Large & Unflattering Study On Aspirin

[General Orange]

What if we take Aspirin with some Boswellia or Ginger to inhibit 5-lipoxygenase LOX-5 ?

 

[Travis]

Wow, this might really explain some things for me. I loved aspirin, and I never had a major standalone asthma attack from taking it, but during my migraines, when I would take aspirin my breathing would be labored and my chest tight. I always attributed it to a symptom of the migraine, and I'm sure it has to do with serotonin, but I'm thinking that the aspirin exacerbated the issue for me. And then when I would feel a migraine coming on I started to take aspirin as a preventative measure along with other things like progesterone and high sugar foods, but I'm thinking that sometimes it would result in me breathing more poorly during the night and then waking up with a raging migraine. Great, several more studies that I need to read. Thanks, Travis!
By the way to all: I'm not trying to get into a philosophical debate about the virtues of aspirin, just sharing my experience!

Sanak, Marek. "Leukotriene C₄ synthase promoter polymorphism and risk of aspirin-induced asthma." The Lancet (1997)

'Aspirin-induced asthma (AIA) is a clear-cut clinical syndrome that affects about 10% of adult asthmatics. In these patients, aspirin and other cyclo-oxygenase inhibitors release cysteine-leukotrienes [sic] (cys-LTs) into airways and precipitate asthmatic attacks. Pretreatment with leukotriene-modifying drugs can attenuate these events. In bronchial biopsy specimens of AIA patients there is a profound over-representation of LTC₄ synthase (LTC4S), the perinuclear membrane enzyme that forms LTC₄, compared with aspirin-tolerant asthmatics (ATA) or controls. The increased numbers of cells expressing LTC₄ synthase in AIA bronchial biopsy specimens correlated with increased LTC₄ in bronchoalveolar lavage fluid and with bronchial hyperresponsiveness to inhaled lysine-aspirin. LTC₄S⁺ cells were predominantly eosinophils and a small number were mast cells. The gene for LTC₄ has been localised to the chromosome 5q35 region, telomeric to other candidate asthma genes. Polymorphism directed to regulation of LTC₄ expression could predispose to this highly leukotriene-dependent asthma. We searched for genetic polymorphism in the LTC₄S locus in our AIA patients.' ―Sanak
​

Christie, Pandora. "The potent and selective sulfidopeptide leukotriene antagonist, SK&F 104353, inhibits aspirin-induced asthma." American Review of Respiratory Disease (1991)

'SK&F 104353 is a selective and potent competitive leukotriene receptor antagonist. It is an effective antagonist against LTC₄...' ―Christie​

'We have now demonstrated that prior inhalation ofthe leukotriene antagonist SK&F 104353 attenuates aspirin-induced asthma in the majority of subjects studied. This provides direct evidence that the sulfidopeptide leukotrienes may be central to the mechanism of asthma provoked by aspirin. This view is consistent with other evidence implicating the role of leukotrienes in the pathogenesis of aspirin-induced asthma.' ―Christie​

 

[Travis]

What if we take Aspirin with some Boswellia or Ginger to inhibit 5-lipoxygenase LOX-5 ?

I suppose you'd then have to deal with free arachidonic and eicosapentaenoic acids unless you also inhibit phospholipase A₂. Baicalein is perhaps the most powerful natural lipoxygenase inhibitor, and also considerably reduces parameters of asthma:

Mabalirajan, U. "Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway." PLOS One (2013).​

 

[Ulysses]

I would say that it's both good and bad, yet this is highly circumstantial. I would also say that the net effect of aspirin depends on a person's eosinophil number and their ω−6/ω−3 ratio, and this is because leukotrienes made from ω−6 fatty acids are considerably more active. Aspirin's effects are too complex to be subjected to a good/bad dichotomy because I think it would come down to this question: 'Are prostaglandins always more physiologically important that leukotrienes?' I would imagine that were to to poll asthmatics and their physicians this question, the response 'no' would be more common than 'yes'—perhaps even more common than 'not sure.'

But, if you polled a group of estrogen-dominant patients with healthy immunity, and their physicians, the response 'yes' would be more common? Just want to make sure I'm following this argument.

 

[Waynish]

Wow, this might really explain some things for me. I loved aspirin, and I never had a major standalone asthma attack from taking it, but during my migraines, when I would take aspirin my breathing would be labored and my chest tight. I always attributed it to a symptom of the migraine, and I'm sure it has to do with serotonin, but I'm thinking that the aspirin exacerbated the issue for me. And then when I would feel a migraine coming on I started to take aspirin as a preventative measure along with other things like progesterone and high sugar foods, but I'm thinking that sometimes it would result in me breathing more poorly during the night and then waking up with a raging migraine. Great, several more studies that I need to read. Thanks, Travis!
By the way to all: I'm not trying to get into a philosophical debate about the virtues of aspirin, just sharing my experience!

