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Canadian Journal of Kidney Health and Disease logoLink to Canadian Journal of Kidney Health and Disease
. 2025 Sep 27;12:20543581251365363. doi: 10.1177/20543581251365363

Vitamin D and Muscle Function in a Diverse Hemodialysis Cohort

Sara Mahdavi 1,2,3,✉, Katie Rosychuk 2, Hulya Taskapan 3, Paul Y Tam 3,4, Tabo Sikaneta 4
PMCID: PMC12476495  PMID: 41024859

Abstract

Background:

Declines in skeletal muscle function and widespread vitamin D deficiency are common in individuals receiving hemodialysis (HD), yet the relationships among serum 25-hydroxyvitamin D (25(OH)D) concentrations, vitamin D supplementation, and muscle strength remain incompletely characterized in this population.

Objective:

To evaluate the associations between serum 25(OH)D concentrations, dietary vitamin D intake, supplementation status, and muscle strength in a multiethnic cohort of patients undergoing HD.

Design:

Cross-sectional study.

Setting:

Two satellite HD centers in Toronto, Canada.

Participants:

Eighty-one adults receiving HD (mean age 58 years; 64% male) were enrolled following screening based on clinical and demographic inclusion and exclusion criteria.

Measurements:

Handgrip strength, measured via digital dynamometry, was the primary outcome and marker of muscle function. Serum 25(OH)D was quantified to assess biochemical vitamin D status. Three-day food and supplement logs were used to estimate dietary vitamin D intake and supplementation. Associations were assessed using multivariable linear and logistic regression, adjusting for age, sex, and dry weight.

Results:

Forty-seven percent of participants exhibited sex-specific weak handgrip strength, and 25% were vitamin D deficient (<27.5 nmol/L). Serum 25(OH)D concentrations were positively associated with handgrip strength (r = 0.298, P = .023), and vitamin D supplementation was similarly associated (r = 0.285, P = .025). Deficient serum 25(OH)D levels were associated with over five-fold increased odds of weak grip strength (odds ratio (OR) 5.33; 95% confidence interval (CI): 1.59-20.67; P = .009). Although dietary vitamin D intake was inadequate in 97% of participants, it was not independently associated with muscle strength. Participants who reported supplement use had significantly higher mean serum 25(OH)D concentrations than those who did not supplement.

Limitations:

This study’s cross-sectional design and single geographic setting limit causal inference and broader generalizability. Self-reported dietary intake may be subject to recall error.

Conclusions:

Biochemically defined vitamin D deficiency and absence of vitamin D supplementation were associated with reduced muscle strength in patients receiving HD. These findings suggest that higher serum 25(OH)D concentrations may support better musculoskeletal function, in addition to other known benefits of higher serum vitamin D levels, in populations undergoing HD treatment.

Keywords: 25-hydroxy-vitamin D, hemodialysis, handgrip strength, dietary recommended intake, vitamin D supplements, chronic kidney disease

Introduction

Chronic kidney disease (CKD) affects 10% of the world’s population and those with end-stage renal disease (ESRD) require lifesaving renal replacement therapy, for which the most prevalent form is hemodialysis (HD). Those receiving HD have comparable 5-year survival rates to most aggressive cancers, with those in North America1,2 having less than a 40% chance of living beyond five years post initiation of dialysis treatment. Patients on HD treatment are prone to an accelerating aging process, which is inclusive of decreasing muscle mass and function. 3 Loss of muscle function and lean body tissue is common in patients undergoing HD treatment,4,5 which can lead to reduced independence in daily activities, diminished physical functional capacity and increased susceptibility to injury and infections. This loss of muscle function, coupled with the metabolic disturbances caused by CKD, may also be exacerbated by a decline in essential nutrients, particularly vitamin D, and human, animal, and cell culture studies have collectively shown that vitamin D affects muscle strength and function.6,7. Muscle function, measured via handgrip strength, and serum 25(OH)D levels are significantly reduced in the CKD population and independently related to mortality.8-10 The pathophysiological mechanisms underlying these features are poorly understood but have been linked together in other populations.11-13 Patients who are undergoing HD are often among patients who are included in these populations with low vitamin D status and poor physical function, including reduced muscle mass, muscle strength and lowered physical activity.8-10 Given the importance of muscle function in this population and the prevalence of poor vitamin D status among patients with CKD, it is important to further to investigate the relationship between muscle function and vitamin D. This is especially relevant in ethnically diverse groups, as we have previously demonstrated marked variations in vitamin D status within a multiethnic pre-dialysis CKD cohort. 14 While vitamin D deficiency and muscle wasting are each common and clinically important features of advanced kidney disease, their interrelationship remains poorly delineated in the HD population. The objective of this study is to investigate the association between muscle function and overall serum 25(OH)D levels in a multiethnic cohort of patients undergoing HD.

