Hajar Ahmed AlBinali, MD

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                                       Fish and Fish Oil Adverse Effects 

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 In my previous articles on Omega-3 in Arabian Gulf fish I emphasized the fact that multiple research papers over the past three decades points to a growing and convincing evidence of the beneficial effects of fish oil or omega-3 polyunsaturated fatty acid (PUFA) in primary prevention, coronary heart disease, post-Myocardial infarction, sudden cardiac death, heart failure, atherosclerosis, and atrial fibrillation.

I ignored some of the negative concerns raised in some research papers, probably due to my bias for fish. In Arabic literature, we say, “the eye of the contented does not see the negative and the lover sees everything in the loved one as good.” In this issue, I will review the literature on the major concerns about the adverse effects of fish and fish oil. Therefore, this article is predominately a review article.

 

Methyl Mercury Contaminants:

One of the major concerns about eating fish is the methyl mercury contaminants. This problem is related to the geographical location of the fish stock and the level of water pollution in that location. Fortunately for us in the Gulf and especially in Qatar, our sea is still clean as proven by our fish testing. The results of the Qatar Ministry of Public Health fish testing seen in (Table1) shows the amount of mercury in our fish is negligible.

Table1. The concentration of Minerals (mg/Kg) in Edible Portion of Fish

 

 

 

 

 

 

 

 

Those who live in other geographical locations may not be as lucky as us in that regard. This is why the United States FDA has advised children and pregnant or nursing women to specifically avoid those fish with a potentially high content of mercury (Table 2) such as swordfish, tilefish, king mackerel, and shark (2,3).

 

Table 2. Fish and Shellfish With Highest Levels of Mercury

 

 

 

 

 

 

 

 

It is not advisable, however, for children and pregnant women to completely avoid all fish. Other dietary sources of omega-3 PUFA, such as salmon, sardines, trout, oysters, and herring, are quite low in mercury(4). A study of nearly 12,000 British women during their pregnancy and beyond found that women who exceeded the U.S. FDA recommendation for fish intake actually had offsprings with better cognitive and behavioral development than offsprings of women who consumed less fish during pregnancy(5).   

Mercury is water soluble and protein bound and hence, it is present in the muscle of the fish but not in the oil. Therefore, fish oil supplements should be safe to consume(6). Some of the adverse effects of fish oil supplementation are nausea, gastrointestinal upset, and "fishy" burp.

 

Bleeding

 Omega-3 PUFA does reduce platelet aggregation. The antiplatelet, anti-inflammatory and triglyceride-lowering effects of omega-3PUFA require relatively higher doses of DHA and EPA (e.g., 3 to 4 g/day). Prolonged bleeding times, as noted in Greenland Eskimos and when feeding "hyper-Eskimo" doses of omega-3 PUFA (e.g., over 20 g/day) to normal volunteers, usually remain in the high end of the normal range (7). These observations, however, raised concerns that higher intakes will increase hemorrhagic complications. However, Harris (8), in a comprehensive review, concluded that there was no increased risk of clinically significant bleeding noted with omega-3 PUFA doses of up to 7 g of combined DHA and EPA per day, even when combined with antiplatelet therapy or warfarin.

 

Atrial fibrillation

Early in 2005 the Danish Diet, Cancer, and Health cohort study, involving more than 47,000 patients, showed that omega-3 fatty acid consumption was associated with an increased risk of developing atrial fibrillation (AF)(9). This was very disturbing news. But in the same year, Dr. Dariush Mozaffarian and colleagues showed that eating fatty fish, either broiled or baked, reduced the risk of AF in the elderly (10). Further studies resolved this contradictory result in favor of PUFA. The Rotterdam Study in 2006 showed the intakes of EPA and DHA and the consumption of fish were not associated with the onset of atrial fibrillation (11). Other Investigators report that pretreatment with omega-3 fatty acids reduced the postoperative incidence of AF by 58%(12).

In an editorial comment on fish oil and prevention of atrial fibrillation, an authority on the subject, Dariush Mozaffarian, MD, wrote in J AM Coll Cardiology 2007:

 

 Among elderly adults, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with a lower incidence of AF (13,14). An open-label randomized trial among 160 patients undergoing cardiac surgery, perioperative fish oil treatment (2 g/day) reduced the occurrence of postoperative AF from 33.3% to 15.2% (p = 0.01) (15). In a prospective observational study among older adults, consumption of tuna or other broiled or baked fish was associated with a 35% lower incidence of AF (p = 0.001), after adjustment for other risk factors (16).

Dr. Mozaffarian  concluded: “A simple, low-risk, and low-cost dietary intervention could reduce the incidence of AF, the most common complication of cardiac surgery and the most common cardiac arrhythmia in the general population.”

