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BZRich t1_ix58zwi wrote

Maybe, maybe not. NSAID usage over a long period is associated with lower incidence of Alzheimer’s Diesease (Rotterdam study), but two prospective clinical trials ADAPT and INTREPAD were both ended early due to major adverse events. There was no benefit when they were ended at two years. NSAIDS are not harmless even though we get them without a prescription in the US. They raise blood pressure, and can cause bleeding in the gastrointestinal tract as well as kidney damage. A few for a sore knee are likely not going to be a problem, but taking over a long period of time? Use caution. There is no free lunch.

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[deleted] t1_ix5medw wrote

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[deleted] t1_ix5x62c wrote

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[deleted] t1_ix6fsbj wrote

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radioactivemagic t1_ix5kkad wrote

There's also evidence emerging that suggests NSAIDS, even OTC, carry similar cardiac risk to VIOX, which makes sense given most are COX-2 selective nonsteroidal anti-inflammatory drugs.

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mwebster745 t1_ix5w0yu wrote

Yes but also significant evidence the risk of naproxen is significantly less, and mixed evidence as to if it really breaks from placebo or not. Thought to relate to the platelet related inhibition like ASA has

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lambertb t1_ix5ui9t wrote

It’s more than just emerging. There is an FDA mandated warning on the label about increased risk of stroke and heart attack, in addition to bleeding, and kidney damage. NSAIDS are not generally safe drugs.

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Duckboy_Flaccidpus t1_ix5zeq1 wrote

All this seems to fly in the face of something like Bayer aspirin that says it helps to reduce heart attacks and can be prescribed a small dose daily to aid in continued blood flow.

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15MinuteUpload t1_ix6bo7m wrote

Aspirin has a different mechanism compared to other NSAIDs and does in fact have well-studied benefit in heart disease protection and clot risk. That being said, that benefit is likely less than previously believed due to more recent studies and evidence and it does not come without risks, but it certainly exists.

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lambertb t1_ix67fdw wrote

It’s complicated. Aspirin is an NSAID, but not Al NSAIDS are the same with respect to adverse effects. Aspirin has cardiac benefits because it’s an anticoagulant. The same basic effect is why NSAIDS can cause bleeding strokes. I can’t explain all the mechanisms. I just know it to be true.

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jaldihaldi t1_ix6ojvo wrote

Though ibuprofen might cause green in high blood pressure patients?

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55peasants t1_ix6y51o wrote

Asprin inhibts COX-1 more than COX-2, last time I read up on it, this was the theory on the difference on cardiovascular safety

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EmilyU1F984 t1_ix7kzvu wrote

Why did anyone even think that? Coxibes cause cardiovascular risk through Cox2 inhibition. All nsaids so that to some degree, or they would be useless. So all NSAID’s have cardiovascular risks associated with them, proportional to dose and duration.

Meaning they are generally save if used according to OTC ‚rules‘ over here: no more than 3 days for fever. No more than 4 days for pain, and not for frequent pain/fever without a physicians recommendation/prescription.

Selling 500 count bottles obviously doesn‘t help making them not look like candy.

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lambertb t1_ix7w4t1 wrote

Agreed that they are generally safe when used as directed. But they are contraindicated in anyone with kidney disease, and probably a poor choice for anyone with cardiac risk, bleeding risk, or stroke risk, which in the US, is a lot of people. Sadly, there are no safe pain meds. It’s all risk/benefit calculation.

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holy-reddit-batman t1_ix87zqa wrote

Holy hell. That's the recommended length of use for each of those? I've been taking naproxin probably 6 times a week for as long as I can remember. I have serious arthritis and widespread pain.

Would a person know if they were having internal bleeding? My GI is screwed up from some other conditions. Now I'm wondering if any of that is going on.

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EmilyU1F984 t1_ix8la31 wrote

Not necessarily, any GP can test for hidden blood in stool though. Black stool is indicative of a bleed higher up in the GI tract anything bright and Tim’s likely hamprrhoids.

(And on the reverse black or blood coloured vomit)

You need to talk to your physician though, daily naproxen might be the best treatment option even with all the risks, But there‘s also other treatment options for arthritis, especially if you are using OTC painkillers daily.

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Adamsmasher23 t1_ix6xj9u wrote

It's not just emerging, vioxx didn't really have much higher risk than other NSAIDs:

> The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations.

> Conclusions All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.

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CabbieCam t1_ix6z4xa wrote

As someone with arthritis I miss viox greatly. It was an excellent anti inflammatory.

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Brevemike t1_ix76t1a wrote

Vioxx was amazing. I’ll take the possible cardiac risk to alleviate the guaranteed pain.

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[deleted] t1_ix7adc2 wrote

You’ll change your tune quick if you do have cardiac problems.

Seriously the scariest thing I’ve ever experienced.

