Wednesday, March 15, 2017

Health Savings Account Benefits

Benefits of Health Savings Accounts
1. Choice. Health does not come from access to health care.  It requires personal healthy behaviors and access to the kind of care that works to support health.  A significant component of psycho-social stress occurs in 87% of diseases.  Many psychosomatic conditions are being addressed with expensive testing instead of compassionate listening. Patients with chronic conditions need to participate in all aspects of their care. A restraint on greedy escalation of prescription drug costs is encouragement  of  low cost natural substances . Integrative physicians  generally use such approaches but are rarely covered by existing managed care plans.  Health savings accounts allow patients to access  the health care provider of their choice not a restricted panel.
2. Health  Promotion. Exercise, yoga, tai chi, dancing, massage, acupuncture, psychotherapy are valuable ways to improve health. Expenditures should be tax exempt and payable through health savings accounts.
3. Nutritional Supplementation. Vitamins, mineral, herbs, nutritional supplements have proven effects in countering cadmium toxicity. Patients should have the right to  use them and purchase them through health savings accounts.  Some patients are intolerant of medications or do not wish to use them.  They can achieve equivalent beneficial effects often at a lower cost.
 Tax Unhealthy Behaviors
Tobacco , alcohol, and marijuana are taxed. High sugar drinks and processed foods contaminated with bis phenol A, and artificial preservatives and dyes that have a toxic effect with cadmium should  be taxed.  Animals that are raised in  a stressful manner should be taxed and incentives used to raise them in a humane condition.   See suggestions for the FDA.
These taxes should fund hospitals to pay for excess illness resulting from their use.
Fund Socially Beneficial Activities
Participation in the arts, music,  theater,  choruses, dance groups, camps, and participatory sports  as opposed to spectator sports decrease stress, increase self esteem, increase NO from eNOS, and lower health care costs.

Fund Senior Centers but increase participation and access for all ages. Boys and Girl Clubs, community centers,  and leaders to  provide their support from birth to death. 

Sunday, December 4, 2016

Revising what is known about cadmium

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

Interpreting blood lead and blood, hair and urine cadmium

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. 

Thursday, November 17, 2016

How does cadmium elevate blood lead levels

How can a toxic effect of cadmium cause a small elevation of blood or hair lead above the average for that environment?

To understand the behavior of metals it is necessary to look at their biochemical behavior.   Statistical correlations can be misleading. It has been known for a long time that zinc and iron deficiencies were associated with toxic effects of lead.  These deficiencies are known to increase the absorption and toxicity of cadmium.   The inhibition of the enzyme ALAD which is considered particularly characteristic of toxicity to lead occurs with cadmium.   Zinc protects this enzyme from inhibition. Cadmium is an anti-metabolite of zinc. Zinc protects cells from cadmium toxicity. So lead toxicity is not just a simple matter of exposure to a toxic metal and a toxic effect that one can measure with blood lead levels or inhibition of ALAD. 
 An excellent article is available regarding the use of dietary strategies for the treatment of lead and cadmium toxicity.
Nutrients. 2015 Jan 14;7(1):552-71. doi: 10.3390/nu7010552.
Dietary strategies for the treatment of cadmium and lead toxicity.

In this article the effects of vitamins, minerals, herbs, and probiotics on toxic effects of lead and cadmium are discussed. In most cases it is clear that a reduction of blood lead with these strategies also reversed toxic effects of cadmium. 

 One could consider that both lead and cadmium are toxic but that elevation of blood lead is the indicator of toxicity, not blood cadmium.  Certainly the toxicity is directly associated with deficiencies of vitamins and minerals. However, one could also consider that lead exposure directly influences the uptake of cadmium.

 Cadmium is very interactive with all nutrient and toxic metals and also with toxic chemicals. Lead is treated more like calcium in the body and is stored in bone. Cadmium is stored in the lining of blood vessels and in the choroid plexus surrounding the brain. It is in the kidney, liver, ovary, testes, thyroid, and adrenals. With acute stress, like handling an animal, cadmium is released into the body.  Consequently, cadmium effects can occur without directly adding cadmium to an experimental animal.   

Cadmium causes a stress response in all cells. Lead does so only through increasing the absorption of cadmium.  For instance, lead in water increases metallothionein production in the liver.  Metallothionein is part of the acute stress response that cadmium produces.  Cadmium activates the promotor of metallothionein  whether cadmium has been added in the experiment or not. When lead is directly added to liver cells there is no increase in metallothionein production. Lead in drinking water increases the uptake of cadmium which promotes the stress response resulting in increased metallothionein production. It is not just that lead and cadmium are both toxic.  Toxic effects attributed to lead are caused by cadmium.

