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Cholesterol: Friend Before Foe

The views expressed are those of the author and are not necessarily those of Scientific American.


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Text by Jeanne Garbarino, animation and images by Perrin Ireland.

Scientific American: Cholesterol from Alphachimp Studio Inc. on Vimeo.

Mention the word cholesterol in front of my grandmother and she’ll automatically clutch her chest and say a little prayer.  It is because she, along with almost one-fifth of the American population over 20 years of age, is battling high blood cholesterol – a condition tightly linked to heart disease.  As a means to try and curb these undoubtedly dangerous cholesterol levels, which are generally the result of a poor diet, various organizations such as the American Heart Association (AHA) have unleashed anti-cholesterol campaigns, ultimately demonizing this unknowing molecule.

Yes, when in excess, cholesterol can be very detrimental to your health and is often the culprit behind heart attacks and strokes.  However, behind the seemingly dangerous exterior lies a molecule that is essential for human life.

In the accompanying animation, I touched upon some of positive aspects of cholesterol.  Here, I’ll talk about these aspects in greater detail, hopefully explaining why cholesterol is a vital component of a normal existence.

Cholesterol is an essential building block of cell membranes

Cells would be just a pile of goo if their contents weren’t somehow contained.  Like a plastic bag, membranes help to keep all the important stuff in while keeping the other stuff out.  The basic blueprint for cell membrane construction involves lipids (fats) and proteins, with specialized lipids called phospholipids acting as the major structural components.  However, the integrity of this phospholipid frame is largely determined by the amount of cholesterol it contains.

To clearly illustrate how cholesterol affects cell membranes, knowing a little bit more about phospholipids would be helpful. Picture a phospholipid molecule as a tennis ball with two long strings attached to it.  The tennis ball represents the head “phospho” group and each string represents a hydrocarbon tail.  When these hydrocarbon tails exist in a saturated form, they are more ordered (think butter) whereas when hydrocarbon tails are unsaturated, they are more fluid (think olive oil).

If a cell membrane was made up of phospholipids with mostly saturated hydrocarbon tails, the membrane would be too stiff.  On the other hand, if phospholipid hydrocarbon tails were primarily unsaturated, the membrane would be too fluid.  Either situation is a problem since basic cellular function relies on a membrane that is sturdy enough to hold everything together but flexible enough to let the important stuff pass in and out.

Consider cholesterol to be the porridge ingredient that makes it taste just right.  Cholesterol will interact with phospholipids and help to make sure that our cell membranes are the perfect consistency.  This interaction keeps saturated phospholipid-rich membranes from becoming too rigid as well as keeping membranes with high levels of unsaturated phospholipids from getting too loose.  Basically, in terms of membrane structure, cholesterol helps to prevent extremes.

Now excuse me if I am being overzealous, but cholesterol is truly nature’s perfect solution for controlling membrane fluidity – it gives cell membranes the structural integrity of a solid while simultaneously giving it the mobility of a liquid.  Not surprisingly, cells will invest a large amount of energy in order to maintain very specific cholesterol levels in membranes, highlighting the value of cholesterol to cells and, of course, to the organism to whom those cells belong.  This is just one of the variety of reasons why cholesterol is essential for life.

Cholesterol is fundamental during our development in the womb

We are constantly bombarded with dangerous statistics relating to high cholesterol levels, yet conditions arising from cholesterol deficiencies are far less known.  In the 1990s, the importance of cholesterol during fetal development became more clear when scientists discovered a link between low cholesterol levels and Smith-Lemli-Opitz Syndrome (SLOS) – a disease characterized by poor growth, developmental delays, reduced mental function, and a range of physical malformations.

Due to a genetic defect, those afflicted with SLOS cannot complete the last step of cholesterol formation, explaining reduced cholesterol amounts.  As discussed above, cholesterol is an important component of cell membranes.  When cell number is quickly expanding, as is the case when developing in the womb, the pace of membrane formation is very rapid.  This puts cholesterol in extremely high demand.  Scientists link reduced cholesterol availability and the resulting compromised cell membrane integrity as one of the explanations for SLOS symptoms.

