Prescription of trace elements in adults on home parenteral nutrition: current practice based on the Canadian Home Parenteral Nutrition Registry.

BACKGROUND: Since the introduction of long-term parenteral nutrition (PN), morbidity due to inadequate replacement or toxicity of routinely administered trace elements has been well described. After decades of experience, much debate still exists about optimal supplementation. In practice, trace elements (TEs) seem to be frequently provided by prescribing an all-inclusive commercial multi-TE admixture with little dosage flexibility. AIM: Our goal was to review TE supplementation practice among 5 PN support centers across Canada, through a retrospective review of the Canadian Home PN Registry. METHODS: Baseline demographic, clinical, and biochemical parameters along with information regarding the PN prescription of 135 patients with complete records were retrieved from the registry database collected between 2005 and 2007. TE supplementation prescriptions were compared with recent guidelines as well as between groups of patients with different PN indications and dietary intake status. Consent was signed by all participating patients. RESULTS: The average daily PN concentrations of TE were as follows: zinc, 8.6 ± 5.5 mg (130.92 ± 84.23 µmol); manganese, 452 ± 184 µg (8.22 ± 3.34 µmol); selenium, 78 ± 45 µg (0.99 ± 0.57 µmol); chromium, 11 ± 5 µg (0.21 ± 0.10 µmol); copper, 0.64 ± 0.35 mg (10.11 ± 5.58 µmol); and iodine, 77 ± 42 µg (0.61 ± 0.33 µmol). The mean daily supplementation of zinc, manganese, copper, and selenium exceeded published recommendations. Patients' underlying anatomy or indication for PN did not significantly influence decisions regarding replacement standards. CONCLUSION: Parenteral TE supplementation in Canadian PN programs needs to be reviewed and adjusted according to most current guidelines. This may require a reevaluation of the commercial TE preparations currently available in Canada and potential new products worldwide to avoid oversupplementation and potential toxicity.

Canadian home parenteral nutrition (HPN) registry: validation and patient outcomes.

BACKGROUND: In Canada, there are an estimated 400 home parenteral nutrition (HPN) patients. In 2006, a registry was created to gather patient outcome information. The aim of this study was to validate the registry and report on HPN patient outcomes. METHODS: Several demographic, clinical parameters were collected. For the validation, paired t test and intraclass correlation coefficient (ICC) were used to assess agreement between repeat entries. For the outcome report, paired t test was used to assess changes, and survival analysis was performed using the Kaplan-Meier method. Results are expressed as mean ± SEM. RESULTS: On validation, there was high correlation/agreement (P < .05) for most parameters except vascular access/line sepsis, liver disease (ultrasound, biopsy, diagnoses), and hospitalizations. For the outcome report, 96 patients had their data entered at 2.24 ± 0.11 years after baseline. Over the period, there was a significant reduction in PN calories (P = .001) and proteins (P < .001). There were no significant changes in nutrition parameters and laboratory results except for lower platelet counts (P = .028), lower plasma potassium (P = .030), and a trend toward an increase in bilirubin from 19.29 ± 4.65 to 29.06 ± 8.73 µmol/L (P = .071). The QOL decreased significantly over time (P < .001) and the survival on HPN was 17.67 ± 1.89 years. CONCLUSIONS: The registry is a valid tool to assess several clinical parameters. On follow-up, HPN patients maintain good nutrition status while PN is reduced but do have a reduced quality of life.

Successful management of the short bowel syndrome.

Intestinal failure manifests as diarrhoea, fluid and electrolyte imbalance and malabsorption caused due to surgical resection of small intestine or very rarely due to nonfunctioning of large segment of bowel. Management of short bowel syndrome is quite challenging which requires better understanding of the site and extent of resected segment, pathophysiology of the remaining segment and the time of adaptation. Initial management includes control of diarrhoea with adequate fluid and electrolyte management which is critical for stabilization of the patient. Multidisciplinary approach to the patient is needed.

Renal effects of long-term treatment with 5-aminosalicylic acid.

