Micronutrient deficiency and supplements in schoolchildren and teenagers.

PURPOSE OF REVIEW: The essential micronutrients are corner stones in the functional and physical development. Early deficiency has life-long consequences. While awareness about iron deficiency is relatively high, it remains lower for other micronutrients. This review aims at reporting on recent data and attracting attention to the high prevalence of micronutrient deficiencies in school-age and adolescent individuals. RECENT FINDINGS: Iron deficiency anaemia remains highly prevalent worldwide and the most frequent deficiency but can be corrected with simple tools ranging from food fortification, nutritional intervention, and to supplements. The link between micronutrient (MN) deficiency and neurobehavioral disorders is increasingly established and is worrying even in Western countries. Paediatric individuals are prone to imbalanced diets and picky eating behaviour, and their diets may then become incomplete: the highest risk for deficiency is observed for iron, zinc and vitamin D. SUMMARY: There is not much new information, but rather confirmation of the importance of health policies. Well conducted randomized controlled trials confirm that deficiencies can be corrected efficiently including with food fortification, and result in clinical benefits. Individual complementation should be considered in children and adolescents with proven deficiency.

ESPEN micronutrient guideline.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE: This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS: The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION: This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.

The nutritional status of people with alkaptonuria: An exploratory analysis suggests a protein/energy dilemma.

BACKGROUND: Alkaptonuria (AKU) is a disorder of tyrosine/protein metabolism leading to accumulation of homogentisic acid. Clinical management historically recommended reducing dietary protein intake, especially in childhood, which has since been discredited in the literature. For the first time, analysis of baseline cross-sectional nutritional surveillance data from a large cohort of AKU patients is presented, which has clinical implications in all aspects of treatment planning. METHOD: Seventy-four patients (mean 55 years) admitted to the National Alkaptonuria Centre (NAC), underwent a global nutritional assessment, which included objective anthropometry, bioimpedance measures, habitual nutritional intake using a 7-day food diary and key nutritional biomarkers, including 24 hours urinary nitrogen, serum albumin, total protein and total 25-hydroxy vitamin D. All data was compared with cohort norms or recommended nutrient intakes for health (RNI). The potential beneficial impact of protein and anti-inflammatory nutrients such as vitamin C, selenium, and zinc were statistically interrogated against the AKU severity score index (AKUSSI)-a validated measure of disease progression stratified by age. RESULTS: Fifty percent of AKU patients reported some level of protein restriction at some point in their lives. In comparison with national data sets, AKU patients present with significantly lower than predicted mid-upper arm circumference, grip strength, BMI, total energy and protein intake, and higher than predicted percentage body fat. They therefore meet the ESPEN criteria as "clinically undernourished." Severity fluctuates over the life course. No statistical association is identified between protein intake, expressed as %RNI or g/kg, or anti-inflammatory nutrients, including vitamin C as a high dose supplement on the severity of the disease, when correlated against the validated AKUSSI score. CONCLUSION: AKU patients are at risk of protein depletion associated with a "perfect storm" of risk factors: historical, poorly evidenced recommendations to reduce total protein intake; limited mobility as the condition progresses, compromising muscle integrity; frequent hospital admissions for major surgery associated with multiple joint replacements, creating pinch points of high metabolic demand and the potential impact of the disease itself. As this is the first time this risk has been identified, the authors consider the dietetic implications of nitisinone treatment, which requires dietary protein control to manage the acquired tyrosinaemia. The lack of statistically significant evidence to support dietary manipulation of any kind to impede disease progression in AKU is demonstrated.

A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market.

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) started an intensive review of commercially available parenteral vitamin and trace element (TE) products in 2009. The chief findings were that adult multi-TE products currently available in the United States (U.S.) provide potentially toxic amounts of manganese, copper, and chromium, and neonatal/pediatric multi-TE products provide potentially toxic amounts of manganese and chromium. The multivitamin products appeared safe and effective; however, a separate parenteral vitamin D product is needed for those patients on standard therapy who continue to be vitamin D depleted and are unresponsive to oral supplements. The review process also extended to parenteral choline and carnitine. Although choline and carnitine are not technically vitamins or trace elements, choline is an essential nutrient in all age groups, and carnitine is an essential nutrient in infants, according to the Food and Nutrition Board of the Institute of Medicine. A parenteral choline product needs to be developed and available. Efforts are currently under way to engage the U.S. Food and Drug Administration (FDA) and the parenteral nutrient industry so A.S.P.E.N.'s recommendations can become a commercial reality.

