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Micronutrient status during pregnancy and outcomes for newborn infants in developing countries.

More than 9 million neonatal deaths occur each year, 98% of them in developing countries. Neonatal deaths account for two-thirds of deaths in infancy and 40% of deaths before age 5 y. The major direct causes of neonatal death are infections, preterm delivery and asphyxia. Important indirect causes include low birth weight and hypothermia. The present body of work on multiple micronutrient interventions is not sufficient for us to draw conclusions on their effects on neonatal well-being. Because studies have generally concentrated on single micronutrients and a range of outcomes, this paper reviews the findings for individual nutrients and then summarizes the situation. The evidence for the contribution of micronutrient deficiencies to perinatal mortality and duration of gestation is limited, and the evidence base for individual micronutrient effects on neonatal mortality and morbidity is patchy. To translate knowledge into policy, community evaluations of effect and an expanded evidence base that includes affordability, acceptability and scalability are also required. A balance between supply-side and demand-side interventions must be struck, with an emphasis on effect and sustainability. Among the key requirements are randomized, controlled community effectiveness trials of the effect of micronutrient supplementation in pregnancy on perinatal mortality and neurodevelopment, studies on improving adherence and studies on the relation between micronutrient deficiencies and sepsis and neonatal encephalopathy. It would also be helpful to look at mechanisms for bringing the periconceptional period within the ambit of trials.

Developing Countries↗

Adequate dosing of micronutrients for different age groups in the life cycle.

Many studies of micronutrient supplementation in developing countries have used single-nutrient supplements with either vitamins or minerals. However, people in these countries often suffer from multiple, rather than single, micronutrient deficiencies. The objective of this paper is to discuss the factors that go into determining the adequate dosing of vitamins and/or minerals for people of different ages. To elaborate on the adequacy of micronutrient doses in supplements, a model described by the US FNB was used, which calculates the difference between the mean observed intake for an individual and the estimated average requirement for a life stage and gender group. This model allows estimating the degree of confidence that a certain nutrient intake (from supplements and diet) is adequate. The US/Canadian DRI values have been used as the basis for these calculations, from which it can be concluded that a daily supplement of one RDA of each micronutrient is adequate to cover the personal requirements of all individuals in each respective age and gender group of the population, provided that 20 to 40% of an RDA is supplied by the diet--likely a realistic value for developing countries. DRI values vary significantly between different age groups, reflecting changing needs over a life cycle. With the objective of a supplement to be adequate and safe, the design of a one-for-all supplement covering all age groups is not realistic. Such a supplement would either underscore or surpass the required intake of some of the age groups. Additionally the dosage of certain micronutrients might exceed the upper level of intake for lower age groups. Therefore, it is suggested that three different supplements following the one RDA concept for all micronutrients be developed for research use in developing countries for the following age groups; 1 to 3 years, 4 to 13 years, and females > 14 years (excluding during pregnancy).

Adolescent↗

Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi.

BACKGROUND: Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis. METHODS: In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, alpha-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting. RESULTS: Body mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 micromol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Wasting, defined as BMI<18.5 was present in 59% of study participants and was independently associated with a higher risk of low carotenoids, and vitamin A and selenium deficiency. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids. CONCLUSIONS: These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.

AIDS-Related Opportunistic Infections↗

Effect of micronutrient supplementation on linear growth of children.

