Perspective: When the cure might become the malady: the layering of multiple interventions with mandatory micronutrient fortification of foods in India.

When public health programs with single nutrients are perceived to have a poor impact on the target health outcome, the policy response can be to supply more, by layering additional mandatory programs upon the extant programs. However, we argue for extreme caution, because nutrients (like medicines) are beneficial in the right dose, but potentially harmful when ingested in excess. Unnecessary motivations for the reactionary layering of multiple intervention programs emerge from incorrect measurements of the risk of nutrient inadequacy in the population, or incorrect biomarker cutoffs to evaluate the extent of nutrient deficiencies. The financial and social costs of additional layered programs are not trivial when traded off with other vital programs in a resource-poor economy, and when public health ethical dilemmas of autonomy, equity, and stigma are not addressed. An example of this conundrum in India is the perception of stagnancy in the response of the prevalence of anemia to the ongoing pharmacological iron supplementation program. The reaction has been a policy proposal to further increase iron intake through mandatory iron fortification of the rice provided in supplementary feeding programs like the Integrated Child Development Services and the School Mid-Day Meal. This is in addition to the ongoing pharmacological iron supplementation as well as other voluntary iron fortifications, such as those of salt and manufactured food products. However, before supplying more, it is vital to consider why the existing program is apparently not working, along with consideration of the potential for excess intake and related harms. This is relevant globally, particularly for countries contemplating multiple interventions to address micronutrient deficiencies. Supplying more by layering multiple nutrient interventions, instead of doing it right, without thoughtful considerations of social, biological, and ethics frameworks could be counterproductive. The cure, then, might well become the malady.

Micronutrient Deficiencies and Anemia in Children with Inflammatory Bowel Disease.

Children with inflammatory bowel disease (IBD) are at risk of developing nutrition deficiencies, particularly because of reduced intake, restrictive diets, malabsorption, and excessive nutrient loss. The aim of this study was to determine the prevalence and predictors of anemia and micronutrient deficiencies at diagnosis and one year follow up in children and adolescents with inflammatory bowel disease (IBD). Children and young adults diagnosed with IBD before the age of 17 years between 2012 and 2018 were included. Laboratory measurements including serum levels of iron, ferritin, zinc, vitamin D, vitamin A, vitamin E, selenium, copper, vitamin B12, and red blood cell (RBC) folate at diagnosis and one-year follow-up were documented as part of the Manitoba Longitudinal Pediatric Inflammatory Bowel Disease (MALPID) Cohort. A total of 165 patients with IBD were included, 87 (53%) with Crohn's disease (CD) and 78 (47%) with ulcerative colitis (UC). The prevalence of deficiencies in our cohort at diagnosis and one year follow-up, respectively, were iron (56% and 27%), ferritin (39% and 27%), zinc (10% and 6%), vitamin D (22% and 13%), vitamin A (25% and 25%), vitamin E (5% and 4%), selenium (10 and 7%), copper (17% and 27%), vitamin B12 (2% and 5%), and Red blood cell (RBC) folate (1% and 17%). Anemia was present in 57% and 25% at diagnosis and follow up respectively. In CD patients, age of diagnosis (15y-younger than 18y) was a predictor of moderate to severe anemia and albumin levels (<33 g/L) were protective against anemia. Many children with IBD suffer from anemia and micronutrient deficiencies at diagnosis and some fail to recover after one year despite being in clinical remission.

Prevalence of inadequate and excessive iodine intake in a US pregnancy cohort.

