Supplements: questions to ask to reduce confusion.

Written and oral statements concerning supplements are delivered daily to audiences that span the full spectrum of demographics. Yet the common reaction of these audiences to these statements is that they are receiving mixed messages. One source of this confusion could be greatly reduced if each statement concerning supplements always defined the specific parameters of the studies on which the statement is based. Those receiving information about supplements must be made aware that extrapolation of data for one form of a supplement to predict the result of another form many be harmful to one's health. If a statement concerning a supplement does not clearly define the route of delivery, its matrix, the quantity of compound, the purity of compound, and the physiologic condition of the recipient, the statement should be disregarded by all audiences. If the creators of all types of supplement information define these parameters, and if audiences critically review the information provided, confusion concerning supplements will be reduced.

Study of skin rashes after antibiotic use in young children.

Immunoglobulin E (IgE)-mediated drug sensitivity in children is uncommon. However, undefined skin rash following antibiotic ingestion in younger children is commonly observed in clinical practice. We studied 86 consecutively referred patients to our allergy clinic over a 5-year period. We found that the majority of children (80%) with skin rashes were under 3 years of age. All the children had been treated with antibiotics for a bacterial upper respiratory infection (URI; otitis media, sinusitis, or pharyngitis), 73 (85%) had erythematous rash, 13 (15%) had urticaria occurring 3-5 days after the treatment, and 43 (50%) reported a repeated rash with the use of two or more different antibiotics. There were no reports of systemic reactions or histories of accompanying food allergy. When patients were given the suspected antibiotics while they were well, none developed rash. However, in the next bacterial infection, 62 (72%) chose to receive dye-free suspensions of the suspected antibiotics. Only three patients (3.5%) elected for the dye-containing suspension. Of the 62 patients who received dye-free suspensions, only eight developed a mild skin rash, which was managed successfully. We conclude that a practical approach for non-IgE-mediated skin rash needs to be evaluated. The current practice of complete avoidance of the suspected antibiotics without further evaluation may be unwarranted.

Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).

Glutathione is a major cellular antioxidant that protects protein thiols and inhibits cellular damage due to oxygen free radicals. It has been reported previously that patients undergoing dialysis have low levels of blood glutathione, which may lead to increased susceptibility to oxidant stress. L-2-oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises cellular glutathione levels by increasing delivery of cysteine, the rate-limiting substrate for glutathione synthesis. This study investigates the effect of OTZ on blood glutathione in a blinded, placebo-controlled study of patients with chronic renal failure treated by peritoneal dialysis. Twenty patients were randomly selected to receive OTZ (0.5 g three times a day orally with meals) or placebo for 14 d. Patients visited the clinic for predose blood collection and safety evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose [follow-up]). Glutathione concentrations were determined in whole blood by HPLC. OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/- 129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139 mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo group at any patient visit, and levels in the OTZ-treated group returned to baseline at follow-up. There were no serious adverse events attributable to OTZ, and the drug appeared to be well tolerated by patients with renal failure treated by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases blood glutathione levels, which may improve antioxidant status in dialysis patients.

Carnitine in neonatal nutrition.

Experimental evidence from several investigators suggests that carnitine is a conditionally essential nutrient for neonates. If carnitine is a conditionally essential nutrient for the neonate, most neonates on total parenteral nutrition in the United States are not receiving adequate nutritional support. The metabolic functions of carnitine are varied and important in several aspects of neonatal physiology. All neonates receiving breast milk receive dietary carnitine and most neonates receiving enteral infant formulas receive dietary carnitine at a level similar to that of the breast-fed neonate. However, most neonates on total parenteral nutrition receive no dietary carnitine. Investigators have been testing the working hypothesis that carnitine is a conditionally essential nutrient for the neonate for many years. This review discusses (1) data supporting the hypothesis, (2) reasons why it has not been either proved or disproved by now, and (3) the author's view of a prudent approach to dietary carnitine supplementation of neonates.

