Injuries induce the initiation of inflammation to control the damage. However, despite the extensive knowledge of the basics of the inflammatory processes, the resolution of the injury-induced inflammation leading to healing is not well characterized. This is due to the recent discoveries of alternative molecular mechanisms that body cells use to induce or suppress inflammation itself. Nonetheless, other previously unknown molecules have been identified that may induce or limit the inflammatory damage as well. Environmental substances induce inflammatory responses in our body. Yet they seem to induce different patterns of these responses. This means that cellular processes differ for each of them and require different patterns and times for resolution. Now a new article by researchers at the Inflammation Research Foundation suggests that the resolution process is under significant dietary control and thus can be optimized by using a highly defined systems-based nutritional approach.
Dr. Barry Sears, President of the institution, explained the principles for this kind of intervention: “In particular, a successful resolution of injury-induced inflammation requires the continuous balance of hormonal and genetic factors. The essential hormones involved in the process are eicosanoids derived from omega-6 fatty acids (the most renown is arachidonic acid, precursor of the well-known prostaglandins) that need to be balanced by resolvins derived from omega-3 fatty acids. Likewise, the gene transcription factor NF-κB that controls inflammation must be offset by the activation of AMPK, which is the genetic master switch of metabolism and repair of damaged tissue. This balancing act of initiation of inflammation and its ultimate resolution that leads to healing is a systems-based approach. The activation of resolution requires a sequential orchestration of reducing, resolving, and repairing of the injury-induced inflammation. Each step of the process can be either enhanced or inhibited by the diet.”
The article outlines an appropriate calorie-restricted anti-inflammatory diet that is needed to reduce inflammation, the levels of omega-3 fatty acids required to resolve inflammation, and the levels of dietary polyphenols required to activate AMPK to repair the tissue damage caused by the inflammation. Furthermore, the appropriate blood markers to indicate success in optimizing each distinct phase of resolution are discussed in the article. Simulatenously to this publication, Dr. Sears has published the results of a clinical trial on omega-3 supplementation to patients with severe traumatic brain injury (TBI). Of course, he best strategy to avoid the detrimental short- or long-term effects of all kinds of TBIs is through primary prevention or avoidance. However, once a TBI occurs, the inexorable secondary injury represents a window of opportunity for therapeutic intervention, with the potential to prevent and reduce brain damage and improve long-term patient outcomes.
Tens of preclinical studies in animal models have shown the benefits of omega-3 in reducing the cellular injury and negative outcomes associated with TBI, stroke, and spinal cord injury. The use of high-dose omega-3 for treatment of severe traumatic and hypoxic brain injuries has recently emerged and attracted interest, due to the potential to mitigate the several critical steps in secondary injury. The small clinical trial published by Dr. Sears’ group, supports the need for a larger clinical trial to further assess the potential for improvement in outcome from severe TBI. Although authors of multiple in vitro and animal studies and case reports have proposed various pharmacological or physiological interventions to mitigate TBI, to date no phase 3 clinical study has revealed a compound with a significant effect in reducing the morbidity and mortality of TBI. Thus the burden of TBI continues globally without a solution other than standard medical therapy and surgical intervention, when indicated and possible.
Dr. Sears, commented on the principles: “Omega-3 may represent a safe and unexpensive mean to treat TBI and other neurological injuries. However, a nutritional approach during meals may be reached, by selecting foods that are naturally rich with these molecules, either in vegetal or animal sources. External supplementation, of course, may help fasten the recovery process. Since injuries are at random, the mechanisms and dietary constraints required for their successful orchestration leading to healing must be continually optimized; that means it should not be done for a couple of days but for several weeks if not months. If not, then unresolved inflammation may become permanent in the form of either fibrosis or the development of senescence cells, leading to earlier onset of chronic disease and acceleration of the aging process”.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in CLinical Biochiemistry.
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