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This Special Issue summarizes the results of several studies aimed at providing information on a series of questions related to the adequate protein and energy intakes that allow adequate growth and function in children and work performance and productivity in adults. The effect of different sources of protein on nitrogen balance and the requirements of essential amino acids in young children were also explored in fully recovered, previously malnourished children housed in the Metabolic Ward of the Biomedical Division of INCAP. The following are the main results of these investigations: » Animal experiments and studies in children recovering from protein–energy malnutrition (PEM) strongly suggest that even when requirements of all nutrients are satisfied, inactivity reduces the rate of linear growth and physical activity improves it as well as lean body mass repletion. » The effects of different energy intakes on nitrogen balance demonstrated how energy intake modifies the need to ingest different amounts of protein to satisfy protein requirements. » Insensible nitrogen losses in preschool children and their relation to protein intake was demonstrated. » The quality of even “good protein sources” modifies the amount needed to satisfy nitrogen requirements, and corn and bean-based diets can satisfy protein needs for health and even growth of young children. » Essential amino acid requirements of 2-year-old children was assessed by diverse measurements of nitrogen metabolism and amino acid levels in blood, and were found lower than those recommended by FAO-WHO. » In rural adult populations the relationship between energy and protein intake, productivity and body composition, and the impact of environmental hygiene on nitrogen balance was demonstrated and measured.

This article summarizes thirty years of intensive clinical metabolic and therapeutic studies of the consequences of severe protein deficiency relative to calories, which results in kwashiorkor, and of a balanced deficiency of protein and calories that results in marasmus. Evidence is provided that these are two different metabolic diseases, but kwashiorkor is usually superimposed on some degree of chronic marasmus and hence most cases studied were marasmic kwashiorkor. The value of the creatinine/height index to indicate the degree of lean body cell mass with any disease is demonstrated.

Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population.

Background Lime-treated corn gruel ( atole) is a common weaning food in iron-deficient populations, especially in Mexico and Central America, and is a potential vehicle for fortification with iron. Objective The objective of this study was to screen promising iron compounds for use in the fortification of atole, using in vitro enzymatic digestion–dialysis techniques, while also considering their response to known iron absorption enhancers and inhibitors. Methods Atole, unaltered or preincubated with phytase, was fortified with iron (10 mg/L) from ferrous sulfate, ferrous bisglycinate, or ferrous fumarate, or with ferric chloride, ferric ammonium citrate, or ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), and submitted to in vitro digestion. Dialysis of calcium, copper, iron, phosphorus, and zinc (analyzed by inductively coupled plasma atomic emission spectrometry) was measured when atole was fortified with iron compounds alone or together with ascorbic acid or disodium ethyl- enediaminetetraacetic acid (Na2 EDTA). Results Iron dialyzability was higher with NaFeEDTA ( p < .05) than with all other iron compounds, which did not differ among themselves in iron dialyzability. Addition of ascorbic acid had no significant effect on iron dialysis, whereas Na2 EDTA enhanced iron dialyzability by 7 to 10 times in unaltered atole and 15 to 20 times in phytase-preincubated atole ( p < .05). Addition of Na2 EDTA always increased intrinsic zinc dialyzability, and most of the time this increase was significant. Phytase pretreatment generally increased mineral dialysis. Conclusions Adding EDTA (either as NaFeEDTA or as Na2 EDTA) to atole can increase the dialyzability of ferrous and ferric iron compounds and enhance the dialyzability of intrinsic zinc without any negative effects on calcium, phosphorus, or copper dialysis.

Zinc and iron compete during intestinal absorption, but postabsorptive interactions between these nutrients are less clear. Understanding these interactions is important to determine when supplementation with iron or zinc is proposed. The effect of zinc supplementation (22 mg Zn/d as zinc gluconate) or of iron supplementation (100 mg Fe/d as ferrous sulfate) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves. Young adult women (ages 20-28 y), nonanemic but with low iron stores (plasma ferritin< 20 microg/L), participated in the 70-d study. The women were divided in two groups (zinc-supplemented, n = 11; iron-supplemented, n = 12). The supplements were taken at bedtime. Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56. Radioiron and stable isotopes of zinc were used to measure iron and zinc absorption from a test meal. In the iron-supplemented group, blood hemoglobin, plasma ferritin and the percentage of transferrin saturation increased (P < 0.01). Zinc indices did not change. In the zinc-supplemented group, plasma ferritin and the percentage of transferrin saturation decreased (P < 0.05), whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased (P < 0.05). Plasma and urinary zinc also increased (P < 0.01). Iron absorption (%) from the test meal increased (P < 0.01), whereas zinc absorption (%) decreased (P < 0.01) compared with baseline in the Zn-supplemented women. Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status. However, use of a modest zinc supplement improves zinc indices, but also appears to induce a cellular iron deficiency and, possibly, further reduce iron status.

