Skip to main content Accessibility help
Hostname: page-component-558cb97cc8-6jfzc Total loading time: 1.414 Render date: 2022-10-07T06:42:10.527Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "displayNetworkTab": true, "displayNetworkMapGraph": true, "useSa": true } hasContentIssue true

Nutritional status of selenium in Alzheimer's disease patients

Published online by Cambridge University Press:  01 December 2009

Bárbara Rita Cardoso*
PRONUT (Program of Applied Human Nutrition)-FSP/FCF/FEA, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Avenue Professor Lineu Prestes, 580 – Bloco 14, 05508-900São Paulo, Brazil
Thomas Prates Ong
PRONUT (Program of Applied Human Nutrition)-FSP/FCF/FEA, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Avenue Professor Lineu Prestes, 580 – Bloco 14, 05508-900São Paulo, Brazil
Wilson Jacob-Filho
Division of Geriatrics, University of São Paulo Medical School (USP), São Paulo, Brazil
Omar Jaluul
Division of Geriatrics, University of São Paulo Medical School (USP), São Paulo, Brazil
Maria Isabel d'Ávila Freitas
Division of Neurology, University of São Paulo Medical School (USP), São Paulo, Brazil
Silvia M. Franciscato Cozzolino
Faculty of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, Brazil
*Corresponding author: Bárbara Rita Cardoso, fax +55 11 3091 3657, email
Rights & Permissions[Opens in a new window]


Studies have shown that various antioxidants are decreased in different age-related degenerative diseases and thus, oxidative stress would have a central role in the pathogenesis of many disorders that involve neuronal degeneration, including Alzheimer's disease (AD). The present study aimed to assess the nutritional status of Se in AD patients and to compare with control subjects with normal cognitive function. The case–control study was carried out on a group of elderly with AD (n 28) and compared with a control group (n 29), both aged between 60 and 89 years. Se intake was evaluated by using a 3-d dietary food record. Se was evaluated in plasma, erythrocytes and nails by using the method of hydride generation atomic absorption spectroscopy. Deficient Se intake was largely observed in the AD group. AD patients showed significantly lower Se levels in plasma, erythrocytes and nails (32·59 μg/l, 43·74 μg/l and 0·302 μg/g) when compared with the control group (50·99 μg/l, 79·16 μg/l and 0·400 μg/g). The results allowed us to suggest that AD has an important relation with Se deficiency.

Short Communication
Copyright © The Authors 2009

Alzheimer's disease (AD) is characterised clinically by progressive loss of memory and cognition, pathologically by senile plaques, neurofibrillary tangles and synapse loss(Reference Butterfield and Lauderback1). Oxidative stress plays a central role in this disease, and it is the first event that precedes the disease, and it is manifested by increase in protein oxidation, lipid peroxidation, DNA and mRNA oxidation and formation of reactive oxygen species (ROS) and reactive nitrogen species in the brain(Reference Lovell and Markesbery2).

The nervous system is particularly vulnerable to the deleterious effects of ROS and reactive nitrogen species, since it has the highest amount of oxygen to produce energy, and the brain contains high concentrations of PUFA that are highly susceptible to lipid peroxidation(Reference Mariani, Polidori and Cherubini3). Indeed, senile plaques and neurofibrillary tangles are directly associated with oxidative damage in AD, since this peptides can produce ROS(Reference Chauhan and Chauhan4, Reference Crouch, Harding and White5).

Cells have mechanisms to prevent or repair oxidative damage caused by ROS and reactive nitrogen species. These include antioxidant molecules and enzymes, such as glutathione peroxidase(Reference Crouch, Harding and White5). However, the brain has a relatively deficient antioxidant system, which contributes to its susceptibility to oxidative damage(Reference Mariani, Polidori and Cherubini3).

Se is an essential nutrient in the diet due to the requirement for selenocysteine in some selenoproteins. This trace element is known to provide protection from ROS-induced cell damage, and the proposed mechanisms mainly invoke the functions of glutathione peroxidase family and selenoprotein P(Reference Chen and Berry6).

Although some studies have shown the increase of oxidative stress in AD patients, there is a lack of information about the importance of Se as part of antioxidant enzymes in this disease. In this context, the present study aimed to evaluate nutritional status of Se in AD patients.



