doses per year of 150,000 IU vitamin D2 (n = 36) or placebo (n = 36) 12 months Muscle force, power velocity, and jumping height during countermovement vertical jumps, grip strength, serum 25(OH)D concentrations, PTH, bone mineral density Serum 25(OH)D concentrations increased by 12.3 nmol·L−1 (p < 0.001) in the intervention group while decreasing by −0.8 nmol·L−1 in the placebo group. Mean PTH decreased in both groups. There were no significant changes between groups for muscle parameters or bone mineral density.
Wright et al., 2018, USA [125] Children age 9–13 years in the United States, mean age: 11.3 ± 1.2 years.

n = 324

0, 400, 1000, 2000, or 4000 IU vitamin D3 per day 12 weeks Serum 25(OH)D and 1,25(OH)2D concentrations, body composition (fat-free mass, fat mass, body fat percent, forearm and calf muscle cross-sectional area, muscle density, intramuscular adipose tissue, and handgrip strength. Changes in muscle mass and strength over the 12 weeks were not related to changes in 25(OH)D, even with a 34.9% (p < 0.001) increase in serum 25(OH)D levels. However, increases in 25(OH)D were inversely associated with forearm intramuscular adipose tissue (r = −0.17, p = 0.029).
Mortensen et al., 2019, Denmark [126] Children aged 4–8 years in Copenhagen, mean age: 6.6 ± 1.5 years.

n = 117

10 μg·day−1 (n = 38), 20 μg·day−1 (n = 39), or a placebo (n = 40) 20 weeks Handgrip strength. BMI, fat mass index, fat-free mass index, and serum 25(OH)D, IGF, and IGF-binding protein concentrations At baseline, serum 25(OH)D concentrations were positively associated with handgrip strength (non-adjusted: β = 0.73–0.74, p = 0.005–0.006, adjusted: β = 0.38–0.39, p = 0.022–0.025), fat-free mass index (non-adjusted: β = (0.26, p = 0.001, adjusted: β = 0.19, p = 0.006), and IGF binding protein (β = 0.19, p = 0.010) in females. Levels of serum 25(OH)D decreased by 24.2 μg·day−1 in the placebo group and increased by 4.9–17.4 μg·day−1 (p < 0.001) in both intervention groups. There were no differences between groups after the intervention for handgrip strength or fat-free mass; however, IGF-1 was higher in the 20 μg·day−1 group compared to the placebo
Author, Year, Country Study Participants Measurements Conclusions
DellaValle & Hass, 2012, USA [46] Female rower athletes

n = 165,

n = 44 of rowers were identified as iron depleted without anemia (IDNA) [serum ferritin < 20.0 μg·L−1]; n = 16, as anemic (hemoglobin < 12.0 g·dL−1).

Physical performance of 48 nonanemic rowers (n = 24 normal, n = 24 depleted) was assessed during a 4 km rowing event (VO2max, time and energetic efficiency), ferritin, sTfR, and Hb levels Rowers with IDNA had 0.3 L·min−1 lower VO2max and VO2peak (p = 0.02–0.03) and higher lactate concentration during a 4 km row assessment (p = 0.02). Relationships between iron status and endurance performance (VO2max, VO2peak, time, and energetic efficiency), between groups was dependent on the rowers’ training load. A positive correlation was present between VO2peak and serum ferritin (r = 0.29, p = 0.05), but no other measures of iron status with performance. IDNA may influence the training load of athletes affecting performance.
Tsai et al., 2019, Taiwan [170] Males Taiwanese Military