Background: Reducing the phytate content in grains by genetic manipulation is a novel approach to increasing nonheme-iron absorption from mixed diets. Fractional iron absorption from a genetically modified strain of low-phytate maize (LPM) increased significantly, by 50%. Objective: We assessed iron absorption from porridges prepared from the same LPM (lpa-l-1 mutant) and unmodified wild-type maize (WTM), both of which were fortified with either ferrous sulfate or sodium iron EDTA. Design: Porridges providing 3.4 mg Fe were fortified with either ferrous sulfate or sodium iron EDTA to provide an additional 1 mg Fe/serving. In 14 nonanemic women, iron absorption was measured as the amount of radioiron incorporated into red blood cells (extrinsic tag method) 12 d after consumption of the study diets. Results: No significant effect of phytate content on iron absorption was found when porridge was fortified with either sodium iron EDTA or ferrous sulfate. Fractional absorption of iron from WTM porridge fortified with sodium iron EDTA (5.73%) was 3.39 times greater than that from the same porridge fortified with ferrous sulfate (1.69%). Fractional absorption of iron from the sodium iron EDTA-fortified LPM porridge (5.40%) was 2.82 times greater than that from LPM porridge fortified with ferrous sulfate (1.91%) (P < 0.0001 for both comparisons, repeated-measures analysis of variance). Thus, the previously identified benefit of LPM was no longer detectable when maize porridge was fortified with additional iron. Conclusion: Iron was absorbed more efficiently when the fortificant was sodium iron EDTA rather than ferrous sulfate, regardless of the type of maize.

Background: There is a need to determine whether iron absorption from iron amino acid chelates is protected from inhibition by dietary phytate and regulated normally by iron status. Objective: The objective of this study was to compare iron absorption from ferrous sulfate ferrous bisglycinate and ferric trisglycinate in whole-maize meal; to determine whether iron from ferrous bisglycinate and ferrous sulfate exchanges in the intestinal pool; and to assess iron absorption from ferrous bisglycinate and ferric trisglycinate over a range of iron statuses. Design: In study 1A 10 iron-sufficient men consumed ferrous sulfate-fortified whole maize meal porridge equilibrated with (59)Fe-sulfate on day 1 and (55)Fe-bisglycinate on day 2. In study 1B these volunteers consumed ferrous sulfate-fortified porridge equilibrated with (59)Fe-sulfate and (55)Fe-bisglycinate simultaneously. In studies 2A and 2B iron absorption from 3 mg Fe as (59)Fe-ascorbate (55)Fe-bisglycinate or (59)Fe-trisglycinate in water and in porridge was compared in 23 subjects with a range of iron statuses. Iron absorption was determined from blood radioactivity on day 16. Results: In study 1A geometric mean iron absorption from ferrous bisglycinate was 6.0% (range: 2.6 - 13.6%) 4 times higher than that from ferrous sulfate (1.7%; range: 1.0-3.3%; P

Numerous studies have shown that iron-loaded diets increase markers of lipid peroxidation in rats, but few have addressed the effects of oral iron supplements on these markers. We investigated the effects of daily and intermittent iron supplements on iron and vitamin E status, and lipid peroxidation. Iron supplements were administered in doses equivalent to those often given to pregnant women in the developing world. In Study 1, iron-deficient (D) and iron-normal (N) rats were fed either 0 or 8000 microgram of supplemental iron daily for 21 d. In Study 2, D rats were fed either the same supplements daily or once every 3 d (8 supplements total). Lipid peroxidation was assessed by breath ethane and pentane and by malondialdehyde (MDA) (using GC-MS). In Study 1, daily supplemented N and D rats had liver nonheme iron concentrations that were 1.8- and 2.7-fold higher, respectively, than those in unsupplemented N rats. Breath ethane levels were also higher in supplemented rats (P < 0.05), but MDA (in plasma, liver, kidney) and liver vitamin E did not differ. Unexpectedly, severely D, anemic rats had significant elevations in the levels of breath ethane, liver MDA and kidney MDA. In Study 2, liver iron and breath ethane decreased progressively (P < 0.05) from 1 d to 3 d after the last iron dose in intermittently supplemented rats. We conclude that iron deficiency results in lipid peroxidation, but that its correction with daily iron supplements results in abnormal iron accumulation and increased lipid peroxidation in rats. These effects are mitigated by intermittent iron supplementation.

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 subject’s 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.

Iron and zinc deficiencies are common in populations dependent on cereal-based diets because of the poor bioavailability of these minerals in those foods. Selective breeding of high-mineral grains can improve the total intake of iron and zinc. However, the additional iron and zinc from those grains may not be available for absorption because of the high phytate content of cereals. Iron and zinc bioavailability needs to be measured before the high-mineral crops are promoted. Iron or zinc bioavailability can be measured from the response of a physiological variable, assessment of body retention, tissue or blood uptake, changes in pool size, or rates of absorption. Iron bioavailability is preferentially measured from erythrocyte uptake of oral radioactive or stable iron tracers; zinc bioavailability is measured from the rate of absorption of an oral isotopic tracer compared with an intravenous tracer. The oral label, which is required for studies of both iron and zinc, may be intrinsically added to the plant during growth or extrinsically added before feeding. Iron and zinc bioavailability from intrinsically and extrinsically labelled normal and high-mineral common bean varieties was tested in young women with low iron stores. The absorption of intrinsic and extrinsic labels of iron and zinc did not differ. The bioavailability of iron and zinc from both varieties was low, about 1.5% and 13%, respectively. Methods to improve the bioavailability of iron and zinc from plant foods need to be developed.

The measurement of ethane and pentane in breath offers a sensitive and noninvasive means to assess in vivo lipid peroxidation in animals and humans. However, numerous technical obstacles inherent in collecting and concentrating air-breath samples have limited the wider application of these measurements for the assessment of in vivo lipid peroxidation. We have developed a relatively simple, inexpensive, rapid, and reliable method to collect, concentrate, and measure breath ethane and total-body pentane from rats. This method, which concentrates alkanes from 4 liters of collected air-breath on adsorbant cooled to -174 degrees C, was found to be superior to similar cryofocusing techniques at -130 degrees C, which fail to effectively trap highly volatile ethane from large volumes of air. We found ethane evolves predominantly through breath, whereas a significant amount of pentane evolves from sources other than breath. Mean evolution rate for ethane was 1.08 pmol/100 g body wt/min. Pentane evolution rates displayed more inter-rat and day-to-day variability with a mean of 0.52 pmol/100 g body wt/min. We also found that excreted rat feces exude large amounts of ethane and pentane.

A 32-mo-long, double-blind field study involving one highland control community receiving only vitamin A-fortified sugar and three vitamin A- and FeNaEDTA-sugar-fortified communities, two in the lowlands and one in the highlands of Guatemala, was undertaken to test the effectiveness of this approach in controlling iron deficiency. The communities' population ranged between 1200 and 17000. Sugar fortified with 1 g FeNaEDTA and 15 mg retinol as retinyl palmitate/kg was stable, did not segregate, and was well accepted by the communities. The impact of fortification on iron nutrition was estimated at 8, 20, and 32 mo of intervention. All pregnant women and subjects with severe anemia received supplements or treatment and were excluded from the analysis. Iron stores in the fortified communities increased significantly except for women 18-48 y of age in one lowland community and > 49 y in the highland community. Iron stores in the control community remained unchanged except for a rise among adult males.

The importance of an unfavorable profile of serum lipids in the atherosclerotic process has been unequivocally established, but the determinants of serum lipids remain a source of controversy. This controversy includes both the importance of diet as a precursor of an unfavorable lipid profile, and the potential importance of social and psychological factors in determining lipid values. These questions were addressed in a study of serum lipids in urban Brazil. It was found that both dietary and social-psychological factors were associated with total serum cholesterol, high density lipoprotein cholesterol, and serum triglycerides. This exploratory study highlights the importance of the careful measurement of dietary intake, and the inclusion of theoretically relevant social and psychological variables, in any study of serum lipids.

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.

Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. Transitional metals, especially iron, which is particularly abundant in the placenta, are important in the production of free radicals. Protective mechanisms against free radical generation and damage increase throughout pregnancy and protect the fetus, which, however, is subjected to a degree of oxidative stress. Oxidative stress peaks by the second trimester of pregnancy, ending what appears to be a vulnerable period for fetal health and gestational progress. Conditions restricted to pregnancy, such as gestational hypertension, insulin resistance and diabetes, exhibit exaggerated indications of free radical damage. Antioxidants as well as avoidance of iron excess ameliorate maternal and early fetal damage. In rats both iron deficiency and excess result in free radical mitochondrial damage. Estimates of gestational iron requirements and of the proportion of iron absorbed from different iron supplemental doses suggest that with present supplementation schemes the intestinal mucosal cells are constantly exposed to unabsorbed iron excess and oxidative stress. Unpublished work carried out in Mexico City with nonanemic women at midpregnancy indicates that 60 mg/d of iron increases the risk of hemoconcentration, low birth weight and premature birth and produces a progressive decline in plasma copper. These risks are not observed in women supplemented with 120 mg iron once or twice per week. Studies on the influence of iron supplementation schemes on oxidative stress are needed.

Extrinsic and intrinsic iron and zinc labels were used to test iron and zinc absorption from two bean (Phaseolus vulgaris) genotypes, containing normal (common beans, CB) or higher (HFeZnB) iron and zinc concentrations, fed in single meals to young women with low iron reserves. The women were divided into two groups, with one receiving a CB test meal (n = 12) and the other, an HFeZnB test meal (n = 11). The beans were intrinsically labeled hydroponically with (55)Fe (CB and HFeZnB) and with (70)Zn (HFeZnB). Concentrations of zinc and iron were 98 and 65% higher, respectively, in HFeZnB as compared to CB, but phytic acid contents were similar. Extrinsic labels were (59)Fe (CB and HFeZnB), (67)Zn (CB), and (68)Zn (HFeZnB). Iron and zinc percent absorption levels were calculated from radio-iron activity in red blood cells and from urinary excretion of zinc isotopes. Intrinsic and extrinsic iron absorption measures were highly correlated (R (2) = 0.986) (average extrinsic/intrinsic ratio was 1.00). Iron absorption was low (geometric mean2%) in both bean types, and total iron absorbed was not different between types. Intrinsic zinc absorption from the HFeZn beans was higher than extrinsic absorption (15.2% vs 13.4%, p0.05) (average extrinsic/intrinsic was 0.90). The correlation between intrinsic and extrinsic zinc measures was not as high as that for iron (R (2) = 0.719). Percent zinc absorption levels were similar in both bean types, but total extrinsic zinc absorbed was 90% higher (p0.05) from the HFeZnB meal. Thus, the less expensive and time-consuming extrinsic labeling may be used to screen various varieties of beans for iron bioavailability in humans, but it underestimates zinc absorption by approximately 10%. Selective breeding for high-zinc bean genotypes may improve zinc status. However, high-iron genotypes appear to have little effect on iron status when fed alone in single meals to women with low iron reserves.

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.

BACKGROUND Genetically modified, low-phytic acid strains of maize were developed to enhance mineral absorption, but have not been tested previously in humans. OBJECTIVES We evaluated the mineral and phytic acid contents of a low-phytic acid "flint" maize (LPM, the lpa-1-1 mutant) and its parent, wild-type strain (WTM) and measured iron absorption from tortillas prepared with each type of maize and from a reference dose of ferrous ascorbate. DESIGN Proximate composition and mineral and phytic acid contents were measured by standard techniques. Iron absorption from tortillas was evaluated by using the extrinsic tag method and was measured as the incorporation of radiolabeled iron into the red blood cells of 14 nonanemic men 2 wk after intake. RESULTS The phytic acid content of LPM was 3.48 mg/g, approximately 35% of the phytic acid content of WTM; concentrations of macronutrients and most minerals were not significantly different between strains. Iron absorption results were adjusted to 40% absorption of ferrous ascorbate. Iron absorption was 49% greater from LPM (8.2% of intake) than from WTM (5.5% of intake) tortillas (P < 0.001, repeated-measures analysis of variance). CONCLUSION Consumption of genetically modified, low-phytic acid strains of maize may improve iron absorption in human populations that consume maize-based diets.