However, cholesterol plays more than one part in the baby-making play.  Yes, it is important for membrane production, but it also has an unexpected role.  Shortly after defective cholesterol formation was linked to SLOS, it was found that it is also essential for developmental patterning – the process that keeps our body parts in order, from our heads to our toes.

More specifically, scientists found that cholesterol becomes attached to a specific family of proteins called hedgehog proteins. (Yes, the naming of these proteins is associated with the Sega Genesis game of my youth – Sonic the Hedgehog.)  These proteins help to determine the fate of cell – i.e. whether the cell will become a part of a finger versus part of a toe – and are indispensable for normal and healthy development.

When the attachment of cholesterol to hedgehog is prevented in mice, it messes up finger and toe formation.  Through experimentation, scientists found that cholesterol helps to regulate how many hedgehog proteins get go to specific areas within the developing embryo.  Without the addition of cholesterol, hedgehog proteins would spread too far, and this has a significant effect on formation in utero.  In essence, cholesterol acts as the parole officer, making sure that the hedgehog protein doesn’t go beyond the proper jurisdiction.

This adds another obvious tick to the “reasons why cholesterol is important” checklist!

Cholesterol gives us balls

Well, sort of – and only for about 50% of the population. More accurately, cholesterol is the starting material for steroid hormones including testosterone, which helps to define the male gender.

You can recognize a steroid hormone by its structure, which is very similar to that of cholesterol.  Like cholesterol, the signature feature of a steroid hormone is the specific arrangement of four rings.  However, hormones differ form cholesterol by the side chain(s) coming off of this multi-ring structure.

In humans and other mammals, using cholesterol to make steroid hormones is officially termed steroidogenesis and the products of these reactions can be classified based on their general role in the body.  As such, most steroid hormones can be placed under five categories:

The importance of cholesterol during steroidogenesis is exemplified by the potentially lethal disease congenital lipoid adrenal hyperplasia (CLAH), a very rare genetic disorder characterized by the inability to use cholesterol to make steroid hormones (and which has its own Facebook page!).  This disease is caused by a defect in the transport of cholesterol into the steroid hormone-making area of the cell (mitochondria), and the inability to produce sex hormones has severe repercussions, including infertility and gender identity issues for males.

Once again, let’s give credit where credit is due…

We use cholesterol to make Vitamin D

To use sunblock or not to use sunblock – when it comes to vitamin D production, it is widely known that the sun plays a role.  But, it is less well known that cholesterol is the precursor to this nutrient.

When we are talking about vitamin D in humans, what we really mean is Vitamin D3, also known as cholecalciferol.  Cholesterol is not directly transformed into vitamin D; more specifically, cholesterol is first converted to a compound called 7-dehydrocholesterol.  Then, upon exposure to ultraviolet radiation (UV light from the sun), the 7-dehydrocholesterol in our skin is transformed to vitamin D3.

Most people are familiar with vitamin D3 as an important factor for bone health.  In fact, it is in this context that vitamin D was first identified.  In the early 20th century, scientists discovered that cod liver oil, which is rich in vitamin D, could be used to treat dogs with rickets.  And thus, the incidence of rickets in developed nations plummeted.

Thanks, cholesterol, for making it all possible.

And now, a personal statement

If our bodies were a high school and molecules were the students, cholesterol would certainly win the “most important for life” superlative.  Well, maybe I am a little biased because without cholesterol, I wouldn’t have a job – at least, I wouldn’t have my current job.  And that would be a bummer.

The whole purpose of this article was to shed light on the positive aspects of cholesterol, the molecule, despite its bad reputation.  But, a word of caution – just because cholesterol is central to a number of biological processes (including many I did not discuss!) doesn’t mean it is all well and good.  This molecule also got the “most likely to kill you if kept at high levels in your body” superlative.

So, the next time you hear about cholesterol, remember that it plays a significant role during life, and that can be good as well as bad.

