Autoimmune diseases, including rheumatoid arthritis (RA), are the
result of malfunction of the immune system, activated by an unknown
agent to attack and destroy the host's tissues. Medical researchers
have postulated many reasons for dysfunction of the immune system,
but the standard approach to the treatment of such patients has
been to suppress the immune response with immunosuppressive drugs,
regardless of their many damaging side effects. Other treatments
offered are merely palliative, designed to relieve pain and other
symptoms linked to the inflammatory process.
Recent research, conducted on sterols and sterolins (plant fats)
by our group at Tygerberg Hospital/University of Stellen-bosch Medical
Faculty and published in the International Journal of lmmunopharmacology,
is providing an entirely new medical approach to the treatment of
auto-immune and other chronic diseases that only manifest themselves
when the immune systems of afflicted individuals are compromised.
The following is a summary of how the immune system functions under
a normal response and how, during a pathological process, the same
system can cause the tissue damage seen in various diseases. A normal
healthy immune system relies on the following:
• B cells, which produce antibodies
(proteins) that destroy invading pathogens such as bacteria, viruses,
parasites, and other foreign proteins before they can enter the
cells of the host.
• T cells, which are the cells controlling and regulating
the immune response. These are divided into either CD4 positive
(also called the T-helper cell) or CD8 positive (called the T
suppressor or cytotoxic cell).
To complicate the matter, there are two types
of T helper cells: the so-called TH1 CD4 cells, which produce IL2
(interleukin 2) and Gamma Interferon (IFN-g), and the TH2 CD4 cells,
which release IL4, IL6 and IL10 which enhance the activity of B
cells to produce antibodies.
Should the activity of TH1 CD4 cells be defective, many chronic
diseases typified by an over-activity of antibody production ensue.
On the other hand, the CD8 positive cells are activated by the TH1
lymphokines to become killer/cytotoxic cells, which kill the host
cells that harbor the pathogen: this is an escape mechanism utilized
by certain organisms in an attempt to evade the initial response
mounted by the antibodies produced by the B cells. This occurs because,
once inside the host cell, the pathogens are inaccessible to the
action of antibodies. Hence, the cellular mechanism typified by
the CD8 T cells evolved as a result of this escape mechanism employed
by the pathogens in question.
The immune system is finely tuned to adapt to changes that can be
induced either when a virus or bacterium invades the host or to
recognize changes that are associated with the development of malignant
characteristics. It therefore stands to reason that when the TH1
arm of the T cells is deficient, the consequence is one of infection,
chronic inflammation, and eventually tissue damage and disease.
What Are They and How Do They Modulate the Immune Response?
Plant sterols and sterolins are amongst the many phytochemicals
(biologically active molecules isolated from plants) that have,
in recent years, stimulated research into the healing and protective
effects of plants. Both sterols and sterolins were identified and
chemically elucidated as early as 1922. They are plant "fats"
present in every single plant (fruits and vegetables) and although
chemically very similar to the animal fat, cholesterol, they are
totally different in biological functions. In the natural state,
they are bound to the fibers of the plant and for this reason, they
are difficult to desorb from the fibers during the normal transit
of digested food through our gut, especially in the case of older
people whose digestion is less effective than that of a younger
person. Seeds are the richest source of the sterols and sterolins,
and yet, the refining processes applied in the food industry render
the staple foods useless because they remove the sterols and sterolins
to make the product more appealing to the eye. (For instance, in
order to prevent the precipitation of the fats in so-called cold
pressed oils, the oil is heated and refined to remove the sterols/sterolins).
Also of importance is the fact that our modern diet is low in fresh
plant materials (vegetables and fruits) because we have recourse
to the fast food outlets or we are generally carnivorous and do
not consume sufficient fruits and vegetables.
Sterols and sterolins have been shown to modulate the functions
of the T cells both in vitro and in vivo by enhancing their cellular
division and their secretion of these important regulatory soluble
factors called lymphokines (IL2 and IFN-g). It is important to note
that only the function of the so-called TH1 cells seem to be enhanced,
leaving the activity of the TH2 helper cells unaffected. This is
crucial because it is these specific lymphokines that are responsible
for controlling the activity of the B cells. Both IL2 and IFN-g
are able to switch off the release of the lymphokines that help
the B cells to make antibodies.
In the case of rheumatoid arthritis, it is thought that the over-activity
of the B cells is directly involved in the release of antibodies
that attach themselves to the synovial tissue and the destruction
thereof. Also, the antibodies form complexes with other antibodies
and precipitate within a joint: this is thought to initiate the
entire process of inflammation.
