Alternative Medicine Review 2001 (Jun); 6 (2): 203 ~ FULL TEXT
Plant Sterols and Sterolins
Sterols and sterolins, also known as phytosterols, are fats present
in all plants, including fruits and vegetables. Although they are chemically
similar to the animal fat, cholesterol, they have been shown to exert significant
unique biochemical effects in both animals and humans. Because they are
bound to the fibers of the plant, they are difficult to absorb during the
transit of digested food through the gut, particularly in individuals with
impaired digestive function.  For this
reason, and because much of the modern diet is over-processed and low in
fresh plant materials, sterols and sterolins appear in the serum and tissue
of healthy humans at 800–1000 times lower concentrations than that of cholesterol.
Beta-sitosterol (BSS) is the major phytosterol in higher plants along with
its glycoside, beta-sitosterolin (BSSG). Animal studies have demonstrated
BSS and BSSG possess anti-inflammatory, antipyretic, antineoplastic, and
immune-modulating properties. In other in vitro, animal, and human studies,
a proprietary BSS:BSSG mixture has shown promise in normalizing T-cell
function, dampening overactive antibody responses, and normalizing DHEA:cortisol
ratios. Research has shown plant oils contain the highest concentration
of phytosterols, nuts and seeds contain moderate amounts, and fruits and
vegetables generally contain the lowest phytosterol concentrations. 
Because only low levels of these substances are found in humans, increased
dietary intake of unprocessed fruits and vegetables or supplementation
with commercial phytosterols may be of benefit in re-establishing optimal
immune parameters. Restoring balance to the immune system may be of therapeutic
benefit in disease processes such as chronic viral infections, stress-induced
immune suppression, tuberculosis, allergies, cancer, and rheumatoid arthritis
and other autoimmune conditions. [3, 4]
Beta-sitosterol is not synthesized endogenously in man, and several
animal studies over the last 70 years [5-7]
have demonstrated its intestinal absorption in mammals is minimal, possibly
as little as five percent of total dietary beta-sitosterol consumed. By
comparison, intestinal absorption of cholesterol is 45-54 percent of intake.
Unlike cholesterol, beta-sitosterol is rapidly secreted into the bile and
is esterified outside the intestinal wall at a much slower rate. 
Beta-sitosterol is secreted into the bile, stored in the gallbladder, and
released intermittently into the duodenum, and subsequently incorporated
Mechanisms of Action
Anti-inflammatory/Antipyretic Agent: Animal research of plant
sterols given to rats demonstrated potent anti-inflammatory properties
similar to cortisone. A proprietary blend of sterols and sterolins was
capable of reducing the secretion of pro-inflammatory cytokines and tumor
necrosis factor-alpha. [1, 9, 10] Phytosterols
also reduced experimentally-induced edema. Animal research found antipyretic
effects of phytosterols was comparable to that of aspirin. 
Immune Modulation: In vitro, animal, and human studies have shown
that a 100:1 BSS:BSSG mixture is capable of enhancing several aspects of
the immune response. By selectively enhancing activity of T-Helper-1 (TH1)
cells and leaving unchanged or dampening the effect of TH2 cells, administration
results in a significant rise in interleukin 2 (IL-2) and gamma interferon
(IFN-g) which enhance direct natural killer (NK) cell activity. Dampening
of TH2 leads to decreased levels of interleukins (IL-4, IL-6, IL-10) involved
in B-lymphocyte differentiation and inflammation. This combination also
resulted in maintenance of cortisol and elevation of DHEA levels, thereby
decreasing cortisol:DHEA ratios and buffering negative stress responses. 
Blood Sugar Control: The hypoglycemic properties of phytosterols
were elucidated in an animal study using normo- and hyperglycemic rats.
Results demonstrated that when either BSS or BSSG were given orally, fasting
glucose levels were lowered and fasting insulin levels increased. This
research also found beta-sitosterol was more effective over time in moderating
glucose levels than its glycoside, beta-sitosterolin. It is thought phytosterol
administration increases circulating insulin levels via stimulation of
insulin secretion from pancreatic beta cells. 
Rheumatoid Arthritis: Rheumatoid Arthritis (RA) is an inflammatory
disease characterized by dysregulation of the immune system. B-lymphocytes
become overactive and secrete antibodies that destroy synovial tissues
of the joint. A BSS:BSSG combination was shown to increase the levels of
TH1 cells, down-regulating antibody production by B-lymphocytes. The phytosterol
mixture also decreased secretion of pro-inflammatory cytokines by macrophages,
thereby decreasing inflammation. Most conventional RA treatments involve
the use of drugs with significant side effects that are designed to control
pain and suppress the entire immune response of the body, without addressing
the actual immune dysfunction. By selectively activating or inhibiting
certain aspects of the immune response, BSS:BSSG compounds can effectively
regulate and control the overactive immune response seen in RA and other
autoimmune diseases. 
