UPFs gave me wagu thighs

Interesting article reproduced this week in the Financial Times from the annual meeting of the Radiological Society of North America held in Chicago. 

One group reported to the conference that in a study of 60 yr olds, whose diet consisted of approximately 40% so called UPF, but who did not consume excessive calories had ‘fatty thighs’!

They  differentiated between fat outside muscle tissue and fat within muscle tissue. In other words fat pads under the skin making the thigh look ‘fat’ and fat within the tissue itself. To those who eat meat, intramuscular fat is recognised and valued as ‘marbling’ because it enhances both taste, succulence and texture.

No hypotheses were put forward but one more nail in the UPF coffin was hammered home and it drew the usual scoff from the food industry who know that as a collective term UPFs are impossible to define…so are UPFs the bad guys here?

As a biochemist I wondered how quickly an hypothesis could be generated and how well it could be pinned to a modern UPFish diet or not..The answer was .. about 10 minutes.

The beef industry values marbling in meat the ultimate expression being in asian cattle and Wagu steaks. The adipocytes ( fat cells) within muscle are different to those outside tissue and respond to different signals most of which are poorly understood or studied. However mild injury and inflammation increases intramuscular adipocyte activity and fat infiltration in to the tissue. Some cattle are genetically disposed to intramuscular fat infiltration but other than the above the only strategy to increase marbling is to add conjugated linoleic acid to the feed. These are called CLAs and can be synthesised as well as being present in natural foods.

Natural sources of CLAs are basically: milk, cheese and meat.. The highest values I found published when a quick web search was carried out are in milk, ground beef and mozzarella cheese.

So, let me think: latte coffees, burgers and pizzas should max out our CLA intake

There you go, nothing to do with bad stuff in the foods, after all you can get the highest quality of unadulterated ingredients in all three of the foods above, but if you have a latte each day, burgers twice a week and a take away pizza, you’ll probably get wagyu-thighs!

Ps if you are wondering what the intramuscular fat is doing in your muscles, quite simply it is an energy store placed as close as possible to the muscle mitochondria which use fatty acids as slow burn fuel. Ideal for a labourer maybe not ideal for an office worker.

Senescence: time for humanity to enter the dying phase

 Time to start dying.

I have just re-read the opening paragraph to my 1979 Ph.D thesis on the Biochemistry of Ageing (Rat Mitochondria). It laid out the goal of the field of study called gerontology. In a nutshell, the goal was: ‘the extension of years of active life before entering the senescent phase’. It also said explicitly that increased life span due to prolongation of the senescent phase was a bad idea, something I feel with which few would disagree.

Unfortunately I think in the last fifty years we have achieved mostly  the latter and in the worst way. There has been an increase in UK average maximum life span ( about 3 years more for men and women) in that time but I am increasingly thinking that the senescent phase is starting earlier. 

In the UK the cost to the taxpayer of supporting the long term sick is large, increasing and unsustainable. I think a great many of this group have entered a  senescent phase, or at least a version of it. This assertion needs a lot of unpacking to sound credible.

Firstly we expect old people to look old. We readily recognise superficial phenotypes denoting ‘old’;  low energy, wrinkles, faltering gait, muscle loss, incontinence and bone fragility to name a few. Some of these such are products of deteriorating connective tissue which is a time-dependent passive chemical process rather than a reflection of physiological or biochemical ageing. Physiological changes, say to do with muscles or the brain on the other hand are under active processes. Processes we now know are ultimately mediated by mitochondria via internal and external signals

Now, the broad signals  for a cell or a body to enter a senescent phase are well known. They are DNA damage ( eg from radiation, pollution,toxins) , epigenetic ( eg onco-viral),  telomere erosion ( the ability for a cell to divide) and mitochondrial dysfunction. All except telomere erosion can be influenced by environment, diet and lifestyle.