It is this effect of lead ingestion increasing the absorption of cadmium that is directly related to the small but significant elevations in blood lead levels and health effects.  Cadmium increases resorption of bone where lead is stored increasing blood lead levels.  So the level of lead in blood is not a measure just of exposure,but exposure plus a toxic effect of cadmium on bone. Blood cadmium is not a helpful measurement because cadmium is taken up rapidly into the blood vessels and the various organs.  The levels are highly variable through the day responding to various stresses.  Blood hair, and urine cadmium levels are not just measures of exposure but also of stressed induced releases.  

 Based on this information alone, it is clear that cadmium is important. It should be measured accurately in air. New approaches are needed to detect these volatile ultrafine fumes of cadmium.  The US EPA needs to fund research on effective ways to measure cadmium.   Children with elevated blood lead levels should be evaluated for toxic effects of cadmium.  Their urine cotinine should be measured to determine exposure to environmental tobacco smoke.  Children in tee highest quartile of urine cadmium have a three fold risk for placement in special education. These children need the dietary strategies suggested by Q Zhai et al.  They need stress reduction and excellent care both at home and at school. They are not permanently damaged.  It is neglect and indifference that leads to permanent damage in most instances.

Time for a change

Sandra M. Pinkham, M.D<   Time for  A Change
. 11-17-2016
> > >
 Since lead was taken out of gasoline in 1980, the public has been told that lead is the most serious toxic agent. Flint Michigan parents were told that their children were being permanently damaged by exposure to lead in water.  The public has been old that removing lead from gasoline which lowered blood lead levels dramatically has made the air cleaner. What is wrong with this message?   
In the last 30 years I have made an extensive search of the world literature on lead and cadmium and other toxic substances known to have an adverse effect on health. This was triggered by a finding in a hair analysis study that I did on children in 1986. The children in my study with the highest levels of lead and cadmium in their hair had the lowest scores on achievement. This was statistically significant for lead but not cadmium.  All the children were exposed to cadmium from a large waste incineration plant in operation for 2 years, a very significant source of cadmium pollution and other chemicals that act in synergy with cadmium. Only 2 of the 60 were exposed to passive smoke, another very significant source of cadmium air pollution exposure in humans.  The children with the higher levels of lead and cadmium were experiencing stress from having learning problems. The hair lead levels were associated with very low levels of blood lead. The children had minimal exposure to lead. Although the cadmium levels were elevated in the children with learning problems, the high variability in hair cadmium compared to hair lead resulted in an insignificant statistical correlation.
> >
From my literature search, I discovered that it is the  statistical correlation of small elevations of blood leads at any level along the line from a blood lead of 20 ug/dL to zero that is the main proof that lead is so toxic. In studies where lead is given for long periods of time to show adverse effects in experimental animals, there was no attempt to see what happens to other metals, especially cadmium in most studies. In the few where that was studied researchers showed that ingestion of lead in water increased cadmium uptake into the brain.  Just the fact that when blood lead levels averaged 15 the toxic children had blood lead levels of 20 and when the average was 5 the toxic children had 10 and now when the average blood lead level is less than one a blood lead level of 5 is considered toxic should make one suspicious that lead exposure may not be the cause of the linear correlation. .  Clearly all the children in the 1960’s and 70s were not being poisoned by lead.

 An alternate explanation which makes more sense is that blood lead is not just an indicator of exposure. Small increases over a background level is actually an indicator of a toxic effect that is increasing the presence of lead ions in blood. My next blog will explain the biochemical basis for this effect.

Tuesday, January 28, 2014

Unintended Consequences revised 1-28-14

Health care costs are at an unsustainable level and rising. In a recent report sponsored by the Institute of Medicine and the National Research Council, Americans under the age of 50 at this time have the lowest life expectancy in the developed world, even though as a nation we spend the most on health care (New York Times (NYT) 1-10-13).  Americans over 75 have increased life expectancy. Something is seriously wrong.  Moreover global warming is causing havoc around the world. Can these two problems have something in common?

It is my hypothesis that climate change,  increase in invasive plant and animal species, decline and extinction of species, and worsening human health are all linked to the increase of cadmium (Cd )in air which affects every living system on our planet and is not adequately measured with air filters designed when lead/Cd precipitates were present in air.

