Herpes Simplex Natural Treatments by Jeffrey Dach MD
Sarah is a 47 year old pediatric ICU nurse who has been plagued with oral and genital herpes breakouts every few months. She is taking Acyclovir, an anti-viral drug which worked at first, but lately doesnt seem to be helping. Sarah called into the office and asked if we had any natural treaments she could try for the herpes break-outs.
Herpes is a common problem I see in the office. Many of these patients are on long term acyclovir, the standard anti-viral medication which is quite effective at suppressing recurrence. However, the virus can develope drug resistance to acyclovir which is not without adverse side effects. Many would like to know about safer natural remedies. This article discusses Lemon Balm, Cimetidine, Aloe Vera, Lysine, Olive Leaf, Lithium and low level laser natural treatments for Herpes which are also quite effective at eradicating infection and suppressing outbreaks.
Two Types of Herpes
Herpes Simplex Type I (HSV-1) is transmitted through kissing, sharing drinking utensils, and other oral contact. (see image at left). Herpes Type II (HSV2) is the main cause of genital Herpes, transmitted via sexual contact. Link to this article,
Anti-Herpes Drugs – Acyclovir and Valcyclovir
Despite an inability to eradicate latent virus, Acyclovir is considered the standard antiviral therapy for herpes simplex virus infection, Acyclovir (Zovirax) and Valacyclovir (Valtrex) are prescribed for labial herpes, genital herpes, cold sores, shingles, and chicken pox. They can be used short term for acute infection, or long term for suppression of outbreaks.
Long term safety studies on these drugs are comforting and show a high safety profile. The drugs are DNA polymerase inhibitors, with preferential activity for viral DNA polymerase. However, the drugs can have an effect on human DNA polymerase as well, and therefore may not be totally free of adverse side effects. The most common adverse effects are headache, nausea and vomiting.
Natural Treatments for Herpes – Lysine
Lysine, a commonly available amino acid with no adverse side effects has been shown in numerous studies to reduce frequency of Herpes outbreaks. Usual Dosage is 750 mg -1000 mg two to three times a day.(1)
Dr. Kathleen Regan’s article summarizes the medical research on Lysine for Herpes citing seven randomized, double-blind, placebo-controlled studies on the effectiveness of lysine in preventing and reducing severity of outbreaks of herpes.(2) Buy Lysine on Amazon
Reduce Arginine Containing Foods
Lysine inhibits viral replication, while Arginine is a requirement for viral replication. Dr Regan mentions the importance of the Lysine to Arginine ratio in the diet. Reducing Arginine containing foods such as cashews, nuts and seeds, etc. while taking the lysine is important for maximal benefit.(2)
Dr Alan Gaby’s article, Natural Remedies for Herpes simplex, also discusses the use of Lysine for Herpes and the importance of reducing Arginine containing foods.(3)
Lithium for Herpes
Lithium is a naturally occurring mineral found in our water supply and is available as a drug called Lithium Carbonate, or as a nutritional supplement called Lithium Orotate. The drug form of Lithium Carbonate comes in 300 mg tablets is used to treat bipolar syndrome, and requires blood levels to avoid toxicity. The Lithium Orotate is low dose 5 mg capsules and regarded as safe, as no blood testing is required,
Over the years, Dr. Amsterdam at the University of Pennsylvania noticed a benefit for recurrent herpes infections in his Bi-Polar patients treated with Lithium Carbonate. (4-15) Further studies show that not only does lithium inhibit herpes virus replication, it also restores host cellular functions which were hijacked by the virus. (4-15)
Dr Jonathan Wright created a formulation called HPX which combines lithium with selenium, lysine, vitamin C, and olive leaf extract as a natural remedy for Herpes. Credit and Thanks goes to the Jonathan Wright MD Newsletter for bringing the benefits of Lithium to my attention. Buy Lithium Orotate on Amazon.
