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International Journal of Hygiene and Environmental Health 218 (2015) 147–152

Contents lists available at ScienceDirect

International Journal of Hygiene andEnvironmental Health

jo u r n al homepage: www.elsev ier .com/ locate / i jheh

eafood intake and blood cadmium in a cohort of adult avid seafoodonsumers

tanford Guana, Tia Palermoa,b, Jaymie Melikera,b,∗

Program in Public Health, Stony Brook University, United StatesDepartment of Preventive Medicine, Stony Brook University, United States

r t i c l e i n f o

rticle history:eceived 17 June 2014eceived in revised form9 September 2014ccepted 24 September 2014

eywords:admiumiomarkerisheafoodntake

a b s t r a c t

Although the benefits of fish consumption are widely recognized, seafood may also be a source of expo-sure to heavy metals such as cadmium. Many types of seafood are rich in cadmium, but bioavailabilityand potential for toxicity after consumption is less clear. This study investigates the relationship betweenseafood intake and the level of cadmium (Cd) in the blood in a 252 person cohort of avid seafood con-sumers in the Long Island Study of Seafood Consumption (New York). Blood cadmium is an establishedbiomarker of cadmium exposure, reflecting both recent and decade-long exposure. Data on the amountsand frequency of eating various types of seafood were self-reported by avid seafood consumers recruitedin 2011–2012. After adjusting for age, BMI, sex, current smoking status, and income in a linear regressionmodel, we found no association between regular seafood intake (ˇ = −0.01; p = 0.11) but did identify anassociation between salmon intake in cups/week (ln transformed) (ˇ = 0.20; p = 0.001) and blood cad-mium. After accounting for salmon, no other types of seafood were meaningfully associated with blood

onsumption cadmium. No association was found between rice intake, blood zinc, or dietary iron or calcium and bloodcadmium. Results suggest that seafood is not a major source of cadmium exposure, but that salmonintake does marginally increase blood cadmium levels. Given that cadmium levels in salmon are nothigher than those in many other seafood species, the association with salmon intake is likely attributedto higher consumption of salmon in this population.

© 2014 Elsevier GmbH. All rights reserved.

ntroduction

The advantages of eating fish are well-known – not only aresh a healthy source of protein and other nutrients, but eating fishay also confer various health benefits. Fish consumption has been

inked to decreased likelihood of developing rheumatoid arthri-is (Cleland et al., 2003; Goldberg and Katz, 2007; Rahman et al.,008; McManus et al., 2011), psychiatric disorders (Cherubini et al.,007; Peet and Strokes, 2005; Song and Zhao, 2007; Perica andelas, 2011), and lung disease (Cerchietti et al., 2007). Perhapsost importantly, eating fish may lead to better cardiovascular

ealth (Harris, 1997; Kinsella et al., 1990; Oomen et al., 2000; Kris-therton et al., 2002; Oomen et al., 2000; Kris-Etherton et al., 2002;ozaffarian et al., 2005; Jarvinen et al., 2006; Mozaffarian and Wu,

∗ Corresponding author at: Graduate Program in Public Health, Department ofreventive Medicine, Stony Brook University, HSC L3, Rm 071, Stony Brook, NY1794-8338, United States. Tel.: +1 631 444 1145.

E-mail addresses: Jaymie.meliker@stonybrook.edu, jrmeliker@gmail.comJ. Meliker).

ttp://dx.doi.org/10.1016/j.ijheh.2014.09.003438-4639/© 2014 Elsevier GmbH. All rights reserved.

2011). The major beneficial cardiovascular effects of eating fishare often attributed to polyunsaturated omega-3 fatty acids, whichbioaccumulate up the food chain from algae and phytoplankton(Judé et al., 2006).

At the same time however, heavy metals such as cadmium arealso able to bioaccumulate in aquatic organisms via waterborne anddietborne exposure pathways (Buchwalter et al., 2008; Svobodovaet al., 1996). The degree of cadmium bioaccumulation in fish isinfluenced by various factors that include biological habitat, chem-ical form of cadmium in the water, water temperature, water pH,dissolved oxygen concentration, as well as characteristics of fishphysiology (Has-Schön et al., 2006). Such a bioaccumulation of cad-mium in fish has been raised as a concern because chronic exposureto cadmium has been shown to have serious deleterious effectson human health (Jarup and Akesson, 2009; Martí-Cid et al., 2007;Wright and Mason, 2000; Satarug et al., 2011).

The International Agency for Research on Cancer classifies cad-

mium as a category 1 known human carcinogen (WHO/IARC, 1993).Epidemiologic evidence has linked cadmium exposure to renal dys-function and kidney disease (Buchet et al., 1990; Jarup and Alfven,2004; Navas-Acien et al., 2009; Thomas et al., 2009; Nordberg

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48 S. Guan et al. / International Journal of Hygie

t al., 2012), decreased bone mineral density (Åkesson et al., 2006;taessen et al., 1999; James and Meliker, 2013), and metabolic syn-rome (Lee and Kim, 2012). Moreover, there is some evidence touggest that cadmium might be associated with hypertension (Eumt al., 2008; Gallagher and Meliker, 2010), stroke and heart failurePeters et al., 2010), and even cardiovascular disease (Tellez-Plazat al., 2010, 2012, 2013) – which suggests that the risks impli-ated in cadmium exposure might counteract any cardio-protectiveffects from eating fish (Guallar et al., 2002).

Furthermore, seafood consumption has been suggested to bene of the primary routes for human exposure to cadmium (Jut al., 2012) and has been estimated to be at levels of concernn risk assessments (Pastorelli et al., 2012; Storelli and Barone,013). Other evidence, however, suggests that seafood may not behe primary route of exposure to cadmium (Hellberg et al., 2012)nd questions remain about whether and how much of the cad-ium eaten in seafood is bioavailable to humans. Absorption of

admium varies between individuals (JECFA, 2004; Kikuchi et al.,003), with zinc, iron, or calcium deficiency identified as possibleffect modifiers that increase cadmium absorption (Brzóska andoniuszko-Jakoniuk, 1998; Evans et al., 1970; Fox, 1988; Jacobs

t al., 1983; Kello and Kostial, 1977; Koo et al., 1978; Reeves andhaney, 2008). Thus, in regards to human health, it is more rele-ant to study a biomarker of cadmium, rather than the levels ofadmium that are present in seafood. Blood cadmium is a reliableiomarker that reflects relatively recent exposure (Madeddu et al.,011) and is also an indicator of the bioavailability of exposureo cadmium. Blood cadmium, therefore, may reflect the amount ofadmium ingested that is ultimately absorbed to reach systemic cir-ulation. Human studies reported both positive (Birgisdottir et al.,013; Oyoo-Okoth et al., 2010) and null associations (Sirot et al.,008; Vahter et al., 1996) between blood cadmium and seafoodonsumption, indicating evidence is mixed and more research iseeded.

The primary aim of the current study is to investigate the asso-iation between seafood consumption and level of blood cadmiummong those who consume high amounts of seafood – specifi-ally whether eating fish would appreciably and significantly raiselood cadmium levels. Moreover, given dangers associated witheavy metals exposure, it is also of interest to examine whetheruman consumption of certain species of fish might meaningfullyontribute to any differences in blood cadmium levels. We hypothe-ized that the correlation between seafood consumption and bloodadmium is not significant since bioaccessibility studies suggesthat cadmium from seafood is not bioavailable to humans andherefore not a meaningful source of exposure.

aterials and methods

ample

Individuals from the general population of Long Island, Nework were recruited over a 13-month period between September011 and October 2012. This purposive sampling process excludedeople who could not read or write in English, were not over the agef 18, or were pregnant. Prospective participants were sought viarint advertisements, online through the study’s website, and also

n person at seafood markets, fishing piers, and seafood restaurants.articipants were screened using a basic food frequency question-aire that queried how often and how much they ate various typesf seafood over the last year. Data on age, gender, and self-reported

eight were also obtained during screening. To provide adequateower to study mercury-related health effects (not presented here),stimated daily mercury intake (�g/kg body weight/day) based onheir self-reported seafood consumption pattern was determined

Environmental Health 218 (2015) 147–152

and individuals with exposure levels that fell under the EPA refer-ence dose of 0.1 �g/kg body weight/day (IRIS, 1994) were excludedfrom the study. All participants with estimated mercury levelsabove the reference dose were considered eligible for participation.A total of 996 individuals completed the screening questionnaire,with the majority being eligible (n = 746). Of those deemed eligi-ble, 290 participants enrolled in the study and completed a clinicalappointment at the Clinical Research Core at Stony Brook Univer-sity Medical Center. Of these, complete data were available for 252individuals in the analyses presented here. We obtained informedconsent from all participants; the study was approved by StonyBrook University’s Institutional Review Board for human subjects(IRB# 185935).

Participants provided blood for analyzing blood cadmium andother trace metals and questionnaires to characterize demograph-ics and food frequency consumption. Participants were asked to noteat any seafood for 3 days prior to their blood test.

Measures

The main dependent variable is blood cadmium, which is a con-tinuous quantity measured in �g/L using an Inductively CoupledPlasma Mass Spectrometry at RTI International’s Trace InorganicLaboratory (RTP, NC, USA), with an average detection limit of0.05 �g/L. Samples below detection limit (n = 29) were calculatedas the detection limit/

√2. The primary independent variable is

total cups of seafood consumption regularly eaten on a weeklybasis. Consumption of various types of seafood was also asked,and includes anchovy; bluefish; canned light/white tuna; catfish;croaker; eel; flounder; halibut; herring; lobster; mackerel; monk-fish; mussels; orange fish; whitefish that includes cod, tilapia, sole,and haddock; pollock; porgy; red snapper; sablefish; salmon; scal-lops; sea bass; sea trout; shellfish; shrimp; squid; striped bass;sturgeon; swordfish; tilefish; tuna steak; and weakfish; as well asa separate category that included fish that were self-caught. Thetotal consumption of each type of seafood was measured categori-cally by frequency (never; few per year; once per month; 2–3 timesper month; once per week; twice per week; 3–4 times per week;5–6 times per week; or everyday), as well as quantitatively by thenumber of cups eaten for each type of seafood (calculated based onanswers to frequency and serving size). We performed a natural-logtransformation on cups eaten of each seafood type.

Since blood zinc, iron, and calcium are implicated as having aninteractive effect on the absorption of cadmium, the level of bloodzinc (measured in �g/L), as well as dietary iron and calcium intake(levels determined from food frequency questionnaire, Nutrition-Quest, Berkeley, CA, USA), were confounders controlled for in ouranalysis. Moreover, smoking (whether the participant is a cur-rent smoker) and vegetable intake (measured as servings per day)may be significant sources of cadmium exposure (ATSDR, 2008)and are therefore included in our analysis to control for poten-tial confounding of the relationship between cadmium exposureand seafood consumption. Other covariates include age (contin-uous), gender (binary), BMI (continuous), income category (lessthan $25k; $25k–$70k; $70k–$110k; $110k–$200k; $200k+), edu-cational attainment (some high school; high school graduate; somecollege or trade school; college graduate), and employment sta-tus (employed, which includes self-employed; unemployed, whichincludes homemaker; student; retired).

Statistical analysis

Analyses were performed using Stata version 13.0 (CollegeStation, TX). A linear regression was performed to examine whetherthe quantity of seafood consumption was associated with bloodcadmium levels. Linear regressions were also carried out separately

S. Guan et al. / International Journal of Hygiene and Environmental Health 218 (2015) 147–152 149

Table 1Distribution of blood cadmium and seafood intake (n = 252).

Variable Mean (std dev) Min Max

Blood cadmium (ng/mL) 0.46 (0.34) 0.04 2.021st quartile 0.10 (0.05) 0.04 0.182nd quartile 0.32 (0.07) 0.18 0.433rd quartile 0.51 (0.05) 0.43 0.604th quartile 0.91 (0.31) 0.60 2.02

Total seafood intake (cups per week) 2.71 (2.58) 0.03 14.01st quartile 0.68 (0.35) 0.03 1.002nd quartile 1.74 (0.05) 1.38 1.75

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Table 2Characteristics of study population (n = 252).

