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Antihyperglycemic and Insulin-Releasing Effects of B-Sitosterol 3-B-D-Glucoside and Its Aglyc

Author: M.D. Ivorra, M.P. D'Ocon, M. Paya and A.Villar Source: Archives of the International Pharmacodyn, v. 296, pp. 224-231, April 1988

An animal experiment was performed to determine the effects of the phytosterols, B-sitosterol and its glucoside, B-sitosterolin on plasma insulin and glucose levels in normal and hyperglycemic rats. The results indicate that when either phytosterol was administered orally, it increased the fasting insulin levels and lowered the fasting glucose levels. In an oral glucose tolerance test, the phytosterols protected the animal from an excessive rise in serum glucose levels due to the glucose loading. The results indicated that the B-sitosterol was more active over time in moderating glucose levels than the glucoside, B-sitosterolin. The anti-hyperglycemic effect of the sterols and sterolins are thought to be due to an increase in circulating insulin levels which is attributable to a stimula-tion of insulin secretion from pancreatic B-cells. These results indicate a possible anti-hypergycemic use for the phytosterols in the prevention and treatment of pre-diabetic and diabetic conditions.

Anti-inflammatory and antipyretic activities of B-sitosterol

Author: M.B. Gupta, R. Nath, N. Srivastava, K. Shanker, K. Kishor and K.P. Bhargava Source: Planta medica (Journal of Medicinal Plant Research) vol. 39, pp. 157-163, 1980

A basic research study using animal experiments was performed to determine whether sterols (plant fats) had any therapeutic properties such as reducing inflammation (anti-inflammatory), reducing fever (antipyretic) and reducing pain (analgesic). An extract of sterols from the seeds of the Indian herbal plant Cyperus rotundus was used in three separate experiments with rats to determine the medicinal properties. It was demonstrated that sterols possess potent anti-inflammatory properties similar to cortisone. Sterols were also demonstrated to reduce experimentally-produced edema. Sterols were also shown to have fever-reducing properties similar to aspirin (ASA). However, the sterols did not possess any pain-reducing or analgesic properties. In separate toxicology tests, sterols were shown to possess a very large margin of safety and produced minimal side effects such as gastric ulceration. The study concluded that sterols possess highly potent anti-inflammatory and antipyretic actions with a high margin of safety, suggesting its application to human medicine.

Beta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: Implications for their use as an immunomodulatory vitamin combination.

Author: Bouic, P.J.D.; Etsebeth, S.; Liebenberg, R.W.; Albrecht, C.F.; Pegel, K.; Van Jaarsveld, P.P. Source: International Journal of Immunopharmacology, vol. 18, no. 12, pp. 693-700, Dec. 1996

This study reports on a series of in vivo and in vitro studies which clearly demonstrate that the plant sterols and sterolins (B-sitosterol and its glucoside, B-sitosterolin) have immuno-modulatory properties. The first experiment performed in vitro demonstrated that sterols and sterolins had a significant proliferative effect on human T-cells. The effect was observed in extremely low concentrations of sterols/sterolins on the order of 1 femtogram which represents only 150 molecules of sterol and 10 molecules of sterolin. The best response was obtained when a 100:1 sterol/sterolin mixture was given. The same study was repeated on a small number of human subjects (8) indicating a T-cell proliferative response from 20% to 920% after 4 weeks on the sterol/sterolin mixture. No increase was observed for the 2 subjects receiving placebos. The peak activity of the sterol/sterolin mixture occurred at 6 hours in the in vitro experiments, indicating an effect in the initial stages of T-cell proliferation and activation of membrane antigens. Another in vitro experiment showed significant increases in the cytokines (immune communication molecules) interleukin-2 and gamma interferon on the order of between 17% and 41%. Another in vitro experiment showed an increase in Natural Killer Cell activity for the lysis of experimental cancer cells with the sterol/sterolin mixture. Although sterols and sterolins are poorly absorbed and are not synthesized in the human body, daily intake is required to maintain an optimal immune response. These experiments prove that a 100:1 sterol/sterolin mixture is a potent immuno-modulator with important implications for the treatment and restoration of immune dysfunctions.

