Serum selenium concentration is associated with metabolic factors in the elderly: a cross-sectional study
© Yang et al; licensee BioMed Central Ltd. 2010
Received: 4 January 2010
Accepted: 6 May 2010
Published: 6 May 2010
Selenium is an essential micronutrient known for its antioxidant function. However, the association of serum selenium with lipid profiles and fasting glucose are inconsistent in populations with average intake of selenium. Furthermore, there were few studies conducted specifically for the elderly. This study examined the relationship of serum selenium concentration with serum lipids and fasting glucose in the Taiwanese elderly population.
This was a cross-sectional study of 200 males and females aged 65-85 years (mean 71.5 ± 4.6 years) from Taipei, Taiwan. Serum selenium was measured by inductively coupled plasma-mass spectrometer. The association between serum selenium and metabolic factors was examined using a multivariate linear regression analysis after controlling several confounders.
The mean serum selenium concentration was 1.14 μmol/L, without significant difference between sexes. Total cholesterol, triglycerides, and LDL cholesterol increased significantly with serum selenium concentration (P < 0.001, P < 0.05 and P < 0.001, respectively) after adjusting for age, gender, anthropometric indices, lifestyle factors, and cardio-vascular risk factors in several linear regression models. Furthermore, there was a significantly positive association between serum selenium and serum fasting glucose concentrations (P < 0.05).
Total cholesterol, triglycerides, and LDL cholesterol, and fasting serum glucose concentrations increased significantly with serum selenium concentration in the Taiwanese elderly. The underlying mechanism warrants further research.
Selenium, an essential trace element, is vital for human normal development, growth, male fertility, and thyroid hormone metabolism. Selenium deficiency is associated with Keshan disease, an endemic cardiomyopathy, and Kashin-Beck disease, a deforming arthritis. Less-overt deficiency may cause disease susceptibility and poor health maintenance . Selenoproteins reportedly possess antioxidant properties and its deficiency plays an important role in the pathogenesis of cardiovascular disease (CVD). However, whether or not selenium concentration contributes to CVD remains uncertain. For example, epidemiologic studies show that low serum selenium is associated with increased cardiovascular mortality [2–4]. On the other hand, there is no significant correlation between selenium and risk of myocardial infarction  and peripheral artery disease  in selenium-replete population such as United States.
Some studies propose that selenium may exert its influence on CVD through its effect on known CVD risk factors, including dyslipidemia and hyperglycemia. Observational studies show positive associations of serum selenium with total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides concentrations in high selenium-replete populations [7–9]. However, in populations with low serum selenium concentrations, the associations are inconsistent [10–19]. Similarly inconsistent is the association between serum selenium and fasting glucose concentrations [7, 20–22]. Potential adverse effects of high selenium exposure on diabetes risk have been noted [23–26]. Nonetheless, most studies involve relatively young populations. Few studies have focused on the elderly.
Since CVD is a leading cause of death in the elderly, the relationship between serum selenium concentrations and metabolic factors deserves further studies. This study aimed to evaluate the relationship between serum selenium and metabolic factors, including serum lipid and glucose concentrations, in a cohort of Taiwanese elderly.
A total of two hundred ambulatory elderly volunteers living in the Taipei area were invited to our study in 2007. Information about age, sex, cigarette smoking, alcohol consumption, physical activity, CVD history, current use of cholesterol-lowering medications, current use of vitamin-mineral supplements, and current use of hormone replacement therapy were obtained by individual interview through questionnaires. Current smokers were defined as those with smoking recently for more than six months. Former smokers were defined as quitting smoking for at least one year. Former smokers and never smokers were grouped together as non-current smokers for further analysis. Current drinkers of alcohol were defined as those with drinking at least one ounce of alcohol per week for six months. Former drinkers were defined as quitting drinking for at least one year. Former drinkers and never drinker were grouped together as non-current drinker for further analysis. Current use of cholesterol-lowering medications was defined as participants using medication regularly. Current use of vitamin-mineral supplements was defined as participants taking supplements daily or at least weekly. Vitamin-mineral supplements included multivitamin, vitamin B complex, calcium supplement, glucosamine sulfate, collagen supplement and cod liver oil, etc. Current use of hormone replacement therapy was defined as taking hormone regularly. Anthropometric measurements, including height and weight, were performed using a standard stadiometer. Body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). Diabetes mellitus (DM) and hypertension were defined based on self-reported history or current medication use for DM and hypertension.
