Resolvins: Firefighters In The Battle Against Chronic Inflammation

Inflammation is a complex, multi-step process. Like an elaborate domino setup, several different molecules need to act together to stimulate and direct the inflammatory response. Over the last two decades, researchers have become increasingly aware of an equally complicated inverse process: the resolution of inflammation. This, too, has its key players, known as specialized pro-resolving mediators (SPMs). Now, researchers at Albany Medical College have harnessed the power of these molecules to target the chronic, low-level inflammation associated with aging. Their work, published in The American Journal of Pathology, shows that treatment with specialized pro-resolving mediators can help combat, and potentially treat, “inflammaging”.

Non Paywalled article: https://archive.ph/c3lVs

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Someone at work had a theory he explained to me, over a decade ago, that involved a resolvin (can’t remember which one).

It involved an interaction between aspirin and omega 3, and I think he was saying that was why you got different results in the various aspirin studies ??

I wished I’d paid more attention to what he was saying, or had a better memory. So many ideas, so little memory space.

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Barry Sears, MD, author of the Zone Diet wrote about this in one of his subsequent books. I fail to recall at the moment, which one. But his theory is that low amounts of aspirin [20 mg to 40 mg (a quarter to a half of baby aspirin)] with EPA/DHA can produce resolvins.

Below is a 12 year old video of his explanation. But he doesn’t use the term “resolvins”.

He even applied for a patent with aspirin, sesamol (from sesame oil/seed) and EPA/DHA, in 2015.

In the patent application’s explanation of its approach, it does use the term resolvins.

The first phase of the inflammatory response is the initiation phase mediated in part by pro-inflammatory hormones such as eicosanoids, which are derived from the omega-6 fatty acid arachidonic acid (AA). The second phase of the inflammatory response is the resolution phase mediated in part by pro-resolution mediators such as resolvins and other pro-resolution compounds, which are derived from omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Any imbalance between the initiation phase and resolution phase of the inflammatory response results in chronic low-level inflammation. Chronic low-level inflammation has been associated with many chronic disease conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders and neurological disorders. Polyunsaturated omega fatty acids have been implicated to play a role in regulating these two significant, yet distinct phases of the inflammatory response. Without adequate levels of omega-3 fatty acids in the target organs, the generation of many of these pro-resolution mediators is compromised. Although it is possible to synthesize these pro-resolution mediators, it is extremely costly and they must be injected. A preferable approach would be to maintain a reservoir of adequate levels of omega-3 fatty acid in every target tissue in the body as well as maintain a constant supply of these pro-resolution mediators in the blood to modulate on-going inflammatory responses. The invention described in this patent application provides such a solution to reduce chronic low-level inflammation by the enhancement of the pro-resolution phase of inflammation as well as reducing the intensity of the initiation phase of inflammation. Methods described in this invention can reduce the production of AA formation as well as increase the formation of pro-resolution mediators such as resolvins derived from omega-3 fatty acids to accelerate the resolution of the acute inflammatory response by reducing chronic low-level inflammation thus significantly enhancing the therapeutic potential of products containing omega-3 fatty acids to treat a wide number of chronic disease conditions.

In situations of improperly regulated inflammation response results in chronic low-level inflammation. For example, the initiation phase can be too strong or the resolution phase may be too weak. Left untreated, this situation will result in chronic low-grade inflammation that can lead to a number of chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders and neurological disorders. A more detailed listing of these conditions can be found in Table 1. Table 1. Conditions That Can Be Improved By Reducing Chronic Low-level inflammation.

Claims

  1. A composition comprising hydrophobic derivatives of aspirin and/or hydrophobic derivatives of sesamol in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for reducing chronic low-level inflammation associated with chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders, ocular and neurological disorders in a mammal.

Thanks for the reminder RapAdmin. I will now take a half baby aspirin with my weekend breakfast sardine omelette. Time to dig out the pill splitter.

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@RapAdmin, The Forbes article isn’t accessible. Can you break down the paywall? Thanks.

Here it is: https://archive.ph/c3lVs

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@RapAdmin, Thanks for the original post and for making it accessible.

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“Dietary intake of EPA and DHA together with aspirin increases circulating resolvin levels in humans (17, 19). Moreover, low-dose aspirin administered to healthy volunteers for cardioprevention is also capable of producing bioactive levels of aspirin-triggered lipoxins.”

“AT-SPMs and Low-Dose Aspirin Suppress Macrophage Secretion of Proinflammatory Cytokines.”