A.S.P.E.N. position paper: recommendations for changes in commercially available parenteral multivitamin and multi-trace element products.

The parenteral multivitamin preparations that are commercially available in the United States (U.S.) meet the requirements for most patients who receive parenteral nutrition (PN). However, a separate parenteral vitamin D preparation (cholecalciferol or ergocalciferol) should be made available for treatment of patients with vitamin D deficiency unresponsive to oral vitamin D supplementation. Carnitine is commercially available and should be routinely added to neonatal PN formulations. Choline should also be routinely added to adult and pediatric PN formulations; however, a commercially available parenteral product needs to be developed. The parenteral multi-trace element (TE) preparations that are commercially available in the U.S. require significant modifications. Single-entity trace element products can be used to meet individual patient needs when the multiple-element products are inappropriate (see Summary/A.S.P.E.N. Recommendations section for details of these proposed modifications).

Randomized controlled trial of zinc and vitamin A as co-adjuvants for the treatment of pulmonary tuberculosis.

OBJECTIVE: To assess the efficacy of weekly zinc or zinc plus retinol as adjuncts for the treatment of pulmonary tuberculosis. METHODS: Double-blind, randomized, placebo-controlled trial in 350 patients >15 years old with smear-positive tuberculosis in Nigeria (ISRCTN36636609). In addition to antituberculous treatment, patients were randomly allocated to weekly supplements of zinc (90 mg), zinc plus retinol (5000 IU) or placebos for 6 months. Primary outcomes were time to sputum smear conversion and resolution of radiographic abnormalities. RESULTS: After 8 weeks of treatment, 68% had achieved sputum smear conversion, and the median conversion time was 6.5 weeks. Hazard ratios (HR, 95%CI) for sputum conversion relative to the placebo group were not significant for zinc (1.07, 0.92-1.29) or zinc plus retinol (0.89, 0.76-1.07). Significant predictors of time to sputum conversion were lung abnormality score, sputum smear grade, age and serum C-reactive protein. HIV co-infection and gender were not independent predictors of time to sputum conversion. There were no significant differences between supplement groups in clinical, radiological or laboratory outcomes at 2 months or 6 months. There were 9, 9 and 2 deaths in patients receiving zinc, zinc plus retinol or placebos, respectively. Mortality in those who received zinc (HR 1.71, 0.88-3.58) or zinc plus retinol (HR 1.54, 0.78-3.26) did not differ significantly from those who received placebos. Most deaths occurred in patients co-infected with HIV. CONCLUSIONS: Supplementation with zinc or zinc plus retinol did not lead to better outcomes than placebos, and caution is warranted regarding routine micronutrient supplementation, particularly in patients co-infected with HIV.

Selenium in intravenous nutrition.

Selenium (Se) is an essential nutrient for human beings, with serious consequences resulting from clinical deficiency. It therefore should be provided intravenously to all patients who require parenteral nutrition (PN). Moreover, because the effects of suboptimal status are variable and unclear, this supplementation should be provided from the beginning of the course of PN. In most patients receiving PN at home or after surgery, 60-100 mcg/day will meet their requirements. Patients who commence PN already depleted in selenium may require more. Critically ill patients or those with severe burns may have higher requirements. There is good evidence that up to 400 mcg/day is beneficial in burn patients, but the evidence is inconclusive regarding the benefit of high-dose selenium in severe sepsis. Where increased Se provision is used, or in long-term PN, selenium status should be monitored by measurement of plasma Se together with a measure of systemic inflammatory response syndrome, such as C-reactive protein. There are many research issues, including which biochemical measurements best reflect tissue function, especially immune function in seriously ill patients, the clinical consequences of suboptimal biochemical Se status, whether high-dose Se improves outcome in critically ill patients, and whether extra Se always should be given with extra intakes of other antioxidants.

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients.