Have you tried cyproheptadine 30m+ before taking the aspirin - and does it still affect your breathing then? Or perhaps strong ginger tea. I bet one of those two timed right would affect the breathing issue.

 

[General Orange]

I suppose you'd then have to deal with free arachidonic and eicosapentaenoic acids unless you also inhibit phospholipase A₂. Baicalein is perhaps the most powerful natural lipoxygenase inhibitor, and also considerably reduces parameters of asthma:

Mabalirajan, U. "Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway." PLOS One (2013).​

Thank you for your reaction. I think some ARA is oke coz I take Aspirin, ginger and coffee before exercise.
ARA supplementation significantly reduces AMPK activation when combined with exercise. Do you have any idea how much ARA would come free with Aspirin and Ginger supplementation in effective mg?

 

[ecstatichamster]

Thank you for your reaction. I think some ARA is oke coz I take Aspirin, ginger and coffee before exercise.
ARA supplementation significantly reduces AMPK activation when combined with exercise. Do you have any idea how much ARA would come free with Aspirin and Ginger supplementation in effective mg?

What is ARA?

 

[Ulysses]

What is ARA?

Arachidonic acid

 

[alywest]

Have you tried cyproheptadine 30m+ before taking the aspirin - and does it still affect your breathing then? Or perhaps strong ginger tea. I bet one of those two timed right would affect the breathing issue.

Interestingly ginger tea seems to really help with migraines, so I think that's the route I'll take in the future if I can. When the migraine is bad the ginger isn't enough, but I think partly why it helps the migraine is because of the effect on breathing, making it deeper and more productive. It helps with the gut in a way that the prescribed medications don't except maybe odansetrone.

 

[ecstatichamster]

Arachidonic acid

Thank you

 

[lollipop]

Interestingly ginger tea seems to really help with migraines, so I think that's the route I'll take in the future if I can. When the migraine is bad the ginger isn't enough, but I think partly why it helps the migraine is because of the effect on breathing, making it deeper and more productive. It helps with the gut in a way that the prescribed medications don't except maybe odansetrone.

I have found ginger tea very helpful for my GI and if you happen to be traveling in an unsanitary region and get traveler’s diarrhea, or even motion sickness, ginger works great .

 

[alywest]

I have found ginger tea very helpful for my GI and if you happen to be traveling in an unsanitary region and get traveler’s diarrhea, or even motion sickness, ginger works great .

Good, to know! Thanks Lisa! Ginger certainly seems to be a popular thing around these parts lately, and I am glad that it doesn't have any caveats from what I can tell. Plus it tastes awesome with lots of honey!

 

[Obi-wan]

The forgotten Med:

Alka-Seltzer is an effervescent antacid and pain reliever first marketed by the Dr. Miles Medicine Company of Elkhart, Indiana, United States. Alka-Seltzer contains three active ingredients: aspirin (acetylsalicylic acid) (ASA), sodium bicarbonate, and anhydrous citric acid.[1] The aspirin is a pain reliever and anti-inflammatory, the sodium bicarbonate is an antacid, and the citric acid reacts with the sodium bicarbonate and water to form effervescence.[2]

It was developed by head chemist Maurice Treneer.[3][4] Alka-Seltzer is marketed for relief of minor aches, pains, inflammation, fever, headache, heartburn, stomachache, indigestion, acid reflux and hangovers, while neutralizing excess stomach acid.[4] It was launched in 1931. -Wikipedia

"Plop, plop, fizz, fizz oh what a relief it is"...

 

[Obi-wan]

Interesting:

Anti-inflammatory

Anti-inflammatory, or antiinflammatory, is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the pain.

Side effects[edit]
Long-term use of NSAIDs can cause gastric erosions, which can become stomach ulcers and in extreme cases can cause severe haemorrhage, resulting in death. The risk of death as a result of GI bleeding caused by the use of NSAIDs is 1 in 12,000 for adults aged 16–45.[4] The risk increases almost twentyfold for those over 75.[4] Other dangers of NSAIDs are exacerbating asthma and causing kidney damage.[4] Apart from aspirin, prescription and over-the-counter NSAIDs also increase the risk of heart attack and stroke. -Maybe Alka-Seltzer for the older crowd...

Antileukotrines[edit]
Antileukotrines are anti-inflammatory agents which function as leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists (cysteinyl leukotriene receptors) and consequently oppose the function of these inflammatory mediators. Although they are not used for analgesic benefits they are widely utilized in the treatment of diseases related to inflammation of the lungs such as asthma and COPD as well as sinus inflammation in allergic rhinitis.[6][7] They are also being investigated for use in diseases and injuries involving inflammation of the brain (ex. Parkinsons disease).[8][9]

Health supplements[edit]
In addition to medical drugs, some herbs and health supplements may have anti-inflammatory qualities: bromelain from pineapples (Ananas comosus).[25] Cannabichromene, a cannabinoid, also has anti-inflammatory effect.[26] Honokiol from Magnolia inhibits platelet aggregation, and works as an inverse agonist at the CB2 receptor. Black seed (Nigella sativa) has shown anti-inflammatory effect due to its high thymoquinone content.[27] St. John's wort's chief constituent, hyperforin, has been found to be a potent COX-1 and 5-LO inhibitor, with anti-inflammatory effect several fold that of aspirin

The concomitant use of NSAIDs with alcohol and/or tobacco products significantly increases the already elevated risk of peptic ulcers during NSAID therapy

From Wikipedia

 

[Travis]

But, if you polled a group of estrogen-dominant patients with healthy immunity, and their physicians, the response 'yes' would be more common? Just want to make sure I'm following this argument.

I would say skateboarders that eat at ω−6 McDonalds would have a very high opinion of cyclooxygenase inhibitors, and this is because prostaglandin E₁ is highly involved in the pain response. While it's true that some simple oxygenated metabolites of linoleic and arachidonic acids also induce pain through the vanilloid receptor, such as 13-hydroxyoctadecadienoic acid, these have a different distribution in the body than do prostaglandin receptors. Cannabinoid receptors also modulate pain, yet they appear to do so more in rodents than in primates. Prostaglandin E₂ also appears to be carcinogenic growth factors, and prostaglandin D₂ involved in hair loss, yet there are more than a few ways to abrogate their formation. Thromboxane A₂ also has thrombotic activity, increasing the risk of stroke.

Patwardhan, A. "Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents." Journal of Clinical Investigation (2010)
Tohgi, H. "Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A₂ and prostacyclin." Stroke (1992)​

 

[Travis]

Thank you for your reaction. I think some ARA is oke coz I take Aspirin, ginger and coffee before exercise.
ARA supplementation significantly reduces AMPK activation when combined with exercise. Do you have any idea how much ARA would come free with Aspirin and Ginger supplementation in effective mg?

I know that arachidonic acid is often found on membranes around 10% of total fatty acids. Phospholipase A₂ is primarily responsible for releasing arachidonic acid from it's phospholipid backbone because it cleaves the fatty acid at the sn-2 position of the glyceride, specifically, the location where arachidonic acid is usually found. Saturated fatty acids are often found in the sn-1 position and the sn-3 position of phospholipids is usually occupied by: ethanolamine, serine, choline, or inositol. Phospholipase A₂ is somewhat of a prerequisite for eicosanoid synthesis that can be induced by cytokines, yet if you are taking supplemental arachidonic acid then some will likely bypass that enzyme entirely. While true that arachidonic acid (20∶4ω−6) does form endocannabinoids as well, so does the safer eicosapentaenoic acid (20∶5ω−3). However, you may not like taking EPA because it does the opposite: it activates AMP protein kinase.

Lorente-Cebrián, Silvia. "Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes." Clinical Science (2009)​

 

[General Orange]

@Travis So with Aspirin and Ginger, the ARA conversion, outside leukocytes, could still be converted via 12-lox and 15-lox then into its metabolites right? And in the leukocytes, I guess the ARA will just sit there doing nothing, waiting or will it be released?
You know if Aspirin also deals its cox inhibition in to cellular membranes other than leukocytes and platelets?

 

[General Orange]

I checked the actions of 5-LOX icw Aspirin and it seems that 5- LOX (ginger) interferes with the formation of "pro-resolvins" and anti-inflammatory lipoxins LXA4 and LXB4.

So I guess a 5-LOX with Aspirin is helpful to reduce asthma but blunt the repairing and anti-inflammatory effect of the Aspirin.
Therefore I will dump the Ginger and only be taking Aspirin with coffee.

Lipid Modulators of Inflammation: Role of Aspirin

IMG
Biological Activities of the Lipoxins
" Both LXA4 and LXB4 have been shown to promote the relaxation of the vasculature (both aortic and pulmonary relaxation). Lipoxins and epi-LXs inhibit polymorphonuclear leukocyte (PMN) chemotaxis, PMN-mediated increases in vasopermeability, and PMN adhesion and migration through the endothelium. The LXs also stimulate phagocytosis of apoptotic PMNs by monocyte-derived macrophages. PMN phagocytosis represents the resolution phase of inflammatory events, thus aspirin promotes this process and increases the rate of return to the normal tissue state. The pro-resolving activity of aspirin is exerted not only through the induced synthesis of the lipoxins, but also via the induced synthesis of an additional class of anti-inflammatory lipid mediators known as the resolvins (Rvs)and the protectins (PDs).

Additional anti-inflammatory actions of the lipoxins and aspirin-triggered lipoxins include blocking expression of the IL-8 gene (a pro-inflammatory chemokine produced by macrophages and endothelial that stimulates neutrophil migration), inhibition of the release and actions of tumor necrosis factor-α (TNF-α), and stimulation of transforming growth factor-β (TGF-β) activity. By regulating the actions of histamine the lipoxins also lead to a reduction in swelling due to edema.

In addition, the actions of LXA4 in some tissues leads to the production of prostacyclin (PGI2) and nitric oxide (NO) both of which are vasodilators and may play roles in the anti-inflammatory properties of the aspirin-triggered lipoxins (ATLs) 15 epi-LXA4 and 15 epi-LXB4. The induction of NO by aspirin is correlated, in a dose-dependent manner, with a reduction in leukocyte accumulation at sites of inflammation. No other NSAID has been shown to exert this effect on NO production making aspirin unique among this class of drug. The induced production of NO by aspirin plays a significant role in the protective effects of aspirin on the cardiovascular system. "

As discussed in detail above the lipoxins and the aspirin-triggered lipoxins represent a clinically significant class of bioactive lipids that are derived from the omega-6 PUFA, arachidonic acid. Numerous bioactive metabolites of the omega-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are also clinically significant molecules and several epimeric isoforms are generated via the action of aspirin. Probably the most important EPA- and DHA-derived bioactive metabolites are the anti-inflammatory lipids called resolvins (Rv), protectins (PD), and maresins (MaR). More precisely, the Rv, PD, and MaR molecules do not inhibit the onset of inflammation but stimulate the resolution of the response resulting in the shutting off of an inflammatory process. Thus far at least nine resolvin molecules have been characterized along with two protectins and two maresin molecules. Collectively, these immune modulating EPA and DHA derivatives are referred to as specialized proresolving mediators, SPM.

The Resolvins, Protectins, and Maresins
"The resolvins were initially identified by their ability to promote the resolution of the inflammatory cycle, hence the derivation of their names as resolvins. The resolvins are divided into two classes with the E-series resolvins (RvE1, RvE2, and RvE3) being synthesized from EPA and the D series resolvins (RvD1–RvD6) being derived from DHA. The resolvin family members share a 17-hydroxy residue that is introduced into DHA by the lipoxygenase, 15-LOX. Several of the resolvins are synthesized in epimeric form via the effects of aspirin. The E-series resolvins, RvE1, RvE2, and RvE3, are the major EPA-derived resolvins. The levels of RvE1 increase spontaneously in individuals taking aspirin or consuming EPA. RvE1 is produced in a transcellular manner involving endothelial cells and leukocytes. Within the endothelium EPA is converted to 18R-HEPE (18R-hydroxyeicosapentaenoic acid) by the COX-2 enzyme following its exposed to aspirin. The 18R-HEPE is released by the endothelial cells and taken up by adherent leukocytes where 5-LOX converts it to RvE1. Certain COX-2 inhibitors block this pathway to RvE1 synthesis but the NSAIDs indomethecin and acetominophen do not. The E series resolvins reduce inflammation, regulate PMN infiltration by blocking transendothelial migration, reduce dendritic cell function (dendritic cells are potent antigen presenting cells which prime T cell mediated inflammatory responses), regulate IL-12 production and lead to resolution of the inflammatory responses. ..."

edit: titles, IMG

 

[GelatinGoblin]

Very nice thread, esp Travis, bump

 

[Dr. B]

Exactly.

Bayer 81 mg Enteric Coated

Inactive Ingredients: black iron oxide, brown iron oxide, carnauba wax, cornstarch, D&C yellow #10, aluminum lake, FD&C yellow #6, aluminum lake, hypromellose, methacrylic acid copolymer type C, polysorate 80, powedered cellulose, propylene glycol, shellac, sodium lauryl sulfate, triacetin, triethyl citrate.

compare it with

Gericare 325 mg Aspirin

Inactive Ingredient: Cornstarch

which aspirin are you and everyone using now?
I have a Bayer brand aspirin i got at target.
it doesnt say "enteric coated" but it does say 'coated tablets"
the ingredients are Carnauba Wax (May Contain This Ingredient), Corn Starch, Hypromellose, Powdered Cellulose, Triacetin.

how safe are carnauba wax and triacetin? it seems theyre not as harmful as magnesium stearate, silica, polysorbate 80, propylene glycol etc...? carnauba wax is considered 'hypoallergenic' and has a melting point higher than beeswax!