Evaluating health benefits and chemical risks of fish intake
Jose L Domingo, Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgili University, 43201 Reus, SPAIN
8 November 2007
In this paper, Stern concludes telling “that there are easily available fish that offer both high polyunsaturated fatty acids (PUFAs) and low methyl mercury and that the consumers should chose wisely among the available fish so as to maximize the benefits and decrease the risks”. Stern is also very critical with a previous statement by Mozaffarian and Rimm [1], who in a recent review paper published in JAMA concluded that for major health outcomes among adults, “the benefits of fish consumption exceeded potential risks”. Based on the long experience of our research group, I would like to add some arguments to that important issue.
Firstly, I would like to note that the evidence supporting the statement by Mozaffarian and Rimm [1] is very limited. Only the risks of a few environmental pollutants: methylmercury, dioxins and furans (PCDD/PCDFs), and polychlorinated biphenyls (PCBs) were included in their review paper, and only these contaminants were the basis to support the main conclusion. Other important chemical contaminants were not included. For example, the polycyclic aromatic hydrocarbons (PAHs). Nowadays, according to the US EPA [2], at least 7 PAHs are known carcinogenic agents in humans. Why environmental pollutants such as polychlorinated diphenyl ethers (PCDEs) or polychlorinated naphthalenes (PCNs), for which some congeners seem act as “dioxin-like” compounds [3, 4] were not evaluated, or what polybrominated diphenyl ethers (PBDEs), a family of contaminants with well known toxic effects [5, 6] were not assessed? The bias performed by Mozaffarian and Rimm [1], not reviewing the potential adverse effects of various groups of pollutants, would explain the reason of such statement: “the benefits of fish consumption exceeded potential risks”.
We recently determined the levels of 16 PAHs, PCDEs, PCNs, and PBDEs together with those of arsenic, cadmium, lead, mercury, hexachlorobenzene, PCDD/PCDFs and PCBs in various widely consumed marine species [7-11]. Surprisingly, neither the results of these studies, nor those of previous investigations of our research group concerning dietary exposure (including fish and other seafood) to environmental pollutants were referenced by Mozaffarian and Rimm [1]. How could this occur? Why the results of these articles were not reviewed/discussed taking into account that all are referenced in the most frequently used databases: Medline, Scopus, etc? According to the authors, Medline was chosen as the main database for preparing their review [1]. Mozafarian and Rimm [1] also concluded that potential risks of fish intake should be considered in the context of potential benefits. I agree, but how most individuals can get this information? Instead of giving a general recommendation, I would recommend an individual balance of the potential health benefits (intake of PUFAs for cardiovascular benefits) and chemical risks (environmental contaminants) related with fish and other seafood consumption, which is more realistic and adequate. Recently, we designed the software RIBEPEIX®, which is currently available in Internet (htpp://www.fmcs.urv.cat/portada/ribepeix/) [12]. For 14 fish and other seafood species, the use of RIBEPEIX® allows optimizing the balance between the health benefits of omega-3 polyunsaturated fatty acids (EPA and DHA) and the chemical risks of fish consumption. It is possible to select the most suitable species (based on the measured concentrations of EPA plus DHA, and pollutants), the frequency of consumption of those species, as well as the most adequate meal sizes. Using RIBEPEIX, we found for example, that for an adult of 70 kg consuming 2 services per week (227 g) of swordfish or red mullet, the intake of mercury (from swordfish) would be 12.52 μg/kg, which notably exceeds the tolerable 5 μg/kg intake, while that of PCDD/PCDFs + dioxin-like PCBs (from red mullet) would be 30.13 pg WHO-TEQ/kg, amount that exceeds the tolerable 14 pg WHO-TEQ/kg intake for these compounds. If the frequency of fish consumption is increased up to 3 meals per week, the intake of PCDD/PCDFs + dioxin-like PCBs from anchovy, for example, or those of PCDD/PCDFs + dioxin-like PCBs and mercury from tuna, would reach approximately the respective tolerable limits [13, 14]. It is obvious that if the weekly fish consumption is increased, the tolerable limits of certain chemical contaminants can also simultaneously increase, with the potential health risks that it would mean [13, 14]. Consequently, I strongly agree with the conclusions of Stern, but I clearly disagree with those of Mozaffarian and Rimm [1].
References
1. Mozaffarian D, Rimm EB: Fish intake, contaminants, and human health. Evaluating the risks and benefits. JAMA 2006, 296:1885-1899.
2. US Environmental Protection Agency. 2002. Polycyclic organic matter. US EPA, Washington, DC. [http://www.epa.gov.ttn/atw/hlthef/polycycl.html].
