Balancing the benefits of n-3 polyunsaturated fatty acids and
the risks of methylmercury exposure from fish consumption
Kathryn R Mahaffey, Elsie M Sunderland, Hing Man Chan, Anna L Choi, Philippe Grandjean,
Koenraad Mariën, Emily Oken, Mineshi Sakamoto, Rita Schoeny, Pál Weihe, Chong-Huai Yan, and
Fish and shellfish are widely available foods that provide important nutrients,
particularly n-3 polyunsaturated fatty acids (n-3 PUFAs), to many populations
globally. These nutrients, especially docosahexaenoic acid, confer benefits to brain
disease in adults. However, fish and shellfish can also be a major source of
brain development. This review documents the latest knowledge on the risks and
benefits of seafood consumption for perinatal development of infants. It is possible
dietary intake of n-3 PUFAs while minimizing MeHg exposures is suggested.
© 2011 International Life Sciences Institute
Fish and shellfish are important food resources globally.
About 20% of the world’s population derives at least one-
fifth of its animal protein intake from fish,which contrib-
utes up to 180 kcal per capita per day in island states such
as Iceland and Japan.1Consuming fish has many health
benefits due in part to the high concentrations of n-3
polyunsaturated fatty acids (n-3 PUFAs) present in many
species. However, fish also contain methylmercury
(MeHg), a well-known and widespread environmental
fish consumption.2–5Fetuses are a high-risk group
because the developing brain is particularly susceptible to
the harmful effects of MeHg exposure.6Therefore, the
effect of dietary seafood intake by pregnant women
remains an important issue,especially in populations that
consume fish frequently.7Reviewing the scientific evi-
dence that forms the basis of dietary and public health
advice on how to balance the benefits and risks associated
with fish consumption is therefore needed.Although this
review is focused on providing advice for women of
childbearing age, risks for the general population associ-
ated with MeHg exposures,such as impacts on the endo-
crine system and cardiovascular health,are the subject of
much ongoing research.8–13
Affiliations: KR Mahaffey (deceased) was formerly with the Department of Occupational and Environmental Health, GeorgeWashington
University School of Public Health,Washington DC, USA. EM Sunderland and AL Choi are with the Department of Environmental Health,
Harvard School of Public Health, Boston, Massachusetts, USA. HM Chan is with the Community Health Sciences Program, University of
Northern British Columbia, Prince George, British Columbia, Canada. P Grandjean is with the Department of Environmental Health,
Harvard School of Public Health, Boston, Massachusetts, USA, and Institute of Public Health, University of Southern Denmark, Odense,
Denmark. K Mariën is with theWashington State Department of Health, Olympia,Washington DC, USA. E Oken is with the Department of
Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA. M Sakamoto is with
the Department of Epidemiology, National Institute for Minamata Disease, Minamata, Fukuoka, Japan. R Schoeny is with the US
Environmental Protection Agency, Office ofWater,Washington DC, USA. P Weihe is with the Faroese Hospital System,Tórshavn, Faroe
Islands. C-H Yan is with the Shanghai Key Laboratory of Children’s Environmental Health, XinHua Hospital, Shanghai JiaoTong University
School of Medicine, Shanghai, China. A Yasutake is with the Biochemistry Section, National Institute for Minamata Disease, Minamata,
Correspondence: HM Chan, Community Health Sciences Program, University of Northern British Columbia, Prince George, British
Columbia, Canada,V2N 4Z9. E-mail: email@example.com, Phone: +1-250-960-5237.
Key words: docosahexaenoic acid, eicosapentaenoic acid, fish, methylmercury, n-3 polyunsaturated fatty acids
Nutrition Reviews® Vol. 69(9):493–508
and n-3 PUFA exposures in women of childbearing age
on subsequent fetal and child development.The scope of
this review includes the following: 1) intake and metabo-
lism of n-3 PUFAs; 2) effects of n-3 PUFA intakes on
child development; 3) MeHg exposure from fish con-
sumption;4) MeHg body burden and child development;
5) transfer of n-3 PUFAs and MeHg from mothers to
fetuses; 6) complexity of the association between MeHg
exposure and dietary sources of n-3 PUFAs; 7) dietary
recommendations for pregnant women;and 8) balancing
the risks and benefits of fish consumption.
INTAKE AND METABOLISM OF n-3 PUFAS
hydrogen in repeating groups of –(CH2)n – that contain
both a methyl (CH3) and a carboxyl (–COOH) group.
