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HISTORY OF MEDICINE
ΙΣΤΟΡΙΑ ΤΗΣ ΙΑΤΡΙΚΗΣ
ARCHIVES OF HELLENIC MEDICINE 2012, 29(2):258
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263
ÁÑ×ÅÉÁ ÅËËÇÍÉÊÇÓ ÉÁÔÑÉÊÇÓ 2012, 29(2):258
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263
Κυαισό – βραχεία ιστορική
αναδροή από το «κυάμων
απέχεσθαι» του Πυθαγόρα
έω σήερα
Περίληψη στο τέλος του άρθρου
Favism
A brief history from the “abstain from beans”
of Pythagoras to the present
Favism is a form of hemolytic anemia and jaundice following the intake of
fava beans and other legumes and various drugs. It is caused by a hereditary
abnormality of the red cell enzyme glucose-6-phosphate dehydrogenase
(G6PD). The condition is common in the Mediterranean basin. Various
disturbances caused by fava beans, and especially toxic hemolytic anemia,
have been recognized even from the period of Pythagoras, and the adage “be
far from the consumption of fava beans” constitutes part of his consultations.
...............................................
J. Meletis
Department of Hematology and Bone
Marrow Transplantation Unit, National
and Kapodistrian University of Athens,
School of Medicine, “Laiko” General
Hospital, Athens, Greece
...............................................
Submitted 10.11.2011
Accepted 30.11.2011
Key words
Favism
Glucose-6-phosphate
dehydrogenase deficiency
G6PD
Pythagoras
Copyright
©
Athens Medical Society
www.mednet.gr/archives
ARCHIVES OF HELLENIC MEDICINE: ISSN 11-05-3992
Favism (favisme, fabismus, favismo, fabism) is a reaction
to the ingestion of the fava plant, its beans, pods and,
most likely, foliage, or to inhalation of fava pollen. It is
due to a hereditary abnormality of the red cell enzyme
glucose-6-phosphate dehydrogenase (G6PD), which can
cause sudden destruction of the red cell with hemolytic
anemia and jaundice following the intake of fava beans,
other legumes or various drugs. Favism is common in the
Mediterranean area, Africa and southern Asia. More than
400 genetic variants have now been recognized.
The consumption of fava beans originated in the Near
East in late Neolithic times and later they were cultivated in
ancient Egypt, Greece and Rome. Fava beans are mentioned
several times in the Iliad of Homer (8th to 9th century BC).
1,2
The ancient Greeks apparently associated the little black
spot on the hilum of the bean with death and, although
the beans were sometimes offered in sacrifices to Apollo,
the priests were strictly forbidden to eat the fava bean or
even to mention its name. Unlike the Egyptians and Greeks,
the Romans held the fava beans in high esteem among
legumes. The beans referred to by Pythagoras (c. 570 to c.
495 BC) are fava beans (vicia fava, vica faba vulgaris), which
botanically are classified as a large seeded vetch. The plant
is well adapted to the Mediterranean region because it is
very hardy to the cold and grows vigorously during the
cool wet months of winter. There is evidence that it has for
centuries been a unique and invaluable part of the diet of
the people living in the Mediterranean basin. Its history is
redolent with superstition, prohibition, magic and fear.3−18
It is well known that for some people fresh fava beans
can be poisonous. Although common and known of for
centuries, favism as a genetically transmitted disease was
recognized only at the beginning of the 20th century and
its mechanism was fully explained only in the last decades.
In Classical Greece doctors had seen the importance
«…κυάμων απέχεσθαι…», “…kyamon apechehesthe…”
“…be far from the consumption of fava beans …”
(part of Pythagorean consultations)
HISTORY OF FAVISM 259
of the environment, natural elements and “aliments” for
maintaining the right balance of the organism. The occurrence
of hemolytic anemia in individuals due to lack of the
enzyme G6PD was known about for many years. It was
called “favism”, relating its occurrence to the consumption
of fava beans (the corresponding Greek words are «κύαοι»,
(“kyamoi”), «κυαισό» (“kyamismos”, i.e., favismus). The
observation that the consumption of fava beans causes
various disturbances was the first instance of recognition of
toxic hemolytic anemia and the rule «κυάων απέχεσθαι»
(“kyamon apechesthe”), “be far from the consumption of fava
beans”, constitutes part of Pythagorean consultations.10,19−28
This rule restricted the consumption of a legume that is
named the Greek fava bean (kyamos Hellenikos, Vicia fava,
Vica faba) that had already been cultivated and used in
the Mediterranean since the Prehistoric era. Theophrastus
(372 to c. 285 BC)29 used the word kyamos (vicia fava) to
characterize the plant as well its kernel. Pliny (23 to 79
AD)
30,31
and Dioscorides (40 to 90 AD)
32
separated the
Greek fava been from the fava Aegyptia, pointing out that
the Pythagorean rule concerns only the Greek fava bean.