3. Domingo JL: Polychlorinated diphenyl ethers (PCDEs): environmental levels, toxicity and human exposure: a review of the published literature. Environ Int 2006, 32:121-127.
4. Domingo JL: Polychlorinated naphthalenes in animal aquatic species and human exposure through the diet: a review. J Chromatogr A 2004, 1054:327-334.
5. Darnerud PO: Toxic effects of brominated flame retardants in man and in wildlife. Environ Int 2003, 29:841-853.
6. Domingo JL: Human exposure to polybrominated diphenyl ethers through the diet. J Chromatogr A 2004, 1054, 321-326.
7. Llobet JM, Falco G, Bocio A, Domingo JL: Exposure to polycyclic aromatic hydrocarbons through consumption of edible marine species in Catalonia, Spain.
J Food Prot 2006, 69:2493-2499.
8. Domingo JL, Bocio A, Falco G, Llobet JM: Exposure to PBDEs and PCDEs associated with the consumption of edible marine species. Environ Sci Technol 2006, 40:4394-4399.
9. Falco G, Llobet JM, Bocio A, Domingo JL: Daily intake of arsenic, cadmium, mercury, and lead by consumption of edible marine species. J Agric Food Chem 2006, 54:6106-6112.
10. Llobet JM, Falco G, Bocio A, Domingo JL: Human exposure to polychlorinated naphthalenes through the consumption of edible marine species. Chemosphere 2007, 66:1107-1113.
11. Bocio A, Domingo JL, Falco G, Llobet JM. Concentrations of PCDD/PCDFs and PCBs in fish and seafood from the Catalan (Spain) market: estimated human intake. Environ Int 2007, 33:170-175.
12. Domingo JL, Bocio A, Marti-Cid R, Llobet JM: Benefits and risks of fish consumption Part II. RIBEPEIX, a computer program to optimize the balance between the intake of omega-3 fatty acids and chemical contaminants. Toxicology 2007, 230:227-233.
13. Domingo JL: Omega-3 fatty acids and the benefits of fish consumption: is all that glitters gold? Environ Int 2007, 33:993-998.
14. Domingo JL, Bocio A, Falco G, Llobet JM: Benefits and risks of fish consumption Part I. A quantitative analysis of the intake of omega-3 fatty acids and chemical contaminants. Toxicology 2007, 230:219-226.
Competing interests
The author declares that he has not competing interests.
Methylmercury and Risk in Adults - A Balanced View, and More Research, Are Needed
Dariush Mozaffarian, Harvard Medical School and Harvard School of Public Health
12 November 2007
We agree with Dr. Stern that the most important question with regard to methylmercury and fish intake is not the main effect, but the interaction: does the presence of methylmercury alter the beneficial effects of fish consumption related to marine n-3 polyunsaturated fatty acids (PUFA)? Unfortunately, most prior studies did not evaluate this interaction. The Kuopio study, however, did evaluate this interaction. Exposure to mercury mitigated the beneficial effect of marine n-3 PUFA consumption, so that less benefit was seen at higher levels of mercury, compared with lower levels of mercury.[1] However, whether mercury levels were higher or lower, greater n-3 PUFA consumption was still associated with lower risk – higher mercury levels simply attenuated the slope of this relationship.[1] In updated analyses from this same cohort,[2] tertiles of mercury exposure were related to higher risk of acute coronary syndromes, but not cardiovascular death, coronary heart disease (CHD) death, or total mortality prior to adjustment for n-3 PUFA consumption; only after adjustment was higher risk of these latter events seen, indicating that the benefits of n-3 PUFA must first be taken into account (i.e., adjusted away) before higher relative risk with mercury exposure was evident.
With only 5 prior studies of mercury and CHD risk,[3] it is very dangerous to pick and choose subjectively the 2 “positive” studies as correct and ignore the 3 “negative” studies. Each of these studies had potential limitations. For example, the study by Guallar et al.[4] was a retrospective case-control study and thus included only nonfatal myocardial infarctions – this is a major limitation given that the predominant benefits of fish consumption are to reduce CHD death and sudden cardiac death, not nonfatal events[3] – thus, the Guallar study would underestimate the benefits of fish consumption. Nonetheless, higher marine n-3 PUFA consumption (reflected by higher DHA levels) was still associated with lower risk, and the lower risk associated with DHA levels was even more pronounced after adjustment for mercury levels. This suggested that mercury exposure attenuated the benefits of fish consumption, but unfortunately the actual interaction was not assessed in this analysis.
