Vitamin D supplementation shows limited benefits for bone and heart health in hypertensive patients

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.Mar 17 2024

In a recent study published in the journal Nutrients, researchers evaluated whether the "functional vitamin D deficiency" classification predicts the benefit of vitamin D supplementation on bone and cardiovascular health.

Study: Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients. Image Credit: NatchaS / Shutterstock

Background 

Measuring serum 25-hydroxyvitamin D (25(OH)D) is widely recognized as the standard method for assessing vitamin D status, though debate continues over the exact thresholds defining deficiency and sufficiency. The relationship between serum 25(OH)D levels and vitamin D needs is complex, as some individuals appear to require significantly different serum levels to meet their vitamin D requirements. The addition of 24,25-dihydroxyvitamin D (24,25(OH)2D) measurements and the calculation of the vitamin D metabolite ratio (VMR) from these two compounds have been proposed as potential markers of "functional vitamin D deficiency," aiming to refine the assessment of vitamin D status beyond serum 25(OH)D alone. Further research is needed to clarify the effectiveness of the VMR in predicting the benefits of vitamin D supplementation and to establish a consensus on defining functional vitamin D deficiency.

About the study 

The present study was a precisely designed, double-blind, placebo-controlled trial targeting 200 hypertensive patients with low serum 25(OH)D levels, specifically those under 75 nmol/L. This initiative was part of a larger screening effort, the Styrian Hypertension Study, which evaluated 518 participants to identify suitable candidates for the randomized controlled trial (RCT). The principal aim was to investigate the effect of daily vitamin D supplementation, dosed at 2,800 international units (IU) over eight weeks, on 24-hour systolic ambulatory blood pressure (ABP) and secondary outcomes, including diastolic ABP and additional cardiovascular risk factors. Ethical approval was secured from the Medical University of Graz's ethics committee, ensuring informed consent from all participants. This trial was rigorously documented in clinical trial registries, adhering to the Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines.

Laboratory analyses were critical to this study, employing a validated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method for determining 25(OH)D and 24,25(OH)2D in serum samples stored at −80°C until October 2023. This method consistently passed internal and external quality controls, including Vitamin D External Quality Assessment Scheme (DEQAS) participation. The study also extended its scope to bone markers, including β-CrossLaps (CTX), osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (bALP), among other laboratory parameters, using various established techniques.

Additional parameters related to bone and mineral metabolism were considered in re-analyzing the primary and secondary outcomes from the initial RCT for this investigation. The statistical analysis was thorough, employing analysis of covariance (ANCOVA) for group comparisons, with a particular focus on individuals with functional vitamin D deficiency. 

Study results 

In the study, data on the VMR were precisely collected for 505 individuals out of the initial 518. Among these, 192 were identified with vitamin D deficiency, indicated by 25(OH)D levels falling below 50 nmol/L. This distinction set the stage for an in-depth exploration of vitamin D metabolites and their health implications, with the participants' baseline characteristics thoroughly cataloged and stratified based on their 25(OH)D concentrations. The division into groups with serum levels below and above 50 nmol/L provided a clear comparative framework for assessing vitamin D status across the cohort.

Further delineation within the data was achieved by comparing those participants with 25(OH)D levels under 50 nmol/L, further categorizing them based on the presence or absence of functional vitamin D deficiency. The data spanned from baseline measurements to follow-up, capturing changes in mineral metabolism and cardiovascular health parameters. This longitudinal perspective was crucial for understanding the dynamic nature of vitamin D's impact on health outcomes over the course of supplementation.

The exploration of cardiovascular risk factors was particularly revealing, offering insights into how vitamin D supplementation might influence heart health and related risk profiles in individuals grappling with low serum 25(OH)D levels and functional vitamin D deficiency. 

Furthermore, when the data were analyzed with a gender-specific lens, the results held steady, indicating that the observed effects of vitamin D supplementation and the implications of functional vitamin D deficiency were consistent across male and female participants. 

Conclusions 

To summarize, the study found that hypertensive patients with vitamin D deficiency, particularly those with functional vitamin D deficiency, did not experience significant improvements in bone health or cardiovascular risk factors from vitamin D supplementation, except for a reduction in parathyroid hormone (PTH) levels. A notable finding was the higher prevalence of diabetes and glucose metabolism disorders among those with functional deficiency. Despite utilizing advanced LC-MS/MS methods for precise vitamin D metabolite measurement, significant health benefits were elusive, highlighting the complex regulation of vitamin D metabolism. This research underscores the need for further studies to explore the impact of vitamin D supplementation on individuals with functional vitamin D deficiency.