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Investigation of the effect of ginger on the lipid levels, a
double blind controlled clinical trial
Reza Alizadeh-Navaei, MD, Fatemeh Roozbeh, MD, Mehrdad Saravi, MD,
Mehdi Pouramir, PhD, Farzad Jalali, MD, Ali A. Moghadamnia, PhD.
179
ABSTRACT
20052004
3g
3g
45
45
40
LDL
VLDL
p
0.05
p
0.05
LDL
HDL
VLDL
p
0.05
Objective: To study the effect of fine powder of ginger
on lipid level in volunteer patients.
Method: is is a double blind controlled clinical
trial study in 2 cardiac clinics Cardiac Disease Clinic,
Babol, north of Iran, between April to May 2004. We
randomly divided the patients with hyperlipidemia
into 2 groups, treatment group (receiving ginger
capsules 3 g/day in 3 divided doses)
Original Articles
and placebo group (lactose capsule 3 g/day in 3
divided doses) for 45 days. All subjects with diabetes
mellitus, hypothyroidism, nephrotic syndrome, and
alcohol drinking, pregnancy and peptic ulcer were
excluded. Lipid concentrations profile before and
after treatment was measured by enzymatic assay.
Results: Forty-five patients in the treatment group
and 40 patients in placebo group participated in this
study. ere was a significant reduce in triglyceride,
cholesterol, low density lipoprotein (LDL), very low
density lipoprotein (VLDL), levels of before and
after study separately in each group (p<0.05). Mean
changes in triglyceride and cholesterol levels of ginger
group were significantly higher than placebo group
(p<0.05). Mean reduction in LDL level and increase
in high density lipoprotein level of ginger group were
higher than the placebo group, but in VLDL level of
placebo was higher than ginger (p>0.05).
Conclusion: e results show that ginger has a
significant lipid lowering effect compared to placebo.
Saudi Med J 2008; Vol. 29 (9):
From the Departments of Pharmacology (Navaei, Roozbeh,
Moghadamnia), Internal Medicine (Saravi, Jalali), and Biochemistry
(Amir), Babol University of Medical Sciences, Babol, Iran.
Received 31st May 2008. Accepted 18th August 2008.
Address correspondence and reprint request to: Dr. Reza A. Navaei,
Department of Pharmacology, Babol University of Medical Sciences,
Babol, Iran. Tel. +98 11114756. Fax. +98 111-2294718.
E-mail: reza_nava@yahoo.com
Hyperlipidemia mirrors the onset of abnormality of
lipid metabolism secondary to the manifestation
and progression of the atherosclerotic disease. In addition
to diet, the use of herbal medicine as a pharmacologic
modality in preventing alteration in lipid metabolism has
received a wide attention from several workers.1 Ginger
(Zingiber officinale, Zingiberaceae), a well-known
spice plant, sweet, pungent, heating appetizer has been
used in traditional oriental medicines for long time. Its
180
Investigation of the effect of ginger on the lipid levels … Alizadeh-Navaei et al
Saudi Med J 2008; Vol. 29 (9) www.smj.org.sa
extract and major pungent principles have been shown
to exhibit a variety of biological activities.2,3 It has been
used to treat a number of medical conditions, including
headache, colds, and arthritis.4 Ginger reduces symptoms
in patients with nausea of pregnancy, motion sickness,
and postoperative nausea and vomiting.5-8 Limited in
vitro studies have shown that water and organic solvent
extracts of ginger possess antioxidant active component
in ginger properties.9-11 e main antioxidant active
materials in ginger are the gingerols and shogaols and
some related phenolic ketone derivatives.12 Ginger acts
as a hypolipidemic agents in cholesterol-fed rabbits.13
Ginger has been shown that can significantly reduce
serum total cholesterol and triglyceride and increase
the high density lipoprotein (HDL) cholesterol
level as compared to pathogenic diabetic rats.13 A
combination of ginger and garlic has been reported to
have hypoglycemic and hypolipidemic effects in albino
rats.14 Etanolic ginger extract consumption has also been
shown to reduce plasma cholesterol and inhibit low
density lipoprotein (LDL) oxidation in atherosclerotic,
a-lipoprotein E-deficient mice.15 It has been suggested
that the aqueous extract of ginger might inhibit the
intestinal absorption of dietary fat by inhibiting its
hydrolysis.16 On the other hand, one clinical study
shows that ginger could not affect the blood lipid and
sugar level,17 but there are no adequate findings of
clinical study of lipid lowering effect of ginger. Evidence
continues to accumulate from epidemiological studies
that elevated plasma concentrations of lipoprotein (a)
[LP (a)] are a risk factor for a variety of atherosclerotic
and thrombotic disorders.18 High plasma levels of LP (a)
are strongly associated with coronary artery disease, and
LP(a) has been established as an independent risk factor
and marker for atherosclerosis.19 On the other hand,
hyperhomocysteinemia is a risk factor for cardiovascular
disease.20 Plasma homocysteine predicts progression of
atherosclerosis.21 On the basis of this, in the present
study we have investigated the effect of ginger on blood
lipids and LP (a) and homocysteine in a double blind,
placebo-control trail study.
