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Antioxidants, Sterols and Inflammation, a Natural Approach

RESEARCH REVIEW
Alan Fergusson. President, Celt Corporation.

Presentation to the Functional Medicine Forum, Seattle, Wa., U.S.A. March, 2007

Introduction:

Allergies, cardiovascular diseases, fibromyalgia, eczema, asthma and some of the other auto immune conditions are all diseases involving inflammation, and are frequently treated with pharmaceuticals.

This paper outlines the potential for the use of natural supplements to combat some of these modern day conditions.

This information is provided for educational purposes only and should not be construed as medical advice. Any reader requiring medical advice is strongly advised to consult a licensed healthcare professional. Any products mentioned are not intended to diagnose, treat, cure, mitigate or prevent any disease. These statements have not been evaluated by Health Canada or the Food and Drug Administration.

1. ANTIOXIDANTS

WHY “ANTI” OXIDANT

Most of you will have heard of antioxidants, but how many of you have wondered why it is necessary to have “anti”oxidants, when oxygen is essential to life?

The answer lies in the atomic structure of oxygen. As most of you know an atom consists of a nucleus and a series of outside rings, or shells, containing electrons. These rings are particularly stable when they contain specific numbers of electrons, 2, 8, 18, 32 to be precise. Oxygen only has 6 electrons in its outside ring, when it really needs 8 for stability.

So what does it do? It grabs two extra electrons from where ever it can. This leaves an atom or molecule one or two electrons short – it becomes a “free radical”; then it goes on the hunt to steal electrons from another atom or molecule, and so the process goes on and becomes a chain reaction – creating more “free radicals” in the process.

SOURCE and EFFECTS of FREE RADICALS

These free radicals can also be produced by the body’s own metabolic process; sometimes the immune system creates them to neutralize viruses and bacteria. However they can also be spawned by environmental factors such as pollution of various sorts, and particularly radiation. If you think you are safe from radiation in this concrete building, then just check your cell, phone! You are also being bombarded by X-rays from your computer.

The problems with free radicals is that they can damage cell membranes through the oxidation of unsaturated fatty acids, and can also be perceived as toxins by the immune system, which can lead to shift towards a Th-2 allergic type response, and all the consequences of an overactive immune system. (1 ,2, 3,)

OXIDATIVE STRESS and INFLAMMATION

What is not so well known is that oxidative stress can trigger the production of Il-6, a pro-inflammatory cytokine (4). Among the factors that normally down regulate this cytokine are estrogen and testosterone, which decline after menopause.

Not surprisingly levels of Il-6 have been fo1. ANTIOXIDANTSund to be elevated in older populations. This age associated rise of Il-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis and Alzheimer’s disease (5).

Epidemiological studies by the National Institute on Aging have linked elevated Il-6 levels with a high risk of death from cardiovascular disease, and with a high risk of mortality in a population based sample of “healthy” older persons. (6, 7) Elevated levels of Il-6 have also been linked to disability onset in older persons, possibly due to a direct effect of Il-6 on muscle atrophy, and/or to the pathophysiologic role played by Il-6 in specific diseases. (8, 9).

The bottom line to all this, and one of the major points that I want to make today, is that Il-6 can play a very important role in disease progression, particularly in members of the older population.

PAIN and INFLAMMATION

Well, pain is often linked to inflammation; inflammation is linked to Il-6; Il-6 is linked to oxidative stress (4), so is it possible to alleviate pain through reduction in oxidative stress? – most of you were probably ahead of me at this point!!

Interestingly, in Pubmed there is documented research of cases of pain reduction through the use of antioxidant therapy. These cases involve chronic pancreatitis, prostatitis, asthma, and diabetic neuropathy, - all these involve inflammation and Il-6. (10, 11, 12, 13, 14,).

