WHAT THESE STUDIES ADD:

• Fish oil may help prevent bronchoconstriction; prenatal exposure to fish oil may lower the risk of allergy.

BLOOMINGTON, IND—Fish oil may help prevent respiratory and allergic disease. Two new studies provide compelling evidence that the n-3 polyunsaturated fatty acids (PUFAs) contained in fish oil can dampen inflammation in the lungs and thereby help prevent bronchoconstriction[1]; prenatal exposure to these PUFAs may also lower the risk of allergy.[2] Not all studies of the use of fish oil for respiratory and allergic disease have produced such promising results, however.

In the first study, three weeks of supplementation with fish oil capsules containing high levels of n-3 PUFAs markedly decreased the incidence of exercise-induced bronchoconstriction (EIB) in elite athletes.[1] These athletes are at increased risk for EIB because of exercise-induced hyperventilation, prolonged exposure to allergens and bronchial irritants, and excessive inhalation of cold, dry air.

“Obviously, the results of the study need to be duplicated,” admitted lead investigator Timothy D. Mickleborough, PhD, Assistant Professor of Kinesiology at Indiana University in Bloomington. “But fish oil seemed to alleviate symptoms of exercise-induced bronchoconstriction dramatically in these athletes and could reduce their need for pharmacologic treatment.”

In the second study, the infants of mothers who took fish oil supplements during pregnancy were found to have decreased expression of inflammatory cytokines in response to allergen in vitro. Although not all of these differences were statistically significant, the study’s results provide preliminary evidence that prenatal exposure to n-3 PUFAs may lower the prevalence of allergic sensitization in infants.

This study was not specifically designed to examine clinical outcomes. However, the investigators noted a lower risk of egg allergy and a reduced severity of atopic dermatitis among the infants exposed to fish oil.

“It is important to understand that these are preliminary data, but they do warrant further study,” asserted lead investigator Susan L. Prescott, MD, PhD, who is the Head of the School of Pediatrics and Child Health at the University of Western Australia in Perth.

FISH OIL FOR EIB

Dr. Mickleborough’s double-blind study included 20 elite athletes: 10 who had EIB and 10 who did not. All 20 athletes were ranked at the collegiate or national level in their sport (triathlon, cross-country, or track and field). At the start of the study, all athletes consumed their normal diet; they were then randomized to three weeks of daily supplementation with capsules that contained either fish oil (3.2 g of eicosapentaenoic acid and 2.2 g of docohexaenoic acid) or placebo (olive oil). After a two-week washout period, the two groups crossed over to the opposite treatment for three more weeks.

Neither the fish oil nor the placebo had any effect on pre-exercise pulmonary function in the athletes with EIB or in the controls. However, the fish oil supplement—but not the placebo—significantly improved postexercise lung function in the athletes with EIB. In the controls, no change in postexercise lung function was seen with either type of supplement.

When taking the supplement, the EIB group experienced an average decline in forced expiratory volume in one second (FEV1, measured 15 minutes after exercise) of only 3%. By comparison, FEV1 fell by a mean of 14.5% when these athletes were taking the placebo and by a mean of 17.3% when they were eating their usual diet. The results for forced vital capacity were similar. Fish oil supplementation was also associated with significantly less bronchodilator use in the EIB group.

The researchers found an explanation for the clinical impact of fish oil in its effect on a variety of proinflammatory markers in serum and urine, including leukotrienes B4 and E4, tumor necrosis factor-alpha, and interleukin-1ß. Postexercise levels of these markers were similar to baseline values in the controls, but they were markedly elevated in the athletes with EIB when that group was receiving placebo or eating a normal diet. However, fish oil supplementation significantly attenuated the postexercise rise in these levels in the EIB group.

Fish oil supplementation could reduce the need for pharmacotherapy in elite athletes with EIB, said Dr. Mickleborough, if it is found that the supplement and drug therapy work through similar mechanisms, such as leukotriene B4 and E4 suppression. “It would also be useful to look at the effect of different dosages, durations, and grades of fish oil,” he added.

SUPPLEMENTATION DURING PREGNANCY

To determine whether n-3 PUFA supplementation can modify immune system development in utero (before allergic disease becomes established), Dr. Prescott and colleagues randomly assigned 98 atopic pregnant women to daily supplementation with fish oil or placebo (again, olive oil); the supplements were started during the 20th week of gestation and continued until delivery. Each fish oil capsule contained a combined 3.7 g of eicosapentaenoic acid and docohexaenoic acid.

To avoid the effects of prematurity, only healthy infants born after at least 36 weeks’ gestation were included in the study. Therefore, at the final analysis, 83 pairs of mothers and infants remained: 40 in the fish oil group and 43 in the placebo group.

At birth, the infants whose mothers took the fish oil supplement had a significantly higher proportion of n-3 PUFAs in their erythrocyte membranes than did the other infants (17.75% vs 13.69%). The infants in the fish oil group also had significantly lower interleukin-10 (IL-10) responses to cat allergen, as well as a trend toward decreased IL-5, IL-13, and interferon-gamma responses to that allergen. In addition, these infants also had a trend toward lower cytokine (interleukin and interferon-gamma) responses to house dust mites, ovalbumin, and mitogen.

Follow-up evaluation demonstrated that, in comparison with the infants whose mothers had been given placebo, those in the fish oil group were three times less likely to be sensitized to egg ovalbumin at age 1. Although the infants whose mothers had received fish oil were almost twice as likely to have atopic dermatitis than were the other infants (not statistically significant), they were 10 times less likely to have severe disease (statistically significant).

In a combined analysis that included both groups of infants, cytokine responses to allergens and mitogens were found to correlate inversely with the proportion of n-3 PUFAs and directly with the proportion of n-6 PUFAs in their erythrocyte membranes. Thus, maternal fish oil supplementation may have altered neonatal immune function by altering the cellular balance of PUFAs in favor of the anti-inflammatory n-3 variety (the n-6 PUFAs, in contrast, are proinflammatory).

“We had to use fish oil supplements in this study because it was double-blind,” remarked Dr. Prescott. “But if we can show in larger trials that improving infant n-3 fatty-acid status during pregnancy or early postnatal life reduces allergic disease risk, then we would obviously recommend direct dietary measures, such as advising pregnant women to eat more fish.”

—Timothy Begany

References
1. Mickleborough TD, Murray RL, Ionescu AA, Lindley MR. Fish oil supplementation reduces severity of exercise-induced bronchoconstriction in elite athletes. Am J Respir Crit Care Med. 2003;168:1181-1189.
2. Dunstan JA, Mori TA, Barden A, et al. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol. 2003;112:1178-1184.

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