Methods. is study was a randomized, double
blind, placebo control trial performed between April
2004 and May 2005. All patients with hyperlipidemia
that returned to 2 cardiac clinic in Babol (Iran) who had
fasting triglyceride of >200 mg/dl or cholesterol >200
mg/dl were enrolled in this trial. Forty-five patients
with hyperlipidemia in treatment group and 40 patients
with hyperlipidemia in placebo group participated in
this study. Exclusions criteria were diabetes mellitus,
hypothyroidism, and nephrotic syndrome, alcohol
drinking, pregnancy and peptic ulcer. We obtained
written informed consent from all the subjects before
the study period. Ethics committee of Babol University
of Medical Sciences approved the study. Patients were
randomized to receive ginger capsules (3 g/day in 3
divided dose) or lactose capsule (3 g/day in 3 divided
dose) for 45 days. e dried rhizome of ginger was
purchased from a valid market (Rezaeian, Tehran,
Iran) and powdered as a fine particle. e fine powder
was handed to a pharmaceutical Lab (Tehran, Iran)
to prepare the capsules containing 500 mg ginger in
each. Lactose (Merck, Germany) was used to prepare
the placebo. Ginger (or placebo) capsules were given
to all patients in one package including 6 bottles of
drugs or placebo. Blood sample (5 ml) was taken before
and after treatment and fasting serum triglyceride,
cholesterol, HDL, LDL, and VLDL were measured by
enzymatic assay and lipoprotein-a and homocysteine
levels were measured using electro immunoassay and
Enzyme-Linked Immuno-Sorbent Assay.
Statistical analysis was carried out using the
Statistical Package for Social Sciences Version 10.5
software. Variations of lipids level were analyzed using
paired sample student t-test. e differences between
the groups were compared by unpaired sample student
t-test, and Mann-Whitney U test and gender distribution
between the 2 groups was analyzed using Fisher’s exact
test. Probability values of less than 0.05 were considered
statistically significant.
Result. e mean ±SD age of patients in the treatment
group was 53.8±11.8 years, and the control group was
53.5±11 years (p=0.905). e mean ±SD body mass
index of patients in the treatment groups was 31±4.4
kg/m2 and in the control group was 34.5±7.7 kg/m2
(p=0.83). ere were 16 (35.6%) males and 29 (64.4)
females in the treatment group and 18 (45%) males and
22 (55%) females in the control group (p=0.387). Tables
1 and 2 show the effects of administration of the ginger
on the levels of lipid lipoprotein-a and homocysteine.
Table 1 demonstrates the serum lipid profile of ginger
and placebo group at the beginning and at the end
of the trial. Within the group analysis, the levels of
triglyceride, cholesterol, LDL, VLDL, Lipoprotein-a
and homocysteine were decreased in both groups at the
end of the trial (p<0.05). e level of HDL increased
in response to ginger (p<0.05) but not in the placebo
group. ere was a significant difference between
the level of cholesterol and triglyceride in the ginger
group compared to placebo (p<0.05). Some alterations
were seen between the level of other parameters.