We are going to come back to Il-6 again later, but first, let’s take a look at:

2. STEROLS

WHAT ARE THEY, WHERE DO THEY COME FROM

Plant sterols are often referred to as “plant fats”, when in fact chemically they are steroidal alcohols – I guess “steroidal alcohols” does not look too good on the label of a natural health supplement! The name sounds intimidating but if I tell you that they belong to the same chemical class as cholesterol and vitamin D they may sound a little more familiar. They are found in the membranes of most vegetables, fruit and nuts.

They are essential to the body, but like vitamin C, the body cannot synthesize them, they have to be ingested. There are number of sterols in the phytosterol family. The most commonly known are beta-sitosterol, campasterol, brassica-sterol, stigmasterol, and so on. The most important of this class is beta-sitosterol.

For many years, when our diet was mainly plants and vegetables, they were a natural part of our diet. However due to the modern processing of food modern diets tend to be deficient in sterols. Furthermore the absorption of the sterols that we do get in our diet is inhibited by the fact that our modern diets generally contain cholesterol, which inhibits the absorption of beta-sitosterol. The dramatic increase in autoimmune and immune related diseases maybe partly related to the absence of plant sterols in our modern diet, as these nutrients help to maintain a balanced immune system.

The main commercial sources of beta-sitosterol are soy (41), sugar cane, canola, and “the pristine forests”. Allusion to the “pristine forests” has great marketing potential, but this source is actually the effluent from pulp mills, - not a source that I would choose for my family! (48). So in looking at sterols for therapeutic use I would be looking at beta-sitosterol from soy, sugar cane or canola.

The molecular structure of sterols, and particularly beta-sitosterol, is similar to that of other organic compounds produced by the body, in particular cholesterol, vitamin D, and testosterone to name a few – only the side chain varies.

ESTERS and STANOLS

You may also hear the terms “esters” and “stanols” associated with sterols. Sterol esters are products of sterols and organic acids, where the organic radical replaces the hydroxyl group.

Stanols are hydrogenated sterols, and not familiar to the body. Like hydrogenated oils, we do not know the long term effects

STEROLS in NUTRITION

Sterols are probably best known for their immune modulating properties.

The body’s response to environmental toxins and radiation is a shift to the Th-2 activity, with a consequent loss in Th-1 activity. Sterols can help to modulate this response (19). This Th-1/Th-2 balance is critical in the development of allergies, eczema and a series of other autoimmune conditions (20).

Sterols are also reasonably well known for their ability to block the absorption of dietary cholesterol. It is important here to be using “free sterols”, as opposed to esters whose effectiveness declines over a couple of months (18).

Stanols which are hydrogenated sterols can also block the absorption of cholesterol. However they are not familiar to the body and we do not know their long term effects. Perhaps more importantly they also block the absorption of all sterols, including the beta-sitosterol that is essential to the body.

The advantage of sterols over statins is that while statins block cholesterol production from the liver, (and also inhibit the production of CoQ 10), the sterols inhibit the absorption of the dietary cholesterol and leave the liver to control the body’s cholesterol levels naturally (21)

Sterols can also be very helpful to older men suffering from BPH, (22). Not only is this problem a social inconvenience, frequent night time visits to the bath room can result in sleep deprivation, which in turn can have an adverse impact on the immune system, and also result in fatigue and depression.

3. STEROLS and INFLAMMATION

Some exciting research is now showing that beta-sitosterol can inhibit the production of the Il-6 that we talked about previously as being a pro-inflammatory cytokine produced by oxidative stress.(23, 24).

You may recall that epidemiological studies by the National Institute on Ageing have linked elevated levels of IL-6 with increased risk of death from cardiovascular disease (6,7).

Il-6 has also been linked with disease progression in the older population in a number of diseases, rheumatoid arthritis, multiple myeloma, osteoporosis, Alzheimer’s, CVD and mortality in general. (5, 6, 7, 8, 9, 25, 26, 27).

So Il-6 is certainly a cytokine whose production you would want to minimize.

In addition to minimizing Il-6, Sterols can also stimulate production of an anti-inflammatory cytokine Il-10.

