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The infectious hypothesis of Alzheimer’s disease

Larry Kaskel, MD
Conditions
October 25, 2025
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When I tell colleagues that I offer Valtrex (valacyclovir) and low-dose lithium orotate to patients worried about developing Alzheimer’s, the silence in the room thickens. Someone always asks, “Where’s the randomized controlled trial?” That’s exactly the problem. We keep waiting for perfect evidence while the disease eats away at people’s brains.

I’m an internist and lipidologist who’s spent years watching the medical establishment chase the wrong villains, like cholesterol, salt, and saturated fat, while ignoring the role of infection, inflammation, and immune dysfunction. Alzheimer’s is just the latest frontier in this blind spot.

The infectious hypothesis of Alzheimer’s isn’t fringe anymore. Studies from Tufts University, Harvard, and Oxford have all found herpes simplex virus type 1 (HSV-1) in the brains of older adults with Alzheimer’s pathology. Epidemiologic data from Taiwan’s National Health Insurance Research Database showed that people with HSV infection had a 2.5-fold higher risk of developing dementia, and that those treated with antiviral drugs like acyclovir or valacyclovir had an 88 percent reduction in that risk. Let that sink in: an 88 percent reduction.

We’ve seen this movie before. In the 1980s, ulcers were “caused by stress” until Barry Marshall drank a beaker of H. pylori to prove an infectious cause. In cardiology, we’ve been slow to admit that Chlamydia pneumoniae has been isolated in atherosclerotic plaques for decades. Yet here we are again, pretending that Alzheimer’s must be purely metabolic, genetic, or bad luck.

Valtrex isn’t a panacea, but it’s cheap, safe, and mechanistically plausible. Ongoing clinical trials are testing high-dose valacyclovir in early Alzheimer’s patients, but the safety data we already have from decades of HSV treatment is solid. I usually start patients who have HSV-1 or HSV-2 seropositivity on 500 mg-1 g daily. I combine that with lithium orotate 5 mg, not for mood but because microdose lithium has been associated with lower dementia rates in multiple population studies and may stabilize tau phosphorylation.

This isn’t reckless; it is a form of preventive empiricism. We treat hypertension to prevent stroke long before the RCTs proved benefit for every drug class. We give metformin to people with prediabetes without knowing which ones will actually develop diabetes. Yet when it comes to the brain, where the stakes are irreversible, we freeze.

So yes, I’m tired of waiting. If a patient with a strong family history or early cognitive complaints wants to act now, I’ll offer a low-cost antiviral and lithium combo with full informed consent. The downside is minimal; the potential upside, enormous. Someday, the RCTs will catch up. By then, some of my patients might still remember my name.

Larry Kaskel is an internist and “lipidologist in recovery” who has been practicing medicine for more than thirty-five years. He operates a concierge practice in the Chicago area and serves on the teaching faculty at the Northwestern University Feinberg School of Medicine. In addition, he is affiliated with Northwestern Lake Forest Hospital.

Before podcasts entered mainstream culture, Dr. Kaskel hosted Lipid Luminations on ReachMD, where he produced a library of more than four hundred programs featuring leading voices in cardiology, lipidology, and preventive medicine.

He is the author of Dr. Kaskel’s Living in Wellness, Volume One: Let Food Be Thy Medicine, works that combine evidence-based medical practice with accessible strategies for improving healthspan. His current projects focus on reevaluating the cholesterol hypothesis and investigating the infectious origins of atherosclerosis. More information is available at larrykaskel.com.

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