BACKGROUND: US iodine intake, estimated from the median urinary iodine concentration of population representative data, has declined by half since the 1970s, which is problematic because maternal iodine intake is critical for fetal neurodevelopment. Relying on median urinary concentrations to assess iodine intake of populations is standard practice but does not describe the number of individuals with insufficient intake. Prevalence estimates of inadequate and excessive intake are better for informing public health applications but require multiple urine samples per person; such estimates have been generated in pediatric populations but not yet among pregnant women. OBJECTIVE: Our aims were as follows: (1) to assess median urinary iodine concentrations across pregnancy for comparison with national data and (2) to estimate the prevalence of inadequate and excessive iodine intake among pregnant women in mid-Michigan. STUDY DESIGN: Data were collected from 2008 to 2015 as part of a prospective pregnancy cohort in which women were enrolled at their first prenatal clinic visit. Few exclusion criteria (<18 years or non-English speaking) resulted in a sample of women generally representative of the local community, unselected for any specific health conditions. Urine specimens were obtained as close as practicable to at least 1 specimen per trimester during routine prenatal care throughout pregnancy (n=1-6 specimens per woman) and stored at -80°C until urinary iodine was measured to estimate the iodine intake (n=1014 specimens from 464 women). We assessed urinary iodine across pregnancy by each gestational week of pregnancy and by trimester. We used multiple urine specimens per woman, accounted for within-person variability, performed data transformation to approximate normality, and estimated the prevalence of inadequate and excessive iodine intake using a method commonly employed for assessment of nutrient status. RESULTS: Maternal characteristics reflected the local population in racial and ethnic diversity and socioeconomic status as follows: 53% non-Hispanic white, 22% non-Hispanic black, and 16% Hispanic; 48% had less than or equal to high school education and 71% had an annual income of <$25,000. Median urinary iodine concentrations in the first, second, and third trimester-including some women contributing more than 1 specimen per trimester-were 171 µg/L (n=305 specimens), 181 µg/L (n=366 specimens), and 179 µg/L (n=343 specimens), respectively, with no significant difference by trimester (P=.50, Kruskal-Wallis test for equality of medians). The estimated prevalence of inadequate and excessive iodine intake was 23% and <1%, respectively. CONCLUSION: Median urinary iodine concentrations in each trimester were above the World Health Organization cutoff of 150 µg/L, indicating iodine sufficiency at the group level across pregnancy. However, the estimated prevalence of inadequate iodine intake was substantial at 23%, whereas prevalence of excessive intake was <1%, indicating a need for at least some women to increase consumption of iodine during pregnancy. The American Thyroid Association, the Endocrine Society, and the American Academy of Pediatrics recommend that all pregnant and lactating women receive a daily multivitamin or mineral supplement that contains 150 µg of iodine. The data presented here should encourage the collection of similar data from additional US population samples for the purpose of informing the American College of Obstetricians and Gynecologists' own potential recommendations for prenatal iodine supplementation.

The Effect of Sheep and Cow Milk Supplementation of a Low Calcium Diet on the Distribution of Macro and Trace Minerals in the Organs of Weanling Rats.

The aim of this study was to investigate the effect of either sheep or cow milk supplementation to a low calcium and phosphorus diet on growth and organ mineral distribution in weanling rats. Rats were fed diets consisting of either a control chow, a 50% reduced calcium and phosphorous chow (low Ca/P), low Ca/P and sheep milk, or low Ca/P and cow milk diet for 28 days. Food intake of the rats, the growth rate of the rats, and the concentrations of minerals in the soft organs and serum were determined. Rats fed the low Ca/P diet alone had lower weight gain than rats consuming either of the milk-supplemented diets (p < 0.05). Both sheep milk and cow milk supplementation overcame the effects of consuming a diet restricted in calcium and phosphorus but the sheep milk was effective at a significantly lower level of milk intake (p < 0.05). Significant differences (p < 0.05) in essential and trace mineral concentrations due to milk type were observed in the kidney, spleen, and liver. For non-essential minerals, significant differences (p < 0.05), related to diet, were observed in all organs for arsenic, cesium, rubidium, and strontium concentrations.

Biotechnological Approaches for Generating Zinc-Enriched Crops to Combat Malnutrition.

The past twenty years have seen the application of biotechnology to generate nutritionally improved food crops. Biofortified rice, cassava, maize, sorghum and other staple crops biofortified with essential micronutrients have great potential to benefit the world's poor, in terms of both health and economics. This paper describes the use of genetic modification to generate crops that are biofortified with zinc. Examples of zinc-enhanced crops which have been developed using biotechnological approaches will be discussed, and new approaches for research and development will be outlined. The impact of these biofortified crops on human health and well-being will be examined. This paper will conclude with a discussion of the obstacles that must be overcome to enable zinc-fortified crops to be accessible for the world's malnourished.

