First Case Report of Fulminant Hepatitis After Laparoscopic Sleeve Gastrectomy Associated with Concomitant Maximal Therapeutic Dose of Acetaminophen Use, Protein Calorie Malnutrition, and Vitamins A and D, Selenium, and Glutathione Deficiencies.

Nonalcoholic fatty liver disease (NAFLD) is increasingly being linked to obesity. Although laparoscopic sleeve gastrectomy (LSG) is effective for weight loss that can ultimately resolve NAFLD, an initial transient deterioration of liver functions could be observed during the first few months post-operatively, after which a subsequent improvement of the liver functions might occur. Rapid weight loss, nutritional deficiencies, and protein malnutrition can all contribute to hepatic dysfunction and can affect the metabolism of medications such as acetaminophen leading to more insult to a compromised liver. We report acute liver failure after LSG associated with protein calorie malnutrition, multiple nutritional deficiencies in addition to concomitant use of therapeutic doses of acetaminophen. Treatment with N-acetylcysteine, and replacement of deficient multivitamins and trace elements resulted in significant improvement in liver functions.

Amino acid profile after oral nutritional supplementation in hemodialysis patients with protein-energy wasting.

OBJECTIVES: Protein-energy wasting (PEW) is highly prevalent in patients on hemodialysis (HD). Oral nutritional supplementation (ONS) is recommended for malnourished patients on HD. The aim of this study was to evaluate ONS on plasma amino acid in HD patients with PEW. METHODS: Thirty-two HD patients with a mean age 59.1 ± 9.5 y with PEW were enrolled into the study. Patients were prescribed ONS (125 mL twice a day for 3 mo) together with dietary advice. The nutritional status was evaluated by means of body mass index, Subjective Global Assessment, and serum albumin and prealbumin levels. The percentages of body fat and lean body mass were measured by means of the near-infrared method. The lean body mass-to-body weight ratios were calculated. Tumor necrosis factor, interleukin-6 and high-sensitivity C-reactive protein, were measured by the enzyme-linked immunosorbent assay method. Serum concentrations of amino acids were measured by the high-performance liquid chromatography method. RESULTS: After 3 mo of ONS, a significant increase of both serum prealbumin and albumin was observed. The concentration of most of the amino acids increased independently on inflammation. CONCLUSIONS: Dietary advice, combined with ONS, is effective in HD patients with PEW. Both dietary advice and ONS are needed to be sure that patients consume an adequate daily amount of calories and protein.

Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Age-related losses of muscle mass, strength, and function (sarcopenia) pose significant threats to physical performance, independence, and quality of life. Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability. OBJECTIVE: To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia. DESIGN: A multicenter, randomized, controlled, double-blind, 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index. The active group (n = 184) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group (n = 196) received an iso-caloric control product to consume twice daily for 13 weeks. Primary outcomes of handgrip strength and SPPB score, and secondary outcomes of chair-stand test, gait speed, balance score, and appendicular muscle mass (by DXA) were measured at baseline, week 7, and week 13 of the intervention. RESULTS: Handgrip strength and SPPB improved in both groups without significant between-group differences. The active group improved more in the chair-stand test compared with the control group, between-group effect (95% confidence interval): -1.01 seconds (-1.77 to -0.19), P = .018. The active group gained more appendicular muscle mass than the control group, between-group effect: 0.17 kg (0.004-0.338), P = .045. CONCLUSIONS: This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in muscle mass and lower-extremity function among sarcopenic older adults. This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability.

Improving the neurodevelopmental outcomes of low-birthweight infants.

Infants born with low birthweight (LBW) have poorer neurodevelopmental outcomes compared with their term counterparts with appropriate weight for gestational age. The perinatal period is a time of high energy and high nutrient needs, and any process, such as preterm birth, poor nutrition or placental insufficiency, that interrupts the concentrated flow of nutrients to the fetus may result in babies with LBW. Therefore, it makes logical sense that at least part of the cognitive deficits may be explained by nutritional deprivation. The nutrients commonly deficient in LBW infants include protein and energy and micronutrients such as iron, zinc and long chain polyunsaturated fatty acids. In this review, we aimed to determine the effect of nutrient supplementation on neurodevelopment in LBW infants. While few trials have supported the hypothesis that nutritional supplementation improves neurodevelopment, many studies are limited by sample size and methodological shortcomings. Further large-scale rigorously designed intervention trials, with long-term neurodevelopment follow-up, are required to determine the optimal nutritional supplements and the timing of their administration to LBW infants.

