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The role of antioxidant micronutrients in the prevention of diabetic complications.

Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake.

Antioxidants↗

Helicobacter pylori infection and micronutrient deficiencies.

It is known that deficiencies of micronutrients due to infections increase morbidity and mortality. This phenomenon depicts itself conspicuously in developing countries. Deficiencies of iron, vitamins A, E, C, B12, etc are widely prevalent among populations living in the third world countries. Helicobacter pylori (H pylori) infection has a high prevalence throughout the world. Deficiencies of several micronutrients due to H pylori infection may be concomitantly present and vary from subtle sub-clinical states to severe clinical disorders. These essential trace elements/micronutrients are involved in host defense mechanisms, maintaining epithelial cell integrity, glycoprotein synthesis, transport mechanisms, myocardial contractility, brain development, cholesterol and glucose metabolism. In this paper H pylori infection in associated with various micronutrients deficiencies is briefly reviewed.

Avitaminosis↗

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.

Anemia, Iron-Deficiency↗

Micronutrient malnutrition--present status and future remedies.

Micronutrient deficiency is a serious public health concern in most of the developing countries which leads to malnutrition syndromes. The micronutient deficiencies which are of greatest public health significance include iron deficiency, vitamin A deficiency and iodine deficiency disorder. National Pilot Programme on Control of Micronutrient Malnutrition was launched in 1995 and the department of biochemistry and nutrition of the All India Institute of Hygiene and Public Health, Calcutta was entrusted to co-ordinate the activities. It presently covers five eastern and north-eastern states. Baseline situation analysis was conducted mainly on iron deficiency anaemia, iodine deficiency disorder and vitamin A deficiency. Comparing with WHO cut off figures, point prevalence of anaemia in various age groups was found to be high. Bitot's spot was mainly noted in the age group of 6-71 months. Nightblindness was found in the children of the age group of 24-71 months. High prevalence of nightblindness in pregnant women is a point of concern. Action needed to control micronutrient deficiency includes: Intervention strategies, extensive nutrition and health education, to support the problem specific programmes, to stregthen various state government programmes and strengthen role of NGOs.

Adult↗

Micronutrients: oxidant/antioxidant status.

Potentially damaging species (reactive oxygen, nitrogen and chlorine species) arise as by-products of metabolism and as physiological mediators and signalling molecules. Levels of these species are controlled by the antioxidant defence system. Several components of this system are micronutrients (e.g. vitamins C and E) or are dependent upon dietary micronutrients (e.g. CuZn and Mn superoxide dismutase). The antioxidant defences act as a coordinated system where deficiencies in one component may affect the efficiency of the others. Oxidative stress may be an important factor in infection if micronutrients are deficient.

Antioxidants↗

Prevalence of micronutrient deficiency particularly of iron, zinc and folic acid in pregnant women in South East Asia.

Micronutrient deficiency, whether clinical or subclinical, may affect growth, cognition and reproductive performance. In pregnant women moderate to severe deficiencies of iron, zinc and folic acid have been shown to increase risk of low birth weight, pregnancy complications and birth defects. Any attempt to introduce a micronutrient supplementation programme during pregnancy must be based on adequate data on the prevalence of micronutrient deficiencies, their adverse effects and the potential for reversing these through supplementation. This paper reviews parameters for assessment of iron, zinc and folic acid deficiencies in pregnancy and the available data on prevalence of these in pregnant women in South Asia. Iron deficiency and anemia affect 50 % or more of pregnant women, the prevalence of folic acid deficiency may be up to 30-50 % and there is evidence to suggest that zinc deficiency is likely to be widespread but supportive data are scarce.

Anemia, Iron-Deficiency↗

Dietary intake of some essential micronutrients in China.

OBJECTIVE: Based on the data collected in the 1992 national nutrition survey in China, the food consumption and nutrients intake were calculated, and the consumption of some micronutrients was evaluated. METHOD: Dietary data were obtained by using a three days' inventory change plus food weighing in combination with 24 hours recall method for three consecutive days. The food consumption and nutrients intake were calculated in accordance with the Chinese food composition table. The consumption of some micronutrients was evaluated in reference to the Chinese RDAs. RESULTS: The average intakes of niacin, ascorbic acid and vitamin E were sufficient, whereas that of zinc, selenium and thiamin were between 80% and 90% RDAs. The consumption of calcium, retinol equivalent and riboflavin was low compared with the Chinese RDAs. Calcium was the most insufficient nutrient in Chinese diet. CONCLUSION: Food fortification seems necessary for improving the nutritional status of some micronutrients in China.