Lithium for Chronic Alcoholism (17-18)
While we are on the topic of Lithium, there may be benefit as treatment for chronic alcoholism, as reported by Dr. Jonathon Wright in his newsletter. Dr Wright advises 10 mg of Lithium Orotate three times daily towean off the chronic alcoholic (17-18)
Cimetidine for Herpes Simplex and Herpes Zoster
Cimetidine (Tagamet) is an old anti-acid drug that is off patent, having been replaced by the newer PPI drugs (proton pump inhibitors). Cimetidine is now available OTC (over the counter). According to Dr Phillip Cohen in a 1988 letter to the editor in J Amer Acad Derm, cimetidine functions as an immune modulator, and is effective for Herpes Simplex of the oral cavity (oro-facial herpes) and genital area (herpes labialis).(25) Cimetidine is a competitive inhibitor of the H2 class histamine receptor, present on a subclass of suppressor T lymphocytes cells, which are inhibited. The anti-viral effect of Cimetidine is due to this augmentation of the host immune system. Dr Kurzrock and Levy report success in 5 immuno-compromised patients suffering from oro-facial Herpes, with rapid clearing of lesions with 1,200 mg per day Cimetidine.(26-28) Cimetidine is useful for Herpes Zoster (Shingles) as well, as reported by Dr Van Der Spuy, Levy and Levin in the Jul 1980 S African Med .(27) They recommended 1600 mg per day for two days to abort a crop of blisters.(27)
Lemon Balm for Herpes
Lemon balm, (Melissa officinalis) is a widely grown garden plant used for centuries for its medicinal properties. The extract and essential oil has been found useful for herpes simplex, having high virucidal properties even at low concentrations. In addition, lemon balm (Melissa officinalis) extract inhibits attachment of herpes simplex virus to host epithelial cells. Extensive studies over the years reveals excellent efficacy for Lemon Balm extracts and oils in prevention and treatment of Herpes Simplex. (29-36)
Aloe Vera Useful for Herpes
The well known anti-inflammatory gel of the Aloe Vera Plant has been found useful for treament of Herpes Simplex One and Two with considerable successs. Aloe Vera is widely available as an outdoor plant in southern climates.(37-39) See my previous article on Aloe Vera.
My previous article on low level laser discussed this device as a useful treatment for Herpes. Considerable research, much of it from Brazil, has been published on the benefits of low level laser to hasten healing and prevent breakouts of herpes.(19-20) Battery operated Low Level Lasers are inexpensive and available for home use. (see left image)
Dipyridimole for Preventing Herpes Reactivation
Conclusion: Cimetidine, available over the counter, in combination of Natural Remedies listed above are available for those wishing to avoid Acyclovir, or if the virus is resistant to Acyclovir.
Oral inosine pranobex is used as an anti-viral drug and immune stimulant.
This article is part one. For part two click here.
Articles with Related Interest:
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314
Links and References
Header image: Herpes Labialis (arrow) courtesy of wikimedia.
Herpes General information
Herpes simplex virus – University of Maryland
Acyclovir- Acyclovir is used to treat infections caused by herpes viruses. Illnesses caused by herpes viruses include genital herpes, cold sores, shingles, and chicken pox.
Valacyclovir (Valtrex) suppressive therapy 500 mg of Valtrex daily
Lysine for Herpes
Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Griffith RS1, Walsh DE, Myrmel KH, Thompson RW, Behforooz A.
A double-blind, placebo-controlled, multicenter trial of oral L-lysine monohydrochloride for the prevention and treatment of recurrent herpes simplex (HSV) infection was conducted. The treatment group was given L-Lysine monohydrochloride tablets (1,000 mg L-lysine per dose) 3 times a day for 6 months. A total of 27 (6 male and 21 female) subjects on L-lysine and 25 (6 male and 19 female) subjects on placebo completed the trial. The L-lysine treatment group had an average of 2.4 (p less than 0.05) less HSV infections, symptoms were significantly (p less than 0.05) diminished in severity and healing time was significantly reduced (p less than 0.05). L-Lysine appears to be an effective agent for reduction of occurrence, severity and healing time for recurrent HSV infection.
The Truth About Arginine, Lysine and Herpes Simplex Virus by Dr. Kathleen Regan, ND on April 17, 2013
3) Natural Remedies for Herpes simplex Alan Gaby
Natural Remedies for Herpes simplex by Alan R. Gaby, MD full pdf avaiable
Lithium for herpes
4) Natural Remedies for Herpes simplex Alan Gaby
Natural Remedies for Herpes simplex by Alan R. Gaby, MD full pdf avaiable
Amsterdam JD, Maislin G, Hooper MB.
Suppression of herpes simplex virus infections with oral lithium carbonatea possible antiviral activity. Pharmacotherapy 1996; 16(6): 1,070-1,075 – 1Department of Psychiatry, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
In vitro studies have shown an inhibitory effect of lithium salts on herpes simplex virus (HSV) replication by mechanisms that interfere with viral DNA synthesis. Moreover, clinical studies have shown that oral lithium carbonate and topical lithium succinate can suppress genital HSV infections in humans. We conducted a randomized, double-blind, placebo-controlled trial of oral lithium carbonate in 11 healthy subjects age 28-65 years (mean +/- SD age 38 +/- 11 years) who had at least four recurrent HSV infections in the year preceding the study. Six patients completed at least 5 months of lithium therapy at a mean (+/-SD) average daily lithium dose of 437 +/- 185 mg (range, 150-900 mg) and an average serum lithium level of 0.56 +/- 0.20 mmol/L. Overall, lithium treatment resulted in a consistent reduction in the mean number of episodes/month, the average duration of each episode, the total number of infection days/month, and the maximum symptom severity. In contrast, treatment with placebo resulted in an increase in three out of the four severity measures. Although the comparisons between the treatment groups did not achieve statistical significance due to the limited sample size, there was a clear “trend” for a reduction in the total monthly duration of all HSV infections with lithium (p = 0.08). Lithium treatment was well tolerated and produced no deleterious effects on renal or thyroid function. These observations lend support to prior observations of an antiviral activity of lithium, and suggest the possibility that oral lithium may represent a safe prophylactic agent in patients with recurrent HSV infections.
