IRON OVERLOAD - THE MISSED DIAGNOSIS
by: Cutler, Paul, M.D.
Dr. Cutler graduated from the University of Toronto medical school, and practiced nutritional and general medicine in Toronto until 1993. He has clinics now in St. Catharines, Ontario and Niagara Falls, New York. He has published many research articles on excess iron in medical journals including Diabetes (Oct. 1989), American Journal of Psychiatry (Jan. 1991), Journal of Neurological and Orthopaedic Medicine and Surgery (Spring 1993), and Canadian Journal of Psychiatry (Feb. 1994).
My interest in iron metabolism began around 1986 when I read an article published in The Mayo Clinic Proceedings by Virgil Fairbanks who was then chief of iron metabolism. His article, Hemochromatosis or Iron Overload - the Neglected Diagnosis was a scathing attack on the medical profession for ignoring excess iron in the body. Physicians were more interested in anaemias and low iron deficiency and did not really perform the necessary tests of iron metabolism to diagnose the opposite end of the spectrum - iron overload. He described conditions directly related to excess iron in the body such as arthritis, diabetes, psychiatric illness, and liver disease.
These conditions were very common in my medical practice, and I decided to find out how many of my patients had excess iron, and it turned out to be a significant number, as many as 30% of my patients. When I began to lower the iron levels, my patients improved, and I published some research articles on the subject in some rather prestigious medical journals. By 1989, doctors began publishing research which showed that iron was also a risk factor in cancer at levels that were far less than what they had thought safe in the past. In September 1992, a classic article in Circulation by Jerome Sullivan showed that excess iron was also a risk factor in heart disease, second only to cigarette smoking as a cause of heart attacks in men. Sullivan's study sent shock waves through the medical and nutritional communities because doctors have been prescribing supplementary iron, and nutritionists have been insisting that food be fortified with iron, and this was a reminder that excess iron is very dangerous. In the following year, studies were published which showed that vitamin E and vitamin C reduced the rates of heart attacks and angina, and when you put all of these studies together, you realize that iron is capable of inducing free radical or oxidative pathology.
EFFECT OF EXCESS IRON ON ANTIOXIDANTS Two thirds of the iron in the body is in the hemoglobin itself where it is believed to be safe, about 6% in muscle and various important iron enzymes, and 27 to 30% in storage and this has now been shown to be no longer safe but it will overwhelm the cells and cause free radical pathology. Free radicals are normally produced in the body for metabolism of oxygen, but free radicals can also be produced by excess ultra violet radiation, excess sunlight, tobacco smoke, and an excess of any metals such as iron or copper and they can deplete the antioxidants such as vitamin C and E in the body. Free radicals are atoms with an unpaired or an extra electron in any orbit, usually the outer one. The free radicals create havoc to normal cells by removing electrons from the normal cells to pair their own missing electron, and this damages the healthy cell which in turn tries to draw electrons from an adjacent cell, and this chain reaction of destruction will continue, unless there are enough antioxidants to step in and donate electrons to these cells or to the free radicals and stop the attack. So as the iron builds up, the antioxidants go down. Therefore in order to offset the adverse affects of excess iron, you need adequate supplies of the antioxidants vitamin C, vitamin E, and beta carotene, often in amounts much larger than the average balanced diet can supply.
CANCER Tumour cells and bacteria need iron to grow, and your body tries to starve them of iron by diverting the iron from the blood to storage sites deep within the tissues. It is well known, biochemically, that if you add iron to tumour cells in cultures, they grow at a much faster rate and that breast cancer cells thrive on iron. In 1988, many studies began to surface showing that iron was indeed a risk in common cancers such as lung, colon, bladder, oesophagus, and at levels that were shockingly less than doctors had previously considered dangerous. A study in the New England Journal of Medicine (Oct. 1988) by Dr. Richard Stevens showed that as iron saturation levels increase, cancer rates go up. Until that time a 65% saturation level was considered to be safe, but this study showed that at a 37% saturation level, the cancer rate started to skyrocket, and doctors began to question the levels they had previously considered safe. In January 1994, in the International Journal of Cancer, Dr. Stevens reported that cancer rates were increasing at levels of only 31%.
ATHEROSCLEROSIS Some interesting findings came out of the 1992 Sullivan study. Many doctors began reporting that as iron levels increase, as ferritin goes up above 200, the cholesterol levels also go up, especially the LDL (bad) cholesterol, regardless of changes in diet such as reducing high cholesterol foods. Blood sugar goes up, blood pressure goes up, triglycerides go up and HDL levels go down. Despite all the recent studies in cardiology and cardiovascular surgery journals, I still don't know of any cardiovascular surgeons who put their patients on vitamin E or attempt to remove excess iron before they do these procedures. Doctors don't seem to want to recommend nutritional supplements. Under 5% recommend vitamin E to heart patients. It's tragic, because they know better.
FATIGUE The most common symptom of iron overload is weakness, lethargy and a fatigue that is disabling. As the iron builds up it disturbs other body processes and depletes certain minerals and vitamins such as zinc, and vitamin E and vitamin C.
CIRRHOSIS OF THE LIVER Abdominal pain is the next most common symptom and this is usually in the right upper quadrant because the liver is involved. In iron overload patients, cirrhosis of the liver is 13 times more common than in the general population.
ARTHRITIS Arthritis caused by iron is common in anywhere from 35 to 60% of people who have arthritis, especially in young people, and it will start with the first three fingers, or the knuckle joints of the thumb, index and third fingers; although any joints can be involved, these will get the brunt of it.
ENDOCRINE IMBALANCE: THYROID, ADRENALS, DIABETES Iron has a marked affinity for the different glands. One of the first glands that is affected is the pituitary, and it is common to find evidence of low pituitary hormones. Testosterone production in the testicles is reduced and this can cause impotence. Iron can also affect the thyroid, and the adrenal glands and will eventually affect all tissues if untreated, but endocrine tissues are the most effected. And the most common endocrine manifestation is diabetes.
PSYCHIATRIC DISORDERS If the iron is not needed by the bone marrow to make new red cells, then it goes to tissues like the liver. The next major source for storage of iron is the brain. Iron affects the neurotransmitters in the brain, affecting the hydroxylase system in the brain, so that psychiatric symptoms and neurological symptoms like confusional states, dizziness, mood disorders, and even ringing in the ears are relatively common.
ALZHEIMER'S DISEASE Dr. Richardson, Chief of Psychiatry at the University of Saskatchewan feels the major cause of Alzheimer's Disease is excess brain iron levels. So as liver iron builds up, brain iron levels build up. Dr. McLachlan at the University of Toronto Dementia Clinic showed that aluminum was the cause of Alzheimer's Disease (D.R.C. McLachlan et al. Desferroxamine. Lancet, June 1991). He is using an iron chelator called deferoxamine to treat Alzheimer's Disease and his results are probably better than any other treatment program for Alzheimer's. He stated that the drug arrests the disease. Dr. Richardson and Dr. McLachlan have been arguing, "Is it the iron, or is it the aluminum?" The same medication lowered both. It is my feeling that iron is a far greater risk in this condition than is aluminum.
PIGMENTATION Iron overload has often been called the "bronze disease", because untreated people can develop this natural beautiful tan without going out in the sun, but that is an end stage and we don't see that any more, but you will see isolated patches of brown that almost look like coffee stains on the skin. These clear up dramatically and the bronzing goes away as the iron is removed.