The simultaneous measurement of 59 Fe and 55 Fe in whole blood by liquid scintillation counting by the Eakins and Brown (EB) method is extensively used in iron absorption studies. The EB method requires many steps which increase the chances of error and decrease its sensitivity. We describe two modifications to the above method consisting of microwave digestion and column purification of iron. This “New Method” (NM) is simpler and more precise, and sensitive than the EB method. Counting efficiencies with the NM are similar for 59 Fe (75%) as with the EB method but are better for 55 Fe (29% for NM vs 22%), and cross counting from 59 Fe into the 55 Fe window is lower with the NM (3.7–4.5%) than with the EB method (10–12%). For the NM, recoveries of radioactive blood samples, in relation to processed standards ranged from 100 to 103% for 59 Fe and 101 to 113% for 55 Fe. For the EB method, recoveries ranged from 94 to 99% for 59 Fe and from 88 to 93% for 55 Fe. Even with very low counts, average intrarun CV with the NM was lower than 5.4% for either isotope, while it was as high as 10.0% for 55 Fe with the EB method.

AIM: To evaluate the anthropometric, iron, B12 Vitamin and folate nutritional condition in patients with short bowel syndrome (SBS) after suspending parenteral nutrition (PN) for no less than 2 years. PATIENTS AND METHODS: We studied 10 pediatric patients with SBS. Anthropometric parameters evaluated: weight, height, brachial perimeter, and width of subscapular, suprailiac, bicipital and tricipital cutaneous folds with Lange caliper. Waterlow′s classification of nutritional condition was used according to weight/height (W/H) and height/age (H/A) fitting percentages, usinge NCHS reference tables. Values, volume and concentration of hemoglobin were assessed, as well as those of ferritin, transferrin, ferremia and percent saturation of transferrin, folic acid, and B12 vitamin. A nutritional survey was also performed. RESULTS: The age range of the patients was 3.3 - 12.9 yrs. The mean of residual bowel was 46.3 cm (range:20–70), jejunum: 30.4 (10–60), ileum 17.9 cm (0–60). The average time of PN dependence was 378.5 days (range:70 – 900). W/H was normal in 8 patients, with a Score I deficit in 2 patients and a low percent of fatty and lean body mass in 1 patient. H/A was abnormally low in 5 patients: 3 Score 1, and 2 Score II. Height was already affected during the PN period The percent of adipose mass was low in 5 patients. Three patients presented anemia, two of which also developed macrocytosis. Such alteration in MCV was also found in two cases where anemia was absent. The levels of B12 vitamin (1 patient) and serum folates (4 patients) were low. The nutritional survey showed that the average daily intake of B12 vitamin and folic acid was adequate, while 50% of patients could not adapt to the intake of iron. Caloric and protein intakes were 110 (range: 67–238) and 326 (r:122–684), respectively. CONCLUSION: Malabsorption of macro and micronutrients can manifest subtly and late. Height in 50% of patients was affected since they were receiving PN. Despite the protein intake fitting percent was well above 100% in all patients, they would apparently not be able to develop a compensatory growth capacity in the post-PN period. Both nutritional control and long-term clinical-biological follow-up should be very strict in SBS patients after PN retrieval.

The mechanisms of the previously described competitive zinc:iron interaction were explored in healthy human volunteers, using the increment in plasma zinc concentration after an oral dose of 25 mg of zinc as zinc sulfate as the index of zinc absorption. Ferric iron in a 2:1 Fe/Zn ratio reduced the plasma uptake of zinc, but to a significantly lesser degree than ferrous iron; addition of 1 g of ascorbic acid increased the magnitude of the inhibitory effect of ferric iron to that seen with ferrous iron. An inverse relationship between some indices of iron status in adult women, or of parenteral iron administration in a child, and the magnitude of zinc:iron interaction was observed. Saturation of the intestinal mucosa with consecutive-day doses of therapeutic iron did not influence the uptake of zinc administered alone or in the context of a 2:1 ferrous iron:zinc ratio in solution. The results are most consistent with a combination of an intraluminal competition of the two minerals and an intracellular competition at a site "distal" to the regulatory step by which iron nutriture modulates the entry of iron into the body, but "proximal" to the site at which the daily administration of therapeutic doses of iron blocked the passage of dietary iron.

Duodenal aspirates from PCM patients and from children with diarrhea present quantitative and qualitative alterations in their content of bile acids, consisting mainly in decreased concentrations of conjugated bile acids (CBA) and increased amounts of primary and secondary free bile acids (FBA). In the absence of diarrhea, PCM was associated with relatively uniform decrements of CBA, increasing to normal levels with nutritional recovery; the amounts of primary and secondary FBA did not change significantly with recovery. The effect of diarrhea on the bile composition of the children varied depending on the patient's nutritional status: a) In recovered children with diarrhea, all CBA, especially the taurine conjugates, were decreased; the glycine/taurine (G/T) ratios were above 1:4 in most of these patients. Although all FBA increased with diarrhea, such an increase was most significant in cholic and lithocholic acids; these children also presented high FBA/CBA ratios. b) In PCM children, the degree of decrement of CBA during diarrhea was similar in taurine and glycine conjugates, the G/T ratio remaining within normal limits. The concentrations of primary and secondary FBA did not change significantly in PCM children with diarrhea when compared with the group without diarrhea. It is believed that the changes in bile acids observed in these children are due to the interaction of malnutrition, diarrhea, and an increased gastrointestinal flora. A theory of how the bile acid events described herein occur is also proposed. Am. J. C/in. Nutr. 27: 788-796, 1974.

In order to investigate the role of vitamin A nutriture in the prevalence of anemia in Central America, a retrospective evaluation of the data of the six Institute of Nutrition of Central Americal and Panama/Office for International Research nutrition surveys of Central America and Panama has been made. Three groups of children; 1 to 4, 5 to 8, and 9 to 12 years old, living between 0 and 2,5000 feet above sea level were studeid. Several biochemical and dietary parameters related to anemia were corrleated with plasma levels of retinol. Children between the ages of 5 and 12 years showed a significant positive correlation between hemoglobin and plasma retinol. Children aged 1 to 4 years did not show a similar correlation. In children of all age groups there were positive correlations between plasma retinol and serum iron. Percent saturation of transferrin was also found to be lower when plasma retinol levels were low. Children with an adequate intake of iron, as classified by both dietary information and socioeconomic level, showed a significant positive correlation between plasma retinol levels and iron in their serum. In contrast, no correlation was found when dietary iron was low. In the light of these findings, a possible relationship between vitamin A deficiency and anemia is suggested.

Studies were performed in seven children and 98 adults to compare the proportion of iron absorbed when administered as ferric sulfate (Fe2(SO4)3), NaFeEDTA, hemoglobin (Hb), and ferrous ascorbate. Studies in children (mostly iron deficient) showed that when the compounds were given with a milk-rice-sugar formula totalling 5 mg Fe, iron from hemoglobin was absorbed best, followed by NaFeEDTA and by Fe2(SO4)3 (mean percent absorption +/-SD = 34.5 +/- 1.5, 8.6 +/- 1.9 and 3.3 +/- 1.5, respectively). Studies in normal or iron deficient adults also demonstrated a better absorption of iron from NaFeEDTA than from Fe2(SO4)3 whether these compounds were given in an aqueous solution (5 mg Fe) or with a standard meal consisting of beans, tortillas, bread, and coffee providing also a total of 5 mg Fe. Hb iron under the same conditions was absorbed in the same proportion to the reference iron ascorbate, always being higher than iron absorbed from the other compounds. Fe2(SO4)3 and NaFeEDTA mixed in the same meal were absorbed in the same proportion as when NaFeEDTA alone was added to the meal and 2 to 3 times better than when Fe2(SO4)3 alone was added to the meal. Addition of desferrioxamine depressed iron absorption from Fe2(SO4)3 and NaFeEDTA, the latter being less affected. Addition of ascorbic acid increased absorption from both. When the compounds were added to the meal to provide 50 mg of iron, percent absorption was depressed in relation to the smaller iron dose in the case of Fe2(SO4)3 and Hb but remained unaltered in the case of NaFeEDTA. Addition of 45 mg Fe as Fe2(SO4)3 or NaFeEDTA to 0.4 mg Fe from the Hb in the meal did not change Hb iron absorption. Addition of 45 mg Fe as Hb or NaFeEDTA to 0.4 mg Fe from Fe2(SO4)3 in the meal enhanced iron absorption from the latter in the same proportions. Addition of 45 mg Fe as Fe2(SO4)3 and Hb to 0.4 mg Fe as NaFeEDTA in the meal respectively depressed and enhanced iron absorption from NaFeEDTA. These studies indicate that NaFeEDTA, Fe2(SO4)3 and nonheme food iron from a common pool different from the heme pool but which is changed in its characteristics by the presence of NaFeEDTA, resulting in a better absorption of iron.

