Fluoroquinolone antibiotics like cipro, levaquin, (and generally anything ending in -ofloxacin), can cause permanent nerve damage and one of the presentations is demyelination of the nerves. [1][2][3]
Permanent nerve damage (neuropathy, pins and needles, tingling, muscle weakness, spasms, muscle twitches, heart palpitations) is a known side effect. There's been no attempt made to study if there's any long term delayed brain effects from fluoroquinolones. "Brain fog" is a commonly reported symptom of those who experience fluoroquinolone side effects. I hope there will be more studies on long term brain health from these drugs, as they're given out liberally.
I can attest. This happened to my wife 15+ years ago. The reaction began after two doses of Levaquin and was 3 months of non-stop living hell. Seriously painful neuropathy, burning all over her body. Profuse sweating all night. Brutal nightmares. Brain fog. Crippling pain in her appendages, melting walls. Extremely distressing.
The doctors were completely dismissive of and uninterested in the symptoms -- it really shook my faith in medical practice. We were on an oddessey to determine what was wrong and could be done to help. It took her 6 months to resume walking more than a short distance. She still has foot and hand problems from permanent neuropathy that affect her daily.
A few years after, Levaquin was black-labelled, and I believe no longer the first line of defense for children at least. The whole thing still burns me.
I suspect this sort of information is no longer rare but if anyone is having this experience then a GABA agonist like benzodiazepine may help you, but be extremely careful as they are quickly dependence forming and must be weened. Small dose.
> The doctors were completely dismissive of and uninterested in the symptoms
I had exactly the same issue! GPs ran a few tests and couldn't figure it out. They labelled is as fibromyalgia, even though I didn't fit the criteria. I pushed to see a neurologist, who ran a few tests and couldn't figure it out - he also labelled it as fibromyalgia, even though when I questioned it he admitted he knew almost nothing about it!
There was a lot of back and forth, with GPs and neurologists being really dismissive. I forget how long this went on for, but a couple of years at least.
So I did my own research over a long period of time. I found only a handful of other cases, but with the symptoms I came to the conclusion that I must have small fibre neuropathy. I pushed the neurologist, who grudgingly did a nerve biopsy, which confirmed small fiber neuropathy. He stopped being dismissive after that.
For pain, I ended up with a similar situation. I tried gabapentin, pregbalin and all the usual things like topical capsicain, TCAs, SNRIs, diazepam, opioids etc. They either didn't help, couldn't be tolerated, or caused more problems. Within the public healthcare systems, the list was eventually exhausted, and they weren't interested in trying anything else. They didn't believe how bad the pain was, and were unwilling in any case to go beyond their list of standard treatments. In the end, I paid to see a private pain specialist, and eventually found ketamine to be really helpful - not just with the pain, but my mental ability to live with it.
I'm unsure of the antibiotics they give post LASIK if they ever do, I'm curious as there is a severe symptom some people get after LASIK called corneal neuralgia that can have similar system wide symptoms to small fiber neuropathy.
Was the cause of this an antibiotic? Could there have been any other cause? Did you have any surgeries or injuries around the same time the symptoms started? Did you ever have LASIK eye surgery?
Thought I replied to this, odd. I don't know what antibiotics they may give after surgery. The reason I asked is some people develop severe corneal neuralgia that has/causes whole body symptoms - central sensitization, hyperalgesia - which sounds somewhat similar to small fibre neuropathy.
> The doctors were completely dismissive of and uninterested in the symptoms -- it really shook my faith in medical practice.
I had a similar experience as a child, where a textbook case of a reasonably common disease went undiagnosed for 2 years by doctors before a toll booth worker at an airport diagnosed me. She recognized the symptoms because her dog had it. Sure enough, after my mother brow-beat a doctor into running the absurdly simple blood test she was proven right.
On the one hand, I want to chalk this up to them being like everyone else: 90% of them are just shit at their jobs. On the other hand, I have it on good authority from nearly every nurse I've ever met that doctors are indeed arrogant, dismissive, and often mistaken.
> On the one hand, I want to chalk this up to them being like everyone else: 90% of them are just shit at their jobs. On the other hand, I have it on good authority from nearly every nurse I've ever met that doctors are indeed arrogant, dismissive, and often mistaken.
I think there's an extra layer. Any public facing jobs tend to take a toll on you, too. Some more than others. With doctors patients lie to you constantly, for a variety of reasons. Some drug seeking, some simply not wanting to admit it.
Yea, i imagine they're like everyone else (shit), but i also imagine it is very easy become very dismissive in that line of work.
It's a fine line to know what to filter and what to ignore, i imagine.
I think the issue is more that the healthcare industry makes doctors gatekeepers to healthcare, which can breed tremendous amount of resentment between doctors and patients. A doctor is pressured/forced to provide service to patients, and patients are not legally allowed to seek healthcare from other types of professionals, like biochemists for example, which often have a much better understanding of some diseases than doctors.
When there is so much coercion and lack of consent, people get very frustrated.
>brow-beat a doctor into running the absurdly simple blood test
I feel like I see this story all the time: "a simple test found the issue that they denied I had".
What we should be examining are the incentives for the doctor to resist running tests. Are they too invasive? Some can be, but blood tests certainly aren't. Are they too expensive? Ah, there's the ticket. The doctors are either losing money on tests that find nothing, or they are getting berated by the managers for wasting money on tests that find nothing, or the insurance company is saying no when they ask to run tests.
We have the technology to have proactive medicine. We could be catching cancers in early stages all the time with some standard sets of annual tests. But the economic incentives are all out of whack, and we're waiting until the last minute to do these tests.
Many tests are simply not that good. It's not that simple, like pay $1 for a test that with absolute certainty tells you if you have disease X or not. It would be good if that was the case because then it WOULD have been just a question of money.
But if you have a test that is wrong 20% of the time, and you take this on all your patients every year, you will end up with a huge amount of mental suffering or possibly physical side-effects (unnecessary biopsies, or even surgery). You might end up giving people long runs of unnecessary meds. OTOH, you might end up missing some diagnoses if you don't do some tests. Balancing all of this is difficult.
Of course this is not news to the medical profession, this is a big input to the standard flowcharts. And you can always find anecdotal edge-cases that think their particular case was crystal clear and should have immediately been diagnosed. But don't assume that medical diagnosis and treatment is as trivial as doing a blood test and some googling.
