Transcript Slide 1

The Importance of Selenium/Mercury
Research in Seafood and Health
Factors
Laura Raymond
Energy & 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 0.1g/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 0.1g/kg bw/day
Reference dose 0.1g/kg bw/day
135-lb. woman:
50-lb. child:
1.5oz. Swordfish or 7 oz. tuna/week
0.5oz. Swordfish or 2.6 oz. tuna/week
Methylmercury concentrations
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Freshwater fish
Ocean fish
Predator fish
Fish in “polluted” water
Fish from Minamata Bay
0.1-0.4 ppm
0.6-0.8 ppm
> 1.0ppm
> 10ppm
~ 50ppm
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•
Whale meat
Whale liver
~4ppm
>1000ppm
Reference Dose 0.1g/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 study
No adverse effects - Seychelles Island study
Increased 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 Physiology
21st amino acid – Selenocysteine
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Development
Thyroid homeostasis
HIV and other viruses
Cancer
Immune system
Cardiovascular disease
Reproduction
Mood
Disease links
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–
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–
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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)
Protective effect of Selenium
Se binds to mercury, so mercury is unavailable to cause harm.
H2Se
+
MeHg
Se-Hg
Binding Affinity ~1045
Extremely low solubility ~10-58 to 1065
Or is it the
Thieving effect of Mercury?
Hg is binding to selenium, so selenium is unavailable for it’s needed roles
MeHg
+
H2Se
Hg-Se
Binding Affinity ~1045
Extremely low solubility ~10-58 to 10-65
Or is it the
Thieving effect of Mercury?
Mercury Inhibition of
Selenoprotein Synthesis
Selenoprotein Synthesis
Food
Selenoprotein
breakdown
products
Selenomethionine
Selenocysteine
Se-methyl selenocysteine
Selenoenzymes
(25+ discrete forms)
H2 Se
(selenide)
SeP Synth.
SePO 4
(selenophosphate)
Food
Selenium
and
MeHg
Hg-Se
Selenoprotein
breakdown
products
H2 Se
SePO 4
(No selenophosphate)
Hg
Selenocysteine
(at active site)
Selenocysteine is the only amino acid that must be
recreated for each cycle of protein synthesis
(No free selenide)
(Se cycle stops)
Selenoenzymes
(loss of functions)
Selenocysteine
(No selenocysteine)
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.
Effects of MeHg in Rats Fed Low,
Adequate, and Selenium-rich Diets
.
500
0.1 µmol Se/kg
1.0 µmol Se/kg
Body Weight (g)
400
10 µmol Se/kg
300
200
100
0
14
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56
70
Study Day
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.
84
98
112
126
Effects of MeHg on Neurobehavior
This rat, fed a selenium-rich diet with
10 ppm methylmercury, showed no
signs of neurotoxicity.
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).
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?
20
Mercury
Selenium
nmol/g
15
10
Pilot Whale
US average
Swordfish
Grouper
Snapper
Cod
Halibut
Pollock
Tuna
Salmon
Flounder
0
Sole
5
• 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); pilot whale from Julshamn et al.(1987)
and swordfish from Friedman et al. (1978).
Selenium Levels
• Worldwide area with Low
Selenium
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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
• [email protected]