Micronutrient malnutrition: policies and programs for control and their implications.

Global progress in social and economic development is occurring, although slowly, in the most needy parts of the nonindustrialized world, where nutritional deficiencies, including micronutrients, remain significant public health problems. Until empowering benefits accrue from development spin-offs, policy guidance for purposeful public health actions can help reduce the unconscionable toll on health and quality of life from micronutrient malnutrition and can interrupt its intergenerational debilitating effects on national development. Narrowly focused control programs including homestead production, plant breeding, fortification, and supplementation are in effect, but in general, they have not been holistically planned and integrated into overall development programs. Such integration is needed to ensure sustainability into the next century. A new paradigm is needed, including a new way of thinking by nutrition scientists and program implementers that includes partnerships with the poor in all aspects of program planning and implementation.

Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol.

Anticonvulsants that induce hepatic metabolism increase clearance of oral contraceptive hormones and thereby cause contraceptive failure. Gabapentin is not metabolized in humans and has little liability for causing metabolic-based drug-drug interactions. In healthy women receiving 2.5 mg norethindrone acetate and 50 microg ethinyl estradiol daily for three consecutive menstrual cycles, concurrent gabapentin administration did not alter the steady-state pharmacokinetics of either hormone. Thus, gabapentin is unlikely to cause contraceptive failure.

PIP: Anticonvulsants that induce hepatic metabolism increase the clearance of synthetic estrogens and progestogens used in oral contraceptives (OCs), thereby potentiating contraceptive failure. In contrast, the anticonvulsant drug gabapentin is not metabolized in humans and has little liability for metabolic-based drug interactions. The present study sought to confirm whether concurrent administration of gabapentin would alter the pharmacokinetics of norethindrone acetate (2.5 mg) and ethinyl estradiol (50 mcg) in healthy US women. A total of 13 women were enrolled for three menstrual cycles each. Pharmacokinetic values did not change appreciably as a result of the addition of gabapentin. The rate and extent of absorption of both hormones were unaffected by the anticonvulsant. Gabapentin plasma concentration time profiles and pharmacokinetic values from this study were similar to historical values after administration of gabapentin alone. The observed lack of interaction between gabapentin and norethindrone acetate or ethinyl estradiol is consistent with the fact that gabapentin is not metabolized, is not an inducer or inhibitor of hepatic drug metabolizing enzymes, is absorbed via a specific transport system for amino acids, and is not bound to plasma proteins. Anticonvulsant drugs that do not interact with OCs should be considered for the treatment of epileptic women of childbearing age who are using this method of fertility control.

From research to global reality: the micronutrient story.

The professional life history of E. V. McCollum exemplifies how sound nutrition-related laboratory research was translated into practical realities that influenced individual and national nutrition-related decisions. Public health and educational programs emerging in the first third of this century improved health and nutritional well-being in the United States. Characteristics that surrounded pioneering efforts early in the century are similar to those that have reinvigorated global micronutrient concerns in the last third of the century. Sound community-oriented scientific research revealed the true consequences of iodine, vitamin A and iron micronutrient malnutrition. Repositioning the image of these three micronutrients from that of a clinical problem affecting relatively few to one with consequences for individual, national and global development affecting many more, and disseminating these facts through high-level political forums incited attention, commitment and actions. As in the early days of McCollum and his contemporaries, current nutrition scientists played a significant role, interacting with politically oriented counterparts, in taking micronutrient research to reality for improving health and quality of life globally. Lessons learned from the process, both past and present, should guide future nutrition-oriented endeavours in moving research to reality for betterment of global community health.

Perspectives from micronutrient malnutrition elimination/eradication programmes.

