Xenohormone transactivities are inversely associated to serum POPs in Inuit.

BACKGROUND: The persistent organic pollutants (POPs) are highly lipophilic and resistant to biodegradation and found in e.g. seafood and marine mammals. Greenlandic Inuit have high intake of marine food and thus high POP burden that varies according to local conditions and dietary preference. We do for the very first time report the serum POP related non-steroidal xenohormone activity of Inuit across Greenland. The aims were 1) to determine the integrated xenohormone bioactivities as an exposure biomarker of the actual lipophilic serum POP mixture measuring the effect on estrogen (ER) and androgen receptor (AR) transactivity in citizens from different Greenlandic districts and 2) to evaluate associations to serum POP markers (14 PCBs and 10 pesticides) and lifestyle characteristics. METHODS: Serum samples from 121 men and 119 women from Nuuk, Sisimiut and Qaanaaq were extracted using SPE-HPLC fractionation to obtain the serum POP fraction free of endogenous hormones. The serum POP fraction was used for determination of xenohormone transactivity using ER and AR reporter gene assays. RESULTS: In overall, the xenohormone transactivities differed between districts as well as between the genders. Associations between the transactivities and age, n-3/n-6 and smoker years were observed. The xenoestrogenic and xenoandrogenic transactivities correlated negatively to the POPs for the combined female and male data, respectively. CONCLUSION: The non-steroidal xenohormone transactivities can be used as an integrated biomarker of POP exposure and lifestyle characteristics. The actual serum POP mixtures antagonized the age adjusted sex hormone receptor functions. Comparison of different study populations requires in addition to age inclusion of diet and lifestyle factors.

AhR transcriptional activity in serum of Inuits across Greenlandic districts.

BACKGROUND: Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors. METHODS: The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors. RESULTS: In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk > or = Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food. CONCLUSION: i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.

Traditional and modern Greenlandic food - dietary composition, nutrients and contaminants.

OBJECTIVES: High levels of n-3 fatty acids and other nutrients in traditional Inuit food appear to provide some protection against the typical diseases of affluent industrialized societies: cardiovascular diseases and type 2 diabetes. An increased intake of imported food among Inuits will probably increase their frequency of these diseases. However, since the 1970s it has become evident that the marine-based Inuit diet also contains high levels of potentially toxic lipophilic organic pollutants and heavy metals. Since these two food related opposing health effects appear to be inseparable, the phenomenon has been known as "The Arctic Dilemma". However, both the fatty acid composition and the contaminant levels vary in Greenlandic food items. Thus in principle it is possible to compose a diet where the benefits and risks are better balanced. Our objectives of this study were to compare traditional and modern meals in Greenland concerning the dietary composition, nutrients, and health indicators among the consumers. STUDY DESIGN: The present study was a cross-sectional dietary survey as part of the Arctic Monitoring and Assessment, Human Health Programme (AMAP). These results were compared with older dietary surveys in Greenland. METHODS: Dietary components, fatty acids, and nutrients in 90 local meals collected by duplicate portion method in Uummannaq town, north Greenland 2004 and in Narsaq, south Greenland 2006, were compared with 177 duplicate meals sampled in the village of Igdslorsuit, Uummannaq, district, 1976 and also compared with other dietary studies in Greenland 1953-1987. Anthropometric measures (weight, height, and body mass index, BMI) and blood lipids were measured as health indicators among the participants. RESULTS: Between the traditional foods sampled or analysed 30-50 years ago and the modern food from 2004 to 2006, significant differences were found in the dietary composition. The percentage of local food had decreased, to a present average of about 20% and with it the dietary content of n-3 fatty acids. Also, the intakes of many vitamins and minerals had decreased, and were below Nordic Nutrient Recommendations in 2004 and 2006. Vitamin A, B(1), (B(2)), B(12), iron, iodine, phosphorus, and selenium contents were correlated with n-3 content, whereas vitamin C, folate, and calcium contents were not and the same time very low. In the traditional food, especially from the villages, the intakes of vitamin A, vitamin D, and iron were extremely high and borderline toxic. The levels of contaminants such as organochlorins and heavy metals were also strongly correlated with the relative content of local food in the diet. The best balance between potentially beneficial and harmful substances was found for 20-30% local food, corresponding to a daily intake of 3-5 g of n-3 fatty acids. Body weight, height, body mass index (BMI), cholesterol, and S-triglycerides had increased significantly between 1976 and 2004. CONCLUSION: The dietary changes to a more western fare were found to be negative resulting in less adequate nutrient coverage but at the same time lower contaminant load. Thus, we recommend not to increase the consumption of local products beyond the present level but rather to improve the quality of the imported food.

