The Role of Zinc and Copper in Autism Spectrum Disorders

Acta Neurobiol Exp 2013 2Children with Autism spectrum disorders (ASDs) appear to be at risk for zinc (Zn) deficiency, copper (Cu) toxicity, have often low Zn/Cu ratio, and often disturbed metallothionein (MT) system functioning. The evidence presented in this paper suggests that providing Zn to autistic children may be an important component of a treatment protocol, especially in children with Zn deficiency. It is important to monitor and follow the values for both Cu and Zn together during Zn therapy, because these two trace elements are both antagonists in function, and essential for living cells. 

The review article by Geir Bjørklund is published in Acta Neurobiologiae Experimentalis (2013; 73 (2): 225–236). This peer-reviewed journal is published by Nencki Institute of Experimental Biology in Warsaw, Poland.

 

Geir Bjørklund

The role of zinc and copper in autism spectrum disorders

Acta Neurobiol Exp (Wars) 2013; 73 (2): 225-236 

 

ABSTRACT

Autism spectrum disorders (ASDs) are a group of developmental disabilities that can cause significant social, communication and behavioral challenges. Several studies have suggested a disturbance in the copper (Cu) and zinc (Zn) metabolism in ASDs. Zinc deficiency, excess Cu levels, and low Zn/Cu ratio are common in children diagnosed with an ASD. The literature also suggests that mercury accumulation may occur as a cause or consequence of metallothionein (MT) dysfunction in children diagnosed with an ASD, which may be one of the causes of Zn deficiency. MTs are proteins with important functions in metal metabolism and protection. Zinc and Cu bind to and participate in the control of the synthesis of MT proteins. Studies indicate that the GABAergic system may be involved in ASDs, and that Zn and Cu may play a role in this system.

 

Exposure to high pollution levels during pregnancy may increase risk of having child with autism

AutismWomen in the U.S. exposed to high levels of air pollution while pregnant were up to twice as likely to have a child with autism as women who lived in areas with low pollution, according to a new study from Harvard School of Public Health (HSPH). It is the first large national study to examine links between autism and air pollution across the U.S.

“Our findings raise concerns since, depending on the pollutant, 20% to 60% of the women in our study lived in areas where risk of autism was elevated,” said lead author Andrea Roberts, research associate in the HSPH Department of Social and Behavioral Sciences.

The study appeared online June 18, 2013 in Environmental Health Perspectives.

Exposure to diesel particulates, lead, manganese, mercury, methylene chloride and other pollutants are known to affect brain function and to affect the developing baby. Two previous studies found associations between exposure to air pollution during pregnancy and autism in children, but those studies looked at data in just three locations in the U.S.

The researchers examined data from Nurses’ Health Study II, a long-term study based at Brigham and Women’s Hospital involving 116,430 nurses that began in 1989. Among that group, the authors studied 325 women who had a child with autism and 22,000 women who had a child without the disorder. They looked at associations between autism and levels of pollutants at the time and place of birth. They used air pollution data from the U.S. Environmental Protection Agency to estimate women’s exposure to pollutants while pregnant. They also adjusted for the influence of factors such as income, education, and smoking during pregnancy.

The results showed that women who lived in the 20% of locations with the highest levels of diesel particulates or mercury in the air were twice as likely to have a child with autism as those who lived in the 20% of areas with the lowest levels.

Other types of air pollution—lead, manganese, methylene chloride, and combined metal exposure—were associated with higher autism risk as well. Women who lived in the 20% of locations with the highest levels of these pollutants were about 50% more likely to have a child with autism than those who lived in the 20% of areas with the lowest concentrations.

Most pollutants were associated with autism more strongly in boys than girls. However, since there were few girls with autism in the study, the authors said this finding should be examined further.

Senior author Marc Weisskopf, associate professor of environmental and occupational epidemiology at HSPH, said, “Our results suggest that new studies should begin the process of measuring metals and other pollutants in the blood of pregnant women or newborn children to provide stronger evidence that specific pollutants increase risk of autism. A better understanding of this can help to develop interventions to reduce pregnant women’s exposure to these pollutants.”

