Aluminum — A Toxic Metal with Potential for Exposure
Those of us that work in the area of clinical metal toxicology have not given aluminum toxicity the attention it deserves. With two excellent presentations by Chris Shaw PhD at EHS2021 and the new book by Prof. Chris Exley PhD on his research (Exley C. Imagine You are an Aluminum Atom Skyhorse Press 2020) it is time to give this toxic metal some attention.
(Al) is the third most abundant metal in the earth’s crust. In nature it is found complexed to silicon (alluminosilicates) and other minerals (phosphate, fluoride, chloride, etc.). According to the ATSDR’s monograph on aluminum:
“Because aluminum compounds occur naturally and are widely used in industry, in the manufacture of household products, and in processing, packaging, and preserving food, the potential for human exposure to these compounds through ingestion of food and water and inhalation of airborne particulates is substantial.”
(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)
HOW ALUMINUM GETS INTO THE BODY
Al can be found in food, water, and air pollution as well as pharmaceuticals, injections, protheses and personal care products. It can be absorbed from the gut, lungs or the skin into the systemic circulation and distributed to the lung, liver, bone, muscle and brain, with the highest levels found in lung tissue (whether or not the lung tissue came from occupationally exposed individuals is not clear) (ATSDR 2008)
DRINKING WATER: Aluminum availability in those with an intact gut barrier is low and Al absorption from water intake is only about 0.3%. Historically when tap water was used in dialysis for kidney patients, it caused dialysis encephalopathy, anemia and osteomalacia due to the patient’s inability to clear aluminum through a compromised renal system. Concentrations of aluminum are highly variable in drinking water, ranging from <0.001 to 1.029 mg/L. The use of alum (aluminum sulfate) as a flocculent in water treatment facilities typically may lead to high aluminum concentrations in municipal water supplies. (ATSDR 2008).
FOOD: Specific plants like tea leaves may contain very high concentrations of aluminum, >5,000 mg/kg in old leaves (ATSDR 2008). Because the bioavailability of aluminum from the gut is so low (.01%) plant food has not been seen to be a source of aluminum in the general public (those with intact gut barrier function).
Aluminum bioavailability in food increases when citrate, maltol, lactate and fluoride are present either in water or food. Aluminum is also better absorbed from the gut in those with magnesium or calcium deficiency. PMID: 32206026
Soy-based infant formulas contain higher concentrations of aluminum compared to milk-based infant formulas or breast milk. The aluminum content of human breast milk generally ranges from 9.2 to 49 mcg/L. (Exley)
Processed food in aluminum cans or aluminum-based foil containers (foil Tetra-Pak) can contain aluminum due to contact with the container material. The general population oral intake of aluminum from diet and drinking water is approximately1 mg/kg body weight/wk. (Exley)
The highest aluminum content in food has been found in ready-to-drink infant formulas where aluminum ranged from 49.9 to 1956.3 μg/L. Unfortunately these are formulas specifically made for underweight infants. PMID: 30871123 (2019)
PERSONAL CARE PRODUCTS: Deodorants may contain aluminum chlorhydrate as the active ingredient. One case study of a woman who applied ~ 1 g of aluminum chlorohydrate-containing antiperspirant to each regularly-shaved underarm daily for 4 years was reported to have experienced bone pain and fatigue. Her serum aluminum was 105 mcg/L and 24 hr. urinary aluminum was 47 mcg. After discontinuation of antiperspirant use, urine and serum aluminum concentrations decreased over 7 months, her bone pain disappeared and her fatigue improved. PMID: 15629736
PHARMACEUTICALS: The highest source of aluminum exposure comes from the long-term use of specific pharmaceuticals. The most commonly used drugs and the amount of aluminum they contain are-
Antacid use: 840-5000 mg/day
Buffered aspirin: 130-730 mg/day
Anti-ulcerative medication: 830 mg/day
Anti-diarrheal agents: 1450 mg/dose
Aluminum-based phosphate binder gels are administered orally in dialysis patients to minimize phosphate accumulation and some part of the aluminum in these medications may be absorbed and bioaccumulated.
INJECTIONS: Injection fluids may contain 10 μg./L (Exley) and aluminum adjuvant-containing vaccines may contain up to 1250 μg of aluminum per administered dose. PMID: 29773196
A recent freedom of information act request (FOIA Case Number 50882, and HHS Appeal No.; 19-0083-AA) revealed that the NIH was unable to provide a single study they can reference in relation to the safety of injection of aluminum adjuvants in infants. PMID: 33887692
JOINT PROSTHESES
Urine aluminum concentrations are likely to be >60 ng/mL in patients with metallic joint prosthesis. Prosthetic devices produced by Zimmer Company and Johnson and Johnson typically are made of aluminum, vanadium, and titanium. But according to Mayo Clinical Labs, these products change occasionally and they recommend that you see prosthesis product information for each device for composition details.
