Safety and efficacy of an olive oil-based triple-chamber bag for parenteral nutrition: a prospective, randomized, multi-center clinical trial in China.

BACKGROUND: Small studies suggest differences in efficacy and safety exist between olive oil-based (OLIVE) and soybean oil-based (SOYBEAN) parenteral nutrition regimens in hospitalized adult patients. This large, prospective, randomized (1:1), open-label, multi-center, noninferiority study compared the delivery, efficacy, and safety of OLIVE (N = 226) with SOYBEAN (N = 232) in Chinese adults (≥18 years) admitted to a surgical service for whom parenteral nutrition was required. METHODS: Treatments were administered for a minimum of 5 days up to 14 days (to achieve approximately 25 kcal/kg/day, 0.9 g/kg/day amino acids, 0.8 g/kg/day lipid). Impact of treatment on anabolic/catabolic and serum inflammatory, chemistry, and hematological markers, safety, and ease of use were assessed. The primary efficacy variable was serum prealbumin level at Day 5. RESULTS: OLIVE (n = 219) was not inferior to SOYBEAN (n = 224) based on the prealbumin least square geometric mean [LSGM] ratio [95% CI] 1.12 [1.06, 1.19]; P = 0.002), improved the anabolic/catabolic status of patients enrolled in the study, and was well tolerated compared with SOYBEAN. Improved anabolic status was supported by significantly higher levels of prealbumin at Day 5, albumin at Day 5 and IGF-1 at Day 14 in the OLIVE group, while catabolism was similar between groups. C-reactive protein, intercellular adhesion molecule-1, procalcitonin, and oxidation were similar in each group, but infections were significantly lower with OLIVE (3.6% versus 10.4%; P < 0.01). CONCLUSIONS: OLIVE provided effective nutrition, was well tolerated, was associated with fewer infections, and conferred greater ease-of-use than SOYBEAN. TRIAL REGISTRATION: NTC 01579097.

Modulation of endothelial cell integrity and inflammatory activation by commercial lipid emulsions.

BACKGROUND: Thrombosis and immune dysfunction are two important complications that result from the administration of parenteral nutrition. Endothelial cells within the vasculature are crucial components necessary for maintenance of normal coagulation and immune function. METHODS: We compared the effects of three commercial lipid emulsions (LEs; Intralipid®, ClinOleic® [or Clinolipid®], and Omegaven®) differing in the levels of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, and saturated fatty acids upon endothelial cell fatty acid composition using Gas chromatography, endothelial cell integrity by assessing measurement of apoptosis and necrosis using flow cytometry, endothelial cell inflammatory activation by assessing the induction of ICAM-1 by lipopolysaccharide [LPS]), and transcription factor activation (phosphorylation of NF-κB) using western blot analysis. RESULTS: Gas chromatographic analysis confirmed cellular uptake of the fatty acids within the LEs; furthermore, these fatty acid changes reflected the composition of the oils and egg phosphatides used in the manufacturing of these emulsions. However, the kinetics of fatty acid uptake and processing differed between LEs. Fish oil LE negatively impacted cell viability by doubling the percentage of apoptotic and necrotic cell populations quantified by flow cytometry using Annexin V/Fluorescein and propidium iodide. The soybean oil LE did not alter cell viability, while the olive oil-predominate emulsion improved cell viability. All LEs were capable of suppressing LPS-induced ICAM-1 expression; however, the fish oil LE was more potent than the other emulsions. Fish oil LE supplementation of cells also suppressed LPS-induced phosphorylation of NF-κB, while the soybean oil and olive predominant LE had no effect upon NF-κB phosphorylation. CONCLUSIONS: Lipid emulsions are readily incorporated and stored in the form of triacylglycerols. Soybean oil-based, olive oil-predominant and fish-oil based LEs differentially affected endothelial cell integrity. Importantly, these three LEs were capable of suppressing endothelial cell inflammatory response despite their fatty acid content.

A retrospective, observational study of patient outcomes for critically ill patients receiving parenteral nutrition.