Psychopharmacol Bull. 1990;26(3):343-7.
Reduced rate of recurrent genital herpes infections with lithium carbonate. Amsterdam JD1, Maislin G, Potter L, Giuntoli R.
Preliminary observations indicate that lithium carbonate may have an anti-herpes simplex virus activity. We conducted a randomized, double-blind, placebo-controlled trial of oral lithium therapy in 10 healthy women with chronic, recurrent genital herpes infections. During one year of lithium treatment at a mean (+/- SD) daily dose of 587 +/- 49 mg and an average plasma lithium level of 0.51 mEq/L, we observed a significant reduction in the total monthly duration of all herpes episodes (p less than .01), the average duration of each herpes infection (p less than .01), the maximum symptom severity (p less than .01), and a clinical severity index score (p less than .004). The onset of prophylaxis was gradual, with the duration of each episode declining by an average of 0.5 days per month. The present data indicate that chronic lithium therapy may be effective in preventing recurrent genital herpes infections.
Biol Psychiatry. 1990 Feb 15;27(4):447-53.
A possible antiviral action of lithium carbonate in herpes simplex virus infections. Amsterdam JD1, Maislin G, Rybakowski J.
1Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia.
There has been considerable interest in the possibility that some psychotropic medications may possess antiviral activity. Several clinical observations suggest that lithium may inhibit the reactivation of latent herpes simplex virus, thereby reducing the number of recurrent infections. We performed a retrospective study examining the putative antiviral activity of various psychotropic agents in 177 subjects receiving lithium prophylaxis and a comparison group of 59 subjects receiving other antidepressant drugs for affective illness. Chronic lithium administration resulted in a significant reduction in the mean rate of recurrent labial herpes infections when compared to the pretreatment period (p less than 0.001). In contrast, the mean rate of herpes infections was unchanged in patients taking other antidepressants (p = 0.53). Although the overall reduction in herpes infections was not significantly different between groups, the proportion of subjects reporting a reduction in infection rate was greater in the lithium group (71%) compared with those receiving other antidepressants (52%) (p = 0.07). These data compliment prior in vitro and clinical studies demonstrating a potential antiviral activity for lithium carbonate.
Med Microbiol Immunol. 1980;168(2):139-48.
The effect of lithium chloride on the replication of herpes simplex virus. Skinner GR, Hartley C, Buchan A, Harper L, Gallimore P.
Lithium chloride inhibited the replication of type 1 and type 2 Herpes simplex virus at concentrations which permitted host cell replication. Virus polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudorabies and vaccinia virus, was inhibited but there was no inhibition of two RNA viruses, namely, EMC and influenze virus.
Biochem Biophys Res Commun. 1989 May 15;160(3):1073-8.
Lithium chloride restores host protein synthesis in herpes simplex virus-infected endothelial cells. Ziaie Z1, Kefalides NA.
1Connective Tissue Research Institute, University of Pennsylvania, Philadelphia.
In previous studies we have shown that herpes simplex virus type 1 (HSV-1) infection suppresses host-cell protein synthesis in human endothelial cells (EC). It has been demonstrated that lithium salts prevent viral replication in HSV-1 infected cells. In the present study, we have measured host-cell protein synthesis in HSV-1 infected EC in the presence or absence of 20 and 30 mM LiCl. Although LiCl restored synthesis of almost all host-cell proteins, [35S]methionine incorporation was most pronounced in thrombospondin and plasminogen activator inhibitor 1 and least in fibronectin and type IV collagen. LiCl was more effective at the higher concentration (30 mM) and when the compound was added to the EC culture at the time of infection rather than after adsorption of HSV-1. Synthesis of virus proteins continued in LiCl-treated EC but at a reduced rate. The data suggest that LiCl not only interferes with virus replication, but may also, to some extent, interfere with the virion-associated inhibition of host protein synthesis.
Lab Invest. 1994 Jan;70(1):29-38.
Lithium chloride suppresses the synthesis of messenger RNA for infected cell protein-4 and viral deoxyribonucleic acid polymerase in herpes simplex virus-1 infected endothelial cells. Ziaie Z1, Brinker JM, Kefalides NA. 1Connective Tissue Research Institute, University of Pennsylvania, Philadelphia.
Patients treated with lithium salts for manic depression had a lower incidence of herpes simplex infections. Initial studies in our laboratory demonstrated that addition of LiCl in cultures of human endothelial cells infected with herpes simplex virus suppressed viral replication and allowed synthesis of host proteins.
