Herpes and Shingles

Herpes and Shingles

1 Overview

Summary and Quick Facts

  • Herpes and shingles are both caused by members of the herpes family of viruses, which can establish infections that lay dormant and then can reactivate under certain conditions. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) cause oral and genital herpes, and varicella zoster virus causes chickenpox in children and shingles later in life.
  • In this protocol you will learn about the viruses that cause herpes and shingles, and how these infections are conventionally treated. A number of natural ingredients that may help ease symptoms of herpes and shingles will also be discussed, and important lifestyle and dietary considerations that may help prevent outbreaks will be examined, as well.
  • The standard treatment for both shingles and herpes is antiviral medication. Although there is no effective cure for herpes virus infections, several natural interventions may help reduce the frequency of outbreaks.

Herpes and shingles are both caused by members of the herpes family of viruses, which can establish infections that lay dormant and then can reactivate under certain conditions. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) cause oral and genital herpes, and varicella zoster virus causes chickenpox in children and shingles later in life.

Risk Factors

HSV-1 risk factors:

  • Age—85% of Americans in their 60s are infected
  • Receiving oral sex increases risk of HSV-1 genital herpes

HSV-2 risk factors:

  • Engaging in sexual activity with partner who has an active, symptomatic infection
  • Being female (twice the amount of women as men have HSV-2)
  • Having many sexual partners and starting at an early age
  • Having another sexually transmitted infection

Shingles risk factors:

  • Age—about half of all patients are over 60
  • Suppressed immune system
  • Being female and Caucasian

Signs and Symptoms

Oral herpes symptoms:

  • Painful sores in or around the mouth
  • The affected area may itch, tingle, or burn before the sores appear
  • There may be a fever, sore throat, and swollen lymph nodes in the neck

Genital herpes symptoms:

  • Sores on penis, buttocks, anus, and around and inside the vagina which may be painful
  • The affected area may itch, tingle, or burn before the sores appear
  • Fever, malaise, muscle aches, swollen lymph nodes in the groin, pain or burning upon urination, and vaginal discharge

Shingles symptoms:

  • First and most common symptom is burning or throbbing pain
  • There may also be headache, malaise, earache, sensitivity to light, and fever
  • Small, raised, reddish bumps that become fluid-filled blisters then appear, usually on one side of the body and localized to a “strip” of skin

Conventional Medical Treatments

Standard treatment for both herpes and shingles include:

  • Antiviral medication like acyclovir (Zovirax) or valacyclovir (Valtrex)
  • For shingles, topical capsaicin is used to treat postherpetic neuralgia, or pain after the blisters are gone

Emerging Therapeutics

Novel therapies for herpes and shingles include:

  • Cimetidine (Tagamet), commonly used for treating acid reflux, has been shown to reduce the severity and duration of both shingles and herpes outbreaks
  • Topical microbicides that have antiviral properties to prevent the spread of the herpes virus, even during asymptomatic periods

Dietary and Lifestyle Changes

Oral herpes:

  • Minimize sunlight exposure and use sunscreen on lips and skin
  • Minimize stress by getting enough sleep, eating a balanced diet, exercising, and using relaxation techniques like yoga or meditation
  • Keep sores clean and dry and avoid touching or scratching them to keep the virus from spreading to other areas of the body, like the eyes

Genital herpes:

  • Minimize stress by getting enough sleep, eating a balanced diet, exercising, and using relaxation techniques like yoga or meditation
  • Use water-based lubricants to decrease irritation caused by friction during sexual intercourse
  • Wash sores with saline and dry with tissues and warm air

Shingles:

  • Minimize stress and depression
  • Eat plenty of fruit and vegetables
  • Cool baths and cool, wet compresses on the blister can help relieve itching and pain

Integrative Interventions

  • Vitamin C: Helps prevent HSV-1 outbreaks when taken within 48 hours of the onset of tingling or itching at the outbreak site.
  • Reishi mushroom: Is known to combat the normal decline of the immune system that accompanies aging and was able to reduce pain caused by herpes and shingles infections.
  • Vitamin D: Combats herpes and shingles outbreaks, as dialysis patients who received iron and vitamin D were less likely to develop shingles and higher vitamin D levels corresponded with more antibodies to HSV-2.
  • Lysine: Lysine helps suppress HSV replication. A study with participants with genital or oral herpes found that consumption of lysine for 6 months reduced the frequency, duration, and severity of herpes outbreaks.
  • Fucoidans: Fucoidans are naturally occurring sugar polymers found in edible seaweeds. Human studies have shown they can help speed the healing and inhibit the reactivation of lesions in HSV-1 and HSV-2 infections and in shingles.

2 Introduction

Herpes and shingles are clinically distinct diseases, with different symptoms and modes of transmission. However, they are both caused by members of the herpes virus family.

Several members of this virus family can cause disease, but this protocol will focus on herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), and varicella-zoster virus.

HSV-1 and HSV-2 cause herpes, whereas the varicella-zoster virus typically causes chickenpox in children and shingles later in life (Siakallis 2009; Odom 2012; Wolz 2012; Roizman 2001; Odom 2012).

Both herpes and shingles are very common: as many as 90% of the people in the United States have been exposed to HSV-1 (Prasad 2010), and the CDC estimates that 32% of Americans will develop shingles at some point in their lifetime (Sampathkumar 2009; Albrecht 2012a).