There are a large number of fatty acids found in nature.14
Highly unsaturated fatty acids (multiple double bonds)
with one of the double bonds located three carbon atoms
from the methyl end are denoted n-3 fatty acids. Those
n-3 PUFAs that are particularly important in human
nutrition15include the following: 18:3 alpha-linolenic
acid (ALA), 20:5 eicosapentaenoic acid (EPA), 22:5
docosapentaenoic acid (DPA),and 22:6 docosahexaenoic
The two fatty acids that are especially important for
human neurological development are EPA (20 carbons in
length with five double bonds including one at n-3), and
ing one at n-3).These essential fatty acids play important
roles in the following areas: 1) cell membrane formation,
integrity, and functions; 2) functioning of brain, retina,
liver, kidney, adrenal glands, and gonads; and 3) local
hormone production for the regulation of blood pressure
and immune and inflammatory responses.16
Humans can synthesize portions of their require-
ments for elongated n-3 fatty acids from the short-chain
as walnuts,flax seed,and soybean oil.However,synthesis
of EPA and DHA from ALA is generally not sufficient to
meet dietary requirements.18,19As EPA and DHA are
essential nutrients, dietary intake from fish and shellfish,
enriched eggs, and/or food supplements is necessary for
The capacity of humans to synthesize EPA and DHA
from ALA is variable. Conversion efficiency is organ-
son.21For example, women appear to be able to convert
dietary ALA to the long-chain fatty acids more readily
than men.17,22,23Synthesis of EPA and DHA in the human
body from ALA is likely inhibited by conditions of
disease (for example, liver toxicity)18,19and appears to
decline with exposure to environmental contaminants,
such as polychlorinated biphenyls (PCBs), drugs, and
It is not known if humans can synthesize DHA from
ALA at a rate sufficient to provide an optimal amount of
this chemical to meet the demands of the developing fetal
brain. Half-lives of DHA in critical tissues, including the
inter-individual variability exists in the ability to synthe-
size DHA, especially among term and preterm infants.18
The fetus may be limited in its ability to form adequate
DHA from precursors18and thus need to receive pre-
formed DHA through placental transfer from the
mother.27Maternal DHA stored in adipose tissue may be
mobilized during pregnancy by placental regulation.28–31
However, fetal DHA does not increase one-for-one with
maternal serum DHA concentration.18,28This complex
topic is the focus of ongoing research.
Globally, the most commonly consumed sources of
n-3 PUFAs are fish and shellfish, which in turn obtain
them from algae that can synthesize these fatty acids.
Concentrations of n-3 PUFAs vary greatly among fish
species.32–37Thus, dietary intake of EPA and DHA from
fish and shellfish is strongly dependent on the species
consumed.32,33,38,39Lipid content of specific fish is moder-
ately predictive of their n-3 PUFA content. For example,
certain fatty fish (especially salmon, mackerel, sardines,
and herring) are also high in n-3 PUFAs.However,other
fish that are low in fat (especially shrimp and trout) are
also good sources of n-3 PUFAs. Table 1 provides a
Weaver et al.34evaluated the species most commonly
consumed in North America and grouped them by n-3
PUFA content into those providing more than 500 mg,
150–500 mg, or less than 150 mg per 100 g of fish con-
sumed.Fish species that provide the highest levels of n-3
PUFAs are sockeye salmon,farmed trout,farmed salmon,
tuna, albacore tuna canned in water, and toothfish.
Species providing less than 150 mg of n-3 PUFAs per
100 g fish meals include mahi-mahi, skate, triggerfish,
canned in oil. Species intermediate in n-3 PUFAs are
haddock, cod, halibut, sole, flounder, crustacea, perch,
black bass, tilapia, and swordfish. These groups reflect
only their n-3 fatty acid content,not the mercury concen-
Dietary intake levels and sources of n-3 PUFAs vary
and edible fats and oils are the most important sources of
average seafood consumption rate of approximately 60 g/
Nutrition Reviews® Vol. 69(9):493–508
intake of n-3 PUFAs is reported to be approximately
3,000 mg/day, mostly from fish species such as horse
mackerel, sardines, and tuna.40In contrast, intake of and,
accordingly,blood levels of DHA in the United States are
among the lowest in the world.41Similarly, there is evi-
not consume enough DHA to meet nutritional require-
ments for optimal fetal development.42,43
EFFECTS OF n-3 PUFA INTAKE ON
DHA is a necessary structural component of the develop-
ing brain and eye (see review by Innis44). Because the
uptake of DHA into these tissues is greatest in the third
trimester of pregnancy and the first 2 years of life, the
Table 1 NHANES (1999–2002) frequency of consumption rank and corresponding concentrations of the long-
chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acid) (from Mahaffey32) and Hg
concentrations (Sunderland80and references therein).
Rank Species EPA + DHA
Tuna (all, average)
Bluefin (7 kg)
Skipjack (3 kg)
Yellowfin (5–20 kg)
Breaded fish products
Mackerel (except King)
* Ranges in Hg concentrations represent variability in sample means across different harvesting regions.
†Data from Mahaffey et al., 20043and references therein.
‡Data from USDA.167
§Tuna canned in water, drained solids.
¶Tuna canned in oil, drained solids.
††Cooked, dry heat.
Nutrition Reviews® Vol. 69(9):493–508
exposure.45,46Randomized trials of prenatal supplemen-
tation and observational studies of maternal fish con-
sumption during pregnancy both provide evidence for
the benefits of prenatal n-3 PUFA intake for child devel-
opment. Helland et al.47conducted a trial in which preg-
nant women were randomly assigned to receive either a
cod liver oil (n-3 PUFA) supplement or a corn oil supple-
ment (n-6 long-chained polyunsaturated fatty acid [n-6
PUFA] control) from 18 weeks of gestation until 3
months postpartum. Corn oil is not a suitable precursor
for n-3 PUFA synthesis. At age 4 years, offspring whose
mothers had received cod liver oil supplements had sig-
nificantly higher mean scores on developmental and cog-
nitive tests than the control group. In another trial by
Dunstan et al.,48children of mothers who received fish oil
supplements during pregnancy had significantly higher
scores on eye and hand coordination tests compared to
those who received olive oil. Eye and hand coordination
scores at 2.5 years of age were positively correlated with
n-3 PUFA levels in cord blood erythrocytes and inversely
correlated with n-6 PUFA levels.48However, no differ-
ences in other outcomes such as child behavior and lan-
guage at age 2.5 years were observed.48Because these
studies used fish oil rather than an n-3 PUFA supplement
from algae, PCB contamination of the fish oils may have
occurred,which could have resulted in underestimates of
the benefits of n-3 PUFA intakes.49In addition,follow-up
rates in both studies were low, which might bias results.
