Viagra

For those who have read my endless series of blogs on cardiovascular disease, you may know exactly where I am going at this point.

Some time ago, Pfizer were developing a drug to treat angina. It blocked an enzyme called phosphodiesterase type-5. [Although I believe that its exact mechanism of action was not known at first]. To put it another way, this drug was a phosphodiesterase type-5 inhibitor (PDE5i).

The moment Pfizer found out what enzyme this drug blocked, they tried to patent the pathway that blocked this enzyme. Pharmaceutical companies trying to patent biological pathways. Perhaps I should try to patent the Krebs cycle, and charge everyone on the planet for having such a thing. Kerchingggg!

‘The U.S. patent office appears to have granted Pfizer a patent covering any drug that blocks this enzyme, meaning that it can sue all of its potential competitors.’¹

Luckily, this time they were rebuffed.

Anyhoo, back to the drug. During phase one clinical trials, where humans are given the drug for the first time to see what effects it may have, many of the volunteers were hanging on to their medication, rather than handing them back. This was very unusual. Almost unknown in fact.

When researchers went out to find out why this was happening it was discovered, not quite sure who admitted to this, that sildenafil/Viagra improved erectile function. Thus, Viagra, the first PDE5i, was born. The first drug that worked simply and effectively to improve erectile dysfunction (ED). As for treating angina… that piffling indication was rapidly shelved as the dollar signs appeared in the sky above Pfizer HQ. Sex, as they say, sells.

In truth, it is actually one of the best drugs ever. Not only does is treat ED, but it can also be used by mountaineers to prevent pulmonary oedema (fluid filling up in the lungs), which is one of the major symptoms of altitude sickness. It does this by reducing the blood pressure in the pulmonary vessels (blood vessels in the lungs).

To explain a little further. If you climb very high, and the oxygen level drops, the heart pumps blood harder and harder through the lungs to get as much oxygen as possible into the system. This can result in fluid leaking out of the vessels and into the lung tissue, so they fill up with fluid. At which point you effectively drown, so you die. Viagra stops this happening, by lowering the blood pressure in the lungs.

Unsurprisingly, Viagra is used to treat people who have pulmonary hypertension (high blood pressure in the blood vessels in the lungs) at sea level. It is sold under the name Ravatio, for this indication – but we know that it is just Viagra. In addition, Viagra can be used to treat Raynaud’s disease, where the small blood vessels supplying the fingers and toes constrict, leading to painful cold fingers.

So, here we have a drug that can treat angina, pulmonary hypertension, erectile dysfunction and Raynaud’s disease at the same time. Thus, you can have great sex at twenty thousand feet above sea level, not get chest pain, or breathless, and stay warm at the same time. What more could a man ask for?

How does it do all these things? The answer is that it increases Nitric Oxide (NO) synthesis in endothelial cells. When it does this in the penis, it stimulates erections. In the heart, it opens up coronary arteries. In the lungs, it dilates the blood vessels, in fingers and toes it opens up arteries. So, all of the many different effects, are all due to exactly the same process – increased NO synthesis. Viagra also lowers blood pressure – as you would expect.

At the risk of blowing my own trumpet, I talked about this in my book ‘Doctoring Data,’ under the heading ‘Viagra and the drugs of unintended consequences.’ I posed the question. ‘If we were to prescribe Viagra as an antihypertensive, which is entirely possible, and it were found to reduce the risk of heart disease and stroke, which effect do you think would be responsible for the benefit? The blood pressure lowering effect, or the anticoagulant effects? Or something else.’

Since I wrote those words, someone has actually looked at the impact of PDE5is on cardiovascular disease. Researchers at Manchester University, in the UK, studied the use of Viagra in people with diabetes – who often have erectile dysfunction. Here is what they found:

‘Viagra could prevent heart attacks, according to research. Patients taking the male impotence drug were found to have a lower risk of having a heart attack or dying from heart failure than those not on the medication. The lead scientist told the Daily Express the findings are “incredibly exciting”.²

The research paper was published in ‘Heart’, a BMJ journal. Actually, this paper was published last year, but only seems to have hit the press in the last few days. I spotted it in the Times a few days ago.

Here are the main results (for those readers who like their statistics)

‘Results: Compared with non-users, men who are prescribed PDE5is (Viagra, Cialis and the like – my words) (n=1359) experienced lower percentage of deaths during follow-up (19.1% vs 23.8%) and lower risk of all-cause mortality (unadjusted HR=0.69 (95% CI: 0.64 to 0.79); p<0.001)). The reduction in risk of mortality (HR=0.54 (0.36 to 0.80); p=0.002) remained after adjusting for age, estimated glomerular filtration rate, smoking status, prior cerebrovascular accident (CVA) hypertension, prior myocardial infarction (MI), systolic blood pressure, use of statin, metformin, aspirin and β-blocker medication. PDE5i users had lower rates of incident MI (incidence rate ratio (0.62 (0.49 to 0.80), p<0.0001) with lower mortality (25.7% vs 40.1% deaths; age-adjusted HR=0.60 (0.54 to 0.69); p=0.001) compared with non-users within this subgroup.’³

For those who don’t like their statistics quite as much as me (shame on you). I shall attempt to simplify.

• Over a seven year period, those men taking PDE5is (Viagra Cialis and the like) had a 4.7% reduction in overall mortality – compared to men who did not.
• Those taking Viagra were 38% less likely to have a myocardial infarction
• If you did have a myocardial infarction, those who were taking PDE5is had a 25.7% death rate. Those who were not taking PDE5is had a 40.1% death rate. So, if you were unfortunate to have a heart attack, you were 14.6% less likely (absolute risk reduction) to die if you were taking PDE5is.

Or, to shorten this even more

• 4.7% reduction in overall mortality
• 38% reduction in MI (relative risk reduction)
• 14.6% reduction in death after an MI

Whilst the first figure of a 4.7% reduction in overall mortality may not sound terrible exciting, it knocks all antihypertensives and cholesterol lowering medication into a cocked hat. Even if you add them together and multiply by two – on their best day. Because 4.7% is an absolute risk reduction. [Absolute mortality reduction in the Heart Protection Study (HPS), the most positive statin trial, was 1.8% over five years]

The benefits of Viagra are even more startling when it comes to having a heart attack (MI). The current ‘gold standard’ treatment of choice is Primary Percutaneous Coronary Intervention (PCI), which basically means popping a stent into a blocked coronary artery to open it up again.

It has been estimated that PCI results in a 2% absolute reduction in mortality⁴. On the other hand, Viagra gives you, very nearly, a 15% reduction in overall mortality. Or, to put it another way, Viagra may be seven and a half times as effective as PCI.

But it does not end here. it was also found that men with heart failure were 36% less likely to die if they took a PDE5i.

‘In the other subgroups, there was an inverse association between PDE5i use and all-cause mortality. Those with a recorded history of congestive cardiac failure, TIA and PVD had 36%, 40% and 34% lower risk, respectively.’ [A TIA is a transient Ischaemic attack/small stroke. PVD is peripheral vessel disease.]

Congestive cardiac failure is usually shortened to heart failure. [This 36% is a relative risk reduction, and I could not work out what the absolute risk was from the paper. I am probably too thick].

The effect on heart failure is almost certainly because another benefit of increasing NO is that you increase ‘angiogenesis’, otherwise known as, ‘the creation of new blood vessels’. If a coronary artery does completely block, this often leads to heart failure, as not enough oxygen and other nutrients can get into the heart muscle downstream.

However, if collateral blood vessels develop, the blood will be directed around the blockage and back into the artery downstream, through these newly created blood vessels. Although collateral circulation is not as effective as a fully patent coronary artery, it will create a significant flow of oxygen and nutrients once more. Thus, heart failure will be greatly improved.

Louis Ignarro, who identified nitric oxide (NO) as the key chemical messenger that dilated blood vessels, and won the Nobel Prize for doing so, decided to start treating people who have end stage heart failure with l-arginine. He had been looking for a substance that would, naturally increase NO, and found l-arginine did the job best. He has had some amazing results. Perhaps he should start using Viagra instead.

This study, I must add, was not interventional, it was observational. However, it strongly supports the hypothesis that increasing NO synthesis is just about the most important thing you can do. If you want to avoid dying from CVD.

Do I think everyone should take Viagra? Well, if you have heart failure, diabetes and a high risk of CVD – probably. Will you get a doctor to prescribe it for you, for CVD prevention? Absolutely no chance. Will anyone ever fund a study on this? With the drugs now off patent – no chance.

Oh, the joys of modern medicine. Unless someone does a controlled randomised double blind study on a medication, doctors will not prescribe – are not allowed to prescribe. However, virtually the only people with the money to do such studies are pharmaceutical companies. If the patent life of a drug has expired, no money can be made. So, no trial will be done. So, drugs that are almost certainly beneficial wither on the vine.

Unusually, for me, I do not blame the pharmaceutical companies for this. They are not charities. They need to make money or they die. You cannot expect them to spend hundreds of millions on a clinical study, without any possible means of gaining a return on their investment. We live in a funny old world.

In the meantime, look to other things that can increase NO synthesis. L-arginine/L-citrulline does this. Potassium does this. Sunlight does this. Exercise does this. Meditation does this. Vitamin D does this, as does Vitamin C. What are you waiting for? Go for a walk in the sun and eat an orange – you will live forever.

