Think cholesterol, and you probably think heart disease. But without this fat-like substance, you wouldn’t be able to think about anything much at all. It is one of the most important substances in the brain. Keep it there.
The brain has the highest concentration of cholesterol in the body, with 25% of the body’s total store. Because it is so crucial, the brain makes its own supply.
With all that in mind, it stands to reason that without enough of this essential brain nutrient, you could run into trouble. That trouble may take the form of memory problems and/or depression, and other issues relating to mental health.
There is a well established link between cholesterol and brain function. In a study of 789 men and 1105 women, which examined the relationship between total cholesterol (TC) and cognitive performance, it was found that:
“Lower naturally occurring TC levels are associated with poorer performance on cognitive measures, which place high demands on abstract reasoning, attention/concentration, word fluency, and executive functioning.”
Cholesterol in action
Your cholesterol dependency begins before you are born. There is rapid accumulation in the brain of this substance during the last three months of pregnancy. After birth, the brain continues to grow at quite a pace, requiring a large and constant supply of cholesterol. That’s why human breast milk is a particularly rich source.
This much-maligned yet essential substance is found in all body tissues. Without it, you wouldn’t be able to make vitamin D, or your sex hormones.
As far as the brain is concerned, cholesterol has four main functions, as outlined below.
1. Antioxidant. The brain is 60% fat, making it vulnerable to damage from chemicals called free radicals. Cholesterol plays a protective antioxidant role in the brain, disabling free radicals before they can do any harm.
2. Insulation. The highest concentration of cholesterol is found in the myelin sheath, the insulating layer that wraps around and protects each nerve cell.
3. Barrier. Cholesterol forms part of the cell membrane, controlling what substances can pass in and out of the cell, and giving the cell structure.
4. Firing of neurotransmitters. Cholesterol ensures that neurotransmitters fire properly between nerve cell synapses.
Cholesterol really is quite the multi-tasker, when it comes to cognitive function. So it is hardly surprising that deficiency can have numerous detrimental effects. Deficiency is associated with various brain conditions, including dementia, depression, Parkinson’s and autism.
Cholesterol and dementia
The cerebrospinal fluid of patients with Alzheimer’s disease has been shown to be substantially low in cholesterol. Not surprisingly, then, high brain cholesterol in later life is associated with reduced risk of developing dementia, and higher memory scores in tests.
“Indeed, high cholesterol level is positively correlated with longevity in people over 85 years old, and in some cases has been shown to be associated with better memory function and reduced dementia.”
Cholesterol deficiency and depression
Writing in European Neuropsychopharmacology, scientists describe how significantly lower levels of cholesterol have been found in patients with depression and mood disorders, including bipolar disorder, major depressive disorder (MDD), schizoaffective disorder and risk of suicide.
“Previous work has identified abnormalities in serum cholesterol levels in patients with mood and anxiety disorders as well as in suicidal patients.”
No one knows precisely why this clear association exists, despite a range of theories. But obviously, if something so important to the healthy functioning of the brain is missing, there have to be consequences.
Cholesterol deficiency and autism
Cholesterol supplementation is a form of medical treatment in some cases of children with autism spectrum disorders (ASD). The Smith-Lemli-Opitz Syndrome (SLOS) is a genetic condition characterised by defective cholesterol biosynthesis. Children with SLOS have a high incidence of autism.
SLOS is treated with dietary cholesterol supplementation, which has been shown to result in less autistic behavior, as well as fewer infections, less irritability and hyperactivity and improved sleep and social interactions.
“Cholesterol ought to be considered as a helpful treatment approach while awaiting an improved understanding of cholesterol metabolism and ASD”.
Cholesterol deficiency and Parkinson’s disease
LDL cholesterol is sometimes referred to as “bad” cholesterol (a myth, as we shall see below). Yet low LDL cholesterol is associated with the development of Parkinson’s disease. One study, which looked at the incidence of Parkinson’s in the elderly, found that those with the lowest LDL had 3.5 times greater risk of developing the disease than those with the highest LDL cholesterol.
So why is everyone on statins?
Good question, in view of the fact that millions of people — most of them elderly — take statins on a daily basis, and for the rest of their lives.
The role of this medication is to reduce blood cholesterol levels.
There is a great deal of controversy surrounding statin use and cognitive decline. Many studies have concluded that statins are not only wholly innocent, they can even improve cognitive function, including memory.
Yet people regularly report that they experience memory problems and mental confusion after taking the drug.
So frequent are these reports that the US Food and Drug Administration decided, in 2012, to issue safety warnings on the labelling of statins concerning possible memory loss. Since then, there have been calls for those warnings to be removed (presumably from pharmaceutical companies, and not from the people reporting memory loss and confusion).
