16th September 2017
Beginning at the end.
Whilst there is significant controversy about how atherosclerotic plaques may start, and grow, the final event in cardiovascular disease is, in most cases, pretty much accepted – even by me. The formation of a blood clot. Yes, there are many caveats here, and also a number of different processes that can occur, but I am not covering them in this blog. I am using the simple ending. The obstructive blood clot.
If a blood clot forms in the coronary arteries – blood vessels supplying blood to the heart – it can fully block the artery, jam up blood flow, vastly reduce oxygen supply, and cause a myocardial infarction (MI). The clot usually forms on the surface of a pre-existing atherosclerotic plaque.
If a blood clot forms in the carotid arteries – main blood vessels supplying blood to the brain – it can then break off, travel up into the brain where it gets stuck, jams up blood flow, reduces oxygen supply, and cause a cerebral infarction (ischaemic stroke). Again, blood clots in the carotid arteries almost always form on the surface of atherosclerotic plaques formed earlier.
What this means is that reducing the formation of blood clots will, or definitely should, reduce the risk of heart attacks and strokes. And, of course, it does. Aspirin, for example, has anticoagulant action, and it lowers the risk of CVD, although not by a huge amount.
However, recently, a study was published in the New England Journal of Medicine which demonstrated that if you add rivaroxaban – an anticoagulant, primarily used to prevent strokes in patients with Atrial Fibrillation – to aspirin, this further reduces the risk of CVD1.
The trial was reported thus, in the Daily Mail on the 11th of September:
‘Phenomenal’ pill slashes the risk of death from heart disease by 22% and could save millions of lives, ‘ground-breaking’ trial finds.’
Oh yes, we do like a phenomenal pill, do we not. Mockery of such ridiculous hype aside, this was an impressive result. Far more impressive than any statin trial, it must be added – with no impact on LDL levels at all. Only one slight problem, it would be rather expensive to add rivaroxaban to everyone taking aspirin. Minimum cost, about £6Bn/years ($8Bn/year) in the UK alone.
Of course, there are other things that can reduce the risk of blood clotting. Omega 3 fatty acids, for example which reduce ability of platelets to stick together2 – an action almost identical to aspirin. Then there is Von Willibrand disease – a condition where people lack a key blood clotting element called the Von Willebrand factor. Patients with this condition have a 60% reduction in the risk CVD.
Those with haemophilia had – prior to the development of clotting factors to replace those that were missing –around 20% the risk of CVD of the surrounding population.
On the other hand, there are situations where the risk of blood clotting increases. Use of non-steroidal drugs e.g. brufen, naproxen, diclofenac etc. These increase the risk of clotting, and CVD. There are conditions, such as Hughes syndrome and Factor V Leiden where the risk of blood clotting goes up, and so does the risk of CVD and so on, and so forth.
In fact, I think it can be stated with complete confidence that any drug, condition, or anything else that reduces the risk of blood clotting, also reduces the risk of CVD, and vice-versa. Of course, if you reduce the risk of blood clotting, you can also increase the risk of serious bleeding. So, it is not all positive. All is balance. Yin and Yang, and suchlike. Even the relatively benign aspirin, in low doses, can lead to chronic blood loss, anaemia, and, in extreme cases, death.
What does this prove. Well it certainly proves that blood clotting and CVD are intimately related. So much so that the word ‘atherothrombosis’ is often used to describe the processes of CVD. ‘Athero-‘ = the atherosclerotic plaque growing then ‘-thrombosis’, the clot that forms top of the plaque that then kills you. That, at least, is the official Soviet party line.
However, I never liked the idea that we have two almost completely different processes going, that are linked together, but only at the final event. I wanted to explore the idea that a single process – blood clotting – could be responsible for plaque starting, growing and then ‘rupturing’ causing the whole spectrum of atherothrombosis. Blood clots, from start to finish.
This took me on a pretty amazing journey, a long and winding route indeed. I have come to believe that the system of blood coagulation must be, just about, the most complex physiological system in the body. It is beyond mind-boggling. Just when you think you have read about every factor involved, another one pops up. Indeed, I think I am forgetting facts about blood clotting faster than I can learn them. My brain is full.
However, the other day, I came across an expression that captured something about blood clotting that I have always struggled to put into words. It described the coagulation system as ‘idling’, as in sitting with the engine running. The blood coagulation system is never ‘off’ it is always turning over in the background, constantly producing small combination of substances that make up a full blood clot.
I suppose this is because, if you suffer a significant wound, or damage to a large blood vessel, the coagulation system cannot hang about. It must accelerate from zero to one hundred in the blink of an eye. Bang, go, stamp on the accelerator. At the same time, if it accelerates out of control, the clot will be too big, it will spread too rapidly, blocking blood vessels all over the place.
So, almost the moment you stamp on the accelerator, you are hammering on the brake. Accelerate, brake, accelerate, brake. Build up the clot, break down the clot. A fantastically dynamic system with feedback loop upon feedback loop. Too little clotting, you die. Too much clotting, you die. This is going on, all the time, in your body. A system constantly hunting, and hunting, to find equilibrium.
What is the greatest, the most powerful trigger, for a clot to form? It is a substance called Tissue Factor (TF). It is found almost everywhere in the body, but it is found in the highest concentrations within the walls of the larger arteries and veins. This, of course, makes perfect sense. If an artery, or vein, is damaged, the place you want a blood clot to form is exactly at that point. Bang, go.
Tissue factor is sometimes called extrinsic factor. It is called this because it does not float about (freely) in the bloodstream, it sits ‘externally/extrinsically’ to the blood. [In fact, platelets and white blood cells also contain TF, but it is inactive/not expressed unless other things are triggered first].
Other parts of the clotting system are often referred to as intrinsic factors that trigger the ‘intrinsic clotting system’. Factors you may have heard of, such as factor VIII, or factors IX and X and Xa etc. The intrinsic system tends to operate more slowly, and less powerfully, than the extrinsic (massive over-simplification warning).
Normally, the ‘intrinsic’ clotting factors, and the extrinsic system operate together to drive and amplify the clotting response once it is triggered. All of which means that, normally, you want to keep the blood well away from contact with TF, because the moment there is contact, all hell breaks loose and a blood clot will form, instantly, at that point.
The single most important barrier that keeps the blood separated from TF is the endothelium. Which means that an intact and healthy endothelium is the best protection against accidental blood clots forming. Yes, blood clots can form with no TF contact. A deep vein thrombosis (DVT) can develop in veins with intact endothelium. The process is different, the blood clot formed is also very different. It is mainly an intrinsic process.
Forgetting other types of blood clot that can form elsewhere in the body, the only way a clot will form in the larger arteries is due to endothelial damage. No endothelial damage, no clot. Once a blood clot has formed, then stabilised, what happens?
Well, normally the clot will not have been allowed to get too big, because all the feedback loops will kick into action to slow things down. So, most clots will not fully block an artery, nor even half block an artery. They also get shaved down in size quickly. Primarily through the action of Tissue Plasminogen Activator (TP(a)).
TP(a) is an enzyme floating about in the bloodstream that converts plasminogen into plasmin. Plasminogen is an inactive enzyme that is incorporated into all blood clots as they form. When TP(a) converts plasminogen to plasmin, it slices fibrin apart, chopping blood clots into small pieces. A process known as fibrinolysis. Two of the major components of a blood clot are platelets – small sticky cells that coordinate the clotting response – and fibrin – long sticky strands of protein that binds the clot together.
However, there will be always be a part of the clot that remains clamped to the artery wall. Because if all the clot was fully broken down/fibrinolysed, the bloodstream would be exposed to TF again, and the entire blood clotting process would simply kick off…. again.
Which means that once a clot has been formed, a part of it will always be left stuck to the artery wall. This then needs to be got rid of. How does this happen? Well, it is not like scratching your skin, whereby a clot (scab) forms, the endothelium re-grows underneath it, then the scab falls to the ground. If this were the process that happened in an artery, where do you think that clot would go? Down the artery, to get stuck where it narrows, to cause an infarction. Not a very good design feature, I would argue.
So, what happens is something far cleverer. A replacement endothelial layer is created from Endothelial Progenitor Cells (EPCs). These are synthesized in the bone marrow, and float about in the bloodstream. Chemicals released, when endothelium is damaged, attract EPCs to the area of damage/blood clot.
Once they arrive they stick to the surface of any remaining clot, then they grow into fully mature endothelial cells, forming a new endothelial layer. What this means is that any remaining blood clot now sits beneath the new endothelial layer, and within the artery wall itself. It cannot now break off and get stuck somewhere else in the body.
Even more clever is the fact that EPCs have the capability, to become something other than mature endothelial cells. They can travel down another road in the developmental pathway, to become monocytes. Monocytes, in turn, mature into macrophages.
Macrophages are white blood cells whose job it is to clear up all alien materials in the body. Dead cells, invading bacteria, any damaged tissue. They squirt nitric oxide out, oxidise dead and damaged material, such as anything found in a blood clot, then engulf it, before travelling off to the lymph glands. Here, the dead, damaged and alien materials are further broken down, before excretion from the body.
Thus, with EPCs, you have the entire repair and clearance system all in one package. Some of the EPCs that arrive on the scene, form the new endothelial layer. The rest turn into monocytes, then macrophages, which clear away the remnant blood clot.
This process of repair and clearance is what I call ‘healing’. Others choose to call it inflammation, and claim it is the underlying cause of CVD. Good for them. I suspect it may not be a fertile route to travel down.
The other thing to note here is that the substance which is most intimately bonded to the exposed endothelium, at least in humans, is lipoprotein (a) (LP(a). Lipoprotein (a) is Low Density Lipoprotein (LDL) with an extra protein attached to it. A protein called apolipoprotein A. This protein is fascinating, because it has an almost identical structure to plasminogen. Identical apart from a single amino acid.
However, this difference, though very slight, is critical, because it means that TP(a) cannot have any effect on apolipoprotein A. There can be no conversion to plasmin. Thus, any blood clot, or part of the blood clot, containing Lp(a) is extremely resistant to fibrinolysis. It cannot be broken apart, and so remains attached to the artery wall, and will be a major component of the remnant blood clot that is then drawn into the artery wall – and then broken down by macrophages.
This is where Linus Pauling, Mattias Rath, vitamin C, and guinea pigs come into play. I have discussed this area before, but I am going to discuss it again…. Soon.
Before fully signing off on this blog I shall leave you with another thought, which is this. Lp(a) is identical to LDL ‘bad cholesterol’ – apart from a single attached protein – apolipoprotein A. So, if you were closely studying the contents of an atherosclerotic plaque, it would be quite easy to think you were looking at LDL, when you were actually looking at Lp(a)?
Of course, what I have done here is to describe a process of clot formation, and repair, that is probably happening all the time. The next question is obvious. When, and how, can this process become ‘abnormal?’ When, and how, does it lead to CVD?
1: http://www.nejm.org/doi/full/10.1056/NEJMoa1709118#t=article
2: https://www.ncbi.nlm.nih.gov/pubmed/8925184?log$=activity
P.S. those interested in a great deal more complexity, this paper is a belter. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2007.02515.x/full
Here is one section that explains a great deal in a few words. ‘Recent evidence suggests that ECs [endothelial cells] in regions of disturbed flow in arteries are primed for activation (they have increased levels of NF-κB in their cytoplasm) and that systemic imbalances (e.g. associated with sepsis or cardiac risk factors) may result in the translocation of NF-κB to the nucleus and increased expression of procoagulants such as tissue factor (TF) and adhesion molecules. TM, thrombomodulin; t-PA, tissue-type plasminogen activator; EPCR, endothelial protein C receptor; TFPI, tissue factor pathway inhibitor; VWF, von Willebrand factor.’ And there, I think you have it, in a nutshell. Although I realise that most people have never heard of any of those things.
Dr. Malcolm Kendrick 
In case you are not signed up for this, today’s is interesting (to me anywAy) because it gives more info about inflammation ….more to think about…And on the level he’s explaining, it’s so intricate and complex.
For several years, medical researchers, doctors and dieticians have known that a low carbohydrate diet and plentiful fat can prevent a range of lifestyle and age-related diseases and thus promote healthy aging. But researchers from around the world have not been able to explain why this is the case. They have just been reasonably certain that the energy metabolism and its chemical intermediates (metabolites) play a central role.
An interdisciplinary team of researchers from Aarhus University has now found more than just an important piece of the puzzle — a piece that suggests that the puzzle that is our metabolism looks somewhat different than science has so far believed. This is also the reason why the research group’s article has made the front cover of the journal Cell Chemical Biology.
On a general level, the researchers have discovered that the fat-metabolism in the cells takes place simultaneously with a detoxification of the harmful substances from the blood sugar, which can avert the damage that can in turn lead to age-related diseases such as diabetes, Alzheimer’s and cancer. This indicates that we have a detoxification system which we were not previously aware of.
Unexpected chemistry
The detoxification takes place in an unexpected chemical process — unexpected because it happens without the involvement of the enzymes that science has so far focused on in understanding the metabolism and the decomposition of sugar.
The newly discovered process involves one type of metabolite, the ketone acetoacetate, which originates from the body’s fat-metabolism, capturing and inhibiting another type of metabolite, methylglyoxal, which originates from the body’s sugar metabolism.
The process is important because methylglyoxal is a reactive metabolite, i.e. it is toxic for the cells. It plays a major role in the above-mentioned age-related diseases. This means that untreated diabetics have increased concentrations of sugars and methylglyoxal in their blood. They also have increased amounts of ketone substances (see the fact box below).
In chemical terms, what happens in the process between the two metabolites is that a third metabolite, 3-HHD, emerges, which does not have the harmful effects of methylglyoxal. The Danish research team are the first to find 3-HHD in blood from people who lacked insulin and/or had fasted the night before — a condition known to give ketosis.
Enormously complex
As suggested above, the study helps to uncover new aspects of the metabolic process in living organisms.
“Previous research partly based on animal experiments using mice and monkeys shows that a diet with less sugar and more fat protects against diseases such as diabetes, Alzheimer’s and cancer. At the same time, it has also been known that methylglyoxal causes age-related diseases. We have found a new metabolite that demonstrates an alternative chemical detoxification of methylglyoxal when we burn fat. It is a surprising discovery, as ketones in themselves can lead to the harmful sugar metabolite methylglyoxal. The explanation may be a delicate balance between creation and detoxification. In any case, this illustrates that biological systems are enormously complex,” said Mogens Johannsen, who is professor of chemical biology at the Department of Forensic Medicine at Aarhus University and one of the leading capacities in the research partnership.
