Vitamin D Repletion and Muscle Strength in Community-Dwelling Older Adults with Sarcopenia: A Randomized Controlled Trial

Raudsepp R¹, Bruun M², Fontaine M³

01-06.

Abstract

Background: Vitamin D deficiency is common in older adults with sarcopenia, and vitamin D receptors are expressed in skeletal muscle, giving biological plausibility to a role in strength. Objective: To synthesise trial and meta-analytic evidence on vitamin D repletion and muscle strength, gait speed, and falls in community-dwelling older adults with sarcopenia or low vitamin D status. Methods: Narrative review of published randomised trials, systematic reviews and meta-analyses, and mechanistic studies. Findings: Pooled data show no significant effect on grip strength (SMD 0.06) but a significant effect on global/lower-limb strength (SMD 0.19), concentrated in participants with baseline 25-hydroxyvitamin D below 25–30 nmol/L; fall-risk reduction is dose-dependent, and benefit is amplified when vitamin D accompanies protein and resistance exercise. Conclusions: Vitamin D repletion modestly improves strength selectively in deficient older adults with sarcopenia, best delivered alongside protein and exercise rather than as monotherapy.

Keywords: vitamin D; sarcopenia; muscle strength; older adults; randomized controlled trial

Introduction

Sarcopenia, the age-related loss of skeletal muscle mass and strength, affects an estimated 10–16% of community-dwelling adults over 60 years and is a leading contributor to falls, fractures, and loss of independence [1,2]. Skeletal muscle expresses the vitamin D receptor and the enzymatic machinery required for local vitamin D metabolism, and vitamin D signalling influences myoblast differentiation, calcium handling, and type II fibre size, providing a coherent mechanistic basis for a causal link between vitamin D status and muscle function [3]. Observational cohorts have repeatedly associated low serum 25-hydroxyvitamin D [25(OH)D] with reduced grip strength, slower gait speed, and incident sarcopenia in older populations, motivating a substantial randomised controlled trial literature testing whether correcting vitamin D deficiency improves muscle outcomes [4,5,6].

Interpreting this literature is complicated by heterogeneity in participant baseline vitamin D status, supplementation dose and duration, co-administered protein or exercise interventions, and the strength outcome measured (handgrip versus lower-limb versus composite physical performance), such that pooled trial results have sometimes appeared contradictory at face value. This review synthesises the published trial and meta-analytic evidence on vitamin D repletion and muscle strength, gait speed, and falls specifically in community-dwelling older adults with sarcopenia or low vitamin D status, considers baseline vitamin D status and dose as effect modifiers, and situates vitamin D within combined nutritional and exercise strategies. It draws on a narrative review of randomised trials, systematic reviews and meta-analyses, and mechanistic studies rather than presenting new primary trial data.

Vitamin D Physiology and Skeletal Muscle Function

Vitamin D undergoes hepatic 25-hydroxylation and renal 1-alpha-hydroxylation to calcitriol, which acts through the nuclear vitamin D receptor to regulate gene transcription in skeletal muscle, including genes governing myogenesis, mitochondrial function, and calcium flux through the sarcoplasmic reticulum [3]. Muscle biopsy and mechanistic studies additionally implicate vitamin D in preserving type II (fast-twitch) fibre cross-sectional area, the fibre type preferentially lost in sarcopenia and most relevant to fall-preventing rapid force generation [7]. Deficiency is further linked to secondary hyperparathyroidism, which independently accelerates muscle catabolism, and to impaired mitochondrial oxidative capacity, giving vitamin D repletion plausible routes to affect strength beyond a single receptor-mediated pathway [8].

01-06.

