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Low Brain Cholesterol: Separating Fact From Fiction

How statin drugs and plant-based diets actually affect your mental health.

Suzi Smith, used with permission
Source: Suzi Smith, used with permission

Where do you find the highest concentration of cholesterol in your whole body? In your brain. The brain is cholesterol-rich on purpose—because it needs large amounts of cholesterol to function properly. So, what does that mean for the growing number of people choosing naturally cholesterol-free plant-based diets? And what about the 15 million Americans who take statin medications like Lipitor to lower their cholesterol levels? People who are trying to lower their cholesterol levels are worried about heart health. But how does lowering cholesterol affect mental health?

What is cholesterol?

Poor cholesterol—so misunderstood. Cholesterol is a waxy substance naturally embedded in our membranes, the flexible packaging surrounding every cell in our bodies. Cholesterol contributes structural firmness to membranes and keeps them from falling apart. Membranes are not simply protective cell wrappers; they are dynamic, highly intelligent structures that participate in cellular signaling and the transport of substances into and out of cells. Cholesterol is also an essential ingredient in vitamin D and many other hormones in the body, including estrogen and testosterone. All animal foods (meat, seafood, poultry, dairy, and eggs) contain cholesterol because all animal cells need cholesterol.

Why does the brain need cholesterol?

Suzi Smith, used with permission
Source: Suzi Smith, used with permission

Although the brain represents only 2% of total body weight, it contains 20% of the body’s cholesterol. What is all that cholesterol doing up there? Synapses— the magical areas where communication between brain cells takes place—are lined by cholesterol-rich membranes responsible for passing neurotransmitters like serotonin, GABA, and dopamine back and forth. Myelin, the white matter that insulates brain circuits, is made from tightly-wound membranes containing 75% of the brain’s cholesterol. Cholesterol also helps guide developing nerve endings to their destinations on “lipid rafts”. If the brain is too low in cholesterol, its membranes, synapses, myelin and lipid rafts can’t form or function properly, bringing all brain activity—including mood regulation, learning, and memory— to a screeching halt.

Do vegans need to worry about low brain cholesterol?

Thankfully, even though plant foods contain zero grams of cholesterol, vegan diets probably do not cause low brain cholesterol. This is because the cholesterol in our brains doesn't come from the cholesterol we eat! Cholesterol is too big and bulky to cross the blood-brain barrier from the body’s blood vessels into the brain tissue—so the brain makes all of its own cholesterol on site. Cholesterol can be manufactured out of anything—carbohydrate, protein, or fat—so regardless of what we eat, we can always make plenty of cholesterol. Case in point: plenty of vegans have “high cholesterol” levels in their blood despite eating a cholesterol-free diet. To see for yourself, simply google “vegans with high cholesterol” to read individual stories or see this interesting case study. We have no way to directly measure brain cholesterol levels in living human beings, so we can’t compare brain cholesterol levels of vegans, vegetarians and omnivores, but there is no reason to think that people who choose a vegan diet would have lower brain cholesterol levels than anyone else would. There are other nutrients vegans do need to worry about, but contrary to popular belief, cholesterol is probably not one of them.

Does low blood cholesterol cause mental health problems?

Probably not. It wouldn’t make sense for low blood cholesterol to cause psychiatric symptoms, because the brain makes its own cholesterol regardless of how much cholesterol is in the blood. Simply put: low blood cholesterol does not cause low brain cholesterol.

Some studies weakly suggest that people with lower total blood cholesterol levels may be more likely to be depressed, violent, or have suicidal thoughts, but other studies do not. All of the studies on both sides are “epidemiological” studies, which are incapable of showing cause and effect relationships—they can only point out possible associations. So, even if every epidemiological study showed a link between low cholesterol and psychiatric problems, the apparent connection between the two could simply be a coincidence. At this point in time, there is no clear scientific support for the notion that low blood cholesterol increases risk for depression, violence, or suicidal thinking.

Do people who take statin drugs need to worry about low brain cholesterol?

Yes. “Statins” are drugs designed to lower your level of LDL cholesterol—the so-called “bad cholesterol.” They work by turning down the activity of HMG-CoA reductase, the enzyme our cells use to build new cholesterol molecules. Unfortunately, statins do cross the blood-brain barrier and enter brain cells, where they reduce the brain’s natural ability to make the beautiful cholesterol molecules the brain needs to do its important work.

We used to think that only certain statin drugs could cross into the brain, but it turns out that they ALL do; it’s just that some reach higher levels inside the brain than others. But don’t let that lull you into a sense of false security—even Pravastatin (Pravachol), which has the hardest time making the journey, penetrates the brain enough to interfere with its cholesterol factory.