HIV/FIV Infection: Animal and human research conducted in South
Africa studied the effects of BSS:BSSG on disease progression of Feline
Immunodeficiency Virus (FIV) and Human Immunodeficiency Virus (HIV). The
initial positive studies were performed on cats infected with FIV (a feline
retrovirus essentially equivalent to HIV) and prompted subsequent research
on human subjects with HIV infection. Subjects given the sterol/sterolin
mixture were able to maintain stable CD4 cell counts, and apoptosis of
CD4 lymphocytes declined slightly, thereby slowing disease progression.
These studies also demonstrated a significant decrease in IL-6 levels,
possibly slowing viral replication rates in infected cells and thereby
decreasing viral load. 
Cancer: A lack of secretion of IL-2 and IFN-g by TH1 cells leads
to NK cells which are not capable of recognizing structures on the surface
of tumor cells. Sterols and sterolins are known to increase secretion of
IL-2 and IFN-g, enhancing NK cell activity and decreasing inflammation.
A double-blind, placebo-controlled study of patients with cervical lesions
caused by Human Papilloma Virus (HPV) is currently being conducted 
Benign Prostatic Hypertrophy (BPH): Two randomized, placebo-controlled,
clinical studies were conducted on 350 men diagnosed with benign prostatic
hypertrophy. Both studies lasted six months and dosages ranged from 60-130
mg beta-sitosterol daily. Although the exact mechanism is still unclear,
beta-sitosterol administration resulted in improved peak urinary flow rate
in both studies, as well as an improvement in subjective symptoms of BPH.
Herbal remedies for BPH include saw palmetto, Pygeum africanus, and pumpkin
seeds, and their effectiveness may be due to their phytosterol content.
An herbal preparation for the treatment of BPH called Harzol, which contains
beta-sitosterol and other phytosterols, has been available in Germany for
the past 20 years. [14, 15]
Immunosuppression in Endurance Athletes: Marathon runners and
endurance athletes often exhibit an increased inflammatory response to
injury, as well as an immune suppression characterized by frequent bacterial
and viral respiratory infections, all a result of high-intensity training.
A double-blind study of marathon runners given a 100:1 BSS/BSSG mixture
found improved maintenance of normal hematologic parameters, normalization
of cortisol:DHEA ratios, and a decreased inflammatory response. This study
indicates the phytosterol mixture acted to buffer cortisol release and
its immunosuppressive effects. 
Diabetes: Animal research found that in an oral glucose tolerance
test BSS and BSSG protected test animals from an excessive rise in serum
glucose levels due to glucose loading. This may be attributable to the
fact that these phytosterols are capable of stimulating insulin secretion
and thereby raising circulating insulin levels for better blood sugar control.
The hypoglycemic effect of BSS and BSSG in animals indicates it might be
an effective therapeutic tool for humans with diabetic and pre-diabetic
conditions.  Also, due to their potential
to down-regulate antibody production, this combination of sterols and sterolins
may intervene in the inflammatory process associated with early-stage type
1 diabetes, protecting pancreatic beta cells from destruction.
Pulmonary Tuberculosis: A double-blind, randomized, placebo-controlled
trial was conducted with 47 culture-positive pulmonary tuberculosis patients.
Patients were divided into two groups, hospitalized throughout the six-month
long treatment, and treated with a standard regimen of isoniazid, rifampicin,
and pyrazinamide. The test group also received a BSS:BSSG mixture. While
several disease markers showed similar results between placebo and test
groups, patients given the sterol/sterolin mixture showed a significantly
faster weight recovery compared to the placebo group. Patients in the phytosterol
group also exhibited notable differences in certain hematological parameters,
including increased lymphocyte, eosinophil, and monocyte counts. The results
of this study suggest the immune modulating activity of phytosterols might
be of therapeutic value in cases of multi-drug-resistant tuberculosis. 
Ongoing research is being conducted with phytosterols and their effects on several other conditions, including chronic allergic rhinitis/sinusitis, asthma, and hepatitis C infection. 
Dosage and Safety
Phytosterols are non-toxic, do not result in general immune suppression, and are rarely associated with side effects. Their high margin of safety make them an attractive therapeutic tool for a variety of conditions. The research has been conducted on a 100:1 BSS:BSSG formula containing 20 mg beta-sitosterol and 200 mcg beta-sitosterolin per capsule. A loading dose
of two capsules three times daily should be given for one month, at which time this can be decreased to one capsule three times daily. Phytosterols work best if taken on an empty stomach, one hour before meals. They should not be taken with animal fats (including milk) as these foods inhibit absorption.
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