The idea that cholesterol is bad for you is rooted in a rather comical and simplistic conception of what cholesterol is.
Imagine the liver as a demon organ holding up your blood vessels, like a plumber might wield a piece of pipe in one hand, while pouring hot bacon fat down that pipe with the other. The more fat it pours down your vessels, the more atherosclerotic they become - increasing your chances of a heart attack or stroke.
Next comes 'good and bad cholesterol' - another simplistic interpretation. The idea is that your liver produces LDL - and high LDL is bad. The story further claims that LDL carries triglycerides and cholesterol to peripheral tissue - which lays down plaque. Whereas HDL transports cholesterol back to your liver.
It's actually quite a cute image if you make the Liver an adorable cartoon character plotting your death.
Of course, this is mostly nonsense. It is not surprising, then, that these ideas came from the same group of charlatans (Ancel Keys et al) who pushed the notion that saturated fats are bad for you (also, nonsense). For the definitive exploration of the decades long fraud that cemented this notion in the medical industry's consciousness, check out Timothy Noakes' breakdown of the evidence:
Is this relevant to your life?
Only you know the answer to that, but yes - extremely.
This information is relevant to everyone from the recently retired, to recent graduates embarking on their new career.
Usually between the ages of 25-30, most young adults get regular health check-ups if not for personal health maintenance, then for our employers or insurance providers. One element of a regular check-up is your lipid profile, which reports such things as:
- Total cholesterol
- HDL cholesterol
From these values they can also calculate (not measure) LDL cholesterol:
LDL = Total - HDL - Triglycerides/5 *Friedewald's Equation
If you have been naughty, your serum cholesterol may go above what a lab considers 'normal.' Once your doctor catches wind of this 'above normal' cholesterol, he may recommend that you start taking a statin.
Statins are HMG-CoA Reductase inhibitors, a class of lipid-lowering agents that are believed to result in lower risk of mortality from cardiovascular disease by virtue of their ability to decrease LDL cholesterol.
Back to Basics
So far, we have used a lot of technical terminology that makes us sound really smart and gives the impression that we understand what is happening. That way, you will do what we tell you to fix the problem we claim to understand.
To understand the scale of the problem, we must first define the terms.
For starters, LDL and HDL are not cholesterol. They are lipoproteins. Lipoproteins contain cholesterol, triglycerides, and other proteins in varying proportions.
Lipids are a general class of macromolecules which are soluble in non-polar solvents. In very broad strokes, things that don't mix with water can be classified as a lipid. Put another way, a lipid is something that is dissolved by another thing that can also dissolve fat.
Fatty acids (like saturated and unsaturated fatty acids), triglycerides and cholesterol are in the category of lipids.
This is cholesterol:
This is a triglyceride, which contains 3 fatty acids:
Very different macromolecules sharing the common attribute that they are dissolved by other non-polar solvents.
Despite our scientific understanding of lipids, WebMD offers a rather misleading conception of cholesterol:
Cholesterol is the building block of hormones, cell walls, nuclear membranes, secretory vesicles, repair mechanisms, and energy storage. It’s not just a 'waxy, fat-like substance.'
Furthermore, it is misleading to say that your 'body needs some cholesterol.'
Cholesterol is the principle sterol synthesized by all animals. Every cell is capable of producing cholesterol, and its production is essential to all animal life. The process of making cholesterol begins with the mevalonate pathway - aka the HGM-CoA Reductase pathway. This pathway produces isoprenoids - a diverse class of over 30,000 molecules which includes cholesterol, vitamin K, coenzyme Q10 and all steroid hormones.
Your liver produces lipoproteins, which deliver fatty acids & cholesterol to every organ in need. Your liver is not trying to give you a heart attack. It is responding to a signal - such as high cell turnover, or presence of oxidative stress requiring repair and regeneration.
What your body needs, it gets.
The trouble arises from two factors:
- Environmental factors (including diet) which contribute to highly reactive lipids (polyunsaturated fatty acids - aka seed oils) being substituted everywhere fatty acids are needed.
- High oxidative stress leading to cell damage and lipid peroxidation, which itself causes more cell damage - and the cycle continues.
Nowhere in this model does it suggest that high LDL cholesterol is the cause of heart disease. With poor lifestyle choices, all lipoproteins can contain highly reactive and consequently damaging fatty acids - including HDL.
But, this article is not just about cholesterol. It is also about statins.
Intro to Statins
Now if you believe that high cholesterol is bad for you, then you will understand the role of Statins - it helps bring the bad number (LDL) down.
Based on how much LDL goes down in response to taking statins, you can then theorize a net benefit it would have. Herein lies the basis for distributing statins worldwide, making it one of the most profitable drugs on the market.
