Fernando E. Viteri

Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (≤5 μg/day) and iron-normal (800 μg/day) rats and in both groups after daily high-iron supplementation (8,000 μg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 μg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 × nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake.

The Consequences of Iron Deficiency and Anemia in Pregnancy

Iron deficiency and its consequent anemia is recognized as the most prevalent specific nutrient deficiency in the world. It is estimated that about 2.15 billion people are iron deficient (WHO, 1991) and that this deficiency is severe enough to cause anemia in 1.2 billion people globally (Viteri, 1991). About 90% of all anemias are due to lack of iron, affecting mostly the developing world where nearly 1/3 of the population is iron deficient. However, the industrial world is not free from it: 11% of its population has iron deficiency (WHO, 1991; Viteri, 1991).

Methods for measuring ethane and pentane in expired air from rats and humans.

Numerous studies in animals and humans provide evidence that ethane and pentane in expired air are useful markers of in vivo lipid peroxidation. The measurement of breath hydrocarbons, being noninvasive, is well suited for routine use in research and clinical settings. However, the lack of standardized methods for collecting, processing, and analyzing expired air has resulted in the use of a wide variety of different methods that have yielded highly disparate results among investigators. This review outlines the methods that we have developed and validated for measuring ethane and pentane in expired air from rats and humans. We describe the advantages of these methods, their performance, as well as potential errors that can be introduced during sample collection, concentration, and analysis. A main source of error involves contamination with ambient-air ethane and pentane, the concentrations of which are usually much greater and more variable than those in expired air. Thus, it appears that the effective removal of ambient-air hydrocarbons from the subjects lungs before collection is an important step in standardizing the collection procedure. Also discussed is whether ethane or pentane is a better marker of in vivo lipid peroxidation.

Social support and arterial pressure in a central Mexican community

&NA; Research on the relationship of social support and arterial blood pressure was conducted in a town in central Mexico. A culturally appropriate measure of social support was developed assessing perceived support from relatives, friends, neighbors, and compadres (ritual kin). The effects of perceived support from these four sources were compared to the effects of the amount of reported social contacts. For males, more support from all four sources was related to lower arterial pressure, whereas amount of social contact was related to higher diastolic blood pressure; support from compadres had the largest inverse correlation with blood pressure. For females the pattern of correlations was dependent on age: support from relatives and friends was related to higher blood pressure for younger females, whereas support from relatives was related to lower blood pressure for older females. This pattern of relationships is consistent with the place of women in the social structure of this Mexican community, and these results point to the need to conceptualize and measure social support in culturally appropriate ways.

Daily supplementation with iron increases lipid peroxidation in young women with low iron stores.

The aim of this study was to determine whether women with low iron stores (plasma ferritin ≤ 20 μg/L) receiving a daily iron supplement for 8 wks at a level commonly used to treat poor iron status develop increased lipid peroxidation as measured by ethane exhalation rates and plasma malondialdehyde. The women served as their own control as pre- and post-supplementation periods were compared. Twelve women participated in the study for a 70-day period and consumed daily iron supplements (98 mg of iron as ferrous sulfate) from day 14 to day 70. Baseline blood and expired air samples were obtained on days 1 and 14; measurements during supplementation were performed on days 56 and 70, that is at 6 and 8 weeks of supplementation. Iron status improved during the iron supplementation period; biochemical indicators of lipid peroxidation also increased. After 6 wks of iron supplementation, serum ferritin almost doubled and body iron more than doubled. Hemoglobin levels increased slightly and other indicators of iron status became normal. However, plasma malondialdehyde (MDA) and breath ethane exhalation rates (BEER) increased by more than 40% between baseline and 6 wks of supplementation; these increases correlated significantly with plasma iron and ferritin levels. MDA was positively correlated with BEER. BEER increased further after 8 wks of iron supplementation. The increased indicators of lipid peroxidation with duration of supplementation and as iron status improved suggest that providing daily nearly 100 mg iron may not be a totally innocuous regimen for correcting iron depletion in women.

Achievements, challenges, and promising new approaches in vitamin and mineral deficiency control.

Micronutrient deficiencies (MNDs) contribute significantly to the worlds disease and mortality burden. Global efforts addressing MNDs have achieved significant yet heterogeneous progress across and within regions and countries. For vitamin A and iodine interventions, enhancing achievements in coverage require further political and financial commitment and targeting of hard-to-reach populations. Anemia control must focus on prevention among preschoolers and adolescent women and on integrated public health programs. Current international guidelines on iron supplementation and cut-off values for anemia need revision. For zinc, advocacy to accelerate the application of revised diarrhea management guidelines is critical, as are efficacy studies on food-based interventions and preventive supplementation.

Blood pressure, ethnicity, and psychosocial resources.

&NA; Research on psychosocial factors and cardiovascular disease has shown that psychosocial resources (including social supports and coping styles) help to protect individuals from the risk associated with psychosocial stressors. Some evidence indicates that this protective effect may extend to standard risk factors as well. This latter hypothesis was examined in greater detail in a study conducted in Brazil, in which it was found that psychosocial resources modified black‐white differences in blood pressure. Highest mean blood pressures were observed among mixed race and black Brazilians who had low psychosocial resources; Afro‐Brazilians with high psychosocial resources had lower blood pressures than white Brazilians. Implications of these results for the mechanisms linking ethnicity, psychosocial factors, and blood pressure are discussed.

A practical and reliable method for measuring ethane and pentane in expired air from humans.

We describe a method for the collection of expired air and further document the performance of our analytical technique that is used to measure ethane and pentane simultaneously. Four minutes of breathing hydrocarbon-free air before collection effectively removed high concentrations of residual ambient ethane and pentane from the lungs, with washout times up to 30 min resulting in no further reductions in breath hydrocarbons. Mean (+/-SE) exhalation rates (pmol/kg b.wt./min) in 11 subjects were 2.4 +/- 0.6 for ethane and 1.5 +/- 1.3 for pentane. Total intraindividual variability in exhalation rates (as percent coefficient of variation, %CV), measured from 4 subjects on at least 6 different days, was greater for pentane (44% CV) than for ethane (29% CV). Analytical variability contributed 6% to the total %CV. Advantages of the method are described, and reasons for the large variability in values reported in the literature are discussed.

Depleted iron stores without anaemia early in pregnancy carries increased risk of lower birthweight even when supplemented daily with moderate iron

BACKGROUND Gestational iron-deficiency anaemia has adverse pregnancy outcomes. Antenatal iron supplementation can be beneficial in anaemic women, but the effects in non-anaemic women are controversial. This observational study assessed the relationship of maternal iron stores (depleted or non-depleted) at gestational Weeks 8-12 with birthweight, in non-anaemic pregnant women following the guidelines of the Ministry of Health of Spain. METHODS Healthy, non-anaemic pregnant women (n = 205) were studied. At the first antenatal visit, a general clinical assessment was conducted, and basal blood taken. Women were classified as having non-depleted or depleted iron stores [serum ferritin (SF) < 12 µg/l)]. Daily antenatal iron supplements (48 mg on average) were started at 17 (range: 16-18) weeks. Blood haemoglobin, SF and transferrin saturation (TS) were measured in each trimester. RESULTS Of the study sample, 20, 54 and 66% had SF < 12 µg/l in the first, second and third trimesters, respectively. The prevalence of iron-depletion (SF < 12 µg/l) and iron-deficiency (SF < 12 µg/l and TS < 16%) was greater during the entire pregnancy in women with initial iron depletion versus no depletion (81.6 and 73.7% versus 61.7 and 55.4%, respectively, in the third trimester, P < 0.05). Women with initial iron-depletion delivered babies weighing on average 192 g less than that with initial iron stores, after adjusting for confounding variables (P = 0.028). CONCLUSIONS Beginning pregnancy with non-depleted iron stores is beneficial for the maternal iron status during pregnancy and infant birthweight. These findings reaffirm the importance of health promotion to ensure that women have adequate iron stores prior to, or early in, pregnancy when supplemented with moderate daily iron doses.

Antenatal iron supplements consumed daily produce oxidative stress in contrast to weekly supplementation in Mexican non-anemic women.

UNLABELLED Universal prenatal daily supplementation with iron (60-120mg iron) plus folic acid (0.4mg), as recommended by INACG/WHO/UNICEF, prevents anemia where iron deficiency is prevalent but may be excessive for non-anemic women. Weekly supplementation with 120mg iron plus various amounts of folic acid similarly prevents significant anemia. OBJECTIVE Determine, in non-anemic pregnant women, if oxidative stress is produced by recommended daily or weekly supplementation schemes. PROCEDURE 100 non-anemic pregnant women, 30% iron-deficient at week 20, were randomly supplemented daily followed by weekly, each for 8 weeks, or in reversed order. RESULTS With daily supplementation thio-barbituric-acid-reacting-substances (TBARS) increased significantly and high serum ferritin, iron, and excessively elevated hemoglobin occurred near term. During weekly supplementation significant anemia and high iron parameters were prevented, and elevated TBARS declined. CONCLUSION In non-anemic pregnant women both schemes prevented significant anemia. Oxidative stress occurred only during daily supplementation periods. Weekly supplementation appears safer.