It’s Not You! Cold Sore Treatments Don’t Work That Well For Most People. But There’s Something New To Try
It’s common knowledge among physicians who treat cold sore sufferers that the leading cold sore medications don’t work that well, at least for most people. And there have been no new drug break-throughs in over 20 years, probably because cold sores are not considered life-threatening and they usually resolve on their own within about a week. Of course, that’s no consolation to the millions of cold sore sufferers who hate the pain and discoloration and the effects on their social life!
Surveys have indicated that about 85% of recurrent cold sore sufferers (which is about 20-25% of adults) are unhappy with the cold sore treatments they have used, and many have stopped trying and just use a lip balm or analgesics to stop the pain and keep the blisters from cracking and bleeding.
Why is it that the major cold sore medications don’t work that well for most? It’s a little-known fact, but the scientific studies on which the FDA approved the main cold sore treatments showed that on average they reduced an outbreak by only half a day to a day. They worked well for some, but not for most. Here are the specifics.
(Incidentally, all of this information is publicly available and can be found on the internet. We recognize that most people aren’t interested in trying to dig it out, so we provide the locations below.)
Abreva®
Abreva (generic name Docosanol 10%) is the leading cold sore treatment by far, with about 70% of the market. It is available over-the-counter without a prescription, so it is more convenient and less expensive than the prescription drugs. It is not considered an anti-viral drug – it blocks the virus from reaching cells rather than acting on the virus to keep it from replicating. But it shortens the time to healing.
Abreva advertises that it “can heal a cold sore in as few as 2½ days* – when used at the first sign of an outbreak. Nothing heals a cold sore faster.**” But notice the double asterisk. In the small print down below, it says: “Median healing time 4.1 days. 25% of users healed within 2½ days.” What it doesn’t say is that 25% of the people in the study who got the placebo healed in 2.7 days. And the median healing time for those who got placebo was 4.7 days, an increase of just 0.6 days. For those in the 75th percentile, healing time with Abreva was 6.3 days and with placebo it was 6.7 days.
So with Abreva, most people experience about half a day shorter healing time in a 5-7 day outbreak, which may not even be noticeable to many. And some have outbreaks that last much longer. Furthermore, the FDA review included two larger studies, one of which showed that the improvement in healing time was not enough to be statistically significant, but the other was, and the pooled result was also significant. But a number of other smaller trials also did not show a statistically significant improvement. Abreva was ultimately approved, but based on the studies provided, the Medical Reviewer recommended against approval due to lack of efficacy, even recognizing that a small improvement in healing time would be valuable to many cold sore sufferers.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-941_Abreva.cfm
See Medical Review(s) Part 2, esp. Tables 15, 28, 38 & Section 12 Recommendations
Valtrex®
The story is similar for Valtrex (generic name valacyclovir), which is the leading prescription drug for cold sores. In two large studies, valacyclovir reduced the median time for healing from 5 days to 4 in one study and from 5.5 to 5 in the other, and it reduced the mean (or average) time for healing from 6.1 days to 5 days in one study and from 6.3 days to 5.3 in the other, using the best of two different doses that were studied (a one-day treatment). So on average, Valtrex reduces a 6-day outbreak by about a day. However, patients started taking Valtrex “at the earliest prodromal symptoms and prior to the first clinical sign of a cold sore (i.e., no redness, swelling, blister, or later stage present)” whereas in the Abreva studies patients were included so long as they started treatment within 12 hours of the start of symptoms, which may account for the slightly lower efficacy of Abreva in its studies. In any event, with both drugs, some lucky people will experience a healing time of a day or two, as will some people who take a placebo. But for most people, the difference in healing time will be about a day or less, and may not be that noticeable to many.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149313
Zovirax®
The other most-used prescription drug is Zovirax cream (generic name acyclovir). In two large studies it reduced the mean (average) time to healing from 4.8 days to 4.3 days in one study and from 5.2 days to 4.6 days in the other when taken within 1 hour of episode onset. A less commonly used, rather expensive antiviral cream is Denavir (generic name penciclovir). In one large study, it reduced healing time by 0.7 days. It has to be applied every 2 hours for 4 days while Zovirax cream is applied 5 times a day for 4 days. In short, these two drugs have a much longer treatment time than Valtrex and reduce healing time by about half a day compared to about 1 day for Valtrex.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC127288
Super Lysine+®
Another non-prescription product that has been around for over 20 years and claims to be “the leading herbal cold sore ointment in the US and Canada” is Super Lysine+â. Despite the name of the product and the website’s description of Lysine as a “well-researched amino acid that nourishes the skin and suppresses the activity of arginine”, the only active ingredient identified for the product is Menthol 0.1%, as a pain reliever. The website states that the product “trims healing time by half.” That statement is difficult to interpret given the widely varying duration of cold sore outbreaks for different people. What the 2005 small pilot study (30 subjects) on the product in the peer-reviewed Alternative Medicine Review states is that 7 patients (23%) had been cured by day 2, 12 (40%) by day 3, 17 (57%) by day 4, 26 (87%) by day 6, and all 30 by day 11. The product was applied every 2 hours.