This review summarizes the results of published, randomized clinical trials that have examined the impact of administration of micronutrients, singly or in combination to infants, preschool and school children on linear growth. Supplementation of single micronutrients resulted in small or no benefits on linear growth. A meta-analysis of zinc supplementation trials confirmed that zinc has a significant but small impact (0.22 sd units) on length gain in children 0-13 years of age. However, a recent study reported a substantially greater benefit (>1 sd) in stunted and non-stunted breast-fed infants 6-12 months of age. With iron supplementation, a beneficial effect was found only in anemic children. Vitamin A supplementation trials have reported little or no benefit on linear growth. Data currently available suggest some impact in children with clinical or biochemical vitamin A deficiency, but this issue needs confirmation. Few studies could be identified where a combination of micronutrients was given as a supplement or as fortified food; in the latter set of studies energy availability was assured. The impact on length without multiple micronutrient supplementation was no greater than that observed with single micronutrients. In conclusion, zinc and iron seem to have a modest effect on linear growth in deficient populations. Vitamin A is unlikely to have an important effect on linear growth. Limited available evidence does not allow us to conclude whether a combination of micronutrients, with or without additional food, would have a greater impact than that seen with zinc alone.

Child↗

Micronutrient antioxidant intake in patients with chronic pancreatitis.

Increased oxidative stress has been postulated to be an important mechanism in the pathophysiology of chronic pancreatitis (CP). Micronutrient deficiency may increase the oxidative stress as they assist in free radical clearance. The present study was undertaken to assess the intake of micronutrients, i.e. vitamins E and C, carotene, selenium, copper, zinc, manganese, magnesium, sulphur, riboflavin, methionine and choline in patients with CP. All consecutive patients with CP attending the Pancreas Clinic at the All India Institute of Medical Sciences were enrolled in the study. The usual dietary intake was estimated by the 24-hour dietary recall method and food frequency questionnaire. Dietary restrictions, if any, were also noted. The micronutrient intake of patients not on any nutritional supplements (n=75, 65 males and 10 females, mean age 31.06 +/- 10.64 years) was compared with age- and sex- matched healthy controls (n=75). The micronutrients were calculated as per the Nutritive value of Indian Foods given by the National Institute of Nutrition, Indian Council of Medical Research, India and the US dietary intake guidelines as applicable. It was found that the Body Mass Index (BMI) of patients was significantly lower than that of healthy controls. The total intake in terms of calorie was lower in patients when compared to controls. The dietary intake of vitamin E, riboflavin, choline, magnesium, copper manganese and sulfur was significantly lower than that of controls as well as the Recommended Dietary Allowance (RDA). Dietary intake of selenium and vitamin C was within the limits of the RDA but was lower than that of controls, while the intake of carotene was similar in both the groups and met the RDA. We conclude that patients with CP had significantly decreased micronutrient intake owing to diet modification due to pain. Micronutrient deficiency might contribute to increased oxidative stress in these patients.

Adult↗

[What is known about micronutrients in Mexico].

OBJECTIVE: To update the information on micronutrients in Mexico regarding: 1. The research lines according to priority of the micronutrient, subjects affected, and its focus (basic, clinical, epidemiological, operational). 2. The laboratory capacity available for micronutrient assays. MATERIAL AND METHODS: We analyzed review articles of what has been published on micronutrients in Mexico since 1950. We also gathered information by questionnaire from the 16 research groups working in Mexico in the area of micronutrients. RESULTS: We generated tables summarizing the situation of the six micronutrients which we identified as the most problematic in Mexico (vitamins A and C, and iron, iodine, zinc and calcium). CONCLUSIONS: We reached 10 conclusions related to populations of study, research line priorities, and desirable operational studies.

Adult↗

Micronutrient status in patients receiving home parenteral nutrition.

