![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
The Johns Hopkins Medical Institutions, Baltimore, MD; * Longitudinal Studies Section, Clinical Research Branch National Institute on Aging, Baltimore, MD; and Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA
2 To whom correspondence should be addressed. E-mail: rdsemba{at}jhmi.edu.
ABSTRACT
Selenium and the carotenoids play an important role in antioxidant defenses and in the redox regulation involved in inflammation. We tested the hypothesis that low selenium and carotenoids predict mortality in older women living in the community. Women who were enrolled in the Women's Health and Aging Studies I and II in Baltimore, MD (n = 632; 70–79 y old) had serum selenium and carotenoids measured at baseline and were followed for mortality over 60 mo. Median (minimum, maximum) serum selenium and carotenoids were 1.53 (0.73, 2.51) µmol/L and 1.67 (0.13, 9.10) µmol/L; 14.1% of the women died. The 5 major causes of death were heart disease (32.6%), cancer (18.0%), stroke (9.0%), infection (6.7%), and chronic obstructive pulmonary disease (5.6%). Adjusting for age, education, smoking, BMI, poor appetite, and chronic diseases, higher serum selenium [hazard ratio (HR) 0.71, 95% CI 0.56–0.90/1 SD increase in loge selenium; P = 0.005] and higher serum total carotenoids (HR 0.77, 95% CI 0.64–0.84/1 SD increase in loge total carotenoids; P = 0.009) were associated with a lower risk of mortality. Women living in the community who have higher serum selenium and carotenoids are at a lower risk of death.
KEY WORDS: • aging • carotenoids • mortality • selenium • women
Antioxidant nutrients, including selenium and the carotenoids (
-carotene, ß-carotene, ß-cryptoxanthin, lutein + zeaxanthin, and lycopene), are important components of the antioxidant defense system. Selenium is a component of selenoproteins that include glutathione peroxidase, thioredoxin reductase, selenoprotein P, and iodothyroxine deiodinases (1). Carotenoids are found primarily in fruits and vegetables and act as antioxidants (2), modulators of immune responses (3), and possible regulators of gene expression (4). Selenium is found in a wide variety of plant and animal foods, but the selenium content depends upon the amount of selenium in the soil in which the plants were grown or in the animal feed. Both selenium and carotenoids play an important role in the redox regulation involved in inflammation (5). Increased oxidative stress and inflammation have been implicated in the pathological processes that are common with aging, including endothelial dysfunction and cardiovascular disease (1,6). Fruits and vegetables are the richest dietary sources of antioxidants, and there is increasing evidence that a diet high in antioxidants may be protective against oxidative stress, inflammation, cardiovascular disease, and mortality (7–9).
In some studies, low serum selenium and carotenoids were each associated with cancer, cardiovascular disease, and mortality among older adults (10–12). In a case-control study performed in Belgium, low serum selenium concentrations were independently associated with cancer mortality among men but not women (10). Low activity of glutathione peroxidase 1, a major selenoenzyme, was associated with increased risk of cardiovascular events among adults with suspected coronary artery disease (11). In the MacArthur Study of Successful Aging, low serum ß-carotene concentrations combined with high IL-6 and C-reactive protein (CRP) concentrations were associated with increased mortality among men but not women (12). The relation between low carotenoids or low selenium and mortality among women has not been well characterized.
We hypothesized that low serum selenium and low serum carotenoid concentrations are independent predictors of mortality among older women living in the community. To address these hypotheses, we conducted a prospective study to examine the relation between serum selenium and carotenoids and mortality among women enrolled in the Women's Health and Aging Studies I and II.
SUBJECTS AND METHODS
Subjects.
