Immune Support for Chronic Health Challenges

By Nieske Zabriskie, ND

Everyone is exposed to a variety of pathogens in the environment. Most individuals quickly overcome an infection without overt, long-term, lingering consequences. However, some infections, usually viral, can become chronic and persist indefinitely. In general, chronic infections develop in individuals with insufficient defense mechanisms due to genetic susceptibility, poor nutritional status, concurrent health conditions such as diabetes or cancer, stress and inadequate sleep. Common persistent viral infections include viral hepatitis, herpes simplex (HSV), Epstein-Barr (EBV), cytomegalovirus (CMV), and human immunodeficiency virus (HIV).

Chronic infections can deplete a person’s energy, weaken overall wellness, and decrease quality of life. Furthermore, chronic low-grade infections are often overlooked as a risk factor for other chronic diseases. Common persistent infections such as viral hepatitis and herpes simplex viruses have been associated with both cardiovascular and nervous system dysfunction.

Common Chronic Viral Infections

Herpes simplex virus (HSV–1) and, to a lesser degree, HSV–2 (genital herpes), are very common and contagious chronic infections. Data from the National Health and Nutrition Examination Surveys (NHANES) indicates that by age 12, 68 percent of the U.S. population tested positive for herpes simplex virus antibodies, and by age 30, the majority of all Americans test positive.¹ Herpes simplex virus causes recurring episodes of small, painful blisters on the skin, mouth, lips, eyes or genitals. After the initial infection with herpes simplex virus, the virus remains dormant in the nerve roots. The infection can become reactivated due to triggers such as sunlight, fever, menstruation, emotional stress, suppression of the immune system or physical trauma.

The most common types of chronic viral hepatitis (liver inflammation) are hepatitis B (HBV) and hepatitis C (HCV). Viral hepatitis can lead to chronic liver disease, cirrhosis and is the leading cause of liver cancer. Conservatively, at least 1.2 million Americans have chronic hepatitis B and another 3.2 million have chronic hepatitis C.² Although some individuals are able to fight the virus, hepatitis C infection becomes chronic in approximately 75-85 percent of cases,³ and hepatitis B infection becomes chronic in approximately 90 percent of infants infected, 25-50 percent of children age 1-5 and 5 percent of adults infected.⁴

Chronic Infection and Disease Risk

Chronic infections have been implicated in the disease process of conditions such as atherosclerosis, stroke and degenerative neurological disorders. Infections stimulate the immune response through various mediators released by white blood cells, including cytokines and chemokines, and induce free radical damage. These mediators also play a role in the inflammatory process, which is likely the common link associating the burden of chronic infection and the development of chronic inflammatory disorders.

Many cardiovascular diseases have an inflammatory component, which can often be measured via the CRP (C-Reactive Protein) laboratory test. Thus, the immune system is integral to the development of these conditions. Researchers suggest that it is the aggregate burden of chronic infections, rather than any single organism, that increases cardiovascular disease risk.⁵

Several studies have implicated inflammation due to chronic hepatitis B and C in the development of atherosclerotic plaques. In one study, researchers investigated the severity of coronary artery disease (CAD) in patients with and without hepatitis C. The subjects were evaluated for measurements of cardiovascular disease including fibrinogen, C-Reactive Protein (CRP), and severity was determined based on the Reardon severity score. The study showed that patients with hepatitis C had significantly higher levels of CRP and fibrinogen and more severe CAD compared to the subjects without hepatitis C.⁶ Another study evaluated subjects with inactive chronic hepatitis B infection and mean platelet volume (MPV, size of platelets). An increased MPV is associated with an increased risk of atherosclerosis, heart attack and atherothrombosis, which is when part of an atherosclerotic plaque breaks off and occludes a vessel elsewhere. This study showed that compared to healthy control subjects, the subjects with inactive hepatitis B virus had increased mean platelet volume and therefore, increased risk of atherothrombosis.⁷

Researchers also have found hepatitis C RNA in atherosclerotic plaques in the carotid arteries in patients with hepatitis C infections, suggesting that the virus may exert local action in carotid atherosclerosis.^8-9 Researchers have also found the DNA of viruses including herpes simplex-1, EBV and CMV in atherosclerotic plaques in aortic tissue. In the tissue collected from autopsies, atherosclerotic aortic tissue tested positive for herpes simplex-1 in 80 percent, EBV in 80 percent, and CMV in 40 percent of cases. This was compared to non-atherosclerotic tissue samples, which showed that aortic tissue only tested positive for herpes simplex-1 in 13 percent, EBV in 13 percent and CMV in 4 percent.¹⁰