He emphasises that the study could only be carried out due to the close collaboration between the individual research groups at the Department of Chemistry, the Department of Clinical Medicine and the Department of Forensic Medicine at Aarhus University.
“It is a unique situation to take a reaction from a chemistry laboratory and use it to finally prove that it takes place in living human beings and potentially can play a role in vital biological processes,” he added.
From chemistry lab to living humans
Mogens Johannsen does not doubt the value of research into the role of ketones and reactive metabolites in biological aging.
“Now we have evidence for saying that ketones can minimise the amount of harmful methylglyoxal in living organisms, and that is a discovery that gets noticed, as it involves two of the most debated substances within biological aging and late diabetic complications. Moreover, these substances react with each other,” said Mogens Johannsen.
The study is relevant for developing treatments of people suffering from complications after diabetes, in particular patients with late diabetic complications such as neuropathy, which can be very painful.
“One perspective could be to follow a diet with fewer carbohydrates and more fat. The fat helps to encapsulate and destroy the sugars that cause the pain,” said Mogens Johannsen. Though he also emphasised that clinical trails will be needed to establish this aspect before he would recommend particular diets.
Story Source:
Materials provided by Aarhus University. Note: Content may be edited for style and length.
Journal Reference:
Trine Salomón, Christian Sibbersen, Jakob Hansen, Dieter Britz, Mads Vandsted Svart, Thomas Schmidt Voss, Niels Møller, Niels Gregersen, Karl Anker Jørgensen, Johan Palmfeldt, Thomas Bjørnskov Poulsen, Mogens Johannsen. Ketone Body Acetoacetate Buffers Methylglyoxal via a Non-enzymatic Conversion during Diabetic and Dietary Ketosis. Cell Chemical Biology, 2017; 24 (8): 935 DOI: 10.1016/j.chembiol.2017.07.012
And, even further off-topic (but not really) I want to share a posting I made about the role of vitamin K2 in cancer:
http://www.collabrx.com/surprise-vitamin-k2-cancer/
Share around, will you?
Just after this posting, this came in:
https://www.ncbi.nlm.nih.gov/pubmed/28849577
Evaluation of the antitumor effects of vitamin K2 (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate.
I confess that I dislike social media, so that means that I don’t promote such as this very well.
I just happen to follow many who speculate on just WHAT DOES cause cardiovascular disease, since I have this hypothesis, and Dr K is one I followed. When I saw this thread, I got on. Usually, I stay pretty isolated. Pretty nerdy. Maybe really nerdy….
I am someone who has really looked into data about this topic of vitamin K2, since it is essential in regulating calcium. And my hypothesis is that calcium dysregulation is a shared etiological factor in all the common chronic diseases. That includes dear atherosclerosis, for which we have the most data about its relationship with vitamin K and with that, the role of this in bone health. It is observed that as calcium levels diminish in bones, we ossify our arteries.
But also please note that the other nutrients and factors that work with K or that are involved in all the processes of calcium are important – I am not only endorsing K2, but since it is essential in calcium regulation and since we have fouled it up, it seems like improving folks’ vitamin K status would offer some pretty quick benefits. Lots of return on investment, but I am more about the foods than supplements. I guess that offers that I have no conflicts of interest. 😉
Micki: I’m also about foods more than supplements even though the latter seem to have their place since so much of the soil has been messed up, at least in the developed world.
I would be interested to know more about what you have learned in your studies. If you don’t mind sharing more information please either post it here (if appropriate) or let me know and I will reply with my email address. Thanks!
Sasha, my email is on my posting.
Feel free to email me!
And the findings are so extensive that it’s difficult to know where to begin.
After about 15ish years of really searching for answers to human health/EDCs/diet, I finally had a little epiphany:
Calcium was mentioned in almost all I was reading in my ‘widely cast net’ and it was often gone awry. So I went back into previous readings and re-looked from the perspective of calcium. Since it is an essential component of hydroxyapatite AND it is a signaling molecule, this meant many diverse areas of interest had to be considered. With the more recent findings about CAC, I speculated that its presence was indicative of fundamental calcium dysregulation; that CAC showed everything from calcium we can ‘see’ to calcium signals in cells in organelles (e.g. ER to mitochondria).
Hence, I look at Calreticulin, UBIAD1, K2 and ALL aspects of it.
Crazy, huh?
I think this reconciles many folks’ thoughts to become a new, over-arching hypothesis.
Instead of saturated fats v monosaturated or aspirin v warfarin v K2 or drugs v supplements, it seems we could do sooo much better with real insights into mechanisms and how nature makes things work.
That’s what I am about.
Thank you, Micki. Yes, I am very interested in what you have found out. I will email you. Thanks again.
Micki,
The mineral electrolytes zip back and forth in their channels causing the heart muscle to do its proper job: beat, relax, regroup, do-it-again, and again . . .
Calcium is a major player, mainly responsible for contractions. Has your research led you to insights about how all this might go wrong – and back to right again – in cardiac arrhythmias?
‘The mineral electrolytes zip back and forth in their channels causing the heart muscle to do its proper job: beat, relax, regroup, do-it-again, and again . . .
Calcium is a major player, mainly responsible for contractions. Has your research led you to insights about how all this might go wrong – and back to right again – in cardiac arrhythmias?”
JDPatten,
There is some strong evidence that messing up this essential role of calcium is fundamental in many heart woes, including arrhythmias.
A search of this topic of calcium signaling/arrhythmias gets a lot of info. Here are two:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535977/
Altered Mitochondrial Metabolism and Mechanosensation in the Failing Heart: Focus on Intracellular Calcium Signaling
http://circres.ahajournals.org/content/120/12/1969.short
Calcium Signaling and Cardiac Arrhythmias
And, from a more ‘back door’ approach to the topic, statins impair mitochondria – they are described as mitochonidrion-toxins
Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms.
http://www.tandfonline.com/doi/abs/10.1586/17512433.2015.1011125
These folks are really interesting. Japanese lipid pharmacologists who actually speak ill of the most spun/oversold/ill-considered drug to date and offer some real insights. They are mostly unheard, but check them out – the first author is interesting especially.
This from these (basically) same folks:
http://onlinelibrary.wiley.com/doi/10.1002/lite.201400010/full
Risks of diabetes mellitus and cancer caused by cholesterol lowering medications
All these heart woes affected by loss of calcium homeostasis may have multiple causes. I do not claim that vitamin K2 is ‘the answer.’ Some diseases are genetic and some are from defects, but the nutritional factors which affect the various physiological factors that control calcium homeostasis (though I prefer the term ‘regulation’ to homeostasis because many think of homeostasis as visible hydoxyapatite via measures of BMD or CAC rather than something as obscure as calcium as a signaling molecule) ARE something that can be addressed. I am claiming that this has been misunderstood in the nutritional/medical worlds with some bad unintended consequences. Based on some really misguided and/or corrupted folks like Keys, Stare, Hegsted, we thought of fats – fats we eat, fats in us – and we missed calcium completely. With the obsession with fats, our data is all about that and misses too many things and then we went down the rabbit hole of thinking fats needed our ‘help.’ To ‘help’ we changed them and we reduced them, never understanding what old fashioned fats contain and that they are healthy.
We created monster fats.
We had to compensate for fat removal in foods with additives like emulsifiers.
Among the other things we like to obsess over: salt, sugar, calories, and misguided ideas about vitamins…and of course, fats.
I would argue that our dogma on all these topics is mostly wrong.
Instead, check out calcium!
and check out the role of vitamin K2 in calcium regulation.
Thanks again Micki. (Now, to study this stuff.)
Woo-hoo! Sci-Hub is working again
http://sci-hub.bz/10.1016/j.chembiol.2017.07.012
put behind my ear for later reading, and may be connected to this one
http://insulinresistance.org/index.php/jir/article/view/25
Chris . . . the bz server was shut down in Russia because of social media attacks on Alexandra by ????
After a little research I found the ‘cc’ server was continuing to work for the rest of the world.
Looks to me that the outcry by the Russian research community, exhorting Alexandra to turn the bz server back on has worked.
Good-oh! My first thought was that the UK Government were blocking the DNS on behalf of Elsevier, probably using anti-terrorist legislation. But then I tend to get paranoid about this stuff . . . or am I?
Though you have touched on this before – why are some endothelium damages handled in the manner described here. While other damaged arterial walls are subsequently covered with calcium deposits leading to arterial calcification?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124018/
Microcalcifications in Early Intimal Lesions of Atherosclerotic Human Coronary Arteries
It appears that these microcalcifications can go on to become CAC.
A CAC=0 is basically a 15 year warranty from death by all causes.
More CAC, worse prognosis.
Endothelial cells and VSMCs need enough vitamin K2 to activate matrix gla protein to ensure that this calcium does not deposit.
The suppression of NFkB is also made possible by more K2.
K2 is more than dietary; we can make MK-4 (the only form of vitamin K2 that is not made by fermentation) endogenously and this MK-4 can bind SXR to affect many genes.
We have inadvertently fouled up vitamin K2 in diet by messing with dietary fats in response to profound misunderstanding of them – K2 is found in the fats – and we have inadvertently lost K2 from fermented foods.
Plus we mess with K2 actions via many drugs (statins, bisphosphonates, warfarin, NSAIDs) and with an aberrant form of vitamin K called dihydrophylloquinone (dK) biomarked by manmade trans fatty acids. It’s NOT ABOUT THE BONDS OF FATS – we have that flat-out wrong – it’s about the fat soluble nutrients in the fats, which we have completely missed for vitamin K.
Vitamin k1 has been the traditional way to see vitamin K and other countries outside the US have so put us to shame regarding K2 that we have the Vitamin K Lab at Tufts FINALLY looking at K2 in food. They still ignore this endogenously made MK-4 though.
Note that the microcalcifications accompany cholesterol crystals and when cholesterol does crystalize (and it doesn’t have to), then really bad things happen.
There are some connectors with calcium regulation, cholesterol regulation and MK-4 biosynthesis: the enzyme UBIAD1 (also called TERE1). Look into it! Crazy important and we keep screwing up everyone’s health by looking at all the wrong things like lipids or salt or even sugar.
Nope. Look at calcium regulation.
It is essential to prevent CVD, cancer, AD, diabetes, and so much more.
We mess up calcium as a component of hydroxyapatite and as a signaling molecule all the time.
MK-4 is available as a supplement. Short half-life. Menatetrenone.
MK-7 is also available. Long half-life. Menaquinone. (Since when is “quin” not 5??)
Is there a difference between these two – as well as all the other K2 forms – for our purposes here?
Micki, agree with K2 but do not rule out sugar.
“Arteriosclerotic calcification is increased in metabolic syndrome, type 2 diabetes mellitus, and type 1 diabetes mellitus—impairing conduit vessel compliance and function, thereby increasing the risk for dementia, stroke, heart attack, limb ischemia, renal insufficiency, and lower extremity amputation.”
Big part of fix is to eat low carb i.e. low blood glucose/insulin response. When in doubt good to check what effect hyperglycaemia has on whatever you are investigating. Looking through a microscope for answers seems to only generate more questions.
Andy S,
I am not a fan of sugar, but in case you missed this, this offers a different etiological view of diabetes and metabolic syndrome:
Colonic microbiota encroachment correlates with dysglycemia in humans
Nature found this same thing in mice and published in 2015, but this shows how these 2 common emulsifiers – or, at least, this effect on guts/microbiomes – led to (seemingly) dysglycemia in humans with this strong correlation between bacteria in messed up mucous lining and dysglycemia. I realize that this is not proof.
Other things mess with our microbiomes and other food additives mess with them, too. So, since our overweight/diabetes situation began almost exactly in 1980, and foods and emulsifiers ‘kicked in’ then, one could wonder. Huh?
I speculate that our misguided thoughts on fat – and initial mistakes of categorizing them via bonds, which is accurate but not pertinent to health effects – led to such as low fat dairy, but to make palatible, we add things like emulsifiers. While fewer calories, less supposedly ‘bad’ fats, we added unrecognized toxic substances that messed with our microbiomes. Oops.
Lots of oops.
So questioning fats from my perspective means saturated fats aren’t the right question(s). But getting nutrients and fostering healthy microbiomes are – and we have gone awry in these in many ways.
I know… off-topic from heart disease, but not really.
Search calcium diabetes. My hypothesis is applicable there, too.
I agree. I think modern food additives and industrial processing (that includes lots of processed sugar) are what messes up microbiome and contributes to the epidemic of metabolic illnesses. We can search forever for the perfect diet, vitamin, ingredient to stop this but the best place to start is to return to traditional ways of raising and processing food.
https://www.sciencedaily.com/releases/2017/09/170915144151.htm
Researchers at the Institute of Molecular Biology (IMB) in Mainz, Germany, have made a breakthrough in understanding the origin of the ageing process. They have identified that genes belonging to a process called autophagy — one of the cells most critical survival processes — promote health and fitness in young worms but drive the process of ageing later in life. This research published in the journal Genes & Development gives some of the first clear evidence for how the ageing process arises as a quirk of evolution. These findings may also have broader implications for the treatment of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease where autophagy is implicated. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole body health.
Erret have you thought of posting this link at one of the blogs which deal directly with anti-aging and have discussed autophagy in the past ?
For example Josh Mitteldorf’s blog : https://joshmitteldorf.scienceblog.com/
or Dennis Mangan’s Rogue Health blog : http://roguehealthandfitness.com
I remember that Dennis Mangan had a longish discussion about the role of autophagy a few months ago.
Autophagy is boosted by fasting, even for 16 hours. And is promoted independently as a way of enhancing the anti-aging processes/
Aha!
Thank you once again Dr K – absolutely fascinating and easy to follow (well, except the last paragraph below the links ! Lol)
Working backwards further from the initiation of the clot and looking at why the endothelium requires repair, would it be feasible that the suggested theory that prolonged, raised levels of insulin damages the protective glycocalyx layer and exposes the endothelial cells directly to the blood flow and the shear stresses or turbulent flow of it ? Would this be sufficient to damage the delicate endothelial layer – requiring the rapid formation of a clot to seal the damage ? (Am thinking of the higher CVD rates of diabetics).
If that is a possibility, then it would seem logical that when the new endothelial layer grows over the clot to prevent it eventually breaking off into the flow of blood – it would initially attempt to produce its own protective glycocalyx layer, but the very condition (prolonged raised insulin levels) that caused the damage in the first place, prevents the new endothelial layer from becoming established and it becomes damaged too. Cue a fresh clot to seal the damage and a new, second endothelial layer growing over this second clot. This would be repeated again and again as the newly forming endothelial layer cannot achieve stabilisation and requires a new clot to provide a temporary repair. The damaged area enlarges as alternating layers of clot/endothelial cells repeatedly forms – what we know as the dreaded plaque ?