> Many tests are simply not that good. It's not that simple, like pay $1 for a test that with absolute certainty tells you if you have disease X or not.
I will note that in my case the test is routine and reliable and has been since before I was born.
Sure you can't take every test at face value. How you approach the results of something that isn't 100% accurate is important. A potential false positive should mean a follow-up test, not a full diagnosis. Or even just holding onto the information until it can be part of a bigger picture with presenting symptoms. You don't even need to tell the patient what the results MIGHT point to, so you don't encourage hypochondria.
> We have the technology to have proactive medicine. We could be catching cancers in early stages all the time with some standard sets of annual tests.
I often wonder why such an expensive device as an MRI machine isn't utilized 24/7. I'd gladly go in for a scan at 3am if it meant paying even as little as 20% less.
The really strange thing about tests is even if you pay out of pocket you still have to get a doctor to sign off on it, which dramatically increases the friction and price for testing.
It's just information about your body. You shouldn't need a doctor's approval for that.
The consequences of being wrong in the comments section is significantly less, imho. Plus, doctors are paid a lot for their expertise. It's really not about craving certainty. It's a question of a system that disincentivizes thinking through a problem that doesn't slot well into the diagnostic framework taught in medical schools to students selected for their ability to think inside the box, with little requirement, or really, possibility, to be very deep in biochemistry, pharmacology, research science, or a host of other inputs. Oh, and they're often very arrogant.
Doctors do save many lives but I fully agree a whole lot of them are indeed terrible at edge cases and what's worse is the arrogance they display when one tries to explain the symptoms clearly. Some of them go as far as recommending a psychiatrist when it is really not called for (sure, there are instances of hypochondriacs but how about the rest who aren't? ).
in my own experience (with my wife's chronic condition), most doctors are extremely dismissive if they don't have the answer off-hand. I don't know why this is - but reactions ranged from saying she was lying or was addicted to painkillers (despite not asking for painkillers) to switching back and forth between two common diagnoses even though they were quite clearly inaccurate. I have no faith in the front-line medical system to be able to deal with anything less blatant than a broken bone or a flu, if only due to what appears to be doctors' near-universal refusal to respond to uncertainty with humility and curiosity.
After many similar experiences with doctors, I have reluctantly come to the conclusion that about 80% are only interested in time preservation and ego preservation.
If they don't know the answer in 5 minutes, then obviously you must be crazy. 2 minutes, if you're a woman.
They are allergic to 3 little words: "I don't know."
This is too accurate. Our medical system treats women as a minority or nonstandard patient. This is crazy when women are actually a slight majority over men. Usually around 51% of the population.
There was a book, Bitter Pills, by a journalist who's wife had years long neurological side effects from a flouroquinolone, iirc. It's an investigation into the world of drug testing, prescribing, and side effects. https://www.amazon.com/Bitter-Pills-Inside-Hazardous-World/d...
I'm sorry to hear about what happened to your significant other.
I developed permanent neuropathy and muscle problems in my lower legs after a course of Levaquin for a respiratory infection. Constant fasciculations, cramping, and pain.
It sounds like you've done your research on potential treatments, however in case you're unaware, I've found considerable relief by soaking my lower legs daily in an Epsom salt bath. I can attest to the fact that magnesium sulfate is without question topically permeable. It may be something for your wife to consider, to see if it helps her.
Frankly, at this point it's pretty clear that the entire healthcare system in the US is parasitical: doctors, hospitals, insurance companies and pharma companies. Their purpose is to extract value, not restore health.
I have a very low opinion of doctors, who are by and large arrogant and of middling intelligence, a dangerous combination when a person's health is at stake.
>The doctors were completely dismissive of and uninterested in the symptoms -- it really shook my faith in medical practice.
This and similar comments here, and my own experience make me realize how elitism can be dangerous. We blame social media and propaganda for mistrust jn science (and rightfully we should criticize those) but part of the mistrust is a problem of medicine's own making. What happened to self-doubt?
I was prescribed Cipro for a urinary tract infection and the doctor didn't once mention anything about dangers or side effects for the drug, just said he's 'prescribing an antibiotic'.
After the very first pill I was feeling pins and needles in my extremities later that day. I stuck with it for a few more days, each pill feeling even more pins and needles, more intensely and in more places on my body. Once I started feeling it in my face, I called the doctor and they got me on a different antibiotic.
Then I started reading horror stories about the drug and it made sense. I also didn't exercise for a year afterwards out of fear that my achilles tendon would snap, one of the biggest warnings that was on the box and one of the things many of the online horror stories said happened to them.
The neuropathy (pins and needles) lasted for six months before it started going away, and it comes and goes periodically, years later (it's mostly gone now, thankfully). I've had other health issues since that are known possible health issues from Cipro (it's so invasive and effects so many systems of your body). One of the more annoying ones lately is the onset of Tinnitus, which Cipro is known to cause. Maybe it's just a coincidence, but I'll never know for sure since most doctors still don't treat Cipro toxicity seriously or know how to test for it.
I don't think it caused brain fog, but who's to say? I don't feel as mentally acute since then, but I'm also older.
Not really looking forward to any future health problems it may lead to, and I only ever took like 5 pills of the damn thing (it was over 7 years ago now).
I'm so pissed off I wasn't even warned about this, and that it was so casually prescribed without warning. I've taken other antibiotics before and only had to worry about my gut biome getting screwed up, so I wasn't expecting to have such a terrible reaction to the meds.
I have a similar story, with an antibiotic that is also an immunosuppressant (I was taking it for that effect). After taking it for just 2 weeks, I had terrible pain in my arms and legs. My doctor suggested I keep taking it for a couple of weeks more, to see if it went away. It got worse, and I stopped it a week or so later. I understand this is a very rare side effect, so rare I don't think it was even mentioned in the leaflet - I'm just incredibly unlucky to have such a reaction.
I was left with small fiber neuropathy (nerve damage) in my arms and legs, and with CFS (Chronic Fatigue Syndrome) too. This means I'm in constant, unending pain (which takes a huge mental toll), that I'm tired all the time, and if I do any more than the gentlest of exercise, I fall asleep and am more tired and in even more pain for days or even weeks afterwards. It's fucking horrible.
