Abstract
Linoleic acid (LA) and α-linolenic acid (ALA) must be supplied to the human body and are therefore considered essential fatty acids. This narrative review discusses the signs, symptoms, diagnosis, prevention, and treatment of essential fatty acid deficiency (EFAD). EFAD may occur in patients with conditions that severely limit the intake, digestion, absorption, and/or metabolism of fat. EFAD may be prevented in patients requiring parenteral nutrition by inclusion of an intravenous lipid emulsion (ILE) as a source of LA and ALA. Early ILEs consisted solely of soybean oil (SO), a good source of LA and ALA, but being rich in LA may promote the production of proinflammatory fatty acids. Subsequent ILE formulations replaced part of the SO with other fat sources to decrease the amount of proinflammatory fatty acids. Although rare, EFAD is diagnosed by an elevated triene:tetraene (T:T) ratio, which reflects increased metabolism of oleic acid to Mead acid in the absence of adequate LA and ALA. Assays for measuring fatty acids have improved over the years, and therefore it is necessary to take into account the particular assay used and its reference range when determining if the T:T ratio indicates EFAD. In patients with a high degree of suspicion for EFAD, obtaining a fatty acid profile may provide additional useful information for making a diagnosis of EFAD. In patients receiving an ILE, the T:T ratio and fatty acid profile should be interpreted in light of the fatty acid composition of the ILE to ensure accurate diagnosis of EFAD.
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Key Points
Patients with EFAD may be treated with PN formulations containing LA and ALA. For PN dependent patients who cannot receive ILE (for example, patients with severe hypertriglyceridemia or an allergy to ILE), oral and topical preparations containing EFAs may be treatment options. There is some evidence that oral preparations containing EFAs may treat EFAD. Several knowledge gaps exist, and numerous research questions need to be addressed. There is a need to determine the contemporary incidence of EFAD in the setting of the newer ILEs. Clarity regarding whether at-risk patients should be screened for EFAD, as well as the criteria for determining the appropriate timing for when such screening should occur, is needed. Currently unanswered questions in the setting of the newer ILEs include how quickly EFAD occurs and for how long does the body need to be depleted of EFAs? Is there a safe period for how long enteral feeding can be withheld before patients develop EFAD, and does short-term EFA depletion have short term or long-term consequences? This last question may be very important in the preterm and infant population, raising concerns about the potential impact of depletion of LA or ALA.
Although EFAD is uncommon in the general population, certain populations of patients are at risk of developing EFAD, including patients receiving PN. The inclusion of ILEs in PN formulations, as a source of EFAs, was found to prevent EFAD in infant and adult patients. An elevated T:T ratio has traditionally been considered biochemical evidence of EFAD. As the assays for measuring fatty acids have improved over the years, the particular assay used and its reference range need to be kept in mind when assessing
whether a patient has EFAD, as well as when evaluating the T:T ratios published in the literature. The optimal balance of fatty acids in ILEs that delivers clinical benefit while reducing adverse effects remains to be determined. Inpatients receiving ILE, the following factors need to be considered when interpreting the fatty acid profile (T:T) and suggesting the diagnosis of EFAD: (1) the fatty acid composition of the ILE, (2) the fatty acid profile levels of the downstream metabolites of LA and ALA (AA, DHA, and EPA) as well as the levels of LA and ALA themselves; (3) the patient’s oral intake and absorption of fatty acids, and (4) the patient’s fatty acid stores.