The People's Perspective on Medicine

Do Cold Sores Increase the Risk for Alzheimer Disease?

Herpes simplex type 1 infections cause cold sores and reactivation of the virus has been linked to Alzheimer's dementia.

We have rarely seen scarier headlines than the ones describing two new studies from Umea University, Sweden, showing that cold sores increase the chance of developing dementia:

“Studies Link Cold Sore Virus to Alzheimer’s Risk” WebMD

“Cold Sores Increase Dementia Risk” Newsmax Health

“Cold Sores may DOUBLE the Risk of Developing Alzheimer’s Disease” Daily Mail

Looking Back at the Research Timeline:

Let’s start with the back story. As long ago as 1974, researchers writing in the British Journal of Psychiatry noted that people with dementia had a greater likelihood of having antibodies to the herpes simplex virus that causes cold sores.

In 1982, Melvyn J. Ball, MD, a pathologist at the Oregon Health and Science University, proposed that herpes simplex virus (HSV) type 1 could be contributing to the brain lesions (plaques and tangles) of Alzheimer dementia (The Canadian Journal of Neurological Sciences). Dr. Ball theorized that the virus “hibernates” in the trigeminal ganglia, a neuronal structure within the brain. In its dormant state, the virus resides within this nerve tissue without seeming to cause mischief. When activated, the virus travels down nerves to the lips and triggers the familiar cold sore lesion.

Dr. Ball suggested that the virus might also travel in another direction, deeper into the brain:

“It is suggested that reactivation of the same dormant viral material travelling centripetally instead might be the cause of the ‘degenerative’ lesions typical both of Alzheimer’s Disease and of the normal aged human brain.”

Dr. Ball Persisted in Studying His Hypothesis:

Most neuroscientists and Alzheimer’s disease researchers ignored Dr. Ball’s hypothesis, but over the last three decades Dr. Ball has tirelessly pursued this idea. In 2006 in the Journal of Alzheimer’s Disease he noted that most research on Alzheimer disease had failed to determine the most important neurological abnormalities of the disease:

“However, during my elusive search, evidence has been slowly gathered that reactivation of latent Herpes simplex virus, traveling from trigeminal ganglia into neighbouring mesial temporal cortex, might best explain the limbic predilection for and earliest site of neurofibrillary tangle formation.”

Other investigators discovered that the herpes virus could be detected within the brain lesions of Alzheimer disease patients (Journal of Pathology, Jan. 2009):

“We discovered a striking localization of herpes simplex virus type 1 DNA within plaques: in Alzheimer’s disease brains, 90% of the plaques contained the viral DNA and 72% of the DNA was associated with plaques…”

The Latest Research on the HSV Type 1 and Alzheimer’s Disease

Although funding agencies and mainstream researchers pretty much dismissed this line of research, some epidemiologists began digging deeper.  The Swedes in particular noted that there seemed to be an increased risk of Alzheimer disease after herpes simplex virus reactivation (Alzheimer’s & Dementia, June, 2015). Researchers tracked 3,432 subjects for over 11 years. They found that reactivated herpes infections were linked to a doubling of the risk for Alzheimer disease compared to individuals who were not infected.

The latest headline-making research comes from Umea University in Umea, Sweden (Alzheimer’s & Dementia, June, 2015). These investigators identified 360 individuals with a diagnosis of Alzheimer’s disease and 360 cases of dementia-free controls. All patients had given blood long before (on average 9.6 years earlier), and it had been stored in a medical “Biobank.” The scientists analyzed the blood for antibodies to herpes simplex virus type 1. The presence of the antibodies was associated with a two-fold increased risk for dementia:

“Among persons with a follow-up time of 6.6 years or more, HSV infection was significantly associated with AD [Alzheimer’s disease]. This may indicate a role of HSV in early AD development…”

“It has been hypothesized that immune system weakening in older individuals might contribute to HSV reactivation and spread to the brain, which then may explain the connection seen among persons older than 60 years in this study whereas causes of AD other than HSV might be relatively more common among those younger than 60 years of age…”

“Converging evidence now supports a relationship between HSV and the early development of at least some cases of AD.”

 What’s the Bottom Line and What to Do?

