Raquel Susana Torrinhas

New Parenteral Lipid Emulsions for Clinical Use

Routine use of parenteral lipid emulsions (LE) in clinical practice began in 1961, with the development of soybean oil (SO) - based LE. Although clinically safe, experimental reports indicated that SO-based LE could exert a negative influence on immunological functions. Those findings were related to its absolute and relative excess of omega-6 polyunsaturated fatty acids (PUFA) and the low amount of omega-3 PUFA and also to its high PUFA content with an increased peroxidation risk. This motivated the development of new LE basically designed along the reduction of omega-6 PUFA and the omega-3 PUFA addition in order to obtain balanced levels of the omega-6/omega-3 ratio. The new LE for clinical use (available in Europe and South America) are differentiated by their content in polyunsaturated (omega-6 and omega-3), monounsaturated, and saturated fatty acids (FA), as well as FA source of their origin, including soy, coconut, olive, and fish oil. This article presents the new LE nutrition and energy functions but also its biochemical, metabolic, and immunomodulating aspects, according to their FA content. LE at 20% when infused from 1.0 to 2.0 g/kg body weight/day rates, either alone or in association with amino acids and glucose, are safe and well tolerated in routine clinical practice. LE combining SO with medium-chain triglycerides and/or olive oil have less omega-6 PUFA and are better metabolized, with less inflammatory and immunosuppressive effects than in relation to pure SO-based LE. The omega-3 PUFA used alone or as component of a new and complex LE (soy, MCT, olive and fish oil) has demonstrated anti-inflammatory and immunomodulatory effects.

Comparison of nutritional risk screening tools for predicting clinical outcomes in hospitalized patients

OBJECTIVE International nutritional screening tools are recommended for screening hospitalized patients for nutritional risk, but no tool has been specifically evaluated in the Brazilian population. The aim of this study was to identify the most appropriate nutritional screening tool for predicting unfavorable clinical outcomes in patients admitted to a Brazilian public university hospital. METHODS The Nutritional Risk Screening 2002 (NRS 2002), Mini-Nutritional Assessment-Short Form (MNA-SF), and Malnutrition Universal Screening Tool (MUST) were administered to 705 patients within 48 h of hospital admission. Tool performance in predicting complications, very long length of hospital stay (LOS), and death was analyzed using receiver operating characteristic curves. RESULTS NRS 2002, MUST, and MNA-SF identified nutritional risk in 27.9%, 39.6%, and 73.2% of the patients, respectively. NRS 2002 (complications: 0.6531; very long LOS: 0.6508; death: 0.7948) and MNA-SF (complications: 0.6495; very long LOS: 0.6197; death: 0.7583) had largest areas under the ROC curve compared to MUST (complications: 0.6036; very long LOS: 0.6109; death: 0.6363). For elderly patients, NRS 2002 was not significantly different than MNA-SF (P>0.05) for predicting outcomes. CONCLUSION Considering current criteria for nutritional risk, NRS 2002 and MNA-SF have similar performance to predict outcomes but NRS 2002 seems to provide a best yield.

Parenteral lipid emulsions and phagocytic systems

Lipid emulsions (LE) for parenteral use are complex emulsions containing fatty acids, glycerol, phospholipids and tocopherol in variable amounts and concentrations. In clinical practice, LE have been employed for more than 30 years. Fatty acids may have different impacts on phagocytic cells according to their structure. Experimental and clinical studies have consistently shown that LE modify monocyte/macrophage and polymorphonuclear phagocytosis. The inhibitory effect of LE on the functional activity of the phagocytic system, although still clinically controversial, may have a harmful impact because total parenteral nutrition with lipids may be recommended in hypercatabolic conditions where inflammation and infection are present. LE based on triglycerides containing long chain fatty acids (termed long chain triglycerides or LCT) are the main parenteral fat source and are typically rich in n-6 polyunsaturated fatty acids. They may have adverse effects on the immune system, especially when given in high doses over a short period of time. However when administered properly they can be used safely. LE containing medium chain triglycerides (MCT) may have some advantages because of their positive effects on polymorphonuclear cells, macrophages, and cytokine production, particularly in critically ill or immunocompromised patients. New parenteral LE containing n-3 polyunsaturated fatty acids or monounsaturated olive oil are already available in Europe. Judicious use of these new LE is mandatory especially relating on their potential impact on the immune system. New experimental and clinical studies are required to further establish the role of LE in clinical nutrition.

