The People's Perspective on Medicine

Can Anti-Herpes Treatments Prevent Alzheimer’s?

There is growing evidence to suggest that herpes viruses contribute to dementia. Could an antiviral supplement or drug like Valtrex prevent Alzheimer's?
Dementia and Alzheimer’s disease medical concept, 3D illustration. Memory loss, brain aging. Conceptual image showing blurred brain with loss of neuronal networks

Does a common virus contribute to Alzheimer’s disease? The herpes theory of Alzheimer’s disease has been ignored by mainstream medicine for decades. Almost 40 years ago a pathologist suggested that the virus that causes cold sores (HSV-1) might be impacting the development of dementia (The Canadian Journal of Neurological Sciences, Aug. 1982). That same year a neuropathologist in the UK wrote an intriguing article in the The Journal of Neurology, Neurosurgery & Psychiatry (Aug., Vol. 45(8): 759-760) titled, “Viruses and Alzheimer’s Disease.” Such reports were overlooked by most neuroscientists. A suggestion nine years ago that L-lysine supplements might prevent Alzheimer’s disease was also ignored.

The Tragedy of Alzheimer’s Disease:

Alzheimer’s disease [AD] is one of mankind’s cruelest afflictions. Patients lose their memories, their personalities and ultimately their ability to care for themselves. The human and financial tolls are overwhelming. The entire family suffers!

The CDC estimates that nearly six million people currently have AD. Within two decades that number is likely to double. The Framingham Heart Study suggests that one in five women and one in 10 men will develop Alzheimer’s dementia during their lifetime (Alzheimer’s & Dementia, March, 2015). 

40 Years of Disappointments:

Current treatments are abysmal. They do not prevent Alzheimer’s disease. They do not reverse cognitive dysfunction or keep people out of nursing homes. Drug research over the last few decades has been disappointing at best. Despite the billions that have been spent, there are no exciting treatments in the development pipeline.

There are also huge disagreements about the underlying factors that cause Alzheimer’s disease. For many years, the loudest shouters blamed a protein called beta-amyloid or A-beta. The pharmaceutical industry invested heavily in drugs to clear the brain of A-beta. They failed miserably.

Here’s how Raymond Tesi, MD, describes amyloid failures for Stat (April 30, 2019)

“If insanity is doing the same thing over and over again but expecting different results, then the last decade or so of Alzheimer’s disease drug development has been insane. Three carefully designed, well-executed, and fully resourced trials targeting amyloid protein in the brain as the cause of Alzheimer’s disease have failed. It’s long past time to take a new approach to this mind-robbing disease.”

Back to the Future: The Viral Theory Returns!

After nearly 40 years languishing on the scrapheap of medical hypotheses, viral infections are reemerging as potential contributors to Alzheimer’s disease. In particular, researchers have been focusing on herpes simplex (Current Neurology and Neuroscience Reports, July 14, 2018). 

HSV-1, which causes cold sores, is commonly found in the brains of older people. The parts of the brain affected by Alzheimer’s disease are especially likely to show evidence of HSV-1 infection (Frontiers in Pharmacology, May 2014). 

The classic signs of Alzheimer’s disease are plaques and tangles in the brain. Neuroscientists have proposed that these may be the consequence of the immune system trying to battle an infection in the brain (Neurochemistry International, Feb. 2011). 

Skeptical? Listen for Yourself!

We interviewed a world-class neuroscientist about this very concept. Robert D. Moir, PhD, is Assistant Professor in Neurology at Harvard Medical School. He is also Assistant Professor in Neurology at MGH Neurology Research. He and his colleague, Rudoph Tanzi, PhD, director of MGH’s Genetics and Aging Research Unit, present evidence that amyloid beta could be an ancient line of defense against herpes virus infections (Neuron, July 11, 2018).  Listen to our interview with Dr. Moir at this link:

Show 1132: Are Infections to Blame for Alzheimer Disease?

You can stream the audio by clicking on the arrow or download the free mp3 file to listen on your computer or mobile device.

Fighting Off Herpes Infections to Prevent Alzheimer’s Disease:

Are there any ways to fight off herpes viruses without damaging the brain in the process? Some researchers are beginning to explore antiviral treatment as a way of dealing with herpes virus in brain tissue. The hope is that such a strategy could prevent Alzheimer’s disease.