Subjects in this study were women, aged 70–79 y, who participated in the Women's Health and Aging Studies (WHAS) I and II, two complementary, population-based studies designed to evaluate the causes and course of physical disability in older women living in the community. Details of the study methods and sampling design of the WHAS studies were published elsewhere (13,14). Participants in WHAS I were recruited from an age-stratified random sample of women 
65 y old selected from Medicare enrollees residing in 12 contiguous zip code areas in Baltimore, MD (13). Women were screened to identify self-reported physical disability that was categorized into 4 domains by report of difficulty with tasks in the following areas: 1) mobility, 2) upper extremity function, 3) higher functioning household management, and 4) self-care. WHAS I enrolled the one-third most disabled women 65 y old, i.e., those with disability in 2 domains. Of the 1409 women who met study eligibility criteria, 1002 agreed to participate in the study in 1992. Sociodemographic and reported health characteristics did not differ between eligible participants and those who declined (13). Standardized questionnaires were administered in the participant's home by trained interviewers. Two weeks later, a trained registered nurse conducted an examination of each study participant in her home, using a standardized protocol that included physical performance measures and a standardized physical examination; 
75% of women also consented to phlebotomy performed during a separate visit by a trained phlebotomist.
WHAS II was specifically designed to be a companion study for WHAS I and included a cohort of women, aged 70–79 y, selected to be representative of the two-thirds least disabled women living in the community. Participants were selected via age-stratified random samples from the same sampling frame as in WHAS I and were screened using the same 4 domains of physical function. Eligible women had either no disability or disability in only 1 domain. In 1994, 880 women were eligible for WHAS II, and 436 consented to participate. Those agreeing were more highly educated and reported more diseases than those who refused, but did not differ significantly in disability characteristics. An interview standardized to that performed in WHAS I was administered at the Johns Hopkins Functional Status Laboratory. Trained technicians then conducted a standardized examination that included a physical examination and physical performance measures. Phlebotomy was performed in 93% of WHAS II participants by a trained phlebotomist following the same protocol as that used in WHAS I. Demographic characteristics, self-rated health, and information about appetite and eating were measured in the WHAS questionnaires. Chronic diseases were adjudicated by WHAS co-investigators based on the questionnaire, physical examination, and physician contact (13). Vital status was determined through follow-up interviews with proxies, obituaries, and matching with the National Death Index over a 5-y period. The Johns Hopkins University institutional review board approved the study protocol, and written informed consent was obtained from all participants.
For comparability with the WHAS II cohort age range of 70–79, we included women from WHAS I only if they were also in this age range, yielding 399 participants in WHAS I and 430 participants in WHAS II. Weights were calculated to adjust for sampling probability and response rates. This pooled sample was used in published studies of the association between mobility disability and insulin-like growth factor (15), obesity and frailty (16), and undernutrition and frailty (17).
Laboratory Analysis.
Blood samples were obtained from nonfasting subjects by venipuncture between 0900 and 1400 h. Processing, division into aliquots, and freezing were carried out at the Core Genetics Laboratory of The Johns Hopkins University School of Medicine. Blood samples were delivered to Quest Diagnostics Laboratories on the day of blood drawing for assays conducted by this commercial laboratory. Serum selenium and carotenoids were measured in the laboratory of one of the investigators (R.D.S.) using additional sample aliquots that were stored at –80°C. Serum selenium was measured by graphite furnace atomic absorption spectrometry using a Perkin Elmer AAnalyst 600 with Zeeman background correction. For selenium, samples were diluted 1:4 with a Triton-X (Sigma Chemical) and nitric acid solution (Fisher Scientific); the matrix modifier was a palladium and magnesium nitrate solution (both Perkin Elmer). The instrument was calibrated daily using SeroNormTM Trace Elements Serum Level 1 (Accurate Chemical and Scientific). Serum -carotene, ß-carotene, ß-cryptoxanthin, lutein + zeaxanthin, lycopene, and -tocopherol were measured using HPLC (18). Total carotenoids were calculated as the sum of -carotene, ß-carotene, ß-cryptoxanthin, lutein + zeaxanthin, and lycopene in µmol/L. Within- and between-assay CV were 5.8 and 4.8% for selenium, 10.7 and 23.9% for -carotene, 7.0 and 19.1% for ß-carotene, 4.7 and 8.5% for ß-cryptoxanthin, 4.1 and 4.6% for lutein + zeaxanthin, 10.0 and 14.0% for lycopene, and 4.1 and 9.7% for -tocopherol. All samples were assayed without knowledge of their source.
