Resolvins and Protectins:  Did You Get Your Anti-Aging DHA Today?

Thursday, March 07, 2013
By: Byron J. Richards,
Board Certified Clinical Nutritionist
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Low-grade inflammation is the telltale sign of many diseases of aging, as well as the inappropriate acceleration of the aging process. Astounding new science explains how DHA works to resolve this and protect you from damage – thus slowing the rate of inappropriate aging and the risk for disease. Since the mechanism involved is relatively new and the information is so important, I will help explain what this means to your health. 

A brief review of what is already well known will help you understand the new discoveries in their proper context. The role of essential fatty acids and inflammation as they relate to disease has been discussed for several decades. This extensive body of literature focuses on fatty acid metabolites called eicosanoids, which are 20 carbons in length (such as arachidonic acid).  All cell membranes in your body have a fatty layer. This membrane needs omega-3 fatty acids (like EPA and DHA) to counterbalance the inflammatory effects of arachidonic acid (AA - a polyunsaturated omega-6 fatty acid that is also in the cell membranes). When your cells come under a stressful situation, your cell membranes communicate to your DNA, which in turn liberates fatty acids in your cell membrane to send out inflammatory signals that are typically used to deal with the stressor that has been encountered. AA starts the inflammatory ball rolling, generating other inflammatory signals such COX2, which many pain meds try to suppress, and lipoxygenase (the pathway that produces leukotrienes that are typically involved in asthma and allergy). 

All of the inflammatory fatty acid eicosanoids are produced by inserting oxygen into the fatty acid molecule, a process that makes a lot of free radicals.  This is a main reason why you must have adequate antioxidants to protect against the by-products of inflammation. It has long been recognized that increasing omega-3 fatty acid intake while reducing omega-6 intake helps offset this inflammatory state of affairs. Our evolutionary diet is a 4:1 ratio, omega-3 to omega-6. The Western diet is often a 25:1 ratio – exceedingly pro-inflammatory and disease producing.

The Dawn of Resolution Biology

A cornerstone belief of Western medicine is that the human body will automatically bounce back from what is done to it – a mechanism defined as homeostasis. Western medicine has believed that homeostasis just happens. This is a very convenient belief system when most treatment strategies dump some type of toxin into the human body.

Once the human genome was mapped, it gave us new tools to view what was actually going on; many of the convenient assumptions of Western medicine that bolster drug sales have been proven false. Unfortunately, that doesn’t mean the practice of medicine has changed. It has just reached new levels of denial, wherein so-called experts claim the benefits outweigh the risks regardless of whatever the risks may be. 

Imagine the shock waves that must be secretly going through Big Pharma and AMA boardrooms when it suddenly becomes obvious that your body has an on purpose method1 of resolving inflammatory stress and balancing homeostasis. Imagine further, the utter horror going through the room when this key method of health is dependent upon having adequate DHA2, a 22 carbon length omega-3 essential fatty acid that works by methods completely different than those explained by our previous understanding of eicosanoids.

The field is called resolution biology3.  It is the science of how your body resolves inflammation so that you do not age any faster than you have to and can prevent the inflammatory diseases that commonly occur during aging (cancer, diabetes, Alzheimer’s, obesity, heart disease, etc.). This new field of science sprung up because fatty acids like EPA and DHA were shown to make specific molecules that actually resolve inflammation and return your body to a state of healthy balance – a true scientific understanding of homeostasis.     

Resolvins and Protectins

In a nutshell, the new science shows that once your body starts an inflammatory process it also starts an anti-inflammatory process that will eventually curtail the inflammation as well as clean up the debris of battle4 – returning your body to like-new condition. It should be rather obvious that the cleaner and more rejuvenated you can keep yourself the longer and healthier you will live. Conversely, the more inflamed you remain, with wear and tear evident, the more your quality of health is at risk. Scientists call these new fatty acid metabolites specialized pro-resolving mediators (SPM).  The two most extensively studied SPMs to date are resolvins and protectins.