This was about 6 years ago, and I'm pretty sure it's permanent. I haven't quite given up hope though - I have several Google Scholar alerts setup, and read several papers every week, in the hope of finding something that might reverse things even a bit.
What type of immunosuppressant were you prescribed? I recently took prednisone for a little over a week and ended up with some nerve issues afterwards, but not as bad as typical small-fiber neuropathy. The symptoms still haven't resolved.
I don't want to mention it's common name specifically, as this is rare enough that it could be linked to me personally.
It is actually an antibiotic (I'd somehow forgotten that - edited my original comment now!), but once that acts as a immunosuppressant, and it's less-common name is diaminodiphenyl sulfone.
I have CFS too, although from a different trigger. FWIW, I found the doctors at the Center for Complex Diseases to be amazing. They're 10x doctors, true scholars of the human body. They specialize in CFS.
I had very horrible side effects from Levaquin for an asymptomatic infection I was diagnosed with. They gave me 12 hour doses, which I took twice .. I had fever, nausea, severe joint pain, and a lot more.
Later, both in the US and the UK, future doctors, when describing this to them, said I was misinformed, that probably I was sick, these are not side effects.
No, they're misinformed, and I'm deeply suspicious of the medical profession.
I was prescribed cipro after a rectal surgery (chronic anal fissure and hemorrhoids) in Feb 2020. By that time, I wasn't aware that cipro was actually a poison. Fortunately, I haven't experienced any such side effects so far, except occasional palpitations (likely due to loneliness, my increased anxiety because of the pandemic and staying indoors all the time).
I have something wrong with my HPA axis resulting in Cushing's syndrome that causes extreme anxiety, high hr & bp persistently. It's usually an adenoma or hypertrophy on a pituitary or adrenal, or metabolic syndrome.
The difference here is that you're not a bacteria and can safely metabolize the drug itself.
Chocolate is poison to dogs. Not to humans.
One course of an antibiotic isn't going to rot your brain or nerves... and even then, chronic use isn't a problem but for a small percentage of people who do experience these adverse reactions.
"The difference here is that you're not a bacteria and can safely metabolize the drug itself."
All eurkaryotic cells have little trapped bacteria inside themm -- your mitochondria. The mutualistic cooperation between the mitochondria and the surrounding cell is an ancient and delecate dance.
And lo and behold, mitochondrial toxicity from antibiotics is a thing, and fluoroquinolones are suspected to cause it.
Don't be so flippant. The standard warning for cipro includes: "Taking ciprofloxacin may affect your brain or nervous system and cause serious side effects. This can occur after the first dose of ciprofloxacin."
The parent is not being flippant - don't be so dismissive. The dose makes the poison. All medications have long lists of side-effects. Most will have a small minority of users who have severe side-effects. We don't go around calling them all poisons.
How do you know what% users have side effects or what doseage that occurs at or what causes this reaction in the subpopulation? You don't and just wave that off, that's why it's flippant.
Look, I don't know anything about this medication. But the grandparent responded to a pure anecdote, including the claim that it is "a poison". It seems an entirely appropriate response to caution against false taxonicity in this context. I don't see why the thread is so full of downvoting and accusations.
If someone wants to claim an approved medication is especially poisonous, the onus should be on them to provide evidence. Note that the great-great-grandparents 3 links are all individual case studies. One of them summarizes the situation: "overall, the frequency and severity of adverse events are rather low".
That's fair enough. I would personally not risk nerve damage even if "frequency and severity are rather low" (1.5% reported in pubmed) unless necessary because the mechanism of action is still there and I don't have any information about why that happens sometimes. It would be great if our medication review could extend past trials and allow people to independently analyze the data in population studies so some causation could be investigated in those rare events when things go wrong.
Bear in mind, with a lot of different types of medications, they're required to report severe reactions found during trials and use... even if those reactions were very specific to that individual (genetic predisposition, for example)... Eg, Stevens Johnson Syndrome (a really severe skin reaction) which has no real general consistency on who reacts to what class or type of drugs.
If one person experiences it in a trial of a group of, say, 60... That becomes a risk of 1.6% in the side effects profile.
Real world cases would be much, much, much lower to the point to where doctors in the ER wouldn't even know what they're looking at when it happens. Sometimes it gets diagnosed as a 'drug eruption' or an allergy, when it's more an immune hypersensitivity response.
I know anecdotal isn't what people want around here, but I had a reaction to Sulfa that was later diagnosed as Stevens Johnson Syndrome. The doctor who prescribed it to me never personally saw a case of it herself until I came along. Even then, she sent me to a dermatologist first.
> SJS is a rare condition, with a reported incidence of around 2.6[10] to 6.1[26] cases per million people per year. In the United States, about 300 new diagnoses are made each year. The condition is more common in adults than in children.
Up to 6 cases per million per year across ALL drugs and not just the one I mentioned here.
Even common over the counter medications like Ibuprofen is known to cause SJS. The odds, however, are vanishingly small.
The risk exists, yes, but the perspective needed is that when you see percentages reported... that's not a "1.5% chance", that is "1.5% of those in a particular group experienced this side effect while 98.5% did not."
I was on prednisolone for a couple of months a few years ago. I can't say I was very intelligent before that, but it's certainly took a toll on my memory and cognitive abilities. (No, it's probably not hypochondria, I didn't even know corticosteroids could have such consequences when I noticed the problem.)
> The medications included prednisone, and methylprednisolone, plus albuterol, beclomethasone, dexamethasone, cromolyn, salmeterol and clarithromycin.
> The treatment with steroids was stopped and three years later (while still taking buspirone, albuterol, fluticasone and salmeterol inhalers, loratadine and theophylline)
Yeah, this was more than just one steroid doing something to him. When you have a situation where someone is on that many different medications, it's no longer a case where you can simply point to one thing and say "that caused it." There's no telling what other underlying conditions were exacerbated in the process and what side effects may be due to the drugs NOT discontinued.
Long term use of steroids is known to cause all kinds of nasty side effects. Prednisone I've actually found rather useful for bootstrapping myself out of depression but it tends to induce mania. Going for longer than a few days results in a huge high followed by a massive crash.
The above sounds like nuclear option amounts of asthma meds and it's reasonable to expect potential long term effects.
That being said, inhaled steroids are considered much, much safer than oral ones, due to much smaller doses and targeted effects.