There haven’t been many human experiments testing the effects of statins on brain function, but the few that have been done suggest there is a real risk of cognitive problems in some people:

“RCTs [randomized controlled trials] on effect of statins and cognitive function have shown debatable and controversial results with three RCTs reporting poorer performance scores in a minority of cognitive tests among statin users. Hence, we conclude that there is a need for more randomized control trials and until then benefits of statins must be weighed against the risks of cognitive decline on an individual basis.” [Chatterjee S et al 2015 Curr Cardiol Rep 17:4]

All statin manufacturer package inserts include the same warning:

“There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).”

Nonserious? Seriously? I don’t know about you, but I wouldn’t want any of those side effects. They say they are rare, but “post-marketing” reports tend to be rare, because most people don’t report side effects directly to the manufacturer. If you feel fuzzy-headed on a statin, trust your experience over the fine print. The only way to know for sure if the statin is the culprit is to stop the statin to see for yourself if the fog lifts. [In most cases, this would not be medically dangerous, but please always consult with your health care provider before making any changes to your medication regimen].

Statins and Heart Disease

Stop the statin?! What about high cholesterol and heart disease? Won’t millions of arteries across the country slam shut?

Statins are a bad idea for most people—not just because they can gum up your brain, slow your hormone production, reduce your coenzyme Q10 levels, cause muscle pain, and put you at risk for other potential side effects, but also because they may not even reduce your risk for heart attacks. Prominent cardiologist Dr. Aseem Malhotra agrees: heart disease is NOT about cholesterol or saturated fat.

Heart disease is about insulin resistance (aka pre-diabetes) and inflammation within your blood vessels. Diets high in refined carbohydrates (like sugar, flour, cereals and fruit juice) can lead to abnormally high insulin levels. It just so happens that insulin boosts the activity of your cholesterol-building enzyme, HMG-CoA-reductase—the very same enzyme that statin drugs suppress! [Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 5th ed. New York, NY: W.H. Freeman; 2008:842.]

That’s right—eating too much processed carbohydrate is most likely what’s raising your “bad” cholesterol (and your triglycerides) in the first place. The call is coming from inside the house. Turn down the refined carbs in your diet and you will naturally improve your cholesterol test results—all without drugs, side effects or co-pays. Chances are, if you have “high cholesterol,” you don’t have a cholesterol problem; you have a sugar problem. Cholesterol is just an innocent bystander, corrupted by too much sugar—guilt by association.

How much cholesterol should we eat?

This is a fascinating question and difficult to answer with certainty. Our cells can make cholesterol from scratch out of foods that don’t contain any cholesterol, so technically, we don’t need to eat any cholesterol. However, making cholesterol is hard work; it takes 30 chemical reactions to build a single cholesterol molecule. For all we know, the body may prefer that we obtain ready-made cholesterol from food so it doesn’t have to bend over backwards to keep us in stock.

So, theoretically anyway, it’s possible to get by without eating any cholesterol, but is it dangerous to eat too much cholesterol? Apparently not.

Even the latest USDA guidelines finally dropped their case against dietary cholesterol:

"available evidence shows no appreciable relationship between consumption of dietary cholesterol and serum cholesterol….Cholesterol is not a nutrient of concern for overconsumption."

WerbeFabrik/Pixabay (modified)
Source: WerbeFabrik/Pixabay (modified)

Why don't we need to worry about dietary cholesterol? The body has elegant mechanisms in place to regulate how much cholesterol we absorb from food. More importantly, the vast majority of the cholesterol in your blood doesn’t come from foods you eat; it is made by your own body. "High cholesterol” occurs when we eat too many of the wrong carbohydrates too often, not when we overeat steak and eggs. For more information, see my cholesterol page.

What is the best diet for the brain?

As you have seen, it’s possible the brain may not care how much cholesterol you eat—so what does the brain care about? What kind of diet does your brain want you to eat? Vegan? Vegetarian? Mediterranean? Paleo? Low-carb? This is a hotly-contested topic, and one that unfortunately often sparks vicious public and private debates. I’ve looked at this issue from many angles, and the short answer is: it depends. Please see my Food Fights article for interesting new ways to think about this question and to improve the quality and tone of the conversation.

Some foods are better than others at nourishing your noggin, and some foods that we think of as healthy can even work against us! To be sure you are getting all the vitamins, minerals, and omega-3s you need to operate at the top of your game, please see my article about micronutrients and brain health.

Regardless of which diet you choose, there are two universal rules we can all agree on: 1) avoid processed modern non-foods and refined carbohydrates like the plague and 2) make sure you are getting all the essential nutrients your brain needs so you can operate at the top of your game. In short: minimize the junk, maximize the nutrition!

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