Applied Nutritional InvestigationsStructured triacylglycerol emulsion, containing both medium- and long-chain fatty acids, in long-term home parenteral nutrition: a double-blind randomized cross-over study
Introduction
Lipid emulsions containing long-chain triacylglycerol (LCTs) have been used successfully as an essential part of parenteral nutrition (PN) treatment for the last 35 y. LCT fat emulsions contain long-chain fatty acids (LCFAs) of chain lengths of 16 to 20 carbon atoms and provide patients with essential fatty acids and a caloric source. During the past decade, emulsions containing medium-chain triacylglycerols (MCTs) have been used as an alternative lipid source. MCTs do not contain linoleic or linolenic acids, considered to be essential fatty acids, but are composed of medium-chain fatty acids (MCFAs) with 8 to 12 carbon atoms. MCFAs are partly independent of the carnitine transport mechanism into the mitochondria and are rapidly and exclusively oxidized for the production of energy.1, 2, 3 MCT emulsions are rapidly hydrolyzed because of their higher availability to the lypolitic enzymes,4 resulting in transient high plasma concentrations of MCFAs with overall faster clearance from the circulation.5 Thus, there is a preferential hydrolysis of the MCT component in mixed emulsions.4 Furthermore, the MCT component has been shown to have an inhibitory effect on LCT oxidation when mixed together.6 However, high doses of MCFAs may lead to side effects such as metabolic acidosis7 and neurologic effects.8 For this reason, MCTs are always given with LCTs as a physical mixture to reduce the potential adverse effects and to ensure provision of essential fatty acids.
With the aim of further improving the safety and efficacy of fat emulsions containing MCT and to circumvent the disadvantages of the physical mixture of MCT and LCT, a structured triacylglycerol (STG) emulsion composed of mixed triglycerol molecules has been synthesized through random reesterification of a mixture of LCFA and MCFA bound to the same glycerol backbone. This approach was designed to provide both simultaneous delivery of LCFA and MCFA and a slower, more controlled release of the MCFA into the bloodstream than that of the physical mixture of MCT and LCT.9, 10
It has been observed that, during infusion of STG, plasma concentrations of MCFA are lower and ketonemia occurs less often than with LCT or a physical mixture of MCT and LCT.11 Preclinical studies have demonstrated that STG emulsion is more rapidly eliminated from the plasma than standard LCT emulsion, with comparable tolerance.6
In rats, STG has been reported to have positive effects on body weight gain, nitrogen balance, and protein kinetics when compared with emulsions containing only LCT12, 13, 14 or to physical mixtures of MCT and LCT. Administration of the STG emulsions has been associated with less hepatic fat infiltration compared with a physical mixture of MCT and LCT emulsions.13, 16
In humans in short-term studies (up to 5 d), STG has been shown to have the same safety and tolerance as Intralipid, with faster elimination.6, 15 Furthermore, STG was well tolerated and could safely be provided to patients after major surgical procedures. No signs of central nervous system toxicity were noted, and there was no tendency to ketosis.16 However, STG has not been studied in long-term treatment such as that of chronic home PN patients.
The aim of the present study was to evaluate the effect of STG on liver functions, plasma lipids, hematologic and biochemical variables, and the overall safety in adult patients for whom long-term (>1 mo) PN is indicated.
Section snippets
Patient characteristics, study design, and randomization
Home PN patients aged 16 to 70 y, with a long-term PN requirement of at least 4 d/wk, were eligible for the study. Some of the patients could tolerate oral intake of small amounts of light food and did not need PN every day. The number of days of treatment ranged from 4 to 7 d weekly, depending on individual requirements. Patients were enrolled from a list of home PN patients. After signing an informed consent, the patient was given a randomization number in chronologic order.
Exclusion criteria
Safety and tolerance
No allergic reactions or central nervous system toxicities were related to either Structolipid or Intralipid. Vomiting was observed in five patients treated with Structolipid emulsion and in four patients treated with Intralipid. Skin desquamation developed in one patient treated with Structolipid emulsion. All clinical adverse events were considered as being unlikely to have been related to the lipid emulsion treatment, and all patients recovered with no modification of their treatment and
Discussion
This study clearly indicates the safety of long-term treatment with structured lipid emulsion containing both MCFAs and LCFAs as used in home PN regimens. The cross-over design employed was considered most suitable for this group of patients who were metabolically stable and had been treated with home PN before the study, often for extended periods. The advantage of the cross-over design is reduction of interindividual differences and the use of each patient as a control; withholding lipids for
Acknowledgements
This work is dedicated to the memory of Prof. David Elwin, who was a continuing inspiration to us. The authors thank Dr. L. Hagenfelt of the Hudding Hospital in Sweden for analyzing the samples for dicarboxylic acids and 3-OH fatty acids and Pharmacia, Stockholm, Sweden for their support.
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