**4.2 Cardiovascular diseases (CVDs)**

Vitamin C supplementation generally has no association to CVD risks, especially among people with normal plasma levels, except among those with deficient vitamin C levels who have increased risks [5]. However, supplementation among diabetic women of postmenopausal age demonstrated a conflicting increased CVD risk [36]. The possible reason given for this phenomenon is the imbalance caused by the supplemented vitamin C at high dosages, upsetting the antioxidant-pro-oxidant balance [44]. However, this is also debatable as it is common knowledge that CVD risk increases with increasing age, and postmenopausal women even have higher risk than men.

In a randomized-controlled double-blind placebo-controlled factorial trial involving 14,641 male physicians aged ≥50 years in the United States [38], about 1245 of them had at least one cardiovascular event in the space of 8 years follow-up. Vitamin C at a dose of 500 mg/day failed to reduce the risk of such CV events and mortality (**Table 1**). However, earlier trials showed the ability of vitamin C at much higher doses (6–7 g/day for 2–3 days) to restore endothelial function in hypertensive patients [45] and in those with coronary artery disease or hyperglycemia-induced endothelial dysfunction [46, 47]. Even in normal individuals without CVDs, arterial wall stiffness and platelet aggregation were ameliorated by ingestion of vitamin C at 2 g/day via a yet to be elucidated mechanism [48].

It is therefore important to consider recent trials that will settle this controversy behind vitamin C supplementation among patients with CVD at both lower and higher dosages. As a water-soluble antioxidant, vitamin C may play a role in the bioavailability of nitric oxide (NO) by activating the endothelial NO synthase, thereby reducing nitrosative stress as well as restoring the endothelial integrity, which is the underlying mechanism behind conditions such as CVDs.
