Serum lipid profiles of young Japanese women with iron deficiency without anemia.

PURPOSE: We aimed to evaluate the association between iron deficiency without anemia (IDNA) and serum lipid profiles in young women of around 20 years of age. METHODS: This study included non-anemic (hemoglobin ≥ 12 g/dL) female volunteers aged 18 to 22 years who were not taking mineral/vitamin supplements and living in the metropolitan area of Tokyo, Japan. These volunteers were classified into two groups based on their sFer (serum ferritin) levels: normal group (sFer ≥ 20 ng/mL, n = 36) and IDNA group (sFer < 20 ng/mL, n = 29). Venous blood samples were obtained from the antecubital veins of these volunteers after 10-12-h fasting to measure the hematological and biochemical parameters, including lipid levels and iron status. The results of each group were compared using Student's t-test or the Mann-Whitney U test (for inhomogeneous variance). RESULTS: The serum cholesterol levels varied depending on the iron status in the women. Serum high-density lipoprotein cholesterol (HDL-C) levels in the IDNA group were significantly higher (P = 0.006) than that in the normal group. However, the levels of total cholesterol (T-CHO), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were not significantly different between the groups. Serum LDL-C levels were positively and significantly correlated with sFer levels in the IDNA group (Kendall's rank correlation 0.264, P = 0.044), but not in the normal group. The sFer level was not correlated with serum HDL-C in both groups. The reason for the high serum HDL-C levels in young women with IDNA is not yet clear. Compared to the normal group, the frequency of eating bread containing bran was significantly higher (P = 0.031) and that for yogurt was significantly lower (P = 0.040) in the IDNA group. The proportion of the women who were susceptible to infection, which was measured using the Cornell Medical Index, was significantly higher in the IDNA group than in the normal group. Among those susceptible to infection, the serum HDL-C level of the volunteers in the IDNA group was significantly higher than that of the volunteers in the normal group (P = 0.024). CONCLUSIONS: Our findings suggest that lipid parameters may be associated with IDNA and susceptibility to infection. Further research is needed to elucidate the mechanisms underlying the changes in the serum cholesterol levels in individuals with IDNA and the clinical significance of these findings.

Iron deficiency without anaemia is a potential cause of fatigue: meta-analyses of randomised controlled trials and cross-sectional studies.

Fe deficiency is a prevalent nutritional disease, and fatigue is a common complaint in the general and patient population. The association between Fe deficiency without anaemia (IDNA) and fatigue is unclear. Here, we performed a meta-analysis to evaluate the therapeutic effect of Fe on fatigue in patients with IDNA and the association between IDNA and fatigue in the population. Articles from the PubMed database up to 19 January 2016 were systematically searched. A total of six relevant randomised controlled trials (RCT) and six relevant cross-sectional studies were identified. All outcomes were converted into effect sizes. In the meta-analysis of the six RCT, we identified a significant therapeutic effect of Fe in fatigue patients with IDNA (pooled effect size 0·33; 95 % CI 0·17, 0·48; I 2=0·0 %; P<0·0001). A sensitivity analysis found that the overall results (i.e. significant association) were robust. In the meta-analysis of the six cross-sectional studies, the association between IDNA and fatigue was not significant (pooled effect size 0·10; 95 % CI -0·11, 0·31; I 2=57·4 %; P=0·362). A sensitivity analysis found that the overall results (i.e. no significant association) were not robust; removal of one study made the outcomes significant. These meta-analyses suggest that improving Fe status may decrease fatigue. Further research is necessary to identify diagnostic criteria for selecting fatigue patients who might benefit from Fe therapy and to assess the prevalence of IDNA with fatigue in the general population.

Iron deficiency without anemia is associated with anger and fatigue in young Japanese women.

Iron deficiency without anemia (IDNA), the most prevalent nutritional deficiency worldwide, affects young women of reproductive age. This study aimed to elucidate the relationship between IDNA and mental and somatic symptoms including anger and fatigue using the Japanese version of the Cornell Medical Index Health Questionnaire (CMI-J). Data regarding demographic characteristics, anthropometry, hematological, and biochemical indices of the iron status, frequencies of selected food intakes assessed by self-administered food frequency questionnaires (FFQs), frequencies of nonspecific symptoms, and grades of neurotic tendencies assessed by CMI-J were collected from 76 young women aged 18-22 years living in the metropolitan area of Tokyo, Japan. The subjects were classified as having IDNA (hemoglobin (Hb)≥12 g/dL and serum ferritin<20 ng/mL; n=29), having iron deficiency anemia (IDA) (Hb<12 g/dL and serum ferritin<20 ng/mL; n=10), or having a normal iron status (Hb≥12 g/dL and serum ferritin≥20 ng/mL; n=36). One subject was excluded from the analyses because of Hb<12 g/dL and serum ferritin≥20 ng/mL. Fisher's protected least significant difference and the Dwass-Steel-Chritchlow-Fligner multiple comparison tests were used to compare the data of the three groups. P values<0.05 were considered significant. Sections M-R (mental complaints) were significantly higher in the IDNA subjects than in the normal subjects. No significant difference in CMI scores was found between the normal and IDA subjects. Sections I (fatigability), Q (anger), and R (tension) were significantly higher in the IDNA subjects than in the normal subjects, regardless of no significant differences between the normal and IDA subjects in those sections. Young women with IDNA demonstrated a significantly higher proportion of neurotic tendencies (grades II-IV). The intake frequency score of canned or bottled green tea fortified with vitamin C was significantly higher in the IDNA subjects than the IDA subjects. The findings suggest that IDNA may be a risk factor for anger, fatigue, and tension in women of childbearing age.