Omega-3 Polyunsaturated Fatty Acid Deficiency and Progressive Neuropathology in Psychiatric Disorders: A Review of Translational Evidence and Candidate Mechanisms.

Meta-analytic evidence indicates that mood and psychotic disorders are associated with both omega-3 polyunsaturated fatty acid (omega-3 PUFA) deficits and progressive regional gray and white matter pathology. Although the association between omega-3 PUFA insufficiency and progressive neuropathological processes remains speculative, evidence from translational research suggests that omega-3 PUFA insufficiency may represent a plausible and modifiable risk factor not only for enduring neurodevelopmental abnormalities in brain structure and function, but also for increased vulnerability to neurodegenerative processes. Recent evidence from human neuroimaging studies suggests that lower omega-3 PUFA intake/status is associated with accelerated gray matter atrophy in healthy middle-aged and elderly adults, particularly in brain regions consistently implicated in mood and psychotic disorders, including the amygdala, anterior cingulate, hippocampus, prefrontal cortex, and temporal cortex. Human neuroimaging evidence also suggests that both low omega-3 PUFA intake/status and psychiatric disorders are associated with reductions in white matter microstructural integrity and increased rates of white matter hyperintensities. Preliminary evidence suggests that increasing omega-3 PUFA status is protective against gray matter atrophy and deficits in white matter microstructural integrity in patients with mood and psychotic disorders. Plausible mechanisms mediating this relationship include elevated pro-inflammatory signaling, increased synaptic regression, and reductions in cerebral perfusion. Together these associations encourage additional neuroimaging research to directly investigate whether increasing omega-3 PUFA status can mitigate neuropathological processes in patients with, or at high risk for, psychiatric disorders.

Effect of Nutritional Interventions on Micronutrient Status in Pregnant Malawian Women with Moderate Malnutrition: A Randomized, Controlled Trial.

Micronutrient deficiencies during pregnancy are common in Africa and can cause adverse outcomes. The objective was to measure micronutrient status and change in moderately malnourished pregnant Malawian women randomized to one of three nutritional interventions. Serum vitamin B12, 25-hydroxyvitamin D, folate, retinol, ferritin, zinc, albumin and C-reactive protein were measured in pregnant women with MUAC ≥20.6 cm and ≤23.0 cm at enrollment (n = 343) and after 10 weeks (n = 229) of receiving: (1) ready-to-use supplementary food (RUSF); (2) fortified corn-soy blend (CSB+) with multiple-micronutrient supplement (CSB+UNIMMAP); or (3) CSB+ with iron and folic acid (CSB+IFA). Each provided 100⁻300% Recommended Dietary Allowance of most micronutrients and 900 kcal/day. Birth length was measured in 272 infants. Enrollment measurements indicated deficiencies in vitamin B12 (20.9%) and zinc (22.3%), low values of ferritin (25.1%) and albumin (33.7%), and elevated CRP (46.0%). Vitamin B12 is known to decrease in the third trimester; the RUSF group had the smallest decrease from enrollment to week 10 (3%), compared to 20% decrease in the CSB+IFA group and 8% decrease in the CSB+UNIMMAP group (p = 0.001). Mean serum 25-hydroxyvitamin D increased most in the RUSF group (+6.4 ng/mL), compared to CSB+IFA (+1.7 ng/mL) and CSB+UNIMMAP (+2.7 ng/mL) (p < 0.001). Micronutrient deficiencies and inflammation are common among moderately malnourished pregnant women and had little improvement despite supplementation above the RDA, with the exception of vitamins B12 and D.

How Could Agronomic Biofortification of Rice Be an Alternative Strategy with Higher Cost-Effectiveness for Human Iron and Zinc Deficiency in China?