Empedocles (495 to 435 BC)33−36 during the 5th century
BC continued the Pythagorean teaching declaring that
«δειλοί, πάνδειλοι, κυάων από χείρα έχεσθαι», “deiloi,
pandeiloi, kyamon apo cheiras echesthe” – “unhappy, lot of
miserables, not touched by fava beans”. Kallimachos (310
to 240 BC) during the 3rd century BC wrote «και κυάων
από χείρα έχει, ανιόντο εδεστού, καγώ Πυθαγόρα
ω εκέλευε» “kai kyamon apo cheiras echeis, aniontos
edestou, kago Pythagoras os ekeleve”– “I say also, as said
Pythagoras, you do not touch upon fava beans, that is
corroded food”.
37
Pythagoras refused to walk through fields
of fava beans and forbade his disciples to eat them. He is
said to have met his death at the hands of the people of
Crotonia in Ancient Italy.38,39 Pursued by them, Pythagoras
died at the hands of his enemies because he would not
flee across a bean field, he came to the edge of a bean
field and, rather than set foot in it, was caught and killed
as reported by Artemidoros (1st century BC), Cicero (106 to
43 BC), Iamblichus (c. 245 to c. 325 AD), Diogenes Laertios
(c. 3rd century AD), Pausanias (2nd century AD), Porphyry
(234 to early 4th century AD) and Grigorios Nanzyanzynos
(329 to 390 AD).20,40−45 Iamblichus tells of the time when
some Pythagoreans were being pursued by their enemies
and they came across a field of fava bean plants in bloom.
Rather than disobey their master’s dictates and flee through
the field, they were slaughtered, and when two who
were captured were questioned about their beliefs, they
refused to answer. The husband chose death and the wife,
a Spartan, bit off her tongue and spit it at her captors to
avoid “spilling the beans”.22
Τhe rejection of fava beans is also reported by philosophers
of India constituting very probably prevention lauded by
the Greeks. Whether or not poisoning was the basis of
Pythagoras’ pronouncement, for many this argument is not
certain. This debate is well summed up by Aristotle (384
to 322 BC) and Aulus Gelius (c. 125 to c. 180 AD), who say
that Pythagoras proscribed fava beans either because they
look like genitals (testicles), or because they resemble the
gate of Hades, for they alone have no joints, since these
two correlate well with traits connecting beans with human
life and generation referred to by other ancient writers.
Alternative interpretations are that they spoil, or that they
resemble the base of the universe, or that it was believed
that beans really mean eggs and the eating of an egg is
similar to eating the animal that comes from it, or because
of oligarchy, as the beans were used or drawing lots.19,23
Aristotle and Diogenes Laertios proposed that the
Pythagoreans rejected fava beans because they are possibly
poisonous and they provoke flatulence, which can destroy
one’s mental peace by keeping one awake with a rumbling
stomach.20
The later sect known as the Orphics believed that
Pythagoras had forbidden the eating of fava beans because
they contain the souls of the dead. “Eating fava beans and
gnawing on the heads of one’s parents are one and the
same,” went one of their sayings.
Herodotus (485 to 421 BC) reports that Egyptian priest
considered beans to be unclean, while Pausanias and
Porphyry note that they were forbidden for Orphics and the
iniates at Eleusis, and they were items not to be touched,
including them in a list along with pomegranates, recently
delivered women and dead bodies, showing a possible
relationship with religious dogmas.34,43,44
All the above testimonies emanate from members
of the population that were not doctors. Although the
Hippocratic doctors could not ignore the Pythagorean
dietetics, the prohibition of fava beans is not reported in
their treatises.19
Around the turn of the 20th century, physicians began
to recognize the occurrence of favism after eating fresh
fava beans and began to notice that some people suffer
a sudden illness that, in some cases, led rapidly to death.