Three other studies of mercury exposure and CHD risk, all with their own potential limitations, did not find higher risk.[3] Based on the conflicting data for effects of mercury on CHD risk (which is conflicting, no matter how one chooses to parse it), and the clear and substantial benefits for CHD death, our conclusions are very reasonable (and the recommendations not very different from Dr. Stern’s): "The effects, if any, of low-level methylmercury exposure in adults are not established; mercury may possibly reduce the cardiovascular benefits of fish intake. One can minimize concerns by choosing fish higher in n-3 PUFAs and lower in mercury or by simply consuming a variety of different seafood. Individuals with high consumption (5+ servings/wk) should limit intake of selected species highest in mercury."[3] Further research on potential mercury effects in adults is also clearly needed at this point.
The PCB/dioxin story simply does not convince for most commercially caught fish (i.e., possibly excepting marine mammals or particular highly contaminated sportscaught freshwater fish): levels of PCBs/dioxins are similar to other major protein sources (beef, pork, chicken, butter, and eggs),[3] the predicted risks are remarkably small (e.g., 8-24 cancer deaths per 100,000 lifetimes, compared with >7,000 fewer CHD deaths per 100,000 lifetimes[5]), and >90% of PCBs/dioxins in the U.S. food supply come from non-seafood sources, such as meats, dairy products, and vegetables.[6]
Dariush Mozaffarian, MD DrPH
Eric Rimm, ScD
Harvard Medical School and Harvard School of Public Health
1. Rissanen T, Voutilainen S, Nyyssonen K, Lakka TA, Salonen JT. Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. Circulation 2000;102(22):2677-9.
2. Virtanen JK, Voutilainen S, Rissanen TH, et al. Mercury, fish oils, and risk of acute coronary events and cardiovascular disease, coronary heart disease, and all-cause mortality in men in eastern Finland. Arterioscler Thromb Vasc Biol 2005;25(1):228-33.
3. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006;296(15):1885-99.
4. Guallar E, Sanz-Gallardo MI, van't Veer P, et al. Mercury, fish oils, and the risk of myocardial infarction. N Engl J Med 2002;347(22):1747-54.
5. Foran JA, Good DH, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. Quantitative analysis of the benefits and risks of consuming farmed and wild salmon. J Nutr 2005;135(11):2639-43.
6. Schecter A, Cramer P, Boggess K, et al. Intake of dioxins and related compounds from food in the U.S. population. J Toxicol Environ Health A 2001;63(1):1-18.
Environmental Health
Evaluating health benefits and chemical risks of fish intake
8 November 2007
In this paper, Stern concludes telling “that there are easily available fish that offer both high polyunsaturated fatty acids (PUFAs) and low methyl mercury and that the consumers should chose wisely among the available fish so as to maximize the benefits and decrease the risks”. Stern is also very critical with a previous statement by Mozaffarian and Rimm [1], who in a recent review paper published in JAMA concluded that for major health outcomes among adults, “the benefits of fish consumption exceeded potential risks”. Based on the long experience of our research group, I would like to add some arguments to that important issue.
Firstly, I would like to note that the evidence supporting the statement by Mozaffarian and Rimm [1] is very limited. Only the risks of a few environmental pollutants: methylmercury, dioxins and furans (PCDD/PCDFs), and polychlorinated biphenyls (PCBs) were included in their review paper, and only these contaminants were the basis to support the main conclusion. Other important chemical contaminants were not included. For example, the polycyclic aromatic hydrocarbons (PAHs). Nowadays, according to the US EPA [2], at least 7 PAHs are known carcinogenic agents in humans. Why environmental pollutants such as polychlorinated diphenyl ethers (PCDEs) or polychlorinated naphthalenes (PCNs), for which some congeners seem act as “dioxin-like” compounds [3, 4] were not evaluated, or what polybrominated diphenyl ethers (PBDEs), a family of contaminants with well known toxic effects [5, 6] were not assessed? The bias performed by Mozaffarian and Rimm [1], not reviewing the potential adverse effects of various groups of pollutants, would explain the reason of such statement: “the benefits of fish consumption exceeded potential risks”.
