Supplements & Drugs: What Is the Evidence for Alzheimer’s Prevention?
Researchers are investigating whether certain supplements and medications developed for other purposes might help reduce the risk of Alzheimer’s disease.
Some—such as omega-3s, magnesium, vitamin D, and creatine—already have roles in general health. Others, including low-dose lithium, metformin, GLP-1 drugs, cholesterol-lowering drugs, and PDE5 inhibitors such as tadalafil (Cialis), are being studied for possible effects on the brain.
None has been established as something cognitively healthy people should take specifically to prevent Alzheimer’s. But definitive prevention trials are difficult and expensive, particularly for inexpensive supplements and generic drugs where commercial incentives for large trials may be limited.
The more established strategy remains addressing risk factors such as insulin resistance, high blood pressure, abnormal lipids, physical inactivity, poor sleep, smoking, and nutritional deficiencies.
Omega-3s & DHA
DHA, an omega-3 fatty acid found particularly in fatty fish, is an important component of brain-cell membranes. Studies have associated fish consumption and higher omega-3 intake with better cognitive health, although randomized trials have not established that supplements prevent Alzheimer’s.
APOE4 may affect DHA metabolism, making omega-3 status particularly interesting in people with this genetic risk factor.
For people who eat little fish, omega-3 supplementation may be a reasonable way to increase EPA and DHA, with potential benefits extending beyond brain health.
Magnesium
Magnesium is involved in energy production, blood-glucose regulation, blood pressure, nerve function, and bone health. Many Americans—particularly older adults—do not consume recommended amounts.
Low magnesium status has been associated with metabolic and cardiovascular problems and possibly cognitive decline, although supplementation has not been shown to prevent Alzheimer’s.
The strongest case is for ensuring adequate intake and correcting deficiency, rather than taking high doses specifically for brain protection.
Vitamin D
Vitamin D is important for bone, muscle, and immune health, especially as we age.
Low levels have repeatedly been associated with greater risk of cognitive decline and dementia, but supplementation trials have produced mixed results.
For people with low blood levels, limited sun exposure, or inadequate intake, correcting deficiency makes sense regardless of whether vitamin D ultimately proves useful for Alzheimer’s prevention.
Creatine
Creatine is best known for its benefits in building muscle, improving strength, and supporting physical performance, particularly when combined with resistance exercise. But its potential benefits extend beyond muscles.
The brain requires enormous amounts of energy, and creatine plays an important role in helping brain cells meet those demands. Growing research suggests that creatine supplementation may improve memory, cognitive performance, and brain function, particularly in older adults or under conditions of increased energy demand.
Creatine monohydrate is inexpensive, widely studied, and generally well tolerated in healthy adults. Its combination of established muscle benefits and promising brain research makes it particularly interesting for healthy aging and cognitive health. Whether it can help prevent Alzheimer's disease remains an important question for future research.
Low-Dose Lithium
Lithium has attracted increasing attention because of possible effects on amyloid, tau, inflammation, and cellular maintenance.
A striking 2025 study found reduced lithium in the brains of people with mild cognitive impairment and Alzheimer’s. In mice, very low-dose lithium orotate reduced Alzheimer’s-like pathology and improved memory.
The human evidence is much less developed. Lithium also deserves caution because prescription doses can affect the kidneys and thyroid and interact with medications. Over-the-counter lithium orotate has not been established as an Alzheimer’s-prevention treatment.
Still, low-dose lithium is one of the more intriguing areas to watch.
Metformin
Metformin improves insulin resistance and glucose regulation and has been used safely for decades in type 2 diabetes.
Because diabetes and insulin resistance are associated with greater dementia risk, researchers have investigated whether metformin users also experience less cognitive decline. Observational studies have produced encouraging but inconsistent results.
Metformin is especially interesting for people who already have metabolic reasons for taking it. Whether it has a role in Alzheimer’s prevention independent of those benefits remains uncertain.
GLP-1 Drugs
GLP-1 drugs such as semaglutide improve blood glucose, reduce body weight, and can lower cardiovascular risk in appropriate patients.
Those effects made them promising candidates for Alzheimer’s research. However, two large phase 3 trials reported in 2025 found that oral semaglutide did not slow clinical progression of early Alzheimer’s disease, despite effects on some Alzheimer’s-related biomarkers.