One of the most clinically-relevant properties of herpes virus (Herpesviridae) is their ability to establish a latent infection (Roizman 2001). This means that the virus can lay dormant in the body, becoming “reactivated” under certain conditions, and manifest symptoms long after the initial infection. This reactivation can occur as a result of local injury, or systemic factors such as emotional stress, fever, trauma, sunlight exposure, or menstrual periods. But perhaps the most prominent factor, especially in regard to shingles outbreaks among older adults, is general age-related decline in immune function, known as immunosenescence (Oxman 2009; Pfister 2008; Steiner 1995; Roizman 2001; Albrecht 2012a).

Although conventional treatments may improve symptoms and shorten the duration of herpes and shingles outbreaks, many physicians overlook the potential therapeutic role of a common over-the-counter heartburn drug called cimetidine in mitigating the impact of Herpesviridae infections (Miller 1989). Despite several published studies showing cimetidine significantly eases shingles symptoms and shortens outbreak duration, the conventional medical establishment fails to recommend this inexpensive treatment to older adults suffering from this debilitating condition. Sadly, this is probably because cimetidine has been off patent for many years and is therefore no longer financially lucrative for pharmaceutical companies, even though it has substantial potential to provide relief to patients suffering from shingles.

In this protocol you will learn about the viruses that cause herpes and shingles, and how these infections are conventionally treated. A number of natural ingredients that may help ease symptoms of herpes and shingles will also be discussed, and important lifestyle and dietary considerations that may help prevent outbreaks will be examined as well.

3 Biology and Pathophysiology

The Herpesviridae family includes viruses that infect animals and humans (Siakallis 2009). Among these viruses, eight members are known to infect humans and are clinically important (Siakallis 2009). These viruses are herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and herpesviruses 6, 7, and 8 (Siakallis 2009; Odom 2012; Wolz 2012). Members of this family of viruses may cause a variety of diseases, including genital and oral herpes (HSV-1 and HSV-2), chickenpox/shingles (varicella-zoster virus), mononucleosis (human cytomegalovirus), and roseola (human herpes virus 6) (Roizman 2001; Siakallis 2009; Odom 2012). The focus of this protocol is typical manifestations of HSV-1 and -2, as well as shingles (varicella zoster).

Infection with any member of the Herpesviridae family involves multiple steps. First, the virus interacts with receptors on the external surface of human cells to gain entry into the cell (Jennsen 2005; Schnitzler 2010). Once inside the human cell, the virus uses the cell to make many copies of itself (replicate) (Mell 2008; Kinchington 2012). This stage is known as the primary infection, and while it can be accompanied by a period of illness, patients may also be completely asymptomatic and remain unaware that they have been infected.

In addition to using the cell to replicate, Herpesviridae viruses make a certain class of gene products known as latency-associated transcripts (LATs), which remain in the body and can reactivate the viral replication process (Block 1997; Kent 2003; Mell 2008; Kinchington 2012).

Members of the Herpesviridae family typically traverse sensory nerves until they reach large nerve clusters called ganglia, where they replicate undetected by the host (Mell 2008; Kinchington 2012; Zwaagstra 1990, 1991; Imai 2009; Hill 1990).

Shingles

The varicella-zoster virus, which causes chickenpox in children, also causes shingles (herpes zoster), a disease that generally occurs in adulthood as a result of the reactivation of the virus (Wallmann 2011; Chisholm 2011).

The primary infection – chickenpox – is a childhood infectious disease that almost always causes symptoms. During this time, patients are extremely contagious (Wallmann 2011). Even people who have mild disease may spread the infection to others (Kaneshiro 2011). Chickenpox causes a characteristic rash that usually occurs 10 to 21 days after coming into contact with someone who had the disease, and typically presents as 250 to 500 small, fluid-filled, itchy blisters over the body (Kaneshiro 2011). Usually chickenpox affects patients for 5 to 10 days (CDC 2011). Chickenpox is highly contagious and can be spread via direct contact or in the air if an infected person coughs or sneezes. A person with chickenpox is typically contagious 1 – 2 days before they develop blisters, and remain so until all their blisters crust over (A.D.A.M. 2011; CDC 2012). Childhood vaccination against varicella zoster (Varivax®) can help protect against chicken pox, and is recommended by the Centers for Disease Control and Prevention (CDC) for most children (CDC 2008).

Once the virus establishes a dormant or latent infection, patients are no longer contagious and do not experience symptoms. However, the virus may become reactivated later in life, leading to shingles (Mayo Clinic 2011; Wallmann 2011; Gharibo 2011).

The varicella zoster virus can be spread from a person with active shingles to a person who has never had chickenpox. In such cases, the person exposed to the virus could develop chickenpox (rather than shingles). The virus is spread through direct contact with fluid from the rash blisters.

A person with shingles can spread the virus when the rash is in the blister-phase. A person is not infectious before blisters appear. Once the rash has developed crusts, the person is no longer contagious. Shingles is less contagious than chickenpox and the risk of a person with shingles spreading the virus is low if the rash is covered (Wallmann 2011).

Although shingles may occur at almost any time, it is more common in the elderly and in those with weakened immune systems. This suggests that reactivation may be triggered by impaired immunity to the virus, which occurs with advancing age (Sampathkumar 2009; Harpaz 2008).

Herpes

Herpes infections can be caused by an infection with HSV-1 or HSV-2 (UMM 2011; Mell 2008; Urban 2009). Manifestations of herpes include: oral herpes (herpes labialis), or “cold sores”, herpes simplex keratitis, which causes sores to appear on the corneas of the eyes, and genital herpes. Another, less common, manifestation is erythema multiforme, which causes bull’s-eye shaped lesions to appear on the skin and can also cause lesions in or around the mouth (Kamala 2011; Sokumbi 2012).