There was an experiment with our planet earth from 1920 until 1980 and a little beyond.  Tetraethyl lead was used in gasoline.  This polluted the air with lead.  Blood lead levels increased in children. In the mid 70's a doctor became convinced that low level lead toxicity was the cause of problems in children. Toxicologists and epidemiologists found that there was a linear correlation between low blood lead levels and various health effects. No such correlations could be found with low blood Cd levels. Extensive research was done and lead became the number one pollutant of concern by the US Environmental Protection Agency. Everyone was informed that lead was very dangerous and regulations were put in place.  Testing of blood lead levels was mandated.  In 1980 lead was removed from gasoline in the United States and by 2000 virtually all countries had removed lead from gasoline.

When lead was removed from gasoline, blood lead levels in children dropped dramatically. It was still possible to find that a small elevation of blood level above the background associated with adverse effects. The drop in blood lead levels was not associated with improvements in mental or physical health as predicted by the research correlating blood lead with these problems.  This is evidence that lead was not the cause of the health effects correlated with blood lead levels.  A better explanation is that toxic effects of low levels of Cd caused the linear correlation of blood lead levels under 15 mcg/dL with health effects.

 In the 1950's, Americans under the age of 50 had the highest life expectancy in the world and the highest exposure to lead air pollution in the world. At the current time, they are at the bottom for the developed countries.  Now our exposure to lead is very low and Cd air pollution is rising.  By understanding sources of  Cd air pollution,  one can say levels in air are rising even though the levels as measured by the air filters are not increasing.  We are the country with the largest consumption of fuel.  Crude oil is not typically analyzed for Cd levels but one sample had  32 ng/gm Cd. Cd is capable of having effects at picomolar levels, a very low level of exposure. It is impossible to directly measure Cd below nanomolar levels.  There are many aspects of life, other environmental exposures, genetics, gender, and age, which increase or decrease a person’s individual response to Cd air pollution.

These variable factors that influence an individual’s response cannot explain the effects of removing lead from gasoline on global warming. From 1960 to 1980 when lead air pollution was at its highest, there was a period in which global warming stopped, temperature variability decreased and there were no droughts. After 1980 the temperature started climbing again, there was more variability and in 2012 the global temperature was the highest in the last 110 years and the US experienced a devastating drought ( Wall Street Journal 1-9-13).  The removal of tetraethyl lead from gasoline increased the bio-availability of Cd air pollution.

I became interested in Cd in 1986 when I found that high achieving children in a white upper middle class suburb had the lowest levels of hair lead and Cd while the lowest achieving children had double the mean values. The correlation was significant for hair lead but not for hair Cd because of the high variability in hair Cd levels. I thought at first that this study provided evidence for a very low threshold for a toxic effect of lead. The children were exposed to a trash burning power plant that had been in operation for two years at the time of the study. This was a source of Cd pollution not lead.

 I studied the effects of lead and cadmium both in human health and the environment. I spent 10 years reading every research paper I could find on effects of cadmium on algae, bacteria, viruses, plants, fungi, marine life, rats, fish, birds, and humans before internet searches made this easy. In addition to the hair analysis study I worked with a psychologist looking at effects of lead and cadmium on the performance of rats on a learning task. The rats exposed to lead had no deficits. With increasing dose (10ppm to 50ppm Cd in drinking water) the rats had increased variability in their performance. The low dose exposure rats had increased weight compared to control and the high dose had decreased weight. One of the Cd exposed rats died of heart disease. Hair levels of Cd were not significantly associated with exposure.  I measured the level of Cd in tree leaves and found the levels were comparable to areas in heavily Cd exposed environments. As a physician, working with over 11,000 patients over the last 25 years  I  have had an opportunity to see how exposures to active and passive smoke, life style, age, gender and genetic background can affect behavior and health. 

By connecting the dots of many pieces of evidence I conclude that the best working hypothesis for understanding Cd is to see it as the biochemical link that explains evolutionary processes and cycles of global warming and cooling.  It is the link that provides a mechanism for how stress of any kind can to lead to both disease and death and recovery and resiliency.  It explains why the young would be particularly vulnerable to increased exposures and the old would be more resilient.  This metal is dispersed globally in air and I am proposing it has global effects on all biological systems.  A global hypothesis will have global implications.  The scientists who influence public policy have not been open to this global hypothesis and its global implications.  However, we are all breathing the earth's air. It behooves everyone to examine the evidence.

