Treatment with Lorenzo's Oil

Lorenzo’s Oil is a 4:1 mixture of glyceryl trioleate (oleic acid - monounsaturated fatty acid) and glyceryl trierucate (erucic acid - monounsaturated fatty acid). It has been found that oral administration of this oil in cerebral ALD patients is able to successfully normalize levels of VLCFA in the plasma, only for boys that are largely asymptomatic. There therapy was first introduced in 1981, with intentions to reduce the level of very long chain fatty acids (VLCFA) in the plasma. It was found that a diet alone with reduced intake of saturated VLCFA did not alter plasma C26:0 levels, due to endogenous synthesis of these fatty acids. In 1986, the addition of monounsaturated oleic acid reduced the levels and the rate of biosynthesis of saturated VLCFA in cultured skin fibroblasts of patients with ALD. From this, it was found that oral administration of gylceryl trioleate for a period of 3 to 4 months significantly lowered plasma C26:0 levels by approximately 50%. Furthermore, in 1989, Augusto Odone, the founder of Lorenzo’s Oil, added erucic acid to the oil, on the basis of a review of lipid manipulation in animal studies and reports that erucic acid and saturated long-chain fatty acids are elongated by the same microsomal enzyme system. The unsaturated fatty acids in Lorenzo’s Oil competitively compete for chain elongation with saturated fatty acids resulting in reduced endogenous synthesis of VLCFA. This led to the final component in Lorenzo’s Oil, and has been shown to normalize levels of saturated VLCFA and delay the progression of neurologic abnormalities within 4 weeks in most patients.

Lorenzo’s Oil is still popularly used in many ALD patients, but has received inconclusive results within studies. A study conducted by Moser et al. (2005) followed-up 89 asymptomatic boys with X-ALD between the years of 1989 and 2002 that have been treated with Lorenzo’s Oil. The oil was taken orally in a dosage that provided 20% of caloric intake while other fat intake was only limited to 10% to 15% of total calories. Patients were followed up at 6-month intervals. 74% (66) of studied patients were well upon their last follow-up, meaning that they exhibited normal neurological status and normal brain MRI results. Results from the study are shown in the table below after the final follow-up. From this study, it is recommended that Lorenzo’s Oil therapy be offered to male patients with ALD who are neurologically asymptomatic, have normal brain MRI results and are at risk of developing cerebral ALD. Intensive Lorenzo’Oil therapy during the ages at which the risk for cerebral ALD is greatest (boys younger than 7 years) may protect against this phenotype until patients reach ages at which the risk for cerebral ALD diminishes (after 10 years of age).

The administration of Lorenzo’s Oil has only been successful in halting the progression of the disease in patients that are largely asymptomatic, and has limited success in patients that already have neurological abnormalities and are symptomatic. There is evidence that dietary therapy can reduce the levels of VLCFA in the plasma, adipose tissue and liver but no significant reduction is observed in the brain (possibly due to the fact that erucic acid cannot enter the brain at a significant quantity). There is also no evidence of a clinically relevant benefit from dietary treatment with oleic and erucic acids in patients with adrenomyeloneuropathy. Early detection of this disease is crucial in order to obtain the benefits of the oil.

Nevena V.

References:

Moser H, Dubey P, Fatemi A (2004) Progress in X-linked adrenoleukodystrophy. Current opinion in neurology 17(3): 263-269.

Moser H et al. (2005) Follow-up of 89 Asymptomatic Patients With Adrenoleukodystrophy Treated With Lorenzo’s Oil. Archives of Neurology 62: 1073-1080.

Aubourg et al. (1993) A two-year trial of oleic and erucic acids ("Lorenzo's Oil") as treatment for adrenomyeloneuropathy. The New England Journal of Medicine 329(11): 745-752.

Rasmussen M., Moser A., Borel J., Khangoora S., Moser H. (1994) Brain, liver, and adipose tissue erucic and very long chain fatty acid levels in adrenoleukodystrophy patients treated with glyceryl trierucate and trioleate oils (Lorenzo's Oil). Neurochemical Research 19(8): 1073-1082.