We recently determined the levels of 16 PAHs, PCDEs, PCNs, and PBDEs together with those of arsenic, cadmium, lead, mercury, hexachlorobenzene, PCDD/PCDFs and PCBs in various widely consumed marine species [7-11]. Surprisingly, neither the results of these studies, nor those of previous investigations of our research group concerning dietary exposure (including fish and other seafood) to environmental pollutants were referenced by Mozaffarian and Rimm [1]. How could this occur? Why the results of these articles were not reviewed/discussed taking into account that all are referenced in the most frequently used databases: Medline, Scopus, etc? According to the authors, Medline was chosen as the main database for preparing their review [1]. Mozafarian and Rimm [1] also concluded that potential risks of fish intake should be considered in the context of potential benefits. I agree, but how most individuals can get this information? Instead of giving a general recommendation, I would recommend an individual balance of the potential health benefits (intake of PUFAs for cardiovascular benefits) and chemical risks (environmental contaminants) related with fish and other seafood consumption, which is more realistic and adequate. Recently, we designed the software RIBEPEIX®, which is currently available in Internet (htpp://www.fmcs.urv.cat/portada/ribepeix/) [12]. For 14 fish and other seafood species, the use of RIBEPEIX® allows optimizing the balance between the health benefits of omega-3 polyunsaturated fatty acids (EPA and DHA) and the chemical risks of fish consumption. It is possible to select the most suitable species (based on the measured concentrations of EPA plus DHA, and pollutants), the frequency of consumption of those species, as well as the most adequate meal sizes. Using RIBEPEIX, we found for example, that for an adult of 70 kg consuming 2 services per week (227 g) of swordfish or red mullet, the intake of mercury (from swordfish) would be 12.52 μg/kg, which notably exceeds the tolerable 5 μg/kg intake, while that of PCDD/PCDFs + dioxin-like PCBs (from red mullet) would be 30.13 pg WHO-TEQ/kg, amount that exceeds the tolerable 14 pg WHO-TEQ/kg intake for these compounds. If the frequency of fish consumption is increased up to 3 meals per week, the intake of PCDD/PCDFs + dioxin-like PCBs from anchovy, for example, or those of PCDD/PCDFs + dioxin-like PCBs and mercury from tuna, would reach approximately the respective tolerable limits [13, 14]. It is obvious that if the weekly fish consumption is increased, the tolerable limits of certain chemical contaminants can also simultaneously increase, with the potential health risks that it would mean [13, 14]. Consequently, I strongly agree with the conclusions of Stern, but I clearly disagree with those of Mozaffarian and Rimm [1].
References
1. Mozaffarian D, Rimm EB: Fish intake, contaminants, and human health. Evaluating the risks and benefits. JAMA 2006, 296:1885-1899.
2. US Environmental Protection Agency. 2002. Polycyclic organic matter. US EPA, Washington, DC. [http://www.epa.gov.ttn/atw/hlthef/polycycl.html].
3. Domingo JL: Polychlorinated diphenyl ethers (PCDEs): environmental levels, toxicity and human exposure: a review of the published literature. Environ Int 2006, 32:121-127.
4. Domingo JL: Polychlorinated naphthalenes in animal aquatic species and human exposure through the diet: a review. J Chromatogr A 2004, 1054:327-334.
5. Darnerud PO: Toxic effects of brominated flame retardants in man and in wildlife. Environ Int 2003, 29:841-853.
6. Domingo JL: Human exposure to polybrominated diphenyl ethers through the diet. J Chromatogr A 2004, 1054, 321-326.
7. Llobet JM, Falco G, Bocio A, Domingo JL: Exposure to polycyclic aromatic hydrocarbons through consumption of edible marine species in Catalonia, Spain.
J Food Prot 2006, 69:2493-2499.
8. Domingo JL, Bocio A, Falco G, Llobet JM: Exposure to PBDEs and PCDEs associated with the consumption of edible marine species. Environ Sci Technol 2006, 40:4394-4399.
9. Falco G, Llobet JM, Bocio A, Domingo JL: Daily intake of arsenic, cadmium, mercury, and lead by consumption of edible marine species. J Agric Food Chem 2006, 54:6106-6112.
10. Llobet JM, Falco G, Bocio A, Domingo JL: Human exposure to polychlorinated naphthalenes through the consumption of edible marine species. Chemosphere 2007, 66:1107-1113.
11. Bocio A, Domingo JL, Falco G, Llobet JM. Concentrations of PCDD/PCDFs and PCBs in fish and seafood from the Catalan (Spain) market: estimated human intake. Environ Int 2007, 33:170-175.
12. Domingo JL, Bocio A, Marti-Cid R, Llobet JM: Benefits and risks of fish consumption Part II. RIBEPEIX, a computer program to optimize the balance between the intake of omega-3 fatty acids and chemical contaminants. Toxicology 2007, 230:227-233.
13. Domingo JL: Omega-3 fatty acids and the benefits of fish consumption: is all that glitters gold? Environ Int 2007, 33:993-998.
14. Domingo JL, Bocio A, Falco G, Llobet JM: Benefits and risks of fish consumption Part I. A quantitative analysis of the intake of omega-3 fatty acids and chemical contaminants. Toxicology 2007, 230:219-226.
