Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age

Objective: To examine the effects of iron deficiency and its treatment by iron supplementation or a high iron diet on fatigue and general health measures in women of childbearing age. Design: Randomised controlled trial to compare supplement and dietary treatment of iron deficiency. Subjects: 44 iron deficient (serum ferritin < 15 mug/L or serum ferritin 15-20 mug/L, plus two of the following: serum iron < 10 mu mol/L, total iron binding capacity > 68 mu mol/L or transferrin saturation < 15%) and 22 iron replete (hemoglobin greater than or equal to 120 g/L and serum ferritin > 20 mug/L) women 18 to 50 years of age were matched for age and parity. Interventions: Iron deficient women were randomly allocated to either iron supplementation or a high iron diet for 12 weeks. Measures of Outcome: Iron deficient and iron replete participants had iron studies performed and completed the Piper Fatigue Scale (PFS) and the SF-36 general health and well-being questionnaire at baseline (TO), following the 12 week intervention (TI) and again after a six-month non-intervention phase (T2). The SF-36 includes measures of physical (PCS) and mental (MCS) health and vitality (VT). Results: MCS and VT scores were lower and PFS scores were higher for iron deficient women (diet and supplement groups) than iron replete women at baseline. Both intervention groups showed similar improvements in MCS, VT and PFS scores during the intervention phase, but mean increases in serum ferritin were greater in the supplement than the diet group. PCS scores were not related to iron status. Conclusions: Treatment of iron deficiency with either supplementation or a high iron diet results in improved mental health and decreased fatigue among women of childbearing age.

Dietary treatment of iron deficiency in women of childbearing age

Background: The Australian Iron Status Advisory Panel advocates dietary intervention as the first treatment option for mild iron deficiency [serum ferritin (SF) = 10-15 mug/L]. However, there appear to be no studies on the efficacy of dietary treatment for iron deficiency. Objective: We compared the effects of iron supplementation and of a high-iron diet on serum ferritin (SF) and hemoglobin in iron-deficient women of childbearing age. Design: Forty-four iron-deficient women (SF < 15 mug/L or SF = 15-20 mug/L plus serum iron < 10 mu mol/L and total-iron-binding capacity > 68 mu mol/L) and 22 iron-replete women (hemoglobin greater than or equal to 120 g/L and SF > 20 mug/L) matched for age and parity categories were enrolled and completed 7-d weighed food records at baseline. The iron-deficient women were randomly allocated to receive iron supplementation (105 mg/d; supplement group) or a high-iron diet (recommended intake of absorbable iron: 2.25 mg/d; diet group) for 12 wk. Hematologic and dietary assessments were repeated at the end of the intervention and again after a 6-mo follow-up. Results: Mean SF in the supplement group increased from 9.0 +/- 3.9 mug/L at baseline to 24.8 +/- 10.0 mug/L after the intervention and remained stable during follow-up (24.2 +/- 9.8 mug/L whereas the diet group had smaller increases during the intervention (8.9 +/- 3.1 to 11.0 +/- 5.9 mug/L) but continued to improve during follow-up (to 15.2 +/- 9.5 mug/L). Mean hemoglobin tended to improve in both intervention groups, but the change was only significant in the supplement group. Conclusions: In iron-deficient women of childbearing age, a high-iron diet produced smaller increases in SF than did iron supplementation but resulted in continued improvements in iron status during a 6-mo follow-up.

Familial corticosteroid-binding globulin deficiency due to a noval null mutation: Association with fatigue and relative hypotension

Corticosteroid-binding globulin is a 383-amino acid glycoprotein that serves a hormone transport role and may have functions related to the stress response and inflammation. We describe a 39-member Italian-Australian family with a novel complete loss of function (null) mutation of the corticosteroid-binding globulin gene. A second, previously described, mutation (Lyon) segregated independently in the same kindred. The novel exon 2 mutation led to a premature termination codon corresponding to residue -12 of the procorticosteroid-binding globulin molecule (c.121G->A). Among 32 family members there were 3 null homozygotes, 19 null heterozygotes, 2 compound heterozygotes, 3 Lyon heterozygotes, and 5 individuals without corticosteroid-binding globulin mutations. Plasma immunoreactive corticosteroid-binding globulin was undetectable in null homozygotes, and mean corticosteroid-binding globulin levels were reduced by approximately 50% at 18.7 ± 1.3 µg/ml (reference range, 30–52 µg/ml) in null heterozygotes. Morning total plasma cortisol levels were less than 1.8 µg/dl in homozygotes and were positively correlated to the plasma corticosteroid-binding globulin level in heterozygotes. Homozygotes and heterozygote null mutation subjects had a high prevalence of hypotension and fatigue. Among 19 adults with the null mutation, the systolic blood pressure z-score was 12.1 ± 3.5; 11 of 19 subjects (54%) had a systolic blood pressure below the third percentile. The mean diastolic blood pressure z-score was 18.1 ± 3.4; 8 of 19 subjects (42%) had a diastolic blood pressure z-score below 10. Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygote subjects (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome. Fatigue questionnaires revealed scores of 25.1 ± 2.5 in 18 adults with the mutation vs. 4.2 ± 1.5 in 23 healthy controls (P < 0.0001). Compound heterozygosity for both mutations resulted in plasma cortisol levels comparable to those in null homozygotes. Abnormal corticosteroid-binding globulin concentrations or binding affinity may lead to the misdiagnosis of isolated ACTH deficiency. The mechanism of the association between fatigue and relative hypotension is not established by these studies. As idiopathic fatigue disorders are associated with relatively low plasma cortisol, abnormalities of corticosteroid-binding globulin may be pathogenic.

Emotional distress induced rhabdomyolysis in an individual with carnitine palmitolytransferase deficiency

A 48-year-old male patient with underlying CPT II enzyme deficiency is described. Emotional stress appeared to precipitate recurrent myalgias, rhabdomyolysis and reversible renal impairment over a 40-year period. Our search of the English literature indicates this to be the first time that the emotional stress has been documented to precipitate the CPT II syndrome. Although the pathogenesis of this syndrome has yet to be established, existing knowledge is briefly reviewed and the likely metabolic and neuroendocrine mechanisms which link emotional stress to muscle metabolism are examined. These mechanisms influence the extent of lipolysis or glycolysis that occurs during the process of muscle ATP generation. It is suggested that neuroendocrine and other stress related changes which favour lipolysis over glycolysis adversely effect muscle energy metabolism in patients whose mitochondria are deficient in CPT II enzyme. Possible treatment strategies are those that favour glycolysis over fatty acid metabolism and include a variety of ways of modulating sympathetic and parasympathetic tone. The use of carbohydrate supplementation P-blockers and anxiolytic agents is discussed.

The mechanism of protection of molten magnesium by cover gas mixtures containing sulphur hexafluoride

Experimental studies have been undertaken, involving in situ observations of the interaction between cover gas mixtures and molten magnesium. It has been shown that, in the presence of sulphur hexafluoride (SF6), the contact angle between solid MgO and molten magnesium is reduced, resulting in the wetting of MgO by magnesium metal. In contrast, it was observed that the absence of SF6 results in a large contact angle, poor wetting of the MgO by magnesium metal and a non-adherent surface film. It is proposed that the formation of an adherent, protective surface film under a cover gas mixture containing SF6 is due to capillary forces acting within the film.

Effects of vitamin E deficiency on fatigue and muscle contractile properties

Radical-mediated oxidative damage of skeletal muscle membranes has been implicated in the fatigue process. Vitamin E (VE) is a major chain breaking antioxidant that has been shown to reduce contraction-mediated oxidative damage. We hypothesized that VE deficiency would adversely affect Muscle contractile function, resulting in a more rapid development of muscular fatigue during exercise. To test this postulate, rats were fed either a VE-deficient (EDEF) diet or a control (CON) diet containing VE. Following a 12-week feeding period, animals were anesthetized and mechanically ventilated. Muscle endurance (fatigue) and contractile properties were evaluated using an in situ preparation of the tibialis anterior (TA) muscle. Contractile properties of the TA muscle were determined before and after a fatigue protocol. The muscle fatigue protocol consisted of 60 min of repetitive contractions (250 ms trains at 15 Hz; duty cycle = I I %) of the TA muscle. Prior to the fatigue protocol, no significant differences existed in the force-frequency curves between EDEF and CON animals. At the completion of the fatigue protocol, muscular force production was significantly (P

Identification of micronutrient deficiency of wheat in the Peshawar Valley, Pakistan

A field experiment was conducted to study the effect of micronutrients, zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), boron (13) and a commercial fritted micronutrient product called Zarzameen, on the yield and the yield components of wheat (Triticum aestivum L.), in the Peshawar valley, Pakistan. Different combinations of Zn, Cu. Fe. Mn, B, and Zarzameen were applied at the rate of 4.0, 2.0, 5.0, 2.0, 1.0 kg ha(-1) and 1.0 kg ha(-1), respectively, along with a basal dose of 100 kg ha(-1) nitrogen(N), 75 kg ha(-1) phosphorus (P) and 50 kg ha(-1) potassium (K). The fertilizer treatments (macro- and micronutrients) increased wheat dry matter, grain yield, and straw yield significantly over an unfertilized control. Soil tests for B and Zn were increased both at boot and harvesting stage, and Fe at boot stage, with the addition of micronutrients. Plants without B had showed classical B deficiency symptoms at grain formation stage, but not at vegetative stage. Boron concentration in the dry matter of wheat plants increased with the addition of the B fertilizer in the soil. Boron deficiency was not observed in plants containing >4 mg B kg(-1) at the boot stage, or in soils containing > 1.4 mg kg(-1) hot water soluble B.

Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II

Human R183H-GH causes autosomal dominant GH deficiency type II. Because we show here that the mutant hormone is fully bioactive, we have sought to locate an impairment in its progress through the secretory pathway as assessed by pulse chase experiments. Newly synthesized wild-type and R183H-GH were stable when expressed transiently in AtT20 cells, and both formed equivalent amounts of Lubrol-insoluble aggregates within 40 min after synthesis. There was no evidence for intermolecular disulfide bond formation in aggregates of wild-type hormone or the R183H mutant. Both wildtype and R183H-GH were packaged into secretory granules, assessed by the ability of 1 mm BaCl2 to stimulate release and by immunocytochemistry. The mutant differed from wildtype hormone in its retention in the cells after packaging into secretory granules; 50% more R183H-GH than wild-type aggregates were retained in AtT20 cells 120 min after synthesis, and stimulated release of R183H-GH or a mixture of R183H-GH and wild-type that had been retained in the cell was reduced. The longer retention of R183H-GH aggregates indicates that a single point mutation in a protein contained in secretory granules affects the rate of secretory granule release.

Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency

Glucocorticoids are pivotal for adipose tissue development. Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue. In humans, both genetic CBG deficiency and suppressed CBG concentrations in hyperinsulinemic states are associated with obesity. We hypothesized that CBG deficiency in humans modulates the response of human preadipocytes to glucocorticoids, predisposing them to obesity. We compared normal preadipocytes with subcultured preadipocytes from an individual with the first ever described complete deficiency of CBG due to a homozygous null mutation. CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. Glucocorticoid receptor number and binding characteristics and 11beta-hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes. We propose that the increased proliferation and enhanced differentiation of CBG-negative preadipocytes may promote adipose tissue deposition and explain the obesity seen in individuals with genetic CBG deficiency. Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia.

Magnesium, insulin resistance and body composition in healthy postmenopausal women

Objective: This study was conducted to determine the association between magnesium (Mg), body composition and insulin resistance in 136 sedentary postmenopausal women, 50 to 77 years of age. Methods: Diabetics, hypertensives and women on hormonal replacement therapy were excluded and the remaining 74 were divided according to BMI≥25 (obese: OG) and BMI<25 kg/m2 (non-obese: NOG). Nutritional data disclosed that intakes were high for protein and saturated fat, low for carbohydrates, polyunsaturated fat and Mg and normal for the other nutrients, according to recommended dietary allowances (RDA). Mg values in red blood cells (RBC-Mg) and plasma (P-Mg), were determined, as were fasting glucose, and insulin levels, Homeostasis Model Assessment (HOMA), body mass index (BMI), body fat percent (BF %), abdominal fat (AF) and free fat mass (FFM). Results: RBC-Mg values were low in both groups when compared with normal values. There were significant differences in body composition parameters, HOMA and insulin levels, with higher basal insulin levels in OG. RBC-Mg was directly correlated with insulin, HOMA and FFM in both groups, according to Pearson correlations. HOMA in OG was also directly correlated with BMI, FFM and AF. In NOG, HOMA was only correlated with FFM. The low RBC-Mg levels observed were probably due to low Mg intake and to deregulation of factors that control Mg homeostasis during menopause. Conclusions: Both Mg deficit and obesity may independently lead to a higher risk for insulin resistance and cardiovascular disease.