Cyclodextrins: A Surprising Ally for APOE4 Brain & Heart Health

If you’ve been following my writing, you know that one of my biggest interests is how to protect brain and vascular health in people with the APOE4 gene variant. APOE4 increases the risk of Alzheimer’s disease and heart disease, partly because it alters the way our bodies handle cholesterol and fats. Today, I want to shine a light on something that’s not yet mainstream but looks very promising: cyclodextrins.

What Are Cyclodextrins?

Cyclodextrins are naturally derived sugar molecules that act a bit like a tiny sponge or molecular donut. Instead of being digested like normal sugar, they’re shaped to capture and “hold onto” certain fat-like molecules.

Think of them as molecular cleaning helpers: they can soak up extra cholesterol or other sticky fats and escort them safely out of the body.

Connection to Niemann-Pick Disease

Cyclodextrins first gained attention in rare genetic conditions like Niemann-Pick Type C disease. In this devastating disorder that leads to premature death, cholesterol gets trapped inside cells, leading to toxic buildup in the brain and other organs.

Researchers found that cyclodextrins could help “unclog” the system, removing trapped cholesterol and improving function. While Niemann-Pick is very rare, it opened the door to understanding how cyclodextrins might help with other conditions linked to cholesterol mishandling—including APOE4.

Why It Matters for APOE4 Carriers

One of the challenges with APOE4 is how it handles fats in the brain and blood vessels. APOE4 carriers are more prone to:

• Cholesterol buildup in arteries (atherosclerosis)

• Sluggish clearance of amyloid plaques in the brain

• Less efficient lipid transport that affects brain cells and synapses

Cyclodextrins may offer a way to “tidy up” these problem areas. By binding to excess cholesterol and sterols, they can reduce some of the harmful buildup that drives both vascular disease and Alzheimer’s risk.

Safety & Delivery: Why Rectal, Low-Dose?

One of the most interesting things is how cyclodextrins are given. In high doses (like those used for Niemann-Pick), there can be kidney toxicity. But at very low doses, especially via rectal delivery, there appears to be no known toxicity.

Why rectal? Two reasons:

1. It bypasses the stomach and liver, so more of it gets into circulation where it can do its work.

2. It’s gentler on the system and allows steady absorption at small, effective doses.

At this level, the focus isn’t treating a rare disease—it’s about supporting vascular health, reducing sterol buildup, and potentially improving brain function in people at higher risk, like APOE4 carriers.

Forward-Thinking Cardiologists Are Paying Attention

Although still under the radar, some forward-thinking cardiologists, like Dr. James Roberts have already started using cyclodextrins with their patient populations. These physicians are finding that small, carefully managed doses can help lower vascular inflammation, improve cholesterol handling, and in some cases even enhance cognitive clarity. While these observations are early and anecdotal, they suggest that cyclodextrins could become a valuable addition to modern cardiovascular and brain-protective care—especially for patients whose genetics put them at higher risk.

Why This Matters Even More for APOE4 + Lp(a)

For those of us who carry the APOE4 gene and also struggle with high lipoprotein(a), or Lp(a), the stakes are even higher. Lp(a) is a sticky cholesterol particle strongly linked to heart attacks and strokes, and it’s notoriously hard to lower with standard treatments. More on lipoprotein lp(a) here. Combine that with APOE4’s tendency toward poor lipid handling, and you’ve got a recipe for accelerated vascular problems.

Cyclodextrins could offer a unique advantage here. By helping clear out cholesterol and sterols from the blood and vessel walls, they may ease some of the burden that Lp(a) and APOE4 together create. In other words, they might give this particularly vulnerable group a much-needed tool for protecting arteries and preserving brain health.

What the Future May Hold

Cyclodextrins are still under research, but here’s why they’re exciting:

• They may help keep blood vessels cleaner, lowering risk of heart disease.

• They might improve lipid handling in the brain, helping neurons function better.

• They’re non-toxic at low doses, especially when used strategically (like rectal microdosing).

In short, cyclodextrins may become one more tool to help APOE4 carriers age with sharper brains and healthier arteries.

The first company to popularize cyclodextrin suppository treatment was Cholrem/Cavadex in Australia. However, due to medical claims made on their website, their shipments were eventually seized by the FDA. At present, Atherocare appears to be available, while the U.S. company Cyclarity is conducting clinical trials in Australia. Taken together, these developments suggest that the future use of cyclodextrins looks quite promising.

Don’t miss this fascinating presentation by Cyclarity’s CEO, Dr. Oki O’Connor, discussing the research and its potential connection to APOE4.

Bottom Line

Cyclodextrins aren’t a magic bullet, but they’re part of a growing toolbox aimed at APOE4-driven risks. What started as a therapy for a rare childhood disease is now showing potential for protecting millions of people at risk for cardiovascular disease and dementia.

As always, more studies are needed—but this is definitely a space to watch. And for those of us who carry APOE4, the idea of a safe, low-dose way to “mop up” excess cholesterol and protect the brain is very appealing.

Want to learn more about cyclodextrins? Below are some links!

Dr. Roberts on Cyclodextrins
Cyclarity’s approach to Atherosclerosis reversal
ScienceDirect Article

👉 Have you heard of cyclodextrins before? Would you consider trying them if more research confirms their safety and benefits? I’d love to hear your thoughts in the comments.