Observational studies have also consistently shown
that mothers who consume more n-3 PUFAs during
pregnancy have children with improved neurobehavioral
development.For example,Oken et al.6,50examined asso-
ciations among maternal prenatal fish intake, mercury
levels, and cognitive development in offspring at 6
months to 3 years of age in Project Viva, a pre-birth
cohort in the state of Massachusetts in the United States.
Greater maternal fish consumption (assumed to indicate
higher n-3 PUFA intake) was associated with higher
more than two servings of fish weekly and sustained low
blood mercury levels (presumably because they con-
highest test scores.The beneficial association of fish con-
additional adjustment for mercury levels, suggesting that
the benefits of prenatal fish consumption might be even
greater in the absence of mercury contamination. Simi-
larly, among a cohort of over 25,000 mothers and chil-
fish intake was associated with higher child developmen-
tal scores at 18 months.51In theAvon Longitudinal Study
mothers who ate more than 340 g (12 ounces) of low-
mercury seafood per week had a lower risk of having
children with suboptimal scores on measures of verbal
IQ,prosocial behavior,fine motor skills,and social devel-
opment compared with women who ate less seafood. In
another UK study,at age 9 years,the children of mothers
who had eaten oily fish in late pregnancy had a reduced
risk of hyperactivity and a higher verbal IQ, but no dif-
ference in full-scale IQ, compared with those whose
mothers did not eat fish.53Finally,in a cohort of children
in NewYork City,maternal fish consumption was associ-
ated with better psychomotor development at 36 months
from fish consumption in many of these studies were
fairly low compared to populations that consume large
quantities of fish on a regular basis.
Dietary n-3 PUFA intake in infancy may also
improve later cognitive development, although evidence
for such benefits is less clear. Breast milk is a rich source
of n-3 PUFAs. Before 2002, commercial infant formulas
in the United States contained ALA, but not long-chain
fatty acids.55A meta-analysis of observational studies
showed a 3–5-point increase in IQ among children who
had been fed breast milk compared to those fed with
infant formula that was not supplemented with long-
chain fatty acids.56The extent to which residual con-
founding explains these results is a major concern.57
However,in a cluster-randomized trial of 17,000 mothers
and children in the Republic of Belarus, children whose
mothers were randomized to a breastfeeding promotion
intervention had higher IQ at age 6.5 years, suggesting
that confounding does not entirely explain the observed
benefit. Several randomized trials have attempted to
determine whether the use of infant formulas supple-
mented with long-chain fatty acids (n-3 and n-6 PUFAs)
is associated with improved outcomes compared to non-
supplemented formula.58,59Meta-analyses of these ran-
domized controlled trials did not find evidence of
persistent beneficial effects of n-3 and n-6 PUFA supple-
mentation of formula milk on the physical, visual, and
neurodevelopmental outcomes of term or preterm
infants followed up to 3 years of age.58–60Thus, the ben-
eficial effects of breastfeeding may be related to factors
other than the elongated fatty acid content of breast milk.
METHYLMERCURY EXPOSURE FROM
In addition to containing n-3 PUFAs, which may benefit
child neurodevelopment,fish also contains MeHg,which
can damage the fetal nervous system.61–65Dose-response
relationships between indicators of neurodevelopmental
effects in children and MeHg exposures have been quan-
Nutrition Reviews® Vol. 69(9):493–508
tified with sufficient confidence66to apply in regulatory
decisions controlling mercury emissions.67,68
Inorganic mercury from atmospheric deposition and
other sources is converted to MeHg, the only mercury
species that biomagnifies in aquatic food webs,69by
microbes in the water and sediments of wetlands, lakes,
reservoirs, rivers, estuaries, and oceans.70–73Larger, older,
from lower trophic levels.69Concentrations in top preda-
tor fish can be up to 10 million times higher than those in
water.69,74,75MeHg levels in fish and shellfish reflect con-
species-specific physiological factors such as metabolism
ers generally have limited access to information about
size of fish sold in the commercial market.
Table 1 shows MeHg concentrations in commonly
consumed fish and shellfish. High-trophic-level species
like shark,tilefish,swordfish,and large bluefin tuna (used
in sashimi grade tuna) are consistently high in MeHg.As
a result, dietary advisories for limiting consumption by
high-risk groups have been issued for these species in
many countries. Fish with low-to-moderate MeHg con-
centrations such as mackerel, salmon, and sardines have
some of the highest n-3 PUFA contents (Table 1). Other
commonly consumed low-MeHg
herring, pollock, flounder, sole, plaice, crabs, shrimp, and
METHYLMERCURY BODY BURDEN AND
Three long-term studies have investigated MeHg impacts
in children exposed prenatally with continued exposure
into adulthood. Two of these studies (based in the Faroe
Islands and the Seychelles) are ongoing, and the third,
conducted in New Zealand, was completed in the
1980s.62,82–92The New Zealand study considered children
whose mothers were frequent seafood consumers and
compared a group with a low MeHg exposure to a group
with hair-Hg concentrations above 6 mg/g (mean,8.3 mg/
full-scale IQ, language development, and gross-motor
skills.64The findings of this study are important because
they reflect effects associated with chronic exposures
from high and relatively constant fish consumption pat-
terns over time and Hg body burdens in homeostasis.