What is Cadmium?
Although Cd is grouped with the heavy metals, it has unique properties that need to be understood. If you do an internet search you can find many articles. The best single book about Cd was edited by Michael Webb in 1979 (The Chemistry, Biochemistry, and Biology of Cadmium). References through 1996 can be found in my published and unpublished papers on my web page. Internet searches can provide documentation of the effects of Cd on stress, signal transduction, gene expression, synergies, and association with cancer, bone disease, and low vit D.  Recently, it has been possible to see a linkage of low and high quartiles of blood or urine Cd and behavioral effects and linkage with cancers (breast, ovary, prostate, lung, pancreas, and kidney, at least). But by looking at linear effects of low dose blood or urine Cd levels one fails to find correlations with disease in humans.

What does Cd do?
Lead is handled by the body as calcium. Ninety to  95% of lead in non-occupationally exposed persons is stored in bone.  Cd decreases the mechanical strength of bone and increases bone resorption. Experimentally, it significantly lowers 25-OH vitamin D, especially in rats made vitamin D deficient. These effects on bone were not due to low vitamin D, however, but to the actual exposure to Cd. In humans smoking is a well recognized risk factor for osteoporosis.  Smoking is a very efficient Cd delivery system.   Although there are 2,000 chemicals in tobacco smoke there is no precise mechanism for any of the others to have this effect. So Cd, if it is not bound up by the special metal binding protein metallothionein, can release lead from bone, where it is stored, into the blood. In any given environment of lead exposure a small but significant elevation of blood lead can (and I predict from my hypothesis does) denote a toxic effect of Cd on bone. In other words, low level lead toxicity was not measuring toxicity from very low levels of lead exposure but was instead measuring the increases in bone resorption from free Cd releasing lead into the blood. When lead exposure fell there was no improvement in health.  The toxic effects found  with  low level blood lead levels under 15 mcg/dL, which are very well documented, are in actuality the effects of low dose free Cd and not low levels of lead exposure. 

Why Can't Cd Health Effects be directly Linked to Blood and Urine Levels?
Although 50% of Cd coming from air into the lung is taken up by the body, it quickly is taken up by the endothelial lining of blood vessels.  Evidence for this is that at autopsy, the level of Cd in cadaver blood in the heart and blood vessels can be 100 times higher than levels found in living humans. The dispersion of Cd into the endocrine system and the choroid plexus was noted in an animal study in which radioactive Cd was injected into the abdomen. This route by-passes the GI tract where one gets just 5% uptake and absorption into the liver, a major source of binding to metallothionein. The quick disappearance of Cd from blood into the endothelial lining of blood vessels makes direct measure blood Cd a poor measure of low level cadmium exposure from air. Moreover, the ability of metallothionein to bind it up breaks up a direct link between exposure and health effects.

Cd, but not lead or mercury, is able to substitute for zinc in critical controls of cell functioning. Cd, but not lead or mercury, gets into the lining of blood vessels and into the endocrine organs throughout the body and the choroid plexus. The choroid plexus, in addition to producing cerebral spinal fluid, is a filtration system, analogous to the kidney, which maintains the environment required by the brain to function optimally.  Therefore, though Cd does not directly get into the brain, it plays an important role in affecting mental health.

Cd has well studied biological effects in all living entities. It can interfere with DNA repair. This contributes on the one hand to evolution. However, increased mutations are found in sperm of fathers with children with autism. It is feature of influenza virus and also HIV-1, the major cause of global AIDS.  Some of the most aggressive cancers are associated with increased mutations.

Cd has bidirectional effects on cell signaling pathways.  Therefore, one would not expect a linear correlation of effects with exposure. On the contrary, it increases variability and flattens the Bell curve of distribution. It increases extremes. If one is looking for proof by looking for significant p values, one would conclude that there is not sufficient evidence to implicate Cd. Instead one must look at the signaling pathways that have been so clearly delineated in recent years.  Cd has very important effects on the immune system. Forty-eight genes associated with immune regulation are affected by cadmium. 700 genes are affected by Cd.

Cadmium’s Role in Stress
Cd gets into the nucleus of the cell and turns off the housekeeping genes and turns on the stress response genes. It can increase intracellular calcium, deplete glutathione, a potent anti-oxidant that protects mitochondria,   and increase tumor-necrosis-factor alpha (TNF-alpha). These are cellular manifestations of stress. It can increase catecholamines and glucocorticoids, hormonal mediators of stress. 

Cd can be looked upon as a messenger of the stress response. The inflammatory effects are necessary to trigger repair from injury but if not handled properly by the host can lead to disease or death. To control the stress response Cd increases the production of a metal binding protein called metallothionein, so that the stress response can be turned off.

