The frequency of fish intake reported for a 30-day period using an FFQ dietary assessment was not consistently associated with depressive symptoms in this study. Furthermore, fish oil supplementation was not independently associated with depressive symptoms in our population-based sample. However, a beneficial role of fish-derived n-3 PUFAs cannot be excluded based on our findings from a 24-hour estimate of EPA+DHA intake via 24-hour dietary recall; any reported EPA or DHA intake in the past 24 hours was significantly, in crude and multivariable analyses, associated with a reduced prevalence of depressive symptoms by 25% although the lack of consistent exposure-response patterns reduces our confidence in this result.
It is scientifically plausible that EPA and/or DHA can improve or prevent depressive symptoms. In the human body, DHA and EPA, and many of their metabolites produced via a variety of biochemical pathways, have substantial anti-inflammatory and tissue protective effects in several tissues[33
]. As DHA is very highly concentrated in the central nervous system and a vital nutrient in its optimum development[34
], its deficiency disrupts serotonin, norepinephrine, and dopamine transmission across cellular membranes, neurotransmitters that contribute to the mood and cognitive dysfunction aspects of depression[10
]. EPA, meanwhile, may play a more important role related to the somatic symptoms which affect up to 80% of individuals with major depression. At the cellular level, EPA can modulate proinflammatory reactions which induce symptoms of physical sickness[10
]. The importance of these fatty acids in the human diet is underlined by the fact that their synthesis from other fatty acids, such as alpha-linolenic acid, has been shown to be quite poor[34
]. This has important implications for central nervous system health at all ages.
EPA and DHA are known to be very safe dietary nutrients and supplements, even at high doses[35
], and promote cardiovascular health[3
] along with optimal brain development[4
] as well as reduce insulin resistance[5
]. They also improve the management of chronic inflammatory diseases[6
]. Very importantly, when combined with prescription pharmaceuticals, fish oil is not associated with serious or very concerning drug-drug interactions[36
]. When suggesting increased fish consumption to increase EPA and DHA intake, there are potential concerns related to pre- and postnatal mercury exposure and cognitive development in children, but recent research does not support these associations, even in populations that consume large amounts of fish[37
]. Thus, fish consumption as well as supplementation with EPH + DHA should be widely recognized as safe, and beneficial to health.
Recent clinical trials indicate that EPA and DHA supplementation can reduce depressive symptoms for individuals with MDD, especially when used as an adjuvant therapy[12
], but do not appear to be an effective preventive intervention in those without MDD. Likewise, our findings did not suggest that supplemental EPA and DHA were significantly associated with depressive symptom severity in the general US population. On the other hand, prior observational studies focusing on dietary intake rather than supplementation are less conclusive in regards to the relationship between fish intake and depressive symptoms[14
]. Observational studies are instrumental to understanding this question, however, as national recommendations regarding dietary fish intake could have a large impact on depression at a population-level. Only one previous study has addressed this question[38
]; Lucas et al did not find an association between n-3 PUFAs from fish and clinical depression in 54,632 women from the Nurses’ Health Study, although they did find that α-linolenic acid (ALA), a plant-based n-3 PUFA, was inversely associated with depression risk in this population. We conducted a large, population-based study addressing this question in a nationally-representative sample of both men and women in the United States. Furthermore, we considered severity of depressive symptoms rather than a dichotomous clinical endpoint which allowed us to better evaluate dose-response patterns. Conducting this analysis with NHANES data opens up the possibility of repeating results with future cohorts, and comparing findings to those using blood sample biomarkers for EPA and DHA content as these variables may be added to NHANES data in the near future. Our findings were inconclusive, however, and may have been substantially affected by exposure misclassification.
Food frequency questionnaires and 24-hour dietary recall estimates for fatty acid intake have been shown to be correlated[38
] and have been shown to correlate with biomarkers for fatty acids[38
]. Despite this, both methods have strengths and weaknesses for measuring dietary EPA and DHA. FFQ is likely to be more representative of a person’s usual diet compared to nutrient computations from 24 hour dietary recalls as a single 24-hour recall only considers the food eaten over a given day. However, we were able to average two 24-hour recalls to improve this. The greatest benefit to dietary recalls is the fact that they take into account factors such as the specific type of fish, portion size, and cooking methods. These factors greatly influence the EPA and DHA content of a fish meal[39
]. Dietary recall data should therefore more accurately reflect EPA+DHA intake during the time period reported. Thus, it is not surprising that in our study EPA+DHA correlated significantly, but weakly with all fish meals, non-breaded fish meals, and shellfish meals from 30-day FFQ data, and was uncorrelated with breaded fish meals from 30-day FFQ data in this study (data not shown). This pattern supports the validity of our classification system for FFQ-based fish intake as breaded fish meals are likely to be fried, and frying fish, as well as the type of fish most often fried, is associated with reduced EPA+DHA content[39
]. At the same time, the low correlations between fish meals and EPA+DHA we observed indicates that reported fish meals in the past 30 days may not be a strong predictor of fish-derived dietary n-3 PUFA. Therefore, we believe EPA+DHA from a 24-hour recall is a more accurate predictor of dietary n-3 PUFAs in this study as findings from this analysis do support the a priori hypothesis that dietary omega-3 poly-unsaturated fatty acids reduce depressive symptoms. One further limitation to note for both FFQ and dietary recall is that both reflect relatively short-term fish intake, and do not help quantify more chronic (over years) intake which is may be important in the long-term development of depressive symptoms. This limitation is inherent to the cross-sectional design of NHANES, however, the dietary patterns of adults do not change dramatically over time. Since blood content of EPA and DHA is a very reliable measure of dietary intake, the addition of this metric to future studies will be very beneficial.
Interestingly, our FFQ findings suggest that breaded-fish meals significantly increase the risk of greater depressive symptoms, yet no consistent exposure-response pattern is observed for the categorical analysis. We would not expect breaded fish meals, which are often fried, to be an important source of dietary EPA and DHA and thus we would not expect consumption of such meals to protect against depressive symptom severity. The significantly increased risk is harder to explain, but breaded fish may simply be a proxy for consuming a higher fat, less healthful diet, which would help explain the association with greater depressive symptoms[40
In conclusion, although our findings do not show consistent patterns across exposure classification methods, they do suggest that higher levels of dietary EPA+DHA may be associated with a reduced number of depressive symptoms. Future longitudinal studies are needed to directly link dietary intake of fish and biomarkers for fish-related n-3 PUFA with depressive symptoms.