Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana.

BACKGROUND: Lysine affects diarrhea and anxiety via effects on serotonin receptors, enhanced intestinal repair, and sodium chloride-dependent opioid peptide transport. OBJECTIVE: The objective was to investigate the effects of lysine supplementation on morbidity, growth, and anxiety in children and adults of peri-urban areas of Accra, Ghana. DESIGN: In a double-blind randomized trial, the effect of lysine supplementation (1 g lysine/d) compared with that of placebo was examined in 2 groups of men, women, and children (n = 271). Primary outcomes included diarrheal and respiratory morbidity, growth, and anxiety and complement C3, C-reactive protein, serum cortisol, transferrin, and ferritin values. Independent-sample t tests, odds ratios, generalized estimating equations, 4-parameter sinusoid regression, and generalized linear models were used. RESULTS: Thirty percent of men, 50% of women, and 15% of children were at risk of lysine inadequacy. Supplementation in children reduced diarrheal episodes [19 lysine, 35 placebo; odds ratio (OR): 0.52; 95% CI: 0.29, 0.92; P = 0.046] and the total number of days ill (21 lysine, 47 placebo; OR: 0.44; 95% CI: 0.26, 0.74; P = 0.034). Mean days ill per child per week (0.058 ± 0.039 lysine, 0.132 ± 0.063 placebo; P = 0.017) were negatively associated with weight gain with control for baseline weight and study group (P = 0.04). Men had fewer coryza episodes (23 lysine, 39 placebo; OR: 0.60; 95% CI: 0.36, 1.01; P = 0.05), total number of days ill (lysine: 130; placebo: 266; OR: 0.51; 95% CI: 0.28, 0.93; P = 0.03), and mean days ill per person per week (lysine: 0.21 ± 0.23; placebo: 0.41 ± 0.35; P = 0.04). Serum ferritin (P = 0.045) and C-reactive protein (P = 0.018) decreased in lysine-supplemented women but increased in placebo-supplemented women. CONCLUSION: Lysine supplementation reduced diarrheal morbidity in children and respiratory morbidity in men in Ghana.

INCAP studies of kwashiorkor and marasmus.

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.

INCAP studies of nutrition and infection.

As soon as the Institute of Nutrition of Central America and Panama (INCAP) began to study the poor nutritional status and stunting of children in the rural villages of Central America, it was apparent that infections, particularly diarrheas, were also a serious problem. Studies of kwashiorkor indicated that infections precipitated kwashiorkor and anemia in children who were already malnourished. In the 1940s there was almost no suggestion in the literature of a relation between nutrition and infection. INCAP gradually identified the mechanisms by which any infection worsens nutritional status and demonstrated that infections were more severe and more often fatal in malnourished children and adults. These studies ultimately led to the 1968 World Health Organization (WHO) monograph "Interactions of nutrition and infection" and widespread recognition by public health workers of the importance of this relationship for morbidity and mortality in poorly nourished populations.

INCAP studies of endemic goiter and its prevention.

The high prevalence of goiter among adults in its member countries of Central America and Panama was observed as soon as INCAP began field studies. This led to systematic studies of goiter in schoolchildren in all of the countries as described, beginning with Guatemala where the rate was 38% nationally. However, efforts to eliminate the consequences of iodine with iodized salt using the water soluble potassium iodate and a process that had proved successful in Switzerland and the United States could not be used with the crude moist salt of the region. INCAP identified potassium iodate that is insoluble in water, and in four schools (two each in El Salvador and Guatemala) proved that the iodine in this compound was as available as that in potassium iodate. It remained evenly distributed in moist salt. When added to salt in Guatemala, goiter rate dropped to 15% in four years and less than 5% in eight years. Compulsory iodation of salt in other developing countries followed with comparable results. This method is now used in worldwide campaigns against iodine deficiency in developing countries.

History and early development of INCAP.

Nevin Scrimshaw was the founding Director of the Institute of Nutrition of Central America and Panama (INCAP), serving as Director from 1949 to 1961. In this article, he reviews the history of the founding of INCAP, including the role of the Rockefeller and Kellogg Foundations, the Central American governments, and the Pan American Health Organization. The objectives pursued by INCAP in its early years were to assess the nutrition and related health problems of Central America, to carry out research to find practical solutions to these problems, and to provide technical assistance to its member countries to implement solutions. INCAP pursued a strategy of selecting promising Central Americans for advanced education and training in the US who assumed positions of leadership on their return. After this early phase, talented non-Central Americans of diverse origins were brought to INCAP, as well as additional researchers from the region. Growth of INCAP, as reflected in its annual budget and in the physical plant, was rapid and this was accompanied by high scientific productivity. Several field studies were launched that contributed impetus and design elements for the Oriente Longitudinal Study, which is the focus of this supplement.

