Most American meat-eaters get much more iron in their diets than they need.  There is evidence that this increases heart disease and dementia.  This is especially true for men, since women lose iron each month during menstruation.  Some women, children, and vegetarians do suffer from inadequate amounts of iron and need iron supplements.  Older adults usually don't need any iron.  "Senior" multivitamins have lower amounts of iron as their main difference from regular multivitamins.  They probably should have any iron in them at all. 

Anemic 3-Year-Olds: Iron Supplement Helped Mental Functioning: In a DB PC study of 21 anemic and 28 healthy 3-year-olds, a 2-month supplementation of 15 mg iron with multivitamins vs. multivitamins alone, the anemic children made significantly fewer errors of commission (14% higher specificity, P<0.05), exhibited 8% higher accuracy (P<0.05) and were significantly more efficient (mean difference=1.09, P<0.05) than those given placebo. These effects of iron were not found among preschoolers with good iron status. Effect of iron supplementation on cognition in Greek preschoolers. Metallinos-Katsaras E, Valassi-Adam E, Dewey KG, Lonnerdal B, Stamoulakatou A, Pollitt E. Simmons College, Boston. Eur J Clin Nutr. 2004 Jun 30 

Athletes with Low Ferritin Benefit from Iron Supplement: DB PC 40 young elite athletes (13-25 yr) with low serum ferritin (< 20 microg.L-1) and normal hemoglobin (males > 13.5 g.dL-1, females > 11.7 g.dL-1) 12-wk ferrous iron 100mg bid. After 12 wk, ferritin levels were within the normal range in the iron-treated group (IG) with a significant (P < 0.001) mean increase by 20 microg.L-1 opposed to a slight nonsignificant decrease in the placebo group (PG). RBV did not change significantly in either group nor did any of the hematological measures. The exercise test results indicated that in young elite athletes with low serum ferritin and normal hemoglobin concentration iron supplementation leads to an increase in maximal aerobic performance capacity without an augmentation of RBV. Univ Heidelberg, Effects of iron repletion on blood volume and performance capacity in young athletes. Friedmann B, Weller E, Mairbaurl H, Bartsch P. Med Sci Sports Exerc. 2001 May;33(5):741-6

Breast-Fed Infants with Low Hemoglobin Helped by Iron Supplement and Hurt Those with Normal: Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). UC Davis. Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras. Dewey KG, Domellof M, Cohen RJ, Landa Rivera L, Hernell O, Lonnerdal B. J Nutr. 2002 Nov;132(11):3249-55. 

Breast-Fed Infants Helped by Iron Supplement: In a DB PC study of 77 infants given 7.5 mg/day of iron sulfate, iron supplementation resulted in higher hemoglobin and mean corpuscular volume at 6 months of age and significantly higher visual acuity and psychomotor developmental indes at 13 months of age. Newfoundland. A double-masked, randomized control trial of iron supplementation in early infancy in healthy term breast-fed infants. Friel JK, Aziz K, Andrews WL, Harding SV, Courage ML, Adams RJ. J Pediatr. 2003 Nov;143(5):582-6

Cancer of the Colon: Zinc Good, Heme Iron Bad: In a 15-year follow-up of 34,708 Iowa women ages 55-70, the risk of proximal colon cancer more than doubled across increasing categories of heme iron intake (meat), but risks for both proximal and distal colon cancer fell by more than 50% across categories on zinc intake. Heme iron, zinc, alcohol consumption, and colon cancer: Iowa Women's Health Study. Lee DH, Anderson KE, Harnack LJ, Folsom AR, Jacobs DR Jr. J Natl Cancer Inst. 2004 Mar 3;96(5):403-7

Deficient Stores Common in Norwegian Teens: S-ferritin <15 microg/l was found in 25% of girls and 30% of boys. Supplementation increased hemoglobin in only 2%. Acta Paediatr. 1999 Aug;88(8):815-21

Depression Not Found Related to Low Iron in Small Study: Of 365 apparently healthy participants, 4% had hemoglobin < 120 g/L, 6% had transferrin saturation < 16%, 20% had ferritin < 12 micrograms/L, and 8% had clinically elevated scores (T > or = 70) on the Depression scale of the MMPI. The frequency of elevated MMPI Depression scores was unrelated to the frequency of low hemoglobin, transferrin saturation, or ferritin. The results do not support the hypothesis that low iron status contributes to symptoms of depression in women. Iron status and depression in premenopausal women: an MMPI study. Minnesota Multiphasic Personality Inventory. Hunt JR, Penland JG. Behav Med. 1999 Summer;25(2):62-8

