Lipidemic effects of an interesterified mixture of butter, medium-chain triacylglycerol and safflower oils.

The objective of this study was to determine if the positional structure of dietary triacylglycerol affected lipidemic responses. Thirty healthy adults (16 men and 14 postmenopausal women) with low-density lipoprotein cholesterol (LDL-C) concentrations >3.37 mM (130 mg/dL) enrolled in a prospective, single-blind, cross-over outpatient clinical trial that consisted of two 5-wk dietary phases. After baseline screening, subjects were instructed to follow individualized meal plans (weight maintenance diets with 36% of total energy from fat, half of which was from a test oil) and randomized to receive either butter (B) or an interesterified mixture (IM) of butter, medium-chain triacylglycerol (MCT), and safflower oils. Blood drawn during weeks 5 and 10 of feeding was analyzed for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C),LDL-C, and triacylglycerols (TAG). Mean plasma levels of TC (B, 6.98+/-1.06 mM; IM, 7.09+/-1.20 mM), HDL-C (B,1.30+/-0.35 mM; IM, 1.29+/-0.34 mM), and LDL-C (B, 4.91+/-0.95 mM; IM, 4.92+/-1.10 mM) were not significantly different between the two dietary treatments. Mean TAG levels were higher for the interesterified B-MCT mixture (B, 1.75+/-0.72 mM; IM, 1.96+/-0.86 mM, P < 0.05). We conclude that an IM of B, MCT, and safflower oils as compared to native B has no appreciable effect on plasma cholesterol concentrations but is associated with a modest rise in plasma TAG.

Risk of symptomatic central venous thrombotic complications in AIDS patients receiving home parenteral nutrition.

BACKGROUND: The acquired immunodeficiency syndrome (AIDS) is frequently complicated by malnutrition that may require parenteral nutritional support. In a non-AIDS population with long-term indwelling central venous catheters, low-dose warfarin therapy has been shown to prevent venous thrombosis. The purpose of this study was to determine the incidence of symptomatic central venous thrombosis in AIDS patients receiving home parenteral nutrition. The incidence of thrombosis on low-dose warfarin was compared with no prophylactic therapy. METHODS: A retrospective review of 47 malnourished AIDS patients started on home parental nutrition was performed. None of the patients had a prior history of venous thrombosis. During this period, 9 of 47 patients were treated with low-dose warfarin therapy. The incidence of clinical and radiologic venous thrombosis was compared in these two groups. RESULTS: Forty-seven patients were treated with parenteral nutrition for 296 patients-months. The rate of central venous thrombosis in patients receiving warfarin (0.016 thromboses per patient-month) was no different from those patients on no prophylactic therapy (0.009 thromboses per patient-month). The most common abnormality in coagulation observed in the entire group during follow-up was thrombocytopenia occurring in 66% of patients. Sixty percent of patients received medications that could interfere with platelet function. CONCLUSIONS: We conclude that routine thrombosis prophylaxis with low-dose warfarin may not be justified in malnourished AIDS patients receiving home parenteral nutrition. Prospective clinical trials are needed to determine the risks and benefits of prophylactic warfarin therapy in this group of patients.

Effect of iron-supplemented total parenteral nutrition in patients with iron deficiency anemia.

Iron deficiency anemia is common among hospitalized patients, and blood losses from diagnostic phlebotomy increase the likelihood of a negative iron balance. The role for iron supplementation of total parenteral nutrition (TPN) in these patients is unclear. Twenty-three patients with iron deficiency anemia were identified. Twelve patients were randomized to receive TPN without iron (group 1) and 11 received TPN supplemented with 10 mg of iron as iron dextran daily (group 2). Both groups were matched for age, serum iron studies, red cell indices, and hemogram. After a 7-d period, the mean serum iron in group 2 increased from 10 to 26 micrograms/dL, with an increased transferrin saturation from 7.3 to 15.3% (each, p < 0.05). No changes in total iron binding capacity, ferritin, reticulocyte count, hemoglobin, hematocrit, or mean corpuscular volume were observed in the two groups. The incidence of infectious complications was not different between both groups. We conclude that iron supplementation of TPN appears safe and is effective in increasing serum iron levels. The use of iron-supplemented short-term TPN needs to be further studied given no change in red cell indices, hemoglobin, hematocrit, or transfusion requirement.