Taurine supplementation restores insulin secretion and reduces ER stress markers in protein-malnourished mice.

Endoplasmic reticulum (ER) stress is a cellular response to increased intra-reticular protein accumulation or poor ER function. Chronic activation of this pathway may lead to beta cell death and metabolic syndrome (MS). Poor nutrition during perinatal period, especially protein malnutrition, is associated with increased risk for MS in later life. Here, we analyzed the effects of taurine (TAU) supplementation upon insulin secretion and ER stress marker expression in pancreatic islets and in the liver from mice fed a low-protein diet. Malnourished mice had lower body weight and plasma insulin. Their islets secreted less insulin in response to stimulatory concentrations of glucose. TAU supplementation increased insulin secretion in both normal protein and malnourished mice. Western blot analysis revealed lower expression of the ER stress markers CHOP and ATF4 and increased phosphorylation of the survival protein Akt in pancreatic islets of TAU-supplemented mice. The phosphorylation of the mitogenic protein extracellular signal-regulated kinase (ERK1/2) was increased after acute incubation with TAU. Finally, the ER stress markers p-PERK and BIP were increased in the liver of malnourished mice and TAU supplementation normalized these parameters.In conclusion, malnutrition leads to impaired islet function which is restored with TAU supplementation possibly by increasing survival signals and lowering ER stress proteins. Lower ER stress markers in the liver may also contribute to the improvement of insulin action on peripheral organs.

Effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition.

Protein-calorie malnutrition (PCM) could occur frequently in cancer patients and alter the pharmacokinetics of drugs. Also cysteine shows anti-oxidative effect and changes the activities of drug metabolizing enzyme and/or transporters. Herein, we investigated the effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of tamoxifen were assessed using control, CC (control with cysteine), PCM, PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of tamoxifen were further investigated through in vitro transport studies using rat intestine. The AUCs of intravenous tamoxifen in PCM rats were significantly greater than control rats due to the decrease in the hepatic metabolism via CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels by oral cysteine supplement. The AUC of oral tamoxifen in PCM rats was significantly smaller than in control rats mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of tamoxifen probably via intestinal P-gp inhibition. The present study demonstrated that PCM state and/or oral cysteine supplement had a profound impact on the pharmacokinetics of tamoxifen in rats. If the present rat data are extrapolated to humans, the alterations in tamoxifen absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM and/or oral cysteine supplement.

Global micronutrient deficiencies in childhood and impact on growth and survival: challenges and opportunities.

Despite numerous advances and improvements in child health, malnutrition still remains as one of the main public health challenges of the 21st century, particularly in developing countries. It undermines the survival, growth and development of children, and is associated with almost 35% of all deaths in children under the age of 5 years worldwide. An estimated 178 million children are stunted globally, and an additional 19 million children have severe acute malnutrition (wasting). These conditions are very often associated with concomitant micronutrient deficiencies, and among these, vitamin A, iron, zinc and iodine deficiencies are the most prevalent in childhood. Vitamin A and zinc deficiency is associated with an estimated 1 million child deaths and 9% of global childhood disability-adjusted life years. Recent data on the timing of growth retardation and stunting in infants suggest that the onset is commensurate with inappropriate complementary feeding and potentially compounded by maternal undernutrition and intrauterine growth retardation, and that the first 24 months represent a critical window of opportunity for intervention. Given the wide prevalence of multiple micronutrient deficiencies in malnourished children in developing countries, the challenge is to implement intervention strategies that combine appropriate infant and young child feeding with micronutrient interventions at scale. Emerging data from community intervention trials now provide evidence that this is both tangible and can lead to alleviation of childhood undernutrition. Some of these recent findings will be discussed.

Global burden and significance of multiple micronutrient deficiencies in pregnancy.