Some research suggests that chronic infections may alter cardiovascular disease risk by inducing an immune response to heat shock proteins, which are proteins expressed by organisms due to increased temperature or stress. High serum levels of antibodies against specific heat shock proteins and heat-shock protein-specific T-lymphocytes (a type of white blood cell) have been associated with atherosclerotic diseases, such as coronary artery diseases and cerebrovascular events.^11-12

Alzheimer’s disease, the most common neurodegenerative disorder, is associated with oxidative stress and inflammation. This disease is characterized by amyloid-beta plaques (insoluble fibrous protein aggregates) and neurofibrillary tangles (aggregates of the protein tau which has become hyper-phosphorylated and accumulates inside the cells) in the brain. Evidence suggests that chronic infection with herpes simplex-1 may be a risk factor for Alzheimer’s disease. Research has shown that herpes simplex-1 infection affects both the excitability of the neurons as well as increases the intracellular accumulation of Abeta protein.¹³ Furthermore, research indicates that herpes simplex-1 infection causes tau phosphorylation.¹⁴ Studies show that individuals with anti-herpes-simplex-virus immunoglobulin M, an indicator of a primary infection or reactivation of the virus, have over 2.5-times the risk of developing Alzheimer’s disease compared to individuals without anti-herpes-simplex-virus antibodies.¹⁵

In addition, hepatitis C virus infection is often associated with cognitive dysfunction. Autopsies have shown that brain tissue from patients with hepatitis C virus have significantly higher levels of pro-inflammatory cytokines and chemokines such as interleukins and tumor necrosis factor alpha, compared to brain tissue from individuals without hepatitis C infection.¹⁶

Immune Support

Immune support is imperative for optimal health. Glycyrrhizin, Phyllanthus and Monolaurin have been shown to be effective in maintaining optimal immunity. Studies show that Glycyrrhizin is a potent immune-enhancing agent that has demonstrated activity against hepatitis B and C and the herpes simplex virus.¹⁷ A review of 22 clinical trials with the botanical Phyllanthus revealed that this herb is effective at boosting the power of the body’s immune system. The studies found that Phyllanthus had similar clearing of the hepatitis B antigens compared to interferon.¹⁸ Monolaurin, the glycerol ester of lauric acid, has also been shown to be effective. Monolaurin acts by preventing the attachment of the virus to susceptible host cells and making the virus more susceptible to host defenses.¹⁹

Another means of nutritional immune support are medicinal mushrooms, which exhibit potent immune-modulating activity due to the 1,3/1,6 beta glucans. Mushrooms including Agaricus blazei, Cordyceps sinensis, Grifola frondosa (Maitake), Coriolus versicolor, Ganoderma lucidum (Reishi), and Lentinula edodes (Shitake), as found in ImmuneAssist® 24/7, alter the number and type of white blood cells and cytokines allowing for an increased immune response.^20-24 EGCG, the polyphenol compound found in green tea, is also found in ImmuneAssist 24/7. EGCG acts as an inhibitor of viral attachment to cells.^25-26 The EGCG found in ImmuneAssist is suspended in a time-released matrix so that it doesn’t break down in stomach acid, allowing much more of this compound into the blood stream than can be obtained by drinking green tea.

In addition, the Saccharomyces cerevisiae fermentation product EpiCor® also exhibits significant anti-inflammatory, antioxidant and immune-modulating activity, and induces direct activation of white blood cells.²⁷

Conclusion

Chronic infections not only affect overall energy and well-being, but also increase the risk of developing additional chronic diseases such as atherosclerosis, stroke and neurodegenerative disorders. Supporting the immune system can reduce the risk of chronic infections and thus, may reduce the risk of long-term effects associated with the infections.

References

1. Schillinger JA, Xu F, Sternberg MR, et al. National seroprevalence and trends in herpes simplex virus type 1 in the United States, 1976-1994. Sex Transm Dis. 2004 Dec;31(12):753-60.

2. Centers for Disease Control and Prevention. Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/. Accessed on: 8-11-10.

3. Centers for Disease Control and Prevention. Hepatitis C Information for Health Professionals. Available at: http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section1. Accessed on: 8-11-10.

4. Centers for Disease Control and Prevention. Hepatitis B Information for Health Professionals. Available at: http://www.cdc.gov/hepatitis/HBV/HBVfaq.htm#overview. Accessed on: 8-11-10.

5. Elkind MS. Infectious burden: a new risk factor and treatment target for atherosclerosis. Infect Disord Drug Targets. 2010 Apr 1;10(2):84-90.