To follow the argument in this post you need to imagine a senescent individual who does not look old. So his/her limbs and body will remain plump, skin smooth-ish, and heads hairy. They will however also be largely inactive ( low energy) and suffering from chronic inflammatory diseases like arthritis and IBS and dementia. Low immune surveillance will also lead to an increase in early onset cancers especially where inflammation is high, eg the gut. Sarcopena ( muscle loss ) will also be evident, though largely hidden by intramuscular fat. Finally, mental health issues such as depression and anxiety come to dominate cognitive processes.. In all respects characteristics of folk in teh senescent phase.

How could this happen? How did the ‘not-old’ enter a senescent phase? ‘Signals’ are received and acted upon by an organism on very many levels. For example mitochondria ‘note’ energetic demands, the amount and character of ‘food’ being delivered, the level of damage in the cell, the activity of endogenous and exogenous viruses, exposure to NIR light at dawn and dusk. The list goes on, and mitochondria proliferate or die or kill the whole cell depending on what they find.

At a more complex  level the mind responds with behavior changes according to the perception of the environment, broadly divided into good times or bad times. Bad times triggers reduction in mating and vice versa. 

As you can see in the profile of the Ist World human there are plenty of candidates to signal ‘it’s all over chums go into senescence’ .  And with very bad luck modern medicine will prolong this phase even longer. Happy days.

Dementia, shingles and statins ...pharma's biggest oops!

I have just returned from my local GP surgery for a routine check and saw a poster informing all that one

in four adults will get shingles. Excuse me! One in four? I would have queried this figure except

for the fact that amongst my 60+ peers I find shingles is, well, rampant.. and consequently

I am looking for my free shingles vaccination as soon as I turn 70.

Shingles is nasty, painful and infectious; especially to those who never had chickenpox or the chickenpox vaccination. Worse, you are not guaranteed to get better. Shingles is a bit like its relative the herpes cold sore, it is a reactivated virus acquired earlier in life. Shingles is a reactivated chickenpox virus once living quietly in nerve cells.

How is it reactivated?  The consensus is that it is a result of an immunosuppressant failure. Duh! This is restating the obvious and has no information associated with it other than some very interesting data.  Patients medicated with statins have an increased susceptibility to shingles. I am not joking.

Studies show that people who take cholesterol-lowering statin drugs are at higher risk for developing shingles. “A possible reason,” says Dr. Cohen, “is that statins may affect the immune system.”  For further info confirming this:

https://bmjopen.bmj.com/content/9/2/e022897

A wide range of viruses ranging from Herpes to Covid to  oncoviruses ( cancer causing) typically target mitochondria once they have gained entry to a cell. The reason is simple, mitochondria control cell death ( apoptosis ) and will cause the cell to commit suicide in response to infection.

Shutting down the cell, the apoptotic response to something going wrong within a cell, is an integral part of the basic immune response to infection (and indeed of the termination of cancerous cell too).

Mitochondrial morphological changes occur as virus Herpes Zoster virus reactivation progresses showing that front line defence against reactivation is being compromised.

So, readers of my posts will be already aware of what comes next:

Statin medication affects mitochondrial health through alteration of cholesterol availability. Lowered mitochondrial health sometimes  leads to apoptosis of muscle cells in some individuals ( muscle pain, sarcopenia) and in others or even the same people  lower immune surveillance of endogenous viruses such as herpes zoster, ie they get shingles.

One in four should expect to get shingles!. What are the figures for those over 60 on statins? A tsunami of statin related health outcomes are coming our way

post script: 

I have just had my shingles vaccination (the recombinant vaccine not the live vaccine) and I am v happy with this especially when a little more research informs me that the vaccine helps protect against dementia. Another 'what!!'  It seems like it does not matter if it's the live or recombinant vaccine, both work. But why? No mechanisms are proposed. 

I have a mechanism. Shingles are linked to statin use. My proposition is that the nerve cells invaded by the resurging Herpes Zoster virus are made disproportionally vulnerable by statin use ( unsuprising maybe given how much cholestrol is needed in the myelinated axon's insulation sheath)  So in the shingles v dementia findings it is simpler to see shingles as a vulnerability sympton rather than a cause of nerve deterioation. Yes, the net is closing in around statins' unforseen consequences.

