Serum Aluminum Research Articles

Effects of Multivitamin/Mineral Supplementation on Trace Element Levels in Serum and Follicular Fluid of Women Undergoing in Vitro Fertilization (IVF)

We investigated effects of multivitamin/mineral supplementation on element levels in serum and follicular fluid of women undergoing IVF. We used three groups in this study. The first group was used as an age-matched and nonpregnant control (n = 13). Group 2 (n = 30) constituted the IVF group and women in the third group who were undergoing IVF also received a multivitamin/mineral tablet daily for 45days. Follicular fluid and serum selenium and zinc levels and follicular fluid copper levels were lower in IVF patients than in controls although follicular fluid aluminum and iron levels were higher in IVF patients than in controls. However, follicular fluid and serum aluminum, copper, zinc and selenium levels, and serum magnesium levels were higher in the multivitamin/mineral group than in the IVF group although follicular fluid iron levels were lower in the multivitamin/mineral group than in the IVF group. In conclusion, we observed that copper, zinc, and selenium in serum and follicular fluid decreased in women undergoing IVF. Multivitamin/mineral supplementation in serum and follicular fluid of women undergoing IVF normalized the trace element levels.

REDUCED CIRCULATING ANGIOGENIC CELLS IN ALZHEIMER DISEASE

I read the article by Lee et al., who reported decreased numbers of circulating angiogenic cells in Alzheimer disease (AD).1 This may be associated with impairment of the blood–brain barrier (BBB) permitting toxic substances such as beta amyloid to penetrate the brain. Brain endothelial cells regulate AD amyloid (Abeta) levels in the neuronal microenvironment. Conversely, Abeta is toxic to neuroendothelial cells, which reduces their survival, yet Abeta(1-42) complexed with Al(3+) or Abeta(1-42)-Al increases the toxicity of neuroendothelial cells.2 Patients with AD have significantly higher levels of serum aluminum than patients with other forms of dementia and age-matched controls.3 Vascular endothelial growth factor (VEGF) phenotypes may also contribute to development of AD. This …

Aluminium and lead abnormalities in children on haemodialysis: relationship with some medications.

IntroductionThe determination of toxic elements in the biological samples of human beings is an important clinical procedure. This study was performed to investigate the prevalence of abnormal blood contents of 2 trace elements (TEs), aluminum (Al),and lead (Pb) in hemodialysis (HD) patients and to analyze their relationship with the medications, such as CaCO3, Ca acetate, 1,25-dihydroxy vit. D3, and erythropoietin (EPO), as well as hematocrit level.Material and methodsWe included 43 patients on maintenance HD and they had continued the previously mentioned medications for at least 3 months. None of the patients were on Al containing phosphate binding agents.ResultsSerum aluminum and lead levels were significantly increased than in the healthy controls, but levels of both of them were far below toxic values. Male patients had higher mean levels of lead than did females. A strong positive correlation was found between serum Al and serum Pb levels among patients (r = 0.075, p = 0.0001).The serum level of Pb was positively correlated with the serum albumin in HD patients (r = 0.45, p = 0.03). Both serum aluminium and lead levels positively correlated with the EPO dose taken by the patients (r = 0.77, p = 0.0001 and r = 0.67, p = 0.0001 respectively).ConclusionsThe blood level of trace metals of these HD patients was not related to their medications except for the EPO dose. However, caution must be exercised in interpreting this result as dose and duration of medication may play an important role. Al and Pb over load may be considered from the causes of inadequate response to epoetin therapy.

Are serum aluminum levels a risk factor in the appearance of spontaneous pneumothorax?

To investigate the relationship between aluminum and spontaneous pneumothorax (SP) development. Materials and methods: A patient group and a control group were formed with 100 individuals in each. The serum aluminum levels of the groups were determined and statistically compared. Results: The mean serum aluminum levels were 5.6 ± 2.4 \mug/L (1.6-11.9) and 23.2 ± 15.4 \mug/L (2-81) in the control and SP groups, respectively (P < 0.001). The specificity and sensitivity of the measurement of aluminum level were 74.4% and 86.4% in the SP group. The risk of SP development was found to be 18 times higher in individuals with high serum levels of aluminum compared to that in individuals with low serum levels of aluminum. Conclusion: A high level of aluminum is a risk factor for the development of SP.

