A summary up to now
Heart disease is really a disease of the larger arteries in the body. Essentially it is a build-up of atherosclerotic plaques (thickenings and narrowings) in the arteries. This could more accurately defined as cardiovascular disease (CVD), in that it can affect all large arteries, not just the arteries in the heart, or neck.
The final stage of plaque formation is complete blockage of an artery due a large blood clot forming, usually, over an existing plaque. This is the underlying cause of most heart attacks. In the case of an ischaemic stroke, the clot breaks off the main artery in the neck (carotid artery) and gets stuck in a smaller artery in the brain.
Other forms of ‘heart attacks’ and strokes can occur due to different mechanisms e.g. atrial fibrillation causes a clot to form in the atria before breaking of and travelling into the brain. Or, sudden acute stress on the heart can lead to catastrophic ischaemia, causing a ‘heart attack’ – without any underlying plaque. These type of stroke and ‘heart attack’ are not covered in this series of blogs.
When it comes to CVD, the cholesterol hypothesis holds sway over the medical profession i.e. when the cholesterol level is high it is deposited on/in the artery creating the thickenings and narrowings.
I have long argued that this hypothesis makes no sense from any perspective, and that CVD is actually caused by another process that that has little, or nothing, to do with cholesterol (in whatever form cholesterol is described). Instead CVD is a four step process:
- Endothelial damage
- Clot formation/dysfunctional clot formation
- Clot repair/dysfunctional clot repair
- The final, fatal, blood clot
In short, plaques are simply blood clots – in various states of repair. The final event (heart attack or stroke) is simply one part of exactly the same process that caused the plaques to form in the first place. Just bigger and more deadly.
In this series, up to now, I have mainly focussed on the process of damaging the endothelium, and explained how this inevitably results in a blood clot forming over the area of damage. Repair of the clot consists of forming a new layer of endothelium over the blood clot, thereby drawing it into the arterial wall. At which point it is attacked and broken down by monocytes and macrophages – amongst other things.
However, if the endothelium is repeatedly and rapidly damaged – at the same spot – the repair systems become overwhelmed and the clot/plaque, rather than being broken down and removed, starts to grow and turn into a dangerous ‘vulnerable’ plaque. I am now going to look at the process of clot formation itself – ‘thrombogenesis’. (Thrombo = clot, genesis = starting)
Clot formation
Clot formation is complicated, very complicated. However, I am going to try and make it as simple as possible by looking at three main players. At least I will to start with.
- Tissue factor
- Platelets
- Fibrinogen/Fibrin
As mentioned earlier, tissue factor (TF) sits within artery walls (and vein walls). It is the key trigger factor for most blood clots. Normally the blood is protected from contact with TF by the endothelium. However, if you damage the endothelium, TF is exposed to blood. This fires the starting gun for a massive and explosive cascade of blood clotting. This is known as the ‘extrinsic pathway.’ By extrinsic I mean basically factors that sit outside the bloodstream. And by this I basically mean TF (at least I do for the purposes of this discussion).
Having said this, it is possible to have blood clots form without TF involvement. This occurs primarily in veins, and is usually due to blood flow stasis i.e. the blood stops flowing in a blood vessel. This happens if you cross your legs, lie in bed, have a plaster cast on, or take a long haul flight, or suchlike. If the stasis lasts too long, the blood can slowly start to form a clot. A big one usually. This is usually referred to as a DVT (deep vein thrombosis).
The other place this can happen is, as described before, in the atria, when you have atrial fibrillation. Rather than the blood being rapidly ejected with each heart beat, when the atria fibrillate, the blood can become trapped in eddies, not moving. Then clotting, then escaping, then stroke.
Blood clots which are created mainly through the action of the intrinsic pathway are, usually, far less strongly bound together – because fibrin is not created to the same extent. Therefore, a DVT that forms in a large vein in your leg can easily break off, travel up the vein and into your heart. It can get stuck there – instant death. Or it can pass straight though the heart and into the lungs, where it gets stuck. Causing a pulmonary embolism. Can be fatal, but not always.
Intrinsic pathway clots are stimulated by all the clotting factors you may have heard of. Factor X, factor IX, factor VIII, prothrombin, and suchlike. If you want to stop these clots forming you can use various anticoagulants such as warfarin, or heparin, or the new oral anticoagulants (NOACs). These block various intrinsic factors making the blood ‘thinner’ and less likely to clot.
Warfarin, for example, interferes the action of vitamin K, which is needed by the liver to synthesize several clotting factors. Indeed, warfarin is often referred to as a vitamin K antagonist. Practically, this means that you can rapidly reverse the actions of warfarin by giving a massive dose of vitamin K.
Sorry, I said I was only going to talk about tissue factor, platelets and fibrinogen. But I think the fact that blood clotting has different pathways can help to explain why, for example, warfarin is very poor at preventing CVD, but very good at preventing stokes caused by atrial fibrillation, and can prevent dearth from DVT.
At times I am just staggered by the amazing ingenuity of human physiology. How the hell, I think to myself, did all of this evolve? Blood clotting is just one physiological system, one small part of how the body works, and just this one part is frighteningly complex.
Anyway, moving on. In the arteries, if you want to get a blood clot to form, you need expose the blood to TF and the clotting system then fires into action. The first part of the process is that platelets are attracted to the site of damage. Platelets are small blood cells which, when ‘activated’ become very sticky and start to clump together. They then release a massive family of different factors, including clotting factors, that stimulate the rest of the clotting cascade. [Platelets also contain quite a lot of TF, which is transferred to them by circulating monocytes – a tale for another day].
The final step of the clotting cascade is to join lots of small fibrinogen stands together. Fibrinogen consists of short thin strands of protein. If you stick hundreds of strands together, end to end, you get fibrin. This is a bit like fishing line. Long, tangly, sticky and extremely strong. It binds platelets together into a furiously strong clot.
At the same time, fibrin drags in almost everything else into the blood stream, and binds it into the clot. White blood cells, red blood cells, lipoproteins etc. Some of these may, or may not, be innocent bystanders in the clotting process. Although, the closer you look, the more you will find that almost all blood elements are actually players in the process.
Just to look at one example here, very low density lipoproteins (VLDLs), also known as ‘triglycerides’. These lipoproteins have significant effects on clotting. To understand how this happens I need to move sideways for a moment, and bring in something that most of you will never have heard of. Plasminogen activation inhibitor 1 (PAI-1).
To explain. Blood clots, when they form, incorporate within them an enzyme called plasminogen. This enzyme, when activated, can slice strands of fibrin apart and, thus, break down blood clots into tiny bits. After a heart attack, or stroke, you can be given tissue plasminogen activator (tPa) – or something very similar. This activates plasminogen within the blood clot, and causes the clot to disintegrate. Thus, a blocked artery will be reopened.
Now, as with everything else to do with blood clots, we have yin and yang. On one side we have plasminogen; on the other side we have plasminogen activator inhibitor – 1 (PAI-1). This does exactly what you would expect. It inhibits the action of plasminogen. This is not surprising. In all parts of the clotting system, for every factor that reduces blood clotting tendency, there is an equal and opposite factor increasing blood clotting. All is in balance.
