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.

 

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.

 

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.

 

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]

 

What is Zinc?

Learn about zinc and how it helps your body.

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

Nutritional Support for Wound Healing

Nutrition plays a crucial role in wound healing. Nutritional status of patients at the time of trauma or surgery influences the biochemical processes necessary for the phases of normal healing to occur. Evidence exists that vitamins A and C, zinc, arginine, glutamine, glucosamine, bromelain, Aloe vera, and Centella asiatica may be beneficial to wounded or surgical patients.

 

Douglas MacKay and Alan L. Miller

Nutritional support for wound healing 
Altern Med Rev 2003; 8 (4): 359-77 

 

ABSTRACT

Healing of wounds, whether from accidental injury or surgical intervention, involves the activity of an intricate network of blood cells, tissue types, cytokines, and growth factors. This results in increased cellular activity, which causes an intensified metabolic demand for nutrients. Nutritional deficiencies can impede wound healing, and several nutritional factors required for wound repair may improve healing time and wound outcome. Vitamin A is required for epithelial and bone formation, cellular differentiation, and immune function. Vitamin C is necessary for collagen formation, proper immune function, and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain reduces edema, bruising, pain, and healing time following trauma and surgical procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic acid production in the wound. Adequate dietary protein is absolutely essential for proper wound healing, and tissue levels of the amino acids arginine and glutamine may influence wound repair and immune function. The botanical medicines Centella asiatica and Aloe vera have been used for decades, both topically and internally, to enhance wound repair, and scientific studies are now beginning to validate efficacy and explore mechanisms of action for these botanicals. To promote wound healing in the shortest time possible, with minimal pain, discomfort, and scarring to the patient, it is important to explore nutritional and botanical influences on wound outcome.

 

Zinc Regulates Communication Between Brain Cells

– Zinc has been found to play a critical role in regulating communication between cells in the brain, possibly governing the formation of memories and controlling the occurrence of epileptic seizures.

A collaborative project between Duke University Medical Center researchers and chemists at the Massachusetts Institute of Technology has been able to watch zinc in action as it regulates communication between neurons in the hippocampus, where learning and memory processes occur – and where disrupted communication may contribute to epilepsy.

“We discovered that zinc is essential to control the efficiency of communication between two critical populations of nerve cells in the hippocampus,” said James McNamara, M.D., senior author and chair of the Department of Neurobiology at Duke. “This addresses a longstanding controversy in the field.”

The study appeared in Neuron Journal online on Sept. 21.

McNamara noted that zinc supplements are commonly sold over the counter to treat several different brain disorders, including depression. It isn’t clear whether these supplements modify zinc content in the brain, or modify the efficiency of communication between these nerve cells. He emphasized that people taking zinc supplements should be cautious, pending needed information on the desired zinc concentrations and how oral supplements affect them.

More than 50 years ago scientists discovered that high concentrations of zinc are contained in a specialized compartment of nerve cells, called vesicles, that package the transmitters which enable nerve cells to communicate. The highest concentrations of brain zinc were found among the neurons of the hippocampus, the center of learning and memory.

Zinc’s presence in these vesicles suggested that zinc played some role in communication between nerve cells, but whether it actually did so remained controversial.

To address this controversy, McNamara and his colleagues at Duke teamed up with Dr. Steve Lippard and colleagues in the Department of Chemistry at the Massachusetts Institute of Technology.

The Lippard team synthesized a novel chemical that bound zinc far more rapidly and selectively than previously available compounds. Use of this chemical let the Duke team rapidly bind the zinc released by nerve cells, taking it out of circulation and preventing enhanced communication.

The Duke team went on to confirm that eliminating zinc from the vesicles of mutant mice also prevented enhanced communication. They also found that increases in the transmitter glutamate seemed to increase zinc-mediated enhancement of communication.

Interestingly, the nerve cells in which the high concentrations of zinc reside are critical for a particular type of memory formation. Excessive enhancement of communication by the zinc-containing nerve cells occurs in epileptic animals and may worsen the severity of the epilepsy.

“Carefully controlling zinc’s regulation of communication between these nerve cells is critical to both formation of memories and perhaps to occurrence of epileptic seizures,” McNamara said.

McNamara also noted that the scientific collaboration between the Duke and MIT scientists was critical to the success of this work. The availability of the novel chemical provided a critical tool that allowed the neuroscientists to unravel the puzzle.

 

Reference

Pan E, Zhang X, Huang Z, Krezel A, Zhao M, Tinberg CE, Lippard SJ, McNamara JO. Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse. Neuron 2011; 71 (6): 1116-1 126.

 

Zinc Lozenges May Shorten the Duration of Colds

Zinc lozenges might be useful as a treatment option for the common cold, according to a meta-analysis published in The Open Respiratory Medicine Journal.  Studies have shown that taking a dose of more than 75 mg of zinc in the form of zinc lozenges per day cut the duration of the common cold by 20 to 42 percent.

 

 

Harri Hemilä
Zinc Lozenges May Shorten the Duration of Colds: A Systematic Review
Breast Cancer Res Treat 2011; 129 (1): 107-16.


ABSTRACT

Background:
A number of controlled trials have examined the effect of zinc lozenges on the common cold but the findings have diverged. The purpose of this study was to examine whether the total daily dose of zinc might explain part of the variation in the results.

Methods:
The Medline, Scopus and Cochrane Central Register of Controlled Trials data bases were searched for placebocontrolled trials examining the effect of zinc lozenges on common cold duration. Two methods were used for analysis: the P-values of the trials were combined by using the Fisher method and the results of the trials were pooled by using the inverse-variance method. Both approaches were used for all the identified trials and separately for the low zinc dose and the high zinc dose trials.

Results:
Thirteen placebo-controlled comparisons have examined the therapeutic effect of zinc lozenges on common coldepisodes of natural origin. Five of the trials used a total daily zinc dose of less than 75 mg and uniformly found no effect. Three trials used zinc acetate in daily doses of over 75 mg, the pooled result indicating a 42% reduction in the duration of colds (95% CI: 35% to 48%). Five trials used zinc salts other than acetate in daily doses of over 75 mg, the pooled result indicating a 20% reduction in the duration of colds (95% CI: 12% to 28%).

Conclusions:
This study shows strong evidence that the zinc lozenge effect on common cold duration is heterogeneous so that benefit is observed with high doses of zinc but not with low doses. The effects of zinc lozenges should be further studied to determine the optimal lozenge compositions and treatment strategies.

 

Preventing Diabetes Damage: Zinc’s Effects On A Kinky, Two-Faced Cohort

In type 2 diabetes, a protein called amylin forms dense clumps that shut down insulin-producing cells, wreaking havoc on the control of blood sugar. But zinc has a knack for preventing amylin from misbehaving.

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