Essential fatty acid deficiency and home total parenteral nutrition patients.

The requirements for essential fatty acids in patients on home parenteral nutrition are not well described. We therefore studied the needs of 12 patients receiving parenteral nutrition for at least 4 mo (range: 4 mo-17.3 yr; mean 7.0 +/- 5.2 yr). Prior to the study, each patient had been receiving intravenous lipids either weekly or biweekly and had a triene to tetraene ratio (TTR) on plasma phospholipids performed at least annually. A TTR > or = 0.2 was considered diagnostic for essential fatty acid deficiency (EFAD). The purpose of this study was to determine the required intravenous lipid supplementation in patients on home total parenteral nutrition (HTPN). Patients with an initial TTR of < 0.2 had their intravenous lipid stopped and changes in their serum phospholipid fatty acids were followed every 3-4 wk. Nine of 12 patients had TTRs > 0.2 at some point in the study. Phase I consisted of patients who at initiation of the study had normal TTRs and were taken off lipid supplementation until their TTR became abnormal. Phases II, III, IV, and V consisted of lipid delivered in total nutrient admixtures in biweekly doses of 0.6, 1.2, 1.8, and 2.4 g of fat/kg bodyweight, respectively. Eight patients normalized their TTRs on the biweekly lipid regimens; one patient expired before his ratio normalized; and three patients could not be made deficient in essential fatty acids after 26 or more wk of fat-free parenteral nutrition. Most patients required 1.2 to 2.4 g of lipid/kg bodyweight/biweekly to correct serologic EFAD. The clinical background, as well as the length of small bowel remaining, did not seem to identify those patients who required lipid supplementation nor the final dose of lipid needed to normalize their TTRs.

Warfarin and reduced central venous thrombosis in home total parenteral nutrition patients.

Central venous thrombosis is a potentially life-threatening complication in patients on long-term home total parenteral nutrition (HTPN). Lack of venous access due to recurrent thromboses can prevent delivery of life-saving nutritional support. The long-term anticoagulation management to prevent thromboses in patients with central venous catheters for HTPN has not been well established. We have reviewed the role of warfarin in reducing the incidence of thromboses and its safety in our HTPN patients. Ninety consecutive HTPN patients were studied retrospectively. Twenty-two thromboses occurred during 1312 patient-mo in 53 HTPN patients on minidose warfarin. A minidose of warfarin is defined as 1-2 mg and does not prolong the prothrombin time. Seven thromboses occurred over 619 mo in 18 patients on a therapeutic dose of warfarin (minidose compared to therapeutic dose, p > 0.05). A therapeutic dose of warfarin is a dose that increases the prothrombin time to 1.2-1.5 times that of control. Twelve patients who had 18 thromboses in 323 patient-mo while on minidose warfarin were subsequently converted to therapeutic warfarin. The incidence of thromboses decreased to 2 in 369 patient-mo (p < 0.005). There were no hemorrhagic complications in the minidose warfarin group and four nonfatal hemorrhagic complications in the therapeutic dose warfarin group (p > 0.05). A therapeutic dose of warfarin is effective in reducing the incidence of thromboses in patients who experience central venous thrombosis despite minidose warfarin with a minimal increase in hemorrhagic complications.

Parenteral iron dextran therapy: a review.

Iron dextran was introduced more than 30 yr ago for the parenteral treatment of iron deficiency anemia that is refractory to oral therapy. Iron dextran is a preparation of ferric hydroxide complexed with a low molecular weight fraction of dextran. Iron deficiency anemia is one of the most common nutritional deficiency diseases and occurs worldwide secondary to inadequate dietary iron, usually with excessive gastrointestinal blood losses. Repletion of iron stores is often complicated by intolerance to oral iron supplementation and may require parenteral iron. Parenteral iron can be administered via the intramuscular or intravenous route either directly or as an additive to total parenteral nutrition. Both routes of administration can cause various side effects and a test dose is recommended before therapeutic administration to assess the risk for anaphylaxis. Although the efficacy and safety of parenteral iron dextran have been convincingly demonstrated, supplementation may be contraindicated in the setting of infection.