A phase I/II trial of intravenous L-2-oxothiazolidine-4-carboxylic acid (procysteine) in asymptomatic HIV-infected subjects.

Twenty-four asymptomatic, HIV-1-seropositive subjects with CD4 cell counts of > or = 400/microliters participated in a Phase I/II, dose escalation trial of intravenous L-2-oxothiazolidine-4-carboxylic acid (OTC: Procysteine). Four groups of six subjects each were consecutively assigned to receive OTC at an initial dose of 3, 10, 30, or 100 mg/kg, followed by the same dose given twice weekly for 6 weeks. Increases in whole-blood glutathione were observed in the highest dosage group after 6 weeks of therapy. No effects on changes in CD4 cell counts, viral load, or proviral DNA frequency were observed among the four dosage groups, although a decline in beta 2-microglobulin levels was apparent in the highest dosage group. One subject withdrew due to headaches; other probable adverse events including rash, flushing, pruritus, lightheadedness, and diminished concentration were self-limited.

Feeding practices and nutrition recommendations for infants with cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease characterized clinically by recurrent respiratory tract infections and malabsorption caused by pancreatic insufficiency. Typically diagnosed during infancy or childhood, CF impairs weight gain and growth, increases susceptibility to infection, and decreases longevity. Until recently, no guidelines for infant feedings were available. A consensus report prepared through the Cystic Fibrosis Foundation summarizes guidelines for the optimal nutrition management of patients with CF. This study identified current feeding practices and nutrition recommendations of dietitians who treat infants with CF and compared them with the recommendations of the consensus report. A survey was developed and sent to dietitians (n = 130) who work in accredited cystic fibrosis centers. Eighty-six dietitians (66%) responded after two mailings, and 75 usable surveys were analyzed. The survey investigated practitioners' recommendations for infant formulas, energy intake, nutritional supplements, and pancreatic enzyme supplementation. Protein hydrolysate infant formulas were recommended by most respondents (69%). Energy intake greater than 130% of the Recommended Dietary Allowances (RDAs) was recommended for well-nourished infants with CF and greater than 140% of the RDAs for malnourished infants with CF at 1 year of age. Formula additives, including fat and carbohydrate modules, were used by all respondents and were frequently added to infant foods to increase caloric density. Enteric coated pancreatic enzymes were used by the majority (76%) of dietitians. These findings indicate that most dietitians follow the nutrition guidelines established by the Cystic Fibrosis Foundation consensus report for goals for energy and protein intake, use of nutritional supplements, and replacement of pancreatic enzymes in infants with CF.

Use of the colostrum-deprived piglet to evaluate parenteral feeding formulas.

Several different neonatal and infant piglet models have been invaluable as animal models in nutrition research. A preterm colostrum-deprived piglet model has been developed that is delivered at the desired gestational age, is cared for using the standard of care provided preterm human neonates including procedures for nutritional support and can be studied during pathological conditions induced under controlled conditions. The absolute values for each nutrient requirement would not be expected to be identical for preterm piglets and preterm human neonates. However, the effect of different levels of gestational maturity and superimposed pathophysiologies on nutrient requirements should be similar in the piglet and human neonate.

Medium-chain triglycerides in formula for preterm neonates: implications for hepatic and extrahepatic metabolism.

Medium-chain fatty acids are an important energy source for preterm neonates. Based on assumptions from earlier investigations, 40% to 60% of fatty acids in formula designed for preterm neonates are C6:0 to C12:0. This review will reevaluate these assumptions about C6:0 to C12:0 fatty acids. More recent investigations have indicated that when C6:0 to C12:0 fatty acids are administered in high concentrations, they are metabolized in several tissues by carnitine-dependent mechanisms. Incomplete oxidation of C6:0 to C12:0 fatty acids may result in elevated dicarboxylic acid levels. Feeding formulas high in C6:0 to C12:0 fatty acids has not improved nitrogen retention or growth of preterm neonates. Current data indicate that the fatty acid profiles of formula for preterm neonates are not optimal. Optimization of the fatty acid profile in the diet awaits an improved understanding of the metabolism of fatty acids of all chain lengths in the preterm neonate.