Plasminogen slices clots apart, PAI-1 prevent this from happening. Clearly, therefore, the more PAI-1 you have, the more difficult it is for a clot to be broken apart. So any factor that increases PAI-1, will make any blood clot that forms bigger and more difficult to shift. Which brings us back to VLDL – a.k.a. triglycerides.
‘In vitro data have shown that triglyceride-rich very low density lipoprotein (VLDL) particles enhance PAI-1 secretion from endothelial cells and liver cells Furthermore, it has been shown that VLDL stimulation of PAI-1 expression in endothelial cells is mediated through transcriptional activation of the PAI-1 gene, and a VLDL response element has been identified in the promoter region.’ 1
Or, to put this more simply. If you have lots of VLDL in your blood, you will stimulate the production of PAI-1. So, you will have impaired breakdown of blood clots (impaired fibrinolytic activity). Which means that (from the same paper):
‘Hypertriglyceridemia is associated with an increased risk of coronary heart disease (CHD). Impaired endogenous fibrinolytic function is a frequent finding in subjects with hypertriglyceridemia.’
The most common condition where you are most likely to find high VLDL levels is type II diabetes. In type II diabetes there is, always, a high PAI-1 level. I am not sure if this needs a reference, but you are getting one anyway, with regard to type II diabetes:
‘The combination of hypertriglyceridemia, glucose intolerance and inflammation is linked with increased production of the primary inhibitor of endogenous thrombolysis, plasminogen activator inhibitor-1 (PAI-1). Recent data suggest that PAI-1 contributes directly to the complications of obesity, including type 2 diabetes, coronary arterial thrombi, and may even influence the accumulation of visceral fat.’2
The bigger picture – other factors
I think, as always, I have become in danger of heading off down a narrow channel here. Time to drag the discussion back to the main process. The point I want to make clear, in this part of the argument, is that after you have damaged the endothelium a clot will form. This is quite natural.
However, if you have factors in the blood that make any clot that forms bigger, or more difficult to break down, the chances are that any clot that forms will end up within the artery wall as a bigger plaque. Or the clot may simply block the artery altogether, first time.
Some of the other factors that make blood clots likely to be bigger, and/or more difficult to clear up, in addition to type II diabetes and high VLDL levels, are:
- Raised fibrinogen levels
- Raised Lp(a) levels
- Antiphospholipid syndrome (Hughes syndrome)
- Smoking
- Raised homocysteine levels
Not an exhaustive list by any manner of means, and I am only going to look at two of these in this blog. Fibrinogen and Lp(a) levels.
Fibrinogen
It would seem common sense that raised fibrinogen levels would make blood clots bigger when they form, and thus more difficult to clear up, as they are a key component of any blood clot.
The importance of a high fibrinogen level was something I first saw in the Scottish Heart Health Study. This was a major study that lasted ten years and included thousands of people. The researchers looked at many different factors which were thought to be involved with causing heart disease (and death from all causes). Raised cholesterol was found to have no effect. Instead they found that:
‘Fibrinogen is a strong predictor of coronary heart disease, fatal or non-fatal, new or recurrent, and of death from an unspecified cause, for both men and women. Its effect is only partially attributable to other coronary risk factors, the most important of which is smoking.’
The increase in (relative risk) between the highest and lowest fibrinogen levels was:
- 301% for men and 342% for women (CVD death)
- 259% for men and 220% for women (Death from any cause)
In fact, a high fibrinogen level was the single most important risk factor they found – just beneath already suffering a previous heart attack. A raised fibrinogen was an even more powerful risk factor than smoking (although smoking can raise fibrinogen levels, which complicates this picture somewhat).
This finding was reinforced by the Prospective Cardiovascular Münster (PROCAM) study.
‘The incidence of coronary events in the upper tertile (top third) of the plasma fibrinogen distribution was 2.4-fold higher than in the lower tertile (bottom third)… plasma fibrinogen was found to be an independent risk indicator for CHD (P < .05). Individuals in the high serum low-density lipoprotein (LDL) cholesterol tertile who also showed high plasma fibrinogen concentrations had a 6.1-fold increase in coronary risk. Unexpectedly, individuals with low plasma fibrinogen had a low incidence of coronary events even when serum LDL cholesterol was high.’ 3
[Ah yes, the old ‘high cholesterol low rate of heart disease conundrum.’ It must be, let me see, a paradox. I do love the word unexpectedly. Mainly, because, here is where scientific truths hide]
I feel the need to add that a 2.4-fold increase in coronary events = relative risk increase of 240%, which is in the same ball park as the Scottish Heart Health study. Some of the things that can raise your fibrinogen levels are:
- Smoking
- Stress (physical or psychological)
- Type II diabetes
- Depression
- Cushing’s disease
- Post-traumatic stress disorder (PTSD)
- Obstructive sleep apnoea
Of course, all of these things are also associated with a greatly increased risk of CVD. You can have hours of fun by typing CVD raised fibrinogen and… (insert favourite risk factor for CVD of your choice here).
Lipoprotein (a) (Lp(a))
There has been much discussion of Lp(a) of late. What it is, what does it do, why does it matter? The first thing to point out about Lp(a) is that it is, essentially, LDL a.k.a. LDL-cholesterol a.k.a. ‘bad cholesterol.’ However, it differs in one way. It has a special strand of protein attached to it, known as apolipoprotein A.
This protein is very interesting, from a blood clotting perspective, in that it is chemically identical to plasminogen. Yes, the one and only clot busting enzyme, switched on by tissue plasminogen activator.
But, big but. Apolipoprotein A is folded into a slightly different structure than plasminogen. Let us say it has a right handed thread, instead of left handed thread. (This is not fully accurate, but it is close enough).
This is important because almost of the receptors in the body have a symmetry to them, as do most of the molecules that nature provides, and most of them are left handed (levo-rotated). If you aim a right handed molecule at a left handed receptor very little happens – or strange and unpleasant things can happen. Thalidomide for example The L handed version causes no problems, but the R handed version causes serious birth defects – or was it the other way round. Remove one, or the other, version and you could give thalidomide perfectly safely in pregnancy. I would dare you to try.
As it is, thalidomide has been relegated to a cancer treatment, under the brand name Immunoporin. How does it work? It works by stopping angiogenesis (formation of new blood vessels) which cancer cells need to grow into a larger tumour mass.
The way that Thalidomide does this is that it damages endothelial cells, and endothelial progenitor cells (EPCs), as discovered in this study: ‘Thalidomide attenuates nitric oxide mediated angiogenesis by blocking migration of endothelial cells.’
‘….thalidomide interferes with nitric oxide-induced migration of endothelial cells at the initial phase of angiogenesis before cells co-ordinate themselves to form organized tubes in endothelial cells and thereby inhibits angiogenesis.’4
Okay, maybe that means nothing to you. What it means is that thalidomide stops new blood vessels forming, by blocking the action of NO on both endothelial cells and endothelial progenitor cells (EPCs). Whilst this is a good thing in cancer treatment, it is not so great in the developing fetus.