OBJECTIVE: To evaluate health care-related utilization for critically ill patients receiving parenteral nutrition (PN) administered via a premixed multichamber bag (MCB) or compounded solutions (COM). DESIGN: A retrospective database analysis of critically ill patients (intensive care unit stay ≥ 3 days) receiving PN and discharged between January 1, 2010, and June 30, 2011, using the Premier Hospital Database. Patients were identified as receiving MCB or COM on the basis of product description codes. Primary outcomes were length of stay (LOS) and total costs. Comorbidities and clinical outcomes were identified using International Classificaion of Diseases, Ninth Revision diagnosis codes. All costs reported were for inpatient services only. Patients receiving MCB and COM were matched on key patient and hospital characteristics using a propensity score methodology. Multivariate regression models for cost and LOS used generalized linear models with a log link and gamma distribution. RESULTS: A total of 42,631 patients met the inclusion criteria (MCB = 5,679; COM = 36,952), and the final matched population included 3,559 patients from each cohort. Baseline patient and hospital characteristics were well matched between groups. Adjusted multivariate models demonstrated a small difference between groups for LOS (MCB = 9.40 days vs. COM = 9.65 days; P = 0.014). In addition, patients receiving MCB incurred approximately 9.1% less in total costs (MCB = $37,790 vs. COM = $41,569; P < 0.001). CONCLUSIONS: Overall, patients receiving MCB and COM experienced similar LOS, though patients receiving MCB had significantly lower overall costs. Interpretation of the study findings is subject to several limitations, and additional studies that include explicit identification of the method for compounding are needed.

Narrative Review of n-3 Polyunsaturated Fatty Acid Supplementation upon Immune Functions, Resolution Molecules and Lipid Peroxidation.

Fish oil supplementation is commonplace in human nutrition and is being used in both enteral and parenteral formulations during the treatment of patients with a large variety of diseases and immune status. The biological effects of fish oil are believed to result from their content of n-3 polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These fatty acids are known to have numerous effects upon immune functions and are described as immunomodulatory. However, immunomodulatory is a nondescript term that encompasses immunostimulation and immunosuppression. The primary goal of this review is to better describe the immune effects of n-3 PUFA as they relate to immunostimulatory vs. immunosuppressive effects. One mechanism proposed for the immune effects of n-3 PUFA relates to the production of specialized pro-resolving mediators (SPMs). A second goal of this review is to evaluate the effects of n-3 PUFA supplementation upon production of SPMs. Although n-3 PUFA are stated to possess anti-oxidative properties, these molecules are highly oxidizable due to multiple double bonds and may increase oxidative stress. Thus, the third goal of this review is to evaluate the effects of n-3 PUFA upon lipid oxidation. We conclude, based upon current scientific evidence, that n-3 PUFA suppress inflammatory responses and most cellular immune responses such as chemotaxis, transmigration, antigen presentation, and lymphocyte functions and should be considered immunosuppressive. n-3 PUFA induced production of resolution molecules is inconsistent with many resolution molecules failing to respond to n-3 PUFA supplementation. n-3 PUFA supplementation is associated with increased lipid peroxidation in most studies. Vitamin E co-administration is unreliable for prevention of the lipid peroxidation. These effects should be considered when administering n-3 PUFA to patients that may be immunosuppressed or under high oxidative stress due to illness or other treatments.

Oleic acid inhibits stearic acid-induced inhibition of cell growth and pro-inflammatory responses in human aortic endothelial cells.

Saturated fatty acids (SFAs), significant components of both enteral/parenteral nutritional formulations (including diet), are linked to cardiovascular disease complications, such as atherosclerosis. We investigated whether oleic acid (C18:1n-9) reduces the growth inhibitory and pro-inflammatory effects of the stearic acid (C18:0) in human aortic endothelial cells (HAEC). Stearic acid induced growth inhibition at concentrations less than 50 µM, whereas higher concentrations invoked cytotoxicity. Stearic acid-induced growth inhibition and cytotoxic effects were eradicated upon cosupplementation with oleic acid (25 µM). Oleic acid (as low as 5 µM) also inhibited the stearic acid-induced increase in intercellular adhesion molecule-1 (ICAM-1) expression. Stearic acid-induced phosphorylation of nuclear factor-kappa B (NF-κB), a transcriptional regulator of ICAM-1, was also reduced by oleic acid. HAECs supplemented with either stearic or oleic acid resulted in cellular incorporation of C18:0 and C18:1n-9, respectively. Stearic acid primarily incorporated into phospholipids without increasing the total fatty acid content in HAECs. In contrast, oleic acid, with or without stearic acid, incorporated into both phospholipids and triglycerides, with a significant increase in total fatty acid amounts in triglycerides. Our data suggest that oleic acid has the ability to reduce the inflammatory effects of long-chain SFAs in HAECs through reducing cellular stearic acid incorporation and NF-κB activation.

n-3 fatty acids prevent whereas trans-fatty acids induce vascular inflammation and sudden cardiac death.

n-3 PUFA have well-recognised cardio-beneficial effects. In contrast, premature coronary deaths are associated with consumption of high levels of trans-fatty acids (TFA). The present study determined the effects of n-3 PUFA and TFA on sudden cardiac death and vascular inflammation. A rat coronary ligation model was used to study the effect of fatty acids on sudden cardiac death, whereas a mouse femoral artery ligation model was used to study compensatory vascular remodelling. Human aortic endothelial cells (HAEC) were utilised for the in vitro studies to investigate expression of inflammatory molecules. Feeding animals an n-3 PUFA-enriched diet caused a sevenfold increase in plasma n-3 PUFA compared with that of the TFA-fed group, whereas a TFA-enriched diet caused a 2.5-fold increase in plasma TFA compared with the n-3 PUFA group. Animals on a TFA diet had a lower survival rate due to sudden cardiac death and exhibited variable degrees of aortic atherosclerotic lesions. Animals on a TFA diet had diminished hindlimb collateral growth, whereas animals on the n-3 PUFA diet exhibited extensive collateral growth about ligated regions. HAEC treated with TFA (trans-18 : 2) showed significantly increased expression of intracellular adhesion molecule-1 and nitrosylation of cellular proteins than those treated with DHA (n-3 PUFA, 22 : 6). The in vivo study demonstrates that, in contrast to TFA, n-3 PUFA improve animal survival after myocardial infarction, prevent development of atherosclerotic lesions and stimulate compensatory vascular remodelling. The in vitro study demonstrates that TFA induce, while n-3 PUFA prevent, vascular inflammation.

Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.

OBJECTIVE: To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients. PARTICIPANTS: A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. In addition, international experts in endocrinology were invited to participate. DESIGN/METHODS: The task force members reviewed published literature and provided expert opinion from which the consensus was derived. The consensus statements were developed using a modified Delphi methodology. The strength of each recommendation was quantified using the Modified GRADE system, which classifies recommendations as strong (grade 1) or weak (grade 2) and the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on factors that include the study design, the consistency of the results, and the directness of the evidence. RESULTS: The task force coined the term critical illness-related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness. Critical illness-related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response. Critical illness-related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents, particularly in the setting of sepsis. At this time, the diagnosis of tissue corticosteroid resistance remains problematic. Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 microg/dL after adrenocorticotrophic hormone (250 microg) administration or a random total cortisol of < 10 microg/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome (PaO2/FiO2 of < 200 and within 14 days of onset). The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids. Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day (10 mg/hr) for > or = 7 days is recommended for septic shock. Methylprednisolone in a dose of 1 mg x kg(-1) x day(-1) for > or = 14 days is recommended in patients with severe early acute respiratory distress syndrome. Glucocorticoids should be weaned and not stopped abruptly. Reinstitution of treatment should be considered with recurrence of signs of sepsis, hypotension, or worsening oxygenation. Dexamethasone is not recommended to treat critical illness-related corticosteroid insufficiency. The role of glucocorticoids in the management of patients with community-acquired pneumonia, liver failure, pancreatitis, those undergoing cardiac surgery, and other groups of critically ill patients requires further investigation. CONCLUSION: Evidence-linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary, multispecialty task force.

Immunonutrition in critically ill patients: a systematic review and analysis of the literature.