than 1,000 singleton births in a population of frequent
fish consumers that also periodically consumes whale
meat and blubber.62,86,90Whale meat is known to contain
mercury and the blubber is known to be contaminated
with PCBs and other persistent organic chemicals.86The
median maternal hair-Hg concentration in this cohort,
collected at delivery, was 4.3 mg/g.86Neuropsychological
tests administered to offspring at ages 7 and 14 years
showed statistically significant indicators of poorer neu-
rodevelopment with higher maternal MeHg expo-
sure.62,90,93,94The test outcomes associated with the
observed effects from MeHg exposure were not affected
when controlling for PCB exposure.95However, the neu-
14 years did increase when controlling for maternal fish
The Seychelles study includes more than 800 infant-
mother pairs and, in contrast to the New Zealand and
significant association between maternal mercury expo-
ticipating in the Seychelles study demonstrated a similar
median maternal hair-Hg level of 6.6 mg/g compared to
those of the other two populations at time of delivery.91
The first series of results was adjusted for the child’s post-
natal MeHg exposure, but not for maternal fish intake.A
direct association between maternal MeHg exposure and
poorer developmental scores, after adjustments were
made for fish intake, was recently reported among a new
cohort of children in the Seychelles study, who were fol-
lowed to 24 months of age.97
Results from these three studies were central to the
conclusions derived by the NationalAcademy of Sciences
in 2000,98which the US Environmental Protection
Agency (EPA) subsequently used to derive the reference
dose (RfD) for MeHg of 0.1 mg/kg/day. This RfD was
based on a series of endpoints associated with a median
cord blood mercury level of about 58.0 mg/L.As noted in
the US EPA Integrated Risk Information System (IRIS),
the EPA did not choose a single endpoint for the RfD:
“Rather than choose a single measure for the RfD critical
endpoint, EPA based this RfD for this assessment on
several scores from the Faroes measures,with supporting
analyses from the New Zealand study,and the integrative
analysis of all three studies.”99In calculating the RfD, the
EPA assumed that cord blood and maternal blood
mercury levels were equivalent.100
Generally,an RfD is defined as the amount of a sub-
by the population, including sensitive subpopulations,
without the expectation of an adverse effect.101It should
be noted, however, that for the MeHg RfD, IRIS says the
following:“It is also important to note that no evidence of
a threshold arose for methylmercury-related neurotoxic-
ity within the range of exposures in the Faroe Islands
Nutrition Reviews® Vol. 69(9):493–508
near or below the current EPA RfD. Lederman et al.54
studied a cohort of children who had the potential for
mercury exposure by virtue of the fact that their mothers
lived within 1 or 2 miles of World Trade Center in New
York City around the time of its collapse on September
11, 2001. Blood mercury levels were significantly higher
in women who consumed fish or seafood while pregnant;
Trade Center site. The authors observed a significant
inverse association between log cord mercury and Psy-
as with performance and verbal and full IQ scores on the
Wechsler Preschool and Primary Scale of Intelligence
Revised (WPPSI-R), administered at 48 months. They
13 mg/L had a full IQ score higher than 100. The authors
state that other published studies reported higher mean
cord blood mercury than those measured in their cohort;
for example, the cord blood geometric mean mercury
level in the Faroe Islands study was 22.9 mg/L.
The MeHg RfD determined by the US EPA has been
used to derive biomonitoring comparison values consid-
ered to reflect exposures equivalent to the RfD; such as
1.2 mg/g (ppm) mercury-in-hair concentration and
5.8 mg/L (ppb) mercury-in-blood concentration.101Addi-
tional evaluations of the amounts of MeHg that produce
adverse health effects have been developed by various
organizations, including the World Health Organization,
and are summarized by Mergler et al.65Governmental
agencies representing a number of countries (such as
Japan, USA, New Zealand, Australia, UK, and Canada)
have developed MeHg intake levels to protect the public
that range from 0.1–0.47 mg/kg/day.98,102–104Differences
among various government assessments are mainly
related to the amounts of exposure considered to be
without adverse effects rather than estimates of exposures
producing adverse effects.Various agencies have applied
different uncertainty factors to extrapolate from expo-
sures known to produce adverse effects to exposures
thought to be safe. For example, the US EPA applied an
uncertainty factor of 10 to results from the Faroe Islands
population, as well as other study results to account for
variability and uncertainty within the human popula-
tion.101In contrast, the Agency for Toxic Substances and
Disease Registry (ATSDR) applied a factor of 4.5 for
human variability and uncertainty in the sensitivity of the
tests used in the Seychelles study, on which their assess-
ment was based.105Uncertainty factors will remain varied
until various issues can be addressed. This imprecision
will bias the estimation of MeHg neurotoxicity toward
null. For example, recent work conducted in the Faroe
Islands population adjusted for the imprecision of expo-
sure biomarkers resulted in a calculated RfD that is about
50% below the level used by the US EPA.106
Various studies suggest that many populations
and/or subpopulations exceed a body burden level that
risk assessors consider acceptable. Results from Project
Viva in the United States, which included 135 mother-
upper-middle-class population, indicated that approxi-
mately 10% of women exceeded a hair mercury level
equivalent to the US EPA RfD.6These results are similar
to those observed in the National Health and Nutrition
Examination Survey (NHANES), which showed that
between 1999 and 2002 approximately 6% of women of
childbearing age exceeded the US EPA’s RfD for MeHg.3
NHANES data are collected across the United States
using a weighted approach to participant selection so as