Maternal mortality, low birthweight infants and childhood stunting continue to be major global public health problems, part of a recurring cycle of disadvantage. Maternal undernutrition in particular is one of the most neglected aspects of nutrition in public health. One possible low-cost public health intervention that might help address these problems is the antenatal provision of multiple micronutrient supplements. If the evidence base could be established, cost-effectiveness found to be acceptable and safety ensured, supplementation could ameliorate the impact of poor nutrition and diets, high disease burdens and the sociocultural factors contributing to these problems. There have been good studies in over a dozen countries addressing some of these issues but with conflicting results. Consequently, at least three meta-analyses have been undertaken to establish significant findings that could help guide policies and programs. They concluded that multimicronutrient supplementation improves birthweight and likely reduces the number of infants born low birthweight. Supplementation with iron-folic acid or multimicronutrients also appears to have positive longer-term impacts on the health and development of the offspring. There remain concerns about possible increased infant mortality in some populations. Given the results of the meta-analyses, cautious scaling-up of country effectiveness trials appears justified with careful monitoring and evaluation.

Effects of cysteine on the pharmacokinetics of docetaxel in rats with protein-calorie malnutrition.

The objective of this study is to report the effects of cysteine on the pharmacokinetics of intravenous and oral docetaxel in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of docetaxel were assessed using control, CC (control with cysteine), PCM and PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of docetaxel were further investigated through in vitro transport studies using rat intestine and Caco-2 cell monolayers. The AUCs (the areas under the plasma concentration-time curve from time zero to time infinity) of intravenous docetaxel in PCM rats were significantly greater than in the control rats because of the significant decrease in the hepatic CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels. The AUC(0-6 h)s of oral docetaxel in PCM rats were significantly smaller than that in the control rats, mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of docetaxel probably via intestinal P-gp inhibition. If the present rat data could be expressed to humans, the alterations in docetaxel absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM state after cysteine supplement.

Effects of renal-specific oral supplementation in malnourished hemodialysis patients.

BACKGROUND: Protein-energy malnutrition is still a problem in patients with chronic renal failure, especially during replacement renal therapy. The chronic inflammatory status in these patients intensifies the malnutrition, as well as making treatment more complicated. The aim of the present study was to estimate the influence of oral supplementation on the nutritional status of malnourished hemodialysis (HD) patients depending on the existence of an inflammatory state. METHODS: To study the influence of oral supplementation on nutrition status, 30 HD patients with protein-energy malnutrition characteristics and 25 well-nourished HD patients were enrolled in the study. Malnourished HD patients were prescribed Renilon 7.5 at an oral intake dose of 125 mL twice a day for 3 months. The nutritional status was characterized based on body mass index, Subjective Global Assessment score, serum albumin and prealbumin concentrations. The intensity of the inflammatory state was determined by C-reactive protein and interleukin-6. Serum concentrations of leptin and adiponectin were also measured. RESULTS: After 3 months of supplementation, malnourished patients had an increase in prealbumin, albumin, and leptin concentrations. No statistically significant differences were observed between patients lacking inflammation and those with inflammation. CONCLUSIONS: The results indicate an improvement in the nutritional status of HD patients who were prescribed an oral supplementation. Furthermore, patients with inflammatory state characteristics also benefited from Renilon 7.5 treatment.

Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats.

AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein-calorie restriction with free access to water (malnutrition group) and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group) were studied. After the undernourishment period (4 weeks with or without alcohol), both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups) and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage) (carnitine groups). No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii) Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P<0·05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (~10 g/100 g, P>·05) was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50 percent protein-calorie restriction with free access to water (malnutrition group) and malnourished rats under the same conditions with free access to a 20 percent alcohol/water solution (alcohol group) were studied. After the undernourishment period (4 weeks with or without alcohol), both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups) and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage) (carnitine groups). No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii) Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P<0.05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (~10 g/100 g, P>.05) was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

Glutamine supplementation does not improve protein synthesis rate by the jejunal mucosa of the malnourished rat.