Nutrition support and the human immunodeficiency virus (HIV).

Nutritional support of patients with HIV or acquired immune deficiency syndrome (AIDS) has many similarities to other disease states in that the same nutritional products and techniques are used. Some patients with HIV, and many with AIDS without secondary infection, experience a metabolic milieu similar to patients with cancer cachexia. In providing dietary counselling to the HIV patient, we encounter many of the obstacles that must be overcome to improve nutrition in cancer: anorexia, gastrointestinal discomfort, lethargy, and poor nutrient utilization, which limit the ability for nutritional repletion. When a secondary infection is superimposed on HIV, patients resemble more highly catabolic trauma patients or patients in the intensive care unit (ICU), where, despite aggressive efforts to feed, there is usually a net nitrogen wasting leading to the more rapid development of cachexia. However, even in this setting, feeding will limit substantially net catabolism when compared to total starvation. Because the nutritional needs of HIV patients vary greatly, individual strategies have to be designed as the patient moves through the stages of disease. Patients are generally able to consume adequate nutrition either as regular food or dietary supplements during the latency period of viral replication. Once secondary infections become prevalent, artificial diets administered by tube or by vein may be required during the period of active secondary infections, with dietary supplements often helpful during more quiescent periods. Patients with HIV are among the most challenging for clinicians providing nutritional support. Knowledge from treatment of patients with other diseases may be useful, but more data must be gathered on the unique aspects of aetiology and treatment of the anorexia, malabsorption, and ultimate wasting associated with AIDS.

Dietary fat level as determinant of protein-sparing actions of structured triglycerides.

This study assessed the effects of total parenteral nutrition (TPN) containing long-chain triglycerides (LCTs), an equimolar physical mixture of LCT and medium-chain triglycerides (MCTs), and a structured triglyceride synthesized from equimolar amounts of MCT and LCT on energy and protein metabolism after thermal injury (25% body surface area full-thickness scald burn). Male Sprague-Dawley rats (245-271 g) received isovolemic diets intravenously that supplied 250 kcal.kg-1.day-1, 2 g amino acid nitrogen.kg-1.day-1, and 50% of nonprotein calories as lipid and 50% as dextrose for 3 days. Whole-body and tissue leucine kinetics were estimated by a 4-h continuous infusion of L-[1-14C]leucine on day 3. Nitrogen balance, plasma albumin, plasma glucose, energy expenditure, and whole-body and liver and rectus muscle protein kinetic parameters were determined. No significant differences were noted in any of the parameters measured. This study suggests that the unique protein-sparing actions usually associated with structured triglyceride administration are not seen when they are provided as 50% of nonprotein calories. In addition, the ratio of MCT to LCT in the starting mixture from which the structured triglycerides are synthesized may be an important determinant of the protein-sparing actions attributed to these lipids.

Left ventricular filling abnormalities in asymptomatic morbid obesity.

Indexes of left ventricular (LV) diastolic filling were measured by pulse Doppler echocardiography in 16 asymptomatic morbidity obese patients presenting for bariatric surgery and were compared with an age- and sex-matched lean control population. No patient had concomitant disorders known to affect diastolic function. All patients had normal systolic function. LV wall thickness and internal dimension were measured in order to calculate LV mass. Fifty percent of morbidly obese patients had LV diastolic filling abnormalities as assessed by the presence of greater than or equal to 2 abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in obese compared with control patients (1.16 +/- 0.26 vs 1.66 +/- 0.30, p less than 0.001). The peak velocity of early LV diastolic filling was significantly reduced in obese patients (75 +/- 15 vs 98 +/- 19 cm/s, p less than 0.001). The atrial contribution to stroke velocity as assessed by the time-velocity integral of late compared with total LV diastolic filling was significantly increased in obese patients (36 +/- 7 vs 27 +/- 4%, p less than 0.001). Obese patients had significantly increased LV mass (214 +/- 45 vs 138 +/- 37 g, p less than 0.001), even when corrected for body surface area (95 +/- 16 vs 76 +/- 16 g/m2, p less than 0.002). However, increased LV mass did not correlate with indexes of abnormal diastolic filling in obese patients. These data suggest that abnormalities of diastolic function occur frequently in asymptomatic morbidly obese patients and may represent a subclinical form of cardiomyopathy in the obese patient.