Enormous thanks to Perrin Ireland, Diane Durand, Patricia Fonner, and the rest of the folks at Alphachimp Studio (http://www.alphachimp.com/)!!!

About the Author: Jeanne Garbarino is a mother of two young girls, aged 2 and 4. In her other (easier) gig, Jeanne is a postdoc at Rockefeller University in the Laboratory of Biochemical Genetics and Metabolism. There, she studies how cholesterol moves inside of our cells and relates this information to human health and the development of cardiovascular disease. In addition to being a scientific researcher, Jeanne is a self-proclaimed scientist-communicator, often blogging about relevant scientific issues on her blog The Mother Geek, as well as co-organizing a monthly science discussion series, Science Online NYC (# SoNYC ), which is open to anyone who is interested about how science is conducted. You can find her tweeting as @ JeanneGarb or can follow The Mother Geek on Facebook.

Perrin Ireland is a graphic science journalist who currently serves as Science Storyteller at Alphachimp Studio, Inc. She uses art and narrative to facilitate scientists sharing their stories, and creates comics about the research process. You can find more of Perrin's work here, and follow her on Twitter at @experrinment.


The views expressed are those of the author and are not necessarily those of Scientific American.






Comments 9 Comments

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  1. 1. RobLL 2:46 pm 09/14/2011

    There are simply too many heart healthy very old women with very high cholesterol.

    There are simply too many studies showing no net benefit of lowering cholesterol, and in particular the alleged deadly LDL.

    There are simply too many side effects for many from taking statin drugs to reduce LDL (and ample evidence that most physicians are in denial regarding these side effects).

    Hence it is time for the medical establishment to come up with a balanced view of cholesterol and statin drugs.

    I appreciated the article.

    Link to this
  2. 2. ABJ 4:54 pm 09/14/2011

    Remember that cholesterol prevents cancer.
    (by killing you before you can get cancer)

    Link to this
  3. 3. drfakadej 7:45 pm 09/14/2011

    The article neglects one extraordinary aspect of the fluidity of the cell membrane with respect to the presence of cholesterol. ALL immune cells (NK, B-cells, T-cells, WBCs, etc) require cholesterol for function. Without cholesterol level, immune system function is compromised and the result is cancer, autoimmune dysfunction, inability to resist infection, etc. In reality, if you want to get cancer, reduce cholesterol. The article also neglects to mention research indicating that in familial low cholesterol (<120) the rate of suicide increases and (<160) the rate of depression increases. The first tissue to inflame in the body are blood vessels – leading to the development of aneurysm and potential stroke. Cholesterol is vascular reinforcement as a direct result of inflammation. Hello – is anyone trying to determine the cause of inflammation? Of is it really better to simply reduce the SYMPTOM of high cholesterol? Science and medicine continue to ignore research and obey the pharmaceutical companies. Talk to the oldest retired doctors that threw statin drug research in the trash because they easily saw that liver dysfunction would result. The new young doctors do not know how to read and interpret research as they completely ignore research bias.

    Link to this
  4. 4. unomas 2:05 pm 09/15/2011

    ABJ. I like your post. Eat fat, die earlier of sudden heart attack or stroke and avoid the longer death from cancer. Sounds good to me!

    The key to eating for us, following husband’s bypass, is moderation in all things.

    I would like to see Scientific American take on the subject of the rise in gluten and wheat allergies.

    Link to this
  5. 5. JeanneGarb 5:31 pm 09/15/2011

    RobLL – I am glad you appreciated the article. While I agree that the side effects of statin use need to be more rigorously taken into consideration when deciding the best course of action in response to high cholesterol levels, there is a lot of evidence showing that, for high risk populations, statin use is effective. I am guessing that when you say “no net benefit of lowering cholesterol…,” you are probably referring to studies reporting on an average of all statin users. As you know, statins are the most widely prescribed medication in the world, and those who are at very low risk (either their cholesterol is just above the threshold or they have normal cholesterol but have some family history) will skew the outcome. To reiterate my point, those in high-risk categories experience the most benefit, whereas low to medium- risk populations probably don’t see as strong of a result.

