Understanding the role of EPA in bone, joint and skeletal health


Skeleton close-up showing normal bone and osteoporosis. Digital

In osteoporosis (red circle) bones lose calcium and become porous, with reduced bone density

When we think about key nutrients that are involved in promoting and maintaining optimal bone health throughout the life span, calcium and vitamin D generally spring to mind.Whilst there is little doubt that these two nutrients play an essential role in bone turnover, there is increasing evidence to suggest that incorporating the long-chain omega-3 fatty acid EPA in the diet may also promote the development of a healthy skeleton and thereby reduce the risk of developing conditions such as osteoporosis in later life. In addition, EPA supplements taken by sufferers of these conditions can help manage symptoms, reduce pain and in some cases reduce the need for pharmaceutical intervention with products such as non-steroidal anti-inflammatory drugs (NSAIDs).

Fish consumption for bone health

Skeletal growth accelerates during puberty and the accumulation of bone mineral reaches its maximum in late adolescence or early adulthood. Ensuring adequate intake of bone-supporting nutrients during childhood is essential for establishing the healthy bone mineral density (BMD) required throughout adulthood to reduce the risk of developing osteoporosis linked to an increased risk of fracture.  When it comes to sourcing all three nutrients in one nutritional package, look no further than the humble fish supper. Oily fish provides a rich source of vitamin D and when consumed with their bones (such as tinned sardines), they provide a good source of calcium. As an excellent source of long-chain omega-3 fatty acids, regular consumption of oily fish makes it ideal for promoting optimal bone and joint health. Studies have shown a direct positive correlation between higher consumption of oily fish and BMD [1]; encouraging consumption of oily fish by introducing it into the diet in the very early years will provide the optimal nutrients required to establish bone health at a young age and on into adulthood.

Inflammation and skeletal health

The skeleton is a living tissue and one that undergoes constant remodelling which is dependent on the correct balance and activity of bone-synthesising osteoblasts and bone-resorbing osteoclasts. Bone homeostasis is regulated by numerous immune-derived proteins. Examples of osteoclast-stimulating proteins include the inflammatory cytokines Interleukin−1 (IL-1), Interleukin−6 (IL-6) and tumor necrosis factor alpha (TNFα), derived from the omega-6 fatty acid arachidonic acid (AA), all of which are mediators of joint damage observed in osteoarthritis. [2]Whilst a healthy inflammation response is beneficial, an excessive or unresolved inflammatory response results in over activity of osteoclasts, leading to an increase in bone resorption. Indeed, excessive osteoclastogenesis and inadequate osteoblastogenesis are responsible for the imbalance in the formation and resorption of bone observed in postmenopausal and age-related osteopenia.

The AA to EPA ratio in relation to bone health

The specific role for the marine derived omega-3 fatty acid eicosapentaenoic acid (EPA) in bone metabolism is gaining considerable interest. One of the primary functions of EPA is as a signalling molecule for the immune system where it exerts potent anti-inflammatory effects. EPA helps inhibit and regulate the pro-inflammatory effects of AA; the ratio of AA to EPA within cell membranes can therefore directly influence the inflammatory driven processes that regulate bone metabolism. An imbalance of this ratio, leading to higher AA levels over EPA, promotes inflammation and can increase the risk of developing diseases like osteoporosis and osteoarthritis because AA activates the pathways that signal osteoclasts to begin resorbing the matrix needed to make new bone. If the signals for this inflammatory driven process continue without resolution (via anti-inflammatory EPA ‘stop’ signals) resorption will continue, eventually causing structural damage to bone.  A higher ratio of omega−6 to omega−3 fatty acids is associated with lower BMD suggesting that the relative amounts of dietary polyunsaturated fatty acids may play a vital role in preserving skeletal integrity, certainly in older age.

The role of EPA in resolving inflammation

Fresh Mackerel Fish

Long-chain omega-3 fatty acids may promote the development of a healthy skeleton and thereby reduce the risk of developing conditions such as osteoporosis in later life.

The ‘resolution’ step of the inflammatory process plays a vital role in the initiation of inflammatory driven diseases. Failure to resolve inflammation leads to overspill of inflammatory end products, resulting in perpetual low-grade inflammation that increases the risk of both physical and mental health conditions. The discovery of specific protein molecules that act to dampen the inflammatory response by effectively turning on the relevant ‘stop’ signals, allowing the body to return to a state of homeostasis, has, unsurprisingly, led to a plethora of studies that aim to isolate and explore their potential health benefits. The family of resolvins consists of omega-3 fatty acid-derived mediators, including E series resolvins generated from EPA, and carry potent anti-inflammatory properties.