Notable is that patients were included if they started treatment within the first 24 hours of the cold sore outbreak (rather than 12 hours as in the Abreva studies). Thus, despite a later start, the median healing time appears to be between days 3 and 4, compared to Abreva’s median healing time of 4.1 days. In addition, the Super Lysine+ study defined “cure” as “the complete disappearance of the lesion, not merely crusting” whereas the Abreva studies defined “complete healing” as “absence of crust with no evidence of active lesion, whether or not there are any residual post-lesion skin changes which may include erythema [redness], flaking or slight asymmetry….”
Although these results of Super Lysine+ seem to be better than Abreva’s, the study concludes: “Due to the preliminary nature of this study, a small sample size was used and therefore no definitive statements can be made. A larger, heterogeneous, double-blind, randomized, controlled clinical trial is necessary in order to definitively determine the efficacy of this product.” Perhaps for that reason the Super Lysine+ website does not link to the study. In addition, the study Abstract begins with this statement: “CONTEXT: L-lysine, an essential amino acid, inhibits normal replication of Herpes simplex virus (HSV), shortening the normal course and duration of the disease.” While this statement is correct, it could be taken as a medical claim (i.e., treating a disease), which would not be appropriate to be associated with a botanical product.
https://altmedrev.com/wp-content/uploads/2019/02/v10-2-123.pdf
Releev®
Releev is another OTC botanical product that has been available for over 20 years. It combines an echinacea extract called Viraceaâ with the active ingredient Benzalkonium Chloride, which is an antimicrobial agent that is widely used as a preservative and in products like hand sanitizers. According to sources summarized in Wikipedia, it can cause eye and skin irritation in certain circumstances. Echinacea is known for supporting the immune system.
Benzalkonium Chloride is included in an FDA OTC monograph, which according to the FDA “establishes conditions, such as active ingredients, uses (indications), doses, routes of administration, labeling, and testing, under which an OTC drug in a given therapeutic category (e.g., sunscreen, antacid) is generally recognized as safe and effective (GRASE).” If an ingredient is covered by a monograph, it can be marketed without getting a specific FDA drug approval.
Releev calls itself “1 Day Cold Sore Symptom Treatment”, which requires some explanation. Releev was created and patented by Meryl Squires, a cold sore sufferer who was motivated to create something better than the available cold sore treatments. She set up a company called Merix Pharmaceutical Corporation to market the product with her two daughters and was successful enough that they caught the attention of Glaxo Smith Kline, the big pharmaceutical company that owns Abreva and Valtrex. GSK sued Merix in 2005 for making unsubstantiated claims about preventing cold sores and “treating” cold sores, as well as having support from published clinical studies for their 1 day treatment and other claims. Merix had to change some of their claims, but the court allowed them to claim 1 day “symptom treatment”, which can refer to relief of pain, burning, tingling and itching, as noted in the Releev.com website FAQs.
Releev also claims on its product label “Fastest Healing Time – Guaranteed!” Apparently this claim is based on Merix’s feedback from friends and customers. In 2019 they widely disseminated a release in the industry press regarding successful laboratory testing at the University of Chicago of their Viracea and Benzalkonium Chloride combination against 40 different herpes virus strains, including acyclovir-resistant strains. They also stated the following: “In a double-blind, placebo controlled, clinical trial VIRACEA® was found to heal cold sores in as little as one day.” Apparently that study was not published, and it is not linked on the Releev.com website.
Also, the current FAQs on the website refer to such a study that they hope to release soon: “We have long been told by consumers that in addition to providing symptom relief, RELEEV is terrific in speeding the healing of cold sores. What consumers are telling us was confirmed in a recently completed double blind, placebo controlled clinical trial. On average cold sores healed in 72 hours and for some in as little as 21 hours. We look forward to reporting the results of that successful clinical trial soon.” Apparently, some issue stopped the release of the study.