Human plasma fatty acid variations and how they are related to dietary intake.

A study was conducted in 12 free-living subjects to determine quantitative and qualitative plasma phospholipid (PL), free fatty acid (FFA), triglyceride (TG), and cholesterol ester (CE) fatty acid (FA) variations over time (0.8, and 22 mo) and to correlate these FAs with dietary intake. Diet, reported by use of a food frequency questionnaire (FFQ), did not change over time. Most FA variations were quantitative, occurring in FFA and CE fractions. Correlations between diet and FAs occurred mostly in men for whom dietary percent fat energy was positively correlated with percent monounsaturated plasma TG FAs, and ethanol (g/d) was positively correlated with plasma CE 16:1 omega 7 (mumol/L). These findings indicate that quantitative variations exist in plasma FAs of a normal population, with no detectable alteration in diet; the FFQ may be used to reflect the qualitative status of plasma FA. Factors such as ethanol consumption and sex differences may influence FA metabolism.

Parenteral nutrient admixtures as drug vehicles: theory and practice in the critical care setting.

Parenteral nutrient (PN) admixtures are the most complex, extemporaneously compounded formulations routinely prepared for hospitalized and home-based patients. In addition, drugs are added with increasing frequency to PN admixtures, thus presenting even greater physicochemical challenges to this highly complex pharmaceutical product. The continuous infusion of selected drugs may provide pharmacokinetic and therapeutic advantages over conventional, intermittent, bolus methods of administration. Fluid conservation, cost savings, and a possible decrease in the risk of infection through reduced catheter manipulation and simplification of therapy provide additional incentives to consider the use of PN admixtures. The many advantages of PN admixtures make them an attractive approach to cost-effective care, with special clinical benefits achieved in the critical care setting. This article reviews our clinical experience using PN admixtures as drug vehicles for selected drugs and presents some theoretical as well as actual benefits associated with this practice.

Alternative lipid sources for enteral and parenteral nutrition: long- and medium-chain triglycerides, structured triglycerides, and fish oils.

This article reviews current investigations of the use of alternative lipid sources to enhance the metabolic and immune functions of hospitalized patients. Conventional lipids have been implicated as the cause of a variety of iatrogenic side effects in critically ill hospitalized patients, and long-chain triglycerides of the omega-6 family have been shown to be potentially detrimental to immune function. Alternative lipids (fish oils, medium-chain triglycerides, and structured triglycerides) have been proposed as substitutes for conventional long-chain, polyunsaturated omega-6 fatty acids. Unlike long-chain triglycerides, medium-chain triglycerides are more rapidly cleared from the blood and are completely oxidized for energy. However, medium-chain triglycerides contain no essential fatty acids. On the other hand, structured triglycerides offer the advantages of long-chain triglycerides (essential fatty acids) and of medium-chain triglycerides (rapid clearance and oxidation). Fish oils, which contain long-chain polyunsaturated omega-3 fatty acids, appear to be anti-inflammatory and to affect immune function differently from the omega-6 long-chain triglycerides.

Thermogenesis from intravenous medium-chain triglycerides.

