Correspondence

Lorenzo's Oil and Thrombocytopenia in Patients with Adrenoleukodystrophy

N Engl J Med 1993; 328:1126-1127April 15, 1993

Article

To the Editor:

Adrenoleukodystrophy is a sex-linked disorder in which very-long-chain fatty acids accumulate in all body tissues1. For this reason, a variety of diets have been formulated to lower the levels of these acids. One diet includes Lorenzo's Oil, a product that contains 20 percent erucic acid (22:1) and 80 percent oleic acid (18:1). During the past two years, 40 male and 6 female patients have received Lorenzo's Oil according to a protocol calculated to provide 20 percent of daily caloric intake. In 19 of these patients the platelet count has decreased significantly (Table 1Table 1Platelet Counts before and after Dietary Treatment with Lorenzo's Oil in 46 Patients with Adrenoleukodystrophy.).

The degree of thrombocytopenia that developed in some of the patients prompted further clinical and laboratory studies. In 17 other patients (6 of whom had thrombocytopenia), levels of platelet-associated IgG were normal. Platelet-aggregation patterns revealed no uniform abnormality. Clotting studies, including determination of the prothrombin time, activated partial-thromboplastin time, and fibrinogen level, were negative. Tests for d-dimer in undiluted plasma were positive in 2 of the 17 patients, both of whom had thrombocytopenia. Platelet levels of erucic acid were markedly elevated, whereas those of linoleic (18:3) and arachidonic (20:4) acid were reduced. In six patients with platelet counts of 99, 122, 151, 128, 114, and 212 × 10⁹ per liter, there was an inverse correlation between the number of platelets and the percentage of erucic acid in platelets, as well as between the number of platelets and their size. In 6 patients with thrombocytopenia, platelet counts became normal within 2 to 3 months after erucic acid was omitted from the diet; in 22 subjects following a normal diet and in 24 following a triglyceryl oleate diet, platelet counts remained normal for a period of 12 months. A few patients had minor bruising, but there was no clinically important bleeding.

Rapeseed oil, some types of which have high concentrations of erucic acid, has been an important dietary source of fat in China and India for centuries, in Germany during and after World War II, and in Canada since 1960. Cardiac lipoidosis can develop in animals fed large amounts of erucic acid2. For this reason the Food and Drug Administration has banned the use of oils containing erucic acid from the food supply. Furthermore, a previous report demonstrated that five of seven normal adults had thrombocytopenia after following a rapeseed-oil diet high in erucic acid for 22 days3. In contrast, only one of seven normal adults following a rapeseed-oil diet low in erucic acid subsequently had thrombocytopenia.

These observations suggest that strategies for the dietary management of adrenoleukodystrophy requiring the administration of large amounts of erucic acid may be associated with thrombocytopenia and that the erucic acid component of Lorenzo's Oil is the cause of the thrombocytopenia. The clinical importance of these changes remains to be established. Patients being treated with erucic acid should be followed closely with determinations of the platelet count.

William H. Zinkham, M.D.
Thomas Kickler, M.D.
Janet Borel, M.S., R.D.
Hugo W. Moser, M.D.
Johns Hopkins University School of Medicine, Baltimore, MD 21205

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   David J. Hufford. (2003) Evaluating Complementary and Alternative Medicine: The Limits of Science and of Scientists. The Journal of Law, Medicine & Ethics 31:2, 198-212
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   Nathalie Doerflinger, Jean-Michel Miclea, Jacqueline Lopez, Christine Chomienne, Pierre Bougnères, Patrick Aubourg, Nathalie Cartier. (1998) Retroviral Transfer and Long-Term Expression of the Adrenoleukodystrophy Gene in Human CD34 ⁺ Cells. Human Gene Therapy 9:7, 1025-1036
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   John K. G. Kramer, Frank D. Sauer, Edward R. Farnworth, Dan Stevenson, Gail A. Rock. (1998) Hematological and lipid changes in newborn piglets fed milk-replacer diets containing erucic acid. Lipids 33:1, 1-10
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   P. Revell, A. Green, S. Green. (1995) Platelets in treated adrenoleukodystrophy: a brief report. Journal of Inherited Metabolic Disease 18:5, 635-637
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   W. Krivit, L. A. Lockman, P. A. Watkins, J. Hirsch, E. G. Shapiro. (1995) The future for treatment by bone marrow transplantation for adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome. Journal of Inherited Metabolic Disease 18:4, 398-412
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   H. W. Moser. (1995) Adrenoleukodystrophy: natural history, treatment and outcome. Journal of Inherited Metabolic Disease 18:4, 435-447
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   John K. G. Kramer, Frank D. Sauer, Edward R. Farnworth, Mark S. Wolynetz, Gwynn Jones, Gail A. Rock. (1994) Hematological and lipid changes in newborn piglets fed milk replacer diets containing vegetable oils with different levels of n−3 fatty acids. Lipids 29:12, 859-868
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   Magnhild Rasmussen, Ann B. Moser, Janet Borel, Surinder Khangoora, Hugo W. Moser. (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
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    Hugo W. Moser. (1994) Reactions to the motion picture “Lorenzo's oil”. Controlled Clinical Trials 15:3, 161-164
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    (1994) Lorenzo's Oil and Lymphocytopenia. New England Journal of Medicine 330:8, 577-577
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    H. Toplak, T. C. Wascher, B. Pleschko, H. Ramschak, P. Sedlmayr, M. Wilders-Truschnigg, S. Stckler. (1994) Reduced stimulability of platelet surface adhesion molecules under treatment with Lorenzo's oil. Journal of Inherited Metabolic Disease 17:5, 628-629
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    Hugo W. Moser. (1993) Lorenzo oil therapy for adrenoleukodystrophy: A prematurely amplified hope. Annals of Neurology 34:2, 121-122
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    Sylvia Stöckler, Brunhilde Molzer, Barbara Plecko, Werner Zenz, Wolfgang Muntean, Ulrike Söling, DonaldH. Hunneman, Christoph Korenke, Folker Hanefeld. (1993) Giant platelets in erucic acid therapy for adrenoleukodystrophy. The Lancet 341:8857, 1414-1415
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