 

Reference

Roberts AL, Lyall K, Hart JE, Laden F, Just AC, Bobb JF, Koenen KC, Ascherio A, Weisskopf MG. Perinatal air pollutant exposures and autism spectrum disorder in the children of Nurses’ Health Study II participants. Environmental Health Perspectives, online June 18, 2013.

 

Zinc and Inflammation

Zinc deficiency affects nearly 2 billion people in the developing world resulting in growth retardation, hypogonadism, immune dysfunction and cognitive impairment. Additionally, the roles of this divalent cation in the human body have not been clearly elucidated, since the essentiality of zinc has only been known within the last 50 years. However, it has been clearly documented that the supplementation of zinc improves many conditions such as; acute diarrhea in children, the common cold, infections in the elderly, oxidative stress and generation of inflammatory cytokines. Janet Ludwig, Ph.D. has worked in this area of study specifically modifying cellular injury by zinc supplementation.

This presentation from a webinar in May 2012 explore the following areas in order to begin to understand the therapeutic role of zinc in many inflammatory conditions:

•             Zinc roles in the body-metalloenzymes

•             Zinc as an antioxidant and anti-inflammatory agent

•             Membrane stabilization by zinc

•             Inflammatory diseases ameliorated by zinc supplementation.

 

 

Janet Ludwig, PhD

Janet Ludwig, PhD has worked in the area of zinc and inflammation for more than 25 years. She was at the Division of Surgical Biology at the Arizona Health Sciences Center studying zinc and cell injury induced by alcohol and carbon tetrachloride, an effective hepatotoxin. Additionally, she studied the mechanisms and structural identification of the potent class of inflammatory mediators, Platelet-Activating Factors (PAFs), at the Department of Pathology, University of Texas Health Sciences Center in San Antonio. She has taught courses in inflammation, biochemistry and nutrition at various Universities. She also travels to Bangkok, Thailand to give nutritional advice in a non-governmental organization that aids in improving the conditions for impoverished women and their children. Currently she is on the Hawthorn University faculty.

 

Hard Metals Disease

“If I poisoned someone, they would put me away for life, but the company I worked for poisoned me and got away with it,” says a disabled worker.

Hard Metals Disease (1987) is the shocking story of the Valenite Corporation, a subsidiary of General Telephone and Electric (GTE) and an international corporation with factories in the U.S., Mexico and Canada. This investigative documentary spent four years tracking Valenite activities. Did Valenite knowingly expose its workers to hazardous substances? What happens to jobs and workers when factories move to Mexico? The trail of dead and sick workers Valenite left behind raises questions about corporate responsibility.

As a correspondent for NBC’s Today Show, Jon Alpert consistently brought investigative reporting on controversial social issues to commercial television. This Emmy® Award winning documentary examines “Hard Metals Disease,” cobalt poisoning among workers in the tungsten carbide machine tool industry. Alpert focuses on workers suffering from this debilitating, incurable lung disease who were exposed to cobalt dust at three plants of the Valenite Metals Corporation. Establishing a close rapport with the workers as they tell their own stories of Valenite’s negligence and subsequent cover-up, Alpert departs from standard television reportage in his powerful and unapologetic indictment of industry.

 

Zinc Saves Kids

450,000 children are at risk of dying every year due to the impact of zinc deficiency on diarrhea, pneumonia and malaria. A few extra milligrams of zinc every day can make a huge difference. Zinc-containing supplements are a quick and easy, effective and inexpensive remedy.

Video from IZA – International Zinc Association (2011)

 

Pneumonia Wonder Drug: Zinc Saves Lives

Respiratory tract infections, including pneumonia, are the most common cause of death in children under the age of five. In a study looking at children given standard antibiotic therapy, new research published in BioMed Central’s open access journal BMC Medicine shows how zinc supplements drastically improved children’s chances of surviving the infection. The increase in survival due to zinc (on top of antibiotics) was even greater for HIV infected children.

In a double-blind, randomized, placebo-controlled trial, 350 children, aged from six months to five years old, were treated with standard antibiotic therapy at Mulago Hospital. Half the children were given zinc and the other half a placebo.

