Effect of High Dose Vitamin C on Epstein-Barr Viral Infection

The Epstein-Barr virus (EBV) is a member of the herpes family that targets lymphocytes and epithelial cells. It binds to B-lymphocytes via the CD21 cell surface protein, and establishes life-long persistence in memory B-cells. While the infection is usually benign, it can in some cases lead to acute infectious mononucleosis and can impair the immune system. EBV is linked to several malignancies, including Burkett’s lymphoma, post-transplant lymph-proliferative disease, Hodgkin’s disease, and several autoimmune diseases.

There is currently no treatment for removing EBV infections. Our clinic has been long interested in the use of vitamin C (ascorbic acid, ascorbate) to combat viral infections. Ascorbic acid is an essential nutrient that functions as a key water soluble antioxidant and is involved in synthesis of collagen, carnitine, and neurotransmitters. It affects wound healing, energy metabolism, nervous system function, and immune cell health. Oral supplementation with vitamin C typically gives rise to plasma ascorbate concentrations less than 0.2 mM, while high dose intravenous infusion of the vitamin can raise plasma concentrations higher than 14 mM. These “pharmacologic” plasma ascorbate concentrations  achieved by intravenous infusion have been linked with benefits to endothelial function, cellular immune function, antioxidative capacity, pain relief, and treatment of cancer and other illnesses.

The motivation for using intravenous infusions of  vitamin C (IVC) to treat viral illnesses comes, in part, from observations that virally infected patients exhibit vitamin C deficiency. This in turn suggests that clinical management of viral infections may benefit from supplementation.

Improved recovery of subjects with viral infection upon supplementation with pharmacologic doses of vitamin C has been observed clinically. In a multicenter cohort study, sixty-seven symptomatic Herpes-Zoster patients were given intravenous vitamin C in addition to standard treatment for shingles. Pain assessments were made and dermatologic symptoms such as hemorrhagic lesions were followed during twelve weeks of treatment. Pain scores and number of dermatomes all showed statistically significant decreases during the treatment.

Several mechanisms of action have been proposed for this potential benefit.

• Since viral infections are often associated with oxidative stress, the ability of ascorbate replenishment to promote a reducing environment could be important in detoxification and neutralization of reactive oxygen species associated with infection.
• Vitamin C is also necessary for neutrophil function, as they typically accumulate ascorbic acid at 80 times the plasma concentration.
• Also considered as potential mechanisms are the ability of ascorbic acid to stimulate the production of interferon and other anti-viral cytokines, its ability to down regulate inflammation, and its direct antiviral properties.

Our study details an analysis of EBV progression, via antibody assays, in patients undergoing intravenous vitamin C therapy. The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection. Our results, detailed below, add further evidence to the idea that ascorbic acid may be useful in treating viral infections.

Our analysis suggests the following:

• High dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels.
• Plasma levels of ascorbic acid and vitamin D correlated with levels of antibodies to EBV.
• There is an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease.
• The relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D.
• Our clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.

• We published our results in a peer-reviewed journal: Effect of high dose vitamin C on Epstein-Barr viral infection. Mikirova N, Hunninghake R. Medical Science Monitor, 2014; 20:725-732