Eighteen hospitalized patients dependent on total parenteral nutrition (TPN) were randomly enrolled into a prospective study comparing intravenous long-chain triglycerides (LCT) with a physical mixture of 75% medium-chain triglycerides (MCT) and 25% LCT. The TPN was given continuously as amino acids and glucose over 5 days with the respective lipid emulsion given intermittently during each day for 10 hr. Indirect calorimetry was measured on each patient before the lipid emulsion was administered in the morning and again 10 hr later near the end of the lipid infusion, on days 1, 3, and 5. Resting energy expenditure, VO2, VCO2, and calculated fat oxidation were shown to increase during MCT infusion but not during LCT administration, (resting energy expenditure 899 +/- 37 to 1085 +/- 40, compared with 978 +/- 23 to 976 +/- 39, kcal/m2 body surface area [BSA]/day, respectively, p less than 0.0002; VO2: 129.9 +/- 5.2 to 157.2 +/- 5.9, compared with 140.9 +/- 3.6 to 141.2 +/- 5.9 ml O2/min/m2 BSA, respectively, p less than 0.0005; and VCO2: 110.7 +/- 4.4 to 127.5 +/- 4.3, compared with 118.3 +/- 2.8 to 118.0 +/- 5.3, ml CO2/min/m2 BSA, respectively, p less than 0.0076; calculated fat oxidation 10.7 +/- 1.5 to 19.3 +/- 2.4, compared with 20.0 +/- 2.7 to 20.0 +/- 3.6, kcal/m2 BSA/hr, respectively, p less than 0.014). Respiratory quotient tended to fall with lipid infusion but did not change statistically. Body temperatures were unaltered by either fat infusion. It is concluded that TPN consisting of MCT causes an increased thermogenesis, most likely through increased fat oxidation, reflective of MCT's property as an obligate fuel. The increased thermogenesis occurs without an increase in body temperature.

Effect of tracer and intravenous fat emulsion on the measurement of reticuloendothelial system function.

Since the addition of lipid to intravenous feeding formulas, animal and human studies have shown impairment of the reticuloendothelial system (RES) due to slow rates of clearance and gradual accumulation of long chain triglycerides (LCT) in the liver. Medium chain triglycerides (MCT) accumulate only minimally in the liver and do not impair the RES. However, results from animal studies using technetium sulfur colloid (TSC) to assess RES function have been inconclusive. The present study reevaluates RES function after lipid infusion in guinea pigs as measured by organ distribution of TSC. Guinea pigs were fed 300 kcal/kg/day of total parenteral nutrition (TPN) for 2.5 days, with 50% of nonprotein calories as fat in the form of LCT or MCT, then injected intravenously with 2.5 or 25 microCi of TSC, and uptake by liver, spleen, and lungs was determined. Liver, lungs, and spleen all increased in size after TPN with LCT or MCT. Liver TSC uptake was significantly affected by the dose of TSC (p less than 0.05), with the high dose probably inducing an increased capacity of the liver to clear TSC from the blood. Liver uptake was not influenced by diet, but feeding MCT did significantly stimulate lung uptake of TSC (p less than 0.0001). This suggests that the hepatic TSC uptake system is not saturable, and may not be an appropriate measure of Kupffer cell function since the colloid is not phagocytosed. However, TSC blood clearance remains an excellent prognostic indicator for bacteremia and mortality in humans, and is useful for measuring global RES function.

Parenteral infusion of long- and medium-chain triglycerides and reticuloendothelial system function in man.