First, you will likely read that researchers in the Alzheimer disease mainstream reject this research. I characterize this as the “not invented here” phenomenon. Funding agencies have spent billions of dollars pursuing other avenues, but so far they have proven almost worthless. The idea that they may have overlooked this approach for nearly 40 years will be hard to swallow.

Dr. Hugo Lovheim, the lead author of this research, has been quoted:

“The identification of a treatable cause [herpes simplex] of the most common dementia disorder is a breakthrough…Whether treatment of herpes infection with antiviral drugs may slow the Alzheimer’s progression is not known, but is certainly worth investigating in clinical studies.”

“Something which makes this hypothesis very interesting is that now herpes infection can in principle be treated with antiviral agents. Therefore within a few years we hope to be able to start studies in which we will also try treating patients to prevent the development of Alzheimer’s disease.”

Many people may not want to wait years and years for such clinical trials to be funded and for the results to be published. As Dr. Lovheim noted, there are effective prescription antiviral medications against herpes simplex virus type 1. They include acyclovir (Zovirax), famiclovir (Famvir), penciclovir (Denavir) and valacyclovir (Valtrex). Such drugs are surprisingly effective against herpes viruses and reasonably safe. They do require a prescription. And clearly, such drugs have not yet been tested for preventing or treating Alzheimer disease. Consequently, we simply cannot tell whether they will be able to inhibit virus that may already have entered the brain.

What About L-Lysine?

You might want to think about a simple over-the-counter approach. Again, we have no evidence that this will help, but the risks are low. For decades, we have been hearing from readers of our syndicated newspaper column, listeners to our syndicated radio show and visitors to this website that L-lysine works against a number of herpes infections.

One reader wrote about using L-lysine for shingles, a painful rash associate with a different herpes virus, herpes zoster:

“In a recent column you answered a question about L-lysine and shingles. I have been taking L-lysine for various forms of herpes for over 20 years, and it has kept me virtually outbreak-free.

“It is also important to avoid nuts and chocolate. Dietary restraint together with L-lysine have worked better for me than acyclovir, which I took for a year as part of a study at the University of Rochester.

“I have read about both nut avoidance and L-lysine, but often when I speak to physicians about it they are not aware of it. A lot of pain and discomfort could be avoided if they were.”

JS agrees that L-lysine can be helpful:

“I too am a firm believer in L-Lysine. At the very first tingle I will take anywhere from 2 to 5 1000 mg pills.  If I know I will have lots of sun exposure, or that I am stressed out or run down, I will take a couple in the morning and a couple before sleep preemptively.

“I keep lysine in my glove box, in my day bag, golf bag, gym bag, and at home. It is so helpful that I literally will not go anywhere without it, so that I can take it immediately if i feel a cold sore coming on, or if I am consciously stressed, tired, sick, etc. I’ve also learned to avoid caffeine, chocolate, most nuts, and other foods that are rich in arginine.

“There are tons of articles explaining how food and diet can assist in preventing and limiting the extent of breakouts. With this current approach, I usually do not get any sores that are visible, and am able to keep them in check.”

Sharon got advice on L-lysine from her dentist:

“My dentist told me many years ago to use Lysine as soon my lip starts to sting. I take three Lysine immediately and the sore will not go on and develop. The second and third days, I take three more. No blisters for me.”

Would you like to read more about controlling recurrent cold sores with L-lysine? Here is a link to some fascinating stories. You’ll find other commentary about whether L-lysine might help protect our brains from Alzheimer disease here.

No one knows whether antiviral drugs or L-lysine will prevent or help Alzheimer disease. But anything that can keep the virus from reactivating is probably worth a try. Since L-lysine seems surprisingly safe, it might be an experiment worth considering. Let us know your thoughts and experience with herpes simplex type 1 in the comment section below.

Could Alzheimer Plaques Be Protecting the Brain?

More recent research demonstrates that two of the beta amyloid compounds that form plaques in the brains of people with Alzheimer disease have antiviral activity (Bourgade et al, Biogerontology, Feb. 2015). In cell cultures, these beta-amyloid peptides inhibit herpes simplex virus growth. The investigators conclude,

“Overproduction of Aβ peptide to protect against latent herpes viruses and eventually against other infections, may contribute to amyloid plaque formation, and partially explain why brain infections play a pathogenic role in the progression of the sporadic form of AD.”