Il-10 has been associated with inhibition of inflammation (23, 28, 29, 30), and what is perhaps particularly important, the inhibition of atherosclerotic lesions and blocking atherosclerotic events (31, 32).

Il-10 has been referred to as an “Immunologic Scalpel” for atherosclerosis, and is under investigation, and in a few cases is at the stage of clinical trials, for therapy for a variety of chronic diseases. These include rheumatoid arthritis, inflammatory bowel disease, psoriasis, and multiple sclerosis (33, 42).

So, what are the potential applications of:

COMBINED ANTIOXIDANT / STEROL THERAPY

Generally speaking this antioxidant/sterol combination can be very helpful in alleviating the symptoms of most autoimmune disease such as eczema, psoriasis, rheumatoid arthritis, asthma, etc.

Probably two of the most prevalent conditions confronting those involved in health care are allergies and fibromyalgia. They both involve oxidative stress and inflammation.

ALLERGIES

A double blind, randomized, placebo controlled trial at the University of Guelph has shown that a patented combination of antioxidants and sterols containing beta-sitosterol, (Immuno-Care), can reduce Il-6 by an average of 35%, and the basophils that release the histamine by an average of 25%. Not surprisingly this antioxidant/ sterol combination has been found in many cases to be effective in alleviating seasonal allergies.

FIBROMYALGIA

Research by Bagis, Tamer at the University Medical School at Mersin in Turkey (34), and by Fulle, Mecocci at the University of Perugia in Italy (35), found associations between oxidative stress and fibromyalgia, and between oxidative stress and chronic fatigue.

As in many cases fibromyalgia also involves pain and inflammation, it is not surprisingly we are hearing of more and more cases where the symptoms of fibromyalgia and chronic fatigue are being alleviated with a combination of antioxidants and sterols.

Another area of major concern in the healthcare field is the cardiovascular system..

CHOLESTEROL / CARDIOVASCULAR SUPPORT

It is well known that “free sterols” can inhibit the absorption of cholesterol. It is important here to focus on the “free sterols” as opposed to sterol esters which only work for a limited time, or stanols that not only inhibit cholesterol absorption, they also inhibit the absorption of the beta-sitosterol that the body needs and cannot make for itself. So it is important to be looking at “free sterols” for cholesterol reduction.

Not only can “free sterols” inhibit the absorption of cholesterol, they can also reduce the levels of the inflammatory cytokine Il-6, which has been associated with CVD and hypertension.

Using Immuno-Care in this natural way of providing cardiac support can have many advantages over statins, not least is the fact that you do not interfere with the function of the liver and it’s production of CoQ-10.

BPH

Immuno-Care is the most effective product on the market for reducing urinary retention, and consequently night time visits to the bathroom that can be a major interruption to a good night’s sleep.

The antioxidant component can also help to prevent the development of prostatitis. Urologists in Germany have been using plant sterols to treat enlarged prostates for over twenty years. As side effects, you will also find that you will have lower cholesterol levels, and get fewer flu’s and colds!

WHY IMMUNO-CARE ?

There are several reasons for using Immuno-Care.

First, it is very important to reduce the oxidative stress within the body. Immuno-Care contains Enzogenol, a very powerful broad spectrum antioxidant derived from the bark of selected pine trees, which contains over 2,000 different flavonoids - probably the most comprehensive complex of natural antioxidants yet discovered.

The patented extraction process, developed by the University of Canterbury in New Zealand, uses only pure water, which ensures that significant groups of antioxidants are harvested, and not lost as in the conventional solvent based process.

The inclusion of a proprietary blend of amino acids, enzymes and peptides designed to facilitate the absorption and retention of the sterols and antioxidants.

As far as we know no other manufacturer of sterol products has paid attention to the issue of absorption and retention of the sterols. And this is important as sterols normally are difficult to absorb and only stay in the body for a short period of time.