SOME BIOLOGICAL RISKS IN RATS AS A RESULT OF COOKING IN ALUMINUM UTENSILS

The effects of cooking and / or storage for 7 days of fresh green peas using aluminum kitchen utensils at three different pH values with or without adding sodium chloride in comparison with stainless steel utensils were examined. Biological demonstration in rats revealed the effects of consuming aluminum contaminated diet on hematological measurements RBC’s, WBC’s, platelets counts and erythrocyte indices. Further more the biochemical changes in blood hemoglobin, hematocrit, and the levels of serum iron, calcium and aluminum, as well as the oxidative stress status and tibia characteristics were also investigated. The results showed that using aluminum utensils at acidic medium significantly increased aluminum concentrations in cooked and / or stored peas samples by about 11.5% and 18.7% , respectively, while adding NaCl dose,.3g/20g peas resulted in progressive increment reaching 14.45% and 26.9% respectively. The levels of aluminum were also elevated markedly in the stored samples with or without adding NaCl in both neutral and alkaline medium, while it’s increment ranged between 4 to 5% in cooked samples in case of adding NaCl or not. Aluminum accumulation decreased hematological measurements due to its toxic effects. The decrease of hemoglobin and hematocrit reached 30.0% and 8.36%, respectively, accompanied by decreasing the levels of iron and calcium in serum by about 6.35% and 18.3%, respectively. In contrast, there was 21% elevation in serum aluminum concentration which significantly lowered the antioxidant mechanisms as shown in plasma level of malondialdehyde (5.76 ± 0.24 nmol/ml) as compared to (1.64 ± 0.10 nmol/ml) associated with decreased level of erythrocytes super oxide dismutase by about 19.4%.Tibia characteristics showed a significant increase in weight and density as aluminum accumulation with calcium demineralization at the end of the experiment (12 week). It could be concluded that aluminum leaching from aluminum utensils, especially during storage of acidic foods, in hematological measurements and its physiological function roles also, will cause undesirable changes in oxidative stress and bone dysfunction.

Study on speciation of aluminum in human serum using zwitterionic bile acid derivative dynamically coated C18 column HPLC separation with UV and on-line ICP-MS detection

A C18 column dynamically coated with zwitterionic bile acid derivative, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), was used for direct injection high performance liquid phase chromatography (HPLC)-ultraviolet visible (UV)/inductively coupled plasma mass spectrometry (ICP-MS) speciation of aluminum in non-spiked human serum. Small-molecule Al-complex compounds of Al-citrate (Al-Cit) and large-molecule Al-protein compounds of Al-transferrin (Al-Tf) were chosen as the model species and their retention behaviors on CHAPS modified C18 column were studied with UV and on-line ICP-MS detection in detail. Under the optimal conditions, large-molecule Al-protein compounds and small-molecule Al-complex compounds could be separated in 4 min, and their concentrations were on-line determined by ICP-MS. The detection limits of the method were 0.74 and 0.83 ng mL(-1) with the RSD of 2.8% and 3.0% (n=7) for Al-Tf and Al-Cit, respectively. The developed method was applied to the speciation of Al in healthy human serum and chronic hemodialysis patient serum. To the best of our knowledge, this is the first report on the simultaneous quantification of both Al-protein compounds (e.g. Al-Tf) and small-molecule Al-complex compounds (e.g. Al-Cit) in healthy human serum at low concentration levels. Compared with the reported methods in the literature, this method has several attractive features such as simplicity, rapidness, no sample preparation required, and it provides a new strategy for the speciation of trace elements in human body fluids.

Comparison of low-dose deferoxamine versus standard-dose deferoxamine for treatment of aluminium overload among haemodialysis patients

Patients on maintenance haemodialysis are at high risk of aluminium overload. While deferoxamine (DFO) has potential adverse effects, lower DFO dosages may afford good efficacy with fewer side effects. We evaluated the therapeutic response of low-dose (2.5 mg/kg/week) DFO among haemodialysis patients with aluminium overload. We recruited the participants via basal predialysis serum aluminium (Al) levels of >or=20 microg/L with clinical suspicion of aluminium toxicity or hyperparathyroidism indicating parathyroidectomy and positive DFO tests. Patients were randomly divided into standard-dose (5 mg/kg/week) and low-dose (2.5 mg/kg/week) groups. We compared the differences of mineral biochemical and haematological parameters before and after DFO treatment. Successful treatment was defined as a serum aluminium increase of <50 microg/L by DFO test. Adverse events during DFO therapy between the groups were also compared. In total, 42 haemodialysis patients completed treatment (standard-dose group, n = 21; low-dose group, n = 21). The demographic characteristics of the groups did not differ. Serum corrected calcium and ferritin decreased in both groups, while serum total alkaline phosphatase increased in both groups. Serum phosphorus increased in low-dose group (P = 0.029), while plasma intact parathyroid hormone increased in standard-dose group (P = 0.004). The successful treatment response rates did not differ between the two groups (standard-dose: 12/21, 57% vs low-dose: 13/21, 62%; P = 0.75). Low-dose DFO may offer similar therapeutic effects as standard-dose DFO therapy.

Aluminum concentration in serum of children on long-term parenteral nutrition and in parenteral nutrition solution components

summary Background & Aims: Aluminum is a contaminant of parenteral nutrition solutions. Children who receive long-term parenteral nutrition are at risk of aluminum overload in tissues and its toxic effect. The aim of this study was to assess the incidence of aluminum overloading in those children and the level of aluminum contamination in parenteral nutrition solutions. Methods: A furnace atomic absorption was used to assess serum aluminum concentration in 24 patients, aged 2–20 years. These patients had received parenteral nutrition therapy ranging from 2 years to 14.7 years. Aluminum concentrations were also determined in parenteral nutrition solution components. Results: We found increased amount of aluminum concentration in calcium gluconate (6000 mg/l), in trace element (Addamel :7 00mg/l), amino acid solution (10% Primene :6 0mg/l), lipid-soluble vitamins (Vitalipid :5 00mg/l), and lipids emulsions (20%ClinOleic :1 10mg/l, Lipofundin MCT/LCT :5 5mg/l). Aluminum intake from parenteral nutrition was 5.81–29.64 mg/kg/day, a dose exceeding the safety limit of 5 mg/kg/day. We found increased aluminum concentration (>20 mg/l) in serum of 10 patients; 7

Convective Interaction Media Monolithic Chromatography with ICPMS and Ultraperformance Liquid Chromatography−Electrospray Ionization MS Detection: A Powerful Tool for Speciation of Aluminum in Human Serum at Normal Concentration Levels

A new analytical procedure using separation support based on Convective Interaction Media (CIM) was developed for speciation of Al in human serum at normal concentration levels. The separation of proteins was performed on a weak anion exchange CIM diethylamine monolithic column. Isocratic elution with buffer A (0.05 M tris(hydroxymethyl)aminomethane-hydrochloric acid + 0.03 M sodium hydrogen carbonate) was applied for 5 min, followed by linear gradient elution from 100% buffer A to 100% buffer B (buffer A + 1 M ammonium chloride) for the next 40 min. Separation of proteins was followed by UV detection at 278 nm. Separated Al species were detected online by inductively coupled plasma mass spectrometry. It was experimentally proven that 91 +/- 7% of Al in human serum was eluted under the transferrin peak. Transferrin was identified on the basis of the retention volume and by ACQUITY ultraperformance liquid chromatography-electrospray ionization mass spectrometry. The problem of extraneous contamination with Al was successfully overcome by using efficient cleaning procedures of eluents and chromatographic supports. The efficient cleaning was of paramount importance to perform Al speciation at extremely low concentration levels. The repeatability of measurement tested for six consecutive separations of unspiked serum was +/-8.6%. The limits of detection and quantification (based on 3 and 10 s of the blank) were 0.15 and 0.49 ng mL(-1) Al bound to transferrin, respectively. This is the first report on quantitative and reliable speciation of Al in human serum at normal concentration levels.

The influence of deferiprone on aluminum and essential elements levels in tissues and serum in aluminum-loaded rats

The influence of deferiprone on aluminum and essential elements levels in tissues and serum in aluminum-loaded rats

Serum aluminum level correlates with arterial stiffness in haemodialysis patients

In addition to pulse wave velocity (PWV), serum aluminum level is predictive of mortality in haemodialysis (HD) patients. This cross-sectional study evaluated the correlations between serum aluminum and brachial-ankle PWV (baPWV). One hundred twenty-seven HD patients (average age 58.46 +/- 9.95 years) were enrolled. Medical data were obtained via chart reviews and hospital database. Associations between biomarker levels and baPWV were analysed by multiple linear regression. Serum aluminum, high sensitivity C-reactive protein (hsCRP), age, pulse pressure (PP), mean arterial pressure (MAP) and diabetes mellitus (DM) are important correlates of baPWV. Further, hsCRP, PP, age and DM are positively related to arterial stiffness in HD patients.