The researchers from Makerere University found that while there was no difference between zinc and placebo in the time it took to recover from the infection (measured by time it took to return to a normal temperature, reparatory rate and oxygen saturation) the risk of death between the groups was very different. 4% of the children taking zinc died compared to 12% of the children without zinc. This means that an extra eight out of 100 children could have been saved by taking zinc. Among the HIV infected children this rose to 26 out of every 100.

Prof James Tumwine explained, “Zinc is known to bolster the immune system and zinc deficiency is rife all over the developed, and developing, world. In Uganda, where this study was performed, zinc deficiency in some areas can be as high as 70%. We would only need to give 13 of these children with pneumonia zinc on top of their antibiotics to save one life. This equates to about 4 USD – a small price to pay.”

 

Reference

Srinivasan MG, Ndeezi G, Mboijana CK, Kiguli S, Bimenya GS, Nankabirwa V, Tumwine JK. Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial. BMC Med 2012; 10: 14.

 

Keeping Track to Selenium Metabolism

The technique allows for infinitesimal amounts of selenium to be quantified in their different chemical forms.

Spanish and Danish researchers have developed a method for the in vivo study of the unknown metabolism of selenium, an essential element for living beings. The technique can help clarify whether or not it possesses the anti-tumour properties that have been attributed to it and yet have not been verified through clinical trials.

“It is vox populi that doctors around the world recommend selenium supplements to complement traditional therapy against cancer and the AIDS virus but the truth is that the basics of these properties are not clear,” explains to SINC Justo Giner, a chemist from the University of Oviedo (Spain).

“Even the general metabolism of selenium has not been completely cleared up,” adds Giner who, along with other researchers at the same university and the University of Pharmaceutical Sciences of Copenhagen (Denmark), has developed a new methodology for discovering how this element moves around living organisms. The study has been published in the March issue of the ‘Analytical and Bioanalytical Chemistry’ journal.

The in vivo study was carried out on laboratory rats, which were administered a stable metabolic tracer of enriched selenium (77Se). According to the researcher, “it opens the door for transferring this method to clinical trials on humans given that innocuous, non-radioactive isotopes are used.”

In line with expected findings, the results reveal that selenium concentrations in biological tissue, blood and urine samples can indeed be analysed. Therefore, mass spectrometry techniques are employed along with a second isotopic tracer (74Se), which helps to quantify “with unequivocal precision” infinitesimal amounts of selenium in its different chemical forms that are distributed by the body.

Selenium is an antioxidant and plays an important role in the body’s immune response. Understanding the path that it takes from the moment it is administered to when it is excreted could help to clarify its metabolism and its possible protecting effect against cancer and HIV.

The ideal dose of selenium

The main sources of selenium come from foods such as yeasts, animal products (meat, seafood, dairy products) and vegetables like broccoli, wheat-germ, nuts (especially Brazil nuts), oats, garlic and barley. The current recommended daily intake of selenium is approximately 55 micrograms for women and 70 micrograms for men.

Selenium deficiency is associated with different pathologies like endemic cardiomyopathy, cystic fibrosis, multiple sclerosis, rheumatoid arthritis, haemolysis and muscular dystrophy. Furthermore, thyroid metabolism is affected by selenium levels since the glands deiodinasa enzymes are in fact selenoproteins.

In contrast though, when intake is higher than nutritional requirements, selenium is considered a ‘nutraceutical’. Mainly thanks to its antioxidant properties this means that it is beneficial for the health as long as it does not surpass the threshold in which it starts to become toxic.

 

Reference

Lunøe K, Martínez-Sierra JG, Gammelgaard B, Alonso JI. Internal correction of spectral interferences and mass bias for selenium metabolism studies using enriched stable isotopes in combination with multiple linear regression. Anal Bioanal Chem 2012; 402 (9): 2749-63.

 

Antioxidant may disrupt Alzheimer’s disease process

According to new study published in the Journal of Alzheimer’s Disease

Alzheimer’s disease (AD) is now the sixth leading cause of death among Americans, affecting nearly 1 in 8 people over the age of 65. There is currently no treatment that alters the course of this disease. However, an increasing amount of evidence suggests that changes in the way the body handles iron and other metals like copper and zinc may start years before the onset of AD symptoms. A new study shows that reducing iron levels in blood plasma may protect the brain from changes related to AD.

