The Use of Herbal and Dietary Supplements in the Treatment of Herpes Simplex Virus

Transcription

1 The Use of Herbal and Dietary Supplements in the Treatment of Herpes Simplex Virus Release Date: 06/14/2011 Expiration Date: 06/14/2014 FACULTY: Kathryn L Haldiman, MS, RN FACULTY AND ACCREDITOR DISCLOSURE STATEMENTS: Kathryn L Haldiman has no actual or potential conflict of interest in relation to this program. ACCREDITATION STATEMENT: Pharmacy PharmCon Inc is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Program No.: H01-P Credits: 1 contact hour, 0.1 CEU Nursing Pharmaceutical Education Consultants, Inc. has been approved as a provider of continuing education for nurses by the Maryland Nurses Association which is accredited as an approver of continuing education in nursing by the American Nurses Credentialing Center s Commission on Accreditation. Program No.: N-677 Credits: 1 contact hour, 0.1 CEU

2 TARGET AUDIENCE: This accredited program is targeted nurses and pharmacists practicing in hospital and community pharmacies. Estimated time to complete this monograph and posttest is 60 minutes. DISCLAIMER: PharmCon, Inc does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced and objective. Occasionally, authors may express opinions that represent their own viewpoint. Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient or pharmacy management. Conclusions drawn by participants should be derived from objective analysis of scientific data presented from this monograph and other unrelated sources. Program Overview: To provide nurses and pharmacists with an understanding of treating the herpes simplex virus types 1 and 2 with herbal and dietary supplements. OBJECTIVES: After completing this program, participants will be able to: Define the epidemiology of herpes simplex virus Define common prescription medications for the treatment of herpes simplex virus Describe common herbal and dietary supplements for the treatment of herpes simplex virus

3 The goal of this continuing education article is to describe the use of herbal and dietary supplements in the treatment of herpes simplex virus type 1 and type 2. At the completion of this article, you will be able to: 1.) Understand the definition and epidemiology of herpes simplex virus. 2.) Define common prescription medications for the treatment of herpes simplex virus. 3.) Describe common herbal and dietary supplements for the treatment of herpes simplex virus. Introduction to the Herpes Simplex Virus The herpes viruses are a leading cause of viral infection that is second only to influenza and cold viruses. The herpes viruses include herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), varicella-zoster virus (type 3), Epstein- Barr virus, and human herpesvirus 6, 7, and 8 (Kaposi sarcoma-associated herpesvirus). Of all the herpes viruses, HSV-1 and HSV-2 are the most common manifestations (McCance & Huether, 2006). Symptoms of a herpes simplex virus (HSV) infection can include blisters or sores, often in the oral, genital, or other mucosal areas, although other areas of the body can also be affected. Prior to the outbreak of the lesions, some patients experience a prodome, or an early onset of symptoms that may consist of itching, pain, or tingling at the site of infection. Headaches, enlarged lymph glands, muscle aches, fever, and other flu-like symptoms can also accompany an HSV outbreak. However, a large percentage of individuals with HSV are asymptomatic and have no recognizable symptoms of the viral infection. According to the Centers for Disease Control and Prevention (CDC), 81.1% of those who are seropositive for HSV are asymptomatic or have symptoms that are so mild that they go undiagnosed (CDC, 2010a). HSV is a widespread Haldiman Herpes Herbal Page 1