BACKGROUND: A number of case reports link the use of 5-aminosalicylic acid (5-ASA) to interstitial nephritis in patients with inflammatory bowel disease (IBD). OBJECTIVE: To investigate whether the long-term use of 5-ASA has harmful effects on renal function in patients with IBD. METHODS: A retrospective analysis of 171 consecutive outpatients with Crohn's disease or ulcerative colitis was conducted. Serum creatinine levels and body weight were measured before and after treatment to calculate the creatinine clearance (CrCl) rate. RESULTS: In 171 patients (93 women, 78 men), the mean (+/- SD) dose of 5-ASA was 3.65+/-0.85 g/day with a cumulative dose of 11+/-7.7 kg over an interval of 8.4+/-5.9 years. Serum creatinine concentrations increased from 76.8 micromol/L to 88.7 micromol/L (n=171; P<0.0001) and the CrCl rate fell significantly from 104.6 mL/min to 93.1 mL/min (n=81; P<0.0001). There was one case of interstitial nephritis reported. Treatment groups included mesalamine (74.3%), sulfasalazine (15.2%) and combination (sulfalsalazine/mesalamine [10.5%]) with treatment durations of 7.2+/-4.5, 12.3+/-8.7 and 11.2+/-6.7 years, respectively. The duration of treatment was the most important covariate for change in CrCl and when analyzed by treatment group, those treated with sulfasazine had a strong correlation (r=-0.54, P=0.0145), while nonsignificant in the mesalamine group (r=0.06, P=0.7017). The decline in CrCl was negatively correlated with the pretreatment CrCl rate (r=-0.34; P=0.0024) and positively correlated with the mean daily dose of 5-ASA (r=0.32; P=0.0034). CONCLUSION: The present study is the first to demonstrate a significant dose- and treatment duration-dependant decline in CrCl. The risks need to be further evaluated because 5-ASA is widely used for long-term maintenance therapy in patients with IBD.

Relationship between metabolism and peripheral blood mononuclear cell mitochondrial complex I activity before and after a short-term refeeding in weight-losing cancer patients.

BACKGROUND AND AIMS: Previous investigations showed that mitochondrial complex I activity seems to be a specific marker of dietary malnutrition in human. Since cancer has a more complex etiology than simple calorie deficiency, the aim of this study was to investigate the relationship between mitochondrial complex I activity and cancer. METHODS: Nine cancer patients (CaPs) with weight loss and 14 age-matched healthy volunteers (HVs) were recruited. Body mass index (BMI), body composition as well as resting energy expenditure (REE) and RQ were measured. Mitochondrial complex I activity was measured as described previously in isolated peripheral blood mononuclear cells. Six patients were investigated again after 7 days of refeeding. RESULTS: Weight loss in CaPs was mainly due to a loss of fat mass (FM), while fat-free mass (FFM) was preserved. The RQ was significantly lower in CaPs compared to HVs (P<0.001) and peripheral blood mononuclear cell complex I activity was significantly correlated with the %FM and RQ in CaPs. Furthermore, complex I activity increased significantly after 1 week of refeeding. CONCLUSIONS: Our study showed that mitochondrial complex I activity was inversely correlated to parameters of increased fat oxidation and reduced FM, which are indices of dietary insufficiency rather than loss of lean body mass, which is an index of increased catabolism in cancer.

Enteral and parenteral nutrition: evidence-based approach.

Nutrition support for patients in hospital has become an essential form of therapy. Total parenteral nutrition (TPN) was the preferred way of giving nutrition to hospital patients for many years but enteral nutrition (EN) is now the preferred route. EN is believed to promote gut function and prevent translocation of intestinal bacteria, thus reducing the incidence of sepsis in critically ill patients. In consequence, the use of TPN has been discouraged as a dangerous form of therapy. Critical review of the data suggests that in the human subject TPN does not cause mucosal atrophy or increase translocation of bacteria through the small intestine. However, overfeeding, which is easy with TPN, can explain the results of studies which have shown that TPN increases sepsis. Furthermore, the risks of TPN-induced complications have been exaggerated. When there is risk of malnutrition and EN is not tolerated, or there is gut failure, TPN is an equally effective and safe alternative.

Total parenteral nutrition: potion or poison?

The role of nutritional support in clinical care has burgeoned over the past 40 y. Initially, total parenteral nutri-tion (TPN) was considered to be the standard of care. Later, the concept that enteral nutrition (EN) promoted gut function and prevented the translocation of intestinal bacteria resulted in EN becoming the standard of care. Furthermore, TPN was consid-ered to be a dangerous form of therapy. Critical review of the data suggests that, in humans, TPN does not cause mucosal atrophy or increase bacterial translocation. Increased sepsis with TPN can be ascribed to overfeeding; the dangers of TPN-induced complications have been exaggerated. TPN is an equally effective alternative to EN when a risk of malnutrition is present and EN is not tolerated or when gut failure is present.