Epidemiological Evidence Linking Vitamin D Status to Sarcopenia

Prospective cohort data support this mechanistic link. The Longitudinal Aging Study Amsterdam found that older adults with serum 25(OH)D below 25 nmol/L had significantly greater two-year decline in grip and lower-extremity strength than vitamin D–replete peers, particularly when accompanied by elevated parathyroid hormone [4]. The InCHIANTI study similarly found low 25(OH)D independently associated with poorer physical performance and lower quadriceps strength across a population-representative older Italian cohort [5], while a Dutch cohort found vitamin D status predicted both physical performance level and its subsequent decline over three years [6]. A further population-based analysis found sex-specific associations between serum vitamin D and physical function, with associations generally stronger in women [9]. These associations, while not proof of causation, established vitamin D deficiency as a plausible, modifiable contributor to sarcopenia and underpinned the subsequent trial programme.

Randomised Controlled Trials of Vitamin D Repletion on Muscle Strength

Trial-level evidence is heterogeneous in population, dose, and outcome (see Table 1). A randomised trial in pre-sarcopenic, vitamin D–insufficient Lebanese older adults found that 12 months of cholecalciferol supplementation significantly improved handgrip and knee-extension strength relative to placebo [10]. In institutionalised, largely deficient nursing-home residents, higher-dose intermittent cholecalciferol regimens raised 25(OH)D more effectively than standard daily dosing, though gains in grip strength were modest and dose-dependent [11]. A twelve-week trial combining whey protein, essential amino acids, and vitamin D with physical activity in sarcopenic older adults produced significant gains in fat-free mass, handgrip strength, and functional performance compared with an isocaloric control, though the multi-component design precludes isolating vitamin D's independent contribution [12]. Conversely, the PROVIDE trial found that reaching vitamin D sufficiency was necessary, but combined with adequate protein intake, for meaningful gains in appendicular muscle mass among sarcopenic older adults, again in a combined nutritional supplement rather than vitamin D alone [13]. In community-dwelling older men, a randomised trial of vitamin D supplementation found modest improvements in lower-extremity function and self-reported health perception without significant grip-strength change [14], while an exercise-training trial in vitamin D–deficient older Chilean adults found that vitamin D repletion augmented, but did not replace, the strength gains achieved through resistance training alone [15]. At a population level, the large DO-HEALTH trial found that vitamin D3 2000 IU/day for three years did not significantly improve Short Physical Performance Battery scores, falls, or infection rates in largely vitamin D–replete community-dwelling adults aged 70 and older [16].

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Study Population Intervention Durati Key strength/fu

on nction outcome Verlaan 2018 Sarcopenic Whey 13 Muscle mass (PROVIDE) older adults, protein + weeks gain required malnutrition vitamin D + concurrent risk leucine oral vitamin D supplement sufficiency Kenny 2003 Community- Vitamin D su 6 mont Improved dwelling pplementati hs lower-extremity older men on vs function, no placebo grip strength change Bunout 2006 Vitamin Vitamin D 9 mont Vitamin D D-deficient +/- hs augmented, did elderly resistance not replace, exe (Chile) exercise rcise-induced training strength gain Bischoff-Ferr Largely Vitamin D3 3 years No significant ari 2020 (DO- vitamin 2000 IU/day improvement in HEALTH) D-replete +/- omega-3 SPPB score or adults aged +/- exercise falls 70+

Baseline Vitamin D Status and Dose as Effect Modifiers

Meta-analyses converge on the conclusion that vitamin D's effect on strength depends heavily on baseline status and dose (see Figure 1). A meta-analysis of randomised trials found no significant pooled effect of vitamin D supplementation on grip strength (standardised mean difference [SMD] 0.06) but a significant effect on global lower-limb muscle strength (SMD 0.19), with the effect concentrated among participants with baseline 25(OH)D below approximately 30 nmol/L [17]. An earlier systematic review and meta-analysis similarly found a significant pooled benefit of vitamin D on muscle strength restricted to studies enrolling markedly deficient participants, with no discernible benefit above this threshold [18]. A meta-analysis focused on gait speed and balance concluded that vitamin D supplementation improved balance measures and reduced fall risk but had no consistent pooled effect on muscle strength or gait speed across unselected older populations [19]. A more recent, larger meta-analysis restricted to placebo-controlled trials likewise found no overall benefit of vitamin D on muscle mass, strength, or physical performance, reinforcing that benefit, where present, is confined to deficient subgroups rather than generalisable to vitamin D–replete older adults [20]. Dose-response analysis of fall-prevention trials found that higher achieved doses (equivalent to roughly 700–1000 IU/day) significantly reduced fall risk (relative risk approximately 0.81), whereas lower doses showed no significant benefit and, in some analyses, a paradoxical increase in risk (see Figure 2) [21]. A landmark meta-analysis had earlier established this fall-prevention signal for vitamin D more broadly, again dose-dependent

[17].

Combined Vitamin D, Protein, and Resistance Exercise

Because sarcopenia is multifactorial, several trials and reviews have tested vitamin D alongside protein and structured exercise (see Table 2). A systematic review and meta-analysis of combined resistance exercise training and vitamin D3 supplementation found that the combination improved musculoskeletal function more consistently than either intervention alone, though heterogeneity in dose and training protocol limited pooled effect size precision [23]. Consensus recommendations from the PROT-AGE study group specify at least 1.0–1.2 g/kg/day protein intake for healthy 01-06.

older adults, rising further with sarcopenia or acute illness, positioning adequate protein as a prerequisite rather than a substitute for vitamin D repletion [24]. A randomised trial of exercise with or without vitamin D supplementation in older women found that exercise training, not vitamin D, was the dominant driver of reduced injurious falls, with vitamin D adding no incremental benefit in this largely non-deficient population [25]. Trial-level evidence on gait speed remains an important null result: a systematic review of vitamin D and physical performance concluded that supplementation alone was insufficient to reliably improve strength, gait, or fall outcomes absent baseline

Safety, Dosing, and Clinical Practice Considerations

Translating this evidence into practice requires attention to dose, duration, and screening. Daily dosing regimens in the range of 800–2000 IU cholecalciferol appear better supported than very high-dose intermittent bolus regimens, which some trials and pooled analyses have linked to a paradoxical increase in falls and fractures, likely reflecting transient supraphysiological metabolite fluctuations rather than a benefit of higher peak dose [21]. Serum 25(OH)D of at least 50 nmol/L is a reasonable treatment target given the deficiency threshold, roughly 25–30 nmol/L, below which trials most consistently demonstrate a strength benefit [17,18]. Routine universal screening of all older adults is not currently endorsed by major guidelines, but case-finding in those with confirmed or probable sarcopenia, malnutrition, limited sun exposure, or osteoporosis is a pragmatic compromise consistent with the trial evidence reviewed here. Clinicians should also recognise that vitamin D repletion alone is unlikely to reverse established sarcopenia; its role is best framed as removing a modifiable deficiency-related ceiling on the response to protein intake and resistance training, rather than as an independent anabolic therapy. Cost, adherence, and the low harm profile of moderate daily dosing further favour a targeted repletion strategy over withholding supplementation pending additional trials, provided very high intermittent bolus doses are avoided.

Across randomised trials and meta-analyses, vitamin D 01-06.

repletion produces a modest but reproducible improvement in muscle strength in older adults with sarcopenia, an effect that is essentially confined to those with baseline 25-hydroxyvitamin D deficiency and appears dose-dependent, with limited or no benefit once vitamin D–sufficient. Vitamin D monotherapy in replete populations, as in the DO-HEALTH trial, does not improve physical performance or reduce falls, whereas combining vitamin D with adequate dietary protein and resistance exercise more consistently improves strength and functional outcomes. Clinically, screening for vitamin D deficiency before initiating supplementation, and pairing repletion with protein and exercise, is more defensible than universal high-dose vitamin D supplementation for sarcopenia. Future trials should stratify by baseline vitamin D status and standardise dosing, duration, and strength outcome measures to permit more precise pooled estimates of clinically meaningful effect.

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