That does not rule out possible long-term brain benefits from improving obesity, diabetes, and cardiovascular health, but it substantially weakens the case for semaglutide as a direct Alzheimer’s treatment.
Because GLP-1 drugs substantially reduce appetite and food intake, researchers are also paying greater attention to protein and micronutrient intake, particularly in older adults. Someone eating smaller amounts of an already nutrient-poor diet may not get enough protein, iron, calcium, magnesium, Vitamin D, or other essential nutrients. Loss of lean mass is another concern during substantial weight loss, making adequate protein and resistance exercise particularly important as we age.
Cholesterol-Lowering Drugs
Vascular health and brain health are closely connected, and abnormal cholesterol—particularly elevated LDL in midlife—is associated with greater cardiovascular and dementia risk.
Statins and other cholesterol-lowering drugs are well established for cardiovascular prevention in appropriate patients. Ezetimibe is also being investigated for possible effects involving amyloid, tau, and cellular cleanup pathways.
For now, the strongest reason to treat abnormal lipids is cardiovascular health, with possible brain protection an additional area of research.
PDE5 Inhibitors — Cialis & Viagra
PDE5 inhibitors such as tadalafil (Cialis) and sildenafil (Viagra) improve blood flow by enhancing nitric-oxide signaling.
Some large observational studies have reported lower Alzheimer’s rates among men taking these drugs, generating interest in possible vascular and brain effects. Other analyses have not found a reduction in dementia risk, so the evidence remains inconsistent.
These drugs also interact dangerously with nitrate medications, an important consideration for older adults.
Use Supplements Selectively
The goal should not be to take every substance that might someday prove helpful.
A better foundation is exercise, good sleep, metabolic and cardiovascular health, a nutritious diet, and correction of genuine nutritional deficiencies. Supplements can then be considered selectively when there is a reasonable rationale.
Some—particularly omega-3s, magnesium, vitamin D, and creatine—may offer broader health benefits regardless of what future Alzheimer’s trials show. Repurposed medications deserve greater caution because benefits must be weighed against side effects, interactions, and an individual’s medical circumstances.
Research into Alzheimer’s prevention will inevitably leave unanswered questions. Absence of a definitive prevention trial is not proof that an intervention works—or that it does not. It tells us how certain we can be about the evidence today.
Learn More
Background & Research
World Health Organization — New Guidelines: Up to 45% of Dementia Risk Could Be Prevented or Delayed
Summarizes WHO’s 2026 recommendations for reducing dementia risk by addressing modifiable factors including physical inactivity, smoking, diet, social isolation, hearing loss, air pollution, hypertension, diabetes, and high cholesterol.
An overview of research on diet, vitamins, supplements, and other nutritional approaches being investigated for cognitive health and Alzheimer’s prevention.
Describes the 2025 research linking reduced lithium levels with Alzheimer’s disease and the experimental finding that very low-dose lithium improved Alzheimer’s-related abnormalities in mice.
Could Lithium Change What We Know About Alzheimer’s? — SuppCo
Explains the emerging research on low-dose lithium and Alzheimer’s, including the difference between promising animal research and the still-limited evidence in humans.
A clinical trial investigating whether metformin can slow cognitive decline and biological changes associated with Alzheimer’s in people with mild cognitive impairment.
Videos
An overview of emerging research on Alzheimer’s prevention and the lifestyle, metabolic, and other potentially modifiable factors that may help protect brain health.
Dr. Norwitz discusses the 2025 Harvard research on lithium and Alzheimer’s disease, including why very low-dose lithium orotate produced particularly intriguing results in mice, and explains how the findings have influenced his own approach to brain health.
Dr. Norwitz discusses emerging research suggesting that ezetimibe may have effects relevant to Alzheimer’s disease that go beyond lowering cholesterol, including possible effects on amyloid, tau, and cellular cleanup mechanisms, while emphasizing that the human evidence remains preliminary.
Dr. Malik discusses research on tadalafil beyond erectile dysfunction, including its possible effects on cardiovascular health, blood flow, and healthy aging.
Ben Bikman explores creatine's role in brain energy metabolism and emerging research on memory, cognition, and neurological health.