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Comment by reedf1 | Hacker News Reader

Terrifying - I was EBV positive 4 years ago. It does not mention an association between EBV severity and MS, but I was very symptomatic and had post viral fatigue for around a year. I had no idea about the MS association!

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> According to epidemiological studies, the EBV is estimated to be positive in more than 90% of the world's populations

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008310/

> A total of 2.8 million people are estimated to live with MS worldwide (35.9 per 100,000 population)

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720355/

Given that you have EBV, I guess you're in the unlucky 90%, increasing your odds from 359 in a million to a ...whopping... 399 in a million.

Since the risk for the non-EBV group is 32x less, you'd be increasing your odds from like 11 in a million to 399 in a million no?

If you knew you were negative yes, if the status was unknown then not.

Calm down... from the article:

"Note, though, that EBV would then be in the "necessary but not sufficient" category. There's something about the interaction of particular human immune systems with EBV infection that pushes things over into the pathological state of multiple sclerosis, and we don't really know how to identify these people. But that fits with what we know about infectious disease in general - everyone's different. The situation with Guillian-Barré is similar - a small number of people tip over into neurological pathology, for reasons unknown, and that one also often seems to follow some sort of viral infection."

That's a good quote, thank you.

About the use of "calm down" as an instruction: while your sentiment is good (to reduce another person's anxiety), it's not always possible for someone to follow that when it is received as an instruction. It's tricky to estimate other people's emotional state based on text, and for them to infer your tone. I'm overexplaining and sure that you probably understand all that; but it feels worth mentioning.

True. My first reaction to the directive, was that it was rude. Reading more of the context attenuated that impression, but I still think it could have been phrased less ... paternalistically?

You could be onto something there, yep.

Communication is hard.

It certainly is.

Here's a (probably totally unrelated) comment that I think is good food for thought: https://news.ycombinator.com/item?id=29917158

Interesting.

It is, but there are some easy heuristics before you get to the hard stuff.

One is that telling people how they should feel about things is usually irritating.

> About the use of "calm down" as an instruction: while your sentiment is good (to reduce another person's anxiety), it's not always possible for someone to follow that when it is received as an instruction.

this is a pet peeve of mine. something i picked up when i was a counselor at a special needs camp was the idea that everyone (regardless of where you lie on any spectrum) has a unique sensitivity to criticism. it's important to NOT treat people how you would like to receive criticism, but to assess how you think they would best consume and digest it. obviously, this is extremely difficult on the internet and i'm just nitpicking but i had an altercation with my sibling earlier when they told me to 'calm down' so i'm still on edge about it.

i'm sure OP doesn't need to hear this but typically i find that a good alternative is to nudge someone into rationality. not to say that the parent comment is irrational, but when you simply show someone why they may be overreacting, they may very well 'calm down' all by themselves. if said person refuses to acknowledge your rationale, it's likely they aren't welcome to any criticism at all and won't be 'calming down' in any capacity.

There is one more condition you may be interested in: CFS/ME. It manifests itself primarily as a chronic fatigue and is believed to onset after a trigger event: virus, intoxication, hypoxia, stress, and the like.

I talked to some people with MS and most of them told me the same story: the trigger event, followed by some time, then onset of a full-blown MS.

I wonder: are those diseases really different? Or maybe this is the very same disease but with a bit different outcomes: myalgic encephalopathy vs sclerous plaques. Both are driven by the inflammation, both have the same initiating sequence.

What leads me to strongly suspect that it may be just different manifestations of the same disease is the involvement of mitochondria in both MS and CFS/ME.

I have this pet theory that CFS/ME is what a lot of long-covid patients are suffering. I knew a few people who have been affected by it, and it really limits them. Just as long-covid seems to.

I came to the same conclusion as well. Moreover, I was somewhat successful in healing post-viral CFS/ME using the therapy targeted at mitochondria with large doses of B1 and B3 vitamins [1].

[1] https://news.ycombinator.com/item?id=29138006

Its worth noting that 80% of those the develop post viral conditions just recover, we don't know why. It is unlikely your intervention is the reason you recovered, the majority of people do even if they do nothing at all. We do know that those that rest and stay below their energy budget have a better chance but that is about it, nothing else has shown efficacy.

Intervention was only applied to people who did not recover by themselves. But almost all of them recovered after intervention which leads me to believe that we are onto something here.

> using the therapy targeted at mitochondria with large doses of B1 and B3 vitamins

commercially available under the brand names... "Red Bull" and "Monster"

Nope. They do not contain the key element - vitamin B1 which is also called thiamine. Instead, they do contain large doses of caffeine which is known to abruptly inhibit thiamine absorption in the body leading to mitochondrial ETC inhibition when a person has deficit.