Adolescent↗

Alcohol consumption and the risk of colorectal cancer at low levels of micronutrient intake.

BACKGROUND: The purpose of our study was to assess the relationship between simultaneous exposure to alcohol and consumption of micronutrients that may have protective properties against colorectal cancer. MATERIAL/METHODS: This hospital-based case-control study of colorectal cancer was carried out between January 1998 and November 1999 in Cracow, Poland. A total of 180 cases of colorectal cancer confirmed by histopathology were recruited from the University Hospital in Cracow. An equal number of controls, individually matched by gender and age (+/- 5 years) were chosen from among patients from the same hospital with no history of cancer. An interviewer-administered food frequency questionnaire covering 148 food items, including the quantity consumed, was used to assess the typical dietary pattern. RESULTS: When the analysis was carried out on quartile intake data, a consistent inverse association was confirmed between the intake of retinol, thiamine or antioxidant micronutrients (carotene, vitamin C and E) and the occurrence of colorectal cancer. Alcohol intake appeared to be an important risk factor for this cancer site, and the risk increased with the amount of pure alcohol intake. The group with deficient intake of retinol, carotene, and vitamins C and E, but with higher consumption of alcohol, incur a noticeably high risk of colorectal cancer (OR=6.79; 95%CI: 2.08-22.18). CONCLUSIONS: The data support the hypothesis that higher consumption of alcohol, when combined with low micronutrient intake, may considerably increase the risk of colorectal cancer.

Adult↗

[Relation among micronutrient intakes with CD4 count in HIV infected patients].

INTRODUCTION: The impact of micronutrients on HIV disease progression has been an area of great interest. Several studies have shown an association between disease progression and micronutrient status. The aim of our study was to assess the correlation between micronutrients intakes and immune status in HIV infected patients. MATERIAL AND METHODS: A total of 119 patients were evaluated. Nobody dropped out. In all patients the following parameters were assessed; age, sex, treatment with anti-retroviral drugs, performed an anthropometric evaluation (weight, tricipital skinfold, midarm circumference, and body mass index (BMI)) and a biochemical evaluation (glucose, albumin, prealbumin, transferrin, total proteins, limphocytes and count of CD4). All patients received instruction in 24-hour written food record keeping. RESULTS: Patients had an average age 37.9 +/- 9.9 years, weight 64.5 +/- 13.2 kg and body mass index 22.5 +/- 3.5. Levels of total proteins, albumin, prealbumin y transferrin were normal. Percentile distribution of anthropometric parameters showed a deep depletion in muscular protein compartiment, 53.1% of patients had tricipital skinfold under P 50, 91.8% had midarm muscle circumference under P 50. The correlation analysis among dietary intake and immune status, showed a positive association among vitamin A intake and vitamin D with CD4+ (r = 0.35; p < 0.01) and (r = 0.51; p < 0.001), respectively. In the multivariant analysis with dependent variable (CD4 count), only vitamin D remained in the model (F = 16.99; p < 0.001), with an increase of 34 (CI 95%: 5.81-167.3) CD4+ (count/uL) with each microgram of vitamin D intake, adjusted by age, sex, energy and protein intake, and anti-retroviral drugs. CONCLUSION: Vitamin A, and D intakes were correlated with CD4 count, only vitamin D remained as a independent predictor parameter in a in multivariant model.

Adult↗

The role of nutrition and micronutrients in paediatric HIV infection.

It has been postulated that micronutrients play a role in the pathogenesis of HIV disease. Though data are sparse, there is evidence that HIV-infected adults and children have a range of micronutrient deficiencies with increasing severity in advanced disease and in the presence of malnutrition. It appears that micronutrient deficiencies contribute to immune dysfunction, infectious morbidity and disease progression. Limited interventive studies suggest that vitamin and mineral supplementation is beneficial to HIV-infected adults and children; however, current, regimens are not evidence-based and there are no randomised controlled trials in children. There are a number of African studies under way addressing these issues.

Child↗

Cigarette smoking, alcohol use and adverse pregnancy outcomes: implications for micronutrient supplementation.