A pregnant women taking thalidomide will find that new blood vessels do not form properly in her baby. This means that arms and legs cannot get blood supply, so they don’t develop, so you are left with a severely deformed baby, often with missing limbs.
It would be interesting to know what impact thalidomide has on CVD risk? We already know what impact Avastin has on CVD risk. It increases it massively. Avastin, like thalidomide, works primarily by inhibiting endothelial cell growth and EPC production. Whilst this stops tumours growing, it also greatly accelerates CVD. Oooh, I do love the way everything is connected.
Anyway. To return to apolipoprotein A again. If you incorporate Lp(a), and thus apolipoprotein A, into a blood clot, it cannot be broken down. This is because tissue plasminogen activator cannot activate it, because it is right handed. Effectively, therefore, apoliporotein A blocks the enzymatic destruction of fibrin, thus protecting the clot from destruction. Why, you may ask, would the body create such a stupid thing?
Well, as with everything the body does, it is not stupid. It is very, very, clever. Lp(a) is only made in animals that cannot synthesize vitamin C. Guinea pigs, fruit bats, great apes and…humans. The reason for this is that, if you are vitamin C deficient, the body cannot manufacture certain important support materials/connective tissue, the most important of which is collagen.
Without collagen, your blood vessels start to crack apart. When this happens, blood escapes, so you start bleeding from the gums, and suchlike. This condition is known as scurvy. In scurvy you start bleeding all over the place and, in the end, you die from blood loss. It is what killed many sailors of in the olden days.
Along to the rescue comes Lp(a).. well, it can rescue you for a bit. Lp(a) sticks to cracks in blood vessel walls and forms, impossible to break up blood clots that ‘plug’ the gaps created by collagen deficiency. So you can see that Lp(a) is actually evolution’s way of protecting animals, that cannot synthesize vitamin C, from the early stages of scurvy.
All of which means that if you don’t eat enough vitamin C, and you have a high level of Lp(a), you will end up with a multitude of very difficult to break up blood clots scattered all over your arterial walls, and inside your arterial walls too. Thus, you are going to develop CVD at a rapid rate.
This, the ‘vitamin C deficiency’ theory of CVD was proposed by Linus Pauling (double Nobel prize winner) and Matthias Rath (and you can look him up too – but be prepared for some interesting information). Here is a short section from their modestly entitled paper ‘A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of This Disease as a Cause for Human Mortality.’
‘We have recently presented ascorbate (Vitamin C) deficiency as the primary cause of human CVD. We proposed that the most frequent patho-mechanism (think of this term as the ‘process) leading to the development of atherosclerotic plaques is the deposition of Lp(a) and fibrinogen/fibrin in the ascorbate-deficient vascular wall. In the course of this work we discovered that virtually every patho-mechanism for human CVD known today can be induced by ascorbate deficiency.’
So there you go, vitamin C deficiency is the answer to CVD? No, it is not THE answer, but it is an answer, or a part of an answer. There is no doubt that a low level vitamin C is a bad thing. There is equally no doubt that a low vitamin C level, associated with a high Lp(a) is a double bad thing. Furthermore, there is absolutely and completely no doubt that taking extra vitamin C would be a good thing for everyone – just in case.
However, Pauling and Rath, brilliant though their thinking was, made the number one error in medicine. They looked for the single cause, and the single cure of a disease. They became so certain they were right, that they stopped looking elsewhere.
Having said this, their ideas about the process of CVD were, in my opinion, absolutely right. They realised that the essential underlying process was: arterial wall damage, followed by blood clots, followed by the development of atherosclerotic plaques. But they thought it could all be explained by a single factor, Vitamin C deficiency. In this they were wrong. It is a great shame they did not look at the wider picture.
However, I hope you can now see what Lp(a) is, what it does, and why it is important in the whole CVD argument. It is not a clotting factor per se, but it has a huge impact on the clots that do form. Unfortunately, it seems that Lp(a) levels are genetically determined and there seems little you can do to alter them. I would suggest that, if you decided to get your Lp(a) level tested, and it is high, you should make sure you get plenty of vitamin C in your diet.
Summary
I realise that you may think I have taken you off on a couple of wide detours in this blog. More than a couple actually. However, my cunning plan was to give a sense of how everything in the physiology of endothelial health and blood clotting can be fitted together. Also, how it can be seen that any factor which has an impact on the development of blood clots (following endothelial damage), will have an impact on CVD through mechanisms that can be easily understood.
Looking at an even wider picture I hope that you can now see, why drugs such as thalidomide – which may seem a million miles away from CVD – are actuallly closely related. How Lp(a), which at first glance may appear to have nothing to do with the four step process of CVD, can be brought into the picture. In addition, where, and how, such things as VLDL and PAI-1 fit in…. to name only a few. Over the years I have followed the story down a million different pathways. Each fascinating, but there are far too many to discuss them all here.
Yes, it is a complex story. Did you really think it would be easy? Did you really think there would be ONE factor that caused everything, and ONE factor that cured everything? CVD is not binary, it is about propensity, chaos theory. It is about changing the odds here and there. It is about the weighting of the dice. You can improve the odds in your favour, but you will never make them zero.
Next….the repair process.
References
1: http://www.jlr.org/content/40/5/913.full.pdf
2: http://www.ncbi.nlm.nih.gov/pubmed/15780823
Dr. Malcolm Kendrick 
“Repair of the clot consists of forming a new layer of endothelium over the blood clot, thereby drawing it into the atrial wall.”
I believe you meant “arterial wall.”
Good stuff – still digesting it.
Thanks for your writing.
Amazing work, Dr. K. Thank you for your time, your perserverence and your ability to explain such complexity so clearly. I’m deeply grateful.
Dr. Kendrick,
Please drag me down any primrose path’s you like as long as you explain it with the common sense and humor that you have shown in this series of posts. Actually, I have found all of your posts to be of intense interest and value, even though I know only layman’s medical knowledge.
Most inspiring!
Terrie
re: Unfortunately, it seems that Lp(a) levels are genetically determined and there seems little you can do to alter them.
If the human race survives the invention of CRISPR-Cas9 gene editing, that might change.
In the meantime, your colleague Dr. William Davis is having some results lowering Lp(a) with a specific diet, high dose fish oil, perhaps some DHEA, and niacin as last choice. No specific advice on Vitamin C, which tends to be ample in the diet.
By way of disclosure, Lp(a) just came up in a user comment on one of his blogs today, where I contribute.
As has been mentioned on this blog PCSK9 inhibitors is the new fix. Interestingly it would appear that it lowers Lp(a) particularly when statins are also taken, albeit through a mysterious process involving the Ldl receptors. On a positive note CETP continues to fail. So looks like it’s toxic substances all the way down. Btw its large doses of vit c through a supplement, diet can’t give you those levels.
Dear Goutboy,
About Lp(a), there are many apocryphal posts on here by people going long and strong with readings way off the scale, so is it the disaster we believe it to be? Perhaps Dr K will have some encouraging suggestions for us.
Very good
A lot for me to absorb, but definitely another masterpiece. So thankful to have found this blog. Thanks.
Oh yes. Thanks for the irreverence, inspiration and your sense of wonder ✊
Thank you for yet another very interesting article
Thank you for new insights!
