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There is no shortage of scientific evidence supporting the health benefits of fish oil. According to the Natural Medicines Comprehensive Database, fish oil is highly effective at lowering triglycerides, high levels of which are associated with heart disease and diabetes. By some estimates, fish oil consumption has the ability to reduce triglyceride levels by 20% to 50%. The FDA has even approved a fish oil prescription medication – Lovaza, containing 465mg EPA and 375mg DHA in a single 1g capsule – to lower triglyceride levels.

Fish oil has also shown efficacy against a variety of other indications, including heart disease, stroke, macular degeneration, autoimmune conditions such as rheumatoid arthritis (it also promotes overall joint health), and cognitive disorders such as ADHD, psychosis and bipolar disorder.

So, what’s the catch? Fish oil is considered “likely safe” when taken by most people, including pregnant and breast-feeding women, at up to 3g/day. Higher doses have been linked to decreased clotting ability and an increased risk of bleeding. There are also concerns over reduced immune system activity, an especially important consideration to those who are already immuno-compromised, such as organ transplant patients and the elderly.

What about the contaminants we here about so often – chief among them, mercury and polychlorinated biphenyls (PCBs)? Short of laboratory testing, we currently have no way of determining levels of either contaminant in our fish products. Ideally, we should have the ability to, at least qualitatively, determine and control contaminant intake should we choose to opt for a salmon dinner, a spicy tuna roll, or even try a regimen of daily fish oil supplementation.

Mercury

Mercury contamination starts at the very bottom of the aquatic food chain with microorganisms in the sediments of fresh and ocean water. For the scientists: at this point in mercury’s ascent up the food chain, the water soluble, inorganic mercury ion, Hg2+, is converted to the methylmercury, the toxic form of mercury we are warned about. The story is uphill from there – plankton consume the microorganism, herbivorous fish consume plankton, and carnivorous fish consume the herbivores. At each stage, methylmercury burden (the amount contained in tissues) increases in a process appropriately named bioaccumulation. An important note: methylmercury preferentially binds to protein (specifically, thiol-containing amino acids such as cysteine) and not fat–an important implication for cooking practices, which we’ll get to shortly.

Some perspective: at the top of the food chain, tissue mercury levels are thought to be 1800 - 80,000 times higher than levels in surrounding waters.

Health Effects

What happens to the methylmercury once we ingest it? About 95% of the methylmercury ingested from fish is absorbed, almost exclusively by the gastrointestinal tract. And after about 30 hours, methylmercury is expected to be distributed among the body’s tissues, with approximately 10% traveling to the brain and 5% remaining in the blood.

Once in the body, methylmercury doesn’t like to remain “unattached,” so it tries to bind to molecules with a sulfur-containing thiol group (like the amino acid cysteine) – typically found in protein-rich tissue. When bound to cysteine, the complex mimics a different sulfur-containing amino acid, methionine, and is able to shuttle across cell membranes, particularly those of the blood-brain barrier (BBB), via specialized transport proteins. Let me be clear–the blood-brain barrier is our brain’s more prominent line of defense against invading organisms or toxins. In this manner, mercury has cleverly “hijacked” its way across the cellular membrane by mimicking an innocuous amino acid.

Once inside the cell, methylmercury is able to bind to other sulfur-containing proteins, disabling their functionality and interrupting crucial processes. It has been noted to interfere with cellular motility, inhibit enzymes, interrupt DNA synthesis and cause oxidative stress. Importantly, these effects are localized largely to the brain, leading to severe neurotoxicity, considered the most prominent effect of methylmercury poisoning. These biochemical processes manifest as paresthesia (a numbness and tingling around the mouth), ataxia (clumsy gait, difficulty swallowing and articulating words) as well as, but less commonly so, sensations of weakness, vision and hearing loss and tremors. If methylmercury poisoning is severe enough and left untreated, coma and death may follow.

Practical Application

So how do we deal with the methylmercury in fish? Will cooking reduce methylmercury concentrations? Methylmercury is known to preferentially bind to protein - not fat. The flesh of fish is expected to be much more mercury-heavy than, say, purified fish oil supplements. A second consequence of mercury’s affinity to protein is that cooking will not decrease levels of methylmercury in your fish. Any fat-soluble contaminants (as we will see) may be eliminated with cooking, which melts and dissolves natural fats.

It should be duly noted, however, that whole fish contains selenium, a trace mineral known to preferentially bind to amino-acids (the building blocks of protein). Scientific research has shown that seleno-protein compounds have a unique ability to bind and sequester methylmercury in the circulation, possibly reducing or preventing its accumulation in human tissue.

Do we still get contamination in purified fish oil? While there is typically some methylmercury contamination in purified fish oil supplements - in our analysis, supplements averaged 2.9 PPB (parts per billion), which is significantly below the 100 PPB limit set by the GOED - the concentration is considered much less than what would be found in whole fish. Fresh or frozen tuna, for example, recorded a mean methylmercury concentration of 0.391 ppm (parts per million) while fresh/frozen salmon scored a much lower 0.022 ppm, according to FDA data on all samples collected from 1991-2010. For reference, the GOED standard of 100 ppb is equal to 0.1 ppm (a limit 10x more strict than the FDA’s, which is set at 1 ppm). For this reason, we typically suggest following the GOED’s 0.1 ppm upper limit, which fresh/frozen tuna has consistently exceeded.