Methods

Study Population

We recruited patients from two satellite HD centers in Toronto, Canada. Eligible participants were independently mobile adults aged 18 years or older who had been receiving thrice-weekly HD for at least 6 months and were medically stable for transfer to an off-site dialysis unit.

Patients were excluded if they had any of the following: active malignancy, active bone disease (including current estrogen replacement or bisphosphonate therapy, diagnosed osteoporosis, or Paget’s disease), an acute illness or infection requiring antibiotic therapy, dialysis vintage of less than 3 months, uncontrolled hypertension, poorly controlled diabetes (more than three hypoglycemic or hyperglycemic episodes, defined as blood glucose <4 mmol/L or >14 mmol/L), recent major surgery, hospital admission >3 days, or the use of mobility aids. Eligibility and exclusion were determined through review of physician notes and diagnoses documented in each patient’s medical chart. Ethics approval was obtained from the institutional research ethics board.

Study Variables

Date of birth, sex, weight, height, dialysis vintage, diabetes mellitus diagnosis, comorbidities, medication list, and history of recent (<3 months) weight loss were recoded from the medical records and confirmed during an interview by a regular health care provider (dialysis nurse or dietitian) with the participants. Ethnicity was self-reported by participants prior to enrollment. Blood samples were collected from the arteriovenous fistula or dialysis catheter just before dialysis treatment on day three of the study. Serum calcium, phosphorus, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) were assessed as markers of CKD-mineral and bone disorder (CKD-MBD) due to their critical roles in vitamin D metabolism and regulatory pathways PTH concentrations were measured on the Roche Modular E170 using an electro chemiluminescent sandwich immunoassay. FGF23 was measured using the human carboxyterminal FGF-23 assay. The intraassay coefficients of variability of c-terminal FGF23 are 6.5% at 40 RU/ml and 7.5% at 175 RU/ml, respectively, with a lower detection limit of 3.0 RU/ml. Serum 25(OH)D was measured using a competitive electro chemiluminescent immunoassay (ECLIA) with 3 incubations and was used as a marker of overall vitamin D (calcidiol) status, with no other vitamin D metabolites assessed. Iron, ferritin, transferrin, total iron-binding capacity (TIBC), and hemoglobin (Hgb) were evaluated to assess anemia. Additionally, TIBC served as a marker of inflammation and malnutrition within the Malnutrition Inflammation Score (MIS) assessment. Glycated hemoglobin (HbA1c) and random blood glucose were analyzed as indicators of glycemic control. All blood measurements, with the exception of FGF-23, were conducted as part of routine clinical care and followed standard clinical pathology procedures.

A modified Subjective Global Assessment (SGA) tool, validated in patients undergoing dialysis, 15 was used to assess nutritional and inflammation status of each participant. This tool, called MIS, 15 consists of two sections. The first section has been adapted from the original SGA, 16 which assesses the patient’s nutritional status using a patient interview about appetite, intake, weight loss, acute illness and gastrointestinal symptoms in combination with a physical assessment of muscle and fat stored at several body sites as well as fluid retention. The second section of the MIS is based on more objective data such as number of chronic comorbidities, serum albumin levels, TIBC and body mass index (BMI). The score for each participant was given out of 30, with zero indicating no malnutrition and inflammation state and 30 indicating severe malnutrition and inflammation state. Given the high degree of overlap between the MIS and other variables already in the model, MIS was not included in statistical analyses to avoid multicollinearity.

