PHYTOTHERAPY RESEARCH, VOL.

12, 233–242 (1998)

REVIEW
Antidiabetic and Hypocholesterolaemic Effects
of Fenugreek

Molham Al-Habori1 and Amala Raman2

1
Department of Clinical Biochemistry, Faculty of Medicine and Health Sciences, University of Sana’a, Sana’a, Republic of Yemen
2
Pharmacognosy Research Laboratories, Department of Pharmacy, King’s College London, Manresa Road, London SW3 6LX, UK

The seeds of Trigonella foenum graecum (fenugreek) have been reported to have antidiabetic and hypo-
cholesterolaemic properties in both animal models and humans. Activity has been attributed largely to
fenugreek’s saponin and high fibre content, and is probably not related to its major alkaloid trigonelline.
Antihyperglycaemic effects have been linked to delayed gastric emptying caused by the fibre content,
and to (unidentified) components that inhibit carbohydrate digestive enzymes. Fenugreek administration
may increase plasma insulin levels in vivo. Its major free amino acid, 4-hydroxyisoleucine, stimulates in-
sulin secretion from perfused pancreas in vitro. The hypocholesterolaemic effect has been attributed to
increased conversion of hepatic cholesterol to bile salts due to loss, in the faeces, of complexes of these
substances with fenugreek fibre and saponins. Fenugreek treatment selectively reduces the LDL and
VLDL fractions of total cholesterol, and HDL-cholesterol has also been reported to increase in alloxan-
induced diabetic rats and type II diabetic individuals following treatment with fenugreek. Fenugreek ad-
ministration has not been reported to cause any toxicological effects. Its regular consumption may there-
fore be beneficial in the management of diabetes and the prevention of atherosclerosis and coronary
heart disease. # 1998 John Wiley & Sons, Ltd.
Phytother. Res. 12, 233–242 (1998)

Keywords: fenugreek; antidiabetic; insulin; hypocholesterolaemic; saponins; fibre.

INTRODUCTION its seeds for their carminative, tonic and aphrodisiac

effects (Chopra et al., 1982). It is assumed to have a
stimulating effect on the digestive process (Fazli and
Fenugreek (Trigonella foenum graecum L.) is an annual Hardman, 1968). Fenugreek seeds, which are described
plant from the family Papilionaceae-Leguminosae, and is in the Greek and Latin Pharmacopoeias, are said to have
extensively cultivated as a food crop in India, the antidiabetic activity (Moissides, 1939; Shani et al., 1974;
Mediterranean region, north Africa and Yemen. Fenu- Bever and Zahnd, 1979). A curative gastric antiulcer
greek seeds are well known for their pungent aromatic action of the seed (Al-Meshal et al., 1985) and hypo-
properties (Max, 1992). As a spice, they are a component cholesterolaemic effects (Singhal et al., 1982; Sharma,
of many curry preparations (Parry et al., 1943) and are 1984) have been reported. The aim of this review is to
often used to flavour food and stimulate appetite. Chronic examine the literature on the antidiabetic, hypochole-
oral administration of an ethanol extract of fenugreek sterolaemic and hypolipidaemic effects of fenugreek.
(10 mg/day per 300 g body weight) significantly in-
creases food intake and the motivation to eat in rats (Petit
et al., 1993), which might be related to the aromatic
properties of the seeds (Girardon et al., 1985). Fenugreek CHEMICAL ANALYSIS
seeds are used in India as a condiment, in Egypt as a
supplement to wheat and maize flour for bread-making, Chemical analysis of fenugreek indicates that the seeds
and in Yemen it is one of the main constituents of the are a rich source of protein, unavailable carbohydrate,
normal daily diet of the general population. Fenugreek mucilages and saponins (Sauvaire and Baccou, 1976,
leaves are consumed widely in India as a green, leafy Baccou et al., 1978; El-Mahdy and El-Sebaiy, 1985;
vegetable, and are a rich source of calcium, iron, b- Udayasekhara Rao and Sharma, 1987). Fenugreek
carotene and other vitamins (Sharma, 1986b). resembles guar gum in its high dietary fibre content,
Trigonella foenum graecum L. (in Arabic, Hulabah) is and its high viscosity (Chatterjee et al., 1982; Valette et
also employed as a herbal medicine in many parts of the al., 1984). Fenugreek seeds are also rich in saponins
world. Its leaves are used for their cooling properties and (Sharma, 1986a). Anis and Aminuddin (1985) have
reported the presence of three steroidal sapogenins,
diosgenin (Fig. 1), gitogenin and tigogenin. The use of
* Correspondence to: M. Al-Habori, Department of Clinical Biochemistry,
Faculty of Medicine and Health Sciences, University of Sana’a, P.O. Box
more sophisticated analytical techniques including
19065, Sana’a, Republic of Yemen. coupled GC-MS have detected and identified ten
Contract/grant sponsor: British Council. different sapogenins (Brenac and Sauvaire, 1996). The

CCC 0951–418X/98/040233–10 $17.50

# 1998 John Wiley & Sons, Ltd. Accepted 20 January 1998
234 M. AL-HABORI AND A. RAMAN

of these treatments (Marles and Farnsworth, 1995; Bailey

and Day, 1989). The hypoglycaemic and/or antihyper-
glycaemic effect of several plants used as antidiabetic
remedies has been confirmed and the mechanisms of their
activity are being studied (Marles and Farnsworth, 1995).
Chemical studies directed at the isolation, purification
and identification of the substances responsible for the
antidiabetic activity are also being conducted (Attaur-
Rahman and Zaman, 1989; Bailey and Day, 1989; Ivorra
et al., 1989; Alarcon-Aguilar et al., 1993; Sadhukhan et
al., 1994; Marles and Farnsworth, 1995).
Fenugreek seeds have been known for a long time for
their antidiabetic action (Moissides, 1939; Mishkinsky et
al., 1967). Fourier (1948) observed that the administra-
tion of coarsely ground fenugreek seeds improved severe
diabetes in human subjects. This property was later
confirmed in alloxan-diabetic rats, where the seed extract
induced a significant hypoglycaemic effect (Bever and
Zahnd, 1979; Khosla et al., 1995a), as did its major
alkaloid, trigonelline (Shani et al., 1974). Ghafghazi et
Figure 1. Putative antidiabetic or hypocholesterolaemic
al., (1977) have shown that an extract of fenugreek
compounds in fenugreek seeds. prevented the hyperglycaemia induced by cadmium and
alloxan in rats. Amin et al., (1988) also showed that
diabetic animals that were treated with 20% fenugreek
diet 5 weeks prior to streptozotocin injection, showed a
presence of a sapogenin peptide ester, fenugreekine (Fig. general improvement in their clinical status. Hypergly-
1) has been reported (Ghosal et al., 1974). Some of the caemia, free fatty acids, cholesterol and triglycerides
biological properties of the purified steroid saponins have were significantly reduced. However, if the pretreatment
been evaluated (Sauvaire et al., 1996) and include hypo- period was not used, a supplementary diet of fenugreek,
cholesterolaemic and antifungal activity as well as effects following the induction of diabetes, did not improve the
on food intake, feeding behaviour and motivation in rats diabetic state, as judged by blood glucose and lipid levels.
(Petit et al., 1995b). Except for differences in fat and Thus a possible preventive role for fenugreek against
saponin content, fenugreek seed powder and the defatted chemically induced diabetes has been suggested.
fenugreek are chemically similar, containing almost A beneficial effect in pre-existing diabetic states has
equal amounts of amino acids, minerals and vitamins. also been shown in numerous studies (Table 1). A
Fenugreek, like other legumes, is rich in arginine, alanine reduction in hyperglycaemia was observed in diabetic
and glycine; but poor in lysine content (Gopalan et al., dogs fed fenugreek seeds (Ribes et al., 1984, 1986), and
1978; Sharma, 1984). However, 4-hydroxyisoleucine in mice where a 40%–80% dilution of a fenugreek
(Fig. 1) has been found to be a major free amino acid decoction and 200–400 mg/kg of an ethanolle-extract
in the seeds (Sauvaire et al., 1984). Like other legumes, were used (Ajabnoor and Tilmisany, 1988). Similar
the protein is deficient in methionine. Trigonelline (Fig. effects were reported in healthy human volunteers given
1) is an important alkaloidal component of the seeds 25 g/day of fenugreek powder mixed in their diet
(Mishkinsky et al., 1967). The seed contains less starch (Sharma, 1986b), Type I diabetics fed 100 g fenugreek/
but higher proportions of minerals (Ca, P, Fe, Zn and Mn) day (Sharma et al., 1990) and Type II diabetics fed 15 g
compared with other grain legumes (Sankara Rao and fenugreek/day (Madar et al., 1988; Sharma and Raghur-
Deosthale, 1981). The total lipid content (7.5%) of the am, 1990). Fenugreek seeds (whole as well as extracted)
seeds consists of neutral lipids, glycolipids and phospho- were found to diminish hyperglycaemia in normal and
lipids (Hemavathy and Prabhakar, 1989). The aromatic diabetic subjects (Sharma, 1986b; Sharma et al., 1990).
constituents of the seeds have been elucidated (Girardon Fasting blood glucose, 24-h urinary sugar excretion and
et al., 1985) and include n-alkanes, sesquiterpenes and serum cholesterol were also significantly reduced in these
some oxygenated compounds such as hexanol and g- subjects.
nonalactone. The seeds are also known to contain Despite a significant reduction in postprandial glucose,
flavonoids, carotenoids, coumarins and other components in some studies no significant change was observed in
(Varshney and Sharma, 1996) with a very low LD50. plasma insulin following fenugreek administration to
non-insulin dependent ‘NIDDM’ diabetics (Madar et al.,
1988), rats (Madar, 1984), or dogs (Ribes et al., 1984,
1986). However, other studies in chemically induced
ANTI DIABETIC EFFECTS diabetic rats have demonstrated a significant increase in
plasma insulin levels (Sharma, 1986b; Petit et al., 1993,
Diabetes mellitus (DM) is a widespread disorder which 1995a). These conflicting results may be due to
has long been recognized in the history of medicine differences in the type of fenugreek preparation used in
(Best, 1962; West, 1978). Before the advent of insulin the various studies (Table 1). The observed increase in
and oral hypoglycaemic drugs the major form of plasma insulin levels following administration of an
treatment involved the use of plants. More than 400 ethanol extract of fenugreek to rats was suggested (Petit
plants are known to have been recommended, and recent et al., 1993) to be due either to a direct stimulatory effect
investigations have affirmed the potential value of some on the b-cells or to an indirect effect related to the
# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
 ANTIDIABETIC EFFECTS OF FENUGREEK 235

Table 1. Summary of the reported antidiabetic properties of fenugreek in vivo

Test substance Administered to Dose Effects observed References
Fenugreek powder Non-diabetic rats 2±8 g/kg for 2 weeks Hypoglycaemic 1
20% of diet for 2 weeks Antihyperglycaemic 2
250 mg (single dose) Antihyperglycaemic 3
Diabetic rats 2±8 g/kg for 2 weeks Hypoglycaemic 1
Non-diabetic humans 10 g per day for 2 days No effect on OGTT 4
25 g (single dose) Antihyperglycaemic 5
NIDDM humans 10 g per day for 2 days Antihyperglycaemic 4
15 g per day for 4±7 days Antihyperglycaemic/ no 6
increase in plasma insulin
25 g per day for 15 days Antihyperglycaemic against 7
intravenous GTT
25 g per day for 3 weeks Antihyperglycaemic 5
IDDM humans 100 g per day for 10 days Hypoglycaemic and 8
antihyperglycaemic
Suspension Non-diabetic rats 0.25 g per 5 mL No effect on OGTT 9
Diabetic rats 0.25 g per 5 mL Antihyperglycaemic 9
Decoction Diabetic and non-diabetic 40%±80% dilution Antihyperglycaemic 10
rats
Oil fraction Diabetic and non-diabetic Corresponding to 7% of whole No effect on blood glucose 11,12
fenugreek seeds
Defatted fraction Non-diabetic dogs Corresponding to 93% of No effect on blood glucose 12
whole fenugreek seeds
Diabetic dogs Corresponding to 93% of Hypoglycaemic 11,12
whole fenugreek seeds Antihyperglycaemic
NIDDM humans 25 g per day for 3 weeks Antihyperglycaemic 5
Defatted subfractions
`a' (®bre) Diabetic dogs Amount corresponding to total Antihyperglycaemic 13,14
defatted fraction fed for 3
weeks
`b' (protein ‡ saponin) As above No effect on OGTT 13,14
`p' (protein) As above No effect on OGTT 14
`s' (saponin) As above No effect on OGTT 14
Ethanol extract Diabetic and non-diabetic 200±400 mg/kg Antihyperglycaemic 10
rats
Non-diabetic 250 mg/kg Antihyperglycaemic 3
Diabetic rats 5 mg/kg for 3 weeks Antihyperglycaemic 15
1, Khosla et al., 1995a; 2, Amin et al., 1987; 3, Ali et al., 1995; 4, Sadhukhan et al., 1994; 5, Sharma, 1986b; 6, Madar et al.,
1988; 7, Raghuram et al., 1994; 8, Sharma et al., 1990; 9, Madar, 1984; 10, Ajabnoor and Tilmisany, 1988; 11, Ribes et al., 1984;
12, Valette et al., 1984; 13, Ribes et al., 1986; 14, Ribes et al., 1987; 15, Shani et al., 1974.

palatability and the flavour-enhancer properties of the and proteins (Ribes et al., 1984; Valette et al., 1984). The
extract. The latter hypothesis was put forward in line with above work led to the suggestion that the active
the effect of the sweet taste of saccharin solution which component was not in the lipid extract but in the defatted
has been reported to trigger a rapid cephalic phase of portion of the seeds, which provoked a decrease in
insulin response in the absence of any significant change hyperglycaemia and hypercholesterolaemia in both
in glycaemia (Berthoud et al., 1981). However, the normal and diabetic dogs. Defatted fenugreek had an
presence in fenugreek of an insulin-secretion stimulating influence on the response to oral glucose tolerance test
compound (4-hydroxyisoleucine) has also been reported (OGTT) and modified not only the blood glucose level
(Hillaire-Buys et al., 1993; Petit et al., 1995a; Sauvaire et but also pancreatic hormone levels (Ribes et al., 1984,
al., 1996). 1986). It decreased the normally observed peak plasma
Apart from biochemical improvements, fenugreek insulin levels in normal dogs following OGTT (Ribes et
seeds remarkably suppressed the clinical symptoms of al., 1984) as well as levels of glucagon (an aggravating
diabetes such as polyuria, polydypsia, weakness and factor of diabetes) and somatostain (observed after
weight losses (Sharma, 1986b). It has also been OGTT) in diabetic dogs (Ribes et al., 1986), which
demonstrated that the hypoglycaemic property of fenu- infers better carbohydrate regulation. This defatted
greek is not destroyed by the cooking or roasting process fraction was further investigated (Ribes et al., 1986) by
(Sharma, 1986b; Khosla et al., 1995a). dividing it into two subfractions subfraction ‘a’ which
A number of investigations have been carried out to contained the testa and endosperm and is rich in fibre
identify the factors responsible for the antidiabetic (79.6%), and subfraction ‘b’ which contained the
activity of fenugreek and the mechanisms involved in cotyledons and axles and is rich in proteins (52.8%)
this effect. One group of researchers have studied two and saponins (7.2%). Their results, like those of Madar
fractions of the seed, namely the lipid extract, and the (1984) and Sharma (1986b), showed that the antidiabetic
defatted seed material which contains fibres, saponins property of fenugreek seeds was contained in the testa
# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
236 M. AL-HABORI AND A. RAMAN

and endosperm subfraction. The authors suggest that, hypoglycaemic effects in normal and alloxan-induced
although rich in fibres, it is not possible to exclude the diabetic rats (Shani et al., 1974), and fenugreekine, a
coexistence of one or more unknown active pharmaco- steroidal sapogenin-peptide ester, which is stated to have
logical compounds in this subfraction of the seed. a hypoglycaemic effect although details are not given
In early reports, the hypoglycaemic effect of fenugreek (Ghosal et al., 1974). The relevance of hypoglycaemic
was attributed to its major alkaloid, trigonelline doses of these compounds to their concentration in
(Mishkinsky et al., 1967; Shani et al., 1974). Trigonelline effective doses of fenugreek preparations needs further
(Fig. 1) is the N-methyl derivative of the vitamin exploration.
nicotinic acid, and is excreted in human and rat urine The endosperm of fenugreek seed is a rich source of
after oral administration of nicotinic acid (Ackerman, fibre (20%) and gum (32.4%) (Sharma, 1986b). It is
1912), but when fed to cats, dogs and rabbits it is excreted known that the addition of fibre to the diet of diabetics
unchanged (Kohlrausch, 1912). However, administration results in a reduction of blood glucose during oral glucose
of trigonelline, in the amounts present in fenugreek, to tolerance test (Jenkins et al., 1978; Jenkins, 1979;
diabetic patients did not show any significant hypo- Monnier et al., 1978). The clinical role of dietary fibres
glycaemic activity (National Institute of Nutrition, 1987). in glycaemic control has been reviewed (Jenkins and
Furthermore, a recently isolated active hypoglycaemic Jenkins, 1984; Vinik and Jenkins, 1988). Furthermore a
principle from fenugreek has been shown to be different high viscosity of gut contents has been reported to inhibit
from trigonelline (Moorthy et al., 1989). Moorthy et al. the intestinal absorption of glucose (Johnson and Gee,
(1989) reported the presence of an orally active principle 1980) and significantly reduce the mean postprandial
isolated from fenugreek seeds, which improves glucose blood glucose and insulin curve (O’Connor et al., 1981).
tolerance for a period of 1 week in alloxan-treated This effect has been attributed, for example, to the
rabbits. This fraction, which was different from and more viscosity of hydrated guar gum which reduces the rate of
potent than trigonelline, was also reported to decrease gastric emptying (Holt et al., 1979; Blackburn et al.,
fasting blood glucose in alloxan-recovered rabbits with 1984). Fenugreek, like guar gum, is very viscous and is
an initial fasting blood glucose level of 180 mg/Dl. rich in galactomannan (Reid and Meier, 1970).
Following treatment with this fraction at a dose of In view of its high content of soluble fibre, it has been
50 mg/kg daily for 1 month, fasting blood glucose also postulated that one mechanism by which fenugreek may
decreased by about 50% in severely diabetic rabbits with modulate plasma glucose levels is by delaying gastric
an initial fasting blood glucose of 400 mg/Dl. In addition, emptying and by direct interference with glucose
there was an improvement in glycosylated haemoglobin absorption at the gastrointestinal level (Madar, 1984).
and serum lipid profile, an increase in the activity of key The latter effect was investigated in vitro using inverted
glycolytic enzymes in muscle but not in the liver and a gut sac from the jejunum of male rats, where the addition
slight, though not statistically significant, inhibition on of 0.1%–1% fenugreek seed powder to the mucosal side
key gluconeogenic enzymes in the liver and kidney. significantly inhibited the 3-O-methyl-D-glucose trans-
However, no reports were found on the chemical port into the serosal side (Madar, 1984). Based on the
composition of this active fraction. finding that whole fenugreek seeds, extracted fenugreek
In 1993, Hillaire-Buys et al. reported the presence of seeds and gum isolate are rich sources of fibre in the form
an insulin-stimulating substance in the seeds of fenu- of galactomannan (Sharma, 1986b), which resembles
greek. This compound was obtained by sequential guar gum in chemical structure and viscosity (16–20 cP)
chromatography from defatted fenugreek seeds and (Ribes et al., 1984), it was concluded that the dietary fibre
identified as 4-hydroxyisoleucine (Fig. 1). At a concen- in fenugreek is the major contributor for reducing plasma
tration of 200 mmol/L 4-hydroxyisoleucine evoked a glucose (Sharma, 1986b; Madar et al., 1988). Further-
biphasic insulin response in vitro, using isolated pancreas more, the fact that fenugreek had no significant effect on
perfused with glucose (Petit et al., 1995a; Sauvaire et al., insulin levels in these studies suggested that it decreased
1996). This response increased in a concentration the glucose levels by inhibition of diffusion or transport
dependent manner both in vitro and in vivo in conscious of glucose without involvement of intestinal hormonal
fasted dogs. It was effective after oral administration and factor (Madar et al., 1988). Degummed fenugreek seed
improved oral glucose tolerance (Sauvaire et al., 1996). was shown to have little hypoglycaemic effect; further
The data showed 4-hydroxyisoleucine, which represents excluding non-mucilagenous fibre as the cause of the
up to 80% of free amino acids in fenugreek seeds effect observed (Sharma, 1986b). It has recently been
(Sauvaire et al., 1984), to stimulate insulin secretion shown that galactomannan, in the gel fraction of the
only in the presence of intermediate to high glucose seeds, is a factor which reduces the plasma glucose in
concentrations and to be effective in a much lower both in vivo and in vitro studies using inverted gut, by
concentration range than its structural amino acid increasing the viscosity of the gut contents (Madar and
congeners leucine and isoleucine. The isolated 4- Shomer, 1990).
hydroxyisoleucine was found to partially affect the In more recent studies, Ali et al. (1995) showed that
K‡-conductance of the b-cell plasma membrane. 4- fenugreek powder, its methanol extract, and the residue
Hydroxyisoleucine is an unusual amino acid that was remaining after methanol extraction all had significant
isolated and identified for the first time by Fowden et al. antihyperglycaemic effects when fed simultaneously
(1973); its conformation was established by Alcock et with glucose. The soluble dietary fibre (SDF) fraction
al. (1989). showed no effect on the fasting blood glucose levels of
Other postulated hypoglycaemic constituents of fenu- non-diabetic or NIDDM model rats. However, when fed
greek (Fig. 1) are coumarin, which was shown to have a simultaneously with glucose, it showed a significant
profound hypoglycaemic effect in normal and alloxan- antihyperglycaemic effect in NIDDM model rats;
induced diabetic rats (Shani et al., 1974), scopoletin, suggesting that fibre might be responsible for the
another coumarin constituent which exerted borderline observed improvement in the glucose tolerance but did
# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
 ANTIDIABETIC EFFECTS OF FENUGREEK 237

not contribute to the hypoglycaemic effects. Thus other

mechanisms and components may be associated with the HYPOCHOLESTEROLAEMIC EFFECTS
decrease in basal glycaemia following fenugreek admin-
istration as observed in some studies (Table 1). The association of raised serum cholesterol with
An additional possible mode of action of fenugreek is cardiovascular disease is well known (Gordon, et al.,
an effect on intestinal carbohydrate digestion. Fenugreek 1977). Some studies suggest that elevated serum
was found to decrease digestion of starch and also triglyceride may also be a risk factor (Carlson et al.,
glucose absorption both in vivo (by following a tolerance 1979; Carlson and Bottiger, 1985) especially in indivi-
test of a meal containing starch) and in vitro using the duals with diabetes (West et al., 1983); there is often a
inverted sac technique (Madar and Shomer, 1990). This marked hyperlipidaemia in diabetes (Maison and
may be the result of a direct inhibitory effect on the Boucher, 1978; Betteridge, 1989). Moreover, diabetic
digestive enzymes or via reducing enzyme–substrate patients experience a 2–3 fold increase in cardiovascular
contact (Wong et al., 1985; Edwards et al., 1988). Amin morbidity and mortality when compared with non-
et al. (1987) demonstrated the existence of a low relative diabetics. The beneficial effect of lowering elevated
molecular mass fraction in the aqueous extract of serum cholesterol levels on the prevention of coronary
fenugreek which inhibits carbohydrate degrading en- heart disease (CHD) has been well established (Lipid
zymes (a-amylase and sucrase) in rat intestines. These Research Clinics Program, 1984). Dietary intervention
results are in line with earlier reports which observed that has been recommended for all subjects with a low density
inhibiting intestinal disaccharidase activities by acarbose lipoprotein (LDL) level of more than 160 mg/dL (Report
moderated the development of diabetes in streptozotocin- of the National Cholesterol Education Program, 1988). In
treated rats (Goda et al., 1982). Recently, Platel and addition to the quantity of fat and the polyunsaturated/
Srinivasan (1996) reported a significant decrease in the saturated fat ratio, other dietary factors also play a role in
activity of intestinal sucrase with the addition of 2% the management of hyperlipidaemia (Grundy, 1987).
fenugreek seeds to the diet of rats; with very little effect Several studies have shown that dietary fibre, particularly
on a-amylase, maltase and lactase. soluble fibre, has considerable influence on serum
The above studies suggest that fibre and other cholesterol levels (Kritchevsky, 1982; Dreher, 1987;
components in fenugreek seed, acting at the gastrointest- Miettinen, 1987).
inal level, may well be responsible for the observed Research carried out on legumes has led to the belief
improvement in oral glucose and starch tolerance. that they are beneficial in lowering total cholesterol levels
However, this does not explain the hypoglycaemic in humans (Madar and Odes. 1990; Sharma et al., 1990;
effects (reduction in basal glycaemia) observed in some Sharma et al., 1996a). Scientific reports indicate that
studies, and other mechanisms are possible. Ajabnoor fenugreek does indeed have therapeutic properties that
and Tilmisany (1988) using both a 40%–80% dilution of may be beneficial in treating hypercholesterolaemia
fenugreek decoction and an ethanol extract (200–400 mg/ (Table 2). Fenugreek seeds have been shown to possess
kg) of the seeds in normal and alloxan-treated diabetic hypocholesterolaemic effect in rats (Singhal et al., 1982;
male albino mice further confirmed the earlier reports of Sharma, 1984, 1986a; Stark and Madar, 1993; Khosla et
hypoglycaemic effects and put forward the argument that al., 1995b) and dogs (Valette et al., 1984). Elevation of
since their experiments were conducted on fasting mice, cholesterol levels in the rat was prevented by adding
the effect could not be due to the gastrointestinal action of fenugreek at 15%–60% to a hypercholesterolaemia-
fibre. The authors went further to suggest that the inducing diet (Sharma, 1984). Fenugreek was demon-
mechanism of antidiabetic action of the seeds may be strated to have a greater effect on exogenous cholesterol
similar to that of tolbutamide, although other mechan- (when given with a hypercholesterolaemia-inducing diet
isms are possible. Moreover, Raghuram et al. (1994) containing 1% cholesterol) than on endogenous choles-
showed that fenugreek powder (25 g) when given in the terol (fenugreek given with a cholesterol-free stock diet)
diet for 15 days to NIDDM patients prior to an (Sharma, 1984). Defatted fenugreek (100 g) incorporated
intravenous glucose load, significantly altered plasma in the experimental diet of hyperlipidaemic non-diabetic
glucose kinetics, reducing the area under the plasma subjects significantly reduced serum total cholesterol,
glucose curve, and increasing the metabolic clearance LDL and very low density lipoprotein (VLDL)-choles-
rate. In addition, fenugreek increased the molar insulin- terol and triglyceride levels (Sharma et al., 1991), with no
binding sites on erythrocytes; however, serum insulin observed changes in high density lipoprotein (HDL)-
levels were not measured (Raghuram et al., 1994). This cholesterol. As a result, there was a significant increase in
study suggests that fenugreek can improve peripheral the ratio of HDL to total cholesterol and HDL to that of
glucose utilization and that it may exert its antidiabetic LDL and VLDL-cholesterol, which have been shown to
activity by effects at the insulin receptor as well as at the be reliable risk assessment factors of CHD (Kannel,
gastrointestinal level. 1983).
Thus the hypoglycaemic and antihyperglycaemic In a short-term study, fenugreek seeds were also found
actions of fenugreek have been attributed both to to exert hypocholesterolaemic activity in diabetic
gastrointestinal effects of local dietary fibre (Madar, patients (Sharma and Raghuram, 1990; Sharma et al.,
1984) and to systemic effects of active principles, such as 1990). In NIDDM patients, ingestion of an experimental
4-hydroxyisoleucine, present in the seeds (Ribes et al., diet containing 25 g fenugreek seed powder for 24 weeks
1986, Moorthy et al., 1989; Hillaire-Buys et al., 1993; resulted in a significant reduction of total cholesterol,
Sauvaire et al., 1996). Trigonelline has been discounted LDL- and VLDL-cholesterol and triglyceride levels
as an active principle by more recent studies (National (Sharma et al., 1996a). Serum cholesterol was signifi-
Institute of Nutrition, 1987), whilst claims for the activity cantly reduced and this fall was mainly due to a reduction
of fenugreekine (Ghosal et al., 1974) remain unsubstan- in LDL and VLDL fractions. Triglyceride levels also
tiated. showed a similar change. On the other hand, HDL-
# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
238 M. AL-HABORI AND A. RAMAN

Table 2. Summary of the reported hypocholesterolaemic and hypolipidaemic effects of fenugreek in vivo
Test substance Administered to Dose Effects observed References
Fenugreek powder Normal rats 2±8 g/kg for 2 weeks Decrease in plasma 1
cholesterol, triglyceride, VLDL-
and LDL-cholesterol
50% of diet for 2 weeks Decrease in plasma cholesterol 2
Diabetic rats 2±8 g/kg for 2 weeks Decrease in plasma cholesterol 1
and triglyceride
Hypercholesterolaemic 50% of diet for 2 weeks Decrease in plasma cholesterol 2
rats
10%±60% of diet for 4±6 weeks Decrease in plasma 3
cholesterol, VLDL- and LDL-
cholesterol
30% of diet for 4 weeks Decrease in plasma cholesterol 4
NIDDM humans 25 g per day for 24 weeks Decrease in plasma 5
cholesterol, triglyceride, VLDL-
and LDL-cholesterol
15 g per day for 4±7 days No effect on plasma lipids 6
following a meal tolerance test
IDDM humans 100 g per day for 10 days Decrease in plasma cholesterol 7
and triglyceride
Oil fraction Diabetic and non-diabetic Corresponding to 7% of whole No effect on plasma 8
dogs fenugreek seeds cholesterol
Defatted fraction Diabetic and non-diabetic Corresponding to 93% of whole Decrease in plasma cholesterol 8
dogs fenugreek seeds for 3 days
Hyperlipidaemic subjects 100 g defatted fenugreek for 20 Decrease in plasma 7
days cholesterol, triglyceride, VLDL-
and LDL-cholesterol
Defatted subfractions Diabetic dogs
`a' (®bre) Amount corresponding to total Decrease in plasma cholesterol 9
defatted fraction for 3 weeks
`b' As above Decrease in plasma cholesterol 9
(protein ‡ saponin) and triglyceride
`p' (protein) As above No effect on plasma lipids 9
`s' (saponin) As above Decrease in plasma cholesterol 9
and triglyceride
Ethanol extract Normal rats 10 mg per day for 2 weeks Decrease in plasma 10
cholesterol, LDL- and VLDL-
cholesterol and increase in
plasma insulin
30 g/kg for 4 weeks Decrease in fasting plasma 11
cholesterol
1, Khosla et al., 1995b; 2, Singhal et al., 1982; 3, Sharma, 1984; 4, Sharma, 1986a; 5, Sharma et al., 1996a; 6, Madar et al.,
1988; 7, Sharma et al., 1990; 8, Valette et al., 1984; 9, Ribes et al., 1987; 10, Petit et al., 1993; 11, Stark and Madar, 1993.

cholesterol showed a slight rise (p > 0.05). The overall hormone has been found (Bhathena et al., 1974) to
results are in agreement with earlier observations made in stimulate hepatic production of VLDL. Based on this, a
diabetic patients (Sharma, 1986a; Sharma et al., 1990). high fibre diet which reduces insulin secretion was used
All the lipid parameters improved rapidly during the in the treatment of hyperlipidaemia in diabetic subjects
initial 8 weeks after the incorporation of fenugreek with a (Paisey et al., 1984). Thus the alterations in lipid profiles
slower change thereafter (Sharma et al., 1996a). An observed after ingestion of fenugreek, which contains
increase in HDL-cholesterol was also observed in dietary fibre, may have been due to a decreased synthesis
diabetic rats fed 2–8 g/kg body weight of unroasted and of VLDL in the liver. However, since ingestion of
roasted fenugreek seeds for 2 weeks (Khosla et al., fenugreek extracts was reported to stimulate insulin
1995b). These results indicate a potential beneficial effect secretion in diabetic rats (Sharma, 1986b; Petit et al.,
of fenugreek seeds in the lipid profile of diabetic subjects 1993, 1995a) the intermediary role of insulin in altering
in addition to the effects on glycaemia reviewed earlier. lipid profiles is unclear.
The ability of fenugreek to selectively reduce the LDL Among the fenugreek fractions, the lipid extract and
and VLDL fraction of total cholesterol could be bene- 0.12% trigonelline had no hypocholesterolaemic effect
ficial in preventing atherosclerosis. A similar selective (Valette et al., 1984) while the defatted fractions, gum
effect on LDL-cholesterol was observed with dietary isolate and the crude saponins, fed to normal and diabetic
fibres such as oat bran (Kirby et al., 1981) and guar gum rats at equivalent amounts to that present in a diet
(Jenkins et al., 1980). Natural carbohydrates rich in fibre containing 30% fenugreek seeds, showed hypocholester-
content have been found to be effective against hyper- olaemic activity without any significant effect on the
lipidaemia and ischaemic heart disease (Trowell, 1972). triglyceride level (Sharma, 1986a). Further studies by
Insulin secretion has been shown to regulate VLDL and Ribes et al. (1987) showed that although subfraction ‘a’
triglyceride concentration (Sparks and Sparks, 1994); the (79.6% fibre) displays both an antidiabetic and hypo-
# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
 ANTIDIABETIC EFFECTS OF FENUGREEK 239

cholesterolaemic activity, subfraction ‘b’ (52.8% pro- metabolism, one of the most important being the capacity
teins and 7.2% saponins) has a clear hypolipidaemic to lower plasma cholesterol concentration in chickens
effect since it reduces elevated cholesterol and triglycer- and rabbits fed cholesterol (Laguna et al., 1962). This
ide levels in diabetic dogs. This latter subfraction was hypocholesterolaemic effect has been suggested to be
further subdivided to two fractions ‘s’ which contains all dependent on the capacity of diosgenin to inhibit
the saponins (22.2%) and subfraction ‘p’ containing the cholesterol absorption, to decrease liver cholesterol
totality of the proteins (70.5%). Administration of concentration, to increase biliary cholesterol secretion
subfraction ‘p’, rich in proteins, had no effect on the and increase faecal excretion of neutral sterols (Cayen
high levels of cholesterol and triglycerides in diabetic and Dvornik, 1979; Uchida et al., 1984; Ulloa and Nervi,
dogs, thus ruling out the possibility of a role for the 1985). Furthermore, Malinow (1985) has shown that
lysine/arginine ratio. This conclusion is in accordance diosgenin glucoside was more efficient than diosgenin in
with that of Sharma (1984) demonstrating that the active reducing intestinal absorption of cholesterol. At compar-
principle was not related to the amino acids, contrary to able small doses, diosgenin glucoside inhibited choles-
the belief that the lysine/arginine ratio might be important terol absorption in vivo and in vitro, whereas diosgenin
in the elevation of serum cholesterol (Kritchevsky et al., did not (Malinow, 1985; Malinow et al., 1987).
1978). However, the presence of saponins seems essential Sauvaire et al. (1991) have examined the transforma-
for the hypolipidaemic activity of fenugreek seeds (Ribes tion of fenugreek subfractions rich in steroid saponins
et al., 1987; Sauvaire et al., 1991). during their passage through the digestive tract, to
Saponins are plant glycosides whose aglycone struc- determine the relative contribution of saponins and/or
ture is triterpenoid or steroidal. They are a heterogeneous diosgenin and other steroid sapogenins to the hypo-
group of amphiphilic compounds, are highly surface- cholesterolaemic effect of fenugreek seeds. In this study
active and have a number of properties. Most saponins faecal samples from alloxan diabetic dogs fed the
are haemolytic, can bind cholesterol, and form stable fenugreek subfractions were analysed by capillary gas
foams (Price et al., 1987). Studies reported so far on the chromatography/mass spectrometry for the presence of
effects of saponins on cholesterol homeostasis concern sapogenins. Their results suggest that saponins, are in
mainly the triterpenoid saponins from lucerne (Malinow, part (about 57%), hydrolysed into sapogenins (disogenin,
1984) and steroidal saponin from soya bean (Sidhu et al., smilagenin, gitogenin) in the digestive tract. The location
1987) which reduce intestinal uptake of cholesterol. It has of fenugreek saponin hydrolysis in the digestive tract was
also been reported that a steroidal saponin, digitonin, not determined. The authors concluded that saponin
prevents or lowers hypercholesterolaemia in monkeys hydrolysis does occur, presumably in the stomach and/or
(Malinow et al., 1978, Oakenfull and Fenwick, 1978) in the proximal small intestine (Sauvaire et al., 1991).
without modifying HDL-cholesterol levels (Malinow et Since hydrolysis was incomplete, saponins may be
al., 1981). In contrast, Gibney et al. (1982) reported no implicated, alone or together with sapogenin, in the
effect of a commercial saponin when fed to rats and observed hypocholesterolaemic effect of fenugreek
hamsters. However, this study mentioned neither the seeds.
chemical structure nor the origin of the saponin used. Another possible mechanism for the inhibition of bile
Saponins derived from lucerne (Medicago sativa, salt absorption may be primarily mechanical, due to the
alfalfa) were found to reduce plasma cholesterol levels formation of a physical barrier by fenugreek extracts,
by direct binding of dietary saponins with cholesterol in such as the gel fraction. The study by Ribes et al. (1987)
the digestive tract and subsequent excretion in the faeces showed that a fibre-rich subfraction (‘a’) separated from
(Malinow et al., 1977, 1981; Story et al., 1984). Other the saponins also displayed a hypocholesterolaemic
types of saponins affect cholesterol metabolism in- effect. Galactomannan derived from fenugreek seeds
directly by interacting with bile acids and increasing has been reported to inhibit intestinal bile acid absorp-
their faecal excretion (Oakenfull et al., 1984). Although tion, reducing the efficiency of their enterohepatic
experiments with lucerne saponins show that they circulation and subsequently decreasing plasma choles-
directly interact with cholesterol (Gestetner et al., terol level (Madar and Shomer, 1990).
1971), soya bean saponins do not (Birk, 1969).
The results of Stark and Madar (1993) indicated that
the saponins present in fenugreek, similar to soybean
saponins, do not interact directly with cholesterol.
However, using the inverted sac technique, an ethanol TOXICITY STUDIES
extract of fenugreek exhibited a strong inhibitory effect
on bile salt absorption (Stark and Madar, 1993), in a
quantitative manner. These results are in agreement with Short-term (90 days) feeding of fenugreek seeds to rats at
that of Bhat et al. (1985) and Sharma (1984) where the levels equivalent to 2 and 4 times the therapeutic dose
fenugreek enriched diets were found to increase both recommended for humans (25 g/day) produced no toxic
faecal weight and excretion of bile acids. The mechanism effects as evidenced by normal liver function tests, lack
that causes this effect is still not clear. One possibility is of any histopathological changes in the liver and no
that large mixed micelles are formed containing bile salts changes in haematological parameters (Udayasekhara
and saponins, and these large molecules are not available Rao et al., 1996). Moreover, long-term (24 weeks)
for absorption (Sidhu and Oakenfull, 1986). Lowering of administration of fenugreek seeds at 25 g/day, exhibited
blood and hepatic cholesterol may be due to increased no clinical hepatic or renal toxicity or haematological
conversion of cholesterol to bile acids by the liver. abnormalities in diabetic subjects (Sharma et al., 1996b).
Fenugreek seed saponins are of steroidal nature with This dose was sufficient to improve glucose tolerance
diosgenin (Fig. 1) as the main sapogenin (Mahato et al., (Raghuram et al., 1994; Sharma et al., 1986b) and lipid
1982). Diosgenin has various effects on cholesterol profile (Sharma et al., 1996a) in NIDDM humans.
# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
240 M. AL-HABORI AND A. RAMAN

galactomannan fibre. However, hypolipidaemic effects

SUMMARY are associated only with the saponins or sapogenins and
not the fibre. The apparent lack of toxicological effects,
Fenugreek seeds have been shown in various human and along with the considerable body of scientific evidence
animal model studies to lower blood glucose, improve reviewed here, suggests that the consumption of defatted
glucose and starch tolerance and have beneficial effects fenugreek may be beneficial in the management of
on serum lipid profiles. The antidiabetic effects have been diabetes and hypercholesterolaemia and thus in the
associated with intestinal effects of the gum fibre prevention of atherosclerosis and coronary heart disease.
(galactomannan), insulin secretagogue activity of a major
amino acid, 4-hydroxyisoleucine, and unidentified com-
ponents with effects on peripheral glucose utilization.
Acknowledgement
Hypocholesterolaemic effects have been associated
mainly with reduced intestinal reabsorption of cholester- The authors thank the British Council for financing a sabbatical visit by
ol and bile acids. This activity has been linked to the MAH to King’s College London to study the antidiabetic effects of
saponins and sapogenins (e.g. diosgenin), and also to fenugreek.

REFERENCES

Ackerman, D. Z. (1912). Biol. 59, 17. In, Shani, J., Gold- composition in the albino rat. Nutr. Rep. Int. 32, 1145±
schmied, A., Ahronson, Z., and Sulman, F. G. (1974). 1151.
Hypoglycaemic effect of Trigonella foenum graecum and Bhathena, S. J., Avigan, J., and Schreiner, M. E. (1974). Effect
Lupimus termis (Leguminosae) seeds and their major of insulin on sterol and fatty acid synthesis and HMG CoA
alkaloids in alloxan diabetic and normal rats. Arch. Int. reductase activity in mammalian cells grown in culture.
Pharmacodyn. Ther. 210, 27±36. Proc. Natl Acad. Sci. 71, 2174±2179.
Ajabnoor, M. A., and Tilmisany, A. K. (1988). Effect of Birk, Y. (1969). Saponins. In, Toxic Constituents of Plant
Trigonella foenum graecum on blood glucose levels in Foodstuffs, ed. by I. E. Liener pp. 169±210. Academic
normal and alloxan-diabetic mice. J. Ethnopharmacol. Press, New York & London.
22, 45±49. Blackburn, N. A., Redfern, J. S., and Jarjis, H. et al. (1984). The
Alarcon-Aguilar, F. J., Roman Ramos, R., and Flores Saenz, J. mechanism of action of guar gum in improving glucose
L. (1993). Plants medicinales usadas en el control de la tolerance in man. Clin. Sci. 66, 329±336.
diabetes mellitus. Ciencia 44, 361±363. Brenac, P., and Sauvaire, Y. (1996). Accumulation of sterols
Alcock, N. W., Crout, D., Gregorio, M., Lee, E., Pike, G., and and steriodal sapogenins in developing fenugreek pods:
Samuel, C. J. (1989). Stereochemistry of the 4-hydro- possible biosynthesis in situ. Phytochemistry 41, 415.
xyisoleucine from Trigonella foenum graecum. Phyto- Carlson, L. A., and Bottiger, L. E. (1985). Risk factors for
chemistry 28, 1835±1841. ischaemic heart disease in men and women. Acta Med.
Ali, L., Azad Khan, A. K., and Hassan, Z. et al. (1995). Scand. 18, 207±211.
Characterization of the hypoglycaemic effects of Trigo- Carlson, L. A., Bottiger, L. E., and Ahfeldt, P. E. (1979). Risk
nella foenum graecum seed. Planta Med. 61, 358±360. factors for myocardial infarction in the Stockholm pro-
Al-Meshal, I. A., Parmar, N. S., Tariq, M., and Aqeel, A. M. spective study. A 14-year follow up focusing on the role of
(1985). Gastric anti-ulcer activity in rats of Trigonella plasma triglyceride and cholesterol. Acta Med. Scand.
foenum graecum (Hu-Lu-Pa). Fitoterapia 56, 232±235. 206, 351±360.
Amin, R., Abdul-Ghani, A. S., and Suleiman, M. S. (1987). Cayen, M. N., and Dvornik, D. (1979). Effect of diosgenin on
Effect of Trigonella foenum graecum on intestinal lipid metabolism in rats. J. Lipid Res. 20, 162±174.
absorption. Diabetes 36 (suppl. 1), 211A. Chatterjee, B. P., Sakar, N., and Rao, A. S. (1982). Serological
and chemical investigations of the anomeric con®gura-
Amin, R., Abdul-Ghani, A. S., and Suleiman, M. S. (1988).
tion of sugar units in the D-galacto-D-mannan of fenu-
Effect of fenugreek and lupin seeds on the development
greek (Trigonella foenum graecum) seeds. Carbohyd.
of experimental diabetes in rats. Planta Med. 54, 286±290.
Res. 104, 348±353.
Anis, M., and Aminuddin, E. (1985). Estimation of diosgenin Chopra, R. N., Chopra, I. C., Honda, K. L., and Kapur, L. D.
in seeds of induced autoploid Trigonella foenum grae- (1982). Chopra's Indigenous Drugs of India, p. 582.
cum. Fitoterapia, 56, 51±52. Academic Publishers, Calcutta, New Delhi, India.
Attaur-Rahman, A., and Zaman, K. (1989). Medicinal plants Dreher, M. L. (1987). Handbook of Dietary Fibre. An Applied
with hypoglycaemic activity. J. Ethnopharmacol. 26, 1± Approach. p. 199. Dekker, New York.
55. Edwards, C. A., Johnson, I., and Read, N. W. (1988). Do
Baccou, J. C., Sauvaire, Y., Ollie, V., and Petit, L. J. (1978). viscous polysaccharides slow absorption by inhibiting
L'huile de fenugreec, composition, properties, possibili- diffusion or conversion? Eur. J. Clin. Nutr. 42, 307±312.
ties d'utilisation dans l'industrie des peintures et vernis. El-Mahdy, A. R., and El-Sebaiy, L. A. (1985). Proteolytic
Rev. Fr. des Corbs Gras. 25, 353. activity, amino acid composition, protein quality of
Bailey, C. J., and Day, C. (1989). Traditional treatments for fermented fenugreek seeds (Trigonella foenum-grae-
diabetes from Asia and the West Indies. Prac. Diabetes 3, cum). Food Chem. 18, 19±33.
190±192. Fazli, F. R. Y., and Hardman, R. (1968). The spice, fenugreek
Berthoud, H. R., Bereiter, D. A., Trimble, E. R., Siegel, E. G., (Trigonella foenum graecum): its commercial varieties of
and Jeanrenaud, B. (1981). Cephalic phase, re¯ex insulin- seed as a source of diosgenin. Trop. Sci. 10, 66.
secretion neuroanatomical and physiological charac- Fourier, F. (1948). Plantes medicinales et venereuses de
terization. Diabetologia 20, 393±401. France. Paris 111, 495.
Best, C. H. (1962). Epochs in the history of diabetes. In, Fowden, L., Pratt, H. M., and Smith, A. (1973). 4-Hydroxyiso-
Diabetes, ed. by R. H. Williams, pp. 1±13. Hueber, leucine from seed of Trigonella foenum graecum. Phyto-
Ismaning. chemistry 12, 1701±1707.
Betteridge, D. J. (1989). Diabetes, lipoprotein metabolism and Gestetner, B., Assa, Y., Henis, Y., Birk, Y., and Bondi, A.
atherosclerosis. Br. Med. Bull. 45, 285±311. (1971). Lucerne saponins IV: relationship between their
Bever, B. O., and Zahnd, G. R. (1979). Plants with oral chemical constituent and haemolytic and antifungal
hypoglycaemic action. Q. J. Crude Drug Res. 17, 139±196. activities. J. Sci. Food Agric. 22, 168±172.
Bhat, B. G., Sambaiah, K., and Chandrasekhara, N. (1985). Ghafghazi, T., Sheriat, H. S., Dastmalchi, T., and Barnett, R. C.
The effect of feeding fenugreek and ginger on bile (1977). Antagonism of cadmium and alloxan-induced

# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
 ANTIDIABETIC EFFECTS OF FENUGREEK 241

hyperglycaemia in rats by Trigonella foenum graecum. Kritchevsky, D., Tepper, S. A., and Story, J. (1978). In¯uence
Shiraz. Med. J. 8, 14±25. of soya protein and casein on atherosclerosis in rabbits.
Ghosal, S., Srivastava, R. S., Chatterjee, D. C., and Dutta, S. K. Fed. Proc. 34, 747.
(1974). Extractives of Trigonella-1. Fenugreekine, a new Laguna, J., Gomez-Puyou, A., Pena, A., and Guzman-Garcia,
steroidal sapogenin-peptide ester of Trigonella foenum J. (1962). Effect of diosgenin on cholesterol metabolism.
graecum. Phytochemistry 13, 2247±2251. J. Atheroscler. Res. 2, 459±470.
Gibney, M. J., Pathirana, C., and Smith, P. (1982). Saponins Lipid Research Clinics Program (1984). The lipid research
and ®bre: Lack of interactive effects on serum and liver clinics coronary primary prevention trial results. 1:
cholesterol in rats and hamsters. Atherosclerosis 45, 365± Reduction in the incidence of coronary heart disease. J.
367. Am. Med. Assoc. 251, 351±364.
Girardon, P., Bessiere, J. M., Baccou, J. C., and Sauvaire, Y. Madar, Z. (1984). Fenugreek (Trigonella foenum graecum) as
(1985). Volatile constituents of fenugreek seeds. Planta a means of reducing postprandial glucose level in
Med. 6, 533±534. diabetic rats. Nutr. Rep. Int. 29, 1267±1273.
Goda, T., Yamada, K., Sugiyama, M., Moriuchi, S., and Madar, Z., and Shomer, I. (1990). Polysaccharide composition
Hosoya, N. (1982). Effect of sucrose and acarbose feeding of a gel fraction derived from fenugreek and its effect on
on the development of streptozotocin-induced diabetes starch digestion and bile acid absorption in rats. J. Agric.
in the rat. J. Nutr. Sci. V. 28, 41±56. Food Chem. 38, 1535±1539.
Gopalan, C., Rama Shatsri, B. V., and Balasubramanyan, S. C. Madar, Z., and Odes, H. S. (1990). Dietary ®bre in metabolic
(1978). Nutritive Value of Indian Foods. Hyderabad, India, disease. In, Dietary Fibre Research, ed. by R. Paoletti, pp.
National Institute of Nutrition, ICMR. 1±54. Karger, Basel.
Gordon, T., Castelli, W. P., Hjortland, M. E., Kannel, W. B., and Madar, Z., Abel, R., Samish, S., and Arad, J. (1988). Glucose
Bawber, T. R. (1977). Predicting coronary heart disease in lowering effect of fenugreek in non-insulin dependent
middle aged and older persons. JAMA 32, 497±504. diabetics. Eur. J. Clin. Nutr. 42, 51±54.
Grundy, S. M. (1987). Dietary treatment of hyperlipidaemia. Mahato, S. B., Ganguly, A. N., and Sahu, N. P. (1982). Steroid
In, Hypercholesterolaemia and Atherosclerosis-Patho- saponins. Phytochemistry 21, 959±978.
genesis and Prevention, ed. by D. Steinberg and J. M. Maison, A. S., and Boucher, B. J. (1978). Diabetes mellitus. In,
Olefsky, p. 169. Churchill Livingstone, London. Price's Text Book of the Practice of Medicine, ed. by R. B.
Hemavathy, J., and Prabhakar, J. V. (1989). Lipid composition Scott, pp. 435±447. ELBS, Oxford Medical Publication.
of fenugreek (Trigonella foenum graecum L.) seeds. Food Malinow, M. R. (1984). Triterpenoid saponins in mammals:
Chem. 31, 1±7. effects on cholesterol metabolism and atherosclerosis.
Hillaire-Buys, D., Petit, P., Manteghetti, M., Baissac, Y., In, Biochemistry and Function of Isopentenoids in Plants,
Sauvaire, Y., and Ribes, G. (1993). A recently identi®ed ed. by W. D. Nes, G. Fuller and L. S. Tsai, pp. 229±246.
substance extracted from fenugreek seeds stimulates Marcel Dekker, New York.
insulin secretion in rat. Diabetologia 36, A119. Malinow, M. R. (1985). Effects of synthetic glycosides on
Holt, S., Heading, R., Carter, D. C., Prescott, L. F., and Tothill, cholesterol absorption. Ann. NY. Acad. Sci. 454, 23±27.
P. (1979). Effect of gel ®bre on gastric emptying and Malinow, M. R., Connor, W. E., and McLaughlin, P. et al.
absorption of glucose and paracetamol. Lancet 20, 636± (1981). Cholesterol and bile acid balance in Macaca
639. fascicularis: Effects of alfalfa saponins. J. Clin. Invest.
Ivorra, M. D., Paya, M., and Villar, A. (1989). A review of 67, 156±162.
natural products and plants as potential anti-diabetic Malinow, M. R., Elliott, W. H., McLaughlin, P., and Upson, B.
drugs. J. Ethnopharmacol. 27, 243±275. (1987). Effects of synthetic glycosides on steroid balance
Jenkins, D. J. A. (1979). Dietary ®bre, diabetes and hyper- in Macaca fascicularis. J. Lipid Res. 28, 1±9.
lipidaemia. Lancet 2, 1287±1289. Malinow, M. R., McLaughlin, P., Kohler, G. O., and Livingston,
Jenkins, D. J. A., and Jenkins, A. (1984). The clinical impli- A. L. (1977). Prevention of elevated cholesterolaemia in
cation of dietary ®bre. Adv. Nutr. Res. 6, 169±201. monkeys by alfalfa saponins. Steroids 29, 105±110.
Jenkins, D. J. A., Reynolds, D., Salvin, B., Leeds, A. R., Malinow, M. R., McLaughlin, P., and Stafford, C. (1978).
Jenkins, A. L., and Jepson, E. H. (1980). Dietary ®bre and Prevention of hypercholesterolaemia in monkeys (Maca-
blood lipids: treatment of hypercholesterolaemia with ca fascicularis) by digitonin. Am. J. Clin. Nutr. 31, 814±
guar crispbread. Am. J. Clin. Nutr. 33, 575±581. 818.
Jenkins, D. J. A., Wolever, T. M. S., and Leeds, A. R. et al. Marles, R. J., and Farnsworth, N. R. (1995). Anti-diabetic
(1978) Dietary ®bres, ®bre analogues, and glucose plants and their active constituents. Phytomedicine 2,
tolerance: importance of viscosity. Br. Med. J. I, 1392± 137±189.
1394. Max, B. (1992). This and That: The essential pharmacology of
Johnson, I. T., and Gee, J. (1980). Inhibitory effect of guar herbs and spices. Trends Pharmacol. Sci. 13, 15±20.
gum on the intestinal absorption of glucose in vitro. Proc. Miettinen, T. A. (1987). Dietary ®bre and lipids. Am. J. Clin.
Nutr. Soc. 39, 52A. Nutr. 45, suppl., 1237±1242.
Kannel, W. B. (1983). High-density lipoprotein: epidemiologic Mishkinsky, J., Joseph, B., and Sulman, F. (1967). Hypogly-
pro®le and risks of coronary artery disease. Am. J. caemic effect of trigonelline. Lancet i, 1311±1312.
Cardiol. 52, 9B. Moissides, M. (1939). Le fenugrec autrefois et aujourd hui.
Khosla, P., Gupta, D. D., and Nagpal, R. K. (1995a). Effect of Janus 43, 123±130.
Trigonella foemum graecum (fenugreek) on blood glu- Monnier, L. H., Pham, T. C., Aguirre, L., Orsetti, A., and
cose in normal and diabetic rats. Indian J. Physiol. Mirouze, J. (1978). In¯uence of indigestible ®bres on
Pharmacol 39, 173±174. glucose tolerance. Diabetes Care 1, 83±88.
Khosla, P., Gupta, D. D., and Nagpal, R. K. (1995b). Effect of Moorthy, R., Prabhu, K. M., and Murthu, P. S. (1989). Studies
Trigonella foemum graecum (fenugreek) on serum lipids on the isolation and effect of an orally active hypogly-
in normal and diabetic rats. Indian J. Pharmacol. 27, 89± caemic principle from the seeds of fenugreek (Trigonella
93. foemum graecum). Diabetes Bull. 9, 69±72.
Kirby, R. W., Andreson, J. W., and Sieling, B. (1981). Oat bran National Institute of Nutrition (1987). Annual Report, p. 11.
intake selectively lowers serum low density lipoprotein Indian Council of Medical Research, Hyderabad, India.
cholesterol concentration of hypercholesterolaemic men. Oakenfull, D. G., and Fenwick, D. E. (1978). Adsorption of bile
Am. J. Clin. Nutr. 34, 824±829. salts from aqueous solution by plant ®bre and cholestyr-
Kohlrausch, A. Z. (1912). Biol. 57, 273. In, Shani, J., Gold- amine. Br. J. Nutr. 40, 299±309.
schmied, A., Ahronson, Z., and Sulman, F. G. (1974). Oakenfull, D. G., Topping, D. L., Illman, R. J., and Fenwick, D.
Hypoglycaemic effect of Trigonella foenum graecum and E. (1984). Prevention of dietary hypercholesterolaemia in
Lupinus termis (Leguminosae) seeds and their major the rat by soybean and quillaya saponins. Nutr. Rep. Int.
alkaloids in alloxan diabetic and normal rats. Arch. Int. 25, 1039±1046.
Pharmacodyn. Ther. 210, 27±36. O'Connor, N., Tredger, J., and Morgan, L. (1981). Viscosity
Kritchevsky, D. (1982). Fibre and lipids. In, Dietary Fibre in differences between various guar gums. Diabetologin 20,
Health and Disease, eds. by G. V. Vahouny and D. 612±615.
Kritchevsky, pp. 182. Plenum Press, New York. Paisey, R. B., Arredondo, G., Villalobos, A., Lozano, O.,

# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)
242 M. AL-HABORI AND A. RAMAN

Guevara, L., and Kelly, S. (1984). Association of differing mic factor of fenugreek seeds (T. foenum graecum). in
dietary, metabolic and clinical risk factors with macro- rats. Nutr. Rep. Int. 33, 669±677.
vascular complications of diabetes. A prevalence study of Sharma, R. D. (1986b). Effect of fenugreek seeds and leaves
503 Mexican type II diabetic subjects 1. Diabetes Care 7, on blood glucose and serum insulin responses in human
421±427. subjects. Nutr. Res. 6, 1353±1364.
Parry, J. W. (1943). The Spice Handbook, Chemical Publish- Sharma, R. D., and Raghuram, T. C. (1990). Hypoglycaemic
ing Co., Brooklyn, New York. effect of fenugreek seeds in non-insulin dependent
Petit, P., Sauvaire, Y., and Hillaire-buys, D. et al. (1995a). diabetic subjects. Nutr. Res. 10, 731±739.
Insulin stimulating effect of an original amino acid, 4- Sharma, R. D., Raghuram, T. C., and Rao, N. S. (1990). Effect
hydroxyisoleucine, puri®ed from fenugreek seeds. Dia- of fenugreek seeds on blood glucose and serum lipids in
betologia 38, S1, A101. type I diabetes. Eur. J. Clin. Nutr. 44, 301±306.
Petit, P., Sauvaire, Y., and Hillaire-buys, D. et al. (1995b). Sharma, R. D., Raghuram, T. C., and Rao, V. D. (1991).
Steroid saponins from fenugreek seed: extraction, puri- Hypolipidaemic effect of fenugreek seeds: a clinical
®cation and pharmacological investigation on feeding study. Phytother. Res. 5, 145±147.
behaviour and plasma cholesterol. Steroids 60, 674±680. Sharma, R. D., Sarkar, A., and Hazar, D. K. et al. (1996a).
Petit, P., Sauvaire, Y., Ponsin, G., Manteghetti, M., Fave, A., Hypolipidaemic effect of fenugreek seeds: a chronic
and Ribes, G. (1993). Effect of a fenugreek seed extract on study in non-insulin dependent diabetic patients. Phyto-
feeding behaviour in the rat: metabolic-endocrine corre- ther. Res. 10, 332±334.
lates. Pharmacol. Biochem. Behav. 45, 369±374. Sharma, R. D., Sarkar, A., Hazar, D. K., Misra, B., Singh, J. B.,
Platel, K., and Srinivasan, K. (1996). In¯uence of dietary and Maheshwari, B. B. (1996b). Toxicological evaluation
spices or their active principles on digestive enzymes of of fenugreek seeds: a long term feeding experiment in
small intestinal mucosa in rats. Int. J. Food Sci. Nutr. 47, diabetic patients. Phytother. Res. 10, 519±520.
55±59. Sidhu, G. S., and Oakenfull, D. G. (1986). A mechanism for the
Price, K. R., Johnson, I. T., and Fenwick, G. R. (1987). The hypocholesterolaemic activity of saponins. Br. J. Nutr. 55,
chemistry and biological signi®cance of saponins in 643±649.
foods and feeding stuffs. CRC Crit. Rev. Food Sci. Nutr. Sidhu, G. S., Upson, B., and Malinow, M. R. (1987). Effects of
26, 27±135. soy saponins and tigogenin cellobioside on intestinal
Raghuram, T. C., Sharma, R. D., Sivakumar, B., and Sahay, B. uptake of cholesterol, cholate and glucose. Nutr. Rep. Int.
K. (1994). Effect of fenugreek seeds and intravenous 35, 615±623.
glucose disposition in non-insulin dependent diabetic Singhal, P. C., Gupta, R. K., and Joshi, L. D. (1982).
patients. Phytother. Res. 8, 83±86. Hypocholesterolaemic effect of Trigonella foenum grae-
Reid, J. S. G., and Meier, H. (1970). Formation of reserve cum (Methi). Curr. Sci. 51, 136±137.
galactomannan in the seeds of Trigonella foenum Sparks, J. D., and Sparks, C. E. (1994). Insulin regulation of
graecum. Phytochemistry 9, 513±520. triacylglycerol-rich lipoprotein synthesis and secretion.
Report of the National Cholesterol Education Program (1988). Biochim. Biophys. Acta 1215, 9±32.
Expert panel on detection, evaluation and treatment of Stark, A., and Madar, Z. (1993). The effect of an ethanol
high blood cholesterol in adults. Arch. Int. Med. 148, 36± extract derived from fenugreek (Trigonella foenum
69. graecum L.) on bile acid absorption and cholesterol
Ribes, G., Da Costa, C., Loubatieres-Mariani, M. M., Sauvaire,
levels in rats. Br. J. Nutr. 69, 277±287.
Y., and Baccou, J. C. (1987). Hypocholesterolaemic and
Story, J. A., Le Pages, S. L., and Petro, M. S. et al. (1984).
hypotriglyceridaemic effects of subfractions from fenu-
Interactions of alfalfa plant and sprout saponins with
greek seeds in alloxan diabetic dogs. Phytother. Res. 1,
cholesterol in vitro and in cholesterol-fed rats. Am. J. Clin.
38±43.
Ribes, G., Sauvaire, Y., and Baccou, J. C. et al. (1984). Effects Nutr. 39, 917±929.
of fenugreek seeds on endocrine pancreatic secretions in Trowell, H. (1972). Ischaemic heart disease and dietary ®bre.
dogs. Ann. Nutr. Metab. 28, 37±43. Am. J. Clin. Nutr. 25, 926±931.
Ribes, G., Sauvaire, Y., Da Costa, C., Baccou, J. C., and Uchida, K., Takase, H., Nomura, Y., Takeda, K., Takeuchi, N.,
Loubatieres-Mariani, M. M. (1986). Antidiabetic effects of and Ischikawa, Y. (1984). Changes in biliary and faecal
subfractions from fenugreek seeds in diabetic dogs. Proc. bile acids in mice after treatment with disogenin and b-
Soc. Exp. Biol. Med. 182, 159±166. sitosterol. J. Lipid Res. 25, 236±245.
Sadhukhan, B., Roychowdhury, U., Banerjee, P., and Sen, S. Udayasekhara Rao, P., Sesikeran, B., and Srinivasa Rao, P.
(1994). Clinical evaluation of a herbal anti-diabetic (1996). Short term nutritional and safety evaluation of
product. J. Indian Med. Assoc. 92, 115±117. fenugreek. Nutr. Res. 16, 1495±1505.
Sankara Rao, D. S., and Deosthale, Y. G. (1981). Mineral Udayasekhara Rao, P., and Sharma, R. D. (1987). An
composition of four Indian food legumes. J. Food Sci. 46, evaluation of protein quality of fenugreek seeds (Trigo-
1962±1963. nella foenum graecum) and their supplementary effects.
Sauvaire, Y., and Baccou, J. S. (1976). Nutritional value of the Food Chem. 24, 1±9.
proteins of leguminous seed, fenugreek (Trigonella Ulloa, N., and Nervi, F. (1985). Mechanism and kinetic
foenum graecum L.). Nutr. Rep. Int. 14, 527±535. characteristics of the uncoupling by plant steroids of
Sauvaire, Y., Baissac, Y., Leconte, O., Petit, P., and Ribes, G. biliary cholesterol from bile salt output. Biochim. Bio-
(1996). Steroid saponins from fenugreek and some of phys. Acta 837, 181±189.
their biological properties. Adv. Exp. Med. Biol. 405, 37± Valette, G., Sauvaire, Y., Baccou, J. C., and Ribes, G. (1984).
46. Hypocholesterolaemic effect of fenugreek seeds in dogs.
Sauvaire, Y., Girardon, P., Baccou, J. C., and Risterucci, A. M. Atherosclerosis 50 105±111.
(1984). Changes in growth, proteins and free amino acids Varshney, I. P., and Sharma, S. C. (1996). Saponins XXXII-
of developing seed and pod of fenugreek. Phyto- Trigonella foenum graecum seeds. J. Indian Chem. Soc.
chemistry 23, 479±486. 43, 564±567.
Sauvaire, Y., Ribes, G., Baccou, J. C., and Loubatiers-Mariani, Vinik, A. I., and Jenkins, D. J. A. (1988). Dietary ®bre in
M. M. (1991). Implication of steroid saponins and management of diabetes. Diabetes Care 11, 160±173.
sapogenins in the hypocholesterolaemic effect of fenu- West, K. M. (1978). Epidemology of Diabetes and its Vascular
greek. Lipids 26, 191±197. Complications. Elsevier, New York.
Shani, J., Goldschmied, A., Ahronson, Z., and Sulman, F. G. West, K. M., Ahuja, M. M. S., and Bennet, P. H. (1983). The role
(1974). Hypoglycaemic effect ofTrigonella foenum grae- of circulating glucose and triglyceride concentrations and
cum andLupinus termis (Leguminosae) seeds and their their interactions with other `risk factors' as determinants
major alkaloids in alloxan diabetic and normal rats. Arch. of arterial disease in nine diabetic population samples
Int. Pharmacodyn. Ther. 210, 27±36. from the W.H.O. multinational study. Diabetes Care 6,
Sharma, R. D. (1984). Hypocholesterolaemic activity of 361±369.
fenugreek (T. foenum graecum) : an experimental study Wong, S., Traianedes, K., and O'Dea, K. (1985). Factors
in rats. Nutr. Rep. Int. 30, 221±231. affecting the rate of hydrolysis of starch in legumes. Am.
Sharma, R. D. (1986a). An evaluation of hypocholesterolae- J. Clin. Nutr. 42, 38±43.

# 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, 233–242 (1998)