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Message: Oxford Professor Weighs-in on Yeast eta Glucan and Avian Flu
Bird ‘Flu and Beta Glucans
by Paul Clayton, PhD *
The next global ‘flu pandemic is coming. By the time this article is published it may already have started. Klaus Stohr of the WHO Global Influenza Programme recently stated: ‘There will be another pandemic. In the best case we expect billions to fall ill, with 2 to 7 million deaths – but it could be far worse.’ Here in the UK, our very own Department of Health predicts as many as 750,000 deaths. Why are the experts so pessimistic?
Introduction
History shows that ‘flu pandemics occur every 30 years or so. After this time the genetic make-up of a ‘flu virus has changed so much that immunity built up from previous strains becomes irrelevant, so that herd immunity, our main defence against pandemics, has become negligible.
There were three pandemics in the 20th century and all spread worldwide within a year of being detected. The Spanish ‘flu in 1918-19 killed up to 50 million people. In the 1950s the Asian ‘flu pandemic killed a mere million and in 1968 Hong Kong ‘flu killed another million or so. That was 37 years ago – so we’re due for the next one. The prime candidate is the bird ‘flu now gathering momentum in Asia and which has already shown human-to-human transmission.
Antibiotics are of no use in treating viral infections and the right vaccines to protect us against the new strain of bird ‘flu won’t be ready until at least six months after the epidemic has started, which will be too late for many. Our benevolent and all-wise government has decided to purchase anti-viral treatments for 14 million Brits – about one in four of the population. That decision was based on two assumptions: first, that the emergency could be managed and, secondly, that the anti-viral drugs (eg. amantadine, Tamiflu) will be reasonably effective.
Both of these assumptions are highly questionable. Our ability to deal with the fall-out of a contagious and highly lethal viral epidemic is, realistically, inadequate. And the efficacy of the anti-virals (which was never very high) is being seriously undermined by Chinese Government-backed schemes to give the anti-viral drug amantadine to infected flocks of poultry in China. Nothing is more likely to breed new drug-resistant viruses. The WHO has asked for urgent ‘clarification.’
Let us assume, however, that the anti-viral drugs are still at least partially effective when the time comes and the emergency plans will actually work. One in four people deemed sufficiently important (army, police, medical personnel and the political classes) will be protected. What should the rest of us, the expendable folk, do?
Boosting your immune system
The best defence against viral infection is to prepare your innate immune system, which is the body’s first line of defence against invasion by bacteria and viruses. Unlike the acquired (or adaptive) immune system, the innate immune system does not recognise every possible antigen. Instead, it is geared up to recognise and react to a small number of highly conserved molecules which are present in the cell walls of many pathogens, including lipopolysaccharide [LPS] (gram negative bacteria), lipoteichoic acids (gram positive bacteria), and 1-3, 1-6 beta glucans (bacteria and fungi).
Once stimulated, the innate immune response mounts both cellular and humoral responses.
These involve:
Phagocytic cells. These include macrophages and related cell species such as Langerhans cells in the epidermis, Kupffer cells in the liver, microglia in the brain and osteoclasts in bone.
Cells that produce inflammatory mediators (mast cells, eosinophils and basophils).
Natural Killer cells.
Mediator molecules such as complement proteins, acute phase proteins and cytokines. These include tumour necrosis factor (TNF), interleukins 1 and 6, hydrogen peroxide and gamma interferon, all of which fight against invading pathogens.
Of all the natural compounds known to stimulate the innate immune system, the best documented and most effective are the 1-3, 1-6 beta glucans, generally derived from brewer’s yeast1,2. These molecules activate the innate immune system very strongly indeed; in humans and other mammals and in birds, fish and even crustacea3,4,5,6. Macrophages have receptors that specifically recognise 1-3, 1-6 beta glucans7 because they occur in the cell walls of many bacteria and fungi. This means that when you ingest beta glucans your innate immune system thinks, not unreasonably, that an enemy has arrived and it rises to the challenge. This important first line of defence is now fully activated and several well-conducted research papers have shown that resistance to infection is greatly enhanced1,8,9.
The beta glucans’ ability to activate macrophages has been extensively tested10-16 and has been shown to protect animals such as mice against otherwise fatal infections15,17-26. Trials have shown the same substantial protective effects in human infections also27-30.
Looking at the references above shows that most of the key studies had already been completed by the mid-1990s; but the work was not thought to be commercial and was not developed for clinical use. Antibiotics still ruled the roost and were highly profitable for the drug companies, while brewer’s yeast extracts were cheap and belonged to everybody. This meant that none of the drug companies were interested in investing in them.
The US Army, however, was taking careful note. Starting in the late 1980s, it ran an exhaustive test programme to measure the immuno-protective effects of beta glucans and over 100 other immuno-stimulants, and as recently as 2004 reported that the beta glucans were the most effective of them all. Not only did they protect against infection with bacteria, viruses and fungi, they also conferred protection against radiation injury31,32.