Resolvins are compounds that help your body resolve inflammation. Two resolvins come from EPA (E1 and E2). Four resolvins come from DHA (D1, D2, D3, and D4).  Resolvins are highly interactive with your mucosal immune system. Deficiencies are associated with a faulty immune response as well as allergy6 and asthma7.  All types of resolvins are highly specific in their actions toward resolution of inflammation, including the cleanup process of general wear and tear or an immune system battle.  Exactly what they do is now under intense scientific exploration.

Protectins come from DHA and were first classified as powerful nerve protectors, protecting your brain and eyesight. They are made by brain cells, nerve cells that involve vision, and were later found to be made by various immune cells and endothelial cells throughout your body. Originally called neuroprotectins, it was then discovered they were also active outside of the brain and so were given the general name of protectins. Emerging science demonstrates that protectins are lacking in cognitive decline and Alzheimer’s. 

Resolvins and protectins are boosted by omega-3 fatty acid supplementation. They have been shown to prevent bone inflammation8 following the removal of ovaries (supporting DHA’s role in bone health). The production of resolvins and protectins is a system wide process in your body, vital to recovery from anything, and to maintain a state of healthy natural balance9.  If you lack omega-3 fatty acids you cannot possibly make them at an optimal rate. These anti-inflammatory DHA metabolites are highly active in tissues all over your body.

Powering Your Brain with DHA

A comprehensive review of the vital role of DHA in your brain, which you can read in full,10 explains in detail the relationship of DHA to AA and other dietary fats. The review points out that “An important turning point in human evolution was the discovery of high quality, easily digested nutrients from coastal seafood and inland freshwater sources. Multi-generational exploitation of seafood by shore based dwellers coincided with the rapid expansion of grey matter in the cerebral cortex, which characterizes the modern human brain. The DHA molecule has unique structural properties that appear to provide optimal conditions for a wide range of cell membrane functions. This has particular implications for grey matter, which is membrane-rich tissue. An important metabolic role for DHA was identified as the precursor for resolvins and protectins.”

Experiments with rats show that deprivation of dietary omega-3 fatty acids11 decreases brain levels of DHA while increasing brain levels of the pro-inflammatory AA, thus creating a handicap in the brain to deal with inflammation. The researchers note that problems such as Alzheimer’s disease, Parkinson’s disease and major depression all involve too much inflammation in the nerves.

Several studies on DHA and brain inflammation emphasize the importance of DHA’s production of the protectin referred to as NPD1 (neuroprotectin D1).  Researchers are now documenting how this DHA protectin helps repair brain injury following stroke12. Researchers believe that this is a front line defense system used in your brain to protect against the first changes to brain cells that indicate some form of stress.  While researchers are conducting detailed experiments13 relating to stroke, Alzheimer’s, and stressed brain cells to prove these mechanisms, it also appears the same mechanisms are vital for protecting your eyesight. Resolvins and protectins work in part by turning off excessive activation of the core inflammatory gene signal NF-kappaB, a method of operation that researchers believe is how DHA helps prevent or reduce the severity of the number one cause of blindness in the world – age-related macular degeneration14.

Resolvins and Protectins for Cardiovascular Health & Weight Management

Researchers are quite excited because the same DHA-related resolvins and protectins that assist your brain and nerves also show great promise in helping your cardiovascular system. It is well known that immune system macrophages interact with the endothelial cells that line your arteries in a way that can promote plaque formation in your arteries. As it turns out, this adverse inflammatory and plaque forming communication can be directly changed and improved by the resolvins and protectins of DHA15.  Researchers are so hopeful about this finding that they state, “We hypothesize that increased endogenous lipid mediators mentioned above [resolvins and protectins] play a vital role in anti-atherosclerosis and plaque stabilization through pro-resolution and anti-inflammation by LOX/LTs [lipoxidase/leukotrienes] pathway. In addition, we predict that the endogenous lipid mediators may be a new target for treatment of atherosclerotic diseases16.”