Also, HDL was increased in the ginger group, but no
significant differences were seen. However, the levels
of LDL decreased, but the difference was not statistical
significant. e dose of ginger (3 g/daily) had no effect
on the concentration of VLDL, lipoprotein-a and
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Investigation of the effect of ginger on the lipid levels … Alizadeh-Navaei et al
homocysteine. Non-significant reduction in LDL was
observed when ginger was administered at 3 g/daily for
45 days. e changes in the ginger treatment compared
to the changes in placebo group are presented in Table 2.
e mean changes in triglyceride and cholesterol levels
of ginger receiving subjects were higher than placebo
(p<0.05) (Table 2). ere was no significant change in
the ginger treatment group compared to placebo for
lipoprotein-a and homocysteine.
Discussion. According to the result, there was a
significant decrease of level of triglyceride and cholesterol
after administration of ginger in comparison with placebo
(p<0.05). ese data were consistent with the previous
studies.17,22 Some investigations have been reported
a decrease in levels of cholesterol and triglycerides in
the serum of rats receiving oral and intraperitoneal
administration of ginger.23 ere was a significant
reduction in level of cholesterol was observed in the rats
given a high dose of ginger (500 mg/kg) either orally
or intraperitoneal. No significant change in triglyceride
was observed in the serum of rats receiving either oral or
intraperitoneal ginger. e anti-hypercholesterolemic
effect of ginger was previously shown in rats fed with a
high-cholesterol diet for 24 days.24 ese workers also
reported that there was no immediate effect of ginger on
serum cholesterol. is confirms our finding that ginger
given daily for a period of 12 weeks orally significantly
reduced the serum cholesterol in the patients (Table 2).
e hypocholesterolemic effect of ginger could have
possibly resulted, at least in part, from the inhibition
of cellular cholesterol biosynthesis observed after
consumption of ginger extract.15 Reduced cellular
cholesterol biosynthesis is associated with increased
activity of the LDL receptor, which in turn leads to
enhanced removal of LDL from plasma, resulting in
reduced plasma cholesterol concentration.25 ese
results are in agreement with previously reported data,
showing that plant foods possess cholesterol-suppressive
capacity.26 It has been previously reported that the plant
food-derived ingredients, ß-carotene and lycopene, also
act as hypocholesterolemic agents, secondary to their
inhibitory effect on cellular cholesterol biosynthesis.27
It has been reported that consumption of 250 mg/day
of ginger extract for 10 weeks resulted in reduction
of triglyceride level in mice.27 On the other hand,
ethanolic extract of ginger (200 mg/kg for 10 weeks)
shows reduce serum triglyceride levels in cholesterol
fed rabbits compared with gemfibrozil.1 Lipid lowering
effect of ginger is possible that ginger decreased lipid by
increasing pancreatic lipase and amylase,24,28 inhibit lipid
hydrolyze in intestinal tract16 reducing lipid peroxidase29
increasing intestinal peristaltism,30 increasing cholesterol
conversion to bile acids.31 Feeding rats ginger significantly
elevated the activity of hepatic cholesterol-7-hydroxylase,
the rate-limiting enzyme in bile acids biosynthesis,
thereby stimulating cholesterol conversion to bile acids,
resulting in elimination of cholesterol from the body.31
In addition, a pure constituent from ginger [E-8 beta,
17 epoxylabd-12-ene-15, 16-dial (ZT)], was shown to
inhibit cholesterol biosynthesis in homogenated rat
liver.32 However, Verma et al reported that air dried
ginger powder (0.1 g/kg per os for 75 days) did not
lower blood lipids to any significant extent in rabbits by
cholesterol feeding (0.3 gr/kg per os).33 In another study,
Table 1 - Fasting lipid, lipoprotein-a and homocysteine levels (Mean ±SEM) before and after treatment (mg/dl).
