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. An article from the BBC (“Alzheimer’s: The heretical and hopeful role of infection”) published October 6, 2021, discusses the role of anti-herpes drugs in the fight against dementia.
This reader is the latest person to wonder about an antiviral drug (valacyclovir) to prevent Alzheimer’s disease:
Q. I have seen that herpes zoster is a risk factor for dementia. What about herpes simplex? Like zoster, it’s a “gift that keeps on giving.” I would guess that it would have similar risks.
At 75, I have had both conditions. I had shingles three or four times over the years, but not since getting the Zostavax and later Shingrix vaccinations.
After dealing with herpes for 50 years, I’ve been doing well on daily valacyclovir. It prevents outbreaks.
Am I at even higher risk for dementia from all the years harboring these two herpes viruses prior to vaccines and prophylaxis?
A. There is growing evidence that herpes viruses are associated with an increased risk of dementia (Alzheimer’s Research & Therapy, March 12, 2024). The shingles vaccine seems to provide a degree of protection and antiviral drugs like valacyclovir may also be somewhat beneficial (Neurotherapeutics, April 2018).
You may want to listen to our free podcast on this topic. It is Show 1394: Viruses, Vaccines and Alzheimer Disease (August 6, 2024).
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.
He 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…
Here is his 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.