to result in a statistical representation of the general
population. The most recent NHANES data for 2004
suggest that blood mercury concentrations in women of
childbearing age may be decreasing, although the
amounts of fish consumed by high-risk individuals have
not changed.4Regional studies indicate that blood
mercury levels in adults living in NewYork City are three
times those of the national average.107Foreign-born
Chinese residents of NewYork City had the highest blood
mercury levels of all ethnic groups, with a geometric
results have been observed within the Korean and Japa-
ric Study (AMIBS), in which many women within both
communities exceed the MeHg RfD.108–110Results of this
study also showed significant differences in MeHg body
burden levels between the two populations, even though
total fish intake is nearly identical, suggesting differences
in fish species selection.108–110Even if body burdens are
decreasing among women in the United States, results
from Project Viva have shown that women with higher
fish consumption patterns leading to elevated mercury
body burden levels may have children with decreased
cognitive scores.6Further,a recently published work con-
ducted in a NewYork City cohort that had average mater-
nal blood mercury levels similar to those observed
nationally based on NHANES results suggests that
impaired cognitive development can occur in children of
mothers with exposure levels near the RfD.54
Further indication that mercury body burden levels
in many individuals are exceeding those recommended
comes from the Korean National Human Exposure and
Bio-monitoring Examination in which one in three
ing 1 mg/g.111,112Blood-Hg levels obtained for this exami-
nation, which was intended to reflect the general
population of Korea, suggested that greater than 25% of
the population have mercury intakes exceeding the US
EPA RfD.111,112In certain locations of China, such as
Guizhou in the southwest, rice harvested from the
Nutrition Reviews® Vol. 69(9):493–508
mercury-rich environment is a significant contributor to
overall Hg body burdens.113–115Mercury-contaminated
rice may also become a significant concern in other areas,
such as the Philippines, where in some locations rice is
grown in Hg-rich soils.116For example, rice paddy fields
along the Naboc River have been irrigated by water from
a contaminated river and Hg intakes from rice for local
residents exceed one-third of their total exposure.116
Because of the importance of fish and rice in Asian diets,
more information on MeHg exposure from these sources
is needed to characterize the risk to Asian populations.
In summary, results of multiple studies have shown
that body burden levels of MeHg in many populations
around the world are exceeding the levels equivalent to
the US EPA RfD. This implies that neurodevelopmental
impacts to offspring of mothers exposed to high levels of
MeHg is a substantial global concern.
TRANSFER OF n-3 PUFAS AND METHYLMERCURY FROM
Maternal and fetal blood DHA concentrations are signifi-
cantly correlated.117,118However, the percentage of DHA
plasma at the time of birth.29,119Several studies show pla-
cental fatty acid transport proteins (FATP) and different
lipolytic enzymes are of key importance in mediating
DHA transport across the human placenta, although the
exact mechanism of preferential DHA transfer remains
unknown.29,119MeHg transport into tissues appears to be
which is transported into cells via a neutral amino acid
carrier protein.120,121Various studies have shown differ-
ence between the concentration of MeHg in cord blood
and maternal blood concentrations.3,65,122,123Stern and
Smith122calculated the geometric mean ratio of fetal to
maternal blood mercury to be 1.7. Since this work was
completed, Lederman et al.54obtained a ratio of 2.2 in a
New York City cohort of pregnant women. As the EPA
assumed that cord blood and maternal blood mercury
levels to be equivalent when calculating the RfD, future
this difference in fetal-maternal blood ratio.
Sakamoto et al.118reported that MeHg was directly
correlated with DHA in fetal circulation. These results
suggest that fish consumption may have been the source
of both MeHg and DHA in maternal circulation that was
subsequently transferred to the fetus. If the types of fish
the children will likely improve,but if the MeHg concen-
trations are sufficiently elevated to cause deleterious out-
comes, the beneficial aspects of DHA intake may be
negated.Accordingly,fish consumption would then have
an adverse effect on children’s development. This salient
issue makes the placental transfer of MeHg and DHA and
their relationship in fetal and maternal blood circulation
important factors for determining the risks and benefits
of maternal fish consumption during gestation.
COMPLEXITY OFTHE ASSOCIATION BETWEEN
METHYLMERCURY EXPOSURE AND DIETARY SOURCES
OF n-3 PUFAS
Amounts of both n-3 PUFAs and MeHg in fish and shell-
fish vary widely across and within different fish varieties
(Table 1).Some kinds of fish have more than 10 times the
amount of EPA and DHA than other species and the
amount of mercury in fish can differ by two orders of
magnitude (e.g., Table 1). Many species that are high in
n-3 PUFAs are low in MeHg and vice-versa, making it
possible to choose species that minimize MeHg exposure
while retaining the health benefits of consuming
fish.32,39,124A number of reports have recommended ways
to choose fish and shellfish species that provide higher
quantities of n-3 PUFAs and relatively low quantities of
MeHg concentrations in fish consistently increase
on a variety of factors outlined in earlier sections.69In
contrast, n-3 PUFAs show irregular retention patterns at
different trophic levels.14Fish cannot synthesize n-3
PUFAs and obtain them from algae. Therefore, even
lower trophic level fish, such as sardines and anchovies,
can have high levels of DHA. The fat content of specific
fish species is moderately predictive of their n-3 PUFA
content, with certain fatty fish (e.g., salmon, mackerel,
sardines, and herring) having especially high levels
(Table 1). However, other species that are low in fat (e.g.,
shrimp and trout) are also good sources of n-3 PUFAs.
