Aluminium Metabolism (1):
The bad news (B), and the good news (G)
B1. Aluminium is toxic in milligram quantities. Yet it is all around us by the ton. It is the most common element in the earth's crust, and 3rd most abundant element in our planet (after oxygen and silicon)[1]. (There seems to be no vital process for which it is essential. [2])
G1. However, its salts are amazingly insoluble [3]. The solubility product (KSP) (at 25º) of
AlPO4 ↔︎ Al3+ + PO43- is 9.8 x 10-21;
of Al(OH)3 ↔︎ Al3+ + 3OH- is 3 x 10-34.
Aluminium metal quickly forms a planar crystalline lattice with oxygen in the ratio 2Al:3O. This aluminium oxide has such stability that, in the form of corundum, it is used as an abrasive for cutting and polishing. With slight impurities (which add colour) it presents in 'nature' as sapphire, and ruby.
B2. Nevertheless, dissolved aluminium is present in freshwater (in rivers, and lakes) at a concentration of up to 400 parts per billion [4] (i.e. 14.8 µM), especially in acidic waters. In seawater the concentration is considerably less at between 0.013 and 5 ppb depending on the ocean. (Atlantic higher than Pacific.) Normal daily intake from water, food, dust, and topical antiperspirants, is estimated to be between 1 and 20 mg per day for an average human, but can be 1,000 mg/day for those taking Al-containing antacids. But a large part of that intake (e.g. 99%) is passed out in the faeces. A bit more is excreted in the urine (12-50 µg/day) setting a minimum estimate for the amount absorbed into blood.
G2. However, it seems we can drink such water and live to a ripe old age, with signs of memory loss not normally showing till the age of 80 years or more, and sometimes not till 140 years. The 'average' human body-load is around 50 mg (30 - 200 mg). Daily intake is from 1 - 20 mg/24 hours, say 10mg. Clearly we would fill up in 5 days were Al not excreted in faeces and urine. Of the daily intake of 10 mg, some 12 µg/day is excreted by the kidney [5,8], and essentially all the rest in faeces. Accumulation of Al is very slow, e.g. "1 mg in 36 years," [5].
B3. Unfortunately that is not true for everyone. Though the loss of Al via the kidney is tiny, it is also crucial. Patients with kidney failure are found to develop Dialysis Encephalopathy Syndrome (DES)[6] and Dialysis Osteomalacia (DOM)[7]. The former syndrome (DES) results from accumulation of aluminium in the brain, where it can bind to proteins and to nucleic acids (DNA and RNA), and can also raise the concentration of redox-active iron by displacement from iron-binding sites. The latter syndrome (DOM) seems to be due to competition between Al3+ and Ca2+ at some stage in the bone-forming process. An aluminium serum level of even 6 µg/L is significantly linked to all-cause mortality within a year [11].
G3. Similar problems were observed with patients being fed 'parenterally', i.e. by intravenous infusion. However, once the importance of Al as a contaminant in the dialysis (or infusion) solution was realised, its concentration could be lowered (though that has proved extremely difficult), and the serum level monitored more closely. Though we ingest c. 5 mg of Al per day, only c. 12 µg per day are absorbed into the blood. [5,8]
B4. Besides binding very tightly to organic and inorganic anions (hydroxide, silicate, phosphate, citrate, etc.), Al3+ binds very tightly to proteins and nucleic acids. Indeed, Al3+ has been used for centuries in the tanning of leather, where it cross-links proteins, forming e.g. P1COO–Al3+ OH- Al3+ O-OCP2 bridges [5]. Naked DNA binds 1Al per 3 phosphorus atoms, but that rises to a 3:1 ratio with time, and to infinity if OH- is able to join in. Histones block 80% of the Al binding, but not all of it. Al-bridges may crosslink double-stranded DNA and prevent 'melting'. [5]
Given the amount of DNA and protein in the human body, it is rather astonishing that we do not gradually fill up with bound aluminium. Indeed, we may [5]. Deposition in bone is probably irreversible, and average aluminium load in humans (30-50 mg) increases somewhat with age, though there is insignificant increase with age in the content of Al in brain [9]. Half of the body load is in bone, and a further 25% in the lungs [5] (perhaps as ingested dust). Average tissue loading on a dry wt. basis is 9 µg Al/gr dry wt. Kidney and spleen have raised levels of Al (up to 100 µg Al/gram dry wt.)
Aluminium uptake from the gut can be increased 10-fold by the presence of citrate, presumably through the formation of electroneutral aluminium citrate [8]. Kidney excretion of Al may also be by the passive filtration of electroneutral aluminium citrate [10].
G4. The normal concentration of Al in the urine is 2–10 μg/L, but can be 10 times that in people exposed to aluminium. [10,8] This suggests a process of passive filtration. But is there perhaps a mechanism for the active secretion of aluminium, via e.g. kidney and/or spleen?
REFERENCES
[1] https://ehp.niehs.nih.gov/doi/10.1289/ehp.8665363
[2] https://www.mdpi.com/2073-4395/12/4/888#, DOI: 10.3109/10408369709006422.
[4] https://www.lenntech.com/periodic/water/aluminium/aluminum-and-water.htm#ixzz7nTDMF4Kz
[5] Ganrot, P.O. (1986) Metabolism and possible health effects of aluminum.https://ehp.niehs.nih.gov › abs › 10.1289 › ehp.8665363
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550484/
[7] https://pubmed.ncbi.nlm.nih.gov/6894520/
[8] DeVoto & Yokel (1994) Environ Health Perspect. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1567445/
[10] R.A. Yokel, in Encyclopedia of Human Nutrition (Third Edition), (2013)
[11] https://doi.org/10.1038/s41598-018-34799-5
No comments:
Post a Comment