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Aluminum Toxicity

  • Author: Jose F Bernardo, MD, MPH; Chief Editor: Asim Tarabar, MD  more...
Updated: Apr 15, 2015


Aluminum is a trivalent cation found in its ionic form in most kinds of animal and plant tissues and in natural waters everywhere.[1] It is the third most prevalent element and the most abundant metal in the earth's crust, representing approximately 8% of total mineral components.[2] Due to its reactivity, aluminum in nature is found only in combination with other elements.

Dietary aluminum is ubiquitous but in such small quantities that it is not a significant source of concern in persons with normal elimination capacity. Urban water supplies may contain a greater concentration because water is usually treated with aluminum before becoming part of the supply. Subsequent purification processes that remove organic compounds take away many of the same compounds that bind the element in its free state, further increasing aluminum concentration.

All metals can cause disease through excess. In addition, essential metals can affect the human body in the case of deficiency or imbalance.[3] Malabsorption through diarrheal states can result in essential metal and trace element deficiencies. Toxic effects are dependent upon the amount of metal ingested, entry rate, tissue distribution, concentration achieved, and excretion rate. Mechanisms of toxicity include inhibition of enzyme activity and protein synthesis, alterations in nucleic acid function, and changes in cell membrane permeability.

No known physiologic need exists for aluminum; however, because of its atomic size and electric charge (0.051 nm and 3+, respectively), it is sometimes a competitive inhibitor of several essential elements with similar characteristics, such as magnesium (0.066 nm, 2+), calcium (0.099 nm, 2+), and iron (0.064 nm, 3+). At physiological pH, aluminum forms a barely soluble Al(OH)3 that can be easily dissolved by minor changes in the acidity of the media.[2]

Approximately 95% of an aluminum load becomes bound to transferrin and albumin intravascularly and is then eliminated renally. In healthy subjects, only 0.3% of orally administered aluminum is absorbed via the gastrointestinal (GI) tract, and the kidneys effectively eliminate aluminum from the human body. Only when the GI barrier is bypassed, such as by intravenous infusion or in the presence of advanced renal dysfunction, does aluminum have the potential to accumulate. As an example, with intravenously infused aluminum, 40% is retained in adults and up to 75% is retained in neonates.[4]

Mayor et al suggested that parathyroid hormone may increase intestinal absorption of aluminum.[5]

Aluminum is absorbed from the GI tract in the form of oral phosphate-binding agents (aluminum hydroxide), parenterally via immunizations, via dialysate on patients on dialysis or total parenteral nutrition (TPN) contamination, via the urinary mucosa through bladder irrigation, and transdermally in antiperspirants. Lactate, citrate, and ascorbate all facilitate GI absorption.

If a significant aluminum load exceeds the body's excretory capacity, the excess is deposited in various tissues, including bone, brain, liver, heart, spleen, and muscle. This accumulation causes morbidity and mortality through various mechanisms.[2]



Toxic effects of aluminum depend on the amount of metal ingested, entry rate, tissue distribution, concentration achieved, and excretion rate.[6, 7, 8, 9] Fatty acids common in food may facilitate the paracellular intestinal absorption of aluminum.[10]

Mechanisms of aluminum toxicity include inhibition of enzyme activity and protein synthesis, alterations in nucleic acid function, and changes in cell membrane permeability.

Aluminum toxicity is usually found in patients with impaired renal function. Acute intoxication is extremely rare; however, in persons in whom aluminum clearance is impaired, it can be a significant source of pathology. Aluminum toxicity was originally described in the mid-to-late 1970s in a series of patients in Newcastle, England, through an associated osteomalacic dialysis osteodystrophy that appeared to reverse itself upon changing of the dialysate water to deionized water (ie, aluminum-depleted water).

Previously, the only known dialysis-associated bone disease was osteitis fibrosa cystica, which was the result of abnormalities in vitamin D production that resulted in a secondary hyperparathyroidism, increased bone turnover, and subsequent peritrabecular fibrosis. In aluminum-related bone disease, the predominant features are defective mineralization and osteomalacia that result from excessive deposits at the site of osteoid mineralization, where calcium would normally be placed.

Since the role of aluminum in disease has been identified, more attention has been paid to the element, leading to its recognition in several other processes. For example, among patients with osteomalacia, there has been a closely associated dialysis encephalopathy, which is thought to be caused by aluminum deposition in the brain. Aluminum brain concentrations should be lower than 2 μg/g.[11] A 10-fold increase in aluminum concentrations was reported in patients with aluminum intoxication through the use of hemodialysis solutions with high levels of aluminum.[12]

Aluminum causes an oxidative stress within brain tissue.[13] Since the elimination half-life of aluminum from the human brain is 7 years, this can result in cumulative damage via the element's interference with neurofilament axonal transport and neurofilament assembly.