BACKGROUND: The role of immuno-modulating diets (IMDs) in critically ill patients is controversial. OBJECTIVE: The goal of this meta-analysis was to determine the impact of IMD's on hospital mortality, nosocomial infections and length of stay (LOS) in critically ill patients. Outcome was stratified according to type of IMD and patient setting. DATA SOURCES: MEDLINE, Embase, Cochrane Register of Controlled Trials. STUDY SELECTION: RCT's that compared the outcome of critically ill patients randomized to an IMD or a control diet. DATA SYNTHESIS: Twenty-four studies (with a total of 3013 patients) were included in the meta-analysis; 12 studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the studies used formulas supplemented with arginine, two with arginine and glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and FO, six with glutamine alone and three studies used a formula supplemented with FO alone. Overall IMD's had no effect on mortality or LOS, but reduced the number of infections (OR 0.63; 95% CI 0.47-0.86, P = 0.004, I(2) = 49%). Mortality, infections and LOS were significantly lower only in the ICU patients receiving the FO IMD (OR 0.42, 95% CI 0.26-0.68; OR 0.45, 95% CI 0.25-0.79 and WMD -6.28 days, 95% CI -9.92 to -2.64, respectively). CONCLUSIONS: An IMD supplemented with FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMDs supplemented with arginine with/without additional glutamine or FO do not appear to offer an advantage over standard enteral formulas in ICU, trauma and burn patients.

Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature.

OBJECTIVES: To compare the design and results of randomized trials investigating prolonged glucocorticoid treatment (> or =7 days) in patients with acute lung injury-acute respiratory distress syndrome (ALI-ARDS), and review factors affecting response to therapy, including the role of secondary prevention. DESIGN: Trials were retrieved from the Cochrane Central Register of Controlled Trials (CENTRAL). Two investigators collected data on study characteristics, treatment intervention, and outcomes. The methodological quality of trials was determined and data were analyzed with Review Manager 4.2.3. MEASUREMENTS AND RESULTS: Five selected trials (n=518) consistently reported significant improvement in gas exchange, reduction in markers of inflammation, and decreased duration of mechanical ventilation and intensive care unit stay (all p<0.05). Two early small clinical trials showed marked reductions in the relative risk (RR) of death with glucocorticoid therapy (RR=0.14, 95% CI 0.04-0.53; p=0.004, I2=0%). Three subsequent larger trials, when combined, although nominally beneficial, did not reproduce the marked reductions observed in the earlier trials (RR=0.84; 95% CI 0.68-1.03; p=0.09, I2=9.1%), but achieved a distinct reduction in the RR of death in the larger subgroup of patients (n=400) treated before day 14 of ARDS [82/214 (38%) vs. 98/186 (52.5%), RR=0.78; 95% CI 0.64-0.96; p=0.02, I2=0%]. CONCLUSIONS: Prolonged glucocorticoid treatment substantially and significantly improves meaningful patient-centered outcome variables, and has a distinct survival benefit when initiated before day 14 of ARDS.

Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health.

Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+-Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects.

Subcutaneous Infusion of Fluids for Hydration or Nutrition: A Review.

Subcutaneous infusion, or hypodermoclysis, is a technique whereby fluids are infused into the subcutaneous space via small-gauge needles that are typically inserted into the thighs, abdomen, back, or arms. In this review, we provide an overview of the technique, summarize findings from studies that have examined the use of subcutaneous infusion of fluids for hydration or nutrition, and describe the indications, advantages, and disadvantages of subcutaneous infusion. Taken together, the available evidence suggests that, when indicated, subcutaneous infusion can be effective for administering fluids for hydration or nutrition, with minimal complications, and has similar effectiveness and safety to the intravenous route. Of note, subcutaneous infusion offers several advantages over intravenous infusion, including ease of application, low cost, and the lack of potential serious complications, particularly infections. Subcutaneous infusion may be particularly suited for patients with mild to moderate dehydration or malnutrition when oral/enteral intake is insufficient; when placement of an intravenous catheter is not possible, tolerated, or desirable; at risk of dehydration when oral intake is not tolerated; as a bridging technique in case of difficult intravenous access or catheter-related bloodstream infection while infection control treatment is being attempted; and in multiple settings (eg, emergency department, hospital, outpatient clinic, nursing home, long-term care, hospice, and home).

Biological and Clinical Aspects of an Olive Oil-Based Lipid Emulsion-A Review.