On 14 occasions, 1.75 g/kg of body weight of lactose was given in whole milk to preschool children who had significant malabsorption with aqueous lactose solution. The volume of hydrogen excreted in the breath was less after the milk meal. Moreover, the hydrogen response to the nonabsorbable disaccharide, lactulose, was greater with aqueous, solution than with a liquid meal but their difference disappeared when metoclopramide was given with the lactulose: meal. The slower hydrogen production is attributed to slower intestinal delivery of lactose in meals; this phenomenon may account for clinical lactose tolerance often seen in children with demonstrated lactose malabsorption.

The principal nutritional problems of school children in Central America and Panama are those of a lack of sufficient protein of good quality, vitamin A, and riboflavin. Where tortillas prepared from lime-treated corn are not used, calcium deficiency is also evident. In many areas the high incidence of endemic goiter reflects an absolute or relative deficiency of iodine. Because supplementary feeding of nursing infants, and particularly the feeding of the child after weaning, are poorly carried out in the area, malnutrition is almost universal among children of these ages in low income and rural groups. This is reflected in the tendency for growth and bone maturation, which parallels that for U. S. children during the first months after birth, to be severely retarded during the period from 1 to 4 years. During these ages either the cumulative effect of the poor diet or the poor diet plus some additional stress, results in the child developing Infantile Pluricarencial Syndrome (I.P.S.). Infectious diarrhea is a frequent precipitating cause. The I.P.S. of Central America, characterized by edema, skin and hair changes, retardation in growth and development, apathy, diarrhea and anorexia, is not essentially different from kwashiorkor. The basically poor nutritional state of many pre-school children is defined and given the name incipient I.P.S. or prekwashiorkor. Nutritional surveys reveal physical signs compatible with a deficiency of vitamin A and sometimes also of riboflavin. In general deficiencies of niacin, ascorbic acid, vitamin D and thiamine are not recognized. Anemias are frequent and usually of a macrocytic type. In hookworm infested areas an appreciable amount of microcytic anemia may also be observed. Investigations in progress by the Institute of Nutrition of Central America and Panama (INCAP) in the area include: continued nutritional and dietary surveys; studies of the effect of vitamin B12 and antibiotics on growth; studies of the physiopathology of I.P.S., and the development of vegetable mixtures and other dietary means of improving child feeding practices at low cost.

NEvIN S. SCRIMSHAW, PII.D., M.D.� O NE of the consequences of the severe protein malnutrition underlying kwashiorkor is a decrease in the activity of various enzymes as measured in blood serum, tissues, and duodenal contents. ‘ Thompson and Trowell’ and G#{243}mez ci a!.’ have reported that the activities of lipase, trypsin, and amylase are reduced in the duodenab secretions of kwashiorkor patients. Of the three enzymes lipase appears to be the first to be affected, followed by trypsin.’ These biochemical findings are consistent with the histologic damage observed in the pancreas and intestine when the disease is severe.4’ A decrease in pancreatic bipase and in bile salts as well as functional alterations of the small intestine, are known to impair the absorption of vitamin A. In the course of studies in children with kwashiorkor in Central America6 very low serum levels of vitamin A have been found and ocular lesions suggestive of vitamin A deficiency are observed. From the Institute of Nutrition of Central America and Panama (INCAP), Guatemala, CA. This study was assisted by funds from the Nutrition Foundation, Inc. and National Institute of Arthritis and Metabolic Diseases of the National Institutes of Health (A-981), Public Health Service. Reported in part at the Annual Meeting of the American Institute of Nutrition

The creatinine height index (CHI), which consists of the following ratio: CHI: 24 hour creatinine excretion of subject 24 hour creatinine excretion of normal child of same height has been devised for estimating the relative muscle mass of children. Age is not considered because children of developing areas are very often retarded in height. The normal CHI is close to 1.0, both in well nourished children and in fully recovered malnourished ones, with heights ranging from 64.8 to 135 cm. Protein calorie malnourished (PCM) children of the edematous type (kwashiorkor and kwashiorkormarasmus) had CHI's ranging from 0.25 to 0.75, lower CHI's were observed in more severely malnourished children and vice versa. In clinically marasmic children (PCM without edema) the CHI ranged from 0.33 to 0.85, independent of the degree of weight deficit or the clinical severity of marasmus, indicating that severe caloric deficiency can occur with a wide range of muscle wasting. No creatinine retention was observed in any PCM children with adequate urine flows. Independent estimates of protein and calorie repletion were obtained during recovery by the use of CHI and weight for height. A significant negative correlation between CHI and N retention was found, indicating the physiological significance of the CHI in estimating protein nutrition.

By serial determination of the change in plasma nickel concentration following a standard dose of 22.4 mg of nickel sulfate hexahydrate containing 5 mg of elemental nickel, the bioavailability of nickel was estimated in human subjects. Plasma nickel concentration was stable in the fasting state and after an unlabeled test meal, but after the standard dose of nickel in water was elevated 48.8, 73.0, 80.0, and 53.3 microgram/1, respectively, at hours 1, 2, 3, and 4. Plasma nickel did not rise above fasting levels when 5 mg of nickel was added to two standard meals: a typical Guatemalan meal and a North American breakfast. When 5 mg of nickel was added to five beverages-whole cow milk, coffee, tea, orange juice, and Coca Cola-the rise in plasma nickel was significantly suppressed with all but Coca Cola. Response to nickel also was suppressed in the presence of 1 g of ascorbic acid. Phytic acid in a 2:1 molar ratio with nickel, however, did not affect the rise in plasma nickel. The chelate of iron and ethylenediaminetetraacetate, NaFeEDTA, an iron-fortifying agent suggested for application in Central America, slightly but not significantly depressed plasma nickel rise at 2 hours, whereas disodium EDTA depressed plasma nickel levels significantly below the fasting nickel curve at 3 and 4 hours postdose. These studies suggest that the differential responses of inorganic nickel to distinct foods, beverages, and chemically-defined dietary constituents could be important to human nutrition.

The absorption of lactose at pharmacological and physiological doses from conventional aqueous solutions and from whole cow's milk has been studied in healthy adults using a noninvasive hydrogen (H2) breath-analysis technique using thermal conductivity gas chromatography and interval collection of expired air. A discomfort score based on the presence or absence of symptoms (meteorism, flatulence, and diarrhea) during a 6-hr observation period was also recorded. Basal breath H2 concentrations were found to be stable for up to 12 hr. Of 20 subjects available for study, seven showed a rise in breath H2 of 20 ppm; they were classified as lactose intolerant mahabsorbers. Follow-up studies using other forms and doses of lactose were conducted in these latter subjects. Fifty grams of lactose as whole mihk produced a significant rise in breath H2 in 10 of the 13 subjects (77%). Nine of the 11 intolerant malabsorbers (82%) ingesting12.5g of lactose in aqueous solution showed an increment in breath H2 concentration of >20 ppm, and eight of these nine low dose malabsorbers (89%) also manifested a >20 ppm rise with 12.5 g of lactose as a 25O-ml glass of milk. However, although no significant differences in symptom score were seen between milk and aqueous administration of equivalent doses of lactose, significantly fewer symptoms were experienced with the physiological (12.5 g) dose than with the pharmacological (50 g) dose. Several subjects who had been classified as intolerant to the 50 g of lactose, had no symptoms with the 12.5-g dosages. Using a technique that indicates the amount of carbohydrate that is not absorbed, no evidence for a difference in gastrointestinal transit between mihk and aqueous solution could be detected. We conclude that the use of physiological doses and natural sources of lactose in combination with the simple H2 breath analysis technology adds a new dimension to the clinical evaluation of lactose malabsorption and milk intolerance in medical practice. Am. J. Clin. Nuir. 33: 545-554, 1980.