From The June 2000 Issue of Nutrition Science News
by Bill Sardi
Recent studies reveal that blood donors exhibit lower rates of many diseases and experience better than average health. Additionally, the centuries-old practice of bloodletting is being revived as a treatment for disorders such as heart disease, cancer and Alzheimer's.  Why would blood reduction improve health parameters? In part, because blood removal helps to control circulating iron levels.
Iron is an essential component of hemoglobin in red blood cells, is associated with strength, and is required for oxygen transport, DNA synthesis and other processes. But it also has a destructive nature. In its free form, unbound from hemoglobin or other binding proteins, it accelerates oxidation or "rusting" of body tissues. Since iron-induced oxidation worsens the course of virtually every disease, iron control could be a universal approach to disease prevention and therapy. 
Whereas poor iron intake, or impaired absorption, may lead to anemia, too much ironiron overloadis even more problematic.  After full growth is achieved, at about age 18 or so, excess iron accumulates in the blood of all humans at the rate of 1 mg per day.  About 80 percent of the body's iron stores are in the blood. Women are less at risk for iron buildup than men because of the blood they lose monthly during menstruation. As a result, women have somewhere around half the circulating iron levels as men. Their rates for heart disease, cancer and diabetes are also about half those of males. Because men have no direct outlet for iron, by age 40 their iron levels are similar to those of a postmenopausal 70-year-old woman. This amount of iron can lead to premature aging and diseases such as arthritis, cancer, cataracts, diabetes, osteoporosis, and retinal, liver and brain disorders.  Postmenopausal women, or women who have undergone early hysterectomy in their 20s, 30s and early 40s, may experience similar problems. 
Recognizing The Problem
Iron overload hasn't gone completely unnoticed. There are a number of books on the topic, but most are written for health professionals, leaving the public largely unaware of the problem. Also, some confusion exists regarding the role of iron in health and disease. First, there is a mistaken idea that the majority of the people affected by iron overload diseases have the genetic form, called hemochromatosis, which affects only about 1 million of the estimated 275 million Americans. In fact, the potential threat of iron overload is universal. It comes with advancing age and regardless of genetic factors. Second, the emphasis on preventing anemia in children and menstruating women has detracted attention from progressive iron buildup in adult men and postmenopausal women. [6 ]
Upon closer inspection, many health-promoting practices inadvertently control iron. For example, taking an aspirin a day to prevent heart attacks and strokes causes blood loss via the digestive tract on the order of about a tablespoon per day. This results in iron loss.  Raymond Hohl, M.D., an assistant professor of internal medicine and pharmacology at the University of Iowa in Iowa City, says even chronic use of a baby aspirin may help to control iron and in some cases can induce iron-deficiency anemia.  Aspirin also appears to increase the production of ferritin, an iron-binding protein that prevents iron from inducing oxidation.  By exercising, a person loses about 1 mg of iron through sweat.  Fasting and vegetarian diets, both of which promote longevity in animals and humans, limit iron consumption because red meat contains the highly absorbable heme iron. Whether or not related to iron consumption, restricting red meat consumption has been shown in various studies to reduce the risk of colon cancer. 
Normal Iron Regulation
In healthy individuals there is little if any unbound iron circulating in the blood. In all disease states, however, unbound iron (also called free iron) is released at sites of inflammation and can spark uncontrolled oxidation.  Fortunately, there are numerous automatic mechanisms in the body that help to control iron, many by chelationcompounds that bind to a toxic substance (such as iron) and render it nontoxic or nonactive. Albumin, a simple protein found in blood, acts as a chelator by loosely binding to iron.  Ferritin, produced in the liver, is another iron-binding protein.  Transferrin is a protein that chelates iron and totes it back to the liver, where it is metabolized and excreted.  The liver produces lactoferrin, another iron chelator, when challenged by infectious agents.  This is important because pathogenic organisms such as viruses, bacteria and fungi require iron for growth. Furthermore, as iron stores increase, the gastric absorption of iron decreases. So the body employs numerous mechanisms to control iron that are activated when threatened by disease. However, these defensive mechanisms can be overwhelmed.
Blood tests for iron levels (i.e., hemoglobin and ferritin levels are checked for transferrin saturation percentages) are often useful, but the results of these tests are confounded in states of prolonged inflammation or disease.  A skilled hematologist is often the best professional from whom to obtain personal information concerning blood iron levels.
Differentiating between anemia and iron overload can be difficult because both conditions cause fatigue. One study at the Department of Medicine, University of Western Ontario in Canada, found that iron overload can produce a wide range of symptoms, such as joint pain (particularly hip), unexplained gastric pain, frequent infections, skin bronzing, elevated liver enzymes, cessation of menstruation, hair loss and heart flutters (fibrillation). Yet, of 410 iron-overload patients, 27 percent experienced no symptoms whatsoever.  Common symptoms of iron-deficiency anemia are lowered resistance to infections, fainting, breath holding, mental fatigue, sleepiness, cold hands and feet, and cravings for ice, meat or tomatoes, all which are more likely to occur among women. 