The cause seems obvious today, but it was not until 1904
when Clemens von Pirquet came up with the medical
definition for allergies. Before this time, it was difficult for
doctors to comprehend the concept that what might be
fine for one person might be poison for another. The first
modern report of favism (favismus, kyamismos) is found in
260 J.C. MELETIS
a Lisbon magazine where in 1843 Manuel Pereira de Mira
Franco reported the case of individual who presented with
jaundice each time where he ingested fava beans.46 From
1856 the Sicilian Antonio Mina La Grua,47 but also other
doctors, such as Di Pietra-Leone, Rizzo-Matera and Pietro
Messina pointed out cases of jaundice from inhalation of
pruducts, possibly ethereal oils, of the fava bean flowers.
They identified the hereditary nature of this illness, and
distinguished this form of icterus from the jaundice of malaria,
and confirmed the main role of fava beans. Giovanni Mule
Bertolo (1900) observed the appearance of hemoglobinuria
and proposed the term “favismus”. The Sicilian patient
Salvare Greco (his surname points to his Greek origin but
also to his “stigma” of favism) suffered from favismus as did
his maternal grandfather and commented that based on
his experience and his inheritance this corresponded with
the instruction of Pythagoras for the non consumption of
fava beans.
On the threshold of the 20th century doctors hypothesized
that the pathophysiology of favismus was hemolysis
(destruction of red corpuscles) and at a congress in Rome
in 1894 G. Montano reported hemoglobinuria (and no
hematuria as was previously believed) as the main symptom
of the disease, and distinguished the “decisive” reason for the
disease, namely fava beans’ and the “predisposed” reason,
idiosyncrasy.48 Cases were also reported in Italy by Girotti
(1899), Camillis (1901), and in Sardinia by Went (1899), and
Steani (1904). In Greece between 1895 and 1905 Doukas,
Skavetzos, Kavvadias, Vellopoulos, Kontogeorgis, Tselios and
others recognized the illness in various regions of Greece,
both mainland and island regions. The epidemiological
studies of Gasparrini in 1905 clarified the clinical picture,
the familial character and the eclectic presentation in
young persons, particularly males.17,49,50
The possible explanation of favism began to appear
in the 1920s, when scientists found that G6PD deficiency
actually provides a defence against malaria, which was the
main health problem in Greece and Southern Italy at that
time. It was not until the 1940s that W. Boyd from Boston
noted that the British, in contrast to Mediterranean people,
never developed favism after ingestion of fava beans,
suggesting a genetic difference as the possible explanation.
This information became more relevant during World War
II, when treating malaria with quinine-based drugs resulted
in a reaction to the medicine in the same people who
presented hemolysis after eating fava beans.51−55
Subsequently, the complex explanation for the illness
became evident from the experience of American doctors
using antimalarial drugs on African Americans observed
the “favismus of blacks” and related it with the favismus of
the Mediterranean origin. Later, lack of the enzyme G6PD
was clarified as the cause of hemolysis. For years various
constituents of the fava beans were incriminated, but also
rarely other flowering plants, in the challenge of hemolysis.
It was observed that the syndrome was released mainly
after consumption of fresh fava beans and, to a lesser
extent, dry or boiled fava beans, and after simple contact
with the fava bean fruits or flowers, even at a distance,
and that the substance may be transported via breast
feeding. The Greek work of Choremis, Doxiadis, Kattamis,
Stamatoyannopoulos, Fessas, Zannos-Mariolea and others
provided new information on the subject of favism and
its extent in Greece, with the discovery of “hot spots” in
various specific regions, and on elements of the nature
and the inheritance of illness.56−70 Later the physiological
polymorphism of the enzyme G6PD was recognized,
together with the existence of irregular molecules of
the enzyme, and details of the hereditary transfer. Greek
pediatricians realized the relationship of G6PD deficiency
with neonatal jaundice, its correlation with bone damage as
in thalassemia, the co-incidence of the illness in the regions
with malaria and also with other thalassemic syndromes,
and the selection advantage offered by lack of the enzyme
in malaria infection in the heterozygous women but not
in the hemizygous men. The “Mediterranean phenotype”
of the illness was recognized, and also variants of the
enzyme, which were named after Greek regions or cities
(e.g., Athens, Corinthus, Orchomenos, Levadeia, Karditsa,
Attica, Thessaly, etc.) became known. It became apparent
that the condition is most common in males, only women
who carry the gene from both sides of the family are
sufferers, and the condition is most severe among infants
and children and that the “poison” can be passed to the
nursing infant in the mother’s milk.64−70
From all these publications it is apparent that even today
it may be acceptable that the Pythagorean prohibition of
the consumption of fava beans is valid.