The timing of exposure is critical.  Cd is particularly toxic during pregnancy and early childhood.  A recent study showed that prenatal exposure to increased  motor vehicle fumes and exposure in the first year of life triples the risk for autism. They did not associate this finding with Cd in the particulates but the exposure was there. The particulates come from combustion of materials containing Cd.  Current filters don’t trap the fine Cd fumes.  Exposure later in life, on the contrary, can increase resiliency and hardiness.

In the setting of chronic stress, mental or physical, there is a chronic elevation of glucocorticoids which break down proteins, preventing the binding and detoxification of Cd. High glucocorticoids short term are protective against acute Cd toxicity. Chronic high glucocorticoids are associated with physical problems such as poor outcome in pneumonia and acute myocardial infarction and mental problems like anxiety, depression and psychosis.  In studies of urinary hormones, there is a national tendency for an increase in glucocorticoid hormones that breakdown proteins over anabolic hormones that build them up.

High glucocorticoids have profound effects on the central nervous system. Low and high dose exposures to Cd in animals given by intraperitoneal injection produce free radicals in the brain and the effects are long lasting. It is possible these effects involve its presence in the choroid plexus as well as effects of glucocorticoids and other stress induced changes.

Sources of Cadmium
Cd is a global, ubiquitous pollutant that has been present in earth's environment since the beginning and it certainly could be a contributor to evolution. Volcanoes and forest fires are sources. .Massive Siberian volcanic eruptions are implicated in the great extinction ending the Permian period.  Combustion of all kinds increases Cd in the air.  All metal industries release Cd fumes. Animal wastes and phosphate fertilizers contribute Cd to soil and water. Through plants it can be transferred to air. Indoors Cd is incorporated into house dust, molds, and danders: common allergens. Outdoors it increases in pollen. Lead exposure actually decreases the Cd content of pollens.  Cd increases the allergenicity of pollens.  For humans, tobacco smoke has always been a source of Cd air pollution.

There is a Cd cycle. In the ocean, Cd is a growth stimulant for plankton. They in turn are eaten by krill.  Birds eating krill deposit guano, a source of super phosphate fertilizer and especially high levels of Cd. All phosphate fertilizers contain Cd because it is present in phosphate rocks.  Tobacco is high in cadmium because the plant concentrates Cd in its leaves. The increasing level of nicotine in tobacco is likely a response to increased cadmium exposure.  The increased toxicity of tobacco smoke recently described is most likely due to the absence of lead that formed a particulate with cadmium, decreasing its absorption.

Cadmium Effects on Global Living Systems
Protozoa feed on bacteria. Cd inhibition of their ability to ingest bacteria can lead to bacterial overgrowth. Bacteria can become resistant to Cd, in doing so they can acquire genes in plasmids that increase their virulence. They can also acquire the multiple drug resistant pump which is also the pump used to exclude Cd from the bacteria. Super-bugs are a major problem. No one is currently looking at the Cd content of these bacteria or how Cd exposure affects their acquisition of drug resistance. This is something that needs to be done. 

Cd can also increase the infectivity and virulence of viruses. The scourge of AIDS developed since 1980. There have been no studies of the effect of Cd on infectivity or virulence of HIV.  They should be done. Cd has been shown to activate Herpes from a dormant state.  Shingles is very common. Physicians and patients are completely unaware of the connection.

The gastrointestinal microflora has a profound effect on human and animal health. Dairy, wheat, and sugar increase the expansion of intestinal gram negative E.coli. This results in weight gain, inflammation and insulin resistance. Vegetables promote a different bacterial composition that doesn't have these effects. It is possible that these bacteria sequester Cd in food, water, and bile secretions so that Cd is released from the host into the stool.  No one is doing these studies at this time. Gram negative bacteria contain lipopolysaccharides (LPS). LPS are synergistic with Cd.  Binge drinkers can drink enough alcohol to kill these bacteria, releasing LPS and Cd, causing liver injury.

Beetles are thriving. They are well adapted to Cd because they bind Cd into their chitin. Fungi are well-adapted to detoxify Cd with Cd binding proteins, as well. Cockroaches are flourishing and aggravate asthma and so do dust mites. Bedbugs have become a major problem.  According to Wikepedia, infestations were decreasing in the developed world from 1930 to 1980 when lead pollution could have inhibited them and they have been rapidly expanding since1980.  Tick borne diseases are a serious problem. Head lice are getting more difficult to treat.  