If aspirin was just now discovered it would be considered one of the miracle drugs and would only be available by prescription. I have been a believer in aspirin for most of my life. I attribute the results of my colonoscopy to aspirin—zero polyps or cancer. I took 1 or two regular aspirin for much of my life. Now I only take “baby” aspirin."
This article is also an endorsement of Omega fatty acid supplementation.

https://www.pnas.org/doi/10.1073/pnas.1804000116

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Isn’t aspirin coated and it’s better not to split it?

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And it would be the source of various conspiracy theories on the internet.

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There is chewable baby aspirin. That low a dose would likely not be a problem with regard to gastric bleeding (a concern that made me stop taking low dose aspirin). desertshores’ experience, and the experience of the Ray Peat crowd with regard to regular strength aspirin is comforting.

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Ford Brewer MD cites the New England Journal for the claim that there is no difference in CV outcomes, nor bleeding rates between full dose and baby aspirin, in minute 4:22 of the video below.

At 4:57, Brewer cites a study found in the Journal of the American College of Cardiology, stating that enteric coated aspirin does not provide the same protection as plain aspirin. Below is the cited study.

The rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200 (a modified-release lipid-based aspirin), and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin-treated subjects had serum TXB2 levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [Cmax] and 77% and 82% lower AUC0-t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB2, with marked interindividual variability.

The main benefits I have found reading some of the literature regarding low-dose aspirin.
Reduces risk of heart attack in those with heart disease
Reduces risk of ischemic stroke
May reduce the risk of colorectal cancer

The literature about the benefits of low-dose aspirin is a mixed bag, but I will continue taking it for the possible colon cancer prevention properties. I find the risk small.

“GI bleeding with low-dose aspirin versus placebo is approximately 0.12% per year, or 1.2 extra cases per 1000 patients treated per year”

“The absolute annual increase in major GI bleeding attributable to low-dose aspirin versus placebo is around 0.12% (95% CI: 0.07-0.19%) based on a meta-analysis”

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Thanks for the reassuring stat.

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Yes, a good paper that I took to heart 18 months ago.

My stack includes; a paediatric dose of aspirin taken with Japanese sourced DHA / EPA and, as of November 23, C15:0 (aka Fatty15). Fatty15 is very expensive but I’ve committed myself to daily use for six months to see how it works for me.

BTW: The Japanese manufacture excellent and reliable supplements although they rarely use English on their labels, contents or instructions.

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Taking a paediatric dose of baby of aspirin when eating fish feels incredibly low risk with potential high gain. And yet, until I read this thread, I had no idea of the potential benefits. Makes me wonder whether we should create a top 5 “no brainers” list.
The top 5 interventions with the least downside risk. I know aspirin isn’t without risk, but a paediatric dose feels incredibly low risk

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BTW There is a Pro-Resolving Mediators supplement from Thorne

Didn’t look into it so I don’t have any opinion about it but but here is what they say:

Pro-Resolving mediators (PRMs) are the end products of the body’s metabolism of EPA and DHA. Thorne’s Pro-Resolving Mediators supplement includes the precursors the body needs to create pro-resolving mediators – two pre-resolving mediators 17-HDHA and 14-HDHA from DHA and one pre-resolving mediator 18-HEPE from EPA, as well as their parents EPA and DHA, to deliver a one-two punch in support of a balanced inflammatory response.* A balanced inflammatory response helps bring the body back into homeostasis after an injury or other insult – essentially helping to “resolve” the problem.* In fact, groups of PRMs produced in the body are called resolvins and protectins – basically members of the body’s “cleanup crew.”

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If you blow up the pic, ingredients are as follows:

18-hydroxyeicosapentaenoic acid (18-HEP)
17-hydorxydocosahexaenoic acid (17-HDHA)
14-hydroxydocosahexaenoic acid (14-HDHA)
Total Omega 3, (from Fish Oil) 500 mg
DHA 250 mg
EPA 160 mg.

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Looking on PubChem it seems there are plenty of patents (mostly Japanese) for anti-inflammatory products with them:

Papers on 18-Hydroxyeicosapentaenoic-\ acid (and patents)

Papers on 17-hydorxydocosahexaenoic acid (and patents)

Papers on 14-hydroxydocosahexaenoic acid (and patents)

I don’t have much time to look at that right now but that looks interesting.

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Dr. Charles Serhan (Harvard): Omega3/Resolvins are 100 to 1000x more potent than traditional NSAID’s (nonsteroidal anti-inflammatory drugs), From a recent ScienceMagazine webinar

Source: https://x.com/npure3/status/1266849346785546241?s=20

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https://www.science.org/content/article/critics-challenge-data-showing-key-lipids-can-curb-inflammation

Non-Paywall Version: https://archive.ph/1np7Q

This says maybe not.

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