Given that soldiers may at any time face an unpredictable range of biological weapons and even, in the worst case, radiation, the US Army began to stock-pile beta glucans. To this day Washington keeps significant amounts of beta glucans in readiness, to be issued as and when circumstances dictate. (To put this in context, all cases of supposed international ‘bacterial warfare’ reported in the US to date - such as the notorious ‘anthrax by post’ episode – have since been identified as being internal affairs; in the case of a genuine bacterial warfare incident, US troops are likely to be given beta glucans.)
I personally think that these valuable compounds are too good to be left to just the armed forces. As bird ‘flu continues to advance, I have put up a couple of kilos of purified beta glucans on the top kitchen shelf. When the time comes I will give them to my children, at a dose of 500 mg of beta glucans per day, armed with the knowledge that in trials with pigs, beta glucans reduce the harm done to the lungs after infection with swine ‘flu virus and reduced replication of the virus itself33. As pigs and people have a good deal in common (metabolically and physiologically speaking), the pig model is very relevant to our own situation. When one looks at the UK Government’s ‘flu management strategy, George Orwell’s porcine metaphors seem more appropriate than ever.
Notes:
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1. Kernodle DS, Gates H, Kaiser AB. Prophylactic anti-infective activity of poly-(1-6)-beta-D-glucapyranosyl-(1-3)-beta-D-glucapyranose glucan in a guinea pig model of staphylococcal wound infection. Antimicrob Agents & Chemother 1998;42:545-9.
2. Wakshull E, Brunke-Reese D, Lindermuth J, Fisette L, Nathans RS, Crowley JJ, Tufts JC, Zimmerman J, Mackin W, Adams DS. PGG-glucan, a soluble beta-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-kappa B-like factor in human PMN: evidence for a glycosphingolipid beta-(1,3)-glucan receptor. Immunopharmacology. 1999 Feb;41(2):89-107.
3. Mansell PWA, Ichinose I-I, Reed RJ, Krements ET, McNamee RB, Di Luzio NR: Macrophage-mediated destruction of human malignant cells in vivo. J Nat Cancer Inst 1975;54:571-80.
4. Hahn MG, Albersheim P. Host-pathogen interactions. XIV. Isolation and partial characterization of an elicitor from yeast extract. Plant Physiol 1978;62:107.
5. Robertsen B, Engstad RE, Jorgensen JB. Beta-glucans as immunostimulants in fish. Immune Responses l994, V. 1, Fair Haven, NJ, USA.
6. Song Y-L, Hsieh Y-T. Immunostimulation of tiger shrimp haemocytes for generation of microbicidal substances: analysis of reactive oxygen species. Developmental and Comparative Immunology, 1994;l(3):201-9.
7. Czop JK, Austen KF. A b-glucan inhibitable receptor on human monocytes: its identity with the phagocytic receptor for particulate activators of the alternative complement pathway. J Immunol 1985;134:2588-93.
8. Onderdonk AB, Cisneros RL, Hinkson P, Ostroff G. Anti-infective effect of poly-beta-1,6-glucotriosyl-beta 1,3glucapyranose glucan in vivo. Infection & Immunity 1992;60:1642-7.
9. Vetvicka V, Terayama K, Mandeville R, Brousseau P, Kournikakis B, Ostroff G. Pilot study: Orally-administered east beta1,3-glucan prophylactically protects against anthrax infection and cancer in mice. J Am Nutraceutical Assoc 2002;5:1-5.
10. Rasmussen LT, Fandrem Jr. and Seljelid R. Dynamics of blood components and peritoneal fluid during treatment of murine E. coli sepsis with beta-1, 3-D-polyglucose derivatives. Scand. J Immunol 1985;63:73-80.
11. Rasmussen LT, Seljelid R. Production of prostaglandin E2 and interleukin 1 by mouse peritoneal macrophages stimulated with beta-1, 3-D-glucan derivatized plastic beads. Scand J Immunol 1987;26(6):731-6.
12. Rasmussen LT, Seljelid R. The modulatory effect of lipoproteins on the release of interleukin 1 by human peritoneal macrophages stimulated with beta 1 -3D-polyglucose derivatives. Scand J Immunol 1989;29:477-84.
13. Rasmussen LT, Seljelid R, Dynamics of blood components and peritoneal fluid during treatment of murine E. coli sepsis with beta-1, 3-D-polyglucose derivatives. II. Interleukin 1, tumour necrosis factor, prostaglandin E2 and leukotriene B4. Scand J Immunol 1990;32(4):333-40.
14. Rasmussen LT, Seljelid R. Dynamics of blood components and peritoneal fluid during treatment of murine E. coli sepsis with beta-1, 3-D-polyglucose derivatives. I: Cells. Scand J Immunol 1990;32(4):321-31.
15. Rasmussen LT and Seljelid, R. Novel immunomodulators with pronounced in vitro effects caused by stimulation of cytokine release, J Cell Biochem 1991;46:60-8. Quote: ‘Beta-1, 3-D-polyglucose derivatives protect mice against otherwise lethal bacterial infections.’
16. Rasmussen LT, Konopski Z, Oian P, Seljelid R. Killing of Escherichia coli by mononuclear phagocytes and neutrophils stimulated in vitro with beta-1, 3-D-polyglucose derivatives. Microbiol Immunol 1992;36(11):1173-88.