Micronutrient malnutrition cannot be eradicated, but the elimination and control of iron, vitamin A and iodine deficiencies and their health-related consequences as public health problems are currently the targets of global programmes. Remarkable progress is occurring in the control of goitre and xerophthalmia, but iron-deficiency anaemia (IDA) has been less responsive to prevention and control efforts. Subclinical consequences of micronutrient deficiencies, i.e. "hidden hunger", include compromised immune functions that increase the risk of morbidity and mortality, impaired cognitive development and growth, and reduced reproductive and work capacity and performance. The implications are obvious for human health and national and global economic and social development. Mixes of affordable interventions are available which, when appropriately adapted to resource availability and context, are proven to be effective. These include both food-based interventions, particularly fortification programmes, such as salt iodization, and use of concentrated micronutrient supplements. A mix of accompanying programmes for infection control, community participation, including education, communication and information exchange, and private sector involvement are lessons learned for overcoming deterrents and sustaining progress towards elimination.

The contribution of vitamin A to public health.

Vitamin A deficiency among children in developing countries remains the leading cause of preventable severe visual impairment and blindness, and is a significant contributor to severe infections and death, particularly from diarrhea and measles. Vitamin A deficiency is also likely to increase vulnerability to other illnesses in both women and children, such as iron-deficiency anemia, and may be an important factor contributing to poor maternal performance during pregnancy and lactation and to growth deficits in children. Benefits to public health can be expected by improving the vitamin A status of deficient populations through an appropriate mix of acceptable, affordable, and available programs including promotion of breast-feeding, control of infections, dietary diversification, food fortification, and supplementation. Benefits include not only improved health and welfare for individuals and their families, but also improved chances of survival for an estimated 254 million children.

Disposition of gabapentin in anuric subjects on hemodialysis.

Gabapentin is an anticonvulsant drug, which in man is cleared solely by renal excretion and is not bound to plasma proteins. Because the clearance of gabapentin is dependent on renal function, the pharmacokinetics of gabapentin were investigated in anuric subjects maintained on hemodialysis. Plasma samples were obtained over an 8-day period after administration of single oral 400-mg doses of gabapentin. Pre- and post-dialyzer plasma samples and dialysate samples from quantitative collection of dialyzer effluent were obtained during hemodialysis sessions performed 2, 4, and 7 days after dosing. A mean (SD) maximum gabapentin plasma concentration of 6.0 (2.4) micrograms/mL was achieved at 4.7 (2.1) hours post-dose. The elimination half-life of gabapentin on non-hemodialysis days averaged 132 hours. Approximately 35% of the gabapentin dose was recovered in dialysate, and mean hemodialysis clearance of gabapentin was 142 (26) mL/min; approximately 93% of the dialyzer creatinine clearance. Gabapentin elimination half-life during hemodialysis was approximately 4 hours. Systemic plasma gabapentin concentrations increased approximately 30% during the first 2 hours after hemodialysis as a result of drug redistribution in the body. It is recommended that patients with end-stage renal disease maintained on hemodialysis receive an initial 300-mg to 400-mg gabapentin loading dose. Plasma gabapentin concentrations can be maintained by giving 200 to 300 mg of gabapentin after every 4 hours of hemodialysis.

Breast-milk vitamin A as an indicator of the vitamin A status of women and infants.

This article reviews the evidence for using breast-milk vitamin A as an indicator of vitamin A status and provides technical information for researchers who want to use this indicator to assess the vitamin A status of women and breast-fed children. Breast-milk vitamin A is a unique indicator for assessing the vitamin A status of lactating women and their breast-fed infants, and has recently been recommended by WHO for use in monitoring global elimination of vitamin A deficiency. Assessing breast-milk vitamin A is less invasive than alternative approaches for assessing a mother's vitamin A status and not at all invasive for her infant. Collection of milk samples in the field is generally feasible and acceptable. Breast-milk vitamin A appears to be an especially good indicator for measuring the impact of vitamin A interventions on women and infants, and for this purpose, it is more responsive than other indicators.

[Hypovitaminosis A: epidemiology of a public health problem and strategies of its prevention and control]. / Hipovitaminosis A: epidemiología de un problema de salud pública y estrategias para su prevención y control.