Twenty-eight (eleven male and seventeen female) elderly diagnosed with probable AD (AD group) according to the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria(Reference McKhann, Drachman and Folstein7) were included in the present study. These patients attended at the Geriatric Cognitive Ambulatory or at the Center of Reference in Cognitive Disorders, both at the Hospital das Clínicas of the São Paulo University Medical School (São Paulo, Brazil).

Twenty-nine (ten male and nineteen female) healthy volunteer elderly with normal cognitive function, mini-mental state examination ( ≥ 20)(Reference Folstein, Folstein and McHugh8, Reference Seabra, Concílio and Villarea9) sex-matched with those in the AD group, who attended at the Multidisciplinary Group of Assistance to the Aged Ambulatory at the Hospital das Clínicas of the São Paulo University Medical School (São Paulo, Brazil), were included in the control group (C group).

Participants were selected for the study according to the following inclusion parameters: aged 60 years or older; absence of acute inflammation, infection, fever, diarrhoea, cancer, diabetes, autoimmune disease and vitamin and mineral supplement intake. AD patients should have an active caregiver.

The present study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving human subjects/patients were approved by Ethics Committee of the Faculty of Pharmaceutical Sciences at the University of São Paulo (no. 455) and by the Ethics Committee of the Hospital das Clínicas of the University of São Paulo Medical School (no. 0710/08). Written informed consent was obtained from participants of the C group and caregivers of AD patients.

Selenium intake

Se intake was evaluated by using a 3-d (2 weekdays and 1 weekend day) dietary food record, up to 7 d before the blood sample was drawn. AD patients and their caregivers were requested to register what they had eaten. Se intake was measured by using NutWin software (version 2.5; EPM-UNIFESP, São Paulo, Brazil).

Software database was supplied with Se data from the study of Ferreira et al. (Reference Ferreira, Gomes and Bellato10). Items consumed by the participants, which were not originally listed in this database, were included in the software as data obtained from food composition tables(Reference Philippi11) or food labels provided by participants.

Se intake was adjusted by the energy, according to Willet(Reference Willet12), using linear regression (linear regression of nutrient intake on total energy intake) and addition of a constant (mean energetic intake of the group). Se intake was compared with dietary reference intake recommendations for the particular age and sex group(13).

Biochemical assays

Se concentration was determinate in plasma, erythrocyte and nail samples by using hydride generation atomic absorption spectroscopy(Reference Gonzaga14).

Plasma and erythrocytes were obtained from a fasting, morning blood sample. Toenails and fingernails samples were collected by the participants after 20 d of nails growth without nail polish, up to 20 d before the blood sample was drawn.

All reagents had analytical grade or higher purity from Merck. Nanopure water was used to prepare all solutions and to dilute the samples.

The standard reference material Seronorm® was analysed for testing the accuracy and precision of the analytical technique.

Statistical analysis

All statistical analyses were carried out using the Statistical Package for the Social Sciences software, version 17.0, for Windows (SPSS, Chicago, IL, USA).

The results were showed as means and standard deviations.

Variables distribution was evaluated by using Kolmogorov–Smirnov test. Differences between AD and C groups were analysed with Student's t test. Pearson's correlation coefficients were used to estimate correlations between nutritional parameters and between cognitive evaluation and nutritional status.

A P value of 0·05 was considered statistically significant.


In the present study, twenty-eight elderly (39·3 % men and 60·7 % women) in the AD group and twenty-nine healthy elderly (34·5 % men and 65·5 % women) in the C group were evaluated. There was no sex difference between the two groups; however, the mean age of the AD group was 80·6 (sd 5·7) years, statistically different from the C group, which showed a mean age of 71·2 (sd 6·2) years (P < 0·05). Therefore, given that age might influence Se concentrations, correlation analysis between Se parameters and age was performed, but correlations were not observed (P>0·05).

Se levels in plasma and erythrocyte were significantly higher in the C group, although in both groups some participants showed values below the normal range(Reference Ortuño, Ros and Periago15). There is no normal values range for Se level in nails, but higher values in the C group were observed when compared with the AD group (Table 1).

Table 1 Selenium concentrations in plasma (μg/l), erythrocytes (μg/l) and nails (μg/g), and selenium content in diet (μg/d) of elderly with Alzheimer's disease (AD) and those in the control (C) group

* P < 0·005.

Higher Se intake was observed in the C group, and it was adequate in 38·5 % of the AD group and in 63 % of the C group (Table 1).