HSV-1 is the usual cause of oral herpes and herpes simplex keratitis, whereas HSV-2 is usually associated with genital herpes. However, HSV-1 can also cause genital herpes, but HSV-2 is associated with more severe outbreaks (Urban 2009; Ehrlic 2011a; Mell 2008; Chirshom 2011; Chentoufi 2012).

HSV-1 is usually spread by skin-to-skin contact with an adult that has been infected with the virus. Many people initially contract this virus as an infant or child (American Academy of Dermatology 2012). HSV-2, on the other hand, is usually spread via sexual contact (American Academy of Dermatology 2012). In either case, the virus gains access to the body through mucous membranes or breaks in the skin (Ehrlic 2011a).

Infection with either HSV-1 or HSV-2 can initially manifest as small fluid-filled blisters on the skin (Mell 2008; Urban 2009; Chrisholm 2011). Once the initial infection subsides, the virus spreads to the nerve cells where it stays dormant until it is reactivated (American Academy of Dermatology 2012).

Factors such as stress, fatigue, sun exposure, surgery, fever, and menstrual periods can trigger the reactivation of HSV viruses. The frequency of these recurrent outbreaks varies from person to person; some individuals never experience any outbreaks (and are termed “asymptomatic carriers”), while others may have monthly outbreaks (Centoufi 2012). It is not known why some individuals remain asymptomatic while others have outbreaks, but both asymptomatic and symptomatic patients are able to infect others (Centoufi 2012).

4 Causes and Risk Factors

Both herpes and chickenpox/shingles are caused by previous exposure to HSV-1 or HSV-2 (for herpes), or to the varicella-zoster virus (for chickenpox/shingles).

Shingles

One of the most important risk factors for shingles is age; about half of all patients are over 60 (Sampathkumar 2009; Fashner 2011). Patients aged 80 to 89 are 10 times as likely to develop shingles as children under age 10 (Albrecht 2012a). This age discrepancy is thought to be due to the gradual weakening of the immune system with age, a process called immunosenescence (Weaver 2009; Levin 2010).

Aside from increasing age, a suppressed immune system also increases risk of developing shingles (Weaver 2009; Fashner 2011; Mayo Clinic 2011; Albrecht 2012a). Patients who are immunocompromised have more manifestations of shingles, and these start earlier than in patients with healthy immune systems (Weaver 2009).

People who have diseases that weaken the immune system, especially HIV/AIDS, have an increased risk of developing shingles (Weaver 2009; Albrecht 2012a; Mayo Clinic 2011). The long-term use of immunosuppressive drugs, such as corticosteroids, increases the risk of developing shingles as well (Mayo Clinic 2011; Weaver 2009; Albrecht 2012a).

Some studies found that women are more likely than men to develop shingles, and African-American individuals are at lower risk than Caucasians (Tseng 2011; Albrecht 2012a).

Herpes

For HSV-1 infection, there are no specific risk factors aside from increasing age, as the ubiquity of this virus means many will become infected; the University of Maryland Medical Center suggests that 62% of Americans are infected by the time they reach adolescence and that 85% of Americans in their 60s have contracted the virus (Ehrlic 2011a). Receiving oral sex increases the risk of developing genital herpes caused by HSV-1 (American Academy of Dermatology 2012; Ehrlic 2011a).

Risk factors for HSV-2 infection are primarily related to sexual activity, as this virus is typically spread via sexual contact. Engaging in sexual activity with a partner who has an active, symptomatic infection (ie, lesions on the genitals) is a very strong risk factor for transmission. Additional risk factors are female sex, having had many sexual partners, having had sexual encounters at an early age, and the presence of another sexually transmitted infection (Berger 2008; American Academy of Dermatology 2012; Ehrlic 2011a). Women have a higher risk of becoming infected with HSV-2 as a result of an unprotected sexual encounter than men (Ehrlic 2011a; Albrecht 2012b). People of African-American or Hispanic descent have a higher risk of HSV-2 than Caucasians (Berger 2008; CDC 2010).

5 Signs and Symptoms

Shingles

Typically, the first and the most common symptom of shingles is pain, which presents in approximately 75% of people who go on to develop a rash (Albrecht 2012c; Mayo Clinic 2011; Gharibo 2011). The pain is sometimes described as a burning, throbbing, or stabbing sensation that is localized to the area of the skin that will later be affected by the rash (Albrecht 2012c). During this time, which is also known as the “prodromal period”, patients may also experience headache, malaise, earache, sensitivity to light, and fever (Weaver 2009; Mayo Clinic 2011; Albrecht 2012c; Wallmann 2011). These symptoms may appear up to 5 days before the rash (Wallmann 2011).

Typically, after prodromal symptoms occur, a rash will develop. However, in some people, a rash may appear before they experience pain (Wallmann 2011). In addition, some patients will have pain, but will not develop a rash; this is called “zoster sine herpetica” (Albrecht 2012c; Sampathkumar 2009; Wallman 2011). It is important to be aware of this type of herpes zoster manifestation because, if the cause of the pain cannot be determined, an inaccurate diagnosis may be made and incorrect treatments given; for example, zoster sine herpetica may be misinterpreted as angina, heart attack, dental problems, or duodenal ulcer (Sampathkumar 2009; Wallmann 2011).

The rash of shingles typically begins as small, raised, reddish lesions that quickly evolve into groups of fluid-filled blisters that later break and form a crust or a scab (Mayo Clinic 2011; Sampathkumar 2009; Albrecht 2012c). Some patients will experience pain after mild or brushing contact to the affected skin areas, a phenomenon known as allodynia (Albrecht 2012c).