Toxicity of so-called edible hijiki seaweed (Sargassum fusiforme) containing inorganic arsenic.

The UK Food Standards Agency and its counterparts in other countries have warned consumers not to eat hijiki (Sargassum fusiforme; synonym Hizikia fusiformis), a Sargasso seaweed, because it contains large amounts of inorganic arsenic. We investigated dietary exposure of hijiki in weaning male F344/N rats fed an AIN-93G diet supplemented with 3% (w/w) hijiki powder for 7 weeks, compared with those fed only an AIN-93G diet. Body weight, body temperature, blood and tissue arsenic concentrations, plasma biochemistry and hematological parameters were measured. We found that feeding rats a 3% hijiki diet led to a marked accumulation of arsenic in blood and tissues, and evoked a high body temperature and abnormal blood biochemistry including elevated plasma alkaline phosphatase activity and inorganic phosphorus, consistent with arsenic poisoning. These findings should prompt further investigations to identify the health hazards related to consumption of hijiki and related Sargassum species in humans.

Comparison of a modified hemoglobin regeneration efficiency method with a slope-ratio assay in measuring relative bioavailability of cocoa powder iron using rats.

The slope-ratio assay is being used as a gold standard for determining iron bioavailability in foods. We compared the modified hemoglobin (Hb) regeneration efficiency (HRE) method (Yokoi K, Konomi A, & Otagi M (2009) Br J Nutr 102: 215-220) with the slope-ratio assay for measurement of iron bioavailability. The relative bioavailability of iron in cocoa powder was measured by both methods using ferric citrate as a control (i.e., 1.00). In the slope-ratio assay, thirty-two 4-week-old male F/344 N rats were depleted in iron stores for 28 days, and then eight groups of four rats each were repleted for 25 days using graded levels of dietary ferric citrate or the cocoa powder. The slope for the cocoa powder 1.720 g Hb/L/(mg Fe/kg) was 0.99 that of ferric citrate 1.727 g Hb/L/(mg Fe/kg). On the other hand, the HRE value of the cocoa powder was 0.96 that of ferric citrate, based on the previous report. The relative iron bioavailabilities measured by both methods agreed, indicating that the modified HRE method is compatible with the slope-ratio assay in measuring the bioavailability of iron in foods.

A possible role of plasma aldosterone in hypotension secondary to iron-deficiency anaemia combined with zinc deficiency in rats.

Patients with Fe-deficiency anaemia are often afflicted by hypotension. However, the mechanism of secondary hypotension in Fe-deficiency anaemia is unknown. To investigate the pathogenesis of secondary hypotension in Fe-deficiency anaemia, we examined the effects of Fe deprivation on plasma aldosterone concentration and blood pressure in rats. A total of forty 4-week-old male Sprague-Dawley rats were assigned into four treatment groups of ten each for the 4-week study: Fe-deficient group (FD), Zn-deficient group (ZD), Fe/Zn-deficient group (FZD) and control group (CON). At days 26 and 27, blood pressure was measured by the tail-cuff method. Plasma aldosterone concentration was determined by ELISA. The data were analysed by Tukey's multiple comparison test. Rats in the FZD had significantly lower mean blood pressure (P < 0·01) and diastolic blood pressures (P < 0·05) and plasma aldosterone concentration (P < 0·01) compared to the CON. These results suggest that blood pressure is decreased in Fe-deficiency anaemia combined with Zn deficiency partly due to decreased circulating aldosterone concentrations in addition to decreased haematocrit.

Iron bioavailability of cocoa powder as determined by the Hb regeneration efficiency method.

