#1

This and related articles resuscitates a older study having much potential for confounding. Does anyone have any thoughts or new evidence on it?

Full article: These four common medicines could help prolong your life (New Scientist)

#2

For starters, this is GPT-4’s assessment.

QUESTION
Evaluate the strength and breadth of the medical research suggesting that Naproxen might be a longevity drug. Look especially for findings for which the potential for alternative causes is significant.

ChatGPT
As of my last update in January 2022, there isn’t substantial evidence to firmly establish Naproxen as a longevity drug. While there have been some intriguing findings suggesting potential benefits, particularly in animal models and certain population studies, the evidence is not robust enough to make definitive conclusions.

Here’s an evaluation of the strength and breadth of the research:

  • Animal Studies: Some animal studies, particularly on nematodes (Caenorhabditis elegans) and mice, have shown promising results regarding the potential longevity benefits of Naproxen. These studies often attribute the effects to its anti-inflammatory properties and potential modulation of aging-related pathways. However, extrapolating these findings directly to humans is challenging due to differences in biology and metabolism.

  • Epidemiological Studies: Some epidemiological studies have reported associations between Naproxen use and reduced risk of age-related diseases such as Alzheimer’s disease and certain cancers. However, these studies often rely on observational data, which cannot establish causation and are prone to confounding variables. For example, individuals who use Naproxen regularly may also have healthier lifestyles or other factors contributing to longevity.

  • Clinical Trials: While Naproxen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) with well-established effects on pain and inflammation, clinical trials specifically assessing its effects on longevity are lacking. Long-term randomized controlled trials (RCTs) are necessary to determine whether Naproxen has any significant impact on lifespan or healthspan in humans.

  • Potential Confounding Factors: There are several potential confounding factors that need to be considered when evaluating the association between Naproxen use and longevity. These include:

  • Other medications: Individuals who use Naproxen may also be taking other medications, which could influence outcomes.

  • Lifestyle factors: Diet, exercise, smoking, and alcohol consumption can significantly impact longevity and may confound the association between Naproxen use and lifespan.

  • Underlying health conditions: Individuals who require Naproxen for pain relief may have underlying health conditions that affect longevity.

  • Safety Concerns: Naproxen, like other NSAIDs, can have adverse effects, especially with long-term use or at high doses. These include gastrointestinal complications, cardiovascular risks, and kidney problems. Considering these safety concerns is crucial when evaluating its potential as a longevity drug.

In conclusion, while there are some suggestive findings regarding the potential longevity benefits of Naproxen, the evidence is not robust enough to support its use as a longevity drug. Further research, particularly well-designed clinical trials, is needed to determine whether Naproxen or other NSAIDs have any significant impact on lifespan or healthspan in humans. Additionally, researchers must carefully consider and control for potential confounding factors in future studies.

#3

Unfortunately, the article you cite is behind a paywall subscription required.

Naproxen is my choice of pain reliever when I need one because of its long half-life and relative safety profile. One tablet usually does the job and the effects last a long time.

More than you wanted to know about Naproxen:

"Dr.Oracle: “Naproxen has relatively strong pain-relieving (analgesic) effects compared to other NSAIDs. In studies comparing the efficacy of various NSAIDs, naproxen has been found to provide similar or greater pain relief than other options like ibuprofen.”

Naproxen has a relatively favorable safety profile compared to other NSAIDs. It has lower rates of gastrointestinal side effects like ulcers and bleeding than drugs like ibuprofen or aspirin. Naproxen is associated with fewer cardiovascular risks like heart attack and stroke compared to other traditional NSAIDs as well. However, naproxen may be more likely to cause fluid retention and high blood pressure than some alternatives. And its long half-life could increase the risk of adverse effects with sustained use. Overall, naproxen is generally considered one of the safer NSAID options, though side effects are still possible. Using the lowest effective dose for the shortest time can help minimize naproxen’s risks."

