What impact does DHA-EE have on liver disease in Zellweger’s?

What impact does DHA-EE have on liver disease in Peroxisomal Biogenesis Disorders, Zellweger’s Syndrome?

In Matthew’s case before he received diagnosis or supplementation with DHA he presented with effects of liver cholestasis (reduced bile flow) such as newborn jaundice, feeding problems of the newborn, deficiency symptoms of vitamin K and D, waxy stools, profuse sweating, and failure to thrive.   The liver normally facilitates fat absorption in the intestines along with absorption of fat-soluble vitamins.  Matthew’s condition of newborn cholestasis was a consequence of inadequate bile acid synthesis stemming from a defect in side chain oxidation in the sterol 25-hydrolation pathway common to children with Peroxisomal Biogenesis Disorders, Zellweger’s Syndrome.

Four weeks before Matthew was on DHA-EE he took 200 mg/day of DHA-TG, a product made by Martek called Neuromins.  He was able to absorb some of the DHA-TG as evidenced by the lower ratios of VLCFA’s in his plasma, however it did not correct the high fat content of his stools nor the mal-absorption of  fat-soluble vitamins.

In Barcelona before DHA-EE treatment began, the gastroenterologist measured Matthew’s steatorrhea at 4+, a value beyond the highest calculable measure. DHA-EE of 100 mg/day graduating to 300 mg/day was given for three weeks, after which a second stool analysis was done.  This time there was only a trace of fat though his dietary intake of fat had increased, and Matthew had gained over two pounds. Liver function tests also confirmed what we were seeing in Matthew clinically (AST 459 to 238, ALT 300 to 141, gamma-GT 123 to 40).  The DHA-EE had a profound effect on Matthew’s cholestasis whereas the DHA-TG did very little.  The photo on the left was taken after Matthew had been on DHA-TG for a month (the day before he received his first dose of DHA-EE); the photo on the right shows Matthew after he had been on DHA-EE for three weeks.

In August of 2003, due to complications with shipping the DHA-EE, Matthew (5.5 years old) again took Neuromins DHA-TG from Martek, 600mg/day, for 27 days.  The results very significantly indicated deterioration.  Matthew lost 4.5 pounds; he lost interest in eating; he reverted from walking to crawling; and he was noticeably more irritable and floppy.  In addition, obvious lethargy and poor school performance accompanied his frequent falls.  Atonic seizures consistently occurred when Matthew woke up.  Oddly, Matthew’s stools floated during this time.  Very interestingly these things still occurred while he was taking cholic acid, a bile precursor.  Within a few days of resuming the DHA-EE supplementation, Matthew’s symptoms resolved.

Matthew is patient #3 in Table II below.

Table II: Initial effects of the treatment with DHA ethyl ester in two patients with generalized peroxisomal disorders.

From www.momtahan.com/mmartinez

In 2001 Dra. Martinez published research indicated that 100% of patients with Peroxisomal Biogenesis Disorder, Zellweger’s Syndrome, had improvement in liver enzyme function tests (ALT, AST, GGT)¹.

¹Restoring the DHA levels in the brains of Zellweger patients. Martinez M. J Mol Neurosci. 2001 Apr-Jun;16(2-3):309-16; discussion 317-21.