When it comes to
discussing the levels of healthy cholesterol there is much more to consider than a single
number. Currently, concern is not necessarily just with cholesterol per se, but with
its various fractions, popularly referred to as 'good', 'bad', 'ugly' and 'deadly'.
While 'good' or high density lipoproteins (HDL) and 'bad' or low density lipoproteins
(LDL) are relatively well known terms, the lesser known and newer additions to the
cholesterol family include 'ugly' (triglycerides) and 'deadly' (lipoprotein a). The
latter is obviously disturbing, particularly since it can be written into our genes, and
when elevated it is responsible for a very high rate of cardiovascular disease at a very
young age. This compounding knowledge of cholesterols, and the growing awareness of
related atherosclerosis and cardiovascular disease -still the number one cause of
mortality in modern society - compet us to seek safer and more effective preventive and
therapeutic solutions to this staggering health problem.
It is a sobering experience to consider that
cardiovascular disease has been afflicting our civilization for centuries.
Atherosclerosis and its resulting cardiovascular disease were understood in principle and
well documented some 2000 years ago. The Ayurvedic medical treatises of Charka
Samhita (1000 BC), Sushruta Samhita (600 BC), Vagbhata (7 th century AD) and Nighantusa
(12 th - 14 th century AD) refer to detrimental health conditions that may result from
unbalanced nutrition and a sedentary life style. These two factors were reported to
contribute to a 'coating and obstruction of channels', which translates into contemporary
terminology as atheromatous changes (fatty streaks) in the blood vessels. To
counteract this process, Ayurvedic practitioners have prescribed an amber-like resin that
oozes from incisions made in the bark of the Commiphora mukul (N.O. Burseraceae) tree, and
commonly known as gum guggul.
In the 1960's, the oleogum resin (gum guggul) was
systematically studied for its potential in the treatment of elevated blood cholesterol,
or hyperlipidemia. This research originated at the College of Medical
Sciences of the Banaras Hindu University in Varanasi, India, and was continued in the
1980's at the Central Drug Institute (CDRI) in Lucknow, India. The structure
function analysis of gum guggul has determined that the ethyl acetate soluble
portion of the gum, specifically its neutral portion, contains most of the hypolipidemic
properties. The neutral fraction was found to be a source of sterol compounds known
as guggulsterone E and Z (pregname derivatives) which are responsible for the lowering of
blood cholesterol. Subsequently, a preparation of gum guggul used by the CDRI
in clinical studies consisted of an extract solid, standardized to contain a minimum 2.5%
guggulsterones E and Z.
These studies on gum guggul indicate that its
hypolipidemic activity could be attributed to more than one mechanism, i.e. sequestration
of bile acids leading to enhanced excretion of cholesterol, inhibition of cholesterol
biosynthesis, degradation of cholesterol by increased activity of the thyroid hormones,
and alteration in catecholamine levels. Gum guggul may further reduce the risk of
cardiovascular disease by inhibition of platelet aggregation, increases in fibrinolytic
activity and as a result of its antiinflammatory and antioxidant properties.
The previously mentioned work done by CDRI
resulted in the first clinically tested gum guggul product. Gugulipid®, a
standardized extract of gum guggul was the subject of the study. Phase 1 evaluated
safety of the extract given in a dose of 400 mg tid for four weeks to 21 hyperlipidemic
patients. This regimen was well tolerated with no subjective or objective side
effects reported. In phase 11, the efficacy of the extract at a dose of 500 mg tid
for 12 weeks was evaluated on 19 patients with hyperlipidemia and a history of
cardiovascular disease. Gum guggul significantly lowered serum cholesterol and
triglycerides in 78% (15 subjects) of the cases. On average, cholesterol was lowered
by 17.3% and triglycerides by 30.3%, and the positive changes in blood lipids were
noticeable starting in week four of the therapy.
Subsequently a multicenter, phase III, clinical
trial was organized by CDRI on 245 patients with dyslipidemia. Eighty percent of the
subjects responded positively to the treatment.
effect was independent of age, sex or body weight, and the treatment was found especially
useful in cases with total cholesterol levels of 220 mg/dl or higher and triglycerides of
170 mg/dl or higher.
Overall, four published clinical trials were done
with this standardized gum guggul preparation. Two of the four studies were placebo
controlled, and one study compared the hypocholesterolemic action of gum guggul with a
similar purpose drug, clofibrate. A typical dose in those clinical studies consisted
of 25 mg of guggulsterones E and Z administered orally three times a day. When
results of the four clinical studies were pooled it was shown that on average 70% of the
patients enrolled lowered both their total cholesterol and triglycerides in response to
the treatment. An additional benefit of the gum guggul treatment was the marked
elevation of 'good' cholesterol or HDL ranging from a 20-36 % increase.
Although a standardized gum guggul preparation
has never been directly compared to statins (commonly used cholesterol lowering
prescription drugs), it appears to reduce 'bad' cholesterol LDL on average by 17%, which
is comparable to results obtained with 20mg of fluvastatin or 10 mg of pravastatin.
Gum guggul also increased HDL by 14%, which is similar to the results obtained with 1200
mg of gemfibrozil, and reduced triglycerides by 24%, a result comparable to treatment with
2 gm of niacin.
It should be noted that major advantage of a
properly standardized gum guggul preparation over currently available drugs is a relative
lack of adverse effects. Most statins can cause liver damage and
gastrointestinal discomfort. Cholestyramine produces constipation, abdominal discomfort,
bleeding tendencies and poor absorption of fat-soluble vitamins. Clofibrate can
cause liver damage, gastrointestinal discomfort and headaches.
Proper standardization of gum guggul is essential
to the safety and efficacy of the preparation. In clinical studies, the
administration of crude (unpurified) guggul caused mild side effects such as skin rashes,
diarrhea and irregular menstruation. The methods of standardization used by
Sabinsa in its Gugulipid® brand of gum guggul assure that potentially harmful
compounds are removed. In a powder, Gugulipid® is standardized to contain a
minimum 2.5% guggulsterones E and Z and quantified by HPLC analysis. In a
standardized soft extract, the minimum is 7.5% gugulsterones E and Z.
The fact that the gum resin of Commiphora mukul
comes with an exceptionally long history of use, systematic safety and
clinical studies points to its increasing importance as the nutraceutical of choice in
lowering blood lipids and the risk of cardiovascular disease.
Gugulipid® is a registered trademark
of Sabinsa Corporation
References available at request.
Vladimir Badmaev, M.D., Ph.D. is
trained in clinical and anatomical pathology at kings county Hospital and Downstate
Medical Center, New York. His Ph.D. degree is in the field ofimmunopharmacology.
He is the author of many articles and book on traditional medicine, with an
emphasis on Ayurvedic and Tibetan medicine. He is Sabinsa's Vice President of
Scientific and Medical Affairs.
Muhammed Majeed, Ph.D. holds a
doctorate in industrial pharmacy from St. John's University in New York. He has over
15 years of pharmaceutical research experience in the US with leading companies such as
Pfizer, Inc., Carter-Wallace, and Paco Research. Dr. Majeed has a broad knowledge of
the pharmacological properties of herbal medicines used in Ayurveda, the traditional
system of botanical medicine of India. He is Sabinsa's President and CEO.