6. Alyan O, Kacmaz F, Ozdemir O, et al. Hepatitis C infection is associated with increased coronary artery atherosclerosis defined by modified Reardon severity score system. Circ J. 2008 Dec;72(12):1960-5.

7. Turhan O, Coban E, Inan D, et al. Increased mean platelet volume in chronic hepatitis B patients with inactive disease. Med Sci Monit. 2010 Apr 1;16(4):CR202-205.

8. Boddi M, Abbate R, Chellini B, et al. Hepatitis C virus RNA localization in human carotid plaques. J Clin Virol. 2010 Jan;47(1):72-5.

9. Boddi M, Abbate R, Chellini B, et al. HCV infection facilitates asymptomatic carotid atherosclerosis: preliminary report of HCV RNA localization in human carotid plaques. Dig Liver Dis. 2007 Sep;39 Suppl 1:S55-60.

10. Shi Y, Tokunaga O. Herpesvirus (HSV-1, EBV and CMV) infections in atherosclerotic compared with non-atherosclerotic aortic tissue. Pathol Int. 2002 Jan;52(1):31-9.

11. Ayada K, Yokota K, Kobayashi K, et al. Chronic infections and atherosclerosis. Ann N Y Acad Sci. 2007 Jun;1108:594-602.

12. Ayada K, Yokota K, Kobayashi K, et al. Chronic infections and atherosclerosis. Clin Rev Allergy Immunol. 2009 Aug;37(1):44-8.

13. Piacentini R, Civitelli L, Ripoli C, et al. HSV-1 promotes Ca(2+)-mediated APP phosphorylation and Abeta accumulation in rat cortical neurons. Neurobiol Aging. 2010 Jul 29. Published Online Ahead of Print.

14. Wozniak MA, Frost AL, Itzhaki RF. Alzheimer’s disease-specific tau phosphorylation is induced by herpes simplex virus type 1. J Alzheimers Dis. 2009 Feb;16(2):341-50.

15. Letenneur L, Pérès K, Fleury H, et al. Seropositivity to herpes simplex virus antibodies and risk of Alzheimer’s disease: a population-based cohort study. PLoS One. 2008;3(11):e3637.

16. Wilkinson J, Radkowski M, Eschbacher JM, et al. Activation of brain macrophages/microglia cells in hepatitis C infection. Gut. 2010 Jul 30. Published Online Ahead of Print.

17. Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza species. Phytother Res. 2008 Feb;22(2):141-8.

18. Liu J, Lin H, McIntosh H. Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review. J Viral Hepat. 2001;8:358-366.

19. Lieberman S, Enig MG, Preuss HG. A review of monolaurin and lauric acid: natural virucidal and bactericidal agents. Alternat Complement Ther. 2006;12(6):310-314.

20. Obi N, Hayashi K, Miyahara T, et al. Inhibitory Effect of TNF-alpha Produced by Macrophages Stimulated with Grifola frondosa Extract (ME) on the Growth of Influenza A/Aichi/2/68 Virus in MDCK Cells. Am J Chin Med. 2008;36(6):1171-83.

21. Deng G, Lin H, Seidman A, et al. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin Oncol. 2009 Mar 1. Published Online Ahead of Print.

22. Cheng Q. Effect of cordyceps sinensis on cellular immunity in rats with chronic renal insufficiency. Zhonghua Yi Xue Za Zhi. 1992 Jan;72(1):27-9, 63.

23. Liu M, Li J, Kong F, et al. Induction of immunomodulating cytokines by a new polysaccharide-peptide complex from culture mycelia of Lentinus edodes. Immunopharmacology. 1998 Nov;40(3):187-98.

24. Gong HY, Wang KQ, Tang SG. Effects of cordyceps sinensis on T lymphocyte subsets and hepatofibrosis in patients with chronic hepatitis B. Hunan Yi Ke Da Xue Xue Bao. 2000 Jun 28;25(3):248-50.

25. Nance CL, Siwak EB, Shearer WT. Preclinical development of the green tea catechin, epigallocatechin gallate, as an HIV-1 therapy. J Allergy Clin Immunol. 2009 Feb;123(2):459-65.

26. Xu J, Wang J, Deng F, Hu Z, Wang H. Green tea extract and its major component epigallocatechin gallate inhibits hepatitis B virus in vitro. Antiviral Res. 2008 Jun;78(3):242-9.

27. Jensen GS, Hart AN, Schauss AG. An antiinflammatory immunogen from yeast culture induces activation and alters chemokine receptor expression on human natural killer cells and B lymphocytes in vitro. Nutr Res. 2007 Jun;27(6):327-335.