This literature review examines whether smoking or alcohol use during pregnancy increases maternal micronutrient requirements and whether smoking or alcohol use interacts with micronutrient deficiencies to affect pregnancy outcomes. Studies suggest that vitamin C requirements increase for pregnant smokers. Studies also indicate that beta-carotene, vitamin B-12, vitamin B-6 and folate concentrations appear lower in pregnant smokers than in pregnant nonsmokers, although it is unclear whether lower serum concentrations are due to increased requirements, lower dietary or supplement intakes or other factors. Experimental animal studies suggest that iron supplementation partially ameliorates impaired fetal growth caused by cadmium, a heavy metal inhaled from cigarette smoke, but studies in humans have not substantiated cadmium's effect on fetal growth. Animal studies also suggest chronic alcohol consumption at levels of 20-50% of energy intake during pregnancy may mobilize fetal vitamin A concentration from the liver and result in increases in vitamin A in fetal organs and subsequent defects. Evidence is lacking, however, on whether zinc metabolism is altered by alcohol intake during pregnancy. Health care practitioners should consider increasing nutrient levels in pregnant women who do not meet the Recommended Dietary Allowances through their diet. Future studies that examine the nutrient levels of women exposed to cigarette smoke and alcohol should control for dietary intake. In addition, randomized controlled studies of the health impact of micronutrient supplementation in pregnant women should consider stratification by exposure to cigarette smoke and alcohol use.

Alcohol Drinking↗

Micronutrients and its correlation with mental performance among schoolchildren in Bario, Sarawak: a preliminary study.

Children who are born in a community with insufficient micronutrients, particularly iodine in remote rural areas are associated with low intellectual functions and mental retardation. The aim of this cross-sectional study is to determine the mental performance of the schoolchildren in Bario, a highland settlement of the Kelabit people in the district of Baram, Sarawak and to determine its correlation with the availability of iodine in the environment, as well as other micronutrients such as selenium, copper and manganese. A total of 25 schoolchildren in Bario age ranging from 7 to 12 years old participated in the study. Mental performance of the schoolchildren were tested using TONI-2 (Test of Nonverbal Intelligence--second edition), a cognitive ability measures with a response format which eliminates language and reduces motoric and cultural factors. The iodine levels from several wells, soils and salt found in Bario were determined using HPLC (software version 3.05.01) whilst serum levels of selenium, copper and manganese were measured using Graphite Furnace Atomic Absorption Spectrophotometer (GFAAS). The results showed that the median and mode scores of intelligence quotient for Bario were 82 and 75, respectively, whilst median and mode scores of intelligence percentile were 11.0 and 5.0, respectively. The maximum score achieved were at the average level with the quotient score between 90-110. It was found that salt produced from one of the wells in Bario contained high quantity of iodine. Based on standards established by the Trace Elements Laboratory, Roben Institute, University of Surrey, United Kingdom, schoolchildren in Bario are having sufficient blood levels of copper and a high selenium and manganese levels. Despite the remoteness of the study area, the schoolchildren in Bario, Sarawak showed higher mental performance compared to other isolated areas. This is probably correlated with the high micronutrients availability, particularly iodine, found naturally in Bario.

Child↗

Chronic heart failure and multiple micronutrient supplementation: realistic hope or idealistic conjecture?

Recent studies have demonstrated the inefficacy of nutritional supplements containing various combinations of vitamins and minerals for otherwise healthy elderly people and patients with ischemic heart disease. However, patients with chronic heart failure (CHF) have, up until recently, been excluded from such studies. CHF has a high mortality and morbidity and patients are often elderly with poor general nutrition and high levels of micronutrient deficiency. It is in this population that nutritional supplementation has the most potential benefit. Evidence is accumulating that a strategy of long-term highdose multiple micronutrient supplementation might improve symptoms and cardiac function in elderly patients with CHF. In this article, we review the effects of individual micronutrients and how they might impact on CHF, and present recent data that dietary supplementation might offer an addition to standard therapy for CHF.

Dietary Supplements↗

Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients.