The lesions caused by shingles have a characteristic location and distribution: they may be limited to one side of the body and are localized to a “strip” of skin, also known as a dermatome, which represents the skin area that is served by the nerves of a single ganglion. In about 20% of patients, adjacent dermatomes can be affected. The most commonly affected areas are on the side of the trunk around the waistline and the second most common is the face around the eye/ forehead (Sampathkumar 2009; NINDS 2013). The skin lesions typically take 2 to 4 weeks, or sometimes even longer, to heal and they may cause permanent scarring or skin pigmentation changes. When shingles affects the eye, it can cause vision changes and sometimes even permanent blindness (Wallmann 2011).

Herpes

Most herpes infections affect either the oral or genital regions. Sometimes, however, infections of other organs may occur without the signs of oral or genital herpes (Sköldenberg 1996; Stuart-Harris 1983; Lahat 1999; Chaudhuri 2002).

Typically, the first oral infection with HSV (usually HSV-1) will cause painful sores to appear in or around the mouth, also known as herpetic gingivostomatitis, but sometimes swollen gums are the only symptom, and other times no symptoms develop at all (Urban 2009, American Academy of Dermatology 2012). The most common location for these sores is the lips, the area around the mouth, and the tongue, though the blisters can appear on any skin-covered area (American Academy of Dermatology 2012; Ehrlic 2011a; Urban 2009).

During the prodromal period, before these sores appear, the skin may itch, tingle, or burn (American Academy of Dermatology 2012). The sores usually appear for the first time 1 to 3 weeks after contact with the infected person and may last up to 14 days (Urban 2009; Ehrlic 2011a). In addition, patients may have fever, a sore throat, and swollen neck lymph nodes, especially during the first episode, which can make eating and drinking difficult (Urban 2009; Mayo Clinic 2011; Mell 2008).

Genital herpes causes similar symptoms, with the appearance of sores on the penis, anus, buttocks, and around and inside the vagina (American Academy of Dermatology 2012; Mayo Clinic 2011; Mell 2008). These lesions may or may not cause pain (Ehrlic 2011a). Other symptoms include fever, malaise, muscle aches, swollen lymph nodes in the groin, pain or burning upon urination, and vaginal discharge (American Academy of Dermatology 2012; Urban 2009; Mell 2008; Mayo Clinic Staff 2011). As with oral herpes, patients may experience a prodromal period with tingling, burning, or itching of the affected areas (Urban 2009; American Academy of Dermatology 2012).

Herpes infections can also cause several complications. Herpes can spread to one or both eyes, and when the cornea is affected (herpes simplex keratitis), it causes pain, sensitivity to light, a gritty feeling in the eye, and discharge (American Academy of Dermatology 2012). Without treatment, scarring may result, which can lead to cloudy vision or even blindness, requiring corneal transplantation (Urban 2009; American Academy of Dermatology 2012).

Both HSV-1 and HSV-2 may also enter into a finger via breaks in the skin, causing a condition known as herpetic whitlow, in which the fingertip becomes swollen, red, and painful; this condition is most frequently seen in health care workers, such as dentists, who are exposed to body fluids while not wearing gloves (Urban 2009). Herpes can also infect the brain, leading to herpes encephalitis, which causes fever, confusion, and seizures; this condition can be fatal (Urban 2009). Other internal organs, such as the lungs and esophagus, can be infected as well, but this is rare.

6 Diagnosis and Conventional Treatment

Diagnosis

Shingles. The typical symptoms of shingles – pain, rash, and blisters extending along a limited area or strip on one side of the body – are very characteristic, so doctors are often able to make the diagnosis based on the clinical presentation (Mayo Clinic 2011; Albrecht 2012c). In people whose immune system is functioning normally, the rash is usually present only on one side of the body (Albrecht 2012c). In immunocompromised individuals, more unusual presentations can sometimes be observed (Gnann 2002). An example of this is abdominal zoster, in which serious abdominal pain occurs hours to days before the rash (Gnann 2002).

In situations when the diagnosis is not certain, a doctor may take a piece of tissue or collect some material from the blisters to look for the varicella-zoster virus, which will confirm the diagnosis (Mayo Clinic 2011; Albrecht 2012d). Doctors can also look for antibodies to the varicella-zoster virus in the blood, which both confirms previous infection (necessary for shingles to occur) and assesses susceptibility to future outbreaks (Albrecht 2012d).

Herpes. Often, doctors can similarly diagnose herpes simplex infections based on the appearance of the sores (Ehrlic 2011a; American Academy of Dermatology 2012; Albrecht 2012e). However, confirmatory laboratory testing is sometimes needed (Albrecht 2012e). Much like shingles, herpes infections can be confirmed by taking material from the blisters and looking for the presence of either HSV-1 or HSV-2 (Mell 2008; Albrecht 2012e).

Treatment

The standard treatment for both shingles and herpes is antiviral medication. The main antiviral medications used for shingles are acyclovir (Zovirax®), famciclovir (Famvir®), and valacyclovir (Valtrex®) (Albrecht 2012f). All three medications can be taken orally and reduce pain and speed healing of the lesions; though famciclovir and valacyclovir are often preferred because they require less frequent dosing (three times per day as opposed to five for acyclovir) (Albrecht 2012f).

Currently, these medications are recommended for patients over the age of 50 who do not present complications and come to the doctor within 72 hours after the onset of symptoms (Albrecht 2012f). Efficacy in patients under the age of 50 has not been studied as thoroughly (Albrecht 2012f). The utility of acyclovir more than 72 hours after the lesions appear is unknown in otherwise healthy individuals. In addition, the benefits of therapy are thought to be minimal after lesions have formed a crust. Treatment with antiviral drugs should be initiated in all immunocompromised patients, even in those who present to the doctor more than 72 hours after their lesions have appeared (Albrecht 2012f).