Previous study demonstrated that patients who received total parenteral nutrition (TPN) with standard intermittent infusion of long chain triglyceride (LCT) at 0.13 g kg-1hr-1 over 10 hr for each of three days showed a significant decline in 99Tc-sulfur colloid (TSC) clearance rate by the reticuloendothelial system (RES). The present studies evaluated eight patients who received the same total lipid dose of LCT infused continuously as in a three-in-one admixture, and another nine patients receiving the same amount of fat as a medium chain triglyceride (MCT)/LCT (75%/25%) emulsion intermittently over 10 hr at 0.13 g kg-1hr-1 for three consecutive days. Patients were given continuous total parenteral nutrition (TPN) comprised of protein, 1.5 g kg-1day-1, and dextrose, 4.5 g kg-1day-1. RES function was examined by measuring the clearance rates of intravenously injected TSC while receiving TPN containing only protein and dextrose, and again after three days of fat infusion. Mean (+/- SEM) clearance rate constants before and after continuous LCT infusion were 0.38 +/- 0.09 and 0.41 +/- 0.08 min-1, respectively, while those before and after intermittent MCT/LCT infusion were 0.50 +/- 0.18 and 0.73 +/- 0.24 min-1, respectively. In contrast to intermittent LCT infusion, the administration of continuous LCT or an intermittent MCT/LCT mixture does not impair TSC clearance by the RES. These findings suggest that condensing the daily period of LCT infusion at standard dosage may exceed the rate of metabolic utilization, resulting in increased fat removal and diminished TSC uptake by the RES.(ABSTRACT TRUNCATED AT 250 WORDS)

The response to endotoxin in guinea pigs after intravenous black currant seed oil.

The influence on the metabolic response to endotoxin of three days of total parenteral nutrition with lipids high in gammalinolenic acid (18:3 omega 6, GLA) compared to soy oil (SO) was examined in acute operatively stressed guinea pigs. GLA is the precursor of dihomogammalinolenic acid (DHLA), the substrate for synthesis of "1" series prostaglandins such as PGE1, which have previously been shown to be protective in endotoxin lung injury and traumatic shock. Guinea pigs fed an intravenous diet containing black currant seed oil (BCO) emulsion (20% GLA) or soy oil emulsion (0% GLA) for 2.5 days had their arterial pH, pCO2, pO2, and bicarbonate measured at baseline and hourly during a 7-hr infusion of endotoxin (lipopolysaccharide (LPS), 2mg/kg) or saline. Plasma lactate and fatty acid profile analyses were performed at the end of the LPS infusion. Increased levels of GLA and DHLA were present in the plasma phospholipid fraction of animals fed the black currant seed oil diet, while soy-fed animals had only trace amounts of GLA. In addition, the ratio of DHLA to arachidonate was higher in animals receiving the black currant seed oil total parenteral nutrition (TPN). After 2 hr of LPS infusion, all animals exhibited the typical shock response resulting in metabolic acidosis characterized by a significant (p less than 0.05) drop in pH from 7.34 +/- .02 (SO) and 7.39 +/- .02 (BCO) at baseline to 7.14 +/- .05 and 7.22 +/- .04 by 7 hr for SO and BCO groups, respectively. Plasma lactate values at the end of the infusion were significantly elevated compared to saline in both groups (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-chain triglyceride emulsions on reticuloendothelial system function in humans.

Parenteral administration of long-chain triglyceride emulsions has been shown to have deleterious effects on reticuloendothelial system function in animal models. It is unknown whether this interference occurs in humans with clinically relevant doses of intravenous fat. Two studies were done. Eighteen patients were prospectively enrolled for study. Patients received full feeding by continuous total parenteral nutrition (amino acids 1.5 g/kg/day and dextrose 4.5 g/kg/day) with 33.1 kcal/kg/day. Forty-three % of the nonprotein calories were provided as soybean oil emulsion (Travamulsion 20%) and was administered intravenously over 10 hr (0.130 g/kg/hr). Reticuloendothelial system function was determined by measuring the change in the clearance rate of intravenously injected 99mTc-sulfur colloid (TSC) in each patient. In study 1 (n = 10), one day of lipid (10 hr) was infused, with the clearance of 99mTc-sulfur colloid measured before the lipid was infused and then during the last hour of the 10-hr infusion. In study 2 (n = 8), the clearance rates were measured before the lipid emulsion was begun, and then during the last hour of the infusion on the 3rd day. Clearance rates for TSC after 10 hr of lipid infusion in study 1 did not differ (0.27 +/- 1/min to 0.26 +/- 0.1/min, p greater than 0.10). However, after 3 days of lipid infusion (10 hr/day), a statistically significant reduction in TSC was seen (0.46 +/- 0.08/min-0.27 +/- 0.03/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)