Depression Related to Low Iron Only with Birth Control Pill: Study of 255 women. Using univariate analysis, iron deficiency (serum ferritin < or = 12 micrograms/L) was not associated with non-specific symptoms or psychological distress. Among iron-deficient subjects, those using the oral contraceptive pill reported significantly more symptoms (depression, irritability, difficulty concentrating) than non-users. Iron status and non-specific symptoms of female students. Rangan AM, Blight GD, Binns CW. J Am Coll Nutr. 1998 Aug;17(4):351-5

Hemosiderosis Linked to HFE Gene Mutation: 0.3-0.5% of European-Americans have excessive iron stores due to excessive intestinal absorption due to having two copies a Y282 mutation of the HFE gene. The mutation started in Swedish and Celtic lines 1,500-3,000 years ago and may have helped cope with iron deficiency. Progressive accumulation of iron deposits in target organs may result in complications such as cirrhosis of the liver, liver cancer, arthritis, diabetes, impotence and heart failure. Calcium channel blockers may be helpful (Univ. Toronto, Nature Medicine 9/15/03). Drawing off blood and sometimes chelating agents are the standard therapies to lower iron levels.

Iron: High Stores Triples Diabetes in Very Large Study: Of 32,826 women who were not diagnosed with diabetes, cardiovascular disease, or cancer, 698 women developed diabetes during 10 years of follow-up. Women who developed diabetes were heavier, had a family history of diabetes, less exercise, less likely to drink alcohol, had higher baseline C-reactive protein, fasting insulin, and hemoglobin A_1c. Baseline dietary intake of heme iron, trans fat, red and processed meats, and total calories also was higher, and intake of cereal fiber and magnesium was lower. Mean baseline ferritin concentration was significantly higher (109 vs. 71.5 ng/mL; P < .001), and the mean ratio of transferrin receptors to ferritin was significantly lower (102 vs. 141; P = .01). Risk ratios for incident cases of type 2 diabetes decreased across increasing quintiles of transferrin receptors to ferritin ratio (P = .01 for trend). Rui Jiang, Harvard. JAMA. 2/11/2004;291:711-717. Avoiding iron supplements and reducing meat would help these women.

Fatigue in Women with Low Ferritin Helped by Iron Supplement: A DB PC Lausanne, Switzerland, study of 155 women 18-55 found 51% had abnormally low ferritin <20 microg/L. The women were given 80 mg ferrous sulfate iron supplement for 4 weeks. Those on iron had 29% decrease in fatigue. Only those with serum ferritin <50 microg/L were helped. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, Bischoff T, de Vevey M, Studer JP, Herzig L, Chapuis C, Tissot J, Pecoud A, Favrat B. BMJ. 2003 May 24;326(7399):1124. Fatigue measured with 10 point visual analog scale. A European study found 20% women in child-bearing ages had ferritin <15microg/L and 4% iron deficiency anemia.; Also, Tissue iron depletion may negatively affect endurance performance and muscle fatigability. Helped by iron supplementation in DB PC of women with ferritin <20. Am J Clin Nutr. 2003 Feb;77(2):441-8

Infants Benefit From Iron Supplement: Healthy, full-term Chilean infants without iron-deficiency anemia at six months were assigned to iron-supplemented group consisting of 1,123 infants for comparison with the no-added-iron group consisting of 534 infants. At 12 months, iron-deficiency anemia in 3.1% of the supplemented group and in 22.6% of the unsupplemented. Global mental and motor test scores were similar in both groups. Specific behavioral and developmental outcomes of motor functioning, cognitive processing, and behavior differed. Infants who did not receive supplemental iron processed information more slowly, and they were less likely than supplemented infants to demonstrate positive affect, to interact socially, or to assess their caregivers' reactions. Unsupplemented infants were less likely to resist giving up toys and test materials or to be soothed by words or objects when upset. Compared with supplemented infants, they crawled somewhat later and were more likely to be tremulous. NIH funded. Pediatrics. 2003;112:846-854

Infant Psychomotor Development Helped by Iron Fortified Milk: Replacing unmodified cows' milk with an iron supplemented formula milk up to 18 months of age in infants from inner city areas prevents iron deficiency anaemia and reduces the decline in psychomotor development seen in such infants from the second half of the first year. At 18 months, 2% iron supplemented group vs. 33% regular milk group anemic. Birmingham, England. BMJ. 1999 Mar 13;318(7185):693-7