In general, when opting for a fish-based meal, think food chain. Are they herbivores or carnivores? Carnivores will have higher tissue levels of mercury due to bioaccumulation. Are they big? Bigger fish eat more, and will ingest larger amounts of methylmercury from all sources. Do they live a long time? Fish that live longer will have more time to accumulate the contaminant. The practical advice: be aware that carnivorous, large fish like shark, swordfish and marlin as well as larger, longer living fish like tuna, bass and pike will have significantly higher mercury levels than smaller, herbivorous fish like tilapia and herring.

Polychlorinated Biphenyls (PCBs)

PCBs were once prized for their unique physical characteristics – according to the World Health Organization, they have “low electrical conductivity, high thermal conductivity and high resistance to thermal degradation.” Due to these properties, they were once the de facto weather- and fire-proofing materials and popular insulators in electronics. Although this is not entirely related to our biological and health-based analysis, it does speak to PCBs chemical character – that of a fat-soluble (lipophilic) substance that does not degrade easily – which plays an important role in the compounds health effects.

So how did PCBs go from electrical equipment insulators to a worldwide health hazard? PCBs volatilize (evaporate) easily and, due to the aforementioned characteristics, persist in the environment for many years. The majority of PCBs are thought to exist in air – a study conducted in the United States found that 92% of PCBs existed in air, according to the WHO. Some PCBs, however, are also found in water. This partitioning depends on the PCB compounds degree of chlorination (how many chloride ions are found per molecule) with those that have a low degree of chlorination dominating in air while those with higher degrees of chlorination dominating in water. In theory, 209 different PCBs may exist (based on the different locations at which chlorination can occur), but only 130 have been identified in products to date.

Health Effects

We mentioned that highly chlorinated PCB compounds tend to dominate in water while the less chlorinated forms persist in air. The logic: fish consume the higher-chlorinated variety of PCB’s and people consume the fish, ingesting their PCB content. The chlorination does not only make the compounds less volatile, but also harder for the liver to metabolize – and rid from the body. Chlorinated PCBs are also slowly excreted, with bioaccumulation beginning to occur even at low levels of exposure, according to the Center for Disease Control (CDC). In rats, the half lives of PCB compounds range from 1 – 460 days, depending on the degree of chlorination; similar trends are expected in humans. While low levels of PCBs are detectable in every body compartment (< 20 ppb), accumulation tends to be highest in fat tissue (1 – 2 ppm).

Due to their lipid soluble structure, PCBs have the ability to cross the cellular membrane and enter cells with greater ease. The result: quicker access to the DNA containing nucleus and a greater ability to alter DNA processing and expression. In fact, a large part of PCB toxicity is mediated by the aryl hydrocarbon receptor (AhR), which, when activated, translocates into the nucleus and mediates DNA transcription. Just as lipid-soluble hormones, PCBs also have the ability to interfere with endocrine function, and have been shown to disrupt both thyroid hormone and estrogenic signaling and function.

PCB poisoning can have a variety of clinical manifestations, including neurotoxicity (to which children are especially susceptible), reproductive damage, cancer formation, immune-modulation, and endocrine disorder.

Practical Application

Is there any way to deal with the PCB content in the fish we eat? Based on our review, there a few things you can do to minimize PCB exposure:

  1. Since PCBs are metabolized by the liver, they tend to accumulate there in larger concentrations then elsewhere in the body (except for fatty tissue). Gutting and cleaning your fish before eating it can lessen PCB exposure, according to the Office of Environmental Health Hazard Assessment (OEHHA).
  2. Since PCBs are stored in fatty tissue, removing any fat from fish should minimize exposure. Trim fat and remove skin for best results.
  3. Cook your fish using a method that gets rid of juices (that typically contain fat), like baking or grilling.

Aside from these fat- and liver-centric approaches, the same “food-chain,” bioaccumulation-based logic that applied to mercury poisoning applies to PCBs: fish that eat other fish tend to have higher levels of PCBs stored in their fat, as do fish that are larger or live longer when compared against younger and smaller fish.

So far, we’ve talked about whole fish. How about fish oil supplements? PCBs are fat-based compounds, so it would be expected that purified fish oil supplements would have higher levels of contamination. Analytical chemistry techniques have long been developed to remove PCBs from purified fish oil. However, in 2010, independent testing laboratories had found that eight fish oil supplement manufacturers recorded variable levels of PCB contamination in their products – with the best performer recording 12 nanograms (~0.012ppm) per recommended dose while the worst offender recorded greater than 850ng/dose (~0.85ppm). Lawsuits were filed against these companies for being in violation of California’s Proposition 65, which requires labeling of chemical exposures.

Sources

  1. Header Image: John Liu (Flickr)
  2. Mercury – National Library of Medicine of the National Institutes of Health
  3. Mercury Contamination in Fish – Food and Drug Administration
  4. Polychlorinated Biphenyls (PCBs) – World Health Organization
  5. Case Studies in Environmental Medicine: Polychlorinated Biphenyls (PCB) Toxicity – Center for Disease Control
  6. Polychlorinated Biphenyls (PCBs) and Polybrominated Biphenyls (PBBs): Biochemistry, Toxicology, and Mechanism of Action – Critical Reviews in Toxicology
  7. PCBs: Structure-Function Relationships and Mechanism of Action – Environmental Health Perspectives
  8. PCBs in Fish Caught in California: Information for People Who Eat Fish – Office of Environmental Health Hazard Assessment
  9. Selenium and Methylmercury – Bioinorganic Chemistry
  10. Polychlorinated Biphenyls (PCBs) and Your Health – Wisconsin Department of Public Health
  11. PCB-related Lawsuit – CBS News
  12. Klassen, Curtis D., Casarett and Doull’s Toxicology: The Basic Science of Poisons. 7th ed. New York City: McGraw Hill, 2008. 947-950
   

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