As far as we know, Immuno-Care contains the only encapsulated sterols that are enteric coated, so that they pass through the stomach acids and dissolve in the alkaline environment of the small intestine. This ensures that the sterols and antioxidants pass through the stomach without being destroyed and also facilitates the absorption and retention of both the sterols and the antioxidants. This is really a technical achievement. Immuno-Care™ enteric coats two piece vegetable capsules containing sterols to ensure the absorption.

References

  1. Free Radicals, Antioxidants and Nutrition. Fang, Yang et al. Dept. Biochem. and Molecular Biol., Beijing Inst. of Radiation Beijing, China. Nutrition 2002, Oct. 18(10)
  2. Antioxidants, Oxidative Damage and Oxygen Deprivation Stress. Blokhina, Vrolainen et al. Dept Bioscience, Helsinki University, Helsinki, Finland. Annals of Botany 2003;91 Spec No 179-94
  3. Antioxidants to Slow Aging, Facts and Perspectives. Bonnrfoy, Drai el. Service de Medicine Geriatrique, Lyon. France. Presse Medicale, (France), 2002 Jul 31(25):1174-84
  4. Serum Antioxidants, Inflammation, and Total Mortality in Older Women. Walston, Xue et al. School of Medicine, John Hopkins University. U.S.A., Am. Jnl. Epidem 2006, 163(1)18-26.
  5. Age Associated Interleukin-6 Expression and Late Life Diseases. Ershler, Keller. Inst. For Advanced Studies in Aging and Geriatric Med, Washington, DC., U.S.A. Annual Rev of Medicine, 2000;51:245-70.
  6. Cardiovascular Disease, Interleukin-6 and Risk of Mortality in Older Women. Volpato, Guralnik et al. National Institute on Aging, Bethesda, U.S.A. Circulation 2001 Feb 103(7)
  7. Associations of Elevated Interleukin-6 and C-Reactive Protein levels with Mortality in the Elderly. Harris, Ferrucci et al. Nat. Inst. On Aging, Bethesda. U.S.A., Am. Jnl. Med. 1999 May;106(5):506-12.
  8. Serum Il-6 Level and Development of Disability in Older Persons. Ferrucci, Harris et al. INRCA, Florence, Italy. Jnl. Am Geriatric Soc. 1999 Jun:47(6):639-46.
  9. Dietary Carotenoids and Risk of Coronary Artery Disease in Women. Osganian, Meir et al. Harvard School of Public Health. Am. Jnl. CL. Nutr. 2003 June. Vol 77(6) 1390-99.
  10. Combined Antioxidant Therapy Reduces Pain in Chronic Pancreatitis. Kirk, White, et al. Royal Victoria Hosp, Belfast, U.K., Jnl. Gastrointest. Surg. 2006 Apr.:10(4):499-503.
  11. Use of Antioxidants in Chronic Pancreatitis. Castano, Paz et al. Valdecilla University Hosp. Spain. Revista Espanola Enfermedades, Digestivas 2000 June;92(6):375-85.
  12. Quercetin In Men with Category 3 Prostatitis. Shoskes, Zeitlin et al. Harbor-UCLA Med Centre, UCLA., Ca., U.S.A., Urology, Dec 1999, Vol 54(6) 960-963
  13. ALA Improves Symptoms of Diabetic Neuropathy. Dyck, Low, Litchy. Mayo Clinic. Diabetes Care, March 2003
  14. Pycnogenol in the Management of Asthma. Hosseini, Pishnamazi et al. School of Medicine, University of Arizona. Med. Food 2001 Winter 4(4):210-209
  15. Plasma C-Reactive Protein Concentrations: Influence of Antioxidant Supplementation. Block, Jensen, et al. Dept. Nutritional Sc. Univ. Cal. (Berkeley). U.A.A. Jnl. AM. Col Nutr vol 23, (2) 141-7.
  16. Importance of Sitosterol in Human and Animal Nutrition. Pegel. University of Natal, S. African Jnl. Sc. S.A. 1997. vol 93 , 263-7.
  17. The Garden of Eden – Plant Based Diets. Jenkins, Kendall et al. St Michael’s Hospital, Toronto. Comp. Biochem. Physiol A Integr Pysiol. 2003, Sep;136
  18. Comparison of Plant Sterol and Stanol Esters on Lipid Metabolism. O”Neil, Brynes et al. Faculty of Medicine, Imperial College London.U.K., Nutr. Metab. Cardiovasc. Dis., 2004 June 14(3):133-42
  19. Flow Cytometric Analysis of the Th1-Th2 Balance. Breytenbach, Clark et al. Dept Medical Biol. Univ Stellenbosch, Capetown, S.A., Cell Biol Intl.2001;25(1):43-9.
  20. Immune Response in Healthy and Allergic Individuals Characterized by Balance between Allergen Specific Th1 and Th2 cells. Akdis, Verhagen et al. Swiss Institute of Allergy and Asthma Research. Davos, Switzerland. Jnl. Exp Med. 2004 June 199(11):1567-75
  21. Efficacy and Safety of Plant Stanols and Sterols in the Management of Blood Cholesterol Levels. Katan, Grundy et al. Mayo Clinic Proceedings. 2003:78:965-78
  22. A Multicentric, Placebo-controlled, Double-blind, Trial of Beta-Sitosterol for BPH. Klippel, Hiltl et al., Dept Urol., Academic Hospital, Germany. Br. Jnl. Urol 1997 Sep;80(3):427-32
  23. Antiatherogenic Effects of Plant Sterols Associated with Inhibition of Proinflamatory Cytokine Production. Nashed, Yeganeh et al. St Boniface Hospital and the University of Manitoba, Winnipeg, Man.,Canada. Am. Soc. Nutr. Sc, Jnl. Nutr 2005 Oct 135:2438-2444
  24. Pilot Study on the Supplement Immuno-Care. Laidlaw. Human Nutraceutical Research Unit. University of Guelph, Ontario, Canada.
  25. Interleukin-6 and Chronic Inflammation. Gabay, C. Div Rheum., University Hospital, Geneva. Switzerland. Arthritis Res. Ther 2006;8 Supp2:S 3.
  26. Associations of elevated Il-6 and C-reactive Protein levels with Mortality in the Elderly. Harris, Ferrucci et al. National Institute on Aging, Bethesda. U.S.A. Am.J.Med 1999 May;106(5):506-12.
  27. Inflammation, Obesity, Stress and Coronary Heart Disease: Is Il-6 the Link? Yudkin, Kumari et al. University College Medical School, London. U.K.,Atherosclerosis 2000 Feb;148(2):209-14
  28. Aging, Longevity, Inflammation and Cancer. Caruso, Lio et al. Dept. Immunol., Univ. Palermo, Italy. Ann. N. Y. Acad. Sc. 2004, vol.1028
  29. Immunoregulatory Role of Interleukin 10 in Inflammatory Bowel Disease. Schreiber, Heinig et al. Dept. Med.. Univ. Hamburg, Germany. Gasteroenterology 1995 May;108(5):1434-44
  30. Essential Role of Il-10 in the Function of T-cells Inhibiting Intestinal Inflammation. Asseman, Mauze et al. Radcliffe Hosp. Univ. Oxford, U.K., and DNAX Res. Inst. Mol. Biol., Palo Alto, Ca. U.S.A. Jnl. Exp. Med. Oct 1999. Vol 190(7)
  31. Protective Role of Il-10 in Atherosclerosis. Mallet, Besnard et al. Inst. Nat. Sante Res. Med, Paris, France. Circulation Res.1999 Oct. 15;85(8) .
  32. Il-10 Blocks Atherosclerotic Events in Vitro and In Vivo. Oslund, Hendrick et al. UCLA Mol. Biol. Inst. Los Angeles, Ca. U.S.A. Arteriosclerosis, Thrombosis, and Vascular Biol. 1999(19)
