Lorenzo’s oil
August 24th, 2010 |X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene that is located at Xq28. It has an incidence of 1:17,000 and all races are affected. It is secondary to a defect in peroxisomal ATPase Binding Cassette Protein (ALDP) resulting in defective peroxisomal beta oxidation and the accumulation of very long chain fatty acids (VLCFA: (see the very long-chain fatty acid page for more details). While all tissues have the genetic defect, the resultant disease affects primarily the myelin, adrenal cortex, and Leydig cells of the testes.
VLCFA restricted diet
The biochemical abnormality of X-ALD was first recognized in 1976. Affected individuals had an elevation of very long saturated fatty acids. The demonstration of this abnormality and the recognition that many of these fatty acids were of dietary origin prompted early attempts to lower the blood levels by changing the diet. This diet was very restricted in food choices since VLCFA are present in many plant and animal products. Unfortunately, in spite of this severely restricted diet, there was no substantial lowering of plasma VLCFA.
Inhibiting the synthesis of VLCFA
This failure of dietary effect led to the understanding that there must also be a significant production within the body of VLCFA. There have been a variety of attempts to interfere with long chain fatty acid elongation. The early focus was on the use of long chain fatty acids with an initial double bond – these administered oils were slightly different than the long chain fatty acids without double bonds that went on to become the saturated VLCFA that accumulated and it was predicted that they would swamp the elongation process driving the production down.
Lorenzo’s oil
The introduction of oleic acid (C18:1) followed by erucic acid (C22:1) when used in combination with a moderately low fat diet resulted in lowering of VLCFA in 6-8 weeks in affected individuals. This oil which is a 4:1 mixture of glyceryl trioleate (GTO) and glyceryl trierucate (GTE) has been named Lorenzo’s oil. This oil is taken orally and is generally well tolerated although a moderate reduction of platelets and elevation of liver transaminases has been seen.
From the initial studies examining the role of this mixture in X-ALD, it was very apparent that it did not alter the progression of cerebral disease in affected individuals. This experience has been demonstrated repetitively. Lorenzo’s oil does not alter the course of childhood or adult cerebral adrenoleukodystrophy and is never indicated in the cerebral form of the condition. In addition, it has never been studied in the preparation for bone marrow transplantation or in the period of time following that treatment.
The use of diet and Lorenzo’s oil in the adult form of X-ALD, adrenomyeloneuropathy (AMN), is not settled. Initial studies used the treatment in small populations with variable presentations for short periods of time without definitive effect.
These very limited clinical trials led to broad statements of a lack of effect and concerns that the active ingredients did not get into the brain. However, recent experimental evidence does indicate that erucic acid does get into the brain and is rapidly metabolized.
In the early 1990’s several groups independently began studying the use of Lorenzo’s oil as a preventative therapy – an agent that would either prevent cerebral disease in boys who were at risk, but unaffected or slow the progression in men with adrenomyeloneuropathy. All of these trials were open trials and were thus somewhat limited in the ability to be definitive.
Moser et al (2005) reported the experience in a large group of boys who had normal MRI at their entry into the study. In this group, VLCFA were lowered by therapy and a relationship could be demonstrated in a reduction of risk of developing childhood cerebral disease and the reduction of VLCFA.
In men with adrenomyeloneuropathy, Kohler et al has shown stabilization in progression of the myelopathy. The limits of this study are the lack of placebo group, slowness of disease progression, and natural variation.
At this time, Lorenzo’s oil continues to be studied. Because of the risks of developing childhood cerebral disease, it is suggested that it be used in identified presymptomatic boys in collaboration with a program to monitor for cerebral disease. Boys on this therapy must lower their VLCFA to potentially benefit and lower the risk of cerebral disease. Given the close supervision that must occur for this to happen, we recommend that this therapy only be undertaken by centers that have the ability to provide monitoring with MRI, nutritional guidance, and the ability to measure VLCFA and other essential fatty acids.
The use in adults is not presently recommended unless it is within a study framework evaluating the efficacy of oil and diet and again it is not indicated in cerebral disease.
Lorenzo’s oil must never be undertaken without physician supervision. While serious untoward reactions have not been seen in the monitored use of the oil and diet, individuals on therapy must be periodically evaluated for safety. Finally, it must be stated firmly that Lorenzo’s oil is only indicated for the biochemical defect of adrenoleukodystrophy and does not have any role in other demyelinating or progressive neurologic conditions since those individuals will have the ability to metabolize very long chain fatty acids.