Then comes sugar - those drinks contain too much of it causing the unneeded insulin spikes. Sugar free variants are even worse - they (esp. aspartame) cause the insulin spikes as well but lead to insulin resistance progression much faster [1]. By the way, Insulin resistance and hyperlipidemia are hallmark signs of mitochondrial dysfunction.

Yes, they do contain some 10-20 mg of B3 (nicotinamide) and that's it. Not enough for the treatment; other key elements are missing.

That's why people with CFS/ME condition do not feel better after energy drinks, usually they feel even worse.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014832/

Super interesting thank you!

They already have B3 B6 B12 (my mistake about M1)

So the energy drinks should contain B1 or be taken with B1, is that what you say? If they don't already have B1, why is it so given the other vitamin B? Could it be for a good reason?

About insulin resistance, Monster contains sucralose and acetasulfame. It's not clear if the effect reported with aspartame also happen with these. Still, a super interesting thing to check - one of the many reasons I love HN!

I guess they do not include B1 because caffeine blocks its absorption anyway. Which is bad.

It is better to have B1 in everything that involves energy instead of caffeine. But B1 will hardly be noticed by the general public while caffeine is addictive for many. Energy drink producers clearly maximize for profits and not for health.

Back in 1980s, there were proposals for a "chronic mononucleosis" or "chronic mononucleosis syndrome" as a diagnosis / standard disease. There were very comprehensive studies trying to investigate the patients who had chronic fatigue and other long lasting debilitating symptoms. After a good decade of studies, the research community found that this group of patients is very consistent (their complaints, symptoms, etiology), but failed to prove EBV as a cause (although the studies did not disprove it either) or at least come up with a clear serological diagnostic criteria. So, in 1990s they decided to define a generic Chronic Fatigue Syndrome (CFS) as a standardized disease. Other viruses and pathogens can cause CFS/ME and a broader definition would sometimes include even psychosomatic patients, so as a result CFS/ME has been quite discredited.

Diagnostic techniques evolved and research progressed. In the recent decade, new studies are very close to proving that EBV is indeed a likely cause of CFS/ME (well, one segment, as there are other causes too). Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912523/

And along with CFS/ME, also look up POTS, MCAS/MCAD, and EDS. My wife had a very bad bout of mono in late high school and 15 years later developed POTS, MCAS, and what the rheumatologist called "unspecified connective tissue disorder," which seems like a mild case of EDS. After 10-15 years of trying treatments, she's significantly worse off. :-/

There are tons of people (mostly women) out there with this set of conditions, and they're only starting to be taken seriously. It's a set of life-altering conditions and dealing with the medical system when you have it can be infuriating and exhausting. I hope you don't have any of these things.

My wife also has MCAS, POTS, and a connective tissue disorder that is not at the level of EDS. Was diagnosed about 4 years ago and is on treatments to suppress some immune responses, that has been helpful at taking the edge off some symptoms. It was like tumblers clicking into place when she saw a specialist and got the diagnosis, so many rather disparate, long-term symptoms all from the same cause.

POTS, MCAD-like (hyperlipidemia) and inflammatory conditions are triggered by CFS/ME as well.

I am really puzzled: are we dealing with the same thing but under different names?

For reference, NSAIDs combined with high-dose vitamin therapy help to resolve those conditions in people with CFS/ME.

In Bergen in Norway we had a big outbreak of Giardia parasite and a lot of people got CFS/ME after that. The Giardia was big because the parasites came into the drinking water from one of the water sources. I myself had this for of this for many years afterwards but one do not notice it since before you get rid of it. I was able to function normally but totally lacked energy, and everything was a chore. It was like the feeling the first time one drinks coffee and experience the way the fog clears up.

Conclusion. The study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection. Obstructive sleep apnoea/hypopnoea syndrome, depression and anxiety were important differential diagnoses, or possibly comorbidities, to post-infectious fatigue in this study.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598369/#:~:tex....

Also very impressed with google when searching for: giardia leads to CFS

One important thing to note is that EBV is extremely prevalent. Almost everyone gets it eventually and very few of those people develop MS.

But a lot of people don't really develop severe symptoms either, right?

When I had it, my doctor said that if I was a professional athlete, the standard outcome would be to just consider the current season lost and switch focus to getting well again in time for the next.

I was relatively useless for two weeks and then spent the next four months getting back to my normal energy levels. "Severe" is a question of definitions, I think. I wouldn't consider that kind of illness severe, but it certainly put a dent in things for a while. Properly inconvenient, I'd say. I think this degree is pretty common.

Some develop no noticeable symptoms and many develop mainly annoying ones for a few weeks to a few months. I had the misfortune to develop symptoms from infectious mononucleosis shortly after minor surgery. My GP and surgeon kept giving me antibiotics and sending me back to uni. Finally after several months of fatigue, nausea, and depressed appetite I wandered into campus health jaundiced with a 104º F fever and a temporarily enlarged liver. I ended up withdrawing from that semester and retroactively from the previous one. I was ordered into a month of bedrest and half a year of decreased physical activity while recovering. So I guess we could say there's a wide range of severity, partly depending on how soon it's addressed.