Dietary Iron Control
Various dietary practices can help control iron levels. In a relatively short period of time, dietary changes can result in anemia, iron overload or an ideal state of iron control. Anemia can be induced in about 120 days, while symptoms of iron overload can come on in just 60 days.
Humans absorb only a fraction of the iron they consume, but there are many controlling factors.  Iron absorption rates from food vary widely, from less than 1 percent to nearly 100 percent.  Cooks who use iron or stainless steel pots increase the amount of iron they consume.  Generally, iron in plant foods is not as well absorbed as iron from meat: Only 5 percent of iron in plant foods is available, vs. 30 to 50 percent of iron from meat.  Olive oil and spices such as anise, caraway, cumin, licorice and mint promote iron absorption,  while antacids, eggs and soy reduce availability.  Since dairy products contain lactoferrin, milk also inhibits the absorption of iron.  Moderate alcohol consumption is unlikely to pose a problem with iron absorption, but excessive amounts of alcohol is associated with iron overload, particularly in adult males. 
Vitamin C also increases iron absorption.  However, there is no evidence that vitamin C leads to iron overload. Thus vitamin C should not be avoided by meat-eaters for this reason, since studies show high-dose vitamin C supplements are associated with a decreased risk for heart disease, cancer, cataracts and other disorders.  A vegetarian diet does not generally cause iron-deficiency anemia because there is more vitamin C in plant-food diets, which enhances absorption. 
A 1982 human study was conducted to assess the effect of various drinks on iron absorption. A subject ate a standard meal of a hamburger, string beans, mashed potatoes and water. When green tea was drunk instead of water, iron absorption was reduced by 62 percent. Coffee reduced iron absorption by 35 percent, whereas orange juice (as a source of vitamin C) increased absorption by 85 percent. Contrary to other studies, milk and beer had no significant effect. 
Bioflavonoids (found in berries, coffee, green tea, pine bark, quercetin and the rind of citrus fruits, particularly blueberry, cranberry, elderberry and grape seed) and phytic acid (a component of whole grains and seeds such as sesame) bind to iron and other minerals in the gastric tract and help to limit iron availability. If bioflavonoids and phytic acid haven't bound to minerals in the digestive tract they will get into the bloodstream, where they can bind to free iron, acting as blood-cleansing iron chelators. Therefore, maximum iron chelation in the blood circulation is achieved when these iron binders are consumed apart from meals.
Phytic acidalso called inositol hexaphosphate, or IP6is comprised of six phosphorus molecules and one molecule of inositol. It has been mistakenly described for decades as an "anti-nutrient" because it impairs mineral absorption. However, in the 1980s food biochemist Ernst Graf, Ph.D., began to tout phytic acid for its beneficial antioxidant properties achieved through mineral chelation. 
Phytic acid in foods or bran should be distinguished from supplemental phytic acid, which is derived from rice bran extract. In foods, phytic acid binds to iron and other minerals in the digestive tract and may interfere with mineral absorption. As a purified extract of rice bran, taken between meals so it will not bind to minerals in the digestive tract, phytic acid is readily absorbed into the bloodstream, where it acts as a potent mineral chelator.  Phytic acid binds to any free iron or other minerals (even heavy metals such as mercury, lead and cadmium) in the blood, which are then eliminated through the kidneys. Phytic acid removes only excess or unbound minerals, not mineral ions already attached to proteins.
Phytic acid is such a potentbut safeiron and mineral chelator that it may someday replace intravenous chelation therapy such as the mineral-chelator EDTA or iron-binding drugs such as desferrioxamine (Desferal). Because of its ability to bind to iron and block iron-driven hydroxyl radical generation (water-based) as well as suppress lipid peroxidation (fat-based), phytic acid has been used successfully as an antioxidant food preservative. 
Phytic acid supplements should not be taken during pregnancy since the developing fetus requires minerals for proper development. Because aspirin causes a small loss of blood and consequently helps to control iron levels, the simultaneous use of phytic acid with a daily aspirin tablet is not advised. A three-month course of phytic acid should achieve adequate iron chelation, and prolonged daily supplementation may lead to iron-deficiency anemia. Anemic individuals who take phytic acid as a food supplement are likely to feel weak shortly after consumption, whereas iron-overloaded individuals are likely to feel increased energy.
For those at risk for iron overload, it may be wise to avoid iron in multivitamins and shun fortified foods that provide more than 25 percent of the recommended daily intake for iron. No doctor should prescribe iron tablets for patients who complain of fatigue without blood tests and a thorough health history. Iron-rich foods such as red meat and molasses may prevent anemia and build strength during the growing years but in adulthood may lead to iron overload among men and postmenopausal women. Those individuals who learn how to achieve iron balance will maintain the most desirable state of health throughout life.
