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Biomedical subjects

L Hallberg

Publications and source records attributed to L Hallberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Iron stores in man in relation to diet and iron requirements.

OBJECTIVE: To calculate iron stores in man and their rates of changes in relation to iron requirements and dietary iron intake and bioavailability. METHOD: Newly established relationships between iron absorption from whole diets and serum ferritin (SF) and between SF and iron stores allow calculations of amounts of stored iron under different conditions (diets, losses) at stationary states when absorption equals losses. Rate of growth of stores can also be calculated. All calculations are based on observations and require no model assumptions. RESULTS: Present calculations of iron stores agree with previously observed phlebotomy values. Differences in intake and bioavailability of dietary iron and in iron requirements had marked effects on amounts of stored iron. A wide range of diets was studied, from a hypothetical high-meat diet typical for early man to diets in developing countries. A new equation is given for the translation of SF into iron stores. Analyses of growth rate of stores under different conditions showed a fast growth from zero iron stores during the first year (reaching about 80% of final amounts) followed by a much slower rate for 2-3 y. A marked inertia was seen in rate of changes in iron stores that was more marked the closer stores were to their stationary states making it difficult to use SF to estimate short term changes in iron absorption in iron replete subjects. CONCLUSIONS: Realistic Western-type diets with good bioavailability can cover iron requirements in most women and can restitute iron stores during lactation. The high prevalence of iron deficiency in menstruating Western women is thus mainly related to a further low bioavailability of iron in present diets. Present analyses also demonstrated an effective control of iron absorption preventing development of iron overload in otherwise healthy subjects even if the diet is fortified with iron and even if meat intake is high.

Absorption↗
PubMed1997

Iron absorption from the whole diet in men: how effective is the regulation of iron absorption?

Iron absorption from the whole diet, which contained a highly bioavailable form of iron, was measured for 5 d in 31 health men, including 12 blood donors. Nonheme iron in all meals was labeled with an extrinsic, inorganic radioiron tracer added in amounts to ensure uniform specific activity in all meals. Heme iron was labeled similarly by using hemoglobin biosynthetically labeled with another radioiron tracer. There was a good inverse relation between total absorption and concentration of serum ferritin up to approximately 60 micrograms/L. In subjects with serum ferritin > 60 micrograms/L there was no relation to iron absorption. At this serum ferritin concentration, absorption decreased to a level just sufficient to cover basal iron losses, implying that at a serum ferritin concentration > or = 60 micrograms/L no further accumulation of iron stores will occur by dietary iron absorption. The findings thus suggest that in normal subjects there is no risk of developing iron overload by iron absorption from the diet even if the diet is fortified. Similar findings were made previously in two studies in women, both of which indicated an effective control of absorption. At the same serum ferritin concentration the absorption per kilogram body weight was the same in men and women served identical diets with a high iron bioavailability. These new observations strongly suggest that translation of serum ferritin concentration into amounts of stored iron should be made with caution and that in subjects with high serum ferritin concentrations, other causes than increased iron stores should be considered. There was effective control of both heme- and nonheme-iron absorption but their relations to iron status were different.

Adult↗
PubMed1996

Monitoring populations for DNA repair deficiency and for cancer susceptibility.