A standard 3-day diet and medication record (3DDMR) was given to each participant on day one of the study with specific instructions on how to record intake. Participants were instructed to keep record of what they ingested over 3 predetermined days during the 7 days of the study (1 dialysis day, 2 non-dialysis days consisting of a weekend day and a weekday). Prior to start of self-reported 3DDMR, a 24-hour food recall interview by an experienced renal dietitian was used to demonstrate recording food intake on the 3-day food record. Participants were also asked to record any medication and/or supplements they were taking, including the use of vitamin D. The 3DDMR required participants to indicate whether they were taking vitamin D supplementation by stating yes or no. This was inclusive of both cholecalciferol (D3) and ergocalciferol (D2). The recorded list was then compared to the patient’s medication list to identify discrepancies relevant to the study and clarified with participants as to what was ingested by them. Three-day average dietary intake of calcium, phosphate and vitamin D were used to assess food sources and compared to daily recommendation of these nutrients as they pertain to serum levels and vitamin D metabolism.

Assessment of Muscle Strength

Muscle function was evaluated by handgrip strength, which was measured using a digital dynamometer (Jamar Hydraulic Handgrip Dynamometer J00105, Lafayette Instruments, Lafayette, Indiana, USA) on day five of the study just prior to the dialysis session. Use of the device was first demonstrated to the patient before they attempted the grip strength test. Dynamometer readings were measured to the nearest kilogram twice in the patient’s dominant hand, and the highest value was noted in the analyses. Weak muscle strength was characterized by a result of <28 kg for males and <18 kg for females as defined by the Asian Working Group for Sarcopenia (AWGS). 17

Statistical Analysis

Statistical analyses were conducted using RStudio (version 4.4.1), including both descriptive and inferential methods. Bivariate relationships between pairs of variables were examined through correlation tests to inform the selection of predictors for multiple regression models. Partial correlation tests were performed to assess associations between variables of interest while accounting for potential confounders. One-way analysis of variance was used to compare means across more than two groups, including differences in serum 25(OH)D levels between individuals who supplemented and those who did not. The daily recommended intake (DRI) of vitamin D is 10 μg per day according to the Kidney Disease Outcomes Quality Initiative. 18 Those whose intake was below 10 μg per day are outlined in our study as not meeting the DRI of vitamin D. Serum 25(OH)D levels below 11.0 ng/mL (27.5 nmol/L) were characterized as deficient, and levels between 11.0 and 30.0 ng/mL (27.5-75 nmol/L) were characterized as insufficient, as defined by Health Canada.19,20

A stepwise, forward multiple linear regression analysis was completed to identify predictors of handgrip strength and serum 25(OH)D status. A standard linear model was created including the effects of predictors with P-values < .05 and removal of those with P-value >.10. Final multiple regression formulas were reported with coefficients of predictors that yielded an effect of statistical significance. Multiple logistic regression models were used to analyze the association between weak handgrip strength and deficient 25(OH)D levels. Potential confounders were accounted for through model adjustment; Model 1 was unadjusted, Model 2 adjusted for age and sex, and Model 3 adjusted for age, sex, and dry weight. Additional multiple logistic regression models were used to determine the association between overall vitamin D intake and weak handgrip strength. Models were designed to adjust for covariates; Model 1 was unadjusted, Model 2 adjusted for serum 25(OH)D status, Model 3 adjusted for age, sex, and dry weight, and Model 4 adjusted for 25(OH)D status, age, sex, and dry weight. In all analyses, sex was coded as 0 = male and 1 = female, with males as the reference group.

Results

Of the 180 patients screened, 99 were excluded due to not meeting inclusion criteria or having incomplete clinical, biochemical, or dietary data. The final analytic sample comprised 81 participants who provided written informed consent and completed all study assessments. Participant flow is detailed in Figure 1.

Figure 1.

“The diagrams depicts patient selection process, showing 180 screened, 89 excluded, 91 eligible, 10 declining, and 81 enrolled, highlighting consent and inclusion criteria through flow chart symbols”

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CONSORT diagram illustrating patient selection process.

