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Free radicals, intermediates in the tissue damage caused by radiation, are formed, inter alia, in interactions catalyzed by iron, which synergizes with radiation and some cytostatics (anthracyclins) in causing cell damage. Conversely, iron chelators can counteract cell damage. Similarly, antioxidants can slow atherogenesis, caused in part by oxidative stress and free radicals. Cell damage is also prevented by physiological defense systems like superoxide dismutase, against endogenous free radicals formed by granulocytes, monocytes, etc. Iron can thus induce free radicals which cause DNA double strand breaks and oncogene activation. This is suggested by four epidemiological studies suggesting a higher cancer risk in patients with larger iron stores than in those with small iron stores. In addition to its effect on carcinogenesis, iron can also maintain the growth of malignant cells as well as growth of pathogens. Breast cancer cells, for instance, display 5-15 times more transferrin receptors than normal breast tissue. Iron-carrying transferrin is in fact a growth factor. Hyposideremia in patients with cancer or infection is not a paraphenomenon but a functioning defense mechanism ('nutritional immunity'). If this immunity is broken by iron administration, relapses of diseases like tuberculosis, brucellosis, and malaria have been described. While iron-deficiency anemia should of course be diagnosed, treated and if possible prevented, there are good reasons to avoid over-utilization of medicamental iron.

The iron metabolism has been studied in 11 patients with porphyria cutanea tarda. Despite significantly increased amounts of iron in the serum and liver, the porphyria patients absorb not less but significantly more radioiron than normal controls. Whereas phlebotomy-induced iron deficiency stimulates the absorption in controls, no further stimulation is found in the porphyria patients. The plasma iron turnover is high in the porphyria patients, and some of this iron is probably deposited in the liver. The relationship between the high iron absorption, high plasma iron turnover, high liver iron, liver damage and uroporphyrin production in the liver is discussed. It is suggested that two concurrent genetic defects may cause porphyria cutanea tarda, one in iron absorption and one in porphyrin synthesis by damaged liver cells. The absorption of inorganic iron was higher than that of hemaglobin iron. The possible damage which fortification with inorganic iron could cause to the very small group of porphyria patients is discussed.

Reduced serum concentrations of nutrients like iron, zinc and folates and of albumin and cholesterol are found, as well as emaciation, both in malnutrition and in cancer. In patients with leukemia, a depletion of intracellular potassium and hypo-potassemia are found in addition. The use of hyperalimentation in cancer was originally based on the concept that too little food is the cause of these disturbances in the nutrition state. However, there is also a disturbed metabolism of nutrients in patients with tumors and inflammatory disease. In the case of folic acid, the disturbed metabolism could not be normalized by hyperalimentation. The more advanced the disease, the more pronounced is the disturbed nutrient metabolism, and this disturbance is related to the macrophage activity. It is not self-evident, therefore, that hyperalimentation can normalize the nutritional state in cancer. Emaciation in cancer patients is not caused exclusively by malnutrition.

In 34 patients with aregenerative anaemia and hypercellular bone marrow, a condition earlier suggested to be of a preleukaemic nature, erythroblast thymidine labelling indices (LI) were significantly decreased, as would be expected in preleukaemia. The 59Fe erythrocyte incorporation after 2 weeks was generally low. The 59Fe plasma clearance was fast in 22 of 31 patients, normal in 5 and moderately prolonged in 4. These 4 patients had a low relative number of erythroblasts in the marrow. A significant relationship between the marrow erythroblast number and the 59Fe plasma clearance could be demonstrated. Cases with an increased number of mueloblasts in the marrow did differ significantly from the rest in LI and iron incorporation.

Iron should not be prescribed to middle-aged men or older women with anaemia unless the possibility that the iron deficiency is caused by a gastrointestinal tumour has been considered. Thus the prescribing of iron to elderly people was investigated by studying four different prescription statistics and by reviewing records. Over one in 10 women aged over 65 were prescribed iron tablets. Men and women in the oldest age groups were prescribed iron most frequently. The reasons for prescribing iron were examined at a rural health centre. Out of 327 records of patients who were prescribed iron during 1975, 157 were randomly selected and reviewed. Only 18 out of 48 (38%) patients aged 45-75 (men) and 55-75 (women) and 29 out of 109 (27%) aged over 75 years had probable or possible iron-deficiency anaemia as established from the records. Only nine (19%) of the younger patients had a plausible reason for the anaemia other than a bleeding tumour. Ten (9%) of the older patients were considered to be inoperable cases. Thus, according to the records, only 18 (17%) of the patients over 75 years and nine (19%) of those in the younger age group have been prescribed iron. About 70% of all the patients were considered not to have iron deficiency; 7% had had iron deficiency previously, and 20% probably had anaemia as a result of chronic disease; for 43% no real reason for the iron prescription could be found in the record. Thus it is concluded that iron is overprescribed in Sweden, particularly for elderly people. It should not be prescribed until the possibility of a bleeding gastrointestinal tumour has been excluded.

Refractory hypochromic anemia was investigated in an adult with Turner's syndrome. Reduced iron absorption, serum iron, and iron incorporation were found in association with increased iron binding capacity and plasma iron turnover. 14 of 57 additional XO subjects were found anemic.

The metabolism of iron-poly (sorbitol-gluconic acid) complex (Ferastral) was studied in 6 blood donors with latent iron deficiency and 13 patients with manifest iron deficiency anaemia. Between 125 and 1 000 mg of iron were injected. In latent deficiency an average of 19% of the dose given was excreted during the first two weeks. The corresponding figure for patients with manifest iron deficiency was 11%. An average of 8% of the dose was retained at the site of injection after 40 days. In the two groups, respectively, 61% (range 47%-70%) and 58% (range 24%-86%) of the iron retained was incorporated into red cells after 40 days, which is judged to be quite satisfactory. Some local side effects were observed.