Those are two cases of one person each, with different specific symptoms. It's important to note that both of the people mentioned developed such negative effects quickly or immediately, which means that the other 99.99% of people do not react the same. Also, the first person got a bunch of active ingredients, of which steroids is just one. So I would temper my warning.
Have you thoroughly researched fluoroquinolones? Millions of people like myself have experienced tendon or nerve damage from one course. And besides the known cases, it often goes unreported because people don't realize their sore ankle might have anything to do with the pill they've been prescribed for a cough.
On the day of the 9th dose of 10, I found that I was limping on my right foot. I've never had tendon issues but it was clearly the tendon that was weakened and sore. I also found my hand grip was weak and it was painful to even wring out a wet face cloth. Luckily my Achilles tendon didn't rupture as sometimes happens with this complication. But limping everywhere isn't fun, and even just climbing or descending a staircase became a difficult chore.
The issues lasted about 6 months, during which time I took a few daily supplements recommended in the research I found. I seem to have fully recovered but I've read about others not so fortunate.
Actually most of us are bacteria on a cell count basis. This is an observation worth taking into account when taking antibiotics. However that does not mean we shouldn't take them.
Confident asides as in '(we) can safely metabolize the drug itself' are unhelpful and indeed wrong for certain people.
"Macrolide antibiotics caused an additional 36 sudden cardiac deaths per million treatment courses. So about 1:8,500 patients will develop a serious arrhythmia, or irregular heartbeat, and 1:30,000 would die because of the antibiotics."
I recently got ear drops for a somewhat mild issue I had. The issue didn't go away, but after your comment I remember occasional "pins and needles" in my leg - just looked it up and those drops contain Ciprofloxacin!
Though it seems a bit unusual that drops in one of my ears would first cause symptoms in a leg. OTOH, that would be a curious coincidence... Luckily the pins and needles were only mild and transient, so if there was a causation I hope it was only temporary.
> Compared to a potent eukaryotic DNA topoisomerase type II poison ... ciprofloxacin produced comparable dose-dependent SCE frequency increases.
Translated: Compared to a chemotherapy drug designed to cause DNA breaks to prevent cell replication, ciprofloxacin produced similar "sister chromatid exchange" counts, which happen when damaged DNA strands need to pull in duplicate material from "sister" strands.
Counting SCEs is also used to measure human DNA mutations from things like carcinogens and radiation.
A sibling comment (https://news.ycombinator.com/item?id=26473638) mentions the difficulty of acquiring pre-event context for these kinds of situations. Could this sort of testing be useful here?
The side effects aren't well known / understood. They also happen to less than 1% of people who take the drugs (at least that's the current estimate, some side effects may not be properly linked to the drugs). There's very little research on how to measure the damage done by fluoroquinolones. Once a patient says they have tingling, the drugs have already caused permanent damage, and a doctor isn't going to know what to measure to assess this damage, nor what they should have been measuring to prevent the side effect in the first place. This lack of understanding may lead to an inflated sense of safety profile.
They're used to treat antibiotic resistant infections in "hard to reach" places, since the fluorine moiety allows them to penetrate most places in the body (which is also likely related to how they cause insidious damage). This power+reach makes them a default drug for some doctors to treat infections.
We shouldn't. You probably don't want to take a quinolone antibiotic unless all other options have failed and your life is at risk. There are decades of reports of permanent, severe nerve damage after as little as a single dose. At one point the FDA even had to step in to force some unusually severe language in warning labels.
But doctors can be a stubborn bunch, and many still prescribe it way too liberally.
Knowing doctors, this comes down more to Hanlon's razor.
Many don't know any better and have a poor grasp of the scientific method. For many being a doctor is more of a trade than a profession.
Their scope of work is too broad and they're far too busy to keep up. As a result, they're perhaps even more susceptible to marketing than average people. They don't have time to dig into pubmed and deeply understand something they see (generously) 1% of the time.
They have to rely on people who otherwise get paid to do the research. If there's no money to be made from a treatment, it won't be able to donate to universities, fund studies, or pay for advertising.
In my experience as a pharmacist, it wasn't first line, but sometimes it's second line. For UTI, respiratory tract infections, and skin and soft tissue infections. Pretty common actually.
It was the first thing prescribed to me, but I was only told "it's an antibiotic" and I had no bad issues with other antibiotics so didn't expect that I needed to be careful.
I probably took at least four more pills than I should have, even though I had a bad reaction after the first pill, I assumed it was something else that was causing it at first.
Glad I eventually made the connection, read some horror stories to confirm the likely cause, and called the doctor to switch my antibiotic before I had taken all 30 pills. Might be a lot worse off now if I had.
Because the benefits of antibiotics vastly outweigh the risks. You're better off taking antibiotics than getting a serious infection.
They should be used rationally though. Ciprofloxacin and other antibiotics in the same class are stronger medications compared to penicilins for example. The ideal situation is to figure out what the bacteria is sensitive to with a culture and antibiogram and then choose the weakest, most specific antibiotic out of that list. Of course, this requires time and resources which may not be available. In some cases, it's been proven that waiting for test results leads to worse patient outcomes so doctors will prescribe antibiotics empirically and adjust treatment later.
> Because the benefits of antibiotics vastly outweigh the risks. You're better off taking antibiotics than getting a serious infection.
But isn't antibiotics something that gets given out in many countries for more or less anything? The US comes to mind. Which to my knowledge is the reason why more and more people in those countries dies of resistent bacterias.
I'm 35 and have been given antibiotics twice in my life, and reading about people getting antibiotics for a cold baffles me.
> But isn't antibiotics something that gets given out in many countries for more or less anything? The US comes to mind.
Yes. Antibiotics have a rich history that dates all the way back to the second world war. Before the risk of bacterial resistance became well-known, use of antibiotics was much more widespread. Understanding of bacterial resistance came after they developed mechanisms to resist the drugs used to treat infections such as betalactamase.
It could be the case that cipro- and levofloxacin are widely prescribed in the USA because bacteria have already become resistant to weaker drugs. Treatment guidelines in my country have more effective options compared to CDC sources. I have no first-hand experience though.
