Mary T Hankinson and Elizabeth A Hankinson

Inflammatory response

The inflammatory response includes activation of white blood cells, release of immune system chemicals, release of inflammatory mediators and prostaglandins. Acute inflammation is the initial response of the body to harmful stimuli mediated by interleukins. Interleukin 1 (IL-1) and interleukin 6 (IL-6) activate neutrophils that recruit macrophages to injured tissue. Neutrophils also release cytotoxic and cytolytic molecules that cause destruction through lysis of muscle cells, fascia and surrounding tissue. IL-6 contributes to painful and persistent joint damage and chronic inflammation in rheumatoid arthritis. Chronic inflammation involves overproduction of IL-1, IL-6 and tumor necrosis factor (TNF), leading to tissue damage; C-reactive protein (CRP) releases IL-1, IL-6 and TNF, which are responsible for cartilage degeneration in arthritic joints. A persistently elevated CRP level is found in patients with rheumatoid arthritis, who are at risk for continuing joint deterioration (Otterness 1994).

Fatty acids: anti-inflammatory properties

Eicosanoids exert control over inflammation and include prostaglandins, prostacyclins, thromboxanes, and leukotrienes derived from the essential fatty acids (EFAs). EFAs must be supplied through dietary intake and cannot be synthesized by the body. Polyunsaturated fatty acids (PUFAs) include short chain alpha-linolenic acid (ALA) and long chain molecules, eicosapentaenoic acid, (EPA) docosapentaeonoic acid (DPA) and docosahexaenoic acid (DHA). Short chain omega-3 fatty acids oppose inflammation through decreased production of inflammatory prostaglandins, leukotrienes, and arachidonic acid. Food sources providing short chain omega-3 fatty acids include flaxseed, walnuts, canola and rapeseed oils. Long chain omega-3 fatty acids oppose inflammation by competing with arachidonic acid for conversion to pro-inflammatory cytokines IL-1 and TNF and additionally compete with COX and LOX enzymes that are up-regulated in the inflammatory process (James et al. 2000; Ringbom et al. 2001). PUFAs, especially total omega-3 fatty acids, are independently associated with lower levels of pro-inflammatory markers (IL-6, IL-1ra, TNF-α, CRP) and higher levels of anti-inflammatory markers (soluble IL-6r, IL-10, TGF-β) independent of confounders, supporting the opinion that omega-3 fatty acids are beneficial in treating diseases characterized by active inflammation (Ferrucci et al. 2006). Long chain omega-3 fatty acids are important constituents of an anti-inflammatory diet and include oily fish from cold northern waters, such as salmon and mackerel, sardines, herring, black cod (sablefish or butterfish), fish oil, algae, and DHA-rich eggs.

The pro-inflammatory eicosanoids prostaglandin E2, thromboxanes and leukotriene B4 derive from the omega-6 fatty acid arachidonic acid, which is maintained at elevated cellular concentrations by the high omega-6 and low omega-3 PUFA content of the modern Western diet (James et al. 2000). Arachidonic acid is a polyunsaturated omega-6 fatty acid found in phospholipids and a precursor for eicosanoid production. Arachidonic acid is obtained from meat, poultry, fish and eggs, or synthesized from linoleic acid. Linoleic acid is an omega-6 fatty acid found in vegetable oils such as corn, soy, safflower, sunflower, cottonseed, sesame and grape seed, some nuts and seeds. Excess consumption of saturated fatty acids such as palmitic and stearic increases inflammatory signaling through activation of macrophages, neutrophils and bone marrow-derived dendritic cells, leading to inflammation, impaired insulin signaling, and insulin resistance in white adipose tissue and muscle (Kennedy et al. 2009).

The ratio of omega-6 fatty acids to omega-3 fatty acids should be low (i.e., 3:1 or 5:1); however, American intake ratios range from 10:1 to 17:1 for omega-6 fatty acids to omega-3 fatty acids (Kris-Etherton et al. 2000).

Trans-fatty acids are unnatural fat species formed after hydrogenation from naturally occurring cis– fatty acids found in margarines and shortenings. Dietary intake of trans elaidic fatty acid supports inflammation through hormonal imbalances that promote defective cell membranes and cancer. Research from the Nurses’ Health Study demonstrated that TFA intake was positively associated with IL-6 and CRP in women with a higher body mass index (Mozaffarian et al. 2004).

Monounsaturated fatty acids, of which oleic acid is the most common, are found in canola, olive and peanut oils, some nuts, seeds, and avocadoes. Reduced concentrations of inflammatory markers are reported for individuals who adhere to the traditional Mediterranean diet that is abundant in olive oil (Chrysohoou et al. 2004). Oleocanthal, a compound found in olive oil, prevents the production of pro-inflammatory COX-1 and COX-2 enzymes similarly to the mechanism of action for NSAIDs, decreasing inflammation and pain sensitivity. The highest oleocanthal levels are found in stronger-flavored oils from Tuscany and regions using the same olive varietal. The consumption of 50 mL (3.5 Tbsp) of olive oil is equivalent to 200 mg ibuprofen. Weight management is required if olive oil is used as a nutritional intervention, to enhance anti-inflammatory properties, as 50 mL olive oil (≈400 kcal) yields a high caloric density (Beauchamp et al. 2005).

Fatty acid dietary supplements: anti-inflammatory properties

Ingestion of fish oil supplements effects reproducible alterations in eicosanoid metabolism that ameliorate inflammation, decrease production of IL-β in patients with rheumatoid arthritis, and alter the fatty acid constituents of cell membranes (Kremer 2000; James et al. 2000). Concentrated omega-3 fatty acids found in fish oil supplements offer benefits associated with fish consumption without exposure to harmful environmental toxins such as mercury, polychlorinated biphenyls (PCB) and organochlorine (OC) that can accumulate in fish. Analysis of five commercial over-the-counter brands of fish oil supplements available in the United States demonstrates that none of the brands contains detectable amounts of PCBs, OCs, nor significant amounts of mercury (Melanson et al. 2005). Additional product information required from companies who manufacture fish oil supplements includes those who employ sustainable fishing practices, and molecular distillation to minimize mercury and other toxins, content labeling to identify omega-3, potential for contamination, and product storage (Cannon 2009).

Schizochytrium microalgae is a DHA-rich fish oil alternative containing small amounts of EPA and almost no arachidonic acid. DHA-rich oils are located along coastal areas as part of the shellfish food chain, unrelated to toxic algae, demonstrate no allergic reactions in humans, and are free of contaminants such as PCB and mercury (Cannon 2009). Neptune Krill Oil (NKO) is a phospholipid carrier of omega-3 fatty acids EPA, DHA, as well as antioxidants, astaxanthin and a flavonoid, that may offer an alternative regimen for management of chronic inflammatory conditions. NKO is extracted from Antarctic krill (Ephausia superba), a zooplankton at the bottom of the food chain. Ingestion of NKO at a daily dose of 300 mg significantly inhibits inflammation and reduces arthritic symptoms within 7 to 14 days (Deutsch 2007).

Evidence exists that avocado/soybean unsaponifiables (ASU) contain sterols that are anti-inflammatory and provide protection against cartilage degeneration. The biologically active compounds found in avocado and soybean oils are classified as unsaponifiable lipids and include phytosterols beta-sitosterol, campesterol and stigmasterol (Lippiello et al. 2008). ASU may help patients reduce their consumption of NSAIDs, as shown by long-term symptomatic relief observed in patients with osteoarthritis of the hip (Soeken 2004). Several clinical trials have confirmed that gamma-linolenic acid (GLA), an omega-6 fatty acid found in borage seed oil, evening primrose oil and blackcurrant oil, reduces inflammation, tender joint scores, morning stiffness and requirement for NSAIDs (Kapoor & Huang 2006).

Patients should consult with their healthcare provider because fish oil supplements taken at certain dosages can cause inhibition of platelet aggregation and require monitoring for patients on anticoagulant drugs or aspirins, or impending surgery (Sanders & Sanders-Gendreau 2007; Cannon 2009).

Culinary spices and herbs: anti-inflammatory properties

The health benefits associated with herbs and spices require identification of specific bioactive substances that oppose inflammation. Unlike their pharmaceutical counterparts, many plants modulate inflammation via a multitude of pathways rather than inhibition of a single enzyme along the inflammatory cascade. Anti-inflammatory actions are reported for spices and herbs, such as ginger, turmeric, saffron, curcumin, bromelain, German chamomile, licorice and capsaicin. Ginger and turmeric have been used to treat arthritis since ancient times (Craig 1999; Wargovich et al. 2001; Low Dog 2006; Tapsell et al. 2006; Aggarwal et al. 2009). Patients should consult with healthcare providers regarding herb ingestion, as large doses can be toxic, promote adverse medical consequences, or interfere with medications. See Table 7.23.1.

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