Venous blood sample was taken after an eight-hour fasting at least. Serum glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglycerides were assessed by automatic spectrophotometric assay (HITACHI 7170, Japan). Fasting glucose was determined using glucose oxidase method. Using free glycerol banking method to determine serum triglycerides. HDL and LDL were determined by chemical modified enzyme and sodium N-(2-Hydroxy-3-sulfopropyl)-3.5-dimethoxyaniline (HSDA). Serum selenium was measured using inductively coupled plasma mass spectroscopy (ICP-MS). Serum samples were diluted 1:24 with diluents of 0.1% nitric acid and 0.1% Triton X-100. The calibration standards were prepared in a blank matrix and run using the standard addition calibration type. The serum samples were analyzed in the peak-jumping mode for 82Se, with the detection limit set at 0.01 μmol/L. Accuracy of the analysis was checked against Seronorm Trace Element Human Serum (batch 704121; Nycomed AS, Oslo, Norway) as reference material. The National Health Institute in Taiwan approved this study. All of the participants provided informed consents.
Data were presented as means and standard deviations (mean ± SD) and percentages. Participants were divided into four groups according to their serum selenium concentrations. Anthropometric and biochemical variables were compared across the four quartiles. Tests for trend across serum selenium quartiles were calculated by entering the quartile as an ordinal number in a regression model. Using one-way analysis of variance, the study had a 83% power to detect the difference in means of total cholesterol levels with 50 subjects in each group and with an alpha of 0.05 characterized by a variance of 0.057, assuming that the common standard deviation is 0.970.
The relationship between serum selenium concentrations and lipids and fasting glucose were analyzed using several multivariate linear regression models with lipids and fasting glucose as dependent variables, and serum selenium as independent variable. Other possible confounders were adjusted for models 1~3 as independent variables. In model 1, age, sex and BMI were adjusted. In model 2, current smoking, current drinking, vegetarian diet, and physical activity were further adjusted. In model 3, hormone replacement therapy, cholesterol-lowering medication, vitamin supplement, diabetes mellitus, and hypertension were also further adjusted. For fasting glucose, a "modified" model 3 was applied after excluding diabetes mellitus from the independent variables in model 3. Log transformation of the variables was performed if they were not normally distributed as assessed by the Kolmogorov-Smirnov test. The least square (LS) means of lipids and glucose concentration were computed by general linear models adjusted for the independent variables among the four selenium quartile groups. Statistical analyses were performed using the SPSS statistical software (13th version, SPSS Inc., Chicago, IL, USA).
General characteristics among quartiles of serum selenium concentrations
Q1 (n = 50)
Q2 (n = 51)
Q3 (n = 49)
Q4 (n = 50)
P for trend a
71.8 ± 5.2
70.1 ± 3.9
71.6 ± 4.8
72.5 ± 4.4
Sex, male (%)
Body weight (kg)
57.7 ± 10.7
58.3 ± 9.8
57.7 ± 8.6
56.2 ± 10.1
82.4 ± 10.6
82.3 ± 8.9
82.2 ± 8.3
80.1 ± 10.3
23.9 ± 3.7
23.7 ± 3.1
23.5 ± 2.6
22.6 ± 3.2
5.06 ± 0.83
5.27 ± 0.88
5.38 ± 1.03
5.72 ± 1.01
0.1 ± 0.44
0.2 ± 0.49
0.29 ± 0.46
0.31 ± 0.51
1.44 ± 0.27
1.49 ± 0.37
1.5 ± 0.46
1.52 ± 0.35
3.01 ± 0.69
3.1 ± 0.64
3.2 ± 0.7
3.47 ± 0.71
5.34 ± 0.73
5.68 ± 1.28
5.63 ± 0.76
5.84 ± 1.45
0.85 ± 0.09
1.07 ± 0.04
1.22 ± 0.05
1.44 ± 0.1
Current smoking (%)
Current drinking (%)
Lipid Tx (%)
340.6 ± 199.3
334.8 ± 224.5
322.8 ± 240.7
333.0 ± 239.2
Vitamin-mineral supplement users (%)
Linear regression models showing standardized betas with serum selenium concentrations as independent variable
In this study, serum selenium concentrations were positively associated with serum concentrations of total cholesterol, LDL cholesterol, triglycerides, and glucose in the elderly, after adjustment for age, gender, anthropometric indices, lifestyles, and traditional CVD risk factors. This suggests that high serum selenium concentrations may be associated with risk factors of CVD in the elderly.
Positive relationships between serum selenium and total cholesterol concentrations are discussed in several studies of various serum selenium concentrations [2, 4, 7, 10–15, 19, 27]. However, most participants have been young and middle-aged adults. Similar to two studies involving the elderly [4, 14, 15], this study showed that serum total cholesterol concentration was positively associated with serum selenium concentration (Table 2; Fig. 1A).
Many studies failed to show a significant association between serum selenium and triglycerides concentrations [10, 12, 27] and only two have shown a positive association [7, 8]. Our study demonstrated that serum selenium concentrations were positively associated with serum triglycerides (Table 2; Fig. 1D).
The association between serum selenium and LDL cholesterol levels was not consistent in previous studies. Five studies showed a positive association [7–9, 13, 14] but others revealed no significant relationship [11, 16–18]. The variable sample sizes, age groups, and lack of adjustments for possible confounders may account for the inconsistencies in those studies. Our present study supported that serum LDL cholesterol concentrations were positively associated with serum selenium levels (Table 2; Fig. 1B).
The association of serum selenium with HDL cholesterol is not consistent in previous studies. Five studies report a positive association [8, 9, 11, 15, 16], one has a negative association , and three do not show any significant association [10, 12, 19]. In our present study, the HDL cholesterol concentrations did not increase significantly with increments of serum selenium (Table 2; Fig. 1C). In addition, the mean HDL cholesterol concentration was higher in our population as compared to those in previous studies.
Interestingly, the effects of selenium supplementation on blood lipids are contradictory in animal and human studies. In rats, selenium supplementation increases LDL receptor activity [28, 29] but decreases 3-hydroxy 3-methylglutaryl co-enzyme A (HMG-CoA) reductase expression , leading to decreased plasma LDL cholesterol and total cholesterol levels. However, one animal study in mice showed a significant increase in plasma cholesterol with the loss of housekeeping selenoprotein expression . In human, selenium supplementation was found to increase total cholesterol and triglyceride levels in French adults . Total cholesterol and LDL cholesterol levels also increased after selenium supplementation in the Chinese population . Another study showed no further decrease in triglyceride or LDL cholesterol concentration but a blunted increment of HDL with selenium supplementation in participants with coronary heart disease receiving simvastatin-niacin treatment . Therefore, the role of selenium supplementation on lipid metabolism in humans deserves further research. Recently, the apoE δ4 gene was found to play a central role between selenium levels and lipid metabolism in rural elderly Chinese . The underlying interactive mechanism between susceptible gene, selenium, and lipids needs further investigation.
High serum selenium concentrations also correlate with high fasting glucose concentrations [7, 20]. The prevalence of type 2 diabetes increases with increment of serum selenium in American adults . Further analysis of the study shows that glycosylated hemoglobin levels increase with increasing selenium concentrations . Similarly, serum selenium level was positively associated with glucose level in Table 2. Stranges et al note increased risk of diabetes after receiving selenium supplements for 7.7 years . Lipman et al also found a statistically non-significant increase in diabetes after selenium supplementation for 5.46 years . Interestingly, over-production of selenium-dependent glutathione peroxidase-1 can induce hyperinsulinemia in mice . In contrast, Hughes et al showed no significant difference in serum selenium levels between diabetic and non-diabetic Singaporeans . Recently, Akbaraly et al found that higher serum selenium status at baseline had protective effect on later occurrence of dysglycemia in a 9-year longitudinal study . Besides, supplementation of selenium can lead to increased insulin sensitivity in rats . Therefore, the inconsistent results of various studies imply that further research is warranted.