Stronger antibiotics also happen to be very easy to use. It's generally much easier to successfully treat someone with a strong antibiotic than a weaker one. One pill once a day for three days is much easier than 3 or 4 pills at regular intervals every day for 10 days. Getting people to take pills correctly is an every day challenge in medicine, complicated treatments means people will often forget to take their pills and reduce their effectiveness.
At least in India, they are often given as first line treatments sometimes even when there is no infection prior to surgery to prevent infections later.
Another reason is that an entire course of Cipro is like five days. It was pretty much the only antibiotic my university health center prescribed while I was there and I knew many people who took it (early 2000s, USA) because getting university students to stick with a longer regimen was very difficult.
There is often no "perfect" ligand because benefits somewhere cause harm somewhere else since evolution reused so many substrates, or the means of regulation similarly ups or down regulates anti-target activities.
Furthermore, compounds that will work are often constrained by many factors.
For those interested, there is lots of discussion of fluoroquinolones on this site. Make sure you're searching for the term in the comments, otherwise you won't get any hits.
I had my own bad experience with them, and know others who did as well.
Whoa. I "only" got very severe painful diarrhea twice from cipro (likely clostridia - https://en.wikipedia.org/wiki/Ciprofloxacin#Other). Since that I always preemptively say to doctor I reject it.
I believe retinal damage (a higher likelihood of spontaneous tears) has been reported too. I was given Cipro as a child for diarrhea in a foreign country and recently suffered tears in both retinas. I have to wonder if that wasn't a contributing factor.
Well that puts you in a high risk group. Any temporarily high increase in IOP can trigger a tear easily, e.g. an accidental poke. Giving birth is risky with such high myopias. Aging of course... once in 50s I'd do annual checkups on the posterior of the eye if I was a high myope.
And drugs for sure didn't affect the shape of your eyeball.
I'm not saying antibiotics don't do any damage, I'm just saying that in such a case those would be at the back of the blame list...
Let's not forget to add aortic dissection risk to this. In the experimental setup, all it took was exposure to Cipro and elevated blood pressure in the lab animals.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233654/
Does gabapentin do something similar? I've seen this prescribed more and more for pain relief, and it seems to have some serious side effects. My wife refuses to take it after taking it for just afew days.
This study shows that myelination increase with a combination of 'healthy fats' and exercise:
"High-fat diet in combination with exercise training increases myelin protein expression. PLP and MBP levels were highest in the group that exercised and consumed a high-fat diet. Exercise training or high fat consumption alone also increased PLP. MBP levels in the ERD and the SHF groups were not significantly different." [0]
Under this lockdown for a year, I've been eating a really un-diverse diet, cooking for myself every day basically, not much variation after I figured out the pattern of groceries, meals, things I generally feel like eating and taking the time to prepare.
Sometimes I wonder if I'm being gradually deprived of some nutrient I don't know about when I at least had 1 meal that came from outside and varied somewhat day to day...
How diverse does a diet have to be exactly? Most humans lived with a rather limited set of food choices until the industrial age. We didn't evolve to eat hundreds of different food items, and sometimes I wonder the opposite - perhaps we eat too many different things which might introduce some outliers that damage our systems.
Not sure about variety effect, but overall they had much healthier diet from certain perspective (fruits + vegetables + lean muscles/whatever part of animal). No processed sugars, preservatives and other slow-poison crap. I don't think the diet was complete and for sure some vitamins/nutrients were often missing (ie in winter).
Combine it with much higher activity and they would look like superman with regard to fitness to average human these days. At least those who survived those harsh conditions, infancy and various easy-to-cure-now ails like tooth infection or appendicitis.
Not all preservatives deserve to be called poisons. BHT is a preservative because it's an antioxidant. It's available as a dietary supplement for that reason. Alpha-tocopherol is a preservative additive but is often used to fortify foods with additional vitamin E. Salt, vinegar, and ascorbic acid are all also preservatives.
I doubt that this is true. In the era of colletion and hunting, the diversity of food is based on the near-by ecosystem, which is larger than modern supermarket.
There is no way that's true. No matter how far a person wandered they're not going to come across a bell pepper, lettuce, carrots, potatoes and any meat they could want.
You're perspective is skewed. Your knowledge only includes the local plants that we have created into our international rummaging choices. Bell Peppers are just one modern variety out from the ~30 species of chilies we've discovered. Same for carrots and potatoes and lettuce. I look at the variety of edible vegetation I can get at the grocery store and the only thing I really think of is it's a good day that I don't have to walk 20 miles to the fruit trees to pick the fruit before all the animals do.
Meat? tons of variety, there are like twenty different cat to dog sized animal species in my Montana wilderness before I even have to get to the large herbivores that have less variety. And meat is special anyways, the mink or weasel you can kill is chock-full of 2-5 years worth of collecting resources from various animal and vegetable sources.
Pine needles "contain more Vitamin C than an orange" (I didn't see it specified if that's by gross weight or dry mass) and make decent tea, and many cultures still boil and eat or cook with pine cones.
Modern crops are amazing, but we are literally surrounded by new and forgotten sustenance. It's not always pretty, tasty, or toothsome, but it's there if you have the time and will to turn it into food.
I'm also reminded of villages that "modernized" by trading their old fashioned cast iron cookware in for aluminum and began to suffer from anemia as a result. Iron is abundant in the crust, and eating mineral-rich clay is still practiced by humans and animals around the planet, but their solution was to put cast iron charms in the new pots for luck. It's possible they were in iron-poor areas, but if they were swayed to abandon their traditions by the appeal of commercial marketing, it seems likely they mught also eschew any dirt-eating practices they once might have had.
Highly sceptical of this if we're talking about the non-animal part of the diet.
Hadza ate only 4 non-animal foods, which is much less than what's available at a supermarket.
Hunter gatherers would've had a more diverse diet when it came to meats, eating the entire animal including most organs, but that's more cultural than what's specifically available at the supermarket (it's pretty easy to get organ meat at the supermarket and especially the butcher, but most people don't opt-in).
Right, but worth noting that raw beef, for example, contains a lot more nutrients than cooked beef[1], and includes most of the essential vitamins you would need to live.
Other parts of the animal, like the liver, would provide sources for A and B12, etc.