1: https://www.forbes.com/2002/10/23/cx_mh_1023pfizer.html

2: http://www.independent.co.uk/life-style/health-and-families/health-news/viagra-could-lower-heart-attack-risk-and-risk-of-dying-from-heart-failure-a7082801.html

3: http://heart.bmj.com/content/early/2016/07/26/heartjnl-2015-309223.full

4: https://www.ncbi.nlm.nih.gov/pubmed/12517460?access_num=12517460&link_type=MED&dopt=Abstract

[Hold the front page]

Last night I watched a you tube presentation which completely astonished me. It was given by Professor Salim Yusuf, who is as mainstream as mainstream can possibly be. Here, from Wikipedia:

‘Salim Yusuf (born November 26, 1952) is an Indian-born Canadian physician, the Marion W. Burke Chair in Cardiovascular Disease at McMaster University Medical School and currently the President of the World Heart Federation, a world-renowned cardiologist and epidemiologist. In 2001, he published a landmark study that proved the benefits of clopidogrel in acute coronary syndrome without ST elevation.’

Here, from Forbes magazine in 2012:

‘McMaster University’s Salim Yusuf has tied for second place in the annual ranking of the “hottest” scientific researchers, according to Thomson Reuter’s Science Watch. Yusuf was a co-author of 13 of the most cited papers in 2011. Only one other researcher, genomic pioneer Eric Lander of the Broad Institute of MIT, had more highly-cited papers than Yusuf.’¹

On February the 12^th he gave a presentation at a cardiology conference in Davos, Switzerland which can be seen on YouTube. In this presentation, he makes the following points:

1. Saturated fat does raise LDL, a bit, but has no effect on CVD – maybe slightly beneficial. Monounsaturated fats are slightly beneficial. Polyunsaturated fats are neutral.
2. Carbohydrate intake is most closely associated with CVD
3. Fruit and vegetable intake has little or no impact on CVD – nor does fish intake [He wonders where the five portions of fruit and vegetable intake recommendations actually came from]. Vegetables in particular have no benefit.
4. Legumes – beans and suchlike – are beneficial.
5. The recommendations on salt intake are completely wrong, and set far too low. For those who do not have high blood pressure, low salt intake increase mortality. On the other hand, high salt intake does no harm.
6. He recommends higher potassium intake.
7. He criticizes Ancel Keys and lauds Nina Teicholz [Author of big fat surprise].

Well, good for him. It seems to have taken him a long time to get there, but he did in the end. Of course, mainstream medicine will remain in shocked silence, so you will likely hear nothing of this in the mainstream media. But, hey, you get to see it here. Perhaps someone would like to send this presentation to the BHF and the AHA and ask them for a comment?

The YouTube presentation is here:

1: http://www.forbes.com/sites/larryhusten/2012/04/25/when-youre-hot-youre-hot-salim-yusuf-second-most-influential-scientist-in-2011/#6ac825575abe

Lead

I have been studying cardiovascular disease for well over thirty years now. I have come across a million different hypotheses about what causes it. There is almost no foodstuff, vitamin, infectious agent, chemical compound, atomic element or activity [lack of, or excess] that has not been proposed at some point.

Many of them can look very promising, and the underlying hypothesis is often elegant – very elegant indeed. But what you must do with any hypothesis is to hold it close to the unforgiving flame of mortality data, and see if it is tempered by the heat – or simply melts.

I resolved very early on in my long and winding study on cardiovascular disease that any hypothesis had to explain everything – not just some things. For example, as almost everyone in the entire world knows a raised cholesterol level is considered the most important cause of cardiovascular disease. But it is exceedingly easy to find facts that seem to completely contradict this.

Here, for example, is a little graph looking at only two countries. It compares the death rate from heart disease in Russia and Switzerland, in men under the age of sixty-five relation to the average cholesterol level in those two countries.

in Russia, with an average cholesterol level of 5.1mmol/l (197mg/dl) had a death rate 834% higher than that in Switzerland, which had an average cholesterol level of 6.4mmol/l (248mg/dl). Yes, this graph is the right way around. Yes, these data come from the World Health Organisation, and can be found on the British Heart Foundation (BHF) website. These particular statistics are now very deeply buried, but can still be found here: https://www.bhf.org.uk/publications/statistics/european-cardiovascular-disease-statistics-2008

I sometimes wonder if anyone at the BHF actually looks at these data, but that is a question for another day. Of course, when presented with facts like this, the dismissals. and creation of ad-hoc hypotheses rapidly reach into the sky. The word ‘paradox’ will be used pretty heavily, that’s always a good, temporary, escape route. In reality these two figures represent a full-blown black swan. But, hey, facts are slippery things.

Anyway, in my quest to explain everything about heart disease, perhaps the hardest single thing to explain is the fact that the rate of cardiovascular disease (heart attacks and strokes) has been going down in pretty much every single Western country for decades. I would say ‘first world’ country, but my son (a geography graduate) informs me that this terminology is now virtually barred for being racist. I shall be considered an ancient, prejudiced reactionary for using such a term.

So, I will say, Western Europe, North American, Australia, Japan, New Zealand and suchlike.

Now, the decline in CVD did not start at the same time, in all these countries. At this point I will make myself a hostage to fortune and make some sweeping statements. The rate of CVD peaked first in the US, in the late 1950s and has been falling since. It peaked next in Finland in the 1960s. In most of the other countries CVD peaked in the 1970s, before falling. It is impossible to say that there was a uniform worldwide effect. [Today, some countries are on the way up the mortality curve e.g. China and India].

However, I will make the general statement that CVD has been falling in most ‘first world’ countries for decades. This started long before any effective medical interventions were available. In the US, in the 1950s, there were no effective blood pressure lowering agents, no stents, no CABG, no clot busters…. Nothing really.

Possibly the greatest single factor has been the reduction in smoking. At the end of the second world war virtually all men smoked. Nearly 90% in the UK in the 1950s. Since that time the number of smokers has fallen, and fallen.

In addition to this, during the 60s, 70s, 80s and onwards, medical interventions have also greatly improved. In-hospital survival from a heart attack or stroke has improved almost year on year. The figures are complex, but around 60% of those admitted to hospital with a heart attack used to die – it is now around 30%, maybe less.

Some of this is due to the fact that ‘strict bed rest’ following a heart attack, the key medical intervention for decades, was abandoned. A piece of medical mismanagement that killed millions and millions… and millions.

What else may have cause the fall? I think that in the UK, the clean air act has a significant effect. The Great Smog of London, in the early 1950s, killed tens of thousands in less than a week. Much of this was from respiratory complications, but also CVD. It is now more clearly established that air pollution, in general, increases the risk of CVD. Most Western countries have drastically reduced air pollution.

Now, I would like to consider something almost never mentioned. Lead. That is the element, not the verb. Or the noun, as in dog lead.

In the 1920s someone discovered that if you put lead in petrol/gasoline it had all sorts of benefits on engine performance and wear and tear – and so on. Unfortunately, lead also caused all sorts of problem for human performance, and wear and tear. It is a heavy metal and, like other heavy metals, a powerful human toxin.

Despite the fact that lead toxicity was known for decades, it took until the nineteen-sixties before countries starting banning it from fuel – and pipes in housing – and the like. Which reversed a long-term trend of lead building up inside human beings. It lasts for decades within bone – gradually leaking out.

With regards to lead and CVD, is there a link?

A researcher called Weisskopf looked at the amount of lead in bones, and the rate of CVD. He found that those with the most lead in their bones were 837% more likely to die from CVD (relative risk)¹ than those with the least lead in their bones. Now, whilst that is a relative risk, it is of the magnitude where we can safely say we are looking straight at a direct cause of CVD.

How does lead cause CVD. Most likely through the following mechanisms

‘Lead causes endothelial dysfunction by binding and inhibiting endothelial nitric oxide synthase and decreasing nitric oxide production.’²

Yes, we are straight back to my old friends, endothelial dysfunction and decreased nitric oxide (NO) production. In the world of cardiovascular disease, if you know where to look, all roads lead to NO.

If lead does cause CVD, is there any evidence that removing lead from the body can reduce the risk of CVD? [‘Reversibility’ and ‘Experimental Evidence’, the two most powerful of Bradford Hill’s canons for causation]. Which brings me to TACT. A trial designed to look at the impact of chelation on CVD. A way of removing heavy metals from the body…

What I love about this trial is that it was set up primarily to prove that chelation was nonsense, to be laid alongside homeopathy, and suchlike – by mainstream researchers. To quote an article in Medscape:

‘The original TACT trial wrestled with enrolment, ultimately taking over a decade to yield results, in part because cardiologists were absolutely convinced that chelation was a load of horse hockey.’ ³

TACT stands for Trial to Assess Chelation Therapy. When I first heard about chelation, I too, dismissed it as horse hockey. However, it turns out that I done the thing that I always advise everyone else against doing. I placed it in the ‘impossible/horse hockey’ category without making the effort of trying to find out what it was really about.

As it turns out, I should have made more effort…

‘TACT found that patients randomized to a regimen involving up to 40 separate three-hour infusions of a chelation-therapy solution (disodium ethylenediaminetetraacetic acid [EDTA], ascorbic acid, magnesium chloride, potassium chloride, sodium bicarbonate, B vitamins, procainamide, and a small amount of standard heparin) experienced an 18% drop in the trial’s primary end point (all-cause death, reinfarction, stroke, revascularization, or hospitalization for angina) compared with patients randomized to a placebo infusion.’³

More extraordinary than this:

‘When we broke the composite down to look at our secondary end points, we found that we had about a 40% reduction in total mortality, a 40% reduction in recurrent MI, and about a 50% reduction in mortality [in patients with diabetes],”’³

A 40% – 50% reduction in mortality. Well, well, well. Eat your heart out statins. In fact, eat your heart out every single pharmaceutical product ever tested. What has been the effect on mainstream thinking on CVD? As you would expect, absolutely nothing has changed in the slightest. Still TACT2 is now being set up – so we can all look forward to that being ignored in about seven to ten years’ time.

