by Ginger Houston-Ludlam
Let me quote a little bit from my favorite iron article, and I think you’ll begin to understand why iron is so worrisome to me. Keep in mind as you read this that our kids with Down Syndrome are producing more Superoxide radical than the average child. It has been measured and found to be higher in kids with Down Syndrome. Reasons for this include:
- mitochondria are leaking superoxide,
- purine synthesis path creates excess superoxide due to GART overexpression, and
- the Superoxide Dismutase (SOD) gene (that converts superoxide to hydrogen peroxide) is triplicated, and therefore there is more hydrogen peroxide for the iron to react with.
Here’s the article: McCord, JM, “Iron, Free Radicals, and Oxidative Injury,” Seminars in Hematology, 1998:35(1) pp. 5-12.
Abstract: “Iron metabolism and superoxide metabolism are clearly interactive, especially under pathological conditions. Each can exacerbate the toxicity of the other. Iron overload may amplify the damaging effects of superoxide overproduction in a very broad spectrum of inflammatory or ischemia-related conditions. Furthermore, chronic oxidative stress may modulate iron uptake and storage, leading to a self-sustained and ever-increasing spiral of cytotoxic and mutagenic events.”
From the introduction: “Iron is physiologically essential and biochemically dangerous. The most common cause of infant death by accidental poisoning is the ingestion of ferrous sulfate tablets. There has always been a natural tendency to associate iron with strength and well-being, even before biochemists realized that it is a necessary trace element, essential for life itself. The ancient Greeks dissolved iron filings in vinegar, hoping that if they drank this liquor, they would acquire the strength of iron. After its recognition as an essential nutrient, the common but faulty assumption followed that “more is better.” This assumption persists today, even among some physicians and nutritionists. Accordingly, for several decades we have produced “iron-fortified” foods in an attempt to eliminate iron-deficiency (which afflicts less than 10% of the US population) with little appreciation of what this supplementation might do to the remaining 90% of the populace who are in a state of iron excess. For the majority of persons, iron supplementation simply results in ever-increasing stores of excess iron in the body. Evolution has given us mechanisms for absorbing dietary iron with about a 10% efficiency, but, oddly, we have no mechanism for the elimination of excess iron. As a result, cells continuously store excess absorbed iron in a complex with the protein ferritin. This protein is found in all tissues, especially the liver. If the body experiences a sudden and significant loss of blood, these stores are drawn on for the synthesis of new hemoglobin to replace that which has been lost. In modern society, transfusion has supplanted even this need. Hence, excessive iron stores serve no known useful function to an otherwise healthy body.”
The author then goes on to give a chemical description and explanation for the action of superoxide, which is long and very involved. It talks about superoxide inactivating a variety of important enzymes in the body. Then, “Even so, many believe that the most generally destructive action of superoxide radical may be bringing about the reductive release of iron from ferritin.” The article then discusses the chemical mechanisms that the body uses to “tie up” iron so that it doesn’t cause trouble.
Here’s where the rubber hits the road biochemically. “Once iron has been liberated in the presence of superoxide and it dismutation product, hydrogen peroxide, the hydroxyl radical (HO-) may be formed by Haber-Weiss chemistry [Ginger’s note: big hairy chemical equation!] Unlike superoxide radical, which is not highly reactive compared to most other free radicals, the hydroxyl radical is an extremely powerful oxidizing species. In oxidizing potential it is second only to atomic oxygen. It may be produced by the radiolysis of water, and is thus responsible for most of the damage resulting from exposure to ionizing radiation. It came as a surprise to many biochemists that hydroxyl radical could be produced by biological systems themselves, by the simple generation of superoxide in the presence of redox-active iron and hydrogen peroxide. This hydroxyl radical can attack all classes of biological macromolecules. It can depolymerize polysaccharides, cause DNA strand breaks [Ginger’s note: this is the mutation and cancer link!!] inactivate enzymes and initiate lipid peroxidation. Because lipid peroxidation is a chain reaction that is geometrically amplified by redox-active iron, it is this action of the hydroxyl radical that may have the greatest pathophysiological consequences in diseases such as ischemic heart disease and stroke.”
Ouch. The article then goes on to describe the chemistry of how lipid peroxidation happens. Keep in mind that nerve cells are particularly vulnerable as they have the highest proportion of fatty acids in their cell membranes. It concludes the discussion of lipid peroxidation with: “Hence, the presence together of superoxide radical and redox-active iron can be devastating to the cell in terms of maintaining membrane structure and function, and, therefore, viability. Figure 1 also shows the cellular defense mechanisms that act to prevent this sequence of events. The antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase act as a first line of defense to intercept the active oxygen species directly. If these defenses are overwhelmed and events progress to lipid peroxidation, a second line of defense exists. The antioxidant enzyme phospholipid hydroperoxide glutathione peroxidase [say that 5 times fast!! J] acts to eliminate peroxidized membrane components by reducing peroxides to alcohols. This action prevents the initiation of new chain reactions by ferrous iron as described above. The antioxidant vitamins E and C also collaborate to terminate chain reactions, stopping further accumulation of peroxides. When all these defenses are either overwhelmed or consumed, cell membranes may be so damaged that the cell dies.”
He then goes on to say that iron becomes even more problematic in disease conditions. Hearts from animals who have been iron-loaded suffer more damage when heart attacks are induced. Also, he talks about the fact that increased production of superoxide, coupled with increased iron promotes carcinogenesis (that means “cancer forming”). He says that there is evidence that the monthly loss of blood over a large part of the lifetime of women accounts in part for their better survival of ischemic heart disease. High levels of stored iron have been implicated as a risk factor for heart disease. In patients with small cell lung carcinoma, those with the lowest serum ferritin (blood iron) levels had longer survival rates. He cites a number of articles that link increased levels of iron with Parkinson’s disease, which is why they think that Parkinson’s hits men more frequently than women. Each of these statements is referenced with at least one, and usually several supporting studies. Let me also add, that, while he did not mention it in this article, a number of metals, including iron and aluminum, are found in the brain deposits associated with Alzheimer’s disease. Down Syndrome is associated with these kinds of deposits much earlier in life and with much higher frequency than the general population.
Vitamin A can become toxic because the body does not have a good mechanism to flush excess out of the body. There are big-time (justified) warnings about toxicity of vitamin A. Iron can also become toxic for the same reason: the body does not have a good mechanism to flush excess out of the body. Yet iron supplementation is pushed for all children, without even doing a blood test to see if it is needed. This is what I mean by a knee-jerk reaction.
So, there is my data to support my contention that iron is not a good idea especially in Down Syndrome.
Originally posted on the DSTNI email list at Yahoogroups on Dec 17, 1999. Used by permission of the author and list moderator.