Aluminum Overview

Image 1 (Source)

Aluminum is one of the most abundant metals in the earth’s crust and is used in numerous applications, from metal alloys to buffers to cosmetics and medications.  Aluminum exposures in the general population are usually low, with the largest being from dietary intake. The average US adult consumes between 7 and 9 mg of aluminum in their daily diet and receives little extra aluminum from air, water, or soil. Very little aluminum that is consumed or contacted with the skin is absorbed systemically. Aluminum can also be found in some vaccines at concentrations of no more than 0.85 mg/dose (far lower than the average dietary intake). Aluminum is not classified as an essential metal.

A brief visual on vaccine aluminum content:

Mechanisms of Toxicity

Image 2 (Source)

Aluminum’s mechanism of toxicity appears multifaceted and incompletely understood. Below are some of the targets of aluminum toxicity as well as their proposed mechanisms of action.

Bones

It has been established that magnesium can compete with other cations in biologic systems, such as magnesium and iron. Aluminum also complexes with and decreases absorption of dietary phosphorous, which is crucial to maintaining bone integrity. This mineral toxicity may lead to osteomalacia, or a softening of the bones. This type of bone mineral toxicity is most commonly seen in patients with markedly decreased renal function, including those on dialysis.

Below is a video discussion of Osteomalacia and Rickets:

Neurons

Aluminum also exhibits a level of neurotoxicity, although multiple mechanisms are proposed and none have been properly established. The best model for neurotoxicity currently implicates aluminum’s ability to induce changes in neuronal cytoskeleton proteins. This may cause neurofilament aggregation not unlike those seen in Alzheimer’s disease. These changes in neuronal function may be linked to aluminum’s interference with calcium homeostasis in the nervous system.

Lungs

The respiratory effects of high levels of inhaled aluminum dust particles are well-documented. General signs of inflammation such as macrophage recruitment and alveolar thickening have been seen in those exposed to high levels of aluminum particles. However, these symptoms appear to be more related to dust overload rather than an inherent toxic mechanism of aluminum. Over time, this constant dust overload may lead to impaired pulmonary function, especially in workers exposed to high levels of these aluminum dust particles.

Carcinogenicity

The carcinogenic effects of aluminum are somewhat unclear and debated. The IARC classifies aluminum production as class 1a, carcinogenic to humans. This classification was due to a number of studies showing increased cancer mortality rate in aluminum industry workers. However, according to the CDC, these effects were more likely due to other potent carcinogens these workers were exposed to. Aluminum oxide, a widely-occurring and more common form of aluminum, is classified by the ACGIH as A4e, not classifiable as a human carcinogen.

 

Toxicokinetics

Image 3 (Source)

Absorption of aluminum via the GI tract (main source of exposure) is incredibly low, with only 0.1-0.6% of the ingested dose generally being absorbed systemically. Aluminum’s absorption is heavily dependent on the formulation in which it is found. For example, in the commercially-available antacid aluminum hydroxide, less than 0.01% of the dose ingested is absorbed. However, in aluminum citrate ingestion, between 0.5-5% of the dose can be absorbed systemically. This unabsorbed aluminum is excreted in the feces. Systemic aluminum is predominantly excreted in the urine, with a much smaller fraction excreted in the bile. The rate of this excretion is also heavily dependent on the biologic form of the aluminum, be it free Al3+, bound in low-molecular-weight complexes, or bound in macromolecular complexes. Aluminum is not able to be metabolized in the liver nor does it undergo transformation in the environment. Aluminum ingestion may be measured via the following biomarkers:

• Blood
• Urine
• Feces
• Bone

However, due to the very poor absorption of aluminum and absorption dependence on formulation, it is very difficult to determine aluminum exposure via any of these markers. The most supported of these diagnostics is urine, where high aluminum exposures appear to be reflected in the urine. This also has limitations, as high amounts of aluminum can be seen in the urine after any exposure due to its rapid excretion. There are currently no reliable biomarkers to assess aluminum overload.