Contaminants, diet, plasma fatty acids and smoking in Greenland 1999-2005.

OBJECTIVES: The purpose of this study is to monitor and assess human exposure to pollution in the Arctic which presents a potential future health risk for the local populations. Epidemiological studies in Greenland have shown that human blood levels of several organic contaminants are very high, especially in the North where people depend on local food. In East Greenland (Ittoqqortoormiit (Scoresbysund)) the population shows the highest blood levels of several persistent organic pollutants found in Arctic countries, especially PCB, the levels of which exceed Canadian guideline levels. As in other Arctic countries, the predominant source of these contaminants is the local diet. However, other factors such as smoking may influence the metabolism and thereby the accumulation of toxic substances. STUDY DESIGN: This project is part of the human health program of the ongoing circumpolar "Artic Monitoring and Assessment Programme". Lifestyle, anthropometric factors, and dietary survey results covering 500 men and women from 6 Greenlandic districts were analyzed along with other factors blood lipids, fatty acid profiles, heavy metals and concentrations of persistent organic pollutants (POPs). RESULTS: The dietary survey showed that the traditional food on the average provided 20-30% of the total energy intake. However, the relative monthly meal intake of seal, whale, polar bear, fish and game, and the composition of imported food, varied between districts. Seal and polar bear intake, and, in particular all the plasma n-3 fatty acids, were significantly correlated with organic contaminant concentrations, (betaHCH, chlordanes, DDTs, Hexachlorobenzene, Mirex, PCBs, and toxaphenes) p<0.01(). After adjusting for age, district, dietary factors or plasma n-3 fatty acids, smoking was significantly correlated with high levels of all the above mentioned POPs. CONCLUSION: The main predictors of high contaminant levels in Greenland were age, district, male gender, smoking and high plasma n-3/n-6 ratio as a marker of high dietary intake of local marine mammals.

Dietary composition and contaminants in north Greenland, in the 1970s and 2004.

OBJECTIVES: The fatty acid composition and other nutrients in traditional Inuit food appear to provide some protection against diseases of affluent industrialized societies, such as cardiovascular diseases and type 2 diabetes. A transition towards increased amounts of imported food might increase the occurrence of these diseases among Inuit. However, since the 1970s it has become evident that the marine-based Inuit diet also contains high levels of potentially toxic lipophilic organic pollutants and heavy metals. Since these two opposing effects on health appear to be inseparable, the phenomenon has become known as "The Arctic Dilemma". However, both the fatty acid composition and the contaminant levels vary in Greenlandic food items. Thus, in theory, it is possible to compose a diet where the benefits outweigh the risks. Our objective was to compare traditional and modern meals in Greenland regarding dietary composition, content of n-3 fatty acids and contaminants. STUDY DESIGN: The present study was part of the Arctic Monitoring and Assessment Programme, AMAP, comparing the results of dietary composition and nutrients in 177 traditional meals collected in Uummannaq municipality, north Greenland in 1976 with 90 meals sampled in Uummannaq town in 2004 under similar conditions. Eleven pesticides, 14 PCB congeners, heavy metals, selenium, and fatty acids were analysed in meals and blood samples from the participants. Contaminant levels were compared between 1976 and 2004 after adjustment for n-3 fatty acids, indicating local food content. RESULTS: Between the traditional meals collected 30 years ago and the meals from 2004, dramatic and significant changes have occurred in the dietary composition. The percentage of local food has decreased, and with it the intake of n-3 fatty acids. Calculated as daily intake, all but three contaminants had decreased significantly. However, this could be explained by the lower intake of local food. After adjustment for n-3 fatty acid content in the food, significant declines of concentration in the local food were evident only for PCBs and lead, whereas for mercury, DDTs, and chlordanes the levels were unchanged, and for hexachlorobenzene, mirex, and toxaphenes, the levels had increased significantly. CONCLUSION: The consumption of locally produced food has decreased in Greenland during the last 30 years and this has led to a reduction in the daily intake of contaminants. However, the concentrations of contaminants in local food items have not decreased, except for PCB and Lead. Therefore, we recommend that the consumption of local products is not increased beyond the present level, until the level of contaminants is reduced to a safer level.

