The effect of a flaxseed oil-based diet on tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) synthesis was examined in healthy volunteers. Use of flaxseed oil in domestic food preparation for 4 wk inhibited TNF alpha and IL-1 beta production by approximately 30%. Fish-oil supplementation (9 g/d) continued for a further 4 wk; TNF alpha and IL-1 beta synthesis were inhibited by 74% and 80%, respectively. There was a significant inverse exponential relation between TNF alpha or IL-1 beta synthesis and mononuclear cell content of eicosapentaenoic acid (EPA), an n--3 fatty acid derived from ingested EPA (fish oil) or metabolism of ingested alpha-linolenic acid (flaxseed oil). Cytokine production decreased as cellular EPA increased to approximately 1% of total fatty acids. Further increases in EPA content did not result in further decreases in cytokine production. The results indicate that vegetable oils rich in n--3 fatty acids inhibit TNF alpha and IL-1 beta synthesis.

Background: Results of many studies indicate that consumption of n−3 fatty acids can benefit persons with cardiovascular disease and rheumatoid arthritis. However, encapsulated fish oil is unlikely to be suited to lifetime daily use and recommendations to increase fish intake have not been effective. Objective: The objective was to examine the effectiveness of a diet that incorporates foods rich in n−3 fatty acids in elevating tissue concentrations of eicosapentaenoic acid and in suppressing the production of inflammatory mediators. Design: Healthy male volunteers were provided with foods that were enriched in α-linolenic acid (cooking oil, margarine, salad dressing, and mayonnaise) and eicosapentaenoic and docosahexaenoic acids (sausages and savory dip) and with foods naturally rich in n−3 fatty acids, such as flaxseed meal and fish. Subjects incorporated these products into their food at home for 4 wk. Fatty acid intakes, cellular and plasma fatty acid concentrations, and monocyte-derived eicosanoid and cytokine production were measured. Results: Analyses of dietary records indicated that intake of eicosapentaenoic acid plus docosahexaenoic acid averaged 1.8 g/d and intake of α-linolenic acid averaged 9.0 g/d. These intakes led to an average 3-fold increase in eicosapentaenoic acid in plasma, platelet, and mononuclear cell phospholipids. Thromboxane B₂, prostaglandin E₂, and interleukin 1β synthesis decreased by 36%, 26%, and 20% (P < 0.05), respectively. Conclusions: Foods that are strategically or naturally enriched in n−3 fatty acids can be used to achieve desired biochemical effects without the ingestion of supplements or a change in dietary habits. A wide range of n−3-enriched foods could be developed to support large-scale programs on the basis of the therapeutic and disease-preventive effects of n−3 fatty acids.

Increased concentrations of cellular eicosapentaenoic acid (EPA) have been shown to be beneficial in coronary heart disease, hypertension, and inflammatory disorders. Successful long-term strategies for increasing cellular EPA concentrations require information on the relationships between cellular concentrations of EPA and dietary amounts of alpha-linolenic acid (alpha-LA), a precursor of EPA, and dietary amounts of linoleic acid (LA), an antagonist of alpha-LA conversion to EPA. A dietary intervention study with healthy human volunteers that incorporated alpha-LA-rich vegetable oil (flaxseed oil), against a background diet low in LA, allowed us to examine these relationships. Linear relationships were found between dietary alpha-LA and EPA in plasma fractions and in cellular phospholipids. By contrast there was no relationship observed between dietary LA and tissue concentrations of its metabolite, arachidonic acid (AA). There was an inverse relationship between dietary alpha-LA and docosahexaenoic acid concentrations in the phospholipids of plasma, neutrophils, mononuclear cells, and platelets. The results indicate that increasing dietary alpha-LA will elevate tissue EPA concentrations in a predictable manner. This insight will facilitate the rational planning of practical dietary strategies for the long-term elevation of EPA concentrations in tissues.