Which Fats Are Inflammatory?

By James Gerber, MS, DC
Diets aimed at reducing inflammatory states typically prescribe changes to fat intake, increasing consumption of omega-3 fatty acid sources and restricting other fats, including omega-6 fatty acid sources that are thought to have pro-inflammatory effects. What is the evidence for the pro-inflammatory nature of omega-6 fatty acids, and what are their effects on health?
Inflammation is mediated in part by the production of prostaglandins and other eicosanoids. Some eicosanoids—those derived from arachidonic acid, a member of the omega-6 family—have pronounced pro-inflammatory effects, while others, such as those derived from the long-chain omega-3 fatty acids, have minimal inflammatory effects. Production of these different eicosanoids is influenced by many factors, such as the availability of each precursor and the competition between precursors for the common enzymes used in eicosanoid synthesis.
Arachidonic Acid
Clinical studies on the effects of fatty acids on inflammation have mainly researched fish oil supplements, but at least one trial1 demonstrated that a low arachidonic acid diet (limiting animal fats) significantly reduced the severity of rheumatoid arthritis in patients. To reduce inflammatory states, clinicians started recommending limiting not only the arachidonic acid consumption from animal fats (the only source of arachidonic acid in the diet), but also other omega-6 fatty acids, typically found in common vegetable oils, nuts and seeds, which can be converted to arachidonic acid in the body. However, this extrapolation oversimplifies the complexity of omega-6 fatty acid metabolism.
The direct precursor of arachidonic acid is di-homo gamma-linolenic acid (DGLA), but DGLA also limits eicosanoids’ inflammatory activity. The omega-6 precursor to DGLA is gamma-linolenic acid (GLA), and supplements rich in GLA, such as evening primrose or borage seed oils, have been shown in short-term therapeutic trials to have anti-inflammatory effects similar to fish oils.
Linoleic Acid
The simplest and most abundant omega-6 fatty acid in the human diet is linoleic acid, which can be a precursor to any of the above molecules. Limiting the plant sources of dietary omega-6 will primarily reduce linoleic acid consumption. Will this, in turn, reduce systemic inflammation and benefit health? Conclusive answers to this question are not available, but certain indirect lines of evidence are useful to review.
The Western diet in many ways deviates from natural human diets. A relative abundance of omega-6 sources—thanks to copious use of vegetable oils in everything from salad dressings to baked goods to fried fast foods—coupled with a relative dearth of omega-3 sources, due to their limited availability in high-fat fish and certain plant oils, has pushed omega-6 to omega-3 ratio (estimated to be at least 10:1) in the Western diet to levels unseen before the latter half of the 20th century.
While it is tempting to blame this change for many of the health crises that have also developed in the same time frame, many other dietary, lifestyle and environmental changes have occurred during this period. In fact, according to recent large epidemiological studies, increased consumption of natural vegetable oils (i.e., those oils not processed by partial hydrogenation, and therefore lacking any trans fatty acid content) reduces the risk of heart disease and diabetes, diseases that are now understood to include inflammatory and other eicosanoid-related components in their pathobiology. (Editor’s note: For more information on cardiovascular nutrition, see the Nov. 2007 issue of ACA News; go to www.acatoday.org/acanews and click ACA News Archives.)
Perhaps non-eicosanoid-related mechanisms, such as lowering LDL cholesterol and improving insulin sensitivity, outweigh any other influences of omega-6 fats on these diseases, but nonetheless, they are helpful, not harmful. In the case of cancer risk, current evidence implicates other dietary factors, such as excessive calories and low fruit and vegetable consumption, as more important influences than differences in fatty-acid intake.
A landmark study by Pischon et al.2 measured blood levels of four mediators of inflammation: C-reactive protein (CRP), interleukin-6 (IL-6) and two soluble receptors for tumor necrosis factor (sTNF-R1 and sTNF-R2) in more than 800 healthy men and women whose diet was analyzed for omega-3 and omega-6 content. Omega-6 intake was not associated with high levels of these inflammatory mediators unless omega-3 was also low. When omega-3 intake was high, high omega-6 improved the beneficial association of omega-3 with reduced levels of these indicators. Thus, this study was in agreement with cardiovascular research showing that high levels of both fatty acid families confer the most protection against pathological states.
Another important recent study3 addressed the theoretical concern that high omega-6 intake could increase free radical pathology because of the vulnerability of polyunsaturated fats to oxidative changes. Surprisingly, this study found that having subjects ingest large amounts of linoleic acid resulted in no significant effects on measures of oxidative damage to DNA. These authors concluded that suggestions to reconsider public health recommendations encouraging polyunsaturated fats intake were unsupportable.
If dietary omega-6 fats other than arachidonic acid from animal sources cannot be implicated in inflammatory or oxidative pathologies, and may even be beneficial against common conditions such as cardiovascular diseases and diabetes, perhaps the best dietary advice for mitigating systemic inflammatory states should be to ensure an abundant supply of omega-3 fatty acids, especially from fish and fish oil supplement sources, coupled with reduction of animal fats that provide arachidonic acid (as well as saturated fat and cholesterol). These changes should most effectively address both inflammatory mechanisms and other pathologies that threaten the health of our patients.
Dr. Gerber can be reached at jgerber@wschiro.edu.
References and sources
1. Adam O, Beringer C, Kless T, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 2003 Jan;23(1):27-36.
2. Pischon T, Hankinson SE, Hotamisligil GS, et al. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 2003;108:155-160.
3. de Kok TM, Zwingman I, Moonen EJ, et al. Analysis of oxidative DNA after human dietary supplementation with linoleic acid. Food Chem Toxicol 2003;41:351-58.
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5. Kapoor R, Huang YS. Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Curr Pharm Biotechnol. 2006 Dec;7(6):531-4.
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10. Joint WHO/FAO Expert Consultation on Diet, Nutrition and the Prevention of
Chronic Diseases. Diet, nutrition and the prevention of chronic diseases: report of a joint WHO/FAO expert. Consultation. Geneva, Switzerland, 2002.
11. Essential Fatty Acids, available from the Linus Pauling Micronutrient Information Center at http://lpi.oregonstate.edu/infocenter/othernuts/omega3fa/index.html.