Variable Mean (std dev) Blood cadmium(ng/mL)

Blood zinc (ng/mL) 4656 (1720)Above median (4380) 0.54Below median 0.38

Blood mercury (ng/mL) 7.88(8.64)Above median (4.58) 0.49Below median 0.42

Dietary calcium (mg) 716.9(419.7)Above median (640.1) 0.42Below median 0.49

Dietary iron (mg) 11.83(6.38)Above median (10.59) 0.44Below median 0.47

Servings of vegetables per week 4.21(3.21)Above median (3.44) 0.47Below median 0.44

Age 46.9(18.6)Above median (49.5) 0.49Below median 0.42

Body Mass Index 25.4(4.66)Above median (24.4) 0.47Below median 0.44

PercentageSex

Male 41.7 0.40Female 58.3 0.50

Current smokerYes 6.0 1.12No 94.0 0.42

Work statusEmployed 52.0 0.44Unemployed 9.5 0.61Student 19.1 0.33Retired 19.4 0.53

Education levelSome high school 0.4 0.56High school graduate 5.6 0.43Some college or trade school 25.8 0.51College graduate 68.2 0.43

Household income<$25,000 17.5 0.56$25,000–$70,000 27.8 0.45$70,000–$110,000 24.6 0.41$110,000–$200,000 23.0 0.45$200,000+ 7.1 0.43

Aware of risks of fish consumptionYes 87.7 0.46

3rd quartile 2.78 (0.68) 2.00 3.504th quartile 7.01 (2.76) 4.00 14.0

or each species of seafood. Chi-square tests and Bonferroni pair-ise comparisons were also evaluated.

Multiple linear regression models were also performed to inves-igate whether patterns of higher consumption of seafood weressociated with higher blood cadmium while accounting for theovariates listed above. Interaction terms for blood zinc, dietary cal-ium, and dietary iron were also separately included in the modelso test whether these variables significantly moderate the associa-ion between seafood intake and blood cadmium.

Multiple ordered logit models predicting higher quartile oflood cadmium were also used to investigate this relationship.ensitivity analyses were performed on samples that were strat-fied by current smoking status (yes/no) and by employment statusemployed, which includes self-employed; unemployed, whichncludes homemakers; student; retired).

esults

Table 1 presents information on the distribution of blood cad-ium in our analytic sample. The distribution of blood cadmium

s positively skewed (skewness = 1.33), though it maintains a nor-ally distributed peak (kurtosis = 2.95). Summary statistics for the

nalytic sample are displayed in Table 2. Characteristics of notenclude the high level of educational attainment in the sample, in

hich 94.4% of the study sample has at least some college edu-ation, as well as the high level of household income, where overalf of the sample has a household income of over $70k, and over

quarter of the sample earns over $110k.A chi-square test comparing quartiles of blood cadmium levels

nd quartiles of total seafood consumption provided no evidenceor a significant association between the two variables (�2 statis-ic = 13.89, p-value = 0.13). Comparing the mean levels of bloodadmium across the four quartiles of seafood intake using conserva-ive Bonferonni post hoc pairwise comparison found no significantifferences in mean blood cadmium between any of the seafoodonsumption quartiles (p-value = 0.08).

When we performed a simple linear regression to predictlood cadmium by seafood intake, the coefficient of regulareekly seafood consumption was not statistically significant (p-

alue = 0.78). Results from multiple linear regression adjustingor age, sex, BMI, smoking, and income are reported in Table 3.nce again, no statistically significant relationship between regular

eafood intake and blood cadmium was observed after adjusting forovariates (p-value = 0.58). However, there were several covariateshich were significantly linked to blood cadmium: age, sex, current

moking status, and income. Older individuals were linked to sig-ificantly higher levels of blood cadmium. Males were observed toave, on average, blood cadmium levels that were about 0.08 �g/L

ower than females. Current smokers have a blood cadmium levelhat is, on average, 0.64 �g/L higher that non-current smokerswhich comprises never and former smokers). Furthermore, indi-iduals in higher income categories were associated with lower