In the current study a group of investigators from led by Dr. Othman Ghribi, PhD, Associate Professor, Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, rabbits were fed a high-cholesterol diet which caused them to accumulate plaques of a small protein called beta-amyloid (Aβ). These plaques are toxic to neurons and central to the development of Alzheimer’s disease. The rabbits also developed changes in tau protein, which is part of the skeleton of neurons. When this protein becomes heavily phosphorylated, the ability of neurons to conduct electrical signals is disrupted. Following treatment with a drug called deferiprone (an iron chelator), the iron level in the rabbits’ blood plasma was reduced and the levels of both beta-amyloid and phosphorylated tau in the brain were returned to normal levels.

Another degenerative process in AD involves the production of reactive oxygen species (ROS) that can damage neurons in the brain. Deferiprone is also thought to suppress this reactive oxygen damage caused by free iron in the bloodstream, however in this study there was no difference in reactive oxygen species in the treated group. It appears that iron in the AD brain is located in the wrong places – in particular it accumulates to very high levels in the cores of beta-amyloid plaques and is very reactive in this setting.

According to Dr. Ghribi, “Our data show that treatment with the iron chelator deferiprone opposes several pathological events induced by a cholesterol-enriched diet…Deferiprone reduced the generation of Aβ and lowered levels of tau phosphorylation.” While there was no effect on ROS levels, he comments that “It is possible that a higher dose of deferiprone, or combination therapy of deferiprone together with an antioxidant to prevent ROS generation would more-fully protect against the deleterious effects of cholesterol-enriched diet that are relevant to AD pathology.”

Noted expert on metals metabolism research on AD Ashley Bush, MD, PhD, Mental Health Research Institute, Melbourne, Australia, adds that “this research highlights the role of metal ions as key modulators for the toxic interactions of risk factors for Alzheimer’s disease, in this case cholesterol. Drugs targeting these metal interactions hold promise as disease-modifying agents.”

 

Reference

Prasanthi JR, Schrag M, Dasari B, Marwarha G, Kirsch WM, Ghribi O. Deferiprone Reduces Amyloid-β and Tau Phosphorylation Levels but not Reactive Oxygen Species Generation in Hippocampus of Rabbits Fed a Cholesterol-Enriched Diet. J Alzheimers Dis. 2012 Mar 9. [Epub ahead of print]

 

A Nutritional Approach to AIDS

According to Bradfield & Foster ( 2006) is it possible to reverse all the  symptoms of AIDS in dying patients using  nutrition alone. This requires selenium and the amino acids, cysteine, tryptophan and glutamine.

Dr. Harold D. Foster, Ph.D. (1933-2009) was one of the giants in orthomolecular medicine with boundless enthusiasm and a prolific gift of writing. He was a researcher with a soaring scientific mind who made unique contributions to the understanding of health and disease.

Starting in 2004, a series of medical trials were conducted based on Dr. Foster’s research into the geographical correlations seen with HIV/AIDS, focusing on the nutritional deficiencies caused by the virus and the disease.

“HIV encodes for one of the human glutathione peroxidases. As a result, as it is replicated it deprives HIV-seropositive individuals of the selenoenzyme glutathione peroxidase and its four key components, namely selenium, cysteine, glutamine and tryptophan. Slowly but surely, this depletion process causes severe deficiencies of all these nutrients. Their lack, in turn, is behind the major symptoms of AIDS, including the collapse of the immune system, increased susceptibility to cancer, myocardial infarction, depression, muscle wasting, diarrhea, psychosis and dementia” (excerpted from hdfoster.com).

Marnie Bradfield & Harold D. Foster concluded in 2006 the following in an article in  Journal of Orthomolecular Medicine:

Several conclusions appear obvious from the African nutritional trials being used to test the efficacy of selenium and amino acids as a treatment for HIV/AIDS. Firstly, it is possible to reverse all the symptoms of AIDS in dying patients using nutrition alone. Secondly, this requires selenium and the amino acids, cysteine,tryptophan and glutamine. Thirdly, while selenium alone can slow HIV replication, eventually HIV/AIDS patients also need amino acid supplements. These can be given temporarily until deficiencies are corrected. The patients can then return to selenium supplementation alone for several months, until the more complex nutritional mixture is again required for another month. There appear to be no adverse side affects from these nutritional treatments and patients are delighted with their greatly improved health status.