Only if the condition causing the damage is removed – would the endothelial layer be granted a sufficient reprieve and chance to become fully established.
Apologies if I have repeated what has been stated previously, I read the Great Cuolesterol Con a couple of years ago and think you described the growth in there ! Since my MI, I have read so much material that I’m unable to remember where some of it has come from – just trying to get the process straight in my mind.
Kindest Regards
Martin T
I think that there are many different factors that can stress/damage the endothelium, leading to repeated damage at the same area. Insulin is probably one, smoking another, toxic metals, infections, a number of medications, stress hormones, dehydration, cocaine use etc. etc. etc.
Follow this girls work, she is on 2ketodudes being interviewed and has started a series on Dave Feldman’s site: http://2ketodudes.com/show.aspx?episode=83 Dave Feldman http://cholesterolcode.com/beyond-the-lipid-hypothesis-plaque-development/ Siobhan Huggins is worth following, she is doing a series on the topic… S
This is my theory, which is mine and belongs to me (Monty Python)
Whatever factor(s) were responsible for the original “epidemic” of CVD have since been decreasing.
They are now being replaced by other causal factors, which are increasing since the adoption of HCLF diets, including but not limited to hyperinsulinemia, hyperglycemia, chronic inflammation from an excess of “heart healthy” omega 6 seed oils which aren’t etc.
The increases and decreases are occurring at different rates in different countries/societies. Hence CVD is simultaneously decreasing and increasing again.
Oh and (saturated) fats and (LDL) cholesterol were never a part of it, and except for a few specific conditions statins are just the most profitable placebos ever produced.
Since this theory can never be proved or disproved, I win!
Seriously though, thanks you to and your contributors I am currently reading as fast as I can just to stand still, I’ve barely caught up with all the information on hydraulics etc. from your previous post and now I have to catch up all over again – before I die from CVD I’d like to know how it happened. More than that I’d like to see more cardiologists looking into things that are not fat or cholesterol too . . .
. . . written while digesting the first herring of the season, that’s got to help.
Well done Chris . . . you have the “First laugh of the day” award
A couple of studies show that high glucose levels of the sort that you might find in diabetics directly damage the glycocalyx; it will reduce its thickness leaving the underlying epithelium less protected (eg more prone to adhering white blood cells and platelets). Perhaps more importantly, the damage suppresses the ability of the glycocalyx to sense the shear movement of the blood . . . (the response to shear movement increases the production of protective NO in the endothelium and underlying tissues) . . . Therefore damaged glycocalyx reduces the amount of protective NO.
Hypothesis: arterial glycocalyx dysfunction is the first step in the atherothrombotic process.
https://www.ncbi.nlm.nih.gov/pubmed/18319293
High Glucose Attenuates Shear-Induced Changes in Endothelial Hydraulic Conductivity by Degrading the Glycocalyx
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078954
I have previously tried to find out if sustained insulin levels can damage endothelial glycocalyx directly. The only thing I found to this point is that there is an association between insulin resistance and glycocalyx health/thickness. But it may be in this context that insulin resistance is just a surrogate measure of peak glucose levels.
Antony, looks like high blood glucose is a big factor in CVD. Hard to separate glucose from insulin, found this study:
http://www.bloodjournal.org/content/112/1/82?sso-checked=true
“Hyperglycemia diminishes inflammation-induced neutrophil degranulation and exacerbates procoagulant responses, whereas hyperinsulinemia inhibits fibrinolysis during the early inflammatory reaction due to extra stimulation of PAI-1 activity.”
Oh, 1-2 knockout punch! Yes I admit for purely personal/familial reasons the insulin/glucose axis is where I’m currently also looking – that plus the large number of other old crumblies who show clear signs of similar disruption while their doctors concentrate only on their cholesterol.
So what about Rutin that stops the clot inside the veins and arteries but not outside. Rutin is being heavily studied now and for years by Harvard Medical – probably for some new drug on the horizon.
Thanks for a further supremely lucid episode.
Thank you
Since progenitor cells arrive at the site of a clot from the bloodstream itself, how do the little buggers get behind the new endothelial cover to become monocytes>macrophages?
Is it that the progenitors>monocytes>macrophages get into the clot substance first, before the new endothelium forms?
JD, perhaps the process of differentiation of endotheliial progenitor cells starts right at the very start ?
Thank you for this very “educational” blog.
And, as has been stated before, it is very easy to get confused in front of this complexity.
Myself, staying away all “heart medication”, am eating a lot of garlic, omega-3 supplement and regularly consuming wild caught Alaskan Salmon on top.
I wonder if this could be dangerous considering the effekt of the common rat poison/heart medicine Warfarin which makes the rats bleed internally to death. Vitamin K2 being the remedy. I wonder what all this is about. “Leaky arteries”?
Wouldn’t surprise me if we should read headlines in the papers telling that garlic will kill you.
Oh – God!
I made the mistake of trying to “understand” – an old philosophical/religious blasphemy. The lesson from the apple tree, the tree of knowledge, in the garden of eden should have taught me something.
Ignoring that lesson, Google Warfarin led me to Wikipedia and at that step I was completely lost among all the factors mentioned involved in the bleeding and coagulation.
But basically I still don’t understand “what is bleeding?” relating to e.g. Warfarin. Are the endothelial or all cells just disintegrating and letting the blood seep out of the arteries everywhere into the surroundings or what is happening? I find this very intriguing.
I though realize when testing for glucose levels that the pricking easily produce a drop of blod but that the blood flow amazingly stops at once – evidently a very effective system as Malcolm points out.
Warfarin is a vitamin K antagonist. It blocks the synthesis of various clotting factors in the blood, so that the bleeding time (time it takes blood to clot) is extended. It has no effect on endothelial cells, that I am aware of. It is used, primarily, to prevent the formation of blood cots in the atria of the heart in atrial fibrillation. These small clots can escape from the heart and travel to the brain, causing a stroke, or travel to other organs, blocking blood vessels there. Because it is a vitamin K antagonist is increases calcification in artery walls – and elsewhere. This paper, though technical, explains the process. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648717/
Malcolm,
Thank you for this intriguing reference (calcification was new to me!) which to me however just adds to the complexity involved, my confusion and perhaps also back to my “natural” garlic. Holistic?
But again, I still don’t understand what the essence of “general bleeding” is. Is it jus local,like with the prick of an needle, or is generalized on a cell adherence level?
Dr. Goran, check out tight junctions. Throwing a monkey wrench (medicines or unnatural foods) into a complex system could produce unexpected results.
Andy,
Tight junctions are as far as I understand it as complex as everything in our physiology but are in my eyes also a reasonably culprit for the “bleeding”. Anyway they allow for some macrophages to pass “when needed” in the environment surrounding the arteries so why not red blood cells?
Isn’t it a wonderful world we are living in?
And besides today it is Sunday.
But how little we do understand!
Dr Kendrick,
VKDPs ARE in endothelial cells.
http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2004.00968.x/full
The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis
These folks published this heresy and were met with crickets, too.
Who in the world thinks heart health has anything to do with vitamin K?
Well, it is fundamental, but missed because of fat mistakes and we tend to ignore calcium.
I believe that we have the etiology of atherosclerosis backward, and that calcium dysregulation leads to plaques not that lipids can be calcified (current dogma).
http://jcb.rupress.org/content/102/5/1971
Participation of endothelial cells in the protein C-protein S anticoagulant pathway: the synthesis and release of protein S.
(old, but pertinent – these are among the 7 VKDPs in coagulation, but they are in other tissues, too)
http://onlinelibrary.wiley.com/doi/10.1111/bcpt.12834/full
Vascular Calcification, Vitamin K and Warfarin Therapy – Possible or Plausible Connection?
(new, and pertinent)
We can measure CAC. With the invention of microscopic measurements, we can watch how microcalcifications grow to become CAC, but no has done this yet. We know that CAC=0 (from old ways of measuring that cannot measure microcalcifications) is hugely beneficial, so how can we devise a way to make a trial of this hypothesis that microcalcifications lead to CAC? THAT is what is needed. Cholesterol will come into the picture with understanding UBIAD1 roles. It IS increased when we have messed up UBIAD1 and thus dysregulated calcium, but instead of acting on it incorrectly by stomping in pathways to inhibit K2, we need to act on vitamin K status and the factors in K actions to then properly regulate cholesterol and calcium.
Actually, it appears that calcium regulates cholesterol.
Ha!
Some folks at McMaster have sort of gone in this direction, but I don’t think that they know about all this. I plan on contacting them.
There is so much, that it is impossible to keep track of everything.
If the finding that CAC status is the best predictor of a cardiovascular event, if a CAC=0 confers body-wide mortality benefits (15 years by some accounts and still substantial but less by others), and K status is fundamental in calcium regulation, along with increasing and compelling data about K in recent times doesn’t make you want to look, then just read one thing:
Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?
Ahhh Goran,, garlic was a major ingredient of witch’s potions… Have to careful around witches & their garlic!..
🙂
Bill,
There you are!
Garlic IS dangerous!
Absolutely 🙂 🙂
I always thought garlic was a great protector against influenza (Search on Lelord Cordell). However here in Birmingham (West Midlands) we had, and may still have, some of the most famous doctors of their day, at least in the 18th century (my period – I guess that’s where some think I belong) it was true.
Regarding heart disease, William Withering, presented a paper using digitalis in the treatment of dropsy (some kind of bodily fluid accumulation). If my memory serves dosage was important and he bought the treatment from a Shropshire woman, Mother Hutton before experimenting himself.
http://scihi.org/william-withering-and-digitalis/
There turned out to be conjecture and contest between Withering and Erasmus Darwin (grandfather fo Charles). So no change there. Darwin was a wise man, He turned down an offer to become George III’s personal physician. George III is currently thought to have been suffering from porphyria.
I am no more a herbalist than I am a physician but my family started and still have in the Isle of Man, a health food store in Douglas. Natural alternatives to aspirin appear to be willow bark and meadowsweet. Dosage again is important. I do not know how much research has been done into this by the drug companies but suspect precious little. Why would they? If the market can get it for free what worth is research?
Yes, leaky arteries, that is where vitamin C could help?
Dr Goran,
I have it on impeccable authority, – my soon-to-be-X Cardiologist, – that garlic has NO useful anti-clotting properties, only clopidogrel (Plavix) AND aspirin would keep my stents safe from re-stenosing… despite GRAMS per day of garlic supplementation…
But They did.
The reply is ambiguous, what does “But They did” refer to?
Warning – this comment is more of a “remark”, and even I can see that it is strictly speaking off-topic. So please ignore if you are hot on the scent!
I was powerfully struck by Dr Kendrick’s statement that the blood clotting system seems like one of the most complex in the body. That exactly echoes my reactions when I first rad about it (at kindergarten level) in Isaac Asimov’s 1960s book “The Bloodstream”. A fantastic spaghetti of factors, each relying on other factors, and interlinked feedback systems.
Which led me to feel that this is not the kind of system I, for one, can imagine being “designed” at all. I have no religious or anti-religious axe to grind, being a strict agnostic, and God (if there is a God) could choose any of an infinity of ways to bring us about.
But doesn’t this whole, immensely complex and highly-tuned, system have more of a feel of having evolved? Being the outcome of literally millions of generations of trial and error, in which all the errors simply got weeded out and disappeared from the scene?
Tom,
Of course the coagulation system is due to the phenomenon that we – to the extent we understand it so far – have labeled evolution.
Why complicate the understanding of such an already complex system with notions from a fantasy realm where you can ask anything you like and get any number of ready and willing responses – – – but no answers whatsoever?
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Which led me to feel that this is not the kind of system I, for one, can imagine being “designed” at all. I have no religious or anti-religious axe to grind, being a strict agnostic, and God (if there is a God) could choose any of an infinity of ways to bring us about.
But doesn’t this whole, immensely complex and highly-tuned, system have more of a feel of having evolved? Being the outcome of literally millions of generations of trial and error, in which all the errors simply got weeded out and disappeared from the scene?
I think you’ve just described irreducible complexity and some would argue (quite convincingly of such systems) that they’re only capable of existence because they have been designed and are simply not capable of having “evolved” into existence as you suggest, because an irreducibly complex system cannot come about in a gradual manner. All the components of blood clotting must be in place before it functions. A step-by-step approach to constructing such a system will result in a useless system until all the components have been added. Blood clotting requires all the components to be added at the same time, in the right configuration, before it works at all. I’m not sure how an evolutionist could explain how the blood clotting system could have been constructed in a gradual manner since it simply wouldn’t work until all the components were present, and Darwinism has no mechanism for adding all the components at once.
Remember, Darwin’s mechanism is one of gradual mutations leading to improved fitness and survival. A less-than-complete blood clotting system simply would not function, and it certainly wouldn’t help the organism to survive. Any precursor to an irreducibly complex system that is missing a part is by definition nonfunctional. Natural selection only preserves or “selects” those structures which are functional. If it is not functional, it cannot be naturally selected.
Evolution simply cannot produce complex structures in a single generation as would be required for the formation of irreducibly complex systems. To imagine that a chance set of mutations ( in a single generation) would produce all the blood clotting and inhibiting factors (as well as the simultaneous evolution of complementary endothelial function) required for blood clotting to work as it does strikes me as impossible. It certainly becomes a belief system in and of itself. Producing one or a few of these clotting factors at a time, in standard Darwinian fashion, would convey no survival advantage because those few clotting factors would have no function – indeed, they would cause the system to fail and death. Darwin recognized this as a potent threat to his theory of evolution – the issue that could completely disprove his idea.
On even the simplest bacterium, Michael Denton, in his book Evolution: A Theory in Crisis, states: “Although the tiniest bacterial cells are incredibly small, weighing less than 10^-12 grams, each is in effect a veritable micro-miniaturized factory containing thousands of exquisitely designed pieces of intricate molecular machinery, made up altogether of one hundred thousand million atoms, far more complicated than any machine built by man and absolutely without parallel in the non-living world.” “In a word, the cell is complicated. Very complicated.”
And that’s just a simple bacterium.
I quote Dr Kendrick on blood clotting: “I have come to believe that the system of blood coagulation must be, just about, the most complex physiological system in the body. It is beyond mind-boggling. Just when you think you have read about every factor involved, another one pops up. Indeed, I think I am forgetting facts about blood clotting faster than I can learn them. My brain is full”.
Perhaps someone could explain how such a, “beyond mind-boggingly” complex system could have evolved? One may choose to simply believe that it did but equally, have to accept that their conviction is in reality, “a belief system”. Others, including lots of biochemists simply accept the existence a creator, of God.