It has been found that fava beans contain several chemical
compounds that resemble those found in quinine. They are
rich in two glycosidic compounds, vicine and convicine,
which constitute about 2% of the dry weight. Upon
ingestion, these glycosides are hydrolysed enzymatically
to form pyrimidine aglycones, divicine and isouramil,
respectively. The proposed mechanism for favism is that
these new compounds consequently undergo redox cycling
and the process depletes reduced glutathione, leading
to the formation of free radicals and hydrogen peroxide.
After decades of research it was demonstrated that fava
HISTORY OF FAVISM 261
beans themselves also fight malaria in the same way as
G6PD deficiency (reducing the amount of oxygen in the
blood). Theoretically, when fava beans are consumed by
people with G6PD deficiency who don’t suffer from favism
(the vast majority), the resistance to malaria is raised. On
a theoretical basis, even if fava beans are dangerous to a
percentage of people, their benefits for the remainder of the
population far outweigh their shortcomings. Additionally
during recent years there is documentation that fava beans
(Vicia faba) have lipid-lowering effects and may also be a
good source of antioxidants and chemopreventive factors.
71−94
Is this the secret behind Pythagoras’ puzzle? It remains
hard to say, 26 centuries later. One thing is for certain:
Pythagoras himself is not talking.
ΠΕΡΙΛΗΨΗ
Κυαμισμός – βραχεία ιστορική αναδρομή από το «κυάμων απέχεσθαι» του Πυθαγόρα έως σήμερα
Γ. ΜΕΛΕΤΗΣ
Αιματολογική Κλινική και Μονάδα Μεταμόσχευσης Μυελού των Οστών, Ιατρική Σχολή,
Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών, Νοσοκομείο «Λαϊκό», Αθήνα
Archives of Hellenic Medicine 2012, 29(2):258–263
Κυαισό είναι η εφάνιση αιολυτική αναιία και ίκτερου ετά τη βρώση κυάων ή και διαφόρων φαρακευτικών
ουσιών, που οφείλεται σε ια κληρονοική ανεπάρκεια τη αφυδρογονάση τη 6-φωσφορική γλυκόζη. Η κλινική
αυτή συνδροή είναι αρκετά συχνή στου κατοίκου τη λεκάνη τη Μεσογείου και είναι γνωστή από την αρχαιότητα,
αφού ο Πυθαγόρα ήδη από εκείνη την εποχή, ανάεσα στι άλλε προτροπέ, καθιέρωσε τη συβουλή τη η
κατανάλωση κυάων ε το γνωστό αφορεσό του «κυάων απέχεσθαι».
Λέξεις ευρετηρίου: Ανεπάρκεια αφυδρογονάση τη 6-φωσφορική γλυκόζη, Κυαισό, Πυθαγόρα
References
1. PLUTARCO. De educatione puerorum, 17
2.
PLUTARCH. Symposium II, 3, 635E
3.
LIPPI D.
The broad bean’s syndrome in ancient Egypt. Med Sec-
oli 1989, 1:301−306
4. ARIE THD. Pythagoras and beans. Oxford Medical School Ga-
zette 1959, 11:75−81
5.
DAVIES P. Favism. Postgrad Med J 1961, 37:477−480
6.
BOURQUELOT E. Remarques à propos des fèves de Pythagore.
Compte Rend Soc Biol 1904, LVI:861−862
7.
BRUMBAUGH RS, SCHWARTZ J. Pythagoras and beans: A medi-
cal explanation. Classical World 1980, 73:421−422
8.
BRUMBAUGH RS.
The philosophers of Greece. Albany, New Yor k,
1981
9. DELATTE A.
Études
sur la littérature pythagoricienne. Champion,
Paris, 1915
10. DE VOGEL CJ. Pythagoras and early pythagoreanism. Van Gor-
cum, Assen, 1966
11.
LARQUIER DES BANCELS J.