Competing interests
The author declares that he has not competing interests.
Methylmercury and Risk in Adults - A Balanced View, and More Research, Are Needed
12 November 2007
We agree with Dr. Stern that the most important question with regard to methylmercury and fish intake is not the main effect, but the interaction: does the presence of methylmercury alter the beneficial effects of fish consumption related to marine n-3 polyunsaturated fatty acids (PUFA)? Unfortunately, most prior studies did not evaluate this interaction. The Kuopio study, however, did evaluate this interaction. Exposure to mercury mitigated the beneficial effect of marine n-3 PUFA consumption, so that less benefit was seen at higher levels of mercury, compared with lower levels of mercury.[1] However, whether mercury levels were higher or lower, greater n-3 PUFA consumption was still associated with lower risk – higher mercury levels simply attenuated the slope of this relationship.[1] In updated analyses from this same cohort,[2] tertiles of mercury exposure were related to higher risk of acute coronary syndromes, but not cardiovascular death, coronary heart disease (CHD) death, or total mortality prior to adjustment for n-3 PUFA consumption; only after adjustment was higher risk of these latter events seen, indicating that the benefits of n-3 PUFA must first be taken into account (i.e., adjusted away) before higher relative risk with mercury exposure was evident.
With only 5 prior studies of mercury and CHD risk,[3] it is very dangerous to pick and choose subjectively the 2 “positive” studies as correct and ignore the 3 “negative” studies. Each of these studies had potential limitations. For example, the study by Guallar et al.[4] was a retrospective case-control study and thus included only nonfatal myocardial infarctions – this is a major limitation given that the predominant benefits of fish consumption are to reduce CHD death and sudden cardiac death, not nonfatal events[3] – thus, the Guallar study would underestimate the benefits of fish consumption. Nonetheless, higher marine n-3 PUFA consumption (reflected by higher DHA levels) was still associated with lower risk, and the lower risk associated with DHA levels was even more pronounced after adjustment for mercury levels. This suggested that mercury exposure attenuated the benefits of fish consumption, but unfortunately the actual interaction was not assessed in this analysis.
Three other studies of mercury exposure and CHD risk, all with their own potential limitations, did not find higher risk.[3] Based on the conflicting data for effects of mercury on CHD risk (which is conflicting, no matter how one chooses to parse it), and the clear and substantial benefits for CHD death, our conclusions are very reasonable (and the recommendations not very different from Dr. Stern’s): "The effects, if any, of low-level methylmercury exposure in adults are not established; mercury may possibly reduce the cardiovascular benefits of fish intake. One can minimize concerns by choosing fish higher in n-3 PUFAs and lower in mercury or by simply consuming a variety of different seafood. Individuals with high consumption (5+ servings/wk) should limit intake of selected species highest in mercury."[3] Further research on potential mercury effects in adults is also clearly needed at this point.
The PCB/dioxin story simply does not convince for most commercially caught fish (i.e., possibly excepting marine mammals or particular highly contaminated sportscaught freshwater fish): levels of PCBs/dioxins are similar to other major protein sources (beef, pork, chicken, butter, and eggs),[3] the predicted risks are remarkably small (e.g., 8-24 cancer deaths per 100,000 lifetimes, compared with >7,000 fewer CHD deaths per 100,000 lifetimes[5]), and >90% of PCBs/dioxins in the U.S. food supply come from non-seafood sources, such as meats, dairy products, and vegetables.[6]
Dariush Mozaffarian, MD DrPH
Eric Rimm, ScD
Harvard Medical School and Harvard School of Public Health
1. Rissanen T, Voutilainen S, Nyyssonen K, Lakka TA, Salonen JT. Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. Circulation 2000;102(22):2677-9.
2. Virtanen JK, Voutilainen S, Rissanen TH, et al. Mercury, fish oils, and risk of acute coronary events and cardiovascular disease, coronary heart disease, and all-cause mortality in men in eastern Finland. Arterioscler Thromb Vasc Biol 2005;25(1):228-33.
3. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006;296(15):1885-99.
4. Guallar E, Sanz-Gallardo MI, van't Veer P, et al. Mercury, fish oils, and the risk of myocardial infarction. N Engl J Med 2002;347(22):1747-54.
5. Foran JA, Good DH, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. Quantitative analysis of the benefits and risks of consuming farmed and wild salmon. J Nutr 2005;135(11):2639-43.
6. Schecter A, Cramer P, Boggess K, et al. Intake of dioxins and related compounds from food in the U.S. population. J Toxicol Environ Health A 2001;63(1):1-18.
Competing interests
None