EXPERIMENTAL DESIGN:Based on the above observations, we decided to study the optimal condition for the lithium effect and determine the process of inhibition of viral replication. Endothelial cell cultures infected with herpes simplex virus-1 were exposed to LiCl at various times postinfection. The levels of host and viral mRNAs were measured by Northern and slot blot hybridization. The pattern of protein synthesis was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot and replication was assessed by plaque assay.
RESULTS:LiCl inhibited virus replication in a dose- and time-dependent manner as was reflected in the sharp decrease or absence of infectious virus production. The condition for optimal effects of LiCl were the addition of the salt between 0-3 hours postinfection, and at a concentration of 30 mM. LiCl suppressed the synthesis of viral polypeptides, whereas the synthesis of host proteins was maintained. Similar results were observed with phosphonoacetic acid, an inhibitor of viral DNA polymerase. NaCl, at the same concentration as LiCl, did not prevent the virus-induced inhibition of host cell protein synthesis. The level of host mRNA for fibronectin, thrombospondin, collagen type IV, actin, and plasminogen activator inhibitor-1 were maintained in the presence of LiCl. mRNAs for viral proteins, ICP-4 and DNA polymerase were nearly undetectable when LiCl was added with the virus (0 time postinfection).
CONCLUSIONS:The data indicate that LiCl treatment results in suppression of herpes virus mRNAs, i.e., mRNAs for ICP-4 and DNA polymerase, thereby inhibiting replication. On the other hand, the levels of host mRNAs are maintained to varying degrees depending on the message. The data suggest that a very early step in the process of viral replication is affected by LiCl, since the drug is maximally effective when added with the virus.
11) Mechanisms of Lithium Chloride on Cell Infection by Transmissible Gastroenteritis Coronavirus
Ren X, Meng F, Yin J, Li G, Li X, et al. (2011)
Action Mechanisms of Lithium Chloride on Cell Infection by Transmissible Gastroenteritis Coronavirus. PLoS ONE 6(5):
Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus. Lithium chloride (LiCl) has been found to be effective against several DNA viruses, such as Herpes simplex virus and vaccinia virus. Recently, we and others have reported the inhibitory effect of LiCl on avian infectious bronchitis coronavirus (IBV) infection, an RNA virus. In the current study, the action mechanism of LiCl on cell infection by TGEV was investigated. Plaque assays and 3-(4,5)-dimethylthiahiazo(-z-
free full Br J Pharmacol. Mar 2011; 162(6): 1410–1423.
Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques
Inge De Meyer,1 Wim Martinet,1 Cor E Van Hove,1 Dorien M Schrijvers,1 Vicky Y Hoymans,3 Luc Van Vaeck,2 Paul Fransen,1 Hidde Bult,1 and Guido RY De Meyer1 1Division of Pharmacology, University of Antwerp, Antwerp, Belgium
2Division of Chemistry, University of Antwerp, Antwerp, Belgium
3Laboratory for Cellular and Molecular Cardiology, Antwerp University Hospital, and Division of Cardiology, University of Antwerp, Antwerp, Belgium
Miss Inge De Meyer, Pharmacology, University of Antwerp, Wilrijk, Antwerp 2610, Belgium.
Mol Vis. 2013 Jul 19;19:1502-14. Print 2013.
Lithium chloride promotes host resistance against Pseudomonas aeruginosa keratitis.
Chen K1, Wu Y, Zhu M, Deng Q, Nie X, Li M, Wu M, Huang X.
To explore the role of lithium chloride (LiCl) in Pseudomonas aeruginosa (PA) keratitis.
METHODS:B6 mice were subconjunctivally injected with LiCl in contrast to appropriate control sodium chloride (NaCl), and then routinely infected with PA. Clinical score, slit-lamp photography, hematoxylin and eosin (H&E) staining, and bacterial plate counts were used to determine the role of LiCl in PA keratitis. Messenger ribonucleic acid and protein levels of inflammatory cytokines in PA-challenged mouse corneas and in vitro cultured macrophages and neutrophils were measured with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Apoptosis of the infiltrating inflammatory cells in the PA-infected murine corneas was assessed using terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling staining and propidium iodide staining associated with flow cytometry. In cultured murine macrophages and neutrophils, cell apoptosis was determined with annexin V/propidium iodide double staining associated with flow cytometry and western blot analysis for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase.
RESULTS:Treatment with LiCl reduced the severity of corneal disease by reducing corneal inflammatory response and bacterial burden. Moreover, LiCl increased anti-inflammatory cytokine interleukin-10 levels, decreased proinflammatory cytokine tumor necrosis factor-α levels, and enhanced apoptosis of infiltrating macrophages and neutrophils in the PA-infected mouse corneas. In vitro studies further confirmed that LiCl elevated anti-inflammatory cytokine expression but reduced proinflammatory cytokine production, as well as promoted cell apoptosis in murine macrophages and neutrophils.