BACKGROUND: Iron and zinc deficiencies affect human health globally, especially in developing countries. Agronomic biofortification, as a strategy for alleviating these issues, has been focused on small-scale field studies, and not widely applied while lacking of cost-effectiveness analysis (CEA). OBJECTIVE: We conducted the CEA of agronomic biofortification, expressed as USD per disability-adjusted life years (DALYs) saved, to recommend a cost-effectiveness strategy that can be widely applied. METHODS: The DALYs were applied to quantify the health burden due to Fe and/or Zn deficiency and health cost of agronomic biofortification via a single, dual, or triple foliar spray of Fe, Zn, and/or pesticide in 4 (northeast, central China, southeast, and southwest) major Chinese rice-based regions. RESULTS: The current health burden by Fe or Zn malnutrition was 0.45 to 1.45 or 0.14 to 0.84 million DALYs for these 4 regions. Compared to traditional rice diets, the daily Fe and/or Zn intake from Fe and/or Zn-biofortified rice increased, and the health burden of Fe and/or Zn deficiency decreased by 28% and 48%, respectively. The cost of saving 1 DALYs ranged from US$376 to US$4989, US$194 to US$2730, and US$37.6 to US$530.1 for the single, dual, and triple foliar Fe, Zn, and/or pesticide application, respectively, due to a substantial decrease in labor costs by the latter 2 applications. CONCLUSIONS: Agronomic biofortification of rice with the triple foliar spray of Fe, Zn, and pesticide is a rapidly effective and cost-effectiveness pathway to alleviate Fe and Zn deficiency for rice-based dietary populations.

Daily Consumption of Lipid-Based Nutrient Supplements Containing 250 µg Iodine Does Not Increase Urinary Iodine Concentrations in Pregnant and Postpartum Women in Bangladesh.

Background: Maternal iodine deficiency during pregnancy and lactation is common in Bangladesh.Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on urinary iodine concentration (UIC).Methods: We conducted a cluster-randomized controlled effectiveness trial in which we enrolled 4011 pregnant women at ≤20 gestational weeks. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe/d + 400 µg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing 22 vitamins and minerals (including 250 µg I). We randomly selected a subsample of 1159 women for repeated urine sample collection, i.e., at enrollment, at 36 wk of gestation, and at 6 mo postpartum, for UIC analysis, a secondary outcome of the trial.Results: The geometric mean UIC at 36 wk of gestation and at 6 mo postpartum did not differ significantly between the IFA and LNS-PL groups. The median (quartile 1, quartile 3) UIC at 36 wk was 27.4 µg/L (16.9, 52.7 µg/L) in the IFA group and 30.2 µg/L (17.7, 56.6 µg/L) in the LNS-PL group; at 6 mo, these were 23.0 µg/L (10.0, 45.9 µg/L) in the IFA group and 22.2 µg/L (9.1, 50.4 µg/L) in the LNS-PL group.Conclusion: Daily consumption of LNS-PL containing 250 µg I did not increase the UICs of pregnant and lactating women in Bangladesh. Iodine from lipid-based nutrient supplements may have been stored in the thyroid gland or secreted in breast milk instead of being excreted in urine. Additional research that uses other biomarkers of iodine status is needed to determine how to meet the iodine requirements of pregnant and lactating women in Bangladesh and similar settings. This trial was registered at clinicaltrials.gov as NCT01715038.

The future for long chain n-3 PUFA in the prevention of coronary heart disease: do we need to target non-fish-eaters?

Dietary guidelines in many countries include a recommendation to consume oily fish, mainly on the basis of evidence from prospective cohort studies that fish consumption is cardioprotective. However, average intakes are very low in a large proportion of the UK population. Some groups, such as vegans and vegetarians, purposely omit fish (along with meat) from their diet resulting in zero or trace intakes of long chain (LC) n-3 PUFA. Although the efficacy of dietary fish oil supplementation in the prevention of CVD has been questioned in recent years, the balance of evidence indicates that LC n-3 PUFA exert systemic pleiotropic effects through their influence on gene expression, cell signalling, membrane fluidity and by conversion to specialised proresolving mediators; autacoid lipid mediators that resolve inflammatory events. The long-term impact of reduced tissue LC n-3 PUFA content on cardiovascular health is surprisingly poorly understood, particularly with regard to how low proportions of LC n-3 PUFA in cell membranes may affect cardiac electrophysiology and chronic inflammation. Randomised controlled trials investigating effects of supplementation on prevention of CHD in populations with low basal LC n-3 PUFA tissue status are lacking, and so the clinical benefits of supplementing non-fish-eating groups with vegetarian sources of LC n-3 PUFA remain to be determined. Refocusing dietary LC n-3 PUFA intervention studies towards those individuals with a low LC n-3 PUFA tissue status may go some way towards reconciling results from randomised controlled trials with the epidemiological evidence.