n = 3666

3000 m run test, 2 min sit-ups and 2 min push-up test, levels of Hb and hematocrit After adjusting for age, service occupation, BMI, waist size, and blood pressure, mild anemic males were more likely to be the worst 10% performers in the 3000 m run test (Odds Ratios 1.47, p = 0.043). However, mild anemic males had a higher possibility to be the best 10% performers in the 2 min push-ups test (Odds Ratio 1.68, p = 0.001). There was no associations between anemic status and 2 min sit-up test.
Shoemaker et al., 2019, USA [171] Male (n = 179; mean age 12.0 ± 2.1 years) and female (n = 70; mean age 12.0 ± 2.2 years) youth athletes Athletic performance (vertical jump, broad jump, agility drill times, 20-yard dash time, power push up force), dietary intakes, levels of ferritin, sTfR, and Hb Athletic performance was consistently related to Hb in males (r = 0.237–0.375, p < 0.001–0.05) and with sTfR (r = 0.521–0.649, p < 0.001–0.004) and iron intake (r = 0.397–0.568, p = 0.001–0.027) in females.
Older Adults
Juárez-Cedillo et al., 2014, Mexico [172] Older adults from the Study on Aging and Dementia, mean age by Hb quintiles: 71.7 ± 7.6, 70.8 ± 7.0, 71.6 ± 7.7, 69.7 ± 7.3, and 70.8 ± 7.4 years from lowest to highest Hb quintile, respectively.

n = 1933

Levels of Hb, frailty status (weight loss, exhaustion, grip strength, and walking speed) Greater risk of frailty was present in those with lower Hb concentrations, with concentrations of Hb of 10.5 and 11.5 g·dL−1 having greater likelihood of frailty (Odds Ratio 6.3 and 2.3) compared to concentrations of 15.0 g·dL−1 (Odds Ratio 0.81).
Kim et al., 2014, Korea [173] Older adults in South Korea from the KNHANES IV study that were 60 years or older, mean age: males, 69.0 ± 6.3; females, 69.3 ± 6.4 years.

n = 2332

Ferritin concentrations, HOMA-IR, sarcopenic status based on appendicular skeletal muscle mass Ferritin concentrations were higher in the sarcopenic females compared to the non-sarcopenic females (70.7 vs. 85.4 ng·mL−1, p = 0.001). Appendicular skeletal muscle was negatively associated with ferritin concentrations (males; r = −0.111, p = 0.001, females; r = −0.104, p < 0.001).
Pires Corona et al., 2015, Brazil [174] Older adults in Sao Paulo, Brazil, mean age 70.0 years.

n = 1256

Levels of Hb, frailty status (weight loss, exhaustion, grip strength, and walking speed) Mean Hb concentrations were lower in frail older adults compared to non-frail older adults (13.3 g·dL−1 vs. 14.3 g·dL−1, p < 0.001). Frail individuals were more likely to have lower Hb than non-frail individuals, independent of confounding health conditions (Odds Ratio 3.27, p < 0.001).
Moon et al., 2015, Korea [175] Korean males 65 years or older from the KNHANES and young males not meeting study criteria included as a reference group, mean ages: 71.6 ± 5.0 and 30.7 ± 5.9 years, respectively.

n = 1464

Levels of Hb, Skeletal Muscle Index Low muscle mass was related to presence of anemia, independent of potential confounding factors (Odds Ratio 2.83).
Ruan et al., 2019, China, Ghana, India, Mexico, Russia, South Africa [176] Older adults in China age 50 years or older that were part of the World Health Organization Study on Global Ageing and Adult Health, mean age 62.6 ± 0.2 # years.

n = 13,175

Levels of Hb, frailty status Presence of anemia was associated with frailty, in which for each 1 g·dL−1 increase in Hb concentration, there was a 4% decrease in the odds of frailty (Odds Ratio 0.96, p < 0.001).
Neidlein et al., 2021, Germany [177] Hospitalized older adults aged 65 years or older, mean age: 81.4 ± 6.2 years.

n = 224

Levels of ferritin, transferrin, iron, and Hb, CRP, handgrip strength, SPPB score, isometric leg extension strength. Iron supplementation protocol was recorded if provided during hospital stay In those with iron deficiency, frailty scores were higher (4 vs. 3, p < 0.05), Hb was lower (males; 11.1 g·dL−1 vs. 12.4 g·dL−1, p < 0.01, females; 10.7 g·dL−1 vs. 11.7 g·dL−1, p < 0.001), and CRP was higher (3.2 mg·dL−1 vs. 1.9 g·dL−1, p < 0.01). There were no differences in muscle strength and function parameters between those with were iron deficient or non-iron deficient. However, a positive association was observed between Hb and handgrip strength at baseline and at hospital discharge in those with iron deficiency (β = 0.242–0.641, p = 0.020–0.039).
Arsenault et al., 2011, Colombia [169] Youth aged 5–12 years in Colombia.