Impact of lysine-fortified wheat flour on morbidity and immunologic variables among members of rural families in northwest Syria.

BACKGROUND: Previous studies have shown an effect of lysine fortification on nutrition and immunity of poor men, women, and children consuming a predominantly wheat-based diet. OBJECTIVE: To examine the lysine value of diets and the effect of lysine fortification on functional protein status, anthropometry, and morbidity of men, women, and children in rural Syria. METHODS: At baseline of a two-phase study using 7-day household food intake inventories (n = 98), nutrient availabilities per adult male equivalent were estimated. In the intervention phase, a 16-week double-blind trial, households (n = 106) were randomly assigned to control and lysine groups. Hematologic and anthropometric data were collected from men (n = 69; 31 control, 38 lysine), women (n = 99; 51 control, 48 lysine), and children (n = 69; 37 control, 32 lysine) at baseline, 12 weeks, and 16 weeks. Total CD3 T lymphocytes as well as T lymphocytes bearing the receptors CD4, CD8, and CD56, IgM, IgG, IgA, complement C3, C-reactive protein, serum albumin, prealbumin, transferrin, retinol-binding protein, hemoglobin, and hepatitis B surface antigen were determined. Health status and flour usage were monitored. Paired- and independent-sample t-tests and chi-square tests were performed. RESULTS: Mean nutrient availability per adult equivalent was 2,650 +/- 806 kcal, 70.1 +/- 26.4 g protein, 65 +/- 14% cereal protein, and 41.9 +/- 0.8 mg lysine per gram of protein. Complement C3 was significantly higher in men receiving lysine than in controls (p < .05). Among women, there were significant differences between the control and lysine groups in diarrhea period prevalence (total number of diarrheal episodes during the period of intervention divided by the total number of observations), (20 in the control group, 6 in the lysine group; p = .014), the mean number of days ill (0.4 +/- 0.7, control, 0.14 +/- 0.4, lysine, p = 0.03), and the number of diarrheal episodes per person per year (1.39 in the control group, 0.47 in the lysine group). No other significant differences between the lysine and the control groups were observed. CONCLUSION: Lysine fortification of wheat flour demonstrated a positive effect on diarrheal morbidity in women. The effect could be attributed to an improvement in protein utilization but possibly also to a direct effect of lysine in gastrointestinal tract. Studies in populations with higher diarrheal prevalence and significant dietary lysine deficiency are needed to determine whether the reported effects on diarrheal prevalence are replicable and whether they are pharmacological or nutritional. It would be particularly desirable to study the effect of lysine on diarrhea in preschool children, who have much higher morbidity and mortality rates from this disease than school-age children or adults.

Fifty-five-year personal experience with human nutrition worldwide.

By 1950 the vitamins had been identified, but little was known of their functions. Beriberi, pellagra, and ariboflavinosis were disappearing, but kwashiorkor and/or marasmus were common in most developing countries. Requirements for protein were still uncertain, and those for essential amino acids or essential fatty acids were unknown. The author's contributions in the field of vitamins began in the 1950s and have been reported in more than 650 publications and in 20 books or monographs. These contributions include establishing the Institute of Nutrition of Central America and Panama, the Department of Nutrition and Food Science at the Massachusetts Institute of Technology, the World Hunger Program of the United Nations University, and the International Nutrition Foundation. His scientific contributions include identification of synergistic interactions of nutrition and infection, use of potassium iodate for fortifying crude moist salt, research in the epidemiology of kwashiorkor and marasmus, development of a successful low-cost protein-rich food for infants and young children, establishment of human protein requirements, and investigation of single-cell protein for food use.

Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan.

