Arsenic in seafood is associated with increased thyroid-stimulating hormone (TSH) in healthy volunteers - A randomized controlled trial.

BACKGROUND: Exposure to exogenous elements like arsenic (As) may influence thyroid enzymes, thyroid-stimulating hormone (TSH), and the two principal thyroid hormones, free thyroxine (FT4) and free triiodothyronine (FT3), but little is known about how this is related to organic arsenicals, the main form in seafood. AIM: To investigate whether a high intake of dietary arsenic from seafood can impact thyroid function and thyroid hormones by examining possible associations with changes in TSH, FT4, FT3 and the FT4:FT3-ratio in plasma. METHODS: Thirty-eight healthy subjects were randomized into four groups. During a 14-day semi-controlled dietary study, the subjects ingested daily portions of either 150g cod, salmon, blue mussels or potato (control). Plasma concentrations of total As, FT3, FT4, TSH and selenium (Se), and urinary concentrations of iodine were monitored. RESULTS: Plasma concentrations of TSH increased significantly in all seafood groups. The change in plasma As, with different coefficients for each seafood group, was the dominant factor in the optimal multiple regression model for change in TSH (R2=0.47). Plasma Se and iodine were negative and positive factors, respectively. There were also indications of changes in FT4, FT3 and the FT4:FT3 ratio consistent with a net inhibiting effect of As on FT4 to FT3 conversion. CONCLUSION: Ingestion of seafood rich in various organic As species was strongly associated with an increase of the TSH concentrations in plasma. Change in TSH was positively associated with total plasma As, but varied with the type of seafood ingested. These findings indicate that organic dietary As, apparently depending on chemical form, may influence thyroid hormones and function.

The impact of iron status and smoking on blood divalent metal concentrations in Norwegian women in the HUNT2 Study.

Low iron (Fe) stores may result in increased absorption of divalent metals, in particular cadmium (Cd). We have previously shown that in non-smoking women participating in the Norwegian HUNT2 cohort study this also included other divalent metals, e.g. manganese (Mn) and cobalt (Co). The diet is the main source of metals in non-smoking individuals, whereas in smoking individuals tobacco smoke contributes significant amounts of Cd and lead (Pb). The aim of the present study was to investigate the impact of smoking on the relationship between low iron status and divalent metals. Blood concentrations of the divalent metals Cd, Mn, Co, Pb, copper (Cu) and zinc (Zn), determined using an Element 2 sector field mass spectrometer (ICP-MS), were investigated in smoking women of fertile age (range 21-55 years) (n=267) from the HUNT2 cohort. Among these, 82 were iron-deplete (serum ferritin<12µg/L) and 28 had iron deficiency anaemia (serum ferritin<12µg/L & Hb<120g/L). 150 (56%) women smoked 10 or more cigarettes daily, 101 (38%) had smoked for more than 20 years, and 107 (40%) had smoked for 11-20 years. Results from the smoking population were compared with results from our previous study in non-smoking women (n=448) of which 132 were previous smokers, all from the same cohort. Increasing concentrations of Cd in blood were observed for previous smokers, low-to-moderate smokers and high intensity smokers in all subgroups compared to never smokers, and according to age groups, education level, BMI and serum ferritin. Smokers had higher Pb concentrations than non-smokers in all subgroups, but less pronounced than for Cd. Smoking was not associated with Mn and Co concentrations in blood. In multiple regression models, low ferritin was associated with increased blood concentrations of Cd, Pb, Mn and Co. Ferritin was strongly associated with Cd at low smoking intensity, but was not a significant factor in heavy smokers, where intensity and duration of smoking emerged as main determinants. Ferritin associations with Co and Pb varied with tertiles of blood Cd. Ferritin emerged as the main determinant of blood Co and Mn, while for blood Pb, age and smoking intensity had higher impact. Cu and Zn remained within reference values and no significant associations with ferritin were found. Strong positive associations between blood concentrations of Pb, Mn, Cd and Co were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the divalent metals studied. Mild anaemia (110

Urinary excretion of arsenicals following daily intake of various seafoods during a two weeks intervention.

The excretion pattern of arsenic (As) species after seafood intake varies widely depending on species ingested and individual handling. We have previously reported the 72 h urinary excretion of arsenicals following a single dose of seafood. Here, we report the excretion patterns in the same 37 subjects following 15 days daily consumption of either 150 g cod, salmon, blue mussels or potato (control), followed by a 72 h period with a low-As diet. In all seafood groups, total As (tAs) in plasma and urinary excretion of tAs, arsenobetaine (AB) and dimethylarsinate (DMA) increased significantly after the intervention. Confirming the single dose study AB and DMA excreted were apparently endogenously formed from other arsenicals ingested. Total tAs excretion was 1386, 763 and 303 µg in the cod, blue mussel and salmon groups, respectively; about twice the amounts after the single dose study indicating accumulation of arsenicals. In the cod group, rapid excretion after the single dose was associated with lower total As in blood and less accumulation after two weeks with seafood indicating lower accumulation. In the blue mussels group only, inorganic As (iAs) excretion increased significantly, whilst methylarsonate (MA) strongly increased, indicating a possible toxicological concern of repeated mussel consumption.