Unfortunately, without being able to see the study, we aren’t able to verify the claim about an average healing time of 3 days, or how they define “healed”. Also, as we have seen above in other studies, many products and even placebo can heal cold sores for some patients in as little as 21 hours. We don’t doubt that Releev appears to work well for many people based on its longevity, apparent success and customer reviews. But it is not possible to know the average or median rate at which it cures cold sores or symptoms or how it compares to other products. But presumably if it worked significantly better than Abreva, it would have taken over the market from Abreva by now.
https://en.wikipedia.org/wiki/Benzalkonium_chloride
https://casetext.com/case/glaxosmithkline-consumer-healthcare-v-merix-pharmaceutical-3
https://www.sciencedirect.com/science/article/abs/pii/S0166354298000278
Mederma®
Mederma patches are thin colloidal patches that cover cold sores and only help healing by keeping the area moist. Mederma recommends using them when out and about during the day, but using a cold sore cream or gel treatment at night to help speed healing. They state that the patches and treatment creams or gels should not be used together. Mederma does not make any claims about healing time because it is not a direct treatment, and healing will depend upon what treatment a person uses and how quickly it works for them. Mederma patches are popular because, as we’ve seen, the treatments are not that effective and many people end up needing to cover over unsightly cold sores.
Campho-Phenique®, Orajel®, ChapStick®, Lip Balms
These products provide relief from pain and itching and help keep the skin moist and avoid cracking of blisters and bleeding. They are used often by cold sore sufferers because they are widely available, they are inexpensive and they work. And as we’ve seen, the cold sore treatments don’t work very well for most and people end up having to deal with a painful and unsightly sore. Some people have given up on the treatments and simply turn to these remedies while covering up the sore with make-up or a patch.
NextLeap™
At the end of 2022, a new type of product was launched for cold sore care, a “cosmetic” treatment that is not a cover-up. It is based on the key ingredient Tranexamic Acid (TXA), which has been used for over 40 years to address melasma (a type of dark spotting of the skin) and other dark spots. More recently it has been used for rosacea and areas of redness from various sources. A company called SkinStasis Skin Care created a TXA formula that they say has been optimized to deal with the cosmetic effects of cold sores as well as those other types of skin discoloration. They claim that the product allows a return to normal appearance in 1-2 days if it is used at first symptom (first tingle).
This is a bold claim and apparently no clinical studies are available to support it. Like Releev, they are relying on their knowledge of the ingredients and feedback from friends and customers. However, there are extensive scientific studies supporting the effectiveness of TXA against melasma and other types of skin discoloration. The reasons for its effectiveness are not entirely clear, but it is plausible that it would also be very effective against the cosmetic effects of cold sores.
It should also be noted that TXA is a synthetic analog of lysine, meaning that it is a man-made molecule that is similar to the amino acid lysine. There are about 20 amino acids, depending on how they are counted. They are the building blocks of all of the body’s proteins, which provide the structures of your body, like skin and bones, and carry out a lot of its internal functions. Lysine, arginine and histidine are 3 of the more important amino acids because they are the 3 positively charged amino acids, so they provide part of the electrostatic bonding required for a lot of protein-protein interactions required for many bodily functions, as well as things like viral replication.
Interestingly, some long-forgotten research from 1963 found that the two biggest amino acid requirements for the herpes virus (HSV) are histidine and arginine, and lysine is not needed. It was later speculated during the 1980s that adding lysine to the diet would interfere with arginine’s activity and inhibit cold sore outbreaks. The results of the clinical trials were mixed, possibly because not all of the trials reduced the amount of arginine-rich foods the patients ate at the same time that lysine was supplemented. Nevertheless, the success of products like Super Lysine+ and natural lysine supplements and topicals against cold sores for at least some people seems to support the theory of lysine interference with arginine to treat cold sores. As a lysine analog, it is possible that TXA has a similar effect. SkinStasis wisely avoids making that claim, which would likely be considered a medical claim. The well-known cosmetic usage and effects of TXA provide sufficient support.
Note:
It should be noted that the reviews on Amazon and other locations on cold sore products should be taken with caution. It is often difficult to tell whether the reviewer started taking the product soon after the symptoms started. There is a suspicion that they often ordered the product when the outbreak started and only began to use it a day or two later. There also seem to be an unusual number of trolls in this product area, perhaps because there are so many resellers of Abreva and some of the other products.
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