Patients with shingles may get pain relief from non-steroidal anti-inflammatory drugs or acetaminophen, which can be used alone or in combination with weak opioids, such as codeine and tramadol (Albrecht 2012f). Another treatment option is to use local creams that contain the compound capsaicin (Zostrix®). Capsaicin is the ingredient in peppers that generates the sensation of “heat” in the mouth. When formulated into a cream or ointment, it can be applied to areas of the body that are still painful after the shingles blisters are gone to reduce pain. When applied, capsaicin creams generate a mild “burning” sensation. Capsaicin causes the release of a neurotransmitter (Substance P) from nerve cells, and its repeated application depletes the nerve stores of the compound, reducing pain transmission (McCleane 2000; Fashner 2011; Sayanlar 2012).

In rare cases of severe or complicated manifestations of herpes, such as massive outbreaks of sores or herpes encephalitis, intravenous antivirals may be needed (Mell 2008, Albrecht 2012g).

7 Novel and Emerging Treatments

Cimetidine

Cimetidine (Tagamet®) is a medication commonly used for treating acid reflux (GERD). It inhibits the production of stomach acid by blocking the signaling pathway for histamine (Hsu 1991). Histamine signaling modulates the immune response to some viruses as well, and researchers have shown that oral administration of cimetidine significantly accelerates the healing of skin lesions and provides pain relief in adults with shingles (Miller 1989). Supporting this finding, an in vitro study performed on cells from 22 people with shingles found that cimetidine improves the body’s immune response, and suggested that healing from skin rash and pain could be accomplished significantly faster (Komlos 1994). Findings from another study, which enrolled 221 patients with shingles, suggested cimetidine may even be efficacious when used during the prodromal period, before manifestation of the characteristic rash (Kapińska-Mrowiecka 1996).

In addition, numerous case studies have been published demonstrating that cimetidine may reduce the severity and duration of symptoms of both shingles and herpes outbreaks (van der Spuy 1980; Mavlight 1984; Hayne 1983). For example, one study made the observation that a patient who developed shingles just before starting a course of cimetidine for gastric ulcer experienced a significant relief of shingles symptoms. Based on this finding, which was unexpected at the time, the researchers prescribed cimetidine to several other patients with shingles and oral herpes, and the vast majority of them experienced relief of their symptoms. Another exciting finding was that in one patient with herpetic keratitis, the attacks occurred less frequently and were shorter in duration following cimetidine administration (van der Spuy 1980).

Topical Antimicrobial Agents

An emerging therapy for infections caused by viruses in the Herpesviridae family is the use of topical microbicides, which are compounds that have antiviral properties. One of the biggest challenges in the field of genital herpes research is to find ways to prevent viral transmission, and this is particularly important because the sexual spread of the virus often occurs during periods when patients have no visible lesions, a phenomenon called “asymptomatic shedding” (Keller 2005).

As a result, compounds that are able to prevent the spread of the virus, even during these asymptomatic periods, would likely reduce the incidence of herpes. Different microbicides are being tested; some of them directly inactivate the virus, while others enhance the body’s immunity to HSV or prevent the virus from entering cells (Keller 2005). One candidate microbicide, tenofovir, was originally developed as a topical gel to prevent HIV transmission. However, it was also found in a human trial that a 1% tenofovir gel inhibited the transmission of HSV-2 by 51% (Andrei 2011; Cates 2010; Celum 2012). As a result, the use of tenofovir may become a strategy to prevent the spread of herpes, though more research is needed.

Vaccines

Another treatment approach for both shingles and herpes is to prevent the virus from becoming reactivated by stimulating the body’s immunity with a vaccine. A vaccine against shingles (Zostavax®) was licensed in 2006 by the US Food and Drug Administration (Tseng 2011). When administered to individuals over the age of 60 with a healthy immune system, this vaccine reduced the risk of developing shingles by 55% (Tseng 2011). Studies of this vaccine found it was safe for patients 60 years and older, with the most common side effects being swelling, redness, warmth, and pain at the vaccination site. A small percentage of participants developed a varicella-like rash, consisting of a small number of fluid-filled vesicles that occurred at the site of the injection and did not spread (Simberkoff 2010). The vaccine is widely available to the public, which means that it has the potential to greatly reduce the number of cases of shingles in the United States and in other developed countries. The biggest barrier to its widespread use is cost, as it is one of the most expensive vaccines recommended for older adults (Hurley 2010).

Researchers have also worked on a vaccine for HSV, as this is thought to be one of the most effective ways to prevent the spread of herpes (Chentoufi 2012). Many different approaches towards creating an HSV vaccine have been tried, and though some have had promising initial results, none of the vaccines tested have proven to be effective at preventing HSV-2 infection (Belshe 2012; Chentoufi 2012; Cohen 2010), but some have shown limited efficacy in preventing HSV-1 infections (Belshe 2012).

A potential explanation for this limited efficacy is that the immune cells (T cells) that facilitate vaccine-mediated immunity have a difficult time gaining access to the female genital tract in the absence of inflammation or infection, and this prevents the vaccine from successfully providing immunity against HSV-2 (Shin 2012). As a result, new approaches for vaccination are under development. One of these, the “prime and pull” approach, is a new two-step strategy, in which a conventional vaccination is performed (via the bloodstream) to generate a T-cell response (“prime”), and in the second step, a compound (called a chemokine) is applied to the genital tract to recruit the activated T cells (“pull”) (Shin 2012). More studies are needed before these vaccines become available.