Fish Oil Lipid Emulsions and Immune Response: What Clinicians Need to Know

Current evidence indicates that omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid and docosahexaenoic acid found in fish oil, can prevent the development of inflammatory diseases by affecting different steps of the immune response. The capacity of omega-3 PUFAs to modulate synthesis of eicosanoids, activity of nuclear receptor and nuclear transcription factors, and production of resolvins may also mitigate inflammatory processes already present. Parenteral infusion of omega-3 PUFAs is advantageous, particularly in severely ill patients, because the fatty acids are rapidly incorporated by cells. In addition, when fatty acids are given parenterally, there are no losses from digestion and absorption as there are with enteral infusion. Recently, lipid emulsions enriched with omega-3 fish oil have been introduced as a component of parenteral nutrition. Currently, there is one lipid emulsion that contains only fish oil; it is infused together with conventionally used lipid emulsions. Other commercially available lipid emulsions contain fish oil in a fat mixture; one contains 10% fish oil and another 15% fish oil. Relevant experimental and clinical data from studies evaluating fish oil lipid emulsions are discussed in the present review. Administration of fish oil lipid emulsion, when compared with soybean oil lipid emulsion (rich in omega-6 PUFA), decreases the length of hospital and intensive care unit stay in surgical patients.

Effect of synbiotic in constipated adult women – A randomized, double-blind, placebo-controlled study of clinical response

BACKGROUND & AIMS Synbiotic intake may selectively change microbiota composition, restore microbial balance in the gut and improve gastrointestinal functions. We have assessed the clinical response of chronically constipated women to a commercially available synbiotic, combining fructooligosaccharides with Lactobacillus and Bifidobacterium strains (LACTOFOS®). METHODS Following 1 week of non-interventional clinical observation, 100 constipated adult women, diagnosed by ROME III criteria, were randomized to receive two daily doses (6 g) of synbiotic or maltodextrin (placebo group), for 30 days. Treatment response was evaluated by patients daily record of evacuation (stool frequency, consistency and shape, according to Bristol scale), abdominal symptoms (abdominal pain, bloating and flatulence) and constipation intensity (Constipation Scoring System AGACHAN). RESULTS Patients treated with synbiotic had increased frequency of evacuation, as well as stool consistency and shape nearer normal parameters than the placebo group, with significant benefits starting during the second and third weeks, respectively (interaction group/time, P<0.0001). There were no significant differences in abdominal symptoms, but AGACHAN score was better in the synbiotic than in the placebo group. CONCLUSIONS Dietary supplementation with a synbiotic composed of fructooligosaccharides with Lactobacillus and Bifidobacterium improved evacuation parameters and constipation intensity of chronically constipated women, without influencing abdominal symptoms.

Impact of parenteral n-3 fatty acids on experimental acute colitis.

The present study was undertaken to investigate the effects of parenteral lipid emulsions (LE) enriched with n-3 fatty acids (n-3 FA) in experimental acute colitis. Seventy-four adult male Wistar rats were randomized into six groups, five of which had acetic acid-induced colitis. The animals received a fat-free diet and water ad libitum in individual metabolic cages. By a central venous catheter, saline was infused (0.5 ml/h) into the control groups CS (without colitis) and CC (with colitis), while the test groups received specific LE for 7 days. The n-3/n-6 FA ratio and the lipidic compositions regarding long chain (LCT) and medium chain (MCT) triglycerides were: group L--1:7.7 (LCT, n = 12), M--1:7.0 (MCT and LCT, n = 12), LW-3--1:4.5 (LCT plus n-3 FA, n = 12) and MW-3--1:3.0 (MCT and LCT plus n-3 FA, n = 13). The frequency of diarrhea, oral intake/body weight ratio, intestinal alterations, macrophage cellularity were evaluated and colonic concentrations of leukotrienes (LTB4, LTC4), prostaglandins (PGE2) and thromboxanes (TXB2) were measured. Groups M, MW-3 and LW-3 had less diarrhea than the CC group (P<0.05). Average oral intake/body weight ratio in MW-3 animals was comparable to the CS and better than the CC group. n-3 FA treated rats (LW-3 and MW-3) presented less intestinal inflammatory alterations than CC rats. Mucosal ulcer formation in MW-3 group did not differ from CS rats. M and MW-3 rats had less macrophages in the colon than the CC group. Compared with CC group, lower concentrations of LTB4 in the CS, LW-3 and MW-3 groups; of PGE2 in the CS, M and MW-3 groups; and of TXB2 in the CS and MW-3 groups were found. Mean concentrations of LTC4 did not differ among the groups. Thus, a LCT-containing LE with a low n-3-n-6 ratio does not modify inflammatory colitis manifestations; LE with a high n-3-n-6 ratio reduces diarrhea, preserves oral intake-weight ratio, attenuates morphological consequences and decreases colonic concentrations of inflammatory mediators; MCT/LCT-containing LE with 1:3 n-3-n-6 ratio exerts the most profound beneficial impact on the inflammatory response.

Parenteral fish oil as a pharmacological agent to modulate post-operative immune response: a randomized, double-blind, and controlled clinical trial in patients with gastrointestinal cancer.

BACKGROUND Fish oil-based lipid emulsions (FOLEs) have shown post-operative immunological and clinical benefits in parenteral nutrition. AIM To assess post-operative immune response after short-term pre-operative parenteral infusion of isolated FOLE in gastrointestinal cancer patients. METHODS The patients (n = 63) received pre-operative peripheral infusion (0.2 g fat/kg body weight/d) of FOLE (Omegaven(®)) or control lipid emulsion (MCT/LCT; Lipovenos MCT(®)) for 3 days. Post-operative concentrations of inflammatory mediators, leukocyte functions, surface molecules, infections, and length of intensive care unit (ICU) and hospital stay were measured. RESULTS FOLE patients had a significant increase of IL-10 levels on day 3, decrease of IL-6 and IL-10 levels on day 6, lower decrease in leukocyte oxidative burst, maintenance of monocyte percentage expressing HLA-DR and CD32, and increase of CD32 neutrophil expression compared to MCT/LCT patients. No changes were observed in the frequency of post-operative infections or length of ICU and hospital stay. CONCLUSIONS Short-term pre-operative infusion of FO alone improves the post-operative immune response of gastrointestinal cancer patients without significantly changing post-operative infections or length of ICU and hospital stay. ID:NCT01218841.

New body fat prediction equations for severely obese patients

BACKGROUND & AIMS Severe obesity imposes physical limitations to body composition assessment. Our aim was to compare body fat (BF) estimations of severely obese patients obtained by bioelectrical impedance (BIA) and air displacement plethysmography (ADP) for development of new equations for BF prediction. METHODS Severely obese subjects (83 female/36 male, mean age=41.6+/-11.6 years) had BF estimated by BIA and ADP. The agreement of the data was evaluated using Bland-Altmans graphic and concordance correlation coefficient (CCC). A multivariate regression analysis was performed to develop and validate new predictive equations. RESULTS BF estimations from BIA (64.8+/-15 kg) and ADP (65.6+/-16.4 kg) did not differ (p>0.05, with good accuracy, precision, and CCC), but the Bland- Altman graphic showed a wide limit of agreement (-10.4; 8.8). The standard BIA equation overestimated BF in women (-1.3 kg) and underestimated BF in men (5.6 kg; p<0.05). Two BF new predictive equations were generated after BIA measurement, which predicted BF with higher accuracy, precision, CCC, and limits of agreement than the standard BIA equation. CONCLUSIONS Standard BIA equations were inadequate for estimating BF in severely obese patients. Equations developed especially for this population provide more accurate BF assessment.

Type 2 Diabetes Mellitus: A Possible Surgically Reversible Intestinal Dysfunction

Type 2 diabetes mellitus (T2DM) is a global public health problem often associated with obesity. Bariatric surgery is effective for treating serious obesity, and techniques involving intestinal bypass have metabolic benefits, such as complete and early remission of T2DM. We present a literature review of the possible mechanisms of early normalization of glycemic homeostasis after bariatric surgery, including intestinal gluconeogenesis, increased antidiabetogenic signals from L cells located in the distal small intestine, and impaired secretion of diabetogenic signals in the upper part of the small intestine. Adding to these potential mechanisms, unknown factors that regulate insulin sensitivity may be involved and altered by bariatric surgery. This review discusses the various hypotheses about the mechanisms of glycemic control after bariatric surgery involving intestinal bypass. Further research is essential to better understand these mechanisms and to identify potential new mechanisms that might help in developing less invasive and safer alternatives for the treatment of T2DM and reveal novel pharmaceutical targets for glycemic control.

New Specific Equation to Estimate Resting Energy Expenditure in Severely Obese Patients

Calculating the estimated resting energy expenditure (REE) in severely obese patients is useful, but there is controversy concerning the effectiveness of available prediction equations (PE) using body weight (BW). We evaluated the efficacy of REE equations against indirect calorimetry (IC) in severely obese subjects and aimed to develop a new equation based on body composition compartments. One hundred and twenty severely obese patients had their REE measured (MREE) by IC and compared to the most commonly used PE (Harris‐Benedict (HB), Ireton‐Jones, Owen, and Mifflin St. Jeor). In a random sample (n = 60), a new REE equation based on fat‐free mass (FFM) was developed and validated. All PE studied failed to estimate REE in severe obesity (low concordance correlation coefficient (CCC) and limits of agreement of nearly 50% of the sample ±10% of MREE). The HB equation using actual BW exhibited good results for all samples when compared to IC (2,117 ± 518 kcal/day by HB vs. 2,139 ± 423 kcal/day by MREE, P > 0.01); these results were blunted when patients were separated by gender (2,771 vs. 2,586 kcal/day, P < 0.001 in males and 1,825 vs. 1,939 kcal/day, P < 0.001 in females). A new resting energy expenditure equation prediction was developed using FFM, Horie‐Waitzberg, & Gonzalez, expressed as 560.43 + (5.39 × BW) + (14.14 × FFM). The new resting energy expenditure equation prediction, which uses FFM and BW, demonstrates higher accuracy, precision, CCC, and limits of agreement than the standard PE in patients when compared to MREE (2,129 ± 45 kcal/day vs. 2,139 ± 423 kcal/day, respectively, P = 0.1).The new equation developed to estimate REE, which takes into account both FFM and BW, provides better results than currently available equations.