Many if not most folks dont' even realize they get it because they catch EBV as a child. In children, it generally causes no symptoms or symptoms so mild that they are dismissed as a normal childhood virus. You know, the sort you miss 2 days of school for and then go on. This is the reason most folks don't know they've had it.

When we get older - teens and adults -, we are more likely to have it develop into mono or other things that realistically make your life difficult for a while.

If you're EBV-positive, you're in good company... It infects something like 90% of the human population.

Makes me wonder how many virii are out there that haven't been identified by modern medicine because their spread vector is so low-impact that they never even trigger symptoms. A virus like that would become real indistinguishable from "behavior of the human body" in not very much time if its infectivity was high.

Great question. A related question: how many undiscovered viruses exist that are beneficial to the host?

There's the anelloviruses which are at least as prevalent and nobody really knows what they do.

> A virus like that would become real indistinguishable from "behavior of the human body" in not very much time if its infectivity was high.

My weird theory: how can we know then if aging (or its acceleration or the diseases usually linked to it) isn't the result of some infection that's super contagious and infects 100% of the people,

It's not weird, it's the same idea I had back in the 1970s, but at that time things like retroviruses weren't known or understood.

Now we know about endogenous retroviruses, and yes, they have infected everyone (going back millions of years) and yes, they do become more active in aging and are responsible for cancers and causing cellular senescence via DNA damage through retrotransposon activity.

You can inhibit them with some of the same anti-retrovirals that work on HIV. Or nutritionally what may work is: high doses of cyanidin plus NAD precursors to stimulate SIRT6, which normally prevents at least one of these endogenous retroviruses, LINE1, from being expressed.

Super interesting. Please tell me more, like what you are taking besides that.

I find it especially interesting how some multicellular macro organisms like jellyfish (one of the oldest ancestor of all non insect animals) have no aging, while humans and most other animals do.

Could it be that their immune system or simply their evolutionary path prevented them from being exposed to such endoviruses, that may simply be too omnipresent (or long integrated) in about every other species to be selected out? (They could also present an advantage at the population scale, by ensuring a quick turnover and therefore more genetic evolution simply by filtering out not just the unadvantageous gene but the older adults, thus offering more opportunities for the new generation to replace them faster)

This could be supported if jellyfish had less requirements for evolution, like a stable ecological niche - something I have no idea about!

Because it's very unlikely the same pathogen or disease would affect shrimp and humans in the exact same way.

If you're going to develop MS as an adult after getting EBV mononucleosis, it's likely that it will be soon (5-10 years) after you have the initial infection as an adult. There's only a long delay in children according to one study. [1] Every passing year the probability of getting MS should decay after that.

Female sex and EBV mononucleosis during adolescence are the biggest risk factors.

[1] https://nn.neurology.org/content/4/3/e308

Interesting. My sister and I both had mononucleosis before puberty, and she was diagnosed with MS in her late twenties.

Scores of folks with MS never had mono. I'm one of those. It isn't mono that is the risk factor, but EBV itself.

The article says EBV is prevalent and is probably necessary but not sufficient for MS. If I was in that position I would look at my gene test results for any markers that correlate with MS. The more of those markers, the more intensely I would prioritize following relevant interventions.

What are the relevant interventions? Which genes correlate with MS?

That's the independent study part. I wish I could be more help but that research is time and money intensive, and not guaranteed to be fruitful. It also involves review of multiple studies, sometimes several dozen. Then it's about seeing which ones are relevant to an individual's specific genetic mutations.

I'm currently going through dozens of reports from SelfDecode, and that's after massive amounts of work on their end. I think I'm out a few hundred bucks so far, but it is an amazing service. I will soon seek their genetic consultation service, which is about $1k, and their lab testing service.

Genuinely curious, what's your ultimate goal here? What do you optimize for? Total life-years, sum quality-of-life, etc.?

Seems like picking out the diseases you don't want to get/die from is a way to go nuts; curious how you're thinking about this.

I did accidentally traumatize myself by focusing on one marker that basically said "You have an increased risk for degenerative disease x". I had a full-blown psychosomatic attack, and I convinced myself that I was going to die in 5 years. After I calmed down I realized it was probably anxiety. I learned a little bit more about statistics in medicine and realized that my layman's understanding of chance is probably way different than what genetic markers point at (I have no idea what the actual numbers are, but maybe they consider 1 in a million an increased risk, for example).

My ultimate goal is to address some weird ADHD-style issues and an autoimmune disease, holistically. When I go to a stomach doctor he gives me stuff for my stomach, but never asks about how my brain feels, about fatigue, about my skin, etc. I don't blame doctors for specialization.