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Brevemike t1_ix8pqn7 wrote

Sorry, mini-rant.

It was a terrifying event, but being in chronic pain denies me the ability to enjoy having survived. There are days I’m disappointed I wake up.

Each day I get to choose to exist somewhere between pain that renders me non-functional or drugging myself free but insensible. And the drugs are not without their own debilitating side effects and risks.

When I was on Vioxx the side effects and toll it took were unnoticeable. The current drugs leave no question that they’re beating the hell out of my body.

Everyday we risk sudden death in the most mundane of ways. Whether strapping ourselves into metal bullets and hurtling along the ground at 120kph or stepping out of a tub onto a wet tile floor.

I’ll take a 10% increased risk of sudden death in exchange for living relatively pain free.

But I haven’t got that choice. Neither do the many people who finds themselves on increasing doses of opioids for continually decreasing returns - sometimes seeking stronger unregulated drugs and risking sudden death anyway. What if those caught in an addiction cycle could’ve been stopped before they started?

Is it worth the risk?

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KaylaKoop t1_ix8euec wrote

I don't take nasaids, but I do take pot, the edible kind, for severe back pain. And it is illegal in my state. If someone told me I would have increased cardiac risk for doing so, I wouldn't hesitate to continue. Until you've had debilitating pain, you have no idea what someone is willing to do. If I got cardiac problems? I figure they would probably put me out of my pain sooner, rather than living with it for year after year.

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TZscribble t1_ix90bsr wrote

Pretty sure a day of terror will out weight daily, happiness sucking pain.

I have fatigue and it affects me daily and makes day to day life difficult. A medication that potentially gives heart problems but improves my day to day fatigue? Sign me up.

In fact, that's exactly what the stimulant I am on can do. Still worth it. I can actually do a full 8 hours of work and still make dinner or do the dishes (mind the or - it is 'or', not 'and'). It has made a huge improvement to my life.

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sneakacat t1_ix7a27r wrote

What is the absolute risk of heart attack, kidney damage, or other issues? I always just see a general "increased risk" but no numbers. Or if there is a number it's the amount of increased risk, not the total risk for a generally healthy person.

If my starting risk for a heart attack is 1%, and NSAIDS increase that by 1%, then I really don't care since NSAIDS allow me to live a pain-free life. I'm always annoyed when doctors advise against using NSAIDS in general without taking these realities into account.

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king-shibby t1_ix6e4wv wrote

So for work, my main tasks is doing research on how conditions, medications, and surgeries can aggravate or lead to other conditions. Unfortunatly, I don't think there is any medications out there that the hypothetical pros outweigh the hypothetical cons.

For example, using steroid based inhalers can aggravate DMII by causing insulin resistance. Even worse, all inhales CAN cause this, steroid based just has a higher number reported in case studies.

Also, you can make an argument for almost any medication and the negative effects on the body. It truly comes down to what works the best for the patient and what doesn't have as many side effects.

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EmilyU1F984 t1_ix7l66x wrote

Every effective medication will have side effects.

As always you gotta weigh the negatives with the be edits.

Which is why 500 count bottles of ibuprofen are so insane: it makes it look like candy. Pill bottles in general make people just grab a hand full.

Like how on earth does a 500 count bottle make sense when the otc guidelines for ibuprofen is 3 a day for 4 days max, and not for frequent use..

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lampcouchfireplace t1_ix70jfn wrote

Additionally, there are emerging data about the negative impact NSAIDs can have on the gut microbiome, which seems to be increasingly important in all manner of surprising ways.

https://med.uottawa.ca/en/news/everyday-drugs-act-surprising-ways-microbiome

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[deleted] t1_ix88u38 wrote

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lampcouchfireplace t1_ix8agdu wrote

NSAIDs have long been known to irritate the stomach, hence the advice to take with food or discontinue in case of heartburn / reflux.

However more evidence is mounting that they actually impact the microbiome more seriously and perhaps even permanently.

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skinnyguy699 t1_ix6iln2 wrote

Follow up question: does this also apply to high strength omega 3 tablets taken everyday?

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EmilyU1F984 t1_ix7lb9z wrote

If you are taking in those fatty acids at much higher levels than the recommended dosages for a balanced diet, then yes.

Every food component you eat will have negative effects at higher dosages, just like eating too much fats, carbohydrates and protein causes eventual problem. The same is true for every micronutrient, bare a few that will just cause diarrhea if overdosed like vitamin C and prevent absorption of systemically toxic amounts.

The exact risk obviously varies massively, something like omega3 won‘t cause as much trouble as overdosing on Vitamin A for example.

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Igggg t1_ix7i9vh wrote

> Maybe, maybe not. NSAID usage over a long period is associated with lower incidence of Alzheimer’s Diesease (Rotterdam study),

Can you cite this result? The one I recall and found appears to have a very mild, and, in any case, non-signficant result.