“The half-life of naproxen is approximately 12-15 hours. This means it takes around 12-15 hours for the level of naproxen in the body to be reduced by half after a dose is taken. Naproxen has a relatively long half-life compared to other NSAIDs like ibuprofen, which has a half-life of only 2-4 hours. The longer half-life of naproxen can be advantageous in providing longer-lasting pain
relief”

Safety:
"The cohort included 48566 patients recently hospitalized for myocardial infarction, revascularization, or unstable angina pectoris with more than 111000 person-years of follow-up. Naproxen users had the lowest adjusted rates of serious coronary heart disease (myocardial infarction, coronary heart disease death) and serious cardiovascular disease (myocardial infarction, stroke)/death from any cause, with respective incidence rate ratios (relative to NSAID nonusers) of 0.88 (95% CI, 0.66 to 1.17) and 0.91 (0.78 to 1.06). Risk did not increase with doses >or=1000 mg. Relative to NSAID nonusers, serious coronary heart disease risk increased with short term (<90 days) use for ibuprofen (1.67 [1.09 to 2.57]), diclofenac (1.86 [1.18 to 2.92]), celecoxib (1.37 [0.96 to 1.94]), and rofecoxib (1.46 [1.03 to 2.07]), but not for naproxen (0.88 [0.50 to 1.55]). Relative to naproxen, current users of diclofenac had increased risk of serious coronary heart disease (1.44 [0.96 to 2.15], P=0.076) and serious cardiovascular disease/death (1.52 [1.22 to 1.89], P=0.0002), and those of ibuprofen had increased risk of the latter end point (1.25 [1.02 to 1.53], P=0.032). Compared to naproxen in doses >or=1000 mg, serious coronary heart disease incidence rate ratios were increased for rofecoxib >25 mg (2.29 [1.24 to 4.22], P=0.008) and celecoxib >200 mg (1.61 [1.01 to 2.57], P=0.046).

Conclusions: In patients recently hospitalized for serious coronary heart disease, naproxen had better cardiovascular safety than did diclofenac, ibuprofen, and higher doses of celecoxib and rofecoxib."

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#4

Your post is helpful @desertshores. I take maybe one ibuprofen a year but have been getting more sports injuries lately and wondering about alternatives. If you are taking naproxen for, say, a week, how do you titrate the dose down to account for the fact that each day’s dose is adding to a cumulative base level of build up?

As for longevity claims, in advance of better data, a guess is that most of it is artifact but there could be some long term benefit in the reduction of inflammation for those with higher levels. Maybe other things too. The claim of 10% is not trivial.

#5

Related discussions here: First report from Epiterna on the search for drugs that can extend human lifespan

and here: These four common medicines could help prolong your life (Viagra, atorvastatin, naproxen, oestrogen)

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#6

Naproxen has a half-life of ~12-24 hrs. If we use 18 hrs. as a compromise:
(from the drug half-life calculator}

“Repeat the dose every 24 hours to reach a steady state in 6 doses or 6 days. Concentration in your body will vary at 143.33 - 363.33mg with an average of 253.33mg.
You will eliminate 97% of the drug in 3.79 days if you quit cold turkey.”

The recommended maximum daily dose of naproxen depends on the formulation:
For immediate release naproxen sodium (e.g. Anaprox, Naprosyn):
Initial dose: 550 mg
Maintenance dose: 550 mg every 12 hours or 275 mg every 6-8 hours as needed
Maximum daily dose: 1375 mg on day 1, 1100 mg after that

Of course, we know that with NSAIDs the lowest dose that does the job is better.
Until I started using Naproxen I was using Ibuprofen for muscle pain caused by exertion.
I was using 2 tablets of Ibuprofen (400mg total) before I went to bed if I still had muscle pain in the evening from exercise etc. Now I find that just 220 mg of Naproxen provides the same pain relief as 400mg of Ibuprofen and works much longer than a dose of ibuprofin

Rather than taking a higher dose of the NSAIDs, you could add a dose of gabapentin if you have it. The doctors I have been going to over the years seem to have no problem prescribing it if you ask them. Just, say you have some neuropathic pain somewhere.

“Several studies have shown improved pain relief with the combination of gabapentin and an NSAID compared to either drug alone in conditions like chronic back pain, arthritis pain, and neuropathic pain. The synergistic effects allow for lower dosages of each drug to be used, reducing side effects.”

Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model - PubMed.

Evaluation of interaction between gabapentin and ibuprofen on the formalin test in rats - PubMed.

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#7

Thank you for the detail @desertshores. I’m going to try it next time.

#8

NSAIDs ramp up my tinnitus, including Naproxen which is my go to for pain. I had chronic headaches for 20 years and used a variety of NSAIDs to deal with that.

About 20 years ago I read that chronic NSAID use caused headaches. I stopped taking NSAIDs for every little thing, including headaches and shortly after that I stopped getting headaches.

To this day I probably get 1 headache a year, if that.

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