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Laval University
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All content following this page was uploaded by Sebastien La Vieille on 04 January 2019.
Affiliation: S. La Vieille, D.E. Lefebvre, and M.R. Decan are with the Bureau of Chemical Safety, Food Directorate, Health Canada, Ottawa,
Ontario, Canada. S. La Vieille and S. Godefroy are with the Department of Food Sciences, Faculty of Agriculture and Food Sciences,
Universite Laval, Quebec City, Quebec, Canada. A.F. Khalid is with the Health Policy PhD Program, McMaster University, Hamilton, Ontario,
Canada. S. Godefroy is with the Institute of Nutrition and Functional Foods, Universite Laval, Quebec City, Quebec, Canada.
Correspondence: S. La Vieille, Bureau of Chemical Safety, Food Directorate, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa,
ON K1A 0K9, Canada. Phone: þ1-343-542-3889; Email: sebastien.lavieille@canada.ca.
Key words: G6PD deficiency, favism, food additive, food coloring agent, herbal product.
C The Author(s) 2018. Published by Oxford University Press on behalf of the International Life Sciences Institute.
V
All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
doi: 10.1093/nutrit/nuy053
Nutrition ReviewsV Vol. 0(0):1–11
R
1
Role of G6PD enzyme in red blood cell metabolism have less than 10% of normal G6PD enzyme activity. In
and integrity some patients with class I variants, the residual levels of
enzyme activity are so low that a sufficient concentra-
In the various types of cells in the body, several antioxi- tion of NADPH cannot be maintained, leading to
var major). Its association with G6PD deficiency is well circulation) is the most common form of favism.
documented in the scientific and medical literature. Individuals who develop favism are almost invariably
Several authors have already reviewed the epidemiol- deficient in G6PD, but, owing to the polymorphism of
ogy,3,12,21 pathophysiological mechanisms,4,22–25 and the deficiency, not all persons with the deficiency are
clinical features of favism.3,4 Therefore, fava beans have sensitive to fava beans.12 Thus, anemia is usually most
already been validated as a food that should be avoided severe and most common with the class I variant and is
in patients with G6PD deficiency. somewhat less so with the Mediterranean variant (class
Known since antiquity,12,26 acute hemolysis caused II).21,32,33 Favism has been observed occasionally in
by fava bean ingestion in patients with G6PD deficiency patients with the G6PD A variant (class III).5,14,34,35 It is
presents strong analogies to hemolysis caused by oxida- considered rare among people from Thailand or
tive drugs.27 Two pyrimidine glycosides (vicine and Southeast Asia, possibly because of different G6PD
convicine) isolated from fava beans have been impli- mutations or a different consumption pattern of fava
cated as favism-inducing factors. There are various ana- beans among these populations.32,36 Whatever the re-
lytical methods and bioassays for their quantification in gion, favism is generally more frequent in children (be-
fava beans.28 The active substances within these pyrimi- tween the ages of 1 and 5) but can occur in adults.14,37
dines are their aglycone derivatives.22,26,29 Divicine is It may also occur on one eating occasion but not on an-
the aglycone derivative of vicine, and isouramil is the other,37,38 possibly because of the amount of fava beans
aglycone of convicine. Both of these oxidizing substan- ingested in the meal, the type of beans prepared (raw,
ces rapidly overwhelm the already diminished fresh, cooked, or dried), or the concentration of pyrimi-
glutathione-generating capacity of G6PD-deficient cells dine glycosides in the fava bean cultivars.39
and also have direct effects on red blood cell function. The species Vicia faba belongs to the genus Vicia.
In vitro studies have shown that divicine reduces the ac- Within that species, Vicia faba var major is the botani-
tivity of catalase, an enzyme that, like glutathione, con- cal variety (subspecies), commonly known as fava beans
tributes to hydrogen peroxide removal and requires or broad beans. Other varieties within the species Vicia
NADPH for maintenance of normal activity.30 faba with seeds reported to be involved in favism are
Similarly, isouramil treatment of erythrocytes in vitro Vicia faba var minor and Vicia faba var equina.40 These
caused a marked decrease in cellular membrane 2 varieties, which have seeds that are smaller in size, are
deformability, which was presumed to be a factor in grown mainly for use as protein supplements in animal
erythrocyte sequestration in individuals with G6PD de- feed. The main feature of Vicia faba var major is the
ficiency.31 Acute intravascular hemolysis (ie, loss of large size of its seeds, intended for human consump-
membrane integrity of erythrocytes in the blood tion. Fresh and raw seeds are harvested at the immature