Table 1 summarizes demographic and clinical variables collected from the 81 participants. The mean age of participants was 58.2 years old, with a standard deviation of 14.1. The majority of participants were male (63%), and the most prominent ethnicity in our study were those of East Asian descent (35%). The mean serum 25(OH)D levels were 17.0 ng/mL (42.4 nmol/L) with a standard deviation of 9.3 (23.1), which is in the insufficient range for serum 25(OH)D. Both hemoglobin and albumin levels were within acceptable range for patients undergoing HD treatment. Vitamin D supplementation was reported in 19 (23%) of participants, and the use of calcitriol analogs (including 1-alpha, rocatrol, and calcijex) was reported in 57 (70%) participants. The mean handgrip strength was 27.0 kg with a standard deviation of 11.4 kg for the group, and a significant difference was found between sexes, with men scoring significantly higher than women (Figure 2) (P < .001). Weak handgrip strength was observed in 47% (n = 30) of participants, and a significant difference in weak handgrip strength was also observed between sexes (P < .001).

Table 1.

Basic Characteristics of Study Participants.

Participant characteristics N Males (N = 51), mean ± SD Females (N = 30), mean ± SD Total mean ±SD P-value of sex differences
Age (years) 81 56.6 ± 13.3 61.2 ± 15.2 58.2 ± 14.1 .150
Hemodialysis vintage (years) 81 2.5 ± 2.0 2.6 ± 2.9 2.5 ± 2.4 .790
Dry weight (kg) 81 77.1 ± 16.3 63.5 ± 15.9 71.9 ± 17.3 <.001*
Height (m) 77 1.7 ± 0.09 1.6 ± 0.09 1.65 ± 0.1 <.001*
25(OH)D (nmol.L-1) 79 38.9 ± 22.9 48.5 ± 22.6 42.4 ± 23.1 .100
Handgrip strength (kg) 62 31.1 ± 11.7 19.6 ± 6.3 27.0 ± 11.5 <.001*
Weak handgrip strength (kg) a 30 22.3 ± 5.6 14.4 ± 2.79 19.7 ± 6.1 <.001*
Hemoglobin (mg.L-1) 80 114.0 ± 13.1 113.3 ± 11.2 113.9 ± 12.3 .954
Albumin (mg.L-1) 81 33.9 ± 3.5 33.6 ± 3.1 33.8 ± 3.30 .954
Calcium (mmol.L-1) 81 2.39 ± 0.16 2.49 ± 0.16 2.39 ± 0.17 .370
Phosphate (mmol.L-1) 81 1.62 ± 0.54 1.57 ± 0.44 1.60 ± 0.05 .639
PTH (ng.L-1) 80 63.7 ± 77.1 60.5 ± 51.4 62.6 ± 68.5 .821
FGF23 (ru.mL-1) 79 5693 ± 10004 4953 ± 7127 5421 ± 9013 .703
Vitamin D supplementation 19 14 (74) 5 (26) 23% .790
Calcitriol intake 57 33 (58) 24 (43) 70% .278
Diabetes mellitus diagnosis 31 20 (65) 11 (35) 38% .790
Ethnicity, number (%)
Black 12 10 (83) 2 (17) 15%
Indian 14 13 (93) 1 (7) 17%
Latin 2 1 (50) 1 (50) 2%
Tamil 10 7 (70) 3 (30) 12%
White b 15 7 (47) 8 (53) 19%
East Asian c 28 13 (46) 15 (54) 35%
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Note. Categorical variables are presented as N (%).

a

Weak handgrip strength characterized as <28 kg for males and <18 kg for females.

b

Participants in the white category included those of English, French, Irish, Italian, Polish, and other white decent.

c

Participants in the Asian category included those of Chinese, Filipino, and Japanese descent.

*

Statistically significant P-value.

Figure 2.

Handgrip strength is significantly higher in males vs females, females: 19.6 ± 6.3 kg, males: 31.1 ± 11.7 kg, p < .001

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Handgrip strength in females versus males.

Handgrip strength was significantly greater in males (males = 31.1 ± 11.7 kg, females = 19.6 ± 6.3 kg).

*P-value < .001.

Table 2 presents the partial correlation between serum 25(OH)D and handgrip strength, adjusted for age, sex, and dry weight (r = 0.298, P = .023). There was a positive association found between dry weight and handgrip strength (r = 0.408, P = .001), and an inverse association between age with handgrip strength (r = -0.310, P = .014). In a stepwise forward multiple linear regression model where handgrip strength was used as the dependent variable, clinically significant variables were entered to determine predictive relationships for muscle strength. Interestingly, the strongest predictor of handgrip strength was serum calcium (P = .006), followed by age (P = .017), sex (P = .022), dry weight (P = .046), and vitamin D supplementation (P = .048). Vitamin D supplementation is also positively associated with muscle strength both before and after controlling for serum 25(OH)D levels (r = 0.285, P = .025, and r = 0.269, P = .037, respectively).