Sur les origines de la notion de l’ame
à propos d’une interdiction de Pythagore. Arch Psychol 1918,
XVII:58−66
12. LEVY I. Recherches sur les sources de la légende de Pythagore.
Leroux, Paris, 1926
13. NAVIA LE. Pythagoras: An annotated bibliography. New York,
1990
14. SANSONE G, PIGA AM, SEGNI G. Il favismo era conosciuto dai
greci antichi (di S. Veras). In: Il favismo. Minerva Medica, Tori-
no, 1958:5−7
15. STAMATIS ES. Pythagoras of Samos (Greek). Athens, 1981
16. VAN DER WAERDEN BL. Science awakening. New York, 1954
17. GASBARRINI A. Il favismo. Policlinico Sez Pratica 1915, 22:1505
18. LIEBER E. Favism in antiquity. Koroth J 1970, 5:331−335
19. HIPPOCRATES. Epidemics I and III. Translation by WHS Jones.
In: Jones WHS, Withington ET, Potter P, Smith WD (Transl) Hip-
pocrates (vol 1). The Loeb Classical Library, William Heinemann,
London; Harvard University Press, London, 1957−1995:139−287
20. DIOGENES LAËRTIUS. Lives of eminent philosophers. Loeb Clas-
sical Library, New York, 1925
21. MARCOVICH M (ed). Diogenis Laertii vitae philosophorum: Ex-
cerpta Byzantina et indices. Teubner BG, Stutgardiae, 1999
22. PORFIRIO. Vita Pythagorae, 44
23. TAYL OR T. Iamblichus’ life of Pythagoras. London, 1818
24. DIELS H, KRANZ W. Die Fragmenten der Vorsokratiker. 6th ed.
Berlin, 1971
25.
DELATTE A.
Faba Pythagorae cognata. In: Serta Leodiensia.
Li
è
ge, 1940:33−57
27. DE CANDOLLE A. Origine des plantes cultivees. Baill
è
re G, Paris,
1883
28.
DETIENNE M.
La cuisine de Pythagore. Arch Soc Rel 1970,
15:141−162
29. DETIENNE M. Les jardins d’Adonis: La mythologie des aromates
en Grèce. Gallimard, Paris, 1972
30. THEOPHRASTUS. Enquiry into plants IV. Translation by AF Hort.
262 J.C. MELETIS
Heinemann & Harvard University Press, London, 1916
31. PLINIO. Natural history. 18, 118
32. EICHHOLZ DE. Pliny natural history. Loed Classics, no 419
33. DIOSCOURIDES. About medical matter ΙΙ.
34. EMPEDOCLES. Aulos-Gelios Noctes Atticae, IV.
35. HERODOTUS. II, 37, 81, 123
36. GUTHRIE WKC. A history of Greek Philosophy II. Cambridge Uni-
versity Press, 1965
37.
RAVEN GE.
The presocratic philosophers. Cambridge University
Press, 1957
38. KALLIMACHOS. Aulus-Gelius. Noctes Atticae. IV
39. TERTULLIANO. De Anima. 31
40. CICERONE MT. De Divinatione. I, 62
41. HERACLIDES PONTICUS. Lydus, Mens. IV, 42
42. DA ORIGEN. Contra Celsum. V, 41
43. ARTEMIDORO. Onirocriticon. I, 68
44. PORFIRIO. De Abstinentia. IV, 16
45. PAUSANIA. Descriptio Graeciae. I, 37, 4
46. GREGORIUS NAZYANZYNOS. Orations ΧΧΙΙΙ
47. PEREIRA DE MIRA FRANCO M. Favas verdes produsindo ictericia.
Revista Universal Lisbonese, 1843
48. MINA LA GRUA A. Sopra l’ itterizia endemica e su malattie or-
dinarie del condadini di Castelbuono. 1856
49. MONTANO G. Del favismoo intossicazione fabacea. XX Congr
Med Internationale, Roma, 1894, 3:301
50.
FERMI C, MARTINETTI P.
Studio sul favismo. Ann Igiene 1905,
15:76
51.
GASBARRINI A.
Su di una forma ancora insufficientemente co-
nosciuta di anemia acuta febbrile con itterizia ed emoglo-
binuria (il favismo). Folia Clin Chim Microscop 1912−1914,
IV:374−389
51.
LUISADA L.
