"Oxidized Cholesterol as a Cause of Alzheimer's Disease"
Too much cholesterol in the blood has long been considered
to act as a primary risk factor for developing Alzheimer's disease,
and possibly Parkinson's disease.
I've shown these striking images of what the brain arteries
of Alzheimer's victims look like on autopsy,
clogged with fat and cholesterol,
compared to non-demented elderly controls.
But wait a second,
cholesterol cannot be directly exported across the blood-brain barrier,
so it can't directly get into the brain or out of the brain.
What if the brain has too much cholesterol
and needs to get rid of some?
As a safety valve, there's an enzyme in the brain that oxidizes the cholesterol,
and in that form it can exit the brain and eventually the body.
Ah, but here's the kicker:
although this fact means that the brain can eliminate excess amounts
of these oxidation products, it could be a two-way street.
It could allow toxic amounts of oxysterols—oxidized cholesterol—
present in the blood stream to go the other way and accumulate in the brain.
This is not just a theoretical concern.
This elegant study showed that by measuring oxidized cholesterol levels
in the blood coming off of the brain,
measured in the jugular vein in the neck,
compared to the levels going into the brain through the artery,
you could measure the difference,
and this shows that if you have too much oxidized cholesterol
in your bloodstream, it can end up in your brain.
This is a problem because the accumulation of oxysterols can be
cytotoxic, mutagenic, atherogenic, possibly carcinogenic—
in other words, toxic to cells, toxic to DNA,
and contributing to heart disease and maybe cancer.
Yes, samples from atherosclerotic plaques on autopsy
contain 20 times more cholesterol than normal arteries,
but contain 45 times higher levels of oxidized cholesterol.
Cholesterol oxidation products may be up to a hundred times more pathological,
more toxic than un-oxidized cholesterol,
contributing to not only heart disease but potentially a variety
of different major chronic diseases including Alzheimer's.
OK, so how can we cut down on the amount of these oxysterols in our body?
One way is by not eating them.
Oxidized cholesterol is found in milk powders, meat and meat products
(including fish), cheese, eggs and egg products.
Until recently, our understanding has been limited
by the lack of testing methods
to accurately analyze the amount found in various foods until now.
Found throughout the animal products.
Canned tuna was surprisingly high, but ghee takes the cake.
Ghee, clarified butter, boiled butter, is commonly used in Indian cooking.
The method of preparation appears to multiply
oxidized cholesterol levels tenfold.
This dietary exposure from oxidized cholesterol
may help explain why the subcontinent of India is ravaged by such heart disease,
even though a significant proportion of the population
stays away from meat and eggs.
A number of Indian dairy-based desserts are also made in a similar way.
Oxidized cholesterol in the diet is a source
of oxidized cholesterol in the human bloodstream,
where it can then readily cross the blood-brain barrier into the brain,
and this could trigger inflammation inside the brain, the buildup of amyloid,
all occurring years before the impairment of memory is diagnosed.
These early studies showing the buildup of oxidized cholesterol in the blood
of those fed meals rich in oxidized cholesterol,
where you get this spike in your bloodstream a few hours after you eat,
was done with things like powdered egg,
which can be found in a lot of processed foods,
but you typically don't sit down to a meal of it.
You get the same thing, though, from eating normal food sources.
Give some folks some salami and Parmesan cheese,
which are naturally rich in cholesterol oxidation products,
and later that day it's circulating throughout their bodies.
And higher levels are not only associated with mild cognitive impairment,
but Alzheimer's disease as well.
Increased concentrations in the brain may promote cellular damage,
cause nerve cell dysfunction, degeneration,
and could contribute to neuro- inflammation, brain inflammation,
and the formation of these amyloid plaques.
You can show the boost in inflammatory gene expression right in a Petri dish.
You can grow human nerve cells in vitro and drip a little cholesterol on
and you get a bump in inflammation,
but add the same amount of oxidized cholesterol and it gets much worse.
And if you look at the changes in brain oxysterols at different stages
of Alzheimer's disease on autopsy, you can see how
the three main cholesterol oxidation products appear to be building up.
Levels have been shown to dramatically increase in Alzheimer's disease brains,
adding to the evidence that oxidized cholesterol may be
a driving force behind the development of Alzheimer's disease.