Carnitine and lipid metabolism.

Carnitine, a short-chain nitrogen containing carboxylic acid, is found in meat and dairy foods. Carnitine aids in a shuttle process that makes long-chain, fatty-acid coenzyme A derivatives available for B-oxidation. Normal healthy adults have adequate carnitine stores and do not require dietary carnitine. However, neonates, chronically and critically ill patients with decreased muscle and liver carnitine store seem to benefit from carnitine supplementation to enhance their tolerance of metabolic stress.

Blood carnitine status after orthotopic liver transplantation in patients with end-stage liver disease.

We determined the effects of orthotopic liver transplantation on plasma and red cell carnitine concentrations in patients with end-stage liver disease. Before transplantation, plasma and red cell carnitine were significantly elevated above normal. The partitioning factor (ratio of red cell carnitine to plasma carnitine) was four times greater than that observed in our reference population. After hepatic replacement, plasma and red cell carnitine approached normal levels within 6 mo. The partitioning factor, however, remained elevated at that time. These results indicate that 1) there is no evidence for carnitine deficiency in severe liver disease on the basis of carnitine concentrations in the plasma and red compartments and 2) altered partitioning of carnitine between plasma and red cells persists for greater than or equal to 6 mo after hepatic replacement.

Creation of a regional medical-nutrition education network.

The Southeastern Regional Medical-Nutrition Education Network (SER-MEN) was developed to coordinate and improve nutrition education in a consortium of the medical schools in Alabama, Florida, Georgia, and South Carolina. SERMEN's central office is at the Medical College of Georgia with the testing office at the University of Alabama at Birmingham. Students, faculty, and consultants in nutrition, education, and computer networking work together on projects on each campus that are coordinated and planned through semiannual meetings. A standardized examination was developed with the Nutrition Test-Item Bank to assess nutrition knowledge at various years of medical students from network schools. Each SERMEN school is connected to a microcomputer system at the central office that provides access to a data base of nutrition education and resources on each campus for developing curricula and syllabi. Funding has been provided by societies, foundations, and government agencies.

Fatty acid oxidation in the myocardium: effects of parathyroid hormone and CRF.

Fatty acids constitute an important substrate utilized by the myocardium as a major fuel for energy production; certain data suggest that oxidation of long chain fatty acids (LCFA) may be impaired in uremia, and such a derangement could, in part, contribute to the myocardiopathy of uremia. The latter is associated with secondary hyperparathyroidism and PTH has been shown to affect myocardial metabolism. The present study evaluated in rats the effects of four days administration of PTH and 21 days of chronic renal failure (CRF) with and without excess PTH on oxidation of alpha-ketoglutarate, beta-hydroxybutyric acid, LCFA and short chain fatty acids (SCFA). PTH impaired oxidation of alpha-ketoglutarate, LCFA, SCFA, but not of beta-hydroxybutyric acid and reduced the activity of carnitine palmitoyl transferase (CPT). Inactivation of the PTH abolished its effects. CRF rats with intact parathyroid glands also had impaired oxidation of LCFA and CTP activity. Carnitine contents of myocardium were not altered. The data show that PTH excess in normal rats is associated with impaired oxidation of LCFA and SCFA, and secondary hyperparathyroidism in CRF animals impairs oxidation of LCFA. This effect is due to: 1) reduction in the activity of CPT, a key enzyme for the transport of LCFA to mitochondrial matrix for beta-oxidation; and 2) impairment in beta-oxidation. The data provide for new and additional pathway through which excess PTH and CRF can affect myocardial metabolism.

Cross-sectional study of nutrition knowledge and attitudes of medical students at three points in their medical training at 11 southeastern medical schools.

