Why does DHA-EE work so well?

Why does the DHA-EE work so well with Peroxisomal Biogenesis Disorder (Zellweger’s Syndrome) children verses giving them the triglyceride form of DHA?

To review, since, according to Martinez, Peroxisomal Biogenesis Disorders (Zellweger’s Syndrome) are characterized by absent or defective peroxisomes that carry out important biochemical reactions, most of them related to fat metabolism, the results in a child are an array of glitches in the field of lipids.  The most characterized defect is in the b-oxidation of very long chain fatty acids (VLCFA);  not broken down, VLCFA’s increase in the plasma and tissues.  Peroxisomes begin the manufacturing of plasmalogens, the special phospholipids of myelin, but due to peroxisome’s inability to function properly, the plasmalogens decrease, while other lipids such as phytanic acid and pristanic acid increase.  Synthesis of the much needed lipids, cholesterol and bile acids, is decreased.  A side effect of the decrease in bile acid synthesis is a decrease in absorption of the fat soluble vitamins A, D, E, and K.   Because of bile acid deficiency, fat in the diet is often lost in the child’s stools (steatorrhea) giving them a greasy or waxy appearance and the child fails to thrive.  But the most severe lipid deficiency in Peroxisomal Biogenesis Disorders (Zellewger’s Syndrome) is in DHA, synthesized in peroxisomes by b-oxidation of polyunsaturated fatty acids (PUFA)1.

As is true in Matthew’s situation, most children with Peroxisomal Biogenesis Disorder (Zellweger’s Syndrome) do not break down lipid triglycerides well because of the liver’s inability to synthesize and release very low density lipoprotein (VLDL) particles due to a reduced synthesis of phosphalidylcholine (a phospholipid plus choline)2,3,4.  DHA-EE bypasses the initial step of lipid entry synthesis because it is esterfied to an ethanol (alcohol) backbone and not a glycerol backbone, making it officially not an oil. The DHA-EE form can be thought of as “pre-digested” and is “more bioavailable in that it is more easily processed by the cells that line the intestines and is also more easily incorporated into cell membranes.”6  It appears that the degree of severity and genetic type of each child’s specific disorder contributes to the child’s DHA-TG or DHA-EE absorption.  Due to Matthew’s inability to break down lipids or lipid soluble compounds, his biochemical response to the DHA-EE has been spectacular, whereas the benefits of DHA-TG were minimal.

Peroxisomal Biogenesis Disorder (Zellweger’s Syndrome) children’s poor response to DHA-TG was disclosed in a double blind study using a microencapsulated powder produced by Martek Biosciences Inc. which contained DHA triglyceride (47% DHA) and AA triglyceride (46% AA) conducted by Asif M. Paker, MD, MPH et al [2010] and published May 13, 2010.  The conclusion of the placebo-controlled, randomized trial with Peroxisomal Biogenesis Disorders (Zellweger’s Syndrome) was that the Martek formulation of oral DHA/AA supplementation had no overall effect on growth, visual function, or biochemical measures including VLCFA’s, red blood cell plasmalogen levels, or liver enzyme function5.

1Peroxisomal disorders and their treatment, by Manuela Martinez, MD, Mar 5, 2003, www.momtahan.com/mmartinez/

2A. Poulos, P. Sharp, D. Johnson, C. Easton, The occurrence of polyenoic very long chain fatty acids with greater than 32 carbon atoms in molecular species of phosphatidylcholine in normal and peroxisomedeficient (Zellweger’s syndrome) brain, Biochem. J. 253 (3) (1988) 645–650.

3S. Steinberg, G. Dodt, G. Raymond, N. Braverman, A. Moser, H. Moser, Peroxisome Biogenesis Disorders, Science Direct, 3.3.1 b-oxidation (2006).  http://www.sciencedirect.com/science/article/pii/S0167488906002874

4M. Martinez, I. Mougan, Fatty Acid Composition of Brain Glycerophospholipids in Peroxisomal Disorders, Lipids 34, 733-740 (1999).

5Paker AM, Sunness JS, Brereton NH, Speedie LJ, Albanna L, Dharmaraj S, Moser AB, Jones RO, Raymond GV. Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind, randomized trial. Neurology.2010;75:826–30.

6Murray, Michael. The Ethyl Ester vs. Triglyceride Form of Fish Oils. Dr. Murray Natural Living, 10/11/2010. http://www.expertomega3.com/omega3-news-item.asp?NoticiaID=71     


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