about aspirin

[Maxone73]

in absence of a good amount of clinical trials, we rely on the source reputation

nature.com/articles/s41416-...

[jazj]

That's a good well-balanced article. Thanks for posting. Aspirin is a subject I recently revisted. A side discussion in another thread more specifically focused on resolvins is what re-peaked my interest.

Unfortuntely, as @Tall_Allen will attest to, there is no well-designed human study showing any significant benefit regarding Prostate Cancer Specific Mortality (PCSM)

bmccancer.biomedcentral.com...

"A total of 10 eligible articles were used in our study.... we found no significant association between aspirin use or its duration and the risk of PCSM (Prostate Cancer Specific Mortality)"

Also a half baby aspirin every other day (40mg) or 20 mg a day is enough to decrease TXA2 by 90% without increasing bleeding time in the latter. Risk of upper GI bleeding is low and dose dependent so at those small doses I'm guessing it's practically insignificant and probably risk of stroke also.

pubmed.ncbi.nlm.nih.gov/879...

"A dose-related increase in bleeding time occurred with 40 mg and 80 mg of LDA, but not with the 20 mg dose or placebo. Platelet aggregation studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA. The PGI2/TXA2 ratio increased with aspirin doses as low as 20mg, with a decrease in TXA2 metabolites but not in PGI2 metabolites. Serum salicylate was not detectable in any sample from any patient.

There is evidence it helps prevent colon cancer.

jamanetwork.com/journals/ja...

"pooled analysis of 2 cohort studies with a total of 94 540 participants... After adjustment for other risk factors, regular use of aspirin was associated with a significantly lower risk of CRC at or after age 70 years compared with nonregular use (HR, 0.80; 95% CI, 0.72-0.90). However, the inverse association was evident only among aspirin users who initiated aspirin use before age 70 years (HR, 0.80; 95% CI, 0.67-0.95). In contrast, initiating aspirin use at or after 70 years was not significantly associated with a lower risk of CRC (HR, 0.92; 95% CI, 0.76-1.11)."

I can find no evidence indicating human trials and necessary dosage for benefit of increased resolvins. (Note that EPA from Omega-3 Fatty Acid also increases resolvins.) But as initially mentioned, if the theory on aspirin and resolvins clearing out dead cancer cells was practically applicable then why would studies involving prostate cancer not see a significant reduction in Prostate Cancer Mortality? My take: because like a lot of other novel treatment ideas, it's more of a theory (based on in-vitro and in-vivo animal studies) than a proven effective treatment for PCa in humans.

Beware, like curcumin, aspirin may act to mask PSA so it may be wise to stop taking it a 5-7 days before a blood test.

ncbi.nlm.nih.gov/pmc/articl...

"Multiple epidemiological studies have reported an increase in high-grade PCa (HGPCa) in aspirin users (Bosetti et al., 2012; Olivan et al., 2015). One suggested explanation found in the literature is that aspirin and other NSAIDs lower PSA levels, but is not itself anti-tumorigenic (Berg et al., 2009; Schroder et al., 2009). If true, this would likely delay diagnosis of the disease, allowing it to progress unnoticed. Alternatively, it was also suggested that these drugs might relieve cancer-associated pain that normally motivates patients to investigate their symptoms earlier on. In contrast, it must also be noted that other studies show decreased levels of HGPCa in chronic aspirin users (Brasky et al., 2010; Dhillon et al., 2011). More conclusive research needs to be conducted to determine the mechanism by which aspirin decreases PSA: whether this is a by-product of the drug's anti-tumorigenic properties or truly a masking effect. Nonetheless, physicians should be weary of the accuracy of the PSA blood test in patients taking aspirin chronically."

If the anti-metastatic mechanism in colon and lung cancer is related to decreasing PGI2 and PGE2, the 20-40 mg doses may be too little.

pubmed.ncbi.nlm.nih.gov/141...