  33. Il-10: An “Immunologic Scalpel” for Arterosclosis. Terkeltaub R.A., San Diego VA Med Centre. Arteriosclerosis, Thrombosis and Vascular Biology 1999 vol 19 (12).
  34. Free Radicals and Antioxidants in Primary Fibromyalgia. Bagis, Tamer et al. Univ. Med .Schl., Mersin, Turkey. Rheumatology International. 2005 Vol 25 (3).
  35. Specific Oxidative Alterations in Vastus Lateralis Muscle in CFS Patients. Fulle, Mecocci et al., Univ Perugia, Italy. Free Radic. Biol. 2000Dec. 15; 29 (12):1252-9.
  36. Reactive Oxygen Intermediates Stimulate Il-6 Production in Human Bronchial Epithelial Cells. Yoshida, Maruyama et al., Toyama Medical Univ., Japan. Am. Jnl. Physiol. Lung Cell. Physiol. June 1999, 276(6).
  37. Ultraviolet Light Induces Increased Circulating Il-6 in Humans. Urbanski, Schwarz et al. Univ of Vienna and Boltzmann Inst., Vienna, Austria. Jnl. Invest. Derm.,1990 vol 94, 808-811.
  38. Il-10 Inhibits Vascular Smooth Muscle Cell Activation in Vitro and in Vivo. Mazighi, Pelle et al., Inst. Nat Health and Med. Res. Central University Hosp. Paris, France. A. J. Physiol. Heart Circ Physiol April 2004, 287;H866-71.
  39. Il-10 Required for Protection Against Atherosclerosis. Potteaux, Esposito, et al.INSERM, Hospital Lariboisiere,Paris, France. Arth. Throm. Vasc Biol. 2004:24:1474
  40. Il-10: An Update on it’s Relevance to Cardiovascular Risk. Girnt, Kohler. Dept Med., Univ. Saarland, Germany. Nephrology Dialysis Transplantation 2003, vol 18 (10), 1976-79.
  41. The Evidence for Soybean Products as Cancer Preventative Agents. Kennedy A.R., Dept Oncol., Univ. Penn. Med. Sch. J. Nutr 1996 Feb;126(2).
  42. Treatment of Psoriasis with Il-10. Reich, Bruck et al. Dept. Derm. Gottingen and Tubingen Univs. Germany. Jnl. Investig. Derm. 1998 Vol 3(6).
  43. Oxidative Stress in Allergic Respiratory Diseases. Russell, Bowler, et al. Nat. Jewish Med. Centre, Denver. Jnl. Allergy Clin. Immunol. 2002. Vol. 110(3).
  44. Oxidative Stress Generated by Intrinsic Pollen… Boldogh, Bacsi, et al. Univ Texas. Jnl. Allergy Immunol. 2004. vol. 113(2)Sup 1.
  45. Oxidative Stress in Allergic and Inflammatory Skin Diseases. Okayama Y. Res. Centre Allergy and Immunology. Yokohama, Japan. Current Drug Targets – Inflammation and Allergy, 2005 vol. 4(4).
  46. Ultrafine Particulate Pollutants Induce Oxidative Stress and Mitochondrial Damage. Li, Sioutas, et al. Dept Med. UCLA., Los Angeles, Ca. Enviro. Health Perspectives 2003 April; 111(4).
  47. Reduced Calorie Orange Juice Beverage with Plant Sterols Lowers C-reactive Protein. Devaraj, Autret et al. Laboratory for Atherosclerosis and Metabolic Res. UCLA at Davis, Ca. Am.J. Clin.Nutr. 2006 Oct;84(4).
  48. Technologies for Reducing Dioxin in the Manufacture of Bleached Wood Pulp. U.S. Congress, Office of Technology Assessment. OTA-BP-O-54 (Washington, DC: U.S. Government Printing Office, May 1989. Library of Congress Cat 89-600719.
  49. “Peace, Love and Healing”. Bernie Siegel, M.D., Harper and Row. ISBN 0-06-091705-9. Lib. Congr. 89-82587.