מחקר חדש מביה”ס לרפואה של הרוורד בבוסטון מוכיח כי חומצת שומן אלפא לינולנית, אומגה 3 ממקור צמחי, וחומצת שומן לינולאית, אומגה 6 ממקור צמחי, אינן חומצות שומן חיוניות כפי שחשבו בעבר. במקום זאת המחקר מוכיח בעזרת ניסויים קליניים בבני אדם ובעכברים כי שמן דגים לבד ללא חומצות שומן צמחיות מונע את התסמינים של מחסור בחומצות שומן חיוניות.
The essentiality of arachidonic acid and docosahexaenoic acid
Hau D.Le a,1, JonathanA.Meisel a, VincentE.deMeijer a, a Department of Surgery, Children’s Hospital Boston, Harvard MedicalSchool, 300 Longwood Ave, Fegan3, Boston, MA 02115, USAKathleen M.Gura b, MarkPuder b Department of Pharmacy, Children’s Hospital Boston, Boston, MA02115, USA
a b s t r a c t
Objective: The purpose of this review is to correlate the clinical finding that patients receiving parenteral nutrition with a fish oil-based lipid emulsion do not develop essential fatty acid deficiency (EFAD) with an experimental murine model, thus showing that arachidonic acid (AA) and docosahexaenoic acid (DHA) are likely to be the essential fatty acids.
Background: Conventional belief is that linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3) are the essential fatty acids (EFAs). We have shown that a fish oil-based lipid emulsion containing AA (omega-6) and docosahexaenoic acid (omega-3) and insignificant quantities of LA and ALA is efficacious in the treatment of parenteral nutrition-associated liver disease (PNALD), a major cause of liver-related morbidity and mortality. The prospect of using a fish oil-based lipid emulsion as monotherapy has raised concerns of EFAD development, hindering its adoption into clinical practice. Design: Data from patients in our institution who received PN with a fish oil-based lipid emulsion was reviewed for clinical and biochemical evidence of EFAD, defined as an elevated triene–tetraene ratio (Mead acid/AA40.2). We also investigated the minimum amount of fish oil required to prevent EFAD in a murine model and determined whether DHA and AA alone can prevent EFAD. Essential FAs are important for human development and various biological functions. Traditional EFAs such as LA and ALA play a major role in preventing EFAD, and are the main precursors for the production of vital metabolites such as AA, EPA, and DHA. While AA produces mostly proinflammatory eicosanoids, EPA and DHA produce anti-inflammatory eicosanoids, as well as other novel molecules such as Resolvin E1 and neuroprotectin D1 that are essential in cognitive and visual functions. LA and ALA are acquired in the human diet in which LA is abundant. Although pregnant women and infants have an increased AA and DHA requirement, the conversions of dietary LA and ALA to AA and DHA are insuficient. AA and DHA supplementation in the form of fish oil ameliorates this problem and prevents EFAD. This explains the effectives of treatment of children with EFAD secondary to fat-free PN with a fish oil-based lipid emulsion as evidenced by complete resolution of their biochemical and clinical evidence of EFAD. This emulsion also prevented and attenuated PN-induced cholestasis in both human and animal models. AA and DHA as the sole FAs demonstrated similar results. Taken together, there is preliminary evidence to suggest that DHA and AA are EFAs, although further investigation is required.
Results: No patients receiving PN with a fish oil-based lipid emulsion in our institution have developed biochemical or clinical evidence of EFAD such as an elevated triene–tetraene ratio, growth retardation or dermatitis. This observation parallels our previously published animal studies, which demonstrated prevention of EFAD when 13% of total calories were from fish oil. Moreover, current work in our laboratory shows that AA and DHA provision alone is sufficient to prevent biochemical and physiologic evidence of EFAD in a murine model.
Conclusions: When dosed appropriately, fish oil-based lipid emulsions contain sufficient EFAs to prevent EFAD. Furthermore, AA and DHA alone may be the true EFAs.