L-Lysine:

Almost a decade ago a retired geriatrician, Dr. Robert Rubey, proposed that supplements of the amino acid L-lysine might discourage HSV-1 growth and prevent Alzheimer’s dementia (Neuropsychiatric Disease and Treatment, Oct. 27, 2010). 

Combined with a diet low in arginine, this approach might reduce the risk that the virus can replicate and lead to damage. Foods that are rich in arginine include nuts and seeds, grains and tofu. Dr. Rubey speculated that avoiding such foods and adding a supplement of L-lysine twice daily might be beneficial.

Dr. Rubey offers the following insights:

“It has been known since 1968 that HSV-1 requires arginine for replication, and that lysine inhibits HSV-1 replication by competing with arginine. These findings led to the use of lysine as a treatment for the common condition known as herpes labialis [cold sores] which, as noted above, is known to be caused by HSV-1. Seven randomized, double-blind, placebo-controlled studies have examined the effectiveness of lysine in preventing outbreaks of herpes labialis and reducing the severity of outbreaks that do occur. Six of these studies found lysine to be effective in preventing or decreasing outbreaks, and only two found that lysine reduced the severity of out-breaks.

Dr. Rubey concludes:

“To summarize, AD [Alzheimer’s disease] is a disease process, not a natural result of the aging process; HSV-1 is present in 70%–90% of the brains of older adults; HSV-1 has been identified in the tissue of patients with AD at autopsy; acute HSV-1 encephalitis affects many of the same regions of the brain that are affected by AD, and leads to long term memory loss; HSV-1 is known to reside in a latent form in the trigeminal nucleus, which projects to areas of the brain known to be affected by AD; there are indicators of an inflammatory process associated with AD, suggesting the possibility of an infectious etiology, possibly as a result of immunosenescence; activated HSV-1 virus is associated with formation of plaques and tangles, which are histologic hallmarks of AD…

Dr. Rubey’s hypothesis to prevent Alzheimer’s:

“This leads to the following hypothesis: HSV-1, latent in brain, becomes activated when in older age the ratio of lysine to arginine in the CSF favors arginine, providing a medium conducive to viral reactivation, and the process of immunosenescence releases the virus from immune system surveillance. Active HSV-1 then in turn causes AD. This process may be prevented or attenuated by increasing lysine, either in the diet, or as a supplement, or both. Studies of lysine treatment of herpes labialis suggest that supplements of 1,500 mg twice a day or more are effective for this purpose.”

Dr. Rubey admits that this is all “highly speculative.” It is also highly testable. Lysine is not patentable. That means no drug company is likely to spend money on such a study. As far as we can tell, no one has tested Dr. Rubey’s hypothesis since it was proposed in 2010.

Antiviral Drugs to Prevent Alzheimer’s disease?

More recently, an epidemiological study in Taiwan compared herpes-infected people taking antiviral medications to those without such treatment (Neurotherapeutics, April 2018). After 10 years, 28 percent of unmedicated patients had gone on to develop dementia. In contrast, only 5.8 percent of those taking antiviral drugs had been diagnosed with Alzheimer’s disease or other forms of dementia.

Ruth Itzhaki, PhD, is Professor Emeritus of Molecular Neurobiology at the University of Manchester and Honorary Senior Research Fellow at the University of Oxford. She is one of the pioneers in this field. She too has studied the connection between herpes viruses and Alzheimer’s disease (Frontiers in Aging Neuroscience, Oct. 19, 2018). Dr. Itzhaki, Dr. Ball and their leading collaborators summarized the state of scientific evidence in a seminal article published in 2016 (Journal of Alzheimer’s Disease).

In our interview with her she discusses the study from Taiwan showing that people who take antiviral drugs are less prone to Alzheimer’s disease.

Here is a link to that interview:

Show 1159: Do Cold Sores Boost Your Risk for Dementia?

Can Valacyclovir Prevent Alzheimer’s Disease?

Research is currently being conducted to determine if the antiviral drug valacyclovir (Valtrex) can be helpful against dementia.. The volunteers for the study are people with early-stage AD who test positive for herpes simplex.

They will receive two to four grams of valacyclovir or placebo daily. We hope that the results will tell us whether antiviral medications can make a difference for people with AD.

It would be great if another study could funded to determine whether valacyclovir could prevent Alzheimer’s disease. Because Valtrex has lost its patent, we are unlikely to see drug companies funding such research. We only wish the Alzheimer’s Foundation or the federal government would sponsor this kind of investigation.

