Methyl-Mercury, Fish and Selenium

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041092/

https://seleniumfacts.com/index.php/selenium-mercury-eating-fish

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https://david-krantz.com/worried-about-mercury-in-fish-read-this/


Updated October 14th, 2019

We've all heard the warnings about fish being high in mercury -- it's one of the most common questions I get when I tell clients their genetics would be suited to a diet higher in fish. With nutrigenomic testing, we can understand your body's need for and ability to process and utilize the polyunsaturated omega-3 fats found in fish. But, often I'll get a little bit of pushback because of the engrained mythology around mercury and fish.

"But isn't fish high in mercury?"

There is a missing piece to this concept that reverses the potentially harmful effects of mercury that wasn't well understood until recently. But, you know when fear is involved, ideas stick around a lot longer than maybe they should. In this post, I'll address the mercury issue, as well as some of the genetic factors that can influence omega 3 requirements and heavy metal detoxification.

Enter Selenium
So first of all let's talk about the relationship of selenium to mercury (specifically methylmercury is the type from fish). Here's a quote from an article entitled "Dietary selenium's protective effects against methylmercury toxicity" that appeared in the journal Toxicology in 2010:

"Dietary selenium (Se) status is inversely related to vulnerability to methylmercury (MeHg) toxicity."

If you want to stop reading there, you've pretty much got the gist of this post. The problem happens when you consume a diet that's higher in molar mercury than molar selenium. Like most things, there are systems in play and reducing them to a single component does little to help us understand how things actually work in the real world.

But, lets go further into detail about what selenium does, why it's protective against mercury, how most fish contain much higher amounts of selenium than mercury, and the history of how we became scared of fish (spoiler alert, it has to do with people eating high amounts of whale and shark in combination with agriculture grown on low selenium soils.)

What does selenium do?
Selenium is an essential trace nutrient in humans, meaning certain levels of it are required for normal function. Selenium can act as a growth factor, has powerful antioxidant and anticancer properties, is essential for normal thyroid hormone production, and plays a role in the immune system as well. Selenium binds to amino acids in the body to form what are called "selenoproteins." The role of selenoproteins are quite varied but play a major role in the glutathione family of proteins and often incorporate the amino acid cysteine as a componant. Glutathione is particularly important as a scavenger of the hydrogen peroxide free radical, as a detoxification binding and transporter molecule, and helps inform proper protein folding. In short, selenium is one of the more important nutrients for making sure we can "clean up the trash" both from exogenous toxins and from the by-products of our own metabolism.

Selenium and Mercury: The Ratio Matters
Mercury has an extremely high binding affinity for selenium. It binds preferentially to selenium, up to one million times higher than it's second-most preferential molecule, sulphur. This means that when mercury and selenium are hanging out in the place, mercury is going to stick to selenium and it isn't going to take no for an answer. Consider the two halves to this coin:

When selenium and mercury are bound to each other, selenium cannot do it's job to make selenoproteins
When selenium and mercury are bound to each other, mercury can no longer act as a neurotoxin and can be excreted out of the body
So, if you were to consume more mercury than you had available selenium reserves to deal with it, you'd have a serious problem on your hands. Not only would you be dealing with the direct toxicity of mercury, you'd also be dealing with the depletion of selenium and inability to create selenoproteins. This inhibition of selenoprotein production is actually now understood to be the primary toxic action of mercury.

However, if you have more than enough selenium to deal bind to the mercury. It shouldn't be a big deal, right?  Here's a quote from the same journal article chock full of citations.

"MeHg (methylmercury) toxicity has been counteracted by providing supplemental dietary Se from yellowfin tuna (Ohi et al., 1976; Ganther et al., 1972), menhaden (Stillings and Lagally, 1974), swordfish (Freidman et al., 1978), and rockfish (Ohi et al., 1980). Most recently, Ralston (2010) showed that Se supplied from delipidated proteins of yellowfin tuna, swordfish, and mako shark were all effective in preventing the onset of growth inhibition and neurotoxic effects of high dietary MeHg exposures. Although there were substantial amounts of additional MeHg in diets prepared with these protein isolates, MeHg from these ocean fish did not accentuate MeHg toxicity, but fish Se prevented it. Therefore, the organic forms of Se present in ocean fish are bioavailable and effective in counteracting MeHg toxicity. This may explain why studies that examined effects of maternal exposure to MeHg from typical varieties of ocean fish (Davidson et al., 1998; Myers and Davidson, 1998; Hibbeln et al., 2007; Oken et al., 2008; Lederman et al., 2008) have not found the adverse effects that had been expected, but have, instead, found substantial beneficial effects accompany increasing seafood consumption (Hibbeln et al., 2007; Oken et al., 2008) including increases of up to 10 IQ points (Lederman et al., 2008)."