Any time overweight people lose weight in a healthy manner, their cardiovascular health is improved. It is now clear that resolvins and protectins help reduce the inflammation of obesity and even help clear out the fatty liver17 that so often occurs in overweight people. In addition to its direct anti-inflammatory properties within white adipose tissue, resolvins and protectins were shown to boost adiponectin, and thereby help resolve insulin resistance. DHA helps weight management by multiple mechanisms, as I previously reviewed in my article, Maximizing DHA Intake Supports Weight Loss.

Summary

Resolvins and protectins are part of the new frontier of nutrition science in the war against common diseases in America today. The anti-inflammatory properties of resolvins and protectins are stunning. This offers great hope for improved brain function and cardiovascular fitness – simply by consuming DHA in food and supplements. Even more stunning is their documented method of operation, which for the first time explains the final steps of homeostasis in the recovery from stress and complete resolution of any stressful event. This latter discovery is adequate to cause the rewriting of the theory of Western medicine.


Referenced Studies:
  1. ^ Specialized Proresolving Mediators as the Foundation of Homeostasis  Biochim Biophys Acta.  Bannenberg G, Serhan CN.
  2. ^ Resolvins and Protectins Come from Omega 3 Fatty Acids EPA and Especially DHA  Prostaglandins Leukot Essent Fatty Acids.  Serhan CN.
  3. ^ Resolvins and Protectins: The New Field of Resolution Biology  Prostaglandins Leukot Essent Fatty Acids.  Levy BD.
  4. ^ Resolvins and Protectins Help Cart of Trash Through the Lymph System  Nature.   Schwab JM, Chiang N, Arita M, Serhan CN.
  5. ^ Specialized Proresolving Mediators for Inflammation Resolution  Am J Pathol.  Serhan CN.
  6. ^ Protectins and Resolvins Help Airway Inflammation  Eur Respir J.  Haworth O, Levy BD.
  7. ^ Resolvins Help Allergy and Asthma  Expert Opin Ther Targets.  Hisada T, Ishizuka T, Aoki H, Mori M.
  8. ^ Resolvins and Protectins Boosted by Omega 3 Supplementation Following Ovariectomy  Am J Hematol.   Poulsen RC, Gotlinger KH, Serhan CN, Kruger MC.
  9. ^ Resolvin and Protectin Metabolites of DHA  J Am Soc Mass Spectrom.   Hong S, Lu Y, Yang R, Gotlinger KH, Petasis NA, Serhan CN.
  10. ^ Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain  Nutrients  Joanne Bradbury
  11. ^ DHA Reduces Neuroinflammation  Curr Opin Investig Drugs.   Orr SK, Bazinet RP.
  12. ^ How DHA Helps Heal Stroke  Prostaglandins Other Lipid Mediat.   Niemoller TD, Bazan NG.
  13. ^ DHA Protects Against Neurodegeneration  Mol Neurobiol.  Palacios-Pelaez R, Lukiw WJ, Bazan NG.
  14. ^ DHA Resolvins and Protectins Reduce NF-kappaB to Help Age-Related Macular Degeneration  Exp Gerontol.  Kaarniranta K, Salminen A.
  15. ^ Resolvins and Protectins Can Help Disrupt Vascular Inflammation  FASEB J.   Merched AJ, Ko K, Gotlinger KH, Serhan CN, Chan L.
  16. ^ Resolvins and Protectins to Help Combat Atherosclerosis  Med Hypotheses.   Chen Y, Wang J, Nie R, Zhou S.
  17. ^ Fish Oil, Obesity, Insulin Resistance, and Fatty Liver  Federation of the American Societies for Experimental Biology Journal.  Ana González-Périz, Raquel Horrillo, Natàlia Ferré, Karsten Gronert, Baiyan Dong, Eva Morán-Salvador, Esther Titos, Marcos Martínez-Clemente, Marta López-Parra, Vicente Arroyo, and Joan Clària .

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