Consumption of lead-shot cervid meat and blood lead concentrations in a group of adult Norwegians.

Several recent investigations have reported high concentrations of lead in samples of minced cervid meat. This paper describes findings from a Norwegian study performed in 2012 among 147 adults with a wide range of cervid game consumption. The main aim was to assess whether high consumption of lead-shot cervid meat is associated with increased concentration of lead in blood. A second aim was to investigate to what extent factors apart from game consumption explain observed variability in blood lead levels. Median (5 and 95 percentile) blood concentration of lead was 16.6 µg/L (7.5 and 39 µg/L). An optimal multivariate linear regression model for log-transformed blood lead indicated that cervid game meat consumption once a month or more was associated with approximately 31% increase in blood lead concentrations. The increase seemed to be mostly associated with consumption of minced cervid meat, particularly purchased minced meat. However, many participants with high and long-lasting game meat intake had low blood lead concentrations. Cervid meat together with number of bullet shots per year, years with game consumption, self-assembly of bullets, wine consumption and smoking jointly accounted for approximately 25% of the variation in blood lead concentrations, while age and sex accounted for 27% of the variance. Blood lead concentrations increased approximately 18% per decade of age, and men had on average 30% higher blood lead concentrations than women. Hunters who assembled their own ammunition had 52% higher blood lead concentrations than persons not making ammunition. In conjunction with minced cervid meat, wine intake was significantly associated with increased blood lead. Our results indicate that hunting practices such as use of lead-based ammunition, self-assembling of lead containing bullets and inclusion of lead-contaminated meat for mincing to a large extent determine the exposure to lead from cervid game consumption.

Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women.

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women. METHODS: This study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003 to 2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks of gestation and a dietary questionnaire was completed at 22 weeks of gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC). RESULTS: Parity was the determinant with the largest influence on plasma PFAS concentrations, with r(2) between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p<0.001 except for PFHxS, p<0.01). In all these models, duration of breastfeeding was associated with reduced PFAS levels. PFOA showed the largest reduction from breastfeeding, with a 2-3% reduction per month of breastfeeding in typical cases. Levels of PFOS, PFOA, and PFNA increased with time since most recent pregnancy. While pregnancy-related factors were the most important predictors, diet was a significant factor explaining up to 4% of the variance. One quartile increase in estimated dietary PFAS intake was associated with plasma PFOS, PFOA, PFHxS, and PFNA concentration increases of 7.2%, 3.3%, 5.8% and 9.8%, respectively, resulting in small, although non-trivial absolute changes in PFAS concentrations. CONCLUSION: Previous pregnancies and breastfeeding duration were the most important determinants of PFASs in this sample of pregnant women.

Major and minor arsenic compounds accounting for the total urinary excretion of arsenic following intake of blue mussels (Mytilus edulis): a controlled human study.

Blue mussels (Mytilus edulis) accumulate and biotransform arsenic (As) to a larger variety of arsenicals than most seafood. Eight volunteers ingested a test meal consisting of 150 g blue mussel (680 µg As), followed by 72 h with an identical, low As controlled diet and full urine sampling. We provide a complete speciation, with individual patterns, of urinary As excretion. Total As (tAs) urinary excretion was 328 ± 47 µg, whereof arsenobetaine (AB) and dimethylarsinate (DMA) accounted for 66% and 21%, respectively. Fifteen minor urinary arsenicals were quantified with inductively coupled plasma mass spectrometry (ICPMS) coupled to reverse-phase, anion and cation-exchange high performance liquid chromatography (HPLC). Thio-arsenicals and non-thio minor arsenicals (including inorganic As (iAs) and methylarsonate (MA)) contributed 10% and 7% of the total sum of species excretion, respectively, but there were large individual differences in the excretion patterns. Apparently, formation of thio-arsenicals was negatively correlated to AB formation and excretion, possibly indicating a metabolic interrelationship. The results may be of toxicological relevance since DMA and MA have been classified as possibly carcinogenic, and six of the excreted As species were thio-arsenicals which recently have been recognized as toxic, while iAs toxicity is well known.

Humans seem to produce arsenobetaine and dimethylarsinate after a bolus dose of seafood.