Just as all other organisms are affected by Cd air pollution, humans are as well. Since 1980 there have been very dramatic changes in health. Although these changes have biochemical links to Cd, scientists have not had definitive proof. The lack of recognition of Cd's role in human disease is due to the poor correlation of direct measures of blood, urine, and hair Cd levels and health effects, while correlations are found for lead and mercury.  Moreover, the conclusion that Cd was not an important source of Cd exposure was made when lead was present in gasoline. In heavy industrial exposure or contaminated water its toxicity was well-recognized. Tobacco smoke was also known to be an important source of Cd exposure and adverse health effects. Because of the large number of pollutants in tobacco smoke, it was not considered possible to attribute effects of tobacco smoke to Cd.

Cadmium Synergy
Of all the toxic metals, Cd has been shown to enhance the toxicity of metals like arsenic, nickel, and chromium. The combined exposure of lead, arsenic and Cd cancels out toxicity.  Cd and arsenic together without lead have a synergistic toxic effect.  Cd alters the metabolism of organic chemicals. The two together can be toxic at doses that would not cause toxicity if there was exposure to either one alone. Many of the endocrine disruptors have this synergistic effect with Cd, which is also classified as an endocrine disruptor.  It is also synergistic with nicotine.

With the current ability to look at gene effects and signal transduction effects in experimental systems, it has been possible to show that toxic effects of tobacco smoke are mediated by Cd.  The US EPA is struggling to find what dose of the various chemicals in the environment may be toxic. They attribute blood levels to exposure, ignoring the effect of Cd on increasing blood levels of the chemicals.  Because they don't see correlations with Cd in blood or urine, they ignore the synergistic effect with Cd. 

Cadmium and Metallothionein
The effect of metallothionein on Cd , mercury and arsenic is critical for understanding the synergy with these metals.  These metals and copper are bound by metallothionein, the principal metal binding protein in animals. Zinc induces the basal isoform and Cd is the strongest inducer of the inducible isoform. There is an entire book devoted to the intricate interactions of hormones, radiation, and toxic insults that affect metallothionein.

A major pollutant of concern that is present in processed food, bis-phenol A, inhibits the ability of liver cells to make metallothionein.  This would increase free Cd exposure and increase liver toxicity. The USA has the highest consumption of processed food on the planet. Metallothionein is very responsive to stress. Hormones, oxidative stress, radiation, all kinds of stresses affect the production of metallothionein. It binds, zinc, copper, arsenic, mercury and Cd.  But the promotor of the gene for one of the metallothioneins is much more responsive to Cd than to zinc.  This is consistent with Cd's role as mediator of the stress response.  It helps turn off the stress response. In chronic stress with chronic elevation of glucocorticoids metallothionein is broken down.

When Cd and mercury are released from metallothionein by any of number of factors, mercury, which is less bio-available, will hang around in the blood and be excreted in the urine while Cd will disappear from the view of toxicologists by uptake into the lining of blood vessels and the choroid plexus.  The dose response that toxicologists find for blood mercury has lead to its placement above Cd as a metal of concern, ignoring the synergy that is generally present when blood mercury is elevated.  In a recent study maternal blood mercury was a marker for a toxic effect in the baby but actual increased mercury exposure by the mother's eating more fish led to a decrease in toxicity.  Rather than monitoring exposure, the maternal blood mercury was monitoring release of mercury from metallothionein.  Routinely, mothers are told to limit consumption of fish because of concern about mercury exposure when actually eating fish is healthful for them and their babies.

Health Changes since Lead Removal from gasoline
In the thirty years since lead was removed from gasoline the world has seen many adverse health effects. In addition to the global emergence of HIV, autism has increased 3 fold.  In 2012 children in the highest quartile for blood or urine Cd,  had a three-fold  increased risk of placement in special education. This is confirmation of the small study I did in 1986.  Clearly, Cd is having a negative effect on the brain health of children.

If one looks at mass shootings, the majority have occurred since 1980.  Violence is a major problem that is of great concern to all of us. Violence has been found by Dr. Daniel Amen to be associated with poor blood flow to the left amygdala and the left prefrontal cortex. We cannot prevent gun violence by back-ground checks of gun buyers. We need to educate gun owners of the need to keep their brains healthy by avoiding alcohol, getting a good night sleep, eating a healthy diet and learning to skillfully manage stress.  The Dept of Defense needs this information to assess recruits and to monitor soldiers in combat and returning from tours to prevent suicides and homicides. Violence is one of the factors lowering the life expectancy of those under the age of 50.

