Some evidence for the essentiality of n-3 fatty acids in humans can be drawn from case reports of patients receiving parenteral nutrition with intravenous lipids containing an emulsion of safflower oil, which is very low in a-linolenic acid and high in linoleic acid. Biochemical changes of n-3 fatty acid deficiency include a decrease in plasma and tissue docosa-hexaenoic acid (DHA) concentrations. There is no accepted cut-off concentration of plasma or tissue DHA concentrations below which functions ascribed to n-3 fatty acids, such as visual or neural function, are impaired. Similarly, there are no accepted normal ranges for eicosapentaenoic acid (EPA) with respect to synthesis of EPA-derived eicosanoids or regulation of arachidonic acid metabolism and its eicosanoid metabolites, nor are there accepted clinical functional endpoints such as immune response.
long-chain fatty acids.
Dietary or intravenous supplementation with oils containing a-linolenic acid, such as soybean oil, has been shown to increase red blood cell and plasma phospholipid DHA concentration in hospitalized patients with a long history of dietary n-3 fatty acid restriction (Bjerve et al., 1987a, 1987b; Holman et al., 1982). Sensory neuropathy and visual problems in a young girl given parenteral nutrition with an intravenous lipid emulsion containing only a small amount of a-linolenic acid were corrected when the emulsion was changed to one containing generous amounts of a-linolenic acid (Holman et al., 1982). Nine patients with an n-3 fatty acid deficiency had scaly and hemorrhagic dermatitis, hemorrhagic folliculitis of the scalp, impaired wound healing, and growth retardation (Bjerve, 1989). The possibility of other nutrient deficiencies, such as vitamin E and selenium, has been raised (Anderson and Connor, 1989; Meng, 1983). A series of papers have described low tissue n-3 fatty acid concentrations in nursing home patients fed by gastric tube for several years with a powdered diet formulation that provided about 0.5 to 0.6 percent of energy (0.65 to 0.86 g) as linoleic acid, and 0.02 percent of energy (30 to 50 mg) as a-linolenic acid (Bjerve et al., 1987a, 1987b). Skin lesions were resolved following supplementation with cod liver oil and soybean oil or ethyl linolenate (Bjerve et al., 1987a, 1987b). Concurrent deficiency of both n-6 and n-3 fatty acids in these patients, as in studies of patients supported by lipid-free parenteral nutrition, limits interpretation of the specific problems caused by inadequate intakes of n-3 fatty acids. Supplementation with cod liver oil and soybean oil, or feeding with a formula providing linoleic acid and a-linolenic acid or ethyl a-linolenic acid for 14 days, increased red blood cell arachidonic acid and DHA concentrations and gave some resolution of skin signs (Bjerve et al., 1987a, 1987b). Because of the lack of data on the n-3 fatty acid requirement in healthy individuals, an EAR cannot be set based on correction of a deficiency.
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