Reactivated EBV Driving Fatigue? A Look At Epstein Barr

Fatigue is one of the top 3 health issues for which people seek functional medicine care, and reactivated Epstein Barr Virus (EBV) is something I look for in patients who have symptoms of not only fatigue, but also chronic aches/pains, Hashimoto’s, and even depression.

Unfortunately, mainstream medicine does not recognize that EBV can play a role in chronic illnesses and symptoms. One of the main reasons for this is that there really aren’t any pharmaceuticals that treat EBV (it’s considered “self-limiting”), and the research on this topic has mixed results on whether chronic reactivated EBV causes symptoms or if it’s just an incidental finding.

Integrative/functional medicine, on the other hand, recognizes the role of “stealth” infections in chronic immune imbalances that lead to various conditions (particularly autoimmune conditions). However, it usually takes more than some pills to truly quell this virus. I’ll touch on the basics for treatment in this article, but let’s start with clarifying some biology, definitions, and how to interpret test results.

How viruses affect humans

Don’t freak out, but the reality is that we have viruses in us (some estimate that over 300 coexist – i.e. live in the body but don’t cause problems – in the human body!).

Most of the time, these viruses aren’t actively reproducing, and our immune system does a good job of keeping them that way. But sometimes periods of high stress, poor lifestyle habits, trauma, and major life changes (especially when it involves hormones like perimenopause or post-pregnancy) can weaken the immune system and lead to new or reactivated viral infections.

Obviously, we can’t control external events but we can develop habits right now to help us stay strong when faced with such events. If we want to prevent viruses from causing harm, we have to remember 2 key elements of basic biology: barriers and immunity.

A virus has to cross through barriers in order to get into our cells and replicate. Most of these barriers are made up of mucous or lipids, and we have to take care of these by staying hydrated, eating healthy fats and sources of fat-soluble vitamins, and more! 

We also have to remember that the severity of symptoms is more often due to the immune reaction (rather than the virus itself, which does not exist without using the DNA/RNA of our cells to replicate), so a balanced resilient immune system is key in preventing and fighting off an infection. When our immune system is out of balance, it is often due to what I call the “burden of responsibilities”. The goal is to decrease the burden so the immune system can do it’s job well when faced with fighting an infection. Some of these responsibilities include:

• Quelling inflammation (including inflammation from poor food choices like alcohol, processed foods, chemicals found in food such as diet sodas, etc)
• Mitigating the damages caused by poor diet and high blood sugar levels (which are particularly damaging to mitochondria and the lining of our blood vessels)
• Managing the negative effects of stress (e.g. cortisol plays a significant role in this, which can cause hyper-permeability of our gut, where 70% of our immune system is located!)
• Recuperating from the effects of poor sleep (our immune system resets and repairs during certain stages of our sleep)

We actually have a lot of control over the aforementioned responsibilities, which are often impacted by our daily lifestyle habits!

What is the Epstein Barr Virus?

It’s important to understand that EBV is one type of virus, and is part of the DNA-based herpes virus family. Over 90% of people around the world have been exposed to EBV, and this exposure usually occurs in childhood or as young adults. Most only have to deal with symptoms for a few weeks, then they recover.

The herpes virus family loves the nervous system and mucous membranes, and each subset of this family prefers different cells. Some prefer the skin and mouth (e.g. those that cause canker sores), some prefer the mucous membranes of the genitals (e.g. the stereotyped “herpes” STD), and others prefer nerves (e.g. shingles, chicken pox).

When an acute Epstein Barr virus infection occurs, initial symptoms can look like a combination of the flu and strep throat (fever, body aches, sore throat, fatigue). In most people, the infection resolves. But in some people, chronic and even reactivated EBV can occur, leading to symptoms/conditions that include:

• Chronic pain in muscles and joints
• Ringing in the ears (tinnitus)
• Fibromyalgia
• Parkinson’s Disease
• Cancers (e.g. various lymphomas)
• Fatigue
• Headaches
• Insomnia
• Swollen lymph nodes
• Rash
• Abdominal pain (e.g. from enlarged spleen)
• Autoimmune conditions (e.g. Hashimoto’s, multiple sclerosis, etc)

*The conditions that I have bolded are the ones where I most commonly see reactivated EBV.

The 5 types of EBV infection

An infection involves invasion of the body, replication, and the body’s reaction to the bug that has invaded the body. Although I list 5 types of infection below, dormant EBV probably shouldn’t be included in this list, since there are no symptoms, but I mention it because it shows up as “positive” on labs.

