Susanne Sandberg

Lead in Tissues of Deseased Lead Smelter Workers

Smelter workers are exposed to a number of metals and other substances in dust, fumes and gases. The concentrations of lead in liver, lung, kidney, brain, hair and nails were determined in 32 deceased, long-term exposed male lead smelter workers, and compared with those of 10 male controls. The lead levels in liver, lung, kidney and brain were analyzed by atomic absorption spectrophotometry. X-ray fluorescence was used for the determinations in hair and nails. Lead in blood had been determined repeatedly in the lead workers since 1950, which made it possible to calculate a time-integrated blood lead index for each worker. The highest lead levels in soft tissues were found in liver, followed in order of concentration by kidney, lung and brain, among both exposed workers and controls. These organ lead concentrations were all significantly higher among the workers as compared with the control group (p < or = 0.02). The largest difference between workers and controls was found in brain tissue (ratio between median values = 5.6). The lead levels in hair and nails were of the same magnitude in the two groups. The workers showed positive correlations between lead concentrations in liver and kidney (Spearmans rho = rs = 0.59; p < 0.001), liver and hair (rs = 0.51; p = 0.003), liver and nails (rs = 0.52; p = 0.002) and hair and nails (rs = 0.52; p = 0.002). Lead concentrations in kidney correlated well with lead levels in hair (rs = 0.57; p = 0.001) and nails (rs = 0.51; p = 0.003), respectively. The positive correlation between the lead concentrations in liver and kidney indicates that these organs belong to the same soft tissue lead pool in the body. In retired lead workers, positive correlations were observed between the lead concentrations in liver and the cumulative blood lead index (CBLI) (rs = 0.50; p = 0.016), as well as between lead levels in kidney and CBLI (rs = 0.51; p = 0.014).

Cadmium, copper and zinc in tissues of deceased copper smelter workers

Workers at a copper and lead smelter in northern Sweden have a multifactorial exposure to a number of heavy metals. The concentrations of cadmium, copper and zinc in liver, lung, kidney and brain tissues have been determined by atomic absorption spectrometry in 32 deceased long-term exposed male lead smelter workers, and compared with those of 10 male controls. Furthermore, copper and zinc levels in hair and nails were determined by energy-dispersive X-ray fluorescence. The highest cadmium concentrations among both workers and controls were observed in kidney, followed in order by liver, lung and brain. The levels in kidney, liver and lung were all significantly higher in the workers than in the controls (p < 0.03). Among the workers relatively strong positive correlations (p < 0.03) were observed between cadmium concentrations in liver and lung, liver and kidney, liver and brain, and lung and brain. In the exposed workers a positive correlation was observed between cadmium and zinc concentrations in the kidney (rs = 0.38; p = 0.034). This is probably mainly due to the protein metallothionein, which is stored in the kidney, binding equimolar amounts of these two metals. The highest concentrations of copper were found in hair and nails among both workers and controls, followed in order by liver, brain, kidney and lung. The tissue concentrations of copper in brain, lung and kidney were all significantly higher among the smelter workers than in the controls (p < 0.036). Copper levels in lung and age at time of death were positively correlated among the exposed workers (rs = 0.39; p = 0.029). In the same group, positive correlations between copper and zinc concentrations in kidney (rs = 0.45; p = 0.009) and nails (rs = 0.68; p < 0.001) were also observed, reflecting possible biological interactions between these two metals. Among both workers and controls, the highest zinc concentrations were found in hair, followed in order by nails, liver, kidney, brain and lung. Significantly higher tissue concentrations among the workers as compared with the reference group were noted in kidney, liver and brain (p < 0.033). Neither copper nor zinc concentrations in hair and nails seemed to provide a useful measure of the trace element status of the smelter workers.

Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: a 2-year randomized trial

Background/Objectives:Short-term studies have suggested beneficial effects of a Palaeolithic-type diet (PD) on body weight and metabolic balance. We now report the long-term effects of a PD on anthropometric measurements and metabolic balance in obese postmenopausal women, in comparison with a diet according to the Nordic Nutrition Recommendations (NNR).Subjects/Methods:Seventy obese postmenopausal women (mean age 60 years, body mass index 33 kg/m2) were assigned to an ad libitum PD or NNR diet in a 2-year randomized controlled trial. The primary outcome was change in fat mass as measured by dual-energy X-ray absorptiometry.Results:Both groups significantly decreased total fat mass at 6 months (−6.5 and−2.6 kg) and 24 months (−4.6 and−2.9 kg), with a more pronounced fat loss in the PD group at 6 months (P<0.001) but not at 24 months (P=0.095). Waist circumference and sagittal diameter also decreased in both the groups, with a more pronounced decrease in the PD group at 6 months (−11.1 vs−5.8 cm, P=0.001 and−3.7 vs−2.0 cm, P<0.001, respectively). Triglyceride levels decreased significantly more at 6 and 24 months in the PD group than in the NNR group (P<0.001 and P=0.004). Nitrogen excretion did not differ between the groups.Conclusions:A PD has greater beneficial effects vs an NNR diet regarding fat mass, abdominal obesity and triglyceride levels in obese postmenopausal women; effects not sustained for anthropometric measurements at 24 months. Adherence to protein intake was poor in the PD group. The long-term consequences of these changes remain to be studied.