Pregnancy Iron Supplementation Helps Decrease Low Birth Weight Infants: DB studies from Mexico and India show iron component of vitamin supplement is responsible for this benefit effect. Am J Clin Nutr. 2003 Mar;77(3):720-5 and BMJ. 2003 Mar 15;326(7389):571

Pregnancy Iron Supplementation Helps Decrease Low Birth Weight: 513 women before the 20th week of gestation. 275 had a hemoglobin > 110 g/L and ferritin > 20 µg/L and were randomized to 30 mg ferrous sulfate or placebo until the 28th week. Then, those with ferritin concentration of 12 to less than 20 µg/L or < 12 µg/L received 30 and 60 mg iron/day, respectively. Iron supplementation did not significantly affect anemia or the incidence of preterm births. However, it was associated with higher birth weight (206 ± 565 g; P = .010), lower incidence of low-birth-weight infants (4% vs. 17%; P = .003), and lower incidence of preterm low-birth-weight infants (3% vs. 10%; P = .017). Am J Clin Nutr 2003;78:778-81; Iron deficiency is the cause of 90% of anemia in pregnancy. 78% of the placebo group had evidence of iron-store depletion and were given iron supplementation for the remainder of their pregnancies.

Stroke Worse with High Iron Stores: 100 consecutive stroke patients studied. A positive correlation between ferritin and glutamate concentrations in plasma (r = 0.81, p < 0.001) and CSF (r = 0.64, p < 0.001). Plasma ferritin concentrations >275 ng/mL in plasma (OR, 33.5) and >11 ng/mL in CSF (OR, 11.4) were independently and significantly related to early neurologic worsening. The effect was reduced by >60% after controlling for glutamate concentrations, but remained significant. Increased body iron stores may contribute to stroke progression by enhancing the cytotoxic mechanisms in cerebral ischemia. Spain. Body iron stores and early neurologic deterioration in acute cerebral infarction. Davalos A, Castillo J, Marrugat J, Fernandez-Real JM, Armengou A, Cacabelos P, Rama R. Neurology. 2000 Apr 25;54(8):1568-74.

Iron May Worsen Alzheimer's Dementia

Increased Iron, Zinc, Mercury Deposits: Study of 59 Alzheimer's patients and 21 control at U Kentucky by Cornett found increases of iron and zinc in multiple areas of AD brain. Notes that selenium is protective against mercury with some increase in mercury in AD and in some controls. Neurotoxicol 6/98;19:339

Transferrin Receptor Concentration in Parkinson’s: Increased transferrin concentration found linked to increased death. Abnormal iron metabolism in Parkinson's Disease. Marder, Columbia U, Neurol 4/98;50:1138

Transferrin C2 Increases in AD: Variant transferrin in Alzheimer's may be cause of disrupted iron and aluminum transport. Van Landeghem, Umea U, Neuroreport 1/98;9-177

Iron Generates Hydroxyl Radicals: Evidence found that iron deposits in brain may be responsible for oxidation. Smith, Case Western, Proc Natl Acad Sci USA 9/97;49:9866

Increased Iron & Zinc Deposits and Decreased Copper Found in Alzheimer's: U Kentucky study. Deibel found increases of iron and zinc deposits in amygdala and hippocampus of AD pts where AD destruction is common but not in cerebellum where AD defects are not common, J Neurol Sci 11/96;143:137

Increased Magnetite Crystals: Jon Dobson, University of Keele, UK, six brain sample found that magnetite levels increased with Alzheimer's disease severity. Biology Letters (DOI: 10.1098/rsbl.2003.0012) 4/9/03

Increase in Loosely/Bound Iron Found: Kala of U Manitoba found increases in Alzheimer's patients compared to controls in autopsy study. Int J Neurosci 96;86:263

Superficial Siderosis: Found 9 cases of SS were found in 8800 MRI patients. Symptoms are cerebellar ataxia, myopathy, dementia, and hearing loss although none had full symptoms and only two had clear SS syndrome. Graz, Neuroradiol 5/96

Psychiatric Illness Caused by Iron: Seven patients with abnormal ferritin, transferrin saturation index, or urinary iron Rx 7-22 weeks with desferrixamine with improvement. Cutler, Can J Psychiatry 2/98;39:8-11

Desferrioxamine Helps Slow Alzheimer's: BID injections 125 mg. IM five days a week slowed progression of AD and lowered brain aluminum to control levels. Specific to trivalent. Single-blind study with lecithin placebo. McLachlan, U Toronto, Ther Drug Monit 12/93 15:602

