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Addressing Fatigue Caused by Chronic Reactivated Epstein-Barr Virus

tired woman from epv

The Epstein-Barr virus causes a very common infection known as mononucleosis. Symptoms of mono include extreme fatigue, sore throat, fever, swollen lymph nodes, swollen tonsils, headache, rash, and sometimes a swollen spleen.

However, some individuals develop a chronic reactivated Epstein-Barr (EBV) problem. [1],[2]  I have noticed this is common in people with chronic fatigue and have seen it quite a bit in competitive athletes.

Detecting Reactivated Epstein-Barr

In a study [3] on elite athletes with persistent fatigue, 27% were found to have chronic viral infections. Viral illness as a cause of long-term fatigue often goes undetected unless specific blood work is requested. In this study, eight of 37 athletes tested (22%) were actively secreting EBV into their saliva at the time of testing. The detection of EBV shedding suggests immune dysregulation and may contribute to the symptoms experienced by these athletes. EBV reactivation has recently been established in swimmers engaged in intensive training and is thought to result from exercise induced alterations in the immune mechanisms responsible for controlling viral reactivation.

Evidence of infection was also found for cytomegalovirus (five cases), EBV (three cases), Ross River virus (one case), toxoplasmosis (one case), and mycoplasma (one case). Eight of the 37 subjects tested (22%) were found to have evidence of EBV viral shedding in their saliva at the time of investigation, indicating EBV reactivation.

Epstein-Barr Symptoms and Reactivation Triggers

Symptoms of Epstein-Barr reactivation include malaise, fatigue, mild sore throat, and headache.  Patients may also complain of fatigue for no reason or feeling unrested in the morning.

EBV is in the herpes family of viruses and can replicate and reactivate when the body is under stress; similar to how cold sores or fever blisters happen when there is exposure to sun, respiratory viruses, or stress.

EBV targets both lymphocytes and skin cells. It binds to B lymphocytes and then lives permanently in memory B cells, another type of immune cell. In most cases there are no symptoms but in others the immune system become becomes impaired. Unfortunately, there is a whole body of research on how Epstein-Barr is related to certain types of cancers including Burkitt’s lymphoma, Hodgkin’s disease and several autoimmune diseases. EBV can inhibit the strength and activity of lymphocytes when they come into contact and battle foreign invaders.

The Reasons Behind Infrequent Testing for Epstein-Barr

Testing includes viral capsid antibodies, nuclear antibodies, early diffuse antigen, IgG/IgM antibodies, and viral load done through quantitative viral DNA testing.

However, there are reasons why most doctors do not test for this condition.

First, elevated antibodies are common in anyone who has had a previous Epstein-Barr infection.  However, doctors familiar with treating this know that very high levels of viral capsid and nuclear antigen are indicative of reactivated Epstein-Barr. There is even a CDC guideline for interpreting reactivated mono based on antibodies.

The second and more important reason is because there is no FDA approved treatment for Epstein-Barr. The third reason is that recognizing and treating anything but simple mono is not taught in medical school. There is quite a bit of research on various antivirals and some promising data on valacyclovir but despite this no FDA approval and therefore conventional insurance-based doctors have no treatment.

Naturopathic Approach to Epstein-Barr

A common and reasonable response to reactivated Epstein-Barr is that the immune system should be treated, not the virus. Though reasonable, it still leaves the patient trying to figure out what to do.  Certainly, more sleep, better diet, stress reduction, and immune support with vitamin C, vitamin A, zinc, vitamin D, monolaurin, herbal tinctures, lysine, and mushroom extracts (Shiitake, Cordyceps, Maitake, Lions Mane) are warranted. I have found light therapy, valacyclovir [4] and intravenous vitamin C to be the most effective.

Some interesting and more aggressive treatments for this include the application of different wavelengths of blue, green and red light similar to the type of light that cold lasers use. This is called low-level laser therapy (LLLT) or photobiomodulation. The best application is sublingual because the vascular density there is high and close to the surface. Therefore, the light can penetrate into the circulation easily. Sublingual application has recently been shown to be the most effective compared to other methods. I am personally experimenting with this machine after recently identifying an outbreak of Epstein-Barr I caught on blood testing. There are studies on the ability of these wavelengths of light to treat a variety of viruses and bacteria.

There is also good human data on intravenous vitamin C. [5],[6] Because there is limited absorption of vitamin C taken through an oral route, intravenous vitamin C has been studied. There are a number of ways that intravenous vitamin C can work: decreasing inflammation caused by acute or chronic viral infection, increasing the activity and antiviral function of immune cells, stimulating antiviral cytokines and direct antiviral (anti-replication) activity. [7]

In summary, if you are experiencing episodic fatigue, or mild cold and flulike symptoms and your medical providers are not able to find anything, consider doing advanced Epstein-Barr testing. Regular laboratories offer all the tests needed. Testing includes viral capsid antibodies (EBV VCA ab), nuclear antibodies (EBV Nuclear ab), early antigen-diffuse, EBV IgG/IgM antibodies and viral load done through quantitative viral DNA testing (EBV PCR quant).

There is no clear consensus on the best treatment. So far, a multipronged approach has been the most effective for my patients.

Contact us to discuss your concerns around Epstein-Barr virus: (303) 884-7557.


[1] Ruiz-Pablos M, Paiva B, Montero-Mateo R, Garcia N, Zabaleta A. Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome. Front Immunol. 2021;12:656797. Published 2021 Nov 15. doi:10.3389/fimmu.2021.656797

[2] Ariza ME. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back! Biomolecules. 2021 Jan 29;11(2):185.

[3] Reid VL, Gleeson M, Williams N, et al. Clinical investigation of athletes with persistent fatigue and/or recurrent infections. British Journal of Sports Medicine 2004;38:42-45

[4] Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up. In Vivo. 2007 Sep-Oct;21(5):707-13.

[5] Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit. 2014;20:725-732. Published 2014 May 3. doi:10.12659/MSM.890423 known

[6] Hemilä H. Vitamin C and Infections. Nutrients. 2017;9(4):339. Published 2017 Mar 29. doi:10.3390/nu9040339

[7] Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit. 2014;20:725-732. Published 2014 May 3.