The objective of this update is to give an overview of the effects of dietary nutrients on the structure and certain functions of the brain. As any other organ, the brain is elaborated from substances present in the diet (sometimes exclusively, for vitamins, minerals, essential amino-acids and essential fatty acids, including omega- 3 polyunsaturated fatty acids). However, for long it was not fully accepted that food can have an influence on brain structure, and thus on its function, including cognitive and intellectuals. In fact, most micronutrients (vitamins and trace-elements) have been directly evaluated in the setting of cerebral functioning. For instance, to produce energy, the use of glucose by nervous tissue implies the presence of vitamin B1; this vitamin modulates cognitive performance, especially in the elderly. Vitamin B9 preserves brain during its development and memory during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters. Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), provided it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin improves cerebral and cognitive functions in the elderly; it frequently improves the functioning of factors related to the frontal lobe, as well as the language function of those with cognitive disorders. Adolescents who have a borderline level of vitamin B12 develop signs of cognitive changes. In the brain, the nerve endings contain the highest concentrations of vitamin C in the human body (after the suprarenal glands). Vitamin D (or certain of its analogues) could be of interest in the prevention of various aspects of neurodegenerative or neuroimmune diseases. Among the various vitamin E components (tocopherols and tocotrienols), only alpha-tocopherol is actively uptaken by the brain and is directly involved in nervous membranes protection. Even vitamin K has been involved in nervous tissue biochemistry. Iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxidase), and for the synthesis of neurotransmitters and myelin; iron deficiency is found in children with attention-deficit/hyperactivity disorder. Iron concentrations in the umbilical artery are critical during the development of the foetus, and in relation with the IQ in the child; infantile anaemia with its associated iron deficiency is linked to perturbation of the development of cognitive functions. Iron deficiency anaemia is common, particularly in women, and is associated, for instance, with apathy, depression and rapid fatigue when exercising. Lithium importance, at least in psychiatry, is known for a long time. Magnesium plays important roles in all the major metabolisms: in oxidation-reduction and in ionic regulation, among others. Zinc participates among others in the perception of taste. An unbalanced copper metabolism homeostasis (due to dietary deficiency) could be linked to Alzheimer disease. The iodine provided by the thyroid hormone ensures the energy metabolism of the cerebral cells; the dietary reduction of iodine during pregnancy induces severe cerebral dysfunction, actually leading to cretinism. Among many mechanisms, manganese, copper, and zinc participate in enzymatic mechanisms that protect against free radicals, toxic derivatives of oxygen. More specifically, the full genetic potential of the child for physical growth ad mental development may be compromised due to deficiency (even subclinical) of micronutrients. Children and adolescents with poor nutritional status are exposed to alterations of mental and behavioural functions that can be corrected by dietary measures, but only to certain extend. Indeed, nutrient composition and meal pattern can exert either immediate or long-term effects, beneficial or adverse. Brain diseases during aging can also be due to failure for protective mechanism, due to dietary deficiencies, for instance in anti-oxidants and nutrients (trace elements, vitamins, non essential micronutrients such as polyphenols) related with protection against free radicals. Macronutrients are presented in the accompanying paper.

Aged↗

A prospective cohort study of intake of calcium, vitamin D, and other micronutrients in relation to incidence of rectal cancer among postmenopausal women.

To investigate whether high intakes of calcium and other micronutrients (carotene, retinol, and vitamins C, D, and E) are related to reduced risks of rectal cancer, we analyzed data from a large cohort study of postmenopausal Iowa women who responded to a mailed survey in 1986. After 9 years of follow-up, 144 incident rectal cancer cases were ascertained among the 34,702 women at risk. Intake levels of micronutrients at baseline were derived from self-reported data on vitamin supplements and dietary intake of 127 foods included in a semiquantitative food frequency questionnaire. After adjustment for total energy intake and other potential confounding factors, a dose-response inverse association was observed between total calcium intake and the risk of rectal cancer: adjusted relative risks (RRs) were 1.00, 0.90, and 0.59 (trend test, P = 0.02) from the lowest to the highest calcium intake tertiles. High intakes of dietary and supplement calcium were both related to a slightly reduced risk of rectal cancer, but neither of the trend tests was statistically significant. Reduced risks of rectal cancer were also observed for high intake of carotene and vitamins A, C, and D, although none of the associations were statistically significant. For vitamin D, the adjusted RRs were 1.00, 0.71, and 0.76 (trend test, P = 0.20) for increasing intake tertiles. Compared with women who consumed low levels of both total calcium and vitamin D, those in the highest intake group of both nutrients were at a 45% reduced risk of rectal cancer (RR, 0.55; 95% confidence interval, 0.32-0.93). This study supports the hypothesis that high intake of calcium and possibly other micronutrients may be beneficial in the prevention of rectal cancer.

Aged↗

Micronutrients and urban life-style: lessons from Guatemala.

