This newsletter is coming to you because I am tired of all the costly misunderstanding about iron deficiency; tired of patients who are iron deficient being told by their doctors they are fine because they do not have anemia. I am tired of seriously iron deficient patients discontinuing their iron pills every time they hear from the media about the over hyped risks of iron excess.

I diagnose iron deficiency in my patients quite commonly and have only seen a problem with excess iron a handful of times. Iron excess is a genetic problem called hemochromatosis occurring mostly in men who are of Northern European background, when it does occur. It rarely develops from the excess supplementation of iron.

I have found that those prone to iron deficiency either by dietary habits, faulty absorption, or some other unknown malfunctioning or risk factor will almost never be able to accumulate excess iron. Indeed, even with supplementation, they have difficulty achieving the security of mid normal levels. I have had to refer a few patients for IV administration of iron because they either could not achieve adequate levels by oral dosages, or they had intolerable side effects from the oral iron.

Iron deficiency is a significant global problem. It is essential we address the iron issue so as to attend to those at risk. Did you know that one third of the world’s population is iron deficient? Did you know that iron deficiency is the most common nutrient deficiency in the world, exacting incalculable tolls which we shall later discuss? Iron deficiency is the most common cause of anemia worldwide. Granted, the problem is four times greater in developing countries than in the U.S. Still, at least 10% of the U.S. population is deficient and since they are rarely males, that means 20% of the women and children are clearly deficient. Iron deficiency is the most common nutrient deficiency in American children.

Check out the following list of those at risk for low iron levels, and you will see at least half of the population is at risk. Only males are relatively safe, unless quite elderly and malnourished, or with specific risk factors.

Iron deficiency early in childhood can have long-term effects on mental development that may be irreversible. Iron deficiency is not easy to detect without a blood test. Most babies, particularly those who are premature or have low birth weight, need an iron supplement. Give as an iron fortified formula or as a separate liquid supplement to breastfed babies.

With all the possible consequences from iron deficiency, you can see the extraordinary impact of low iron and why this is such an important topic. An iron deficient person would not have all of these symptoms, but some constellation of them. With 5 or more, consider iron problems.

Seventy five to ninety percent of the iron in your body is in hemoglobin which carries oxygen to all parts of your body to keep you from being anemic. There is the mistaken belief (even among those who should know better) that if you do not have anemia you have enough iron. Unfortunate and gross misinformation is given to the general public. In truth, the development of anemia is the last stage of iron deficiency occurring after many functions are already impaired.

Iron is a major player in multiple bodily processes and is needed for the function of about 100 enzymes and coenzymes in your body. For more details about these, you can see http://www.expasy.org/enzyme/ . If you go there, click search by cofactor and then click on the 3 listings of iron and the one of heme. These enzymes allow necessary biochemical reactions and transformations to take place. Some of the more studied of these enzymes are cytochrome C, cytochrome C oxidase, catalase, aconitase, and aromatic amino acid hydroxylases. The iron related enzymes are quite sensitive to depletion with even minor iron deficiency.

Hydroxylases are needed for the conversion of the amino acids tyrosine, phenylalanine and tryptophan to form critical brain neurotransmitters which are responsible for essential brain functions. This is why depression, learning and memory problems, and other brain malfunctions may be early signs of iron deficiency. The enzymes can malfunction with minor iron deficiency and before any manifestation of anemia. This is why there are so many symptoms associated with iron deficiency which may not necessarily be related to anemia.

Catalase breaks down and removes hydrogen peroxide from your body by turning it in to harmless water and oxygen. Hydrogen peroxide is a toxic waste product of metabolism which can accumulate and cause symptoms if not removed regularly.

The cytochrome enzymes are located in the inner membrane of the mitochondria, the energy generating part of each cell in your body. These enzymes participate in the process of changing your food to energy. Too little or too much iron in the mitochondria will cause malfunction of energy production.

Iron is also required for the synthesis of collagen and elastin which are the main supportive structures holding your body together.

Iron starvation arrests cell proliferation, presumably because the metal is required by ribonucleotide reductase and other enzymes involved in cell division. It is also required for DNA synthesis which allows cells to multiply and regenerate.