Seafood is the predominant food source of several organoarsenic compounds. Some seafood species, like crustaceans and seaweed, also contain inorganic arsenic (iAs), a well-known toxicant. It is unclear whether human biotransformation of ingested organoarsenicals from seafood result in formation of arsenicals of health concern. The present controlled dietary study examined the urinary excretion of arsenic compounds (total arsenic (tAs), iAs, AB (arsenobetaine), dimethylarsinate (DMA) and methylarsonate (MA)) following ingestion of a single test meal of seafood (cod, 780 µg tAs, farmed salmon, 290 µg tAs or blue mussel, 690 µg tAs or potato (control, 110 µg tAs)) in 38 volunteers. The amount of ingested tAs excreted via the urine within 0-72 h varied significantly among the groups: Cod, 74% (52-92%), salmon 56% (46-82%), blue mussel 49% (37-78%), control 45% (30-60%). The estimated total urinary excretion of AB was higher than the amount of ingested AB in the blue mussel group (112%) and also ingestion of cod seemed to result in more AB, indicating possible endogenous formation of AB from other organoarsenicals. Excretion of iAs was lower than ingested (13-22% of the ingested iAs was excreted in the different groups). Although the ingested amount of iAs+DMA+MA was low for all seafood groups (1.2-4.5% of tAs ingested), the urinary DMA excretion was high in the blue mussel and salmon groups, counting for 25% and 11% of the excreted tAs respectively. In conclusion our data indicate a possible formation of AB as a result of biotransformation of other organic arsenicals. The considerable amount of DMA excreted is probably not only due to methylation of ingested iAs, but due to biotransformation of organoarsenicals making it an inappropriate biomarker of iAs exposure in populations with a high seafood intake.

Supplementary selenium influences the response to fatty acid-induced oxidative stress in humans.

The mutual influences of wheat selenium (Se) and n-3 polyunsaturated fatty acids (n-3 PUFA) on plasma Se and indicators of increased oxidative stress were investigated in a randomized, double-blind study with 31 women (23.5 +/- 3.4 yr). Groups 1 and 2 ingested 5.4 g n-3 PUFA daily (as ethyl esters), whereas groups 3 and 4 received placebo capsules. Groups 2 and 3 received 3 slices of high-Se bread daily, providing 115 micrograms Se, in addition to the 77 +/- 26 micrograms Se in the diet. Groups 1 and 4 received placebo slices. Blood samples were drawn at baseline and at 3 and 6 wk. Serum Se concentrations increased in both groups given Se-enriched bread, but significantly less in subjects given n-3 PUFA (group 2). There were no changes in the plasma ratio alpha-tocopherol:mg cholesterol or plasma ascorbic acid levels. In group 1, plasma-conjugated dienes and thiobarbituric acid-reactive substances (TBARS) rose by 130% (p < 0.005) and 126% (p < 0.005), respectively. Two-way ANOVA showed significant interaction effects of Se and n-3 PUFA on changes in conjugated dienes (p = 0.03) and TBARS (p = 0.015), Se treatment apparently modifying the peroxidative effects of n-3 PUFA. In subjects receiving n-3 PUFA, changes in conjugated dienes and TBARS were negatively correlated with changes in serum Se. In summary, n-3 PUFA modified the effect of Se supplementation, whereas Se seemed to modify the peroxidative effects of n-3 PUFA.

Does dietary arsenic and mercury affect cutaneous bleeding time and blood lipids in humans?

Fish species may contain considerable amounts of trace elements, such as selenium (Se), arsenic (As), and mercury (Hg). The present study investigated the relationships between dietary intake of these elements and cutaneous bleeding time and blood lipids in 32 healthy volunteers. For 6 wk, one group (n = 11) consumed approx 250 g Se-rich fish daily, providing them with an average Se intake of 115 +/- 31 micrograms Se/d, Hg intake of 18 +/- 8 micrograms/d, and As intake of 806 +/- 405 micrograms/d, all values analyzed in 4-d duplicate food collections. To study the effect of Se alone, one group (n = 11) included Se-rich bread in their normal diet, giving them a Se intake (135 +/- 25 micrograms/d) that was comparable to the fish group. A control group (n = 10) ate their normal diet, providing 77 +/- 25 micrograms Se/d, 3.1 +/- 2.5 micrograms Hg/d, and 101 +/- 33 micrograms As/d. The dietary As load strongly correlated both with bleeding times and changes in bleeding times (r = 0.48, p < 0.01 and r = 0.54, p < 0.002, respectively). Dietary Hg showed a positive correlation with LDL-cholesterol (r = 0.55, p < 0.01), whereas dietary Hg in the fish group showed a strong negative relationship with HDL-cholesterol (r = -0.76, p < 0.01). Selenium seemed to have only a modest effect on bleeding time. Our results suggest that mercury and arsenic from fish may be factors contributing to or modifying some of the known effects of fish ingestion.