Treatment of Epstein-Barr virus (EBV) in ME/CFS Context

While working on a pending post [ME/CFS after EBV in Competitive Athlete] on their microbiome sample I was pleasantly surprised to see their top suggestions have literature on the same substances helping reduce EBV. In one sense, I should have expected it, given the premise that I am working off.

Premise: An infection (including virus) alters the microbiome to be optimal for it survival. Correcting the dysbiosis, weakens the infection (i.e. you may starve it of essential metabolites)

I decided to collect these items in this post for people with ME/CFS and positive for EBV, i.e. chronic active EBV (CAEBV)

Suggestions

Note: [More Info] are links to perplexity.ai, the information may be questionable in some cases.

  • Vitamins, Minerals and similar
    1. Selenomethionine {Selenium supplement}
      • Selenium deficiency is associated with increased susceptibility to EBV infection and its complications [more info]
    2. Zinc {Zinc Supplements}
      • Zinc is directly required for EBV gene regulation.[more info]
    3.  Silver nanoparticles {Colloidal silver}
      • Inhibition of EBV replication: Silver nanoparticles stabilized in citrate buffer can inhibit EBV replication by up to 70% [more info]
    4. Magnesium Compounds {Magnesium supplements}
      • Magnesium plays a critical role in the immune response to Epstein-Barr Virus (EBV), particularly in individuals with genetic defects affecting magnesium transport: [more info]
    5. alpha-tocopherol {Vitamin E}
      • Vitamin E has demonstrated inhibitory effects on Epstein-Barr Virus (EBV) transformation of human B cells, particularly under conditions of oxidative stress: [more info]
    6. Vitamin C
  • Herb or Spice
    • Olea europaea {Olive leaf}
      • Olive leaf extract (OLE) has been shown in multiple studies to have significant antiviral and antioxidant activity against Epstein-Barr Virus (EBV): [more info]
    • Azadirachta indica {Neem}
      • Neem (Azadirachta indica) demonstrates notable antiviral activity against Epstein-Barr Virus (EBV) and other herpes-type viruses: [more info]
    • Allium sativum {garlic}
      • Garlic (Allium sativum) and its organosulfur compounds (OSCs) exhibit notable antiviral activity against Epstein-Barr Virus (EBV) in preclinical studies: [more info]
    • Kaempferol 
    • Commonly recognized antiviral medicinal plants in Ayurveda Medicine. Those with [citation] after them have explicit literature for EBV, most have literature for other virus.
      • Zingiber officinale – Ginger
      • Caesalpinia bonducella – Fever Nut or Bonduc Nut
      • Allium sativum – Garlic
      • Glycyrrhiza glabra – Licorice or Liquorice
        • ts antiviral activity is clearly demonstrated by different studies on the herpes simplex virus, Epstein–Barr virus (EBV), [2023] [2020]
      • Ferula assafoetida – Asafoetida or Hing
      • Gymnema sylvestre – Gymnema or Gurmar (Sugar Destroyer)
      • Gossypium herbaceum – Levant Cotton or Cotton Plant
      • Phyllanthus niruri – Stonebreaker or Chanca Piedra
      • Trachyspermum ammi – Ajwain or Carom Seeds
      • Withania somnifera – Ashwagandha or Indian Ginseng
      • Andrographis paniculata – Andrographis or King of Bitters
        •  has a pronounced effect in inactivation or the inhibition of Epstein Virus (EBV) [2021] [2021] [2021]
      • Centella asiatica – Gotu Kola or Indian Pennywort
      • Curcuma longa – Turmeric
        • significantly induced EBV reactivation [2018] [2021]
      • Woodfordia fruticosa – Fire Flame Bush or Dhawai
      • Phyllanthus emblica – Indian Gooseberry or Amla
      • Terminalia chebula – Chebulic Myrobalan or Haritaki
      • Tamarindus indica – Tamarind
      • Terminalia arjuna – Arjuna or Arjun Tree
      • Azadirachta indica – Neem
      • Ficus religiosa – Sacred Fig or Peepal Tree
      • Moringa oleifera – Moringa [2021] [2021]
      • Quercetin [2021]
      • Resveratrol [2023]
      • Saururus chinensis – Chinese lizard’s tail ,  三白草  [2019]

