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.”



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]


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.



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.

Metal Filings In Your Freaking Cereal

This video by Dr. Thomas E. Levy illustrates that the nutrients present in your “enriched” foods may not be as nutritious as you thought. Manufacturers of cereals are allowed to use indigestible iron filings in breakfast cereal. These cereal products can be dangerous for children and all patients with inflammatory diseases.