4 infection with worldwide seroprevalence rates ranging from 65 to 90% (Chayavichitzilp et. al, 2009). In the United States, among those ages 14 to 49, HSV-1 affects 57.7% of the population, while HSV-2 is seropositive in 17% (Xu et al., 2006). HSV is transmitted by direct contact with a lesion or skin to skin contact during periods of asymptomatic shedding of the virus. After the initial infection, both HSV-1 and HSV-2 establish latency in the nervous system and reactivate at intervals of weeks, months, or years. A suppressed immune system, emotional stress, menstruation, surgery, physical injury, sunlight exposure, and certain dietary factors have been associated as triggers of HSV reactivation and subsequent outbreaks or asymptomatic viral shedding (University of Maryland Medical Center, 2011). All individuals who are seropositive for HSV, regardless of whether they have a clinically silent infection or not, will have periods of asymptomatic viral shedding in which the virus can be easily transmitted to other individuals. Asymptomatic viral shedding is most frequent in the first year after acquiring the virus and tends to decrease over time (CDC, 2010b). This asymptomatic viral shedding is a key characteristic in the epidemiology of HSV. Although they tend to decrease over time, viral shedding rates and reoccurrences of the infection are highly variable and unpredictable. The primary difference between HSV-1 and HSV-2 is where the virus prefers to establish latency. HSV-1 usually establishes latency in the trigeminal ganglion, while HSV-2 prefers the sacral ganglion region (American Social Health Association, 2011). For this reason, HSV-1 is usually associated with infection of the lips, mouth, and face, while HSV-2 is associated with infection of the genital area. However, it is possible to have an HSV-2 infection of the lip, mouth, or face, just as HSV-1 can occur in the genital area. Although HSV-2 is still the cause of Haldiman Herpes Herbal Page 2

5 the majority of genital herpes infections, about half of newly diagnosed cases of genital herpes in developed countries are now attributed to HSV-1 (Gupta, Warren, & Wald, 2007). Antiviral Medications Antiviral medications are a commonly prescribed treatment for HSV. Treatment with antiviral medications can help lesions heal faster during an initial outbreak, lessen the frequency and duration of symptoms during recurrences, reduce the frequency of outbreaks, and decrease viral shedding. Acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) are the three nucleoside analogues that are approved by the Federal Drug Administration (FDA) for the treatment of HSV. The medications may be used for episodic treatment to reduce the severity and duration of symptoms during an outbreak or as suppressive therapy to decrease the occurrence of frequent outbreaks. Clinical trials indicate that acyclovir, famciclovir, and valacyclovir are equally effective in the episodic treatment of HSV, although famciclovir is slightly less effective in reducing viral shedding. Valacyclovir has been proven to reduce the rate of transmission of HSV (CDC, 2010b). Although topical antiviral medications can be useful for treating oral herpes, their effectiveness in the treatment of genital herpes is limited and not generally recommended. Common side effects of oral antiviral medications for the treatment of HSV include headache, nausea, vomiting, malaise, decreased appetite, and abdominal pain. Less frequently reported but more serious side effects may include mania, psychosis, hallucinations, confusion, liver enzyme abnormalities, renal failure, thrombocytopenia, leucopenia, and alopecia. Acyclovir, famciclovir, and valacyclovir are pregnancy category B medications. All antiviral medications can be fairly expensive, especially when used as suppressive therapy (Herpes- Coldsores Support Network, 2011). Haldiman Herpes Herbal Page 3

6 Although antiviral medications have proven effectiveness, the increasing popularity of complementary and alternative treatments has led many HSV-positive individuals to experiment with the use of herbal and dietary supplements. Patrick et al. (2004) found that 17% of patients in the study that were being treated for genital herpes reported using an alternative therapy, such as herbal or dietary supplements. In general, there is insufficient empirical evidence on the efficacy and safety of herbal and dietary supplements for the treatment of HSV. Despite the lack of research, it is important for pharmacists to be aware of the common supplements that patients may be using, as there are often side effects and drug-herb interactions. Herbal and Dietary Supplements in the Treatment of HSV There are a variety of herbal and dietary supplements that have been touted as treatments of HSV. For the purposes of this article, the focus will be on those supplements that have been the subject of research studies. Research on the effectiveness of herbal and dietary supplements is complicated by the general lack of regulation and standardization within the industry. Supplements often contain multiple pharmacologically active components and product formulations may differ significantly. Andrographis (Andrographis paniculata) Andrographis is an Asian herb known for its immune-boosting abilities that has been used for centuries to treat a variety of viruses and other infectious diseases, including HSV. Walt et al. (2005) demonstrated that Andrographis has viricidal activities against HSV-1 and interferes with reproduction of the virus. A recent study by Seubsasana et al. (2011) confirmed the herb s inhibitory effects on replication of the virus and also found inhibitory effects on viral entry to the cell. These findings suggest that Andrographis is useful in reducing the reoccurrence of outbreaks and severity and duration of symptoms, as well as possibly reducing the risk of Haldiman Herpes Herbal Page 4

