Research & Education

Vitamin C: Fueling Nitric Oxide for Healthy Blood Vessels

While most people are familiar with vitamin C’s role in promoting immune health, its lesser-known role is promoting cardiovascular health through its interactions with nitric oxide (NO) and the blood vessel lining, or endothelium. Vitamin C (also referred to as ascorbate) plays a beneficial role in promoting endothelial function and maintaining vascular integrity

Collagen Synthesis

Vitamin C promotes endothelial cells to proliferate and to form capillary-like structures in vitro, likely due to its ability to increase the synthesis of type IV collagen, which is required for basement membrane formation and endothelial cell adhesion. Furthermore, vitamin C has also been shown in vitro to prevent apoptosis of endothelial cells induced by high glucose conditions, tumor necrosis factor-alpha, and lipopolysaccharides. In vitro studies also suggest that vitamin C can tighten the permeability barrier of endothelial cells in long-term culture. 

Antioxidant Support

As a potent antioxidant, vitamin C may help attenuate the oxidative stress and inflammation associated with vascular dysfunction. Vitamin C can scavenge free radical species that have entered the cells or been produced endogenously from normal cellular reactions, such as mitochondrial energy production or uncoupling of nitric oxide synthase (NOS).

Supporting the Endogenous Synthesis of Nitric Oxide 

Nitric oxide is endogenously produced as a by-product of the oxidation of the amino acid L-arginine, catalyzed by endothelial nitric oxide synthase (eNOS) – an isoform of NO synthase (NOS) enzymes. Vitamin C helps promote eNOS activity by changing its phosphorylation and S-nitrosylation status and upregulating eNOS expression. This is important because one of NO’s primary functions is to serve as a vasodilator to promote increased blood supply to tissues and to relax the inner muscles of blood vessels. As a result, NO helps to promote normal blood pressure and blood flow, increasing the delivery of oxygen and nutrients to tissues and facilitating the clearance of metabolic by-products. 

Along with arginine, BH4 (tetrahydrobiopterin) is a required co-factor for eNOS activation in NO production. During the enzyme cycle, BH4 donates an electron to the active dimeric form of eNOS and becomes a tetrahydrobiopterin radical. This radical needs to be efficiently reduced back to BH4 by vitamin C specifically. Failure to reduce BH4 does two primary things: it inhibits NO production and increases the production of superoxide (instead of NO), which can further react with NO to form peroxynitrite – another source of oxidative stress. Vitamin C’s antioxidant properties allow it to scavenge both superoxide and peroxynitrite. However, by helping recycle BH4 in the first place, vitamin C helps mitigate the loss of BH4 and sustains eNOS activity. 

Supporting the Exogenous Synthesis of Nitric Oxide

Another pathway the body uses to maintain optimal NO status is an exogenous pathway called the enterosalivary pathway. The enterosalivary pathway produces the same biologically active NO produced through the endogenous pathway but with dietary nitrates as the precursor rather than L-arginine. In this pathway, dietary nitrate is converted into salivary nitrite. Once salivary nitrates are swallowed into the stomach, the nitrites must be reduced to NO by the acidic environment and in the presence of endogenous reductants, such as vitamin C. Thus, vitamin C further helps promote NO production and bioavailability. 


Due to its numerous roles in promoting endothelial health and NO production, vitamin C is a water-soluble vitamin that may help support healthy blood pressure in the general population. Supporting adequate vitamin C intake may be especially clinically relevant to older individuals or those with hypertension, type 2 diabetes mellitus, or hypercholesteremia

By Danielle Moyer Male, MS, CNS, LDN