Anyway, in an attempt to bring some structure to this blog, I am going to return to the start. Why has the rate of CVD gone down in most first world countries over the last fifty years? One of the reasons, I believe, is that the level of heavy metal pollutants (in particular, lead) has been dropping since around the mid nineteen sixties.

I think it could be argued that the US was the first country to embrace the motor car. Thus lead toxicity would have hit the US before anywhere else. I am not going to argue this too strongly, but I place it before you, for your consideration.

I shall finish by saying that, if you want to look for reasons for the pattern on CVD over the last sixty years, or so, you really need to start looking outside the box. For there are more things in heaven and earth Horatio, than are dreamt of in your philosophy.

1: Weisskopf MG, Jain N, Nie H, et al. ‘A prospective study of bone lead concentration and death from all causes, cardiovascular diseases, and cancer in the Department of Veterans Affairs Normative Aging Study’. Circulation 2009;120(12):1056-64.

2: Natalia V. Solenkova et al: ‘Metal pollutants and cardiovascular disease: Mechanisms and consequences of exposure.‘ Am Heart J 2014;168:812-22

3: http://www.medscape.com/viewarticle/814643?pa=QYKVfN05tfWXqq6%2BfjZ30whyKyHVDGvMW4WYyHO8jprcrUBo6WRIR4VFzOaThtqB8SIvl8zjYv73GUyW5rsbWA%3D%3D

In my long and winding road around cardiovascular disease I have often visited the same themes a few times. In part, this is because we are not dealing with Newtonian physics here. If billiard ball A strikes billiard ball B, at five metres per second, at an angle of 45 degrees, billiard ball B will move off at angle C at velocity D, assuming perfect elasticity. This will always happen, every single time.

On the other hand, with CVD, the complexity of human physiology and psychology, environmental factors, genetics the time of day, even sunspot activity – can have an effect – so some people have reported.

‘Space proton flux and the temporal distribution of cardiovascular deaths.

The influence of solar activity (SA) and geomagnetic activity (GMA) on human homeostasis has long been investigated. The aim of the present study was to analyse the relationship between monthly proton flux (> 90 MeV) and other SA and GMA parameters and between proton flux and temporal (monthly) distribution of total and cardiovascular-related deaths. The data from 180 months (1974-1989) of distribution in the Beilinson Campus of the Rabin Medical Centre, Israel, and of 108 months (1983-1991) from the Kaunas Medical Academy, were analysed and compared with SA, GMA and space proton flux (> 90 MeV). It was concluded: monthly levels of SA, GMA and radiowave propagation (Fof2) are significantly and adversely correlated with monthly space proton flux (> 90 MeV); medical-biological phenomena that increase during periods of low solar and/or geomagnetic activity may be stimulated by physical processes provoked by the concomitant increase in proton flux; the monthly number of deaths related (positively or negatively) to SA are significantly and adversely related to the space proton flux (> 90 MeV).’¹

Oh yes, I do cast my net far and wide when looking at cardiovascular disease, as I feel I must. Quite what we are all supposed to do when the space proton flux is greater than 90MeV, I am not certain. Perhaps a tin foil hat would become appropriately protective headgear. By the way, this paper can be found in the National Institutes of Health on-line library – Pubmed. Referenced, peer-reviewed, and everything.

The point being? The point being that if you are looking for ‘billiard ball’ certainty, you are not going to find it here. If you were to do absolutely everything that I believe to be protective against cardiovascular disease, you will shift the odds in your favour, but you could still get struck down by a heart attack or stroke.

Anyway, with that proviso firmly in place, I shall move ahead, or maybe backwards. On the basis that some subjects need a second visit, I have decided to return to look at vitamin C again. First, because I have just been harangued by someone who believes that if you take high doses of vitamin C every day, you can reverse/cure heart disease completely and utterly. He also felt that I had completely ignored the work of G C Willis ‘The reversibility of atherosclerosis’, and also the research of Pauling and Rath on vitamin C.

It is true that I have not actually mentioned Willis before, but I have certainly written at length of Pauling and Rath. However, I realise that time passes, people forget things, and previous blogs settle to the bottom of the sediment layer. Therefore, it is not a bad idea to refresh things from time to time. I am also returning to vitamin C and the issues around it, because I have been getting a lot of correspondence about lipoprotein (a) (Lp(a)) recently. It seems this lipoprotein is gaining increasing attention. Of course, vitamin C and Lp(a) are tightly bound together.

Time, I think, for a quick refresher about this whole area. Particularly as it helps to confirm my central hypothesis that CVD is a disease of blood clotting, and you would struggle to explain the vitamin C/Lp(a) axis in any other way.

To begin. At some point in the distant past, our ancestors lost the ability to manufacture vitamin C. This happened, so I recently read, around sixty-one million years ago. Seems a long way back, but there you go. It has happened to some other animal groups, but not many. Quite why it occurred is unclear. You probably think you know, but I suspect you are wrong.

Interestingly, and as a bit of an aside, vitamin C is synthesized through a multi-step process, and the original molecule is glucose. Humans lack the last step in the process. Perhaps, because of this, glucose and vitamin C have some interesting interactions in the body. Mainly, it seems, that high levels of glucose prevent vitamin C from entering cells. Particularly immune cells, which need a lot of vitamin C to operate effectively. Make of that what you will.

Moving on, because humans cannot synthesize their own vitamin C, we must obtain it from within our diet. If we do not manage to eat enough, we will end up with scurvy. Scurvy presents with many different symptoms, but the one I am going to focus on in this blog is bleeding.

Bleeding occurs, because vitamin C is essential for collagen synthesis – a critical building block of supportive tissue throughout the body. Loss of collagen leads to break down of various structures in the body. For example, the walls of blood vessel walls which, start to break down and ‘crack.’

As blood vessel walls crack, they leak, and bleed. This leads to the best known symptom of scurvy, which is bleeding gums. This was well recognised several hundred years ago, mainly in sailors who had a highly-restricted diet during long voyages. In scurvy there is also bleeding in many other blood vessels, but you can’t easily see it. The usual cause of death in severe scurvy is internal bleeding.

On the positive side, after sixty-one million years, or so, evolution came up with a partial solution to the early stages of scurvy. Namely, the synthesis of a substance to block the cracks in the blood vessel walls, and control the bleeding. This substance is, or course, lipoprotein (a).

Lipoprotein (a) (Lp(a)) is synthesized in the liver, and it travels around in the bloodstream, looking for any cracks in blood vessels walls a.k.a. damaged endothelium. When a crack is spotted Lp(a) is attracted to the area and sticks very firmly, and cannot easily be removed. Of course, the rest of the blood clotting system also moves into action, so all hell breaks loose. Therefore Lp(a) becomes mixed up with platelets, red blood cells, fibrin, and almost everything else in the blood, including all the other lipoproteins.

However, Lp(a) has a very special trick up its sleeve. It mimics plasminogen.

After a blood clot forms, anywhere in the circulation, it has to be broken down, and removed – once the blood vessel underneath it has repaired. I liken this (not very accurately) to road works. If the road surface is damaged, the repair team comes in, sets up barriers and traffic lights and suchlike, then they repair the road. Then all the barriers, and traffic lights, and suchlike, must be removed.

Within a blood vessel, removal of barriers, and traffic lights, is a tricky exercise. Where does the blood clot go? Once a large blood clot has formed, over a ‘crack’ in the wall, it cannot stay there forever, restricting, or totally obstructing, blood flow. On the other hand, if the entire clot simply broke off, and travelled down the artery, it would get stuck as the artery narrowed – causing a complete blockage. Not a good idea.

Ergo, there is a need for a process that removes blood clots that have formed within blood vessels. It is called thrombolysis, or fibrinolysis. To ‘lyse’ means to break down.

The main player in thrombolysis is plasminogen. It becomes incorporated into (almost) all blood clots that form. It is activated by tissue plasminogen activator (t-PA). This turns plasminogen into plasmin, the ‘active’ enzyme that slices fibrin apart [fibrin is a long, and very strong, string of fibrinogen molecules that wraps round blood clots and binds them together].

t-PA can be manufactured and given to people who have heart attacks and strokes, to break apart the blood clots that are blocking the arteries in the brain, or the heart. You may have heard of t-PA referred to as a ‘clot-buster.’ Great stuff, but not so good if your stroke is due to a bleed in the brain, rather than a blood clot. In which case….

t-PA has been around for a while now and, with heart attacks at least, has mainly been superseded by angioplasty. Which is to open up the blocked artery, and stick a metal support (stent) into the artery. T-PA is still use in ischaemic strokes. That is, after you have had a brain scan to work out what sort of stroke you are having.

Sorry to appear to be going off in different directions here, but the systems of blood clotting are highly complex, and I think that explaining where Lp(a) fits in, is important.

Lp(a) is actually a lipoprotein, just like LDL. In fact, it is exactly like LDL, because it is basically LDL. It is the same size and shape, it contains triglyceride and cholesterol. However, it differs in one important aspect. Whilst LDL has a protein stuck to it called apolipoprotein B-100, Lp(a) has another protein stuck to it called apolipoprotein (a). Which is why it is called lipoprotein (a).