 

Shellfish and blood cholesterol

We know that omega-3 PUFA reduces the hepatic synthesis of triglycerides and increase hepatic fatty acid beta-oxidation. The triglyceride-lowering effects require high doses of DHA and EPA in the range of 3 to 4 g/day. This does typically reduces triglyceride levels by 30% to 40% (17). Generally, there are no significant improvements in levels of low-density lipoprotein (LDL) cholesterol with fish oil therapy. There is, however, general public concern about the effect of shellfish food on blood cholesterol level.

Many of my friends, as well as an increasing number of educated and health-conscious men in the Gulf, have blood cholesterol level checked several times a year. I am very liberal in advising them to take a statin, even if their cholesterol level is normal. Not many are following such advice, but it has made people more concerned about the ill effects of cholesterol. Since 1978 when I started practicing cardiology in Qatar, I often face a popular question from friends and guests whenever I am invited to lunch or dinner containing shrimp dishes: Is it not bad for you to eat shrimp because of the high cholesterol content? I usually make sure that I have enough shrimp on my plate before I answer such a question. I tell them that it was thought in the past that shrimp has a very high content of cholesterol, but in reality, it is not that high. I advise people not to avoid shrimp because of the fear of increasing blood cholesterol level but do not eat an excessive amount of it.

In general, a small amount of cholesterol in the blood comes directly from our food. My clinical practice convinced me that we rarely could succeed in significantly reducing abnormally high blood cholesterol by diet alone. Most of the cholesterol in the blood is produced in the body by the liver, where the action of statin drugs takes place. Even though cholesterol from food has little effect on blood cholesterol level, we do advise patients with high cholesterol to avoid or reduce intake of food with high level of cholesterol. The amount of saturated fat in food is far more important to avoid.

One day my statement that it is OK to eat shrimp did not go without a challenge. A guest told me that he was given an instruction paper from our hospital listing the foods to avoid completely because of high cholesterol. Shrimp was one of the foods to avoid. I was surprised and embarrassed. I asked the nutrition section about that. They insisted that what they wrote was “fact.” In 1978 we did not have the luxury of the internet to get a quick answer. Therefore, I wrote a letter to my professor of clinical nutrition who was famous for his work on cholesterol, Dr. William E. Connor in the University of Oregon. He answered me saying that he does not advise patients to avoid shrimp and that the cholesterol in shrimp is not too far from that in chicken meat. During my cardiology fellowship I spent two months with Dr. Connor taking care of patients with high cholesterol in the clinic. He advised me not to be too strict with patients. "Allow them to eat small to moderate amounts of the food they like once a week to achieve better adherence to the dietary recommendations"; he said. I applied his approach in caring for patients in my clinic in Qatar.

Dr. Connor died last year at the age of 88. I wonder if his healthy diet contributed to his longevity. William Connor published almost 400 articles on diet and metabolism. His research focused on how omega-3 fatty acids (such as fish oil) may prevent sudden death from heart attacks. He and his wife Sonja Connor sent me as a gift their best-selling cookbook “The New American Diet”. They pioneered a philosophy of eating to maximally protect oneself against heart disease. 

Many health-conscious people are concerned about eating not only shrimp but also shellfish as a class. But even though small dietary cholesterol is present in prawns, crabs, and lobsters, as well as in squid and octopus, they contain very little saturated fat. Shellfish such as cockles, mussels, oysters, scallops and clams are low in cholesterol, about half as much as chicken, and contain much less cholesterol than red meats. Table 3 lists the fat level in 100 gram of cooked shellfish compared to chicken and table 4 list raw shellfish content of fat and cholesterol.

Table 3 all values are per 100g serving (cooked) (18)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4. The content of 3.5 oz (100 g) portions of raw shellfish (19)

 

 

 

 

 

 

 

 

 

 

 

 

 

So, why does shellfish have such a bad reputation, causing it to be blacklisted for high cholesterol? The answer was due to primitive testing. The nutritional profile of shellfish includes chemical compounds called sterols. Although cholesterol is just one among many sterols, less sophisticated testing methods used in the past grouped all sterols under cholesterol. So, the cholesterol levels for shellfish generally looked high. Now, laboratory tests can differentiate cholesterol from non-cholesterol sterols.

Molluscan shellfish (oysters, clams, squid, and mussels) have large sterol content, but only one-third of the sterols are cholesterol, while crustaceans (shrimp, crabs) contain more cholesterol. The effects of diets rich in individual types of crustaceans or mollusks on plasma lipids of 18 men with normal plasma lipids were evaluated. The levels of animal-derived proteins and fats were strictly controlled on these diets. None of the shellfish caused increases in plasma cholesterol levels (20).