The effects of B-sitosterol (BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: Inhibition of post marathon immune suppression and inflammation.

Author: P.J.D. Bouic, P.P. van Jaarsveld, A. Clark, J.H. Lamprecht, M. Freestone, & R.W. Liebenberg Source: International Journal of Sports Medicine, 1999

A double blind study was performed on marathon runners to see if the addition of a sterol/sterolin mixture would prevent the immune suppression and inflammatory reaction characteristic to high intensity athletics. Twenty marathon runners were recruited to take part in the trial and blood draws and medical histories were taken 4 weeks prior to the marathon event and three days after. Half the group received a placebo and the other half received a 100:1 mixture of sterols/sterolins. The RBC count went down significantly for the placebo group but remained the same for the treatment group. Neutrophils rose significantly for the treatment group, indicating infection, but remained constant in the treatment group. The lymphocyte count went down for the placebo group, specifically the CD3, CD4, and CD8 subsets. The treatment group actually experienced a significant rise for the CD3 and CD4 lymphocyte subsets. Interleukin 6 levels, which indicate an inflammatory reaction, went up for the placebo group, but down in the treatment group. As well, the cortisol levels, which indicate stress levels and degree of immunosuppression, were significantly elevated for the placebo group, but remained constant in the treatment group. The treatment group showed an increase in DHEA levels and a decrease in the cortisol/DHEA ratio, indicating that the sterol/sterolin mixture was helping to buffer the negative side effects of the stress response. The results of this experiment clearly show that taking a sterol/sterolin mixture prior to a highly stressful physical event protected the treatment group from the immunosuppression typically exhibited by the placebo group. As well, the sterol/sterolin mixture protected against the excessive inflammatory response typical of anyone running a marathon. Thirdly, the sterol/sterolin mixture buffered the excessive release of cortisol with its immunosuppressive effects. As well, the sterol/sterolin mixture raised DHEA levels and lowered the cortisol/DHEA ratio, indicating a more adaptive response to stress. These results indicate that sterols/sterolins are adaptogenic in that they modulate the immune and stress response. This makes them extremely valuable adjuncts to the prevention and treatment of a wide range of stress-mediated disorders, as well as immune dysregulation and inflammatory diseases.

An immunoendocrinological hypothesis of HIV infection

Authors: M. Clerici, M. Bevilacqua, T. Vago, M.L. Villa, G.M. Shearer & G. Norbiato Source: Lancet, v. 343, pp. 1552-1553, June 18, 1994

This paper advances the hypothesis that the progression of AIDS and the dysregulation of the immune system may be due to the immunosuppressive effects of increased cortisol levels and a decrease of DHEA levels resulting in an increased cortisol/DHEA ratio. Patients with AIDS have been observed to have a shift from type-1 to type-2 production of the immune mediators called cytokines. A reduction of Th1 lymphocytes results in the progressive reduction of interleukin-2, interleukin-12, and gamma interferon which are cytokines controlling cell-mediated immunity. Cell-mediated immunity is responsible for the control of pathogens such as viruses. At the same time Th2 lymphocytes, which stimulate humoral immunity through the secretion of the cytokines interleukin-4, interleukin-6 and interleukin-10, are increased in AIDS patients. Normally, these two cytokine subsets promote their own secretion and suppress the other cell line, resulting in a homeostasis between these two cell lines of the lymphocytes. In AIDS patients, there is a shift to type-1 suppression and type-2 dominance, thus destroying the equilibrium of the immune system. It is postulated that the Th2 cell lines are B-cells which are naturally more resistant to HIV infection.

