Vitamin D Deficiency

Efforts taken to fortify foods with vitamin D in the last century led health care professionals to believe that most major diseases caused by its deficiency were dealt with. But with people getting less exposure to sunlight these days, vitamin D deficiency is on the rise. Even though rickets is assumed to be the main disease caused by vitamin D deficiency, it can even lead to growth stunting, osteoporosis, muscle weakness and even cardiovascular disease (CVD) (Horlick, 2007). This review focuses on the role vitamin D deficiency plays in cardiovascular disease and the possible mechanisms by which optimum levels of vitamin D improves cardiovascular health.

Vitamin D can be synthesized as vitamin D3 in the epidermis, with exposure to UVB radiation, or can be obtained through food in the form of vitamin D2 and D3. Subsequently, it is quickly transported and changed to 25-hydroxyvitamin D in the liver, after which it is converted to the hormonal form, 1,25-dihydroxyvitamin D in the kidney (Judd & Tangpricha, 2008). It is in this form that it binds to the vitamin D receptors of various cells, including myocytes and endothelial cells.

Hypovitaminosis D can be described as a level of 25-hydroxyvitamin D under 20 ng per millilitre of serum (Horlick, 2006). But further data from studies showed that levels of 30 ng per millilitre and above could be regarded to demonstrate adequate levels of vitamin D (Horlick, 2007). Sunlight exposure plays a crucial role in the determination of one’s vitamin D status. Geographical location and seasons, skin colour, obesity and even age are all factors that influence vitamin D levels. The INTERSALT study which examined over ten thousand participants worldwide found that blood pressure and distance from the equator had a direct correlation (Ullah, Uwaifo, Nicholas & Koch, 2010). Pregnant and lactating women, their infants and children have a high possibility of suffering from hypovitaminosis D .

Coronary artery disease (CAD) also known as ischemic heart disease occurs when there is a build-up of plaque along the lumen of the coronary arteries, which results in the hindrance of nutrient and oxygen supply to the cardiac muscles. (Zittermann & Koerfer, 2008). A study conducted by Siadat et al. (2012) shows that CAD is more prevalent in individuals with hypovitaminosis D and their risk of CVD was four times as much as individuals with adequate vitamin D levels. It is only reasonable to conclude that vitamin D deficiency alters a variety of pathways that are responsible for pathogenesis of atherosclerosis (Muscogiuri et al., 2016).

Hypertension is a condition where there is a persistent elevation of arterial blood pressure. Hypovitaminosis D is hypothesised to be a factor that raises the risk of developing hypertension. A recent study conducted by Gul et al. (2017) on the correlation of hypervitaminosis D and cardiovascular disease in obese children observed that children with hypertension showed lower levels of vitamin D. The mechanism proposed by Anderson et al. (2010) is the activation of the renin-angiotensin system by hypervitaminosis D, which leads to hypertrophy of the left ventricle and an increase in blood pressure.

As we discussed above, vitamin D deficiency considerably affects the cardiovascular system. In a cross sectional study conducted by Pilz et al. (2008) on patients that were referred for coronary angiography, they  reported that having an optimum level of vitamin D assists in the prevention and even in the treatment of CVD. Similar findings were reported by Maiya et al. (2007). In a study aimed as reviewing the occurrence of vitamin D deficiency and hypocalcaemia in neonatal cardiomyopathy , they found convincing evidence that reveals the association of hypovitaminosis D and the severity of heart failure.

All the data points towards the clear proof that a vitamin D deficiency can lead to a cardiovascular disease, or even aggravate a pre-existing condition. 1,25-dihydroxyvitamin D is a suppressor of the Renin-angiotensin system. The Renin angiotensin system plays a vital function in the control of homeostasis, blood pressure and blood volume. As a pathogenic contributor to hypertension, the RAS is linked to the increased risk of heart failure, strokes, CAD and renal failure. The renin gene is suppressed by 1,25-dihydroxyvitamin D (Li, 2004). Therefore developing RAS inhibiting analogues of Vitamin D is a potential drug target for the treatment of hypertension.

The effect hypovitamin D has on endothelial function has also been explored by many researchers. “Vitamin D receptor knock-out mice showed an impaired cardiac relaxation and contractility and developed left ventricular hypertrophy” (Judd & Tangpricha, 2008). Studies done by Rahman et al. (2007) showed an up-regulation in metalloproteinases, factors in cardiomyocytes that respond to injury, in vitamin D receptor knockout mice. It is also observed that Vitamin D improves endothelial function and improves vascular compliance. Oxidative stress is one of the mediators in pathobiology of cardiovascular disease. Lipid peroxidation is one of the biomarkers of oxidative stress. Vitamin D replacement showed decreased levels of TBARs (thiobarbituric acid reactive substance), which are indicative of lipid peroxidation. Therefore the effect vitamin D on endothelial function can be described as a decrease in oxidative stress (Tarcin et al., 2009).

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