It has been demonstrated that glutamine, a conditionally essential amino acid, improves nitrogen balance, acts as a stimulant of protein synthesis, and decreases proteolysis in myopathic children. In contrast, other studies have shown no beneficial effect of glutamine supplementation on burn victims or critically ill patients. Nonetheless, we hypothesized that glutamine supplementation would increase the fractional protein synthesis rate (FSR) in the jejunal mucosa of malnourished male Wistar rats. Thus, the objective of the present study was to test the effect of daily oral glutamine supplementation (0.42 g kg(-1) d(-1) for 14 days) on the FSR of the jejunal mucosa of healthy and malnourished rats. A 4-hour kinetic study with l-[1-(13)C]leucine was subsequently performed, and jejunal biopsies were obtained 1.5 cm from the Treitz angle and analyzed. Malnourished rats showed a 25% weight loss and increased urinary nitrogen excretion. Plasma amino acid concentration did not differ between groups. (13)C enrichment in plasma and jejunal cells was higher in the malnourished groups than in the healthy group. The FSR (percent per hour) was similar for the control and experimental groups (P > .05), with a mean range of 22%/h to 27%/h. Oral glutamine supplementation alone did not induce higher protein incorporation by the jejunal mucosa in malnourished rats, regardless of total food intake or the presence or absence of glutamine supplementation.

Zinc increases the effects of essential amino acids-whey protein supplements in frail elderly.

UNLABELLED: Protein undernutrition is frequent in the elderly. It contributes to the development of osteoporosis, possibly via lower IGF-I. Dietary zinc can influence IGF-I production. OBJECTIVES: To determine the influence of dietary zinc addition on IGF-I and bone turnover responses to essential amino acids-whey (EAA-W) protein supplements in frail elderly. DESIGN AND SETTING: A daily oral protein supplement was given to hospitalized patients for 4 weeks. On a randomized, double-blind basis, patients received either an additional 30 mg/day of zinc or control. PARTICIPANTS: Sixty-one hospitalized elderly aged 66.7 to 105.8, with a mini-nutritional assessment score between 17 and 24 were enrolled. MEASUREMENTS: Activities of daily living; dietary intakes; serum IGF-I, IGF-BP3, CrossLapsTM, osteocalcin and zinc were measured before and after 1, 2 and 4 weeks of protein supplementation. RESULTS: Serum IGF-I rapidly increased in both groups. Zinc accelerated this increase with changes of +48.2 +/- 14.3 and +22.4 +/- 4.7% (p < .05) by 1 week, in the zinc-supplemented and control groups, respectively. Zinc significantly decreased the serum bone resorption marker CrossLapsTM by already 1 week. Activities of daily living improved by +27.0 +/- 3.1 and +18.3 +/- 4.5% in zinc-supplemented and control groups, respectively. CONCLUSION: In the elderly, zinc supplementation accelerated the serum IGF-I response to EAA-W protein by 1 week and decreased a biochemical marker of bone resorption.

Effects of dietary medium-chain triacylglycerol on mRNA level of gluconeogenic enzymes in malnourished rats.

We have reported previously that dietary medium-chain triacylglycerol (MCT) improved serum albumin concentration and protein balance in malnourished rats. To clarify the mechanisms for this effect of MCT, hepatic messenger RNA levels of gluconeogenic enzymes, pyruvate dehydrogenase (PDH) and alanine aminotransferase (ALT) were measured in rats fed low-protein diets containing either MCT or isocaloric long-chain triacylglycerol (LCT) for 2 wk. The serum albumin concentration in rats fed the MCT diet was significantly higher compared with those fed the LCT diet. Serum free fatty acids and ketone body fraction were higher in rats fed MCT compared with those fed the LCT diet. The hepatic mRNA level of PDH was significantly lower in rats fed MCT than those fed LCT. But, there was no significant difference between the two groups in mRNA of gluconeogenic enzymes or ALT. These results suggest that ketone bodies, which are an alternative energy source and might spare blood glucose, increase by MCT feeding, and the reason for the PEM (protein-energy malnutrition)-improving effect of MCT is not caused by suppression of gluconeogenesis.

Effect of daily low dose of vitamin A compared with single high dose on morbidity and mortality of hospitalized mainly malnourished children in senegal: a randomized controlled clinical trial.

