Immunologic Effects of National Cholesterol Education Panel Step‐2 Diets With and Without Fish‐Derived N‐3 Fatty Acid Enrichment

In an attempt to reduce the risk of heart disease caused by atherosclerosis, the National Cholesterol Education Panel suggests that Americans follow the Step‐2 diet, which is low in total fat, saturated fatty acid (SFA), and cholesterol. Step‐2 diet recommendations prescribe an overall fat intake of less than 30% of total calories (less than 7% of total calories from SFA, 10% to 15% of total calories from monounsaturated fat, equal to or less than 10% of total calories from polyunsaturated fatty acid [PUFA]) and a dietary cholesterol intake that is less than 200 mg/d. Inasmuch as dietary fat has previously been shown to influence the immune function in critically ill patients, the authors of this study investigated the effects of long‐term (24 weeks), low‐fat, low‐cholesterol, high‐PUFA feeding on immune response in normal volunteers. Two versions of the Step‐2 diet were studied: a fish‐oil‐enriched Step‐2 diet containing 1.23 g/d of omega‐3 PUFAs from eicosapentaenoic and docosa‐hexaenoic acid and a low‐fish Step‐2 diet containing only 0.27 g/d of omega‐3 PUFA. Both have a moderately high amount of vegetable‐derived PUFAs. For an initial 6‐week baseline period, 22 healthy normolipidemic men and women over the age of 40 years were fed a diet fashioned after the current American diet with a relatively high percentage of overall fat, cholesterol, and SFA (35% of the total calories coming from fat, 14.1% from monounsaturated fat, 6.1% from n‐6 PUFA, 14.1% from SFA, 0.8% from n‐3 PUFA, and 147 mg of cholesterol per 1000 kcal). After the equilibration period, the group was divided (two groups each with 11 subjects) and placed on one of the two National Cholesterol Education Panel diets for a period of 24 weeks. Immune‐response tests were completed after each diet period at weeks 4, 5, and 6 of the initial diet period and at weeks 22, 23, and 24 of the study diet period. Long‐term intake of the Step‐2 diet rich with omega‐3 PUFA seemed to profoundly alter results of in vitro and in vivo immune‐response measurements, including changes in lymphocyte proliferation, eicosanoid formation, and cytokine production. In response to a mitogenic challenge with T‐cell‐dependent Con A, lymphocyte proliferation of the high‐fish group significantly decreased from baseline. After stimulation of the peripheral‐blood mononuclear cells, significantly less prostaglandin (PG)E‐2, interleukin (IL)‐1B, IL‐6, and tumor necrosis factor (TNF) were produced ex vivo in the high‐fish group. In addition, there was a significant decrease in the percentage of helper T‐cells in the high‐fish group and coincident increases in the percentage of suppressor T‐cells. Finally, the high fish diet resulted in a depressed response to the delayed‐type hypersensitivity skin test, an in vivo test of cell‐mediated immunity. Conversely, the Step‐2 diet low in eicosap‐entaenoic and docosahexaenoic acid had almost no effect on these immune parameters except that there was an increased mitogenic response to Con A at week 24, compared with baseline, and an increased production of two cytokines (TNF and IL‐1B). Thus, the authors conclude that a long‐term, omega‐3‐enriched, low‐fat diet may be useful therapy for treatment of diseases related to the inflammatory response and atherosclerosis; however, the changes in immune function produced increased vulnerability of the host to invasive pathogens.