Selenium supplementation in patients with peripartum cardiomyopathy: a proof-of-concept trial.

BACKGROUND: We studied the efficacy and safety of selenium supplementation in patients who had peripartum cardiomyopathy (PPCM) and selenium deficiency. METHODS: We randomly assigned 100 PPCM patients with left ventricular ejection fraction (LVEF) < 45% and selenium deficiency (< 70 µg/L) to receive either oral Selenium (L-selenomethionine) 200 µg/day for 3 months or nothing, in addition to recommended therapy, in an open-label randomised trial. The primary outcome was a composite of persistence of heart failure (HF) symptoms, unrecovered LV systolic function (LVEF < 55%) or death from any cause. RESULTS: Over a median of 19 months, the primary outcome occurred in 36 of 46 patients (78.3%) in the selenium group and in 43 of 54 patients (79.6%) in the control group (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.43-1.09; p = 0.113). Persistence of HF symptoms occurred in 18 patients (39.1%) in the selenium group and in 37 patients (68.5%) in the control group (HR 0.53; 95% CI 0.30-0.93; p = 0.006). LVEF < 55% occurred in 33 patients (71.7%) in the selenium group and in 38 patients (70.4%) in the control group (HR 0.91; 95% CI 0.57-1.45; p = 0.944). Death from any cause occurred in 3 patients (6.5%) in the selenium group and in 9 patients (16.7%) in the control group (HR 0.37; 95% CI 0.10-1.37; p = 0.137). CONCLUSIONS: In this study, selenium supplementation did not reduce the risk of the primary outcome, but it significantly reduced HF symptoms, and there was a trend towards a reduction of all-cause mortality. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03081949.

Selenoprotein-P Deficiency Predicts Cardiovascular Disease and Death.

Selenoprotein-P (SELENOP) is the main carrier of selenium to target organs and reduces tissue oxidative stress both directly and by delivering selenium to protective selenoproteins. We tested if the plasma concentration of SELENOP predicts cardiovascular morbidity and mortality in the primary preventive setting. SELENOP was measured from the baseline exam in 2002-2006 of the Malmö Preventive Project, a population-based prospective cohort study, using a validated ELISA. Quintiles of SELENOP concentration were related to the risk of all-cause mortality, cardiovascular mortality, and a first cardiovascular event in 4366 subjects during a median (interquartile range) follow-up time of 9.3 (8.3-11) years using Cox proportional Hazards Model adjusting for cardiovascular risk factors. Compared to subjects in the lowest quintile of SELENOP, the risk of all three endpoints was significantly lower in quintiles 2-5. The risk (multivariate adjusted hazard ratio, 95% CI) decreased gradually with the lowest risk in quintile 4 for all-cause mortality (0.57, 0.48-0.69) (p < 0.001), cardiovascular mortality (0.52, 0.37-0.72) (p < 0.001), and first cardiovascular event (0.56, 0.44-0.71) (p < 0.001). The lower risk of a first cardiovascular event in quintiles 2-5 as compared to quintile 1 was significant for both coronary artery disease and stroke. We conclude that the 20% with lowest SELENOP concentrations in a North European population without history of cardiovascular disease have markedly increased risk of cardiovascular morbidity and mortality, and preventive selenium supplementation studies stratified for these subjects are warranted.

Zinc deficiency and its management in the pediatric population: a literature review and proposed etiologic classification.

Zinc is a trace element essential to the gastrointestinal, immune, integumentary, reproductive, and central nervous systems. Zinc deficiency is prevalent in many areas of the world and is a diagnostically challenging condition. Cutaneous manifestations typically occur in moderate to severe zinc deficiency and present as alopecia and dermatitis in the perioral, acral, and perineal regions. Zinc deficiency is a potentially fatal disease process. The aim of this review is to focus on the cutaneous manifestations, diagnosis, and treatment of zinc deficiency in children, and to propose an etiologic classification system.

Selenium and kidney disease.