Speciation of Aluminium in Human Serum Investigated by HPLC/High Resolution Inductively Coupled Plasma Mass Spectrometry (HR-ICP-MS): Effects of Sialic Acid Residues of the Carbohydrate Chain on the Binding Affinity of Aluminium for Transferrin

Aluminium (Al) in the blood is bound to transferrin (Tf), a glycoprotein of about 80 kDa that is characterized by its need for a synergistic anion. The binding affinity of both Al and iron (Fe) for Tf is surveyed in the context of our recent studies by on-line high-performance liquid chromatography/high-resolution inductively coupled plasma mass spectrometry (HPLC/HR-ICP-MS). First, Al in human serum without any in vitro Al-spikes was present in a form bound to the N-lobe site of human serum Tf (hTf). Next, the effects of sialic acid in the carbohydrate chain of hTf on the binding affinity of Al (or Fe) for hTf were studied by using asialo-hTf obtained by treating hTf with sialidase. The binding affinity of Fe fo ra sialo-hTf and native-hTf was similar, but the binding affinity of Al for asialo-hTf was greater than that for native-hTf. These findings are discussed in relation to diseases in which the serum concentrations of carbohydrate-deficient Tf and oxalate are increased.

Functional impairment in aged rats chronically exposed to human range dietary aluminum equivalents

Aluminum salts are ubiquitous in modern life. Yet, their possible adverse effects on human health remain to be determined. A longitudinal study was conducted in rats to assess whether chronic aluminum exposure at human-relevant dietary levels can alter performance on a hippocampal-dependent continuous alternation spatial memory discrimination T-maze task. From age 12 months onwards, three groups of rats trained to perform this task were chronically exposed to 0, 2, and 20 ppm of aluminum in drinking water. When combined with the aluminum in their feed, these regimens resulted in approximately 0.4, 0.5 and 1.7 mg aluminum (kg bodyweight day), designated as low, intermediate and higher aluminum doses. These levels are within the urban American dietary aluminum range. The rats were tested weekly during middle age (≥12 to <24 months) and old age (≥24 months) or until their terminal condition became apparent. Of the 30 rats that survived to at least 28 months, 0/10 on the lowest aluminum dose, 2/10 on the intermediate dose, and 7/10 on the higher dose attained significantly lower performance in old age than in middle age. Compared with rats whose T-maze performance remained intact, the rats with impaired performance had significantly higher serum aluminum levels ( p < 0.01) and cell counts indicating a larger percentage of aluminum-loaded pyramidal cells in their entorhinal cortex ( p < 0.05). Moreover, their percentage of aluminum-loaded entorhinal cortex cells correlated inversely with the decrease in their T-maze performance scores between middle age and old age ( r = 0.76, p < 0.0005). The functionally-impaired rats also displayed aberrant behaviors including inability to focus attention on their task, perseverative activity, and incontinence while in the T-maze. Hence, in this longitudinal study, ingestion of 0.5 mg aluminum/(kg bodyweight day) or more, consumed throughout most of adult life led, in old age, to a slowly-progressing condition that impaired cognitive function in susceptible rats.

Behavior of aluminum in aluminum welders and manufacturers of aluminum sulfate—impact on biological monitoring

The suitability of determining aluminum in serum or urine as a form of biological monitoring was critically assessed. Airborne and internal aluminum exposure was assessed for 12 aluminum welders in a shipyard and 5 manufacturers of aluminum sulfate. Particles were characterized with X-ray diffraction and scanning electron microscopy. Aluminum in air and biological samples was analyzed using electrothermal atomic absorption spectrometry. Basic toxicokinetic features were inferred from the data. The mean 8-hour time-weighted average concentration of aluminum was 1.1 (range 0.008-6.1) mg/m(3) for the shipyard and 0.13 (range 0.02-0.5) mg/m(3) for the aluminum sulfate plant. Welding fume contained aluminum oxide particles <0.1 microm in diameter and their agglomerates, whereas bauxite and aluminum sulfate particles ranged from 1 to 10 microm in diameter. The shipyard welders' mean postshift serum and urinary concentrations of aluminum (S-Al and U-Al, respectively) were 0.22 and 3.4 micromol/l, respectively, and the aluminum sulfate workers' corresponding values were 0.13 and 0.58 micromol/l. Between two shifts, the welders' S-Al concentration decreased by about 50% (P<0.01), but their U-Al concentration did not change (P=0.64). No corresponding temporal changes occurred among the aluminum sulfate workers. After aluminum welding at the shipyard had ceased, the median S-Al concentration decreased by about 50% (P=0.007) within a year, but there was no change (P=0.75) in the corresponding U-Al concentration. About 1% of aluminum in welding fume appears to be rapidly absorbed from the lungs, whereas an undetermined fraction is retained and forms a lung burden. A higher fractional absorption of aluminum seems possible for aluminum sulfate workers without evidence of a lung burden. After rapid absorption, aluminum is slowly mobilized from the lung burden and dominates the S-Al and U-Al concentrations of aluminum welders. For kinetic reasons, S-Al or U-Al concentrations cannot be used to estimate the accumulation of aluminum in the target organs of toxicity. However, using U-Al analysis to monitor aluminum welders' lung burden seems practical.

