M G Herrera

Brain Metabolism during Fasting

Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that beta-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism. A strikingly low respiratory quotient was also observed, suggesting a carboxylation mechanism as a means of disposing of some of the carbon of the consumed substrates.

Hormone-fuel interrelationships during fasting.

Over 50 years ago, Benedict (2) published his extensive monograph on the metabolism of fasting in man, in which he demonstrated that carbohydrate stores provide a small but significant component of the bodys fuel for only the first few days. Thereafter, protein and fat are the sole sources of fuel, the former contributing 15% of the calories and the latter the balance. The primary role of fat as fuel was apparent to Benedict and his contemporaries; it is plentiful and expendable. The significance of the protein requirement, however, was less clear; in fact, it was not fully understood until nearly 20 years later when the obligatory dependence of the central nervous system on glucose was firmly established (3). Since glycogen stores in man were known to approximate only 200 g, it was readily apparent that glucose has to be derived from protein in order to maintain cerebral metabolism during a prolonged fast. More recently, our understanding of the fasted state has been further clarified by the demonstration that free fatty acid is both the major transport form of lipid leaving adipose tissue (4, 5) and a substrate that is

Nutritional supplementation, maternal education, and cognitive development of infants at risk of malnutrition.

Infants born to families at risk of malnutrition were studied prospectively from the beginning of the 3rd trimester of the mothers pregnancy until the child reached 3 yr of age to ascertain the effects of nutritional supplementation and/or a maternal education program on their cognitive development. Four hundred thirty-three families were assigned randomly to six groups: group A served as a control; group B received the supplement from the age of 6 months to 3 yr; group C received the supplement during the 3rd trimester of pregnancy and the first 6 months of the childs life; and group D received the supplement throughout the entire study period. In addition, group A1 was enrolled in a maternal education program but received no nutritional supplement and group B1 received both treatments. The Griffiths test of infant development was administered at 4, 6, 12, 18, 24, and 36 months of age, and the Corman-Escalona Einstein scale was administered at each age up to 18 months. Children who received food supplementation performed better than those who did not, especially on subtests that were primarily motoric. The effect of food supplementation on behavior appeared to be contemporaneous. In addition, the treatment effects were more pronounced for girls than for boys in this sample. Although these interventions reduced the gap in cognitive performance between lower and upper socioeconomic classes, a disparity nevertheless remained by the end of the study.

A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania

OBJECTIVES To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children. DESIGN Randomized, double blind, placebo-controlled trial. METHODS Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1). RESULTS Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01). CONCLUSION Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children.

Vitamin A supplementation and child survival

Previous studies of the effect of 6-monthly vitamin A supplementation on child mortality have given conflicting results. In other trials, more frequent doses of vitamin A have significantly reduced mortality among children at risk of vitamin A deficiency. We have done a double-blind, placebo-controlled trial of vitamin A supplementation in the Sudan among 28,753 children aged 9-72 months at risk of vitamin A deficiency. Children were assigned to receive either 200,000 IU vitamin A and 40 IU vitamin E every 6 months (vitamin A group) or 40 IU vitamin E alone (placebo group). During the 18 months of follow-up, there were 120 deaths (8.4/1000) in the vitamin A group and 112 (7.9/1000) in the placebo group (relative risk 1.06, 95% confidence interval 0.82-1.37). Controlling for geographic site, round of observation, anthropometry, morbidity, dietary intake of vitamin A, sex, and all baseline differences between the two groups did not change the results. Children living in poor and unsanitary environments, younger children, and those sick, stunted, wasted, or consuming diets low in vitamin A were at a significantly higher risk of dying. The lack of an effect of large-dose vitamin A supplementation on mortality, despite a clear association between dietary vitamin A and mortality, underscores the need to identify factors that modify the efficacy of vitamin A supplements as a public-health measure. Reducing poverty, improvements in sanitation, and access to adequate diets should remain the main goals to improve child survival.

Non-hormonal factors in the control of gluconeogenesis☆

Abstract Increasing the concentration of alanine in the medium in a perfused rat liver preparation increases net hepatic glucose production. A high perfusate-glucose concentration diminishes while a low perfusate-glucose concentration enhances hepatic glucose release into the medium. This phenomenon is observed with both fed and fasted livers, suggesting a modulation of glycogenolysis and/or gluconeogenesis by the level of medium glucose. Provision of fatty acids enhances conversion of alanine to glucose and net hepatic glucose production while concurrently reducing alanine oxidation and its incorporation into fatty acids. On the other hand, gluconeogenesis in kidney appears to be also related to both acute and chronic changes in pH and acid-base balance.

Water and sanitation associated with improved child growth

Objective: To examine the relation between household water and sanitation, and the risk of stunting and reversal of stunting in Khartoum and Crezira regions Sudan.Design: Prospective cohort study.Setting: A total of 25 483 children aged 6–72 months from rural Sudan enrolled in an 18-month field trial in 1988 to study the effect of vitamin A supplementation on child health and survival.Results: The mean height-for-age z-scores at baseline and the end of study were −1.66 and −1.55, respectively, for the group with water and sanitation facilities, and −2.03 and −1.94 for the group without water and sanitation, after adjustment for age, region, gender, mothers literacy, intervention group (vitamin A vs placebo), family wealth, breastfeeding and cleanliness. Among children of normal height-for-age at baseline, the risk of stunting (<−2 height-for-age z-score) was lowest in the group that came from homes that had both water and sanitation compared to children from homes without these facilities (multivariate RR=0.79, 95% CI 0.69–0.90). Among children stunted at baseline, those coming from homes with water and sanitation had a 17% greater chance of reversing stunting than those coming from homes without either facility (adjusted RR=1.17, 95% CI 0.99–1.38). We did not detect a synergistic association between access to water and sanitation.Conclusions: Water and sanitation are independently associated with improved growth of children.Sponsorship: None.

Dietary vitamin A intake in relation to child growth.

Severe deficits in ponderal and linear growth are problems of major public health significance among children in developing countries. We prospectively examined the association of dietary vitamin A intake with child growth among 28,740 Sudanese children ages 6–72 months. At baseline and at each 6‐month visit, all subjects were weighed and measured. Dietary vitamin A intake during the prior 24 hours was assessed using recall of vitamin A‐containing foods. Dietary vitamin A intake was associated with attained height and weight after controlling for age, sex, morbidity, and socioeconomic variables. Compared with children in the bottom quintile of intake, those in the top quintile were 11 mm taller [95% confidence interval (CI) = 8–13] and 237 gm heavier (95% CI = 153–320). Higher dietary vitamin A intake was also associated with reduced risk of stunting [relative risk (RR) for 5th vs 1st quintile = 0.7; 95% CI = 0.5–0.9] and wasting (RR = 0.7; 95% CI = 0.5–0.9). Adequate intake of foods containing vitamin A may improve child growth where vitamin A deficiency prevails, but this relation may not be due to vitamin A per se.

Passage of Insulin and Inulin Across Vascular Membranes in the Dog

The equilibration of IRI and NSILA between arterial plasma and lymph was studied at different sites in sixteen anesthetized dogs. Lymph was collected from the thoracic duct in one group, from the main hepatic lymph vessel in another, and from the leg lymphatic in a third group. No baseline gradients were observed between arterial serum and lymph IRI concentrations. Lymph/serum NSILA concentration ratios were 0.62 ± 0.29 for leg lymph, 0.66 ± 0.20 for thoracic duct lymph and 0.84 ± 0.63 for hepatic lymph. Two tests were carried out in each dog: (1) IVGTT (0.5 gm./kg.) Evans Blue was injected concurrently in some cases. Net glucose disappearance rate and serum IRI and NSILA patterns were similar in the three groups. Serum IRI passed rapidly into hepatic and thoracic duct lymph reaching plateau levels of 40 and 35 μU. per ml. respectively within 15 min. Leg lymph glucose concentration increased immediately but IRI appearance was delayed: A plateau of 20 μU, per ml. was reached after 30 min. No significant passage of Evans Blue into paw lymph was observed. Glucose injection was followed by a significant decrease in serum NSILA. Hepatic and thoracic duct lymph NSILA levels decreased slightly but NSILA concentration remained unchanged in leg lymph. (2) One hour after the first test 0.2 U. per kg. of pork insulin and 25 uc 14C-inulin were injected intravenously. The patterns of distribution of these two substances were similar. Both reached peak concentrations first in hepatic lymph then in thoracic duct lymph. In paw lymph their appearance was delayed and the maximum concentration achieved was lower. It is concluded that differences in capillary permeability are likely to determine in part the distribution of IRI and NSILA in body fluids and thus may influence their biological activity.

Undernutrition in relation to childhood infections: a prospective study in the Sudan.

Objective: The aim of the study was to examine the relationships between nutritional status and diarrhoea and respiratory infections.Design: Prospective cohort study within the framework of a randomized double-blind placebo-controlled intervention trial.Setting: In rural communities in the Khartoum and Gezira regions, in Northern Sudan.Subjects: 28, 753 Sudanese pre-school children between 6 months and 6 y old.Methods: Relative risks of subsequent diarrhoea and respiratory infections in relation to nutritional status measured by anthropometry (Z-scores of height-for-age (H/A), weight-for-height (W/H), and weight-for-age (W/A), which reflect stunting, wasting and underweight, respectively) were estimated using odds ratios from logistic regression adjusting for various covariates.Results: H/A, W/H and W/A were significantly and inversely associated with subsequent diarrhoea and febrile diarrhoea (P for trend <0.001) with risks being 2.00 times higher (95% confidence interval, CI (1.64, 2.43)) among children with W/A Z-scores below −4 Z, and 1.75 times higher (95% CI (1.56, 1.96)) among those with a W/A Z-score between −4 and −3 Z compared with children having a W/A Z-score ≥1. Age, gender, region of residence and seasonality modified these associations. Also, febrile cough was inversely associated with W/A and W/H (P<0.03), with risks ranging from 1.41 times higher (95% CI (1.02, 1.97)) to 1.21 times higher (95% CI (1.04, 1.41)) in the group of underweight children with W/A Z-scores below −4 and between −2 and −1 Z, all compared with normally nourished children (≥−1 Z).Conclusions: The reduction of severe but also mild and moderate undernutrition is necessary through nutrition, health and socio-economic improvement in order to prevent morbidity.Sponsorship: This study was carried out under cooperative agreement no. DAN-00450G-SS-6067 of the Office of Nutrition, US Agency for International Development, Washington DC, and the Harvard Institute for International Development.European Journal of Clinical Nutrition (2000) 54, 463–472