BACKGROUND: In vitamin A-deficient populations, children hospitalized with infections and/or malnutrition are at particular risk of developing severe vitamin A (VA) deficiency. High-dose VA supplements are recommended as part of the treatment but results on its effect on recovery from morbidity and on prevention from nosocomial morbidity are conflicting. OBJECTIVE: We aimed to assess the effect of a single high dose and daily low dose of VA on hospitalized malnourished children's morbidity. DESIGN: We carried out a double-blind, randomized trial in 604 and 610 Senegalese hospitalized children. The first mentioned batch received a high-dose VA supplement (200,000 IU) on admission, the second a daily low-dose VA supplement (5000 IU per day) during hospitalization. Children were followed up until discharged. Data on all-cause morbidity were collected daily. RESULTS: Survival analysis showed that the incidence of respiratory disease was significantly lower in the low-dose group than in the high-dose group, hazard ratios (HR): 0.26, 95% CI: 0.07-0.92. The duration of respiratory infection was also significantly lower in the low-dose group than in the high-dose group (HR of cure: 1.41, 95% CI: 1.05-1.89). Duration and incidence of diarrhoea were not significantly different between treatment groups. In children with oedema on admission, mortality was significantly lower in the low-dose group (Adjusted odds ratio: 0.21; 95% CI: 0.05-0.99). CONCLUSIONS: Daily low dose of VA compared with single high dose significantly reduced duration and incidence of respiratory infection but not of diarrhoea in hospitalized children.

Polyunsaturated fatty acid (PUFA) changes in serum and liver of undernourished rats given dietary vitamin B6 supplementation.

The influence of vitamin B6 on linoleic (LA), alpha-linolenic (ALA), arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid content in serum and liver of rats fed with protein-energy deficient diets for 90 d, was studied. To estimate the effect of dietary supplementation with vitamin B6 on the composition and level of fatty acids in the serum and liver of rats, two experiments were performed. In these experiments control rats were fed ad libitum semisynthetic isocaloric diets of 1,466.5 kJ/100 g (350 kcal/100 g) throughout 90 d while the examined rats were offered 50% and 30% of the previously determined daily intake of the diet consumed in the control group. The experimental diet was supplemented with vitamin B6 to the level 4-times higher than in the control diet. A reduction to the half consumption of a standard diet supplemented with vitamin B6 caused a significant decrease of LA and ALA in blood serum at 30 and 60 d. At 90 d of the experiment the value of LA was lower and the content of AA was higher in comparison to the control group. After 30 d of consumption of vitamin B6 enriched diet in rats subjected to feed restriction to only 30% of the control intake, an increase of ALA and a decrease of AA, EPA and DHA were noticed in serum. At 60 d an increase of DHA was observed. Ninety days of feeding this diet caused a significant increase of AA level. Feeding animals for 90 d with a vitamin B6 enriched diet, with limited consumption to 50%, caused a significant increase of ALA content in liver. Further limitation of this diet consumption to 30%, caused a significant decrease of LA and ALA and an increase of EPA content.

Effects of cysteine on the pharmacokinetics of intravenous torasemide in rats with protein-calorie malnutrition.

Effects of cysteine on the pharmacokinetics of torasemide were investigated after intravenous administration at a dose of 2 mg/kg to control rats and rats with PCM and PCMC. Torasemide was reported to be mainly metabolized via hepatic CYP2C9 in humans, and human CYP2C9 and male rat CYP2C11 proteins have 77% homology. It has also been reported that in male rats with PCM, the CYP2C11 level decreased to approximately 20% of the control level, but the decreased CYP2C11 level in rats with PCM partially returned to the control level by oral cysteine supplementation (rats with PCMC). Hence, it could be expected that in rats with PCM, some pharmacokinetic parameters of torasemide could be significantly different compared with those in control rats and rats with PCMC; however, they could be not significantly different between control rats and rats with PCMC. This was proven by the following parameters; the AUC (1880, 4080, and 2290 microg x min/mL for control rats and rats with PCM and PCMC, respectively), terminal half-life (188, 277, and 139 min), MRT (154, 323, and 155 min), CL (1.06, 0.491, and 0.943 mL/min/kg), CL(NR) (0.992, 0.430, and 0.874 mL/min/kg), and in vitro intrinsic torasemide disappearance clearance, CL(int) (0.102, 0.0842, and 0.0997 mL/min/mg protein).