If valacyclovir works, people could start benefiting very soon. This drug is both affordable and relatively safe. A month’s supply of generic valacyclovir would cost between $50 and $60. Side effects may include headache or dizziness. When people take valacyclovir long-term to suppress genital herpes, symptoms may also include fatigue, rash and elevated liver enzymes. 

The Future of Alzheimer’s Research:

It has taken decades to get mainstream neuroscientists to consider the possibility of a viral contribution to dementia. Much work needs to be done to confirm this hypothesis. We think you will find our two interviews with brilliant neuroscientists quite enlightening:

Show 1132: Are Infections to Blame for Alzheimer Disease?

Show 1159: Do Cold Sores Boost Your Risk for Dementia?

Share your own thoughts or experience with Alzheimer’s disease in the comment section. 

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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.” .
    Show 1132: Are Infections to Blame for Alzheimer Disease?
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    Pharmaceutical scientists have been striving to get amyloid plaques out of the brain to treat Alzheimer disease. New research suggests that amyloid may be acting to protect the brain from microbes. What are the implications?

    Show 1132: Are Infections to Blame for Alzheimer Disease?
    Citations
    • Ball MJ, "Limbic predilection in Alzheimer dementia: Is reactivated herpesvirus involved?" Canadian Journal of Neurological Sciences, Aug. 1982.
    • Esiri MM, "Viruses and Alzheimer's disease." The Journal of Neurology, Neurosurgery & Psychiatry, Aug. 1982. doi: 10.1136/jnnp.45.8.759
    • Chene G et al, "Gender and incidence of dementia in the Framingham Heart Study from mid-adult life." Alzheimer’s & Dementia, March, 2015. DOI: 10.1016/j.jalz.2013.10.005
    • Tesi RJ, "After amyloid failures, it’s time to take a new tack for treating Alzheimer’s." https://www.statnews.com/2019/04/30/amyloid-failures-new-tack-treating-alzheimers/ Accessed 8/5/2019
    • Devanand DP, "Viral hypothesis and antiviral treatment in Alzheimer’s disease." Current Neurology and Neuroscience Reports, July 14, 2018. doi: 10.1007/s11910-018-0863-1
    • Piacentini R et al, "HSV-1 and Alzheimer's disease: More than a hypothesis." Frontiers in Pharmacology, May 2014. DOI: 10.3389/fphar.2014.00097
    • Carter CJ, "Alzheimer's disease plaques and tangles: Cemeteries of a pyrrhic victory of the immune defence network against herpes simplex infection at the expense of complement and inflammation-mediated neuronal destruction." Neurochemistry International, Feb. 2011. DOI: 10.1016/j.neuint.2010.12.003
    • Eimer WA et al, "Alzheimer's disease-associated beta-amyloid is rapidly seeded by Herpesviridae to protect against brain infection." Neuron, July 11, 2108. DOI:https://doi.org/10.1016/j.neuron.2018.06.030
    • Rubey RN, "Could lysine supplementation prevent Alzheimer's dementia? A novel hypothesis." Neuropsychiatric Disease and Treatment, Oct. 27, 2010. doi: 10.2147/NDT.S14338
    • Tzeng N-S et al, "Anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections–a nationwide, population-based cohort study in Taiwan." Neurotherapeutics, April 2018. doi: 10.1007/s13311-018-0611-x
    • Itzhaki RF, "Corroboration of a major role for herpes simplex virus type 1 in Alzheimer's disease." Frontiers in Aging Neuroscience, Oct. 19, 2018. DOI: 10.3389/fnagi.2018.00324
    • Itzhaki RF et al, "Microbes and Alzheimer's disease." Journal of Alzheimer's Disease, 2016. doi: 10.3233/JAD-160152.
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    is there evidence that valtrex can cross the blood brain barrier under normal conditions?

    I am concerned your readers will take your statement: “The classic signs of Alzheimer’s disease are plaques and tangles in the brain” to mean that this is a definitive diagnosis for Altzheimers when it most certainly is not as the famous Nun’s study proved:
    “Sister Bernadette (not her real name), who had shown no outward signs of Alzheimer’s and whose youthful autobiography was rich with ideas and grammatical complexity, turned out at death to be riddled with the plaques and tangles of Alzheimer’s (see diagram). Says Snowdon: “Lesson No. 1 in my epidemiology training is that there are hardly any diseases where one factor alone, even in infectious disease, will always cause illness.” (http://content.time.com/time/world/article/0,8599,2047984,00.html).

    Jeannette,

    You are quite correct that the Nun’s study demonstrated that people could have plaques and tangles but no significant signs of Alzheimer’s disease. That said, here is what Daniel P. Perl, a leading neuroscientist, writes about definitive diagnosis of Alzheimer’s disease (Mt. Sinai Journal of Medicine, Jan-Feb., 2010) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918894/

    “Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer’s disease are the neurofibrillary tangle and the senile plaque.”

    These remain the primary ways doctors diagnose this disease on autopsy, even if they are not perfect.

    Hmmm…high levels of arginine and low levels of lysine in older people who test positive for HSV-1 are linked to increased incidence of Alzheimer’s disease, and other ailments of aging. Foods high in arginine include nuts, grains, and tofu. Foods rich in lysine include red meat, eggs, and dairy.

    How have doctors and nutritionists been tellng us to eat for at least the past 40-50 years? Limit, or avoid altogether: red meat, eggs and dairy (lysine rich); while increasing intake of nuts, whole grains, tofu (arginine rich)!

    Now autopsies of Alzheimer’s victims show high arginine levels and low lysine levels. Is there autopsy data available prior to the past 50 years to enable comparison of current data to data of patients who had been diagnosed as having had dementia at the time they died? Those people are less likely to have been following the current, so-called “healthy” diet advice.

    Could Alzheimer’s be a man-made or diet induced, “unbalanced” condition, brought on by well-meaning, but increasingly isolated, single-focused medical, nutritional and health “specialists? Are these so-called”experts” so focused on the health of individual organs, they fail to see how they interact with or impact the rest of the body?

    What about increases in other epidemic health conditions over the last 50 years? Do we really have the “best” health care system in the world, or just the best “profit-driven” system? Who benefits from staying healthy except the patients?

    the article lists foods high in arganine — to be avoided in this context but highly recommended in all kinds of other descriptions of a healthy diet. OK, we’re between a rock and a hard place.
    Now what about foods high in l-Lysine? A guide to tilting the diet to counterbalance the arganine.
    Better to do these things via natural sources whenever possible, as many examples have already taught.

    Ever since I saw in one of your newsletters that L-lysine was helpful in preventing cold sores, I started taking it daily. I went for over a year with no breakouts at all, and recently I spotted what looked like the beginning of one so I immediately got my prescription for Valtrex filled. The next morning it was gone, just a small red spot. Before all of this I had a breakout that was the worst ever, and I was even worried I’d managed to get it in one of eyes (fortunately I didn’t).

    I’m so grateful to you for the information, not only because cold sores are very uncomfortable and unsightly, but I also worry about Alzheimer’s. I wish we had some solid evidence, or better yet, a way of preventing it. Aging is difficult enough without having this hanging over your shoulder.

    I am 72 year old female and remember getting cold sores back in high school. For years I have been taking antiviral meds to control once I notice an outbreak. I carry a small supply wherever I go. About two years ago I started taking L-Lysine 1,000 mg daily. I haven’t had a cold sore in over a year until just recently I had a very tiny one. I controlled with the antiviral med. My cold sore was not really visible and went away very quickly. I credit taking L-Lysine and plan to continue, especially after reading your Alzheimer article and the potential link to cold sores. Thank you.

    What about shingles? I’ve had it around my L eye? Does that make me more susceptible?

    Other hypotheses, with supporting evidence, have invoked infections by P gingivalis, the organism most responsible for gingivitis ( gum disease).

    And there are references to a link with other organisms, like fungi…

    It could be that immune deficiencies, most commonly due to aging, are not coping with a mixture of possible infections, leading to chronic brain inflammation and hence the neuro-degeneration of Alzheimer’s Disease and other brain diseases.

    This is a very plausible hypothesis. We need the neuroscience community to start looking into such possibilities sooner rather than later.

    This is very interesting. I have Meniere’s disease and one theory on this still-incurable condition is that the herpes virus is involved. Some Meniere’s regimens recommend daily supplements of L-Lysine to help combat the condition. Although Meniere’s originates with a disorder of the inner ear, the Meniere’s “attacks” are essentially neurological. Unfortunately the drug many physicians recommend to stifle the attacks (Meclizine) is anti-cholinergic and implicated with dementia.

    Both my mother and uncle (by marriage) developed dementia after serious bouts of C-dif.

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