We don’t know if Dr. Ball is still alive, and if so, whether he feels vindicated. But increasingly, other neuroscientists are coming around to his view. One review published last year referred to “a compelling argument for a pathogen-based etiology of AD” [Alzheimer Disease] (McNamara & Murray, Current Alzheimer Research, 2016).

Revised 5/25/17

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    About the Author
    Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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    My husband from the time he was a young teen suffered from cold sores & excruciatingly ulcers in his mouth. Drs were of no help. Finally a man mentioned taking Lysine. It has worked very well, however he continued to have the mouth ulcers to a lesser extent. A year or so ago I read about eating sauerkraut (possibly on PP) for cold sores, we wondered if it would belp with the mouth ulcers. Its been a miracle for him, no mouth ulcers. He eats a small amount a couple of times per week ( not as a meal veggie) but just a couple or so TBS. I buy Bubbies brand from a natural grocer ( no additives). My daughter in law has cold sores & uses a kraut soaked Qtip to apply it directly to the sore several times a day. Hi

    Since childhood, I would get cold sores outbreak once or twice a month even with no illness. When about 38 years old, a secretary in our office told me to lake Lysine. I took a 500 mg tablet once a day for a period of time but found no benefit. She told me to take a larger dose.

    I tried 1000 mg and when that didn’t work I took 1500 mg a day. That was the dose I needed! Since then (I’m 79 now) I have only had an outbreak if I had a very bad case of the flu or had stopped taking lysine for a while. Even in those cases, taking lysine would stop the progress of the infection and reverse the effect in a few days; not the usual two weeks with no lysine.

    We all have slight genetic variations that I believe affects our body’s needs and reactions to both good and bad influences. I have been laughed at by medical professional for suggesting lysine could help with cold sores, in spite of my personal experience.

    In my life, I have found most doctors hate getting medical opinions from patients. If they didn’t learn it in medical school, “it ain’t true!”. It seems as though drug companies will only research cures with big money making potential.

    The government spends considerable amounts of money promoting research. Some of it should go to investigating some of these time-tested folk remedies. All researchers should also remember our genetic variability and that people react differently to a multitude of things from drugs to peanuts.

    I would like to be involved in any research regarding Alzheimer’s and dementia. They run in my family, as do cold sores. My mother had cold sores, anxiety, early onset of dementia and died from Lewy Body Dementia. I’ve had cold sores my whole life which are frequent and monstrous if I don’t treat them immediately. I’ve been on Acyclovir since I was 10 years old and just recently switched to Valtrex. At the first sign of a break out, I take 2 grams twice a day for one day but then take an extra day since they don’t ease up until the end of the 2nd day. Even then, more times than not, I still get a scab.

    If there are any research studies I’d like to be a participant. I’d say the chances are that I’ll be like my mom, and if there is any way that I can prevent it or help others from getting it, I’m in.

    My mother had cold sores, and died with dementia. I have had them for years, and a long time ago my chiropractor told me about L-lysine. I take 1500 mg daily unless I have an outbreak, then I take more. This limits the outbreaks to about once per year.

    OOps. I attributed this report on Dr. Ball’s work and the connection with Alzheimers to Cosmos
    Magazine, an Australian popular science periodical that I get on line. It’s great. But all credit for
    this reporting goes to The People’s Pharmacy.

    Vitamin C is an excellent preventive/medicine for virus related diseases. It is important to use the crystals (I take 2-2 grams/day), since the tablets have a limited shelf life. When I contracted chicken pox at age 50, I took ten grams/day for three weeks and recovered without any problems.

    It seems that Dr. Ball is no longer practicing, but I found no obituary. I am a retired teacher who first contracted cold sores about 12 years ago. I used Abreva for about 3 years, and found it expensive and ineffective. About 9 years ago, an herbalist friend started making a lip balm with Melissa officinalis (Lemon Balm).

    I apply it whenever my lip tingles (usually high stress, low immune levels of winter). I carry it with me, so I always have it when away from home. I haven’t had a cold sore since I started using the lip balm. Last year, she retired, and I bought her herbal products business. I need that lip balm! I also make and drink many herbal teas that include lemon balm. Perhaps the combination of herbal teas and lip balm will stave off both cold sores and Alzheimers!