Statistical Analysis. Probability weights specific to WHAS I and II were used in the analysis to make inferences about community-dwelling women aged 70–79 y based on our study sample. The procedures used to calculate the weights for the WHAS samples are described elsewhere (13,15). Descriptive statistics were used to characterize the study population and give the distribution of biochemical measurements of micronutrients. The measurements of carotenoids and selenium had a skewed distribution; they were analyzed using loge transformation and are presented as geometric means and 95% CI. Univariate and multivariate logistic regression was used to examine the relation between selenium or carotenoids and mortality, with sequential models adjusting for demographic, chronic disease, and inflammation variables that were significant (P < 0.05) in univariate analyses. To assess the relative strength of associations of mortality with selenium and carotenoids, odds ratios and 95% CI associated with a 1 SD increase in loge selenium and loge total carotenoids were reported. A serum creatinine concentration >14 mg/L was considered consistent with renal disease (13).
Cox proportional hazards models were used to examine the survival probability over 5 y of follow-up for women in each quartile of serum selenium or carotenoids, or as these respective analyses per SD increase. Quartiles of selenium were defined as <1.38, 1.38 to 1.52, 1.53 to 1.67, and 1.68 µmol/L. Quartiles of serum total carotenoids were defined as <1.038, 1.038 to 1.452, 1.453 to 1.994, and 1.995 µmol/L. Survival curves were compared using the log rank test. The statistical programs used were SAS (SAS Institute) (19) for data management and Stata (Stata Corporation) (20) for weighted analyses. P 
0.05 was considered significant.
RESULTS
Serum selenium and carotenoid concentrations were measured at baseline for 632 of the 829 women in WHAS I and II who were 70–79 y old. Their geometric mean serum total carotenoid concentration was 1.630 µmol/L and that of selenium was 1.52 µmol/L. During 60 mo of follow-up, 89 of 632 women (14.1%) died. The main causes of death among the women who died were cardiovascular disease (32.6%), cancer (18.0%), stroke (9.0%), infection (6.7%), chronic obstructive pulmonary disease (5.6%), accidents (3.4%), diabetes mellitus (2.0%), renal disease (2.0%), other (13.5%), and unknown (6.7%). The demographic and disease characteristics of women who died and women who did not die during 60 mo of follow-up are shown in (Table 1). Women who died were older and more likely to be black, current smokers, have a BMI <18.5 kg/m2, a fair-to-poor appetite, diabetes mellitus, cardiovascular disease, renal disease, and lower serum selenium and total carotenoid concentrations than women who survived. Geometric mean serum concentrations in women who died compared with those who survived were as follows: -carotene, 0.059 and 0.0849 (P < 0.0001); ß-carotene, 0.357 and 0.391 (P = 0.35); ß-cryptoxanthin, 0.097 and 0.120 (P = 0.018); lycopene, 0.452 and 0.575 (P = 0.002); and lutein + zeaxanthin 0.326 and 0.371 (P = 0.07) µmol/L, respectively. After excluding women who were current smokers, geometric mean total carotenoid and selenium levels were 1.52 and 1.75 µmol/L (P = 0.039) among women who died and 1.43 and 1.54 µmol/L (P = 0.003), respectively, among women who survived.
|
2 test for linear trend (P = 0.003). Crude and adjusted Cox proportional hazards models for serum selenium and 5-y all-cause mortality are presented (Table 2). Selenium was significantly associated with mortality in a Cox proportional hazards model after adjusting for age and education (model 2) and even after adjusting for age, education, current smoking, alcohol use, BMI, fair-to-poor appetite, diabetes mellitus, cardiovascular disease, and renal disease (model 3). In this final model, BMI <18.5 kg/m2 and diabetes mellitus were also significantly associated with mortality.
|
|
2 test for linear trend (P = 0.039). Crude and adjusted Cox proportional hazards models for serum total carotenoids and 5-y all-cause mortality are presented (Table 3). Total carotenoids were significantly associated with mortality in a Cox proportional hazards model after adjusting for age and education (model 2) and even after adjusting for age, education, current smoking, alcohol use, BMI, fair-to-poor appetite, diabetes mellitus, cardiovascular disease, and renal disease (model 3). In this final model, age, BMI <18.5 kg/m2, diabetes mellitus, and renal disease were also significantly associated with mortality.
|
DISCUSSION
The present study shows that both low serum selenium and low serum total carotenoids are independent predictors of all-cause 5-y mortality among older women living in the community.