Most shellfish are naturally low in total fat as well as saturated fats. They do contain omega-3 fatty acids but not as high as in Salmon, Anchovy, Sardines, Herring or Mackerel (21) (Table 5). It is healthy to eat clams, shrimp, scallops, mussels, crayfish, lobster,crab or oysters. But the cooking methods should be broiling, grilling or steaming not frying. Deep frying seems to destroy the heat sensitive EPA and DHA and the protective effect diminishes (22).

Table 5: Omega-3 content in fish and shellfish
          (quantities in grams per 100g portion)

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In conclusion, eating fish is very beneficial for humans but only harmful to fish. Encouraging people to eat more fish may deplete the worldwide fish stocks in a few decades. This last side effect of fish eating is real but it is beyond my field of therapy. Fish farming and international conservation measures may provide man with fish for a longer period. Alternative sources of omega-3 fatty acids from plants, algae, or yeast may become commercially available in the future.

 

References:

1. Kotb Ahmed et al: Omega-3 Polyunsaturated Fatty Acid Content of Some Popular Species of Arabian Gulf Fish. Food Chemistry 1991; 40:185-190.

2. U.S. Food and Drug Administration, Department of Health and Human Services Backgrounder for the 2004 FDA/EPA Consumer Advisory: What you Need to Know About Mercury in Fish and Shellfish http://www.fda.gov/oc/opacom/hottopics/mercury/backgrounder.html 2007Accessed January 24, 2008.

3.  From FDA (http://www.fda.gov/Food/FoodSafety/Product-SpecificInformation/Seafood/FoodbornePathogensContaminants/Methylmercury/ucm115644.htm).

4. Lee JH, O'Keefe JH, Lavie CJ, Marchioli R, Harris WS. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc 2008; 83:324-332.

5. Hibbeln JR, Davis JM, Steer C, et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood. ALSPCA study: an observational cohort study. Lancet 2007; 369:578-585.

6. Foran SE, Flood JG, Lewandrowski KB. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med 2003;127:1603-1605.

7. Sinclair HM. The diet of Canadian Indians and Eskimos. Proc Nutr Soc 1953;12:69-82.

8. Harris WS. Expert opinion: omega-3 fatty acids and bleeding—cause for concern? Am J Cardiol 2007;99:44C-46C.

9. Frost Lars, Vestergaard Peter. n-3 Fatty acids consumed from fish and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study. American Journal of Clinical Nutrition 2005; 81(1):50-4.

10.  American Journal of Clinical Nutrition 2005; 81(1): 50-54,

11.  Brouwer IA, Heeringa J, Geleijnse JM, Zock PL, Witteman JC. Intake of very long-chain n-3 fatty acids from fish and incidence of atrial fibrillation. The Rotterdam Study.Am Heart J. 2006; 151(4):857-62.

12.  Calo' L, Bianconi L, Colivicchi F, et al. Preoperative administration of N-3 polyunsaturated fatty acids prevents postoperative atrial fibrillation after coronary artery bypass surgery. Heart Rhythm Society Scientific Sessions Abstract. May 4-7 2005; New Orleans, LA. P1-35.

13.  Am Coll Cardiol, 2007; 50:1513-1514, doi:10.1016/j.jacc.2007.05.045 (Published online 21 September 2007.

14.  Mozaffarian D; Psaty BM; Rimm EB; Lemaitre RN; Burke GL; Lyles MF; Lefkowitz D; Siscovick DS. Fish intake and risk of incident atrial fibrillation. Circulation. 2004;110 (4):368-73.

15.  Calo L; Bianconi L; Colivicchi F et al. N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol 2005;45:1723-1728..

16.  Mozaffarian D, Psaty BM, Rimm EB, et al. Fish intake and risk of incident atrial fibrillation Circulation 2004;110:368-373.

17.  Harris WS. N-3 fatty acids and serum lipoproteins: human studies Am J Clin Nutr 1997;65(Suppl):1645S-1654S

18.  "http://en.wikipedia.org/wiki/Shellfish_Association_of_Great_Britain".

19.   U.S. Department of Agriculture, Human Nutrition Information Service Handbook 8-15.

20. MT Childs, CS Dorsett, IB King, JG Ostrander, and WK Yamanaka. Effects of shellfish consumption on lipoproteins in normolipidemic men. American Journal of Clinical Nutrition. 51: 1020-1027.

21.   USDA Nutrient Database for Standard Reference (http://www.isodisnatura.co.uk/omega-3_and_food.htm)

22. Dariush Mozaffarian et al. Circulation 2003:107:1372.