An Animal-Source Food Supplement Increases Micronutrient Intakes and Iron Status among Reproductive-Age Women in Rural Vietnam.

Background: Few studies have examined the impact of local animal-source foods (ASFs) on the nutritional status of reproductive-age women in developing countries.Objective: We hypothesized that a midmorning snack of local ASF for 6 mo would reduce dietary micronutrient deficiencies [usual intake less than the estimated average requirement (EAR)] and improve blood biomarkers of iron, zinc, and vitamins A and B-12 status among nonpregnant, reproductive-age women in rural Vietnam.Methods: One hundred seventeen women, 18-30 y old, were randomly assigned to receive either an ASF (mean: 144 kcal, 8.9 mg Fe, 2.7 mg Zn, 1050 µg retinoic acid equivalent vitamin A, and 5.5 µg vitamin B-12) or a control snack (mean: 150 kcal, 2.0 mg Fe, 0.9 mg Zn, 0 µg retinoic acid equivalent vitamin A, and 0 µg vitamin B-12) 5 d/wk for 6 mo. Usual nutrient intakes were estimated by repeated 24-h dietary recalls. Blood samples were collected at baseline and 3 and 6 mo. Because of the relation between nutritional status and inflammation, serum C-reactive protein, α-1-acid-glycoprotein, and urinary tract infections (UTIs) were also monitored.Results: Eighty-nine women (47 in the ASF group and 42 controls) completed the study. In the ASF group, intakes of iron and vitamins A and B-12 below the EAR were eliminated, and the prevalence of a low zinc intake was reduced to 9.6% compared with 64.7% in controls (P < 0.001). At 6 mo, a modest increase (P < 0.05) in hemoglobin and iron status occurred in the ASF group compared with the control group, but plasma zinc, retinol, and serum vitamin B-12 concentrations did not differ. UTI relative risk was 3.9 (P < 0.05) among women assigned to the ASF group who had a low whole-body iron status at baseline.Conclusions: Adding a small amount of locally produced ASF to the diets of reproductive-age Vietnamese women improved micronutrient intakes and iron status. However, the increased UTI incidence in women in the ASF group with initially lower iron stores warrants further investigation.

The Prevalence of Micronutrient Deficiencies and Inadequacies in the Middle East and Approaches to Interventions.

Micronutrient deficiencies and inadequacies constitute a global health issue, particularly among countries in the Middle East. The objective of this review is to identify micronutrient deficits in the Middle East and to consider current and new approaches to address this problem. Based on the availability of more recent data, this review is primarily focused on countries that are in advanced nutrition transition. Prominent deficits in folate, iron, and vitamin D are noted among children/adolescents, women of childbearing age, pregnant women, and the elderly. Reports indicate that food fortification in the region is sporadic and ineffective, and the use of dietary supplements is low. Nutrition monitoring in the region is limited, and gaps in relevant information present challenges for implementing new policies and approaches to address the problem. Government-sponsored initiatives are necessary to assess current dietary intakes/patterns, support nutrition education, and to reduce food insecurity, especially among vulnerable population groups. Public-private partnerships should be considered in targeting micronutrient fortification programs and supplementation recommendations as approaches to help alleviate the burden of micronutrient deficiencies and inadequacies in the Middle East.

The Role of Elements in Anxiety.