But your explanation presupposes that less complex species have same clotting mechanisms as us, for example. Isn’t it possible that as species progress they develop different clotting mechanisms?
“A less-than-complete blood clotting system simply would not function, and it certainly wouldn’t help the organism to survive.”
Actually, the clotting system seems to be multiply redundant. There are diseases which affect the clotting system (Dr Kendrick has mentioned a few) yet still it functions, if less well, and the organism is able to survive. And given the complexity of biochemicals, if we were to compare e.g. my Lp(a) and your Lp(a), would they be identical in every respect? I doubt it. Very likely there are small differences which make no difference under current circumstances, but might prove beneficial or deleterious at some other time, like Familial Hypercholesterolemia in Dutch families is protective in some decades but not in others.
Then there is the question of why do we have a clotting system at all? It is to make up for the fact that other parts of the body don’t function too well. For instance, we have a thin skin, easily damaged, which could lead to loss of blood. Why not have a thick skin like an elephant?* It’s all a matter of compromises and trade-offs, and finding an ecological niche to ourselves that we can keep other organisms out of.
Humans examining the clotting system is rather like a Martian examining the United States. He might report back to Mars that it is all wonderfully well organized, with units riding in specialized metal vehicles in and out of breeding and production organs, timed to the passage of the sun, while other specialized units manage growing areas, and further units transport produce from growing areas to breeding and production areas, blah-de-blah, with collisions avoided by a system of coloured lights, and more specialized units to pick up any wrecks. In short, the Martian would think such a wonderful and complex system must surely have been designed, but we know it is continually changing under pressure from population growth and technological change. There is no grand plan, only local adaptations.
* meant to add: Does an elephant have the same clotting system as us? I would imagine it has less need of one because of the thick skin.
Without a clotting system, the smallest cut would kill you, thick skin or not. Or you would bleed into your joints, and die, as some haemophiliacs did. Or a small stomach ulcer would kill you. Or a bruise would grow and grow, until you died. The blood must clot. I would imagine that the clotting system of an elephant would be virtually identical to ours. I would be amazed if it were not. We are closely related animals.
Of course, I had to look at some things. Here is an interesting paper ‘The evolution of vertebrate blood coagulation as viewed from a comparison of puffer fish and sea squirt genomes.’ Yes, the coagulation system was there, and complex, an awfully long time ago. http://www.pnas.org/content/100/13/7527.full
Does it evolve to be more complex with more complex species? Does puffer fish have a clotting system that’s virtually identical to ours? Does cold blood clot the same as hot blood?
Full disclosure: The ‘Martian looks at earth’ analogy isn’t original. For an entertaining and thought-provoking take on the subject, check out the “What on Earth!” video.
Given the importance of vitamin C to blood vessel integrity (see e.g. scurvy), I would postulate that animals not able to synthesize vitamin C (humans, bats, and guinea pigs) would need a more efficient clotting system than other animals, e.g. rats, mice, and elephants. Yet rats and mice seem to be the experimental animals of choice for investigating human clotting. I wonder if guinea pigs might not be a better experimental animal.
Probably, more expensive
As I said somewhere (can’t find it now) – the more I read about the incredible complexities of the human body the less credible evolution shows itself to be. And it is still, after all, a theory.
I agree, Tom. No-one would bother to think up such a complex system, when there must be infinite ways of making it simpler.
But your explanation presupposes that less complex species have same clotting mechanisms as us, for example. Isn’t it possible that as species progress they develop different clotting mechanisms?
But how? Everything has to be in place for it to function and each and every feedback loop upon feedback loop upon feedback loop etc is, “mind-boggingly” complex and is there for a reason. Without even one feedback loop the system would fail. I’ve never read any convincing article to explain how it could possibly have come about, apart from, it just did. That is, just believe. Choose your god, or God I suppose.
I think I am just going to stick to discussing the coagulation system as it exists. I shall let others argue as to how it came to be. That is rather too big and issue for this humble blog.
The more I read on this blog of the mind boggling complexities of the human body, the less I believe in evolution.
I can’t argue about the Evolution Theory as I don’t know enough about it but why do you think physiological systems can’t develop with time? Mammals have more complex nervous systems, for example, than other species. Why can’t we assume that they would also have more complex clotting mechanisms?
Mark Johnson: I think it instructive to examine the role of symbiosis as part of the amazing complexity in evolutionary history. Mitochondria, for example, were once free-living bacteria, but the chance capture of one cell by another , which proved fruitful, led the way for the development of multi-cellular life. Darwin and Wallace got it right, in the main, about what happened, but they didn’t have enough information about how it happened, and so couldn’t have explained it fully. There is to this day a lively and interesting debate among evolutionary biologists about the how.
Gary: I know next to nothing about Darwin’s work except the general outline. However, I was talking to a friend the other day who at one point was a pretty accomplished physicist. He told me that most of his physicist friends don’t believe in Darwin’s theory because they can’t figure out how it can happen (from the standpoint of physics). I assume he was talking about evolutionary jumps. I will ask him more about it the next time I see him since I always assumed that Darwin was right… Interesting how we often just accept things that are taught to us.
The theory of evolution by natural selection is, without doubt, one of the great scientific hypotheses. Unfortunately, if you try to question any aspect of it, you are instantly dismissed as a flat-earth creationist, and suchlike. I do love to question things, and attack them. It is only through attacks, and debate, and discussion, that science can move forward, hypotheses be improved and suchlike. Unfortunately, the theory of evolution by natural selection is fiercely guarded, and the slightest perceived dissent is ruthlessly crushed. You may find parallels with other current scientific hypotheses.
I was intrigued by that conversation and I am looking forward to questioning him more. Physics is one discipline I had difficulty with when studying. The rest of the sciences are easier, IMO. When physicists talk, I always pay attention and these are pretty accomplished physicists he’s talking about. So, there must be a reason why many of them question some aspects of the theory. It will be interesting to find out what it is.
Ironic that Darwin’s hypothesis was only accepted in the first instance after rigorous debate, spearheaded by Darwin’s bulldog, T H Huxley. In all things Huxley was an agnostic, questioning everything – he would have been appalled to learn that debate has been virtually shut down on evolution.
Says a Huxley, with great wisdom.
Sasha: Yes, this is why there is lively debate about the mechanisms of change through time in organisms, which change is clear and compelling through multiple lines of evidence. Darwin and Wallace only shed light on a small part of the puzzle. Genetics was unknown to science then, and the fossil record fairly meager compared to today. What they did was attempt to explain what they saw. Some religious authorities continue to miss the distinction between allegorical truth and literal truth, which I find a deep insult to the intelligence of the ancients who told their insights in story. It is my contention that the microbial world plays an enormous, largely unknown and under-appreciated role in evolution and in how all living things reproduce, grow, and interact.
Yes, microbes. Much more important than we thought. An Epidemic of Absence talks about this…
Sasha: From the review I read, it seems this writer is on the trail of something important. I suspect, though, that the trans-kingdom interactions among life forms is orders of magnitude more complex than the biology of individual organisms. Trusting in the validity of this doesn’t make me want to throw my hands in the air; it whets my curiosity.
Yes, the book is very good, IMO. It attempts to answer some very interesting questions. Like: Why, for example, the incidence of T1D in rich, comfortable Finland is 30 times that of rural China?
I agree, Tom. No-one would bother to think up such a complex system, when there must be infinite ways of making it simpler.
Since evolution has an infinite amount of time (OK, just an allegedly very, very, very long time) to develop any of the infinite, simpler systems you suggest, why didn’t it? And if it is the simplest system, how could all the the seemingly infinite feedback loops and inter-dependencies have come into existence simultaneously?
The biological micro-machinery which operates in each and everyone of us is exquisite in its operation. Each of us I suppose, ultimately chooses their own belief system, or god. Some just choose God.
But no, all the simpler specimens died before sexual maturity. What you have is what works. Granted, there’s always excess baggage to be found, but it’s usually stuff bound to essentials.
Sasha,
One difference between the theory of evolution and physics is that physics can make predictions and they can be tested by an experiment to be performed in the future.
Evolution can only be tested by experiment in the past, e.g. you can predict there must have been an intermediate form between past X and present Y, and if you dig around a bit you might find a fossil XY. But you can’t predict that Y will eventually evolve into Z, because there are just too many ways organisms can evolve. It’s only ‘evolution’ when you look backwards. It’s ‘adaptation’ when you look forwards.
I’m a believer in evolution, but I realized its limitations when watching Widow Birds struggle to fly over the grain fields in the Free State. During the mating season the males develop enormously heavy tails and they fly with great difficulty. The evolutionary explanation is that they are showing off their fitness to prospective mates. But of course their clumsy flying makes them very vulnerable to predators. You’d think a better bet would be to blend in with the surroundings and survive to raise a brood like the many Little Brown Job birds.
I put the question to militant evolutionists: what makes some birds choose outrageous display while other birds choose remaining inconspicuous as a mating strategy? *crickets*
Martin, I will check with my friend what aspects of the theory they don’t believe in but if I understood him correctly, they find some of the explanations physically impossible. They evaluate it from the standpoint of physics to which all other sciences must conform.
I think that stating something to be physically impossible is a position of hubris. I much prefer people to say. ‘I cannot currently see how it is possible’ – or suchlike. Once you say something is impossible you have, in effect, closed the door to further discussion or investigation. Regarding evolution my own view on the matter has been, for some time, ‘Give me the first functioning, dividing cell, and I will give you the rest of evolution.’
It’s quite possible that’s what he meant (in the way that you said it). I was paraphrasing the conversation (and translating it from Russian). He was quite polite about it but he did say that many of the physicists he knows do not believe in the theory. I will definitely ask him again the next time I see him which aspects of the theory they have difficulty with and will post it here.
Re Evolution..I thought that ‘punctuated bursts’ had now been accepted as normal in evolution.
Unlike 20 years ago when it was considered a major heresy ! Then only slow gradual evolution was ‘permitted’ by the orthodox biological scientists of the day. So change in hypotheses does happen.
Sasha,
I wouldn’t worry your physicist friend. They have enough problems in their own discipline, e.g.
– Why is there something rather than nothing, i.e. why does the universe exist?
– Why is ‘inflation’ — an impossible faster-than-light process — necessary to explain the Big Bang?
– Why did they have to invent undetectable Dark Matter and Dark Energy to make their equations balance?
Martin, I’ve heard those arguments about Big Bang and the structure of the universe before and they very well may be true. But it doesn’t negate the validity of questions about evolution theory (possibly). As I said, I have to dig deeper into what they find questionable about it
@Martin something to add to your list of ‘physics problems’….
Gravity ! All the explanations I have read about it leave me confused. And there is the energy ‘problem’ of gravity..Why do things fall towards each other ?
Bugger ! We had a great late night dancing last night..And my brain is till to sleepy to deal with this now..More caffeine needed ! 🙂
If God did it, he must have first created Managers and they must have had lots of Meetings and set up Steering Committees.
It would have helped if He had first created engineers.
I like this idea of idling, oscillating between too much and too little. Too often we want to totally destroy some factor that can cause problems rather than living in balance with just a little.
BG control is similar, as both too much and too little glucose are bad.
Malcolm,
I noticed that you blame the NSAIDS for increasing blood clotting. Do all NSAIDS operate the same way, or is it that anti-inflammatory drugs inevitably raise blood clotting?
Thank you. Another treat for the weekend, though how you find the time I’ll ever know. A splendid read.
“The single most important barrier that keeps the blood separated from TF is the endothelium.”
This would refer to the blood flowing through the lumen of the artery. But what about the blood suffusing the artery walls via the vasa vasorum — why doesn’t it contact the TF and start clotting?
You raise a very interesting point. I have been looking at this for a very long time. It appears that, without any ‘injury’ the clotting factors, even TF expression, is held in check.
” Lp(a) is identical to LDL ‘bad cholesterol’ – apart from a single attached protein – apolipoprotein A. So, if you were closely studying the contents of an atherosclerotic plaque, it would be quite easy to think you were looking at LDL, when you were actually looking at Lp(a)?”
And what does our system do when there isn’t enough Vitamin C, ascorbic acid around to fix and endothelial issue? It uses Lp(a)?
Can’t wait until you get back to the C issue.
Realized there is a difference between the ApoA molecule that identifies HDL particles and Apo (a) which is “which is covalently bound to the apoB of the LDL like particle” – giving the Lp(a) particle.
Presumably in its endothelial support duties it is the simple apolipoprotein (a) that is involved – minus the LDL-type baggage.
Grateful for clarification.
So, part 37 ends in another cliff hanger with Linus Pauling et al/etc (vit C) making an appearance at the very end. From 5/2016 onwards I was playing catch up with Dr Kendrick’s blogs and (in its entirety) it all read like an unputdownable thriller with plenty of twists and turns and cliff hangers along the way.
In this part (3) Dr K states “lp(a) is identical to LDL…apart from a single attached protein” and “it would be quite easy to think that you were looking at LDL when you were looking at lp(a).”
But would it?
Referring to my own self funded blood testing, the readings between the 2 can be vast: a high total cholesterol averaging in double figure mmol/Ls (with a genetic test looming for familial hypercholesterolaemia (i.e. high levels of LDL in the blood stream) and normal lp(a) levels (according to the normal ranges for 3 different labs).
So, I’m not sure if there is a similarity or link. But I’m reading and writing this with a glass of red.
And does fibrinogen appear in the next part?
Fell into the trap someone alluded to in a previous comment about the writing/proof reading process…meant part 37 in my second para not part 3.
Thank you again Dr K. How on earth do you find time to do all this research and be a GP, husband, family man etc etc. Are you cloned at home?
Sue, Dr K is … ‘a man of many parts’ !!!
In bits, would be more accurate probably
Hoping your ironic SoH will keep you together, Dr K! We can’t have you dissolving into bits when you are one of a very small band brave enough to talk sense!
Again a very good stimulus piece.
Thank you for an Intriguing blog, yet again. As ever, I’m left with more questions, so am looking forward to the comments and the next instalment.
More to get immeresed in.
I was a member of the drug trail referred to at the start of this article. It was sponsored by Bayer, the manfacturer of Aspirin and rivaroxaban (trade name Xarelto in higher dosages). It was called the COMPASS trial (acronym styood for something “smart”). I had to drop out because of severe and lengthy bleeding after a cut or injury; I must have been in the higher dosage group. I had no other side effects other then the excessive bleeding. I have gone back to low dose aspirin. Apprently the trial was stopped early because of the very positive results. I had wondered what the outcome was and now I know thanks to Dr. Kenrick.