Probiotics

Only Lactobacillus casei Shirota (Yakult) has studies, Effects of Lactobacillus casei Shirota ingestion on common cold infection and herpes virus antibodies in endurance athletes: a placebo-controlled, randomized trial [2016]

In the above pending post, two probiotics were computed to have significant impact:

Bottom Line

My general advice would be to do the mineral supplementation with appropriate dosage (This Dosages page may help) for at least 2 weeks, then start on some of the Herbs and Spices (Rotating every 2 weeks). Be warned that “die off” like effect may occur with some. Then rotate on to the probiotics for 2 weeks at a time.

Postscript and Reminder

As a statistician with relevant degrees and professional memberships, I present data and statistical models for evaluation by medical professionals. I am not a licensed medical practitioner and must adhere to strict laws regarding the appearance of practicing medicine. My work focuses on academic models and scientific language, particularly statistics. I cannot provide direct medical advice or tell individuals what to take or avoid. My analyses aim to inform about items that statistically show better odds of improving the microbiome. All suggestions should be reviewed by a qualified medical professional before implementation. The information provided describes my logic and thinking and is not intended as personal medical advice. Always consult with your knowledgeable healthcare provider.

Implementation Strategies

  1. Rotate bacteria inhibitors (antibiotics, herbs, probiotics) every 1-2 weeks
  2. Some herbs/spices are compatible with probiotics (e.g., Wormwood with Bifidobacteria)
  3. Verify dosages against reliable sources or research studies, not commercial product labels. This Dosages page may help.
  4. There are 3 suppliers of probiotics that I prefer: Custom Probiotics Maple Life Science™Bulk Probiotics: see Probiotics post for why

Discussion with a Long COVID patient on using Microbiome Prescription

Today I had a nice 70 minute discussion with a user. This shows pretty much all of the new features and options for building your own plan. This applies also for ME/CFS. In fact, the top forecasted symptom for him was ME/CFS without IBS. He has no IBS.

There are Captions on this presentation.

Issues are discussed on many choices.

Reviewing recent study on Fibromyalgia

This is based on this April 24,2035 paper: The gut microbiota promotes pain in fibromyalgia. There are two interesting finings:

  • “transplantation of a healthy microbiota [FMT] is associated with reduced pain and improved quality of life. ” This option is rarely available since FMT is only authorized for  recurrent Clostridioides difficile infections
  • And  “Since mice transplanted with the FM gut microbiota showed reduced levels of specific bile acids (e.g., ursocholate) and bile-acid-metabolizing bacteria (Lachnoclostridium scindens [sic: Clostridium scindens] ), we treated mice that received FM FMT with UDCA, a host-derived primary bile acid metabolized in the mouse gut into various secondary bile acids.57,58,59 “

This post is running from this data into a model and thus a theoretical protocol (not tried in any clinic) if there is evidence to support a model.

Ursocholate Deficiency

This is available as a prescription drug: Actigall, Urso 250, Urso Forte. More details from WebMD. This is not always possible to get prescribed. This leads us to look for production by bacteria. We find that we have information about it on the KEGG: Kyoto Encyclopedia of Genes and Genomes. Going though databases, we do not find any known bacteria (including probiotics) that produces it 😦 . Going to a secondary data resource we get some bacteria involved in production:

Bacterial SpeciesRole in Ursocholate Production
Blautia obeumInitiates conversion of cholic acid
Collinsella aerofaciensConverts intermediate to ursocholic acid
Clostridium limosum/absonumCan perform full conversion in one species
Eggerthella sp.May contribute relevant enzymes
Ruminococcus gnavusProduces related bile acids (UDCA)