Although this study shows that elevated serum selenium concentrations are associated with metabolic factors in an elderly population, it has some limitations. First, the study has a cross-sectional design and causal inference cannot be established. Second, the participants are volunteers rather than randomly selected. External validation is necessary in future studies. In addition, there is no human selenium survey in Taiwan. Thus, a comparison of serum selenium concentrations between the data here and the Taiwanese data is not possible. Thirdly, there is no available data on food intake and selenium supplementation, which may indicate a possible residual confounding effect. Fourth, multivariate analyses adjusted for lipid-lowering medications might bias the results . Finally, only the serum fasting glucose without insulin levels was available in the study. Therefore, the relationship between selenium with insulin resistance could not be explored.
In conclusion, serum selenium concentration was associated with serum concentrations of total, LDL cholesterol, triglycerides, and glucose in the elderly after adjustment for potential confounders. The role of selenium on lipid and glucose metabolism in humans deserves further research in the future. Thus, recommendations on selenium supplementation should be carefully evaluated.
This study was funded by the National Health Institute of Taiwan (GE-096-PP-08). The authors would like to thank Miss J-WW and F-CH for their work.
- Rayman MP: The importance of selenium to human health. Lancet. 2000, 356: 233-241. 10.1016/S0140-6736(00)02490-9.View ArticleGoogle Scholar
- Salonen JT, Alfthan G, Huttunen JK, Pikkarainen J, Puska P: Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet. 1982, 2: 175-179. 10.1016/S0140-6736(82)91028-5.View ArticleGoogle Scholar
- Virtamo J, Valkeila E, Alfthan G, Punsar S, Huttunen JK, Karvonen MJ: Serum selenium and the risk of coronary heart disease and stroke. Am J Epidemiol. 1985, 122: 276-282.Google Scholar
- Akbaraly NT, Arnaud J, Hininger-Favier I, Gourlet V, Roussel A-M, Berr C: Selenium and mortality in the elderly: results from the EVA study. Clin Chem. 2005, 51: 2117-2123. 10.1373/clinchem.2005.055301.View ArticleGoogle Scholar
- Salvini S, Hennekens CH, Morris JS, Willett WC, Stampfer MJ: Plasma levels of the antioxidant selenium and risk of myocardial infarction among U.S. physicians. Am J Cardiol. 1995, 76: 1218-1221. 10.1016/S0002-9149(99)80344-0.View ArticleGoogle Scholar
- Bleys J, Navas-Acien A, Laclaustra M, Pastor-Barriuso R, Menke A, Ordovas J, Stranges S, Guallar E: Serum selenium and peripheral arterial disease: results from the national health and nutrition examination survey, 2003-2004. Am J Epidemiol. 2009, 169: 996-1003. 10.1093/aje/kwn414.View ArticleGoogle Scholar
- Obeid O, Elfakhani M, Hlais S, Iskandar M, Batal M, Mouneimne Y, Adra N, Hwalla N: Plasma Copper, Zinc, and Selenium Levels and Correlates with Metabolic Syndrome Components of Lebanese Adults. Biol Trace Elem Res. 2008, 123: 58-65. 10.1007/s12011-008-8112-0.View ArticleGoogle Scholar
- Bleys J, Navas-Acien A, Stranges S, Menke A, Miller ER, Guallar E: Serum selenium and serum lipids in US adults. Am J Clin Nutr. 2008, 88: 416-423.Google Scholar
- Laclaustra M, Stranges S, Navas-Acien A, Ordovas JM, Guallar E: Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004. Atherosclerosis.Google Scholar
