February 25, 2015

The Impact of Vitamin C on Endothelial Function

Safe, effective nutrient proves beneficial to patients with heart disease and diabetes
This analysis highlights the positive impact vitamin C has on endothelial function, which is good news for some of our most vulnerable patients—those with heart disease and diabetes.


Ashor AW, Lara J, Mathers JC, Siervo M. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomized controlled trials. Atherosclerosis. 2014;235;1:(9-20).

Study Design

Systemic review and meta-analysis of MedLine, Embase, Cochrane Library, and Scopus databases (from inception to May 2013) for studies meeting the following criteria: 1) randomized controlled trial (RCT) with adult participants, 2) vitamin C administered alone, and 3) studies that quantified endothelial function (EF) using commonly applied methods including ultrasound, plethysmography, and pulse wave analysis


Data were pooled from 44 RCTs of various sizes. Studies were designed to assess vitamin C’s effect on EF in healthy volunteers and in atherosclerotic, diabetic, and/or heart failure patients.

Study Parameters Assessed

All studies assessed EF using commonly applied methods including ultrasound, plethysmography, and pulse wave analysis.

Aim of Review

To determine whether there is any effect of vitamin C supplementation on EF and if so, whether this effect is associated with health status, study duration, dosage, and/or means of vitamin C administration

Key Findings

Pooling the data showed a clear and significant benefit of vitamin C supplementation in amounts over 500 mg per day (standard mean difference [SMD]:0.50, 95% confidence interval [CI]:0.34-0.66, P<.001). It appeared those participants with heart failure derived the greatest benefit (SMD:0.48, 95% CI: 0.08-0.88, P<.02). Those with diabetes as well as atherosclerosis also had significant improvements in EF (SMD:0.52, 95% CI:0.21-0.82, P<.001; SMD:0.84, 95% CI:0.41, 1.26, P<.001, respectively). Vitamin C did not have any impact on EF in healthy volunteers. The improvements in EF remained unaffected and unchanged when study design, duration, baseline plasma vitamin C concentration, and means of administration were taken into consideration. In the meta-regression analysis, the improvements in EF appeared to be dependent only on dosage (β:0.00011; 95% CI:0.00001-0.00021, P=.03).

Practice Implications

The endothelium is in direct contact with our blood supply. As such, it is constantly under the influence of vasodilating and vasoconstricting molecules in the blood and is itself a contributor to this pool of opposing molecules. In the past, the endothelium was thought to be a passive barrier between blood and blood vessels, but we now know that it is an active participant. EF is integral to maintaining the delicate balance that allows for healthy blood vessels, as well as the health of the tissues they perfuse.
The current study simply suggests that vitamin C should always be included in protocols for our patients with cardiovascular conditions.
EF is of primary significance in the pathophysiology of numerous forms of cardiovascular disease.1 EF  can be affected negatively by a wide variety of well-known risk factors, including smoking, hypercholesterolemia, hyperhomocysteinemia, hypertension, and diabetes mellitus.2,3 Additional factors detrimental to EF not commonly considered in conventional medicine but frequently addressed in integrative practice settings include heavy metal toxicity, organic toxicants, chronic infections, inflammatory foods, intestinal dysbiosis, and chronic stress, all of which appear to negatively affect EF.4-9 This makes the endothelium a highly vulnerable yet critically important anatomical structure, one with an apparently endless supply of potentially damaging factors—not a favorable situation by any stretch of the imagination. 
Under such circumstances, the availability of a therapeutic substance that will improve EF and lead to better outcomes, regardless of the situation or insult, would be highly desirable. Vitamin C appears more than qualified. 
It is important to note that when the therapeutic approach utilized is open-minded, seeks to address causal factors vs suppress symptoms, and uses the least harmful treatments first, there will likely be many therapies available for use. The current study simply suggests that vitamin C should always be included in protocols for our patients with cardiovascular conditions. This is especially true given vitamin C’s essential vitamin status, its many other positive benefits, its ubiquity, and its low cost.  
Finally, while the study analyzed here is important because it clearly displays the positive effect vitamin C can have on EF, an additional motivation for focusing on this study was to help alert any readers not already savvy to the details of EF and its importance to the pathophysiology of cardiovascular disease in particular and health in general.

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