Immunomodulation in HIV/AIDS: The Tygerberg/Stellenbosch University Experience

Authors: Bouic, P.J.D. Source: AIDS Bulletin, v. 6, #3, pp. 18-20, Sept. 1997 Published by the Medical Research Council of South Africa

This review article discusses both animal and human experiments performed in South Africa to determine the effect of plant sterols/sterolins on the disease progression of HIV. Two pilot studies were done on cats infected with the retrovirus FIV, which is considered the feline equivalent to HIV. In both studies the cats receiving the sterol/sterolin mixture maintained stable CD4 lymphocyte counts and suffered no deaths due to FIV, three years later. These positive results prompted the research group to conduct an open trial of 80 human patients over a 3 year period, with clinical monitoring every 3 months. The results for CD4 lymphocyte counts have remained stable over 27 months with no significant declines, similar to the results of the cat study. As well, the programmed cell death of the CD4 subset, which is responsible for the rapid loss of CD4 lymphocytes in typical HIV populations, actually declined slightly. The pro-inflammatory lymphokine, interleukin-6 has been implicated in the induction of HIV replication in infected cells. This study has shown a significant decrease in interleukin-6 levels in the sterol/sterolin treated group leading to a decrease in viral load levels. Although the sterols/sterolins have no anti-viral activity, this immunomodulatory activity on interleukin-6 levels leads indirectly to lower viral load levels. These preliminary findings suggest an important role for plant sterols/sterolins in the multi-stage treatment of HIV. Com-bined with potent plant antivirals, a non-drug AIDS treatment strategy that is highly effective may be possible.

The importance of sitosterol and sitosterolin in human and animal nutrition

Author: Karl H. Pegel, Department of Chemistry and Applied Chemistry, University of Natal, Durban, South Africa. Source: South African Journal of Science, v. 93, pp. 263-268, June 1997

Recent research indicates that the health-promoting benefits of a plant-based diet may be due to the presence of plant-derived cholesterol analogs known as sterols and sterolins. These compounds, which are structurally similar to cholesterol, are ubiquitous throughout the plant kingdom. Although absorbed at a rate 800 to 1,000 times less than cholesterol, they appear to have important immuno-modulatory and anti-inflammatory activities in human and animal physiology. Human research indicates plant sterols and sterolins have important anti-inflammatory, anti-ulcer, anti-diabetic, anti-cancer and T-cell proliferative activities. Medical uses already include the treatment of hyper-cholesterolemia, benign prostatic hypertrophy and rheumatoid arthritis. Plant sterols and sterolins are thought to be responsible for the health benefits of a variety of medicinal herbs including saw palmetto, pygeum, pumpkin seeds, devilÂ’s claw, milk thistle, ginkgo, Panax and Siberian ginseng. They have adaptogenic properties which make them an essential part of an optimal diet. Modern food processing and dietary choices have resulted in a daily intake less than the optimal 200-300 mg. Even some vegetarian diets appear to result in a deficient quantity of plant sterols and sterolins. Supplementation of the diet with plant sterols and sterolins provides important therapeutic as well as preventative health benefits.

Interleukins and the Immune System

Author: Anne O'Garra Source: Lancet, v. 1, #8644, pp. 943-946, 1989

The immune response has two ways of dealing with foreign pathogens. The B-lymphocytes synthesize specific antibodies called immunoglobulins. This is known as humoral immunity. The other system involves T-lymphocytes which regulate the synthesis of antibodies as well as direct killer cell activity and the inflammatory response of delayed type hypersensitivity. This system is known as cell-mediated immunity. The T-cells are further divided into helper lymphocytes (Th) and cytotoxic (Tc), also known as suppressor cells. When the T-cells encounter a foreign pathogen (antigen) they further secrete a number of communication molecules called lymphokines, cytokines, interleukins or interferons. These factors further elaborate and direct the immune response to a specific antigen. The whole process is a symphony of many co-factors which are orchestrated into a sophisticated immune response. The T-helper cells are directly involved in assisting B-cells as well as co-ordinating their own cell-specific defense. The T-helper cells are further divided into two distinct lines of defense. The Th1 cells promote the cell-mediated line of defense and inhibit the other line known as Th2 cells which regulate the humoral defense. The Th2 cell lines control the B-cells and inhibit the cell-mediated response of the Th1 lymphocytes. A careful balance between these two functions is thus achieved. When one line predominates, there is the opportunity for immune dysregulation to occur resulting in either a hyper-immune response causing an autoimmune disease or a hypo-immune response resulting in an uncontrollable infection such as AIDS or tuberculosis. The Th1 helper cells secrete lymphokines such as interleukin-2 and gamma interferon. Th2 helper cells secrete pro-inflammatory lymphokines such as interleukin-6, interleukin-4 and interleukin-10. Interleukin-1 appears to be released in response to a specific injury and acts as an inflammatory mediator. Interleukin may be over-expressed in diseases such as rheumatoid arthritis and osteoarthritis. Interleukin-1 deficiency is associated with metastatic tumors, nutritional deficiencies and certain autoimmune diseases. Interleukin-6 is associated with pro-inflammatory responses as well as mediating the proliferation and maturation of T-cells. High levels of interleukin-6 have been associated with a variety of autoimmune conditions such as rheumatoid arthritis, Sjogren's syndrome, multiple myelomas, and some cancers such as cervical and bladder. Interleukin-2 is a growth factor for T-cell maturation as well as an inducer of T-cell cytotoxicity and natural killer cell activity. Interleukin-2 deficiency would cripple the cell-mediated immune response and its stimulation would enhance the overall efficacy of the immune system. Immune dysregulation occurs when the two sides of the immune response become imbalanced. A greater appreciation of immunotherapies is achieved with a more detailed understanding of the complexity of the immune system.