    @ABJ – High cholesterol is certainly linked to heart disease and stroke and there is some indication that a cholesterol imbalance is associated with cancer. Though, how the age of onset for the former compares to the latter is not necessarily a known phenomenon.

    @drfakadej – The entire first section of the text portion addresses the effect of cholesterol on membrane fluidity is some depth. Additionally, there are many studies that examine the causes of inflammation, and how this relates to heart disease. With regard to your other comments, it was my intention to only discuss the biological functions centered on cholesterol, the molecule, as well as touch on its biochemical properties. There is a great deal of literature about the negative effects associated with high blood cholesterol and most of it is easily accessible. But, to address your issue with the relationship between science/medicine and big pharma – I have been conducting cholesterol and lipid research since 1999 and have yet to see someone in an academic institution conduct their research as directed by a some pharma/biotech company. There is a ton of legitimate, unbiased, and VERY important cholesterol research happening at this very moment and it is unfortunate that are some negative connotations associated with biomedical research.

    Link to this
  6. 6. openeyes999 5:28 pm 09/16/2011

    Good article, Jeanne. Adds some nuance to the health discussion. Most things in diet are not bad by themselves, but are just bad in the wrong *amounts.* Poison is in the dosage. I do wonder how dangerous not having enough cholesterol can be. Perhaps this is one reason while vegans don’t live as long as vegetarians; too extreme a reduction in cholesterol and other necessary molecules/nutrients. (not that diet makes that much of a difference in lifespan once you account for confounding factors like economics, healthcare access, exercise, etc.)

    Link to this
  7. 7. bergamotley 2:45 pm 09/20/2011

    Nice rundown on what cholesterol actually does in the body. It’s an important first step in giving Americans the tremendous amount of information they need to understand what they’re really getting into in taking statins. It’s shocking how little they tell us about this complex and important issue. Cholesterol is not a poison; statins are not magic bullets that save the lives of all who take them. How many people know, just for starters, that high blood pressure (much more easily controlled) is the biggest risk factor for coronary heart disease?

    Why is it that high LDL is so hard to fix, so hard to relate to health habits? Could it be that we just don’t understand the relationship there? Could it be that certain nutritional deficiencies cause this sign in people who keep their weight down, avoid “bad” fat, and eat their veggies? Could it (or the underlying disease process that causes it) be aggravated by psychological stress or environmental pollutants? What about the levels of certain hormones? And does lowering LDL make a person healthier? If it makes some people feel worse, is this a sign that their health is suffering?

    What goes wrong with cholesterol in the body? Does some of it arrive denatured? Is the body lacking in the molecules needed to process it so it goes to the right places in the right form? We know that the size of LDL particles is important: the bigger the better. We know the liver emulsifies fat with lecithin and bile, and it might have something to do with that. But so far, all the public hears is: 1) follow certain simple dietary rules, and when they don’t work, which is obviously often, 2) hurry and reach for that statin before you die of a heart attack or stroke. And of course, your doctor will figure out the details from there.

    Educating the public about this thorny issue is tough, but it’s good you’re getting the ball rolling.

    Link to this
  8. 8. thiruvelan 10:46 pm 01/19/2012

    one-fifth of the American population over 20 years of age, is battling high blood cholesterol – a condition tightly linked to heart disease. Still Cholesterol is an essential building block of cell membranes, development in the womb, for hormones production, and vitamin D.

    Cholesterol is important for various bodily functions, but if it becomes higher than normal then it is harmful to your hearts. Therefore maintain you cholesterol level at normal for further information visit http://healthy-ojas.com/cholesterol/cholesterol-details.html

    Link to this
  9. 9. iamcrystal 3:51 am 01/27/2012

    So is it true that if you are vitamin D deficient, you will get fat? I also read from http://www.mercola.com/Downloads/bonus/vitamin-d/report.aspx that several vitamin D deficiency has been linked to cancer, diabetes, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and autism. Guess, I really have to get enough of this vitamin.

    Link to this

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