Interpretation of blood lead and blood and urine cadmium
In the previous two blogs I have shown that blood lead is not a simple measure of exposure. In an given setting of environmental exposure from air pollution, water pollution or ingestion, blood lead levels are influenced by vitamin deficiencies, magnesium, potassium, zinc, and iron deficiency. These deficiencies influence the uptake of cadmium as well as lead.
In comparing 16 metals, cadmium was the most toxic and about 200 times more toxic than lead in an experiment where metals were given to a rodent and the toxic effect was lowering body temperature and negatively influencing mitochondrial function as evidenced by decreasing consumption of oxygen (Gordon 1990). Cadmium is a ubiquitous pollutant. It is present in all cells. In a setting of stress, free cadmium appears to be released from the lining of blood vessels and or the choroid plexus and triggers an acute stress reaction. Cadmium influences bone metabolism resulting in activation of osteoclasts (Sughis 2011). This is an effect blocked by zinc (Baljit S 1995). Resorption of bone releases lead which is stored in bone into blood, elevating blood lead levels from a toxic effect of cadmium.
Children who live in poverty with dietary deficiencies, emotional stress, and often co-exposure to cadmium in environmental tobacco smoke or other chemicals which are synergistic with cadmium, will have blood lead levels that are higher than children without these factors. Blood lead elevations are a useful marker of children in need of intervention. The lead programs set up to help these children need to focus on the dietary deficiencies and cadmium exposures. The lack of correlation with blood cadmium is not evidence that cadmium is not involved. It disappears readily into the blood vessel lining so that blood cadmium levels do not necessarily correlate with exposure or toxic effect.
In the 1994-2004 NHANES study, children aged 6 to 15 in the highest quartile of urine cadmium had a three fold risk of placement in special education placement (Ciesielski et al 2012). Urine cadmium, however, is not a simple measure of exposure, either. This study is consistent with my finding that children exposed to cadmium and in the highest quartile of hair cadmium had the lowest achievement. Although there was no linear correlation with hair cadmium and achievement, there was a correlation with hair lead even though there was no increased lead exposure in the affected children.
In a Japanese study, the urine cadmium of women with breast cancer who knew they had breast cancer was much higher than the urine cadmium of women who were screened for breast cancer and did not know they had the disease (Nagata C 2013). In an American study (McElroy et al 2005) women in the highest quartile for cadmium had twice the risk of breast cancer. In the most recent American study ( Adams et al 2016) there was no correlation between quartiles of urinary cadmium and breast cancer.
Urine cadmium in men in NHANES III, however, was associated with all cause mortality, cancer mortality, and specifically prostate cancer mortality ( (Cheung M 2014). Urine cadmium in women was higher but not associated with any specific disease. Urine cadmium in the same NHANES III was correlated with impaired glucose tolerance and diabetes.
Just as with lead, deficiencies of vitamins and minerals and processed food that contains bisphenol A can increase the uptake and toxicity of cadmium. Children and adults with higher urine cadmium need the same assessment and treatment as those with small elevations of blood lead .
Toxicity to cadmium can occur in the absence of any exposure to lead. Toxicity to lead except in acute ingestions resulting in blood lead levels over 40 mcg/dL occurs with co-exposure to cadmium but correlations with blood, hair, and urine cadmium levels are inconsistent. Neither blood, urine, or hair cadmium is a marker of acute or chronic exposure. It is variable and strongly influenced by stress which transiently releases it from blood vessels.
The magnitude of this reservoir is evident from a study by Koizumi in 1994 in Japan. Blood cadmium levels at autopsy were a hundred times higher than while living. This increase was seen only for cadmium and not other metals. Blood cadmium levels would undoubtedly be higher in current smokers and past smokers. Blood cadmium of non smokers at autopsy would provide useful information regarding environmental exposure to cadmium, especially cadmium air pollution.