Why Fortify Foods?
1. Bonkovsky HL, et al. Iron in liver diseases other than hemochromatosis. Semin Liver Dis 1996;16:65-82.
2. Gutteridge JMC, Halliwell B. Antioxidants in nutrition, health and disease. New York: Oxford University Press; 1994. p 24-39.
3. McCord JM. Iron, free radicals, and oxidative injury. Sem in Hem 1998;35:5-12.
4. Crawford RD. Proposed role for a combination of citric acid and ascorbic acid in the production of dietary iron overload: a fundamental cause of disease. Biochem Mol Med 1995;54:1-11.
5. Emery TF. Iron and your health. Boca Raton (FL): CRC Press; 1991. p 1-13.
6. Arthur CK, Isbister JP. Iron deficiency. Drugs 1987;33:171-82.
7. Rider JA, et al. Double-blind comparison of effects of aspirin and namoxyrate on pH of gastric secretions, fecal blood loss, serum iron and iron-binding capacity in normal volunteers. Curr Ther Res 1965;7:633-8.
8. Bankhead C. In assessing anemia, doctors must decipher role of iron deficiency. Med Tribune Clin Focus 1997 Mar; 20:24.
9. Oberle S, et al. Aspirin increases ferritin synthesis in endothelial cells: a novel antioxidant pathway. Circ Res 1998;82:1016-20.
10. Vellar OD. Studies on sweat losses of nutrients. Scand J Clin Lab Invest 1968;21:157-67.
11. Kampman E, et al. Meat consumption, genetic susceptibility, and colon cancer risk. Cancer Epid Biomarker Prev 1999;8:15-24.
12. Griffiths, E. Iron and infection. New York: John Wiley & Sons;1987. p 1-25.
13. Goldwasser P, Feldman J. Association of serum albumin and mortality risk. J Clin Epid 1997;50:693-703.
14. Aust SD. Ferritin as a source of iron and protection from iron-induced toxicities. Toxicol Lett 1995;82:941-4.
15. Aisen P, Brown EB. The iron-binding function of transferrin in iron metabolism. Sem Hematol 1977;14:31-46.
16. Baker EN, et al. Three-dimensional structure of lactoferrin. Adv Exp Med Biol 1998;443:1-14.
17. Hulten L, et al. Iron absorption from the whole diet in men: how effective is the regulation of iron absorption? Am J Clin Nut 1997;66:347-56.
18. Adams PC, et al. The relationship between iron overload, clinical symptoms and age in 410 persons with genetic hemochromatosis. Hepatology 1997;25:162-6.
19. Marinella MA. Tomatophagia and iron-deficiency anemia. N Eng J Med 1999;341:60-1.
20. Monsen ER. The ironies of iron. Am J Clin Nutr 1999;69:831-2.
21. Hurrell RF. Preventing iron deficiency through food fortification. Nut Rev 1997;55:210-22.
22. Park J, Brittin HC. Increased iron content of food due to stainless steel cookware. J Am Diet Assoc 1997;97:659-61.
23. U.S. Agricultural Research Service, USDA Bulletin. 1998 Dec 23.
24. El-Shobaki FA, et al. The effect of some beverage extracts on intestinal iron absorption. Z Ernahrungswiss 1990;29:264-9.
25. Morris ER. An overview of current information on bioavailability of dietary iron to humans. Fed Proc 1983;42:1716-20.
26. Davidsson L, et al. Influence of ascorbic acid on iron absorption from an iron-fortified chocolate-flavored milk drink in Jamaican children. Am J Clin Nut 1998:67:873-7.
27. Fletcher LM. Alcohol and iron: one glass of red or more? J Gastro Hepatol 1996;11:1039-41.
28. Derman DP, et al. Importance of ascorbic acid in the absorption of iron from infant foods. Scand J Haematol 1980;25: 193-201.
29. Gerster H. High-dose vitamin C: a risk for persons with high iron stores? Int J Vitam Nutr Res 1999;69:67-82.
30. Craig WJ. Iron status of vegetarians. Am J Clin Nut 1994 May; 59(5 Suppl):12335-7.
31. Hallberg L, Rossander L. Effect of different drinks on the absorption of non-heme iron from composite meals. Hum Nutr Appl Nutr 1982;36:116-23.
32. Graf E, et al. Phytic acida natural antioxidant. J Biol Chem 1987;262:11647-50.
33. [No authors listed] Phytic acid: new doors open for a chelator. Lancet 1987 Sept 19:2;2(8560):664-6.
34. Lee BJ, Hendricks DG. Phytic acid protective effect against beef round muscle lipid peroxidation. J Food Sci 1995;60:241-4.
Return to the NUTRITION ARCHIVES Section