Jump to content

Recommended Posts

[Admin Note - This thread started with this post on the "Organ Donation" thread, where Thomas asked about aspirin in the context of kidney donation, where he said:


One thing that I didn't know before, and that I would like to learn more about, is that people who donate a kidney can't take aspirin anymore. I wonder why that is. It also gives me pause since aspirin might be pretty beneficial. I don't currently take a baby aspirin, but after watching that interview with Judith Campisi I wonder if it could be useful to suppress low-grade inflammation.


Lifelong aspirin supplementation as a means to extending life span. 



Thanks Dean. Do you think there is wisdom in regularly (or semi-regularly) taking a baby aspirin to suppress low-grade inflammation? I've just gotten started looking into it, and as usual, I feel like it is hard to keep perspective. As a layperson with limited time I can go down a rabbit hole and end up more confused than when I started. To some degree I feel like I need to rely on the general sense of a larger community of interested laypeople and experts. I'm not quite sure what that is in this case. Aspirin seems promising, but I'm wary of the side effects.

Link to comment
Share on other sites



I'm not an expert and haven't looked into aspirin in quite some time. But my impression is the reduction in inflammation it affords is not worth the risk (primarily increased chance of gastrointestinal bleeding) for people who follow a healthy diet and lifestyle.


Many years ago I took a baby aspirin a day for a while, but stopped after I reached this conclusion.



Link to comment
Share on other sites

FWIW, I seem to recall some discussion of aspirin years back, and MR made the observation that the inflammation suppressing properties of aspirin did not translate into any life prolonging benefits, contrary to expectations. Unfortunately, I don't remember if there were any studies he cited. And like Dean, I too investigated aspirin, particularly with the view of it possibly being helpful wrt. to cancer. given that according to 23andme I am vulnerable to PC. I concluded back then (some years ago), that the risks were not worth it, especially that the cancer benefits were unclear and largely consisted of benefits vis a vis colon cancer and only in those individuals who had a particular genetic profle where their colon cancer vulnerability was impacted by aspirin, so unless you knew if you were one of those people, the colon cancer aspect was irrelevant. Meanwhile the risks were not limited to gastric issues, but also to stroke, damage to hearing and a few other things. However, things might have shifted somewhat, in that the latest studies seem to indicate that the cancer benefit is more robust, so it may be time to look into preventive aspirin again. YMMV.

Link to comment
Share on other sites

Thanks Tom. You may have seen Dr. Greger's recent video on the cost benefit analysis of taking a baby aspirin for cancer suppression: 


As you might be able to guess, the conclusion he comes to is that instead of taking a baby aspirin, we should all just eat a whole food plant based diet full of dark green leafy vegetables.


I'd be curious to read the studies MR used to come to his conclusion. As best I can tell so far it is still sort of an open question. It seems like aspirin *should* lead to longevity, but we really don't know for sure yet. Given that aspirin seems like one of the more magical medicines out there, one that is still surprising us, I want to weigh any possible inability to take aspirin in the future in terms of kidneys. Of course by then it will likely be possible to print or grow a second kidney and go back up to two if that is helpful. It's hard to predict the future. I'd just like to have as much info as I can so I don't do something I later regret for some reason.

Link to comment
Share on other sites

Thanks for that, Thomas, certainly true - I guess I must be getting a fair amount of salicylates in my food. Anyhow, I couldn't locate the exact discussion I remember, but I took a brief look at my gmail archives and there is an interesting discussion of aspirin with MR on 05/29/12 on the list - I can't reproduce it here, as I doubt I'd be able to get clearance to repost from the many participants who are no longer active and probably can't be contacted. But if anyone already has access to list archives, that's the date to look for.

Link to comment
Share on other sites

There are some  potential gastroprotective agents that might mitigate the negative  effects of aspirin.  I haven't researched the subject too deeply, but below are a few possibilities (putting aside proton pump inhibitors and helicobacter pylori eradication.) I'm sure there are others to be considered.


  At this point, I don't do the low-dose aspirin thing, following Dean's reasoning, but it's an interesting topic.  If there were safe and effective gastrprotective measures that could be taken, that might tilt things in aspirin's favor.



Dietary nitrate and reductive polyphenols may potentiate the vascular benefit and alleviate the ulcerative risk of low-dose aspirin.




The recent revelation that daily low-dose aspirin not only lowers risk for vascular events, but also can notably decrease risk for a range of adenocarcinomas, decreasing total cancer mortality by about 20%, makes it highly desirable to implement this protective strategy on a population-wide basis. Nonetheless, the fact that low-dose aspirin approximately doubles risk for serious gastrointestinal bleeding may impede health authorities from recommending its use by people judged to be at low cardiovascular risk. Nitric oxide (NO) exerts gastroprotective effects by boosting blood flow and mucus production in the gastric mucosa - effects which demonstrably oppose the pro-ulcerative impact of aspirin and other NSAIDs. A nitrate-rich diet, as well as ingestion of reductive catechol-bearing polyphenols, can collaborate in promoting NO generation in gastric juice, and they are protective in rodent models of gastric ulceration. Moreover, a high-nitrate diet, as well as certain reductive polyphenols such as epicatechin and quercetin, can exert platelet-stabilizing effects complementary to those of aspirin, and act in other ways to preserve vascular health. Hence, diets rich in nitrate and reductive polyphenols have the potential to amplify the vascular-protective benefits of low-dose aspirin, while diminishing its pro-ulcerative risk. Low-dose aspirin may be more unequivocally recommendable within the context of such a dietary strategy.


PMID:  23265354



[Typical nitrate-rich foods:  arugula, spinach, lettuce, beets, radishes, celery, dill, cilantro.. -- Sibiriak.]



Gastroprotective [6]-Gingerol Aspirinate as a Novel Chemopreventive Prodrug of Aspirin for Colon Cancer

Ginger (Zingiber officinale) is widely used as a spice and an ingredient in traditional herbal medicine. The rhizome of ginger has been shown to ameliorate symptoms such as inflammation, rheumatic disorders, gastrointestinal discomforts, and nausea and vomiting associated with pregnancy1. Considerable evidences in preclinical and clinical studies have been reported regarding the gastroprotective effects of ginger root extracts or ginger essential oils2,3,4,5. Recently, ginger powder has been shown to prevent the aspirin-induced gastric ulcer formation but does not affect gastric juice, acid production or mucosal prostaglandins (PGs) content in rats6. [6]-gingerol (6G) is one of the major active components of fresh ginger7, and has been reported to exert antioxidant, anti-inflammatory, and anti-cancer activities1. Recent reviews demonstrate the role of 6G in prevention and treatment of gastrointestinal cancer8, suggesting 6G as a cancer chemopreventive agent9. Besides antiproliferative properties, 6G has also been reported to reduce the formation of HCl/ethanol- or aspirin-induced gastric lesion in rats6,10. With reported anti-cancer and gastroprotective properties, 6G can serve as a lead compound for the discovery of new anticancer drug.





Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humans.


Melatonin and its precursor, l-tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l-tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E(2), and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA induced gastric lesions and microbleeding. Gastric mucosal generation of PGE(2) was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone.


We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan.


PMID: 20443220


The present study included 21 healthy, Hp-negative male volunteers with intact gastro-duodenal mucosa aging 20-50 yr. They were divided in 3 groups; group1: 7 volunteers receiving daily 2 x 1g ASA (Polfa, Rzeszow) during 11 days; group 2: 7 healthy volunteers receiving 2x1g ASA and MT (Lekam, Zakroczyn) (5 mg 30 min prior to ASA) during 11 days and group 3: 7 healthy volunteers receiving 2x1g ASA and Trp (Ardeytropin, Germany) (0.5 g 30 min prior to ASA) during 11 days. Mucosal damage was evaluated at 3rd, 7th and 11th days of ASA administration by endoscopy using Lanza score. Plasma melatonin was measured using RIA and gastric mucosal generation of PGE2 was assessed also by RIA. ASA caused marked mucosal injury at all days of its administration except day 11th when only moderate lesions were evident. Pretreatment with MT or Trp alone was accompanied by a significant decrease in gastric mucosal lesion score.





Mucosal strengthening activity of central and peripheral melatonin in the mechanism of gastric defense



Gastroprotective Effects of Flavonoids in Plant Extracts


We conclude that plant-originated flavonoid substances are highly gastroprotective probably due to enhancement of the expression of constitutive NOS and release of NO and neuropeptides such as calcitonin gene related peptide (CGRP) released from sensory afferent nerves increasing gastric microcirculation.





The Protective Effect of Aged Garlic Extract on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Inflammations in Male Albino Rats



A combination of aspirin and γ-tocopherol is superior to that of aspirin and α-tocopherol in anti-inflammatory action and attenuation of aspirin-induced adverse effects



Aspirin and Vitamin C Together at Last  [ gastroprotection from Vitamin C,  SAMe,  deglycyrrhizinated licorice (DGL) ]



Regular ingestion of cinnamomi cortex pulveratus offers gastroprotective activity in mice.



Gastroprotective capability of exogenous phosphatidylcholine in experimentally induced chronic gastric ulcers in rats. PMID:8430278



Preventive maintenance for your stomach, liver and pancreas



Gastroprotective effect of L-carnitine on indomethacin-induced gastric mucosal injury in rats: a preliminary study. PMID:17668703


Link to comment
Share on other sites

On a related note:

Buck Institute for Research on Aging:


Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of
Tryptophan Import



The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.


PMID:  25521617



Link to comment
Share on other sites

Another potential gastroprotective agent--capsaicin.



Capsaicin may have important potential for promoting vascular and metabolic health



PMCID: PMC4477151


[...]there is evidence that capsaicin tends to prevent and accelerate healing of gastric ulcers.68–70 This phenomenon reflects capsaicin's ability to inhibit gastric acid secretion, boost secretion of alkali and mucous, and stimulate gastric blood flow. A clinical study found that the gastric tissue damage and microbleeding induced acutely by indomethacin or ethanol ingestion was blunted if capsaicin was administered concurrently.69These findings have prompted the suggestion that capsaicin could be used as a protective adjuvant to non-steroidal anti-inflammatory drug therapy.6970 Limited epidemiology suggests that gastric ulcers may be less common in ethnic groups that prefer spicy foods.68
Capsaicin as new orally applicable gastroprotective and therapeutic drug alone or in combination with nonsteroidal anti-inflammatory drugs in healthy human subjects and in patients.
PMID: 24941671

Capsaicin decreased the gastric basal output, enhanced the "non-parietal" (buffering) component of gastric secretory responses, and gastric emptying, and the release of glucagon. Capsaicin prevented the indomethacin- and ethanol-induced gastric mucosal damage; meanwhile capsaicin itself enhanced (GTPD). Capsaicin prevented the indomethacin-induced gastric mucosal microbleeding. The expression of TRVP1 and CGRP increased in the gastric mucosa of patients with chronic gastritis (independently of the presence of Helicobacter pylori infection), and the successfully carried out eradication treatment. The human first phase examinations (the application of acetylsalicylic acid (ASA), diclqfenac, and naproxen together with capcaicinoids) (given in doses that stimulate capsaicin-sensitive afferent vagal nerves) showed no change in the pharmacokinetic parameters of ASA and diclofenac and the ASA and diclofenac-induced platelet aggregation.


Capsaicin represents a new orally applicable gastroprotective agent in healthy human subjects and in patients with different chemical and Helicobacter pylori-induced mucosal damage and in many other diseases requiring treatment with NSAIDs.



Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).





Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.



Capsaicin has the added benefit of  working synergistically with cold exposure to increase BAT development,  as Dean Pomerleau pointed out in his brilliant exploration of that topic.


See:  https://www.crsociety.org/topic/11488-cold-exposure-other-mild-stressors-for-increased-health-longevity/page-6?do=findComment&comment=15538)

Link to comment
Share on other sites

  • 3 weeks later...

Gastroprotective effects of phospholipids (PLs):



Health Effects of  Dietary Phospholipids

Küllenberg et al. Lipids in Health and Disease 2012, 11:3


Since NSAIDs (e.g. aspirin and ibuprofen) are not specific in inhibiting COX-2, the cyclooxygenase isoenzyme which is expressed under pathological conditions, they also affect the activity of the constitutively expressed COX-1 isoenzyme. COX-1 is - among other functions - in charge of regulating the production of natural mucus in the stomach to protect it from the secreted gastrointestinal (GI) acid and from pepsin hydrolysis during digestion, by catalyzing the production of PGE2 from AA, which reduces gastrointestinal acid production. This is the reason for the well known GI side effects of NSAIDs, since the GI protective effects of the mucus production are impaired by the unwanted inhibition of COX-1.


However, a GI protective effect of PLs was shown with soybean PC (Phospholipon®100 [100% native soybean PC [phosphatidylcholine] as a powdered compound]), which reduced gastric mucosal lesions in  rats after the treatment with NSAIDs (aspirin, indomethacin,  phenylbutazone, diclofenac, piroxicam and sudoxicam). Co-administration of Phospholipon®100 with NSAID improved the drug tolerability and reduced  the typical GI side effects, likely due to an increased  production of cytoprotective mucosal PGE2 [13]. Since soy PC not contain AA [arachidonic acid] the necessary AA for the production of PGE2 was probably formed by the conversion of linoleic acid (n-6 FA) to AA by the enzymes delta-6-desaturase, elongase and delta-5-desaturase.


These GI-cytoprotective effects of PLs were also seen in patients presenting GI symptoms caused by a regular use of NSAIDs [14]. All patients were supplemented  with Phospholipon®100 for 14 days resulting in ulcer healing as well as diminished upper abdominal pain. Another study by Dial et al. describes the beneficial effects of PC pretreatment (Phospholipon®90G [94-100% PC, LysoPC and tocopherol as powdered compound]) in preventing LPS [lipopolysaccharide] induced permeability changes  of the GI tract in rats. This study shows that PC has protective effect not only due to supporting the PGE2-production [15].


Already in 1984 it has been found that (milk) PLs have a protective effect against gastric acid. An investigation in rats showed that treatment with milk reduced the ulcerating effects of intraluminal application of HCl. This effect was attributed to the concentration of di-palmitoyl-PC (DPPC), which is one of the major components of milk PLs [16]. During the following years the same group of researchers could substantiate their original findings with a large number of animal and human studies [17-19].


[...]In addition, PLs have shown to improve the pharmacokinetics of some drugs including NSAIDs. Lichtenberger  et al. and Dial et al. have demonstrated soybean PC (formulation of NSAIDs with Phospholipon®90G, see table 2) to increase the anti-inflammatory and analgesic activity of NSAIDs in acute and chronic models of arthritis, by enhancing its transport and bioavailability [13,23-25]. Therefore, the administration of NSAIDs together with PLs could be an interesting attempt to not only enhance their analgesic activity, but also in diminishing the known side effects and reducing the risks caused by their regular use.

[emphasis added]

Link to comment
Share on other sites

I'm just wondering, why not to take the natural parent of aspirine, salicilyc acid itself?




Salicylic acid activates adenosine monophosphate-activated protein kinase (AMPK) and this action may play a role in the anticancer effects of the compound and its prodrugs aspirin and salsalate. The antidiabetic effects of salicylic acid are likely mediated by AMPK activation primarily through allosteric conformational change that increases levels of phosphorylation.


Original research article

Naturally occurring dietary salicylates: A closer look at common Australian foods







Dietary salicylates may have similar benefits and/or adverse symptoms as documented for Aspirin. To develop dietary strategies, data on salicylate content of food is essential, but the available literature is limited and controversial. Hence the aims of this study are to apply and validate a reliable methodology to determine the salicylate content of common foods, and compare with recently published data. Gas chromatography-mass spectrometry (GC–MS) was used with SA-d6 (deuterated salicylic acid) as an internal standard to analyse 112 common Australian food items pooled from ten different sources. Technical sextuplicates show a coefficient of variation of 3.03%. SA content ranged from 1.28–26.93 (vegetables), 2.13–36.90 (fruits), 2.80–604.97 (herbs/spices) and 2.04–51.48 (beverages) mg/kg. SA was undetected in oils, sugars and cereals analysed. The results reveal inconsistencies within the extant literature and a pressing need for further research extending the analysis to a broader range of food items.

Link to comment
Share on other sites

And let's not forget that aspirin isn't the only NSAID with potential healthspan/lifespan-increasing potential-- ibuprofen is another option (see post above.)




Another example:


Ibuprofen enhances TRAIL-induced apoptosis through DR5 upregulation


Colorectal cancer is the second most common cancer in developed countries (1); therefore, chemoprevention for colorectal cancer is indispensable. Clinical and preclinical studies provide strong evidence that non-steroidal anti-inflammatory drugs (NSAIDs) can prevent numerous types of malignant tumors (2,3), particularly colorectal cancer (4-7). Also in Japan, double-blind randomized clinical trials have been registered to elucidate the preventive effects of low-dose aspirin on colorectal cancer and adenoma growth (8,9). Among these studies, many reports on aspirin have been published; however, a greater risk of bleeding complications remains with aspirin (10), and its chemopreventive potential might be limited. Thus, we focused on ibuprofen, one of the most commonly used NSAIDs as a worldwide over-the-counter (OTC) drug. The anti-inflammatory effect of ibuprofen was found to exceed aspirin (11) and the side effects are fewer than other NSAIDs.

Link to comment
Share on other sites

A fast read of the cited article and its tables reveals that dietary SA can be reasonably assumed in quantities that hardly can be higher than 10-20% max of the 81 mg ASA in a baby aspirin. Of course compounds from natural foods often have been observed to be more active and effective than as supplements, so Dr. Gregers conclusions: just eat lots of plant-based foods may not be so unreasonable after all .

Link to comment
Share on other sites

  • 3 weeks later...
Effects of NSAIDs on the risk factors of colorectal cancer: a mini review

Genes and Environment  2016



Excerpts (emphasis added) :


A large number of epidemiological and experimental studies have shown that NSAIDs reduce the risk of colorectal cancer (CRC). Meta-analysis of randomized trials revealed that use of aspirin for approximately 5 years reduces incidence and mortality due to CRC by 30–40 % after 20 years of follow-up [1].


The effectiveness of NSAIDS may be attributed to their potent inhibition of cyclooxygenase (COX) enzymes because COX-2 expression and prostaglandin (PG) E2 synthesis are elevated in CRC. The COXs/PGH synthases have two enzymes, COX-1 and COX-2, and COX is the limiting enzyme of the PG synthesis pathway. The constitutive enzyme COX-1 has low expression in normal human colorectal tissue, whereas the inducible enzyme COX-2 is elevated in tissue involved in inflammation and in cancer.


Traditional NSAIDs block the actions of both COX-1 and COX-2, and selective COX-2 inhibitors are a special category of NSAIDs. In addition, aspirin can inhibit proliferation and induce apoptosis of colon cancer cells [2]. The inhibition and induction by aspirin include the following: (i) the interruption of nuclear factor kappa B (NF-κB), (ii) the interruption of extracellular signal-regulated kinases, (iii) the induction of caspase 8 and 9, and (iv) the inhibition of β-catenin signaling.


As shown above, the function and molecular targets of NSAIDs have been well studied, and several pieces of evidence have shown their chemopreventive effects on CRC.


Aging and NSAIDs

Disruption of normal tissue function dramatically accelerates in old age. Aging is the greatest risk factor for numerous pathologies, including cancer, stroke, neurodegenerative disorders, heart disease and type-2 diabetes [5]. Chronic inflammation is one of the main processes that contributes to age-related disease and causes disruption of normal functioning of tissues. Notably, there is a robust increase of mRNA and secretion of numerous cytokines, chemokines, growth factors and proteases in the senescent cells, and these cells may cause a low level of chronic inflammation systemically during aging [39].


Yeast, nematodes and flies have been recognized as excellent model systems for studying the underlying mechanism of aging and identifying chemicals altering longevity, mainly because of their short lifespans. A growing number of reports showed the effects of NSAIDs on the lifespan extension in yeast [40], nematodes [40, 41], flies [40, 42] and mice [43]. He et al. [40] reported that ibuprofen extended the replicative life span of Saccharomyces cerevisiae cells by destabilizing the high-affinity tryptophan transporter. He et al. also found that ibuprofen caused small size at birth and moderate delay in initiation of cell division, which was observed in most long-lived yeast mutants. Meanwhile, celecoxib extended both mean and maximum lifespans in C. elegans



[...]  Thus, NSAIDs might be effective for slowing aging and prevention of age-related diseases through not only their anti-inflammatory effects via COX-2 inhibitory action but through potential secondary targets including PDK-1 inhibition and the anti-oxidative effect.


 [..] Metformin, an insulin resistance-improving, anti-diabetic agent, has been reported to reduce risks of various cancers including colon cancer in diabetic and non-diabetic populations [22, 23]. Metformin inhibits cell proliferation via activation of AMP-activated protein kinase (AMPK) [24]. Serum adiponectin is decreased in obese people, and also activates AMPK and inhibits cell proliferation of colon cancer cells [24].


Recently, it has been reported that aspirin activates AMPK and inhibits mTOR signaling in colon cancer cells [25]. Not all, but several NSAIDs, such as salicylic acid, ibuprofen or diclofenac, which have acidic structures, also induce AMPK activation [26, 27]. This effect is considered to be a COX-independent anti-inflammatory property of aspirin and a subgroup of NSAIDs and may contribute to decrease obesity-related cancer risks


Alcohol and NSAIDs

In a meta-analysis of cohort and case–control studies, there are reports describing moderately increased risks of CRC with a dose–response relation for rising alcohol consumption. A polled analysis of eight cohort studies also recorded a dose–response relation between the risk of CRC and the amount of alcohol consumption [28].


The mechanisms by which alcohol intake exerts its carcinogenic effect are not fully understood yet. Acetaldehyde, a metabolite of alcohol, is implicated in esophageal carcinogenesis but is not strongly implicated in colorectal carcinogenesis. Recently, single nucleotide polymorphisms (SNPs) in the alcohol dehydrogenase, ADH1B, and aldehyde dehydrogenase, ALDH2, of moderate/heavy drinkers were shown to be contributing factors for CRC [29]. Aspirin and salicylate could inhibit both human ADH (metabolize ethanol to acetaldehyde) and ALDH (degradation of acetaldehyde) activities [30]. To date, the effect of aspirin on acetaldehyde production is not fully understood yet.


Ethanol is known as an irritant for the digestive tract. Ethanol intake is known to be an independent risk factor for GI bleeding. It is posited that the GI bleeding risk from aspirin is high in individuals who consume three or more alcoholic drinks every day [31].


Several reports suggest that ethanol exposure alters the cytokine levels and inflammatory status in a variety of tissues in vitro and in vivo, including the colon [32, 33]. Furthermore, chronic alcohol intake promoted intestinal tumorigenesis and tumor invasion in Apc Min/+ mice [34]


[...]These reports suggest that the carcinogenic effect of alcohol may be partly through the induction of acetaldehyde and inflammation, and NSAID use may effectively protect CRC development in a social drinker.


Triglycerides and NSAIDs


[...] high TG might be understood as a risk factor for CRC [47, 48].


On the other hand, there are a variety of discussions about whether NSAIDs can adjust the TG value. NSAIDs can inhibit the enzymatic activity of COX and attenuate the expression level of PGE2. PGE2 is activated through an EP3 receptor at the thermoregulatory center in the hypothalamus and functions to raise the set point of body temperature by increasing the cellular metabolism. This linkage means NSAIDs decrease TG levels. Furthermore, PGE2 induces the expression of TNFα, and the TG value also increases because of the inhibition of lipoprotein lipase (LPL) [49]. LPL catalyzes the hydrolysis of plasma TG.


* * *

[...]This TG-lowering effect could not be explained by enhanced VLDL-TG clearance, but aspirin selectively reduced hepatic production of VLDL-TG in both APOC1 (−28 %, P < 0.05) and wild-type mice (−33 %, P < 0.05) without affecting VLDL-apoB production [52]. In humans, higher proportions of patients in the salsalate (one of the NSAIDS) treatment groups experienced decreasing circulating TG values and increasing adiponectin concentrations [53].


For preventing colorectal carcinogenesis, significant consideration should be given to the use of NSAIDs to decrease plasma TG levels.

Link to comment
Share on other sites


This topic is now archived and is closed to further replies.

  • Create New...