Conditioned nutritional deficiencies in the cardiomyopathic hamster heart.

BACKGROUND: Evidence indicates that nutritional factors may be important in the maintenance of myocyte structure and energetics. The failing myocardium has been reported to exhibit a depletion of several nutrients that are important for the maintenance of intracellular calcium homeostasis and cellular energetics, and levels of oxidative stress. This nutrient depletion may contribute to the progressive deterioration in myocardial structure and function observed in heart failure. OBJECTIVE: To examine the extent to which advanced cardiomyopathy results in a depletion of nutrients and/or metabolites and antioxidants, and whether supplementation with these nutrients may influence cellular structure or function. SUBJECTS AND METHODS: Cardiomyopathic hamsters were randomly placed to one of the three following diet groups: chow; control gelled diet; or a supplemented gelled diet that provided taurine, carnitine, coenzyme Q10, selenium, vitamins E and C, creatine, thiamine and L-cysteine. After approximately three months of supplementation, one group of hamsters underwent functional testing using a modified Langendorff technique with biopsy samples taken for electron microscopy. Myocardial nutrient concentrations were determined in a second group of diseased and nondiseased hamsters of the same age. RESULTS: Cardiomyopathy resulted in a depletion of vitamin E, creatine, carnitine, taurine and coenzyme Q10. Supplementation resulted in improved cardiac ultrastructure, function and contractility compared with nonsupplemented hamsters. CONCLUSIONS: These studies suggest that heart failure results in 'condition-related nutrient deficiencies' that, once corrected, can significantly impact on heart function and structure.

Effect of hypoenergetic feeding and refeeding on muscle and mononuclear cell activities of mitochondrial complexes I--IV in enterally fed rats.

BACKGROUND: Previous studies suggested that cell energetics are altered by malnutrition. OBJECTIVE: We hypothesized that nutritional manipulations influence mitochondrial enzyme activities of the electron transport chain in both skeletal muscle and blood mononuclear cells. DESIGN: After a gastrostomy tube was inserted, 44 rats were randomly assigned to 1 of 4 experimental groups: control fed (CF; 364 kJ/d for 7 d), hypoenergetic fed (HF; 92 kJ/d for 7 d), hypoenergetic protein refed (HPR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d), and hypoenergetic glucose refed (HGR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d). The protein and glucose contents of the liquid formulas were different for the HPR and HGR groups. After mitochondria were isolated from the soleus muscle, the activities of complexes I--IV were measured spectrophotometrically. Because of the lack of available tissue, only the activity of complex I was measured in the mononuclear cell extract. RESULTS: The recovery of complex activities in the CF and HF groups was not significantly different in the mitochondrial fraction of the soleus muscle. Compared with that in the CF group, the activities of complexes I--III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly lower in the HF group. The activities of complexes I--III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly higher in the HPR than in the HF group. The activity of complex IV was generally not affected by nutritional manipulations. CONCLUSION: Malnutrition decreases activities of mitochondrial complexes, which are restored by protein but not glucose refeeding.

A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure.

BACKGROUND: Oxidative stress is increased in patients with congestive heart failure and can contribute to the progressive deterioration observed in these patients. Increased oxidative stress is the result of either an increased production of free radicals or a depletion of endogenous antioxidants, such as vitamin E. OBJECTIVE: We aimed to determine whether vitamin E supplementation of patients with advanced heart failure would modify levels of oxidative stress, thereby preventing or delaying the deterioration associated with free radical injury. DESIGN: Fifty-six outpatients with advanced heart failure (New York Heart Association functional class III or IV) were enrolled in a double-blind randomized controlled trial for 12 wk. At a baseline visit and at 2 follow-up visits, blood and breath samples were collected for the measurement of indexes of heart function and disease state, including malondialdehyde, isoprostanes, and breath pentane and ethane. Quality of life was also assessed at baseline and after 12 wk of treatment. RESULTS: Vitamin E treatment significantly increased plasma concentrations of alpha-tocopherol in the treatment group but failed to significantly affect any other marker of oxidative stress or quality of life. In addition, concentrations of atrial natriuretic peptide (a humoral marker of ventricular dysfunction), neurohormonal-cytokine markers of prognosis, tumor necrosis factor, epinephrine, and norepinephrine were unchanged with treatment and were not significantly different from those in the control group. CONCLUSION: Supplementation with vitamin E did not result in any significant improvements in prognostic or functional indexes of heart failure or in the quality of life of patients with advanced heart failure.

