Aluminum Toxicity

Background
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]

http://emedicine.medscape.com/article/165315-overview