BODY BURDEN AND TOXICITY
With long-term exposure, aluminum can bioaccumulate and levels may remain elevated for many years following cessation of occupational or other exposure.
It is present in breastmilk and is found in the placenta and fetus.
Urine is the main route of elimination and the elimination half-life of Al depends on kidney function and level of exposure. Following acute exposure, it is in the order of days, but may be much longer in chronic exposure; the half-life in the brain is 7 years. PMID: 18085482, 21057782
If it is not removed by renal filtration, aluminum accumulates in the blood where it binds to albumin and ultimately accumulates in the brain and bone. In bone, aluminum replaces calcium and alters normal osteoid formation and normal calcium exchange, resulting in secondary hyperparathyroidism. Low-turnover bone disease with lower PTH (<50 pg/mL) and high aluminum (>60 ng/mL) indicates aluminum intoxication. (Mayo Clinical Laboratories Interpretive Guide: https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/8373)
The question of whether aluminum is stored in the brains of individuals without kidney disease or prosthetic-induced aluminum toxicity has been argued for the last 50 years.
Aluminum has been shown to be neurotoxic in animal models and in dialysis patients who have acquired aluminum-toxicity encephalopathy. Aluminum is known to:
impair cognitive and motor function,
alter DNA and chromatin RNA structure
block neuronal signaling
inhibit antioxidant enzyme action
interfere with synaptic transmission and disrupt mitochondrial function
act as an endocrine disruptor in brain
elicit genotoxic. pro-inflammatory, immunotoxic effects in brain
induce autoimmunity as ASIA syndrome (Autoimmune Syndrome Induced by Adjuvants) PMID:22108899 PMID:26275795
Recently, Chris Exley and his team at Keele University have published several papers looking at aluminum deposition in the brains of individuals with Alzheimer’s disease, multiple sclerosis, and autism spectrum disorder and compared them to normal healthy brain tissue. They found that aluminum levels were significantly increased in brain tissue in each of these disease groups compared to control tissues. PMID:32385326
Aluminum also acts as a metalloestrogen and epidemiologic research has shown a relationship between use of underarm deodorant containing aluminum chlorhydrate and earlier age of breast cancer diagnosis. PMID:31945389, 14639125, 28629908, 2387017, 17629949, 23870171
Biopsy data looking at aluminum in breast tissue and breast cancer tissue also correlates aluminum exposure with breast cancer. A compelling case-control study has also shown a direct link between exposure to underarm deodorants that contain aluminum chlorhydrate and risk for breast cancer. PMID: 28629908
In this study of age-matched controls, the use of antiperspirants was significantly associated with risk of breast cancer (p = 0.036). In women who reported using standard underarm antiperspirants several times daily starting at an age earlier than 30 years, the risk for breast cancer increased by an OR of 3.88 (95% CI 1.03–14.66). Aluminum in breast tissue was found in both cases and controls and was significantly associated with self-reported underarm antiperspirant use (p = 0.009).
Aluminum is excreted in sweat, urine and feces and significant amounts of aluminum were found in sweat of individuals without known aluminum exposure participating in sauna therapy. PMID:21057782
WHO ARE THE AT-RISK POPULATIONS?
According to the ATSDR (Agency for Toxic Substances and Disease Registry) the at-risk populations for aluminum toxicity are:
individuals with chronic kidney failure requiring long-term hemodialysis treatment
infants fed a formula diet containing high levels of aluminum
individuals consuming large quantities of antacid formulations for gastric disorders, anti-ulcerative medications, buffered analgesics for arthritis, or antidiarrheal medications
the general population living in the vicinity of industrial emission sources and hazardous waste sites. Substantially higher concentrations of aluminum have been detected in localized areas (food, air, water) around some industrial and hazardous waste disposal sites.
How can we measure aluminum in our patients?
Urine aluminum: Daily excretion >50 mcg/L indicates exposure to excessive amounts of aluminum. Normal values have not been determined for random specimens.
Serum aluminum reference ranges: 0-6 ng/mL (all ages) and <60ng/mL in dialysis patients-all ages.
Serum levels in healthy individuals range from 1 to 3μg/L. (Exley)
Mean 24 hr. urine levels in healthy individuals: 27 mcgs. (Exley)
Provocation testing with orthosilicic acid (found in high-silica mineral waters) has been demonstrated in Chris Exley’s lab and published in clinical trials giving a standard amount of orthosilicic acid to Alzheimer’s patients and controls. PMID: 22976072 PMID:16988476