> Because of its content in highly valuable
> nutrients such as iron, zinc, selenium, fatty
> acids, and vitamins, meat is a unique and
> necessary food for the human diet in order
> to secure a long and healthy life, without
> nutritional deficiencies.[2]
That's a bit of a myth. Life expectancy was vastly less than it is now, but that is because of infant mortality, death in childbirth, lack of emergency medicine, etc. Those that survived all that lived about the same as today, about 70-80 years:
This clinic has researchers and they publish, plus they cure the incurable, it's not something to be dismissed as a "fad". If anything, the fad diet is whatever we're doing since the 50s, or all the way up to the invention of agriculture.
I don't think you're deprived of any nutrients. Sticking to a well-chosen, consistent diet is a feature, not a bug. Most of us living in modern cities have a dizzying array of options to the point that today more humans die due to obesity today than to malnutrition.
Heck, even more than 2000 years ago, people were conscious of too much food variety. Here, look at Seneca riffing on it in a letter to his friend (titled 'A beneficial reading program'):
"You must stay with a limited number of writers and be
fed by them if you mean to derive anything that will dwell reliably with you [...] 'But I want to read different books at different times,' you say. The person of delicate digestion nibbles at this and that; when the diet is too varied, though, food does not nourish but only upsets the stomach."
Fair question. I did anticipate it, as my argument wasn't watertight.
I mean to say that the sheer variety aggravates our boundless appetites, which are difficult to restrain as-is. Couple that with the unhealthy eating habits our modern age "encourages" (I put it in air quotes because we have personal agency to push back). And we can see where this is going. The details are very much debatable, but the broader point stands.
If you found a set of foods that leave you satisfied every day and you’re never craving something else, it sounds like you’re doing pretty great. And if you’re worried about getting enough trace minerals, you could easily add some dark chocolate, seeds, nuts, and fresh herbs.
I find myself having weird food cravings when this happens. I take a multivitamin every day but during the pandemic I've also been eating the same half-dozen things, over and over and over.
It's definitely missing something (that the multivitamin is insufficient in completely replacing) because sometimes I'll order delivery takeout from somewhere and feel like a new person after eating it.
Increasing omega3 was a major one for me, definitely decreased chronic inflammation. The problem occurs if one's omega6:omega3 ratio is off, and most westerner's diets are very high in predominantly omega6 fatty acids[0] (such as olive oil, and most other oils). Though if you choose to supplement omega3, make sure it is controlled for mercury-contaminants.
With fat-soluble vitamins such as Vitamin D, be vary of vitamin toxicity (Hypervitaminosis[1]), as they accumulate in the body. But you'd probably have to take a huge amount over a long time to get there.
Another interesting supplement might be L-Carnitine[2], especially if you eat little/no meat.
I'm a bit shy to admit, but the most objective marker was a significant reduction in acne (on my shoulders). But overall I also feel a lot calmer, I digest food better, I sleep better, and some other things that are hard to pinpoint. I just have an overall greater feeling of well-being. I know this is only n=1 and hard to prove that it's due to omega3, but I just really feel like it is closely related.
I also have to point out that I've eaten a vegetarian diet since about 2008. I always thought I had a pretty healthy diet and blood work confirmed that, but it appears that it didn't control for omega3 concentrations. Part of that diet was that I consumed large amounts of (in particular) olive oil (omega6), and almost negligible amounts of omega3.
If you want to know your situation, I believe that you can just go to a general doctor and ask for a blood test. I heard that's common for people with vegan diet.
(I haven't done it myself yet, so I'm not sure what metrics they can give you)
I switched to a whole food plant based diet after reading "How not to Die", and I believe it's served me well during the pandemic, cooking for myself and hitting my micronutrients pretty much every day. I check using cronometer.com, and in pretty much every category I'm getting more than enough.
Eating the same thing every day isn't the problem; it's not eating enough different things to get all your nutrients. Just for example, I pretty much eat beets, broccoli, blueberries, almonds, bananas, mango, dates, oatmeal, greens, legumes (lentils, chickpeas or kidney beans), turmeric, flax seed and nutritional yeast (for B12)) every day. My labs a week ago were perfect, I'm actually over for vitamins D and B12.
I think a blood test can answer these questions, at least to some degree. My doctor had me undergo a blood test at my physical and it exposed my lack of vitamin B12
Why is it assumed that a diverse diet is necessarily better for you? If you're cooking for yourself, fresh, unprocessed foods, you're already way ahead of the game.
To be fair, the OP wondered if he was missing out on some nutrient. That was the reason for scurvy in the past, limited diet of a ship, lack of vitamin C.
> That was the reason for scurvy in the past, limited diet of a ship, lack of vitamin C.
AIUI, it wasn't the limited diet, but the lack of fresh food. What I heard was that basically everything you eat has vitamin C in it (which is why our bodies forgot how to manufacture it on their own -- why bother making your own when it's already all around you?), but that it decays fairly rapidly. So it doesn't matter how diverse your food supply is, if it's all canned / salted / preserved, you're going to have problems.
I guess it depends on how "routine" OP's routine is. If they're eating just potatoes and bacon every meal, they're going to have problems. But if they have 2-3 forms of starch, 2-3 types of vegetables, and 2-3 forms of protein mixed together, I think they're probably doing about as well as most human beings have done throughout time.
That said, never hurts to take a good multivitamin. :-)
Vitamins are determined by their biological functions, not by chemical structure. Compounds which satisfy the functions of a particular vitamin are known as vitamers of that vitamin. For example cyanocobalamin and methylcobalamin are both vitamers of B12 despite being chemically distinct.
It's true that some vitamers are more easily metabolized by certain routes than others. In the example I gave, methylcobalamin is superior when it comes to oral supplements.
Also if you can, try taking a multivitamin without minerals, and take a mineral supplement separately. A lot of minerals interfere with one another's absorption along with that of many vitamins (zinc, calcium, and iron should all be taken away from each other and from vitamin supplements).
I read somewhere that a large part of the "quality" of vitamin pills come down to how crumbly they are. Small dense vitamins are so good. Big pills are.
Not a shill, have Crohns so can get absorbsion issues with food/nutrients. This stuff noticeably helps over a multivitamin pill... maybe placebo but I absolutely feel the difference.
Look, I can write a bullshot article telling you that you need to take vitamine frroorofrom and then offer to sell it to you for $20 a pill. If you want to believe it and spend your money, good for me!
On the other hand the $5 a jar multivits cover all your actual supplement needs.