We, Gen AZ are different.

  

Do you find nowadays that you ‘start a cold’ or go to bed feeling that ‘something is coming' on’ fully expecting a minor illness only to wake up with it gone? Can you remember the last time you went to bed with a bug? If not you are probably a member of Gen AZ.

‘Boomers’ plus Gens X, Y,  Z  and now A, are shorthand labels that conveniently divide the spread of population ages into chunks that facilitate ‘targeted messaging’. The letters replace terms such as  ‘old’, ‘middle aged’, young, adolescent and child which enables ‘market targeting’ to sound a bit more academic than it is really.

This post is about a very different generation..Gen AZ. Gen AZ is anyone old enough to be vaccinated against Covid 19 in the early 2020s who received the adeno-virus vaccine delivery vector designed to produce the now famous ‘spike-protein’ which in turn primed the immune system in order to fight the then deadly Covid-19 virus 

Sounds complicated? Yes indeed, it’s sufficiently esoteric to be utterly incomprehensible to non-biochemists. However incomprehensibility does not mean insignificant. Known colloquially as the ‘Oxford-vaccine’ and manufactured by Astra-Zenica only a relatively few people globally can lay claim to be GenAZ. Gen AZ  has indeed received the ultimate in ‘targeted messaging’. 

Back in the day, as they say, when Covid 19 was rampant and the race for mass, global vaccination was on, only three pharma companies understood the RNA recombinant technology and had the expertise to safely, in quantity, make an effective  Covid 19 vaccine. These were Astra-Zenica, Pfizer and Moderna. Many companies around the globe  could not do this. In Russia, China, India and Europe there were famous mega-pharma companies who simply could not master the technology. 

Of the effective new vaccines there were two types. The so-called mRNA vaccines made by Pfizer and Moderna and the Adeno-virus DNA vector made by Astra Zenica . Given the vast scale of the vaccination programmes both technologies proved to be remarkably safe as well as amazingly effective. However AZ vaccinations which dominated the initial program in the UK were soon superseded in subsequent immunization programs by either Pfzer or Moderna. For example in my own instance, as a boomer gen member in the UK, I got my first two early jabs from AZ. Subsequently I have had only Pfizer and Moderna. Friends in nearby Ireland, slightly late to the party, never got the AZ vaccination at all. AZ quietly disappeared following ‘bad reaction scares’ which in hindsight were not significant.

We, Gen AZ are different. 

Some readers may remember trolling memes emanating from Russia at the beginning of the pandemic when the announcements that the vaccines were coming brought relief and hope to millions. Crudely put the vaccines, they said, would modify our DNA and turn us into apes or something. Vaccine fear was born ‘bigly’ as the USA president at the time may have said. Even though simian traits have been displayed by many of our leaders this prophecy has needless to say not come to pass. But the trolls were right in an important way.

After Astra Zenica bowed out leaving the field to Pfizer and Moderna they moved a development  lab from their UK base to Ireland. Shortly after that, a paper from the Basedo lab at Trinity Dublin1, was published showing ‘non-target’ immunity from Gen AZ. In other words some generalized immunity to infection seemed to persist in those who had had AZ vaccine. Cue, end of trail.

Introducing attenuated and genetically modified ( ie it is engineered so that it can't reproduce) adenovirus DNA into a cell is wholly different to introducing mRNA. mRNA has a short shelf life before it is broken down and its components recycled. The fate of introduced DNA is far less certain. 

Introduced DNA may be broken down in the cell, or it may not; it may persist as free epigenetic DNA, it may be incorporated into nuclear or mitochondrial DNA; it may be repaired; it may be transcribed fully or in part to make mRNA and thence proteins identical to to alike to the ‘spike protein’. So logically it is overwhelmingly likely that Gen AZ has modified DNA.

What does this mean? Firstly I think this is the first and last time the Adenovirus vector is used en-masse and secondly Gen AV is being followed very closely. What fate is in store for chimeric Gen AZers? We’ll see.