Guatemala is a nation of 10 million persons, at the northern point of the chain of five Republics derived from Spanish colonies on the Isthmus of Central America. The country is diverse in its ethnicities, its climate and terrain, and its agricultural pursuits. The majority of its population is poor, illiterate, and under-employed. It has had a unique and turbulent political history, and only recently has emerged. The traditional basis of the diet, dating to Mayan times, is maize and beans. Guatemala City, with its population in excess of 2 million inhabitants, having doubled since the Earthquake of 1976, is the only major metropolis. The pattern of dietary selection and the format of eating meals is changing in relationship to the size, congestion, economic evolution, and modernization of the capital city. A wider selection of foods is consumed in the city, but preparation follows the traditions of the rural cuisine. Street vendors play an ever larger role in the feeding of the urban poor. Quantitative data are only available for vitamin A and zinc, and only in certain subsegments of the population. The vitamin A in fortified foods, notably table sugar which is fortified with retinyl palmitate by legal mandate, makes up over one-third of the intake. The maize tortilla is an important sources of calcium, iron, zinc and copper. Average zinc intakes are appropriate, but the biological availability of the metal is low. The intake of iodine is totally dependent upon table salt which is inconsistently fortified. Data on micronutrient status exists for vitamin A, iron, iodine, riboflavin and zinc. With respect to rural areas, no major advantages or disadvantages in the adequacy of micronutrient nutriture can be claimed for the urban population. It is possible that, in the metropolitan area, vitamin A nutriture is slightly better and riboflavin status somewhat poorer than in the countryside. The prospects for future directions in urban lifestyle, in micronutrient status and in their interaction are uncertain. The pressure of growth are straining the ability of the municipal infrastructure and the industrial base to respond with provision of services and employment.

Feeding Behavior↗

Reproducibility of erythrocyte polyamine measurements and correlation with plasma micronutrients in an antioxidant vitamin intervention study.

Erythrocyte polyamine measurements have been previously investigated as candidate biomarkers for hyperproliferation and recently as a potential intermediate endpoint in clinical chemoprevention trials with difluoromethylornithine, an inhibitor of polyamine biosynthesis. This study was performed to determine the reproducibility of erythrocyte polyamine measurements and their possible correlation with plasma micronutrients in seven healthy adults in an antioxidant vitamin intervention study. As part of this cross-over intervention study, three subjects took beta-carotene (31.4 mg/day) plus D-alpha-tocopherol acetate (720 IU/day) supplements during the first 3 months and four subjects took the supplements during the second 3 months. Heparinized blood samples were collected at baseline and every month over total 6 months for simultaneous determination of erythrocyte polyamines and plasma micronutrients by the high-performance liquid chromatographic method. For all the measures of erythrocyte polyamines the intraindividual variation was smaller than that between subjects, and three or four measurements required to accurately characterize long-term erythrocyte polyamines for an individual. The intra-class correlations were moderately high for all erythrocyte polyamine measurements, indicating a good reproducibility for intra-individual erythrocyte polyamine measurements. Based on monthly values, significant inverse correlations were found between erythrocyte spermidine and the plasma levels of retinol (r = -0.50) and lutein (r = -0.52). There were also significant inverse associations between erythrocyte spermine and plasma levels of alpha-tocopherol (r = -0.29), lutein (r = -0.44), lycopene (r = -0.29), beta-cryptoxanthin (r = -0.30), and total carotenoids (r = -0.29). The effects of supplementation upon the associations between erythrocyte polyamines and plasma nutrient levels were additionally addressed. The results indicate an acceptable longitudinal reproducibility of erythrocyte polyamine measurements, support the hypothesis that erythrocyte polyamine measurements may be correlated with plasma levels of certain nutrients, and suggest a further biomarker application in cancer prevention trials involving dietary modifications or specific relevant micronutrients.

Adult↗

Dietary intake of selected micronutrients and breast-cancer risk.

The relation between 17 micronutrients and breast-cancer risk was analyzed in a case-control study conducted between 1993 and 1999 in the Swiss Canton of Vaud. Cases were 289 women with incident, histologically confirmed breast cancer, and controls were 442 women admitted to the same hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were obtained after allowance for age, education, parity, menopausal status, body mass index, total energy intake and alcohol drinking. For several micronutrients, the ORs tended to decline with increasing tertile of intake, with significant inverse trends in risk for potassium (OR for the highest tertile = 0.21), total carotenoids (OR = 0.42), lycopene (OR = 0.43), folic acid (OR = 0.45), vitamin C (OR = 0.19), vitamin E (OR = 0.37) and vitamin B(6) (OR = 0.54). In a model including a continuous term for the 7 micronutrients significantly related to breast cancer, the only persisting significant inverse relations were for vitamin C (OR = 0.23) and lycopene (OR = 0.64).

Adult↗