It has been shown that the secretion of inflammatory cytokines released
by macrophages is very effectively inhibited by the sterols/sterolins.
We have shown that the synthesis and release of both IL6 and TNF-a
(both factors are referred to as pro-inflammatory factors because
they initiate and maintain inflammation) are switched off when macrophages
are cultured in the presence of a mixture of sterols/sterolins.
This work confirms earlier observations in an animal model (rats)
in which an inflammatory process was inhibited by pretreatment with
sterols/sterolins. It appears the plant fats offer effective anti-inflammatory
activity at sites of chronic inflammation by switching off the very
factors that initiate the process.
Evidence for Involvement
of the Immune Response and Its Mediators in the Disease Process
of Rheumatoid Arthritis
Synovium from a patient afflicted with RA contains the cellular
infiltrate made up of T cells, macrophages and B cells. At sites
of active tissue destruction, very high levels of cytokines (e.g.,
IL1, IL6, and TNF-a) are directly involved in the inflammatory process,
and this destruction can be prevented by specific cytokine inhibitors.
Furthermore, it has also been shown that damage can be induced in
normal healthy cartilage by adding the fluid from a rheumatoid arthritis
patient's synovium to the healthy cartilage.
More recently, high levels of TH2 cells (as opposed to TH1 cells)
have been discovered in the synovium of RA patients. It appears
that TH2 cytokines may be directly involved in the destruction of
the synovium by antibodies that we often refer to as rheumatoid
factors (RFs). RFs form complexes with other antibodies and often
precipitate at the site, initiating recruitment of inflammatory
cells. These immune complexes can be demonstrated in the synovial
fluid and even the serum of RA patients.
Understanding the modulatory activity of sterols/sterolins, it is
not surprising that these plant fats are beneficial in control of
this chronic disease. We have been able to show that sterols/sterolins
enhance preferentially the activity of TH1 cells and inhibit the
synthesis and release of other inflammatory factors. The disease
can therefore be controlled by reversing the immune abnormality
at the site of disease, preventing damage caused by inflammation.
The major differences between the use of conventional medicines
and the sterols/ sterolins in the control of rheumatoid arthritis
is that conventional drugs are mainly aimed at inhibiting the entire
immune response and the inflammatory process with the use of anti-inflammatory
compounds and immunosuppressive drugs (cortisone, etc). Such treatments
are not without side effects and dangers because of their non-specificity.
Chronic use of immunosuppressive medications eventually leaves the
individual totally open to infections. Such immune-suppressed patients
are also more prone to development of cancer.
Sterols/sterolins are entirely different in their function in that
they target the abnormality, correcting the immune dysfunction.
Many factors can lead to malfunction of the immune response, including
infection by pathogens that specifically target TH1 cells (e.g.,
HIV), chronic stress (physical as well as psychological), and poor
nutrition. It therefore stands to reason that many chronic diseases
could be totally preventable by ensuring the intake of essential
micronutrients, including sterols and sterolins.
The major advantage of the use of sterols/sterolins in the management
of rheumatoid arthritis is that these fatty plant constituents are
natural, non-toxic, and without side effects (no general immune
suppression). This revolutionary approach to the treatment of autoimmune
diseases will certainly be the approach of the future.
to Dr. Bouic, "The company that has sponsored the above-reported
research has encapsulated these molecules and the recommended dosage
is one capsule three times per day on an empty stomach. There is
no drug-induced adverse effects based on the usage of the capsules
by over 25,000 clinical trial volunteers. The company is currently
marketing the capsules here in South Africa under the trade name
of ModuCare™. It is available retail in Canada from Purity
Life and in the US from Natural Balance and Rexall Sundown. The
sole provider for licensed health care professionals is Thorne Research.
The formulation is patented internationally including the United
States, and any questions should be directed to the sponsoring company
in South Africa at telephone number 27-11-3151430 or fax 27-11-3151462."
Dr. Bouic is currently running a placebo-controlled double blind
trial in rheumatoid arthritis patients using ModuCare™, eventually
to be published in a peer-reviewed journal. Most of the data to
date has been based on individual cases.
Prof. Patrick JD Bouic
Chief Specialist Scientist, Head: Immunology, Department of Medical
Tygerberg Hospital/University of Stellenbosch
Faculty of Medicine
PO Box 19063