The fascinating thing about the protein, apolipoprotein (a), is that is has almost exactly the same chemical structure as plasminogen. So close, that you could hardly tell it apart. However, apolipoprotein (a) is completely unaffected by t-PA. It does not convert to plasmin, it is inert. So, when you want to break down a clot (fibrinolysis), the parts that have Lp(a) incorporated into it, cannot be broken down.

Which means that if you have a high Lp(a) level, you will develop bigger and more difficult to break down blood clots. Exactly what evolution had in mind for creatures that cannot manufacture vitamin C, and need to plug cracks in artery walls when the vitamin C level falls. However, not so good, if you want to stop atherosclerosis from developing.

Because these Lp(a) rich blood clots have to go somewhere, and the only place that they can go is to be absorbed into the artery wall itself, and then broken down. However, these clots are more difficult to break down, so, with repeated clots over the same area of artery wall, bigger and bigger plaques will grow.

That, anyway, is the theory.

What G.C. Willis did in 1957 was to study guinea pigs. Guinea pigs are another animal that does not synthesize vitamin C. He made them scorbutic (vitamin C deficient a.k.a. scurvy). Actually, he did not make them all scorbutic. He had a control group of twelve guinea pigs that he put on a vitamin C deficient diet, then injected them with vitamin C. None of these twelve guinea pigs developed any measurable atherosclerosis.

On the other hand, those guinea pigs on a scorbutic diet rapidly developed atherosclerosis. When I say rapidly, I mean within days. I think this point is worth repeating. If you make a guinea pig scorbutic, it will develop plaques, identical to those found in human arteries within days.

Willis then started feeding his guinea pigs vitamin C, and he found that the lipid filled plaques quite rapidly disappeared. He describes what he saw happening to the guinea after they were fed vitamin C.

‘The results of this investigation indicate that early lesions of atherosclerosis are quickly resorbed. The stages of this process are first a fading of lipid staining in the region of the internal elastic membrane with later a disappearance of all extracellular fat. Active phagocytosis of lipid by macrophage occurs, and when these macrophages finally disappear no evidence of the lesion remains.’ ²

I shall translate that passage for those with a non-science background.

What Willis found was that if you remove vitamin C from the guinea pig diet, they develop fat filled atherosclerotic plaques within days. If you then add vitamin C to the diet again, the plaques rapidly disappear (within days). The process of removal appears to be that the fat/lipid is ingested (phagocytosed) by white blood cells – known as macrophages.

However, if you let the plaques grow for too long, it is far more difficult to get rid of them.

‘More advanced lesions are considerably more resistant to reversal. Extensive lipid deposits clear in some parts of plaque but islands of intensely staining lipid persists in other parts. The macrophage response to such areas is only slight.’

It seems that if you don’t get rid of the plaque pretty much straight away, you don’t get rid of it at all. [Or maybe he didn’t wait long enough to see what happened over months, or years. Although my childhood memory of guinea pigs is that they tend to drop dead at the slightest excuse].

Of course, this was guinea pigs, not humans, so we must be careful not to extrapolate too far. However, previously, Willis had studied humans. Not many, only sixteen. Ten people with identified plaques were given vitamin C, six were not. In those ten treated with vitamin C, the plaques got bigger in three, stayed the same in one, and reduced in size in six. In those six not given vitamin C, three remained the same, and in three the plaques got bigger. Interesting, but hardly cast-iron proof of anything.

At this point there are a number of strands to gather together. We now know that humans cannot synthesize vitamin C, so we need to eat it. Without enough vitamin C, our blood vessels crack and bleed, and in severe cases we bleed to death.

In order to provide a degree of protection against vitamin C deficiency (scurvy), we produce lipoprotein (a) to fill up the cracks the blood vessels. However, unsurprisingly, a high level of lipoprotein (a) Lp(a) is associated with a higher rate of CVD.

‘In summary, elevated Lp(a) levels associate robustly and specifically with increased CVD risk. The association is continuous in shape without a threshold and does not depend on high levels of LDL or non-HDL cholesterol, or on the levels or presence of other cardiovascular risk factors.’ ³

This raises two inter-connected questions. Does vitamin C supplementation lower Lp(a) levels, and does it reduce the risk of CVD? It is of course entirely possible that vitamin C could reduce CVD risk by protecting blood vessels from ‘cracking’ without having any effect on Lp(a) levels.

Now you would think that this would have been an area of research interest to someone…. Anyone. However, the only people who seem to have looked at this area in any details are Linus Pauling (double Nobel prize winner, now dead) and Matthias Rath. A man whose reputation within the mainstream medical profession makes that of Andrew Wakefield look like mother Teresa. This from Wikipedia:

‘The Sunday Times (Johannesburg) has described Rath as an “international campaigner for the use of natural remedies” whose “theories on the treatment of cancer have been rejected by health authorities all over the world.”

On HIV/AIDS, Rath has disparaged the pharmaceutical industry and denounced antiretroviral medication as toxic and dangerous, while claiming that his vitamin pills could reverse the course of AIDS. As a result, Rath has been accused of “potentially endangering thousands of lives” in South Africa, a country with a massive AIDS epidemic where Rath was active in the mid-2000s. The head of Médecins Sans Frontières said “This guy is killing people by luring them with unrecognised treatment without any scientific evidence”; Rath attempted to sue him.

Rath’s claims and methods have been widely criticised by medical organisations, AIDS-activist groups, and the United Nations, among others Former South African President Thabo Mbeki and former Minister of Health Manto Tshabalala-Msimang have also been criticised by the medical and AIDS-activist community for their perceived support for Rath’s claims According to doctors with Médecins Sans Frontières, the Treatment Action Campaign (a South African AIDS-activist group) and a former Rath colleague, unauthorised clinical trials run by Rath and his associates, using vitamins as therapy for HIV, resulted in deaths of some participants. In 2008, the Cape High Court found the trials unlawful, banned Rath and his foundation from conducting unauthorised clinical trials and from advertising their products, and instructed the South African Health Department to fully investigate Rath’s vitamin trials.’

Matthias Rath even managed to fall out with Linus Pauling, before Pauling’s death, and law suits ensued. Rath has also successfully sued the BMJ, received £100,000 in damages. So, as you can see, not really a poster boy for mainstream medical research.

I include this information, as I think it is critical to the entire Vitamin C discussion. Because Matthias Rath is viewed as absolute scientific poison this has made the whole area of vitamin C supplementation a complete no-go area for any respectable scientist. If, as a doctor, you try to suggest that vitamin supplementation may be a possible treatment for, say, CVD, you might as well hand you licence over to the authorities at the same time – to save them the trouble of striking you off the medical register (almost a joke, but not quite).

So, essentially, we have a huge void here. The only research that I have ever seen (maybe I missed some) to establish if vitamin C supplementation does actually lower Lp(a) levels was done by Matthias Rath. And, according to him, it does. More so, in those with higher levels to start with. I am not referencing this research, but I would suggest you have a look around Rath and Pauling and vitamin C and Lp(a). See what you think. I think the research is robust.

With regard to the critical question, does vitamin C reduce the risk of CVD [with or without lowering Lp(a)]. I would say, case currently unproven. This does not mean that it does not (in fact I believe that it probably does). What I mean by ‘case currently unproven’ is that no-one has done a large scale interventional study using vitamin C to find out if it really reduces CVD.

The problem here is that such a study is almost certainly never going to be done. There is no way anyone can make money from doing such a study. Vitamin C cannot be patented, so if a company spend several hundred million ‘proving’ that vitamin C reduced CVD death, they would never get any money back.

You would have to find a Governmental organisation, tax payer funded, to do such a study. And with Matthias Rath around, that just ain’t going to happen. No-one would touch it.

However, there is one way to definitely reduce Lp(a) levels, and that is to take l-carnitine. Here, from a study called ‘L-carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a)’

‘L-carnitine, a natural compound stimulating fatty acid oxidation at the mitochondrial level, was tested in a double blind study in 36 subjects with Lp(a) levels ranging between 40-80 mg/dL, in most with concomitant LDL cholesterol and triglyceride elevations. L-carnitine (2 g/day) significantly reduced Lp(a) levels… the reduction being more dramatic in the subjects with the more marked elevations. In particular, in the L-carnitine group, 14 out of 18 subjects (77.8%) had a significant reduction of Lp(a) vs only 7 out of 18 (38.9%) in the placebo group. In a significant number of subjects the reduction of Lp(a) resulted in a return of this major cardiovascular risk parameter to the normal range.’ ⁴

Does this then result in a reduction in CVD risk? The answer is that I do not know, for sure. A meta-analysis of L-carnitine supplementation has been done. This consisted of five trials on three thousand people. L-carnitine supplementation did show some benefit – which did not reach statistical significance, but came very, very close.

For those of you who like a bit of statistics, here we go

‘The interaction test yielded no significant differences between the effects of the four daily oral maintenance dosages of L-carnitine (i.e., 2 g, 3 g, 4 g, and 6 g) on all-cause mortality (risk ratio [RR] = 0.77, 95% CI [0.57-1.03], P = 0.08)’⁵

CI [0.57 to 1.03] – close, but no cigar.

To put this into figures anyone can understand. In the intervention groups (those taking L-carnitine) there were 83 deaths. In the control group (those not taking L-carnitine) there were 106 deaths. Total study population was 3108, split in two groups: control and intervention. This gets as close to statistical significance as you can get (virtually). In fact, if this had been a statin trial, you would never have heard the end of it. ‘Ladies and gentlemen a 22% reduction in overall mortality with L-carnitine supplementation.’ [Oh, what fun statistics are].

So, what do we know?

• A high level of Lp(a) is associated with a higher risk of CVD.
• There is a probable causal mechanism linking Lp(a) to CVD death
• Lp(a) is synthesized in animals that cannot make their own Vitamin C
• A lack of vitamin C causes blood vessels to crack open – and potentially leads to atherosclerotic plaques development
• Animal models have shown that a lack of vitamin C does lead to rapid atherosclerotic plaque development, and that replacement of vitamin C causes rapid regression of atherosclerosis
• Some evidence from humans suggest that vitamin C supplementation causes regression of atherosclerotic plaques
• Vitamin C supplementation does seem to lead to a reduction in Lp(a) levels
• L-carnitine supplementation does lead to a reduction in Lp(a) levels
• L-carnitine supplementation may reduce overall mortality.

What would I now recommend? If you have a high Lp(a) level take lots of vitamin C and l-carnitine and see if your Lp(a) level falls. If it does, keep taking lots of vitamin C and l-carnitine for the rest of your life. If it does not fall? Not sure.

As for the rest of us? Well I have no idea how much vitamin C anyone should take, or how much l-carnitine is required. There is literally no area of medicine that is less clear than our true vitamin requirements. You can find a thousand shouty people supporting high vitamin supplementation – any or all vitamins.

My view. I do not think the RDAs for vitamins are remotely accurate, or useful. They were established in times of absolute deficiency. The agreed Vitamin B12 levels, for example, were based on seven people, over sixty years ago, and remain unchanged to this day. All seven had pernicious anaemia (caused by vitamin B12 deficiency).

So, I do not believe in the RDAs at all. They are often, I believe, too low for optimal health. I can see no harm coming to people from taking lots of vitamin C or lots of l-carnitine. So, supplement away. You will probably reduce your risk of dying from CVD.

References
1: https://www.ncbi.nlm.nih.gov/pubmed/9140214

2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1823880/?page=3

3: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295201/

4: https://www.ncbi.nlm.nih.gov/pubmed/11213533

5: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223629/

As 2016 draws to an end, I believe that a change is in the air. The dietary guidelines, or perhaps I should call them the ‘dietary misguidedlines’, are under a sustained attack. This, finally, may actually result in success. We will be able move on from believing that fat, or saturated fat, in the diet is responsible for cardiovascular disease or, indeed, any form of disease.

But where to then? The current dogma is that saturated fat in the diet raises cholesterol levels and this, in turn, leads to cardiovascular disease. However, as many of you may have spotted earlier this year, in the Minnesota Coronary Experiment (MCE), substituting saturated fat with polyunsaturated fat was effective at lowering cholesterol levels. However, it had absolutely no effect on deaths for heart disease, and greatly increased the overall risk of death.

The summary of this trial was, as follows:

• It involved 9423 women and men aged 20-97
• A cholesterol lowering diet was used, replacing saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine).
• The low saturated fat group had a significant reduction in serum cholesterol compared with controls.
• There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts.
• For every 0.78mmol/l reduction in serum cholesterol [Around a 20% reduction], there was a 22% higher risk of death [This is about a 30% reduction in cholesterol level]

Big deal, you might think. This is just one trial, so what difference does it make. However, this was no ordinary trial. It was absolutely pivotal for four main reasons:

• It was the largest controlled trials of its kind ever done. That is, substituting saturated with polyunsaturated fats.
• It was done by Ancel Keys (who started the entire diet-heart hypothesis in the first place)
• It was finished, before the main clinical nutritional guidelines were developed
• It was not published at the time, for reasons that have never been explained, by anyone.

As the authors of the re-analysis note.

“Whatever the explanation for key MCE data not being published, there is growing recognition that incomplete publication of negative or inconclusive results can contribute to skewed research priorities and public health initiatives. Recovery of unpublished data can alter the balance of evidence and, in some instances, can lead to reversal of established policy or clinical practice positions.” ¹

Which is a polite way of saying that a bunch of liars hid the results. Almost certainly because the results contradicted their self-promoted message that saturated fats are unhealthy. It is clear that these researchers, in particular Ancel Keys, did this quite deliberately, and then continued to promote their own dietary dogma.

I think it is almost impossible to overestimate the long-term impact of the non-publication of this trial.

• For want of a nail the shoe was lost.
• For want of a shoe the horse was lost.
• For want of a horse the rider was lost.
• For want of a rider the message was lost.
• For want of a message the battle was lost.
• For want of a battle the kingdom was lost.
• And all for the want of a horseshoe nail.

Here is my updated version

• For want of the MCE trial evidence the McGovern hearings were lost
• For want of the hearings the guidelines were lost
• For want of the guidelines the message was lost
• For want of the message battle was lost
• For want of the battle saturated fat was lost
• All for the want of the MCE trial data.

The McGovern hearings which set the entire direction of nutritional thinking, and guidelines, took place in 1977. The MCE trial ran from 1968 to 1973. Had the data from this study been made available, the dietary guidelines in the US, the UK and the rest of the world (In their current form, demonising saturated fat) simply could not have been written.

If those guidelines had not been written, then the entire world of cardiovascular research would almost certainly have gone off in a different direction. The role of LDL in causing CVD would have been consigned to the dustbin history. Goldstein and Brown wouldn’t have done their research on Familial Hypercholesterolaemia, statins would never have been developed, and we not have been forced to endure fifty years of the damaging, destructive diet-heart/cholesterol hypothesis.

The fact that the diet-heart/cholesterol hypothesis is complete nonsense, has been clear as day to many people for many years. In 1977 George Mann, a co-director of the Framingham Study, writing in the New England Journal of Medicine called it ‘the greatest scam in the history of medicine.’ In my view, anyone with a moderately functioning brain, can easily see that it is nonsense.

So, if not fat and cholesterol, what does cause cardiovascular disease, and more importantly, what can be done to prevent it, or at least delay it? At last (some of you are thinking) I will state what I believe to be one of the most important things you can do to reduce the risk.

Returning to the central process of cardiovascular disease (CVD), for a moment. If you are going to reduce the risk of cardiovascular disease, you must do, at least, one of three things:

• Protect the endothelium (lining of blood vessels) from harm
• Reduce the risk of blood clots forming – especially over areas of endothelial damage
• Reduce the size and tenacity (difficulty of being broken down) of the blood clots that develop

If you can do all three, you will reduce your risk of dying of a heart attack, or stroke, to virtually zero.

What protects the endothelium?

There are many things that that can do this, but the number one agent that protects the endothelium is nitric oxide (NO). Thus, anything that stimulates NO synthesis will be protective against CVD. Which brings us to sunshine and vitamin D.

• Sunlight on the skin directly stimulates NO synthesis, which has been shown to reduce blood pressure, improve arterial elasticity, and a whole host of other beneficial things for your cardiovascular system, not least a reduction in blood clot formation.
• Sunlight on the skin also creates vitamin D, which has significant impact on NO synthesis in endothelial cells, alongside many other actions. It also prevents cancer, so you get a double benefit.

Therefore, my first direct piece of direct advice for those who want to prevent heart disease, is to sunbathe. In the winter when the sun is not shining take vitamin D supplementation. Alternatively, go on holiday to somewhere sunny. Or get a UVB sunbed, and use it.

My only note of warning here is to say, don’t burn, it is painful and you don’t need to.

By the way, don’t worry about skin cancer. Sun exposure protects against all forms of cancer to a far greater degree than it may cause any specific cancer. To give you reassurance on this point, here is a Medscape article, quoting from a long-term Swedish study on sun exposure:

‘Nonsmokers who stayed out of the sun had a life expectancy similar to smokers who soaked up the most rays, according to researchers who studied nearly 30,000 Swedish women over 20 years.

This indicates that avoiding the sun “is a risk factor for death of a similar magnitude as smoking,” write the authors of the article, published March 21 in the Journal of Internal Medicine. Compared with those with the highest sun exposure, life expectancy for those who avoided sun dropped by 0.6 to 2.1 years.

Pelle Lindqvist, MD, of Karolinska University Hospital in Huddinge, Sweden, and colleagues found that women who seek out the sun were generally at lower risk for cardiovascular disease (CVD) and noncancer/non-CVD diseases such as diabetes, multiple sclerosis, and pulmonary diseases, than those who avoided sun exposure.

And one of the strengths of the study was that results were dose-specific — sunshine benefits went up with amount of exposure. The researchers acknowledge that longer life expectancy for sunbathers seems paradoxical to the common thinking that sun exposure increases risk for skin cancer.

“We did find an increased risk of…skin cancer. However, the skin cancers that occurred in those exposing themselves to the sun had better prognosis,” Dr Lindqvist said.”²

In short, avoiding the sun is a bad for you as smoking. In my opinion ordering people to avoid the sun, is possibly the single most dangerous and damaging piece of health prevention advice there has ever been. The sun has been up there, shining down, for over four billion years. Only very recently have we hidden from it. If you believe in evolution, you must also believe that sunshine provides significant health benefits. It cannot be otherwise.

Happy, sunny, CVD risk reduced, 2017

I have just added a little poem that was just sent as a comment on my blog. Thanks for the laugh.

Ancel Benjamin Keys
Researched dietary disease.
When the facts turned out contrarian,
He simply up and buried ’em. [Martin Back]

1: http://www.bmj.com/content/353/bmj.i1246
2: http://www.medscape.com/viewarticle/860805

‘The greatest scam in the history of medicine’ George Mann

I have been a bit quiet of late, mainly because I got a cough that ended up as a nasty chest infection, that also caused my brain to turn to mush for about three weeks. Maybe it was the antibiotics. Anyway proof, as far as I am concerned, that the mind and body are closely connected.

Yes, another little detour from my series, trying to explain what causes cardiovascular disease. But I thought I need to look, once again, at the hypothesis that saturated fat consumption is a cause – perhaps the cause of cardiovascular disease?

To be honest, I have studied saturated fat consumption many, many… many, many, times. The one thing that has always stood out, most starkly, is the complete lack of any real evidence to support the idea that it causes cardiovascular disease.

On the other hand, evidence contradicting it arrives on an almost daily basis. The following study was sent to me a few days ago, although it is now almost ten months since it was first published. The researchers looked at nearly thirty-six thousand people over twelve years. It was done in the Netherlands. The main conclusions were that that:

‘Total saturated fat intake was associated with a lower IHD (Ischaemic Heart Disease) risk (HR per 5% of energy 0.83). Substituting SFAs with animal protein, cis-monounsaturated fats, polyunsaturated fats or carbohydrates was significantly associated with higher IHD risks (HR 1.27 – 1.37).’¹

One thing scientific researchers have learned over the years is that you can never say anything in a straightforward way. I think the game is that, if anyone can easily understand your findings, you lose. A game played to its illogical conclusion by French Philosophers. Something I remarked to my son, who was trying to quote Derrida at me. Here would be one snappy Derrida quote:

“Every sign, linguistic or nonlinguistic, spoken or written (in the usual sense of this opposition), as a small or large unity, can be cited, put between quotation marks; thereby it can break with every given context, and engender infinitely new contexts in an absolutely nonsaturable fashion. This does not suppose that the mark is valid outside its context, but on the contrary that there are only contexts without any center of absolute anchoring. This citationality, duplication, or duplicity, this iterability of the mark is not an accident or anomaly, but is that (normal/abnormal) without which a mark could no longer even have a so-called “normal” functioning. What would a mark be that one could not cite? And whose origin could not be lost on the way?”

Yes, indeed. Couldn’t agree more.

As with Derrida, so with scientific papers. What these researchers should have said is the following. ‘The more saturated fat you eat, the lower your risk of dying of cardiovascular disease, and vice-versa.’ A thirteen per cent reduction in death for every five per cent increase in energy obtained from saturated fat consumption. Why do they run away from making such easy to understand statements? I think Derrida could probably tell us. If we could ever understand anything he ever wrote, or said.

However, I am not going to bombard you with endless facts contradicting the saturated fat hypothesis, I am going to get a little more philosophical here. To ask, what is it about some scientific ideas/hypotheses that they become so quickly entrenched – without the need for the tedious requirement of any actual facts.

My thoughts were drawn to this issue by something seemingly unconnected. Which is a legal hearing the UK concerning shaken baby syndrome. Most experts in paediatrics are absolutely convinced that there is such a thing. It is quoted in textbooks as an undisputed fact. Many parents, and other adults, have been convicted, and sent to jail, for shaking their babies so hard that it caused the ‘triad’ of shaken baby syndrome: subdural hematoma, retinal bleeding, and brain swelling

On the other hand, we have Dr Waney Squier, a paediatrician who used to provide expert opinion on child abuse cases in the UK. She was struck off by the General Medical Council (GMC) for, well the exact judgement is, as per Derrida, impossible to understand.

The GMC judgement has certainly been criticized:

‘Michael Mansfield, Clive Stafford Smith and others argue that the General Medical Council is behaving like a “21st-century inquisition” in the case of Dr Waney Squier (Shaken baby syndrome doctor struck off, 22 March).’

The GMC responded thus:

‘Far from wishing to suppress different views, we recognise that scientific advance is achieved by challenging as well as developing existing theories, and importantly in this context we are absolutely clear that neither the GMC nor the courts are the place where such scientific disputes can be resolved. To be clear, it is possible that a doctor who ultimately was proved to have the correct theory could present their evidence in such a way as to mislead, just as it is possible for a doctor advocating a theory ultimately proved to be flawed to present their case in context and with integrity.’

Niall Dickson

Chief executive, General Medical Council

The only possible response to Niall Dickson’s remark is ‘bollocks.’ You can present the correct theory in a way to mislead, and you can present a flawed hypothesis with integrity? George Orwell would surely nod in approval of such perfect doublethink. You are right, but we don’t like the way you present being right. We would rather listen to someone talk absolute nonsense using the correct professional manner. Can I have my knighthood now, please?

Leaving the machinations of the GMC aside, the main issue is simple. Dr Waney Squier does not believe that shaken baby syndrome exists. Of course she knows that the triad of subdural haematoma, retinal bleeding and brain swelling exists. But she believes there could be other explanations. Including, perish the very thought, an accidental fall.

Because she does not believe in shaken baby syndrome, she has presented evidence in court which has tended to undermine the prosecution case against parents and carers, accused of shaking a baby and causing severe brain damage. Much to the annoyance of the police and they then, for it was indeed them, reported Dr Squier to the GMC.

Now, I know what most of you are thinking. Surely ‘shaken baby syndrome’ exists. This must have been proven. Well, it has not. If you think about it, how could it be proven? How do you think a study on shaken baby syndrome could ever be done? Get five hundred children, shake them forcefully and see what happens to their brains. I suspect you might find gaining ethical approval for a such a study might be tricky.

Despite this, and the fact that shaken baby syndrome represents an ‘unproven hypothesis’ almost all experts around the world are convinced that shaken baby syndrome exists. Dr Squier, who seems a well-rounded and sensible lady, has made the terrible mistake of questioning that this dogma. There could be, shock horror, other possible causes.

The police objected, judges objected, her peers objected, and she has been struck off. No longer able to practice medicine anywhere in the world. She has become a medical pariah.

The good news is that her case in going in front of an actual court of law in the UK. I strongly suspect (maybe I just hope) that her ‘conviction’ will be overturned. She does have the support of a number of other paediatricians around the world. However, in the meantime, other doctors, who do not believe in shaken baby syndrome, will not dare go to court to testify in support of those accused of shaking babies. Such is the power of the Spanish Inquisition.

Shaken baby syndrome: saturated fat consumption.

On the fact of it shaken baby syndrome and saturated fat consumption have very little in common. However, from another perspective the parallels are clear. Both are seductively simple ideas that appeal to common sense. That most deadly of all senses.

Most people can clearly see how a small, vulnerable, baby will suffer significant brain injury if it is shaken too hard. Close your eyes and you can virtually see it happening. If you can bear having that image in your head for any length of time.

Most parents, I think, can almost see themselves doing it, or having done it – when their child will ‘just not dammed well stop crying.’ In short, shaken baby syndrome can easily be visualised, and it triggers a kind of visceral horror. We can easily see how a feckless parent may lack the self-control required to stop themselves doing it. ‘Shut up, shut up, shut up….’

And that, dear reader, is as scientific as shaken baby syndrome gets. A hypothesis based on visceral fear, prejudice, and knee-jerk judgement. This makes it almost perfectly resistant to any contradictory evidence. Try to argue against it, and you will meet anger and bluster and the idee fixe.

I was once told a story which goes as follows. It concerns a psychiatrist trying to convince a patient that he is not dead. A battle that that had gone on for many years, eventually the psychiatrist comes up with a brilliant idea….

Psychiatrist:       ‘Do dead people bleed?’

Patient:                                   ‘No, I guess not.’

Psychiatrist:       (Takes pin from lapel and pricks the patient’s thumb, and a drop of blood appears). ‘Aha, do you see that?’

Patient:                 (Looks at thumb) ‘What do you know, I guess dead people do bleed then.’

The ‘saturated fat causing heart disease hypothesis’ comes from a very similar place called – well, it’s obvious isn’t it, just common sense. Heart disease is basically a build of fat in the arteries, isn’t it.? Where can that possibly come from? Fat in the diet. Especially the thick, sticky, gooey stuff that you get on a pork chop, or suchlike. That’s got to be it hasn’t it? The thick horrible squidgy gooey fat that you eat, ends up as thick horrible squidgy gooey fat in your arteries. Serves you right for eating fat, and MacDonald’s, and suchlike.

There rests the entire scientific argument against saturated fat. As such it is difficult to argue against. Facts simply bounce off. As demonstrated very clearly to me in a more recent publication. A very major review was published a few weeks ago on the Journal of Food and Nutrition Research called ‘Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries.’ ²

‘The aim of this ecological study was to identify the main nutritional factors related to the prevalence of cardiovascular diseases (CVDs) in Europe, based on a comparison of international statistics.’

What did they find? Well, they found lots of things, but the key things they found were the following:

‘We found exceptionally strong relationships between some of the examined factors, the highest being a correlation between raised cholesterol in men and the combined consumption of animal fat and animal protein (r=0.92, p<0.001). The most significant dietary correlate of low CVD risk was high total fat and animal protein consumption.’

Now that paragraph really needs a however in it. Just after p<0.001 and the ‘The.’ Yes, they found that animal fat (mainly saturated fat) and animal protein did indeed raise cholesterol. However, animal fat and animal protein consumption showed the most powerful correlation with low risk of cardiovascular disease.

Which food items showed the highest correlation with increased CVD risk? Have a guess.

‘The major correlate of high CVD risk was the proportion of energy from carbohydrates and alcohol, or from potato and cereal carbohydrates.’

The conclusion of the authors:

‘Our results do not support the association between CVDs and saturated fat, which is still contained in official dietary guidelines. Instead, they agree with data accumulated from recent studies that link CVD risk with the high glycaemic index/load of carbohydrate-based diets. In the absence of any scientific evidence connecting saturated fat with CVDs, these findings show that current dietary recommendations regarding CVDs should be seriously reconsidered.’

When the British Heart Foundation was presented with the findings from this study they found a Dr Mike Knapton to make the following statement:

“Other studies, however, show diets high in saturated fat are linked to raised cholesterol levels, which is a risk factor for heart disease. So, for you and me, we should consider our diet as a whole to reduce our overall risk, such as a traditional Mediterranean style diet, which is a style of eating associated with a lower rate of coronary heart disease. The key is a balanced diet over all, rather than considering individual foods. There are many factors which cause heart disease and stroke and no single food or nutrient is solely responsible for this. We will continue to recommend switching saturated fat for unsaturated fat.”

As you can see, when presented with evidence, the BHF refuses to consider it, and turns to gibberish. Dr Mike Knapton argues that this study should be ignored, because other studies have shown that saturated fat raised cholesterol levels, and this is a risk factor for heart disease.

‘Hellooo Dr Knapton. This study also showed that saturated fat increased blood cholesterol levels. However, what it also showed is that this reduced the risk of heart disease. Did you even read that bit, or do you simply dismiss papers contradicting the diet-heart hypothesis on the basis they must be wrong – so what it the point of actually reading them?’

On many occasions I, and others, have tried to engage the BHF in debate. However, you can’t. They just provide ‘statements’. The statements never change, the evidence they use never revealed. However big a study, however contradictory it is, it will be met with statement such as Other studies, however, show diets high in saturated fat are linked to raised cholesterol levels, which is a risk factor for heart disease.

Made up scientific hypothesis are, I find, very difficult to dislodge with evidence.

1: ‘The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer andNutrition–Netherlands cohort’ Jaike Praagman, Joline WJ Beulens, Marjan Alssema, Peter L Zock, Anne J Wanders, Ivonne Sluijs, and Yvonne T van der Schouw. Am J Clin Nutr doi: 10.3945/ajcn.115.122671

2: http://www.foodandnutritionresearch.net/index.php/fnr/article/view/31694

[Yes, this one took a long time to write]

When I started looking at heart disease, or cardiovascular disease (CVD) it was initially because I was interested to know why the Scots and the French had such different death rates. I had also just finished a book by James le Fanu called ‘Eat your heart out’ in which he made it very clear, or at least he did to me, that fat/saturated fat in the diet had nothing to do with CVD in any way shape of form.

However, at the time le Fanu was very much a voice crying in the wilderness. The experts had a very different song, or dirge. Namely that the Scots diet was terribly unhealthy, and this fully explained why they kept keeling over from heart attacks. Their bad diet raised cholesterol levels and…. thud (sound of Scots person falling over dead).

This is still very much the case. All of our medical authorities still announce the absolute truth of the ‘terrible Scottish diet’ with adamantine confidence. They usually bring out the almost mythical ‘deep fried mars bar’ as the perfect example as to why the Scots die of heart attacks, and strokes, and suchlike. ‘Well, what can you expect of a nation that eats deep fried mars bars… ho, ho.’

The truth is that hardly any Scotsman, or women, has ever eaten such a thing. And if they did it once, they will most certainly never do it again (I was certainly put off for life after one drunken foray on a Saturday night). Of course, there is also a perfect irony here. A mars bar is almost entirely made up sugar (not fat). When you fry it, it will be in vegetable/polyunsaturated fat – as saturated fats have been virtually banned in deep fat fryers. So, in theory, a deep fried mars bar should be somewhat more heart healthy than a ‘virgin’ mars bar. As it now contains a mass of hot sugar plus some heart ‘healthy’ polyunsaturated fat.

I suppose this example, at least to me, highlights the complete lack of any consistent logic or thought in the diet heart world. A fact that I became very painfully aware of, over many years. Indeed, I came to realise that there is no area of human existence where more nonsense is spouted than the ever-changing beliefs about what constitutes a healthy, or unhealthy diet. Frankly, it is almost entirely wall to wall rubbish.

At one point I made an effort to look at the classical ‘risk factors’ for heart disease between France and Scotland. This was done some years ago as part of a paper I wrote called ‘Does Insulin Resistance cause atherosclerosis in the post-prandial period?’ Something which I still think is at least part of the picture of CVD.

Here is the table I put together from a number of different sources – there was no single source for the data I was looking for. [I could not find separate UK and Scottish figures for a number of the factors, so I had to look at the UK as a whole. In addition, at there were no clear cut data on saturated fat, so I used animal fat as a proxy – which is almost the same thing]

As you can see, there was virtually no difference in the classical risk factors for UK men and French men. Despite this, the French had one quarter the risk of death from ischaemic heart disease [what you or I would tend to call heart disease]. Since that time the French rate of heart disease has continued to fall, as it has also done in the UK, whilst the French consumption of saturated fat has risen. Interestingly total cholesterol levels have fallen in both countries.

So, whatever was going on had very little to do with diet. And if it had very little to do with diet, then it also had little to do with cholesterol either. If your hypothesis is that eating saturated fat increases cholesterol, or LDL cholesterol levels, which then causes CVD then how can two countries with exactly the same saturated fat consumption and cholesterol level (and all other risk factors equal) have such a different rate of CVD? And how could France, whilst continuing to eat more saturate fat, have a falling cholesterol levels? And how does the Ukraine, which currently has the lowest saturated fat intake in Europe, end up with the highest rate of CVD etc. etc. etc.

When you start looking at facts like this you must start to question the diet-heart cholesterol hypothesis. Or at least I thought you must. How wrong I was. Virtually the entire medical profession was wedded to the diet-heart cholesterol hypothesis – still is. Facts appear to have no impact whatsoever on this belief system.

Anyway, once I started to look at CVD in more detail, I was confronted with a choice. Accept that I must be wrong. After all, how can all the researchers and experts and Nobel prize winners be wrong. They must surely be seeing things that I cannot. Or, accept that the diet-heart cholesterol hypothesis was wrong. The blue pill, or the red pill.

Dear reader, I chose the red pill, in the sure and certain knowledge that rejecting the conventional thinking was certainly not going to be an easy path to follow. I also knew that if I was going to reject the diet-heart/cholesterol hypothesis, then I had to try and find out what does actually cause CVD. When I looked around at first there, were few alternative voices, or hypotheses out there. If truth be told, there seemed to be none (at least initially). But if not cholesterol, then what?

Over time, as I looked around, some ghosts in the machine began to emerge. I was aware of a doctor (whose name I cannot even remember) who firmly believe that fibrinogen was the main cause of CVD, and I went to a talk that he gave on the subject – not paying it much heed in truth. Then the Scottish Heart Health Study was published, and the single most powerful risk factor that emerged for CVD risk was… fibrinogen. A blood clotting factor. Aha. Could CVD actually be due to blood clotting abnormalities?

This was a time before the internet, before search engines, before finding information was so easy. This was an era when you had to traipse down to the medical library and pull actual books from actual shelves if you wanted to find out stuff. After pulling a lot of books off a lot of shelves I learned of Duguid, a Scottish doctor, who argued that blood clotting was the cause of CVD (I paraphrase).

His work was published shortly after the second world war, and has remained mostly unread. Then I went all the way back to Karl von Rokitansky who, in 1852, felt that atherosclerotic plaques were, in fact, just blood clots – in various stages of repair. An observation which, from time to time, other researchers have noted. Most particularly a doctor called Smith, from Aberdeen. He is no longer active in this area of research.

Here is the abstract from his paper ‘Fibrinogen, fibrin and fibrin degradation products in relation to atherosclerosis’. I have quote the abstract in full, for those who like to see a bit more detail. Others may glaze over, or skip to the last sentence:

‘Many human atherosclerotic lesions, showing no evidence of fissure or ulceration, contain a large amount of fibrin which may be in the form of mural thrombus on the intact surface of the plaque, in layers within the fibrous cap, in the lipid-rich centre, or diffusely distributed throughout the plaque. Small mural thrombi are invaded by SMCs (smooth muscle cells) and collagen is deposited in patterns closely resembling the early proliferative gelatinous lesions. In experimental animals, thrombi are converted into lesions with all the characteristics of fibrous plaques, and in saphenous-vein bypass grafts, fibrin deposition is the main cause of wall thickening and occlusion. There seems little doubt that fibrin deposition can both initiate atherogenesis and contribute to the growth of plaques.

Epidemiological studies indicate that increased levels of fibrinogen and clotting activity are associated with accelerated atherosclerosis, and although blood fibrinolytic activity has given inconsistent results, in arterial intima both fibrinolytic activity and plasminogen concentration are decreased in cardiovascular disease. Fibrin may stimulate cell proliferation by providing a scaffold along which cells migrate, and by binding fibronectin, which stimulates cell migration and adhesion. Fibrin degradation products, which are present in the intima, may stimulate mitogenesis and collagen synthesis, attract leukocytes, and alter endothelial permeability and vascular tone.