Iron is needed for the synthesis of the amino acid carnitine, which plays a role in fatty acid metabolism.

Iron plays a critical role in the major detoxification pathways of the liver.

And I include all of these gory details for two reasons; to see how much iron we may not be eating, and to guide those who are know iron deficients to eat more carefully and consciously.

The average American diet contains about 10-15 mg of iron daily, of which only 10% is absorbed, so about 1-1.5 mg daily. This about equals the daily amount of iron which is lost from the body through shed intestinal cells, sweat, and blood loss ( which may be minor, but chronic). Chronic loss of even small amounts of blood may significantly increase iron requirements. The average daily menstrual loss is 0.6-0.7mg. In Fe depletion, dietary absorption increases but rarely to > 6 mg of Fe unless supplemental Fe is added.

Defective iron absorption is caused by diets low in iron , high in cereal/grain content, and low in animal protein. Some amino acids in animal protein facilitate the absorption of iron.

Certain foods and drinks reduce your body's ability to absorb iron, including:

Cow's milk products are very low in iron, thus, if they become a major part of one's diet, iron deficiency is more likely. In addition, clinical studies have shown that infants consuming cow's milk lose small amounts of blood from their digestive tracts. For this reason, the American Academy of Pediatrics recommends that infants below one year of age not be given whole cow's milk. "We now think that iron deficiency at that age can lead to brain damage" - Dr. Lewis Barnes, University of Wisconsin Pediatrician. If you consumed only dairy products, you would have to drink 50 cups of milk to reach your RDA's for iron.

Endurance performers are susceptible to iron-deficiency because the absorption of iron cannot balance the losses incurred through training. Women in intensive athletic training may particularly need 100-200 mg of supplemental iron daily.
   

All those in the high risk groups should receive some form of supplemental iron and attempt to eat a diet high in iron. Doses would range from 15-100 mg of elemental iron. The amino acid chelated organic forms of iron or something such as liver extracts would be better tolerated from a gastrointestinal perspective than the inorganic forms such as ferrous sulfate. The supplement, ferritin, is an iron binding protein which is rapidly absorbed, bioavailable and free of gastrointestinal side effects.

I hate to tell you that the usual screening tests doctors order to check for iron deficiency are hemoglobin (Hgb) and hematocrit (Hct) which are tests for anemia only!!! We have already visited that area. Secondly, they may check a serum iron level which may be fine if adequate iron has been absorbed in the last 24 hours (even if the person is suffering from iron deficiency and has very low storage levels available for daily life processes). This method of testing is partially economic as these tests are cheaper, but what use if only measuring the extremes? Cheaper for whom? Not those who will suffer lasting consequences from iron deficiency.

Because changes in Hgb concentration and Hct occur only at the late stages of iron deficiency, both tests are late indicators of iron deficiency; nevertheless, these tests are essential for determining anemia caused by low iron.

Total body iron averages 3800mg in men and 2300mg in women. Iron is stored primarily as ferritin, but some is stored as hemosiderin. Iron is transported in the blood by the protein, transferrin. Ferritin is an active soluble storage fraction found in the serum, liver, bone marrow, spleen, and red blood cells. Hemosiderin is relatively insoluble and in stored primarily in the liver and bone marrow.

.Serum ferritin is a test for total body iron storage and is my favorite and the best test to measure iron status. Low serum ferritin ALWAYS identifies iron deficiency.

A problem is that serum ferritin levels may be falsely increased with liver damage, inflammation, some infections and some cancers. In these unusual cases, it would fail to identify iron deficiency.

The normal range of serum ferritin in most labs is 30-300 mcg/L. In the United States, the average serum ferritin concentration is 135 mcg/L for men , 43 mcg/L for women , and approximately 30 mcg/L for children aged 6-24 months. Serum ferritin 1 mcg/L concentration is equivalent to approximately 10 mg of stored iron. So a level of 30 would equal 300 mg of stored iron.