I am happy that ‘my’ Pauling ‘survived’ 🙂
And that I can continue to sip my 6 g C-vitamin a day without ‘fear’.
I guess that it is in the human nature to look for ‘unified theories’ and fall in love with the ones of your own creation.
Being sincerely impressed by the life and deeds of Pauling I have though noted some of his mistakes. The worst was of course when he kicked out Dan Shechtman from his lab when Shechtman claimed the existence of a the ‘odd’ feature of fivefold symmetry in the crystallography of matter and Pauling telling him “There is no such thing as quasicrystals, only quasi-scientists.” It is kind of an irony that Shechtman as Paulin received the Nobel in chemistry though almost 60 years later.
Goran
Vitamin C as a salt is not well absorbed. Have you ever tried liposomal vitamin C.
• 1,000 mg vitamin C tablet or capsule
Absorption 19% = 190 mg into blood stream
• 1,000 mg liposomal vitamin C
Absorption 93% = 930 mg into blood stream
So it is possible to get large amounts of vitamin C into the body without causing diarrhoea.
Right, so now we know how thalidomide did so much damage to developing babies, and we have an inkling of how and why making sure we have plenty of Vit C will help. I’m looking forward to the next chapter in the whodunnit. Thank you again, Dr K
I have read that individuals on ketogenic diets seem not to need extrinsic vitamin C supplementation beyond that derived from protein and fat of animal origin. This was demonstrated by Stephanson in 1928 and earlier by mariners who subsisted on carbohydrate based diets versus animal based ones.
if you stay away from sugar(s), your vitamin C does not deplete rapidly – if at all.
In addition to the comment by Dr. Kendrick on the effect of sugar consumption on vitamin C depletion, if you keep your carbs low as well in your diet, as is implied by low carb and ketogenic, triglycerides will remain low, which seems like a good idea! So, maybe diet can have something to do with CVD?
Maybe. I tend to stay away from talking too much about diet as there is no subject on Earth that creates so much heat – with so little associated light. Far too many people sit within their super-triple-fortified castles of thought, and instantly lob poisonous mortar bombs at anyone who dares hint at having even a wafer-thin difference of opinion.
Excellent article by Dr. Kendick once again! Seems I’ve been on right track for years now: studied the work of Linus Pauling and Dr. Rath about 5 years ago and started larger doses of vit. C (not megadoses, but 2g and eventually decresed to current 750mg). In the same time reducing carbs to 20-100g/day, which reduces the requirement of vit.C. Too much of a good thing may also be too much!
Collagen in addition to vit.C also needs sulfur. There seems very few comments on this. I have good results of this experimenting with myself.
What is your opinion of supplementing with sulfur, Dr. Kendrick?
“…and instantly lob poisonous mortar bombs at anyone who dares hint at having even a wafer-thin difference of opinion.”
Malcolm!
How very true!
But why?
Though, especially the “establishment” seems to be well equipped in the defence of ‘the rules’ also in nutrition.
Very interesting in this respect is how Professor Noakes in South Africa now has been brought to an incredulous series of ‘trials’ for ‘misconduct’ when he on Twitter suggested a mother to wean off her baby to a LCHF diet. A hoard of judges and advocates have been involved so far in a series of proceedings which are also scheduled to continue in October this year.
Well, it took well over three years, 2005 – 2008, for our medical authorities in Sweden to clear our Dr. Annika Dahlqvist from the accusation of misconduct when she suggested her obese DM patients to go LCHF and with excellent clinical results and well in tune with with the rules of ”well established experience and science” according to the final clearing verdict but to the shock of the surrounding world who had expected her to hanging from the gallows tree.
What about a GP who officially suggests a CVD patient not to take the statins – same rules – same trials and a final clearance or the gallows tree?
When you are wrong, the only defence of your position is to become extremely angry and go on the attack. It is part of the general sequence. First they ignorre you, then they attack you, then they claim that what were saying was self-evident all along. Attacking individuals is the first step of, inevitably, losing the argument. Of course, those in power never actually lose power. As was once said of a famous UK politician Lloyd George. (sic) ‘He doesn’t care what direction the carriage is going, so long as he is holding the reins.’
I would prefer to see what Dr. Kendrick has to say about the cause of heart disease or atherosclerosis, respectively, wait for the series to be completed, before jumping to hot debates about diets. In my opinion it does not belong here (yet).
But seeing this, should I break my self-imposed rule?
“a mother to wean off her baby to a LCHF diet.”
What a nonsense, not providing a high fiber (= complex polysaccharides) diet also after weaning, after the baby enjoyed and thrived! on mother’s milk full of very special sugars, HMOs (human milk oligoSACCHARIDES).
Do people realize that what may be a therapeutic approach in certain diseases (maybe short-term), should not be considered as the only right approach to human nutrition? Or our gut microbiome nutrition, to be precise?
http://highsteaks.com/f/index.php?topic=542.0;msg=3054
>>Ascorbic Acid and the Immune System
>>…
>>The inhibitory effect by glucose of the actions of ascorbic acid could well explain the lack of beneficial effect of ascorbic administration in many studies reported in the literature because few, if any, such studies controlled for dietary carbohydrates.
>>
>>In light of the current dietary sugar excesses and concomitant obesity epidemic, clinicians should be reminded of the great importance of the long recognized but largely unappreciated inhibitory action of glucose against ascorbic acid.
>>
>>In summary, ascorbic acid is essential for effective immune system function and, further, it can be a potent immune system stimulator when high glycemic dietary carbohydrates are restricted.
>
> – http://orthomolecular.org/library/jom/2005/pdf/2005-v20n03-p179.pdf
>
>Point being, people who don’t consume significant carbohydrates are able to utilise what little Vit C they get from their food, whereas those who consume a bunch of carbs will end up suffering from autoimmune dysfunction and the end-points that come from them.
>
>Think scurvy and sailors who supposedly subsisted for long periods on biscuits and such but with no citrus fruit or other significant sources of Vit C. If they skipped the cookies and just ate meat their immune system wouldn’t be compromised.
@ Diana,
the amount of GOS (fibre) in milk is very low, but lactobacillus (“unexpectedly”) also metabolises saturated fats. It cannot, however, metabolise polyunsaturated fats, one reason why milk is low these and high in SFA.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274236/
puddleg58
“the amount of GOS (fibre) in milk is very low”
Low? Oh please. And what GOS? I said HMOs. Human breast milk contains around 20 g/l of HMOs, plus 70 g/l lactose – which is a sugar too. A newborn drinks maybe 0,75 l/day. Quite some saccharides for a tiny baby, don’t you think?
Human milk oligosaccharides: Every baby needs a sugar mama (Bode, 2012)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406618/
“Oligosaccharide amount and composition vary between women and over the course of lactation (reviewed in Kunz et al. 2000). Colostrum, the thick, yellowish fluid secreted by the mammary gland a few days before and after parturition, contains as much as 20–25 g/L of HMO (Coppa et al. 1999; Gabrielli et al. 2011). As milk production matures, HMO concentrations decline to 5–20 g/L (Coppa et al. 1999; Kunz et al. 1999; Newburg et al. 2000; Chaturvedi, Warren, Altaye, et al. 2001; Davidson et al. 2004; Bao et al. 2007; Gabrielli et al. 2011), which still exceeds the concentration of total milk protein.”