Checking against published literature on National Library of Medicine Citations for Fibromyalgia we see:

  • Several blautia species are identified but the above is not cited.
  • Collinsella, Clostridium, Ruminococcus gnavus is not reported
  • Eggerthella is reported high
  • [Clostridium] scindens is high which is contrary to expectations

This is less than ideal. We really want

We have a secondary resource: Bacteria by Symptoms by Lab that are high or low. By lab for Fibromyalgia, we found:

  • No matches for Biomesight data
  • No matches for uBiome data
  • No matches for Thryve data
    • One Blautia species was low

Lachnoclostridium scindens encouragement

We have the list of known items that impacts this species on this page. We note that 80% of the items listed decreases it — we want to increase it.

  • High-fibre diet {Whole food diet}
  • Rheum × hybridum {Rhubarb} & Rhubarb x Peony {Rhubarb Peony Decoction}
  • bacillus subtilis {B.Subtilis }
  • Coffee (Caffeine)

Bottom Line — No evidence confirming the proposed mechanism

Science is endless iteration of tossing out hypothesis and then testing them. Revising as needed. In the study, it is probable that FMT does help; the speculation as to the cause appears unsupported and suspect.

No theoretical protocol will be produced.

Virus, Microbiome and ME/CFS – a connected story

When it comes to virus and ME/CFS there are several schools of belief.

  • A Virus caused ME/CFS and thus eliminating the virus should cause remission
  • Virus are re-activated (or no longer suppressed) by the immune changes associated with ME/CFS
    • De-activating the virus may improve (but not cure) ME/CFS

Past Posts on Virus

Quick Summary

The literature is below:

  • 1. Epstein-Barr Virus (EBV)
    EBV, which causes infectious mononucleosis, is one of the most frequently implicated viruses in ME/CFS. Studies show that 8–15% of people who develop infectious mononucleosis go on to meet ME/CFS criteria, and a subgroup of ME/CFS patients show evidence of EBV reactivation or immune response abnormalities related to EBV5 7.
  • 2. Human Herpesvirus 6 (HHV-6)
    Reactivation of HHV-6, another common herpesvirus, has been hypothesized to contribute to ME/CFS symptoms, particularly in combination with EBV reactivation7.
  • 3. Enteroviruses
    Historical and contemporary evidence links enteroviruses (a group that includes polioviruses, coxsackieviruses, and echoviruses) to ME/CFS. Outbreaks of ME/CFS have coincided with enteroviral epidemics, and some researchers consider enteroviruses a likely culprit, especially in cluster cases1.
  • 4. Influenza Viruses
    Influenza infection has been associated with a more than two-fold increased risk of developing ME/CFS in the years following infection17.
  • 5. SARS-CoV-2 (COVID-19)
    Many individuals with long COVID meet criteria for ME/CFS, and SARS-CoV-2 is recognized as a trigger for ME/CFS in some cases67.
  • 6. Other Herpesviruses
    Varicella zoster virus (which causes chickenpox and shingles) and other herpesviruses have also been reported as potential triggers7.
  • 7. Ross River Virus
    This mosquito-borne virus has been linked to ME/CFS onset, likely through immune system dysregulation3.
  • 8. Retroviruses (e.g., XMRV)
    Early studies suggested an association between the retrovirus XMRV and ME/CFS, but this link has been discredited by subsequent research and retraction of the original findings2.

Model

It is well known that virus will alter the microbiome. This alteration is to trick/hijack the microbiome to produce chemicals/metabolites that the virus needs (and to reduce those that hurt it) [SEE BOTTOM FOR CLARITY]. Once the virus is eliminated, then sometimes the microbiome gets “stuck” in this state. People have symptoms of the virus (symptoms caused by the metabolites!) but do not have the virus any more.

It is this persistent change of the microbiome: dysbiosis; that I believe is the path to relief and possible remission.