A study found a positive response to iron treatment in those with ferritin levels less than 50. Another study found that those with ferritin levels less than 50 had a 50% chance of iron deficiency in the bone marrow.

When actually diagnosed with low serum ferritin levels, iron treatment needs to be in higher doses than that used for supplemental maintenance and higher still if there are many symptoms of deficiency or the actual onset of anemia. It takes 6-12 months of iron treatment to replenish the stores of iron in the body after becoming depleted. It is a mistake to discontinue treatment too soon. Further, my position is that once stores are back to normal the person prone to low iron should decrease their treatment dose to a maintenance dose, but continue to take some iron indefinitely. When they stop completely, the problem tends to recur over time…usually because the precipitating cause is not recognized or understood.

Ferrous sulfate, 325 mg three times daily, is the usual prescriptive treatment. Only 10mg of this is usually absorbed since it has about a 3% absorption rate. Patients who cannot tolerate iron on an empty stomach should take it with food.

Inorganic salts are ferrous sulfate and carbonate.

Chelated forms are ferrous citrate, lactate, fumerate, gluconate, succinate, glycinate ,picolinate. These may be better absorbed and better tolerated by the stomach. Avoid enteric coated supplements as they are not well absorbed.

Take iron supplements in several small doses, since one large dose is likely to be unabsorbed and unutilized! It is useful to give with Vitamin C and L-cysteine to enhance iron absorption. Those low in stomach acid may need to add Betaine HCL. Chlorophyll, blue green algae, and spirulina also mysteriously help in building blood and absorbing iron.

Oral iron treatment may fail in patients with low stomach acid, other forms of malabsorption syndrome, chronic diarrhea, continued blood loss, or those who have had part or all of the stomach removed. I have also seen it fail in others for as yet unclear reasons. They will require shots or intravenous iron, as will those who cannot tolerate oral iron treatment.

Accidental overdose of iron containing products is a leading cause of fatal poisoning in children under 6. So do not be careless in properly sealing and storing containers.

Recent studies have shown that under experimental conditions ferrous sulfate (iron) may reduce the gastrointestinal absorption of orally administered levothyroxine sodium in patients with primary hypothyroidism. A patient became hypothyroid while taking ferrous sulfate. The hypothyroid status was corrected by increasing the dose of levothyroxine. Subsequently, when ferrous sulfate was discontinued, the patient became hyperthyroid while taking the higher dose of thyroid hormone preparation. Since both hypothyroidism and iron deficiency anemia may coexist, additional thyroid function testing is recommended in patients treated concurrently with ferrous sulfate and L-thyroxine.

Low iron which is not corrected by giving iron is a common clinical signs of copper deficiency and may be corrected by adding copper supplementation. The low iron results from defective iron mobilization. Copper deficiency may also result in abnormally low numbers of white blood cells, which can make you susceptible to infections and unable to combat them when they occur. We need copper for proteins involved in growth, nerve function and energy release. It is vital for the formation of some important proteins. It is a critical functional component of a number of essential enzymes, known as cuproenzymes. Two copper-containing enzymes, ceruloplasmin ferroxidase I and ferroxidase II are involved in iron metabolism. Copper is stored in appreciable amounts in the liver. It also has anti-oxidant properties and involved in the regulation of gene expression.

The body normally absorbs less iron if its stores are full, but some individuals are poorly defended against iron toxicity. Once considered rare, iron overload has emerged as an important disorder of iron metabolism

Hereditary hemochromatosis (HH) is an iron overload genetic disease caused by a gene which enhances the absorption of iron. It is the most common inherited metabolic disease among the white population worldwide. The body absorbs excess iron and stores it in the major organs (heart, pancreas, liver, etc.). If untreated, this can eventually cause cirrhosis of the liver, diabetes mellitus, and cardiac complications HH is treated by phlebotomy--blood-letting until the serum ferritin normalizes.

The frequency of those with 2 copies of the gene and therefore the disease is about 1%. Those having 1 copy of the gene and therefore a tendency to abnormal iron metabolism are 4-19% depending upon the study. They may have some form of iron overload or hemosiderosis, characterized by large deposits of the iron storage protein, hemosiderin, in the liver and other tissues.