Symptoms of Toxicity

Image 4 (Source)

As described in the Mechanisms of Toxicity section above, the signs and symptoms of aluminum toxicity vary based on the target organ. Below are symptoms categorized by the target organ. Please note that many of these symptoms may be observational, subclinical, or yet to be determined in humans.

Bones

The decreased absorption of phosphate due to chelation with aluminum may cause osteomalacia, or a marked weakening of the bones. As phosphate is necessary for bone calcification, this process occurs at a slower than normal rate. Clinically, this may present as decreased calcification, decreased bone density, or fractures.

Neurons

Some studies have linked high levels of aluminum to Alzheimer’s disease, although this relationship is not causal nor reliably replicated. Alzheimer’s disease is complex, with many different factors affecting the outcome. In animal models, decreased cognitive and motor functions have been noted. Patients on hemodialysis for long periods of time have exhibited signs of neurologic impairment. Some studies of aluminum workers indicated decreased function on nervous function tests.

Lungs

Aluminum workers who inhale larger amounts of aluminum dust may present with signs or symptoms of pulmonary distress. This may include coughing, wheezing, shortness of breath, or pulmonary fibrosis.

Overall, the toxic effects of aluminum appear to be far more prevalent in those with progressive chronic kidney disease. This may be due either to the decreased urinary elimination of aluminum in these patients or, in certain cases, excess aluminum exposure through hemodialysis. Most notably, the bone mineral effects caused by chronic kidney disease may be exacerbated by the bone toxicity of aluminum. Brain disease has been specifically noted in children with kidney diseases.

Management of Poisoned Patients

The most common method for management of aluminum toxicity is avoidance. Decreasing exposure to aluminum containing products such as cosmetics, foods, antacids (aluminum hydroxide), phosphate binders, dialysates, and parenteral injections is recommended. As described above, citrate drastically increases the absorption of aluminum, and thus co-administration of these products should be avoided. Chelating agents such as desferrioxamine (DFO) may be used to chelate aluminum in order to be removed via urine or hemodialysis. This can be especially useful if aluminum deposits are present in the bone (shown by bone biopsy). In rat models, administration of DFO drastically decreases the half-life of aluminum from 150 days to 55 days.

Historical Exposures

One historical exposure of note took place in England in 1989. During this incident, an unknown level of aluminum sulfate was added to drinking water, leading to neurologic symptoms in 5 documented children. These symptoms included memory loss, fatigue, depression, behavioral changes, and learning impairment. However, the validity of this exposure is called into question due to the high levels of copper and lead, known neurotoxins. Other historical exposures have occurred in aluminum-dust-exposed workers as described in the Mechanisms of Action section above.

 

Conclusion

Overall, aluminum toxicity is very poorly described and the mechanisms still require further elucidation. Aluminum appears to have clear toxic effects in bones, although the pulmonary and neurologic effects require more study.

 

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). 2008. Toxicological profile for Aluminum. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.
2. National Center for Biotechnology Information. PubChem Compound Summary for CID 5359268, Aluminum. https://pubchem.ncbi.nlm.nih.gov/compound/Aluminum. Accessed June 14, 2021.
3. Crisponi, Guido & Fanni, Daniela & Gerosa, Clara & Nemolato, Sonia & Nurchi, Valeria & Crespo-Alonso, Miriam & Lachowicz, Joanna & Faa, Gavino. (2013). The meaning of aluminium exposure on human health and aluminium-related diseases. Biomolecular concepts. 4. 77-87. 10.1515/bmc-2012-0045.
4. Attitude Pictures Ltd. Vaccines: Aluminium Demonstration [Video]. YouTube. https://www.youtube.com/watch?v=_24rPCn-5PQ. Published August 6, 2018. Accessed June 14, 2021.
5. MedLecturesMadeEasy. Metabolic Bone Disorders [Video]. YouTube. https://www.youtube.com/watch?v=dmkuUXOZ4EQ&t=328s. Published August 28, 2016. Accessed June 14, 2021.