DHA is primarily found in phospholipids of cell mem-
branes, accumulates in fatty tissues, and shows little rela-
appears to be determined by the taxonomic composition
of the food web.14Differences among factors affecting the
species explain the divergent concentrations of these
chemicals across species.
Generally, the quantity of MeHg in a particular fish
and/or shellfish species and the amount of n-3 PUFAs
present in the fish or shellfish species are not consistently
associated.32,33NHANES data for women of child-bearing
age in the United States show moderate correlations of
total fish intake with dietary MeHg intake (r = 0.68) and
n-3 PUFA intake (r = 0.66).127These relationships are
strengthened when intakes of MeHg and n-3 PUFAs are
considered on a species-specific basis, indicating that the
ratio of n-3 PUFAs to MeHg intake depends on the
species of fish consumed.127
Nutrition Reviews® Vol. 69(9):493–508
One challenge for interpreting the effects of MeHg
and n-3 PUFA exposures on child development relates to
exposure estimates that are based on frequency of fish
consumption rather than the specific species of fish con-
sumed (e.g., Daniels et al.,128Hibbeln et al.52). Many
of fish consumption to estimate total fish intake or fish
intake by category, such as fatty fish. One of the limita-
tions of this approach is that the size of the fish serving
may be categorically grouped as small (e.g.,30 g) or mod-
erate (e.g., 180–250 g), making it difficult to quantify
exposures to n-3 PUFAs or MeHg. Many studies do not
collect data on the species of fish that are consumed by
study participants. Thus, drawing conclusions about
exposures from total fish consumption data is particu-
larly difficult when biomonitoring data (i.e.,blood or hair
mercury concentrations and blood levels of the n-3
PUFAs) are not available.
DIETARY RECOMMENDATIONS FOR PREGNANTWOMEN
EPA and DHA are considered to be among the major
beneficial nutrients obtained from fish consumption.129
There are many recommendations for the inclusion of
pre-formed EPA and DHA in the human diet.130–132DHA
doses of approximately 2,000 mg/day result in near
maximal increases in plasma DHA because dietary DHA
results in a dose-dependent, saturable increase in plasma
DHA concentration.133It is not clear that eating fish in
amounts that provide more than 2,000 mg/day of EPA
and DHA offers any benefits. Different countries suggest
various levels of n-3 PUFA intakes, with recommenda-
tions from expert groups ranging from 100 mg/day to
1,600 mg/day of EPA and DHA (summary statement
by Gao et al.134). The Food and Nutrition Board of the
National Research Council in the United States15has
developed an acceptable macronutrient distribution
range for n-3 PUFAs of 0.6–1.2% of energy intake. This
recommended intake would translate to a recommenda-
tion of eating two servings of fish (with at least moderate
PUFA content) per week.
Many non-fish sources of pre-formed EPA and DHA
are available and are especially important for vegetarians
and others who cannot or choose not to eat fish.135
Sources include DHA and/or EPA supplements extracted
from fish organs or tissues (i.e., fish oils) and production
by algae.Algae have great capacity for synthesis of the n-3
fatty acids136,137and are responsible for more than half the
production of n-3 fatty acids at the base of the food
chain.138Algae supplements and fish oils can be taken
than 100 food products in the United States contain
added n-3 PUFAs from synthesized micro algae rich in
EPA and DHA. DHA from algal-oil capsules has been
shown to have the same bioavailability as DHA from
Eggs are another major non-fish source of n-3
PUFAs. Feeding chickens special diets fortified with fish
oil, algae, or ground flax seed can substantially increase
the amounts of n-3 PUFAs in hen eggs.144,145Chickens
consuming diets fortified by fish oil or algae produce eggs
containing EPA and DHA, while added flax seed pro-
duces eggs that primarily contain ALA.146,147Hens fed
these diets produce eggs containing between 100 mg to
more than 500 mg of n-3 PUFAs per 50 g egg.Free-range
n-3 content of their eggs and specialized chicken-raising
procedures are not necessarily required.148Poultry meat
may also be a source of n-3 fatty acids.131
If human exposure to MeHg were independent of
nutrition from fish,we would aim for zero mercury expo-
sure. Given the nutritional values and cultural impor-
tance of fish,much effort has been made by governments
at various levels to develop advisories and recommenda-
tions to minimize risks associated with MeHg exposures
waterscience/fish/publicinfo.html). Advisories are typi-
cally based on measured levels of MeHg in fish that are
combined with values for body weight and portion size to
produce an estimate of an acceptable frequency of con-
sumption (e.g.,eat no more than once per month).Other
advisories suggest choosing fish species at lower trophic
levels to lower intake of MeHg levels without decreasing
Since fish are a source of nutrients and contami-
nants, both the nutritional elements and contaminant
concerns need to be incorporated into dietary recom-
mendations. Public health protection for pregnant
women as well as the general public will be improved by
the nutritional benefits when offering these types of
Dietary recommendations in the form of fish con-
sumption guidelines frequently attempt to provide quan-
titative values limiting consumption. One approach for
incorporating the beneficial aspects of fish consumption
into such recommendations involves quantitatively con-
sidering the levels of n-3 PUFA in fish tissue when devel-
oping such advice. This approach may allow individuals
to concomitantly minimize exposure to contaminants
while also ensuring that optimal n-3 PUFA intake is
MeHg levels in their local fish to help public health pro-
fessionals make the appropriate recommendations. The
results of such an approach have been reported, for
example, in Bermuda,149Canada,150France,151Spain,152
and the United States.32Recommendations on limiting
Nutrition Reviews® Vol. 69(9):493–508
consumption of specific amounts of MeHg, particularly
among women of child-bearing age,while promoting fish
consumption were made in each case.