Table 2.

Correlates and Partial Correlates of Muscle Strength.

Correlate Controlled variables r P
Age −0.310 .014*
Sex −0.482 <.001*
Dry weight 0.409 <.001*
Vitamin D supplementation 0.285 .025*
Calcitriol intake 0.0051 .970
25(OH)D Age, sex, and dry weight 0.298 .023*
Vitamin D supplementation 25(OH)D 0.269 .037*
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Note. Univariate correlation analysis to justify inclusion of variables in multivariable models. Sex was coded as 0 = male and 1 = female, with male as the reference group.

*

Statistically significant P-value.

Table 3 presents the results of a multivariable logistic regression analysis examining the association between deficient serum 25(OH)D levels and weak handgrip strength. Twenty participants were classified as 25(OH)D deficient (<11.0 ng/mL or <27.5 nmol/L). In the unadjusted model (Model 1), vitamin D deficiency was significantly associated with weak handgrip strength (<18 kg for females, <28 kg for males), with an odds ratio (OR) of 4.33 (95% CI: 1.41-14.66; P = .013). This association remained significant after adjusting for sex and age in Model 2 (OR 4.48; 95% CI: 1.40-15.96; P = .014) and after further adjusting for dry weight in Model 3 (OR 5.33; 95% CI: 1.59-20.67; P = .0096).

Table 3.

Multivariate Logistic Regression Analysis to Assess the Association Between Deficient Serum 25(OH)D and Weak Handgrip Strength.

Variables Model 1
 Model 2
 Model 3
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
25(OH)D < 27.5 nmol.L-1
(n = 20)		 4.33 (1.41-14.66) 0.013* 4.48 (1.40-15.96) 0.014* 5.33 (1.59-20.67) 0.0096*
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Note. All models assess the association between deficient serum 25(OH)D and weak handgrip strength. Model 1: unadjusted. Model 2: adjusted for age and sex. Model 3: adjusted for age, sex, and dry weight. All yielded significant results.

*

Statistically significant P-value.

Sources of Vitamin D and Serum 25(OH)D

None of our participants met the DRI for vitamin D and supplemented with vitamin D (n = 0), and only one participant met the DRI for vitamin D and did not supplement (n = 1). For the purpose of this multivariate analysis, this individual was excluded. The remaining participants did not meet their DRI for vitamin D, with 14 of them saying they supplemented and 38 saying they did not (n = 14 and n = 38, respectively). We analyzed the association between those who had insufficient vitamin D intake (defined as those who both did not meet their DRI for vitamin D and did not supplement with vitamin D (n = 38)) weak handgrip strength, using those who did not meet their DRI for vitamin D but did supplement (n = 14) as the reference group. Results are displayed in Table 4. The analysis was split into four models: Model 1 was unadjusted, Model 2 adjusted for serum 25(OH)D levels, Model 3 adjusted for age, sex, and dry weight, and Model 4 adjusted for serum 25(OH)D levels, age, sex, and dry weight. In all models, those who had insufficient vitamin D intake had higher odds of having weak handgrip strength compared to those who also did not meet their DRI for vitamin D intake but did supplement. However, none of these results were statistically significant.

Table 4.

Multivariate Logistic Regression Analysis to Assess the Association Between Vitamin D Intake and Weak Handgrip Strength.

Variables Model 1
 Model 2
 Model 3
 Model 4
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Insufficient vitamin D intake
(n = 38)* 		2.03 (0.56-8.54) 0.302 1.29 (0.30-5.99) 0.736 2.70 (0.67-12.92) 0.179 1.62 (0.33-8.80) 0.559
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Note. All models assess the association between insufficient vitamin D intake (did not meet DRI of vitamin D and did not supplement with vitamin D) and weak handgrip strength. Model 1: unadjusted. Model 2: adjusted for serum 25(OH)D levels. Model 3: adjusted for age, sex, and dry weight. Model 4: adjusted for serum 25(OH)D levels, age, sex, and dry weight. None of the models yielded significant results. Those who did not meet their DRI for vitamin D and supplemented with vitamin D is the reference group (n = 14).