Transferrin saturation is the recommended screening test for hemochromatosis; a repeated high value indicates hemochromatosis . Also the ferritin level will be greater than 300.

Other causes of Excess iron include many blood transfusions and iron therapy given in excessive amounts or for too long. Excess iron consumed all at once causes vomiting, diarrhea, and damage to the intestine. Excess iron consumed over a period of time may damage coronary arteries. Treatment often consists of the drug deferoxamine, which binds with iron and carries it out of the body in urine.

Iron overload is most often diagnosed when tissue damage occurs, especially in iron-storing organs, such as the liver. Ironically, some of the signs of iron overload are analogous to those of iron deficiency: fatigue, dizziness, nausea, vomiting, headache, weight loss, shortness of breath, irritability, lowered work performance, and possibly a grayish skin color. Other common symptoms of iron overload include enlarged liver, skin pigmentation, joint diseases, loss of body hair, loss of menstrual periods, and impotence.

1- Children who had severe, chronic iron deficiency in infancy scored lower on measures of mental and motor functioning. After control for background factors, differences remained statistically significant in arithmetic achievement , written expression, motor functioning, and some specific cognitive processes (spatial memory, selective recall, and tachistoscopic threshold). More of the formerly iron-deficient children had repeated a grade and/or been referred for special services or tutoring. Their parents and teachers rated their behavior as more problematic in several areas, agreeing in increased concerns about anxiety/depression, social problems, and attention problems.

2- Changes in behavior and development have been consistently observed in previous studies that included careful measurement of iron status and appropriate comparison groups. All studies found lower mental test scores, and most reported lower motor scores as well in those with lower iron levels. Other behavioral differences, such as increased fearfulness, unhappiness, fatigue, wariness, or proximity to the mother, have also been noted. Four of 5 studies that assessed change after a full course of iron treatment found that a majority of infants with iron deficiency anemia continued to have lower developmental test scores, despite iron therapy for 2 to 6 months and correction of anemia. Other behavioral differences were also still observed. Available follow-up studies at early school-age show that formerly anemic children continue to test lower than peers.

3- Anemia is associated with less than optimal behavior in infants and children. Iron-deficient children scored lower on tests of development, cognition, learning and school achievement. The impairment of performance has been put at a 5—10 point deficiency in IQ. Studies of infants have shown conclusively that iron deficiency anemia delays psychomotor development and impairs cognitive development. This negative impact in children is not likely to be reversed by subsequent iron therapy.

4- One study, done in Israel, evaluated 14 ADHD boys for the effect of short-term iron administration on behavior. Each boy received iron daily for 30 days. Both parents and teachers assessed the behavior of the children. The parents found significant improvement in the behavior of the children. However, the teachers noticed no improvement.

5- In a study, 33 iron-deficient, but otherwise normal, children were given an iron supplement. The children became less hyperactive. This study suggests that iron deficiency may cause hyperactive behavior in some children and that hyperactive behavior is reversible when the deficiency is treated.

6- A study tested the effects of iron supplementation on a group of teen-aged high school girls who were discovered to be iron deficient. At the end of the 8-week study, the researchers found that girls who received iron supplementation performed better on verbal learning and memory tests than those who did not.

7- A study found that compared with children with normal iron levels, iron-deficient youngsters were more than twice as likely to score below average on a standardized math test. The increased risk was found even in children who were iron deficient but hadn't developed anemia.

The difference in performance was most striking in adolescent girls, who also had the highest prevalence of iron deficiency, said the study lead by Dr. Jill Halterman of the University of Rochester. It was published in the June issue the journal Pediatrics.

"Past studies have shown a superiority of females in math achievement during elementary and middle school years and a reversal of this of this trend with male superiority ... in high school and college years," the researchers said. "This study suggests that iron deficiency may contribute to this gender discrepancy."