Favism: Singular disease affecting chiefly red blood
cells. Medicine (Baltimore) 1941, 20:229
54. TURCHETTI A. Forme poco frequenti di emoglobinuria dafar-
maci in consodi infezione malarica. Reforma Medica 1948,
62:325
55. SANSONE G, SEGNI G. Sensitivity to broad beans. Lancet 1957,
ii:295
56. SANSONE G, PIGA AM, SEGNI G. Il favismo. Minerva Medica, To-
rino, 1958
57.
BEUTLER E, KUHL W, VIVESCORRONS JL, PRCHAL JT.
Molecular
heterogeneity of glucose-6-phosphate dehydrogenase A.
Blood 1989, 74:2550−2555
58.
CHOREMIS C, JOANNIDES T, KYRIAKIDES B.
Severe ophthalmic com-
plications following favism. Br J Ophthalmol 1960, 44:353−356
59.
DOXIADIS SA, FESSAS P, VALAES T.
Erythrocyte enzyme deficiency
in unexplained kernicterus. Lancet 1960, ii:44
60.
ZANNOSMARIOLEA L, KATTAMIS C.
Glucose-6-phosphate
dehydrogenase deficiency in Greece. Blood 1961, 18:34−47
61. FORNAINI G, LEONCINI G, LUZZATTO L, SEGNI G. Glucose metabo-
lism in human erythrocytes from normal and fava bean-sen-
sitive subjects. J Clin Invest 1962, 41:1446−1453
62. BOYER SH, PORTER IH, WEILBACHER RG. Electrophoretic hetero-
geneity of glucose-6-phosphate dehydrogenase and its rela-
tionship to enzyme deficiency in man. Proc Natl Acad Sci USA
1962, 48:1868−1876
63.
VALAES T, DOXIADIS SA, FESSAS P.
Acute hemolysis due to naph-
thalene inhalation. J Pediatr 1963, 63:904−915
64.
STAMATOYANNOPOULOS G, FESSAS P.
Thalassemia, glucose-
6-phosphate dehydrogenase deficiency, sickling, and ma-
larial endemicity in Greece. Br Med J 1964, 1:875−879
65. STAMATOYANNOPOULOS G, FRASER GR, MOTULSKY AC, FESSAS P,
AKRIVAKIS A, PAPAYANNOPOULOU TH.
On the familial predispo-
sition to favism. Am J Hum Genet 1966, 18:253−263
66.
KATTAMIS CA, CHAIDAS A, CHAIDAS S.
G6PD deficiency and
favism in the island of Rhodes (Greece). J Med Genet 1969,
6:286−291
67.
KATTAMIS CA.
Some clinical and biochemical aspects of favism
in childhood. Ann Soc Belges Med Trop Parasitol Mycol 1969,
49:298−302
68. KATTAMIS CA, KYRIAZAKOU M, CHAIDAS S. Favism: Clinical and
biochemical data. J Med Genet 1969, 6:34−41
69. STAMATOYANNOPOULOS G, VOIGTLANDER V, KOTSAKIS P, AKRI
VAKIS A. Genetic diversity of the “Mediterranean” glucose-
6-phosphate dehydrogenase deficiency phenotype. J Clin
Invest 1971, 50:1253−1261
70. KATTAMIS C. Favism in breast-fed infants. Arch Dis Child 1971,
46:741
71.
KATTAMIS C, KARAMBULA K, METAXOTOUMAVROMATI A, MATSA
NIOTIS N. G-6-PD deficiency and age. Lancet 1971, i:235
72. KATTAMIS C, KARAMBULA K, IOANNIDOU V, HATZIKOU V. Jaudice
and bilirubin levels in Greek children with favism. Arch Dis
Child 1976, 51:233−235
73.
LUZZATTO L.
Regulation of the activity of glucose-6-phosphate
dehydrogenase by NADP+ and NADPH. Biochim Biophys Acta
1967, 146:18−25
74.
LUZZATTO L, USANGA FA, REDDY S.
Glucose-6-phosphate dehydro-
genase deficient red cells: Resistance to infection by malarial
parasites. Science 1969, 164:839−842
75. BIENZLE U, AYENI O, LUCAS AO, LUZZATTO L. Glycose-6-phos-
phate dehydrogenase and malaria. Greater resistance of fe-
males heterozygous for enzyme deficiency and of males with
non-deficient variant. Lancet 1972, i:107−110
76.
LUZZATTO L, BATTISTUZZI G.
Glucose-6-phosphate dehydroge-
nase. Adv Hum Genet 1985, 14:217−329, 386−388
77. CLARK IA, COWDEN WB. Antimalarials. In: Sies H (ed) Oxidative
stress. Academic Press, London, 1985:136−137
78. LUZZATO L. Glucose-6-phosphate dehydrogenase and other
genetic factors interacting with drugs. Prog Clin Biol Res 1986,
214:385−399
79. BEUTLER E, YOSHIDA A. Genetic variations of glucose-6-phos-
phate dehydrogenase: A catalog and future prospects. Med-
icine (Baltimore) 1988, 67:311−334
80. SENOZAN NM, THIELMAN CA. Glucose-6-phosphate dehydro-
genase deficiency − an inherited ailment that affects 100 mil-
lion people. J Chem Educ 1991, 68:7−10
81.
CORCORAN CM, CALABRÒ V, TAMAGNINI G, TOWN M, HAIDAR B, VUL
LIAMY TG ET AL. Molecular heterogeneity underlying the G6PD
Mediterranean phenotype. Hum Genet 1992, 88:688−690
82. BEUTLER E. G6PD deficiency. Blood 1994, 84:3613−3636
83. BURBANO C, CUADRADO C, MUZQUIZ M, CUBERO JI. Variation of
favism-inducing factors (vicine, convicine and L-DOPA) dur-
ing pod development in Vicia faba L. Plant Foods Hum Nutr
1995, 47:265−275
HISTORY OF FAVISM 263
...................................................................................................................................................
xxxxxxxxxxxxx
84. LUZZATTO L, MEHTA A. Glucose 6-phosphate dehydrogenase
deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds)
The metabolic and molecular bases of inherited disease. 7th
ed. McGraw-Hill Inc, New York, 1995
85.
LUZZATTO L, MEHTA A, MELONI T.
Haemoglobinuria and hapto-
globin in G6PD deficiency. Br J Haematol 1995, 91:511−512
86.
MEHTA A, MASON PJ, VULLIAMY TJ.
Glucose-6-phosphate de-
hydrogenase deficiency. Bailliers Best Pract Res Clin Haema-
tol 2000, 13:21−38
87.
LUZZATTO L, MEHTA A.
Glucose-6-phosphate dehydrogena-
se deficiency. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds)
The metabolic and molecular bases of inherited disease. 8th ed.
McGraw-Hill, New York, 2001:4517−4553
88. HART GD. Descriptions of blood and blood disorders before the
advent of laboratory studies. Br J Haematol 2001, 115:719−728
89. MADAR Z, STARK AH. New legume sources as therapeutic agents.
Br J Nutr 2002, 88(Suppl 3):S287−S292
90. BEUTLER E. Erythrocyte disorders: Anemias due to increased
destruction of erythrocytes with enzyme deficiencies, glu-
cose-6-phosphate dehydrogenase deficiency. G6PD defi-
ciency favism association [from Williams’ Hematology, 6th
ed]. Available at: http://www.rialto.com/favism/english/in-
dex.mv?pgid=beutler_01
91. DYE J. Explaining Pythagorean abstinence from beans. Avail-
able at:
http://www.soci.edu/~phildept/Dye/Beans.html
; Users.
ucom.net/~vegan/beans.htm
92. PARSONS R. The long history of the mysterious fava bean. Los
Angeles Times, 1996. Available at:
http://www.s-t.com/dai-
ly/0-596/05-29-96/c01li096.htm
93. HO HY, CHENG ML, CHIU DT. Glucose-6-phosphate dehydroge-
nase − from oxidative stress to cellular functions and degen-
erative diseases. Redox Rep 2007, 12:109−118
94. ΚΑΤΑΜΗΣ Χ. Ανεπάρκεια αφυδρογονάση τη 6-φωσφορική
γλυκόζη (G6PDd). Κλινικέ και βιοχηικέ πτυχέ. ελτ Α΄
Παιδιατρ Κλιν Παν Αθηνών 1991, 38:125–128
Corresponding author:
J. Meletis, National and Kapodistrian University of Athens,
School of Medicine, Department of Hematology and Bone
Marrow Transplantation Unit, “Laiko” General Hospital, 17
Agiou Thoma street, GR-115 27 Athens, Greece
e-mail: imeletis@cc.uoa.gr
