The Importance of Selenium/Mercury Research in Seafood and Health

Factors

Laura RaymondEnergy & Environmental Research Center

Grand Forks, ND

March 28, 2007

History

• Minimata Bay, Japan 1950’s– From 1932 to 1968, Chisso

Corporation, dumped an estimated 27 tons of mercury compounds into Minamata Bay.

– Hundreds of people died.– Over 3,000 victims have been

recognized as having "Minamata Disease".

• Iraq 1971-1972– Grain treated with mercury

containing fungicide– 459 people died– Hospitalization of over 6,000– Hair Hg levels up to 674 ppm

(today <1.4 ppm)

The Great Debate

• Faroe Island study – Neurological defects in children neonatally exposed to Hg

from fish and whale consumption:

• Seychelles Island study – No adverse effects in children born to mothers exposed to

eating fish:– Fish consumption levels are 10-20X higher than common U.S.

consumption.

Reference dose 0.1g/kg bw/day

• Based on Faroe Island study • Benchmark Dose Lower Limit (BMDL)

– U.S. has the lowest BMDL • World health organization, British Food

Standards Agency, United Kingdom, Canadian government

• Centers for Disease Control and Prevention indicate that no one in the U.S. tests anywhere near the BMDL.

• Add an “uncertainty factor” of 10 • Reference Dose value 0.1g/kg bw/day

Methylmercury concentrations• Freshwater fish 0.1-0.4 ppm• Ocean fish 0.6-0.8 ppm• Predator fish > 1.0ppm• Fish in “polluted” water > 10ppm• Fish from Minamata Bay ~ 50ppm

• Whale meat ~4ppm• Whale liver >1000ppm

Reference dose 0.1g/kg bw/day

135-lb. woman: 1.5oz. Swordfish or 7 oz. tuna/week 50-lb. child: 0.5oz. Swordfish or 2.6 oz. tuna/week

Reference Dose 0.1g/kg bw/day

• The 2000 National Research Council Report stated that 60,000 newborns annually are born at risk due to methylmercury. – Assuming that women eating the most fish (the top 5%) are risking their

babies health.

• 2002 government hearing - this number was assumed to be increased to 400,000 pregnancies per year.

• July 2006 national survey conducted by Opinion Research Corporation found that 40% of Americans believe at least 10,000 childhood cases of mercury poisoning are documented by scientists each year.

• There are NO documented cases of mercury poisoning from fish consumption.

Third Study United Kingdom Study

• Increased risks for neurodevelopmental defects with decreased fish consumption:– Maternal compliance with the EPA RfD increased risks of their

children scoring in the lowest quartile for verbal IQ, and increased risks for pathological scores in fine motor, communication and social skills compared to mothers exceeding the RfD recommendation.

Huh?????

Neurological defects - Faroe Island studyNo adverse effects - Seychelles Island studyIncreased risks with decreased fish consumption -UK Study

Selenium?

• “Protective effect” of selenium• Numerous reports indicating selenium

supplementation counteracts the negative impacts of exposure to mercury.– Neurotoxicity– Fetotoxicity– Developmental toxicity

• Protective effects of selenium against Hg toxicity has been shown in all investigated species of mammals, birds, and fish.

Selenium Physiology21st amino acid – Selenocysteine

• Development • Thyroid homeostasis• HIV and other viruses• Cancer• Immune system• Cardiovascular disease• Reproduction• Mood• Disease links

– Congenital muscular dystrophy– Autism– Alzheimer's, Downs syndrome– Brain tumors– Diabetes– Liver diseases– Any condition associated with increased oxidative stress or inflammation

(rheumatoid arthritis, pancreatitis, asthma, obesity, septic diseases)

Se-HgH2Se +MeHg

Protective effect of Selenium

Binding Affinity ~1045

Extremely low solubility ~10-58 to 10-65

Se binds to mercury, so mercury is unavailable to cause harm.

Hg-Se

Binding Affinity ~1045

Extremely low solubility ~10-58 to 10-65

MeHg +H2Se

Or is it the Thieving effect of Mercury?

Hg is binding to selenium, so selenium is unavailable for it’s needed roles

Or is it the Thieving effect of Mercury?

Mercury Inhibition of Selenoprotein Synthesis

H Se2

(No free selenide)

SePO(No selenophosphate)

Selenoenzymes (loss of functions)

Selenoproteinbreakdown

products

Food SeleniumandMeHg

4

Selenocysteine (No selenocysteine)

Hg-Se

Hg

(Se cycle stops)

Selenoprotein Synthesis

H Se2(selenide)

SePO(selenophosphate)

Selenoenzymes (25+ discrete forms)

Selenoproteinbreakdown

productsFood

SelenomethionineSelenocysteineSe-methyl selenocysteine

4

Selenocysteine is the only amino acid that must be recreated for each cycle of protein synthesis

Selenocysteine (at active site)

SeP Synth.

Significance to mercury toxicity

• During Se depletion, there is retention and redistribution of Se to the brain, endocrine organs and reproductive organs.

• Mercury has the ability to cross the placental and blood-brain barriers and diminish Selenoenzyme activities!

Research Focus

• Investigating the role of Se in Hg bioaccumulation, toxicity and retirement from the environment.– Molecular– Cellular– Tissue– Animal– Population– Environmental

Effects of MeHg in rats fed low, normal, and selenium-rich diets

Objective: To investigate the effect of dietary mercury on selenium distributions and selenoenzyme activities in rats fed varying concentrations of mercury and selenium.

All of these rats were fed diets prepared with 10 ppm methylmercury added. The rat on the left has been fed a selenium deficient diet, the center rat was fed a selenium adequate diet and the rat on the right was fed a selenium rich diet.

Effects of MeHg in Rats Fed Low, Adequate, and Selenium-rich Diets

100

200

300

400

500

0 14 28 42 56 70 84 98 112 126

Study Day

Body W

eig

ht (g) .

0.1 µmol Se/kg

1.0 µmol Se/kg

10 µmol Se/kg

Effects of MeHg on Neurobehavior

This rat, fed a selenium-deficient diet with 10 ppm methylmercury, showed significant signs of neurotoxicity. (hind limb crossing, uneven gait, poor motor coordination and loss of balance).

This rat, fed a selenium-rich diet with 10 ppm methylmercury, showed no signs of neurotoxicity.

SELENIUM’S THERAPEUTIC EFFECT

To exam potential therapeutic effects of selenium, at week 11 the toxicity group was further divided into three groups

•No change in diet•Same amount of Hg with added Se •No Hg with added Se

Results show…

• Hair and blood Hg levels accurately reflect exposure BUT not risk.– Increased Hg in hair, blood and brain was associated with decreased

toxicity.

– The lowest Hg concentrations in hair, blood and brain were associated with the highest toxicity.

– It was the molar ratios of Hg to Se that determined toxicity.

• MeHg toxicity was only apparent with Se-deficient diets.– The increased molar excess of Hg:Se indicated toxicity.

• Se-therapy effects were nearly identical in treatment groups regardless of whether MeHg exposure was discontinued or not.

Why is this important?

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Mercury

Selenium

• Fish are among the richest sources of nutritional selenium in the American diet.

• Out of 1100 foods commonly consumed in the United States, 16 of the top 25 sources of dietary selenium are from fish.

Fish data depicted from Hall et al. (1978); Fish data depicted from Hall et al. (1978); pilot whale from Julshamn et al.pilot whale from Julshamn et al.(1987) (1987) and swordfish from Friedman et al. (1978).and swordfish from Friedman et al. (1978).

Selenium Levels

• Worldwide area with Low Selenium– Northern Europe

– Finland

– Sweden

– New Zealand

– Parts of China

– Africa

Can selenium explain “The Great Debate”?

• Faroe Island study – Neurological defects in children neonatally exposed to Hg from fish and

whale consumption

• Seychelles Island study – No adverse effects in children born to mothers exposed to eating fish:– Fish consumption levels are 10-20X higher than common U.S.

consumption.

• United Kingdom Study– Increased risks for neurodevelopmental defects with decreased fish

consumption– Maternal compliance with the EPA RfD increased risks of their children

scoring in the lowest quartile for verbal IQ, and increased risks for pathological scores in fine motor, communication and social skills compared to mothers exceeding the RfD recommendation.

FDA and EPA Message

• The reference dose is based on mercury levels only

• “Avoid shark, swordfish, golden bass, and king mackerel. Limit your fish intake to two meals per week and choose low mercury containing fish.”

• 74% of women of childbearing age and 85% of pregnant women consume <6 oz/wk.

• By focusing only on MeHg exposure without consideration and measurements of additional nutrients in fish, these warning statements are inadequate, inaccurate, misleading and potentially dangerous.

Thank You!

• www.undeerc.org

• lraymond@undeerc.org