CONCLUSIONS:This study demonstrates a protective role of LiCl in PA keratitis. LiCl promotes host resistance against PA infection by suppressing inflammatory responses, enhancing inflammatory cell apoptosis, and promoting bacterial clearance.
Medical Hypotheses Volume 7, Issue 7, Pages 885–890, July 1981 Immunopotentiation and inhibition of herpes virus activation during therapy with lithium carbonate
J. Lieb 41 Village Lane, Bethany, CT. 06525 USA
Recurrent respiratory tract infections and other recurrent manifestations of defective immunity remitted in nine patients taking lithium. Remission of viral activation in four patients with recurrent herpes labialis also appeared to be due to lithium therapy.
15) The immunostimulating and antimicrobial properties of lithium and antidepressants Julian Lieb, M.D is a retired Yale medical school professor,
Remission of such manifestations of viral infections as sinusitis, sinobronchitis, frequent colds, sorethroats, cold sores and genital herpes in patients taking lithium carbonate has been reported.[61 – 65]
In a retrospective study of the antiviral activity of various psychotropic agents, chronic lithium administration reduced the mean rate of recurrent labial herpes infections. Lithium and antidepressants reduced the mean yearly rates of common, ‘ﬂu-like’colds.[63,64] In a randomised, double blind, placebo  controlled study lithium reduced the frequency andduration of recurrences of genital herpes.
The polymorphonuclear leukocytes (PMN) of a 29-year-old woman with eczema and recurrent staphylococcal and streptococcal skin infections were unresponsive to standard chemotactic stimuli.
In vitro addition of lithium to her PMN preparations restored their chemotactic response. After receiving lithium carbonate, 1 g per day for 5 weeks she became free of infection and relapsed when lithium was withdrawn.
Lithium chloride prevents replication of type 1 and 2 herpes virus in baby hamster kidney cells. Virus particle production, polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudo rabies and vaccinia virus was inhibited but two RNA viruses, EMC and inﬂuenza virus were not inhibited.
16) olive leaf extract exhibits antiviral activity
Antiviral Research 66 (2005) 129–136
The olive leaf extract exhibits antiviral activity against viral
haemorrhagic septicaemia rhabdovirus (VHSV)
Vicente Micol 1, Nuria Caturla 1, Laura P´erez-Fons,
Vicente M´as, Luis P´erez, Amparo Estepa ∗
Instituto de Biolog´ıa Molecular y Celular, Universidad Miguel Hern´andez, E-03202-Elche, Alicante, Spain
Received 10 November 2004; accepted 11 February 2005
Lithium Orotate for alcoholism
Alcohol. 1986 Mar-Apr;3(2):97-100.
Lithium orotate in the treatment of alcoholism and related conditions.
The subjects were 42 alcoholic patients (33 males and 9 females) who were treated with lithium orotate during an alcohol rehabilitation program in a private clinical setting for at least six months. They derive from a total number of 105 patients who received this treatment initially, while the remainder discontinued the treatment within six months. The data were collected from a private practice record and the follow-up varied between six months and 10 years. The 42 patients studied displayed a multitude of complaints in addition to chronic alcoholism. These included liver dysfunction, seizure disorders, headaches, hyperthyroidism, affective disorders. Meniere’s syndrome, liver and lung cancers. Thirty-six of the 42 patients studied had been hospitalized at least once for the management of their alcoholism. Lithium orotate was given, 150 mg daily, with a diet low in simple carbohydrates and containing moderate amounts of protein and fat. In addition, calcium orotate (for hepatic involvement), magnesium orotate, bromelaine, and essential phospholipids (for cardiac problems), and supportive measures were instituted, if required. Lithium orotate proved useful as the main pharmacologic agent for the treatment of alcoholism. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. Lithium orotate therapy was safe and the adverse side effects noted were minor, i.e., eight patients developed muscle weakness, loss of appetite or mild apathy. For these patients, the symptoms subsided when the daily dose was given 4 to 5 times weekly.(ABSTRACT TRUNCATED AT 250 WORDS)
Lithium for treatment of alcoholism
18) For “practicing” alcoholics, I recommend a trial of lithium orotate,
10 milligrams three times daily (along with diet advice, niacin,
glutamine, and other supplements). I ask recovering alcoholics to
try 5 milligrams, three times daily (occasionally more). The
majority of these patients report improved mood and decreased
desire for alcohol after about six weeks using lithium therapy.
