January 15, 2009
This information is distributed solely for the purpose of pre-dissemination peer and public review under applicable information quality guidelines. It has not been formally disseminated by FDA. It does not represent and should not be construed to represent any agency determination or policy.
(a) Purpose of this Project
The benefits and risks of fish that are commercially distributed for human consumption have both been the subject of much scientific research. On the one hand, fish provide a source of easily digestible protein of high biological value, micronutrients including vitamins A and D, minerals such as iodine and selenium, and high levels of the amino acids taurine, arginine and glutamine (EFSA 2005; He and Daviglus 2005). Additionally, many fish provide a uniquely rich food source of long chain omega-3 fatty acids (also called n-3) long-chain polyunsaturated fatty acids (n-3 LC PUFA), most notably docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). There is a large and growing body of research on the extent to which fish, and nutritional components of fish such as omega-3 fatty acids, convey health benefits, especially protection against heart disease and promotion of nervous system development. Specifically, a number of research studies have reported associations between consumption of fish, fish oil, or n-3 LC PUFA and reduced risk of cardiovascular events such as heart attack and stroke (Kris-Etherton et al., 2002). Moreover, the n-3 LC PUFA, docosahexaenoic acid, has been shown to be essential for development of the central nervous system (EFSA 2005) (page 30). Consequently, there is considerable interest in whether there is an association between fetal, infant or child neurodevelopment and maternal intake of fish or n-3 LC PUFA during pregnancy and lactation (SACN, 2004).
On the other hand there are safety concerns associated with the consumption of fish. The safety issue most frequently raised is that of methylmercury, a neurotoxin, since it is generally present in all fish, at least in trace amounts.
The National Academy of Sciences' Institute of Medicine (IOM) recently reviewed the science on human risks and benefits associated with of consuming commercially available fish. In October 2006, the IOM published its findings in a report titled, "Seafood Choices: Balancing Benefits and Risks" (IOM 2006). The report states that:
- "New tools apart from traditional safety assessments should be developed, such as consumer-based benefit-risk analyses. A better way is needed to characterize the risks combined with the benefits analysis."
- "Consolidated advice is needed that brings together different benefit and risk considerations, and is tailored to individual circumstances, to better inform consumer choices. Effort should be made to improve coordination of federal guidance with that provided through partnerships at the state and local level."
This report reflects an effort by the U.S. Food and Drug Administration (FDA) to improve its understanding of the consequences of eating commercial fish for some health endpoints for which methylmercury is a potential risk factor. The current analysis takes the IOM recommendations into account by attempting to quantify the risk-benefit relationship for selected health endpoints. This type of analysis could lead to the development of better tools to inform decision-making about commercial fish consumption, e.g., to allow for the maximization of benefits consistent with the minimization of risk. A risk/benefit approach can provide a holistic view of the overall consequences of any risk management strategy.
The need to take health benefits from fish into account along with the risks that methylmercury and other hazards may pose has been recognized by other health organizations. For example, the Codex Alimentarius Commission (Codex 2006) has asked the Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization to convene an Expert Consultation to:
- "Develop a methodology and identify the data necessary for carrying out quantitative risk assessments of risks and benefits related to fish and other seafood consumption;" and
- "Compare nutritional benefits against the possibility of adverse effects, including the uncertainties, taking into consideration all groups in the population, and, if possible, allowing quantitative comparisons of human health risks and benefits of fish and other seafood consumption."
This FDA report presents a quantitative risk and benefit assessment of the effect of eating commercial fish on verbal development in young children as an indicator of fetal neurodevelopment, and on coronary heart disease and stroke in the general population. We refer to it as a risk and benefit assessment because it attempts to estimate the net effect of eating commercial fish on these selected health endpoints. A net effect can include an adverse contribution from the methylmercury in the fish and a beneficial contribution from the nutrients in the fish. The net effect could be adverse, or it could be neutral or even beneficial, depending on the circumstances. It is quantitative because it attempts to estimate the size and nature of the net effect through the range of exposures to methylmercury that U.S. consumers are experiencing through the consumption of commercial fish.
Verbal development is one of many aspects of neurodevelopment. We used verbal development in young children as an indicator of neurodevelopment because we had data on it sufficient to develop dose-response functions for both an adverse contribution of methylmercury to the net effect and a beneficial contribution of fish to the net effect. It is not necessarily the aspect of neurodevelopment that is most sensitive to methylmercury, however. In order to determine whether it is sufficiently representative in terms of its sensitivity to methylmercury, we performed a comparative analysis by matching the results against dose-response functions developed for the effect of methylmercury on IQ (Axelrad et al., 2007) and on a wide range of neurodevelopmental tests (Cohen et al., 2006b).
This assessment has several limitations. Because this assessment does not distinguish among types or species of fish in terms of their beneficial constituents, it is not possible to directly translate the results of this analysis into fish-specific advice to consumers about what types or species of fish to eat to maximize net health benefits. In addition, this assessment does not take a comprehensive look at all neurodevelopmental or cardiovascular endpoints. Furthermore, judgments about the clinical significance of the estimates themselves are beyond the scope of this report. Risk management decisions are not addressed in this report. Finally, the assessment is not intended to make a case one way or another for the adequacy of any proposed or existing "health claim" on labeling for any product. "Health claims" are evaluated under standards of evidence that have been developed specifically for that purpose.(1)
This assessment is intended to be nationally representative of the U.S. population. It does not address risk to segments of the population whose exposure to methylmercury or patterns of fish consumption may be substantially different from the population as a whole as a result, for example, of their own subsistence or sport fishing in localized bodies of water that might be subject to unusual conditions. Separate assessments would be needed to predict effects in such sub-populations. Because these kinds of situations would tend to not generally involve interstate commerce, they would not normally fall within FDA's regulatory purview under the Federal Food, Drug, and Cosmetic Act.
There is a companion document to this report that inventories the state of the research on the benefits of fish consumption relating to neurodevelopment and coronary heart disease and stroke. Much of the research has been on omega-3 fatty acids. The main purpose of the companion document is to explore potential biological explanations for the beneficial effects from fish that are being reported in the research studies. The companion document is entitled "Summary of Published Research on the Beneficial Effects of Fish Consumption and Omega-3 Fatty Acids for Certain Neurodevelopmental and Cardiovascular Endpoints."
(1) See section 403(r)(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 343(r)(3), 21 CFR 101.14(c), and FDA's draft guidance entitled "Evidence-Based Review System for the Scientific Evaluation of Health Claims (FDA 2007).