Variable Ginger Placebo
Before After P-value* Before After P-value*
Triglyceride 320.2 ± 13.1 284 ± 11.5 0.000 331.4 ± 17.1 304.7 ± 15 0.004
Cholesterol 269 ± 4.9 241.5 ± 7.5 0.000 263.8 ± 5 249.2 ± 4.9 0.001
HDL 39.8 ± 0.7 42.6 ± 0.8 0.002 41.5 ± 1.3 41.3 ± 1 0.845
LDL 168.5 ± 5.4 151.2 ± 4.9 0.000 162.6 ± 5.3 152.7 ± 4.5 0.005
VLDL 28.9 ± 1.3 25.6 ± 0.9 0.001 31.5 ± 2.3 27.4 ± 1.4 0.008
Lipoprotein-a 23.1 ± 2 19.3 ± 1.6 0.000 29.6 ± 1.4 24.3 ± 3 0.009
homocysteine 10.7 ± 0.5 9.5 ± 0.4 0.012 10.8 ± 0.9 9.3 ± 0.5 0.012
* Paired t-test, HDL - high density lipoprotein, LDL - low density lipoprotein, VDL- very low density lipoprotein
Table 2 - Mean (±SEM) differences (mg/dl) lipids, lipoprotein-a and
homocysteine between groups before and after treatment.
Variable Ginger Placebo P-value
Triglyceride 36.2 ± 7.7 26.7 ± 8.6 0.039*
Cholesterol 27.5 ± 5.6 14.5 ± 4 0.027*
HDL 1.8 ± 0.5 0.17 ± 0.8 0.058†
LDL 17.3 ± 2.9 9.9 ± 3.3 0.093†
VLDL 3.3 ± 0.9 4 ± 1.3 0.638†
Lipoprotein-a 3.8 ± 0.9 5.2 ± 1.7 0.451†
Homocysteine 1.2 ± 0.4 1.5 ± 0.5 0.638†
* T-test, †Mann-Whitney, HDL - high density lipoprotein, LDL -low
density lipoprotein, VLDL - very low density lipoprotein
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Saudi Med J 2008; Vol. 29 (9) www.smj.org.sa
patients with coronary artery disease, ginger failed to
lower blood lipids when it was given in powdered form
(4 g) daily for a period of 3 months.31 In the present
study, significant difference (p<0.05) in HDL response
before and after ginger was considered after 45 days of
daily intake of 3000 mg of ginger powder but there was
no significant difference in placebo group. Bhandari
et al13 reported that the ethanolic extract of Zingiber
officinale (200 mg/kg for 20 days) significantly increased
the HDL-cholesterol level. Fuhrman et al15 showed that
consumption of 250 mg/kg of ginger extract resulted in
reductions in LDL of apolipoprotein E-deficient mice.15
Ginger extract consumption can result in accumulation
of active ingredients within the cells, as well as in the
cell plasma membrane, thus affecting cellular enzymes,
and plasma membrane receptors. It has been shown that
ginger extract consumption reduces the cellular uptake
of oxidized LDL, possibly due to steric modification of
plasma lipoprotein receptors.15 We have observed no
significant reduction in serum LDL levels in present
study. However, the result of our study, regarding LDL
level was not consistent with the previous study.15 It may
be due to the level of given dose of ginger to our patients.
Since the equivalent dose of ginger extract with powder
that was used in this study was 90 mg crude extract
of ginger daily. at is in contrary with the previous
study.15 It was suggested that the study to be continue
with different doses or different procedures. In this
study, the finding of a non-significant HDL lowering
effect lends itself to several possible interpretations; it
is possible that ginger powder has no effect on LDL.
e limitation of this study was having a single center
and multicenter study with larger patients should be
conducted.
In conclusion, the significant reduction in serum
cholesterol by ginger could possibly play an important
in the prevention and development of atherosclerosis.
e unique ability of ginger to lower serum cholesterol
and triglyceride levels is clinically important, because
its daily intake for a prolonged period will neither lead
to side-effects nor to complications as normally occurs
with anti-hyperlipidemic drugs.
Acknowledgment. e authors would like to thank the Babol
University of Medical Sciences for financial support of this study and
the laboratory technicians for their collaboration in measurement of the
samples.
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