Intravenous lipid emulsions (ILEs) have been an integral component of parenteral nutrition for more than 50 years. Numerous formulations are available and are based on vegetable (soybean, olive, coconut) and animal (fish) oils. Therefore, each of these formulations has a unique fatty acid composition that offers both benefits and limitations. As clinical experience and our understanding of the effects of fatty acids on various physiological processes has grown, there is evidence to suggest that some ILEs may have benefits compared with others. Current evidence suggests that olive oil-based ILE may preserve immune, hepatobiliary, and endothelial cell function, and may reduce lipid peroxidation and plasma lipid levels. There is good evidence from a large randomized controlled study to support a benefit of olive oil-based ILE over soybean oil-based ILE on reducing infections in critically ill patients. At present there is limited evidence to demonstrate a benefit of olive oil-based ILE over other ILEs on glucose metabolism, and few data exist to demonstrate a benefit on clinical outcomes such as hospital or intensive care unit stay, duration of mechanical ventilation, or mortality. We review the current research and clinical evidence supporting the potential positive biological and clinical aspects of olive oil-based ILE and conclude that olive oil-based ILE is well tolerated and provides effective nutritional support to various PN-requiring patient populations. Olive oil-based ILE appears to support the innate immune system, is associated with fewer infections, induces less lipid peroxidation, and is not associated with increased hepatobiliary or lipid disturbances. These data would suggest that olive oil-based ILE is a valuable option in various PN-requiring patient populations.

Parenteral nutrition in adult inpatients with functioning gastrointestinal tracts: assessment of outcomes.

Malnutrition is a common comorbidity that places inpatients at risk of complications, infections, long length of stay, higher costs, and increased mortality. Thus, nutrition support has become an important therapeutic adjunctive to the care of these patients. For patients unable to feed themselves, nutrition can be delivered via the parenteral or enteral routes. The formulations used to deliver nutrients and the route of nutrient delivery, absorption, and processing differ substantially between parenteral and enteral nutrition. Over the past two decades, many randomised clinical trials have assessed the effects of parenteral versus enteral nutrition on outcomes (ie, complications, infections, length of stay, costs, mortality) in diverse inpatient populations. From a search of medical publications, studies were selected that assessed important clinical outcomes of parenteral versus enteral feeding or intravenous fluids in patients with trauma/burn injuries, surgery, cancer, pancreatic disease, inflammatory bowel disease, critical illness, liver failure, acute renal failure, and organ transplantation. Our goal was to determine the optimum route of feeding in these patient groups. The available evidence lends support to the use of enteral over parenteral feeding in inpatients with functioning gastrointestinal tracts.

Modulation of lipid rafts by Omega-3 fatty acids in inflammation and cancer: implications for use of lipids during nutrition support.

Current understanding of biologic membrane structure and function is largely based on the concept of lipid rafts. Lipid rafts are composed primarily of tightly packed, liquid-ordered sphingolipids/cholesterol/saturated phospholipids that float in a sea of more unsaturated and loosely packed, liquid-disordered lipids. Lipid rafts have important clinical implications because many important membrane-signaling proteins are located within the raft regions of the membrane, and alterations in raft structure can alter activity of these signaling proteins. Because rafts are lipid-based, their composition, structure, and function are susceptible to manipulation by dietary components such as omega-3 polyunsaturated fatty acids and by cholesterol depletion. We review how alteration of raft lipids affects the raft/nonraft localization and hence the function of several proteins involved in cell signaling. We focus our discussion of raft-signaling proteins on inflammation and cancer.

Safety and Efficacy of Subcutaneous Parenteral Nutrition in Older Patients: A Prospective Randomized Multicenter Clinical Trial.

BACKGROUND: Many patients who cannot tolerate adequate enteral nutrition could benefit from parenteral nutrition support but fail to receive it due to difficult intravenous (IV) access. The objective of this study was to compare the safety and efficacy of subcutaneous (SC) administration of parenteral nutrition with the peripheral IV route. MATERIALS AND METHODS: This was a prospective randomized multicenter study of 121 older hospitalized patients. The primary outcome was the composite end point of major local side effects, defined as local edema, blistering, erythema, phlebitis, cellulitis, unbearable pain, or route failure requiring a switch in route. Secondary outcomes were nutrition parameters, biochemical parameters, clinical outcomes, and safety. RESULTS: The SC route (n = 59) was noninferior to the IV route (n = 61) for major local side effects. Major local side effects trended higher in the IV group ( P = .059). Local edema was more common in the SC group ( P < .05), while route failure was more common in the IV group ( P < .001). Nutrition and biochemical parameters, safety, and clinical outcomes were similar between groups. CONCLUSIONS: The SC route of nutrient administration was better tolerated than the peripheral IV route. SC administration of parenteral nutrition represents a safe alternative to IV nutrition.

Nutrition modulation of cachexia/proteolysis.

Cachexia represents progressive wasting of muscle and adipose tissue and is associated with increased morbidity and mortality. Although anorexia usually accompanies cachexia, cachexia rarely responds to increased food intake alone. Our knowledge of the underlying mechanisms responsible for cachexia remains incomplete. However, most states of cachexia are associated with underlying inflammatory processes and/or cancer. These processes activate protein degradation and lipolytic pathways, resulting in tissue loss. In this article, we briefly review the pathophysiology of cachexia and discuss the role of specific nutrient supplements for the treatment of cachexia. The branched chain amino acid leucine, the leucine metabolite beta-hydroxy-beta-methylbutyrate, arginine, glutamine, omega-3 long chain fatty acids, conjugated linoleic acid, and polyphenols have demonstrated some efficacy in animal and/or human studies. Optimal treatment for cachexia is likely aimed at maximizing muscle and adipose synthesis while minimizing degradation.

Trans fatty acids and coronary heart disease.

Epidemiologic evidence has linked trans fatty acids (TFAs) in the diet to coronary heart disease in human populations. It has been estimated that dietary TFAs from partially hydrogenated oils may be responsible for between 30,000 and 100,000 premature coronary deaths per year in the United States. Although it is known that TFAs increase low-density lipoprotein (LDL) cholesterol levels and decrease high-density lipoprotein (HDL) cholesterol levels (markers of coronary heart disease), there is little known about the mechanisms by which TFAs actually function at the cellular level. It is unknown what levels of TFAs are clinically significant and it is unclear how TFAs are associated with cardiac arrhythmias or sudden cardiac death. We hypothesize that TFAs affect membrane structure, thus altering enzymatic pathways that may subsequently induce cardiac arrhythmias and sudden death.

Distribution of Tocopherols and Tocotrienols in Guinea Pig Tissues Following Parenteral Lipid Emulsion Infusion.

BACKGROUND: Tocopherols and tocotrienols possess vitamin E activity and function as the major lipid-soluble antioxidants in the human body. Commercial lipid emulsions are composed of different oils and supply different amounts of vitamin E. The objective of this study was to measure all 8 vitamin E homologs within 4 different commercial lipid emulsions and evaluate their distribution in guinea pig tissues. MATERIALS AND METHODS: The distribution of vitamin E homologs within plasma and guinea pig tissues was determined using a high-performance liquid chromatography (HPLC) system. Lipid hydroperoxides in lipid emulsions were determined using a commercial kit (Cayman Chemical Company, Ann Arbor, MI), and malondialdehyde tissue levels were determined using an HPLC system. RESULTS: The lipid emulsions contained variable amounts of tocopherols, which were significantly different between emulsions. Tocotrienols were present at very low concentrations (≤0.3%). We found no correlation between the amount of vitamin E present in the lipid emulsions and lipid peroxidation. Hydroperoxides were the lowest with an olive oil-based emulsion and highest with a fish oil emulsion. The predominant vitamin E homolog in guinea pig tissues was α-tocopherol. No tissues had detectable levels of tocotrienols. Vitamin E levels (primarily α-tocopherol and γ-tocopherol) were highly variable among organ tissues. Plasma levels were a poor reflection of most tissue levels. CONCLUSION: Vitamin E levels within different lipid emulsions and plasma/tissues are highly variable, and no one tissue or plasma sample serves as a good proxy for levels in other tissues. All study emulsions were well tolerated and did not significantly increase systemic lipid peroxidation.

Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells.

INTRODUCTION: Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent employed today and is nontoxic to humans at high levels (50 microg/ml). Clinically relevant concentrations of propofol (3 to 8 microg/ml; 20 to 50 microM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA). METHODS: The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells. RESULTS: At low concentrations (25 microM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells. CONCLUSION: These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer.