Major Breakthrough: SPMs, Resolving Inflammation in the 21st Century


Major Breakthrough: SPMs, Resolving Inflammation in the 21st Century

Specialized pro-resolving mediators, or SPMs, are a portion of the omega-3 fatty acid spectrum that have been shown to have a powerful effect on reducing inflammation. In fact, SPMs represent a paradigm shift in how we regulate the inflammatory response in our patients. SPMs are poised to be the most effective inflammation treatment of the 21st century. They resolve inflammation very effectively, without compromising the immune response and without risky side effects.

Stopping the Inflammatory Process

Helping a patient resolve a chronic inflammatory condition is one of the biggest challenges a holistic practitioner faces. Even when patients are very compliant with dietary and lifestyle changes and take all the recommended supplements and medications, inflammation can stubbornly persist. We know now that resolving inflammation is not a passive process. Rather, it’s complex and highly active and can sometimes happen slowly or even stall. Inflammation can linger long after the acute phase of the injury or illness has passed. Without resolution, the body never truly returns to homeostasis—inflammation becomes chronic.

A super family of naturally occurring lipid mediators called specialized pro-resolving mediators (SPMs) plays a crucial role in switching off the inflammatory response. SPMs don’t block the initial inflammation—inflammation is a desirable natural response to injury and illness. Instead, when the immune response has served its purpose, SPMs down-regulate the process to resolve the inflammation. Produced in the tissues around the affected area, SPMs function as “resolution agonists” targeting the immune cells that mediate the inflammatory response. By binding to specific cellular receptors, particularly the types known “G-protein coupled receptor,” SPMs modify cell behavior to promote resolution.

The SPMs mediators, known as lipoxins, resolvins, protectins, and maresins, are derived from arachidonic acid and omega-3 fatty acids, as shown in the illustration. (Arachidonic acid is often seen as an undesirable pro-inflammatory metabolite of omega-6 fatty acid, but as in many other aspects of the immune system, push and pull both have their place.) SPMs in effect signal the immune system to stop actively responding and instead to accelerate the return to homeostasis. SPMs play a unique role in helping the body finally shut down the immune response, inhibit additional inflammation, clear away the damaging byproducts of the inflammatory process, and aid tissue remodeling. SPMs can facilitate the resolution even of prolonged or chronic inflammation. And once the SPMs have done their job, the body naturally breaks them down and eliminates them.

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The Limits of SPMs Production

For decades, we thought that EPA and DHA from fish oil helped relieve inflammation by competing with pro-inflammatory omega-6 fatty acids metabolites. This isn’t the whole story. In fact, fish oil probably helps relieve inflammation by providing the raw material to build specialized pro-resolving mediators.

SPMs are the end result of a multi-step conversion process in the body that begins with dietary omega-3 fatty acids. This is converted to EPA and DHA; numerous steps further downstream, EPA and DHA are then converted to a number of different SPMs metabolites. Two that have been carefully studied and shown to have therapeutic value are known as 17-HDHA and 18-HEPE.

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SPMs production in amounts large enough to help with resolving inflammation relies on good nutrition and a healthy lifestyle. These fundamental factors aren’t always sufficient to help an individual naturally produce enough endogenous SPMs to overcome and resolve an inflammatory condition. Factors that can limit SPMs production include:
Overload of environmental irritantsUnfortunately, the complex conversion process that ultimately leads to the production of SPMs in the inflamed area is slow and inefficient, even in the healthiest individuals. Normal genetic variation means that some people will convert even more slowly than average. For occasional inflammation from an injury or illness, a healthy individual may be able to produce enough SPMs to resolve the inflammation in a timely way. But what about more serious or ongoing inflammation? What about people with suboptimum health? If the body can’t produce enough SPMs, the inflammation will be slow to resolve. It may linger on and become chronic. The protective effect of inflammation becomes destructive instead.

  • High intake of low-quality dietary fats
  • High intake of processed carbohydrates
  • Too little exercise or overexertion
  • Other physical stressors, such as poor quality sleep
  • The aging process

While lifestyle and dietary changes can help improve SPMs production somewhat, they don’t have large effects. The aging process continues every moment—and SPMs production naturally decreases with age. Simply increasing the intake of fish oil or DHA and EPA even to high levels isn’t sufficient to significantly increase SPMs production. Even when intake is high, the conversion process simply remains too complex and inefficient to be improved.

The Value of Supplementing

A more direct and targeted way to raise SPMs levels is to supplement with them directly. These supplements are made from fish oil using a patented fractionation process to create an SPMs-enriched product. Recent research has shown that daily dosing with two to six soft gels over six weeks produces reductions in standard inflammation blood markers such as hs-CRP, interleukins, fibrinogen, and TNF-alpha.

Because SPMs are naturally produced as a normal part of resolving inflammation, the supplements don’t suppress immunity. This makes them much safer than anti-inflammatory drugs such as glucocorticoids or methotrexate or even aspirin. SPMs supplements can be taken indefinitely. They have no known side effects or interactions with other supplements or drugs.

