Two underground supplements for chronic pain and inflammation + a new perspective on inflammation

Article at a glance (TLDR)

1. Stoping inflammation with advil or prescription anti-inflammatories is bad because it blunts the arm of the inflammatory cascade necessary for healing.

2. Supplements like SPM’s and PEA (which can both be supplemented) are involved in the resolution phase of the inflammatory process: the resolution phase involves promoting authentic healing and clearing out debry, waste and cellular damage accumulated after an injury or insult. Lipid mediators reduce inflammation as well as prescription anti-inflammatories (so they’re great for acute pain) but also promote authentic healing: something NSAID can’t do and actually inhibit.

3. SPM’s are one of the first supplements I’ve noticed a benefit from for post training soreness. In-season athletes can benefit from taking SPM’s prophylacticly for recovery and possibly preventing injuries. Similar to BPC but without the need for an injection and aren’t an issue for drug tested athletes.

What really is inflammation?

Inflammation is a protective response by the body's immune system to harmful stimuli such as pathogens, damaged cells, and irritants. It involves the recruitment of immune cells to the site of injury or infection, the release of signaling molecules, and the activation of various biochemical pathways. We know that uncontrolled or chronic inflammation can lead to tissue damage and various diseases, including arthritis, cardiovascular disease, and neurodegenerative disorders.

So how do we tackle it without blunting the inflammatory cascade necessary for tissue repair? Remember, inflammation signals the body to repair and regenerate. But prolonged inflammation can further exacerbate it.

For a long time, the resolution of inflammation was considered a passive process where inflammatory signals simply dissipated over time. However, recent research has found that resolution is an active and highly regulated phase of the immune and inflammatory cascade, involving specific biochemical mediators collectively known as specialized pro-resolving mediators.

Supplement # 1: Specialized pro resolving lipid mediators (SPM’s)

SPMs represent a significant advancement in our understanding of inflammation and it’s resolution. Both from a biochemical and interventional standpoint. SPM’s play a crucial role in actively orchestrating the resolution phase of inflammation, a process that was historically thought to be passive.

For a long time, the resolution of inflammation was considered a passive process where inflammatory signals simply dissipated over time. However, recent research has found that resolution is an active and highly regulated phase of the inflammatory cascade, involving specific biochemical mediators collectively known as specialized pro-resolving mediators.

SPMs include a family of bioactive lipid compounds: resolvins, protectins, maresins, and lipoxins. Those mediators are derived from essential fatty acids like omega-3’s. In fact, most of the benefits associated with fish oil seem to be attributable to these lipid mediators, minus the downsides (rancid oil, lipid perioxidation etc). Unlike pro-inflammatory mediators that initiate and propagate the inflammatory response, SPMs actively promote the resolution of inflammation and tissue repair.

Immune mechanisms

One mechanism through which SPMs work is by reducing the migration of neutrophils to the site of inflammation. Neutrophils are one of the first immune cells to respond to injury or infection, but their prolonged presence can exacerbate tissue damage. SPMs also enhance the ability of macrophages to engulf and clear apoptotic cells ( efferocytosis) and cellular debris. This is important for preventing secondary necrosis and the release of further pro-inflammatory signals. By promoting the clearance of debris and supporting the resolution phase, SPMs create a conducive environment for tissue regeneration and repair.

(Treatment with SPM’s early after an injury can be very important for augmenting ‘authentic’ healing after an injury, surgery, or even something like a heart attack . This can greatly help to preventing pathological remodeling and scar tissue formation)

How do they different from prescription anti-inflammafories?

NSAIDs like Advil are widely used to reduce inflammation and alleviate pain. They exert their effects primarily by inhibiting the COX enzyme, which is involved in the synthesis of prostaglandins. Prostaglandins are lipid compounds that mediate various aspects of the inflammatory response, including pain, fever, and swelling.

The fundamental difference between SPMs and NSAIDs lies in their approach to managing inflammation. While NSAIDs are anti-inflammatory agents that block the production of inflammatory mediators, SPMs are pro-resolving agents that actively promote the resolution and termination of the inflammatory response. In many ways, you can think of SPM’s as being very similarly effective (if maybe not even more effective acutelyg at reducing inflammation than NSAID. But without the downside of blunting the portion of the inflammatory cascade necessary for healing.

I’ve had many individuals who have used SPM’s for pain management, arthritis, swelling, and even delayed onset muscle soreness wirh great success. In fact, they’re one of the few supplements that truly help with DOMS after a workout! Think of them as Advil 2.0. Because SPM’s are naturally occurring molecules in the body, they pose none of the risks associated with prescription anti-inflammatories like ibuprofen.

How do I take SPM’s?

SPM’s can be taken daily (for general inflammatory balance, 2-3 capsules daily is ideal) or at higher doses after an acute injury. I like to take SPM’s on my hard training days (so only twice a week at a mega dose of 6 capsules, divided into two servings). For delayed onset muscle, acute infection (they work great when you’re sick) soreness, arthritis compex pain and acute injuries, you may need higher doses daily (6-8 capsules) for a prolonged period of time (2-3 weeks before reducing your dose down to maintain,3. SPM’s aren’t cheap, so you can experiment with different dosages and frequencies to find what works best for you.

My source: metagenics

https://amzn.to/3RJ5zU6

Supplement # 2: PEA

Another supplement with profound anti-inflammatory benefits (particularly in the context of pain management) is PEA or palmitoylethanolamide. Many of the benefits of PEA were though to be associated with (and still are) it’s ability to modulate mast cells and by interacting with cannabinoid receptors, such as CB1 and CB2 receptors. some recent data suggests that the benefits of PEA (particularly in the CNS, brain and vascular system) may actually have similar mechansims of action to SPM’s.

For example, some studies have shown that PEA may be able to promote a proresolving macrophage phenotype In atherosclerosis. Macrophages play a role in the development and progression of atherosclerosis, a chronic inflammatory disease of the arteries, as well as tissue damage and repair.

In the context of atherosclerosis, proresolving macrophages are those that promote the resolution of inflammation, clearance of dead cells and debris, and tissue repair. So it’s definitely safe to assume that PEA may promote the polarization of macrophages towards a proresolving phenotype, which can help in resolving inflammation in general. I think this could be (in addition to its other, well-documented benefits for inflammation via some of the other pathways mentioned ) a large component of its ability to reduce inflammation and promote healing, particularly in the central nervous system.

My theory is that PEA may have a slight advantage for inflammation particularly in the nervous system and brain. PEA has been shown to be effective for traumatic head injuries and chronic idiopathic pain. Some of this may be due to it’s pro-resolving mechanisms of action.

How to take PEA

PEA has poor bio-availability and needs to be emulsified into a fat source. The capsules should be opened and blended into a shake or smoothie containing fat. Anytime I’ve used PEA in the past, Ivr typically put it in a protein shake with MCT oil, or my nutritional shake with avacodo and sheeps yogurt. The effective dosage for PEA can range anywhere from 600-1200mg daily. PEA needs to be taken consistently for a time to see benefits. For pain, most notice a benefit within 2 weeks. PEA should likely be cycles on and off (5-8 weeks on and a couple weeks off) to avoid dependence.

My source:

https://amzn.to/45CtOJB

Conclusion

It’s important to note that these supplements are not outright solutions for chronic pain and inflammation. While they can be fantastic coping devices and safe tools (especially compared to prescription meds), we still need to change the underlying dietary and lifestyle factors that are likely contributing to pain and chronic inflammation