1. https://www.irishtimes.com/health/2023/01/18/covid-wider-benefits-to-astrazeneca-vaccine-trinity-research-indicates/

https://www.tcd.ie/news_events/articles/2023/research-indicates-wider-benefits-to-astrazeneca-vaccine/

For a clear description of the methods of vaccine delivery into cells the article below from Nature is worth reading.

https://www.nature.com/articles/s41541-021-00356-x

Girls in school computing...it's a man's world

 

Mea Culpa. About twenty years ago I campaigned with others to get rid of compulsory ICT at GCSE in UK schools and replace it with computing, ( Computer Science as it would be called).  We fought bitter battles with EduGeek, the DFE, Microsoft, Research Machines (RM) and others. Good days for the Open Source world.

The reasoning was clear in that:

1) it was obvious that ICT served simply as vocational traing in the use of Microsoft Office and that the cost of MSOffice licencing in schools was a scandalous rip off, all aided and abetted by a now defunct but then powerful quango called BECTA.

2) Coding, egineering and programming skills were, as a result of the above, absent from a generation of students and that this was a 'bad thing'.

To cut a long story short, indeed ICT was dropped as a complsory subject and replaced by computing but no-one saw the Micheal Gove reforms coming! Basically GCSEs were now too easy ( by UK HM Gov Dept of Education's reckoning) and were made harder, a lot harder.

Unexpectedly having long retired I returned to school teaching in 2015 to fill a part-time vacancy for Computer Science despite being well into my sixties. Apparently the old ICT teachers were struggling and failing with computing, so duly left.

By 2017, no-one in the school was getting any ICT but oh boy was GCSE Computing tough! 

The syllabuses were not dull if you were a full on geek, full of abstractions and concepts. Interesting for a mixed class of 15 yr olds? Not at all. Could you wing you way through it? No you could not. 

Once computing became optional then although every student would acknowledge its importance in the modern world its numbers crashed. Worse it attracted a certain type ( yes we all know who we are) of student. Inevitably proportionally speaking, few of which were female. 

Today The Guardian newspaper reports that in 2023, 4 out of every 5 Computing students at GCSE are male.  

They did not have figures for A Level Computing ( really quite tough now) or university entrance numbers but it is safe to assume on past experience that the numbers of females falls proprortionately at each step. In other words, as The Guardian has worked out for itself ,the 'New World' dominated by IT and of course AI,  is overwhelmingly male.

With hinsight I regret our success in wiping out ICT, and I regret the elitist approach to computing. Sorry. Unintended consequences. Can I blame the Tories? Only for putting a narrow ideology above pragmatism and cocking up the implementation but that's not exactly a surprise to anyone in any sector in 2024.

Does it matter? Again past experience shows that when males have complete dominance over their world they create it in their image. 

Maybe that's not a good thing?

Biological AI, a unit of cognition?

Biological AI, a unit of cognition?

Flabby guts and arteries 2024

 

Flabby guts and arteries 2024

Why we need to look after Smooth Muscle

What is smooth muscle?

We have three distinct types of muscle: skeletal, cardiac and smooth. All three are connected to the nervous system: skeletal muscle is under conscious control, cardiac and smooth muscle are not. The latter two are largely automatic but can and do respond to sensors (receptors) connected to the nervous system. We are conscious of  skeletal and cardiac muscle activity but largely and sometimes entirely, unaware of smooth muscle and its activities.

Where is smooth muscle found?

Smooth muscle is found in the circulatory system particularly arteries; throughout the digestive system; in the urino-genital system; the reproductive organs;  the eyes and lungs. In other words, it’s the most widespread and unappreciated of all our musculature.

Briefly here are some of the functions for different tissues performed automatically by smooth muscle:

Arteries: SM enables the artery to change its internal diameter. When relaxed the artery is wider and vice versa. This has a direct effect on blood pressure and the distribution of blood to organs such as skin, heart, liver as well as  skeletal muscle.