No 10.7 0.43Not sure/Don’t know 1.6 0.55

blood cadmium levels when compared with individuals in thelowest income category. Blood zinc (p < 0.001) and dietary iron(p < 0.05) were correlated with blood cadmium but were not signifi-cant predictors after accounting for the variables shown in Table 2.No correlation (p = 0.53) was found between blood mercury andblood cadmium. Interaction terms for blood zinc levels, dietaryiron, and dietary calcium were separately included in multiple lin-ear regression models and there were no statistically significantinteraction effects of any of the proposed moderators.

When examining whether consumption of individual seafoodtypes was associated with blood cadmium, salmon had thestrongest association. After adjusting for salmon, no other typesof seafood were associated with blood cadmium. Adding salmon tothe multiple regression model increased the R2 from 0.28 to 0.31(Table 2).

In ordered logistic regression, regular seafood intake was not

associated with being in a higher blood cadmium quartile. The sin-gle most significant determinant of blood cadmium in this modelwas current smoking status, where current smokers had 32.2 timesgreater odds of being in a higher quartile of blood cadmium in the

150 S. Guan et al. / International Journal of Hygiene and Environmental Health 218 (2015) 147–152

Table 3Results from regressions predicting blood cadmium levels (n = 252).

Variable Multiple linear regression (adjusted R2 = 0.28) Multiple linear regression (adjusted R2 = 0.31)

Coefficient p-Value Coefficient p-Value

Regular weekly seafood consumption (cups) −0.004 0.58 −0.012 0.11Age 0.006 <0.01 0.005 <0.01Body mass index 0.001 0.81 0.001 0.77Male sex (female is reference) −0.078 0.04 −0.088 0.02Current smoker (not a current smoker is reference) 0.641 <0.01 0.616 <0.01Income (less than $25k is reference)

$25,000–$70,000 −0.154 <0.01 −0.131 0.02$70,000–$110,000 −0.139 0.02 −0.141 0.01$110,000–$200,000 −0.119 0.05 −0.115 0.05

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ample as compared to non-current smokers (95% CI: 10.9, 95.3) though it should be noted that current smokers accounted for

small proportion (6.0%) of our analytic sample. Similarly, a ln-ransformed measure of cups of salmon per week was also observedo be highly significant in this model (OR: 2.03; 95% CI: 1.45, 5.89).

As a secondary analysis, we also categorized seafood species byrophic level (low-level, mid-level, predator) since heavy metalsccumulate up the food chain. In a linear regression the relation-hip between cups of seafood eaten per week in each trophic levelategory and blood cadmium was not significant.

iscussion

Our results suggest that blood cadmium levels are not stronglyorrelated with seafood consumption. Overall seafood consump-ion measured in cups/week was not associated with bloodadmium. Salmon intake also measured in cups/week was sig-ificantly associated, but explained only 3% of the variability inlood cadmium levels. No other types of seafood were associatedith blood cadmium levels after controlling for salmon. Our find-

ngs suggest that even though cadmium levels are considerablylevated in seafood they do not have a major influence on bloodadmium levels, and therefore are likely not a major source of cad-ium exposure because of limited bioavailability. Further, there

re no indications from our results to suggest that the relationshipetween seafood consumption and blood cadmium is moderatedy blood zinc, dietary iron, or dietary calcium.

Our main findings echo similar conclusions from studies thatid not report any correlation between ingested seafood andlood/urinary cadmium levels (Sirot et al., 2008; Vahter et al.,996). However, at least one other study with a cohort of higheafood consumers noted a significant but weak positive corre-ation between seafood consumption and urinary cadmium (ˇ:.009; 95% CI: 0.003, 0.015), though the study authors noted a

imitation in not accounting for smoking (Birgisdottir et al., 2013).nother study that examined hair and nails to biomonitor cadmium

evels in children observed a strong correlation between cadmiumnd fish consumption (Oyoo-Okoth et al., 2010), however the studyuthors cite elevated levels of cadmium present in regional fishamples around Lake Victoria, Kenya (as high as 0.38 �g Cd/g dryeight in R. argentea).