I always wonder about those supposed positive results. Why? First of all the drug manufactures use relative risk results, a made up marketing term, instead of absolute risk, which is the bottom line fact. Ex., statins supposedly reduce heart attacks 33% of the time (relative), when in fact they reduce 2nd heart attacks less than 1% (absolute risk). There are many other ways that drug companies fudge the results. In fact I’m wondering about your experience. So you had a bad reaction and dropped out, but I’m wondering if your result was included in the final tally. I’m not saying that you know this information, just that drug companies actually don’t always count these people like yourself who had to drop out. You are also thinking that because you had excessive bleeding you must have been in the high dose group. It’s possible of course but maybe you weren’t, maybe that drug even in a lower dose causes this problem. Btw, xarelto has an incredible amount of pending lawsuits but I can’t help notice that it is very heavily marketed still (TV).
Clinical trials have become a masterclass in obfuscation.
Dr., you have to be kind i understand, so i will say it for you, it’s outright criminal.
as a sidenote, who went to jail at Merck for Vioxx? which killed around 100,000 americans (died of heart related issues) While how many pot dealers/smokers are jailed for causing 0 deaths?
Money buys the legal system, claiming that Statins work is a fraud nothing else.
Dr K. Thanks for this clear statement of what is known about clot development in the arteries. I think in order to really respond intelligently to this latest paper I need to print it off and reread it.
Again thanks.
I have no idea how you are able to do your ‘regular’ job as a doctor in Cheshire, respond intelligently to the veritable flood of comments that happens on the blog and in addition write each of these papers for our information. And of course you have a family life.
Thanks again, Dr. Kendrick. Again I’m taking notes, to help me remember what I’ve learned from previous posts. Only one thing I don’t understand: What are “regions of disturbed flow?” Also, it occurred to me, when you discussed the lymph glands breaking down damaged and alien materials, that this may be one of the reasons staying physically active promotes health and longevity, by keeping the lymph system active throughout the day.
Undisturbed flow would occur when a fluid (blood) would flow down a pretty straight tube – I think they call this lamina flow. At a point where there is a branch in an artery there will be areas where this smooth lamina flow is disrupted => region of disturbed flow.
I imagine it is what you see in a stream that has rocks in it – flow is so disturbed you end up with eddies.
Antony,
I suspect that blood flowing down a straight channel would take a helical course.
I say this because I know that the best chimney liner is cylindrical – allowing for a much more efficient exit from your house than the spiraling (helix-ing) smoke that runs into the corners of a rectilinear lining. It’s what warm fluid smokey gasses want to do.
Extrapolating — is blood the same? Would spiraling blood present special problems when it hits a bifurcation?
Hemodynamics is the study of blood flow (I learned a new word!). “Generally in the body, blood flow is laminar. However, under conditions of high flow, particularly in the ascending aorta, laminar flow can be disrupted and become turbulent. When this occurs, blood does not flow linearly and smoothly in adjacent layers, but instead the flow can be described as being chaotic. Turbulent flow also occurs in large arteries at branch points, in diseased and narrowed (stenotic) arteries (see figure below), and across stenotic heart valves.”
http://www.cvphysiology.com/Hemodynamics/H007
JD,
Blood flow patterns might follow the helical pattern of smoke flow you describe as happening in a flue. i cannot say I have come across this being described in arteries. (Desperately trying not to google it . . . to many threads on the go)
Martin,
Nice reference . . . The reason this laminar/turbulent flow issue has been raised is as an explanation of why plaques form in areas of low shear stress in arteries. The proposal is that laminar flow results in high shear stress at the luminal surface, elements of the glycocalyx react to the shear forces, which stimulates the production of protective NO in the epithelium. Areas of turbulent flow such as at artery branch points have lower shear stress at the luminal surface and so the production of NO is less compromised, epithelium not so well protected. It is at the branch points that plaques tend to occur.
What the reference portrays is that at an artery narrowing (stenosis?) there is a region of turbulent flow. Cannot help speculating that once the stenosis begins to form there will be an increase in endothelial dysfunction and . . . . does this speed up the growth of the stenosis? make it more susceptible to external insults?
One of many things I was reminded of by the previous post – fluidics, once used in process control before electronic computers took over.
As far as I can recall, fluids tend to “stick” to the side of a channel and hence divert down a second channel. A mechanical or hydraulic pulse would “flip” the flow to the other wall and hence down a different second channel. From this you could set up a series of logic gates.
I am also recalling school geography lessons and oxbow lakes. And how you can alter erosion patterns by changing the flow upstream of where it is having an effect. Ties in with that paper on the glycocalyx I suspect.
Blood clots all the way brings to mind: “Turtles play positive roles in the folklore of many Native American tribes. In the creation myths of some East Coast tribes (such as the Iroquois and Lenape), the Great Spirit created their homeland by placing earth on the back of a giant turtle. This is why some contemporary Native Americans refer to North America by the name “Turtle Island.”” This works if there are turtles all the way down.
Oh, interesting! I got the “from then on it’s turtles all the way down” from Terry Pratchett.
Lots of turtles in cardiology
You mentioned repeated damage at the same point in the artery….so, once EPC’s have formed new endothelium, and the clot has been drawn backward into the walls, will the artery at that point be the same diameter as it was before the process, or will it’s diameter be slightly less. In other words, creating a point where there might be extra turbulence and further damage and clot formation.?
Hello y’all!
What about 1000 IU of dl-alpha-tocopherol every day? Just how much do Doctors hate it when someone brings up the vitamin E trope?
One surprising thing for me when I first started learning about human biochemistry is that vitamins A, K and E and CoQ10 (which perhaps should be considered a vitamin) are all chemically related, and all of them have a lot to do with the blood, and with calcium, magnesium and DNA synthesis.
Also, vitamin E is related to the recycling of vitamin C. It seems that gamma-tocopherol helps with collagen synthesis, which, perhaps, is a good thing for people recovering from myocardial infarction, or people who are at risk of MI.
And vitamin E seems harder to find in natural foods than A and K. One more thing, supplements mongers like to push the newer and more expensive formulation of “mixed tocopherols and tocotrienols”. I don’t know if these more expensive supplements are any better to reduce blood clotting risk, but it seems a marketing ploy to me.
Nuno,
I am presently on 2400IU/day on vitamin E which seems to keep my angina at bay. Add to that about 15 g/day of vitamin C. Any GP understands that I must be “doomed”.
Vitamin E in the natural form is not that very expensive at least when compared with most “heart medicines”.
https://www.lambertshealthcare.co.uk/natural-vitamin-e-400iu-p8708/
Taking six pills per day the bottle of 180 will last for a month at the cost of 30 pounds. I guess that it is about the cost of a bottle of the genuine (the best?) Scottish Ardbeg 10 years malt whisky. Garlic is less expensive. 🙂
Well, there are costs involved in living! – and keeping out of the reach of Big Pharma.
Anyway I am a chemist at base so one may understand that the “teachings” Linus Pauling makes me weak.
Wow, that is a lot of vit C. What about the kidneystones, which could be caused by supplementing high (2000 mg +) doses of vit C? At least, that is the story.
Very good
DR K, I went & looked at the source for your comments about rivaroxaban. I note that they used a dose of 100mg of aspirin in this trial.
100 mg of aspirin with 2.5 mg or 5 mg of rivaroxaban in group 1
100 mg of aspirin daily in group 2
2.5 or 5 mg if rivaroxaban alone in group 3.
Ummmm that is a very high dose of aspirin. Usually the dose of aspirin suggested for it’s ‘anti-coalgulent’ effects is much lower- ‘baby aspirin’ 20-30 mg.
I am puzzled at this.
In the UK, the dose of aspirin used for ‘prevention’ is, normally, 75mg. Not sure about other countries.
I seem to remember that it is 85 mg in the US. This lead to an absurd conversation with a pharmacist there.
“Do you have those 75 mg asprin tablets, meant to reduce heart disease?”
“I’m not sure we have any of those, we only have these 85 mg tablets, and I don’t know if they would be suitable for you!”
I took 75 mg daily for 3-4 years til October 2016. I did so after reading in New Scientist that it prevented colon cancer. But it definitely caused gastrointestinal bleeding and anemia for me, at that dose .
I think I read about much lower dose of 20-30 mg. being just as effective at preventing colon cancer but less likely to to cause intestinal bleeding on Rogue Health earlier this year. But I may have mis-remembered this.
Isn’t it true that NNT for aspirin in primary prevention is something close to infinity?
Pretty much. It is a little better than infinity, but the benefit is certainly not terribly exciting.
One thing in favour of aspirin, is that big pharma doesn’t really benefit if we take it. I am not joking – it seems to me entirely likely that the studies that have been done are biased against aspirin in subtle ways – just as it would seem they are biased in favour of expensive prescription drugs.
David,
Many drugs have a high price tag because it is part of the placebo effect on the patients. In many studies they found that just increasing the price of pills worked better than making the pills very cheap. That’s how humans think, cheap = dont work, pricey = must work. Most rx drugs barely work more than a placebo. Most of the times we are talking 1%.
Maybe you knew that already…
Also I checked with Wikipedia about rivaroxaban. Here is that it states about side effects..
“The most serious adverse effect is bleeding, including severe internal bleeding.[7][8][9] Rivaroxaban is associated with lower rates of serious and fatal bleeding events than warfarin but is associated with higher rates of bleeding in the gastrointestinal tract.[5] There is currently no antidote for rivaroxaban (unlike warfarin, the action of which can be reversed with vitamin K or prothrombin complex concentrate), meaning that serious bleeding may be difficult to manage.”
and
“As of 2015, post-marketing assessments showed liver toxicity, and further studies are needed to quantify the risk.[13][14] The drug is contraindicated in people with significant liver disease and end-stage kidney disease, in whom the drug was not trialed.
Rivaroxaban has a boxed warning to make clear that people using the drug should not discontinue it before talking with their health care professional, because it can increase the risk of stroke.[15]
In 2015, rivaroxaban accounted for the highest number of reported cases of serious injury among regularly monitored drugs to the FDA’s Adverse Events Reporting System (AERS).[16]”
Ummm ! Now that puts a real dampener on the press’ ‘phenomenal’ claims for rivarocaban !
Apparently, cycling should be promoted as the best excercise ( guardian today) . Gives the cardiovascular system a workout of great benefit. The density of traffic on the UK roads is surely prohibitive though. Don’t know the sources but it seems cyclists are healthier.
Could we give up all medication and just pedal everywhere!
Of topic : DR K I have just read an article on the THINKS website from Nov 14, 2003 ( 14 years ago ! )
” WHAT PROTECTS THE FRENCH FROM HEART DISEASE?”
http://thincs.org/Malcolm.French.htm
No author is Malcolm. And the writing is in your own unique style. Also the argument put forward is convincing also.
Eating good food in good company in a relaxed enjoyable way : the secret behind the French paradox !
Indeed, and I still believe this.
And heart disease is all down to stress…
Tonight I ate dinner with my lovely wife : baked purple fleshed sweet potato with pastured egg omelette. And to top it off a glass of a nice glass of wine : A Victorian grown red named ‘Duriff’ which is rare French wine.
Cheese and pate are super rich in long chain K2.
This is missed because no one is identifying K2 as we obsess over bonds of fats and calories.
In those fats are the long chain K2 forms – the menaquinones.
In US cheese from Kraft, they use a ‘fast ferment’ method, so who knows how much K2 is in the ‘cheeses’ we consume from our biggest manufacturer?
However, the folks at the Vitamin K Lab at Tufts have recently looked at K2 content of US dairy foods and discovered that the ‘artisan’ cheeses and the full-fat dairy had more K2.
Remove the fat, you remove the K2.
Calories were the basis for this ridiculous thinking, and now we have lost the fat soluble nutrient K2, which we really need in our daily diet. W/o it, we get fat, calcify our soft tissues and weaken our bones.
It is nice to eat with friends.
It is nice to eat in a leisurely fashion.
But it is REALLY nice to eat lots and lots of K2 in long chain forms.
Pretty sure Chris Masterjohn has the subject of K2 well covered, either on the WAPF site or one of his own blogs. I’ve been trialling supplementing but it doesn’t taste half as nice as a decent cheese. ISTR from somewhere that both Jarlsberg and Brie were particularly good sources. It’s synergistic with D3 so best eaten while sitting in the sun.
Hi – Re your comments about cheese. I just want to tell the world that I now prefer cheese to chocolate. Milk chocolate I can’t bear and good black chocolate is …..okay, sort of, but cheese. That’s something else altogether. So good to know that ones little weaknesses are actually beneficial even though friends fall about in horror – Aargh – the fat, the fat.
Yum, I say, yum.
I eat about half a pound of full fat cheeses most days and the equivalent of at least 3 large eggs, and a big dollop (scientific quantity) of double cream. Not only do I fit in my once too small clothes, I need to make another hole in my belt as it’s too loose. I think I could have been healthy instead of having to live with glycated tissue, but at least I believe I will be better off than I might have been had I continued to believe the official guidelines, or the “everything in moderation” mantra.
AH Notepad: Impressive. I eat that many eggs and that much cream (about a pint a week), but only about half that much cheese, though I eat it at both meals, and it is my main trail food.
chris c: Also Gouda. I heard a presentation by Dr. Katie (can’t remember how to spell her name) from Toronto, and it was at or near the top of the list of cheeses.
Last Gouda I had tasted like plastic 😦
Currently I’m waiting for Vacherin Mont d’Or to come back into the shop – it’s seasonal and a bit like Brie with a turbocharger, and a delightfully lemony flavour.
I recently discovered Red Storm – an especially good Red Leicester, and one of my other favourites is Wells Alpine, from just over the border in Norfolk. Lots of other favourites too, and I’m particularly entertained by my GP’s expression when I start enthusing about cheese and grass-fed butter. So that’s a win-win, I get to stuff my face with delicious healthy saturated fat with K2 and CLA and she stays horrified for 12 years now.
Ahhhhh cheese & cheeses ! I am so pleased to have found this discussion. I remember long ago as a child my English mum forced me to eat Kraft process cheese.. And I loathed.. I thought it was soap.
Then one time she did not have enough time to do the weekly supermarket shopping ( in the days when they shut early here at 5.00 pm ) And I found real cheeses and bought a heap for the family. They all disappeared in days.. Now I still love bries, camenberts, fetta, crumbly Mersey valley ( from Tasmania ) and even good strong vintage cheddar…
I mentioned vitamin K2…crickets.
Well, coagulation and many other essential processes are all dependent on sufficiency and proper actions of K2. It does not work alone, but it is essential and it tends to be fouled up in its actions via all sorts of things – diet, drugs, EDCs, etc.
