FENUGREEK SEEDS IN PREHYPERTENSION

1. EFFECTS OF FENUGREEK SEEDS ON
BLOOD PRESSURE AS ADJUNCTS TO DIET
IN PATIENTS WITH PREHYPERTENSION
Dr. Ghizal Fatima
Assistant Professor
Department of Biotechnology
Era’s Medical College and Hospital
Lucknow, India

2. Introduction:
• Fenugreek belongs to Fabaceae family; it was named,
Trigonella, from Latin language that means “little triangle”
due to its yellowish-white triangular flowers. It is being
commercially grown in India, Pakistan, Afghanistan, Iran,
Nepal, Egypt, France, Spain, Turkey, Morocco, North Africa,
Middle East and Argentina.
• Fenugreek is one of the oldest medicinal plants with
exceptional medicinal and nutritional profile.

3. • It may grow well under diverse and a wide
range of conditions; it is moderately tolerant
to drought and salinity, and can even be
grown on marginal lands in profitable way.
• It is a rich source of flavonoids (quercetin) as
well as other flavonoids which may have
antihypertensive effects. The total content of
polyphenols in fenugreek seeds are (9.47±0.10
mg GAE/g dry seeds) as major antioxidant
principle, including quercetin (215.814 µg)/g
of dry seed extract.

4. • Hypo-cholesterolemic, hypoglycemic and antioxidant
effects have been reported for fenugreek seeds but
other therapeutic effects are not known and it has been
used as adjunct to National Cholesterol Education
Program (NCEP) step 1 diet, for the first time to our
knowledge, for reducing blood lipoproteins and blood
glucose.
• The Food and Drug Administration (FDA) in the USA lists
fenugreek as being a generally recognized as safe (GRAS)
plant and in India, it is used as spice, although it is
originated in Greece.

5. • There is a need to augment nutritional
approaches with functional foods and
flavonoid supplements as an additional step
before prescribing drugs for greater safety
related concerns and low cost.
• The goal of this trial is to find out the effects
of adjunct therapy with fenugreek seeds by
targeting its flavonoid contents and
antioxidant actions.

6. Out of 71 subjects, 51 subjects with
prehypertension, satisfied the criteria of
inclusion in the study and rest 20 subjects
were excluded. All subjects received dietary
instruction on NCEP Step I diets.
• Design and Setting. Randomized, double
blind, placebo controlled trial.
Subjects and Methods

7. • All subjects (n=51) with prehypertension,
were assigned to NCEP step 1 diet for a period
of 12 week and then randomized by computer
generated random numbers; to receive two
different test agents in identical sachets for
another 12 weeks, blind to both, investigators
as well as patients.
• The test agents were fenugreek seeds powder
(60.0g/day) and cellulose placebo (3.0g/day),

8. Inclusion Exclusion
The main criteria for
inclusion of patients
age 25-65 years,
Systolic blood
pressure 120-139 mm
Hg and/or diastolic
blood pressure 80-89
mm Hg.
The exclusion criteria of subjects were
presence of significant CVD (n=5),
normal blood pressures (<120/80 mm
Hg, n=10), metabolic, endocrine,
gastrointestinal, renal, pulmonary,
hematopoitic or for the therapeutic
use of fish oils, lipid lowering
medications or other soluble fibre or
herb supplements.

9. • Study Procedures
• The study procedure consisted of a 12 week diet
adoption period then 12 week parallel, placebo
controlled treatment period.
• All subjects during this period augmented their
diets with either fenugreek seeds or placebo
cellulose.
• The consumption of total fat, dietary fat,
cholesterol and salt among these subjects were
similar to the recommendations of NCEP step I
diet, therefore, all subjects were asked to eat
vegetable oils in place of butter, clarified butter
and hydrogenated fat to avoid trans fat and
saturated fat.

