Sterols / Sterolins for the Immune System
Reference: Bouic PJD. Sterols and sterolins: new drugs for the immune system?
Drug Discovery Today 2002; 7:775-78.
Introduction:
Despite the rapid increase of scientific knowledge in immune cells and their various subsets over the last 10 years, the medical and drug management of chronic inflammatory and allergic conditions has not changed in the light of these new discoveries. However, a greater understanding of the immune system and how it is controlled by two unique subsets of CD4 lymphocytes (TH1 versus TH2) has led to the re-classification of certain types of disorders into specific categories depending on the ratios of these unique cells. As such, chronic conditions can now be specifically targeted through restoration of the TH1:TH2 balance.
Plant sterols: new therapeutic agents
Although beta-sitosterol (BSS) is employed primarily as a natural treatment to help control hypercholesterolemia, the glucoside of beta-sitosterol (beta-sitosterol glucoside, BSSG or sitosterolin) has not been as rigorously researched due to their low levels in human plasma. However, since 1996, Dr. PJD Bouic and his associates have investigated the immunomodulatory effects of a proprietary mixture of plant sterols and sterolins (BSS:BSSG). This combination, they determined, not only enhances the in vivo and in vitro action of T lymphocytes, but also increases the cytotoxic effects of natural killer cells against a specific cancer cell line (K562). Further experimental studies concluded that this specific sterol-sterolin mixture preferentially enhanced CD4 TH1 cells and therefore could restore the delicate TH1:TH2 balance. Unfortunately, this balance is often tipped towards a predominantly TH2 response resulting in a poor cellular and humoral immune response. Moreover, at physiological concentrations, this same combination of plant sterols/sterolins helped prevent the release of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor alpha by 98% in endotoxin stimulated monocytes. This confirmed the results of other researchers who found that the extracts of leaves (or other parts of plants) were rich in sterols and had profound anti-inflammatory effects, which in some cases, were comparable in action to the anti-inflammatory drug hydrocortisone. Given that sterols and sterolins exhibited both immunomodulatory and anti-inflammatory actions, it was only logical that clinical trials begin with these non-toxic natural products.
Clinical studies on sterols/sterolins
Tuberculosis (TB)
In a double-blind controlled study, the use of sterols/sterolins as adjunctive therapy helped TB patients recover faster, gain more weight, and exhibit less inflammation than those taking a placebo.
Marathon Runners and Immunosuppression
In this double-blind controlled trial, marathon runners who utilized the unique sterol/sterolin mixture did not exhibit any of the typical post-event immuno-suppression (e.g. neutrophilia, leucocytosis, lymphopaenia) seen in the placebo group. Moreover, those supplementing with plant sterols/sterolins were able to inhibit the inversion of CD4:CD8 ratios thereby blunting the temporary immunosuppresive effect of the race. In addition, the cortisol/DHEA-s ratio was maintained to that of pre-event levels in runners employing the BSS:BSSG mixture.
HIV Infection
In an open label study, HIV positive patients with CD4 cell counts above 500 cells/µl blood and who were not using anti-retroviral drug therapy showed stable CD4 cells counts and a decrease in their plasma viral loads after employing the BSS:BSSG mixture for up to 40 months. This group of patients maintained a predominantly TH1 profile indicating that their cell mediated immunity response accounted for both their viral control and prevention of CD4 cell loss.
Rheumatoid Arthritis
In a recent controlled trial, patients with rheumatoid arthritis (RA) had a significant reduction in their disease activity (according to American College of Rheumatology criteria) when employing the sterol/sterolin mixture. Although both the treatment group and a placebo group in this study employed anti-inflammatory (e.g. diclofenac) and analgesic (e.g. paracetamol) medications, those patients using the plant sterol/sterolin mixture had a 48% response to the treatment compared to only 21% in the placebo group. Moreover, patients in the active group utilized fewer prescription medications suggesting that their quality of life was better. Plant sterols/sterolins, the authors note, may work similarly to the product Flemun from the German Company Intermuti Pharma which decreases cyclooxygenase and lipoxygenase activity in vivo and in vitro.
Allergic Rhinitis/Sinusitis
Those suffering with allergic conditions exhibit a predominantly TH2 profile which implies more inflammatory IL-4 secretion and hence greater release of IgE. In testing this hypothesis, 24 individuals with allergic rhinitis/sinusitis were given the sterol/sterolin mixture over a 12-week period and found to have significant reductions in their objective- (e.g. reduced rhinorrea, post-nasal drip, nasal turbinate hypertrophy, IgE levels) and subjective clinical symptoms.
Conclusion: Although the ability to control symptoms and the inflammation arising from a disordered immune system has been the mainstay of modern medical therapy, we stand on the brink of new knowledge that certain CD4 cell subsets and their soluble messengers can have a significant impact on the course of chronic disease.
While there are numerous natural products that contain phytosterols such as Ginkgo and Cat's claw, it is only the 100:1 standardized mixture of plant sterols to sterolins that has been found to be optimal in balancing the delicate TH1:TH2 ratio at relatively low concentrations. Sterols and sterolins may then usher in a new era of treatment in which we try to repair the underlying abnormality rather than suppress the symptoms of disease.