Cadmium and low 25-OH vit D3
There has been a dramatic increase in the finding of low levels of 25-OH vit D3 in all kinds of chronic diseases that are major contributors to the dramatic increase in health care expenditures. These diseases are autism, Alzheimer's disease, obesity, diabetes, cancer, auto-immune disease, severe allergies, gluten sensitivity, epilepsy, kidney disease, insomnia, anxiety, depression, ADHD, alcoholism, drug addiction, psychosis, traumatic brain injury, degenerative joint disease, chronic fatigue, etc. The list goes on and on. All these diseases are in some way associated not only with low vitamin D but also stress and inflammation. They are clearly not caused by lead exposure although they may be associated with mild blood lead elevations. Instead the removal of lead from gasoline appears to have had the unintended consequence of increasing the availability of Cd.  Cd can lower vit D and cause stress and inflammation. It can cause all these problems in association with many other factors.

Implications for Improving Health and Lowering Health Care Costs
To paraphrase Tolstoy in Anna Karenina, healthy individuals are all alike. Their genetic make-up, life style, social support, and stress management techniques protect them from Cd induced chronic stress, inflammation, and reduction of vitamin D. Unhealthy individuals are unhealthy in a myriad of ways. Low vitamin D and markers of chronic stress and inflammation point to a role for Cd in their disease.

To lower health care costs, a wellness check should focus on whether vitamin D levels are in the mid range between 50 and 70 ng/mL without large doses of supplemental vitamin D. Signs and symptoms of physical or mental stress should be assessed. Deviations from the mean in blood parameters, insomnia, chronic fatigue, muscle weakness, chronic pain, high or low BP, high or low adipocity, high or low body temperature could all be used by health care providers to identify the population at risk for adverse health effects. A ten minute wellness check focused on updating immunizations and treating high BP and high cholesterol with medications instead of life style changes is not going to reduce health care costs. 

Double blind controlled trials have been considered to be the best way of coming up with effective treatments for individual diseases when the cause of disease was not understood at a biochemical level. At this time much more is known about the cause of disease. There are many modifying factors in individuals. These trials are not enabling physicians to discover the most cost-effective ways of promoting health or treating chronic disease in specific patients. Using a single subject design, one can observe abnormalities at baseline, institute a therapeutic plan in cooperation with the patient and follow the outcome to determine efficacy. By looking at gene expression in circulating tumor cells in patients with pancreatic cancer, physicians were able to predict the best treatment and determine when changes needed to be made.

The current emphasis on coding for specific diseases is driven by the conviction that diagnosis of disease determines the appropriate treatment based on evidence from double blind controlled trials. Instead, physicians need to really listen to their patients and work with them to find ways to work with the body’s natural healing ability to promote mental and physical health. This is not the direction being fostered by Heath Care Reform.

Ophthalmologists are able to directly observe blood vessels. They have found changes observable in the eye predict chronic disease. Robert Ritch, a Canadian Ophthalmologist describes 22 natural compounds that are protective to the eye. They have virtually all been found helpful in experimental studies of Cd toxicity. As non-patent-able natural products, they are much lower in cost that pharmaceuticals, usually.

Physicians need to be aware of these helpful tools that could safely be used in a single subject research design.  Any time a patient is given a drug. It is an experiment.  Just because the drug has been tested in a very large double blind controlled study does not mean that a patient given that drug will have an optimal outcome.  The unintended consequence of using statins is muscle pain in patients that have low muscle carnitine at baseline. Those with low co-enzyme Q10 also suffer from statin side effects.  Neither carnitine nor co q 10 are measured before giving patients statins.  Excessive lowering of blood cholesterol has the unintended consequence of increasing depression, Alzheimer’s disease and cataracts.   Fish oils lower the inflammatory cytokine interleukin-6 which statins also lower but without these side effects.

If individuals  were given a tax credit of $2,000 per person to use for nutritional supplements, vacations, massage, hypnosis, acupuncture, yoga, gluten free foods, whatever they felt was necessary for their health. It would help to motivate them to see that their behavior has a major impact on their health.  Universal health Insurance does not lower health care costs. But changing individual decisions about diet, exercise, smoking, alcohol, recreational drugs, nutritional supplements, and stress management can improve health and lower health care costs together with a high deductible universal health insurance. 