Administration of home parenteral nutrition (HPN) to patients with intestinal failure requires attention to caloric content of feeds, fluid, electrolyte balance, and micronutrient status. Peripheral blood estimations of vitamins and trace elements may be abnormal, but their clinical significance in relation to deficiency or toxicity states is not always clear. We sought to determine the incidence and nature of clinical micronutrient abnormality in our HPN program. Clinical assessment and case record review of 49 patients actively receiving HPN was undertaken, and, in 32 of these patients, serum micronutrient levels were assayed. Clinical evidence of micronutrient deficiency was identified in 16 patients (33%). Iron deficiency anemia occurred in 14 patients which resolved after iron supplementation in all except 1 patient who had persistent intestinal blood loss. Anemia was precipitated in six patients by identifiable clinical events (acute gastrointestinal disease in five and menorrhagia in one), and in two others folate deficiency coexisted. Biotin deficiency developed in three patients, manifested by dry eyes and angular cheilitis or hair loss. Vitamin A deficiency resulting in visual disturbance developed in one patient who was not receiving multivitamin supplements at that time. Serum levels of zinc, copper, selenium, manganese, vitamin A, and vitamin E were measured in 32 patients. No patient had normal levels of all six micronutrients. Nevertheless, there was no clinical evidence of toxicity or deficiency in any of these patients at the time assays were performed. In conclusion, abnormalities of micronutrient status are common in HPN patients, but serious sequelae appear to be unusual.

Adult↗

Dietary intake and micronutrient status of adolescents: effect of vitamin and trace element supplementation on indices of status and performance in tests of verbal and non-verbal intelligence.

Relationships between micronutrient intake and status, and micronutrient status and performance in tests of intelligence were investigated in a group of adolescents (13-14 years old). Dietary intakes were assessed using a 7 d weighed dietary record method, coupled with the collection of duplicate diets. Vitamin and trace mineral intakes calculated using food composition tables were compared with those obtained by direct analysis of duplicate diets. Micronutrient status was judged via a range of biochemical indices measured in blood samples taken after a 12-15 h fast. Blood samples were taken both before and after a 16-week period of vitamin and trace mineral supplementation. Individual tests of verbal and nonverbal intelligence were also performed pre- and post-supplementation. The results of this study indicate that the use of food table data may lead to substantial over- or underestimation of the intake of several micronutrients. In general, the total calculated or analysed amount of a specific micronutrient consumed did not adequately predict status, as judged by a range of biochemical indices. There were significant changes in status measurements over the 16-week study period, irrespective of supplementation, and these changes were markedly influenced by the initial status of the subject. There was no effect of supplementation on performance in tests of intelligence. However, there was a significant association between plasma ascorbic acid and initial non-verbal intelligence quotient (IQ) in the boys, and between whole blood glutathione peroxidase (EC 1.11.1.9) activity and non-verbal and verbal IQ in both sexes. These findings are discussed in relation to other recent studies of the influence of micronutrient supplementation on the psychological performance of children.

Adolescent↗

Micronutrients and cancer aetiology: the epidemiological evidence.

Micronutrient deficiencies occur most commonly in poor countries and, therefore, are most likely to be associated with cancers common in these countries. Epidemiological studies are hampered by inaccurate measurement of micronutrient intake and by the correlations between intakes of many nutrients. The strongest evidence for a protective effect of micronutrients is for oesophageal cancer. The identity of the micronutrients is not certain, but may include retinol, riboflavin, ascorbic acid and Zn; alcohol, smoking and dietary nitrosamines increase the risk for oesophageal cancer. For stomach cancer there is good evidence that fruit and vegetables are protective. The protective effect of these foods might be largely due to ascorbic acid, but other nutrients and non-nutrients may also be important; the risk for stomach cancer is increased by salt, some types of preserved foods, and by infection of the stomach with the bacterium Helicobacter pylori. The risk for lung cancer appears to be reduced by a high intake of fruit and vegetables, but it is not clear which agents are responsible and the major cause of lung cancer is cigarette smoking. Diet is probably the major determinant of the risk for colo-rectal cancer; there is evidence that fruit and vegetables and fibre reduce risk and that meat and animal fat increase risk, but there is no convincing evidence that these relationships are mediated by micronutrients. The risk for cervical cancer is inversely related to fruit and vegetable consumption and, therefore, to consumption of carotenoids and ascorbic acid, but the major cause of this cancer is human papillomavirus and it is not yet clear whether the dietary associations indicate a true protective effect or whether they are due to confounding by other variables. The evidence that micronutrients are important in the aetiology of either breast cancer or prostate cancer is weak, but the possible roles of 1,25-dihydroxycholecalciferol and alpha-tocopherol in prostate cancer require further study.