Dietary composition in Greenland 2000, plasma fatty acids and persistent organic pollutants.

UNLABELLED: Human exposure to pollution in the Arctic presents a potential future health risk for the local populations. Epidemiological studies in Greenland have shown that human blood levels of several organic contaminants are very high, especially in the North where people depend on local food. In East Greenland (Ittoqqortoormiit (Scoresbysund)) the population shows the highest blood levels of several persistent organic pollutants found in Arctic countries, especially PCB, the levels of which exceed Canadian guideline levels. As in other Arctic countries, the direct source of these contaminants is the diet, and it is, therefore important to monitor the composition of the diet along with other factors which may influence the metabolism and thereby the accumulation of toxic substances. This project is part of the human health program of the ongoing circumpolar 'Arctic Monitoring and Assessment Programme'. Dietary survey results (Semiquantitative Food Frequency questionnaire from 192 men and women from East Greenland and 48 men from Uummannaq West Greenland) were analysed along with other factors (lifestyle and anthropometric factors), blood lipids, fatty acid profiles, and concentrations of persistent organic pollutants (POPs). The dietary survey showed that the contributions of traditional food provided 25-30% of the total energy intake. However, the relative monthly meal intake of seal, whale, polar bear, fish and game, and the composition of imported food, varied between districts. The blood fatty acids (FA), e.g. the n-3/n-6 ratio (Uummannaq 0.70, Ittoqqortoormiit 0.37 Tassiilaq 0.45) showed moderate associations with the overall reported food composition. The n-3 fatty acids were associated with the well-known lowering effect on serum-triglyceride levels. The strongest associations between diet and plasma fatty acids were found for docosapentaenoic acid, C: 22.5.3 which strongly correlated with reported seal, and polar bear intake (P=0.01** and 0.04*, respectively), consistent with the fact that seal and polar bear blubber contain much higher concentrations of C: 22.5.3 than other sea mammals and fish. Seal and polar bear intake, and in particular all the plasma n-3 fatty acids, were significantly correlated with organic contaminant concentrations, (betaHCH, chlordanes, DDTs, Hexachlorobenzene, Mirex, PCBs, and toxaphenes) P<0.01**. CONCLUSIONS: The strongest correlations between POPs and fatty acids were found with C: 22.5.3, strongly indicating seal and polar bear blubber as the main contributors of POPs to the local population.

Selenium status in Greenland Inuit.

In Greenland, the human intake of selenium has always been relatively high and is closely connected to intake of the traditional food of marine origin. Analyses of historic and present day human and animal hair samples have indicated that the selenium level in the marine environment has been constant over time, while the levels in humans have declined corresponding to a decrease in intake of traditional food. The Inuit population in Greenland is in dietary transition where western-style food will increasingly dominate. As a consequence, the ample supply of selenium may not be sustained in the future. We report here the selenium status in three Greenlandic population groups, Ittoqqortoormiit and Tasiilaq on the east coast and Uummannaq on the west coast. Mean whole blood concentrations ranged from 178 microg/l in Tasiilaq men to 488 microg/l in Uummannaq men. Plasma concentrations ranged from 79 microg/l in Tasiilaq women to 113 microg/l in Uummannaq men. With increasing Se concentrations in whole blood, the plasma concentrations increased but tended to stabilise a level approximately 140 microg/l. Selenium blood levels were highly significantly correlated with long chain marine fatty acids. Dietary survey and food composition data from the west coast showed that whale skin, muktuk, is the main source of Se followed by birds, seal meat and organs, and fish. Terrestrial animals contributed only insignificantly to the selenium intake. In West Greenland, daily Se intake (235 microg/day) was estimated by dietary survey; it corresponded well with a calculated intake (220 microg/day) based on the mean blood concentration.

Smoking as a determinant of high organochlorine levels in Greenland.

The authors investigated the accumulation of organochlorines among smoking and nonsmoking Inuit hunters (n = 48) in Uummanaq, Greenland, a population with high dietary exposure to persistent organic pollutants (POPs). Human plasma organochlorine levels were positively correlated with age, marine diet, and smoking or plasma cotinine in multiple linear-regression models (p < 0.001). Body mass index was inversely correlated with organochlorine accumulation, independent of smoking status. These findings confirm that the source of POPs among the Inuit in Greenland is diet, but smoking is an important determinant of POP bioaccumulation. Smoking cessation may provide a means to lower the body burden of POPs.