CAUSES OF IRON OVERLOAD
HEREDITARY Hereditary hemochromatosis is a genetic disease in which abnormal genes permit the individual to absorb too much iron from an ordinary diet. This hereditary factor is probably the most common way people get overloaded with iron. There is no real mechanism for controlling iron absorption in the body. Outside of menstruation, the body really has no way of getting rid of extra iron. Normally the average diet contains 15 to 25 mg. of iron and yet all we need is one mg. per day for normal metabolism. In hemochromatosis, 3 or 4 mg. of iron per day are absorbed instead of the 1 mg. we need, and over the years this results in massive overloading and accumulation of iron in the vital organs. As many as 20% of the population has the genetic potential to overload with iron from what we would call a normal dietary intake. Jerome Sullivan who has published papers on iron as a cause of heart disease since 1981 believes that hereditary hemochromatosis is basically the reason some families have a greatly increased risk of heart disease.
TRANSFUSIONS Certain anemias require a lot of transfusions and patients can be overloaded with iron in this way.
SUPPLEMENTS If you take iron supplements over an extended period of time when you don't need them, you will overload with iron. Many in the medical profession have been guilty of abusing prescription of iron supplements without even performing iron blood studies because they felt iron was safe. Also, people who have too much iron can get very sick from taking vitamin C and must use vitamin C carefully because it increases iron absorption especially when taken during or after meals.
NUTRITIONAL INTAKE There are sources of nutritional dietary iron which raise the iron levels in the body such as red meat and alcohol. Iron exists in two forms and this is important to remember because they are absorbed differently. The heme iron, meat iron or ferrous iron has probably around 12 to 15% absorption, whereas the non-heme, ferric or plant iron has only 2 to 5% absorption. This is why the studies by Sullivan and others have shown that it is the red meat iron that really has to be restricted in diets for people with iron overload, and plant iron is not considered to be a major offender in iron overload states. Iron fortified enriched foods can raise iron levels and are now being questioned. Water with excessive iron levels can cause something called Kachung's Disease, a disease reported in China, which is an arthritis and heart disease from excess iron. There is the classic Bantu disease occurring in Bantus who brewed beer in pots that are excessively high in iron. Iron cooking utensils can increase the iron content in the food from 3 to 10 fold. This is especially true of acidic foods such as tomato sauce. Alcohol per se is not high in iron, but it's a potent reducing agent and reducing agents can convert the ferric from plant iron to the ferrous or heme iron, and will increase the absorption of iron from the intestine.
SCREENING FOR EXCESS IRON There are four necessary tests: serum iron, TIBC (total iron binding capacity), percent transferrin saturation and serum ferritin. Acceptable transferrin saturation was previously 60%; it is now less than 30%. The safe level of stored iron, called ferritin, was previously 500; after Sullivan's 1992 study, most people accept 120 as normal and 200 as being significantly toxic. So now we have figures which are about half of what was considered safe only a year or two ago.
TREATMENT Dr. Fairbanks at the Mayo Clinic said that conditions that are related to iron will often be completely cured when the iron is removed, and scientists are now doing research to show that you can reverse all of these problems which increase with iron overload by drawing the blood or lowering the iron. Excess iron is toxic and it doesn't matter whether your excess iron is genetic or acquired, it has to be removed. Most iron related problems seem to occur in men in their late 40's around 49 to 55, and in women around 60 to 65. The accepted treatment for most people is by removal of blood. If you draw out the blood, the iron comes out with it. Most of the time we do it once per week for around 15 to 20 blood removals. We do the same as the Red Cross, we remove 400 or 500 ml. to correct this. 95% of the time we use blood removal or phlebotomy and 5% we use iron chelators like deferoxamine. There are certain problems which do not respond to blood letting such as the type of arthritis caused by iron overload. Chelators are used in these cases to draw the iron out of the joints and the arthritis is cured. The Hospital for Sick Children is now researching an oral iron chelator which may replace all of this but it will require years of testing.
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For more information see Iron Balance (1991) by (Harvard Medical School). You may contact the Canadian Hemochromatosis Society, Box 94303, Richmond, B.C. V6Y 2A6.