1. Acute illness (lasts 2-4 weeks). This is also known as mononucleosis, or “mono”.
2. Chronic active illness (acute illness symptoms lasting more than 3-6 months).
3. Dormant EBV (i.e. no symptoms, but labs results are positive).
4. Reactivated simple illness (appears months or years after initial illness/exposure; can present as an autoimmune condition such as Multiple Sclerosis, Rheumatoid Arthritis, and Hashimoto’s; can resolve within a few months – with or without treatment)
5. Reactivated complex illness (a worse version of reactivated simple illness, and often involves co-infections with bacteria like H. pylori or tick-associated bugs, significant mitochondrial damage, biofilm formation, and more; this can also occur with incomplete treatment)

An important clarification (and one that many practitioners don’t often understand):

…reactivated EBV is implicated when someone has both significant symptoms PLUS high abnormal ranges on blood tests.

The specific tests matter, too!

Testing

Testing for EBV is best done via basic blood testing. Just because a marker comes back abnormal or positive does NOT indicate reactivation. It is important to check other markers that impact immune function such as vitamin D levels, nutrient levels, and certain hormones. I also will consider use of functional medicine testing (specifically cortisol testing and stool testing), if symptoms are not improving with treatment.

The following are found in most commercial (i.e. insurance covered) labs.  Note, the MOST IMPORTANT marker, which must be ordered separate from an EBV panel, is the EBV EA IgG:

1. EBV Viral Capsid Antigen (VCA) IgM: Positive if current active infection (but can be falsely elevated if over the age of 60, or if another infection is present)
2. EBV Viral Capsid Antigen (VCA) IgG: Positive for life if previously exposed (which is 90+% of people!); will be present 2-4 weeks after exposure; cannot determine virus replication based off this. 
3. EBV Nuclear Antigen (EBNA) IgG:  Positive if current or past infection. Will be positive 2-4 months after initial exposure; cannot determine virus replication based off this.
4. EBV Early Antigen (EA) IgG: If positive, this commonly indicates active virus replication, but can be positive for 3-6 months after replication ends. Many immunologists agree that this has to be 3-5x higher than the max reference range for it to indicate reactivation (thus, under “30” on most U.S. labs is not considered reactivation even if it’s marked as high on a lab). This one is commonly left out of most tests but is the most important for accurate diagnosis of reactivation.  BUT…the degree of elevation does NOT correlate with viral load (it is an IMMUNE REACTION, not a marker of quantity of a virus).  
5. EBV PCR testing: Looks at quantity of the virus, but the virus mainly lives in cells not in the bloodstream (so often can have a “false negative” result). 
6. CBC with differential: In this basic test, I particularly like to know the quantity of the WBCs, the lymphocytes, and the neutrophils.

Reactivated EBV

How do you determine an EBV reactivation based off the above tests? For the most part you can identify reactivated EBV by keeping in mind the following:

1. The IgG-based tests are generally positive for life, but the degree of elevation can increase the likelihood that reactivation is occurring. A general rule of thumb? If a test result is 5x higher than the top value in the lab’s reference range, it is more likely to indicate reactivation but never go off just the EBV VCA IgG (need multiple elevated markers).
2. The EA IgG and PCR test are more direct at looking for replication and viral load (at least one of which is needed to truly identify reactivation).
3. If WBC levels are in a good range, but lymphocyte percentages are either over 35% or under 25%, this can suggest that the body is actively fighting off a virus. Sometimes we have to look further at other areas of the immune system, but this is a good “big picture” test.

Treatment overview

As I mentioned earlier, acute (and chronic) EBV typically resolves on its own with rest and hydration.

Of note, there are no pharmaceutical drugs that are patented to treat EBV (acute, chronic, or reactivated), but we know that some of the anti-virals that treat other herpes viruses can help with EBV by decreasing replication of other viruses that challenge the immune system. I rarely use these on their own, and am very cautious in using these if a patient has depression or anxiety (if viral load is high, we can see suicidal ideations in these patients or other significant side effects).

Treatment for reactivated viral infections is more complex, and there is no one-size-fits-all protocol. Initial pill-based treatments should be taken for 3-6 months, but these must be part of a comprehensive approach that involves modifying lifestyle habits (in particular focusing on sleep and stress). It can take longer than a year to truly resolve symptoms, but most people should feel some benefits within the first 4-6 weeks if EBV truly is the culprit (and treatment doses are appropriate).

