presented at a seminar at the University of Ghent 27.11.2003

1. THE RIDDLE OF LATHYRISM Dirk Enneking PhD Quedlinburg, Germany [email_address]

2. Riddle of the sphinx: "What has one voice, and is four-footed, two-footed and three-footed?" A human being.

3. Lathyrism , a neurodegenerative disorder, three progressive stages: limping ( two-footed ) walking withstick ( three-footed ) crawling ( four-footed ).

6. The Greeks have used Lathyrus sativus (grasspea), L. clymenum and L. ochrus (greek: fava) as food since antiquity.

9. Global Production 1-1,5 Mio ha 0.7 - 1 Mio t of grain +/- forage Also in Chile Canada China Australia Food & Feed No problem with toxicity

12. Neurolathyrism is intricately linked to famine (due to drought or conflict), poverty and malnutrition.

13. Malnutrition is also an important factor associated with other neurodegenerative afflictions such as Konzo (neuro-cassavaism) and optic neuropathy.

15. Eradicate lathyrism ! Reduce toxicity (ODAP) in cultivars and provide adapted non-toxic varieties to grasspea eaters Manage nutritional stress (famines, poverty) & excessive grasspea consumption

16. Identify undernourished grasspea eaters during times of hardship Monitor grasspea production, consumption and prices Educate about processing options (detoxification) + supplements

28. Intensive educational programme Fight against lathyrism is part of the fight against poverty and ignorance Arya, L. S et al. (1988). Lathyrism in Afghanistan. Indian Journal of Pediatrics 55 (3):440-442

30. Governments need to pay attention to the potential threat of neurolathyrism and provide contingency plans to deal with high risk areas during times of famine. (Enneking, 1998)

31. Reduction of poverty and malnutrition in lathyrism prone areas are likely to provide the best solution to this problem (Enneking, 1998)

32. Grain legumes are deficient in sulfur amino acids Except, Non Protein sulfur amino acids, not available for nutritional utilisation: Vigna & Acacia spp. (glutamyl-S-methyl-cysteine sulphoxide) Vicia (V. narbonensis et al.) (glutamyl-S-ethenyl-cysteine)

33. Their anti-nutritional factors deplete sulfur amino acids in predators Many target glutathione (glu-cys-gly) dependent systems

34. Lathyrus sativus seeds contain: Low levels of sulfur amino acids Trypsin inhibitors [high SAA] Tannins Lectins ODAP

35. Thiol Oxidation and Loss of Mitochondrial Complex I Precede ODAP mediated neurodegeneration = thiol reversible, male/female differences Sriram et al. Journal of Neuroscience 1998,18(24):10287–10296 see also review by Ravrindranath (2002) Neurochemistry Intl. 40, 505-509

36. Hypothesis: A lack of reduced thiols predisposes to lathyrism This is caused by depletion through antinutrients, low intake of SAA, oxidative stress and/or genetic defect (s) in thiol metabolism