Serum aluminum levels in glue-sniffer adolescent and in glue containers

Serum aluminum levels in glue-sniffer adolescent and in glue containers

Towards a model of non-equilibrium binding of a metal ion in a biological system

AbstractWe have used a systems biology approach to address the hitherto insoluble problem of the quantitative analysis of non-equilibrium binding of aqueous metal ions by competitive ligands in heterogeneous media. To-date, the relative proportions of different metal complexes in aqueous media have only been modelled at chemical equilibrium and there are no quantitative analyses of the approach to equilibrium1. While these models have improved our understanding of how metals are used in biological systems they cannot account for the influence of kinetic factors in metal binding, transport and fate2. Here we have modelled the binding of aluminium in blood serum by the iron transport protein transferrin (Tf) as it is widely accepted that the biological fate of this non-essential metal is not adequately described by experiments, in vitro and in silico, which have consistently demonstrated that at equilibrium 90% of serum Al(III) is bound by Tf3-5. We have coined this paradox &amp;apos;the blood-aluminium problem&amp;apos;6 and herein applied a systems biology approach which utilised well-found assumptions to pare away the complexities of the problem such that it was defined by a comparatively simple set of computational rules and, importantly, its solution assumed significant predictive capabilities. Here we show that our novel computational model successfully described the binding of Al(III) by Tf both at equilibrium and as equilibrium for AlTf was approached. The model provided an explanation of why the distribution of Al(III) in the body cannot be adequately described by its binding and transport by Tf and it highlighted the significance of kinetic in addition to thermodynamic constraints in defining the fate of metal ions in biological systems. This is the first model of non-equilibrium metal binding in a biological system and it should prove to be a valuable predictive tool in furthering our understanding of the bioinorganic chemistry of metals.

Serum Aluminium Levels in Glue‐Sniffer Adolescent and in Glue Containers

Glue sniffing is a serious medical problem among teenagers. Various chemical substances such as toluene and benzene containing glues have been reported to be toxic. It has been demonstrated that some toxic metals such as lead are elevated in the blood of solvent-addicted patients. Whereas aluminium is an element that has toxic effects on neurological, hematopoetic system and bone metabolism. We want to determine the serum levels of aluminium in glue-sniffer adolescents in comparison with healthy subjects. In addition, we compared aluminium levels of different commercial glue preparations (i.e. metal and plastic containers), to determine which type of container is better for less aluminium toxicity. We measured serum levels of aluminium in 37 glue-sniffer and 37 healthy subjects using atomic absorption spectrophotometry. The average duration of glue-sniffer was 3.8 +/- 0.8 years. We also measured aluminium levels of 10 commercial glue preparations that seven of them with metal and three with plastic containers. We found that serum levels of aluminium were 63.29 +/- 13.20 ng/ml and 36.7 +/- 8.60 ng/ml in glue-sniffer and in control subjects, respectively (P < 0.001). The average aluminium level in the glues was 8.6 +/- 3.24 ng/g in the preparations with metal containers, whereas 3.03 +/- 0.76 ng/g with plastic containers (P < 0.001). Therefore, to decrease the incidence of aluminium toxicity in glue-sniffers, it may be a good step to market of glue preparations in plastic instead of metal containers.