Fe deficiency is a public-health problem worldwide, and effective measures for preventing Fe deficiency are needed. The aim of the present study was to determine the bioavailability of Fe in cocoa using the Hb regeneration efficiency (HRE) method. Thirty-five F344/N male weanling rats were fed a low-Fe diet for 4 weeks to deplete body Fe stores. Then, four groups of seven animals each were repleted for 20 d using a modified AIN-93G diet fortified with ferrous sulphate, ferric citrate or two brands of cocoa powder to provide a total dietary Fe concentration of 20 mg/kg. As a negative control, seven rats were maintained on the low-Fe diet. The HRE were 0.733, 0.350, 0.357 and 0.336 for ferrous sulphate, ferric citrate and the two brands of cocoa powder, respectively. The relative biological values (RBV), defined as the ratio of the sample HRE to that of ferrous sulphate, were 0.478, 0.488 and 0.459 for ferric citrate and the two brands of cocoa powder, respectively. The Fe bioavailability of cocoa was significantly less than that of ferrous sulphate and was similar to that of ferric citrate. The difference in Fe bioavailability between the two brands of cocoa powder was negligible. When the negative control was used to correct the data, estimates of the RBV derived from Hb gain were similar to those derived from the HRE. These results suggest that cocoa is a significant source of moderately bioavailable Fe.

Dermal absorption of inorganic germanium in rats.

So-called germanium 'health' products including dietary supplements, cosmetics, accessories, and warm bath service containing germanium compounds and metalloid are popular in Japan. Subchronic and chronic oral exposure of germanium dioxide (GeO(2)), popular chemical form of inorganic germanium causes severe germanium toxicosis including death and kidney dysfunction in humans and experimental animals. Intestinal absorption of neutralized GeO(2) or germanate is almost complete in humans and animals. However, it is not known whether germanium is cutaneously absorbed. We tested dermal absorption of neutralized GeO(2) or germanate using male F344/N rats. Three groups of rats were treated with a 3-h topical application of hydrophilic ointment containing graded level of neutralized GeO(2) (pH 7.4): 0, 0.21 and 0.42 mg GeO(2)/g. Germanium concentration in blood and tissues sampled from rats after topical application of inorganic germanium was measured by inductively coupled plasma-mass spectrometry. Animals topically applied 0.42 mg GeO(2)/g ointment had significantly higher germanium concentrations in plasma, liver, and kidney than those of rats that received no topical germanium. The results indicate that skin is permeable to inorganic germanium ion or germanate and recurrent exposure of germanium compounds may pose a potential health hazard.

Effects of zinc and/or iron deficiency on rectal temperature in rats.

O'Dell et al. reported that rectal temperature was decreased by zinc deficiency in rats. However, it is not known whether a combined deficiency of zinc and iron affects rectal temperature. Forty 4-wk-old male Sprague-Dawley rats were assigned into four dietary treatment groups of 10 rats each for the 4-wk study: zinc-deficient group (4.5 mg Zn and 35 mg Fe/kg diet; -Zn), iron-deficient group (30 mg Zn/kg diet, no supplemental iron; -Fe), zinc/iron-deficient group (4.5 mg Zn/kg diet, no supplemental iron; -Zn-Fe), and control group (AIN-93G; Cont). At d 24-27, the rectal temperature was determined. The rectal temperature of the -Zn group was significantly lower than the Cont group. The rectal temperature of the -Zn-Fe group was similar to that of the Cont group, although thyroid-stimulating hormone and total thyroxin concentrations were the lowest in the -Zn-Fe group among all groups. The pattern of the plasma nitrate/nitrite concentrations across groups was similar to rectal temperature. Although observation of the rectal temperature is not conclusive, the balance between zinc and iron intake seems to determine the body temperature set point. These results suggest that the thermogenic effect of thyroid hormones is not thought to influence the paradoxical maintenance of rectal temperature in combined deficiency of zinc and iron.

Zinc deficiency decreases plasma erythropoietin concentration in rats.

In 1985, Paterson and Bettger found hypoplastic hematopoiesis in severely zinc-deficient rats. Therefore, we investigated plasma erythropoietin concentration in zinc-deficient rats. Forty 4-wk-old male Sprague- Dawley rats were assigned into 4 dietary treatment groups of 10 for the 4-wk study: zinc-deficient group (4.5 mg zinc and 35 mg iron/kg; -Zn), iron-deficient group (30 mg zinc/kg, no supplemental iron; -Fe), zinc/ iron-deficient group (4.5 mg zinc/kg, no supplemental iron; -Zn-Fe), and control group (AIN-93G; Cont). Water intake determined at d 19 was similar among all treatment groups. At d 27-28, bioimpedance was measured. The intracellular water/extracellular water ratio was significantly increased in the -Zn group (p < 0.05). Compared to the Cont, group, the plasma erythropoietin concentration was increased by iron deficiency and decreased by zinc deficiency (p < 0.01). Hematocrit was significantly decreased in both the -Fe and -Zn-Fe groups and was significantly increased in the -Zn group (p < 0.01). Transferrin saturation in the -Fe and -Zn-Fe groups was significantly lower than the Cont group (p < 0.01), and that of the -Zn group was highest among all groups. The low plasma erythropoietin concentration might account for depressed hematopoiesis associated with zinc deficiency.