For more information on the science and research based on Dr.Foster’s work, visit The Harold Foster Foundation and Foster Health

 

References

Bradfield M, Foster HD. The Successful Orthomolecular Treatment of AIDS: Accummulating Evidence from Africa. Journal of Orthomolecular Medicine 2006; 21 (4): 193-196.

Foster HD. What Really Causes AIDS. TraffordPublishing, Victoria BC. 2002.

 

 

Low Iron Levels in Blood Give Clue To Blood Clot Risk

Computed tomography (CT) scan of the lungs of a patient with a large pulmonary embolus. Blood vessels should appear white, but the grey material is a blood clot which is blocking the flow of blood to the left lung.

People with low levels of iron in the blood have a higher risk of dangerous blood clots, according to new research published in the journal Thorax. A study of clotting risk factors in patients with an inherited blood vessel disease suggests that treating iron deficiency might be important for preventing potentially lethal blood clots.

Each year, one in every 1,000 people in the UK is affected by deep vein thrombosis – blood clots that form in the veins. These can cause pain and swelling, but can also be fatal if the clot is dislodged and travels into the blood vessels of the lungs. Although some risk factors for blood clots are recognised, such as major surgery, immobility and cancer, often there is no clear reason for the blood clot.

To look for new risk factors for blood clots, scientists at Imperial College London studied patients with hereditary haemorrhagic telangiectasia (HHT). HHT is an inherited disease of the blood vessels, the main symptoms of which are excessive bleeding from the nose and gut. Previous research by the same group had found that HHT patients have a higher risk of blood clots, but the reason for this was unclear.

“Most of our patients who had blood clots did not have any of the known risk factors ,” said the paper’s lead author Dr Claire Shovlin, from the National Heart and Lung Institute at Imperial College London and an honorary consultant at Imperial College Healthcare NHS Trust. “We thought that studying people with HHT might tell us something important about the wider population.”

Dr Shovlin and her team analysed blood from 609 patients reviewed at the HHT clinic at Hammersmith Hospital from 1999 to 2011, to look for differences between the patients who had blood clots and those who did not. Many of the patients had low iron levels because of iron lost through bleeding. The researchers found that low levels of iron in the blood were a strong risk factor for blood clots. Patients who took iron supplements did not have higher risk, suggesting that treatment for iron deficiency can prevent blood clots.

“Our study shows that in people with HHT, low levels of iron in the blood is a potentially treatable risk factor for blood clots,” Dr Shovlin said. “There are small studies in the general population which would support these findings, but more studies are needed to confirm this. If the finding does apply to the general population, it would have important implications in almost every area of medicine.”

Iron deficiency anaemia is thought to affect at least 1 billion people worldwide. The association with blood clot risk might not have been found before because the iron levels demonstrating the link fluctuate during the day, and other markers of iron deficiency can be spuriously high if other medical conditions are present. Consistent timing of blood samples, as in this study, is therefore important for establishing correlations with health outcomes.

The link between iron levels and blood clots appears to be dependent on factor VIII – a blood protein which promotes normal clotting. High levels of factor VIII in the blood are also a strong risk factor for blood clots, and low iron levels were strongly associated with higher levels of factor VIII. The gene encoding factor VIII has sites where iron-binding proteins can bind, making it plausible that iron levels could regulate the factor VIII gene, and that this might be the mechanism for the link.

“We can speculate that in evolutionary terms, it might be advantageous to promote blood clotting when your blood is low in iron, in order to prevent further blood loss,” Dr Shovlin said.

 

Reference

Livesey JA, Richard A Manning RA, Meek J, Jackson JE, Kulinskaya E, Laffan MA, Shovlin CL. Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax, published online 15 December 2011. doi:10.1136/thoraxjnl-2011-201076

 

What is Iron?

Learn what iron is and how it can help your body and health.

What is Iron? Videogram. Colorado Springs, CO: Mineralife LLC, 2011.