Vitamin A deficiency occurs when body stores are low enough to result in adverse health consequences, even though there is no clinical sign observable, a situation that exists in parts of Latin America and The Caribbean. Deficient populations can be identified by using a combination of biological and ecological indicators. Such populations generally live under conditions of economic, social and ecologic deprivation where young children and women in their reproductive years are most vulnerable, particularly during periods of seasonal food shortage and of peak infection incidence. Sustainable preventive strategies are those that support changes in diet and conditions at the household level that increase the intake of vitamin A-containing foods in quality and quantity by the vulnerable groups and decrease the frequency they suffer infections. The use of vitamin A supplements in areas lacking clinical deficiency, such as in Latin America and The Caribbean, should be carefully considered (perhaps by targeting to high-risk groups) so as not to deter efforts to reach permanent solutions.

Hypovitaminosis A: international programmatic issues.

The virtual elimination of vitamin A deficiency and all its consequences is high on the political agenda as a solvable public health problem by the end of the decade. Five to six times more children in the developing world are likely to be subclinically than clinically deficient. Subclinical deficiency can be detected by newer methodological approaches. Subclinically deficient children are at increased risk of severe and fatal infections. The problem at a population level is avoidable by the appropriate selection and application of a mix of available interventions. Countries are challenged to assess, analyze and take actions to incorporate nutrition concerns into development planning to attain end-of-decade goals.

PIP: This article is based on a presentation given at a nutritional symposium at the Experimental Biology '93 Conference. The author describes the worldwide problem of vitamin A deficiency. Children of developing countries are particularly affected and may develop keratomalacia. Keratomalacia remains the major cause of preventable childhood blindness in developing countries. In 1987 WHO identified 37 developing countries that exhibited an increased risk for eye disease because of a deficiency of vitamin A. Vitamin A deficient populations may be identified by classic xerophthalmia (clinical symptoms) or by using 1-2 biological measurements. No single biological measurement of a subclinical deficiency was considered best. Subclinical indicators might include: plasma and/or breast milk retinol levels, dose-response testing, and functional tests measuring night blindness and eye conjunctival impression cytology. Treatment is immediate and given in 3 doses of vitamin A at concentrations related to the child's age. Children 1 year old and older are given 200,000 international units (IU), infants aged 6-12 months are given 100,000 IU, and for those aged under 6 months 50,000 IU are recommended. Intervention efforts should be customized to fit the country. WHO recommends that any strategy include the following: public awareness, infectious disease control, improved agricultural and horticultural programs, nutritional and health education programs, breast feeding promotion, vitamin A supplemental programs, and world health leaders' conferences.

Was the "anti-infective" vitamin misnamed?

Meta-analyses on 6 of 12 studies of the effect of improvement of the vitamin A status of deficient children living in poverty and social and biological deprivation conclude that mortality reduction can be expected. The demonstrated effects on incidence, prevalence and severity of specific morbidities under these conditions have been variable.

Maternal vitamin A status and its importance in infancy and early childhood.

Early fetal vitamin A supplies must be regulated to avoid teratogenic consequences from too little or too much. Late in gestation, adequate maternal vitamin A status is important for newborn reserves and for sustaining adequate breast-milk concentrations. Vitamin A supplements are not needed for most pregnant women in Western countries who consume the recommended dietary allowance during their reproductive years. Increased consumption of vitamin A-rich foods can meet increased needs during lactation. Women in developing countries whose habitual intakes are near basal needs should receive an additional 100 micrograms retinol equivalents (RE) during pregnancy and 300 micrograms RE during lactation. Supplements not above 3000 micrograms RE (10,000 IU) daily are safe for fertile women where circumstances preclude obtaining the needed increment through diet. The first postpartum month is the only safe period during which to provide deficient lactating women with a single high-dose supplement to benefit the mother and breast-feeding infant for several months.

The role of vitamin A in child growth, development and survival.

Vitamin A is essential for growth, development and survival. For children in deprived settings an adequate vitamin A status may be more critical to survival protection than to growth and development. During infancy breast milk from malnourished mothers is protective against the development of xerophthalmia; it needs to be complemented after six months by other dietary sources of vitamin A to provide full health protection. Correcting the low vitamin A content of breast milk from malnourished mothers within the first four weeks of delivery by a high dose oral vitamin A supplement can be an effective short-term preventive strategy while efforts are made to improve the dietary intake for the long-term solution.