High Levels of HDL are a Risk for Dementia

February 25, 2024

Very High Levels of HDL Lipids are a High Risk for Dementia

You have always been told that HDL is your "good" cholesterol, the more the better. Well, the shine has come off the apple. HDL over 80 isn't so good. There appears to be a U-shaped curve with increasing benefit up to 80, and then a sharp increase over HDL of 80. Published in the LANCET this January is a great study using 16,703 participants over age 70 (from Australia) and 2411 participants over age 65 from Kaiser Health in California. It was part of a randomized, placebo-controlled trial of baby aspirin. 830 cases of dementia developed over the 6 years of the study. Comparing HDL levels to dementia risk in that population showed a 27% increased risk when HDL rose over 80. That's alarming. No matter how they analyzed the data, that association continued.

This study confirms the findings now of multiple other studies over the last decade that appear to show much the same finding. One of the largest was from Great Britain, looking at some 415,00 adults that found an increase in all-cause mortality of some 11% for HDL over 80. In their data, that held true only for men.

What is a bit confounding is that we don't know how to lower that high HDL. All we find are pablum recommendations of "eat right" and "exercise more". Ok, ok, nice try. Let's first understand what HDL is and what role it plays. Here is a brief physiology lesson.

HDL is part of cholesterol transport. Cholesterol is made in the liver. It is a critical membrane lipid that is rigid and strong. It's water-insoluble and needs a transport protein that can carry it through the blood. Some 40% of cellular membranes are made of cholesterol, wherein it provides the strength and firmness to make a strong membrane. Like the joists or framing of a house that give a house rigid structure and form, you need structural strength to make a cell wall and the requisite shape of a cell. That's the role of cholesterol. But a house has to have windows and doors to see out and get in and out. Ditto for a cell. Part of every cell are membrane regions with much less cholesterol and more plasmalogens which can shape shift and move. Embedded proteins that allow cross-membrane communication need that ability to shapeshift to communicate.

Cholesterol is absolutely indigestible. The only way to get rid of it is to excrete it in your bile. To get from your cell, where there is too much cholesterol, back to your liver, you need a transport protein. Voila, therein lies the role for HDL particles. They are the taxi ride to the airport.

There you have it. Cholesterol is always coming (LDL particles) and going (HDL particles). If you eat a lot of animal protein, you ingest more cholesterol. Plants have virtually none (except for some "sterols" in some nuts and seeds).

The issue with coronary artery disease isn't the coming and going of cholesterol. It is the inflammation and endothelial dysfunction that make the artery wall naked and amenable to absorbing the cholesterol that's the problem with coronary artery disease. Taking a statin lowers the production of cholesterol but doesn't do much for endothelial dysfunction driven mostly by the inflammation caused by visceral fat, and inflammatory foods (sugar etc).

How to lower your HDLs? We are still dancing around that. My suspicion is that we will eventually see the role for Nitric Oxide. The inexorable march of NO decline with age can now be reversed with NO lozenge therapy.  What is most interesting is that we are finding that HDLs are much more than just passive taxis. They have all sorts of antiinflammatory properties and even can be shown to protect mitochondria.  Stay tuned.  This is interesting.

www.What will Work for me. I'm such a sugar addict, I don't know how I'm going to even get my HDL up above 40. I've hovered in the 28-30 range for decades. I finally got above 40 when I started taking plasmalogens. Now, I'm a year into NO which will start generating research studies now that we can easily obtain it. My bet is that NO/plasmalogen therapy will have a much, much greater effect on reducing vascular disease than statins. It's going to take 10 years to show that. I don't have 10 years to wait. My expiration date is probably sooner than that.

References: The Lancet, American Jr Cardiology, Adv Exp Med Bio., ATVB, Biomedicine and Pharmacotherapy,

Pop Quiz

1. What role does the HDL particle play in our lives?                           Answer: It's the shuttle bus for cholesterol from the cell back to the liver to be excreted in bile.


2. What does a "healthy" level of HDLs mean?                         Answer: Your cells are happy. They have enough cholesterol for their needs and are shipping the extra back to be excreted. Everything appears to be copesthetic. Calmness prevails.

3. Except when your HDL is above 80. What happens then?                            Answer: There appears to be a biphasic curve with increasing mortality and dementia, maybe only for men. This occurs only in 5-6% of the population and may not be relevant for women.

4. What role does cholesterol play in the body?                         Answer: Critical component of all membranes, giving them structural firmness and integrity. And the skeleton to make many hormones (Cortisol, estrogen, testosterone, progesterone, DHEA...) all of which have to be excreted in the bile.

5. What role does NO play with HDLs?                          Answer: There is strong evidence that HDLs stimulate more NO production. That may be why there is a protective effect from HDLs. But it may be the other way around, that NO induces better HDLs. This needs to be parsed out. Time will tell.