Previous studies suggested that low serum selenium concentrations are predictive of cancer mortality among men but not women (10,21). In a study performed in the Netherlands, men with serum selenium concentrations in the lowest quintile (<1.28 µmol/L) at baseline had an increased risk of death from cancer (relative risk 2.7, 95% CI 1.2–6.2) (21). In a case-control study conducted in Norway, low serum selenium concentrations among men and women were associated with an increased risk of cancer mortality (22). Low serum selenium concentrations may be related to cardiovascular mortality (23), but this relation has not been consistent among studies (24). There may be large differences in selenium levels, depending upon the population being studied (25). Among children and adults with HIV infection, low serum selenium was an independent predictor of disease progression and mortality (26–28).
The present study shows that low total carotenoid concentrations were predictive of mortality; to our knowledge, this is the first study to show that total carotenoids are an independent predictor for mortality among women. Previous observational studies examined the relation between serum ß-carotene, one of the 6 major dietary carotenoids, and mortality; this relation has not been consistent (29). Low serum ß-carotene concentrations were associated with increased mortality among men after combining ß-carotene levels with high IL-6 and CRP concentrations (12). In the Japan Collaborative Cohort Study of 39,140 people, ages 40–79 y, a lower risk of death from lung cancer was significant or of marginal significance for the highest serum concentrations of -carotene, ß-carotene, ß-cryptoxanthin, zeaxanthin + lutein, canthaxanthin, total carotenoids, vitamin E, and total cholesterol, compared with the lowest concentrations (30).
The underlying biological mechanism by which low selenium and carotenoids could contribute to an increased risk of mortality may be related to increased oxidative stress and inflammation. A low-grade inflammatory state is common among older adults and is characterized by increased concentrations of cytokines and acute phase proteins (6,31). The age-related proinflammatory state is associated with the metabolic syndrome, atherosclerosis, cardiovascular disease, and cerebrovascular disease (6,31). Serum carotenoids are considered the best biological marker for fruit and vegetable intake (32). Recent studies suggest that a high intake of fruits and vegetables reduces biomarkers of inflammation such as CRP, IL-6, and IL-18 (8,9,33) and protects against cardiovascular disease (34,35). The findings from the present study are also consistent with recent observations that the Mediterranean diet, characterized by a higher intake of fruits, vegetables, and nuts, is associated with decreased mortality in older men and women (36,37). A limitation of the present study is that information on dietary intake was not collected.
Low serum selenium was implicated in the pathogenesis of atherosclerosis through its effects on arachidonic acid metabolism (25). In the Uppsala Longitudinal Study of Adult Men, high serum selenium levels were predictive of lower urinary F2 isoprostane concentrations, a biomarker of lipid peroxidation and oxidative stress (38). Another possible mechanism by which low selenium may compromise health could be through the effect of low selenium on the synthesis and activity of deiodinase, the enzyme that transforms thyroxine into the biologically active triiodothyronine (39). The thyroid contains the highest tissue concentration of selenium in the human body (39). Additionally, low serum selenium levels were associated with low triiodothyronine:thyroxine ratios among older euthyroid adults (40).
In conclusion, low serum selenium and total carotenoid concentrations are associated with an increased risk of death among older women living in the community. This work provides some early insight into the relation between antioxidant nutrients and mortality among older women. Further work is required to validate and extend these findings in other populations so that appropriate groups can be targeted for interventions to reduce mortality in older populations.
FOOTNOTES
1 Supported by the National Institute on Aging Grant R01 AG11703-01A1, National Institutes of Health-National Center for Research Resources, Outpatient Department-General Clinical Research Center grant RR00722, R01 AI41956, NIA Contract N01-AG12112, and R01 AG027012-01. 
Manuscript received 30 August 2005. Initial review completed 16 September 2005. Revision accepted 17 October 2005.
