The study indicates that vitamin C and dietary nitrates could be promising in improving endothelial function and reducing the risk of cardiovascular disease.


A recent study published in feed The journal discussed the role of vitamin C and dietary nitrate in endothelial function (EF).

Study: Does vitamin C enhance the effects of dietary nitrates on endothelial function?  Physiological reasoning and implications for research.  Image credit: Tatjana Baibakova/

Stady: Does vitamin C enhance the effects of dietary nitrates on endothelial function? Physiological reasoning and implications for research. Image credit: Tatjana Baibakova/


The central feature of cardiovascular disease (CVD) is the rupture of the endothelial lining, which has been identified as endothelial dysfunction (ED). ED is an early sign of vascular damage and an essential step in the pathogenesis of atherosclerosis.

Endothelial cells secrete nitric oxide (NO) among other molecules and are involved in inflammatory responses.

Availability of vasodilators, especially NO, is reduced in ED. Thus, the integrity of blood vessels is disrupted, which promotes the development or progression of chronic diseases such as CVD.

Given the potential for reversing ED, early implementation of interventions can provide preventive and therapeutic benefits for patients with or at risk of developing cardiovascular disease.

Interventions such as dietary nitrate, vitamin C, arginine, or polyphenols, aimed at increasing bioavailability, could positively affect the pathogenesis of CVD and EF.

In this study, the authors discuss the putative mechanisms of the synergistic effect of dietary nitrate and vitamin C on EF.

Dietary nitrate and endothelial function

It does not spread rapidly through tissues to reach target cells and exert biological effects. It is spontaneously oxidized to nitrate or nitrite in the circulation by oxyhemoglobin.

Therefore, nitrate and nitrite act as stable end products and may indirectly reflect systemic levels of NO. On average, nitrate intake following a Western diet is about 110 mg/day.

Nitrate is rapidly and efficiently absorbed, with peak plasma concentrations reaching within 90 to 120 minutes. High intake of nitrates positively affected metabolic, immune and vascular functions. Several studies have evaluated the effect of dietary nitrate or nitrite on EF in humans and animals.

One study noted a significant improvement in ED with dietary nitrate supplementation in a hypercholesterolemic rat model. Studies report contradictory results in humans with nitrates.

For example, dietary nitrate consumption did not affect flow-mediated dilation (FMD) in obese/overweight subjects. Similarly, EF was not improved with beetroot consumption for 2 weeks in those with type 2 diabetes.

By contrast, one study noted positive effects on foot and mouth disease with a single dose of nitrates in healthy young participants. Similarly, another study reported improvement of foot and mouth disease in hypercholesterolemic individuals after a six-week intervention of high-nitrate beet juice.

A systematic review and meta-analysis concluded that inorganic nitrate supplementation and beetroot are associated with beneficial effects on EF.

Endothelial function and vitamin c

The benefits of taking vitamin C over EF may be due to the increased bioavailability of NO. A systematic review reported significant improvement in EF with vitamin C supplementation, with effects varying depending on health status.

Vitamin C promotes foot-and-mouth disease and reduces serum levels of a biomarker of oxidative stress in patients with the metabolic syndrome.

A study examining the effects of vitamin C on oxygen delivery in individuals with mild or moderate chronic heart failure noted an improvement in pulse wave velocity after treatment with vitamin C.

Intravenous administration of high doses of vitamin C was found to reverse the effect of free fatty acids on forearm blood flow (FBF).

Synergistic effects of vitamin C and dietary nitrate on endothelial function

Evidence strongly suggests that increasing the bioavailability of NO may improve potency and effect. Recent studies have highlighted the potential interactive and positive effects of combined inorganic nitrate and vitamin C supplementation on blood pressure and EF, suggesting that their synergistic effects could far exceed their capabilities.

A combined dose of inorganic nitrate and vitamin C significantly reduced arterial stiffness in adults and older subjects and lowered systolic blood pressure (BP) and mean arterial blood pressure in older individuals. These findings were confirmed by two independent studies, which observed improved EF in older individuals with hypertension and in subjects with ED, respectively.

The vasodilating effect of nitrite in an acidic solution was enhanced in in the laboratory Rat aorta model, which was further improved by vitamin C supplementation.

Moreover, the animal and in the laboratory Studies have shown that inorganic nitrates and vitamin C may improve tetrahydrobiopterin (BH4) stability. when bh4 depletion, superoxide free radicals are formed in place of NO. Vitamin C can scavenge reactive oxygen species, especially superoxide, by activating superoxide dismutase (SOD).

Concluding remarks

In summary, co-supplementation of dietary nitrate with vitamin C could improve NO synthesis, conversion of nitrite to NO, and improve EF. Preliminary evidence suggests that their synergistic effects may be more effective than individual effects.

More studies are needed to evaluate the effect of combined supplementation of the two compounds on vascular outcomes in larger cohorts and to test whether population genetic or phenotypic characteristics influence their synergistic effects.


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