*

Those who both did not meet their DRI for vitamin D and did not supplement with vitamin D is the exposure (n = 38).

Individuals who met their DRI for vitamin D without supplementation exhibited higher mean serum 25(OH)D levels compared to those who neither met their DRI nor took supplements (Figure 3). Those who did not meet their needs via dietary intake, but were on a vitamin D supplement, had a statistically significantly higher mean 25(OH)D than those who did not take a supplement (Figure 3). Vitamin D supplementation was significantly associated with higher serum 25(OH)D levels when comparing the mean differences between those who took supplements and those who did not (Figure 4). Vitamin D supplementation, along with serum albumin, positively related to serum 25(OH)D, whereas dietary intake of vitamin D and sex did not relate to serum 25(OH)D levels.

Figure 3.

This bar graph shows serum 25(OH)D levels in participants with different vitamin D intake and supplementation statuses. The data suggests that supplementation increases serum 25(OH)D levels significantly, regardless of the intake level.

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Serum 25(OH)D levels by vitamin D intake from all sources.

Groups: N = inadequate intake, no supplementation (n = 38); D = adequate intake, no supplementation (n = 1); S = inadequate intake, with supplementation (n = 14). No participants met dietary requirements and supplemented (n = 0). Indicates statistical significance; error bars represent standard deviation.

Figure 4.

The image is a bar graph that compares the serum 25(OH)D levels between individuals using vitamin D supplements (YS) and those who are not (DS).

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Mean serum 25(OH)D levels from supplement vs non-supplement groups.

Serum 25(OH)D levels among participants who reported supplementation (YS; n = 19) were significantly higher than those who reported they did not use vitamin D supplements (DS; n = 62) and those. Error bars represent standard deviation. Asterisk indicates statistically significant difference between groups.

Dietary analysis of the 3-day food records revealed that participants consumed only 65% of the recommended energy intake and 80% of the recommended protein intake. Mean vitamin D intake was just 25% of daily requirements, and 97% of participants had inadequate dietary vitamin D from food sources. Serum 25(OH)D concentrations were consistently low, irrespective of intake of other nutrients, with 62% of participants falling within the range of vitamin D insufficiency. The average MIS was 5 out of 30, indicating a low prevalence of overt malnutrition in the cohort.

Discussion

In this study we investigated the association between serum 25(OH)D levels and muscle function in an ethnically diverse cohort of 81 patients undergoing HD treatment. We also explored the association between overall vitamin D intake and muscle function in the same group, where 97% of participants had insufficient dietary intake of vitamin D, and 25% had vitamin D deficiency ((25(OH)D < 27.5 nmol/L; n = 21). Our findings show that those with lower serum 25(OH)D levels were more likely to have weaker handgrip strength, an indicator of total muscle function. We also found that vitamin D supplementation was correlated with greater muscle function and higher serum 25(OH) levels.

Insufficient serum 25(OH)D concentrations may contribute to loss of muscle strength and function in various ways. Skeletal muscle dysfunction is widely prevalent in patients on HD and has debilitating effects on quality of life and physical function. 21 New discoveries in the past decade have revealed roles of vitamin D beyond bone-mineral metabolism and vitamin D receptors (VDRs) have been identified in many cell types, including skeletal muscle cells which indicate the potential for paracrine and autocrine functions in muscle tissue.22,23 Additionally, the VDR found in muscle cells may be both directly and indirectly regulated by calcium and phosphate concentrations through 25(OH)D; a mechanism which has been linked to the onset of type II muscle fiber atrophy. 24 Vitamin D insufficiency has also been linked to fibrosis infiltration, accumulation of glycogen granules, and enlarged interfibrillar spaces, which can cause muscle weakness. 24

Vitamin D levels are measured using 25(OH)D, which some studies have shown to be significantly associated with sarcopenia and weak muscle function in individuals undergoing HD treatment.17,25 These findings suggest that monitoring 25(OH)D levels and treating vitamin D deficiency are important in this population, and that 25(OH)D may serve different functions than just a substrate for circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D). It has also been suggested, in this study and in others involving patients on dialysis, 26 that vitamin D deficiency may contribute to muscle function deterioration. Taskapan and colleagues demonstrated that treating vitamin D deficiency with supplementation resulted in serum 25(OH)D values within the sufficient range and alleviation of some muscle dysfunction in patients on peritoneal dialysis (PD) such that they took a significantly shorter time to complete the Timed Up and Go test, gait velocity test, the timed chair stand test and stair climb test. 26 Despite the prevalence of suboptimal serum 25(OH)D concentrations in most patients on dialysis in this study (only 10% of participants had sufficient or ideal serum 25(OH)D levels), vitamin D supplementation and 25(OH)D level monitoring were not common practice for this group of nephrologists as shown with others.27,28