A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia.

Author: Klippel K.F.; Hiltl D.M.; Schipp B. (German BPH-Phyto Study group.) Source: British Journal of Urology, v. 80(3):pp. 427-32, Sept. 1997

This randomized placebo-controlled study involved 177 patients with an enlarged prostate gland (benign prostatic hyperplasia). This study was designed to asses the safety and efficacy of using b-sitosterol in treating this condition. Over the 6 month duration of this study individuals received 130 mg of b-sitosterol daily. Parameters used to monitor the effectiveness of this novel treatment approach included post-void residual urinary flow rate (PVR), peak urinary flow rate (Qmax), and qualitative determinators provided by the international prostate symptom scores (IPSS) and changes in the quality of life index value. Statistically significant results over the placebo control were noted. Qmax values increased by 4.5 ml while improved PVR values were noted (decrease of 33.5 ml). Quality of life scores and IPSS values also showed a statistically significant improvement. These results indicate that b-sitosterol is in fact an effective treatment option for individuals with BPH.

A randomized placebo-controlled trial of the efficacy of beta-sitosteol and its glucoside as adjuvants in the treatment of pulmonary tuberculosis

Author: P.R. Donald,*J.H. Lamprecht, M. Freestone, C.F. Albrecht, P.J.D. Bouic, D. Kotze, **P.P. van Jaarsveld Source: International Journal of Tuberculosis and Lung Disease, v. 1 (5), pp. 518-522, July 1997

This is a double-blind study of 43 persons positively infected with pulmonary tuberculosis receiving conventional multi-antibiotic treatment to ascertain if the addition of a plant sterol/sterolin mixture could improve the clinical outcome. The study took place over 6 months and the patients were closely monitored with a variety of lab and radiographic tests. The group receiving the sterol/sterolin mixture showed a significant weight gain over the placebo group. As well, the treatment group showed a significant increase in lymphocytes and eosinophils. The increase in lymphocytes is consistent with previous experiments indicating a T-cell proliferative effect with the oral intake of phytosterols. The increase in eosinophils is difficult to explain, since no previous allergic response has been attributable to the ingestion of the phytosterols. However, other data indicate there may be a relationship between the rise of CD4 lymphocytes and eosinophils. Plant sterols/sterolins have been demonstrated elsewhere to selectively increase CD4 lymphocyte counts. Other lab parameters remained the same between the two groups including hemoglobin, hematocrit, neutrophil count, serum globulin, creatinine, and urea. This preliminary study indicates that plant sterols and sterolins may have a positive role to play in the complementary treatment of immunocompromised patients.

Other lab parameters remained the same between the two groups including hemoglobin, hematocrit, neutrophil count, serum globulin, creatinine, and urea. This preliminary study indicates that the plant sterols and sterolins may have a positive role to play in the complementary treatment of immuno-compromised patients.