INTRODUCTION: Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 microg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo. RESULTS: Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 +/- 3.2 versus -4.2 +/- 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045). CONCLUSION: The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation. TRIALS REGISTRATION: Clinical Trials.gov RCT Register: NCT00515736.

Trace element requirements in critically ill burned patients.

Critically ill burned patients are characterized by a strong oxidative stress, an intense inflammatory response, and months-long hypermetabolism, all of which are proportional to the severity of injury. Trace element (TE) deficiencies have repeatedly been described. The clinical course is complicated by organ failures, infections, and delayed wound healing, which can be partly attributed to TE deficiencies. Among critically ill patients, TE deficiencies are the most severe in major burns, who suffer a specific copper deficiency. Plasma TE concentrations are low during any critical illness, as a result of TE losses in biological fluids, low intakes, dilution by fluid resuscitation, and redistribution from plasma to tissues mediated by the inflammatory response. The large exudative losses cause negative TE balances. Intravenous supplementation trials show that early substitution improves recovery, reduces infectious complications (particularly nosocomial pneumonia), normalize thyroid function, normalize skin tissue levels, improve wound healing and shorten hospital stay. Nevertheless, prolonged high dose delivery may be deleterious, as TE have potential for toxicity. In major burns, supplements up to 4 mg of Cu/day, 500 mcg [DOSAGE ERROR CORRECTED] Se/day and 40 mg Zn/day for 3 weeks have been found to be safe and effective. The intravenous route appears the only way to deliver the doses required to achieve antioxidant and clinical effects. Further research is required to determine the optimal combination and doses for different severities of injury.

Autopsy tissue trace elements in 8 long-term parenteral nutrition patients who received the current U.S. Food and Drug Administration formulation.

Iron, zinc, copper, manganese, chromium, and selenium levels were measured in autopsy tissues of 8 people with short bowel syndrome who received home parenteral nutrition (HPN) and the U.S. Food and Drug Administration (FDA)-approved trace element formulation for an average duration of 14 years (range, 2-21). Iron, zinc, copper, manganese and selenium were measured by inductively coupled plasma methods; chromium, by graphite furnace atomic absorption spectrometry. The levels in the 4 tissues studied, heart, skeletal muscle, liver, and kidney, were compared with levels in 45 controls who died without chronic gastrointestinal disorders. Results showed normal HPN patient values for iron and selenium, mild elevation of zinc, and major elevations of copper, manganese, and chromium. The implications of these results for trace-element supplements in long-term PN adult patients are discussed, and the need for reformulation of commercially available multi-trace element products in the United States is stressed.

Effect of intraocular surgery and ketamine on aqueous and serum cytokines.

PURPOSE: To determine the effect of intraocular surgery and anesthesia on aqueous and serum cytokines. METHODS: Patients undergoing routine cataract surgery under general and local (peribulbar) anesthesia were randomized to those given general anesthetic with and without the use of ketamine and those having local anesthesia. Aqueous and serum levels of cytokines were collected at commencement of surgery and were determined by an immunoassay using multi-analyte biochip array technology at 18 h post-operatively. RESULTS: At 18 h postoperative, all patients (37) showed significant and many fold increases in their aqueous levels of interleukin (IL)-1alpha, IL-1beta, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, epidermal growth factor (EGF), and monocyte chemotactic protein (MCP)-1. There was little to no increase in IL-2 and IL-10. Significant increases in some cytokines (EGF, IL-6, and IFN-gamma) in the serum were also found (p=0.038). There were no significant differences in aqueous cytokine levels following the use of ketamine or between those patients who had general and local anesthesia (0.11

Trace element supplementation after major burns increases burned skin trace element concentrations and modulates local protein metabolism but not whole-body substrate metabolism.