The induction of a mutator phenotype has been hypothesized to cause the accumulation of multiple mutations in the development of cancer. Recent evidence suggests that the mutator phenotype is associated with DNA repair deficiencies. We have been using a challenge assay to study exposed populations to test our hypothesis that exposure to environmental toxicants induce DNA repair deficiency in somatic cells. In this assay, lymphocytes were irradiated in vitro to challenge cells to repair the radiation-induction DNA strand breaks. An increase of chromosome aberrations in the challenged cells from toxicant-exposed populations compared to nonexposed populations is used to indicate abnormal DNA repair response. From studies of cigarette smokers, butadiene-exposed workers, and uranium-exposed residents, the assay showed that these exposed populations had mutagen-induced abnormal DNA repair response. The phenomenon was also demonstrated using experimental animals. Mice were exposed in vivo to two different doses of N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) and their lymphocytes were challenged with one dose of a radiomimetic chemical, bleomycin, in vitro. These challenged lymphocytes showed an MNNG dose-dependent increase of abnormal DNA repair response. In a population that was potentially exposed to teratogens--mothers having children with neural tube defects--lymphocytes from these mothers did not have the abnormal response in our assay. In studies with patients, we reported that lymphocytes from Down's syndrome patients have the abnormal DNA repair response. Lymphocytes from skin cancer-prone patients (epidermodysplasia verruciformis) have normal response to gamma-ray challenge but abnormal response to UV-light challenge. These patient studies also indicate that the challenge assay is useful in documenting the radiosensitivity of Down's syndrome and the UV sensitivity in EV patients. In most cases, the challenge assay is more sensitive in detecting biological effects than the standard chromosome aberration assay. Our series of studies indicates that the challenge assay can be used to document biological effects from exposure to mutagens and that the effect is an abnormal DNA repair response. This abnormality can increase the risk for development of cancer. The repair deficiency is currently being validated using a plasmid transfection (host-reactivation) assay. The need to integrate chromosome aberration and the challenge assays with other relevant assays for better documentation of biological effects and for more precise prediction of health risk will be presented. Our experience in using genetic polymorphism and host-reactivation assays will be discussed.

Animals↗
PubMed1995

Induction of deletion mutations by methoxyacetaldehyde in Chinese hamster ovary (CHO)-AS52 cells.

We have reported previously that methoxyacetaldehyde (MALD), a metabolite of 2-methoxyethanol, induces gpt gene mutations in Chinese hamster ovary (CHO)-AS52 cells but not hprt gene mutations in the standard CHO-K1-BH4 cells. In addition, MALD induces chromosome aberrations in both CHO cell lines. The data presented suggest that MALD induces deletion-type mutations. In this study, we analyzed MALD-induced CHO-AS52 mutants for deletion-type mutations using the nested-polymerase chain reaction (nested-PCR) assay. Spontaneous CHO-AS52 mutants are used as untreated control. Ethylnitrosourea (ENU)-induced CHO-AS52 mutants are used as negative control for multilocus deletions since ENU is a potent inducer of point mutations. The results show that the frequency of MALD-induced mutants containing total deletion of the gpt gene is 42.4% which is 2.3-fold higher than that from spontaneous mutants (18.6%). The frequency of ENU-induced deletion mutation is 3%. The data substantiate our hypothesis that MALD induces major deletion mutations.

Acetaldehyde↗
PubMed1995

Iron absorption from the whole diet: comparison of the effect of two different distributions of daily calcium intake.

The possibility of reducing calcium inhibition of iron absorption by decreasing calcium intake in lunch and dinner meals, which provided the most dietary iron, was examined in 21 healthy female volunteers. During a 10-d period, nonheme iron in all meals was extrinsically labeled with radioisotopic iron to a uniform specific activity. Iron absorption from two identical 10-d periods was compared when meals were labeled with two different iron radioisotopes and when the same amount of calcium (937 mg) was distributed in two ways, in either mainly breakfast and late evening meals or more evenly in all meals. About 30-50% more iron was absorbed when no milk or cheese was served with lunch or dinner. The difference was statistically significant. Median iron requirements (1.61 mg/d) calculated from body weight and menstrual iron losses agreed with the mean value of median iron absorption in the two 10-d periods (1.54 mg/d), which supports the validity of the present method. A reasonable separation of calcium and iron intakes would improve iron nutrition.

Adult↗
PubMed1995

Results of surveys to assess iron status in Europe.

Many studies have been undertaken to assess the iron status of Europeans. However, differences in dietary patterns, methodology, contraceptive choice, and epidemiologic factors lead to confounding factors that need consideration as the data from available studies are reviewed.

Adolescent↗
PubMed1995

Iron balance in menstruating women.

