The researchers emphasise the significance of these opposing findings, noting the potential of such sub-standard studies wrongly influencing the future of vital dietary recommendations to prevent disease onset and progression.
Additionally, the large-scale data obtained from the study did not identify significant associations with cardiovascular morbidities (CVMs) and vitamin D supplementation, despite previous high-quality data noting strong science to suggest the opposite.
“The present findings have the potential to provide insights into the divergent nature of the existing scientific literature assessing the impact of vitamin D supplementation on health outcomes," the Spanish researchers emphasise.
They add: "It warrants consideration of whether excluding substandard RCTs is necessary to ensure that recommendations are solely derived from robust investigations.”
Vitamin D and disease
The importance of vitamin D in maintaining health and preventing subsequent adversities has been a long-established area of interest, with functions stretching from immune health to cardiovascular function. It has been established the many roles of vitamin D result from the expression of its receptor within many tissues within the body.
The active metabolite of 1,25-dihydroxy-vitamin D (1,25(OH)2D), used within supplementation, has been observed to exhibit anti-inflammatory, antioxidant, and immunomodulatory effects. Yet, the benefits of taking vitamin D supplements for reducing overall risk of mortality, particularly cardiovascular disease risk, has proved inconsistent in previous studies.
Following an increased number of trials being conducted to assess this potential association, the researchers from Spain sought to conduct the systematic review of available evidence assessing the association between vitamin D supplementation and ACM, CVM, non-CVM and CVD.
The systematic review and meta-analysis involved the collation of RCTs published between 1983 and 2022, that utilised a follow-up period of one year. This resulted in the collation of 80 studies including 82,210 participants with a mean age of 66.1 years.
From this data, it was established that there was a significant association with vitamin D supplementation and a lower risk of ACM. Yet, this was not observed in the lower-quality RCTs.
Furthermore, no such relationship was established for a reduced risk of non-CVM or CVMs in all studies observed.
The review establishes apparent health benefits associated with vitamin D supplementation to overall health, following the collation of large amounts of high-quality RCT data.
With regards to this observation, the researchers explain: “The possible association between low vitamin D levels and CVD, diabetes, cancer, and inflammatory disorders may be due to a large number of genes acting under the control of 1α,25(OH)2D.
“It may also be caused by the fact that the vitamin D receptor (VDR) and CYP27B1 1α-hydroxylation enzyme expression are located in most tissues and cells, including vascular endothelium and cardiomyocytes. Measurements of vitamin D concerning the GC, CYP2R1, and DHCR7 genotypes in Mendelian randomization studies have shown associations of genotypes with vitamin D concentrations and all-cause mortality but not with CVM,” they add.
The review further identifies important disparities between available studies, potentially explaining the inconclusive nature of previous studies in this area. These lower-quality types may be wrongly influencing future study and dietary recommendations.
Following this, the researchers call for further study into this area to address these apposing findings, whilst utilising higher levels of control to account for factors such as the different dosages used by the included participants.
“Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials”
by Antonio Ruiz-García, Vicente Pallarés-Carratalá, Miguel Turégano-Yedro, Ferran Torres, Víctor Sapena, Alejandro Martin-Gorgojo and Jose M. Martin-Moreno