LITERATURE CITED
1. Klein EA. Selenium: epidemiology and basic science. J Urol. 2004;171:S50–3.[Medline]
2. Mecocci P, Polidori MC, Troiano L, Cherubini A, Cecchetti R, Pini G, Straatman M, Monti D, Stahl W, et al. Plasma antioxidants and longevity: a study on health centenarians. Free Radic Biol Med. 2000;28:1243–8.[Medline]
3. Hughes DA. Carotenoids and immune responses. In: Krinsky NI, Mayne ST, Sie H, editors. Carotenoids in health and disease. Marcel Dekker: New York; 2004, p. 503–17.
4. Sharoni Y, Danilenko M, Dubi N, Ben-Dor A, Levy J. Carotenoids and transcription. Arch Biochem Biophys. 2004;430:89–96.[Medline]
5. McEligot AJ, Yang S, Meyskens FL Jr. Redox regulation by intrinsic species and extrinsic nutrients in normal and cancer cells. Annu Rev Nutr. 2005;25:261–95.[Medline]
6. Morley JE, Baumgartner RN. Cytokine-related aging process. J Gerontol A Biol Sci Med Sci. 2004;59:M924–9.
7. Lopes HF, Martin KL, Nashar K, Morrow JD, Goodfriend TL, Egan BM. DASH diet lowers blood pressure and lipid-induced oxidative stress in obesity. Hypertension. 2003;41:422–30.
8. Chrysohoou C, Panagiotakos DB, Pitsavos C, Das UN, Stefanadis C. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the Attica Study. J Am Coll Cardiol. 2004;44:152–8.
9. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, D'Armiento M, D'Andrea F, Giugliano D. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA. 2004;292:1440–6.
10. Kornitzer M, Valente F, De Bacquer D, Neve J, De Backer G. Serum selenium and cancer mortality: a nested case-control study within an age- and sex-stratified sample of the Belgian adult population. Eur J Clin Nutr. 2004;58:98–104.[Medline]
11. Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, Smieja M, Cambien F, Meyer J, Lackner KF for the AtheroGene Investigators. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med. 2003;349:1605–13.
12. Hu P, Reuben DB, Crimmins EM, Harris TB, Huang MH, Seeman TE. The effects of serum beta-carotene concentration and burden of inflammation on all-cause mortality risk in high-functioning older persons: MacArthur Studies of Successful Aging. J Gerontol A Biol Sci Med Sci. 2004;59:849–54.[Medline]
13. Guralnik JM, Fried LP, Simonsick EM, Kasper D, Lafferty ME. The Women's Health and Aging Study: Health and social characteristics of older women with disability. Bethesda (MD): National Institute on Aging. NIH Publication No. 95-4009; 1995.
14. Fried LP, Bandeen-Roche K, Kasper JD, Guralnik JM. Association of comorbidity with disability in older women: the Women's Health and Aging Study. J Clin Epidemiol. 1999;52:27–37.[Medline]
15. Cappola AR, Bandeen-Roche K, Wand GS, Volpato S, Fried LP. Association of IGF-1 levels with muscle strength and mobility in older women. J Clin Endocrinol Metab. 2001;86:4139–46.
16. Blaum CS, Xue QL, Michelon E, Semba RD, Fried LP. The association between obesity and the frailty syndrome in older women: the Women's Health and Aging Studies. J Am Geriatr Soc. 2005;53:927–34.[Medline]
17. Michelon E, Blaum C, Semba RD, Xue QL, Ricks MO, Fried LP. Vitamin and carotenoid status in older women: associations with the frailty syndrome. J Gerontol A Biol Sci Med Sci. In press 2005.
18. Sowell AL, Huff DL, Yeager PR, Caudill SP, Grunter EQ. Retinol, alpha-tocopherol, lutein/zenxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection. Clin Chem. 1994;40:411–6.
19. SAS Institute. SAS languages and procedures: introduction, Version 6. Cary (NC): SAS Institute; 1990.
20. Stata Corporation. Stata User's Guide. College Station (TX): Stata Press; 1996.
21. Kok FJ, de Bruijn AM, Hofman A, Vermeeren R, Valkenburg HA. Is serum selenium a risk factor for cancer in men only? Am J Epidemiol. 1987;125:12–6.
22. Ringstad J, Jacobsen BK, Tretli S, Thomassen Y. Serum selenium concentration associated with risk of cancer. J Clin Pathol. 1988;41:454–7.