La antiagregación plaquetaria incrementa los requerimientos de eritropoyetina en pacientes en hemodiálisis

BackgroundThe optimal use of human recombinant erythropoietin therapy is important to maximize the effectiveness of treatment of anemia and cost-effectiveness in hemodialysis (HD) patients. To achieve this, all the factors that can counteract the positive action of erythropoietin therapy should be identified. ObjectiveTo evaluate the possible influence of antiplatelet therapy on erythropoietin requirements in HD patients. Patients and methodA cross-sectional study was performed in 181 HD patients with autologous arteriovenous fistulae (55% males; mean age 65±14 years). Data were collected in 10 hemodialysis units in Aragon (Spain). Patients were divided into 2 groups according to whether they were receiving antiplatelet therapy or not. ResultsHemoglobin levels were similar in the 2 groups but erythropoietin requirements were higher in patients on antiplatelet therapy (129.8±59.8 versus 103.2±62.2 U/kg/week, p=0.0094). No differences between the 2 groups were found that could explain this finding. When diabetic patients were analyzed separately, erythropoietin doses were higher in the group of patients on antiplatelet therapy than in those not on antiplatelet drugs (130.9±58.2 versus 94.7±39.1 U/kg/week, p=0.0357). Multiple regression analysis revealed that antiplatelet therapy, low serum ferritin, low serum calcium, and high serum aluminium levels were independent predictors of erythropoietin hyporesponsiveness. In a subgroup of 95 patients in whom absolute lymphocyte count was available, patients on antiplatelet therapy showed lower lymphocyte count (1,127±394 versus 1,432±520 lymphocytes/μl, p=0.006) and higher erythropoietin requirements (138.6±63.1 versus 109.9±61.5 U/kg/week, p=0.0393) than individuals not on antiplatelet therapy. ConclusionsThe present study suggests that antiplatelet therapy may be an important factor in determining erythropoietin requirements in HD patients.

Biliary Function in Workers Occupationally Exposed to Aluminium Dust and Fumes

This study investigated biliary secretory function in workers occupationally exposed to aluminium dust and fumes. It included a group of 34 male workers aged (44.1+/-7.8) years and exposed up to 4.6 mg m-3 of aluminium dust and fumes in workplace air for (21.6+/-2.5) years, and a group of 30 unexposed control male workers. Serum and urine aluminium levels were measured in both groups before and after chelating treatment with 1 g deferoxamine by intramuscular injection. Biliary function was assessed by measuring gamma-glutamyl transpeptidase, alkaline phosphatase, 5-nucleotidase, cholesterol and its fractions, total and indirect bilirubin, and bile acids. We then analysed the relationship between Al exposure and biliary function. In the exposed group mean serum aluminium was significantly higher [(4.91+/-3.86) microg L-1] than in controls. The same was true for urine Al before [(1.57+/-1.93) microg L-1] and after deferoxamine [(11.51+/-14.97) microg L-1]. Total and indirect bilirubin and alkaline phosphatase were significantly higher in the exposed than in control workers, and they correlated with urine Al after the chelating treatment. Our findings suggest that chronic occupational exposure to aluminium dust and fumes leads to a significant body retention of aluminium. The impaired biliary secretion in the exposed workers manifested itself in subclinical signs of cholestasis.

Effects of Acute Exposure to Aluminum on Cognition in Humans

There is epidemiological evidence suggesting an association between aluminum in drinking water and Alzheimer's disease (AD), and between aluminum in dialysate and dialysis dementia. The exact role of aluminum in the pathogenesis of these and other dementias is not clear. This study examined the acute effects of aluminum on cognitive function in patients with AD and related dementias and in age-matched and younger volunteers with normal cognitive function. Whether individuals with AD and/or the APOE ϵ4 genotype had enhanced gastrointestinal absorption of aluminum was tested, and whether individuals with elevated blood aluminum concentrations exhibited acute cognitive effects was determined. Subjects were randomized to receive a single dose of aluminum orally (Amphojel plus citrate) for 3 d followed by a 3-wk washout, and then 3 d ofmatched placebo administration, or vice versa. Serum aluminum levels were measured and the daily dose of Amphojel was adjusted to a target aluminum level between 50 and 150 μg/L. Neuropsychological tests were administered at baseline and 90 min after the third dose of Amphojel or placebo. There was a large interindividual variation in aluminum serum levels in all study groups after the same initial dose of Amphojel. There were no significant differences in neuropsychological test scores after aluminum ingestion in normal volunteers or in patients with cognitive impairment. There was no association between APOE ϵ4 genotype and aluminum absorption. The results did not support the hypothesis that aluminum ingested at these doses produces acute effects on cognition or adverse effects, nor did they reveal that AD patients are more vulnerable to such outcomes. Further inquiry is required to explore any possible association between aluminum and cognition, but controlled trials may be limited by safety concerns.