Cholesterol and Statins

(First posted on 2014/02/27 by ianwest2; reposted 2017/08/25)

A year or two ago (Feb, 2014) I heard Professor Ian Young, (Director of the Centre for Public Health, Queen’s University Belfast) give the Albert Latner lecture at Newcastle University on “My cholesterol — why is it so high?”. It was a most frustrating affair. Why?
The man presented no chink of doubt, he missed some serious points, and he spoke like a missionary, or a man whose salary is largely augmented by the manufacturers of statins. We must all take statins from infancy up (we were told). He kept saying that a 1mM(*)  drop in total cholesterol causes a 25% lowering of risk of vascular event; but, while his curves showed a steep line of correlation for 40 year olds, it was an almost flat line for 80 years. (So for me there is practically no benefit).

But a more important point: In no case was the vertical axis on any of his graphs ‘General health’; he was only talking about ‘Rate (or risk) of vascular event’. It has been said that "to a hammer, everything looks like a nail", and to a cardiologist the only objective is to lower the risk of a ‘vascular event’. What about the adverse side-effects; the muscle pains, and increased risk of diabetes (both of which Young conceded), Alzheimer’s, ALS, and Parkinson’s (which were mentioned by Stephanie Seneff; https://people.csail.mit.edu/seneff/)?

Cholesterol is essential. Ian Young correctly remarked that blocking the synthetic pathway at HMGCoA synthase (which is what statins do), will indeed cause a shortage of cholesterol and lead to scavenging pathways and the relocation of existing cholesterol. If the scavenged cholesterol is from coronary plaques, well-and-good; but what if it is scavenged from brain myelin or muscle cell membranes (as emphasised by Stephanie Seneff)? And what about ubiquinone and dolicol, which are also essential and also on the pathway blocked by statins (as emphasised by Stephanie Seneff )? If there ARE INDEED adverse side effects of statins, it is easy to see why!

So the clinical debate should be about the side effects versus benefits. I heard a paper in a Glasgow Heart meeting in the late 1990s which concluded that for over 40 year olds (or was it over 50?) the OVERALL benefits of statins do not outweigh the OVERALL damage. I was impressed (staggered, indeed) at the failure of the clinical cardiologists to see that this—if true—trumped the undenied fact that statins lower cardiovascular risk.

In 2014, aged 72 but in perfect health, I concluded I was certainly not going to take statins. I did not feel I needed them. And whether or not I should lower blood cholesterol there is something too utterly daft about poisoning myself at great expense in order to achieve that; and simply to switch from a healthy death from a coronary to a lingering death from mental, muscular and neurological decay. If I were under 40 and had familial hypercholesterolaemia (**), I think I would try diet, red-wine, and niacin (e.g. brewer’s yeast) before I tried statins.   

Professor Ian Young talked away about nuts, expensive margarine, salt, exercise, the ‘J’-curve for alcohol, etc. But he conceded that only 10% of our cholesterol comes from diet. So, surely the question is why do we MAKE too much? What regulates the synthetic pathway? [***] Does alcohol in excess of 2 units per day, or smoking, etc, up-regulate the synthetic pathway, or affect the partitioning between pools of cholesterol, e.g. by enhancing oxidative damage? What is the rôle of lipid oxidation (briefly mentioned by Young)?

Young pointed out that HDL-cholesterol is “good”; that low ‘cardiovascular risk’ correlates with higher HDL (in the 1 – 2 mM range, independently of LDL or total Ch.); in fact high HDL-Ch is 10-fold healthier than low HDL-Ch (while low LDL-Ch is only 3 times healthier than high LDL-Ch); the best predictor of heart disease is therefore the ratio LDL/HDL, the next best is HDL, the least good is LDL or total blood cholesterol. So, further good questions would be: what determines partitioning of cholesterol between the various ‘pools’ of cholesterol (HDL, LDL, cell membranes and atherosclerotic plaque, its locus operandi (where it is needed, in muscle and nerve membranes), and its locus morbidus (i.e. coronary plaques where it appears to be deleterious)?  Also, what is the rôle of lipid oxidation in affecting the partitioning? Presumably the HDL particle is picking up and re-locating cholesterol and is wholly good. But it is 'HDL-cholesterol' that is measured, so we do not know if the HDL is largely unloaded or nearly full; the latter giving the impression of plenty of HDL particles, but actually being nearly useless as a scavenger. There is a route for elimination of lipid, lipid-cholesterol-ester and cholesterol which involves liver, bile and gut. Guessing here, and maybe naively, but is it damaged (e.g. oxidized) fat/cholesterol that is eliminated, rather than merely surplus? So, there are plenty of unanswered questions.

Perhaps the coronary plaques are, in a wider sense, beneficial. After all, they protect us against suffering from Alzheimer’s disease, and a lingering death! What, in any case, are the evolutionary benefits (to the genes) of surviving beyond the age of 70? The benefits must be very small and may be negative; a little ‘grandparenting’ perhaps, and some dubiously relevant ‘advice’; but does that pay for the food and the space?

(*  mmol total cholesterol per litre blood)
(**  There are many types of familial hypercholesterolaemia; the most common by a factor of 2 is a defective LDL-receptor, which presumably hoicks LDL particles out of the circulation and into some (presumably) removal pathway.) 
(***   My erstwhile colleague Loranne Agius suggested that the ingestion of excess carbohydrate feeds into fat production in the liver which requires cholesterol for its excretion.)


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