The tissue distribution of tumor necrosis factor-alpha in rats: a compartmental model.

Tumor necrosis factor (TNF) is widely accepted to be the mediator of the cascade of metabolic abnormalities associated with both critical and chronic illness. TNF binding to cell surface receptors mediates its physiologic actions, although the exact mechanism of TNF action is unknown. Therefore, this study was designed to investigate the in vivo metabolism of TNF using a mathematical model to examine tissue uptake and loss of TNF over time. Two distinct patterns of TNF uptake were observed. Muscle tissues were found to accumulate TNF over the entire experimental period, whereas the visceral organs were found to have a rapid initial accumulation of TNF followed by a rapid loss of TNF back to the plasma or out into the bile or the urine. These patterns of TNF binding and retention may reflect the number of TNF receptors or their affinity for TNF, as well as the balance between cell surface and soluble TNF receptors. Furthermore, TNF binding patterns provide insight into the biologic action of TNF at these sites.

Conditioned nutritional requirements and the pathogenesis and treatment of myocardial failure.

The majority of symptomatic patients with congestive heart failure have been shown to be significantly malnourished. Myocardial and skeletal muscle energy reserves are also diminished. Total daily energy expenditure in these patients is less than that in control individuals, and high protein-calorie feeds do not reverse the abnormalities; thus, the wasting that occurs in patients with congestive heart failure is metabolic rather than because of negative protein-calorie balance. Several specific deficiencies have been found in the failing myocardium: a reduction in the content of L-carnitine, coenzyme Q10, creatine and thiamine, nutrient cofactors that are important for myocardial energy production; a relative deficiency of taurine, an amino acid that is integral to the modulation of intracellular calcium levels; and an increase in myocardial oxidative stress, and a reduction of both endogenous and exogenous antioxidant defences. In addition, these processes may influence skeletal muscle metabolism and function. Cellular nutritional requirements conditioned by metabolic abnormalities in heart failure are important considerations in the pathogenesis of the skeletal and cardiac muscle dysfunction. A comprehensive restoration of adequate myocyte nutrition would seem to be essential to any therapeutic strategy designed to benefit patients suffering from this disease.

Nutritional and metabolic effects of the endotoxin bacterial lipopolysaccharide in orally and parenterally fed rats.

BACKGROUND: Animals treated with tumor necrosis factor alpha (TNF-alpha) developed severe metabolic abnormalities despite receiving sufficient protein and energy by total parenteral nutrition (TPN). OBJECTIVE: We sought to investigate the nutritional and metabolic effects of bacterial lipopolysaccharide (LPS) in rats. DESIGN: Rats were randomly allocated to 5 groups: oral nutrition (ON control; n = 7), TPN control (n = 7), ON+LPS (n = 6), TPN+LPS (n = 9), and pair fed (PF) in relation to ON+LPS (n = 6). RESULTS: Body weight decreased significantly as diet consumption decreased in the ON+LPS and PF groups compared with the ON control group. Relative carcass weights were significantly lower in the TPN+LPS and ON+LPS groups than in their respective control groups. Diaphragm and extensor digitorum longus weights were significantly lower in the ON+LPS and PF rats, but not in the TPN+LPS rats, compared with their respective controls. Biochemical abnormalities and plasma corticosterone concentrations were greater in the TPN+LPS group than in the other groups. CONCLUSIONS: These data suggest that provision of sufficient protein and energy by TPN does not prevent general carcass wasting induced by LPS but may protect individual muscles. However, compared with an oral ad libitum diet, TPN providing sufficient protein and energy worsens the biochemical abnormalities induced by LPS. More rapid clearance of TNF-alpha and low corticosterone concentrations in weight-losing animals may help reduce the severity of the metabolic effects of LPS.

Vegetable proteins: are they nutritionally equivalent to animal protein.