Gut ( alimentary canal): The gut has smooth muscle along its entire length. SM waves of contraction (peristalsis) move food and liquids in a ‘mexican wave’ fashion through the gut from swallow to defecation. It is so effective we can even drink fluids standing on our head! SM provides the no-return valves (sphincters) on entry and exit to the stomach as well as the anus and finally powerful SM allows the stomach to wring and churn food into a liquid digestible state called chyme. 

Eyes: Our eyes have smooth muscle to alter the shape of the lens allowing us to focusnear and far using circular (ciliary) muscles which when relaxed pull the lens into a flatter shape for long distance and when contracted allow the lens to round up enabling closer focus. Muscles in the iris open and reduce the pupil letting more or less light into the eye.

Bladder: the bladder is a sheet of smooth muscle which enables us to empty the bladder when the stretch receptors tell us it is full.

The above is by no means a complete list but it serves to give a sense of the range of vital but unconscious activities on which we depend.

Conditioning Smooth Muscle, can they get flabby ..is it a real thing?

‘Health-aware’ folk take care of their skeletal and cardiac muscle through exercise and diet but they do not, at least do not deliberately, take care of smooth muscle. Does this matter? If smooth muscle can look after itself in pretty much any scenario then the answer is ‘no’; if smooth muscle, like other muscle is vulnerable to the ‘life-style’ of an individual then it does matter. 

Contemporary First World life can be usefully characterised by its environment, activity and diet. For a great many this means living in a largely temperature and light controlled environment; being for the most part sedentary; being medicated for blood pressure and cholesterol levels and finally eating mostly UPF (ultra-processed food). What this means really is that variation (in diet, activity, light, temperature) has been replaced by constant. Unfortunately for us, smooth muscle is conditioned ( or exercised) by variation; variation that was once so normal as to be sufficient to put smooth muscle onto ‘automatic’ and allow us to ignore it. No more I fear is this the case.

Variation versus Constant

This is the point of the post. Smooth muscle has an easy time of it nowadays. 

Consider the gut first: modern food is mostly cooked, processed,  soft, pulped,  predigested, emulsified. The gut has very little work to do compared to working with food of the recent past. IBS, Crohns and reflux are common complaints.

The variation on arterial pressure and diameter is minimised if a life style is sedentary, temperature controlled and  medicated with blood pressure controlling drugs. Atherosclerosis or as it was called, hardening of the arteries, is a classic 21st century pathology.

Eyes too do not get a work out when living in permanent near constant daylight and with focal distances ranging from a computer screen to the office wall. 

Even the bladder does not escape with access to ‘comfort breaks’ being the norm.

My hypothesis is simple. Smooth muscle needs exercise to remain strong and healthy just like any other muscle. Today, for many, it does not get the variation it needs to stay fit. Gut and arterial diseases will have a component that is a direct consequence of flabby smooth muscle.

Homo Algorithmicus II...life after Sapiens

Homo sapiens, the planet's last  surviving species of the once diverse* genus Homo, currently numbers about 80 billion souls. Sapiens has multiplied to cover the globe in a way that its recent** cousins, the Neanderthals and the Denisovans failed to do. The latter two, to all intents and purposes were modern humans possesing culture and tools. They interbred with sapiens and their echos are seen in the DNA of the present human populations. Broadly, Neanderthal in the west, Denisovan in the east and neither in Africa.

The reasons that individual Homo species died out are of course speculative and range from ( in no particular order): killed by Sapiens; out-competed by Sapiens; out-adapted by smarter more flexible Sapiens; assimilated genetically by Sapiens and inevitably climate-change. But basically no-one knows.

What is sure, and this applied to Sapiens also, that numbers matter. Smaller isolated populations are in any species not just Homo, vulnerable to poplation collapse. In-breeding leads to a smaller less diverse gene pool with the risk of accumlating genetic faults and in addition anihilation by novel dieases. It may be that by chance alone that Sapiens escaped that fate and lived to spread its genes globally, hitting basically a virtuous cirlce of diversity which even the black death could not beat into extinction***

But no more, Homo sapiens in  the 21st Century  is very reluctant to pro-create  causing alarm from London to Bejiing. Global population has already levelled off and is about to crash. Developed countries are maintaining economic viability only through mass immigration (which itself  is causing unrest) and technological development of automation and AI.