There is a concept of bioavailbility. Some vitamins & minerals are more absorbable than others, and if you have issues you can be asorbing or converting certain ones not as well as you may think:
Also do we know all the nutrients people need and amount also considering what is optimally healthy, genetics, age, medical conditions? Definitely not.
Terry Wahls, the doctor who claims she reversed her MS through diet would only partly agree. In her book 'The Wahls Protocol', she spells a diet regime out from a functional medicine perspective.
Unfortunately for people with MS (like myself) she’s wrong. Her original experience is in fact quite “normal” for the behaviour of MS. It gets significantly worse, then significantly better, then worse, etc etc.
Her study that then followed up did find a positive result, but had a very small sample size, nowhere near large enough for a highly variable condition like MS. Drug companies have to spend billions running 5-10-20 year studies with 1000’s of participants to verify the efficacy of their MS treatments for good reason.
A recent Cochrane review on diet interventions for MS which references her study (amongst others obviously) concluded that “at present there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on MS related outcomes.”
The biggest giveaway that a medical treatment is snake oil in my experience is when it comes with a book for sale for £20 on Amazon.
Meta: I deeply appreciate this article explicitly stating "The evidence is current to May 2019." It's so hard for noobs like me to sherlock this stuff.
> supplementation with antioxidants or other dietary interventions
Those other interventions are macronutrients, to benefit your mitochondria. I'll go back and look, but I don't recall Wahls saying much about antioxidants.
FWIW, I believe, but cannot prove, that Wahl's advice to resume eating meat, esp organ meat, benefitted me. I had been working towards vegetarian and suffering terribly from inflammation and autoimmune stuff. I have no idea how or why. I only know that whenever I resume my prior dietary habits (more carbs, less meat), I decline. My fat and produce consumption has remained more or less constant. A lot coconut oil, olive oil, and every big leafy green that fits into the blender.
Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70 to 85%) and, consequently, a low proportion of protein (15 to 30%). In contrast, most biological membranes have a higher ratio of proteins to lipids.
In addition to cerebroside, the major lipids of myelin are cholesterol and ethanolamine-containing plasmalogens
Just to give a bit more detail, those cerebrosides are Glycosphingolipids. They're galactose or glucose attached to a ceramide. So the major components of myelin are lipids/carbohydrate! (Don't know exact proportion of carbohydrate)
My dad had MS, they knew that MS was caused by demyelination years ago. Is this study important because they found the gene (or a gene?) that corresponds to that?
MS is not inherited, but it looks like they’ve already identified genes as well that increase risk, and risk increases if a family member has it.
> Is this study important because they found the gene (or a gene?) that corresponds to that?
The paper only concludes that the gene is inactive when there's demyelination, the paper doesn't actually say that it causes it.
The previous research I've read says that it is expressed during repair (i.e it is the repair tool, so is in play during repair of the cells).
So even for those of us who have GPR17, making sure it is expressed for repair (if it does repair) would mean a longer active brain life.
I've got half-a binder full of research on PRRT2 from a family incident & then the opposite with conductivity research for SCN1A.
The developmental myelination defects are really weird to read about, because if they are about expression rather than presence of a gene & often a single CNV doesn't mean anything (or everything, argh), the environmental factors overwhelm things ("what kind of fat and how much did you eat during your childhood synaptic pruning period").
University press release. The real science is too technical and boring, so the press release states the background of the research as the breakthrough, or makes wild unsupported speculative claims about applications, or both.
The word "discover" is a bit of a stretch here, but I suspect they mean that the "discovery" was that the loss of myelin is a part of age-related cognitive decline as well as MS.
But MS is not the only disease is in which demyelination occurs, not by a long shot. Even the definition of MS (when it comes to getting a diagnosis) is a lot more complex than just "degeneration of myelin".
> This new study found that the cells that drive myelin repair become less efficient as we age and identified a key gene that is most affected by ageing, which reduces the cells ability to replace lost myelin.
FYI. Sounds like it's related but maybe not directly.
A whole bunch of genes and environmental risk factors correlated but current knowledge is basically "something causes autoimmune attack of oligodendrocytes (myelin) for some reason"
That's the entire state of bio-medicine; nothing is known for sure and everything is too complicated to understand. And all treatments are based on general statistics. I can't wait for this stage to end.
A bio professor of mine described the field as being like “the ancient Greeks trying to reverse engineer extraterrestrial technology.”
Biology does not work the way humans design things. It’s not one part one function. It’s all parts some functions to varying and often dynamic degrees, a web of interrelationships that is itself in constant flux. It makes us look like cave men disassembling a UFO.
Pharmaceuticals is basically “we throw this molecule in and it seems to do that.” Sometimes we can divine some cause and effect understanding but it’s always surface level and incomplete. How SSRIs supposedly work for depression comes to mind as an example of such an oversimplification.
Tangentially related, this brought to mind the study that showed a reduction in myelination in young children who were exposed to "excessive" screen time. [0]
Can't find it right now, but there was also an interesting paper ~7 years ago that showed that myelination occurs more readily if myelination occurs regularly (vs. the first time in a longer timespan).
That always stuck with me, as it could potentially mean on a higher level that learning itself is a skill that can and needs to be exercised regularly. I'm wondering if that could also explain the decline in neuroplasticity with age. Would love to hear if anyone knows about some newer research in that area!
>> Higher ScreenQ scores were associated with lower brain white matter integrity, which affects organization and myelination — the process of forming a myelin sheath around a nerve to allow nerve impulses to move more quickly – in tracts involving language executive function and other literacy skills.
But doesn't this have to do with what you're doing? The article only mentions screen, but that could be a TV or endless YouTube where there's only 'consumption' happening, in contrast with playing either strategy based games or even taking part in online classes where interaction is important, where a large amount of 'cognitive skills' are also being utilized.
Just scanning the paper and there are other major limitations that didn’t make it into the summary. They don’t control for other activities that screens may substitute for such as active physical play, having books read to them, active exercise, etc all of which may be positively associated with white matter integrity, or may require a certain threshold of activity which isn’t being met for kids who spend too much time watching tv so there’s no time to do other helpful activities. Other studies show negative associations are much more strongly correlated at the high end of exposure, suggesting that substitution for other beneficial activities could be a bigger issue than the exposure itself.