The vitamin K-dependent proteins (VKDPs) actually control calcium when properly activated – some ensure NO calcium deposits, some make very sure calcium DOES deposit and coagulation has 7 VKDPs which act in both ways – some are pro-coagulation and some are anti-coagulation – to make the noted yin-yang of coagulation behave properly. Coagulation IS ABOUT VITAMIN K, FOLKS!!!
Coagulation is about calcium regulation!!
Pay attention, this is huge!
I mentioned UBIAD1, the enzyme that ‘connects’ calcium, cholesterol and endogenously made K2.
Crickets.
Dr Kendrick, are you looking at this?? Please do. This is really important.
So here is something about this enzyme.
https://www.ncbi.nlm.nih.gov/pubmed/28901410
Depletion of ubiA prenyltransferase domain containing 1 expression promotes angiotensin II‑induced hypertrophic response in AC16 human myocardial cells via modulating the expression levels of coenzyme Q10 and endothelial nitric oxide synthase.
These days we have lots more heart failure while MIs are dropping. One cause is statins, which lead to HF, but we have fouled up quinones beyond just K2 to include CoQ10 via these toxic drugs.
Endothelial cells need to have enough K2 to stop inappropriate calcification by activating matrix gla protein. W/o this, we have CAC.
I made the case that microcalcifications are the first cause, unmeasured by traditional CT, but can be seen via a microprobe (God knows what that is, but maybe can be seen with a microscope if we look?).
Calcium folks, it is about calcium regulation or lack thereof.
You want to avoid heart attacks, cancer, AD, diabetes, fractures, etc?
Be K replete.
Almost no one is.
But this is unidentified while we consider K status to be represented by coagulation time.
Nope, this is a low bar…essential, but low.
If we are truly K replete, all sorts of tissue-wide VKDPs are activated.
Ones we missed, but they are super important over time.
I thing that vitamin K deficiency has a part to play in the story. A few years ago I became involved with a group of people hoping to sell a supplement called ProKardia. I felt they were good people, with a good grasp of some important issues. I agreed to help them, but they could not gain sufficient funding to make a success of it. ProKardia was to contain: Vitamin K2, Thiamine, Folic Acid, Potassium, Magnesium, L-arginine HCL, L-carnitine, L-cirtrulline, Co-Enzyme Q10. I would have liked vitamin D and D (and a couple of other things), but one tablet can only contain so many things. So, yes, I have been on the vitamin K bandwagon for some time.
Great!
But the K bandwagon is not about supplements.
Instead of supplements – and there are some influential folks who have patented a MK-7 supplement and have tended to put a lot of research into this topic – let’s look at the foods that contain it.
Also, the creation of K3, carried by the lymph system to become MK-4 is a huge and underappreciated topic. Can’t measure in serum, so we miss this.
There are some Japanese lipid pharmacologists who are onto all this, but they, too, are met with crickets. No one wants to hear what they have to say…negative about statins and canola oil, for example.
NOT supplements…it is foods!
We lost the foods, we created ‘monster’ fats, we sickened ourselves by screwing up all the things that contribute to vitamin K status:
lost foods with K2
impaired K actions with drugs (statins, bisphosphonates, warfarin, NSAIDs)
impaired K actions with dihydrophylloquinone (dK) made when we hydrogenate the new,
aberrant dietary oils like soy and canola
impaired K actions with loss of dietary fats to make bile to actually be able to absorb the K
vitamink2.org
Yes, they are affiliated with the patent folks, but there is interesting info
Eat liver, offal, full-fat dairy, fermented foods, stock, animal fats
Micki,
So, what’s to be done then?
Why not supplements? Is K2 not K2 – whatever the source?
Cheese is fine. I worry about the geese concerning pate. No way to know what the “dosing” is, though, when the source is food.
I’ve been taking this for years since learning my CAC was 1,640:
https://www.iherb.com/pr/Life-Extension-Super-K-With-Advanced-K2-Complex-90-Softgel/66835
This is a reply to JDPatten’s post, which for some reason doesn’t offer the opportunity to reply.
The product you use as a supplement has both forms of vitamin K2 that have been the most studied. That last part – the most studied – means that we haven’t looked very much at other forms of K2. Do these forms represent the dominant forms in food? Not necessarily. MK-9 seems to dominate in fermented dairy. And, interestingly, in these foods there is almost always some MK-8, with speculation that the various bacteria fermenting make this form concomitantly. So who says that MK-8 isn’t important? I am critical of our narrow approach to the choices of only these two forms, but they do represent a broad duality of MK-4 (the specific form not made by fermentation and considered a short chain form) and MK-7, representative of long chain menaquinones. With increasing side chain length we get more lipophilicity and longer life in body, as described in the sales pitch for your supplement.
Turns out that there are about 14 forms of menaquinones (vitamin K2) with MK-n to describe each one where n=the number of isoprenoid side units or the length of the side chain. So MK-4 has four units and MK-7 has 7. The thing about MK-4 is that it is the only form not made by fermentation and, as I described previously, it can be made endogenously AND consumed and it also happens to be the most common form of menaquinone in us, in our tissues. We tend to store long chain forms in our livers (why eating liver is so healthy) but lots of forms can co-exist in various tissues, too. And they do.
When we consume something, it doesn’t just absorb and land in the body intact (usually) so like the dopes who thought that someone could consume a certain fat and then…bam! it landed in arteries, this is not how our bodies work. Nope. So eating MK-4 also doesn’t just get into us and then travel around. Some might, but most forms of consumed K will be absorbed and potentially
converted, transferred all around (and, interestingly, MK-4 is also sometimes carried by LDL and longer chain forms by HDL) and then reconverted in complex processes. This nutrient, vitamin K, is so important that we even recycle it to ensure coagulation. Does this mean we can’t eat supplements or eat menaquinones? No. In fact, in spite of lack of knowledge about how much K2 is consumed in many cultures (take the Blue Zones, for example), it is recognized that there is no toxicity for any of the naturally occurring forms (except if you take warfarin, and then you should consider a change because you are set up to calcify – why the NOACs were invented).
With your high CAC, K supplements probably make sense, but are you ensuring all the other nutrients that work with it? Mg, D, other minerals – and don’t supplement calcium. Real foods CAN offer so much, but we have just missed K2 in the US. A recent thing showed that pretty high doses of K2 improved cardiac output, so that is an indication of safety beyond just what folks in government say:
https://www.ncbi.nlm.nih.gov/pubmed/28646812
I am not sure what form that they used. Likely, MK-4.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941825/
Menaquinones, Bacteria, and the Food Supply: The Relevance of Dairy and Fermented Food Products to Vitamin K Requirements
This above is kind of older and recently these folks have been looking more:
Click to access cdn.117.000638.full.pdf
Multiple Vitamin K Forms Exist in Dairy Foods
(nice charts)
Turns out long chain K2 is more prevalent in pork than was realized. But the Vitamin K Lab folks buy the pork in stores, with bones, and then cut up all the meat and fat to determine content and forms of K in these foods. Only we have been taught to cut off visible fat, so I am critical of their assessments. The K2 is in the fat mostly. Our fat phobia has impaired K2 intake. Plus that dihydrophylloquinone has messed up processes that needed K sufficiency. I would also recommend shunning all fried foods, too. Weird fats that are overheated for way too long to make for God-knows-what.
I am sure I don’t like liver. I am wrong, but I am brainwashed; food is cultural
That said, I eat natto every day.
How about you consider that? A pack a day along with your supplements and some nice blue cheese or brie and you are getting some real diversity of K2 forms. Natto also has MK-8 along with the MK-7 so heavily discussed and even some K1 – it is a plant food after all. And make homemade stock! Great stuff for soups with some nice veggies. Then you are ensuring that you are getting many forms of K in large amounts and all the other minerals and vitamins that co-exist in these foods.
Foods…it’s what’s for dinner (and lunch and breakfast).
Micki Jacobs: Thank you for this. Lots of great information. I can no longer stomach natto, but love liver, cheese, fermented veggies, and bone broth.
Mickie,
Thank you very much. That’s a carload more info than I’ve scared up myself.
Yes, mag and D (and others), no calcium. Love blue. Just discovered “Grand Noir”. Eat it as dessert. Great on Comice pear slices! Liver, not so much. Perhaps some fatty pork.
I’ve gotten so used to toeing the line of Low Fat, the received wisdom of the last several decades, that I’ll need to reintroduce the good stuff bit by bit. (Call me gullible, but all the people in white coats were saying it was the right thing.)
Micki I love the use of ‘crickets’ in your story it made me chuckle. Am very interested in this as my bro has calcific tendonosis which by all accounts is a deposition of calcium where it shouldn’t be. He also has partial tears of the Achilles which = lots of pain. He takes K2 Magnesium and VitC and also eats lots of Brie. 7 years with condition. Just had blood spun and injected into site and has a rigorous physio regimen. Tis quite a coincidence in reading Dr K’s blog and seeing your post. No crickets here. Thanks for posting.
Dr Kendrick, The more I read on this astonishing site, the more I am filled with admiration for your tireless commitment to discovering the cause of heart disease. As a lay person with this disease I find hope and inspiration each time I come back to your writing. Thank you from the bottom of my ❤
Found on Mark’s Daily Apple – posters here might find this amusing (or distressing?).
Click to access PlaintiffsFourthAmendedComplaint.pdf
It’s a lawsuit against Costco for promoting coconut oil as “healthy.” Lawyers have apparently figured this all out, so we don’t really need what it is written here!
24. Moreover, “[t]here is a positive linear trend between total saturated fatty acid
intake and total and low density lipoprotein (LDL) cholesterol concentrat
ion and increased
risk of coronary heart disease (CHD).”
25.
This linear relationship between saturated fat intake and risk of coronary heart
disease is well established and accepted in the scientific community.
This could be similar to what happened in Sweden and South Africa, “scientific community” on trial re danger of LCHF.
It is an interesting “Popperian refutation fact” that people in the Pacifics e.g on the iland of Tokelau living primarily on coconut oil never experienced any heart ailments or any other “modern diseases” for that matter before they encountered the “western diet treat”. And it then took about 20 years to “catch up”!
KidPsych: I saw that today, too. Complete rot. Surprised it hasn’t been thrown out of court, but may yet be.
Perhaps the defense attorneys can argue that physicians don’t constitute a “scientific community”?
Good luck with that))
This reminds me of a joke that a lawyer told me some years ago.
“A 20 seat plane crashed with 19 lawyers on board killing all of them.
Question “What can one say about this ?”
Answer : “Waste of a space.”
Turning to the national aspect of this : The USA legal system seems to generate such law suits with extraordinary ease compared to other English speaking countries. So is this an example of the saying ; “Only in America” ?
I suspect that here in Oz such a case would be tossed out as vexatious litigation. And the defendents awarded costs.
Turning to the science aspect of the issue : I thought it was now settled science that saturated fat does not cause heart disease. But clearly these lawyers have no idea about the science. I wonder whether the judge in the case has any idea of the science.
Expect that saturated fat will be bad until standard of care guidelines updated (another 10 years). The bigger problem will be to accept that LDL-C is not bad and statins do more harm than good. Cannot move too fast on revising guidelines otherwise patients will be confused. If saturated fat is good and LDL-C is good then what causes CVD? Could it be the low fat/high carb diet as currently recommended by cardiologists?
Bill in Oz: The judge probably doesn’t have a clue, either. Law and science are so dissimilar. In law proof, to varying standards, is decisive. In science it is disproof which is decisive. Not common, I would expect, for a judge’s mind to be trained to see such a distinction.
Gary, I have here in my hand, David Evans book ” Cholesterol & Saturated Fat Prevent Heart Disease – Evidence from 101 Scientific Papers” Published in the UK by Grosvenor House Publishing in 2015 I think.
I suggest it should be tendered as evidence. Even a ( reasonably literate ) judge could understand it.
Bill in Oz, this will be trial by jury. The deck can be stacked, Costco should plead guilty.
Lawyers are interested only in winning their case. Truth is not the main concern.
This is a curious conversation here – on the sins of the US legal system. I once had a bit to do with a brother who was a lawyer. ( I do not have contact now ). He said to me once that lawyers are the servants of the court. And that hypothetically, any lawyer who abused this could be barred from practice.
Presenting false evidence is such an abuse.
Dead simple to my non legal mind ! 🙂
Two questions please, if anyone can help:
1. With all the discussion around Vitamin K and it’s ability to counteract the anti-clotting effects of warfarin – does the same reasoning apply to the effect of Vitamin K on Aspirin’s anti-clotting effect ? Or for that matter the anti-clotting effect of fish oil ?
2. I have sardines or a small portion of mackerel at some point each day. Is there a point (a sufficient dose) where the fish oils from my sardines/mackerel are providing the same, or better anti-clotting protection than 75mg of Aspirin ?
Thanking you in advance.
Martin T
Martin,
As far as I understand the anti-clotting effects from different sources add. Garlic and omega-3 (wild caught fish/ grass fed beef) are well acknowledged “blod- thinning” components (Eskimo bleeding nose!) . (Even my cardiologist admitted to this fact.)
Thus, you have to be careful when running dual track – myself keeping away from the Big Pharma track to play safe 🙂
The problem as I see it is that you can only be supported by the NHS if you ar going the “wrong track”.
I took 75mg/day aspirin for a long time hoping it would be a counter to clotting. Alas when I got a short-term knee pain I took 300mg aspirin tablets at the maximum permitted dose for a few days. Within 10 days I was hospitalised with anaemia (severe shortage of breath). Turned out I had developed a duodenal ulcer, my red blood cell count was dangerously low and was losing blood faster than they could infuse it.
They managed to close the ulcer and I made a full recovery but as far as I’m concerned aspirin at any dose is off-limits and I’ll trust in dietary changes such as increasing my omega 3s. Luckily I love sardines.
Correction: ‘… losing blood faster than they were infusing it…’
20 years ago when I “slashed” all heart medicines the aspirin was the last one I dropped since that was the only thing the then reasonable cardiologist didn’t approve of although he thought the garlic I took was a good alternative.
Reading what you now tell us I think I made a good decision on this point as well.
My cardiologist believes I’m taking low-dose aspirin, but I’ve read too many mixed studies of it. I don’t take it. It does benefit clotting/heart disease, but causes more internal bleeding. It seems to be a wash. I’ve instead been using intermittent fasting, a low to zero (all meat) carb diet, and fish to get anti-clotting. I eat anchovies and sardines close to daily (on the days I’m not fasting) and try to add in some salmon and other fish. Also, I really try to avoid seed oils (canola, soybean, etc.) and actually reduce all oils, including olive oil. A lot of the canned fish is in olive oil, though, so I can’t completely get rid of it, and I do like a salad every once in a while (mainly, as an opportunity to eat more anchovies). I cook with animal fats (tallow, lard, duck fat, ghee, butter, etc.). You really have to read labels, as seed oils are in anything that’s prepared, at least in the US. I’ve even had them in condiments such as mustard. Not sure why they are in mustard. Also used to like white anchovies in oil…until I realized the oil was seed oils. Also, if you eat out, you’re getting seed oils for many things that are cooked. I still go out though; I just keep to safer foods, but even then I can’t prevent foods from being cooked in seed oils.
Is mechanism of action the same for aspirin and warfarin?
No, not at all. Aspirin blocks cyclo-oxygenase, which helps platelets stick together. Warfarin is a vitamin K antagonist that blocks production of several intrinsic clotting factors – thus inhibiting formation of fibrin from fibrinogen.
Thank you. I asked it in response to an earlier question on whether taking aspirin can lead to artery calcification similar to what happens with warfarin.
No, don’t think so.
Actually, in response to a question on whether vitamin K can counteract effects of aspirin. Sorry…
Martin Thomason: I really don’t know what a good answer to your queries would be, but my thinking is thus:
1. Taking a bit of fatty fish daily is likely to be health-promoting, certainly from the omega 3 FA’s, along with the protein and so forth.
2. I would be very cautious about taking any dose of aspirin on a regular basis. It is, after all, not food, and has been used for only a brief moment in the history of the human species. Magnesium actually has a better track record than aspirin in CVD prevention.
3. Read Dr. Kendrick’s THINCS article from 2003 linked to above by Bill in Oz. In other words, eat and enjoy the foods you like in a relaxed atmosphere among congenial people. I think he’s absolutely right about this. Perhaps our obsession with minutia, while interesting, may be counter-productive to our health and to understanding this puzzle.
Definite thumbs up, particularly number 3.
All statins cross the blood-brain barrier and harm the brain, according to Dr Ede, a psychiatrist. The following is a brief part of her article in ‘Psychology Today’:
Do people who take statin drugs need to worry about low brain cholesterol?
YES. “Statins” are drugs designed to lower your level of LDL cholesterol—the so-called “bad cholesterol.” They work by turning down the activity of HMG-CoA reductase, the enzyme our cells use to build new cholesterol molecules. Unfortunately, statins do cross the blood-brain barrier and enter brain cells, where they reduce the brain’s natural ability to make the beautiful cholesterol molecules the brain needs to do its important work.
https://www.psychologytoday.com/blog/diagnosis-diet/201709/low-brain-cholesterol-separating-fact-fiction
A couple of points — it is APO(a) and LP(a) – often pronounced ‘L’ ‘P’-little-‘a’ (there is a capital-‘A’ in the blog.. )
There is a correlation of elevated Lp(a) with CAD – but once again – is it a cause or effect? I don’t think we know. Lp(a) varies – the number of Kringle repeats might matter.. some types don’t seem to be associated with CAD.. Interventions that lower Lp(a) have not been shown to change mortality – they might, just that the type and quality research does not exist.
The idea that clotting is particular complex – I get – but I would suggest that most of biology is way more complex than it is assumed to be. We are sexual creatures with most bits regulated with nested and redundant feedback loops – often non linear – sometimes integrating – sometimes differentiating – thus single point mutations are often survivable – increasing the diversity of the gene pool. But the complexity is mostly ignored in medicine – replaced with narratives that are based on ego rather than hard science. There is much that is unknowable today.
Managing the clots matters – but I think confounds the understanding of causation – it seems like a normal healing process to me – but fiddling with it can extend lives.
But that gets us back to the question of why some people get CAD and others don’t – I don’t think clots cause CAD – but are the result.
Great blog.. This is the level of thinking that is generally missing from med school.
Part 37 and quite possibly the best yet, thanks Malcolm!
Superb, really starting to bring the whole series together now, and making lots of sense.
Absolutely loving this series, great work.
Off topic but relevant : This link is a study of ‘spin’ in biomedical research papers.
It happens. !
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002173#sec019
Apparently in London they used to test everyone for platelet adhesiveness. (The dates in this article appear to be a bit messed up – the test was developed in the 1970s, but used in the 1960s?)
http://www.drkaslow.com/html/clotting_risks.html
Platelet Adhesiveness
In the 1970s at the National Heart Hospital in London a platelet adhesiveness index (PAI) was developed. In this test a blood sample was taken and split into two portion. In the first portion, the platelets were counted just as they would in routine blood cell count. The second portion of the sample was passed over glass beads and the resulting platelets counted. The more platelets that stuck to the glass beads, the lower the platelet count and the higher the platelet adhesiveness index (PAI). If half the platelets stuck to the beads, PAI was 50. What was observed was patients who had survived a heart attack would have a higher PAI (50 for example) and were at risk of death from a second heart attack. Young women who never suffer from MI had a low PAI (20) and yet had proper blood clots in wounds.
From 1960 – 1965 at the National Heart Hospital, a PAI test was performed on every patient. Not a single patient with PAI less than 40 was seen at this hospital for heart disease. Anyone with a PAI 40mg/day, EPA/DHA from fish oil, purple grape juice at 10 oz/day, GLA in evening primrose oil (supposed to reduce PAI better than anything else), the oils of onion and garlic, ground ginger, etc.
Very interesting. Thank you for this
More references to inflammation as an indication of healing in the body. I wonder how this relates to Behçet’s dis
ease? This is on my mind, because a young man I know suffers from BD and has had several small strokes. I wonder what the process is there?
Suzanne, maybe inflammation is not all about healing. Had a quick look at Behcets on the internet. Appears that leaky gut with related food sensitivities could be involved. In this case inflammation is bad and has no relation to healing. A good place to start would be to eliminate gluten and allergy causing foods. Apparently glyphosate can also trash the gut tight junctions. Check out restore4life.com, they promote a product that claims to heal gut health and prevent glyphosate damage.
Soon after the end of the American Civil War, Dr. Jacob Mendez Da Costa, a Philadelphia physician, reported evidence linking what we now term post-traumatic stress disorder (PTSD) with increased risk for cardiovascular disease (CVD; Wooley, 1982). Based on analysis of ca. 300 soldiers in a dedicated hospital in wartime Philadelphia, Da Costa’s report may have been the first ever example of a modern “big data” clinical study. Da Costa termed the relationship “soldiers heart ” or “irritable heart,” More recently, this relationship has been described in different groups of combat veterans and civilians with PTSD (Cwikel et al., 1997; Paulus et al., 2013; Sidney, 2013; Turner et al., 2013; Wentworth et al., 2013; Beristianos et al., 2014; Roy et al., 2015).
Until very recently, there was no biological evidence to link PTSD to CVD. However, the possibility of a genetic mechanism for the link was recently raised by twin studies from the Viet Nam Era Twin (VET) Registry (Vaccarino et al., 2013). This study showed that if both twins had PTSD, the risk of CVD was doubled in both twins. Strikingly, the increased risk was unrelated to smoking, blood lipids, obesity or lack of exercise. By contrast, no significantly increased familial risk for Type II diabetes could be found in the same cohort (Vaccarino et al., 2014). Together, these epidemiological and experimental data suggest that a hitherto unknown genetic mechanism might be responsible for the link between PTSD and CVD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033971/
In a previous post there was a discussion about essential nutrients. These have been known for a long time and all are found in food. It got me thinking…the health system sets ranges of all kinds of things from cholesterol to Magnesium to ideal blood pressure which…at a guess could not be based on definitive evidence. The experts tinker with these ranges all the time and there is always a synthetic drug that can ‘save you’ but the catch is you have to take it for the rest of your life…statins…insulin…etc. That’s what the health system is all about…meds for life. What’s laughable is that we all have to die of something…and many drugs will extend your life by days/weeks at best, with lots of side effects…the irony is that as much as the health system is collapsing under the weight of the cost of drugs it would also collapse if we abandoned drugs for natural substances
how human beings ever survived without rx drugs?
Plato lived up to 80 y.o. 300 years before christ, he was not an exception. Aspirin? Statin? high/low blood pressure? NSaids? really?
they are treating human beings like cars, and it has to do with the mechanistic view of the world, which started somewhere back in time with guys like Descartes
Not only that, but optimising N parameters in a complicated nonlinear system (e.g. the human body) isn’t an easy process. Imposing a jump change on one parameter – say prescribing a statin to reduce cholesterol level – is likely to upset other parameters. Imagine you took the back off an old fashioned radio with internal adjusters, and twiddled with one. You just might manage to adjust it slightly so that your radio sounded better, but then if you went on to twiddle another and another, the result would soon be a mess!
Now imagine that you didn’t twiddle the adjusters, but adjusted them in discrete amounts – such as the 50mg of Simvastatin (regardless even of a my weight) I was prescribed, or my 20mg dose of omeprazole that pushed me from making too much stomach acid, to making too little. It is easy to see how easily people can become seriously ‘detuned’ by the health service!
David,
Check out the practice of ‘muntzing’. Earl Muntz was a pile-em-high-and-sell-em-cheap retailer who sold TVs in the late 1940s. He would take expensive TV sets and remove components until they stopped working, repeating this until he found the absolute minimum number of components needed for a working TV, then he manufactured the minimal TVs and sold them cheaply. (They only worked near broadcast stations, not where the signal was weak.)
So evolution doesn’t always mean ‘more complex’.
Here, Dr. Davis discusses phytates, the compounds in wheat and grains responsible for several important nutrient deficiencies. Contrary to popular opinion, grains are NOT necessary for nutrition. https://www.youtube.com/watch?v=4X5vCqwcluU
Siobhan Huggins is doing a series that will complement this site very well, if no one has looked at Dave Feldman’s work, it is also worth the effort… Siobhan is interviewed on 2ketodudes and she has started a series on Dave Feldman’s site, Cholesterol Code links: http://2ketodudes.com/show.aspx?episode=83
and http://cholesterolcode.com/beyond-the-lipid-hypothesis-plaque-development/ Another development , re Ketosis is
http://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(17)30270-2
Dr. K:
This was just posted on Dr. Grant Schofield’s site:
https://profgrant.com/2017/09/19/a-short-guide-to-reverse-cholesterol-transport/
What do you think about what they say at 3:25 in the video regarding “excess APOB containing particles [invading] the arterial wall”?
How?
I don’t know, but this is another citation they used:
[12] Welty FK. How Do Elevated Triglycerides and Low HDL-Cholesterol Affect Inflammation and Atherothrombosis? Current cardiology reports. 2013;15(9):400. doi:10.1007/s11886-013-0400-4.
In which it is said:
“When TG levels are high, the apoB particles are TG-enriched and hepatic lipase then hydrolyzes the TGs within the TG-rich LDL to release FFAs, a process which remodels the LDL particles into smaller and denser LDL particles which can enter the arterial intima more easily than larger LDL particles, thus making them more atherogenic (Fig. 1)”
I’m with you that it is more likely that LDL comes
in through the vasa vasorum. (Where’s that paper where
they showed that the particles are more concentrated
farther from the blood vessel intima? Wish I could find it.)
.
William,
One paper that shows micrographs of lipids in the part of the intimal layer farthest away from the arterial lumen is . . .
“Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target” (2016)
https://www.ncbi.nlm.nih.gov/pubmed/27265770
The micrographs he uses come from work by Nakashima, Y. et al (2007)
“Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration”
http://atvb.ahajournals.org/content/27/5/1159
In the above references evidence of macrophage infiltration via the lumen is described.
In an August blog on by Siobhan Huggins on the chlosterolcode.com site she reviews scenarios where renegade oxidised LDL monocyte/macrophages (NB damaged before they see the inside of the intimal layer) can be trapped by the scavenger receptors on the surface of the epithelial cells. Her logic for the arrangement is that it is beneficial to the system to stop the oxLDL moving around, making it easier for the macrophages to phagocytise the captured oxLDL.
At this point we part company . . . She then says the lipid laden macrophages pull in more oxLDL “storing them in lipid pools and becoming foam cells . . . the implication is that this takes place in the near lumen sub-epithelial zone . . . but where is the supply of oxLDL in the intimal layer coming from?
The blog is worth a read – good stuff on receptors.
http://cholesterolcode.com/beyond-the-lipid-hypothesis-plaque-development/
The work of Nakashima shows macrophage infiltration in the near luminal sub-epithelial zone, well away from the lipid concentrations (which lie at the deeper part of the intimal layer). There is strong evidence that macrophages are equipped to temporarily unlock the tight junctions of the epithelium and squeeze into the intimal layer. Those macrophages entering into the near luminal sub-epithelial zone might well take with them oxLDL they are processing? I see a sort of mopping up operation before they pass through the epithelium.. Why they enter the intimal layer and concentrate there I do not know.
Can’t reply to Antony Sanderson, but Thanks to him.
That is the paper by Subbotin that I couldn’t find,
about the deposition of lipid particles coming in
through the vasa vasorum. Thanks Antony!
Anthony, that first link you suggested to the review article by Subbotin is interesting. But it is a real mouthful. I have booked marked it so I can easily go back to it later when my brain is up to speed. ( Coffee needed with breakfast ! )
Thanks !
Off Topic : Dr K I now have. your 2014 book, “Doctoring Data”. I am enjoying reading it as it is enlivened by your clear way of writing, sardonic wit and heretical approach. By ‘heretic’ I mean it In the way that Galilleo was also a ‘heretic’ – good company !
Still I am dismayed at the extent of the sheer duplicity that takes place in modern research papers.I have before me this paragraph :” The simple fact is that you will find it very difficult to come across any research that is not biased in some way or other.Some of this is just basic human nature in action.We like to confirm, rather than confront.However some of this bias is far from innocent.Much of it is deliberately conceived and done with a clear end in sight.”
I wonder if there is a honest reference web blog site which lists the ‘scientific’ authors of such ‘research’ (? ) papers ? If such a blog exists, it would save us all time and energy when they publish new research to confuse the honest.
Another off topic Dr K. On Josh Mittelldorf’s antiaging blog there has just been a discussion of heart disease and a research report in 2014 by G Belcaro G ” Pycnogenol and Centella Asiatica for asymptomatic atherosclerosis progression” Int Angiol 2014 33 (1) 20-26.
They took a group aged from 45 to 60 with atherosclerotic plaque lesions and divided them at random into 2 groups, a control & a trial group. .
The control group was only instructed on diet and exercise, The trial group followed those recommendations as well but took 100mg of pine bark extract with 100mg of gotu kola extract.