I've given up on expecting them to be able to "fix my car". That would be silly to ask of an actual mechanic. What I'm doing instead is studying, tweaking and fixing what I can through lifestyle and careful supplementation. Basically, I'm starting with filling the tires with air, changing the oil, etc. Then once I realize my car is still violently wobbling, I'll have a list of what I've fixed myself, and the mechanic can focus on more complex wobble factors.

Thanks for the response, that seems like a healthy way to look at it. I’ve avoided touching any of self-genetics, for fear of finding out I’m going to die of something terrible, thanks for the point about medical stats being nuanced .

EBV causes more severe symptoms the older you are. So everyone here who remembers getting it and it being terrible? That's because you got it as an adult. If you get it as a kid, it can be asymptomatic.

I got it at 36 and had a fever that leveled me for 3 weeks. Between "wait 1 week before bothering your doctor" and multiple rounds of tests, they didn't even diagnose it as EBV until the 3rd week.

I got at 21 IIRC and I was in bed for a few weeks and the doctor started fearing I had a blood cancer or something given how abnormal the tests were until he finally got the idea to test for EBV and it came back super positive.

Never before was I so happy to get tested positive for something lol

It's been a few years and I think I'm fine but due to hedonic adaptation etc maybe for all I know I operate at like 70% of my previous capacity and don't even realize it

So I'm super interested in all that new research and I can't wait until we get mRNA vaccines against EBV!!

How do you even test for EBV? The GP I asked laughed it off when I was living in Canada basically saying I am already positive and no need to test.

This was a study conducted by the military on soldiers. They all contributed three blood samples over a period of time that were tested for a large number of conditions. EBV was the only one that contributed to MS.

You can test for pretty much anything in a research setting.

In a clinical setting, doctors will rely a lot on heuristics and practical considerations, and there may not be any clinical testing available.

Even if there is a test, sometimes it is insanely expensive and so they won't give it if they can find any other way to decide.

There are at least two tests for it, or at least there were in the mid 1990s. One's a quick clinical test with lots of false negatives than can be done in-office but unless it's a campus healthcare clinic at a university they probably don't bother. The other is a more sensitive lab test that takes a few days. If you're having a really serious set of symptoms they may test to confirm it's not something else. If it's a minor case, two weeks of bedrest fix a lot of issues in a young adult and you do probably already have it anyway.

If you want to test whether you already had EBV, then it would be a test for Immunoglobulin G (IgG) antibodies to the EBV viral capsid antigen (VCA). It shows whether the virus has established the latency in your body. Most laboratories would just label it as "EBV IgG", so just ask for that.

If you are in your 30 or older, then you most likely have had it already.

thanks for sharing.

does this test for EBV in both latent and lytic phases?

EBV seems very adept at evading the immune system. does this also impact our ability to perform accurate detection (i.e., could current methods yield false negatives)?

They have like 2 separate tests: one for old EBV (IGG) and one for new EBV (IGM or maybe it's the other way around?)

IDK about false positive though

EBV VCA IgG antibodies remain present for the rest of your life, as your immune system maintains certain antibody levels to keep the virus in check (it's a delicate host-virus balance).

EBV VCA IgM indicates a primary EBV infection and these antibodies remain for a few months, until seroconversion happens. They might not necessarily be present immediately. During the primary infection, the virus is in active lytic replication which can accurately be shown by an EBV PCR test.

Once the virus establishes latency, EBV PCR will be negative. It may occasionally become positive when EBV reactivates, but it may also reactivate in other compartments i.e. it infects more than just B-cells and the standard PCR test wouldn't show that. There are more antibodies involved and the whole thing is more complex than just the lytic and latent cycles.. the immune system is very complex.

thanks! this answers many questions already. a few more if you don't mind:

1. if VCA IgG antibodies persist for life, how does EBV reactivate?

2. when you say, "may also reactivate in other compartments," this implies that standard PCR tests only verify infection in b-cells? what tests verify infection/activity in epithelial cells?

3. are you on social media? would love to follow you.

4. does VCA IgG detect EBNA2?

Wow, I was also EBV positive ~4 years ago (45 months), was symptomatic and I had post viral fatigue for around a year. It was 12 months before I could do light physical training and it was around 2.5 years before I could train physically at high intensity.

Do you have a baseline to compare or are you only relying on your memory?

I got it at 21 and now I fear I may operate at a lower overall potential since I don't have a baseline to compare to

Possibly a co-factor, since many get EBV and few MS.

Found this in my news feed, so this timely. Good news I guess!

https://www.forbes.com/sites/roberthart/2022/01/14/moderna-s...

Is there any evidence that the vaccine wouldn't also cause MS? From my understanding, MS is caused by the immune response, and the vaccine would trigger a similar (or same?) immune response.

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