BACKGROUND: After major burns, patients exhibit an intense catabolism, and the wounds require surgery and grafting for closure. Complications, such as weight loss and delayed wound healing, are worsened by trace element (TE) deficiencies. OBJECTIVE: We aimed to assess the effects of TE supplements on systemic substrate turnover and local protein metabolism during wound healing after major burns. DESIGN: This was a prospective, randomized, placebo-controlled trial in 21 patients aged 35 +/- 11 y with burns on 45 +/- 16% of their body surface area; 12 had skin biopsies performed on days 3, 10, and 20, and 10 patients underwent a stable-isotope investigation on day 10. Intravenous copper, selenium, and zinc (TE group) or vehicle (V group) was given with a saline solution for 14-21 d. On day 10, [(13)C]phenylalanine (600-microg/kg bolus followed by 12 microg x kg(-1) x min(-1)) plus 6-[(2)H(2)]glucose and [(2)H(5)]glycerol were infused for 6 h to determine skin protein turnover. Biopsies were performed 1 and 6 h after the start of infusion to determine [(13)C]phenylalanine enrichment. RESULTS: The patients' mean age and burn severity did not differ significantly between the groups nor between the skin investigations subgroups. Plasma TE concentrations were significantly higher in the TE group. In the burned areas, the skin contents of selenium (P=0.02) and zinc (P=0.03) increased by day 20. The supernatant-to-plasma (13)C enrichment ratio in burned skin was 0.363 +/- 0.094 (TE group) and 0.286 +/- 0.130 (V group) after 1 h (NS) and 0.592 +/- 0.153 (TE group) and 0.262 +/- 0.171 (V group) after 6 h, which reflected lower catabolism in the TE group (P=0.03). No significant differences in whole-body substrate turnover were found between the groups. CONCLUSION: TE supplementation was associated with an increased skin tissue content of selenium and zinc and with a reduction in skin protein catabolism.

Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations.

BACKGROUND: After major burns, patients can develop nutritional deficiencies including trace element (TE) deficiencies. Various complications, such as infections and delayed wound healing, influence the clinical course of such patients. OBJECTIVES: We aimed to investigate the effects of large, intravenous doses of TE supplements on circulating and cutaneous TE tissue concentrations, on antioxidant status, and on clinical outcome after major burns. DESIGN: This was a prospective, randomized, placebo-controlled trial in 21 patients aged 35 +/- 11 y (x +/- SD) with burns on 45 +/- 21% of their body surface area. Intravenous copper, selenium, and zinc (TE group) or vehicle (V group) was given with a saline solution for 14-21 d. Blood and urine samples were collected until day 20, and skin biopsy specimens were collected on days 3, 10, and 20. RESULTS: The age of the patients and the severity of their burns did not differ significantly between the groups. Plasma TE concentrations were significantly higher in the TE group. In burned areas, skin contents of both selenium (P=0.05) and zinc (P=0.04) increased significantly by day 20. Plasma and tissue antioxidant status was improved by supplementation. The number of infections in the first 30 d was significantly lower in the TE group (P=0.015), with a median number of 2 versus 4 infections per patient in the TE and V groups, respectively, as a result of a reduction in pulmonary infections (P=0.03). Wound healing was improved in the TE group, with lower requirements for regrafting (P=0.02). CONCLUSIONS: TE supplementation was associated with higher circulating plasma and skin tissue contents of selenium and zinc and improved antioxidant status. These changes were associated with improved clinical outcome, including fewer pulmonary infections and better wound healing.

Effect of selenium supplementation on biochemical markers and outcome in critically ill patients.

BACKGROUND & AIMS: This study aimed to assess the effect of high dose selenium (Se) supplementation on Se status in blood, oxidative stress, thyroid function and possible effects on requirement for renal replacement therapy (RRT) in severely septic patients admitted to the intensive care unit (ICU). METHODS: This prospective single-centre study was carried out in 40 septic ICU patients who were randomized to high dose Se (Se+ group, N=18 (474, 316, 158 microg/day), each for 3 consecutive days followed by a standard dose of 31.6 microg/day of Se given as sodium selenite whereas the control group (Se-, N=22) received only the standard dose of Se. Plasma Se, glutathione peroxidase (GSH-Px), F2 isoprostanes, thyroid function tests (total T4 and total T3), C-reactive protein (CRP) and red blood cell (RBC) GSH-Px were estimated on day 0, 3, 7, 14. RESULTS: In the Se+ group, plasma Se increased by day 3 and 7 (P<0.0001) and day 14 (P=0.02), plasma GSH-Px increased by day 3 and 7 (P=0.01) as compared to Se- group. There was a significant negative correlation between plasma Se and SOFA (sepsis related organ failure assessment) (r=-0.36, P=0.03) along with low plasma Se and high CRP at the time of admission. Requirement for renal replacement therapy was not significantly different between the groups. CONCLUSION: Although high dose Se supplementation increased plasma Se and GSH-Px activity, it did not reduce oxidative damage or the requirement for RRT. Se levels in blood are influenced by redistribution and severity of illness and therefore should be interpreted with caution.

Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials.

INTRODUCTION: Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia. METHODS: Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 mug/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20. RESULTS: The patients, 42 +/- 15 years old, were burned on 46% +/- 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 +/- 1.2 to 2.0 +/- 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023). CONCLUSION: Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.

Update on clinical micronutrient supplementation studies in the critically ill.

PURPOSE OF REVIEW: During the past 2 years a number of studies, meta-analyses and reviews have shown that micronutrient supplementation may be beneficial in critical illness. Selenium is emerging as a particularly important micronutrient. This paper reviews the evidence from trials in the critically ill, putting mechanisms, methods and shortcomings into perspective. RECENT FINDINGS: There is growing evidence that antioxidant supplements, particularly high-dose selenium, may reduce mortality, infectious complications, and improve wound healing. Deleterious effects may result from prolonged high doses, whereas short-term high dose supplements are probably safe in most critically ill populations. SUMMARY: Plasma micronutrient concentrations are low during critical illness, as a result of losses, low intakes and dilution, and redistribution from plasma to tissues. An assessment of status is difficult. Micronutrient supplements appear beneficial in conditions such as major burns, trauma and sepsis and stroke, and are most likely to benefit patients with previous or actual depletion. The intravenous route seems more efficient than the enteral. Although chronic high intakes may be harmful, short-term interventions appear to be free of deleterious effects. Further research is required to determine the optimal micronutrient combinations and the doses required according to the timing of intervention and severity of disease.

Vitamins and trace elements: practical aspects of supplementation.

The role of micronutrients in parenteral nutrition include the following: (1) Whenever artificial nutrition is indicated, micronutrients, i.e., vitamins and trace elements, should be given from the first day of artificial nutritional support. (2) Testing blood levels of vitamins and trace elements in acutely ill patients is of very limited value. By using sensible clinical judgment, it is possible to manage patients with only a small amount of laboratory testing. (3) Patients with major burns or major trauma and those with acute renal failure who are on continuous renal replacement therapy or dialysis quickly develop acute deficits in some micronutrients, and immediate supplementation is essential. (4) Other groups at risk are cancer patients, but also pregnant women with hyperemesis and people with anorexia nervosa or other malnutrition or malabsorption states. (5) Clinicians need to treat severe deficits before they become clinical deficiencies. If a patient develops a micronutrient deficiency state while in care, then there has been a severe failure of care. (6) In the early acute phase of recovery from critical illness, where artificial nutrition is generally not indicated, there may still be a need to deliver micronutrients to specific categories of very sick patients. (7) Ideally, trace element preparations should provide a low-manganese product for all and a manganese-free product for certain patients with liver disease. (8) High losses through excretion should be minimized by infusing micronutrients slowly, over as long a period as possible. To avoid interactions, it would be ideal to infuse trace elements and vitamins separately: the trace elements over an initial 12-h period and the vitamins over the next 12-h period. (9) Multivitamin and trace element preparations suitable for most patients requiring parenteral nutrition are widely available, but individual patients may require additional supplements or smaller amounts of certain micronutrients, depending on their clinical condition.

The key role of micronutrients.

Micronutrients play a central role in metabolism and in the maintenance of tissue function, but effects in preventing or treating disease which is not due to micronutrient deficiency cannot be expected from increasing the intake. There is a highly integrated system to control the flux of micronutrients in illness, and this demonstrates just how important the body perceives the micronutrients to be. An adequate intake therefore is necessary to sustain metabolism and tissue function, but provision of excess supplements to individuals who do not need them may be harmful. Clinical benefit is most likely in those individuals who are severely depleted and at risk of complications, and is unlikely if this is not the case. Much more research is needed to characterise better markers of micronutrient status both in terms of metabolic effects and antioxidant effects, so that at-risk patients can be identified and supplementation modified accordingly. Large-scale trials of different doses of micronutrients are required with precise outcome markers to optimise intakes in different groups of patients as well as in the general population.