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BZRich t1_ix8jmo8 wrote

This was the initial finding suggesting this in a really small group: McGeer, P. L., et al. (1990). Lancet 335(8696): 1037.

Here is the Rotterdam Study: in t' Veld, B. A., et al. (2001) N Engl J Med 345(21): 1515-1521.

This showed a 5 fold reduction for people who took NSAIDs for more than 2 years. See Table 3 relative risk = 0.2. This caused a lot of excitement.

Alas John Breitner's RCTs say otherwise: ADAPT Research Group. (2008). Arch Neurol 65(7): 896-905.

Meyer, P. F., et al. (2019). Neurology 92(18): e2070-e2080

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Igggg t1_ixat4qm wrote

Thank you for the citations!

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Responsible_Ad2463 t1_ix79k8x wrote

Even naprozen ? For kidney pain

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EmilyU1F984 t1_ix7ljd2 wrote

Naproxen has cox2 inhibitory effects, if thus increases cardiovascular health risks. And like any nsaid it can cause chronic interstitial nephritis (kidney damage) in long term and or high dose use.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869646/ for the kidney specific part.

This is true for aspirin, ibuprofen, naproxen, Diclofenac etc.

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BZRich t1_ix8jufs wrote

Unfortunately yes. naproxen is very effective and has a long half life but it is not free from side effects.

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UserWithReason t1_ix6zzvm wrote

Sometimes there is free lunch though. Beggars can't be choosers and those free meals may not be the food you need. Also, some are heavily reduced lunch. Obviously if you take the same lunch every day instead of diversifying then you won't be healthy, but there are free snacks to add to your lunch at least.

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Dr_Vanc_Zosyn t1_ix4ulkd wrote

More context please. Do you mean inflammation of the central nervous system (meningitis, cerebritis, ventriculitis), peripheral nervous system (neuritis), or...? Do you have a specific clinical or research concern?

NSAIDs cross the blood-brain barrier in rats. Since they are anti-inflammatory by definition, maybe yes? Again it depends what you're really looking for here -- "neuroinflammation" is a subtype of inflammation and I'm not sure the distinction is really relevant beyond the BBB, but it's not my field.

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One-Garden-1294 OP t1_ix4uq73 wrote

I mean chronic neuroinflammation as seen in depression, long COVID etc

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Dr_Vanc_Zosyn t1_ix4vjb1 wrote

I think this is a cutting edge basic science question. From what I can tell (eg this 2021 review) we are still in the early stages of understanding the link between inflammation and depression in the first place. Similar with COVID-19, though even more nascent.

In general NSAIDs have not been found to effectively treat depression or COVID-19. They have been extensively studied and I suspect we would have discovered a correlation if one existed.

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LynnOnTheWeb t1_ix5hxgf wrote

What about for something like encephalitis caused by a UTI or other infections in the elderly?

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rookieseaman t1_ix5ckm8 wrote

He’s not asking if it treats depression or Covid, just the inflammation associated with those thingsz

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Dr_Vanc_Zosyn t1_ix5ihkw wrote

I assumed that one would care about disease-related inflammation in order to treat the symptoms of the disease, but yes

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unsigned1138 t1_ix6h732 wrote

So you mind if I interject here, being specific for neuralgia’s. Trigeminal, Geniculate, occipital, glossopharyngeal, etc.

I think I know the answer that medication with anti-convulsive properties are more effective, but the question stands. Are there anti-inflammatory properties to NSAIDS that may help?

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Dr_Vanc_Zosyn t1_ix6kex3 wrote

That would make sense to me. Trigeminal neuralgia at least is caused by direct compression of the trigeminal nerve root, which certainly causes some degree of inflammation. Inflammation is probably a minor contributor though; demyelination seems to be the main cause of pain in that condition. NSAIDs can treat the pain and inflammation there. Anticonvulsants are more effective because they directly modulate the firing of those nerve fibers and prevent them from generating a pain signal in the first place.

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t313nc3ph410n t1_ix582xv wrote

I am leaving the depression/inflammation link aside, because I am completely unqualified in that regard.

In COVID-19 there have been some off-label uses of Relafen (nabumetone) in myalgic encephalomyelitis, which is close enough to have some idea. I guess we'll have some publications on that one in the coming months.

For the time being, a review of the literature in https://pubmed.ncbi.nlm.nih.gov/21504126/ seems to suggest that NSAID and COX-2i in neuroinflammation in Alzheimers does not show any efficacy.

https://www.sciencedirect.com/science/article/abs/pii/S0197458099000287?via%3Dihub suggests, that NSAID use may have some efficacy if implemented before inflammation develops. As a purely neuroprotective agent, if you will.