Virus and Microbiome Treatment

Using herbs know to be both anti-viral and anti-bacterial is my favored approach. You may get severe die-off from these (along with a herxheimer effect). Die off will usually start to ebb by day 10-14 after starting.

My personal favorites are:

  • Tulsi
  • Haritaki
  • Neem
  • Wormwood (Artemisia)
  • Olive Leaf

The list of Anti-viral herbs

HerbNotable Antiviral Actions
Tulsi (Holy Basil)Herpes, hepatitis, influenza, coronaviruses
 Inhibits viral replication and modulates immunity28.
NeemHerpes simplex virus (HSV-1 and HSV-2)27,
Influenza viruses:10, Dengue virus:58,
Hepatitis C virus (HCV)6, Coxsackie virus, polio, and HIV57, SARS-CoV-2 (COVID-19)49.
Olive LeafInhibit viruses such as herpes simplex virus (HSV), influenza virus, hepatitis B and C, human papillomavirus (HPV), HIV, and notably, SARS-CoV-2 (the virus causing COVID-19)125678.
Haritaki (Terminalia chebula)Antiviral activity against a range of viruses, including SARS-CoV-2 (the virus responsible for COVID-19), herpes simplex virus type 2 (HSV-2), and influenza A virus. In particular, Haritaki demonstrated inhibition of the SARS-CoV-2 main protease in laboratory assays, suggesting it may halt viral replication15.
Curcumin (from turmeric):Antiviral against influenza, HIV, hepatitis, and coronaviruses8.
Ginseng:Traditional use for immune support and antiviral activity5
SageHIV-1, herpes simplex, Indiana vesiculovirus
Rich in safficinolide and diterpenoids; active against HIV-1, herpes simplex virus, and Indiana vesiculovirus157.
OreganoRotavirus, norovirus, general antiviral
Contains carvacrol and thymol; effective against rotavirus, norovirus, and other viruses1578.
FennelHerpes, respiratory viruses
Contains trans-anethole; shown activity against herpes viruses and respiratory viruses27.
Peppermint (Mentha piperita):Contains menthol and rosmarinic acid; antiviral against herpes simplex and influenza viruses2.
Lemon balmHerpes simplex, respiratory viruses
 Contains flavonoids and essential oils; active against herpes simplex and respiratory viruses7.
GingerInfluenza, RSV, calicivirus
Contains gingerols and zingerone; effective against influenza, RSV, and feline calicivirus5.
GarlicInfluenza, HIV, HSV-1, rhinovirus
Contains allicin; antiviral against influenza, HIV, HSV-1, viral pneumonia, and rhinovirus53.
EchinaceaColds, respiratory infections
Boosts immune function and reduces duration of colds and respiratory infections8.
ElderberryInfluenza, cold viruses
Traditionally used for influenza and cold viruses1.
AstragalusGeneral antiviral, immune boost
Immunomodulatory and antiviral properties1.
Aloe veraCoronaviruses, herpes, influenza, HPV
Contains compounds effective against coronaviruses, herpes, influenza, HPV, and more2.
ThymeHerpes, influenza, general antiviral
Contains thymol and carvacrol; antiviral and antimicrobial7.
AndrographisInfluenza, hepatitis C, dengue
Contains andrographolide; active against influenza, hepatitis C, and dengue8.
Artemisia annua (Wormwood)Hepatitis B & C, malaria
Used for malaria; also shows antiviral activity against hepatitis B and C48.

My Personal Protocol

Do one at a time for 7-14 days, then move to the next one. Take notes on die-off or symptom changes with each. Constant rotation is strongly encouraged. Repeat but with only that cause a die-off or change.

You may or may not have a virus or re-activated virus. Most ME/CFS patients are not tested for all of the candidates virus listed above. Prescription antivirals with ME/CFS are very sensitive to which virus that a person has.