10. • All the subjects following the dietary advice
during the 12 week of follow-up met entry
criteria on blood pressures, approved for this
study.
• The eligible patients were stratified by sex and
blood pressure levels after 12 week of dietary
intervention and randomly assigned to one of
the 2 agents; fenugreek seeds, or cellulose
placebo.
• The patients were returned for follow up at
weekly intervals for clinical examination and
dietary counseling; while both groups and
examining doctor were blind to treatment.

11. Study Formulations
Fenugreek seeds (Trigonella foenum graecum) are
rich in polyphenol flavonoids and quite bitter in
taste.
The seeds which contain moisture 9.0%, protein
28.3%. starch 6.5% and total fiber 51.7%
(gum19.2% and neutral detergent fiber 32.5%),
were defatted.
The total phenolic content of fenugreek seed
extract was between 13.08 to 14.23 mg GAE/g as
assessed in other studies. The defatted seeds were
packaged in a single dose sachet containing 20.0g
of powder in each sachet (270 mg flavonoids per
sachet).

12. • The placebo contained microcrystalline cellulose
and was supplied in powder form in single dose
(1.0g) sachets.
• The dosages of fenugreek (60.0g/day) and
cellulose placebo (3.0g/day) were based on other
studies (1,2).
• All the subjects were interviewed on each weekly
visit by counting the number of unused sachets
returned at each visit, to monitor the adherence
to test agents.
• In each group, all the subjects took one dose of
test material each time (three times a day) in at
least 300ml of water before meals.

13. Data Collection:
• Nutrient intakes were calculated by computation of Indian food
composition tables based on the result of dietary adherence.
Body weight was measured 2 to 3 times in a week.
• Prehypertension is diagnosed in presence of a systolic pressure
from 120 to 139 mm Hg or a diastolic pressure from 80 to 89 mm
Hg. Readings greater than or equal to 140/90 mm Hg are
considered hypertension. After a five-minute rest, a blood
pressure was recorded in a supine position, on the right arm with
a standard mercury manometer.
• All subjects had a 12 lead electrocardiogram with minimum 10
complexes in lead 2, to count the heart rate, which were assessed
by the physician performing the physical examination.

14. • Laboratory data
• Complete blood profiles, including nitrite,
thiobarbituric acid reactive substances
(TBARS) , diene conjugates and malon-
dialdehyde (MDA), blood lipoproteins and
glucose were obtained by colorimetric
methods at entry and at baseline and 24
weeks.
• A visit to clinic was scheduled for each subject
in the morning after minimum 12-hour fast for
collection of blood

15. Results
• In this study, 61 out of 71 volunteers were randomly
selected to participate in the study and all completed
the 12 week dietary intervention and began the
fenugreek or fiber treatment.
• Of 61 subjects, 26 in the fenugreek group and 25 in the
control group completed the trial and 10 subjects (5 in
each group) were excluded due to normal blood
pressure.
• Both the group of subjects were comparable at
baseline with respect to age, sex, body weight, body
mass index. Risk factors such as tobacco and alcohol
intake, excess salt consumption and sedentary
behavior were comparable in the two groups.

16. • Both groups maintained constant and comparable
nutrient intakes during the study period.
• However, during treatment, total dietary polyphenol
flavonoids including fenugreek polyphenols consumption
was significantly greater in the fenugreek group
compared to placebo group, although, pretreatment
flavonoid intakes were similar.
• There was no change in body weight by more than 0.5%
from baseline in any of the treatment group. The
pretreatment dietary fat and cholesterol intake were
within the limits of NCEP Step I diet and the reduction in
fat and cholesterol intake was modest.
• There was a mild reduction in energy intake however it
was comparable in both the groups.

17. Data Fenugreek(n=26) Placebo (n=25)
Sex (no.)m/f 22/4 23/2
Age (years) 46.6 (8.2) 46.8 (7.7)
Body weight (kg) 65.8 (8.8) 65.7 (8.9)
Body mass index (kg/m2) 24.4(3.1) 24.1(2.8)
Risk factors, n (%)
Tobacco intake > 0nce/week 8(30.7) 7 (28.0)
Alcohol intake >Once/week 5(19.2) 6 (24.0)
Sedentary behavior 18 (76.1) 16 ( 64.0)
Excess salt intake >5.0g/day 19 (73.0) 20 (80.0)
Baseline clinical data in the two groups
Value are means (standard deviations)

18. Mean energy and nutrient intake during treatment and at baseline.Values
are mean (standard deviation), P<0.001
Dietary intakes Fenugreek
(n=26)
Placebo
(n=25)
During treatment
Total energy (kJ/day)
(kcal/day)
9280(732)
2218(175)
9351(711)
2235(170)
Carbohydrate (% of total energy) 62.1(8.3) 61.6(7.3)
Protein (% of total energy) 12.8 (3.0) 14.0(3.2)
Total fat (% of total energy ) 25.1(2.1) 24.4(2.5)
Saturated (% of total energy ) 8.7 (1.7) 8.3(1.5)
Monounsaturated fat (% of total
energy)
8.4 (1.8) 8.0 (1.6)
Polyunsaturated fat (% of total fat) 8.0(1.8) 8.1(2.7)
Omega-6 fatty acids (% of total fat) 7.77 (1.9) 7.86 (2.0)
Omega -3 fatty acids (% of PUFA) 0.23 (0.08) 0.24 (0.09)
Salt (g/day ) 7.8 (1.7) 8.0 (1.5)
Total polyphenols (mg/d) 1115 (320)** 323 (98.2)

19. Mean energy and nutrient intake during treatment and at baseline.
Values are mean (standard deviation), P<0.001
Pretreatment
Total energy (KJ/day) 9400(745) 5452(716)
Carbohydrate (% of total ) 58.1 (6.2) 57.9 (7.1)
Total protein (% of total energy) 13.4 (3.0) 12.8 (3.2)
Total fat ((% of total energy ) 28.5 (4.1) 29.3 (3.7)
Saturated fat (%of total ) 11.8 (1.8) 11.9 (1.9)
Monounsaturated fat (% of total
energy)
9.3 (1.6) 9.6 (1.8)
Polyunsaturated fat (% of total ) 7.4(1.5) 7.8(1.6))
Omega-6 fat (% of total) 7.19(1.3) 7.58 (1.4)
Omega 3 fat (% of PUFA) 0.21(0.04) 0.22 (0.06)
Total flavonoid intake (mg/day) 306 (85.2) 314 (94.2)

20. Blood Pressure
• Systolic and diastolic blood pressure were comparable
in the two groups without any significant decline after
12 week of NCEP step 1 diet.
• However, after 12 week treatment with fenugreek and
placebo, both systolic and diastolic blood pressures
showed significant reduction in the fenugreek group
from baseline levels, whereas the changes were non-
significant in the placebo group.
• The incremental differences were significant for
fenugreek group without such changes in the placebo
group.

21. Data Fenugreek (n=26) Placebo
(n=25)
Systolic, mm Hg
Entry 129.6(16.5) 127.0 (14.5)
Baseline-after 12 week on diet 127.5 (14.8) 124.8 (12.2)
Final-after 12 week on fenugreek 122.5 (11.2)* 124.7 (12.5)
Change from baseline (%) -3.92 (5.00 mm Hg) -0.08 (0.1 mm Hg)
Diastolic, mm Hg
Entry 85.6 (6.2) 84.2 (6.4)
Baseline 85.2 (6.3) 84.0 (6.2)
Final 82.2 (5.9) 84.5 (6.1)
Change from baseline (%) -3.52* (3.0 mm Hg) +0.59 (+0.5 mm Hg)
Heart rate, per min
Entry 84.7 (7.2) 82.5(8.2 )
Baseline (12 week ) 84.7 (7.1) 83.0 (8.1)
Final (24 week) 81.0 (6.0)* 82.8 (8.5)
Change from baseline(%) -4.37 (3.7 per min) -0.2 (0.20 per min)
Effect of fenugreek seeds flavonoids on blood pressures.
*=P<0.02

