Body Iron Excretion by Healthy Men and Women
Hunt JR, et al.
Am J Clin Nutr 2009;89:1792-8.
Iron excretion measured by isotope dilution has been a primary basis for the factorial derivation of recommendations for iron intake, but the results have been available for men only. Objective: The objective of this study was to confirm iron excretion measurements in healthy men and extend them to women. The turnover rate of 55Fe that had been administered greater than or equal to 1 y earlier was determined from blood sampled semiannually for up to 3 y from 53 subjects in the community. Body iron was determined from hemoglobin, serum ferritin, and transferrin receptor. Complete menstrual collections were obtained from 13 women. The total median (range) iron excretion was 1.18 (0.11-2.07) mg/d for 29 men, 1.58 (0.65-4.88) mg/d for 19 menstruating women, and 0.99 (0.86-1.57) for 5 postmenopausal women. When hormonal contraceptive users were omitted, the median for 15 menstruating women increased to 1.66 mg/d. The distribution of iron excretion was normal for the men and postmenopausal women and was highly skewed for the menstruating women; menstrual iron accounted for 90% of the variation. Iron excretion was not strongly related to body weight. Body iron in menstruating women decreased somewhat (by 4.6%) in the men and tended to increase (by 1.5%) during the study. The results extend direct iron excretion measurements in men to include similar measurements in women. The results emphasize the wide range of iron excretion in humans, which results in a 40-fold range of requirements for absorbed iron.

Regular Consumption of a Complementary Food Fortified with Ascorbic Acid and Ferrous Fumarate or Ferric Pyrophosphate is as Useful as Ferrous Sulfate in Maintaining Hemoglobin Concentrations >105 g/L in Young Bangladesh Children
Davidsson L, et al.
Am J Clin Nutr 2009;89:1815-20.
Non-water-soluble iron compounds have been reported to be less well absorbed than ferrous sulfate in young children, and concern has been raised about their usefulness as food fortificants. The objective was to evaluate the usefulness of ferrous fumarate and ferric pyrophosphate, compared with ferrous sulfate, in maintaining hemoglobin concentrations >105 g/L in Bangladeshi children. Two hundred thirty-five children aged 7-24 mo (hemoglobin> 105 g/L) were randomly assigned in a double-blind study to receive an infant cereal fortified with ferrous fumarate, ferric pyrophosphate, or ferrous sulfate. One serving of cereal (9.3 mg Fe; molar ratio of ascorbic acid to iron of 3:1) was consumed per day, 6 d/wk, for 9 months. Blood samples were drawn at 4.5 and 9 mo. Raw data were reformatted, and a "time to event" was calculated that corresponded to reaching the following thresholds: hemoglobin < 105 g/L, plasma ferritin < 12 µg/L, or plasma C-reactive protein >10 mg/L at baseline, 4.5 mo, or 9 mo. Data were censored when children did not reach the threshold or were lost to follow-up. A Kaplan-Meier approach was used to compare the 3 groups. No statistically significant differences were observed for hemoglobin < 105 g/L (P = 0.943), plasma ferritin < 12 µg/L (P = 0.601), or plasma C-reactive protein> 10 mg/L (P = 0.508). Contrary to earlier concerns, these results do not indicate differences in usefulness between water-soluble and non-water-soluble iron compounds in maintaining hemoglobin concentrations and preventing iron deficiency. These data will be important in the development of food-fortification strategies to combat anemia and iron deficiency in highly vulnerable population groups.

Copper Reduces Striatal Protein Nitration and Tyrosine Hydroxylase Inactivation Induced by MMP+ in Rats
Rubio-Osornio M, et al.
Neurochem Int; 2009 Jun; 54(7):447-51.
Striatal administration of 1-methyl-4-phenylpyridinium (MPP(+)), the active metabolite of 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP), causes nigrostriatal dopaminergic pathway damage similar to that observed in Parkinson's disease. Copper acts as a prosthetic group of several antioxidant enzymes and recent data show that copper attenuated MPP(+)-evoked neurotoxicity. We evaluated the effect of copper (as a supplement) upon proteins nitration (60 kDa) and tyrosine hydroxylase (TH) inactivation induced by MPP(+) (10 microg/8 microL) injection into the rat striatum. Copper pretreatment (10 micromol/kg i.p.) prevented both MPP(+)-induced proteins nitration and TH inactivation. Copper treatment also prevented the dopamine-depleting effect of MPP(+) injection. Those results were accompanied by a significant reduction of enzymatic activity of the constitutive nitric oxide synthase (cNOS), whereas, the protein levels of the three isoforms of NOS remained unchanged. Results indicate that the effect of copper against MPP(+)induced proteins nitration and TH inactivation in the striatum of rat may be mediated by a reduction of cNOS activity.

Reversal of Physiological Deficits Caused by Diminished Levels of Peptidylglycine Alpha-amidating Monooxygenase by Dietary Copper
Bousquet-Moore D, et al.
Endocrinology; 2009 Apr;150(4):1739-47.
Amidated peptides are critically involved in many physiological functions. Genetic deletion of peptidylglycine alpha-amidating monooxygenase (PAM), the only enzyme that can synthesize these peptides, is embryonically lethal. The goal of the present study was the identification of physiological functions impaired by haploinsufficiency of PAM. Regulation of the hypothalamic-pituitary-thyroid axis and body temperature, functions requiring contributions from multiple amidated peptides, were selected for evaluation. Based on serum T(4) and pituitary TSH-beta mRNA levels, mice heterozygous for PAM (PAM(+/-)) were euthyroid at baseline. Feedback within the hypothalamic-pituitary-thyroid axis was impaired in PAM( +/-) mice made hypothyroid using a low iodine/propylthiouracil diet. Despite their normal endocrine response to cold, PAM( +/-) mice were unable to maintain body temperature as well as wild-type littermates when kept in a 4 C environment. When provided with additional dietary copper, PAM( +/-) mice maintained body temperature as well as wild-type mice. Pharmacological activation of vasoconstriction or shivering also allowed PAM(+/-) mice to maintain body temperature. Cold-induced vasoconstriction was deficient in PAM(+/-) mice. This deficit was eliminated in PAM (+/-) mice receiving a diet with supplemental copper. These results suggest that dietary deficiency of copper, coupled with genetic deficits in PAM, could result in physiological deficits in humans.
Dietary Protein and Calcium Interact to Influence Calcium Retention: A Controlled Feeding Study
Hunt JR, et al.
Am J Clin Nutr; 2009;89:1357-65.
The effect of meat protein on calcium retention at different calcium intakes is unresolved. The objective was to test the effect of dietary protein on calcium retention at low and high intakes of calcium. In a randomized controlled feeding study with a 2 X 2 factorial crossover design, healthy postmenopausal women (n = 27) consumed either almost equal to 675 or almost equal to 1510 mg Ca/d, with both low and high protein (providing 10% and 20% energy) for 7 wks each, separated by a 3-wk washout period. After 3 wks, the entire diet was extrinsically labeled with 47Ca, and isotope retention was monitored by whole-body scintillation counting. Clinical markers of calcium and bone metabolism were measured. High compared with low dietary protein significantly increased calcium retention from the low-calcium (29.5% compared with 26.0% absorbed) but not the high-calcium diet (18% absorbed). For the low-calcium diet, this effect nearly balanced a protein-related 0.5-mmol/d greater urinary calcium excretion. Protein-related calciuretic effects were independent of dietary calcium. Testing at 1,2,3,5, and 7 wk showed no long-term adaptation in urinary acidity or urinary calcium excretion. High compared with low dietary protein decreased urinary deoxypyridinoline and increased serum insulin-like growth factor I without affecting parathyroid hormone, osteocalcin, bone specific alkaline phosphatase, or tartrate-resistant acid phosphatase. In healthy postmenopausal women, a moderate increase in dietary protein, from 10% to 20% of energy, slightly improved calcium absorption from a low-calcium diet, nearly compensating for a slight increase in urinary calcium excretion. Under practical dietary conditions, increased dietary protein from animal sources was not detrimental to calcium balance or short-term indicators of bone health.

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