OBJECTIVES: To study factors determining iron balance in menstruating women by examining the relationships between total iron requirements, based on menstrual iron losses and basal iron losses, and serum ferritin concentration, transferrin saturation, blood haemoglobin concentration, bone marrow haemosiderin and absorption of iron from a test dose of ferrous sulphate (0.56 mg Fe). SUBJECTS: The study was made in 203 women all aged 38 years, randomly selected from the census register of Göteborg. The study was originally made in 1968-69. Serum ferritin in frozen sera was first analysed in 1978. Reanalyses, calibrated to the International Standard 80/602, and studies on the effect of storage of sera, were made in 1992. This allowed a complete re-examination of the importance of different determinants of iron balance in women. RESULTS: With increasing iron requirements there was an increase in iron absorption, and a decrease in serum ferritin concentration and transferrin saturation. Above a certain level of iron requirement there was a rather sudden decrease in haemoglobin concentration and in stainable iron in bone marrow smears, indicating the critical level of iron requirements in these women that could be balanced by an increased iron absorption from the present diet. This level represents the maximal adaptation to maintain iron balance in an iron-replete state that can be achieved with this diet and corresponds to a prevalence of iron deficiency of about 25%. CONCLUSIONS: The continuous regulation of iron absorption from iron deficiency to iron repletion has a critical balance point determined by the properties of the diet.

Absorption↗
PubMed1995

Iron absorption from the whole diet. Relation to meal composition, iron requirements and iron stores.

OBJECTIVE: To validate a new method of measuring iron absorption from the whole diet over several days, to compare iron absorption from two types of diets and to relate iron absorption to iron requirements and iron stores. DESIGN: Iron absorption from two diets was studied in 21 healthy young women. All non-haem iron in all meals was labelled to the same specific activity with an extrinsic radio-labelled iron tracer. Haem iron absorption was calculated from the amount of haem iron and absorption from a reference dose of iron. RESULTS: Iron absorption was concordant with individual iron requirements measured from menstrual blood losses and body weights. Total iron absorption from one diet designed to be highly bioavailable, would cover iron requirements in about 94% of menstruating women. Iron absorption was reduced by half from a diet with less meat, more phytate and more calcium with main meals. This type of diet would cover iron requirements in only 65% of adult menstruating women. For both diets there was a marked reduction in iron absorption with increasing serum ferritin. Iron balance was not positive above a serum ferritin of about 60 micrograms/l. CONCLUSIONS: Bioavailability of dietary iron is a key factor in iron nutrition. A diet with much lean meat, ascorbic acid and a low phytate content can cover iron requirements in most non-pregnant women. The powerful control of iron absorption implies that dietary iron overload cannot develop in normal subjects, even with diets having high iron content or high bioavailability.

Adult↗
PubMed1995

Iron and vitamins.

(1) Ascorbic acid has a key role in the absorption of dietary nonheme iron. (2) Natural and synthetic ascorbic acid have the same effect. (3) Ascorbic acid has a log/log dose-effect relationship in iron absorption. (4) The absorption is not reduced by prolonged intake of higher amounts of ascorbic acid. (5) There is a very efficient regulatory system for the absorption of iron preventing the development of dietary iron overload in normal subjects. (6) Each main meal should contain at least 50 mg ascorbic acid--more if a meal contains much phytate, and more if energy expenditure is low.

Ascorbic Acid↗
PubMed1994

Prevention of iron deficiency.

This chapter discusses different methods to prevent iron deficiency--to reduce iron losses (e.g. reducing menstrual iron losses by using a contraceptive pill or combating of hookworm infestation) or to increase iron absorption. Iron absorption can be increased (1) by modifying the composition of meals--increasing the content of dietary factors enhancing iron absorption (e.g. meat and ascorbic acid) or reducing the content of factors inhibiting iron absorption such as phytate and iron-binding phenolic compounds, (2) by increasing the iron content of the diet by fortification with iron, or by (3) supplementation with iron tablets. Several factors to consider in the choice of strategy are discussed such as the importance of the bioavailability of the diet for the efficacy of iron fortification, the choice of vehicle for iron fortification that is compatible with the iron compound used, the feasibility to increase the bioavailability of the dietary iron by modification of the composition of the diet and the short time available in pregnancy to ensure a sufficient supply of the extra iron needed limiting the effective measures available to supplementation with iron tablets.

Adult↗
PubMed1993

Inhibition of haem-iron absorption in man by calcium.