Selenium (Se) is a trace element that participates as a cofactor in several enzymes (selenoproteins) which act in the regulation of thyroid hormone metabolism, enzymatic antioxidant defenses and the immune system. Se deficiency has been linked to atherosclerosis-related cardiovascular disease, increased risk of viral infections and even with an increased risk of mortality. Low serum Se levels are a frequent finding in patients with acute kidney injury or chronic kidney disease. The relationship between hyposelenemia and the comorbidities associated with renal disease has not been extensively evaluated. It has been reported that both low serum Se levels and renal insufficiency are associated with an increased risk of coronary heart disease mortality and an increased risk for all-cause mortality in adults older than 35 years. A recent report has suggested that hyposelenemia may contribute to immune dysfunction, increasing the risk of death from infectious disease in hemodialysis patients. Some studies have reported that Se status and immune function improve after oral and intravenous Se supplementation in renal patients, reducing the products of oxidative stress. In summary, although there are intriguing relationships between Se physiology and several derangements and comorbidities associated with acute and chronic kidney disease, only a few studies have analyzed the clinical consequences of hyposelenemia in these patients to date. Available data are encouraging and stimulate interest in further studies to clarify the real extent of Se deficiency and the need for Se supplementation in patients with kidney disease.

Effect of dietary selenium on the progression of heart failure in the ageing spontaneously hypertensive rat.

Oxidative stress has been directly implicated in hypertension and myocardial remodelling, two pathologies fundamental to the development of chronic heart failure. Selenium (Se) can act directly and indirectly as an antioxidant and a lowered Se status leads to a higher risk of cardiovascular disease. This study examined the role of Se on the development of hypertension and subsequent progression to chronic heart failure in spontaneously hypertensive rats (SHR). Three dietary groups were studied: (i) Se-free; (ii) normal Se (50 µg Se/kg food); and (iii) high Se (1000 µg Se/kg food). Systolic blood pressure and echocardiography were used to detect cardiac changes in vivo. At study end, cardiac tissues were assayed for glutathione peroxidase activity, thioredoxin reductase activity, and protein carbonyls. The major finding of this study was the high heart failure-related mortality rate in SHRs fed an Se-free diet (70%). Normal and high levels of dietary Se resulted in higher survival rates of 78 and 100%, respectively. Furthermore, high dietary Se was clearly associated with lower levels of cardiac oxidative damage and increased antioxidant expression, as well as a reduction in disease severity and mortality in the SHR.

Preventive zinc supplementation among infants, preschoolers, and older prepubertal children.

Zinc supplementation trials carried out among children have produced variable results, depending on the specific outcomes considered and the initial characteristics of the children who were enrolled. We completed a series of meta-analyses to examine the impact of preventive zinc supplementation on morbidity; mortality; physical growth; biochemical indicators of zinc, iron, and copper status; and indicators of behavioral development, along with possible modifying effects of the intervention results. Zinc supplementation reduced the incidence of diarrhea by approximately 20%, but the impact was limited to studies that enrolled children with a mean initial age greater than 12 months. Among the subset of studies that enrolled children with mean initial age greater than 12 months, the relative risk of diarrhea was reduced by 27%. Zinc supplementation reduced the incidence of acute lower respiratory tract infections by approximately 15%. Zinc supplementation yielded inconsistent impacts on malaria incidence, and too few trials are currently available to allow definitive conclusions to be drawn. Zinc supplementation had a marginal 6% impact on overall child mortality, but there was an 18% reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc supplementation increased linear growth and weight gain by a small, but highly significant, amount. The interventions yielded a consistent, moderately large increase in mean serum zinc concentrations, and they had no significant adverse effects on indicators of iron and copper status. There were no significant effects on children's behavioral development, although the number of available studies is relatively small. The available evidence supports the need for intervention programs to enhance zinc status to reduce child morbidity and mortality and to enhance child growth. Possible strategies for delivering preventive zinc supplements are discussed.

Global and regional child mortality and burden of disease attributable to zinc deficiency.

BACKGROUND/OBJECTIVES: Zinc is an essential micronutrient and deficiency can lead to an increased risk for infectious diseases and growth retardation among children under 5 years of age. We aimed to estimate disease-specific and all-cause mortality attributable to zinc deficiency. SUBJECT/METHODS: We estimated the prevalence of zinc deficiency in Latin America, Africa and Asia, where based on zinc availability in the diet and childhood stunting rates, zinc deficiency is widespread. The relative risks of death among zinc-deficient children for diarrhea, malaria and pneumonia were estimated from randomized controlled trials. We used the comparative risk assessment methods to calculate deaths and burden of disease (measured in disability-adjusted life years, DALYs) from each of these three diseases attributable to zinc deficiency in these regions. RESULTS: Zinc deficiency was responsible for 453,207 deaths (4.4% of childhood deaths), and 1.2% of the burden of disease (3.8% among children between 6 months and 5 years) in these three regions in 2004. Of these deaths, 260,502 were in Africa, 182,546 in Asia and 10,159 in Latin America. Zinc deficiency accounted for 14.4% of diarrhea deaths, 10.4% of malaria deaths and 6.7% of pneumonia deaths among children between 6 months and 5 years of age. CONCLUSIONS: Zinc deficiency contributes to substantial morbidity and mortality, especially from diarrhea. Zinc supplementation provided as an adjunct treatment for diarrhea may be the best way to target children most at risk of deficiency.

