I have now read right through the Stephanie Seneff (2011) essay to the end. Very anti-statin, and full of challenges. But I have also just heard (25th Feb, 2014) 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?"; very pro-statin and a most frustrating affair. I shall comment first on Ian Young.
The man presented no chink of doubt. We must all take statins from infancy up. He kept saying that a 1mM (mmol total cholesterol per litre blood) 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).
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'. To a hammer everything looks like a nail and to a cardiologist the object is to lower 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)?
Cholesterol is essential. Ian Young correctly remarked that blocking the synthetic pathway at HMGCoA synthase (as 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 in 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 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 trumped the (undenied) fact that statins lower cardiovascular risk.
I am certainly not going to take statins. I do not feel I need 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. (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.
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)? [** My colleague Loranne Agius suggests that excess carbohydrate feeds into fat production in the liver which requires cholesterol for its excretion]
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); 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, what determines partitioning between the various 'pools' of cholesterol: HDL, LDL, its 'locus operandi' (where it is needed, in muscle and nerve membranes), and its 'locus morbidus' (i.e. coronary plaques where it is not wanted - we suppose)? What is the rôle of lipid oxidation (briefly mentioned by Young) 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 particle, 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 many unanswered questions.
Perhaps the coronary plaques are, in a wider sense, beneficial. After all, they protect us against Alzheimer's disease, and a lingering death! What are the evolutionary benefits (to the genes) of surviving beyond age 70? They must be very small and may be negative; a little 'grandparenting', and 'advice' (perhaps), but is that sufficient to pay for the food and space?
Coming to Stephanie Seneff (2011), I believe this contains errors, and her fundamental technique is strange and (I suspect) fallible; that of looking at a bunch of statin-based and non-statin-based reviews and counting in each the incidence of words like 'dementia'. If 'Statin' reviews mention dementia, that does not necessarily mean that Statins cause dementia. What if statins PROTECT against dementia, or the paper says STATIN DOES NOT CAUSE dementia, while on the other hand diuretic pharmacologists may focus on salt balance and blood volume, even it their drugs do actually cause hallucinations. I do not follow Seneff's argument about lactate and acidosis; splitting ATP to ADP and Pi generates H+, but there is 10 - 100 times as much lactic acid synthesized as ATP split (and ATP is resynthesised while lactate accumulates). I think she has the oxidation of cholesterol-sulphate to cholesterol-sulphide wrong, for that is surely a reduction, and I have never heard of there being any useful energy available from that. (Indeed, I had not heard about cholesterol-sulphate or cholesterol-sulphide.) But she is right about cholesterol being needed. And statins being toxic. Is she right about statins causing raised fructose, or dementia, or ALS, etc? That needs checking, not dismissing.
But I am no expert.
Ian West, (12 Longhirst Village, MORPETH, NE61 3LT)