Since the introduction of statins in 1987, some early clinical trials demonstrated effective reduction in coronary heart disease (CHD). However, this was prior to changes made in reporting of conflicts of interest. After the instantiation of new reporting rules in 2004, all clinical trials demonstrating that statins reduce LDL have shown no significant benefit for prevention of CHD. Sad time for Pfizer and the American Heart Association.
As you can see from the figure above, after new penal regulation for clinical trials in 2004, lowering LDL cholesterol is associated with varying changes in risk of CHD - notably, no significant reduction in CHD.
If you make bad lifestyle choices, such that all of your circulating lipoproteins can cause damage to the organs they serve, then taking cholesterol lowering drugs may provide some benefit.
Like all medication, statins come with side effects.
Unfortunately for the lay public (and the lazy doctor), the pharmaceutical companies who develop these drugs would only like us to be aware of the side effects they believe we will overlook for the benefit of reduced heart disease, including:
- Muscle pain - which mayoclinic.org suggests could be a placebo-type effect, and not related to the drug itself...
- Liver damage
- Increased blood sugar, or even Type 2 Diabetes
- Neurological side effects - "...there is limited evidence to prove a cause-effect relationship..."
As you've been reading this, I'm sure the following thought has occurred to you:
"If cholesterol synthesis is so critical to the life of almost every cell in your body...what happens to those cells when you block the activity of one of their core enzymes - HMG-CoA Reductase?"
That is a great question - and the topic of this article published in Expert Review of Clinical Pharmacology:
The authors lay out the argument & molecular pathways in which the use of statins can lead to coronary artery calcification (atherosclerosis) and heart failure. Because the heart is one giant muscle, anything that depletes the ability of the muscle to generate energy (ATP) will lead to dysfunction, which can manifest as congestive heart failure (CHF).
Basics of Metabolism
Mitochondria are organelles inside our cells which generate energy (ATP) by burning fatty acids & sugars. One of the principle mechanisms is via the electron transport chain, situated within the wall of the mitochondria.
In the mitochondria, electrons are stripped from hydrogen atoms (H) and passed along the chain, while the remaining proton (H+) is concentrated in the space between the inner and outer wall.
This gradient of positive (H+) charge in the intermembrane space and negative (electron) charge inside the mitochondria drives the production of ATP.
Heart & Muscle Failure
Coenzyme Q10 and heme A are essential components of the transport chain, and are made from intermediates of cholesterol synthesis. Thus, by depleting the cells ability to embark on cholesterol synthesis, statins deplete the formation of cofactors needed for metabolism.
This is particularly dangerous for cells that are very metabolically active (such as the heart and brain). Furthermore, CoQ10 is a clinically important antioxidant which also protects mitochondria from DNA damage.
Coronary Artery Calcifications
Vitamin K2 is a rather important nutrient that is synthesized from Vitamin K1. The enzyme that makes this transformation is present in many organs, including the brain. Statins inhibit this conversion.
Vitamin K2 is particularly important because it has the capacity to bind calcium and protect blood vessels from calcification - thus statins accelerate coronary artery calcification by blocking the production of a molecule which binds and 'neutralizes' calcium.
Given what we've learned above, it is small wonder that most people I've spoken to who have started using statins report all sorts of vague side effects.
One rather interesting finding - in light of the information presented by Okuyama et al - is the effect on cognition and mental acuity.
Notice how the authors use the term reversible cognitive impairment. As if to say "nothing to worry about here." This usage of terminology is rather interesting, because usually those words are used to describe something like delirium - which is a very short-term cognitive phenomenon.
As it turns out, the authors cite an article which demonstrated that approximately 50% of people on statins developed cognitive impairment (rather euphemistic term for early signs of dementia). They further found that some of the patients who development this side-effect had some improvement in their symptoms when they stopped using statins.
However, almost all patients in whom statins were re-introduced developed cognitive impairment again. Thus, they cannot continue to use it - unless they want worsening dementia.
The mechanism for the onset of 'cognitive impairment' with statin use are several. In my view, they all fundamentally boil down to one problem:
Cholesterol and fatty acids are ubiquitous and critical in cellular life, as well as the maintenance of neural connections within the brain (as neurons are covered by fatty tissue to insulate their connections and improve conduction). Stop the production of these critical macromolecules and the consequences are clear.
All this, for what?
Statins taken daily for 5 years in patients with known heart disease provides:
- 1.2% lower chance of death
- 2.6% lower chance of heart attack
- 0.8% lower chance of stroke
Statins taken daily for 5 years in patients without known heart disease provides insufficient benefits over harms:
These are not long-term solutions.
We can conclude this with the following thoughts from Okuyama et al: