Warning: Improving your methylation may trigger an Epstein Barr virus relapse

What is the Epstein Barr Virus?

Many people know the Epstein-Barr virus (EBV), or mononucleosis, as “the kissing disease” because it forms massive reserves in the saliva and mouth and it easily transmitted through kissing. It can also be caught from swimming pools, dirty cutlery and other physical contact. In England it is usually called Glandular fever and in America it is called Mono.


The symptoms are very severe sore throat, and painful inflammation in all the lymph glands, salivary glands, and ovaries. It also causes extreme tiredness which lasts months – usually longer in menstruating women than in men because of the ovary involvement. Long-term EBV infections are associated with higher risk of lymphoma, ovarian cancer, stomach cancer and other types of cancer in the organs it particularly affects.

Some mouldy-looking tonsils with EBV in them. Take it from me, this HURTS


How does it reproduce?

Like all viruses, EBV is just a small piece of protein that can reproduce itself using the reproductive mechanisms of a living animal’s cells. The Epstein-Barr virus chooses the B-cells of the host’s immune system to reproduce, which is why an infection particularly affects the lymph glands – this is where your B-cells are made. Once it has entered the body it is never eliminated but becomes a latent infection which can recur at any time the immune system is weakened.

Methylation is normally part of the cell’s protective mechanism against viruses. When the cell’s DNA replicates, methylation processes work along it and deactivate viral sequences by methylating them.

EBV is a true wolf in sheep’s clothing, however, because it as learnt to adapt and benefit from being methylated. It actually makes your body OVER-methylate some DNA sequences and this is how it increases the risk of cancer.

It is also associated with particular forms of cancer, such as Hodgkin’s lymphoma, Burkitt’s lymphoma, gastric cancer, nasopharyngeal carcinoma, and some research has found that infection with EBV is associated with a higher risk of certain autoimmune diseases,[3] especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome,[4][5] and multiple sclerosis.[6]

The frills all over this human B cell are Epstein-Barr visus in its lysic phase, just about ready to rip the cell apart and go off with flaps of its dead cell wall hanging off them


EBV has three reproductive stages. These were discovered by a German team. You can read their research HERE.

1. In the first prelatent phase the viral DNA acquires nucleosomes, histone marks are established, and 5′-methyl cytosine residues become detectable. In other words, it picks up parts of the infected person’s cell-reproduction equipment.

2. In the latent phase, repressive histone marks and extensive DNA methylation silence the majority of viral promoters sparing a few latent genes. In other words, at this stage your methylation processes are doing what they are supposed, to, keeping the virus repressed.

3. DNA methylation is a prerequisite for the induction of EBV’s lytic phase in order to escape from latency and give rise to viral progeny. This is the final stage where the virus turns your methylation processes against you, in fact it needs them to be able to break your body cell into pieces, taking parts of the cell wall stuck onto it as another cloak to hide it from your immune system.

So it uses your methylation processes to replicate itself?

So, just to explain it again, here’s what it does:

  • EBV must first establish a latent B cell infection in order to keep them alive long enough to produce new viral particles
  • EBV DNA is unmethylated upon infection, but becomes methylated over time by the host B cell
  • The BZLF1-encoded protein, Zta (a cousin to AP-1), induces the viral lytic cycle (this means part of the reproductive cycle), but it prefers binding sites that are methylated. So the lytic phase gets delayed until enough methylation has occurred.

You can read more about this HERE at Epigenie.com and the original research article HERE on Pubmed.

An article on bloodjournal.org explains how EBV viruses allow themselves to be methylated (by you) as a way of hiding from your immune system:

…methylated EBV DNA can be detected in the normal lymphocytes of healthy volunteers. Whereas methylation of foreign DNA has been recognized as a potential cellular defense mechanism, methylation of EBV DNA may be an essential part of the virus life cycle in vivo, explaining the persistence of virus-infected B cells in the face of immune surveillance.

This is not only how the infection flourishes for so long before the immune system dampens it down, but also how it protects itself from the body’s natural defences once it has triggered cancer, and it explains why cancer cells associated with this virus are partly under-methylated and partly hyper-methylated:

First recognized in tumors, methylation-associated evasion of immune surveillance is not an aberration restricted to tumor tissue but is detected in normal EBV-infected lymphocytes. Methylation of the viral genome in latency also provides an explanation for the CpG suppression associated with EBV but not other large DNA viruses.

 What does this mean for patients?

Essentially, anyone with weak methylation (due to genetic polymorphisms and/or altered gene expression) gains the benefit of restricting the ability of a latent EBV viral infection to replicate itself and flare up. Taking supplements to improve methylation can therefore trigger a glandular-fever relapse.

Some anti-herpes antiviral drugs, including Zovirax, can help work against EBV. However, they only affect the virus in the lysic phase, once it has already done a lot of its damage.

A natural aid is to take Lysine supplements. This is an amino acid that the immune system uses to fight against viruses of the herpes family. Against the EBV virus higher doses are needed than for herpes simplex, for example: sometimes 5,000mg a day.

Other articles

The role of promoter methylation in Epstein-Barr virus (EBV) microRNA expression in EBV-infected B cell lines


Epstein-Barr virus-specific methylation of human genes in gastric cancer cells


This article explains how the modifications EBV makes to your methylation processes predisposes those cells to become cancerous


37 thoughts on “Warning: Improving your methylation may trigger an Epstein Barr virus relapse

  1. Frankincense can help repair DNA. Other herbs and essential oils can help support the immune system to keep EBV and other latent viruses from expressing.


  2. I wouldn’t worry at all if I were you.

    Methylation happens every single second of every day, and as someone pointed out on another site, if this were a problem, with hundreds of thousands of people taking methylation supplements over the last 8+ years, surely a trend would’ve showed up by now.

    Also, as someone pointed out on another forum, EBV is a common virus, not a retrovirus. That’s why it’s not called EBRV.



    1. Ah yes, you’re right about it not being a retrovirus. Thanks for pointing that out!

      I don’t agree with you about doctors spotting a trend though. Most people who take methylation supplements don’t have a practitioner helping them figure out why it is working well or badly, so who is there to notice the trend? Also lots of people who take methylation supplements stop because they feel worse not better, and most of them never find out why.
      Even among the people who do have a specialist doctor supervising their attempts to improve methylation, the number of people taking methylation supplements it a teensy proportion of the population and if doctors still haven’t noticed there’s a Lyme disease epidemic going on under their noses, why would they notice a tiny trend among the tiny number of people who take methylation supplements?

      Liked by 1 person

      1. Thank you for such an illuminating, well written, well-documented look at the interactions between EBV and host methylation. Seems worth screening EBV titers in patients eager to explore methylation support, so they can become aware of the double-edged sword phenomenon. In my experience it is common for patients to find the “sweet pocket” for methylation support dosing, only to witness the tables turn over a period of time. Creating a norepinephrine-serotonin mismatch (ie, norepinephrine dominance associated with irritability) could account for some of this table-turning. But EBV activation and replication surely plays a role in some. Thanks again for a most enlightening and succinct review of a very important phenomenon.


      2. Thank you very much for your very kind comments.
        Your comments about a norepinephrine-serotonin mismatch are very interesting and I can instantly think of various online friends in my Lyme disease support group who may well have this problem. Do you know of any useful articles about this?


      3. Sorry for the late reply.The NE dominance theory is drawn from animal studies linking NE stimulation to anxiety and defensive behaviors. GABA receptor blockade can draw out defensive behaviors as well. There are a fair number of such studies out there. In practice, I find that a high proportion of my anxious/irritable patients respond well to 5-HTP and the precursor to GABA (phenylated GABA, which passes the BBB more easily than GABA itself). I also find that low doses of propranolol help some of these patients, especially the ones with hyperflexible connective tissue. A lot more to discover, for sure, but the animal studies lend some face validity to the concept that NE dominance correlates with anxiety and irritability.



        Liked by 1 person

  3. How about correcting methylation does activate EBV but also gives the body the opportunity to resolve and eliminate it? Certainly when you correct methylation, there can be a lot of old toxins and pathogens that the body can now deal with and that can take a long time but is positive in the long run…


    1. The only things I know of are lysine in high doses (it’s proportionate to body weight but 3000mg daily is right for the average woman) and olive leaf extract which has general antiviral properties. All antivirals seem to work great for some people and not at all for others and it depends on the persons DNA according to some research I have read.

      Liked by 1 person

  4. You Can also trigger shingles….So the funny thing is that i really wasn’t trying to detox myself or do anything drastic. I was just trying to get healthier, support my son’s mutations and get through menopause. I am a pretty healthy person who is able to manage my anxiety problems without medication. I never smoked but I do enjoy drinking wine. I never liked taking medication and only take it when absolutely necessary (except nasal spray – my only bad habit). I always had an obsession with spinach and organic berries (and now I understand why). Last year I wasn’t feeling well and was having hot flashes and increased anxiety. I started making Spinach, triple Berry and flax seed smoothies in my nutrobullet and it helped me feel better. My body always has a way of telling me what I need. But, the last couple of years have been really hard. Much of my stress came from my son’s problems. Well I found out that my 15 year old was homozygous for C677T (and having MANY problems) and my younger son was homozygous for A1298C – so that meant by default that hubby and I have to be compound Hetro MTHFR. I found a great multi (real vitamins – not synthetic) that practically stopped my hot flashes and I was feeling great. I was also taking, calcium, magnesium and probiotics and added a fully active B complex vitamin since I was giving them to my son (and knew about my mutation). I added NAC because I read that it could help clear out my mucus problem (hence my nasal spray usage) and that worked too. I stopped drinking artificial sweeteners in my tea (switched to honey). Since my entire family has MTHFR mutations, we started avoiding foods with Folic Acid, and in doing so I decrease my intake of receptor blocking Folic Acid. So everything was going great…. getting healthier and then……..Bam Shingles. That MTHFRing gene!

    Liked by 1 person

    1. MKM, OMG! How do you manage and afford everything for your family? I’ve suffered from CFS, EBV flare-ups, etc., the last 15 years, had my DNA done and found out had a multitude of mutations including MTHFR. I’m working with Dr. Rostenberg with Red Mountain Clinic and have made some headway on my gut and bacterias I have along with candida and fungus. It’s a struggle. But now my 20-year-old son is full-blown EBV for 18 months now and needs testing ($$$) and I now feel my 19-year-old high-functioning autistic son needs it also ($$$). All my of my assets are gone from paying for testing health insurance refuses to pay for, not including the expense of supplements,and I’m trying to figure ways to bring in an income. How do you do it?


  5. Thank you for this article. I am still putting together the pieces of my puzzle, but it totally fits my current struggle. I have managed my auto-immune condition well (pain free) for the past 18 years. I have suspected that I have MTHFR but have not tested. I recently tested positice for EBV and cocksackie virus and started an anti-viral that has put me in myofacial dysfuntion overload. I am currently trying to push through to the other side with a major focus on detoxing and nutritional support. I am determined to live pain free again!


    1. Thank you! I have corrected the blog post now. I think someone already pointed that out and I thought I had corrected it some time ago. Sorry for the mistake.


  6. So would it make sense to simply address EBV before mthfr mutations? Like, could you do a 1 to 6 month regime of L-Lysine, immune building herbs such as echinacea and the like?


    1. Well, I think in theory that would be the right approach, because I think if you could get the EBV level low and keep it low, then the methylation supplements could be tolerated.
      I have been doing everything that should reduce my EBV levels, though, and for me it just hasn’t worked. When I add in methylation supplements, it feels as if the EBV level flares up in a matter of days. I have just been going by feel as to how low the EBV is, because I can’t afford frequent testing, so it may be I have just been going in for the methylation too soon. Or it could be that the methylation supplements will increase the viral load rapidly no matter how low you get it before starting methylation supplements. Based on a sample of one person I cannot say!
      But I personally think it is a valid experiment to try.
      If it does work, or in fact if it doesn’t, please post your conclusions here, because it could be really helpful for others.


  7. Thanks for valuable informations.
    How can treat &/or suppress EBV/CMV naturally, if traditional medicine has no solution.


    1. That is a really good question! So far I have only found out that lysine helps as it works against all the viruses in this family, and various herbal antivirals. Olive leaf extract seems to be particularly good for EBV and a lot of people say they find coconut helpful too. The effectiveness of antiviral drugs is known to vary greatly from person to person and I think that applies to antiviral herbs as well, so I would be willing to experiment a bit.
      If you find any other good ways to help, please share them here.


  8. The core problem of undermethylation is that it produces a glutathione deficiency. This deficiency is responsible for most of the ills of chronic fatigue syndrome. Glutathione does many things including controlling viral replication. So low glutathione encourages viral replication and high glutathione inhibits replication. So if you are undermethylating and it is causing low glutathione then it is encouraging ebv replication. So I am not so sure about this theory of methylation will increase ebv replication as it should do the opposite.