Five aspects of treatment for Reactivated EBV

Over the years, I’ve realized that there are 5 essential elements needed to treat chronic viral infections (EBV, CMV, and others) when symptoms are present and labs show high likelihood of reactivation.  Before pursuing any of these, however, I highly recommend ruling out subclinical/over hypothyroidism or mycotoxin-induced illness as the causes of symptoms and lab findings:

1. Stop the virus from replicating.

   • One of my mentors calls this “virus birth control”, and we can use prescriptions and/or supplements to do this.
   • My favorite supplements for this are Lomatium and monolaurin.
   • This is only 10-20% effective in a treatment plan, though, since EBV is not the cause of symptoms (symptoms are a result of the body’s immune response to EBV or something similar to EBV).

2. Rest.

   • Simple but not easy! When we are tired, we want more energy and we try to gain more energy with a variety of external tools (e.g. caffeine). But we have to listen to the body…take more naps, go to bed earlier, decrease exercise…and sometimes we have to do this for months! It requires patience, but is necessary.
   • Connected to this is the role of cortisol. Sometimes we need to look at cortisol levels with functional testing, and work on balancing these to follow an appropriate circadian rhythm. In general, we want cortisol to be highest in the morning, and lowest in the evening, and there are many nutraceuticals or herbs we can use to “teach” the body to get back into a natural rhythm.

3. Support at the nutrient level.

   • In particular, vitamin A (retinoid form, i.e. from animal sources), vitamin C, selenium, and zinc are needed (not in excess, though!).
   • We must optimize vitamin D levels as well, and do so by monitoring with lab testing (50-80 on a blood test is ideal). Most people require 5000 IU of vitamin D3 per day to achieve this goal.

4. Balance/support the immune system.

   • This step is not easy to summarize, but it has to do with boosting the innate immunity, supporting the Th1 response of the immune system (how we fight off viruses), and modulating a dominant Th2 response of the immune system.  In its most basic definition, Th1 responses addresses the cells that are allowing a virus to replicate, and Th2 responses create the “soldiers” (antibodies) that address circulating viruses while turning down a Th1 response (but most viruses are in cells, not outside of cells, so more soldiers is not necessarily better).
   • Treatments for this may include mushroom extracts, NAC, quercetin, berberine, resveratrol, and more (but must be tailored to a set of lab results and individual symptoms).

5. Support and repair the mucous and cell membranes.

   • This is highly dependent on gut function, so nutrition and stress management are key.
   • Treatments are focused on a 5R gut protocol, healthy dietary fats, fat-soluble vitamins/supplements, low inflammatory foods and/or treatments, and antioxidants if needed.

Treatment success

It is important to note that successful treatment of reactivated EBV is not due to simply addressing the virus. We must address the underlying reasons why the immune system is not controlling the virus, and these are often not treated with a pill. In particular, gut health, cortisol levels, inflammation, and sleep/stress imbalances must be addressed. Pills can certainly help, but I’d estimate that this covers only 50% of the treatment and we shouldn’t rely on these long-term.

Finally, the goal is not to make labs normal (even though many “experts” may advocate for this), but what we should see is a drop in the labs over 6-24 months. But in my opinion, if a patient has improved significantly (my goal is always 80% improvement from baseline), we don’t need to follow the labs (unless monitoring antibody levels associated with an autoimmune condition)!

Summary

• Epstein-Barr Viruses can cause acute or chronic persistent symptoms
• Reactivated EBV is not recognized as an illness to treat in mainstream medicine
• The symptoms associated with reactivated EBV are primarily due to the immune system’s response to the virus, rather than the virus itself
• The most common symptoms of EBV are significant fatigue and pain
• Treatment is not straight-forward and simple, can take over a year to work, and are focused on 5 primary steps: stop the virus from replicating, rest, support nutrient levels, balance the immune system, and address the health of physical barriers (in particular, cell membranes, gut barrier, lungs, mitochondria)
• Treatment Goal: symptom improvement +/- decrease in antibodies on testing (goal is NOT to get normal test results)
• Ultimately, EBV reactivation is never the ONLY driver of symptoms or illness, and to truly improve health we have to address other contributors (especially gut health, sleep quality, and stress management)!

Before thinking that a supplement regimen is the answer to your health ailments, please focus on the elements of health that you can control (without the need to spend money on me!): prioritize sleep, implement a daily relaxation habit (no screens involved!), and eat foods that are plant-based and minimally processed!