There is a new clinical trial using a pharmaceutical drug for Alzheimer's disease. The double blind trial will be expensive and if efficacy is found, insurance companies will be obligated to cover a very expensive drug for a common disease. In a recent study, vitamin D3 and curcumin, a tumor necrosis factor inhibitor, enabled macrophages to ingest amyloid, the toxic product that builds up in Alzheimer's disease. Giving sufficient vitamin D3 to maintain levels at 50-70 ng/mL and sufficient curcumin to inhibit TNF-alpha to patients at risk for Alzheimers would be a much less expensive approach. The doses would need to be individualized. Recognizing that Alzheimer's is a Cd induced disease would trigger additional interventions, such as the supplements reviewed by Dr. Ritch.   Already noted to be helpful are the following: a healthy diet, avoiding processed, inflammatory food, keeping blood sugar stable with multiple smaller meals, exercise, social engagement, and novelty.

The unintended consequence of the removal of lead from gasoline has been an increase in global warming and a drop in vitamin D levels in virtually all chronic diseases.  These changes parallel an increase in the bio-availability of Cd and an absolute increase in Cd pollution driven by population growth, industrial activity, and intensive agriculture with phosphate fertilizers.  Clearly, low level blood lead elevations are a marker of a toxic effect of Cd on bone rather than exposure to environmental sources of lead. Mild elevations in blood mercury can be a marker for breakdown of metallothionein and not always environmental mercury exposure. Elevations of blood arsenic should raise suspicion that free Cd may be elevated as well. Such suspicions can be reinforced by finding low 25-OH vitamin D3 levels or other indications of stress. 

No single line of evidence is conclusive. With the weight of evidence along so many lines of inquiry there is enough evidence to conclude that Cd needs to become the number one pollutant of concern.  It is an essential component of the stress response. Both too much and too little can be a problem.  Currently, there is too much.  All disciplines need to become knowledgeable about its far-reaching effects in order for our policy makers to come up with successful strategies to  improve health, lower health care costs, and prevent devastating global warming.  A global air pollutant doesn't work alone. It is magnifying the toxic effect of other metals, chemicals, viruses, bacteria, archae, fungi, protozoa, and parasites around the world. 


Monday, December 30, 2013

Low testosterone,Bi-polar disorder, Alzheimer's and Re-versal of Cadmium effects by Lithium

Abnormalities seen in Bi-polar disorder and Alzheimer's appear to be at least partially reversed by lithium. See The following link:

If you look then look at the effects of lithium in reversing cadmium effects on the  rat testes you see that some of the same abnormalities noted in the previous article can be caused by cadmium  and  are reversed by lithium.

 Assist Reprod Genet. 2010 August; 27(8): 469–476.
Published online 2010 May 9. doi:  10.1007/s10815-010-9426-3
PMCID: PMC2941593

Cadmium is a ubiquitous pollutant that is more bio-available in air since lead was removed from gasoline in 1980 in much of the world.  The body tends to bind it up into a protein called metallothionein. In a state of chronic stress and low testosterone the ability to build protein diminishes. With the breakdown of metallothionein cadmium, mercury, arsenic, copper, and zinc are released.

In a setting of low testosterone zinc is not efficiently absorbed.  Supplemental zinc by antagonizing  cadmium can increase testosterone. Low levels of zinc have may adverse effects throughout the body.  It is major factor in the increase in gluten intolerance  and type II diabetes. Cadmium is an anti-metabolite of zinc and it can be more  toxic combined with copper, arsenic, and mercury. Attention is not given to cadmium because it so quickly moves out of the blood into the lining of blood vessels and into endocrine organs.

There is heavy advertising for treatment of low testosterone with testosterone replacement.  This carries a very real risk of promoting prostate cancer.  The use of nutritional lithium in the from of lithium orotate which is available without RX can be  used safely in a dose of 5 mg elemental lithium 1-3 times a day.  Since it is generally easy to tell if testosterone levels are adequate, a person can listen to the body to determine if this is effective.  Since cadmium lowers 25-OH vit D it is wise to supplement with up to 10,000 units of vit D3 and at least 100 mcg of vit K2 to keep calcium in bones and teeth and out of soft tissue.  Do not supplement with calcium but do supplement with magnesium which is required in greater amounts with cadmium exposure to maintain testosterone. Poor stomach acid decreases the uptake of magnesium and zinc. The amino acid taurine enhances their uptake.   Moderate exercise, a healthy diet, a good night sleep and skillful stress management are equally important for testosterone and general health and lower toxic effects of cadmium.

 The psychiatric dose of lithium is 30 to 90 mg of elemental  lithium a  day. 10 mg of elemental  lithium a  day through drinking water  is naturally found in some areas of the world where mental health problems are strikingly low.  Patients on higher levels of lithium  need to consult with their physician before making any changes in their medication regimens.

Lithium is alkalinzing and enhances the uptake of B-12 into neurons.