# Exploring Vitamin D Synthesis and Function in Cardiovascular Health: A Narrative Review
## 4 Vitamin D Deficiency and Cardiovascular Risk
### Vitamin D Supplementation and CVD  
Recent investigations into the potential benefits of Vitamin D supplementation in the prevention of CVD have led to conclusions that question the efficacy of such interventions in a large population. Vitamin D supplementation did not significantly reduce the incidence of CVD events [68]. This finding is supported by [PERSON] et al. [69], who demonstrated that Vitamin D3 supplementation did not reduce the incidence of major CVD events among older adults, potentially due to the sufficiency of baseline Vitamin D levels in participants. The efficacy of high-dose Vitamin D (200,000 IU, followed a month later by monthly doses of 100,000 IU, or placebo for a median of 3.3 years) supplementation in preventing CVD was questioned in a study by [PERSON] et al. [70] that revealed no preventive benefit, suggesting the need for further research into the effects of different dosing regimens. Complementing this, [PERSON] et al. [71] reported that the monthly administration of Vitamin D3 (60,000 IU per month) did not reduce all-cause mortality in unscreened elderly subjects. A randomized controlled trial [72] showed that high-dose Vitamin D supplementation \begin{table}
\begin{tabular}{c c c} \hline
**CVD Risk Factor** & **Role of Vitamin D3** & **Refs.** \\ \hline Blood pressure regulation & Regulation of the renin–angiotensin–aldosterone system (RAAS), which controls vasoconstriction and fluid volume. A Vitamin D deficiency leads to an overexpression of renin and thus the activation of the RAAS. & [62] \\ \hline Inflammation & Low Vitamin D levels have been linked to elevated levels of inflammatory biomarkers, such as C-reactive protein. Chronic inflammation is a known risk factor for the development of atherosclerosis and other cardiovascular disorders. & [63] \\ \hline Endothelial function & Vitamin D plays a role in regulating the function of endothelial cells. A Vitamin D deficiency can lead to endothelial dysfunction, a precursor to plaque formation and atherosclerosis. & [64] \\ \hline Glucose metabolism & Vitamin D is involved in the regulation of glucose metabolism and insulin sensitivity. Vitamin D deficiency may contribute to insulin resistance, a risk factor for type 2 diabetes and cardiovascular disease. & [65] \\ \hline Arterial stiffness and left ventricular hypertrophy & Vitamin D may influence arterial stiffness and the development of left ventricular hypertrophy, both of which contribute to CVD risk. & [66] \\ \hline Atherosclerosis & Vitamin D reduces foam cell formation and cholesterol uptake by macrophages, and it facilitates the transport of HDL (high-density lipoprotein) cholesterol. Lower levels of serum 25-hydroxy Vitamin D have been linked with metabolic syndrome and its components, particularly affecting HDL cholesterol levels. & [67] \\ \hline \end{tabular}
\end{table} 
Table 1: The role of Vitamin D3 on CVD risk factors. did not improve markers of blood glucose, inflammation, neurohormonal activation, or lipids. Similarly, [PERSON] [73] observed a small favorable effect on atherosclerotic CVD risk score in individuals with prediabetes not selected for Vitamin D insufficiency, but no decrease in major adverse cardiovascular events. Further studies [74; 75] found no reduction in major CVD events or improvement in post-stroke outcomes with Vitamin D or omega-3 fatty acid supplementation. [PERSON] et al. [76] and [PERSON] et al. [77] also reported no significant improvements in cardiovascular risk factors, with the latter study noting an increase in triglycerides with Vitamin D supplementation in hypertensive patients with low 25-hydroxy Vitamin D levels. Finally, [PERSON] et al. [78] concluded that improving Vitamin D status through dietary supplementation is unlikely to reduce conventional CVD risk factors, highlighting the complexity of Vitamin D's role in cardiovascular health and disease prevention.