Deficient Se intake was observed in the most of the AD patients, although the dietary reference intake recommendation was only partially achieved by the C group. Since Se content of foods is largely related to the Se content of soil, it is important to reveal that in São Paulo state there is low Se concentration in the soil, and thus high deficiency of this mineral is observed in this population(Reference Cozzolino16).

Assessment of Se intake from the diet has many difficulties, namely the absence of specific food composition tables for this trace element and Se variation in different regions(Reference Combs17Reference Al-Saleh, El-Doush and Billedo19). This is probably the main reason for the lack of studies describing in detail the Se intake in AD patients.

Assessment of Se levels in blood is a useful biomarker of Se status. Plasma is a marker of current exposure, while erythrocytes reflect longer-term nutritional status, due to its incorporation in erythrocyte synthesis, which have a half-life of 120 d(Reference Thomson20, Reference Navarro-Alarcon and Cabrera-Vique21). Nail clippings are considered a superior marker of Se status because they provide a time-integrated measure of exposure of up to a year(Reference Satia, King and Morris22). Some authors suggest that Se status should be assessed by determination of two or more biomarkers, in order to avoid possible misunderstandings arising from the hierarchy of importance of selenoproteins(Reference Thomson20, Reference Slotnick and Nriagu23). According to these authors, our assessment of Se status covered different periods of exposure, allowing us to verify Se intake in different periods.

There is a lack of studies correlating Se status and AD, and most of them only assessed Se levels in plasma or whole blood. The studies about Se in AD patients are inconclusive. Ceballos-Picot et al. (Reference Ceballos-Picot, Merad-Boudia and Nicole24) observed higher Se plasma and erythrocyte levels in AD patients when compared with the control group. However, Smorgon et al. (Reference Smorgon, Mari and Atti25) assessed the association between micronutrients and cognitive function, and observed that AD patients showed lower plasma Se when compared with control subjects. Other studies noticed that Se levels were positively correlated with cognitive function in elderly subjects, and thus Se deficiency could be a risk factor for AD(Reference Berr, Balansard and Arnaud26Reference Akbaraly, Hininger-Favier and Carrière28). Although the average plasma and erythrocyte Se concentrations in the AD and C groups were below the recommended levels, individual values were significantly different in each group, revealing that AD has an important role in Se deficiency. Confirming these data, Se level in nails was significantly lower in the AD patients when compared with control subjects.

Some studies have shown that Se status decreases slightly in elderly compared with younger adults(Reference Chen, Lai and Wu29Reference Letsiou, Nomikos and Panagiotakos31). It can reflect lower bioavailability, increased requirements, metabolic changes, or a diet limited in energy which may not be sufficiently nutrient dense to provide adequate levels of micronutrients(Reference Arnaud, Akbaralyc and Hininger30, Reference Planas, Conde and Audivert32). In the present study, no significant correlation between Se parameters and age was observed. However, the age difference between the AD and C groups could be a bias in the present study, since nutritional status of Se can decrease with age. Indeed, the present study has a small sample size, and this can limit the interpretation of our data.

The brain is the last organ to be depleted in Se deficiency and, in repletion, it is the first one to establish adequate levels of Se. This preferential treatment suggests the importance of this antioxidant mineral in brain functioning, since it is a main constituent of selenoproteins(Reference Benton33). Glutathione peroxidase is an essential line of defence against free radicals acting against hydrogen peroxide and lipid peroxidation, protecting the brain against oxidative stress, which has a central role in AD. Besides, selenoprotein P, which is synthesised at the cerebral level and protects the brain against oxidative damage, is the most important selenoprotein for cerebral functions(Reference Schweizer, Schomburg and Savaskan34, Reference Crack, Cimdins and Ali35). Thus, Se may affect the rate of disease via protection against ROS, directly as an antioxidant or indirectly by improving metabolism(Reference Staehelin36).

Oxidative stress has an important role in AD aetiology, and it is the earliest event preceding this disease, although some structures formed in AD are related to formation of ROS(Reference Zhu, Lee and Perry37). Thus, the relationship between Se and AD could have two meanings: Se could be depleted owing to the oxidation that accompanies ageing and AD progression; and change in Se levels could be the first event in relation to dietary intake(Reference Luchsinger and Mayeux38). However, as we did not evaluate oxidative stress in the present patients, we cannot establish direct association between Se deficiency and oxidative stress in AD patients. In this way, more studies with larger population are needed in order to find the exactly relationship between Se and AD, since a limitation of the present study was the small number of participants.


AD patients showed lower Se levels, although a Se deficiency was also observed in the C group. Thus, we can suggest that the oxidative stress present in AD has an association with Se deficiency observed in the present AD patients. In order to overcome the problem of Se deficiency in AD patients, new strategies should be developed.


The work was generously supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). The authors made the following contributions to the study: B. R. C., S. M. F. C. and T. P. O. did the study concept and design, analysis and interpretation of data; B. R. C. did the preparation of the manuscript; W. J.-F. and O. J. did the subject recruitment and review of the manuscript; M. I. D. F. did the cognitive function assessment and review of the manuscript. The authors indicate that they have no financial relationships relevant to the present article to disclose.


1Butterfield, DA & Lauderback, CM (2002) Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 32, 10501060.CrossRefGoogle ScholarPubMed
2Lovell, MA & Markesbery, WR (2001) Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid. Arch Neurol 58, 392396.CrossRefGoogle ScholarPubMed
3Mariani, E, Polidori, MC, Cherubini, A, et al. (2005) Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J Chromatogr B Analyt Technol Biomed Life Sci 827, 6575.CrossRefGoogle ScholarPubMed
4Chauhan, V & Chauhan, A (2006) Oxidative stress in Alzheimer's disease. Pathophysiology 13, 195208.CrossRefGoogle ScholarPubMed
5Crouch, PJ, Harding, SME, White, AR, et al. (2008) Mechanisms of Aβ mediated neurodegeneration in Alzheimer's disease. Int J Biochem Cell Biol 40, 181198.CrossRefGoogle Scholar
6Chen, J & Berry, MJ (2003) Selenium and selenoproteins in the brain and brain diseases. J Neurochem 86, 112.CrossRefGoogle ScholarPubMed
7McKhann, G, Drachman, D, Folstein, M, et al. (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease. Neurology 34, 939944.CrossRefGoogle ScholarPubMed
8Folstein, MF, Folstein, SE & McHugh, PR (1975) ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12, 189198.CrossRefGoogle Scholar
9Seabra, MLV, Concílio, GV, Villarea, JB, et al. (1990) Avaliação do teste “Mini-mental state” em voluntários e pacientes brasileiros (Assessment test ‘Mini-Mental State’ in volunteers and patients in Brazil). Rev ABP-APL 12, 129.Google Scholar
10Ferreira, KS, Gomes, J, Bellato, CR, et al. (2002) Concentrações de selênio em alimentos consumidos no Brasil (Selenium content of Brazilian foods). Rev Panam Salud Publica 11, 172177.CrossRefGoogle Scholar
11Philippi, ST (2001) Tabela de Composição de Alimentos: suporte para decisão nutricional (Adapted food pyramid: a guide for a right food choice). São Paulo: ANVISA, FINATEC/NUT-UnB.Google Scholar
12Willet, WC (1998) Nutritional Epidemiology, 2nd ed.New York: Oxford University Press.CrossRefGoogle Scholar
13IOM – Institute of Medicine (2002) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: The National Academy Press.Google Scholar
14Gonzaga, IB (2002) Avaliação nutricional relativa ao selênio em crianças com dieta enriquecida de castanha-do-Brasil (Bertholletia excelsa, L.) (Selenium nutritional status in children with diet enriched with Brazil nut (Bertholletia excelsa, L.)). PhD Thesis, University of São Paulo..Google Scholar
15Ortuño, J, Ros, G, Periago, MJ, et al. (1997) Importancia nutricional del selénio (Nutritional importance of selenium). Arc Latinoam Nutr 47, 613.Google Scholar
16Cozzolino, SMF (2007) Deficiências de minerais (Mineral deficiencies). Estudos Avançados 21, 119126.CrossRefGoogle Scholar
17Combs, GF (2001) Selenium in global food systems. Br J Nutr 85, 517547.CrossRefGoogle ScholarPubMed
18González, S, Huerta, JM, Fernández, S, et al. (2006) Food intake and serum selenium concentration in elderly people. Annu Nutr Metab 50, 126131.CrossRefGoogle ScholarPubMed
19Al-Saleh, I, El-Doush, I, Billedo, G, et al. (2007) Status of selenium, vitamin E, and vitamin A among Saudi adults: potential links with common endemic diseases. J Environ Pathol Toxicol Oncol 26, 221243.CrossRefGoogle ScholarPubMed