23. 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. 1992;2:175–9.
24. Kok FJ, de Bruijn AM, Vermeeren R, Hofman A, van Laar A, de Bruin M, Hermus RJ, Valkenburg HA. Serum selenium, vitamin antioxidants, and cardiovascular mortality: a 9-year follow-up study in the Netherlands. Am J Clin Nutr. 1987;45:462–8.
25. Alissa EM, Bahijri SM, Ferns GA. The controversy surrounding selenium and cardiovascular disease: a review of the evidence. Med Sci Monit. 2003;9:RA9–18.[Medline]
26. Baum MK, Shor-Posner G, Lai S, Zhang G, Lai H, Fletcher MA, Sauberlich H, Page JB. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;15:370–4.[Medline]
27. Campa A, Shor-Posner G, Indacochea F, Zhang G, Lai H, Asthana D, Scott GB, Baum MK. Mortality risk in selenium-deficient HIV-positive children. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20:508–13.[Medline]
28. Kupka R, Msamanga GI, Spiegelman D, Morris S, Mugusi F, Hunter DJ, Fawzi WW. Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania. J Nutr. 2004;134:2556–60.
29. Fletcher AE, Breeze E, Shetty PS. Antioxidant vitamins and mortality in older persons: findings from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community. Am J Clin Nutr. 2003;78:999–1010.
30. Ito Y, Wakai K, Suzuki K, Tamakoshi A, Seki N, Ando M, Nishino Y, Kondo T, Watanabe Y, et al. Serum carotenoids and mortality from lung cancer: a case-control study nested in the Japan Collaborative Cohort (JACC). Cancer Sci. 2003;94:57–63.[Medline]
31. Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM, Longo DL. The origins of age-related proinflammatory state. Blood. 2005;105:2294–9.
32. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington (DC): National Academy Press; 2000.
33. Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE, Hu FB. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004;80:1029–35.
34. Liu S, Manson JE, Lee IM, Cole SR, Hennekens CH, Willett WC, Buring JE. Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. Am J Clin Nutr. 2000;72:922–8.
35. Bazzano LA, He J, Ogden LG, Loria CM, Vupputuri S, Myers L, Whelton PK. Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Am J Clin Nutr. 2002;76:93–9.
36. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348:2599–608.
37. Knoops KTB, de Groot LCPGM, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA. 2004;292:1433–9.
38. Helmersson J, Ärnlöv J, Vessby B, Larsson A, Alfthan G, Basu S. Serum selenium predicts levels of F2-isoprostanes and prostaglandin F2 in a 27 year follow-up study of Swedish men. Free Radic Res. 2005;39:763–70.[Medline]
39. Beckett GJ, Arthur JR. Selenium and endocrine systems. J Endocrinol. 2005;184:455–65.
40. Olivieri O, Girelli D, Stanzial AM, Rossi L, Bassi A, Corrocher R. Selenium, zinc, and thyroid hormones in healthy subjects: low T3/T4 ratio in the elderly is related to impaired selenium status. Biol Trace Elem Res. 1996;51:31–41.[Medline]
This article has been cited by other articles:
|
|
 |
|
  M. G. Boosalis The Role of Selenium in Chronic Disease Nutr Clin Pract, April 1, 2008; 23(2): 152 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sharafkhaneh, S. Velamuri, V. Badmaev, C. Lan, and N. Hanania Review: The potential role of natural agents in treatment of airway inflammation Therapeutic Advances in Respiratory Disease, December 1, 2007; 1(2): 105 - 120. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Meplan, L. K. Crosley, F. Nicol, G. J. Beckett, A. F. Howie, K. E. Hill, G. Horgan, J. C. Mathers, J. R. Arthur, and J. E. Hesketh Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study) FASEB J, October 1, 2007; 21(12): 3063 - 3074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lauretani, R. D Semba, S. Bandinelli, A. L Ray, J. M Guralnik, and L. Ferrucci Association of low plasma selenium concentrations with poor muscle strength in older community-dwelling adults: the InCHIANTI Study Am. J. Clinical Nutrition, August 1, 2007; 86(2): 347 - 352. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