    I have a question: I have read that Lysine causes an increase in blood pressure. Does anyone know if this is true or has anyone had it happen? As I already have treated high blood pressure and also have HSV-1, the question is important to me. Thanks!

    The revelation that cold sores may be related to Alzheimers is stunning. Dr. Ball’s commitment to his research is admirable.

    The experience of the commenters and me is not medical evidence. But there is enough there that a more systematic approach is worthy. Congratulations to Dr. Ball for exemplary courage and commitment.

    My experience and those of the earlier commentators indicates that the preventive for cold sores is contained in B-vitamins L-Lysine perhaps. For years, I have been able to prevent them blossoming by taking B-vitamins, simple over-the-counter versions. It also helps to eat whole grains regularly. Growing up, I took Brewer’s Yeast every day. That works miracles. It contains B vitamins and protein. Before BigPharma grew into the monster it is today, doctors often prescribed Brewer’s Yeast to pregnant women as a strengthener. It is the main ingredient in Marmite, which the British love, and Australia’s Vegemite. This makes one wonder if Alzheimers is less pervasive there than here.

    On the web, there are references to the connection between suppressing viruses and B-vitamins, but they are diffuse. Still, even webmd refers to it. News of this doesn’t reach most people. There isn’t much profit in simple vitamins, and television ads are how most people get their “information” about diet and pharmaceuticals/nutricuticles, etc.

    More important, B-vitamins, Brewer’s yeast, Marmite, Vegamite, also prevent shingles. They won’t cure them, but they will keep them from blossoming.

    This new research has staggering implications. Its publication in Cosmos of great value.

    It is not unprecedented. Decades ago, the late John Lindenbaum, Columbia University Medical Center, posited that adding B-vitamins to cheap wines and other drinks favored by alcoholics would prevent the otherwise inevitable development of dementia. No profit in that simple change for producers, but for the public health, almost unimaginable.

    Is there some reason why you are reviving this old, troubling article? I see nothing other than a cryptic “Revised 5/25/17.” I’ve had cold sores since I was young and have spoken with doctors about them, innumerable times. Lysine has not shown efficacy in peer-reviewed, clinical trials, as far as I’ve ever heard; it remains one of the home-remedy folk “cures” that frequent your columns. Even acyclovir and valcyclovir are of limited efficacy. I feel it’s irresponsible to raise these fears while really having nothing new to offer other than a bunch of “can’t hurt, so why not?” suggestions.

    I used to get frequent and sometimes very severe outbreaks of cold sores. My dental hygienist suggested L-lysine. I started taking one capsule a week several years ago. I’ve had only one mild outbreak since. Don’t know if it will help with cognitive decline, but seems to work for cold sores better than anything else I’ve found.

    Need information on how to protect the brain for sure. Tried to read ‘Grain Brain’ -Dr. Perlmutter but someone stole it from the library. Next best was his recipe book which had some but minimal information. All these suggestions for good health, but what supplements are good for the health of the brain, what is to be avoided. Perhaps I have not searched the site properly. Any guidance greatly appreciated. Thank you

    I have had a recurring “sore” on my hip for 75 years. It itches and burns. It came in the spot I had had a bedsore in the hospital. The doctor identified it as herpes simplex.

    I simply endured it for years until I heard of Llysine for cold sores. When the itching starts I take 4 pills….and 4 at night for 3 days. By then the episode was on the wane. This works!

    Having regular cold sores and having had shingles -both apparently from the chicken pox virus in the system this article is most frightening. Especially since beginning to forget in a way that I feel is more than regular aging [being 69]. Lysine does help, as well I use astragalus, but these are immediate ‘fixes’ only and temporary. This article makes me feel doomed. What should be done on a regular basis then? IS there anything?

    To Mary: Take B-vitamins every day.

    I contracted genital herpes in 1974, 42 years ago. I am now 71. I have had dozens of outbreaks and they have increased exponentially as I have aged. I can’t discern any cognitive decline at all. I do take curcumin, fish oil, and other supplements to protect my brain; I eat well, exercise, and use my mind as much as possible. If genital herpes can bring on dementia, wouldn’t have I noticed something BY NOW?? After 42 years?? I seem to be sharper than ever since I started taking curcumin with bioperine. I use lysine, 5,000 mg/day, during outbreaks and it works well to stop the flare-up. I’ve tried the prescription antivirals with less success. I avoid foods high in arginine. Lack of sleep and emotional stress will trigger a flare-up. The person who gave me herpes is now 73 and has no cognitive deficits.