In SARS-CoV-2 infections, use of NSAID may thus, and this is a hypothesis, prevent neurological sequelae. I would caution against hedging a bet on it, though, the data are thin on that one.

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PresidentialCamacho t1_ix5f8n8 wrote

Conclusion: Free ibuprofen, flurbiprofen, and indomethacin rapidly cross the BBB, with ibuprofen exhibiting a saturable component of transport. Plasma protein binding limits brain NSAID uptake by reducing the free fraction of NSAID in the circulation. https://link.springer.com/article/10.1007/s11095-006-9905-5

The article says in the real world NSAIDs, free ibuprofen, are bounded to plasma which limits the concentration that can actually cross the BBB.

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[deleted] t1_ix4wrz5 wrote

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[deleted] t1_ix5l5ad wrote

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Feline_Diabetes t1_ix5hsf9 wrote

There's no easy answer to this one.

It depends what kind of evidence you want to consider (ie human clinical data vs. animal models) and what you count as neuroinflammation (ie cytokine concentrations, gene expression patterns, peripheral immune cell infiltration).

Human clinical data is sparse, variable and usually reliant on sub-par proxy measures so it's difficult to say. Animal data will tell you they do, but you need to pay careful attention to exactly what each study did, what they measured and whether it's of any relevance to a human disease.

If you want to start reading more about it, review articles can help but they are often specific to a particular pathological setting. To go into the primary literature you really need to pick a specific scenario and read around that.

Sorry I couldn't be any more specific, but there really isn't a short or satisfying answer of any value.

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Eimai145 t1_ix6ufhg wrote

I'd like to ask you knowledgeable folks about this.

I take Advil a fair amount. Estimated intake is maybe 2 to 3 pills a day one to two days a week for chronic headaches, and 4 to 6 piils for 1 to 2 days per month for a monthly migraine.

Potential damage? What signs should I watch for? Tylenol doesn't cut through the pain.

Thank you.

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samstown23 t1_ix76y3t wrote

Depends on the strength but assuming 400mg/tablet, it's kind of borderline. While the unsupervised recommended daily dose is a mere 1200mg, higher amounts (up to 3200mg) are possible but require some degree of care (particularly when other drugs are involved, such as MTX, SSRIs, diuretics and others). Body mass should be taken into consideration beyond 2400mg as well.

To cut a long story short, acute toxicity likely isn't the problem but the long term use might be somewhat problematic, if only from the gastrointestinal side. I would definitely consult with a GP on that matter.

On a side note, since you mentioned it, please be careful with paracetamol/acetaminophen (e.g. Tylenol): recommended doses and toxic doses are comparatively close together and a lot of OTC meds (often cold remedies) list it as an ingredient. Accidental overdose is an issue and happens relatively frequently (and I doubt you want a liver transplant). It's not unsafe or bad, quite the contrary, but it is comparatively error-prone.

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Eimai145 t1_ix8hy5w wrote

Thank you. I will speak to my GP about the long term use and side effects. I will continue to avoid Tylenol. I really appreciate your response.

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Henri_Dupont t1_ix84bye wrote

You and I are in the same boat, buddy. I was suffering from migraines and migraine associated vertigo, which can take a month to resolve. I did a sort of study on my self, keeping notes and alternating NSAIDS, and concluded that Naproxen at highest recommended dose helped my symptoms more than Ibuprofen (advil) at highest recommended dose.

Nothing in this thread is reassuring. Tylenol sounds like the least safe option.

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Eimai145 t1_ix8hkec wrote

I also get vertigo. Not fun.

I have purchased Naproxen but not tried it yet. Next time.

Thank you for your input. Much appreciated.

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_dang t1_ix8jzav wrote

I heard an interview on NPR the other day with Kareem Abdul-Jabbar. He suffered his whole adult life from migraines. Did a sleep study in 1990 and it was determined he wasn't getting enough oxygen during sleep. Prescribed a home oxygen therapy - which he does to this day. Says it changed his life. I don't suffer from migraines but it connected some thoughts I've had about things I've been dealing with.

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HodloBaggins t1_ix6lz21 wrote

There are studies out there that mention how people taking ibuprofen for a long period of time for reasons like arthritis tend to have lower rates of Parkinson’s/Alzheimer’s, and neuroinflammation seems to play a part in those diseases.

That’s as far as my knowledge goes though. Would it be advisable to take NSAIDS for “no reason” to prevent neuroinflammation? I don’t know. There’s definitely side effects.

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Ituzzip t1_ix921ae wrote

My sense from this question is that it depends.

They reduce some kinds of inflammation which would include neuroinflammation when there cross the blood brain barrier, but they don’t have the same action as other anti-inflammatory drugs like antihistamines and steroids.

The answer, if taken literally, is yes, but the question would be whether it is useful and beneficial to prevent or treat various conditions, and I don’t know if that’s conclusive.

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