      1. However I have not found anything in relation to glutathione depletion playing a role in nurturing epstein barr reproduction. I think that may be a theory of Fred’s based on the impact that glutathione depletion is proven to have on the immune system in general?


      2. Nice dig! This review lays an evidence-based foundation for the idea that glutathione can play an important role in immune cell efficiency. Would seem relevant to intracellular infections in that cells hosting viruses, bacteria, fungi, or protozoa are likely to experience resource depletions and glutathione is in charge of intracellular redox balance. Ask and ye shall receive. Thanks VH and Fred. Happy Holidays to all.

        Liked by 1 person

  9. VDR I first heard the term reading about the Marshal protocol Trevor Marshal. The theory is the invader hides in the vitamin D receptor and does it’s damage from this hiding place. The protocol lowers sources of Vit D including sunlight while taking a bp drug that also I think lowers vit D…. I can’t quite recall this correctly but it is something along those lines seems to me it may be a bacteria they are trying to kill as antibiotics are used once the Vit D is low low doses of antibiotics are used to kill the invader so it must be a bacteria they are hunting.

    So if this is the same idea with a virus hiding in the VDR gene… maybe the same protocol using low dose antivirals would work? I read about this years ago and there was to be a study done and maybe it has been done by now.

    I have at least CFS and more… won’t go into it all now. Had it for years and the Marshal protocol is suppose to cure it… I am not sure I did not do the program.

    Recent testing shows I have had EBV even more recent 23 and me results show I have VDR Bsmrs1544410 TT +/+

    I cannot tolerate Vit D I can’t sleep or think after a few days on 400mg and feel worse when I take it tho I test low… a month of taking it as much as I dared a few days on a couple days off to get some sleep… at the end of the 30 day test my blood test showed vit D lower than before I supplemented.

    I am very new to all this just go my 23 results last night… but I know I can’t take Vit D. I also know B12 is bad for me… I can’t recall the reaction just now but I know it is bad.

    I have chemical sensitivities and recently acquired a movement disorder. I am trying to sort this one thing at a time…
    MAO-A R297R rs6323 TT is next close second is CYP2D6 S486T rs1135840 GG
    GSTT1 absent…

    Nothing like a bit of Chinese with the morning coffee….

    I am baby steps new and don’t always think so well but I am going to give this a try… thanks for the site it is helpful Any input is appreciated.

    Liked by 1 person

    1. I think this vitamin D debate is so confusing! I tried the Marshall protocol for a while but just got worse and worse, and did improve when I started supplementing vitamin D. Though I am hearing from more and more patients that they supplement with D but their levels don’t increase. Either it interacts with an infection as you say, or there is some other reason they have this problem. There’s so much still to be figured out!
      Good luck with your research and experimenting.


  10. what helps me or what I take and hope it helps

    B1 helps me think
    Co Q10
    Vit E
    Lysine 😉 was hit and miss think I will take it daily after reading this
    Vit C
    Glycine mollybedum when I feel I need it to dump toxins like perfume.. I could be wrong on all this and likely am… so don’t copy me please mostly lost in the dark and gathering medical care from books and online…
    B5 hit and miss…. taurine hit and miss … mag ,malate hit and miss


  11. Common Side Effects of Spironolactone
    Vomiting, diarrhea, and stomach pain or cramps.
    Dry mouth and thirst.
    Dizziness, unsteadiness, and headache.
    Gynecomastia (enlarged breast tissue) in men, and breast pain in women.
    Irregular menstrual periods and post-menopausal vaginal bleeding.
    Erectile dysfunction.
    that was bad enough but there is hope
    cause the SM protein exists on all forms of the herpes virus, potential uses for spironolactone may not be limited to just treating EBV. At the moment, spironolactone is not yet ready for use as a herpes virus antiviral. According to Swaminathan, in its current form, spironolactone is far too toxic to use for treating the herpes virus and its side effects range from compromising kidney function to increasing secretion of salt. However, the team is confident that they will be able to separate spironolactone’s heart failure properties from its antiviral properties, making it not only effective but also safe for use.

    “We think there is great potential to modify this molecule so that it can work as an antiviral without having undesired side effects,” explained Swaminathan in a recent statement. “We think it can be developed it into a new class of antiviral drugs to help overcome the problem of drug resistant infections.”
    They are working on it…

    for validation I too got shingles when I went on a super juice diet… which makes me wonder if the shingles vaccine if any are brave enough to take it … would it work on ebv… and other like viruses?

    Liked by 1 person

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