The decline in birth rates especially in developed countries is spectacular. For example, today in Afghanistan birth rates are similar to those of Ireland and Italy a mere 35 years ago. that is a figure between 4 and 5. Ireland and Italy today are at 1 or below. 2.2 is the replacement figure for reference. Immigrants from countries with birth rates similar to Afghanistan into developed countries reduce their birth rate to the cultural norm within a generation.

The question now arises as to whether reproduction in sapiens like in other mammals is  responding  to extrinsic or intrinsic factors. This is an important question. We, that is Us, are very good at proposing extrinsic factors that affect our behaviour and very poor at proposing intrinsic factors. 

Extrinsic factors to reduce reprodcution are: 

1) Capitalist/consumerist economic models of society where increasing family size is inversely correlated with wealth and therefore limiting full participation in the 'good life'.

2) Access to the means to control births, that is to say female access to chemical contraception and/or abortion.

Intrinsic factors are less tangible. Mammals, specifically female mammals of course, can regulate their reprodcution intrinsically; they can re-absorb their embryos. There is no hint by the way that male mammals have any role to play in the regulation of reproduction. Re-absorbtion is common in rat populations kept in laboratory conditions. In fact in my own work as a  PhD student I went an entire year with a colony of rats 'refusing' to reproduce!

Why female mammals intrinsically regulate their reproductive roles is again a matter of speculation. Such speculation inlcudes obvious perceived ( by the animal)  extrinsic factors such as food availability, food quality and the current climate as all being restrictors on a successful outcome regarding their infants' chances of reaching maturity. 

It's all about signalling.  That is to say extrinsic signals are preceived as funadamentally meaninful and which bring about profound changes in reproductive behaviour. P D James' book The Children of Men in 1992 described a future where for unknown reasons human reproduction had stopped. It reminded me of my lab rats. In fact 'lab-rat' is also a good descriptor of humans in advanced societies; temperature and light controlled, well-fed, good access to sexual mates and under-exercised. So I do wonder if in such an environment a signal is being recieved, the nature of which is unknown which says 'stop' to reprodcution. 

What could this signal be? Is it a misreading of an ancient extrinsic signal? Is it existential, a form of self-conscious despair?  Did a similar fate befall the Neanderthals/Denisovans  20,000-50,000 years ago?

Loads to speculate about but there surely will not be Sapiens around to speculate in 20,000 years time at the rate of depopulation emerging. What may remain is the logical descendant of the long journey of Homo, yes Homo Algorithmicus our AI progeny.

As a footnote, a falling population will have a powerful effect on the relationship between labour and capital, or indeed between serfs and their feudal lords. The aftermath of the Great Plague which destroyed so much of the population of europe, saw wages and life conditions improve radically for the survivors. Even with AI  robot labour on the rise human labour will increase in value under any economic system. One day it may be priceless!

* 12 and counting

** 20-50, 000 years ago

*** 50 million deaths in Europe alone with 50-80% mortality, 

Saturated fat is still not 'bad' in 2024

 

This post has been prompted by an article about diet in a respectable journal and repeated in respectable papers. In a nutshell, the claim is 'dietary saturated fat' is bad for you because it is associated with increased risk of cardio vascular disease (CVD) especially atherosclerosis ( aka 'hardening of the arteries through accumulation of fatty plaques).

Ok, no alarm bells raised with me so far; demonising saturated fat is an old trope harking back to the days when the food industry (which sold plant oils), was making saturated fats by saturating unsaturated fats (plant oils)  with hydrogen. Or, in plainer english, they were turning oils (unsuitable for baking) into hard fats (suitable for baking); unfortunately they were also producing novel, almost-saturated fats called trans-fats. Trans-fats it turned out were indeed harmful to the heart and were eventually banned.

So why are foods high in saturated fats, chiefly hard fat from pork (lard) beef (dripping) and butter back in the 'bad for you' news? 

The answer is probably commercial.