Appendix

Viruses lack their own metabolic machinery and rely entirely on host cell metabolites and metabolic pathways to reproduce. While viruses do not carry out metabolism independently, they hijack and reprogram the host cell’s metabolic processes to obtain the energy, nucleotides, lipids, and amino acids required for replication. Key findings include:

Metabolic Reprogramming by Viruses

  • Aerobic glycolysis (Warburg effect): Most viruses induce glycolysis to rapidly generate ATP and intermediates like pyruvate/lactate, even in oxygen-rich conditions12. This provides energy and substrates for viral genome replication (e.g., nucleotides from glucose metabolism)13.
  • Fatty acid synthesis: Enveloped viruses (e.g., herpesviruses, SARS-CoV-2) upregulate lipid biosynthesis to create viral envelopes136.
  • Nucleotide production: Viruses like HSV-1 redirect the pentose phosphate pathway and TCA cycle to boost purine/pyrimidine synthesis for genome replication3.

Host Dependency Examples

  • Human cytomegalovirus (HCMV) increases glycolytic flux, TCA cycle intermediates, and fatty acid synthesis to support its 96-hour replication cycle13.
  • Herpes simplex virus (HSV) prioritizes nucleotide synthesis over glycolysis, reflecting its faster 24-hour replication timeline3.
  • SARS-CoV-2 hijacks folate metabolism and one-carbon pathways to facilitate RNA synthesis6. Inhibiting these pathways reduces viral replication.

Experimental Evidence

  • Glycolysis inhibitors like 2-deoxyglucose (2-DG) block late-stage herpesvirus assembly1.
  • Adenovirus activates Myc oncogene signaling to drive glycolysis and nucleotide synthesis1.
  • Vaccinia virus is an exception, showing minimal glycolysis dependence and instead utilizing alternative carbon sources like sorbitol1.

In summary, viruses co-opt host metabolites by reprogramming cellular metabolism to meet their replication demands. This metabolic hijacking is a nearly universal feature of viral reproduction, making host metabolic pathways potential therapeutic targets126.

Comparing AI Answers on ME/CFS Microbiomes

My focus for the last few years has been on the ME/CFS Microbiome. I decided to test a variety of AI sites for their answering of the question below. Why do I ask this question? Simple, the rate of ME/CFS is very different between men and women, hence the differences of the microbiome may account for this.

What is the difference of reference ranges between 30 year old men and women microbiomes

From Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome

DeepSeek.com

Key Differences

Bacteria GroupWomen (30 y/o)Men (30 y/o)Notes
LactobacillusHigherLowerLinked to estrogen & vaginal cross-colonization
BacteroidesSlightly lowerHigherAssociated with high-protein diets
PrevotellaLowerHigherLinked to plant-rich diets in men
AkkermansiaHigher (post-menopause changes start later)LowerAssociated with gut barrier health

Functional Differences

  • Women may have more short-chain fatty acid (SCFA) producers (RoseburiaFaecalibacterium), influencing metabolism.
  • Men may have more bile-tolerant bacteria (Bilophila), linked to high-fat diets.

Perplexity.com

Alpha Diversity

  • Women generally exhibit higher microbial richness (SV richness) and Shannon diversity indices compared to men in young adulthood,

Taxonomic Composition

  • Females show higher abundances of BacteroidesPrevotella, and Faecalibacterium, while males tend to have more Clostridium clusters and Enterobacteriaceae124.

Gemini.google.com/

Diversity: Some studies suggest that women in their younger adult years (including around age 30) tend to have a higher alpha diversity (a measure of the variety of species within an individual) in their gut microbiome compared to men of the same age.