Is Placenta a Good Indicator of Cadmium and Lead Exposure

Distribution of lead and cadmium was studied in 25 placentas. Samples were taken from 6 different lobuli, and lead and cadmium concentrations were not determined by graphite furnace atomic absorption spectrometry. Lead and cadmium were not distributed uniformly, and the concentrations differed by a factor > or = 2 among different lobuli within the same placenta in 36% and 52% of the placentas, respectively. Placental lead and cadmium concentrations were also determined in homogenized samples from smelter (n = 49) and control (n = 53) areas in northern Sweden. Mean lead and cadmium concentrations were low, even in the smelter area (geometric means = 10 ng/g and 3 ng/g wet weight, respectively). The significant differences observed (i.e., higher blood lead concentrations in the smelter area during pregnancy and in umbilical cord blood) were not reflected in the placenta. We concluded, therefore, that the placenta is not a suitable organ to use for the monitoring of environmental exposure to lead. It could be used to monitor cadmium exposure, but if pregnancy outcome is to be studied, consideration should be given to the sampling procedure.

The susceptibility to nephrotoxicity of streptozotocin-induced diabetic rats subchronically exposed to cadmium chloride in drinking water

Streptozotocin-induced diabetic rats and normal non-diabetic (ND) rats were exposed to cadmium chloride in drinking water in doses of 0, 50 and 100 ppm for 90 days. There was a dose-related increase in urinary protein and enzymes in the diabetic group, but an increase in proteinuria only in the high exposure subgroup of the ND group. It is suggested that diabetic rats induced by streptozotocin are more susceptible to cadmium nephrotoxicity than normal (ND) rats. Metallothionein synthesis in liver was estimated to be similar in both the diabetic and non-diabetic groups after exposure to cadmium. Less excretion of cadmium in urine and greater accumulation of cadmium in kidney were observed in the diabetic group, and this may be one of the mechanisms underlying the susceptibility of diabetic animals to the effects of cadmium. Further biochemical and histological studies are required in order to explain the detailed events involved in inducing such changes in the toxicokinetics of cadmium.

A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women

Ectopic fat accumulation in liver and skeletal muscle may be an essential link between abdominal obesity, insulin resistance and increased risk of cardiovascular disease after menopause. We hypothesized that a diet containing a relatively high content of protein and unsaturated fat [mainly monounsaturated fatty acids (MUFAs)] but limited carbohydrates and saturated fat would reduce lipid content in liver and muscle and increase insulin sensitivity in postmenopausal women.

Determination of cadmium in very low concentration urine samples by electrothermal atomic absorption spectrometry

Urine samples were collected that contained concentrations of Cd between 0.05 and 0.5 µ g l -1 . When using ETAAS for the analysis of these samples, spectral interference is present that can obscure low masses of Cd and deteriorate the precision and accuracy of the analysis. Instrumental advances such as electrodeless discharge lamps, the use of echelle monochromators, solid-state detectors and end-capped spatially isothermal atomizers have been combined to reduce detection limits. Spatially isothermal atomizers provided with end-caps and modified contact cones were found to double the sensitivity for Cd, compared with a standard atomizer configuration. A combined chemical modifier of Pd and NH 4 NO 3 can reduce interference from molecular alkali halides, on atomization of Cd. Samples were decomposed with boiling HNO 3 to destroy carbon compounds and ensure homogeneity. Calibration was by standard additions to ensure accuracy in the determination; however, standard calibration may be used with a deterioration in accuracy of about 6%. For a sample containing 0.1 µ g l -1 Cd, the method including sample pre-treatment gives a precision of about 15%. The accuracy of the method was established by standard additions to samples and the analysis of a urine reference material; the instrumental detection limit is 0.008 µ g l -1 Cd in urine.

Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention.

Background/Objectives:Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD).Subjects/Methods:Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included.Results:Liver fat decreased after 6 months by 64% (95% confidence interval: 54–74%) in the PD group and by 43% (27–59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25–75%) in the PD group and 49% (27–71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes.Conclusions:A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.

Plasma metabolomic response to postmenopausal weight loss induced by different diets

BackgroundMenopause is associated with increased abdominal fat and increased risk of developing diabetes and cardiovascular disease.ObjectivesThe present study evaluated the plasma metabolic response in relation to insulin sensitivity after weight loss via diet intervention.MethodsThis work includes two studies; i) Ten women on a 5 weeks Paleolithic-type diet (PD, 30 energy percent (E%) protein, 40 E% fat, 30 E% carbohydrates), ii) 55 women on 6 months of either PD or Nordic Nutrition Recommendations diet (NNR, 15 E% protein, 30 E% fat, and 55 E% carbohydrates). Plasma metabolic profiles were acquired at baseline and post diet using gas chromatography time-of-flight/mass spectrometry and investigated in relation to insulin sensitivity using multivariate bioinformatics.ResultsBoth the PD and NNR diet resulted in significant weight loss, reduced waist circumference, improved serum lipid profiles, and improved insulin sensitivity. We detected a baseline metabolic profile that correlated significantly with insulin sensitivity, and of which components increased significantly in the PD group compared to NNR. Specifically, a significant increase in myo-inositol (MI), a second messenger of insulin action, and β-hydroxybutyric acid (β-HB) increased while dihomo-gamma-linoleic acid (DGLA) decreased in PD compared to NNR, which correlated with improved insulin sensitivity. We also detected a significant decrease in tyrosine and tryptophan, potential markers of insulin resistance when elevated in the circulation, with the PD but not the NNR.ConclusionsUsing metabolomics, we detected changes in the plasma metabolite profiles associated with weight loss in postmenopausal women by different diets. The metabolic profiles following 6 months of PD were linked to beneficial effects on insulin sensitivity compared to NNR.Graphical Abstract

A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women

Background/Objectives:Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet.Subjects/Methods:A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium.Results:At baseline, median 24-UIC (71.0 μg/l) and 24-UIE (134.0 μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0 μg/l (P=0.001) and 24-UIE to 77.0 μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group.Conclusions:A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.