20Thomson, CD (2004) Selenium and iodine intakes and status in New Zealand and Australia. Br J Nutr 91, 661672.CrossRefGoogle ScholarPubMed
21Navarro-Alarcon, M & Cabrera-Vique, C (2008) Selenium in food and the human body: a review. Sci Total Environ 400, 115141.CrossRefGoogle ScholarPubMed
22Satia, JA, King, IB, Morris, JS, et al. (2006) Toenail and plasma levels as biomarkers of selenium exposure. Ann Epidemiol 16, 5358.CrossRefGoogle ScholarPubMed
23Slotnick, MJ & Nriagu, JO (2006) Validity of human nails as a biomarker of arsenic and selenium exposure: a review. Environ Res 102, 125139.CrossRefGoogle ScholarPubMed
24Ceballos-Picot, I, Merad-Boudia, M, Nicole, A, et al. (1996) Peripheral antioxidant enzyme activities and selenium in elderly subjects and in dementia of Alzheimer's type-place of the extracellular glutathione peroxidase. Free Radic Biol Med 20, 579587.CrossRefGoogle ScholarPubMed
25Smorgon, C, Mari, E, Atti, AR, et al. (2004) Trace elements and cognitive impairment: an elderly cohort study. Arch Gerontol Geriatr 9, 393402.CrossRefGoogle Scholar
26Berr, C, Balansard, B, Arnaud, J, et al. (2000) Cognitive decline is associated with systemic oxidative stress: the EVA study – Etude du Vieillissement Artériel. J Am Geriatr Soc 48, 12851291.CrossRefGoogle ScholarPubMed
27Gao, S, Jin, Y, Hall, KS, et al. (2007) Selenium level and cognitive function in rural elderly Chinese. Am J Epidemiol 165, 955965.CrossRefGoogle ScholarPubMed
28Akbaraly, NT, Hininger-Favier, I, Carrière, I, et al. (2007) Plasma selenium over time and cognitive decline in the elderly. Epidemiology 18, 5258.CrossRefGoogle ScholarPubMed
29Chen, C, Lai, J, Wu, C, et al. (2006) Serum selenium in adult Taiwanese. Sci Total Environ 367, 448450.CrossRefGoogle ScholarPubMed
30Arnaud, J, Akbaralyc, TN, Hininger, I, et al. (2007) Factors associated with longitudinal plasma selenium decline in the elderly: the EVA study. J Nutr Biochem 18, 482487.CrossRefGoogle ScholarPubMed
31Letsiou, S, Nomikos, T, Panagiotakos, D, et al. (2009) Serum total selenium status in Greek adults and its relation to age. The ATTICA study cohort. Biol Trace Elem Res 128, 817.CrossRefGoogle ScholarPubMed
32Planas, M, Conde, M, Audivert, S, et al. (2004) Micronutrient supplementation in mild Alzheimer disease patients. Clin Nutr 23, 265272.CrossRefGoogle ScholarPubMed
33Benton, D (2002) Selenium intake, mood and other aspects of psychological functioning. Nutr Neurosci 5, 363374.CrossRefGoogle ScholarPubMed
34Schweizer, U, Schomburg, L & Savaskan, NE (2004) The neurobiology of selenium: lessons from transgenic mice. J Nutr 134, 707710.CrossRefGoogle ScholarPubMed
35Crack, PJ, Cimdins, K, Ali, U, et al. (2006) Lack of glutathione peroxidase-1 exacerbates αβ-mediated neurotoxicity in cortical neurons. J Neural Transm 113, 645657.CrossRefGoogle Scholar
36Staehelin, HB (2005) Micronutrients and Alzheimer's disease. Proc Nutr Soc 64, 565570.CrossRefGoogle ScholarPubMed
37Zhu, X, Lee, H, Perry, G, et al. (2007) Alzheimer disease, the two-hit hypothesis: an update. Biochim Biophys Acta 1772, 494502.CrossRefGoogle ScholarPubMed
38Luchsinger, JA & Mayeux, R (2004) Dietary factors and Alzheimer's disease. Lancet Neurol 3, 579587.CrossRefGoogle ScholarPubMed
Figure 0

Table 1 Selenium concentrations in plasma (μg/l), erythrocytes (μg/l) and nails (μg/g), and selenium content in diet (μg/d) of elderly with Alzheimer's disease (AD) and those in the control (C) group

You have Access
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Nutritional status of selenium in Alzheimer's disease patients
Available formats

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Nutritional status of selenium in Alzheimer's disease patients
Available formats

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Nutritional status of selenium in Alzheimer's disease patients
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *