Vishwanath Dhruwansh

Trigonella foenum- graecum (Methi)

Commonly known as Methi, it is an integral part of Indian condiments and has been in use as medicine in India and China historically.
Seeds and leaves of the herb have been used in various medications. The major chemical constituents are saponins, coumarins,
flavonoids, alkaloids, amino acids and carbohydrates. Its well-known medicinal and pharmacological activities include:

Synonyms Trigonella foenugraecum

Safety Profile Since Methi has been used as part of food, it is considered safe. However it should be used
with caution in individuals on diabetes medication because it may potentiate the action of other hypoglycemic
agents.

Chemical Constituents:
The composition of fenugreek seeds was extensively studied and their composition reveals a few specific features
 Proteins: High content, around 30% of the seed weight.
 Lipids: 5.5-7.5%. The fatty acids are dominantly linoleic acid (~40%) and linolenic acid
 Galactomannans: ~15% of the seed weight.
 4-Hydroxyisoleucine 1, a non-proteogenic amino-acid, 0.6% of the seed weight, 85% of the free amino
acids.
 A pseudo alkaloid, trigonelline 2 (0.1-0.15% of the seed weight).
 Phenolics: coumarins, flavonoids (~0.1%)
 Volatile compounds: Over 50 volatile compounds were identified. However, the characteristic flavour of
the seeds is mainly provided by a small g-lactone, sotolone 3.
 Steroids and steroidal saponins: Free sterols, dominated by sitosterol, make about 0.2% of the seed weight.
Steroidal saponins (4-6% of seed weight) include a homogenous series of steroidal sapogenins with
furostan 4 and spirostan 5 skeletons and two glycosidic chains on C-3 and C-26.

Traditional Used:
Fenugreek is above all a condiment used in Indian and North African cuisine. As a traditional medicine, there is a
variety of claims relative to its use. It is widely considered as antidiabetic and anticholesterol herb. It is used as a
tonic and appetite stimulant in North Africa. In India, it is used to treat various GIT disorders. It is also said to be
galactogogue and uterine stimulant.

Pre-Clinical Data Pharmacology

Hypoglycaemic activity:
 Vishwanath Dhruwansh

The hypoglycaemic activity of fenugreek seeds was demonstrated on several animal models (normal mice and
rats, insulin-dependent dogs, alloxan-induced diabetic mice, rats and dogs). The activity was related to various
components of the seeds. The soluble dietary fibre fraction, the main components of which are the
galactomannans, was shown to reduce glycaemia after glucose administration. This fraction was further shown to
decrease the serum fructosamine level with no significant change in insulin level . Another experiment using
fenugreek seed mucilage administrated to streptozocin-induced diabetic rats confirmed the antidiabetic properties.
Trigonelline is known to have some hypoglycaemic effect. However, most attention was given to 4-
hydroxyisoleucine. In vitro, it was shown to increase the insulin secretion by isolated Langerhans islets in a dose-
dependant manner. It was also shown to induce a biphasic insulin response in isolated perfused rat pancreas. In
vivo, it was shown to be effective in type 2 diabetic rats as well as in conscious fasted dogs in improving oral
glucose tolerance after oral administration . 4-Hydroxyisoleucine has been shown to increase glucose-induced
insulin release without interacting with other agonists of insulin secretion such as tolbutamide and
glyceraldehydes, thus demonstrating a novel in vitro insulinotropic activity . The bio-molecular mechanism is still
unclear. However, it was shown that seed powder was able to both increase the glutamate deshydrogenase and
decrease that of D-b-hydroxybutyrate dehydrogenase in aloxanized rats. Ultrastructures of the rat liver showed a
reduction in abnormalities . An alcoholic seed extract exerted an anti-cataract in alloxanized diabetic rats .
Hypocholesterolemic activity:
Fenugreek seeds showed some hypocholesterolemic activity. This activity was credited to both the
galactomannans and the saponins. Galactomannans decrease the uptake of bile acids, lower blood and liver
concentration of cholesterol and decrease hepatic cholesterol synthesis .Indeed, the soluble dietary fibre fraction
of the seeds significantly decreases the atherogenic lipids in type 2 diabetic rats . Saponins were also shown to
interact with bile salts in the GIT.
Nutritive activity:
Studies to verify these traditional claims provide somewhat contradictory results. Some studies using fenugreek
seeds as food supplement did not alter the food intake of animals . When given to type 2 diabetic patients, no
significant changes were observed on the food consumption, mean energy intake or body weight. However, the
seed extract was reported to increase appetite and food intake in rats. The saponins seem to be responsible for this
effect, as a total saponin extract significantly increased appetite and body weight of normal as well as diabetic
animals.
Gastroprotective activity:
An aqueous extract and a gel fraction of fenugreek seeds were shown to protect the gastric mucosa as efficiently
and more efficiently, respectively than omeprazole in protecting rat from HCl-ethanol-induced gastric ulcers.
Antioxidant activity and chemopreventive activity:
Consumption of an aqueous extract of fenugreek seeds concurrently with ethanol for 60 days reduced liver and
brain damage in rats compared with use of alcohol alone. The aqueous extract had an in vitro antioxidant potential
in liver cells comparable to vitamin E and glutathione. Ethanol-induced lipid peroxidation was prevented to rise in
rats by an aqueous extract of fenugreek seeds. Similarly, during 1,2-dimethylhydrazine-induced rat colon
carcinogenesis the circulatory lipid peroxidation was decreased and chemoprevention was exerted by adding
fenugreek to the diet .A water extract of fenugreek seeds showed chemopreventive activity against 7,12-
dimethylbenz-(a)-anthracene (DMBA)-induced breast cancer in rats . A polyphenolic extract was able to prevent
ethanol-induced cytotoxicity and apoptosis in Chang liver cells. The same extract was also shown to protect
erythrocytes from H2O2-induced oxidative damage .
Immunomodulatory activity:
Fenugreek seeds showed some stimulatory effect on immune functions in mice .
Toxicities:
Fenugreek seeds are considered as essentially non-toxic, either in acute or sub-chronic studies. There is a report
that links fenugreek (whole plant) with myopathy in ruminants.
Genotoxicity and Mutagenicity Studies
 Vishwanath Dhruwansh

No genotoxicity found when fenugreek seeds were evaluated by the standard battery of tests recommended by the
US FDA for food ingredients .

Clinical Data Clinical Trials

Hypoglycaemic activity:
A study on cyclists showed that a fenugreek extract increases insulin concentration and glycogen resynthesis after
exercise .Various clinical trials of fenugreek showed improvement in glucose tolerance in healthy volunteers as
well as in type 2 and type 1 diabetic patients . However, all these studies were considered as methodologically
weak and classified as preliminary .
Hypocholesterolemic activity:
A clinical trial on hyperlipidemic non-diabetic patients whom diet was supplemented in defatted fenugreek
showed significant reduction of serum total cholesterol, LDL and VLDL cholesterol and triglyceride levels, while
HDL cholesterol levels were unchanged . In another trial, fenugreek seed powder did not affect the blood profile
in healthy subjects, but significantly reduced the total cholesterol and triglyceride without affecting the HDL-
cholesterol in patients with coronary artery disease .Similar results were obtained with germinated seeds, which
are less bitter . Long lasting hypo-cholesterolemic activity was also demonstrated in diabetic subjects. Altogether,
the methodology of these studies were considered as poor.
Galactogogue activity:
One study involving ten women indicated that fenugreek seeds would increase milk production . However a
stronger methodology would be required before this claim could be endorsed.
Adverse Effects in Human:
- Minor gastrointestinal symptoms (diarrhoea, flatulence) subsidising after few days.
- Allergy after inhalation of the seed powder or topical application of a seed powder paste .
Used in Certain Conditions:
Pregnancy / Breastfeeding
- Fenugreek may increase lactation .
- Ingestion of fenugreek by mothers during labour resulted in syrup-like odour in their new born infants,
leading to a false suspicion of maple syrup urine disease (MSUD). This is due to the fact that fenugreek, maple
syrup and urine of MSUD patients share sotolone as common component .
Age Limitations
Neonates / Adolescents
No documentation
Geriatrics
No documentation
Chronic Disease Conditions
No documentation
Interactions Interactions With Drugs
- Potential interaction with antiplatelet/anticoagulant drugs (incl. NSAIDs): the presence of coumarin in
fenugreek may theoretically increase the risk of haemorrhage (speculative) .
- Potential interaction with exogenous insulin in diabetic patients who do not adjust insulin dosage: could lead
to hypoglycaemia (speculative).
- Potential interaction with oral hypoglycaemic drugs sulfonylurea, biguanides, or both: could lead to
hypoglycaemia (speculative).
- Potential enhancement of the activity of cholesterol-lowering agents due to additive effects (speculative).
Interactions With Other Herbs / Herbal Constituents:
Fenugreek seeds extract and garlic extract are less effective in the regulation of hyperthyroidism in rats than
administrated independently .
Contraindictions Contraindications
Type 1 and type 2 diabetes (speculative).
 Vishwanath Dhruwansh

Case Reports:
Interaction with warfarin
- A woman stabilized on warfarin developed an elevated INR after several weeks of using a capsule of
fenugreek before meals and 10 drops of boldo extract after meals. Her INR returned to the normal range after
stopping the herbal products but became elevated again after resuming their use. It may be that warfarin
metabolism was reduced or the serum protein bond of warfarin was modified (speculative) .
Allergy
- An Algerian student using fenugreek as an appetite stimulant and topically as healing agent developed a
respiratory allergy. Handling this powder induced rhinitis and asthma. The prick test performed with fenugreek
was strongly positive.
- A 36-year-old housewife experienced sneezing, rhinorrhea and excessive tearing after opening a jar
containing fenugreek and smelling it for identification. This was followed by persistent coughing, wheezing and
fainting. She was admitted to the hospital in a state of shock. The past history revealed allergy to chickpeas and
occasional mild asthma. On the day of the incident took place she had not consumed chickpeas .
- A 45-year-old woman with a history of allergic rhinitis and asthma since childhood developed pruritus and
dandruff. On advice from a relative she applied fenugreek seed paste on her scalp. Within minutes, she developed
nasal congestion and hoarseness. Later, she experienced facial angiodema, wheezing and numbness of the head.
She was rushed to the hospital casualty ward .
False maple syrup urine disease (MSUD)
- A male infant was born at term by normal delivery weighing 3470 g, with Apgar score of 9 and 10 at 1 and 5
min, respectively. Several hours after birth, the nursing staff in the nursery noted a strong smell emanating from
the skin and the diaper of the infant. The odour resembles maple syrup, leading the staff to suspect MSUD.
Physical examination revealed an alert infant with normal vital signs, normal primitive reflexes and without any
abnormal physical signs. All biological analyses yielded normal results. It was subsequently realized that the
mother, of Yemenite Jewish origin, had ingested a spicy paste prepared from fenugreek seeds during the early
hours of her labour. The same maple syrup-like odour could be detected on the mother’s skin.