Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: other route
Remarks:
other: review article on parenteral nutrition
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only secondary data

Data source

Reference
Reference Type:
publication
Title:
Lipid Emulsions in Parenteral Nutrition
Author:
Adolph, M.
Year:
1999
Bibliographic source:
Ann Nutr Metab 43:1ā€“13

Materials and methods

Principles of method if other than guideline:
The article provides a brief overview of the evolution of different types of lipid emulsions, which are already in widespread clinical use for parenteral nutrition or are in a final stage of development.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Lipid emulsions containing a physical mixture of medium and long chain triglycerides
(MCT/LCT)

Test animals

Species:
other: human

Administration / exposure

Route of administration:
intravenous

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Long Chain Triglycerides in Parenteral Nutrition

Over the last 3 decades lipid emulsions based on long-chain triglycerides (LCT) derived from soybean or safflower oil have been used in parenteral nutrition. For many years, lipid supply was considered as a means of preventing or correcting essential fatty acid deficiency and of providing an efficient fuel to many tissues of the body. In the 1970s, the first reports of an interference with the immune system were published [2, 3] and were confirmed by further observations in the 1980s [4] and 1990s [5]. Obviously these effects are related to the dose and infusion rate of lipid emulsions. The mechanisms are not totally clear, but an excessive intake of linoleic acid seems to be one of the major reasons [6]. Therefore, efforts at further developing and optimizing lipid emulsions have focused on replacing part of the LCT by medium- chain triglycerides (MCT) synthesized from coconut oil.

Medium Chain Triglycerides in Parenteral Nutrition

Since 1984, a MCT/LCT-containing lipid emulsion has been available on the European market and later on worldwide. Numerous research teams have studied the parenteral application of this physical MCT/LCT mixture in a clinical environment and during long-term home parenteral nutrition (HPN). MCT have several advantages in comparison to LCT. Because of their physical and chemical properties, MCT have a better solubility and are more readily hydrolyzed by lipases. They are more quickly eliminated from the circulation and taken up by peripheral tissues. They are not stored as body fat but oxidized more rapidly than LCT. MCT are ketogenic and consequently both medium- chain fatty acids (MCFA) and ketone bodies are carnitine-independent substrates. For these and other reasons the comparison of LCT and MCT with respect to several effects is of interest.

MCT/LCT versus LCT: Conclusion

Directly compared with pure LCT emulsions, MCT/LCT emulsions are a more efficient fuel, put less strain on the liver, and have significantly less impact on the immune system and RES function. MCT/LCT emulsions appear to be of particular benefit to patients with systemic inflammatory response syndrome or sepsis because, containing only half the amount of LCT, they supply a significantly smaller amount of nā€“6 fatty acids and hence of the precursors of potentially immunosuppressive prostaglandins.

Applicant's summary and conclusion

Conclusions:
The parenteral route = central intravenous route of application of medium and long chain triglycerides is a well-proven concept in the parenteral nutrition of critically ill patients.