Diet↗

Micronutrients in women's reproductive health: II. Minerals and trace elements.

It is widely accepted that micronutrients have a major function in many periods of women's life, particularly during pregnancy and lactation. Inadequate stores or intake of micronutrients might have adverse effects both to the mother (hypertension, anemia, complications of labor) and the fetus (congenital malformations, pre-term delivery, intrauterine growth retardation). The effect of improper nutrition is influenced by gestational age, severity of deficiency, or both. Generally, the daily requirements in minerals and trace elements are easily met in women having a balanced diet. Such diet during pregnancy should provide the recommended daily allowance of all nutrients except elemental iron. Consequently, deficiency states are supposed to be rare in developed countries, and supplementation should be made on an individual basis. On the other hand, nutritional deficiencies during pregnancy might be difficult to detect. Studies from developing countries where micronutrient malnutrition is common during pregnancy gave us strong evidence that supplementation of certain trace elements and minerals could prevent some of the most severe adverse pregnancy outcomes. While some micronutrients have been studied extensively (e.g. calcium, iron, zinc, iodine), much less is known about others. It has been shown that multiple micronutrient deficiencies, rather than single deficiencies, are common. Our knowledge about the significance of interactions between micronutrients in relation to pregnancy outcome is limited. The role of these interactions in improving pregnancy outcome need to be investigated more precisely. According to the summarized data, the potential benefits of routine supplementation seem to outweigh any potential adverse reaction that can be attributed to their consumption.

Adult↗

Micronutrients and their supplementation in chronic cardiac failure. An update beyond theoretical perspectives.

Physicians' use of micronutrients to improve symptoms or outcomes in chronic illness has until recently been guided by limited data on the actions of individual agents in vitro or in animal studies. However several recently published clinical trials have provided information about which groups of patients are likely to benefit from which combination of micronutrients. Patients with chronic cardiac failure (CCF), particularly elderly individuals, have several reasons to be deficient in micronutrients including reduced intake, impaired gastrointestinal absorption and increased losses on the background of increased utilisation due for example to increased oxidative stress. Studies of nutritional supplementation in CCF patients have usually concentrated on specific agents. However given that many micronutrients have synergistic influences upon metabolic processes this strategy might merely lead to a shifting of a limiting step. Rather, a strategy of increasing the availability of multiple agents at once might be more logical. The aim of this article is to briefly review the experimental rationale for each of the micronutrients of potential benefit in chronic heart failure and examine the current clinical trial evidence supporting their use.

Animals↗

Effect of micronutrient supplement on health and nutritional status of schoolchildren: mental function.

OBJECTIVE: We evaluated the effect of a micronutrient-fortified beverage on mental function in schoolchildren. METHODS: This double-blind, placebo-controlled, matched-pair, cluster, randomized feeding trial assessed baseline before supplementation and after 14 mo in a cohort of 608 children aged 6 to 15 y who received a micronutrient-fortified beverage or placebo. Children in two classes (clusters) in each of nine grades were assessed for intelligence, attention and concentration, memory, and school achievement. RESULTS: Mean intelligence quotient scores of the micronutrient-fortified beverage group and the placebo group at baseline and final follow-up were not significantly different. Mean verbal and performance scores and increments were also not different. After supplementation, attention-concentration increment scores of the micronutrient group were significantly higher (P < 0.05) than those of the placebo group. Mean and incremental scores of the supplemented group on the memory scale were not significantly different from those of the placebo group. CONCLUSIONS: Supplementation with a beverage fortified with a range of micronutrients significantly improved attention-concentration over 14 mo, but not intelligence quotient, memory, or school achievement among middle-income schoolchildren.

Adolescent↗

Parental influences on young girls' fruit and vegetable, micronutrient, and fat intakes.