17. Williams DL et al. Protective effect of glucan in experimentally induced candidiasis. J Reticuloendothel Soc 1978;23:479-90.
18. Williams DL, Diluzio NR. Glucan induced modification of experimental Staphylococcus aureus infection in normal, leukemic and immunosuppressed mice. Adv Exp Med Biol 1979;121(A):291-306.
19. Williams DL, Diluzio NR. Glucan-induced modification of murine viral hepatitis. Science 1980;208:67-9.
20. Williams DL, Diluzio NR. Modification of experimental viral hepatitis by glucan induced macrophage activation. In: The Reticuloendothelial System and Pathogenesis of Liver Disease, Liehr and Grun, eds. Elsevier/North Holland Biomedical Press, 1983, pp. 363-8.
21. Leibovich SJ, Danon D. Promotion of wound repair in mice by application of glucan. J Reticuloendothelial Soc 1980;27:1-11.
22. Lahnborg G, Hedstrom KG, Nord CE. The effect of glucan - a host resistance activator - and ampicillin on experimental intra-abdominal sepsis. J Reticuloendothelial Soc 1982;32:347-53.
23. Di Luzio NR, Williams DL. The role of glucan in the prevention and modification of microparasitic diseases. In: Assessments of Chemical Regulation of Immunity in Veterinary Medicine. Gainer JH, ed. NY: Scientific, Medical and Scholarly Pub., 1983.
24. Williams DL, Sherwood ER, Browder IW, McNamee RB, Jones EL, Di Luzio NR. Preclinical safety evaluation of soluble glucan. Int J Immunopharmacol 1988;10:405-11.
25. Browder W, Rakinic J, McNamee R, Jones E, Williams D, Di Luzio N. Protective effect of non-specific immunostimulation in post splenectomy sepsis. J Surg. Res.1983;35:474-9.
26. Tzianabos AO, Cisneros RL. Prophylaxis with the immunomodulator PGG glucan enhances antibiotic efficacy in rats infected with antibiotic-resistant bacteria, Ann NY Acad Sci 1996;797:285-7.
27. de Felippe JJ, da Rocha-Silva FM, Maciel FM, Soares A de M, Mendes NF. Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). Surgery, Gynec and Obst 1993;177(4):383-8.
28. Babineau TJ, Hackford A, Kenler A, Bistrian B, Forse RA, Fairchild PG, Heard S, Keroack M, Caushaj P, Benotti P. A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients. Arch Surg. 1994 Nov;129(11):1204-10.
29. Babineau TJ, Marcello P, Swails W, Kenler A, Bistrian B, Forse RA. Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients. Ann Surg. 1994 Nov;220(5):601-9.
30. Dellinger EP, Babineau TJ, Bleicher P, Kaiser AB, Seibert GB, Postier RG, Vogel SB, Norman J, Kaufman D, Galandiuk S, Condon RE. Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group. Arch Surg. 1999 Sep;134(9):977-83.
31. Patchen ML, D`Alesandro MM, Brook I, Blakely WF, McVittie TJ. Glucan: mechanisms involved in its ‘radioprotective’ effect. J Leuc Biol 1987;42:95-105.
32. Patchen ML, McVittie TJ. Stimulated hemopoesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice. Int J Immunopharmac 1985;7:923-32.
33. Jung K, Ha Y, Ha SK, Han DU, Kim DW, Moon WK, Chae C. Antiviral effect of Saccharomyces cerevisiae beta-glucan to swine influenza virus by increased production of interferon-gamma and nitric oxide. J Vet Med B Infect Dis Vet Public Health. 2004 Mar;51(2):72-6.
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*Paul Clayton is a visiting lecturer at the Universities of Westminster and Amsterdam, and at the Centre for Nutrition Education and Lifestyle Management. He is also the author of numerous books and articles on pharmaco-nutrition. He is a member of the scientific boards of Food & Behaviour Research (Oxford), the Allergy Research Foundation (London), the Nutritional Therapy Council, the Alliance for Natural Health, Leatherhead Food International and the Scandinavian Healthcare Group.
Paul Clayton graduated summa cum laude in Medical Pharmacology from Edinburgh University, prior to obtaining his PhD.
He is a Fellow of The Royal Society of Medicine and a former Senior Scientific Advisor to the UK government`s Committee on the Safety of Medicines.
He has worked with leading doctors and clinical scientists at centres of clinical expertise in the UK and abroad, and trained the pharmacists in Britain` s largest chemist chain in preventative nutrition. He is now a consultant to several well-known international companies.
Dr Clayton designs clinical trials for nutritional therapies at leading teaching hospitals and lectures widely on nutrition and health. He has directed TV and radio programmes on health issues, and written extensively on these topics.
Dr Clayton has recently been appointed as Research Director of Medical Nutrition Matters, a post-graduate course in Oxford registered with, and approved by the BMA. Its function is to teach nutrition to GP`s and other health care providers.
He frequently presents at and chairs international conferences on nutrition and health - most recently at the prestigious Academie de France.
www.i-c-m.org.uk/journal/2006/jan/a03.htm
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