Our study showed that both serum 25(OH)D and muscle function were positively correlated with vitamin D supplementation, whereas different studies showed otherwise.29,30 Bataille and colleagues 31 found a positive association between serum 25(OH)D and muscle strength, but no association between vitamin D supplementation and muscle strength in patients on HD. Hewitt et al found similar results, where 60 patients undergoing HD were randomized to receive 50,000 IU oral cholecalciferol or a placebo once weekly for 8 weeks over a 6-month period. Patients given the supplement had higher 25(OH)D levels than the placebo group, but there were no significant differences in muscle strength found between those receiving the supplement and those receiving placebo. 32 These conflicting results may be due to the lack of power and the short duration of the studies, as well as methodological approaches that might require specialized nutritional expertise, amongst other specialized skills as discussed in this perspective review. 33

Our study observed significantly lower serum 25(OH)D levels in participants with weak handgrip strength compared to those with normal muscle function. Similarly, Kang et al 34 reported a positive association between serum 25(OH)D and handgrip strength in a cohort of 84 patients undergoing HD. However, their analysis did not account for dietary vitamin D intake or its potential contribution to muscle function independent of serum levels. In contrast, another study examining overall vitamin D intake found no association with muscle strength in patients on HD, aligning with our observation that dietary intake alone was not predictive of functional outcomes. 35

Participants who took vitamin D supplements generally had higher serum 25(OH)D concentrations; however only stratification by biochemical status identified differential associations with muscle strength. Given the local autocrine and paracrine functions of 25(OH)D in skeletal muscle amongst other tissue and cell types, functions that may not be replicated by circulating 1-25(OH)2D, these findings may highlight the importance of assessing and correcting 25(OH)D levels directly, particularly in populations with impaired renal conversion, where these functions may be upregulated to meet local tissue needs no longer supported by endocrine circulation of activated vitamin D.

A key strength of our study is the comprehensive assessment of vitamin D status, incorporating serum 25(OH)D concentrations, dietary intake, and supplementation use. Dietary and supplemental sources of essential nutrients are seldom examined together in this population; in this cohort, we have previously reported distinct and opposing associations between calcium from food and calcium carbonate supplementation in relation to CKD bone–mineral metabolic outcomes36. In the present analysis, we found no significant association between total or dietary vitamin D intake and muscle strength. However, patients not taking vitamin D supplements had higher odds of weak handgrip strength compared with those who were supplemented with vitamin D, consistent with the hypothesis that supplementation provides more reliable source of vitamin D for HD patients. Despite low mean dietary vitamin D intake and lower serum 25(OH)D levels, supplementation was uncommon in our cohort, highlighting a gap in clinical practice that warrants attention.

Our study had some limitations. One limitation of this study was its short duration and cross-sectional nature. These factors combined could have potentially led to misrepresenting nutritional intake or serum measures. Some subgroup analyses, particularly those stratified by sex, were constrained by small sample sizes, which may have limited statistical power and widened confidence intervals. While meaningful trends emerged, these findings should be interpreted cautiously and warrant replication in larger cohorts. Since measures were taken only at one given point of time and were not repeated for the same participants, it is difficult to assess if the serum levels measured represent usual readings for each patient or an unusual reading compared to their historic blood results patterns. There was only a one-time assessment, and a single indicator of muscle strength used. Handgrip dynamometers are subject to human error in methods and interpretation of maximal effort by the participant, although we used highest value of three consecutive attempts by each participant. Serum 25(OH)D concentrations are influenced by exposure of bare skin to ultraviolet rays. This factor was not controlled for in this study, although seasonal timing was considered to be representative of relatively lower sun exposures within latitude and all participants’ serum measures were taken within a three-week span. Skin color may have potentially been another confounder in measuring serum 25(OH)D concentrations, driven from sun exposure in the sample, since participants were of heterogeneous ethnicities. 14 An additional limitation was how vitamin D supplementation was recorded. Vitamin D was recorded as a dichotomous variable, only indicating presence or absence of any vitamin D supplementation. Actual doses and sources of the supplement varied within the group which may have had a direct impact on quantifying serum levels and some differences observed in the outliers. Furthermore, since subjects were recruited from two satellite outpatient HD units and several exclusion criteria were used in the screening and recruitment process, this cohort may represent a healthier and higher functioning group compared to other studies conducted by in center or in-patient dialysis units.