Elements (bioelements) are necessary factors required for the physiological function of organisms. They are critically involved in fundamental processes of life. Extra- and intracellular message and metabolic pathway factors as well as structural components include one or many elements in their functional structure. Recent years have seen an intensification in terms of knowledge gained about the roles of elements in anxiety disorders. In this chapter we present a review of the most important current data concerning the involvement of zinc, magnesium, copper, lithium, iron, and manganese, and their deficiency, in the pathophysiology and treatment of anxiety.

New perspectives on the regulation of iron absorption via cellular zinc concentrations in humans.

Iron deficiency is the most prevalent nutritional deficiency, affecting more than 30% of the total world's population. It is a major public health problem in many countries around the world. Over the years various methods have been used with an effort to try and control iron-deficiency anemia. However, there has only been a marginal reduction in the global prevalence of anemia. Why is this so? Iron and zinc are essential trace elements for humans. These metals influence the transport and absorption of one another across the enterocytes and hepatocytes, due to similar ionic properties. This paper describes the structure and roles of major iron and zinc transport proteins, clarifies iron-zinc interactions at these sites, and provides a model for the mechanism of these interactions both at the local and systemic level. This review provides evidence that much of the massive extent of iron deficiency anemia in the world may be due to an underlying deficiency of zinc. It explains the reasons for predominance of cellular zinc status in determination of iron/zinc interactions and for the first time thoroughly explains mechanisms by which zinc brings about these changes.

Omega 3 polyunsaturated fatty acids and the treatment of depression.

Depression is a common, recurrent, and debilitating illness that has become more prevalent over the past 100 years. This report reviews the etiology and pathophysiology of depression, and explores the role of omega 3 polyunsaturated fatty acids (n-3 PUFA) as a possible treatment. In seeking to understand depression, genetic factors and environmental influences have been extensively investigated. Research has led to several hypotheses for the pathophysiological basis of depression but a definitive pathogenic mechanism, or group thereof, has hitherto remained equivocal. To date, treatment has been based on the monoamine hypothesis and hence, selective serotonin reuptake inhibitors have been the most widely used class of medication. In the last decade, there has been considerable interest in n-3 PUFAs and their role in depression. These fatty acids are critical for development and function of the central nervous system. Increasing evidence from epidemiological, laboratory, and randomized placebo-controlled trials suggests deficiency of dietary n-3 PUFAs may contribute to development of mood disorders, and supplementation with n-3 PUFAs may provide a new treatment option. Conclusions based on systematic reviews and meta-analyses of published trials to date vary. Research into the effects of n-3 PUFAs on depressed mood is limited. Furthermore, results from such have led to conflicting conclusions regarding the efficacy of n-3 PUFAs in affecting reduction in symptoms of depression. PUFAs are generally well tolerated by adults and children although mild gastrointestinal effects are reported. There is mounting evidence to suggest that n-3 PUFAs play a role in depression and deserve greater research efforts.

Feeding the brain - The effects of micronutrient interventions on cognitive performance among school-aged children: A systematic review of randomized controlled trials.

BACKGROUND & AIMS: Micronutrients are essential for brain development with deficiencies in specific nutrients linked to impaired cognitive function. Interventions are shown to be beneficial to children's mental development, particularly in subjects who were micronutrient-deficient at baseline but results on healthy subjects remain inconsistent. This systematic review evaluated the effect of micronutrient inventions on different cognitive domains. Studies conducted in both developing and developed countries, and trials that investigate the effect of both single and multiple micronutrient intervention were reviewed. METHODS: Systematic searches of Medline, CINAHL Plus and Academic Search database were undertaken to identify trials published after year 2000. Randomized controlled trials (RCTs) that evaluate the effect of micronutrients on cognitive performance or academic performance among children aged 4-18 years were included. RESULTS: 19 trials were identified from 18 articles. The major cognitive outcomes assessed included fluid intelligence, crystallized intelligence, short-term memory, long-term memory, cognitive processing speed, attention and concentration, and school performance. Eight of ten trials assessing fluid intelligence reported significant positive effects of micronutrient supplementation among micronutrient-deficient children, especially those who were iron-deficient or iodine-deficient at baseline. The effects of micronutrient interventions on other domains were inconsistent. CONCLUSION: Improvement in fluid intelligence among micronutrient-deficient children was consistently reported. Further research is needed to provide more definite evidence on the beneficial effects of micronutrient inventions on other cognitive domains and the effects in healthy subjects.

