Lorenzo's Oil

Scientific Name(s):Glyceryl trierucate and glyceryl trioleate

Common Name(s): Lorenzo's oil , glyceryl trierucate with glyceryl trioleate , erucic acid , oleic acid

Uses

Open-label studies in asymptomatic boys (average age at diagnosis, 7 years) with negative magnetic resonance imaging (MRI) and in adults with “pure” adrenomyeloneuropathy (AMN) (ie, noncerebral) suggest that the administration of daily Lorenzo's oil can prevent or slow the progression of the disease. However, there have been no controlled clinical trials.

Dosing

Information is limited and dosage adjustment may be necessary to avoid adverse thrombocytopenia. Lorenzo's oil 2 to 3 mL/day in children 8 years of age (average) has been used in a clinical study. Case studies in Zellweger syndrome report using Lorenzo's oil 2 g/kg daily.

Contraindications

None well documented.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Thrombocytopenia has been reported following treatment with Lorenzo's oil.

Toxicology

Information is lacking.

History

A widely publicized 1992 film ( Lorenzo's Oil ) about a triglyceride mixture used in the treatment of adrenoleukodystrophy (ALD) made the general public aware of the product. 1

Chemistry

Lorenzo's oil is a combination of glyceryl trierucate (an ester of erucic acid, a 22-carbon monounsaturated fatty acid) and glyceryl trioleate (an ester of oleic acid, an 18-carbon monounsaturated fatty acid), which are generally combined in an approximate ratio of 1:4 (glycerol trierucate:glycerol trioleate) when used for clinical evaluation. 2

Uses and Pharmacology

Peroxisomal disorders

Peroxisomal disorders are a group of inherited metabolic disorders that result in demyelination, progressive brain damage, and premature death.

In ALD, a deficiency in a transporter protein results in a lack of the enzyme required to oxidize very long chain fatty acids (VLCFA) with a consequent accumulation of these fatty acids in body fluids and tissues. This X-linked recessive disorder is characterized by demyelination of cerebral nerves resulting in a variety of neurological symptoms, including peripheral neuropathy, blindness, and spastic tetraplegia. The disease is also associated with adrenocortical insufficiency and hypogonadism. 2 , 3 , 4 Treatment includes adrenal steroid replacement, bone marrow transplantation, and Lorenzo's oil. Alternative therapies based largely on animal studies include lovastatin, phenylbutyrate, arginine butyrate, and gene therapy. 2 , 5

Distinct forms of ALD exist. The most common form of ALD is adrenomyeloneuropathy (AMN), a slowly progressing, non-inflammatory form occurs mostly in adults. Childhood cerebral ALD, another of the most common forms, progresses rapidly, while adolescent cerebral ALD affects a small number of patients and progresses more slowly. AMN is estimated to affect about 1 in 40,000 men and 1 in 30,000 women 6 ; while the incidence of cerebral ALD is estimated at 1 in 17,000. 3 Addison disease can be an early indicator of ALD, and screening for ALD is recommended. 4

Zellweger syndrome is a related disorder in which an absence of peroxisomes in the kidney, liver, and brain results in the accumulation of VLCFA with consequent damage to these organs. 7

Animal data

In vitro studies (using cells obtained from patients affected by ALD) and animal studies show that mono-unsaturated fatty acids inhibit the synthesis of toxic, saturated VLCFA and reduce their accumulation in cells. 2 , 4 , 8 Researchers evaluating the biochemical responses of Lorenzo's oil have shown an absence of effect on oxidative stress processes and positive effects on plasma levels of hexacosanoic acid and other long-chain fatty acids. 9 , 10 Mitochondrial abnormalities are being evaluated with a potential role for coenzyme Q10. 11

Clinical data

Reviews of ALD and AMN studies are becoming more consistent in their recommendations about the place of Lorenzo's oil in therapy, although the number of researchers in this field is limited. 4 , 12 A few long-term studies (up to 13 years) are available. 4 , 13 , 14

Open-label studies in asymptomatic boys (average age at diagnosis, 7 years) with a negative MRI, and in adults with “pure” AMN (ie, noncerebral), suggest that the daily administration of Lorenzo's oil can prevent or slow the progression of the disease. 4 , 10 , 15 Single-group trials consistently show a lack of effect in disease progression among those patients who are already symptomatic. 4 , 12 , 16

Double-blind, placebo-controlled, randomized clinical trials are lacking; however, 1 study meeting these criteria to investigate the effect of Lorenzo's oil in pure AMN is underway. 6 Limited case reports of patients with Zellweger syndrome exist with conflicting results. 7 , 17