The usual dosing for SPMs is three capsules two times daily for during the acute inflammation stage. As inflammation becomes subacute, the dosage can be reduced to two capsules twice daily. For ongoing mild inflammation and for maintenance, the suggested dosage is two capsules once daily.

Clinical Uses for SPMs

The potential clinical uses for SPMs are basically any condition related to chronic inflammation. Research suggests that SPMs can be particularly valuable for asthma, arthritis, diabetes, atherosclerosis, and cognitive decline. SPMs have also been used very effectively to treat gut problems, particularly leaky gut syndrome and irritable bowel disease, and to aid recovery in bone and muscle injuries.

SPMs are a valuable addition to the Five Rs protocol used in integrative medicine for healing the gut:

  • Remove chemicals (artificial sweeteners, for example), allergens, processed foods, gluten, lactose, sugar, and bad bacteria.
  • Replace what was removed with an improved diet and lifestyle and the addition of digestive enzymes and stomach acid.
  • Reinoculate the gut with probiotics to restore a better balance of good bacteria.
  • Regenerate and repair the damage to the intestinal lining with supplements, including natural anti-inflammatories such as bioavailable curcumin, rosemary, ginger, quercetin, and omega-3 fatty acids.
  • Retain the gains with ongoing careful attention to diet and the microbiome.

SPMs are helpful at every stage of the protocol, but they are particularly useful for regeneration and repair because they reduce inflammation and promote healing. Clinicians often find that this step in the protocol can be very slow and discouraging for the patient. Symptoms such as bloating and pain continue, even when the patient is very compliant. This is where SPMs can make a big difference by filling the gap in our treatment of inflammation. SPMs supplements can give the patient’s immune system the final element it needs to calm the inflammation and move on to healing and a return to homeostasis.

After the protocol is complete, daily SPMs supplementation helps retain the gains by controlling any inflammation that may develop from illness, lapses in diet, stress, and other unavoidable factors.

Healing Bones and Muscles

SPMs may be a highly effective treatment for preventing bone loss and stimulating bone regeneration. In particular, the resolvins found in SPMs may mediate bone preservation by direct inhibitory action on osteoclasts. For treating bone injuries, SPMs may be very helpful by improving bone regeneration and remodeling. For treating osteopenia and osteoporosis, SPMs offer a significant improvement in safety and patient comfort. Bisphophonate drugs such as alendronate (Fosamax) and ibandronate (Boniva) for osteoporosis inhibit osteoclast-mediated bone resorption. However, these drugs can cause dangerous side effects, such as osteonecrosis of the jaw. Selective estrogen receptor modifiers (SERMs) such as raloxifene (Evista) slow bone loss, but carry a high risk of dangerous blood clots and stroke.

SPMs may also be valuable for treating unresolved inflammation in muscle injuries. When inflammation lingers on in damaged muscles, it leads to inefficient tissue repair, which in turn leads to long-term loss of muscle mass and function. The tightly choreographed inflammatory response to muscle injuries can be thrown out of step by a wide range of factors, such as reinjury or dietary deficiencies. The final step in resolution isn’t reached and the inflammation continues at a low level, preventing a full return of normal function. Supplementing with SPMs as the injury heals can reduce or eliminate lingering inflammation and speed tissue remodeling.

About the Author


Dr. Silverman graduated Magna cum Laude from the University of Bridgeport College of Chiropractic and has a Masters of Science in human nutrition. His extensive list of educational accomplishments includes his designations as a certified nutrition specialist, certified clinical nutritionist, certified strength and conditioning specialist, certified Kinesio® taping practitioner, NASM-certified corrective exercise specialist, and a certified sports nutritionist from The International Society of Sports Nutrition. Dr. Silverman is a diplomate with the American Clinical Board of Nutrition and diplomate with the Chiropractic Board of Clinical Nutrition. Dr. Silverman is also HardStyle Kettlebell Certified instructor, a certified RockTape – Fascial Movement Taping (levels 1 & 2) provider, and also a CrossFit Level 1 trainer. He has a full-time successful private practice in White Plains, NY, where he specializes in the treatment of joint pain with innovative, science-based, non-surgical approaches and functional medicine. He is a nationally and internationally known speaker and author, contributing to articles published in Dynamic Chiropractic, JACA, ACA News, Chiropractic Economics, The Original Internist, Holistic Primary Care. Dr. Silverman is also on the advisory board for the Functional Medicine University, a health contributor to Fox News Radio and has appeared on Fox & Friends and CBS News as a health expert.

Dr. Silverman is awarded the “2015 Sports Chiropractor of the Year” by the ACA Sports Council.

Dr. Silverman can be reached at his office: 914.287.6464; email: [email protected]

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Dr. Robert Silverman
Dr. Robert Silverman, on in SPM's