McMillan TM. Lithium and the treatment of alcoholism: a critical review. British Journal of Addiction 1981; 76: 245-258
Low intensity Laser for Herpes
Lasers Med Sci. 2013 Apr 13. [Epub ahead of print]
Laser treatment of recurrent herpes labialis: a literature review.
de Paula Eduardo C1, Aranha AC, Simões A, Bello-Silva MS, Ramalho KM, Esteves-Oliveira M, de Freitas PM, Marotti J, Tunér J. Author information 1Special Laboratory of Lasers in Dentistry (LELO), Department of Restorative Dentistry, School of Dentistry of the University of São Paulo (USP), Av. Prof. Lineu Prestes, 2227, 05508-000, São Paulo, SP, Brazil,
Recurrent herpes labialis is a worldwide life-long oral health problem that remains unsolved. It affects approximately one third of the world population and causes frequent pain and discomfort episodes, as well as social restriction due to its compromise of esthetic features. In addition, the available antiviral drugs have not been successful in completely eliminating the virus and its recurrence. Currently, different kinds of laser treatment and different protocols have been proposed for the management of recurrent herpes labialis. Therefore, the aim of the present article was to review the literature regarding the effects of laser irradiation on recurrent herpes labialis and to identify the indications and most successful clinical protocols. The literature was searched with the aim of identifying the effects on healing time, pain relief, duration of viral shedding, viral inactivation, and interval of recurrence. According to the literature, none of the laser treatment modalities is able to completely eliminate the virus and its recurrence. However, laser phototherapy appears to strongly decrease pain and the interval of recurrences without causing any side effects. Photodynamic therapy can be helpful in reducing viral titer in the vesicle phase, and high-power lasers may be useful to drain vesicles. The main advantages of the laser treatment appear to be the absence of side effects and drug interactions, which are especially helpful for older and immunocompromised patients. Although these results indicate a potential beneficial use for lasers in the management of recurrent herpes labialis, they are based on limited published clinical trials and case reports. The literature still lacks double-blind controlled clinical trials verifying these effects and such trials should be the focus of future research.
J Invest Dermatol. 1999 Aug;113(2):221-3.
Low-intensity laser therapy is an effective treatment for recurrent herpes simplex infection. Results from a randomized double-blind placebo-controlled study. Schindl A1, Neumann R.
Recurrent infection with herpes simplex virus is a common disease. Recently, alternative therapies have been introduced. Among those, low-intensity laser therapy mainly used for the acceleration of wound healing and in pain therapy has previously been shown to be of benefit in herpes zoster infections. In this study we evaluated the influence of low-intensity laser therapy (wavelength 690 nm, intensity: 80 mW per cm2, dose: 48 J per cm2) in 50 patients with recurrent perioral herpes simplex infection (at least once per month for more than 6 mo) in a randomized, double-blind placebo-controlled trial design. Patients in the laser group received daily irradiations for 2 wk, whereas patients in the placebo group were sham-irradiated. After completion of the laser/sham treatment, patients were asked to return to the Department of Dermatology, University of Vienna Medical School at the time of recurrence. All except two patients completed the study and were monitored for 52 wk. The median recurrence-free interval in the laser-treated group was 37.5 wk (range: 2-52 wk) and in the placebo group 3 wk (range: 1-20 wk). This difference was found to be statistically significant (p < 0.0001; Wilcoxon’s Rank Sum Test). In conclusion, we demonstrated that a total of 10 irradiations with low-intensity laser therapy significantly lowers the incidence of local recurrence of herpes simplex infection. Since this athermic phototherapeutic modality represents a safe, noninvasive treatment, it might be considered as an alternative to established therapeutic regimens in this indication.
BHT for herpes
Science. 1975 Apr 4;188(4183):64-6.
Butylated hydroxytoluene inactivated lipid-containing viruses.
Snipes W, Person S, Keith A, Cupp J.
Butylated hydroxytoluene (BHT) is widely used as a food preservative for its antioxidizing property. This small, hydrophobic molecule has been found to be a potent inactivator of lipid-containing mammalian and bacterial viruses.
Poult Sci. 1978 Nov;57(6):1526-9.
Studies on the effect of butylated hydroxytoluene on Mycoplasma synoviae. Vardaman TH, May JD, Drott JH.
Butylated hydroxytoluene (BHT) is one of the antioxidants added to human and animal feed products in concentrations ranging from 50 to 200 ppm to delay degradation of the labile lipid components. BHT is known to be an inactivator of mammalian and bacterial viruses that contain lipid. Results of in vitro studies showed that 10 ppm of BHT in Mycoplasma medium prevented growth of each of the six Mycoplasma synoviae (Ms) isolates. BHT added at 100, 200, and 400 ppm in the feed did not have any significant in vivo effect on the Ms serological responses or show any chemoprophylactic effect on birds infected with Ms.
Cimetidine for Herpes Simplex
25) Cohen, Philip R., and Razelle Kurzrock. “Herpes simplex virus infections and cimetidine therapy.” Journal of the American Academy of Dermatology 19.4 (1988): 762-763. Herpes simplex and cimetidine Cohen Philip Razelle Kurzrock J Amer Acad Derm 1988
26) Kurzrock, R., M. Auber, and G. M. Mavligit. “Cimetidine therapy of herpes simplex virus infections in immunocompromised patients.” Clinical and experimental dermatology 12.5 (1987): 326-331.
Five severely immunocompromised patients with progressive mucocutaneous manifestations of culture‐proven herpes simplex virus infection were treated with cimetidine—1200 mg per day by mouth (four patients) or by i.v. infusion (one patient). Treatment resulted in rapid improvement as evidenced by decreased local pain and crusting of lesions within 24–48 h. Complete resolution was observed within 3–13 days. These encouraging, albeit preliminary, findings suggest that cimetidine warrants further, large‐scale trials in patients with herpes virus infections.
27) Levy, D. W., and W. Levin. “Cimetidine in the treatment of herpes virus infections.” South African medical journal 58.3 (1980): 112-116.Cimetidine treatment of herpes virus Levy D W Levin S African med J 1980
28) WAKEFIELD, DENIS. “Cimetidine in recurrent genital herpes simplex infection.” Annals of internal medicine 101.6 (1984): 882-882.
Lemon Balm for Herpes
29) Świąder, Katarzyna, Katarzyna Startek, and Christofora Hanny Wijaya. “The therapeutic properties of Lemon balm (Melissa officinalis L.): Reviewing novel findings and medical indications.”Therapeutic properties of Lemon balm Melissa officinalis medical indications Świąder Katarzyna J Appl Botany 2019
The lemon balm essential oil, secreted by glandular trichomes, has a pale-yellow colour with lemony aroma
The water extract of lemon balm leaves and rosmarinic acid also have antiviral activity. In in vitro studies, it inhibited the binding of HSV-1 (herpes simplex virus 1) to host cells and virus penetration in cells (aStani et al., 2014).
30) Moradi, Mohammad-Taghi, Mahmoud Rafieian-Kopaei, and Ali Karimi. “A review study on the effect of Iranian herbal medicines against in vitro replication of herpes simplex virus.” Avicenna journal of phytomedicine 6.5 (2016): 506.
Leaves of Melissa officinalis (lemon balm), a member of the Lamiaceae family (Saller et al., 2001 ▶; Wolbling and Leonhardt, 1994 ▶) contain polyphenols such as rosmarinic acid and flavonoids (Carnat et al., 1998 ▶). M. officinalis has been evaluated for its activity against HSV, in vitro (Geuenich et al., 2008 ▶; Nolkemper et al., 2006 ▶). Aqueous extract of M. officinalis has been shown to interact directly with free viral particles of two acyclovir-resistant and one acyclovir-sensitive strains of HSV-1 at low IC50 values of 0.13, 0.23 and 0.4 μg/ml and high selectivity indices of 2692, 1522 and 875, respectively with inhibiting attachment of these strains to the host cells in a dose-dependent manner. The results of this work indicated that anti-HSV-1 activity of Melissa extract was mainly due to its rosmarinic acid contents (Astani et al., 2014 ▶).
31) Astani, Akram, Mojdeh Heidary Navid, and Paul Schnitzler. “Attachment and Penetration of Acyclovir‐resistant Herpes Simplex Virus are Inhibited by Melissa officinalis Extract.” Phytotherapy research 28.10 (2014): 1547-1552.
Medicinal plants are increasingly of interest as novel source of drugs for antiherpetic agents, because herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. An aqueous extract of Melissa officinalis and the phenolic compounds caffeic acid, p-coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) acyclovir-sensitive and clinical isolates of acyclovir-resistant strains in vitro. When drugs were added during the intracellular replication of HSV-1 infected cells, no antiviral effect was observed by plaque reduction assay. However, Melissa extract interacted directly with free viral particles of two acyclovir-resistant HSV strains at low IC50 values of 0.13 and 0.23 µg/mL and high selectivity indices of 2692 and 1522, respectively. The Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner for acyclovir-sensitive and acyclovir-resistant strains. These results indicate that mainly rosmarinic acid contributed to the antiviral activity of Melissa extract. Penetration of herpes viruses into cells was inhibited by Melissa extract at 80% and 96% for drug-sensitive and drug-resistant viruses, respectively. Melissa extract exhibits low toxicity and affects attachment and penetration of acyclovir-sensitive and acyclovir-resistant HSVs in vitro.
33) Astani, Akram, Jürgen Reichling, and Paul Schnitzler. “Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro.” Chemotherapy 58.1 (2012): 70-77.
However, the Melissa extract demonstrated a high virucidal activity against HS V-1, even at very low concentrations of 1. 5 g/ml, whereas similar results for phenolic compounds were only achieved at 100 times higher concentrations. Besides the virucidal activity, the Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner. These results indicate that rosmarinic acid was the main contributor to the antiviral activity of Melissa extract. However, the selectivity index of Melissa extract of 875 against HSV is superior to the selectivity indices of single constituents.
