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

In a recent study published in the journal nutrientsresearchers evaluated whether the classification of “functional vitamin D deficiency” predicted 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

Measurement of serum 25-hydroxyvitamin D (25(OH)D) is widely accepted as the standard method for assessing vitamin D status, although debate continues regarding the precise 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 needs. The addition of measurements of 24,25 -dihydroxyvitamin D (24,25(OH)2D) and the calculation of the vitamin D metabolic ratio (VMR) of these two compounds have been proposed as potential markers of “functional vitamin D deficiency” aimed at refining the assessment of vitamin D status D beyond serum 25(OH)D alone. Further research is needed to clarify the effectiveness of VMR in predicting the benefits of vitamin D supplementation and to reach a consensus on the definition of functional vitamin D deficiency.

About the research

The present study was a well-designed, double-blind, placebo-controlled trial targeting 200 hypertensive patients with low serum 25(OH)D levels, specifically those below 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 primary objective was to investigate the effect of daily vitamin D supplementation dosed at 2800 international units (IU) for eight weeks on 24-hour ambulatory systolic blood pressure (ABN) and secondary outcomes including diastolic ABP and additional cardiac vascular risk factors. Ethical approval was secured from the ethics committee of the Medical University of Graz, which ensured informed consent from all participants. This trial was rigorously documented in clinical trial registries, adhering to the 2010 Consolidated Standards for Reporting Trials (CONSORT) guidelines.

Laboratory analyzes were critical to this study, using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine 25(OH)D and 24,25(OH)2D in serum samples stored at -80°C until October 2023. This method consistently passes internal and external quality checks, including Vitamin D’s participation in the External Quality Assessment Scheme (DEQAS). 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 when reanalyzing the primary and secondary outcomes of the original RCT for this study. Statistical analysis was performed using analysis of covariance (ANCOVA) for group comparisons, with a special focus on individuals with functional vitamin D deficiency.

Research results

In the study, VMR data were accurately collected for 505 individuals out of the original 518. Among them, 192 were identified as having vitamin D deficiency, indicated by 25(OH)D levels falling below 50 nmol/L. This distinction initiated an in-depth study of vitamin D metabolites and their health implications, with participants’ baseline characteristics carefully cataloged and stratified based on their 25(OH)D concentrations. The separation of groups with serum levels below and above 50 nmol/L provided a clear comparative framework for assessing vitamin D status in the cohort.

Further delineation within the data was achieved by comparing those participants with 25(OH)D levels below 50 nmol/L, further categorizing based on the presence or absence of functional vitamin D deficiency. Data ranged from baseline measurements to follow-up, capturing changes in mineral metabolism and cardiovascular health parameters. This longitudinal perspective was critical to understanding the dynamic nature of the effects of vitamin D on health outcomes during supplementation.

The study of cardiovascular risk factors was particularly revealing, offering insight into how vitamin D supplementation may affect heart health and associated risk profiles in individuals struggling with low serum 25(OH)D levels and functional deficiency of vitamin D.

Furthermore, when the data were analyzed with a gender-specific lens, the results remained robust, indicating that the observed effects of vitamin D supplementation and the consequences of functional vitamin D deficiency were consistent among male and female participants.

Conclusions

To summarize, the study found that vitamin D-deficient hypertensive patients, particularly those with functional vitamin D deficiency, did not experience significant improvements in bone health or cardiovascular risk factors from vitamin D supplementation, except the decrease in parathyroid hormone (PTH) levels. . A notable finding was the higher prevalence of diabetes and disorders of glucose metabolism among those with functional deficits. Despite the use of advanced LC-MS/MS methods to precisely measure vitamin D metabolites, significant health benefits have been elusive, highlighting the complex regulation of vitamin D metabolism. This study highlights the need for further studies to investigate the effects of vitamin D supplementation D on individuals with functional vitamin D deficiency.