The lifestyle habits and decisions of societies today such as poor nutrition, alcohol and tobacco consumption, inadequate physical activity as well as pollution and stress, give rise to 75% of the chronic disease suffered today including cardiovascular disease (CVD), atherosclerosis, metabolic syndrome, cancer, osteoarticular health, and neurodegenerative diseases among others. These illnesses are caused or exacerbated by unresolved or uncontrolled inflammation and have a deficit of ‘Specialized Pro-resolving Mediators’ (SPMs), or an imbalance in the mediators of the inflammatory response. A familiar occurrence of uncontrolled inflammation is one suffered by patients following a severe Covid-19 infection, a disease characterized by pulmonary hyper-inflammation and potentially life-threatening “cytokine storms”1.
The increasing challenge of inflammatory health conditions
Metabolic conditions such as Non-Alcoholic Fatty Liver Disease (NAFLD) or diabetes have a global prevalence of 25% and 8% in adults respectively2-3. Importantly, diabetes is projected to increase to more than 10% by 2040 where more than 90% of those diabetics are type 2 diabetes specifically.3
Meanwhile, the global impact of osteoarthritis (OA) is estimated at 3.8%, specific to knee and hip4. Chronic pain affects an estimated 100 million Americans, one-third of the adult population of whom approximately 25% experience moderate to severe chronic pain resulting in limited activity and diminished quality of life with limited treatment options that are safe and effective5.
The increasing prevalence of inflammatory chronic disease is becoming a greater public health concern.
Role of SPMs in the inflammatory response
Greater scientific understanding of the inflammatory response – including the molecules and pathways involved – highlights the essential role of Specialized Pro-resolving Mediators in helping resolve inflammation and infection. SPMs are active metabolites derived from their precursors, omega-3 EPA/DHA, and are biosynthesized endogenously through the body’s normal physiological pathways of the inflammatory process, restoring tissue environments to normal condition, positively influencing infection and pain, in addition to protecting tissue and organs6.
The inflammatory response is protective and part of our body’s defense mechanism. The resolution of inflammation triggered by SPMs and the return to tissue homeostasis is vital to prevent progression to chronic and systemic inflammation.
Under normal conditions our bodies naturally and effectively biosynthesize SPMs, although in some cases the conversion from their precursors EPA & DHA is insufficient in quantity, therefore failing to successfully end the resolution process, allowing uncontrolled inflammation to potentially lead to inflammatory health conditions. In cases lacking SPM biosynthesis where the acute response becomes chronic, insufficient quantities of SPMs have been observed in affected tissue (metabolic diseases including type 2 diabetes, fatty liver, obesity, atherosclerosis, etc.). Inadequate SPM production can hinder the body’s natural recovery, leaving the immune response incomplete and the resolution process unresolved. This can occur due to various issues including receptor defects, enzyme synthesis, intracellular signaling or nutritional deficiencies in essential omega-3 fatty acids7.
Nutritional intervention through dietary supplementation is beneficial and offers an innovative approach to immune-nutrition for those who seek safe and effective solutions for managing inflammation and/or pain to improve their quality of life.
SPMs represent a large family of Lipid Mediators including the monohydroxilated 18-HEPE, 17-HDHA, 14-HDHA as well as Lipoxins, Resolvins, Protectins and Maresins. Over the past several years, these same lipid mediators have been identified in various human tissues such as placenta, breast milk, synovial fluid, brain and blood, and have been determined to be key components of our immune system6.
Azur Global Nutrition – pioneers in SPM science and technology, delivers LIPINOVA SPMs, a unique IP-protected ingredient concentrated in standardized levels of SPMS, 18-HEPE, 17-HDHA, and 14-HDHA. LIPINOVA is a bioactive ingredient designed to support the body’s natural capacity to resolve inflammation and clinical results demonstrate its safety and efficacy without immunosuppression or evidence of side effects to date. Additionally, LIPINOVA maintains GRAS status (Generally Recognized as Safe) as determined by the USFDA.
Supplementation with SPMs – Clinical Evidence
Initial clinical studies were recently published featuring healthy patients as well as patients with peripheral arterial disease, or PAD (an inflammatory disease with high cardiovascular risk) who supplemented their diets with Azur’s LIPINOVA SPMs. Results indicated an increase in the concentration of SPMs in blood, as well as a modulation of the immune system towards pro-resolution phenotypes of inflammation after supplementation, promoting improvement in the inflammatory state8-9. Similar studies conducted in patients with PAD with Omega-3s instead of SPMs, did not show effectiveness from a clinical point of view, neither in regard to inflammatory parameters nor SPMs profile10-11.