Effects of bovine serum concentrate, with or without supplemental micronutrients, on the growth, morbidity, and micronutrient status of young children in a low-income, peri-urban Guatemalan community.

OBJECTIVE: To determine the effects of dietary supplements containing bovine serum concentrate (BSC, a source of immunoglobulins) and/or multiple micronutrients (MMN) on children's growth velocity, rates of common infections, and MN status. DESIGN: Randomized, controlled, community-based intervention trial. SETTING: Low-income, peri-urban Guatemalan community. SUBJECTS: Children aged 6-7 months initially. INTERVENTIONS: Children received one of four maize-based dietary supplements daily for 8 months, containing: (1) BSC, (2) whey protein concentrate (WPC, control group), (3) WPC+MMN, or (4) BSC+MMN. RESULTS: There were no significant differences in growth or rates of morbidity by treatment group. Children who received MMN had lower rates of anemia and (in the group that received WPC+MMN) less of a decline in serum ferritin than those who did not, but there were no differences in other biochemical indicators of MN status by treatment group. CONCLUSIONS: MMN supplementation reduced anemia and iron deficiency in this population, but the MMN content and source of protein in the supplements did not affect other indicators of MN status, growth or morbidity.

Experimental copper and chromium deficiency and additional molybdenum supplementation in goats. II. Concentrations of trace and minor elements in liver, kidneys and ribs: haematology and clinical chemistry.

Since the mid-1980s a previously undescribed disease has affected moose in south-western Sweden. Investigations made to reveal evidence of a viral aetiology have proved unsuccessful. Trace element studies in apparently healthy moose shot during regular hunting suggested a trace element imbalance, with excessive molybdenum uptake causing secondary copper deficiency. The results also indicated a possible chromium deficiency. To verify this hypothesis, an experimental study was performed in male goats fed a semi-synthetic diet for 1.5 years. The animals were kept and treated in four groups: Controls, Cu-deficient group (group 1), Cr-deficient group (group 2), and combined Cu- and Cr-deficient group with additional supplementation of tetrathiomolybdate for 10 weeks at the end of the study (group 3). The present paper presents tissue contents of trace and minor elements, haematology and clinical chemical parameters. Feed consumption and weight development, as well as pathological and histopathological investigations, were also performed in this study, but these results are presented elsewhere. Changes in trace element concentrations were determined by comparing groups 1, 2 and 3 with the control group. Increased concentrations were observed for Al, Ca, Co, Fe, Mo, Pb, Se in the liver; for Al, Cd, Co, Cr, Mo in the kidneys; and for Mn and Mo in the ribs. Considerable accumulation of Mn in ribs seems to be a useful way to determine oxidative stress. Decreases in Mg and P in all organs and blood serum is characteristic of Cu deficiency and molybdenosis. Also the ratio of Ca/Mg was increased as the result of tissue lesions causing an intracellular increase in Ca and decrease in Mg. The trace element changes observed in group 1 were enhanced by the Mo supplementation in group 3, resulting in characteristic patterns, 'spectra' of changes. The alterations were not as remarkable in group 2 as in the two other groups. However, Cr deficiency considerably influenced Al, Co, V and to a smaller extent also Mn in ribs. In groups 1 and 2, only a few minor changes were detected in the haematological parameters, probably caused by increased adrenal activity after transportation of the animals. In group 3, severe anaemia was present but also a leukopenia. For the different clinical chemical parameters measured, all three groups showed changes, explained mainly by the altered activity of enzymes induced by trace element deficiencies and imbalance. Impaired carbohydrate and lipid metabolism was seen in groups 1 and 3, with increased concentrations of glucose, lactate and triglycerides in serum. Increased concentrations of total bilirubin were measured in all three groups (bile stasis was also seen post mortem). A considerably increased concentration of serum urea was found in group 3, although there were no indications of renal insufficiency or dehydration. Regarding hormones, a substantial decrease was seen in thyroxine (T4) in group 3 as a result of the molybdenosis, but a minor decrease was also seen in group 1. Insulin on the other hand showed increased levels in group 3--and especially in group 2 due to the Cr deficiency but also affected by the molybdenosis. As could be expected, Cu deficiency (groups 1 and 3) caused low levels of caeruloplasmin, secondarily affecting the Fe metabolism in these animals. Protein abnormalities, detected as altered electrophoretic patterns of serum proteins, were also seen mainly in group 3. The findings were also confirmed by multivariate data analysis, where PCA revealed the overall impact of the deficiencies, and PLS regression coefficients indicated the influence on the various analytes.