Overall it's an interesting subject but unfortunately I can't find any convincing evidence it makes a significant different in actual humans with prostate cancer. The evidence found in Colon and Lung cancer does not appear to have translated to Prostate Cancer. But I think possibly taking an ultra-low dose to reduce TXA2 production may only have potential upside in general (assuming one is not on blood thinners) but it does not appear to have a significant effect on Prostate Cancer.

A couple other studies (thanks to Tall_Allen)

thelancet.com/journals/lanc...

ncbi.nlm.nih.gov/pmc/articl...

This is not to say there isn't a single study showing benefit but the vast majority of evidence shows no statistically significant benefit at least as far as prostate cancer. I was able to find this one with positive evidence:

pubmed.ncbi.nlm.nih.gov/229...

[Maxone73 in reply to jazj]

most take it because they have lynch syndrome or they try to delay metastasis spread, evidence exists but it’s not very consistent and people tend to underestimate aspirin, which would effect the platelets count for 96 hours even at low dosage, so I would stay away from it daily unless there was a real risk of trombosis

The effect of aspirin on metastatic spread is of importance because metastases are responsible for much of the pain and the complications of cancer [20] and many of the deaths are attributable to metastases [21]. Platelets play a significant role in metastatic spread, and the relationship between these effects and the clinical outcomes has been detailed elsewhere [2, 22].

There appears to have been no systematic literature search and meta-analysis of clinical data on metastatic cancer, but many studies and overviews give evidence of substantial reductions by aspirin (ranging from about RR 0.48 (95% CI 0.30 to about 0.75), to RR 0.62 (0.52 and 0.75) [23, 24].

It is important to note that an effect on cancer spread indicates a value of aspirin that is independent of its effects upon cancer mortality [24,25,26]. Indeed any delay in the diagnosis and initiation of treatment would seem to make a reduction in metastatic spread of increased value.

November 2023 article

nature.com/articles/s41416-...

anyway, my role here (as it was when I was a researcher) is to inform, not to suggest treatments, and I always specify when it’s clinical or in vivo/in vitro, so any help is welcome 😊

[jazj in reply to Maxone73]

I've decided to add 20 mg aspirin to my daily regimen. I think that dose in the context of preventing or delaying PCa metastasis may have the lowest risk/reward ratio based on all the info I digested. (I agree with you about staying away from taking it daily but at higher doses than 20mg.) I bought a cheap pill cutter off Amazon but cutting a baby aspirin in quarters is still not clean so I imaging the actual does is ranging 18-22 mg probably. Thats fine as the TXA2 suppression effect lasts a long time (full suppression potential isn't reached until 7-10 days of dosing). But this also means I'll have to remember to stop taking it at that low of a dose probably at least 5-7 days before blood tests to make sure any potential PSA masking effect is non-significant.

ahajournals.org/doi/pdf/10....

"Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI, produced by vascular tissues of control subjects who received no aspirin preoperatively (51 ± 10 pg 6-keto-PGF1J/mg aortic wet weight [mean + SEM] in aspirin-treated subjects vs 130 ± 16 pg/mg in control subjects, and 71 + 8 pg/mg saphenous vein wet weight vs 131 + 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 ± 229 ml in aspirin-treated subjects vs 645 + 271 ml in control subjects), hematocrit nadir (31.2 ± 1.9% vs 31.8 1.7%), or transfusions (2.2 + 1.3 units of red blood cells vs 2.2 ± 1.7 units)"

[Maxone73 in reply to jazj]

looks like a good plan! I wanted to test the effect of baby aspirin every other day myself, and platelets were 50% of what they were before, still normal but in the low range, I think 2 times per week might work and limit side effects

[jazj in reply to Maxone73]

A half baby aspirin every other day is easier to break up the pills. I would imagine any increase in risk of GI bleeding or bleeding time increase is probably not very different than 20mg a day. I just prefer to maintain a very consistent steady state.