Ratios in Fish
So, what do the ratios of selenium to mercury in fish look like? Well, in most commonly eaten ocean-caught fish, they're pretty good. The issues come when you get into farmed fish, freshwater fish, and less commonly eaten fish like shark or whale. Nearly all the studies that have shown harmful effects of fish were done on populations that were eating fish with ratios of mercury higher than than selenium content. Such as this one where 85% of the seafood consumed was pilot whale meat. Or this one that examines the mercury and contaminant effects of whale on a Japanese population.



So as you can see, the story isn't so clear as "high mercury fish are problematic." Tuna is typically known for being a high mercury fish, however it has an extremely high molar selenium concentration. That being said, its not so clear that this is the only picture either. Studies such as this one have found moderate variability in both mercury and selenium ratios, so its clearly best to avoid fish, like sword fish, escolar, or marlin that even come close to a 1 to 1 ratio of mercury and selenium. Additionally there is variation within species based on fish size. This means that if you have the choice between a large or small tuna, choose the small tuna. Unfortunately, most people don't ever get to see the fish they're eating.

Other studies have found that variations in the mercury content are directly related to the selenium content available on the seafloor that become infused into the food chain. The selenium binds to mercury the exact same way it does in the human body and creates lower mercury concentrations up the food chain. So, location matters too.


Selenium concentrations in seafloor silt deposits lead to lower mercury concentrations in top predator fish

Cost/Benefit Analysis of Fish Consumption
So, how should we interpret this data? How does this actually effect people in real life? One of the big concerns about fish consumption is mercury load during pregnancy. The current official recommendations in the United States are that pregnant mothers cut their fish consumption while pregnant.

Lets turn to two of the largest epidemiological studies ever conducted that focused on fish consumption to see what they found. Epidemiology is the study and analysis of the patterns, causes, and effects of health and disease conditions in specific populations. It is the cornerstone of public health, and shapes policy decisions and evidence-based practice by identifying risk factors for disease and targets for preventive healthcare.

The ALSPAC Study
A study done in the UK looked at maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood. This studied followed 11,875 pregnant women and their children over 8 years following developmental, behavioural, and cognitive outcomes. The study controlled for other contributing factors such as social disadvantage. As an aside, epidemiological studies only work if they have a high N value, or amount of people in the study. This was a massive undertaking.

What were the results?

"After adjustment, maternal seafood intake during pregnancy of less than 340 g per week was associated with increased risk of their children being in the lowest quartile for verbal intelligence quotient (IQ) (no seafood consumption, odds ratio [OR] 1.48, 95% CI 1.16-1.90; some, 1.09, 0.92-1.29; overall trend, p=0.004), compared with mothers who consumed more than 340 g per week. Low maternal seafood intake was also associated with increased risk of suboptimum outcomes for prosocial behaviour, fine motor, communication, and social development scores. For each outcome measure, the lower the intake of seafood during pregnancy, the higher the risk of suboptimum developmental outcome."

"Maternal seafood consumption of less than 340 g per week in pregnancy did not protect children from adverse outcomes; rather, we recorded beneficial effects on child development with maternal seafood intakes of more than 340 g per week, suggesting that advice to limit seafood consumption could actually be detrimental. These results show that risks from the loss of nutrients were greater than the risks of harm from exposure to trace contaminants in 340 g seafood eaten weekly."

The Seychelles Study
The Seychelles Child Development study was done in 1989 on an island near Madagascar where pregnant women ate fish up to 12 times per week. The study followed 711 women and their children through 66 months, or about 5 and a half years. There are numerous post analyses of the study and further follow ups as those children grew up into their 20's, and they all agree: there was no threat to developmental outcomes.



