First International Conference on METALS AND THE BRAIN: From Neurochemistry
to Neurodegeneration (University of Padova, Italy: 20-23 September 2000)




Aluminum is an environmentally abundant element to which we are all exposed. The neurotoxicity of this metal has been known for more than a century. More recently, it has been implicated as an etiological factor in some pathologies (including encephalopathy, bone disease, anemia) related to dialysis treatment . In addition, it has been hypothesized to be a cofactor in the etiopathogenesis of some neurodegenerative diseases, including Alzheimer's disease (AD), although, despite many studies in several laboratories in different countries, direct evidence is still, so far controversial. Thus, examples of aluminum neurotoxicity are well recognized-in experimental animals and in individuals with renal failure (consequent upon aging, intoxication or renal disease) - and there are grounds to link neurodegenerative disorders to aluminum exposure. Furthermore, an increased concentration of Al in infant formulas and in solutions for home parenteral nutrition has been associated with neurological consequences and metabolic bone disease, characterized by low-bone formation rate, respectively.

For all these reasons and on the basis of our many years of scientific experience in this field, we propose the following recommendations as guidelines to avoid risks due to aluminum accumulation and potential intoxication. These recommendations are not rigid and will be updated when relevant new scientific data is available.


  1. It would be valuable to define as completely as possible which patient groups are at risk for iatrogenic aluminum loading, and under which conditions aluminum represents a health hazard. The more complete knowledge we have for the clinical, iatrogenic setting, the better basis we will have to judge whether different types of aluminum exposure are hazardous to the general population or to susceptible subgroups.

  2. A provisional list of patients groups at risk of iatrogenic aluminum loading should include, at least, people with impaired renal function,
    infants, old people and patients on total home parenteral nutrition. Where such exposure occurs, serum aluminum concentrations should be less than 30 µg/l and possibly lower. However, further studies are necessary.

  3. Urinary aluminum is also an indicator of aluminum absorption, the excreted Al/retained Al ratio depends on the integrity of the renal function.

  4. Al may enter human body by mouth, intravenous infusions and by environment. Specific controls have to be adopted in order to reduce each risk of exposure.

    Oral exposure

  5. Aluminum in drinking water should be less than 50 µg L-1. Silicon is relevant to aluminum toxicity and, therefore, the water silicon
    concentrations should be monitored in parallel.

  6. The aluminum content should be declared in all food preparations and pharmacological products.

  7. Citrate-containing compounds appear to increase the bioavailability of ingested aluminum. Therefore, particular care should be taken to avoid these compounds in combination with Al-containing drugs. With citric acid, the enhanced gastrointestinal absorption may by compensated for by a parallel increase in urinary Al excretion, where there is good renal function. However, it is strongly suspected from recent simulation studies that other dietary acids (e.g., succinic and tartaric acids) also increase Al-bioavailability but do not cause any compensatory increase in urinary excretion. Ascorbate and lactate also significantly enhance gastrointestinal absorption of Al, as was recently demonstrated in animal studies.

  8. It is recommended that acidic food, e.g., acid cabbage, tomato, etc. should not be cooked or stored in aluminum ware. In this connection, it has been demonstrated that in the juice of acidic cabbage, cooked in aluminum, the
    metal ion content is up to 20 mg/ L.

  9. Individual susceptibility to aluminum has been reported by the scientific literature. Thus, special efforts should be taken to prevent contamination of food and beverages etc. with aluminum either directly or during preparation, with special regard to infants, old people or individuals with suboptimal renal functionality.

  10. Magnesium depletion is considered a high risk for aluminum accumulation especially during pregnancy and in the neonate with possible consequent problems for normal development and growth. Magnesium depletion is also
    common with aging.

  11. Iron depletion is considered a high risk for aluminium accumulation, as iron and Al share common carriers.

    Parenteral exposure:

  12. Aluminum in all intravenous (i.v.) fluids should be controlled monitored and labeled. There is a general consensus that the aluminum content of i.v. fluids used in children and adults with renal failure or undergoing dialysis, should be as low as possible and in any case no higher than 10 µg/L.

  13. The use of parenteral nutrition fluids that are high in aluminum should be eliminated or significantly reduced.

CONTRIBUTORS (Provisional list)

* P. Zatta, CNR Center on Metalloproteins. University of Padova, Italy. Coordinator of the Project: Interdisciplinary Approach to The Study of Aluminum Toxicity. E.C.COST D8 "Metals in Medicine".

* C. Canavese, (On the behalf of the Italian Nephrological Society) Le Molinette Hospital, Torino, Italy.

* S. Costantini, Istituto Superiore di Sanit&Mac195;, Roma, Italy.

* M. Gallieni, Dept. of Nephrology, San Paolo Hospital, University of Milano, Italy.

* M. Andriani, +Chief Nephrologist, Dolo General Hospital, Venice, Italy (On the behalf of the SIN-Italian Nephrological Society).

* G. Berthon, CNRS FR1744, Università Paul Sabatier, Toulouse, France.

* D. Boggio - Bertinet, on the behalf of the Italian Society of Parenteral and Enteral Nutrition

* J. Domingo, Faculty of Medicine, Rovira I Virgili University, Reus, Spain.

* T. Flaten, Dept. of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway.

* M. Golub, Dept. Internal medicine. University of California, Davis, USA.

* N. Goto, Laboratory of General Toxicology, Dept. Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan.

* M. Kawahara, Metropolitan Institute for Neuroscience, Tokyo, Japan.

* T. Kiss, Dept. of Inorganic and Analytical Chemistry, University of Szeged, Hungary.

* W. Lukiw, LSU Neuroscience Center, New Orleans, LA, USA.

* W. Markesbery, University of Kentucky Alzheimer's Disease Research Center, Lexington, KY, USA.

* R. Milacic, Josef Stefan Institute, Ljubljana, Slovenia.

C. Ronco, Director of the Renal Research Laboratory, Beth Israel Med. Ctr, New York, NY, USA.

* H.H. Sandstead, University of Texas, Med. Branch, Galveston, TX, USA.

* A. Taylor, Center for Clinical Sciences and Measurement, School of Biological Sciences, University of Surrey, Guilford, U.K.

This document will be published in relevant scientific journals, and will be sent to all Health Ministers of the European Community as well as to other Public Health Authorities. (FDA, WHO etc.). For further information, please contact Prof. P. Zatta:

Padova 20-23 September 2000



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For more information on Alzheimer's Disease (AD) see:

* Alzheimer's Disease Education and Referral (ADEAR)

* Alzheimer's Association