Dosage

Information is limited, and dosage adjustment may be necessary to avoid adverse thrombocytopenia. 4 Lorenzo's oil 2 to 3 mL per day in children 8 years of age (average) has been used in a clinical study. 10 Case studies in Zellweger syndrome have reported using Lorenzo's oil 2 g/kg daily. 7

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Thrombocytopenia has been reported following treatment with Lorenzo's oil, but the condition can be managed by a dosage adjustment. No evidence of abnormal bleeding has been reported. 4

Purpura, petechiae, bleeding, and depression of natural killer cells have been reported. 18 , 19

Toxicology

Information is lacking.

Bibliography

1. Hudson Jones A. Medicine and the Movies: Lorenzo's Oil at Century's End. Ann Intern Med . 2000;133(7):567-571.
2. Moser H, Dubey P, Fatemi A. Progress in X-linked adrenoleukodystrophy. Curr Opin Neurol . 2004;17(3):263-269.
3. Moser HW, Raymond GV, Dubey P. Adrenoleukodystrophy: new approaches to a neurodegenerative disease. JAMA . 2005;294(24):3131-3134.
4. Moser HW. Therapy of X-linked adrenoleukodystrophy. NeuroRx . 2006;3(2):246-253.
5. Pai GS, Khan M, Barbosa E, et al. Lovastatin therapy for X-linked adrenoleukodystrophy: clinical and biochemical observations on 12 patients. Mol Genet Metab . 2000;69(4):312-322.
6. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Raymond GV. A phase III trial of Lorenzo's Oil in adrenomyeloneuropathy. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2005-[cited 2010 Jun 7]. Available from: http://clinicaltrials.gov/show/NCT00545597NLMIdentifier:NCT00545597 .
7. Arai Y, Kitamura Y, Hayashi M, Oshida K, Shimizu T, Yamashiro Y. Effect of dietary Lorenzo's oil and docosahexaenoic acid treatment for Zellweger syndrome. Congenit Anom (Kyoto) . 2008;48(4):180-182.
8. Rizzo WB. Lorenzo's oil—hope and disappointment. N Engl J Med . 1993;329(11):801-802.
9. Deon M, Wajner M, Sirtori LR, et al. The effect of Lorenzo's oil on oxidative stress in X-linked adrenoleukodystrophy. J Neurol Sci . 2006;247(2):157-164.
10. Deon M, Garcia MP, Sitta A, et al. Hexacosanoic and docosanoic acids plasma levels in patients with cerebral childhood and asymptomatic X-linked adrenoleukodystrophy: Lorenzo's oil effect. Metab Brain Dis . 2008;23(1):43-49.
11. Making rare diseases a public-health and research priority. Lancet . 2008;371(9629):1972.
12. Semmler A, Köhler W, Jung HH, Weller M, Linnebank M. Therapy of X-linked adrenoleukodystrophy. Expert Rev Neurother . 2008;8(9):1367-1379.
13. Moser HW, Raymond GV, Lu SE, et al. Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil. Arch Neurol . 2005;62(7):1073-1080.
14. Restuccia D, Di Lazzaro V, Valeriani M, et al. Neurophysiologic follow-up of long-term dietary treatment in adult-onset adrenoleukodystrophy. Neurology . 1999;52(4):810-816.
15. Moser HW, Mahmood A, Raymond GV. X-linked adrenoleukodystrophy. Nat Clin Pract Neurol . 2007;3(3):140-151.
16. Suzuki Y, Imamura A, Shimozawa N, Kondo N. The clinical course of childhood and adolescent adrenoleukodystrophy before and after Lorenzo's oil. Brain Dev . 2001;23(1):30-33.
17. Tanaka K, Shimizu T, Ohtsuka Y, Yamashiro Y, Oshida K. Early dietary treatments with Lorenzo's oil and docosahexaenoic acid for neurological development in a case with Zellweger syndrome. Brain Dev . 2007;29(9):586-589.
18. Chai BC, Etches WS, Stewart MW, Siminoski K. Bleeding in a patient taking Lorenzo's oil: evidence for a vascular defect. Postgrad Med J . 1996;72(844):113-114.
19. Pour RB, Stöckler-Ipsiroglu S, Hunneman DH, et al. Enhanced lymphocyte proliferation in patients with adrenoleukodystrophy treated with erucic acid (22:1)-rich triglycerides. J Inherit Metab Dis . 2000;23(2):113-119.

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