OBJECTIVE: To evaluate parents' fruit and vegetable intake and their use of pressure to eat in child feeding as predictors of their 5-year-old daughters' fruit and vegetable, micronutrient, and fat intakes. SUBJECTS: Data were obtained from 191 non-Hispanic white families with 5-year-old girls. DESIGN: Parent data included reports of pressure in child feeding and their own fruit and vegetable intake. Girls' intakes of fruits and vegetables, selected micronutrients, and fat were the main outcomes of interest. STATISTICAL ANALYSIS: Structural equation modeling was used to test a model describing relationships among parents' fruit and vegetable intake, parents' use of pressure in child feeding, and daughters' fruit and vegetable, micronutrient, and fat intakes. RESULTS: The model provided a good fit to the data, revealing that girls' fruit and vegetable intake was positively related to their parents' reported fruit and vegetable intake. Parents who consumed fewer fruits and vegetables tended to report greater pressure in child feeding and had daughters who consumed fewer fruits and vegetables. Girls' reported fruit and vegetable intakes were positively related to their micronutrient intakes and negatively associated with fat intake. APPLICATIONS/CONCLUSIONS: This research demonstrates that parents' own fruit and vegetable intake may encourage fruit and vegetable intake in their daughters, leading to higher micronutrient intakes and lower dietary fat intakes. Conversely, pressure to eat may discourage fruit and vegetable intake among young girls.

Child Nutritional Physiological Phenomena↗

DNA damage from micronutrient deficiencies is likely to be a major cause of cancer.

A deficiency of any of the micronutrients: folic acid, Vitamin B12, Vitamin B6, niacin, Vitamin C, Vitamin E, iron, or zinc, mimics radiation in damaging DNA by causing single- and double-strand breaks, oxidative lesions, or both. For example, the percentage of the US population that has a low intake (<50% of the RDA) for each of these eight micronutrients ranges from 2 to >20%. A level of folate deficiency causing chromosome breaks was present in approximately 10% of the US population, and in a much higher percentage of the poor. Folate deficiency causes extensive incorporation of uracil into human DNA (4 million/cell), leading to chromosomal breaks. This mechanism is the likely cause of the increased colon cancer risk associated with low folate intake. Some evidence, and mechanistic considerations, suggest that Vitamin B12 (14% US elderly) and B6 (10% of US) deficiencies also cause high uracil and chromosome breaks. Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables (five portions a day is advised) has about double the cancer rate for most types of cancer when compared to the quarter with the highest intake. For example, 80% of American children and adolescents and 68% of adults do not eat five portions a day. Common micronutrient deficiencies are likely to damage DNA by the same mechanism as radiation and many chemicals, appear to be orders of magnitude more important, and should be compared for perspective. Remedying micronutrient deficiencies should lead to a major improvement in health and an increase in longevity at low cost.

DNA↗

Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs).

Diet as a key factor in determining genomic stability is more important than previously imagined because we now know that it impacts on all relevant pathways, namely exposure to dietary carcinogens, activation/detoxification of carcinogens, DNA repair, DNA synthesis and apoptosis. Current recommended dietary allowances for vitamins and minerals are based largely on the prevention of diseases of deficiency such as scurvy in the case of vitamin C. Because diseases of development, degenerative disease and aging itself are partly caused by damage to DNA it seems logical that we should focus better our attention on defining optimal requirements of key minerals and vitamins for preventing damage to both nuclear and mitochondrial DNA. To date, our knowledge on optimal micronutrient levels for genomic stability is scanty and disorganised. However, there is already sufficient evidence to suggest that marginal deficiencies in folate, vitamin B12, niacin and zinc impact significantly on spontaneous chromosome damage rate. The recent data for folate and vitamin B12 in humans with respect to micronucleus formation in blood and epithelial cells provide compelling evidence of the important role of these micronutrients in maintenance of genome integrity and the need to revise current RDAs for these micronutrients based on minimisation of DNA damage. Appropriately designed in vitro studies and in vivo placebo controlled trials with dose responses using a complementary array of DNA damage biomarkers are required to define recommended dietary allowances for genomic stability. Furthermore these studies would have to be targeted to individuals with common genetic polymorphisms that alter the bioavailability of specific micronutrients and the affinity of specific key enzymes involved in DNA metabolism for their micronutrient co-factor. That there is a need for an international collaborative effort to establish RDAs for genomic stability is self-evident.