Conclusions

This study demonstrates a significant association between serum 25(OH)D levels and muscle strength in patients undergoing HD, with deficient 25(OH)D levels strongly linked to weak muscle strength. Vitamin D supplementation positively correlated with both serum 25(OH)D and muscle strength, highlighting its potential importance in mitigating muscle decline. Dietary vitamin D intake, however, showed no significant relationship with muscle strength, suggesting supplementation may be more effective in this population. Further research is needed to confirm these results and to establish long-term benefits relationships to other mineral disturbances that might interfere with neuromuscular function. Vitamin D supplementation shows promise for providing a positive impact on muscle strength in those undergoing HD treatment, or at a minimum, correction clinical vitamin D deficiency that frequently occurs in this population. At present, vitamin D supplementation is not included in the standard of care that patients on HD receive. These findings highlight the potential importance of assessing serum 25(OH)D status in HD care and support further investigation of targeted supplementation strategies in this population. Carefully designed interventional trials are warranted to clarify the causal relationship and to evaluate the long-term effects of vitamin D supplementation on muscle function in the population of individuals undergoing HD treatment.

Acknowledgments

We recognize and thank all participants for their cooperation in this study as well as the clinicians, staff, and administrators at the Scarbrough Hospital Network who made this study possible.

Footnotes

Ethics Approval and Consent to Participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the University of Toronto. All participants provided written informed consent.

Consent for Publication: All authors provided consent for publication.

Availability of Data and Materials: The data are available from the corresponding author upon reasonable request.

Author Contributions: SM designed research idea. SM conducted the study and collected all data, assessments, and preliminary analyses. SM outlined the manuscript idea and wrote the first draft and supervised KR. KR wrote a revised daft and conducted secondary analyses. SM, TS, KR, HT, and PYT revised subsequent drafts. SM, KR, TS, and PYT conducted research and had intellectual input throughout the stages of this manuscript; PYT secured and provided philanthropic funding via IKLT.

Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Kidney Life Sciences and Technologies (IKLT), Toronto, Ontario, Canada.

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SM has received funding for advisory board activities, consulting roles, educational grants, travel grants, and speaker/moderator honoraria from the American Academy of Nutrition, World Congress of Aesthetics and Anti-Aging Medicine, Canadian Board of Aesthetic Medicine, Canadian Association of Medical Aesthetics, Canadian Association of Aesthetic Medicine, Los Angeles Multi-Specialty Cosmetic Academy, Allergan, Galderma, Sanofi, Shire, Genzyme, Gambro, Nutrigenomix, and Abbott. SM has received fellowship, educational, and research funding from Harvard University, the University of Toronto, and Mitacs. SM has provided in-kind educational speaker services to the University of Miami Dermatology Department and has served on the Editorial Board of the Canadian Journal of Kidney Disease and Health, the official journal of the Canadian Society of Nephrology. SM is an associate editor of the Canadian Journal of Kidney Disease and Health and an assistant editor of BMJ Nutrition, Prevention & Health. PT has received funding for advisory board activities and speaker honoraria from Otsuka, Bayer, GSK, Amgen, Boehringer-Ingelheim, Merck, Janssen, Baxter, Fresenius, and Amgen. PT received study grant funding from Janssen for conducting a clinical trial. PT is a co-owner of patents related to the treatment of PD patients and a co-director of the Kidney Health Life Sciences Institute. TS has received funding for advisory board activities and speaker honoraria from Sanofi, Shire, Seaford, Scarborough Health Network, Ontario Renal Network, and the Kidney Health Life Sciences Institute. The funders and organizations listed above have had no involvement in the writing, interpretation, or conclusions of this manuscript. KR has no conflicts of interest to declare.

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