    I have had terrible cold sores since I was 6 or 7 lasting 2-3 weeks my mom gave me every vitamin she could think of to no effect in 24 now about 2 years ago I found olive leaf extract capsules and tried them when I got a cold sore within 5min the swelling started to stop pain subsided and started to heal now I can heal within at least a week with very little pain.
    But I do have a terrible memory and this article is a little scary to me.

    I have suffered from cold sores for years and have tried many remedies, some even administered by a doctor when I was a teenager. My brother and I often would infect each other in the early stages of eruption. Zovirax, though quite expensive, works well in shortening the time of suffering.

    Another interesting study concerning cold sores came from The Netherlands in 2012. It suggests that the cytomegalovirus (CMV) infection may be a risk factor for type 2 diabetes in very elderly people. They suggest that “CMV might be involved in accelerating pancreatic failure to compensate for insulin resistance pancreatic cells directly; secondly, it might act indirectly by influencing the immune system, which in turn affects the pancreas.”

    I suffered with severe multiple, huge cold sores on my lips for 25 years. Dentist tried painful laser. No results.

    Internist saw I had them one visit (I had never mentioned this problem to him). He prescribed Zovirax pills – incredible results. For the past 15 years I have not had one ugly outbreak. The minute I feel tingling I take a pill; usually that does it.

    If it begins to show signs of a little swelling I will take another one. In the past five years I have not had any tingling on lips indicating that the virus is about to recur. As a precaution, I make sure I have a new Rx written at time of my annual physical.

    My father and one sibling were also plagued with cold sores for many years.
    I graduated from college 2 years ago at age 73, – hopefully I wont get Alzheimers; neither father nor sister had any signs of dementia. So far, none of my 3 daughters or seven grandchildren have this virus. My husband occasionally had them on his mouth. He never had them before he was with me.

    I am a young healthy 80 year old and have a strong family history of Alzheimer’s and have been doing a lot of research on what and what not to do to try and prevent it. This is the first I have heard that cold sores may contribute. This is quite upsetting to me as I have frequent cold sores. I have just recently started using L-Lysine tablets and ointment which appear to be helping. Can cold sores be transmitted to another person?

    Yes, the herpes virus which causes cold sore is infectious and transmissible.

    I read a few months ago that holding an ice cube inside a wash cloth on a cold sore as soon as you start to feel the stinging, and the stinging will stop – about a half hour or so (I haven’t timed it), and the blisters will not develop. I have tried this twice and it has worked both times.

    I have one grandson who gets cold sores and have a strong feeling I may have been getting one when he was and infant and passed it on. Both my children get them, but one grandson does not.

    Does Genital Herpes also have a possible connection with Alzheimer’s or is it just herpes simplex type 1?

    We don’t know. The Swedish researchers focused on herpes simplex type 1.

    I have used lysine for years as well for cold sores. Too much sun exposure will trigger a breakout so when we snow ski I start a week before taking lysine and continue for a week after. Nuts also trigger it especially pecans and walnuts so I stay away from them. Valtrex makes an outbreak go away in a hurry so sometimes I resort to that

    When I used Metro-gel for Rosacea on my face, I started getting horrendous cold sores for a year, but didn’t realize that was a side effect. My dr. told me to use the L-lysine and I take one 500 mg. every day and have not any any unless I forget and will start to feel a tingle. This article does upset me as mom died of dementia. I am 77.

    This is an excellent article. After 40 years in Family Practice your “not invented here” syndrome has been made very obvious to me. Your citing of the data in a way understandable to all of us is a great help for people wanting to know what’s happening to them. Thought not mentioned, your discussion makes it clear that medical research is not a quick or a black and white process. (Remember the 180 with estrogen and heart disease.)

    I’m a bit disappointed in your heavy use of anecdotes in urging L Lysine. Anecdotal evidence has little use in objective decision making. It does, however, signify a need to look further. One more caveat regarding the apparent safety of lysine or anything else; If something can do good it is causing a change. If something can cause a change it can do harm. Be aware.

    Geoff

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