Extremely well done and most valuable to me in my practice.
THANK YOU!!! I have been trying, beyond inflammation, to understand the connection between high triglycerides and CVD risk, so that I can explain it to patients. NOW IT MAKES SENSE. (sorry for the all caps yelling but I do feel like stepping onto the deck to yell this down the street)
Hi Malcom,
Thanks for doing these blog posts. I find them fascinating.
I thought I read somewhere that vitamin C is structurally similar to glucose and that it uses the same pathway to get into cells, which has lead me to wonder if there’s a potential for either excess glucose to somehow get in the way of vitamin c making into the endothelium, thereby disrupting collagen synthesis, or through insulin resistance causing vitamin c to be “resisted” as well. I favour the first theory because a) it helps me sleep at night knowing that managing insulin resistance through diet may be enough to save me and b) because non insulin resistant type 1 diabetics can also make their blood vessels fall apart if they let their glucose levels get out of control (or is this just lack of insulin to mediate vit c into cells or just different processes?) . I managed to find one study that seems to make the same arguement (Google the scorbutic metaplasia hypothesis). I’d be interested to know what you think and in particular, if insulin resistance is still a problem even if one is able to manage it via diet to the extent that all metabolic syndrome markers appear reversed.
Thanks
Of course, this too is connected. As is everything. Vitamin C and glucose play a complex dance in the body.
>It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down uric acid, also a characteristic of primates. Uric acid and ascorbate are both strong reducing agents. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.
– https://en.wikipedia.org/wiki/Vitamin_C
Dr. K – Thank you!
As one of my previous comments mentioned, I have been “blessed” with a high genetic Lp(a) number (over 100) as your post mentions. However, I am in great health otherwise and asymptomatic for CVD. However, as a result of NOT being a fruit eater or vitamin taker, my first calcium score test was over 700 last year and sent me and my family over the edge.
I think my personal life example verifies your description of someone that has high Lp(a) and did not take enough C = high calcium score (which I assume is a part of the repair process which you will explain in your future posts.)
Just FYI, as a result of the high calcium score and the high Lp(a), my vitamin C intake is now much increased, as well as supplements of fish oil, vitamin K and a slo-Niacin.
I have an LP(a) of 253 nmol/L in one test and 310 nmol/L (12 mg/dL), from two different labs at two different times. However, the “high” level cutoff for each is different: “high” for the 253 test is 125 nmol/L, whereas “high” for the test where I got 310 nmol/L was 260 nmol/L. And then I’ve read studies which indicated these levels really aren’t that high, and others than indicate these are high.
This one, for instance, with an LP(a) of 12 mg/dL, indicates basically near 1 relative risk ratio (see Figure 2):
http://www.ncbi.nlm.nih.gov/pubmed/19622820
But mg/dL would put me in Quintile 5, which is the worst Quintile in this study:
http://www.nejm.org/doi/full/10.1056/NEJMoa001066
However, Quintile 5 goes from 8.2-47.5 mg/dL, which seems a bit ridiculous.
I’ve not gotten a calcium score done, though, as I’m having difficulty finding a place that does this. Also, I have to pay for the LP(a) test myself, as neither my cardiologist nor my GP will do this test.
Oddly, the test with the higher number was when I was taking more fish oil and the test with the lower number was when I was taking less. Will have another test done soon.
Dr Kendrick
Brilliant and clearly explained.
For those of us over 30 on lipoprotein a, are we, as your your compatriot Private Fraser would say ” doomed, all doomed”?
What about Pauling’s mixture, vitamine C and Lysine, or is the answer to be found in the next instalment?
Thank you again for this monumental work
Pauling and Rath can suck you in to their world and there’s some compelling evidence. The problem I have is that how does it explain the somewhat big differences in population CVD. Do the French have large doses of vit c. I think the strength of this blog is that it seems to say there are various, maybe independent causes some are manageable some it’s luck. We should also look after our liver first and foremost.
Goutboy,
It doesn’t and nor would I expect it to. Vitamin C is just one factor of many and nothing works in isolation. To remain healthy requires that we supply our body with everything it needs to maintain/repair itself otherwise an increasing degree of triage will occur in an attempt to keep going in the short term at the expense of long term health. Deficiency of any nutrient will have an effect – some subtle and long term, others more noticeable and apparent in the short term. Modern life has increased the need of some nutrients more than others to the extent that even those eating a good diet may still be deficient. Doesn’t matter which population you look at there will always be differences because of genetic, environmental and lifestyle choices. Only in the broadest sense can you point to disease and a nation’s health e.g. Western diet and Western health.
The prime reason we suffer so much illness in modern society is that we are facing an ever more hostile environment that we (in ignorance and greed) have created while at the same time the food we consume has, overall, significantly deteriorated in quality – a direct result of commercial profit driven interests. Although many foods may look the same (perhaps even better) then they did a hundred years ago the nutrient content has significantly declined (genuine organic food excluded). Add to that the endless supply of “dead” processed foods and a barrage of less than useful medications taken in an attempt to correct problems caused by lifestyle choices is it any wonder that we are so ill? The human body can adapt and deal with a certain amount of abuse but there comes a point when the onslaught becomes too great and health suffers.
For many the road to a compromised life starts in the womb as a direct result of the mother’s poor nutrition decisions and postnatal feeding decisions (formula vs. breastfeeding – for those that disagree take a look at this http://www.westonaprice.org/childrens-health/the-scandal-of-infant-formula/ and http://pediatrics.aappublications.org/content/115/2/496.full ). Then what happens? Many modern mums feed their growing children with too much junk food and pacify/reward with sugary “treats” and have no idea of the harm they are doing because a poor diet is all-pervasive in modern society.
Dr Kendrick,
I truly feel privileged to be among the first ones to read about the development of a cohesive explanation of the cause(s) of a disease that so far has confused and eluded medical science. My agreement or disagreement with your explanations so far would be irrelevant as I have no background in the field. My interest in various fields of science has thought me however that the elegant processes (some at first appearing ‘stupid’) you describe woven into a nearly impossibly complex system of checks and balances has an unmistakable ring of truth to it.
I remember you saying in an interview something along the lines that your father had not been able to impart on you his mathematical skills but you might be wrong on that. Whether through nature or nurture it seems that you cannot stray from rigorous logical thinking. 🙂 .
Thank you for sharing your process of discovery.
Once again, concise and thoughtful data, coupled with the good doctor’s pragmatism and honesty. Having ‘suffered’ first-hand and survived, I really DO want to gain a better understanding of CHD, ( which I’ve always considered a misnomer. I don’t feel that I had/have a disease as such: merely almost total coronary artery blockage leading to infarction). Anyway, this latest part of the saga, although containing some very esoteric jargon, is written in such a way that a moderately educated person can understand it. The vitamin C connection was priceless. I really didn’t know about the animals non-synthesis ability connection. And, whilst the Pauling ‘single’ cause theory was only part of the ever-evolving picture, it was nonetheless important, and ironically for perhaps another reason. The Doctor often apologises for going off on the odd tangent before returning to the main topic. I would opine that he continues to do this without fail. It gives us all a bigger picture to look at in a very complex book but it also prevents us from forming just one answer or opinion. A reminder based on past study. Cannot wait for the next episode .