It is intriguing that we found a small association between salmonntake and blood cadmium levels. There are mixed results whenxamining cadmium levels in salmon. Prior studies have drawnttention to increasing cadmium levels in certain types of fishAndreji et al., 2006; Li et al., 2013; Sissener et al., 2012) including

almon (Jóhannesson et al., 1981), whereas other studies did notnd evidence for a burdensome level of cadmium in fish (Burgernd Gochfeld, 2005) – but when compared to other fish species,admium levels found in salmon appear to be comparatively low

0.02 −0.180 0.030.201 <0.01

(Falcó et al., 2006). Thus, the significant correlation between bloodcadmium and salmon intake might be attributable to higher salmonconsumption. In our study population, salmon, tuna, and shrimpwere the three most frequently consumed types of seafood, withmedian consumption of 0.23, 0.47, and 0.29 cups/week respec-tively. Perhaps cadmium is slightly more bioavailable from salmon,although this is merely speculation and requires further evidence.

The observation that females have, on average, higher blood cad-mium levels than males is supported by many prior studies (Sirotet al., 2008; Olsson et al., 2002; Oskarsson et al., 2004; Boonprasertet al., 2011; Berglund et al., 1994; Buchet et al., 1990). Similarly, ourfinding that smokers had higher blood cadmium levels than non-smokers is corroborated by the literature (Boonprasert et al., 2011;Madeddu et al., 2011).

The American Heart Association suggests eating fish at leasttwo times per week (or 1.5 cups) to increase the intake of omega-3 fatty acids (Kris-Etherton et al., 2002). Despite the fact thatwe purposefully sampled people who consume high amountsof seafood (about 67% of the analytic sample reported eatingat least 1.5 cups of seafood a week), the mean blood cad-mium level in this sample was 0.46 �g/L. The observed samplemean is no different from the national geometric mean bloodcadmium level for adults of 0.47 �g/L (ATSDR, 2008), again sug-gesting the limited degree of bioavailability of cadmium fromseafood.

The study sample comes from the Long Island Study of SeafoodConsumption which recently reported associations betweenseafood intake and blood mercury levels (Karimi et al., 2014). How-ever, blood mercury was not found to be associated with bloodcadmium in this cohort, and therefore was not a confounding factorin this study.

It should be noted that fish contain varying amounts of cadmiumand this study lacked any data on cadmium levels in seafood whichmay be a limitation. It should also be noted that the analyses per-formed in this study only account for seafood intake, while the totaldietary intake of cadmium might be higher. Though seafood hasbeen implicated in having high levels of cadmium, vegetables suchas lettuce and spinach, potatoes, grains, peanuts, soybeans, andsunflower seeds as well as rice may also contain high levels of cad-mium and thus might be significant sources of cadmium exposure.The average number of vegetable servings or quantity or frequencyof rice consumption did not correlate with blood cadmium in ourstudy.

Interaction effects of iron may not have been accurately testedsince dietary iron was used as a proxy for iron in the body. We alsodid not collect data on former smokers or lifetime smoking – only

current smoking status. As our results were observed to be sensitiveto smoking status, lacking information on smoking is a limitation,but may not influence the relationship between seafood intake andblood cadmium.

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onclusion

Even though seafood is rich in cadmium, our results suggesthat seafood intake does not correlate with blood cadmium levelsith the exception of salmon intake which marginally increased

lood cadmium. Our findings in humans combined with lab-basedioavailability studies (Saha and Zaman, 2012; Madeddu et al.,011; Li et al., 2013; Ju et al., 2012) point to limited bioavailabilityf cadmium after seafood consumption. Exposure models and riskssessments of cadmium in food need to account for bioavailability,nd not only use total cadmium levels as measured in foods.

cknowledgements

We gratefully appreciate the time and effort of study partici-ants. Data used in this study came from the Long Island Studyf Seafood Consumption funded by The Gelfond Fund for Mercuryesearch and Outreach. This work was conducted independentlyf the funding body.

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