On the basis of the rate of animal growth, proteins have been traditionally classed as high quality, such as egg and milk protein, or low quality such as gluten. In general, vegetable proteins are of low quality but soy protein is an exception. The paper by Capristo et al. in this issue of the journal has shown that enteral formulations consisting of soy protein are as effective nutritionally as enteral formulations containing milk protein.

Recurrent Crohn's disease in the duodenum and jejunum following extensive small bowel resection and jejunocolonic anastamosis: radiologic findings in twenty-five patients.

BACKGROUND: To evaluate the radiologic features of recurrent Crohn's disease after extensive enteric resection and jejunocolostomy. METHODS: We reviewed the small bowel studies of 25 patients with recurrent enteritis and less than 125 cm of jejunum following enteric resection and jejunocolostomy and the studies of 27 patients with jejunitis in an intact jejunum. RESULTS: Twenty-three patients with recurrences had neoterminal jejunitis, six under 10 cm, 10 over 10 cm and continuous, and seven with skip lesions (six jejunal, one duodenal). Two had isolated jejunitis or duodenitis. Three with continuous disease had lengthy recurrences. Enteritis showed only one or two abnormalities in 12 of 25 patients with recurrences and in two of 27 with disease in the intact jejunum. Recurrent jejunitis and jejunitis in the intact jejunum showed similar frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, featureless mucosa, and polyps, and significantly different frequencies only of mesenteric masses. Recurrent jejunitis and terminal ileitis showed significantly different frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, and mesenteric masses, and similar frequencies only of a featureless mucosa. CONCLUSIONS: The neoterminal jejunum is the most common site of recurrence and the only site in almost 25%. Jejunitis remote from the fecal stream is also frequent, but duodenitis is not. Recurrences are seldom extensive and often show only one or two radiographic findings. The frequencies of most lesions in recurrent jejunitis do not differ significantly from those in jejunitis in the intact jejunum but do differ from those in terminal ileitis.

Effect of nutrition on tumor necrosis factor receptors in weight-gaining and -losing rats.

Previous studies showed that weight-gaining rats had greater retention and reduced turnover of 125I-labeled tumor necrosis factor (TNF)-alpha in the circulation compared with weight-losing animals. We therefore tested the hypothesis that protein-energy restriction with weight loss reduces the levels of soluble TNF-alpha receptor (sTNFR) and membrane TNFR (mTNFR) and the cellular expression of TNF-alpha mRNA. Twenty-six male rats weighing 200-220 g were fed a liquid formula diet for 10 days and divided equally into weight-gaining rats meeting all nutritional requirements (WG rats) and weight-losing rats with protein-energy restriction (WL rats). 125I-TNF-alpha binding was demonstrated in plasma and plasma membrane to proteins of molecular masses of 92 and 243 kDa, a finding identical to that seen with purified human p55. Excess unlabeled TNF-alpha displaced the binding showing its specificity. The degree of binding to plasma protein and liver plasma membrane was markedly reduced in WL rats. Northern analysis showed that the expression of p55 mRNA was increased in the lungs and reduced in kidneys of WL compared with WG rats. The expression of p75 mRNA was not influenced by the nutritional status. We conclude that levels of sTNFR and mTNFR were reduced in WL rats. Reduced sTNFR and liver mTNFR are not due to a reduction in the expression of either p55 or p75 mRNA in WL rats. Reduced mTNFR, together with reduced shedding of soluble receptors, may have a protective role in WL rats.

The role of chromium in nutrition and therapeutics and as a potential toxin.

Since the 1950s it has been known that chromium is important for the expression of glucose tolerance and that in chromium deficiency the use of glucose is impaired. Chromium has been recognized as an essential nutrient since the finding of low-molecular-weight chromium as a biological modifier of insulin action and the clinical demonstration of deficiency associated with glucose intolerance that responded to the administration of chromium. The major impediment to the use of orally administered chromium is poor absorption of trivalent chromium in its inorganic form. Trivalent chromium is more available in yeast and, more recently, as chromium picolinate for oral absorption. The widespread use of these supplements has resulted in controversy regarding chromium's role as a nutrient, its use for treatment of insulin resistance, and its potential toxicity. This report reviews the evidence for the potential toxicity of chromium supplements in contrast with its usefulness as a nutrient or therapeutic agent in the treatment or prevention of insulin resistance.