It also controls for family income and age but not cognitive scores prior to screen exposure. It could also be that kids starting with “less integrated” brains find more active tasks less engaging and end up watching more screens as a result.
I don’t let my toddler spend much time on screens aside from FaceTime and the odd episode of Tik Tak[1] while we’re cutting her nails. These studies’ data are often presented as simplistic linear regressions suggesting that like lead, there is no safe exposure to screens, when it’s just as likely that a small exposure that doesn’t get in the way of a lot of other activities is helpful and helps kids feel comfortable and less confused in our modern screen-filled world.
Anyway, I just needed to get that off my chest because I see too many families get overly stressed and paranoid by the AAP guidelines which are speculative at best.
Hericium erinaceus (Lion's mane mushroom) has isolates called Hericenones and Erinacine that promote nerve growth factor synthesis and a lot of other Neurohealth benifits being found to do with the compounds the fungi produces.
Protip: If/When buying supplements -- There's many that are just selling capsules of ground myceliated brf (brown rice flour - the substrate inoculated/grown on). Mycelium is the 'roots/pre fruiting stage' of the fungi -- The fruit body/ mushroom itself has much greater concentrations of the desired compounds.
Nothing definitive. After 1 week I managed to achieve life-time high score in focus and short-term memory task (my previous high-score was from Uni while studying Physics), but I'm susceptible to placebo so I can't rule out that effect.
I feel like I have less "brain-fog" or rather, brain-fog induced procrastination though. But taking this coincided with a less-stressful time of my life so It might be related to both.
I tried taking this for a while, but found that I started having really bad headaches. I was taking a well known brand from Amazon. I couldn't be 100% sure the headaches were due to the Lion's mane, but felt better after I stopped taking it.
I was pretty bummed, I was hoping for a little boost from this as I had read good things about it, including the NIH articles you posted.
I can also confirm, finding the supplements that are not just mostly the ground brown rice flour is also a little difficult.
The ingredients list / packaging should say something like dried fruiting body... or if you're getting the rubbish = myceliated grain or mycelial biomass. The reddit link provided by NalNezumi is very good.
They say similar things about psilocybin and magic mushrooms, but some people still eat the mycelium to get the effects. I guess it's more economical to just grow mycelium.
I learned today that senolytics are molecules that "... can selectively induce death of senescent cells ..."[1]
Which is interesting but you can already do this with exercise.
Nick Lane wrote a fascinating book[2] about this subject which suggests that your internal mitochondrial population is under selection pressure from your own activity.
If you don't put any pressure on it, energetically ill-performing cells are allowed to thrive.
I like Rhonda Patrick, but a lot of her recommendations seem to be speculation on what should work, given what she understands about a subject and relating it to a new study. Not that it's not valuable, but it's the sort of thing Reddit would class as "science" rather than realising it is a hypothesis that needs testing.
I like to understand this too, substance called ‘myelin. Is there some intake of food that can help? Just like my parents to be including anything in their diet that can help.
I'd be surprised if we manage to reverse deterioration in such a complex system as the human body, especially in the brain, in our lifetime. We are barely scratching the surface, trying to understand the most basic interactions between this massive amount of variables of which we can only control a few reliably.
The problem is conceptually quite simple:
Ageing is an accumulation of degradations in our DNAs.
We just need to reset/monkey patch our DNAs with a prior younger version through CRIPSR + viral vectors.
The only issue is the scale of the gene therapy (changing whole organs) but I'm quite sure it is doable, just underresearched/underfunded.
1 March – Scientists use lipid nanoparticles to deliver CRISPR genome editing into the livers of mice, resulting in a 57% reduction of cholesterol levels.[160]
Rejuvenation is not science fiction, it just require funding but expecting this from humanity might be considered science fiction and the situation isn't going to improve given than the Flynn effect is reversing..
My biggest regret is to have never studied ancient-greek. So much mental load associated to pure mnemonics would just disappear in favor of upfront understanding.
Myelin seems a step or two down the causation chain. There is interesting theorising that the root cause in regular aging is lossy copying of the epigenome.
My friend just told me about a potential gene therapy. I'm blanking on the name, but there is a gene which inhibits myelin regeneration, and a gene which inhibits that gene. By using an adeno-associated virus which has an affinity for CNS tissue, you can induce the latter, resulting in an increase in re-myelination.
My friend's partner has suspected MS. They are also experimenting with helminth therapy. They have taken 5 Necator Americanus eggs and anecdotally, their symptoms have not been progressing as fast.
A quick search shows a whole mess of various genes and proteins associated with myelin but I'm not sure what the front runners are.
Edit: it's LINGO1
> Lingo-1 antagonists are able to promote re-myelination in CNS by means of stimulating OPCs differentiation which was before blocked by this protein. This has been seen in several experiments that resulted in significant increases of oligodendrocytes differentiation by targeting Lingo-1 with its antagonists, such as the antibody Anti-LINGO-1 (BIIB033)
I recently saw a video of Paul Stamets talking about mushrooms and how they increase connections in the brain. I think I remember hearing the term myelination thrown in there somewhere. Granted I don't know enough about him to say that hes a credible source.
But, it would be a good place to start (research). Its a shame that the science community seems to steer clear of certain topics entirely.
If you’re asking yourself “why does an insulator speed conduction?” Then it’s worth reading the “function” section of the Wikipedia article on myelin, for an introduction on the role of these short, interrupted sections of insulator and why it makes conduction faster. Nerves don’t conduct electric signals like wires so (much slower, for one thing) making it hard for us to keep up with the processing of computers.
Somehow I read that as "Britain's "wiring insulation"" and got through the whole article looking for some chemical that the British insulate their wires with thinking "talk about burying the lede. It's not even here!"
To curb your urge, cloth insulation was common until the 60s in GB and if you are a very unlucky contractor you dig up paper insulated wires and nope out.
Permanent nerve damage (neuropathy, pins and needles, tingling, muscle weakness, spasms, muscle twitches, heart palpitations) is a known side effect. There's been no attempt made to study if there's any long term delayed brain effects from fluoroquinolones. "Brain fog" is a commonly reported symptom of those who experience fluoroquinolone side effects. I hope there will be more studies on long term brain health from these drugs, as they're given out liberally.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006604/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667412/
[3] https://pubmed.ncbi.nlm.nih.gov/10832955/