UC Agriculture & Natural Resources California Agriculture Title Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health Permalink https://escholarship.org/uc/item/1231m2fm Journal California Agriculture, 65(3) ISSN 0008-0845 Authors Zivkovic, Angela M Telis, Natalie German, Bruce et al. Publication Date 2011 Peer reviewed eScholarship.org Powered by the California Digital Library University of California ReseaRch aRticle ▼ dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health by Angela M. Zivkovic, Natalie Telis, J. Bruce German and Bruce D. Hammock This article focuses on the role of omega-3 fatty acids as precursors for lipid signaling molecules known as Claes Torstensson/iStockphoto Claes oxylipins. Although omega-3 fatty acids are benefi cial in autoimmune disor- ders, infl ammatory diseases and heart disease, they are generally underrepre- sented in the American diet. A literature review confi rms that the consumption of omega-3 fatty acids — whether in food sources such as walnuts, fl ax seeds Srdjan Stefanovic/iStockphoto Srdjan and fatty fi sh (including salmon and sar- dines), or in supplements — is associated with decreased morbidity and mortality. This growing body of evidence, including Walnuts, fl ax seeds and salmon the results of a recent study of patients are good sources of omega-3 fatty acids, important nutrients with kidney disease, highlights the that are generally defi cient in need to measure omega-3 fatty acids American diets. woodleywonderworks and their oxylipin products as markers of metabolic health and biomarkers of have also been shown to stabilize athero- diseases such as Alzheimer’s disease sclerotic plaques, thereby reducing the (Schaefer et al. 2006) and mental disorders disease. In addition, there is substantial likelihood of fatal and nonfatal cardiovas- such as schizophrenia (McNamara et al. evidence of the need to increase the cular events (Thies et al. 2003). EPA and 2007) and depression (Sanchez-Villegas omega-3 fatty acid content of American DHA additionally reduce the synthesis et al. 2007). Taken in supplement or food diets to optimize metabolic health. of triglycerides (fat molecules) and secre- form, omega-3 fatty acids have been tion from the liver, and increase the size found to reverse the progression of a of low-density lipoproteins, which con- number of infl ammatory diseases, from any of the most signifi cant U.S. tribute to the reduction of cardiovascular infl ammatory bowel disease to diseases Mhealth concerns today are modu- disease risk (Griffi n et al. 2006). EPA and of the skin and joints, to other autoim- lated by omega-3 fatty acids, particularly DHA improve liver health by reducing mune diseases such as lupus and multiple eicosapentaenoic acid (EPA) and doco- steatosis (accumulation of fat in the liver) sclerosis (Simopoulos 2002). This review sahexaenoic acid (DHA). Omega-3 fatty in patients with nonalcoholic fatty liver focuses on the basic biology of omega-3 acids are associated with the prevention disease (Capanni et al. 2006). They also fatty acids as nutritional modulators of or reduction in severity of a multitude of improve kidney health by attenuating or infl ammation and presents preliminary diseases, from metabolic diseases such as even reversing the loss of kidney func- results of a study of oxylipin biomarkers heart disease, diabetes and kidney disease tion and reducing hypertension in kidney in kidney disease patients. to neurodegenerative diseases such as diseases involving the glomerulus, the Intake, food sources and metabolism Alzheimer’s to an array of other infl am- main fi ltering part of the kidney (Donadio matory diseases including osteoarthritis. et al. 1994). Omega-3 fatty acids affect Saturated and monounsaturated fatty EPA and DHA attenuate the devel- the joints and are used as analgesics or acids, which have no double bonds or opment of atherosclerosis, or arterial pain reducers in rheumatoid arthritis a single double bond, respectively, can plaques, by reducing concentrations of (Goldberg and Katz 2007). be synthesized in the liver. In contrast, infl ammatory signaling molecules called The omega-3s even play a role in cytokines and adhesion molecules at brain health: high blood plasma levels of Online: http://californiaagriculture.ucanr.org/ the arterial wall where plaque forms omega-3 fatty acids are associated with landingpage.cfm?article=ca.v065n03p106&fulltext=yes (De Caterina et al. 2004). EPA and DHA a reduced risk of neurodegenerative DOI: 10.3733/ca.v065n03p106 106 CALIFORNIA AGRICULTURE • VOLUME 65, NUMBER 3 polyunsaturated omega-3 and omega-6 consumed by Americans. Certain fatty acids, which have multiple double foods — including leafy greens, walnuts, bonds, are considered essential in the hu- canola oil, fl ax-fed chicken eggs and fatty man diet: they cannot be synthesized and fi sh (e.g., wild