The inhibiting effect of Ca on non-haem-Fe absorption is well established. Present studies showed that Ca inhibited haem-Fe absorption to the same extent when the same amount of Ca (165 mg Ca as CaCl2) was added to a meal. Attempts were made to examine the mechanism for this inhibition in the present studies. Meat is the only known dietary factor influencing haem-Fe absorption. The present studies were designed to examine whether Ca interfered with the enhancing effect of meat on haem-Fe absorption. We found that the inhibition was the same whether biosynthetically radio-Fe-labelled haemoglobin was given in meals with or without meat. The haem-Fe absorption ratio with:without added Ca was 0.59 (SE 0.07) when Ca was added to a hamburger meal, and 0.52 (SE 0.03) when added to a wheat roll. These values were not significantly different (t 0.95; P = 0.35). The inhibition of haem-Fe absorption by Ca is, thus, a direct effect on the absorption of haem-Fe and not an indirect counteracting effect of the well-known enhancing effect of meat on haem-Fe absorption. Control studies were conducted to ensure that haem-Fe had not been degraded to non-haem-Fe during preparation of the foods. Since Ca inhibits the absorption of haem- and non-haem-Fe to the same extent, the present results strongly suggest that Ca interferes with the transport of Fe through the mucosal cell, and at a late stage, is common for haem- and non-haem-Fe transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Screening for iron deficiency: an analysis based on bone-marrow examinations and serum ferritin determinations in a population sample of women.

Efficacy of different methods in screening for iron deficiency was re-examined in a randomly selected sample of 38-year-old women (n = 203) with known iron status based on absence/presence of stainable iron in bone-marrow smears. The study was made in 1968-69. Serum ferritin (SF) was determined in 1978 in frozen sera using the Ramco IRMA and, in 1992, samples were re-analysed using a RIA calibrated with the International Standard 80/602 for SF determination. The effect of storage on SF was calculated from a previously established relationship (courtesy of Dr Mark Worwood, Cardiff) between the results obtained with the Ramco assay and assays calibrated with IS 80/602. The distributions in iron replete and iron deficient women showed less overlap (diagnostic efficiency 91%) for SF than for other haematological parameters. The best discrimination was obtained at SF < 16 micrograms/l (specificity 98%; sensitivity 75%). Absence of iron stores was associated with signs of an iron deficient erythropoiesis, starting already at SF 25-40 micrograms/l. Use of multiple criteria to diagnose iron deficiency falsely reduces prevalence figures for iron deficiency.

Adult↗
PubMed1993

Prevalence of iron deficiency in Swedish adolescents.

The prevalence of iron deficiency was determined in Göteborg, Sweden, in a sample of 15- to 16-y-old girls (n = 220) and boys (n = 207) using serum ferritin (SF). In a recent study in women on the relationship between SF and stainable bone marrow iron, it was established that at a cutoff value for SF of < 16 micrograms/L in 75% of women with no iron stores SF concentration was below this value (sensitivity 75%), whereas in 98% of iron-replete women it was above this cutoff value (specificity 98%). The present study showed that in 40% of the girls and 15% of the boys SF was below this cutoff value, indicating iron deficiency. Low SF concentration was associated with significant decreases in transferrin saturation, Hb concentration, mean corpuscular Hb, and mean corpuscular volume. The results from this cross-sectional study showed that, with decreasing SF, the decrease of values for these parameters occurred already before SF had reached the level 16 micrograms/L, suggesting that SF can be validly used as a single criterion of iron deficiency. Using the cutoff value SF < 16 micrograms/L, the figures for the prevalence of iron deficiency in adolescents in different countries were compared and found to be rather similar in Australia, Canada, the United States, and Sweden. High iron requirements combined with the present low-energy life-style leading to an insufficient supply of dietary iron may be a reasonable main explanation for the paradoxical, high prevalence of iron deficiency in adolescents in affluent societies.

Adolescent↗
PubMed1993

Duration of the inhibitory effect of calcium on non-haem iron absorption in man.

We investigated the duration of the inhibitory effect of calcium from milk and cheese (340 mg) in a breakfast meal on non-haem iron absorption from a hamburger meal eaten 2 or 4 h after the breakfast. The effect of calcium on iron absorption was studied in 21 human subjects by using paired observations and a dual-radioisotope method (55Fe and 59Fe). No duration effect of calcium on iron absorption was observed in this study. The present findings offer an opportunity for theoretical improvement of iron nutrition by a redistribution of the daily intake of calcium to the meals with a minor iron content, i.e. breakfast and the evening meal.

Adult↗