Ulcerative Colitis and Crohn's Disease Are Associated with Decreased Serum Selenium Concentrations and Increased Cardiovascular Risk.

The incidence of inflammatory bowel disease (IBD) and associated oxidative stress is increasing. The antioxidant mineral selenium (Se) was measured in serum samples from 106 IBD patients (53 with ulcerative colitis (UC) and 53 with Crohn's disease (CD)) and from 30 healthy controls. Serum Se concentrations were significantly lower in UC and CD patients than in healthy controls (p < 0.001) and significantly lower in CD patients than in UC patients (p = 0.006). Se concentrations in patients were significantly influenced by sex, body mass index (BMI), the inflammatory biomarker α-1-antitrypsin, surgery, medical treatment, the severity, extent, and form of the disease and the length of time since onset (p < 0.05). Se concentrations in IBD patients were positively and linearly correlated with nutritional (protein, albumin, prealbumin, cholinesterase and total cholesterol) and iron status-related (hemoglobin, Fe and hematocrit) parameters (p < 0.05). A greater impairment of serum Se and cardiovascular status was observed in CD than in UC patients. An adequate nutritional Se status is important in IBD patients to minimize the cardiovascular risk associated with increased inflammation biomarkers, especially in undernourished CD patients, and is also related to an improved nutritional and body iron status.

Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle.

Carnitine is needed for transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent ß-oxidation. Carnitine can be synthesized by the body and is also obtained in the diet through consumption of meat and dairy products. Defects in carnitine transport such as those caused by defective activity of the OCTN2 transporter encoded by the SLC22A5 gene result in primary carnitine deficiency, and newborn screening programmes can identify patients at risk for this condition before irreversible damage. Initial biochemical diagnosis can be confirmed through molecular testing, although direct study of carnitine transport in fibroblasts is very useful to confirm or exclude primary carnitine deficiency in individuals with genetic variations of unknown clinical significance or who continue to have low levels of carnitine despite negative molecular analyses. Genetic defects in carnitine biosynthesis do not generally result in low plasma levels of carnitine. However, deletion of the trimethyllysine hydroxylase gene, a key gene in carnitine biosynthesis, has been associated with non-dysmorphic autism. Thus, new roles for carnitine are emerging that are unrelated to classic inborn errors of metabolism.

Anthracycline-Induced Cardiotoxicity in Young Cancer Patients: The Role of Carnitine.

While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling. Even if several guidelines currently exist for monitoring cancer patients treated with cardiotoxic therapies who are at high risk for heart failure, much work remains to be done in finding reliable markers for screening for cardiac dysfunction. Studies from our group have identified alterations in L-carnitine in cancer survivors. While additional investigations are needed, preliminary studies suggest a role for carnitine in primary prevention (during treatment) and secondary prevention (to improve function after treatment).

Round Table Discussion.

The 1st International Carnitine Working Group concluded with a round table discussion addressing several areas of relevance. These included the design of future studies that could increase the amount of evidence-based data about the role of carnitine in the treatment of fatty acid oxidation defects, for which substantial controversy still exists. There was general consensus that future trials on the effect of carnitine in disorders of fatty acid oxidation should be randomized, double-blinded, multicentered and minimally include the following diagnoses: medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency. Another area that generated interest was trials of carnitine in cardiomyopathy and, especially, the use of biomarkers to identify patients at greater risk of cardiotoxicity following treatment with anthracyclines. The possibility that carnitine treatment may lead to improvements in autistic behaviors was also discussed, although the evidence is still not sufficient to make any firm conclusions in this regard. Preliminary data on carnitine levels in children and adolescents with primary hypertension, low birth weight and nephrotic syndrome was also presented. Lastly, the panelists stressed that there remains an objective need to harmonize the terminology used to describe carnitine deficiencies (e.g., primary, secondary and systemic deficiency).