Deferoxmine Helps Slow: Treatment group had 50% slower progression and no deaths in 2 yr vs. 5 deaths in no Rx group. However, 5 of 25 in Rx groups developed anorexia. Pts with high MAO metabolite MFO-1 concentration in urine at greater risk. If high level found, recommend isoniazid or other MAOI. Kruck, U Toronto, Clin Pharmacol Ther ’93;53:30. Isoniazid used to decrease MFO-1 which fell from 81% to 8% while MFO-2 increase from 2% to 24% and big jump in unmetab deferoxamine from 17% to 68%. S-E disappeared and regained weight. Anorexia and wt loss only S-E. Kruck, U Toronto, Clin Pharmacol Ther 10/90;48:439

Iron in Heart Disease

Iron: Increased Stores Unfavorable: Three Studies: Men with low serum transferrin receptor concentration/serum ferritin ratio 2.9 and 2.0 times risk of acute MI compared to men in highest third. 99 Finnish men after heart attacks vs. 98 control. Tuomainen, U Kuipio, Circ 4/98;97:1461; Heme iron, supplemental iron, Vit C, alcohol all assoc with increased iron and caffeine associated with decreased iron stores measured by serum ferritin in Framingham elderly. Fleming, Tufts, Am J Clin Nutr 4/98;67:722; Increased LDL, apoB, and electrophoretic LDL associated with increased iron stores as measured by ferritin. Ferritin 200-500 strong risk factor for heart disease in Finnish.; Among elders, intakes of highly bioavailable forms of iron (supplemental iron and red meat) and of fruit, a dietary source of an enhancer of nonheme-iron absorption (vitamin C), promote high iron stores, whereas foods containing phytate (whole grains) decrease these stores. Individual dietary patterns may be important modulators of high iron stores. Am J Clin Nutr. 2002 Dec;76(6):1375-84

Iron: High Serum Iron in Elderly Good: A study of 3,936 elderly with 4.4 years of follow-up found that in the highest quartile vs. lowest CAD death in males had a risk ratio of 0.22 and overall death RR 0.68 and females CAD RR 0.48. Corti, NIH, Am J Cardiol ’97;79:120. Ed: This study is hard to believe since so many studies have documented the harmful effects on a diet high in meat, which is a major source of iron. See Meat and Fat

Iron: Iron Stores Not Related to Heart Disease and Only Possible Link to Stroke: 1612 adults with long follow-up. Hazard Ratio for coronary heart disease of highest ferritin tertile to lowest 0.96. and for stroke 1.48. Serum ferritin and cardiovascular disease: a 17-year follow-up study in Busselton, Western Australia. Knuiman MW, Divitini ML, Olynyk JK, Cullen DJ, Bartholomew HC.

Iron: No Relationship with Coronary Arteriosclerosis: In larger study of patients undergoing angiography, 200 with and 200 without arteriosclerosis were compared. Serum levels of ferritin and of other organic iron indicators--transferrin saturation, total iron-binding capacity, hemoglobin and hematocrit--were neither risk factors nor risk markers for coronary atherosclerosis. Sao Paolo. Serum ferritin levels and other indicators of organic iron as risk factors or markers in coronary artery disease. Armaganijan D, Batlouni M. Rev Port Cardiol. 2003 Feb;22(2):185-9

Iron: Review of Iron Stores Says Unproved: Says 8 epidemiological studies find an association between coronary heart disease and iron stores, but 18 did not. Meyer, Kansas, Clin Cardiol, 12/96;19:925

Reducing Iron by Phlebotomy Helps: At Near Iron Deficiency levels, caused by phlebotomy of 31 patients, a significant increase of HDL-cholesterol (p < 0.001) and reductions of blood pressure (p < 0.001), total and LDL-cholesterol (p < 0.001), triglyceride (p < 0.001), fibrinogen (p < 0.001) and glucose and insulin responses to oral glucose loading (p < 0.001) were noted, while homocysteine plasma concentration remained unchanged. These effects were largely reversed by a 6-month period of Fe repletion with reinstitution of Fe sufficiency. Thus, although individuals at high risk for ASCVD are not Fe-overloaded, they seem to benefit, metabolically and hemodynamically, from lowering of body Fe to levels commonly seen in premenopausal females. Ann N Y Acad Sci 2002 Jun;967:342-51

Thomas E. Radecki, M.D., J.D.

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