An additional clinical study, conducted with the same ingredient in 44 patients suffering from chronic pain, demonstrated statistically significant reductions in pain intensity, incidence of pain, depression and anxiety, as well as an improvement in mobility and physical activity, therefore translating to a better quality of life5.
In this context, supplementation with SPMs in patients with chronic inflammatory conditions can be an effective alternative to improve quality of life, activate metabolic pathways, restore unbalanced levels of SPMs and reestablish the resolution of inflammation process.
Traditional treatment for inflammation is often focused on the short term, and blocks the inflammatory response causing unwanted side effects resulting from suppression of the immune system. Immune-nutrition through dietary supplementation with SPMs represents an alternative approach for patients suffering from inflammation and pain.
A study examining lipidomic profiles after unaccustomed resistance exercise indicates that Ibuprofen (a cyclooxygenases COX-1 and COX-2 inhibitor) blocked the prostaglandin (PG) response to exercise but also reduced SPMs response during postexercise recovery due to sharing the same enzymes with PGs for their biosynthesis. Therefore, the use of anti-inflammatories for pain and inflammation management can delay and/or decrease the natural resolution of the inflammatory response12.
A dietary supplement “Sports ProResolve” containing LIPINOVA SPMs, targets athletes’ recovery and has shown great results reducing recovery periods, NSAID intake as well as pain reduction and joint discomfort.
An alternative study conducted with patients suffering from different forms of arthritis, who consumed supplementation with omega-3s, detected high SPM synthesis from their precursors, locally. This also correlated with a decrease in pain, thus suggesting the importance of SPM synthesis to the site of inflammation, a mechanism by which SPM supplementation is associated with relief from arthritis symptoms13.
Numerous study results combined with scientific evidence published on SPMs and their role in the inflammatory response, demonstrates the importance of completion of inflammation and the process of resolution. SPMs can help prevent the inflammatory response from getting out of control and contributing to chronic conditions, the genesis of numerous inflammatory diseases. In this sense, exogenous supplementation with LIPINOVA SPMs may replenish appropriate levels of Specialized Pro-Resolving Mediators, responsible for modulation of the immune system and the resolution of inflammation.
To learn more about LIPINOVA SPMs, safe and effective immune-nutrition supplements to address the growing challenge of inflammatory health conditions and improve quality of life, visit Azur-gn.com and contact us.
- Panigrahy, D., et al. Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?. Cancer Metastasis Rev 39, 337–340 (2020).
- Younossi ZM, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84.
- International Diabetes Federation. IDF Diabetes Atlas, 7th edn. Brussels: International Diabetes Federation, 2015. http://www. diabetesatlas.org (accessed May 5, 2021)
- Hawker GA. Osteoarthritis is a serious disease. Clin Exp Rheumatol. 2019 Sep-Oct;37 Suppl 120(5):3-6.
- Callan et al. Early evidence of efficacy for orally administered SPM‑enriched marine lipid fraction on quality of life and pain in a sample of adults with chronic pain. J Transl Med (2020) 18:401.
- Charles N. Serhan. Discovery of Specialized Pro-Resolving Mediators Marks the Dawn of Resolution Physiology and Pharmacology. Mol Aspects Med. 2017 December; 58: 1–11.
- Dalli J. Does promoting resolution instead of inhibiting inflammation represent the new paradigm in treating infections? Mol Aspects Med. 2017;58:12-20.
- Souza P.R., et al. Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses. Circulation Research. 2020;126:75–90.
- Schaller M.S., et al. Treatment With a Marine Oil Supplement Alters Lipid Mediators and Leukocyte Phenotype in Healthy Patients and Those With Peripheral Artery Disease. J Am Heart Assoc. 2020;9:e016113.
- Grenon S.M., et al. Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid–Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial). Am Heart Assoc. 2015;4:e002034
- Ramirez J.L., et al. Fish Oil Increases Specialized Pro-resolving Lipid Mediators in PAD (The OMEGA-PAD II Trial). Journal of Surgical Research, Volume 238, 164 – 174.
- Markworth JF, et al. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment. Am J Physiol Regul Integr Comp Physiol. 2013;305(11):R1281-96.
- Barden AE. et al. Specialized pro-resolving mediators of inflammation in inflammatory arthritis. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2016; 107:24–29.