General theory of paradigms in health.

In Costa Rica, three sequential health paradigms have been identified over the last 50 years. The first began to develop during the 40's and has been called that of the deficiency diseases, since with a diachronic approach it placed excessive emphasis on malnutrition. The second began in 1970 and it is known as that of the infectious diseases, since through a holistic or synchronic approach, it underlined the importance of infections in high rates of morbidity and mortality. The third and last is the paradigm of the chronic diseases, it appeared in the 80's and is presently in process, doing battle with the chronic ailments, life styles, and environment, and it also utilizes a holistic approach. The recognition of these three paradigms has permitted Costa Rica a rapid advance in improving the health of its population, to the point that with a per capita outlay of $130 (US dollars), it has indices similar to those of the industrialized nations. This particular experience could be useful for other less-developed countries that are still applying the paradigm of the deficiency diseases.

PIP: Costa Rica's health care experience is explained in terms of 3 sequential paradigms. The 1st malnutrition paradigm (1940-69) considers the causes of ill health as poverty, ignorance, exploitation, and food shortages. The problems are malnutrition, parasitosis, infectious diseases, high mortality, high rates of hospitalization, and requiring health and hospital based services. The strategies were to improve diet through food distribution, create nutrition departments within the Ministries of Health, increase the number of doctors and nurses, and politicize medicine. Socialism was the model and economic growth and industrialization were seen as prerequisites. Curative medicine was practiced. The attitude was hopelessness is being able to solve problems and acceptance of the status quo. The 2nd infectious disease paradigm (the 1970s) focused the causes as infectious diseases, intestinal parasitosis, unwanted pregnancy, low birth weight, artificial feeding, and limited health services supply, which were given priority. Primary health care for all and health sector reform were some of the strategies. Healthier families were thought to contribute more to economic and social development. Full health services were promoted and the politicization of medicine was reduced. The attitude changed to one of being able to solve one's own problems. The National Health System began to evolve based on a holistic approach where the environment and the life cycle were integrated. Implementation of the national framework was replicated at the regional and local levels; institutions and programs were integrated in a synchronic approach so that the effects of infection, malnutrition, and fertility on human growth and development were considered. Infant mortality dropped by 70%, and infectious diseases were eliminated or greatly reduced. The 3rd chronic disease paradigm (1980s) assumes the causes to be unwanted children, insufficient prenatal and maternity care, inadequate environmental conditions, inadequate life style, and social pathology. The approach is holistic. The philosophical base is the development of individual responsibility and efficient use of science and technology; health contributes to democracy and peace. Prevention, cure, and rehabilitation are equal. The application to other countries must consider that there are more technological options but fewer resources. Rigid and dogmatic plans will not work.

Essential dietary amino acids for growth of larvae of the yellow mealworm, Tenebrio molitor L.

Larvae of the yellow mealworm, Tenebrio molitor L., have been used to evaluate nutritional quality of proteins and protein isolates. However, such investigations have been complicated by lack of knowledge of dietary requirements of the larvae. To determine essential dietary amino acids for growth of Tenebrio molitor, single amino acids were deleted from the amino acid mixture of the diet. Diets were maintained isonitrogenous with supplementary glycine and, in the case of deleted glycine, with glutamic acid. Growth, as measured by gain in weight, and survival were observed over a 4-week period at 27 plus or minus 0.25 degrees and 65 plus or minus 5% relative humidity. The results indicate that larvae of Tenebrio molitor require a dietary source of the same 10 amino acids essential for growth in rats, other vertebrates, and some protozoa. They also showed that serine, tyrosine, glutamic acid, and possibly glycine were dispensable for growth in this insect. Alanine, cystine, proline, and aspartic acid appeared semidispensable. Survival over the 4-week experimental period was unaffected by deleting amino acids from the diet. The results are discussed in relation to amino acid requirements of other insects and to suggested improvement of the diet of the present investigation.