Claude 3.7 Sonnet

Key microbiome differences between 30-year-old men and women:

  • Bacterial diversity: Women often show slightly higher overall microbial diversity
  • Firmicutes/Bacteroidetes ratio: Men typically have higher levels of Bacteroidetes, while women tend to have higher levels of Firmicutes
  • Sex-hormone influenced taxa: Women generally have higher abundance of Akkermansia, Bifidobacterium, and certain Lactobacillus species
  • Bile acid metabolism: Different bile acid profiles between sexes influence microbiome composition
  • Prevotella vs. Bacteroides: Women often show higher relative abundance of Prevotella compared to men

Grok.com

Women: Higher relative abundance of Firmicutes and Actinobacteria, lower Bacteroidetes. This may contribute to a higher Firmicutes/Bacteroidetes (F/B) ratio, associated with energy extraction from food. Premenopausal women show enriched species like Bifidobacterium, Ruminococcus, and Akkermansia, which are linked to beneficial metabolic effects.Men: Higher Bacteroidetes (e.g., Bacteroides, Prevotella), with men three times more likely to have a stool community type dominated by Prevotella over Bacteroides.

At age 30, women generally show higher gut and oral microbiome diversity, with enriched Firmicutes and Actinobacteria in the gut and Lactobacillus-dominated vaginal microbiomes. Men have higher skin microbiome diversity and gut Bacteroidetes abundance. These differences stem from hormonal and immune interactions, impacting disease susceptibility.

storm.genie.stanford.edu

It identify it sources before giving an answer 🙂

“Understanding these differences is essential, as they can have profound implications for health, particularly in conditions like irritable bowel syndrome (IBS) and metabolic disorders. “

“Research has shown that the microbiome of male mice exhibits higher levels of Firmicutes and lower levels of Bacteroidetes compared to females, contributing to differences in health outcomes and susceptibility to diseases such as CRC”

None of the other bacteria listed below were reference. Lots of discussion on hormones. The response was disappointing.

ChatGPT.com

Similar to DeepSeek above (not a surprise!).

Relative Abundances of Bacterial Genera (typical trends):

Bacterial GenusMore Abundant InNotes
BacteroidesMenLinked with protein and fat-rich diets
PrevotellaWomenOften higher in fiber-rich diets
AkkermansiaWomenLinked to estrogen levels; supports mucosal health
FaecalibacteriumBothAnti-inflammatory, usually similar in healthy individuals

And this summary

FeatureMenWomen
Microbial diversityLowerHigher
Dominant genusBacteroidesPrevotella, Lactobacillus
Hormonal effectLowerHigher
Butyrate productionLowerHigher

Bottom Line

Differences were cited for the following bacteria. I suspect everyone has been reported in one or another study. All of the AIs appear to have incomplete answers. Incompleteness is expected, given their methodology of assembling data. The knowledge level is likely typical of most medical professional: reflecting what they have recently read (and not the entire body of available literature)

  • Actinobacteria
  • Akkermansia
  • Bacteroides 🎯
  • Bacteroidetes
  • Bifidobacterium 🎯
  • Bilophila 🎯
  • Clostridium 🎯
  • Enterobacteriaceae
  • Faecalibacterium 🎯
  • Firmicutes
  • Lactobacillus 🎯
  • Prevotella 🎯
  • Roseburia 🎯
  • Ruminococcus  🎯

I then went to National Library of Medicine Citations for Chronic Fatigue Syndrome bacteria list and flags those with reported associations to ME/CFS 🎯

It was interesting to note that some of the differences were ascribed to male or female eating habits.

My great disappointment is that no microbiome testing company that I am aware of, uses reference ranges that are gender and age based. That makes identifying truly abnormal shifts questionable.

To give a practical example, suppose that you are getting reference range for height instead. You measure people on the street (it happens to be in front of shipyard). We know women tend to be up to 14cm shorter than men, so a bias to males in your sample is ignored. If the shipyard is in India, you get 154 cm. In Holland, 184 cm. So conclusions about a person having “stunted growth” or “excessive growth” based on their height without any reference to appropriate context becomes very suspect. A female that is 140 cm in India could be deemed to have stunted growth — yet is the average height for a woman in India.