Cadmium is element 48, in the middle of the natural elements of the periodic chart. Vertically, it lies between zinc and mercury but it is quite different from both in its chemical and biochemical properties.
Cadmium, but not zinc or mercury, captures a photon of light producing the largest band gap. This makes it very useful in night vision for the military and as a component of solar panels. It is essential in technology.
It is not thought to have ANY essential biological function. It is looked upon as a highly toxic substance, which it is. As an air pollutant in tobacco smoke it doubles the cadmium content in the kidney and in the placenta. It is present in a very fine particle size in tobacco smoke.
There are no filters in use designed to analyze the amount of cadmium exposure in air coming from such particles. The analysis of 2.5 micrometer particles has a drying step that can lead to losses of cadmium species. When lead chloride was in the air from combustion of leaded gasoline the lead cadmium particulates were measured. With the elimination of lead the cadmium measurements show a fall in cadmium exposure from air. When one looks at the known sources of cadmium air pollution coming from combustion and from the planetary biome, there is no reduction.
Cadmium is a known stress agent in all organisms. Stress is actually a necessary function of all living entities. It is the pathway to resiliency and hardiness. That is an essential feature. Cadmium can combine with other metals , chemicals, heat, cold, UV, endotoxins from bacteria and fungi and all kinds of other stressors. The combined effects can cause far greater harm than they could alone. But cadmium can activate pathways that are protective against certain cancers and infections. It truly has bi-directional effects.
What is even more remarkable is that this ability to capture a photon of light and turn it into chemical energy, may have made cadmium indispensable in evolution. The energy that it can provide is equivalent to that of one ATP molecule. Just this year (K Brown 2016) cadmium sulfide was used to furnish the energy for a reaction that normally requires ATP. Before mitochondria evolved, cadmium sulfide could provide energy to make molecules. The first molecule that is both a structure that stores information in its sequence of nucleic acids and acts as an enzyme is the ribozyme. Cadmium binds to the nucleic acids of this structure and increases its catalytic function dramatically (Sigel 2013).
Cadmium has a strong affinity for the amino acid cysteine, especially in peptides and proteins. This amino acid has a dominant role in cell biology ( Z. Chen 2001, V Laverne 2012). Cadmium is always in the cell. It is present in sperm and ova. A cysteine rich enzyme is needed for the sperm to penetrate the tough lining of the ovum.
Cadmium triggers the gene expression of proteins needed for rapid cell division. Because it also triggers the gene expression of proteins that result in cell death, the amount of free cadmium in the cell must be carefully controlled. In rapidly growing cells it is able to enter the cell through multiple pathways.
The irony is that cadmium is not considered essential because there is no way to make a cell deficient in cadmium. It is so completely essential that life would not exist as we know it without cadmium.
During the great extinctions there were increased exposures to cadmium air pollution. Since cadmium interferes with DNA repair and can increase gene copy number, it can promote the modifications that can lead to new information systems.
An element with a linear effect could not promote evolution. Life is not linear and evolution is not linear. Adaptive responses to changing stressful environments in the planetary biome produced the big blue marble we call home. Cadmium played an essential role and still does.
Now we are confronted with a world that is showing stress at every level from climate change to mental illness, heroin overdose, and in the USA the lowest life expectancy in persons under the age of 50 in the developed world. The ability of cadmium to inhibit an enzyme that removes phosphates can mess up the delicate balance required for successful adaptation.
Our children are the canaries in the mine shafts warning us that we are exposed to something in the air that at the current dose and in conjunction with other pollutants is toxic to humans even though kudzu and Japanese knotweed are flourishing.
What needs to be done? We need a change in research funding. We need the media to provide information regarding the health effects of this element, its sources, and the available dietary and life style interventions needed to reverse its adverse effects. Scientists at environmental protective agencies around the world need to devise biological traps for measuring fine fumes of cadmium air pollution. Cadmium levels in blood of dead wild life and at autopsy, of persons from stillborns on up, especially non smokers, would provide some needed information on current levels of cadmium being absorbed. Because it quickly disappears out of the blood into the lining of the blood vessels, using blood cadmium levels under-estimates exposures in the living.
Cadmium may be present in exhaled breath secretions. It is possible to monitor FENO (fractional exhaled nitrogen oxide). Cadmium can exit plant leaves with NO. The interactions of cadmium with NO, which was the molecule of the year in 1992, will be the subject of my next blog.
Perhaps cadmium will become the element of the year in 2017. There is no dearth of information about cadmium, it just doesn't fit conventional ideas about proof. It is time to change these ideas.
Saturday, November 19, 2016
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.