The Effect of Vitamin D Supplementation on Functional Outcomes in Patients Undergoing Rehabilitation After an Ischemic Stroke: A Prospective, Single-Blind, Randomized, Placebo-Controlled Study

 Your competent? doctor has known of this for years. What was done? NOTHING? So, you don't have a functioning stroke doctor, do you?

vitamin D3 (6 posts to June 2013)

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The Effect of Vitamin D Supplementation on Functional Outcomes in Patients Undergoing Rehabilitation After an Ischemic Stroke: A Prospective, Single-Blind, Randomized, Placebo-Controlled Study            

                                 by

Wojciech Borowicz

¹,

Lucyna Ptaszkowska

²,

Rafał Małecki

^3,4 and

Małgorzata Paprocka-Borowicz

^5,6,*

¹

Department of Pediatric Infectious Diseases, Wroclaw Medical University, 50-368 Wroclaw, Poland

²

Institute of Health Sciences, University of Opole, 45-060 Opole, Poland

³

Department of Non-Procedural Clinical Science, Faculty of Medicine, Wroclaw University of Science and Technology, 51-377 Wroclaw, Poland

⁴

Department of Internal Medicine with Angiology Subdivision, Regional Specialist Hospital in Wroclaw, 51-124 Wroclaw, Poland

⁵

Division of Clinical Physiotherapy and Rehabilitation, University Centre of Physiotherapy and Rehabilitation, Faculty of Physiotherapy, Wroclaw Medical University, 50-368 Wroclaw, Poland

⁶

Department of Neurological Rehabilitation, Regional Specialist Hospital in Wroclaw, 51-128 Wroclaw, Poland

^*

Author to whom correspondence should be addressed.

J. Clin. Med. 2025, 14(6), 1848; https://doi.org/10.3390/jcm14061848

Submission received: 13 January 2025 / Revised: 25 February 2025 / Accepted: 6 March 2025 / Published: 9 March 2025

(This article belongs to the Special Issue Advances in Rehabilitation Care for Geriatric Diseases)

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Abstract

Background/Objectives: 

A vitamin D deficiency is prevalent in post-stroke patients and may impair neurological recovery. While observational studies highlight the neuroprotective role of vitamin D, there is limited evidence from interventional studies evaluating its impact on functional recovery during stroke rehabilitation. This study aimed to assess whether daily vitamin D3 supplementation enhances functional recovery. 

Methods: 

 This prospective, randomized, placebo-controlled, single-blind study included 159 patients (mean age: 62.5 ± 8.4 years) with a first ischemic stroke that were admitted for early rehabilitation. The participants were randomly allocated to receive 2000 IU of vitamin D3 daily (n = 79) or a placebo (n = 80) for six weeks. The functional outcomes were measured using the Barthel index (BI) and modified Rankin scale (mRS) at baseline and after 42 days. The serum 25-hydroxyvitamin D [25(OH)D] and insulin-like growth factor 1 (IGF-1) levels were analyzed. 

Results: 

Vitamin D3 supplementation significantly increased the serum 25(OH)D levels (p < 0.001). Supplementation was associated with improved BI scores (β = 0.07, p = 0.006). A higher BMI (β = −0.06, p = 0.033), higher NIHSS scores (β = −0.18, p = 0.036), hypertension, and statin use negatively impacted functional recovery. Anticoagulant use was correlated with higher mRS scores, indicating greater disability (p = 0.04). 

Conclusions: 

 Vitamin D3 supplementation positively influences the functional outcomes during post-stroke rehabilitation, supporting its potential role in enhancing neuroplasticity and recovery. Larger multi-center trials are needed to confirm these findings and optimize vitamin D supplementation strategies.

Keywords:

ischemic stroke; vitamin D3 supplementation; rehabilitation; Barthel index; modified Rankin scale; neuroplasticity; randomized controlled trial

1. Introduction

Every year, millions of people worldwide experience a stroke, regardless of race, origin, or socioeconomic status [1]. Cerebrovascular diseases, including strokes, rank as the second leading cause of death globally [2]. The full recovery of function and perception occurs in only 10% of patients. Approximately 15% of stroke patients die in the early phase, while 25% experience a recurrent stroke. The risk of recurrence is highest within the first and second years following the initial event. Individuals who have experienced a stroke are at a significantly greater risk of a second stroke compared to their peers of the same age and sex who have not had a stroke [3]. Stroke prevention strategies focus primarily on behavioral and lifestyle factors [4]. Hence, managing risk factors plays a crucial role in medical care. Strokes are the leading cause of disability in individuals over the age of 45 [5].

Stroke timing critically influences the potential for neuroplasticity and functional recovery, particularly during the early phase of rehabilitation. Indeed, recent findings underscore the importance of initiating therapy promptly to leverage optimal brain reorganization [6]. It is generally accepted that cortical reorganization peaks 7–14 days post-stroke and persists for approximately one month [7]. Early rehabilitation reduces disability at the end of the rehabilitation period, lowering future healthcare costs. Global concerns about vitamin D deficiencies are increasing, affecting nearly half of the population worldwide [8,9].

A vitamin D deficiency is now recognized as a public health issue. Recent population-based studies indicate that low vitamin D levels predict future strokes. Poland, characterized by limited sunlight exposure, is among the countries where vitamin D deficiencies are prevalent [10,11]. Low serum 25-hydroxyvitamin D (25[OH]D) levels are linked to cardiovascular, musculoskeletal, infectious, autoimmune, and malignant diseases [12]. Vitamin D has been shown to have neuroprotective, neuromuscular, and osteoprotective properties, potentially reducing cognitive and functional impairments in post-stroke patients [13]. The current literature suggests that vitamin D supplementation and neuroprotective diets can enhance the efficacy of stroke rehabilitation and recovery.

Vitamin D is believed to support neurological function and recovery through several interconnected pathways. First, vitamin D receptors (VDRs) are expressed in various regions of the central nervous system, including the cortex and hippocampus, suggesting that vitamin D can exert both genomic and non-genomic effects on neuronal survival and plasticity [14,15]. In the setting of an ischemic stroke, vitamin D may mitigate neuroinflammation by downregulating pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), potentially limiting secondary neuronal damage [16,17]. Furthermore, vitamin D has been shown to influence the expression of neurotrophic factors—such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—which are crucial for neuronal repair and synaptic plasticity [18]. Additional research also points to an improvement in endothelial function and microcirculatory blood flow under optimal vitamin D levels, contributing to reduced ischemic injury in the affected brain tissue [19]. Collectively, these mechanisms support the hypothesis that an adequate vitamin D status may facilitate improved functional recovery and neurorehabilitation outcomes in post-stroke patients.

However, interventional studies remain scarce, highlighting the urgent need for randomized controlled trials (RCTs) to evaluate the impact of vitamin D supplementation on stroke outcomes [20]. Therefore, this study aimed to determine whether vitamin D3 supplementation influences the functional recovery in patients undergoing a 6-week neurological rehabilitation program during the regenerative–compensatory phase.

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