CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
280
AFRICA
Review Article
The grapefruit: an old wine in a new glass?
Metabolic and cardiovascular perspectives
PETER MO OWIRA, JOHN AO OJEWOLE
Summary
Grapefruit is a popular, tasty and nutritive fruit enjoyed
globally. Biomedical evidence in the last 10 years has,
however, shown that consumption of grapefruit or its juice is
associated with drug interactions, which, in some cases, have
been fatal. Grapefruit-induced drug interactions are unique
in that the cytochrome P450 enzyme CYP3A4, which metab-
olises over 60% of commonly prescribed drugs as well as
other drug transporter proteins such as P-glycoprotein and
organic cation transporter proteins, which are all expressed
in the intestines, are involved. However, the extent to which
grapefruit–drug interactions impact on clinical settings has
not been fully determined, probably because many cases are
not reported.
It has recently emerged that grapefruit, by virtue of its
rich flavonoid content, is beneficial in the management of
degenerative diseases such as diabetes and cardiovascular
disorders. This potentially explosive subject is reviewed here.
Keywords:
grapefruit juice, naringin, hesperidin, drug interac-
tions, diabetes mellitus, cardiovascular disease
Submitted 22/8/09, accepted 10/3/10
Cardiovasc J Afr
2010;
21
: 280–285
Grapefruit (
Citrus paradise
Macf., family: Rutacaeae) is popular
worldwide, not only because of its taste and nutritive value, but
it is also considered to be a functional food that promotes good
health.
1
Scientific evidence backed by molecular biological
techniques has shown that grapefruit is most probably a hybrid
between pummelo (
C grandis
) and sweet orange (
C sinensis
),
followed by introgression back to pummelo.
2-4
The original grapefruit was white-fleshed and very seedy, but
other mutated fruit varieties have been selected for either being
seedless or increasingly red in colour.
2
Such varieties include:
Duncan/Walters (seedy white), Marsh (seedless, white), Foster
(seedy, pink), Thompson (seedless, pink), Redblush (seedless,
red), and Ruby, Ray Ruby and Flame (seedless, very red).
2
These
pigmented cultivars have now become more popular and are
generally preferred to white grapefruit in the market.
5
Claims of medicinal properties of grapefruit have led to
increased worldwide consumption and renewed interest from
basic and clinical research laboratories trying to unravel the
‘mystery’ of this ancient fruit.
Phytochemistry of the grapefruit
A wide variety of bioactive compounds in grapefruit have been
isolated and characterised. Their relative abundance varies
according to the variety, geographical location, time of harvesting
and the method of processing the grapefruit.
6
Flavonoids consti-
tute the most abundant bioactive constituents of the grapefruit,
and four types of flavonoids (flavanones, flavones, flavonols
and anthocynanins) have been identified in the
Citrus
fruits.
7
Other chemical constituents identified in grapefruit include:
limonoid aglycones, glucosides, furanocoumarins (bergamottin,
6
′
,7
′
-dihydroxybergamottin), ascorbic acid, folic acid, glucaric
acid, carotenoids, pectin and potassium.
8-11
The flavanones (naringin and hesperidin) and limonoids
(limonin) are responsible for the bitter taste commonly associ-
ated with grapefruit.
12
Naringin is the most abundant flavanone
in grapefruit, but it is converted to its corresponding aglycone
(naringenin) and sugars by intestinal bacteria following inges-
tion
1,12
(Fig. 1). The list of bioactive compounds in grapefruit is
by no means exhaustive, and understanding their chemistry in
relation to the claimed medicinal benefits is the biggest chal-
lenge facing the scientific community.
A cardiovascular drugs prescriber’s nightmare
A sensational case report published in the
Lancet
last year,
13
describing a 42-year-old woman who developed venous throm-
bosis after taking grapefruit for three days while on a contra-
ceptive, ethynylestradiol, marked the return of the ‘dragon’.
Grapefruit–drug interactions have been known for nearly a
decade now, but unlike drug–drug interactions, food–drug inter-
actions are difficult to legislate. Hence, nothing has been done
to address the dangers that patients often expose themselves to
while taking grapefruit with prescribed medications.
Cardiovascular drugs constitute more than 50% of the close
to 40 or more drugs so far known to interact with grapefruit, and
the list is growing.
14
The accidental observation of pharmacoki-
netic interaction between ethanol and dihydropyridine calcium
channel antagonist (felodipine) when grapefruit juice was used
as a flavour to mask the ethanol taste in a study by Bailey
et al
.
15
opened a Pandora’s box. Other calcium channel blockers that
have been discovered to interact with grapefruit include nifed-
ipine, verapamil, diltiazem, nisoldipine, nimlodipine, nitren-
Department of Pharmacology, School of Pharmacy and
Pharmacology, Faculty of Health Sciences, University of
KwaZulu-Natal, Durban, South Africa
PETER MO OWIRA, BSc, BSc (Med Hons), MSc (Med), PhD
(Pharmacol),
JOHN AO OJEWOLE, BPharm (Hons), MSc (Clin Pharm), PhD
(Pharmacol)