22. Oxidative Stress
• All the parameters of oxidative stress; TBARS, MDA and
diene conjugates showed significant reduction in the
fenugreek group from the baseline and compared to
placebo group, whereas the changes in these parameter
were non-significant in the placebo group.
• After 12 weeks treatment with fenugreek and placebo,
changes recorded in the placebo group were non-
significant decline in serum levels of TBARS, MDA and
diene conjugates which were slightly higher in both the
groups at baseline.
• However, in the fenugreek group, significant reductions
and changes from baseline were observed in all the
markers of oxidative stress (Table 4)

23. Data Fenugreek (n=26) Placebo
(n=25)
TBARS (nmol/ml)
Entry 2.08 (0.16) 1.89(0.14)
Baseline 2.01 (0.14) 1.84 (0.13)
Final 1.50 (0.12)** 1.74 (0.12)
Change from baseline (%) -25.3 -5.4
Malondialdehyde (MDA) (nmol/ml)
Entry 3.26 (0.24) 3.22 (0.24)
Baseline 3.21 (0.22) 3.11 (0,22)
Final 2.21 (0.18) 3.04 (0.18)
Change from baseline (%) -31.1** -2.2
Diene conjugates (OD unit )
Entry 28.4 (1.1) 29.3 (1.2 )
Baseline (12 week ) 27.6 (1.2) 28.0 (1.1)
Final (24 week) 24.1 (1.1)* 28.1 (0.8)
Change from baseline(%) -12.7 +0.35
Oxidative stress, nitric oxide (nitrite) and cytokines during follow up.
TBARS=Thiobarbituric acid reactive substances., **=P<0.001, *=P<0.05

24. Blood Lipids and Blood Glucose
• The study shows that total cholesterol at baseline were similar but
after 12 weeks of fenugreek therapy, mean total cholesterol was
significantly lower in the fenugreek group compared to placebo
group, respectively.
• Mean levels of serum triglycerides and HDL cholesterol at baseline
show no significant differences but after 24 week administration of
fenugreek, mean levels of triglycerides was significantly lower and
mean HDL cholesterol was significantly higher in the fenugreek
group compared to placebo group as reported earlier.
• Fasting and postprandial blood glucose levels at baseline show no
significant differences in the two groups but after 24 week of
fenugreek administration; fasting and postprandial blood glucose
were significantly lower in the intervention group compared to
control group, respectively

25. Side effects and compliance
We observed an excellent compliance to
treatment for subjects completing the study in
both the groups. Among both groups, subjects
consumed 92.0% of the fenugreek doses and
94.5% of placebo doses. No significant adverse
reactions occurred in any of the treatment
groups,

26. Conclusion
• This study revealed that treatment with
fenugreek can cause significant decline in in
both systolic and diastolic blood pressures as
well as heart rate.
• Reduction in all these risk factors suggests
that fenugreek may have anti-hypertensive
effects.
• Larger and long term follow up studies are
necessary to confirm our results.

27. • Acknowledgements
• The financial support was provided by the
Sandoz Foundation of Gerontologic Research,
Switzerland (S076345) and International
College of Nutrition (ES243B)

28. Era’s Lucknow Medical College
and Hospital,

29. • Protein: Fenugreek endosperm is rich in proteins
(43.8 g/100 g): globulin, lecithin and albumin
• Fat: Seeds contain 5.5–7.5% lipids in total mainly comprised of
neutral lipids (85%), phospholipids (10%) and glycolipids (5%).
Unsaturated lipids constitute oleic (14%), linolenic (25%) and
linoleic (40%) acids.
• Fiber: Fenugreek seeds are a rich source of fiber (50–
65 g/100 g) mainly non-starch polysaccharides
• Vitamins and minerals: Fenugreek seed is a rich source of
vitamins viz. choline, vitamin A, B1, B2, C, nicotinic acid and
niacin, sulfur, phosphorus, calcium