Fish consumption advisories issued by public health
professionals require careful formulation to ensure effec-
tive communication of the risks and benefits in a manner
that is accessible to different demographic groups. Such
communication represents a considerable and ongoing
challenge. For example, Burger and Gochfeld126surveyed
of the risks and benefits of fish consumption, well over
tion.Chienet al.153alsofoundthat67.7%of 263womenof
childbearing age in Taiwan indicated they would not
told that some fish containing high levels of mercury may
be harmful for unborn babies.Verger et al.154studied the
effectiveness of advisories for children and women of
childbearing age in France. The authors found that
in total fish consumption, they had a minimal impact on
exposure reductions for high-risk groups because of
cluded that dietary recommendations should be carefully
tested to evaluate long-term memorization in order to
pregnant women in a US cohort reduced their consump-
tion of fish (including tuna, dark-meat fish, and white-
meat fish) after dissemination of a well-publicized federal
advisory recommending that pregnant women limit con-
sumptionof certainfishbecauseof concernsaboutMeHg
contamination. In contrast, results from the NHANES
data analysis by Mahaffey et al.4showed a statistically sig-
nificant decline in blood mercury levels for women of
childbearing age at the highest exposure levels between
1999 and 2003, and there was no change in reported fish
for MeHg to the federal fish advisory program. These
results highlight the importance of effective risk commu-
nication for maintaining nutritional benefits associated
with fish consumption.
BALANCINGTHE RISKS AND BENEFITS OF
Many review articles discussing the risk-benefit consid-
erations of fish consumption have been published in
recent years (e.g., Costa156), and a number of nutritional
factors have been reported to potentially ameliorate the
deleterious effects of MeHg exposure (see review by
Chapman and Chan157). The challenges associated with
tiple nutrients and contaminants in fish have typically
meant that most studies address the balance of risks and
of these qualitative studies emphasize the importance of
maintaining or increasing fish consumption in the
general population and minimizing exposure to toxic
contaminants for high-risk groups, such as children,
iting consumption of certain species. Another approach
used in a variety of studies is to compare nutrient and
contaminant intakes with published recommended or
tolerable intake levels, respectively. For example, Sioen
et al.158used the seafood consumption data from the
Global Environment Monitoring System and nutrient
and contaminant data and calculated exposure to nutri-
ents and contaminants for different countries in the
world. They found that countries that consumed high
amounts of pelagic oily fish, such as Japan, Korea, Mada-
gascar, the Philippines, and the Nordic-Baltic countries,
have high n-3 PUFA and vitamin D intake levels.
However, intake of these nutrients is still below the rec-
contaminant concentrations of these countries were
above the maximum limits established for the European
Union. Therefore, they concluded that the benefits of
increased seafood consumption for non-sensitive sub-
populations outweigh the risks.It is important to empha-
size the need to conduct a more detailed risk-benefits
analysis for the sensitive subpopulations that eat the most
fish and/or for individuals who eat fish with the highest
amounts of MeHg.
Other studies have focused on the epidemiological
evidence for specific endpoints, such as cardiovascular
risk159,160or child neurodevelopment.161,162Such analyses
of epidemiological evidence for the risks and benefits of
fish consumption vary substantially in methodology and
not surprisingly have shown a variety of results.39,95,160,163
Some studies suggest that the benefits from fish con-
sumption may exceed the possible health impacts from
contaminant exposure (e.g., Mozaffarian and Rimm160;
Hibbeln et al.52), while others (e.g., Budtz-Jorgensen
et al.95; Oken et al.50; Lederman et al.54; Daniels et al.128)
have concluded the benefits of fish consumption are
overcome or greatly diminished at moderate MeHg expo-
sure levels. Confounding caused by the simultaneous
benefits from n-3 PUFAs and the negative effects of
MeHg exposures from fish consumption presents a chal-
lenge for risk-benefit analysis.9,95Both the risks of MeHg
neurotoxicity and the benefits of fish consumption
can be underestimated if there are inadequate statistical
adjustments for these confounding effects and imprecise
Several quantitative approaches to evaluating the
risks and benefits of fish consumption have recently been
Nutrition Reviews® Vol. 69(9):493–508
proposed. Guevel et al.164developed a common metric
based on the quality-adjusted life year method. Their
methodology considered the beneficial effects of n-3
PUFAs on the cardiovascular system (CHD mortality,
MeHg on fetal neuronal development (IQ loss or gain).