A possible etiologic link between aluminum exposure and Alzheimer disease emerged from a 1965 study showing that aluminum causes neurofibrillary tangles in the brains of rabbits. Subsequent research has largely failed to support this hypothesis, however. For example, the clinical manifestations and underlying neuropathology of aluminum-induced encephalopathy in dialysis patients bear no resemblance to those of Alzheimer disease.[14]

Blaylock et al suggest that the heterogeneous symptoms of autism spectrum disorders have a connection with dysregulation of glutamatergic neurotransmission in the brain along with enhancement of excitatory receptor function by proinflammatory immune cytokines as the underlying pathophysiological process.[15]

In this regard, dietary excitotoxins including aluminum can exacerbate the clinical presentation by worsening of excitotoxicity and by microglial priming. This opens the discussion to the use of nutritional factors that reduce excitotoxicity and brain inflammation as a maneuver to alleviate neurotoxic effects of aluminum.[16, 17] The central nervous system appears to be extremely sensitive to metal-induced oxidative stress. High aluminum concentrations have been found in postmortem brain specimens of patients with Parkinson disease and in animals models where administration of aluminum caused a strong decrease in dopamine content of the striatum.[18]

Aluminum also has a direct effect on hematopoiesis. Excess aluminum has been shown to induce microcytic anemia. Daily injections of aluminum into rabbits produced severe anemia within 2-3 weeks. The findings were very similar to those found in patients suffering from lead poisoning.

Aluminum may cause anemia through decreased heme synthesis, decreased globulin synthesis, and increased hemolysis. Aluminum may also have a direct effect on iron metabolism: it influences absorption of iron via the intestine, it hinders iron's transport in the serum, and it displaces iron's binding to transferrin. Patients with anemia from aluminum toxicity often have increased reticulocyte counts, decreased mean corpuscular volume, and mean corpuscular hemoglobin.

Other organic manifestations of aluminum intoxication have been proposed, such as a slightly poorer immunologic response to infection, but the mechanism by which it exerts its effect is complex and multifactorial. It has also been linked to vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome, thus highlighting the potential dangers associated with aluminum-containing adjuvants as described recently.[19]




United States

The American Association of Poison Control Centers’ National Poison Data System reported 813 single exposures to aluminum in 2013, with seven moderate outcomes, no major outcomes, and no deaths.[20] However, the overall incidence of aluminum toxicity is unknown. The greatest incidence is observed in patients with any degree of renal insufficiency. A higher incidence is observed in populations who have aluminum-contaminated dialysate or who are taking daily oral phosphate-binding agents. Patients who require long-term TPN are at increased risk as well.

Brown et al determined the potential for aluminum toxicity caused by parenteral nutrition in patients (n=36; age 50.4±20.4 y, weight 90.2±32.8 kg) who have risk factors of both acute kidney injury and parenteral nutrition support.[4] Aluminum exposure was determined for each patient by multiplying the volume of each parenteral nutrition component by its concentration of aluminum. The initial serum urea nitrogen and serum creatinine levels were 47±23 and 3.3 ± 1.4 mg/dL, respectively. Twelve patients received supportive dialysis. The mean aluminum exposure was 3.8±2 μg/kg/day in the 36 patients; the majority of patients, 29 out of 36, had safe calculated aluminum exposure (< 5 μg/kg/d), and 7 had high calculated aluminum exposure (>5 μg/kg/d). Patients with high aluminum exposure received more aluminum from calcium gluconate compared with those who had safe aluminum exposure (357±182 vs 250±56 μg/d).

Brown et al concluded that, using their calculations, most patients with acute kidney injury who require parenteral nutrition do not receive excessive exposure to aluminum from the parenteral nutrition formulation. The limitation of the study was its retrospective design, which resulted in calculated versus direct measurement of aluminum.


Some evidence suggests that, in developing countries where contaminated dialysis water is still used, aluminum-related disease is more prevalent. Also, as people still use over-the-counter aluminum-containing phosphate binders, aluminum deposition within the bone will continue and serve as a reservoir for continued exposure because of its long elimination half-life.


The mortality rate may be as high as 100% in patients in whom the condition goes unrecognized. Currently, however, recognition by nephrologists is the norm, and increased awareness by all practitioners has led to earlier detection and overall avoidance of the syndrome. Morbidity and mortality have been diminished significantly. In the past, bone pain, multiple fractures, proximal myopathy, and the sequelae of dementia have been the main sources of morbidity.

Animal studies in rats and case reports have implicated the use of oral aluminum-containing antacids during pregnancy as a possible cause for abnormal fetal neurologic development.[21, 22]

Advances in nanotechnology have led to the exposure of humans to engineered aluminum nanomaterials (NMs) that could potentially induce genomic changes (using a rat model, Balasubramanyam et al[23] found that Al2 O3 NMs were able to induce size- and dose-dependent genotoxicity in vivo[23]


Race-, Sex-, and Age-related Demographics

Aluminum toxicity has no predilection for any race, and has no predilection for either sex. Aluminum toxicity is observed in all age groups, but its end-organ effects are more prevalent in elderly persons, who may have diminished renal function.

Contributor Information and Disclosures

Jose F Bernardo, MD, MPH FASN, Associate Professor, Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine

Jose F Bernardo, MD, MPH is a member of the following medical societies: American Society of Nephrology, American Society of Transplantation

Disclosure: Nothing to disclose.


Barbara Barnett, MD Associate Program Director, Assistant Professor, Department of Emergency Medicine, Albert Einstein College of Medicine

Barbara Barnett, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Michael R Edwards, MD Physician, Department of Emergency Medicine, Beebe Medical Center; Physician, Department of Emergency Medicine, Catholic Medical Center

Michael R Edwards, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Association for Physician Leadership

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Lisa Kirkland, MD, FACP, FCCM, MSHA Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; Vice Chair, Department of Critical Care, ANW Intensivists, Abbott Northwestern Hospital

Lisa Kirkland, MD, FACP, FCCM, MSHA is a member of the following medical societies: American College of Physicians, Society of Hospital Medicine, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

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