Meanwhile, in the UK (described as the statins capital of Europe), these drugs are currently the most widely prescribed medication. The UK also has higher than average rates of dementia in Europe (1.65% in the UK, 1.55% across the EU), according to the organisation Alzheimer Europe.
Whatever statins are doing, they don’t appear to be preventing the rise in dementia cases.
To determine whether there was any truth in claims that statins could benefit memory loss, a review of all the research examined the evidence from trials covering 748 people aged 50–90 with Alzheimer’s and taking statins. The results?
“There is insufficient evidence to recommend statins for the treatment of dementia.”
The evidence seems to suggest the opposite, in line with anecdotal reports of memory loss from the people taking the drug. A small study of eighteen elderly people with dementia and taking statins describes what happened when they were taken off the medication, and then put back on them.
The participants underwent tests to measure brain function using established tests. Significant changes were observed: an improvement in cognition with discontinuation of statins and worsening when they were reintroduced. In their conclusion, the researchers state:
“Statins may adversely affect cognition in patients with dementia.”
The reason for this effect is probably that statins are able to cross the blood-brain barrier and remove cholesterol from the brain. It was once thought that only the fat-soluble statins — atorvastatin, lovastatin, fluvastatin, simvastatin — were able to cross the blood-brain barrier. Now recent research suggests that the water soluble statins are able to do the same.
“If high cholesterol plays a protective role against dementia in the elderly, then the risk-benefit ratio of lowering cholesterol in this population may need to be reevaluated.”
What’s in a name?
You may have heard of “good” and “bad” cholesterol. The fact is, there is only one type of cholesterol, and it’s called cholesterol. That’s it. There are, however, different types of cholesterol transport systems.
Cholesterol is transported around the body by different carriers, known as lipoproteins. There are several types, the main ones being high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL).
High LDL is considered “bad” because it delivers cholesterol from the liver to other parts of the body, including the arteries.
HDL is considered “good” because it transports cholesterol to the liver, for recycling.
So the premise is that anything that lowers cholesterol is good, and anything that raises it is bad.
How can something so bad be so good?
This is where it all starts to get messy. There are plenty of studies that find that HDL is protective against heart disease, and high LDL levels to be a risk factor. However there are also plenty of studies that find no association whatsoever between total cholesterol levels and risk of heart disease. It’s hard to know what to make of it.
The vilification of cholesterol began with the famous Framingham Heart Study. This study was launched in 1950 with the aim of examining aspects of diet and lifestyle that might predispose people to heart disease. Framingham in Massachusetts was chosen because it was considered a typical American community.
Participants were examined every two years to see who had developed heart disease. Risk factors taken into consideration were smoking, obesity, high blood pressure, abnormal electrocardiograms and genetic predisposition.
Bizarrely, even though this was the study that originally fingered cholesterol as a significant risk factor in heart disease, what it actually found was that high cholesterol was only a risk factor in people under the age of 47. For everyone over the age of 47, it was no longer a risk factor.
What’s more, the study revealed that levels of heart disease and death were higher in those whose cholesterol had decreased during the period of the study, compared to those whose cholesterol had gone up. The lower the cholesterol, the greater the risk.
So men over 47 with low cholesterol were more likely to get heart disease than men with high cholesterol.
Similarly, the link between heart disease and cholesterol was found to be non-existent in women over 50.
The cholesterol paradox
The mystery deepens. It is well established that patients in hospital with coronary artery disease are more likely to survive if they have high cholesterol. This protective effect of high cholesterol is known in the scientific community as the cholesterol paradox.
The greatest paradox is perhaps the observation, which has been made on many occasions, that low levels of LDL cholesterol (that’s the “bad” one) are linked to higher overall mortality in patients with heart failure. If you want to survive, you’re better off with high levels of not-so-bad-after-all LDL cholesterol.
You’ll find quite a bit about the mysterious “cholesterol paradox” on-line, including this:
“The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of evacetrapib (cholesterol-lowering medication) despite dramatically lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol in high-risk patients with coronary disease.”
Asking the right questions
There are so many paradoxes in nutrition that they are becoming the norm. Anything that contradicts old, entrenched beliefs can be explained away as a paradox, a mystery. Giving up those beliefs and studying the evidence is out of the question.
Surely it would be more useful to ask: is it appropriate to prescribe older people medication to lower cholesterol? Especially when it has been found that in people over 85, the higher the blood cholesterol level the longer the remaining life.
“Cholesterol-lowering therapy in the elderly is questionable”.
Which takes us back to mental health in general and cholesterol. Here the question that arises is: If something is so essential to mental health, why would you take a medication that enters the brain and removes it? If you’re taking statins, it’s a question for your physician to answer.
I started the publication Feed Your Brain because I saw a real need to highlight the link between diet and mental health. If you can fix your body through diet, why not your brain?
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