n = 1945

Standing long jump, 36 m shuttle run, and levels of Hb, ferritin, vitamin B12, complete blood count, CRP, erythrocyte folate There were no differences in performance measurements between anemic and non-anemic youth. Females with low ferritin had 0.6 s slower performance on the shuttle run than females with normal ferritin levels (p = 0.020). Males with low ferritin had 7 cm lower jump scores than those with normal ferritin (p = 0.030).
Gracia-Marco et al., 2012, Sweden, Greece, Italy, Spain, Hungary, Belgium, France, Germany, Austria [99] Adolescents aged 12.5–17.5 years old across Europe that completed the blood sample analysis as part of the HELENA-CSS study.

n = 1089; males, n = 509, females, n = 580

Standing long jump, 20 m shuttle run to estimate VO2max, red blood cell parameters, biomarkers of iron status (sTfR and ferritin), other micronutrients (vitamins A, E, C, B6, and B12, folate, and serum 25(OH)D) concentrations Concentrations of Hb was positively associated with estimated VO2max (from 20 m shuttle run) in male adolescents (β = 0.192, p = 0.002).
Author, Year, Country Study Participants Supplemental Iron Treatment Duration Measurements Conclusions
DellaValle & Hass, 2014, USA [179] 31 Rowers Treatment group: 100 mg·d−1 FeSO4 (n = 15)

Placebo: (n = 16)

6-weeks Iron status (Hb, iron ferritin, transferrin receptor), body composition, performance (4 km time trial, VO2max, energetic efficiency, and blood lactate) Treatment group showed a 0.3 g·dL−1 improvement in Hb (p = 0.04), slower lactate response during the 4 km time trial, and (12.2 nmol·L−1 vs. 11.4 nmol·L−1 at post-treatment compared to placebo, p < 0.001), and a 4.3 kcal higher energy expenditure (p = 0.03) post-treatment.
Garvican et al., 2014, Australia [180] 27 distance runners with low or suboptimal iron status Intravenous (IV) iron (550 ± 171 mg for low iron status, 375 ± 39 mg for suboptimal iron status) or oral supplementation of one (low) or two (suboptimal) tablets of 305 mg ferrous sulfate and 105 mg elemental iron) daily 6-weeks Iron status (Hb, sTfR, ferritin, erythropoietin, transferrin, Hb mass) and performance (VO2max, lactate threshold, running economy) Both IV and oral supplementation showed a 83.7–417.5% increase ferritin at 6 and 8 weeks and a −5.6–−9.9% decrease in sTfR concentrations. VO2max increased, with a more profound increase in runners with low iron status (1.2–3.3 mL·kg−1·min−1).
Mielgo-Ayuso et al., 2015, Spain [181] 22 Elite female volleyball players (27.0 ± 5.6 years) Treatment group: 325 mg·d−1 ferrous sulphate daily (n = 11)

Placebo: (n = 11)

11-weeks Iron status (serum iron, ferritin, transferrin saturation index, Hb), and strength (bench press, military press, half-squat, power clean, clean and jerk, and pull-over) Treatment group showed significantly greater levels of serum iron, ferritin, transferrin saturation index, Hb compared to placebo group. Improvements in bench press (38.2 to 43.1 kg) clean and jerk (27.7 to 35.1 kg), power clean (33.3 to 35.1 kg), and total mean strength (35.2 to 41.9 kg occurred after the 11 weeks in the treatment group compared to placebo group (p < 0.05).

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Shoemaker, M.E.; Salmon, O.F.; Smith, C.M.; Duarte-Gardea, M.O.; Cramer, J.T. Influences of Vitamin D and Iron Status on Skeletal Muscle Health: A Narrative Review. Nutrients 2022, 14, 2717.

Shoemaker ME, Salmon OF, Smith CM, Duarte-Gardea MO, Cramer JT. Influences of Vitamin D and Iron Status on Skeletal Muscle Health: A Narrative Review. Nutrients. 2022; 14(13):2717.

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Shoemaker, Marni E., Owen F. Salmon, Cory M. Smith, Maria O. Duarte-Gardea, and Joel T. Cramer. 2022. “Influences of Vitamin D and Iron Status on Skeletal Muscle Health: A Narrative Review” Nutrients 14, no. 13: 2717.

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