A large number of studies indicate that lower intake of long-chain omega-3 fats (found in fish) during pregnancy is associated with growth retardation, delayed or suboptimal depth perception, lower scores in tests which measure neurodevelopment, deficits in fine motor skills, speed of information processing in infants, and irreversible deficits in the release of key neurotransmitters like serotonin and dopamine.

So, it appears that the risk of mercury toxicity is outweighed by the benefits of the benefits that omega-3's provide. Seafood is by far the most abundant and bioavailable source of omega-3 fats and eating whole fish is a much better way to get to get omega-3's due to the oxidation potential of extracted oils.

I'd also like to point out that this study looked at women living largely a traditional lifestyle. While it is not covered in the study, I imagine they were getting more than adequate sun exposure and exercise while minimizing processed food, EMF, and the toxin exposure and other harmful lifestyle variables associated with a western lifestyle. Its something to take into consideration when looking at the whole picture. Are you more at risk to having an adverse reaction to high fish consumption and mercury toxicity if the rest of your lifestyle is poor? I don't know, but I would lean towards yes. Certainly, additional consumption of selenium would play a role.

I hope this clears up some of the misconceptions about mercury and fish, and the protective role of selenium. However, are there still reasons why some people may want to eat more or less fish? Absolutely.

Genetic Factors Involved in Fish Consumption
Since my focus with clients is on nutrigenetic and nutrigenomic diets, let's talk about some of the factors in play that might create individual differences regarding the need for omega-3's, heavy metal detoxification, and selenium metabolism.

MYRF, FADS1, and FADS2

Fatty acid desaturase is a protein coded for by the FADS1 and FADS2 genes, and helps regulate the metabolism. Single nucleotide polymorphisms in these genes have been change our body's ability to convert ALA into EPA, and correlations have been made with tissue and red blood cell levels. A SNP (rs174537) in the myelin regulatory factor gene (MYRF) has been shown to have an effect on DNA methylation of the FADS1 gene, changing the need for omega 3's. Some people simply may have a requirement for more or less omega 3 fatty acids, especially in relationship to omega 6 fatty acids in the diet.

COMT and MTHFR

Worried about mercury in general, even despite knowing about selenium's role? Well, don't worry, your body may have a backup plan for that. Catechol-O-methyltransferase is an enzyme that is reponsible for breaking down dopamine, norepinephrine, and other other d rugs and substances that have a catechol structure. COMT is also a major player in the the methylation cycle, along with MTHFR and several other genes, that helps our body create methyl donors. Methylation is ubiquitious process used in a wide variety of ways, but one of them is as a phase 1 detox molecule that helps prepare mercury or selenomercury to be excreted from the body. These are complex topics I'll cover in other blog posts. People with these polymorphisms can greatly benefit from targeted supplementation with things like SAM-e, methylfolate, or TMG. There are several studies that show correlations between COMT polymorphisms and sensitivity to mercury.

Selenium and Glutathione Metabolism

Some of the more common, and more important, polymorphisms I see in clients are related low functioning glutathione system. Glutathione, as mentioned above is a critical component of our bodies' antioxidant and detoxification system. Some people refer to it as "the master antioxidant" although I tend to see as just another tool in the box. Variations in the GPx1, GSTP1, GSTM1, GSTT, and GLCL genes all modify our body's ability to produce glutathione one of the selenoproteins we were talking about above. Understanding these SNPs, along with selenium related SNPs like the selenium transporter SEPP1 gene can help us to understand if you may have a higher requirement for selenium as a genetic predisposition.

The Bottom Line - Three Final Points
Mercury toxicity from fish is overblown. If you focus on selecting fish with a high selenium to mercury ratio that are lower on the foodchain, there's minimal risk as compared to the benefits that fish provides. There are certainly issues with farmed fish, and potentially radiation from pacific-caught fish but consuming moderate amounts of wild caught fish with good selenium to mercury ratios is beneficial to most everyone.
Epidemiological studies point to not only the benefits of fish consumption but the potential harm of low fish consumption during pregnancy. There is major risk associated with eating fish with a high mercury to selenium ratio; however, if the selenium levels are kept high relative to mercury, the benefits outweigh the risks.
Genetic variables can influence your need for omega 3's and ability to process mercury effectively. Understanding your needs and bolstering your system where it needs help can greatly optimize your response to this or any other food. As an epigenetic coach, I can help you understand how to eat for your genes and support your detoxification pathways for better health, performance, and longevity.
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