, the phenolic compound rosmarinic acid in the Melissa extract contributed mainly to the vi-rucidal activity,
Melissa extract highly inhibits HSV attachment to host cells.
Melissa extract exhibits low toxicity, is virucidal and affects HSV-1 attachment to host cells in vitro.
34) Schnitzler, P., et al. “Melissa officinalis oil affects infectivity of enveloped herpesviruses.” Phytomedicine 15.9 (2008): 734-740.
Extracts and essential oils of medicinal plants are increasingly of interest as novel drugs of antimicrobial and antiviral agents, since herpes simplex virus (HSV) might develop resistance to commonly used antiviral agents. Melissa officinalis essential oil was phytochemically examined by GC-MS analysis, its main constituents were identified as monoterpenaldehydes citral a, citral b and citronellal. The antiviral effect of lemon balm oil, the essential oil of Melissa officinalis, on herpes simplex virus was examined. The inhibitory activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on monkey kidney cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of balm oil for herpes simplex virus plaque formation was determined at high dilutions of 0.0004% and 0.00008% for HSV-1 and HSV-2, respectively. At noncytotoxic concentrations of the oil, plaque formation was significantly reduced by 98.8% for HSV-1 and 97.2% for HSV-2, higher concentrations of lemon balm oil abolished viral infectivity nearly completely. In order to determine the mode of antiviral action of this essential oil, time-on-addition assays were performed. Both herpesviruses were significantly inhibited by pretreatment with balm oil prior to infection of cells. These results indicate that Melissa oil affected the virus before adsorption, but not after penetration into the host cell, thus lemon balm oil is capable of exerting a direct antiviral effect on herpesviruses. Considering the lipophilic nature of lemon balm essential oil, which enables it to penetrate the skin, and a high selectivity index, Melissa officinalis oil might be suitable for topical treatment of herpetic infections.
35) Wölbling, R. H., and K. Leonhardt. “Local therapy of herpes simplex with dried extract from Melissa officinalis.” Phytomedicine 1.1 (1994): 25-31.
An overt multicentric study involving 115 patients and another subsequent placebo-controlled double-blind study involving 116 patients contributed significantly to the corroborative evidence of the antiviral activity in vitro of a specially prepared dried extract from Melissa leaves (Melissa officinalis L.) against herpes simplex infections. The studies provided the proof that the ingredient gave protection against herpes simplex infections. The initiation of the treatment in the very early stages of the infection revealed itself as most effective.
36) Koytchev, R., R. G. Alken, and S. Dundarov. “Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis.” Phytomedicine 6.4 (1999): 225-230.
A double-blind, placebo-controlled, randomized trial was carried out with the aim of proving efficacy of standardized balm mint cream [active ingredient: 1% Lo-701–dried extract from Melissa officinalis L. leaves (70:1)] for the therapy of herpes simplex labialis. Sixty six patients with a history of recurrent herpes labialis (at least four episodes per year) in one center were treated topically; 34 of them with verum and 32 with placebo. The cream had to be smeared on the affected area four times daily over five days. A combined symptom score of the values for complaints, size of affected area and blisters at day 2 of therapy was formed as the primary target parameter. There was a significant difference in the values of the primary target parameter between both treatment groups: verum 4.03 +/- 0.33 (3.0); placebo 4.94 +/- 0.40 (5.0); values given are mean +/- SEM (median) of the symptoms score on day 2 of therapy. The tested formulation is effective for the treatment of herpes simplex labialis. The significant difference in the combined symptom score on the second day of treatment is of particular importance having in mind that the complaints in patients suffering from herpes labialis are usually most intensive at that time. In addition to the shortening of the healing period, the prevention of a spreading of the infection and the rapid effect on typical symptoms of herpes like itching, tingling, burning, stabbing, swelling, tautness and erythema, the balm mint cream has a further advantage. The different mechanism of action of the balm mint extract rules out the development of resistance of the herpes virus. Some indication exists that the intervals between the periods with herpes might be prolonged with balm mint cream treatment.
37) Zandi, Keivan, et al. “Antiviral activity of Aloe vera against herpes simplex virus type 2: An in vitro study.” African Journal of Biotechnology 6.15 (2007).
38) Kambizi, L. G. B. M., et al. “Anti-viral effects of aqueous extracts of Aloe ferox and Withania somnifera on herpes simplex virus type 1 in cell culture.” South African Journal of Science 103.9-10 (2007): 359-360.
39) Syed, T. A., et al. “Management of genital herpes in men with 0.5% Aloe vera extract in a hydrophilic cream: a placebo-controlled double-blind study.” Journal of Dermatological Treatment 8.2 (1997): 99-102.
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Pirtle EC, Sacks JM, Nachman RJ. Antiviral effectiveness of butylated hydroxytoluene against pseudorabies (Aujeszky’s disease) virus in cell culture, mice, and swine. Am J Vet Res. 1986;47(9):1892-5.
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Jeffrey Dach MD
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