Eleven southeastern medical schools cooperated to evaluate nutrition knowledge and attitudes of medical students. This study complements previous reports of an examination of entering freshmen and seniors. Average knowledge scores for 165 students tested after basic sciences (preclinical) training in this study were 67 +/- 7% compared with 53 +/- 6% for freshmen and 69 +/- 8% for seniors. The upperclassmen's scores were higher than the freshmen's (p less than 0.001) and varied with the amount of required nutrition teaching. Only 13% of preclinical students perceived nutrition as important to their careers compared with 74% of entering and 59% of graduating students, suggesting that preclinical teaching reduces their sense of relevance of nutrition to medicine. These findings suggest that nutrition knowledge can be increased through preclinical coursework and that the knowledge level can be maintained through the clinical years. However, the positive attitude of freshmen toward nutrition is lost after preclinical training and is only partially regained after the clinical years.

Chronic renal failure, parathyroid hormone and fatty acids oxidation in skeletal muscle.

Fatty acids are an important source of skeletal muscle energy, and certain data suggest oxidation of long-chain fatty acids (LCFA) may be impaired in uremia. This abnormality may in part be responsible for uremic myopathy. Uremia is associated with hyperparathyroidism and PTH affects muscle metabolism; PTH enhances muscle proteolysis and impairs muscle bioenergetics, and it is possible that PTH also affects fatty acids oxidation. The present study examined in rats the effects of 4 days administration PTH and of 21 days of chronic renal failure (CRF) with and without excess PTH on oxidation of LCFA and short-chain fatty acids (SCFA). Both 1-84 and 1-34 PTH impaired oxidation of LCFA but not of a SCFA (beta-hydroxybutyric acid) and reduced the activity of carnitine palmitoyl transferase (CPT). Inactivation of the PTH abolished its effects. CRF rats with intact parathyroid glands had also impaired oxidation of LCFA and of CPT activity. Parathyroidectomy in CRF rats normalized these abnormalities. Carnitine contents of muscle were not altered. The data show that PTH excess in normal or in CRF rats is associated with impaired oxidation of LCFA and this effect is due to reduction in the activity of CPT, a key enzyme for the transport of LCFA to mitochondrial matrix for beta-oxidation. The data demonstrate another toxic effect of PTH on muscle in CRF and provide an additional pathogenic mechanism for uremic myopathy.

Plasma carnitine compartment and red blood cell carnitine compartment of healthy adults.

Carnitine is needed for a variety of important physiological functions in energy metabolism. Assessment of the carnitine status of an individual is compromised by limited data on the number of metabolic compartments of carnitine and their interrelationship, if any. Possible compartmentalization of carnitine in the blood of healthy adults was investigated because blood is one of the more readily available samples for the assessment of carnitine status. The data suggest that blood carnitine is partitioned into a plasma carnitine compartment and a red blood cell carnitine compartment, compartments that are separate and distinct metabolic compartments.

The neonatal piglet as a model for human neonatal carnitine metabolism.

Investigations concerning carnitine metabolism and possible requirements for exogenous carnitine in human preterm neonates are limited by ethical considerations. The neonatal piglet is a potential animal model for these investigations. Tissue carnitine concentrations were determined in fetuses from cross-bred domestic gilts at stages of gestation corresponding to those of neonates found in neonatal intensive care units. Fetal piglet plasma and red blood cell carnitine levels decreased from approximately 90 d to term. Skeletal muscle carnitine increased from 60 d to term. Temporal changes in fetal carnitine concentrations in plasma, red blood cells and skeletal muscle throughout gestation are similar to the pattern reported by our laboratory for the human neonate. Cardiac muscle carnitine increased earlier than skeletal muscle but also continued to increase to term. Carnitine concentrations in fetal liver, kidney and intestine were maximal at 90 d and decreased until term. Similarities in physiology, metabolism and profiles of tissue carnitine concentration between the newborn piglet and the human neonate indicate that the neonatal piglet is an appropriate animal model for investigations concerning neonatal carnitine metabolism.