salmon, anchovies, mack- must be consumed. Terrestrial plants con- erel and tuna) — have relatively large tain the omega-6 fatty acid linoleic acid concentrations of omega-3. Historically, and the omega-3 fatty acid alpha-linolenic humans consumed diets with much acid but not the long-chain metabolites higher relative proportions of omega-3, Omega-6 (LA) Omega-3 (ALA) arachidonic acid, or EPA and DHA. Both with ratios of omega-6 to omega-3 of linoleic acid and alpha-linolenic acid can 1-to-1 or 2-to-1, in contrast to modern diets Desaturase be converted to their respective long- with ratios as high as 15-to-1 to 25-to-1 chain metabolites in the liver through a (Simopoulos 2008). Elongase Kathleen StuartNolan meat, sardines, Monk/iStockphoto; red series of enzymatic conversions (fi g. 1). The disproportionate consumption of However, since omega-3 and omega-6 omega-6 as compared to omega-3 fatty Desaturase fatty acids compete for the same en- acids is the result of common U.S. dietary zymes, the relative dietary proportions patterns. Foods such as salmon, walnuts, of precursor fatty acids determine the kale and eggs from chickens fed fl ax have ARA EPA net rate of conversion to their respective higher omega-3 fatty acid content than long-chain derivatives (Goyens et al. 2006; do more common American foods, like E/E/D/β-ox Zbigniew Ratajczak/iStockphoto; axseed, Clark; Jack Kelly fl walnuts, Yasonya/iStockphoto; Corn, Liou et al. 2007). Linoleic acid is readily corn oil, beef and potatoes (USDA 2011). converted to its long-chain metabolite For example, raw pink salmon has 419 arachidonic acid, and this conversion is milligrams of EPA and 586 milligrams of DHA driven by the amount of linoleic acid in- DHA per 100 grams, whereas raw ground gested. However, most humans convert beef contains none. Walnuts contain a smaller proportion of ingested alpha- 3,800 milligrams of linoleic acid and 9,080 linolenic acid into EPA and even less into milligrams of alpha-linolenic acid per DHA (Pawlosky et al. 2003). Most studies 100 grams. On the other hand, peanuts Fig. 1. dietary sources and enzymatic conversion agree on estimates of about 5% conver- contain 15,600 milligrams of linoleic and pathways of omega-3 and omega-6 fatty acid sion to EPA and less than 1% conversion only 3 milligrams of alpha-linolenic acid precursors. The omega-3 precursor alpha- to DHA (Burdge and Calder 2006). Due per 100 grams. These ratios mean that linolenic acid (ALA) is found in walnuts and fl ax seeds, and the omega-6 precursor linoleic acid to this low rate of conversion of alpha- the typical American diet is defi cient in (LA) is found in corn and vegetable oils. Both linolenic acid to EPA and DHA, and a omega-3 fatty acids, especially when con- are converted by desaturase and elongase generally low consumption of preformed sidered in relation to omega-6 fatty acids enzymes into their long-chain derivatives: ALA is converted to eicosapentaenoic acid (ePA) dietary long-chain omega-3 fatty acids, (Kris-Etherton et al. 2000). and docosahexaenoic acid (dHA); and LA is many Americans are likely defi cient in Because of the increasing levels of con- converted to arachidonic acid (ARA). ARA is EPA or DHA. taminants, like mercury and dioxins, in found in animal products, such as beef, and ePA Omega-6 fatty acids are abundant in both domestic and imported fi sh (Stahl et and dHA are found in fatty fi sh, such as sardines. the Western diet and are found in high al. 2009; Sunderland 2007), the consump- proportions in most cooking oils, grains tion of fi sh as a main source of long-chain to heart attack by stabilizing the heart and grain-fed animal products. On the omega-3 fatty acids is problematic, and muscles against arrhythmia (irregular other hand, omega-3 fatty acids are gen- some types of fi sh are not recommended heartbeat or abnormal heart rhythm) erally defi cient in the foods typically for consumption by pregnant women (Ballantyne 1999). For example, 200 milli- and small children (Jedrychowski et al. grams DHA per day decreases the chance 2007). Since terrestrial plants contain of death from cardiac arrest by 50% only the short-chain omega-3 precursor (Horrocks and Yeo 1999). alpha-linolenic acid, and since alpha- EPA and DHA metabolites stimulate Dennis S. Hurd linolenic acid is poorly converted into its the dilation of arterioles (small arteries) long-chain metabolites EPA and DHA, (Ye et al. 2002), which decreases blood it is likely that the American diet will pressure and inhibit the expression of continue to be relatively defi cient in these infl ammatory genes (Bouwens et al. important molecules unless signifi cant 2009). A literature review covering 2002 to dietary changes are made. 2004 — including a pooled analysis of 48 randomized, controlled trials and 41 co- Reducing disease risks hort trials — found no signifi cant benefi t Cardiovascular disease.