DNA Damage↗

Micronutrients: highlights and research challenges from the 1994-5 National Diet and Nutrition Survey of people aged 65 years and over.

The aims of the National Diet and Nutrition Survey series are summarized, and the new National Diet and Nutrition Survey of people aged 65 years and over is explored, with particular emphasis on micronutrient intakes and status indices. Mean nutrient intakes were generally satisfactory for most micronutrients, but intakes of vitamin D, Mg, K and Cu were low. Intakes of vitamin D were far below the reference nutrient intake for people aged 65 years and over, and there was also biochemical evidence of vitamin D deficiency, for 8% of free-living and 37% of institution participants, attributed partly to limited exposure to sunlight. A substantial proportion of people living in institutions had inadequate biochemical status indices, notably for vitamin C, Fe and folate. Relationships between intake and status were close for vitamins. Mineral intakes did not correlate well with currently used status indices. Some intakes and indices, especially those of vitamin C, carotenoids, Na and K, were strongly correlated with socio-economic status and with north-south gradients in Britain. Future research challenges should address the functional and health significance of low intakes and sub-optimal biochemical indices for certain micronutrients, especially for people living in institutions; the shortcomings of mineral status indices especially as indicators of mineral intake; the social and geographical inequalities of micronutrient intakes and status, and why micronutrient status deteriorates with increasing age. The answers to these questions will help to define the characteristics of nutritional risk for older people in Britain, and to clarify future needs for education and intervention.

Aged↗

Micronutrients in cancer chemoprevention.

The selection of micronutrients, defined as essential and nonessential dietary components consumed in minute quantities, for testing in clinical chemoprevention trials is based on the totality of evidence arising from epidemiologic, in vitro, animal, and clinical studies. Those micronutrients that surface with chemopreventive potential, in terms of high efficacy and low toxicity, in early-phase clinical studies are then candidates for large-scale, randomized clinical chemoprevention trials with cancer endpoints. Micronutrients currently being examined in National Cancer Institute (NCI)-sponsored phase I, II, or III chemoprevention trials for prostate, breast, and colon cancers include isoflavones, lycopene, selenized yeast, selenomethionine, selenium, vitamin E, perillyl alcohol, folic acid, vitamin D, calcium, and curcumin. The response to micronutrients may vary not only in magnitude but also in direction. This variation and response likely depend on individual genetic polymorphisms and/or interactions among dietary components that influence absorption, metabolism, or site of action. Research priorities include investigation of possible molecular targets for micronutrients and whether genetic and epigenetic events dictate direction and magnitude of the response.

Animals↗

Caries and micronutrient intake among urban South African children: a cohort study.

OBJECTIVE: To report on associations between caries and micronutrient intake among a 'true cohort' group of 5-year-old urban black South African children. METHODS: The study sample was a true cohort that had nutrition as well as dental information for 1991 and 1995 (n = 259). Micronutrient intake and dental caries associations were examined with SAS using the linear logistic analysis and a critical level of statistical significance of P < 0.05. RESULTS: Of the 21 micronutrients investigated, vitamin B12, riboflavin, magnesium and biotin were individually significantly associated with caries incidence, but taken together only magnesium was significant. CONCLUSIONS: The association of micronutrient intake with caries was weak, isolated and not clinically relevant. Micronutrient intake was not an indicator of the presence or absence of caries among the children studied.

Biotin↗