They looked at the development of plaques progressing from class 4 to class 5 over a 30 month period. The control group saw a 21.3% progression over this period, the supplement group had a 1% progression. That is a huge difference in outcomes.
The Belcaro research paper now seems to be unavailable on the web. Fortunately it was written up at length by Life Extension magazine in the May 2017 issue.
http://www.lifeextension.com/Magazine/2017/5/Arterial-Plaque-Rupture/Page-01
Both supplements are available from Life Extension or Iherb. But the French Maritime Pine extract is very expensive.
I wonder what you think Dr K of these supplements and whether they are worth buying. And yes, in my thinking is the question as to whether the Life Extension magazine article is just boosting sales of items offered by it’s ‘parent’ company.
Or am I jumping the gun and raising something that you want to deal with in your own time ?
https://www.sciencedaily.com/releases/2017/09/170921141159.htm
A team led by Olefsky, associate dean for scientific affairs, took macrophages found in adipose tissue of obese mice and harvested their exosomes. Lean, healthy mouse models were treated with these “obese” exosomes and once-normal mice began exhibiting obesity-induced insulin resistance despite not being overweight.
When reversing the process, the team found that they could restore insulin sensitivity to obese mice by treating them with exosomes from lean mice. The obese mice remained overweight, but were metabolically healthy.
Similarly, during an in vitro study, when human liver and fat cells were treated with “obese” exosomes, these cells became insulin resistant. Conversely, when they were treated with “lean” macrophage exosomes, they became highly sensitive to insulin.
“This is a key mechanism of how diabetes works,” said Olefsky. “This is important because it pins the pathophysiology of the disease in inflamed adipose tissue macrophages which are making these exosomes. If we can find out which of the microRNAs in those exosomes cause the phenotype of diabetes, we can find drug targets.”
DR K. I have just worked out something about this website. And I think it is important especially newcomers like myself.
If we type the blog’s web address into your web brouser followed by the year date…We get the complete list of all your posts for that year !
Here is an example
https://drmalcolmkendrick.org/2014.
It has all your posts arranged by date for that year 2014..And if we hit the reply buttom at the end of each post, up pop all the comments made for each post…
Bloody marvelous !
I am now wondering how far back in time it all goes….For newcomers a voyage of exploration into what has been missed !
Bill, thanks for that gem of information. I can find blogs from 2012 onwards. Eek!!! That means I have another four years of blogs to trawl through.
AH, I agree ….Take a look at the one about Eskimos and nose bleeds.. There is lot’s of meat in that post and in some of the comments…..
By the way Dr K. did you write posts before 2012 ?
IF so they are not at this website location.
AH and Bill,
See here: http://www.thincs.org/Malcolm.index.htm
Phil
Renfrew, PA USA
WOW!!! Thank you Philip. MK is obviously a special cookie. How lucky we are to be able to have these documents, The correct sciientific approach would be of course, to be sceptical, and not just believe them because of the author. However, unlike most of the medical fraternity, he does question rather than meekly accept.
Phillip, thanks for that link to THINCS.. I will bookmark it for reading later. That list of articles starts in 2002 and ends in 2006.. I suppose there are yet more in the period 2006-2012 somewhere as well….but maybe the topics are covered in what we already know ?
My thanks also, Phil. Lots of great reading to catch up on!
Philip
Thank you for the link to the previous writings of Malcolm as I see go back to 2003!
The quality of these early writing are in my eyes are as good as those we see today and driven by the same disgust towards the obvious corruption and criminality in medicine for the one who wants to see this.
This criminality also makes me so frustrated.
Today I met with two of friends though at different occasions. The first one is a former colleague of mine and with the same CVD situation as I am in. He admitted that I had been right all the time about food and medicine but he had realized this only by time through the adverse side effects of the standard heart medicines and which made him drop the beta blockers and the statins with immediate improvements of his health.
My other friend who had turned diabetic when I “converted” to LCHF and after which the nurse told him that he was no longer diabetic. He also quit the statins after my persuasion. However. he is also acquainted with an experienced heart surgeon who had been “kind enough” to review his medication list and put him back on the statins. Although he experiences evident muscle weakness it is impossible to again get him off the statins. His daughters, one of which is a nurse, have forbidden him to discuss medicin matters with me.
Frustration continues!
August 29, 2017 PURE Shakes Up Nutritional Field: Finds High Fat Intake Beneficial. A new study of dietary habits in 135,000 people around the world is set to shake up the nutrition field, with results showing high fat intake—including saturated fat—was associated with a reduced risk of mortality. http://www.medscape.com/viewarticle/884937
If you want to see a video of Yusef (one of the leaders of the PURE research group) giving a very good presentation of the PURE results, clear and in a very digestible form then . . . .
It is well worth the time.
With his background his talk is actually a “block buster” which though doesn’t seems to make any headlines. MSM is as corrupt as the medical industry!
No macrophages not heart regeneration? Animal model https://www.sciencedaily.com/releases/2017/09/170920154948.htm
Interesting. Those macrophages are fascinating little creatures. I have long thought, in a kind of staring into space kind of way, that macrophages are key to everything to do with CVD.
Looks like we need macrophages after all. Statin benefit based on inhibition of macrophage production. Now there is zero benefit for statin therapy.
I want to talk about liposomal vitamin c.
Here is a US Patent for a “Method of making liposomes, liposome compositions made by the methods, and methods of using the same”.
https://www.google.com/patents/US20120171280
There are many patents on this liposomal technology. And it is somewhat dated. My guess is that orally administered liposomes never catched up because they taste horrible and they are impossible to sell, unlike pills and capsules.
There is a kind of scam going on these days. People are mixing water, soy lecithin (also sunflower lecithin and even egg yolk lecithin) with vodka and ascorbic acid (also sodium ascorbate), then put it in a blender and claim it is “home-made liposomal vitamin c”. (Watch on youtube). They also use a sonic jewelry cleaner to “help form liposomes”. But I read that the “sonication” part of the liposomal process is meant to evaporate the water from the mixing, because using heat to evaporate water would damage the vitamin c. I don’t think they are getting any liposomes out of this. Perhaps some micelles, which may enhance the absorption of the ascorbate or whatever they put in. The end product of this “home-made” process does not look at all as that expensive (relatively speaking) product which name I will not mention.
These liposomes are not micelles (or micellae) . They are a micelle within a micelle. These are invisible particles (they cannot be seen under an optic microscope, but can be “seen” (more or less) using very expensive electron microscopes). According to the experts in this field, they are supposedly composed of a layer of lipids that form a border that separates the interior of the micelle from the exterior. Lipids (including phospholipds) are “amphipathic” or “amphiphilic” organic substances, meaning they have one functional group which is lipophilic and another functional group which is hydrophilic. Our beloved fatty acids are lipophilic on one end, the hydrocarbon end, and hydrophilic on the carboxilic end, which is the part where they join with glycerol to form tryglycerides. Liposomal particles are composed of two layers of phospholipids. They are like a very small cell, which can be easily absorbed by another cell. But if you try to make liposomes at home you have no way of knowing wether you have succeded. Or perhaps this popular method is good enough and the companies selling the pricey liposomal vitamin c don’t want to see how people manufacture their own liposomes at home and stop buying their products. I don’t know.
This technology was invented with the idea of delivering drugs precisely in the tissue where the drug was meant to go. It was not mean as an oral medication (although it works fine that way). The idea is that oral medications are almost always pro-drugs which have to survive stomach acids, get to the liver and be processed there and transformed into the real drug (if all goes well) and then go to the bloodstream, and circulate through all the body, hoping that the drug will get to the tissue the doctor wants the drug to reach. One problem of this traditional strategy is that the drug also affects other tissues, creating sometimes dangerous side effects. Also, most of the drug is wasted anyway. So if we could only give the right amount of the correct drug right where is “needed” and in the right moment, without affecting the rest of the organs, this would not only be more economical but be more safe. Or so the story goes. At some point, someone decided to try to enhance the absorption of non-drugs, such as vitamins, using this complex technology.
Some people claim this is the future of pharmacology, as it is one way where tailored drugs, adapted to every individual, could be delivered precisely where they are needed. The problem, of course, is that patents are a monopoly. As all monopolies, they allow the monopolist to keep prices very high, control the production and prevent competition from profiting or finding a cheaper way to manufacture the same product. Which means that even if this technology could cure horribel chronic diseases such as arthritis, Congestive Heart Failure, Alzheimer, Multiple Esclerosis, only the very rich could use them until the patents would expire, many decades in the future, when all the laboratories would be allowed to compete and generate a cheap enough version of the liposomal-encapsulated drug that could be affordable and beneficial. Patents greatly hinder technological progress, and create the perverse incentives for companies to focus on achieving large margin profits from the monopoly position, instead of creating an affordable product that may be sold to a large number of clients. The long term profits of economies of scale are sustainable, the short term profits monopolies always come crashing down, hurting investors and creating turbulences in the financial markets, which ultimately evolve into a crisis that Governments try to solve by destroying the jobs, the income and the savings of citizens. Without patents, there would be much less trouble, I think.
Back to liposomal ascorbate.
We can find “liposomal vitamin c” in the Mercola brand. It is cheaper than the “official”, monopolistic liposomal c products. Does it work? I have no idea, but being in a capsule form they surely don’t taste as bad as “the real deal”. One popular claim is that taking four grams of liposomal vitamin c will help the body fight viral infections, such as the flu or measles. Which sounds wonderful, because modern medicine still to this day does not have any treatment for viral infections. At all. When you catch a bug, you are on your own. Official, politicised, pseudoscientific modern medicine can only offer “palliative care”. Either your immune system triumphs over the infection or you die. And this is true for babies and for the elderly, and everybody in between. They don’t know how to stimulate the immune system, only how to shut it down. They only beleive in vaccines, which may very well prevent some infections, if you are healthy and your immune system works well enough to use the vaccine to its advantage, but are worthless once you are infected. We all are at risk, and nobody, except for the charlatans, seem to be seeking for a real treatment for viral disease. What a mess!
I have read about HCl therapy (injecting a small quantity of hydrochloric acid in vein), Ozone therapy, hyperbaric-ozone therapy, vitamin c therapy, autohemotherapy with Ultraviolet Irradiation of blood, N-acetyl-cysteine therapy, GSH therapy, Potassium Iodide therapy, vitamin D therapy, vitamin A therapy and a few more for the uncharted territory of viral infections. Of course, the homeopathic doctors claim their stuff is wonderful and should be financed by every countries National Healthcare System. But everything seems inconclusive. For, if any of these things work against viral infections, how come the official science does not aprove its use? And if all of these things are darned scams, as the “rationalists” claim, why are they not prohibited by the Law?
Buying 30 packets of one-gram liposomal vitamin C costs about 30 USD. If you could cure CVD or cancer with, let’s say, five grams of this stuff every day for two months, that would be about 300 USD. It seems to cheap to be true, doesn’t it? If this was possible, wouldn’t it mark the end of most political corruption, as this unexpensive treatments would destroy the pharmaceutical industry? Money would stop flowing. A huge deflation would happen as prices would fall. Anyone who had any savings would become rich, as the currency gained value. People and companies drowned in debt would be wiped out, and all States would have to default. Major banks would be ruined forever. And people would be cured. This daydream of mine, isn’t it completely terrifying? To think that we have to choose between illness and wealth!
I really want liposomal vitamin c to turn out to be worthless against heart disease and cancer, and everything else. It would be too horrible to realise that many people could have avoided extreme pain if only other people would not have been recklessly greedy and corrupt.
Does anyone here have experience with liposomal encapsulation of drugs of vitamin C?
Dr K I am perplexed. A couple of days ago, somebody ( I forget who ) posted a comment about an article by By Thomas S. Cowan, MD from December 18, 2014. I think it was published on the Weston A Price Foundation’s website.
I followed up and read that article and even printed it off for further study. And Dr K you made the comment that it was very interesting ‘but not quite right’. Cowan’s main point is that heart attacks do not take place because of arterial blockages. In fact he believes that the MI’s take place because of problems between the symathetic & parasympathetic nervous system. This happens in response to stresses of many various kinds.
In this I think very similar to your stress hypothesis on CVD. However he also invokes Yin Yang as part of his argument….Unnecessarily in my opinion.
Cowan also discusses the development of ‘collateral arteries; which prevent the heart from becoming oxygen deficient. This may of interest to you Goran as I remember you making a comment about wanting more information about this subject.
I cannot find the original comment on this bog with the link to Cowan’s article. But it is also available in a slightly modified form here:
https://www.westonaprice.org/health-topics/what-causes-heart-attacks-part-two/
I have also been looking at a couple of Cowan’s sources. One of them is a website by Dr Knut Sroka : heartattacknew.com
Sroka is interesting & I feel valuable. He also makes the comment that for 50 years in Germany, prior to the triumph of the diet/cholesterol heart disease hypothesis, Ouabain, was the standard drug offered to relieve heart disease symptoms.
I found this section fascinating as it seems that Ouabain has been discredited and this fallen out of favour in Germany in recent years via the exact same heavy handed processes used in the English speaking world. Again for those interested here in the link.
http://heartattacknew.com/faq/what-can-be-done-to-prevent-a-heart-attack/ouabain-the-wasted-opportunity/
Sroka in turn provides a link to a 140 page pdf version of Baroldi’s 2007 book “The Etiopathologies of Coronary Heart Disease: a Heretical Theory based on morphology”
This last source I have ploughed through also. But my lack of medical knowledge makes it a hard task. It seems that every second word is a technical medical term. ( Why could he not write in plain English ? ) But some here may be intrigued and interested.
Click to access baroldi.pdf
And it seems that Ouabain is available in Australia ! What a pleasant surprise.. I will think about getting some..
https://www.miherbnz.com/collections/sanum-kehlbeck/products/strophanthus-d4-80-tablets?variant=11964358913
Dr Kendrick, I realise that I forgot to actually pose the question which was in my mind when I started writing my comment 2 above. re Dr. Cowan’s hypothesis on CVD.
Why is it ” interesting but not quite right’ ?
Does this mean partially right or an ironic remark meaning “completely wrong”
I hope you have the time to clarify this.
Bill in Oz
Dr Kendrick,
I found your explanation so beautiful and although I am not a scientist I was also able to follow the trail you laid for us. Thank you. It all made sense. Isn’t the human body wonderful. Would that we could learn to trust nature more. We are provided with what we need.
Nice article, nice info for who is suffering from anxiety and depression.
https://www.hupcfl.com
My 90 year old female friend has just had a letter from her gp saying her blood sugars are 14mmo which might lead to type 2 diabetes. Has made her really worried. Is that high for a 90 year old.