Randomized, placebo-controlled, double-blind clinical trial of B-sitosterol in patients with benign prostatic hyperplasia

Author: R.R. Berges, J. Windeler, H.J. Trampisch, T.H. Senge and the b-sitosterol study group* Source: Lancet v. 345, no. 8964, pp. 1529-32, June 1995

This is a randomized, double-blind, placebo-controlled, multi-center study of 200 men with BPH (benign prostatic hyperplasia) treated with the phytosterol, B-sitosterol. Two hundred men were selected and followed for 6 months using a variety of lab tests, and subjective and objective symptom indicators for BPH. Half the group received the active treatment, 20 mg B-sitosterol three times daily and the other half received the placebo. The results indicate that the group treated with B-sitosterol improved in both subjective symptoms of BPH and the objective measurement of improved urine flow. These results occurred independent of a reduction in actual prostate size. Only minor side effects were observed with the phytosterol treatment group compared to the more toxic side effects associated with the 5-alpha-reductase inhibitor drugs such as finasteride. No mechanism for the effects of B-sitosterol on the prostate has been elucidated as yet. This study indicates that traditional herbal treatment of BPH with saw palmetto, Pygeum africanus and pumpkin seeds may be attributable to the phytosterol content of these herbs. A German herbal preparation sold for the last 20 years under the trade name Harzol for the treatment of BPH contains a mixture of phytosterols including B-sitosterol.

Sterol content of foods of plant origin.

Author: Weihrauch J.L., Gardner J.M. Source: Journal of the American Dietetic Association, v. 73, pp.39-47, July 1978

Available data on phytosterols from the world's literature have been compiled and summarized. There still exists a paucity of data on the quantities of plant sterols in many foods. More extensive data are available on the relative sterol compo-sitions. Our compilation shows that plant oils are excellent sources of phytosterols. Nuts and seeds contain moderate levels, and fruits and vegetables generally contain the lowest concentrations of plant sterols. Analysis of the minor sterols, namely, the delta5- and delta7-phytosterols, have become available only recently.

Sterols/Sterolins, the natural, nontoxic immunomodulators and their role in the control of rheumatoid arthritis

Author: P.J.D. Bouic Source: Published in the newsletter of the Arthritis Trust of America, Summer 1998

A natural and non-toxic treatment of rheumatoid arthritis (RA) and other autoimmune diseases has been developed by Professor Bouic and his team from South Africa using the immunomodulatory properties of a group of plant fats known as sterols and sterolins. Research into RA has demonstrated it to be a disease characterized by dysregulation of the immune system in response to an initial infection or trauma. Overactivity of the immune system's B-cells which secrete antibodies attack and destroy the synovial tissues located in the joint. This overactivity is mediated by a group of T-helper cells known as Th2 CD4 cells which release pro-inflammatory communication molecules known as cytokines. These inflammatory cytokines are interleukin-1 (IL1), interleukin-6 (IL6) and Tumor Necrosis Factor alpha (TNF-a) which have been found in extremely high concentrations in the joints of patients with rheumatoid arthritis. As well, it is thought that another group of T-helper cells known as Th1 which normally control the immune and inflammatory response are deficient or damaged in patients with rheumatoid arthritis. Existing treatments employ highly toxic drugs to suppress the entire immune response of the body or to palliate pain and the inflammatory process without correcting the underlying immune dysfunction. Recent research into the plant fats, sterols and sterolins, has demonstrated these substances to effectively correct the underlying immune dysfunction characteristic to RA and the autoimmune diseases. A sterol/sterolin combination has been experimentally demonstrated to reduce the secretion of the pro-inflammatory cytokines controlled by the Th2 helper cells and to increase the number of Th1 cells which regulate the secretion of antibodies from the B cells. This selective activation and inhibition of the immune system results is an effective control of the dysfunctional autoimmune response. Sterols and sterolins are a normal part of a plant-based diet and may be missing in the modern diet which is typically high in processed food and animal fat and protein. A supplement containing extracts of sterols and sterolins may correct a dietary deficiency which has produced a number of autoimmune diseases thought to be incurable.

Nothing within these pages should be construed as medical advice. All information on these pages is intended for educational use only. Nothing herein is intended to diagnose, treat or cure any specific disease. Please consult your health care provider if you have a serious condition.


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