The food industry sells plant oils including the ubiquitous palm oil as well as rapeseed oil, sunflower oil, corn oil and coconut oil. Palm oil is the only one of these that can be used 'hard-enough' for baking but there is currently push-back from consumers unhappy with the ecological devastation caused by palm oil plantations. Consequently 'margarines' which have many oil-like ingredients, have been re-invented as an ingredient term. This slight of hand partially covers up/obscures the use of palm oil as a major ingredient in margarine.

Worse though for industry is the increasing use by consumers of animal fats, especially from the dairy industry, as people shy away from UPF ( ultra-processed foods). So call me cynical, but the industrial drive is on to demonise animal fats once again. Called to the rescue, on time and updated, is our old friend cholesterol. Cholesterol the ultimate food demon which was so successful in the past at destroying the animal fat business.

Imagine my surprise ( this is ironic in tone)  to find then a 'top-nutrionalist' stating that a diet high in saturated fat raises the levels of our newest villain  'bad-cholesterol' ( LDL or low-density lipoprotein) in the blood. Better still, a mechanism is presented that states that saturated fat lowers the number of LDL receptors in the liver, receptors whose function is to remove LDL from the blood ...  and as we all know LDL is associated with increased risk of CVD. Job done as they say.

This actually did get my full attention, for as a bicochemist I would struggle to ascribe such a signalling or biologically active role to a set of molecules as chemically inert as saturated fats.

 A little bit of research showed much more expectedly that 'the LDL receptor is a highly conserved cell membrane glycoprotein' which is regulated by a  'kexin type 9 (PCSK9)  protein that promotes degradation of cell surface LDL receptors'.  So, PCSK9, a complex hormone-like metabolicly-potent signal controls LDL receptor levels ... not saturated fat!

I did find that very ill people with high levels of disilpdidemia (plasma fats in  pathological levels and ratios) got worse with high levels of dietary saturated fat and had higher levels of PCSK and hence fewer LDL receptors. This is hardly, as in improbably remote, a paper saying dietary saturated fat lowers LDL receptors in the liver in a wider context.

There are a few technical terms in the paragraph above, and this may seem patronising, but it's all but unintelligable to a nutritionalist or a medical profressional, let alone the general educated and interested public;a public that is being re-fed a simplified version of the non-logic:  'fat makes you fat, and being fat is bad and so fat is bad'. 

What the techical paragraph actually says is 'nuts to the assertion that saturated fat increases LDL by decreasing the LDL receptors.

More delving into the latest LDL literature was actually surprising ( I should keep up to date more). It looks like the science world is getting closer to unravelling the underlying mechanisms of a predisposure to CVD ...still the biggest killer in the developed world. Modern drugs can affect LDL (bad cholesterol) and HDL (good cholesterol) levels and ratios differentially: specifically, some drugs selectively lower LDL. 

However data from such drug induced manipultion of lipoprotein levels and ratios has shown pretty unequivocably that high HDL is not 'good' per se neither is low LDL 'good' pe se  with regard to CVD either. 

Ah, now that is surprising, sorry Doc, here is my prescription back.

Lipoproteins in the blood are a complex heterogeneous bunch of entities but one is coming to the fore: Apolipoprotein-C3. The gene involved in the expression of this regulatory protein is coming into focus as a causal agent in disposition to CVD as APOC3 is powerfully assocaited with atherosclerosis. 

So to summarsise to date: CVD is something to do with the regulation of bio-active plasma lipoproteins but  it's now unlikely to be the two cholesterol-conjugated ( ie a cholestrol molecule is part of the structure) lipoproteins LDL and HDL.  Dietary cholesterol and dietary saturated fat unequivocably  are not  part of the story. 

This post was difficult to write because it is so steeped in technical molecular concepts. In an academic paper it would be easy but almost entirely inaccessible, whereas to simplfy the story risks falling into serious error. 

The risk of error is compounded when one suspects sophisticated bad actors with deep pockets and research funds are happy to confuse the living daylights out of any one casually encountering their self-serving nonsense.

Saturated fat is not bad for you.