8 Dietary and Lifestyle Considerations

Shingles

Reducing stress is one way to prevent shingles outbreaks. Psychological stress has been linked to shingles outbreaks, and major depression was shown to decrease cellular immunity to the varicella-zoster virus and increase the risk of shingles (Irwin 1998). In addition, a study reported that people who developed shingles experienced, in the six months preceding the outbreak, significantly more frequent events that they perceived as being stressful. Higher levels of perceived stress were also identified as a risk factor for oral lesions with HSV-1 (Schmader 1990; Stock 2001).

In addition to relieving stress, other techniques can help relieve symptoms associated with shingles. Cool baths and using cool, wet compresses on the blisters can help dry the blisters and relieve itching and pain (Mayo Clinic 2011; Schoenstadt 2011). Good hygiene and daily washing is another important consideration; maintaining trimmed fingernails may help reduce the damage caused by scratching and it also prevents secondary bacterial infections (Schoenstadt 2011). Moreover, eating a healthy, well-balanced diet and getting plenty of rest can strengthen the immune system (Schoenstadt 2011). One study showed that individuals who ate less than one serving of fruit per week had a more than three-fold higher risk of shingles as compared to those with more than three servings per day (Thomas 2006).

Herpes

Oral herpes (HSV-1) outbreaks can be triggered by exposure to sunlight and by the common cold, but there is currently no indication that these are involved in triggering genital herpes outbreaks (Bridges 2012a, Randall 2012). Although it can be difficult to avoid sunlight entirely, minimizing sunlight exposure may help reduce outbreaks, and it is recommended to use sunscreen on the lips and skin (Randall 2012).

Genital herpes can be triggered by the irritation caused by friction during sexual intercourse (Bridges 2012a). Using water-based lubricants can help reduce this irritation. However, lubricants that contain the spermicide nonoxynol-9 can irritate mucous membranes (Bridges 2012a).

Stress is also implicated in causing herpes outbreaks: ongoing stress lasting for over a week appears to be a stronger trigger for genital herpes outbreaks than any other single factor. Therefore, reducing emotional stress is one of the most important strategies for preventing herpes outbreaks (Longo 1989; Rand 1990; Padgett 1998; Buske-Kirschbaum 2001; Chida 2009; Kushnir 2010; Bridges 2012b; Bridges 2012a). Getting enough sleep, eating a balanced diet, exercising, and using relaxation techniques such as yoga or meditation may help reduce stress (Bridges 2012b).

Finally, one important technique for managing HSV flare-ups is to minimize the length of time that the blisters are present and to avoid complications. This can be done by keeping the sores clean and dry and avoiding touching or scratching them, which will also help keep the virus from spreading to other areas of the body, such as the eyes (Randall 2012). For genital herpes, washing the sores with saline and then drying them with tissues and warm air is another helpful strategy (Royal Adelaide Hospital 2010).

Bioidentical Progesterone and Herpes Infection in Women

Bioidentical hormones, especially natural progesterone, may confer some protection against herpes virus infection compared to progestins (synthetic progestogens) such as medroxyprogesterone acetate. Studies have shown multiple aspects of immunity in the female genital tract are controlled by sex hormones, and that hormones influence susceptibility to several sexually transmitted diseases (Kaushic 2003).

Evidence from an animal study showed that treatment with natural progesterone conferred some protection against vaginal HSV-2 infection (Gillgrass 2005), whereas, administration of a progestin significantly increased susceptibility in a similar model (Kaushic 2003). This may be because the progestin prolonged a phase of the animals’ estrous cycle – the diestrus phase – more so than natural progesterone; some aspects of susceptibility to vaginal infection with sexually transmitted diseases are increased during this phase (Gallichan 1996).

Although human trials have yet to evaluate the potential of natural progesterone to protect against herpes infection, women who require hormone replacement therapy are nonetheless encouraged to pursue bioidentical hormone replacement (BHRT) instead of conventional HRT, which relies upon synthetic hormones. Bioidentical hormone replacement therapy may confer myriad other advantages over conventional HRT as well; more information is available in the Female Hormone Restoration protocol.

9 Targeted Natural Interventions

Although there is no effective cure for herpes virus infections, several natural interventions may help reduce the frequency of outbreaks. Both shingles and herpes can manifest when the immune system is unable to prevent the latent viral infection from reactivating. Therefore, natural interventions that maintain the health of the immune system may help prevent outbreaks.

Antioxidants help neutralize reactive oxygen species, which can damage cells of the immune system (Cannizzo 2011; Hughes 2000). This is especially important for the elderly, whose immune systems function less optimally than in younger individuals. Supplementation with antioxidants may help combat this age-related immunosenescence and help avoid nutritional deficiencies, which are common among the elderly (Chen 2012).

Vitamin C

Vitamin C, also called ascorbic acid, is a potent antioxidant and has natural antiviral properties (Brinkevich 2012; Uozaki 2010; Lopez 2009). Laboratory studies show that vitamin C and some of its metabolites prevent HSV-1 from replicating (Furuya 2008; Uozaki 2010; Brinkevich 2012). A study on human volunteers with active HSV-1 lesions found that a formula containing vitamin C was able to prevent HSV-1 outbreaks when taken within 48 hours of onset of tingling or itching at the outbreak site. Moreover, even when the vitamin C formula was taken after this period of time, it helped reduce the severity and the duration of the outbreaks (Lopez 2009).

In addition to supporting the immune system and potentially helping prevent outbreaks, vitamin C may provide relief from the nerve pain that often accompanies shingles (Johnson 2004). Researchers found that intravenous administration of vitamin C can help reduce pain and skin manifestations of shingles (Schencking 2012; Byun 2011). The pain-relieving effects of vitamin C may be due to its ability to modulate levels of two inflammatory chemicals: interleukin-6 (IL-6) and interleukin-8 (IL-8) (Kapoor 2012). It also appears that people who experience severe pain after a shingles outbreak have lower levels of vitamin C, and vitamin C supplementation was shown to reduce the spontaneous pain that these individuals experienced (Finnerup 2005; Chen 2009).

Reishi mushroom

The reishi mushroom, also known as Ganoderma lucidum, is a fungus that has been used medicinally for centuries in China, Japan, and Korea (Paterson 2006). Some of the components of reishi appear to have antiviral properties (Paterson 2006). Researchers have identified two different compounds in the reishi mushroom, known as GLPG (Ganoderma lucidum proteoglycan) and APBP (acidic protein bound polysaccharide), which showed strong antiviral activities against both HSV-1 and HSV-2 in vitro (Liu 2004; Li 2005; Kim 2000).

Preparations of the reishi mushroom have also shown promising results in human trials. Reishi was very effective in reducing pain caused by herpes and shingles infections that did not respond to standard treatment. Also, an herbal mixture containing reishi reduced shingles pain. In addition, another reishi-containing herbal mixture shortened the duration of symptoms in patients with oral and genital herpes infections (Hijikata 1998; Hijikata 2005; Hijikata 2007).

Much of reishi’s benefit may be due to its ability to combat immunosenescence – the normal decline of the immune system that accompanies aging. Reishi mushrooms attack and reverse immunosenescence through the combined effects of three compounds: first, a group of long-chain carbohydrates called polysaccharides, second, a unique protein named LZ-8 and third, a small group of steroid-like molecules called triterpenes (Bao 2001; Xu 2011; Yeh 2010).

Together, these three reishi components achieve the dual goals of promoting healthy immune responses against viral, bacterial, or fungal infections, while suppressing excessive or chronic inflammation that threatens long-term health.

Among its broad-spectrum immune-boosting effects are the following:

  • Reishi promotes specialization of dendritic cells and macrophages. These cells are essential in allowing individuals to react to new threats, to vaccines, and cancer cells (Cao 2002; Lai 2010; Jan 2011; Ji 2011; Chan 2005).
  • Reishi's effects on dendritic cells have been proven to boost the response to tetanus vaccine. The mushroom's proteins are also under investigation as "adjuvants" to emerging cancer DNA vaccines and other immune-based cancer treatments (Lai 2010; Chu 2011; Lin 2011; Zhu 2012).
  • Reishi polysaccharide triggers growth and development of bone marrow, where most immune cells are born. Following bone marrow eradication by chemotherapy, reishi increased production of both red and white blood cells (Zhu 2007).
  • Reishi increases numbers and functions of many cell lines in the immune system, such as natural killer cells, antibody-producing B cells, and the T cells responsible for rapid response to a new or "remembered" antigen (Jan 2011; Wang 2012; Jeurink 2008).

On the other side of the immunosenescence coin, reishi's various components work to suppress inflammatory cytokines produced during chronic inflammation, as seen for example in rheumatoid arthritis, while maintaining normal acute inflammatory responses (Ji 2011; Kohda 1985; Ho 2007; Ko 2008; Xi Bao 2006). Under conditions of chronic inflammation, reishi reduces inflammatory promoters (Dudhgaonkar 2009).

Vitamin A

Vitamin A and its precursor, beta-carotene, are potent antioxidants (Cerezo 2012; Liebler 1996; Stahl 2012). In addition, vitamin A and beta-carotene may have some unique properties relevant in context of HSV infections: beta-carotene can help protect the skin from sunlight damage, which is a known trigger of HSV-1 outbreaks (Stahl 2012). In addition, serum vitamin A levels appear to have an effect on HSV viral shedding: it was reported that in non-pregnant women not taking hormonal birth control, low vitamin A levels were associated with increased shedding of HSV from the female genital tract (Mostad 2000). This suggests that vitamin A may help prevent the transmission of herpes to others.

Vitamin D

While in the past vitamin D was appreciated for its role in maintenance of bone health, more recent evidence suggests it may be a potent immunomodulator as well (Aranow 2011; Lang 2012). For example, vitamin D deficiency is associated with impaired immune function and increased susceptibility to infections (Aranow 2011).

Several lines of evidence suggest vitamin D may help combat herpes and shingles outbreaks. In one study, dialysis patients who received iron and vitamin D supplementation were less likely to develop shingles outbreaks (Chao 2012). Vitamin D may also be able to alleviate the pain associated with shingles (Bartley 2009). In addition, as of the time of this writing, a study was underway to see if vitamin D can contribute to a more robust immune response to shingles vaccination (Ginde 2012).

With regard to herpes outbreaks, one group of researchers studied the relationship between the vitamin D status and antibody levels to several viruses, including herpes viruses, in children with multiple sclerosis and controls. They found that higher vitamin D levels corresponded with more antibodies against HSV-2 among children with multiple sclerosis, suggesting increased vitamin D levels may allow the immune system to better respond to the infection (Mowry 2011). Vitamin D is also able to increase the levels of an immunologic antimicrobial peptide called cathelicidin, which has antiviral properties against HSV-1 and other viruses (Beard 2011).

Zinc

Zinc plays a role in many aspects of the immune system. Zinc deficiency has been associated with immune dysfunction and an increased risk of infection (Overbeck 2008; Prasad 2008). Studies reveal that zinc levels tend to decrease with age, in parallel with declining immune function (Haase 2009).

In laboratory studies, zinc sulfate caused up to a 98% inhibition of replication of HSV-1 (Gordon 1975). In addition, another form of zinc – zinc oxide – was found to be effective in preventing HSV-2 from entering cells (Antoine 2012). Animal models have shown that zinc solutions protect against vaginal or rectal HSV-2 infections (Bourne 2005; Fernandez-Romero 2012). Also, topical zinc ointments have been used successfully to treat cutaneous outbreaks of herpes simplex in humans (Gaby 2006). In addition, topical ointments containing zinc oxide along with other natural ingredients were shown to cause significant improvement in oral herpes lesions (Ulbricht 2012; Godfrey 2001; Singh 2005).

Lysine

The herpes simplex virus requires large amounts of the amino acid arginine to replicate properly (Tomblin 2001). Lysine, another amino acid, has a similar structure to arginine and antagonizes its effects, making it harder for HSV to replicate (Tomblin 2001). For example, diets rich in lysine and low in arginine have been shown to help suppress HSV replication (Rubey 2010).

A double-blind, placebo-controlled study that included participants with oral-facial or genital herpes, found that consumption of one gram of L-lysine three times per day for 6 months reduced the frequency, duration, and severity of herpes outbreaks (Griffith 1987). Other studies have also found that lysine supplementation can reduce the frequency of cold sores that occur during HSV-1 infection (Ozden 2011). Overall, lysine appears to be able to reduce the intensity and the frequency of HSV flare-ups when it is used regularly (EBSCO CAM Review Board 2011).

Propolis

Propolis is a resin-like substance obtained from beehives and has a long history of medicinal use (Natural Medicines Comprehensive Database 2012). It contains a mixture of several compounds, including flavonoids and polyphenols, many of which have anti-HSV-1 activity (Schnitzler 2010). The variety of effects that it has on the immune system, together with its anti-inflammatory properties, may allow it to help the body more effectively fight infections (Storcin 2007).

In one study, a constituent of propolis was found to significantly inhibit the synthesis of HSV in cell cultures (Amoros 1994). Another study showed that a propolis extract has potent antiviral activity against HSV-2 in cell cultures (Nolkemper 2010). Notably, an ointment containing flavonoids from propolis was more effective in aiding the healing of genital herpes lesions and reducing local symptoms than the antiviral medication acyclovir (Vynograd 2000). Propolis, as a 3% ointment, was also shown to reduce the duration of cold sores caused by oral herpes and decreased pain associated with the lesions (Ehrlic 2011a).

Lactoferrin

Lactoferrin is a protein found in both cow and human milk (Berlutti 2011). It has natural antimicrobial properties and is able to help protect the body from bacterial, fungal, parasitic, and viral infections (Valenti 2005; Berlutti 2011; Jennsen 2008). In particular, many studies have shown that lactoferrin is able to inhibit the replication of HSV-1 and HSV-2 and also block the virus from entering cells (Fujihara 1995; Välimaa 2009; Andersen 2004; Marr 2009; Jennsen 2008; Jennsen 2005). Although clinical trials are needed to corroborate these findings, lactoferrin appears to be a promising therapeutic agent against HSV infections.

Curcumin

Curcumin is a compound found in the spice turmeric (Aggarwal 2007). It is thought to help the body combat many infections, including those caused by viruses, and has anti-inflammatory and antioxidant activities (Chainani-Wu 2003). In addition, topical creams containing curcumin have been used in Indian traditional medicine for diseases causing blisters, such as shingles (Chainani-Wu 2003). Curcumin was shown to provide protection against infection with HSV-1 and HSV-2 (Zandi 2010; Khan 2005; Kutluay 2008). The activity against HSV-1 was shown to occur due to curcumin’s ability to keep the virus from expressing genes necessary for infection and replication (Kutluay 2008).

Fucoidans

Fucoidans are naturally occurring sugar polymers found in edible seaweeds and some other oceanic sources (Fitton 2005). Fucoidans have been shown to stimulate the immune system (Fitton 2005). In addition, many fucoidans have potent antiviral activity against several common viruses, including HSV-1 and HSV-2 (Li 2008; Ly 2005; Feldman 1999; Lee 2004; Fitton 2005; Hayashi 2008). Animal models have found that fucoidans protect against HSV-1 by a combination of direct inhibition of viral replication and by stimulating the body’s immune response against the virus (Hayashi 2008). Human studies showed that oral fucoidan, administered for 10 days, can help speed the healing and inhibit the reactivation of lesions in HSV-1 and HSV-2 infections and in shingles (Fitton 2005).

Lemon Balm

Lemon balm (Melissa officinalis) is a form of mint used traditionally to treat numerous of ailments, including herpes outbreaks (Yarnell 2009). Several laboratory experiments have shown lemon balm extracts possess a variety of antiviral activities against both HSV-1 and HSV-2 (Mazzanti 2008; Astani 2012; Schnitzler 2008; Geuenich 2008; Nolkemper 2006; Allahverdiyev 2004; Dimitrova 1993). Clinical trials have evaluated the efficacy of topical lemon balm preparations and shown positive results. In one trial, a lemon balm ointment improved symptoms of oral herpes compared to placebo when applied 4 times daily for 5 days; the lemon balm treatment also prevented the spread of the outbreak, and the authors suggested that lemon balm may increase the time between outbreaks (Koytchev 1999). Two additional trials involving 115 and 116 patients, respectively, also found that local therapy with lemon balm extract effectively eases oral herpes symptoms (Wolbling 1994).

Licorice

Licorice (Glycyrrhiza spp.) has demonstrated antiviral activity against several viruses, including HSV-1 and varicella zoster (Fiore 2008; Takahara 1994). In an animal model of herpes simplex encephalitis, licorice root extract reduced HSV-1 viral replication in the brain by 45% and significantly improved the survival rate of treated animals (Sekizawa 2001).

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