Wheat provides more than 50% of the protein and calorie intake of the population of Pakistan. Legumes and animal protein that could complement the amino acid pattern of wheat, in which lysine is the first limiting amino acid for utilization of protein, are not affordable by members of lower socioeconomic groups in developing countries. The purpose of the study was to determine whether lysine fortification of wheat flour would have a positive impact on populations consuming a predominantly wheat-based diet. A double-blind study was carried out for three months on the outskirts of Peshawar, Pakistan. Forty families received wheat flour fortified with lysine, and 40 families received wheat flour without lysine. Wheat provided 59% of the protein for men, 65% for women, and 58% for children. The weight and height of the children in both groups increased during the study, but the increase was significantly greater in the lysine group. Hemoglobin increased significantly in the women receiving lysine-fortified flour. Transferrin levels increased significantly in men, women, and children in the lysine group as compared with those in the control group. Prealbumin increased significantly in adults receiving additional lysine but decreased in children. Men, women, and children in the lysine-supplemented families had significant increases in CD4, CD8, and complement C3 as compared with controls. These results indicate that lysine fortification of wheat flour can significantly improve sensitive indicators of nutritional status in a population consuming a diet in which 58% to 65% of the protein, depending on age and sex, is supplied by wheat.

Lysine-fortified wheat flour improves the nutritional and immunological status of wheat-eating families in northern China.

The purpose of this study was to determine the impact of the fortification of wheat flour with lysine on selected health indicators among farm families obtaining 58% to 67% of their dietary protein from wheat. A man, a woman, and a child aged 5 to 12 years were studied from each of 88 families in a village near Huixian City, Henan Province, China. Half of the families received wheat flour fortified with 3 g of lysine per kilogram for three months, and the other half received wheat flour without fortification. The results showed a significantly greater gain in the height and weight of children receiving lysine-fortified wheat flour. Hemoglobin values were not affected. The mean prealbumin values of adult men and women were higher in those receiving lysine. The numbers of CD3 T cells increased significantly in women and children, as did the complement fraction C3 and IgG in men, IgA in women, and IgG, IgA, IgM, and C3 in children. These results indicate that lysine fortification of wheat flour can significantly improve some indicators of the nutritional status and immune function of family members consuming a wheat-based diet.

Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria.

Lysine is a limiting amino acid in diets based on wheat as the staple. In experimental animals, prolonged dietary lysine inadequacy increases stress-induced anxiety. If observed in humans, such a result would have a strong implication for the relationship between nutrition and communal quality of life and mental health. As part of a 3-month randomized double-blind study, we tested whether lysine fortification of wheat reduces anxiety and stress response in family members in poor Syrian communities consuming wheat as a staple food. In the lysine-fortified group, the plasma cortisol response to the blood drawing as a cause of stress was reduced in females, as was sympathetic arousal in males as measured by skin conductance. Lysine fortification also significantly reduced chronic anxiety as measured by the trait anxiety inventory in males. These results suggest that some stress responses in economically weak populations consuming cereal-based diets can be improved with lysine fortification.

Historical concepts of interactions, synergism and antagonism between nutrition and infection.

In the 1950s textbooks of nutrition made little or no mention of a relation to infection. The same was true for treatises on infectious disease. Relevant studies in experimental animals and a number of classical clinical observations were available pointing out the role of infection in precipitating nutritional disorders. However, clinicians and nutritionists did not recognize the importance of the relationship. The field and metabolic studies of the Institute of Nutrition of Central America and Panama (INCAP) in the 1950s demonstrated that malnutrition and infection in humans are generally synergistic. These studies stimulated the review of available evidence that resulted in the 1968 WHO monograph on "Interactions of Nutrition and Infection." It provided extensive evidence for the role of infections in precipitating clinical malnutrition and for the impact of malnutrition on morbidity and mortality from infection. The high frequency of diarrhea in underprivileged young children led to intensive studies in many countries of its effect on nutritional status and to recognition of the high prevalence of "weanling diarrhea." The effects of infection on nutritional status were then extensively and elegantly investigated at Fort Detrick, MD, and hormonal and cytokine mechanisms identified. The subsequent explosion in knowledge of cell-mediated immune mechanisms has led to an understanding of how malnutrition lowers this resistance. Today, recognition of the synergistic relationship between nutrition and infection influences most public health interventions to prevent malnutrition.

The nutrition and health transition of democratic Costa Rica / The nutrition and health transition of democratic Costa Rica

The remarkable improvement in health and nutrition statistics in Costa Rica from those of a developing country to those of industrialized countries in a single decade in the 1970s is without precedent. In 1970 the infant mortality rate in Costa Rica of 68 per 1,000 did not differ markedly from that of other Central American Countries and, in common with these countries, less than 10 por ciento of the health budget was alllocated to preventive health measures