The authors applied the model to analyze the risks and
benefits for high fish consumers in France; they found
that increasing fish consumption may have a beneficial
impact on health but the confidence intervals of the total
quality-adjusted life years have a negative lower bound,
meaning the benefits may not apply to all individuals,
with the uncertainty caused mostly by the impact of
MeHg on cognitive development. The authors also
discussed the limitations of this approach, including
population specificity, uncertainty associated with the
dose-response relationship,possible interactions between
different elements, and the respective weight effects of
different nutrients and contaminants. Moreover, the cul-
tural or economic preferences of the population were not
considered. Therefore, this quantitative approach is a
theoretical exercise and further development is needed
before it can be applied to public health decision-making.
Two other quantitative approaches that incorporate
recommendations regarding the risks and benefits of n-3
PUFAs and MeHg in fish consumption have been sug-
gested.108,163The method developed by Ginsberg and
Toal163estimates intakes of MeHg and n-3 PUFAs from
individual fish species and then evaluates resulting risks/
and n-3 PUFA benefits from the literature. The method
described by Tsuchiya et al.108attempts to define a ratio
between the intake of n-3 PUFA (DHA) and exposure to
Hg that is de minimus,such that an individual consuming
a particular fish species can meet the daily recommended
intake for this nutrient while not exceeding the US EPA
RfD. The intake ratio (using a minimum daily intake for
DHA of 100 mg/day, a daily consumption rate of 60 g/
day, and a body weight of 60 kg) was defined as 17 mg
DHA to 1 mg Hg. As an exercise, the authors used this
ratio with published concentrations of MeHg and PUFA
in fish tissue to illustrate which species may be most ben-
eficial for consumption (Figure 1).The figure depicts fish
species that are below and above the 17:1 ratio,while also
indicating which species are above this ratio and provide
for less than 6 mg of MeHg exposure per day. The 6 mg
level is the daily intake of a 60 kg individual at, but not
exceeding,the US EPA RfD.Approaches like those devel-
oped by Ginsberg and Toal163and Tsuchiya et al.108have
limitations yet may be able to provide a useful foundation
from which to improve dietary recommendations for fish
consumption until the relationships between maternal
nutritional status and the effects from prenatal MeHg
exposure are better defined.
Controlling global mercury sources is the best long-
term solution for reducing MeHg concentrations in fish
and shellfish. The safety of fish and seafood consump-
tion will remain a concern even while such pollution
issues are being addressed. Public health officials world-
wide must provide appropriate dietary advice using the
best-available understanding of the risks and benefits of
seafood consumption.In the last two decades,significant
advances have been made in understanding the toxicol-
ogy and epidemiology of MeHg exposures as well as the
nutritional benefits of n-3 PUFAs. However, a number
of knowledge gaps still remain. For example, much more
information is needed on the quantities of n-3 PUFAs
(EPA, and especially DHA) that can be synthesized from
ALA through maternal metabolism. Cohort studies in
the Seychelles and Faroe Islands continue to shed light
on the impacts of fish intake and MeHg exposures on
pre- and post-natal development84,94,162Other longitudi-
nal studies are considering the association between fish
intake and child development at relatively low exposure
levels in the United States and Denmark,6,51as well as
populations in Canada, China, and Japan that routinely
rely on fish as a major dietary staple.134,165,166Unfortu-
nately, not all studies provided detailed seafood con-
sumption results. This makes conducting a quantitative
benefit/risk assessment of DHA intake and MeHg expo-
sure challenging because seafood consumption remains
a major determining factor. The ratio of n-3 PUFAs and
MeHg concentrations in individual fish and shellfish
species varies considerably.32,33,39Fortunately, it is pos-
sible to choose fish species that are both high in n-3
PUFAs and low in MeHg (e.g., Figure 1). This issue
becomes more complex when exposure to lipophilic
organic contaminants, such as PCBs, are considered (as
they also tend to accumulate in predatory fish) or when
additional factors, such as other nutrients or variability
in individual body weights, are taken into account. Fish
and shellfish provide most of the EPA and DHA in diets
of people around the world.1Maintaining adequate
nutritional intakes of n-3 PUFAs while minimizing
exposure to MeHg from fish remains an important
public health goal and quantitative solutions for
addressing this issue are beginning to be developed.
Ultimately, protecting public health requires dietary
strategies, communication, and most of all, longer-term
efforts to reduce biological contaminant levels through
On June 9, 2009, the National Institute for Minamata
Disease in Japan sponsored a special session titled“Meth-
Nutrition Reviews® Vol. 69(9):493–508
ylmercury (MeHg) and n-3 polyunsaturated fatty acid
(n-3 PUFA) exposure from fish consumption” at the 9th
International Conference on Mercury as a Global Pollut-
ant held in Guiyang,China.The session was international
in scope, with speakers from Canada, China, Denmark,
Faroe Island, Japan, and the United States and with over
100 participants from all over the world. This paper was
written by the presenters of the sessions based on their
presentations at the Conference.Dr.Kathryn R.Mahaffey
was one of the organizers of the session and co-wrote the
first draft. Dr. Mahaffey passed away suddenly in June 2,
2009, after decades of significant contributions in the
advancement of environmental health particularly in
applying the lessons from academic research to protect
the public health. All the speakers of the session would
like to dedicate this review paper to her memory.We also
thank the anonymous reviewers for their constructive
comments and suggestions.
Declaration of interest. The authors have no relevant
interests to declare.
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