- Suadicani P, Hein HO, Gyntelberg F: Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males. Atherosclerosis. 1992, 96: 33-42. 10.1016/0021-9150(92)90035-F.View ArticleGoogle Scholar
- Coudray C, Roussel AM, Mainard F, Arnaud J, Favier A: Lipid peroxidation level and antioxidant micronutrient status in a pre-aging population; correlation with chronic disease prevalence in a French epidemiological study (Nantes, France). J Am Coll Nutr. 1997, 16: 584-591.Google Scholar
- Jossa F, Trevisan M, Krogh V, Farinaro E, Giumetti D, Fusco G, Galasso R, Panico S, Frascatore S, Mellone C: Serum selenium and coronary heart disease risk factors in southern Italian men. Atherosclerosis. 1991, 87: 129-134. 10.1016/0021-9150(91)90015-U.View ArticleGoogle Scholar
- Lopes PA, Santos MC, Vicente L, Rodrigues MO, Pavão ML, Nève J, Viegas-Crespo AM: Trace element status (Se, Cu, Zn) in healthy Portuguese subjects of Lisbon population: a reference study. Biol Trace Elem Res. 2004, 101: 1-17. 10.1385/BTER:101:1:01.View ArticleGoogle Scholar
- Gámez C, Ruiz-López D, Artacho R, Navarro M, Puerta A, López C: Serum selenium in institutionalized elderly subjects and relation to other nutritional markers. Clin Chem. 1997, 43: 693-694.Google Scholar
- Bates CJ, Thane CW, Prentice A, Delves HT: Selenium status and its correlates in a British national diet and nutrition survey: people aged 65 years and over. J Trace Elem Med Biol. 2002, 16: 1-8. 10.1016/S0946-672X(02)80002-5.View ArticleGoogle Scholar
- Salonen JT, Salonen R, Seppänen K, Kantola M, Parviainen M, Alfthan G, Mäenpää PH, Taskinen E, Rauramaa R: Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men. Atherosclerosis. 1988, 70: 155-160. 10.1016/0021-9150(88)90109-8.View ArticleGoogle Scholar
- Viegas-Crespo AM, Pavão ML, Paulo O, Santos V, Santos MC, Nève J: Trace element status (Se, Cu, Zn) and serum lipid profile in Portuguese subjects of San Miguel Island from Azores'archipelago. J Trace Elem Med Biol. 2000, 14: 1-5. 10.1016/S0946-672X(00)80016-4.View ArticleGoogle Scholar
- Karita K, Yamanouchi Y, Takano T, Oku J, Kisaki T, Yano E: Associations of blood selenium and serum lipid levels in Japanese premenopausal and postmenopausal women. Menopause. 2008, 15: 119-124. 10.1097/gme.0b013e31806bf32c.View ArticleGoogle Scholar
- Stranges S, Laclaustra M, Ji C, Cappuccio FP, Navas-Acien A, Ordovas JM, Rayman M, Guallar E: Higher selenium status is associated with adverse blood lipid profile in British adults. J Nutr. 2010, 140: 81-87. 10.3945/jn.109.111252.View ArticleGoogle Scholar
- Czernichow S, Couthouis A, Bertrais S, Vergnaud AC, Dauchet L, Galan P, Hercberg S: Antioxidant supplementation does not affect fasting plasma glucose in the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France: association with dietary intake and plasma concentrations. Am J Clin Nutr. 2006, 84: 395-399.Google Scholar
- Ozkaya M, Sahin M, Cakal E, Gisi K, Bilge F, Kilinc M: Selenium Levels in First-Degree Relatives of Diabetic Patients. Biol Trace Elem Res. 2009, 128: 144-151. 10.1007/s12011-008-8263-z.View ArticleGoogle Scholar
- Akbaraly TN, Arnaud J, Rayman MP, Hininger-Favier I, Roussel A-M, Berr C, Fontbonne A: Plasma selenium and risk of dysglycemia in an elderly French population: Results from the prospective Epidemiology of Vascular Ageing Study. Nutrition & metabolism. 2010, 7: 21-View ArticleGoogle Scholar
- Bleys J, Navas-Acien A, Guallar E: Serum Selenium and Diabetes in U.S. Adults. Diabetes Care. 2007, 30: 829-834. 10.2337/dc06-1726.View ArticleGoogle Scholar
- Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, Cappuccio FP, Ceriello A, Reid ME: Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007, 147: 217-223.View ArticleGoogle Scholar
- Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA: Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009, 301: 39-51. 10.1001/jama.2008.864.View ArticleGoogle Scholar
- Laclaustra M, Navas-Acien A, Stranges S, Ordovas JM, Guallar E: Serum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004. Environ Health Perspect. 2009, 117: 1409-1413.View ArticleGoogle Scholar
- Hercberg S, Bertrais S, Czernichow S, Noisette N, Galan P, Jaouen A, Tichet J, Briancon S, Favier A, Mennen L, Roussel AM: Alterations of the lipid profile after 7.5 years of low-dose antioxidant supplementation in the SU.VI.MAX Study. Lipids. 2005, 40: 335-342. 10.1007/s11745-006-1391-3.View ArticleGoogle Scholar
- Dhingra S, Bansal M: Hypercholesterolemia and LDL receptor mRNA expression: modulation by selenium supplementation. Biometals. 2006, 19: 493-501. 10.1007/s10534-005-5393-z.View ArticleGoogle Scholar
- Dhingra S, Bansal M: Attenuation of LDL receptor gene expression by selenium deficiency during hypercholesterolemia. Mol Cell Biochem. 2006, 282: 75-82. 10.1007/s11010-006-1266-1.View ArticleGoogle Scholar
- Dhingra S, Bansal M: Modulation of hypercholesterolemia-induced alterations in apolipoprotein B and HMG-CoA reductase expression by selenium supplementation. Chem Biol Interact. 2006, 161: 49-56. 10.1016/j.cbi.2006.02.008.View ArticleGoogle Scholar
- Sengupta A, Carlson BA, Hoffmann VJ, Gladyshev VN, Hatfield DL: Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism. Biochem Biophys Res Commun. 2008, 365: 446-452. 10.1016/j.bbrc.2007.10.189.View ArticleGoogle Scholar
- Zhang L, Gail MH, Wang YQ, Brown LM, Pan KF, Ma JL, Amagase H, You WC, Moslehi R: A randomized factorial study of the effects of long-term garlic and micronutrient supplementation and of 2-wk antibiotic treatment for Helicobacter pylori infection on serum cholesterol and lipoproteins. Am J Clin Nutr. 2006, 84: 912-919.Google Scholar
- Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001, 345: 1583-1592. 10.1056/NEJMoa011090.View ArticleGoogle Scholar
- Gao S, Jin Y, Hall KS, Liang C, Unverzagt FW, Ma F, Cheng Y, Shen J, Cao J, Matesan J: Selenium level is associated with apoE epsilon4 in rural elderly Chinese. Public Health Nutr. 2009, 12: 2371-2376. 10.1017/S1368980009005102.View ArticleGoogle Scholar
- Wang XD, Vatamaniuk MZ, Wang SK, Roneker CA, Simmons RA, Lei XG: Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice. Diabetologia. 2008, 51: 1515-1524. 10.1007/s00125-008-1055-3.View ArticleGoogle Scholar
- Hughes K, Choo M, Kuperan P, Ong CN, Aw TC: Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore. Atherosclerosis. 1998, 136: 25-31. 10.1016/S0021-9150(97)00180-9.View ArticleGoogle Scholar
- Faure P, Barclay D, Joyeux-Faure M, Halimi S: Comparison of the effects of zinc alone and zinc associated with selenium and vitamin E on insulin sensitivity and oxidative stress in high-fructose-fed rats. J Trace Elem Med Biol. 2007, 21: 113-119. 10.1016/j.jtemb.2006.12.005.View ArticleGoogle Scholar
- Tobin MD, Sheehan NA, Scurrah KJ, Burton PR: Adjusting for treatment effects in studies of quantitative traits: antihypertensive therapy and systolic blood pressure. Stat Med. 2005, 24: 2911-2935. 10.1002/sim.2165.View ArticleGoogle Scholar
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