Resolvin E1 and bone metabolism

There are several resolvin molecules derived from EPA, with RvE1 the first to be isolated and hence the most studied. Using animal models of disease, RvE1 has been shown to dramatically reduce dermal inflammation, peritonitis, the production of inflammatory cytokines and the migration of numerous immune cell types. Neutrophil (polymorphonuclear leukocytes [PMN]) infiltration, for example, plays a central role in inflammation and is also a major cause of tissue damage.Periodontitis is an excellent example of leukocyte-mediated bone loss and inflammation that has pathogenic features similar to those observed in other inflammatory diseases such as arthritis. [3] RvE1 blocks PMN infiltration in periodontal disease in several animal models of inflammatory diseases, RvE1 has proven to be a potent counter-regulatory mediator that protects tissues against PMN-mediated injury and excessive expression of pro-inflammatory genes. With regard to the impact on the skeletal system, RvE1 also inhibits osteoclast growth and bone resorption by interfering with osteoclast differentiation.[4] The actions of RvE1 on bone metabolism are not limited to inflammation resolution; there are also direct actions in bone remodelling.[5] Osteoporosis, characterised by a decrease in bone mass and density, is a particular health problem among postmenopausal women. Indeed, those women with a high omega-6 to omega-3 and low red blood cell levels of EPA are known to be at an increased risk of developing osteoporosis, making them an ideal target for EPA intervention.[6]

EPA and osteoarthritis

Osteoarthritis is characterised by the progressive breakdown of the cartilage extracellular matrix and loss of key structural components such as collagen, thereby culminating in joint cartilage destruction and the exposure of the underlying bone. The elevated levels of IL-1 associated with osteoarthritis are known to stimulate the production of matrix metalloproteinases (MMPs) leading to degradation and loss of structural components.[7] With the anti-catabolic effects of EPA leading to reductions in tissue degradation, EPA supplements therefore offer therapeutic benefits in addition to those relating to osteoporosis, through their potential for preventing cartilage degradation associated with chronic inflammation in joints.

Summary

Osteoarthritis and osteoporosis patients experience joint pain and impaired joint mobility which often leads to disability. The results of numerous studies indicate that inflammation is the foundation of these diseases. The management of both osteoarthritis and osteoporosis includes a combination of manual therapies and pharmacological treatments such as paracetamol and/or non-steroidal anti-inflammatory drugs (NSAIDs). In addition to non-pharmacological interventions such as calcium, glucosamine & chondroitin, the symptoms of these conditions are effectively reduced by the omega-3 fatty acid EPA. The use of purified EPA also has the additional benefit of decreasing the need for non-steroidal drugs and may lessen some of the adverse events induced by some pharmaceuticals.  EPA exerts anti-inflammatory effects, inhibits catabolic processes and stimulates the processes involved in both cartilage and bone metabolism.  Accumulating evidence continues to validate the use of EPA in alleviating the progression of osteoarthritis and osteoporosis, also indicating that early dietary intervention has major implications as a therapeutic intervention, particularly in high-risk individuals.

References

  1. Zalloua PA, Hsu YH, Terwedow H, Zang T, Wu D, Tang G, Li Z, Hong X, Azar ST, Wang B et al: Impact of seafood and fruit consumption on bone mineral density. Maturitas 2007, 56(1):1-11.
  2. Westacott CI, Sharif M: Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin Arthritis Rheum 1996, 25(4):254-272.
  3. Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, Chiang N, Petasis NA, Levy BD, Serhan CN, Van Dyke TE: RvE1 protects from local inflammation and osteoclast-mediated bone destruction in periodontitis. FASEB J 2006, 20(2):401-403.
  4. Gyurko R, Van Dyke TE: The Role of Polyunsaturated omega-3 Fatty Acid Eicosapentaenoic Acid-Derived Resolvin E1 (RvE1) in Bone Preservation. Crit Rev Immunol 2014, 34(4):347-357.
  5. Herrera BS, Ohira T, Gao L, Omori K, Yang R, Zhu M, Muscara MN, Serhan CN, Van Dyke TE, Gyurko R: An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. Br J Pharmacol 2008, 155(8):1214-1223.
  6. Moon HJ, Kim TH, Byun DW, Park Y: Positive correlation between erythrocyte levels of n-3 polyunsaturated fatty acids and bone mass in postmenopausal Korean women with osteoporosis. Ann Nutr Metab 2012, 60(2):146-153.
  7. Wann AK, Mistry J, Blain EJ, Michael-Titus AT, Knight MM: Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1beta-mediated cartilage degradation. Arthritis Res Ther 2010, 12(6):R207.

 

 

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Dr Nina Bailey

About Dr Nina Bailey BSc, MSc, PhD, RNutr

Nina is a leading expert in marine fatty acids and their role in health and disease. Nina holds a master’s degree in Clinical Nutrition and received her doctorate from Cambridge University. Nina’s main area of interest is the role of essential fatty acids in inflammatory disorders. She is a published scientist and regularly features in national health publications and has featured as a nutrition expert on several leading and regional radio stations including SKY.FM, various BBC stations and London’s Biggest Conversation. Nina regularly holds training workshops and webinars both with the public and health practitioners.