8- The effects of iron deficiency anemia (IDA) on nerve conduction and efficiency of iron therapy were investigated by peripheral nerve-electrophysiological measurements. Eighteen children (10 boys, eight girls; mean age 31 +/- 1.3 months) with IDA and 12 healthy children (six boys, six girls; mean age 29 +/- 1.3 months) were enrolled into the study. Nerve conduction velocity was measured in the median and posterior tibial nerve. After nerve conduction values were determined in the patients and controls, 6 mg/kg/24 h ferrous sulphate was given orally to the patients for 3 months and nerve conduction velocity tests were performed again. Median/motor and sensory nerve conduction velocity and tibial/motor nerve distal-amplitude values of children with IDA were lower than for the control group (p < 0.05, p < 0.01 and p < 0.001 respectively). With iron supplementation these values increased to the normal levels and even higher than control levels for some parameters. In correlation studies between whole blood parameters and nerve conduction velocity results, there was a correlation between median/sensory nerve conduction velocity values and serum iron levels. Additionally there was a correlation between some nerve conduction velocity values and age.

In conclusion, the evidence from this preliminary study suggests that peripheral neuropathy may develop in children with IDA. Peripheral neuropathy symptoms in these patients may be improved by iron therapy

9- Introduction: Sleep disorders, including sleep disruption through restless leg syndrome (RLS) are often reported in Attention Deficit/Hyperactivity Disorder (ADHD) children. RLS and Periodic limb movement disorder (PLMD) are associated with low serum ferritin levels in adults. Iron deficiency (ID) in childhood (10-15 mcg/L) could affect the developing central nervous system. ID is also known to affect the modulation of motor activity in sleeping infants.
Methods: Forty-three ADHD children , 36 boys and 7 girls, mean age 9.2 ± 2.2 years, were included in the study. Children were assessed for RLS according to International Restless Legs Syndrome Study Group criteria and for hyperactivity/impulsivity and inattention severity with the Conners Parent Rating Scales (CPRS). Children were investigated for serum iron level and ferritin level . Children were medication free for at least 2 months and none of them had previously been supplemented with iron.
Results: Serum ferritin levels were abnormally low (mean: 13 ± 2 mcg/L) in 11 (25%) ADHD children and subnormal (mean: 23 ± 5 mcg/L) in 22 (51%). Serum ferritin levels were not correlated with age or gender. ADHD index was significantly correlated with ferritin level (R = - 0,407 ; p<0.001). Nineteen (44%) ADHD children met positive criteria for RLS.
Conclusions: This is the first study reporting low serum ferritin levels in ADHD children. Serum ferritin levels correlated with ADHD index and RLS severity in ADHD children. These findings strongly suggest that iron supplementation could enhance the effects of dopaminergic agents which have been used to treat ADHD.

In children with ADHD and iron deficiency, supplementation with iron may improve both behavior and performance in school. Even some children with ADHD who are not iron-deficient may benefit from iron supplementation, though the benefits seem to be less pronounced in those children.

10- Mild Iron Deficiency May Harm Women's Memory

Supplements Can Improve Thinking When Iron Low

April, 19, 2004 news release (Washington) -- Even moderate iron deficiency can impair a woman's thinking. But iron supplements appear to help reverse any learning and memory deficits caused by a lack of iron, a new study shows.

The study is one of the first of its kind to link iron deficiency with a slow down in thinking and memory and to show that replacing iron can remedy the deficits. The researchers warned that supplements have no benefit for women with normal iron levels and that women should have their blood levels checked before using them.

Researchers gave a series of learning and memory tests to more than 100 women between the ages of 18 and 35, about half of whom also had mild iron deficiency but without anemia.

In one test, women were asked to remember a lineup of pictures displayed on a computer screen. On average, those with normal iron levels missed eight questions out of 54, while those with deficiencies missed twice as many, according to Laura Murray-Kolb, PhD, a nutrition researcher at Pennsylvania State University and the study's lead researcher.

"There were in fact differences. The women who were iron deficient did not perform as well as the women who were not deficient,"

But researchers then gave the iron-deficient women 60 milligrams of elemental iron per day and then measured iron levels to be sure that the pills returned iron levels to normal. After four months, the deficient women performed as well on the tasks as women who started out normal.