7 transmission if taken by a healthy individual with an HSV-positive partner. Limitations of the studies are that the effects of the herb were studied in vitro and the impact on frequency and severity of outbreaks and transmission rates when consumed by humans is not known. Andrographis has also been shown to stimulate production of antibodies and macrophages, increasing resistance to infection and reactivation of the latent virus (Mishra et al., 2007). The herb s immune-stimulating abilities may be enhanced when combined with other herbs or dietary supplements, such as Echinacea, zinc, and vitamin C. Andrographis has hepatoprotective properties, which may be useful to counteract the effects of those who have been on long-term suppressive antiviral therapy (Mishra et al., 2007). Echinacea (Echinacea purpurea) Echinacea is a popular North American herb that is known for its many medicinal purposes, particularly that of immune stimulation. Echinacea is one of the most well-researched herbs and it has been established to have strong antiviral properties against viruses, including HSV (Binns et al., 2002). The antiviral effects of the herb are believed to be caused in part by the inhibition of the enzyme hyaluronidase, thereby strengthening resistance to viral infection. Echinacea also increases the production of macrophages, promotes the cytotoxic killing of cells infected with viruses, and promotes the release of interferon to fight viruses. The herb may also block virus receptors on cell surfaces and inhibit the transcription of viral ribonucleic acid (RNA) to prevent replication (Herpes-Coldsores Support Network, 2011). In an in vitro study of Vircea, an herbal supplement containing Echinacea and benzalkonium chloride, the Echinacea phytochemicals demonstrated antiviral activity against both acyclovir-resistant and susceptible strains of HSV-2 (Thompson, 1998). Another study conducted in 2009 found that, in animal subjects, Echinacea promoted an immune response that Haldiman Herpes Herbal Page 5

8 diminished the ability of HSV-1 to establish latency after initial infection. This reduced the incidence and severity of subsequent outbreaks of the infection (Ghaemi et al., 2009). Despite these positive findings, one double-blind, placebo-controlled, cross-over study investigating the efficacy of an Echinacea product in the treatment of genital herpes found no statistically differences between the Echinacea product and a placebo. However, the study had a small sample of 50 subjects and a dropout rate of 38%, which limited the ability to detect statistical power (Vonau et al., 2001). As with most herbal products, more research in human subjects is needed to determine the true effectiveness of Echinacea in treating HSV. Olive Leaf (Olea europaea) Olive leaf is an herb that shows great promise in the treatment of HSV and other viral infections. Research has demonstrated that a compound in olive leaf, calcium elenolate, has strong in vitro antiviral activity against both HSV-1 and HSV-2. The mechanism of action of olive leaf is by the ability of the herb to interfere with amino acid production that is essential for virus replication. Olive leaf has also been proven in vitro to prevent viral shedding (Renis, 1970), suggesting an alternative to prescription suppressive therapy. The research on the use of olive leaf in the treatment of HSV is limited due to the lack of human studies, but promising case studies, anecdotal reports, and research on the effectiveness of the herb in treating other viral infections have lead to the promotion of olive leaf as an herbal treatment of HSV. Olive leaf has known interactions with several prescription medications, including antibiotics and hypoglycemic agents, and should not be used concurrently with these medications (Khan et al., 2007). Haldiman Herpes Herbal Page 6

9 Siberian ginseng (Eleutherococcus senticosus) Siberian ginseng is a Siberian herb that is popular for its medicinal effects. In a doubleblind, placebo-controlled study, a product that contained an extract of Siberian ginseng was found to reduce the severity, duration, and frequency of outbreaks in individuals with HSV-2. This effect was noted after more than three months of dosing, which suggests that Siberian ginseng may be more effective in suppressive treatment of HSV (Williams, 1995). Despite the promising findings from this study, an in vitro study on the effects of Siberian ginseng on the inhibition of viral replication did not find the herb effective against HSV-1 (Glatthar-Saalmuller, Sacher, & Esperester, 2001). Lysine Lysine is an amino acid that is naturally contained in foods such as fruits, vegetables, dairy, chicken, fish, beef, and lamb. Lysine is antagonistic to the production of arginine, an amino acid that is required by HSV for viral replication (Flodin, 1997). The amino acid can be taken as a dietary supplement to assist in the prevention of HSV outbreaks by suppressing arginine. A double-blind, placebo-controlled, cross-over study found that subjects had significantly fewer oral herpes outbreaks while receiving treatment with lysine supplements. However, there was no difference on the severity or duration of symptoms during outbreaks (Milman, Scheibel, & Jessen, 1980). In another double-blind, placebo-controlled study, researchers found that subjects who received treatment with lysine supplements for six months had significantly less outbreaks and decreased severity and duration of symptoms when outbreaks of HSV did occur (Griffith et al., 1987). Studies examining the role of lysine in the prevention of HSV outbreaks are complicated by varying dosages of the supplement, as well as dietary recommendations being given in Haldiman Herpes Herbal Page 7

10 conjunction with supplementation. These studies do suggest that lysine supplementation may be useful in suppressive treatment of HSV. More research is necessary to determine the role of dosing and frequency of lysine supplementation in preventing reoccurrences of HSV. Bioflavonoids and Vitamin C Bioflavonoids include the compounds of quercetin, rutin, and hesperidin and are responsible for the bright color pigmentation found in many fruits and vegetables. Bioflavonoids have gained recognition as an antioxidant that assist in the maintenance of healthy skin cells. The compounds are essential for the absorption of vitamin C, a vitamin that has numerous immunestimulating and skin healing properties. In a placebo-controlled study, the use of a combination of a bioflavonoid and Vitamin C supplement prevented outbreaks or decreased the severity and duration of symptoms when taken by individuals with oral herpes. The supplement was most effective when initiated with prodome symptoms (Terezhalmy, Bottomley, Pelleu, 1978). Bioflavonoids have also been demonstrated to have antiviral properties and inhibit viral replication (Kaul, Middleton, & Ogra, 1985), although the specific impact on HSV deserves further study. Zinc Zinc is an essential trace mineral that is known for its role in supporting the immune system and skin healing. Zinc is naturally high in foods such as seafood, dairy, beans, legumes, and yeast products. Zinc assists in the regulation of intercellular killing and the production of numerous immune cells, including neutrophils, natural killer cells, macrophages, lymphocytes, and antibodies (Shankar & Prasad, 1998). An in vitro study found that zinc combined with picolinic and aspartic acids and an alkaloid inhibited viral replication of HSV-1 (Angelova & Varadinova, 2000). Similar studies have also confirmed zinc s inhibitory effects on the Haldiman Herpes Herbal Page 8

11 replication of HSV (Pesheva & Varadinova, 2000). Anecdotal reports find that oral zinc supplements may be beneficial in the treatment of HSV (Fitzherbert, 1978), but more research is necessary. The use of topical zinc for the treatment of HSV demonstrates promise in reducing the severity and duration of symptoms (Wahba, 1980). Conclusion HSV is a common life-long infection that has a worldwide seroprevalence rate of 65 to 90 percent. Although the majority of individuals who are seropositive do not experience symptoms, asymptomatic viral shedding plays an important role in transmission of the virus. There are three antiviral medications that are approved by the FDA for treatment of HSV. However, because of the growing popularity of complementary and alternative treatments, many individuals are treating HSV with herbal and dietary supplements. Popular supplements include Andrographis, Echinacea, Olive leaf, Siberian ginseng, lysine, bioflavonoids, vitamin C, and zinc. Many of these herbal and dietary supplements demonstrate antiviral properties against HSV and some level of success in treating HSV. However, there is a general lack of data available on the efficacy and safety of herbal and dietary supplements. There is not enough information to determine how effective these treatments are or what dose and frequency is most beneficial. Although more research is necessary to investigate the impact of herbal and dietary supplements on the treatment of HSV, pharmacists should still be aware of the use of these supplements. Haldiman Herpes Herbal Page 9

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