In the advanced plaque fibrin may be involved in the tight binding of LDL and accumulation of lipid. Thus there is extensive evidence that enhanced blood coagulation is a risk factor not only for thrombotic occlusion, but also for atherogenesis. Enhanced blood coagulation frequently coexists with hyperlipidaemia and, together, these may have a synergistic effect on atherogenesis.’ ¹

For those whose eyes did glaze over, concentrate only on the last sentence. ‘Enhanced blood coagulation frequently coexists with hyperlipidaemia and, together, these may have a synergistic effect on atherogenesis.’

Here, ladies and gentlemen, lies my little secret. My evil twin brother who I have kept in the attic for the last twenty years, gnawing at the floorboards. The terrible truth that there is an association between LDL levels/familial hypercholesterolemia and CVD. Something which I appear to have argued against for many, many, years.

Does this mean that the experts have been right, all along? High LDL cholesterol levels do cause CVD? Well maybe, maybe not. At this point I need to take you back to the statement again. ‘Enhanced blood coagulation frequently coexists with hyperlipidaemia.’

Does this mean that hyperlipidaemia actually causes enhanced blood coagulation? Or does it mean that something else causes both. Here is the old ‘yellow fingers and lung cancer’ discussion.

‘People with yellow fingers are more likely to die of lung cancer.’

Why… because people with yellow fingers smoke, and smoking causes lung cancer. Ergo yellow fingers are simply a sign of smoking, they do not actually cause lung cancer.

‘People with raised LDL are more likely to die from CVD’

Why… because people with raised LDL are also more likely to have enhanced blood coagulation. Ergo, raised LDL levels are only associated with enhanced blood coagulation, they do not actually cause CVD. It is the blood coagulation factors.

Alternatively, raised LDL may actually enhance blood coagulation, all by itself.

Where does the answer lie? In truth the answer has been very difficult to tease out. Even now, after many years, I do not feel that I can fully disentangle the data. Here for example, is a paper called ‘Maternal familial hypercholesterolaemia (FH) confers altered haemostatic profile in offspring with and without FH.’

‘Children with (n=9) and without (n=7) FH born of mothers with FH, as well as control children (n=16) born of non-FH mothers were included in the study. The concentrations of tissue plasminogen activator, plasminogen activator inhibitor (PAI-1), tissue factor (TF), TF pathway inhibitor (TFPI), thrombomodulin, fibrinogen, prothrombin fragment 1+2 and von Willebrand Factor were measured. Our findings show i) higher levels of PAI-1 and TFPI in children with and without FH born of mothers with FH compared with control children, ii) lower levels of thrombomodulin in children with FH compared with control children, and iii) significant correlations between maternal PAI-1 levels during pregnancy and PAI-1 levels in the offspring.^’2

What this tells us is that, if a mother has Familial Hypercholesterolaemia, she passes on abnormalities of blood coagulation to her children. Both those that have, and those that do not have FH. [Not all children of mothers with FH will end up with the FH gene]. Some of this may be epigenetically modulated. In short, it is not the LDL that is important, it is simply the mother’s genes….

Or is it? Here is a paper suggesting that the LDL itself, independently of anything else, makes platelets more likely to stick together (a key step in blood clotting).

‘The interaction of platelets with lipoproteins has been under intense investigation. Particularly the initiation of platelet signaling pathways by low density lipoprotein (LDL) has been studied thoroughly, since platelets of hypercholesterolemic patients, whose plasma contains elevated LDL levels due to absent or defective LDL receptors, show hyperaggregability in vitro and enhanced activity in vivo. These observations suggest that LDL enhances platelet responsiveness….’ ³

However, maybe these researches misinterpreted what they were seeing. For example, another paper found that the level of LDL in those with FH was not related to their risk CVD. It was purely the level of clotting factors that was related to CVD. This paper entitled: ‘Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolaemia.’

‘Haemostatic variables were measured in 61 patients with heterozygous familial hypercholesterolaemia, 32 of whom had evidence of coronary heart disease. Age adjusted mean concentrations of plasma fibrinogen and factor VIII were significantly higher in these patients than in the 29 patients without coronary heart disease, but there were no significant differences in serum lipid concentrations between the two groups. Comparisons in 30 patients taking and not taking lipid lowering drugs showed lower values for low density lipoprotein cholesterol, high density lipoprotein cholesterol and antithrombin III, and a higher high density lipoprotein ratio while receiving treatment. The results suggest that hypercoagulability may play a role in the pathogenesis of coronary heart disease in patients with familial hypercholesterolaemia.’⁴

So it is not the high LDL? It is the raised blood clotting factors that are found in some, but not all of those with FH. As you can see, it is not straightforward at all.

Just to complicate the picture further, here is a paper strongly suggesting that HDL is directly anti-coagulant.

‘Native HDL prevents platelet hyperreactivity by limiting intraplatelet cholesterol overload, as well as by modulating platelet signalling pathways after binding platelet HDL receptors such as scavenger receptor class B type I (SR-BI) and apoER2′. The antithrombotic properties of native HDL are also related to the suppression of the coagulation cascade and stimulation of clot fibrinolysis. Furthermore, HDL stimulates the endothelial production of nitric oxide and prostacyclin, which are potent inhibitors of platelet activation. Thus, HDL’s antithrombotic actions are multiple and therefore, raising HDL may be an important therapeutic strategy to reduce the risk of arterial and venous thrombosis.’ ⁵

And what about VLDL?

‘There is a considerable body of evidence supporting an association between hypertriglyceridaemia (high level of VLDL), a hypercoagulable state and atherothrombosis. A disorder of triglyceride metabolism is a key feature of the metabolic syndrome that increases risk of both ischaemic heart disease and type 2 diabetes approximately 3-fold. An increasing prevalence of obesity and metabolic syndrome is likely to contribute markedly to the prevalent ischaemic heart in the foreseeable future, and therefore it is crucial to understand mechanisms linking hypertriglyceridaemia and a hypercoagulable state. Activation of platelets and the coagulation cascade are intertwined. VLDL and remnant lipoprotein concentrations are often increased with the metabolic syndrome. These lipoproteins have the capacity to activate platelets and the coagulation pathway, and to support the assembly of the prothrombinase complex. VLDL also upregulates expression of the plasminogen activator inhibitor-1 gene and plasminogen activator inhibitor-1 antigen…’ ⁶ etc.

You can go back and forward in this area, finding research that contradicts itself upside down and inside out again. What I think I know for certain is the following:

• High LDL levels/familial hypercholesterolemia is closely associated with increased blood coagulation (in a high percentage of those with FH, though not all) – through many different interrelated mechanisms. Some genetic, some possibly directly due to LDL itself.
• VLDL (triglyceride) seems to increase blood coagulation – and this seems a very consistent finding
• HDL has anticoagulant effects

I don’t know how powerful these different pro and anti-coagulant effects are, but they certainly exist. To an extent I could just say what does it matter if LDL does, or does not increase blood coagulation directly – but is simply associated with blood clotting abnormalities. It all fits within the processes that I have outlined in this series of blogs. Namely, anything that increases the risk of blood clotting increases the risk of CVD. And LDL (directly, or through genetic association) does increase the risk.

However, I thought it would be dishonest of me not to highlight the fact that there could well be a causal association between LDL (and VLDL) and CVD. Also there does seem to be a causal protective mechanism provided by HDL.

Or, to put this another way, perhaps all the experts were (a bit) right all along. Even if they have consistently promoted a process that does not make any sense at all i.e. LDL leaks into artery walls causing inflammation and plaque growth etc.

A further proviso is that I cannot see that the LDL/VLDL/HDL effects are very strong. After all I just co-authored a paper showing that higher LDL levels in the elderly are associated with increased life expectancy and a slight reduction in CVD risk. [There are many other factors clouding the issue here – too many to discuss in one go]. Confused yet… welcome to my world.

So where did I get to. I think I got to the point where I accept that:

• LDL is pro-coagulant and – at very high levels e.g. in FH – increases the risk of CVD [though it is difficult to disentangle this from intertwined genetic pro-coagulant factors]
• VLDL is pro-coagulant, and increases the risk of CVD
• HDL is anticoagulant and protects against CVD

Which then brings onto statins, and how they work. First to re-iterate that statins do reduce the risk of CVD [Something, I have never disputed]. However, they do it not by lowering LDL, but because they have anticoagulant effects. Not that potent, about the same as aspirin, but the effect does exist.

Here from a paper entitled ‘statins and blood coagulation’:

‘The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation…. Treatment with statins can lead to a significant downregulation of the blood coagulation cascade….’ ⁷ An effect confirmed by their protection against DVT.

‘Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin.’ ⁸ Yet, the experts continue to tell us that statins work, purely, by lowering LDL levels. Ho hum.

Whilst I could have written this series and simply pushed LDL, VLDL and HDL to one side. I thought I needed to bring them into the discussion. Not to dismiss them but, I hope, to explain what their role within CVD may actually be – pro and anti-coagulant agents. Here is where they fit, and make sense. Looking at lipoproteins in the light also helps to explain how statins actually work.

References:
1: http://www.ncbi.nlm.nih.gov/pubmed/3524931
2: http://europepmc.org/abstract/med/23199546
3: http://www.ncbi.nlm.nih.gov/pubmed/16877876
4: Br Heart j 1985; 53: 265-8
5: http://www.ncbi.nlm.nih.gov/pubmed/24891399
6: https://www.karger.com/Article/Pdf/93221
7: http://www.ncbi.nlm.nih.gov/pubmed/15569822
8: http://www.ncbi.nlm.nih.gov/pubmed/22278047