Great series!
Re this: “Unfortunately, it seems that Lp(a) levels are genetically determined and there seems little you can do to alter them.”
Some studies have shown diet can change it significantly:
Low Fat (56g), Low Vegetable: increase by 7%
Low Fat (59g), High Vegetable: increase by 9%
http://atvb.ahajournals.org/content/24/3/498.long
but
Low Carb (13%): decrease by 11.7%
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1481590/
PCSK9 does it even better particularly with added statins. The new wonder drug as has been outlined on this blog. The LDL is dead, long live the LDL.
If spikes to blood glucose and insulin cause damage to nerves, eyes, toes etc. then perhaps they cause damage to the endothelium as well. I image blood glucose and insulin spikes cause damage to every cell in the body? During a documentary called Inside Natures Giants researchers were looking at a whale. One researcher commented on its clean blood vessels. Whales eat a low carb diet.
As always – Wow – and thanks for the discussion. All of this makes so much sense and is clearly not a secret so why, oh, why are our doctors still hanging on to the cholesterol hypothesis. My question from your blog report is why would my clogged artery have been stented instead of giving me something to dissolve the clot instead? Keep writing, I continue to buy your book and hand them out!
I am totally fascinated by how you have fit everything together, but why is there no mention of calcium? I can’t see that calcium is simply one of the random things pulled into the formation of the plaques.
Not at the healing process yet
re: …why is there no mention of calcium?
Whilst we await the next installment, some observations on calcium…
Calcium in the modern diet is not in the ancestrally consumed forms (the hydroxyappatite form found in animal bones, and as a trace mineral mix from unfiltered ground waters). Modern supplements tend to be other compounds (citrate, carbonate, malate). Calcium, usually carbonate, is also pervasive as a not-so-inert filler and binder in tablets of all sorts, not to mention abundant in processed food-like substances. We get too much Ca, largely in inappropriate forms. This junk Ca rarely ends up as bone.
We are generally deficient in vitamins needed to get the Ca to go where we’d like: bones. The Vitamins in question are D3, K1, and K2 (MK4, MK7). RDA and consensus titer for these are likely too low. Formulations matter. The result may be that Ca ends up in places we’d rather it didn’t, but to swing around to the topic, there is surely ample in circulation for the etiology yet to be elucidated in this series.
Ötzi the Iceman, who lived 3300 years ago, apparently had a fully expressed genetic tendency to heart disease (and bad teeth). He would have been getting minerals in their ancestral forms. What he probably could have done without, on those scores, was the neolithic grain he was eating (einkorn, an heirloom wheat). Carbohydrates become triglycerides and VLDL (denovo lipogenesis). The amylopectin in wheat, and its ancestors, is an especially high glycemic carb; more provocative than sucrose. So modern consensus diets aren’t helping here, for multiple reasons.
The ancient Egyptians also, apparently, ate a high carb diet from their abundant agriculture, and suffered from all the heart disease problems – and cheese cake and Mars bars hadn’t even been invented 🙂
Apolipoprotein A…
To paraphrase Dr. Göran Sjöberg: I am also happy that my microbial theory of CVD survived. Mammalian ApoA resembles (based on primary amino acid sequence and predicted structure similarity) microbial lipid droplets proteins.
Very inspiring, as always – thank you Dr K
Thanks Doc. Really interesting and informative.
Peter
Sent from my iPad
>
Can I ask what might seem obvious to more scientific readers: does the current measurement of blood cholesterol differentiate between LDL cholesterol with Lp(a) and LDL cholesterol without Lp(a)? Or have I misunderstood the section on lipoproteins effect on CVD?
Lorna – In my case, the test for Lp(a) had to be ordered separately from the “standard” chol. test. Also included in this test was additional detail about particle size, LDL and HDL size, etc.
I do not know – or understand how the value for the Lp(a) flows into the LDL number (if it does at all). I have also heard there are a couple of different ways of measuring Lp(a), some using a calculation, others an actual testing of the particle number. There are also several different ways of calculating the Lp(a).
It’s all quite confusing and complicated – mainly because the testing of it by citizens is fairly new and there is disagreement as to its importance, purpose, etc.
Thanks, Dr. Kendrick. You write with clarity, and are always a pleasure to read. I find it all quite accessible to this non-scientist. I am curious about Lorna’s question, though. It isn’t clear from rereading the passage whether all LDL has Apo A, or some do, and others do not. Since LDL is the ship, perhaps some have only cholesterol as passengers, and in others, Apo A has snuck aboard.
Only Lp(a) has apolipoprotein A attached.
Malcolm, this is confusing me. You say Lp(a) is “essentiallay” a LDL with apolipoprotein A attached. Is the apolipoprotein A same as apoliporotein A1 which sits on the HDL?
No, it is apoliprotein(a), sometimes called apolipoprotein A. Not A1, nothing to do with A1
Fascinating! It seems with CVD, as with most things in Nature, a corollary of Murphy’s Law applies” “Everything is more complicated than it looks”. Which only makes sense — with the infinite number of conditions animals are exposed to, there would have to be a Plan B, a Plan C, etc., for the creature’s body to manage a damaging event, or its kind would quickly go extinct.
Malcolm, this is an excellent piece of writing and a fascinating series of blogs.
Here’s a paper about lp(a) and psoriasis which may interest some.
http://www.ncbi.nlm.nih.gov/pubmed/19335423
This line caught my eye: “the VLDL concentration was calculated according to the formula: VLDL cholesterol = triglycerides/5”
Is that the usual method?
Can we just say itts; ‘it’s the triglycerides stupid’ ?
I believe that calcification begins when there is insufficient vitamin K2 to carboxylate matrix GLA, which is the mechanism to prevent calcium being deposited in the artery walls. I took high dose D for a while without realizing that if I didn’t also have K2 I was accelerating the deposition of calcium in my artery walls.
How much D3 and K2 do you take.
Anyone recommend a good book on low carb. Can you drink wine on low carb.
Hi Ben, there are good blogs of this lifestyle:
dietdoctor.com marksdailyapple.com and https://intensivedietarymanagement.com/
The Art and Science of Low Carbohydrate Living sits on my bookshelf. Those should help you getting started. There’s a good guide in many languages what to eat and what not on Dietdoctor.com
Dry drinks are allowed – including red and white wine (see above)
Hi Ben, 6000 IU gets me to about 50 ng/ml. I take 30mg of K2 mk4 and 180mcg of K2 mk7.
I’d also recommend Volek and Phinney’s ‘The Art and science of low carbohydrate living’. I think it’s written with doctors and nurses in mind, but I managed and it’s clearly written.
It’s a good reference to go back to.
I’d like to ask a question those people who supplement with vitamin d and vitamin K2 (MK7). Assuming you stop taking vitamin d in the summer, do you also stop taking vitamin K2? If vitamin d is produced naturally by some time in the sun, do we still need to help it by taking K2?
Personally, during the winter I take 10,000IU vitD/day & 1000mcg K2-m4 + 100mcg K2-m7 in supplements (+5min UVB lamp when at home) + plenty (ca. 50g/day) of “MK2 cheese”. During the summer, no supplements but plenty of cheese to go with the D3 from sun. Who knows if that’s ‘ideal’.
Ben, I’ve been LCHF for 4+ years and I certainly drink wine! :-))
Ben,
Recommend you have a look at The Real Meal Revolution: The Radical, Sustainable Approach to Healthy Eating by Prof Tim Noakes, Sally Ann -Creed and Jonno Proudfoot. Great food, the pictures will make you want to try the recipes and you’ll be supporting Prof Tim Noakes.
Re supplementing vitamin D and K2 – don’t forget vitamin A and magnesium. Here’s Dr Kate’s recommendation for dosage http://doctorkatend.com/faq/ . With respect to magnesium supplementation you can try applying a saturated solution of magnesium chloride (buy magnesium flakes sourced from the Zechstein Sea – much better value than prepared magnesium oil but discard the residue that settles out) to as much skin as possible (magnesium ions will be absorbed in approx. 20 mins after which you can rinse off the residue). It will not upset your stomach and it’s a great skin conditioner, however some people find that the solution stings (you can dilute to suit but this obviously reduces the amount of magnesium available). Alternatively supplement with magnesium (Dr Kate’s book provides details) but according to her magnesium citrate represents the best value however if you find it has too great a laxative effect magnesium taurate is a better choice and, quoting Dr. Kate “.. is the recommended form of magnesium for people with heart problems”.
” I took high dose D for a while without realizing that if I didn’t also have K2 I was accelerating the deposition of calcium in my artery walls.” And creation of kidney stones. I took a lot of of D and got a lot of kidney stones. Then I started taking some K2 but an osteopathic doc convinced me to take a prescription level dose of D. Lots more kidney stones. Now I take lots of K2.
Fortunately, I don’t appear to have suffered from kidney stones…just two heart attacks 😉 I have taken quite a lot of C so perhaps that has helped?
Thank you, thank you, thank you.
This series is rather like an elegant seduction! Thank you again Dr Kendrick, for making this very technical subject understandable by non-medics – a rare talent indeed. As ever, on tenterhooks for the next instalment.
Sulfur?
It seems, that this element is even more important for the elastic properties of the arteries, than for collagen: http://www.ncbi.nlm.nih.gov/pubmed/12868588
https://en.wikipedia.org/wiki/Elastin
This in turn has significant implications on blood pressure – one of the most important risk factors of CVD.
What do you think?
Ari
Try http://people.csail.mit.edu/seneff/
Dr Seneff has some interesting ideas on sulphur and other things as well, and, as far as I know she is medically “unconflicted”
Yes, I communicate with Stephanie on a reasonably regular basis. She is an incredibly bright lady who has, however, in my opinion, done a Linus Pauling. All of heart disease can be explained by factor x.
Thanks Mike!
I’ve read all her studies and been in correspondence with her. Not about this, but about GMO, glyphosate and mad-cow disease.
The reason, why I suspect sulfur to be beneficial for heart health is the fact, that many countries with low levels of CVD reside in areas with volcanic activity eg. lots of sulfur in surface of earth (Japan, Mediterranean countries). Also, because it is a main building-block of arteries / collagen / elastin as well as some hormones (eg. insulin, which is essential for good glucose metabolism).
Hasn’t she also done some research on cholesterol sulfate, which is water soluble and circulates in the blood stream freely? Any idea how this all fits in or what the purpose of this is?
There are natural ways to reduce some of the risk by diet;
https://www.sciencedaily.com/releases/2012/05/120508124545.htm
They began by conducting a high-throughput screen of a wide array of compounds to identify PDI inhibitors. Among the more than 5,000 compounds that were screened, quercetin-3-rutinoside (rutin) emerged as the most potent agent. “Rutin was essentially the champion compound,” says Flaumenhaft.
A bioflavonoid that is naturally found in many fruits, vegetables and teas including onions, apples and citrus fruits, rutin is also sold as an herbal supplement, having received a special designation for safety from the U.S. Food and Drug Administration (FDA). Surprisingly, studies of the rutin molecule demonstrated that the same part of the molecule that provides rutin with its ability to inhibit PDI also prevents the compound from entering cells.”That finding explained how this compound can be both a potent inhibitor of PDI and a safe food supplement,” says Flaumenhaft. “Our next questions were, ‘Is this compound anti-thrombotic? Can it prevent blood clots?'”
The team went on to test rutin in a mouse model of thrombosis. Because they knew that humans would be taking rutin in pill form, they included studies in which the compound was administered orally and determined that it successfully retained its anti-thrombotic properties when it was metabolized following oral ingestion.
“Rutin proved to be the most potently anti-thrombotic compound that we ever tested in this model,” says Flaumenhaft. Of particular note, rutin was shown to inhibit both platelet accumulation and fibrin generation during thrombus formation. “Clots occur in both arteries and in veins,” explains Flaumenhaft. “Clots in arteries are platelet-rich, while those in veins are fibrin-rich. This discovery suggests that a single agent can treat and prevent both types of clots.”
Interesting to note that a tissane of Rue is a traditional herbal remedy for varicose veins.
But the question arises, do you always want to be interfering with the innate clotting processes? Seems to me that there would be both indications and contra-indications for doing that.
BTW parsley has rutin and other flavonoids, calcium, vit K and more vit C per gramme than citrus. Have some medicinal tabouli but leave out the cracked wheat.
The gathering plaque area at the same site, rather like an unexploded bomb, can blow at any time. Only very lately does the diet become important to many of us. It would seem prudent to modify, reduce our simple carbs, at least to help our bodies Give nature a chance, so angry with Ancell Keys, which is futile and daft of course, but there you go. You have such a deep and passionate interest in CVD Dr Kendrick, but with the wonderful balance of an objective mind. So much information out there it is good to have such guidance. Have to say though, I bake occasionally, did so often when the children were small, my healthy Parkin! And equally healthy cream cakes, have to be experienced at times. Sorry, don’t follow my advice
I just finished your first book on the subject, The Great Cholesterol Con. Fantastic read; informative and humorous, to boot. I feel much less in the dark as to where you are taking us than I did a couple of weeks ago. And feel that I truly, for the first time, understand the utter insanity of the cholesterol (diet-heart) hypothesis. Also, as someone who’s HPA-axis has been taking repeated, enormous hits over the last decade, I now have something I feel I can really work with. A big thank you for explaining it to me in such as clear and succinct, and convincing way.
You seem to have shifted a bit on some ideas from back then (Indeed, I think you might have taken yourself to task in 2008 for saying something like: Unfortunately, it seems that Lp(a) levels are genetically determined and there seems little you can do to alter them. You weren’t much of a fan of genetic predisposition). But all is well; people’s ideas evolve with new evidence. As a reader of your book, am I to expect a twist in parts VII, VIII, etc?
I deposited some calcium where is certainly wasn’t wanted last summer when I developed calcific tendonitis in my elbow. I wouldn’t recommend it.
Hoping the next healing and repair installment might enlighten me as to how I stop plopping down unwanted calcium in my tendons or anywhere else for that matter.
Rachel…vitamin D, vitamin K2 mk4 and mk7 plus cooked carrots for your vitamin A 🙂
Thanks Andrew – and yep, already on the case ;-D Learned the hard way about the importance of K2. And yet the elbow specialist had nothing to offer on the subject. Funny what knowledge one can pick up from the internet.
Google is my friend.
Where do you get vitamin K2?
Hi Bob, AOR has Peak K2 mk4 which are 15mg capsules and I buy the Jarrow K2 mk7 (90mcg). Cheers, Andrew.
Why not try some grassfed liver?
Andrew, I eat liver for Vit A.
Gouda is a good source too. And clarified butter (ghee) from cows grazing in the summer.
Andrew – not carrots for vit A. Dr Kate (Vit K2 and the Calcium Paradox) explains that carrots only have Beta Carotene and the conversion to Retinol is pretty unreliable. Once again its liver for large amounts and smaller amounts in eggs etc.
Angela, point taken, however, I have trouble with the idea of eating something which is the main detoxification mechanism for anything… 🙂
Dr. K – if I had a brain like yours I’d write a blog. Thank goodness you did. You are absolutely brilliant. I don’ understand it all – I am a bearer of very little brain, but I understand enough. Just one thing, I can’t let it go, you said ”At times I am just staggered by the amazing ingenuity of human physiology. How the hell, I think to myself, did all of this evolve?”. I know the answer to that one: it didn’t. Far too amazing to be just evolutionary chance. How absolutely, utterly and completely amazing physiology is. Even Apple couldn’t design a computer as mind boggling as the human body. It’s a reasonable conclusion, though I know not many of us conclude it.
Evolution isn’t chance. It’s adaptation to one’s environment. We are finding how readily this can happen with the current study of epigenetics. All the things the good doctor and other commenters spoke of — the way our ancestors lost the ability to manufacture Vitamin C (too costly a process when it was so abundant in food), developed the ability digest dairy when animals became domesticated (allowing exploitation of an easily-available nutrient resource), etc.– are adaptations (responses) to environmental conditions. Please, let’s keep the discussion science-based.
Science is a slippery concept to keep hold of, I find. The main problem I have is in trying to decide which of the million rabbit holes I should follow. Magnesium, K2, Homocysteine, Sulpher, Vitamins B12/6/folate, Vitamin D, Flvainoids, anti-oxidants, Vitamin C, Vitamin A – the ratio of one vitamin to another…. Where do they all end? One of the problems, I think, is that modern processed food, during the processing, removes many vital substances. Then the manufacturers try to put them back – in strange ratios – based on recommended daily intakes that bear no relationship to any known outcome data, or any science frankly. Whilst the problem fragments into a billion pieces, the solution seems simple. Eat food that is as close to ‘natural’ as you can manage. Evolution probably designed us to eat it this way.
Don’t worry Annielaurie, I have no intention of causing any trouble with my unscientific views, however entitled to them I may be. I just couldn’t resist that one. It’s worth mentioning though, regarding keeping things science-based, that science itself doesn’t give us answers to everything, and we can’t always believe the Scientists. The End.
Ah, well, Sue, NOTHING gives us the “answer to everything”, whatever that may mean. And as far as believing “the scientists”, there is no monolithic group “the scientists”. Scientists, like you, are entitled to their opinion, and science embraces a spectrum thereof. Difference is, if scientists can’t produce facts to back up their opinions, eventually they are ignored. Even the ones that think saturated fats are BAD. The cholesterol haters have already gotten their comeuppance — even the USDA is ignoring them.
Annielaurie. True, we don’t know the answers to everything, but at least Dr K and others are having a jolly good go at giving us some good ones. I don’t think that ‘the scientists’ are ignored when they can’t back up their facts though. Otherwise there would be no need for blogs like this, and everyone would all be happy eating butter and bacon 😉. In the UK we are still urged that we should eat a low fat diet, a recommendation which we are assured is backed up by ‘scientific’ research. My nurse at the Diabetic Clinic still gives me this advice, in spite of the fact that she was amazed that my blood sugar dropped after following a LCHF diet since I saw her 6 months ago. What can she do? That’s how she was trained, and presumably she believes in the science behind her training. I’m thinking of giving her a copy of Dr K’s book next time I go!
Dr Kendrick,
based on recommended daily intakes that bear no relationship to any known outcome data, or any science frankly..
How very very true – unfortunately this attitude tends to prevail. I think ina previous blog you said there was an attitude that “something must be done”. The example as I remember was six weeks strict bed rest.
Malcolm,
“Science is a slippery concept to keep hold of, I find. The main problem I have is in trying to decide which of the million rabbit holes I should follow.”
Excellent!
Exactly my own view!
My approach now is to have a very broad approach to the CVD issue and my LCHF life style is then part of that together with wood chopping, vitamin C, D, K2 and E. It doesn’t seem to hurt anyway. If you find ‘proofs’ that something may beneficial, add it, and if finding ‘proofs’ that something could harm you, refuse it; e.g. CABAG and ‘all’ heart drugs.
I believe what Sue Richardson was saying is that the evolution of the life forms and their complex biology is not something that could have arisen by random mutation and natural selection alone. But the adaptations and changes within existing organisms such as losing the ability to synthesize vitamin C and the subsequent alterations to the blood clotting cascade is well within the type of evolution you are talking about. I don’t think they are the same thing, nor is it unscientific to mention it.
Annie:
Of course it’s chance. Every tiny – or major – chance change that occurs in each person’s genetic make-up gets passed to the next generation, provided the age of procreation is reached. If it doesn’t change anything, it stays. If it’s an advantage – major or minor – it stays. If it’s a disaster or just a disadvantage, it dies – quickly or gradually, respectively – in succeeding generations.
What’s difficult to imagine and accept is the immense amount of time involved for all the changes to occur. This amazing human machinery we have resulted from the enormous number of chance changes that it took. Nothing more.
We’re wasting time playing semantic games. “Chance” as a concept the “intelligent design” folks use to disparage evolution and “chance” in the sense you are using it are two different things. And perhaps epigenetic changes that can affect genetic material are something else again.
Annie,
What, you don’t think a good semantic discussion is a fun thing to do while waiting for VII?
Anyhow… “adapt” is an active verb implying intention, the result of which is “adaptation”. If anything sounds – to me – like a word that would be used by the “intelligent designers” (I also refuse to dignify them with Capitals!) it’s the word “adaptation”. Wait now. Written English is a funny language. I believe I now understand where your sympathies lie. I sympathize.
(Save epigenetics for another day.)
It could be fun if I had more time. One could postulate that some evolutionary changes were “intentional”, for want of a better word, perhaps not on a conscious level, even among nonhuman animals. Perhaps “cultural” would be a better word, but that word, too, carries a certain baggage. A population that learned a behavior that gave them a survival advantage would teach this behavior to its offspring, and it might spread to other populations. Eventually, if we are to believe the epigeneticists, this behavior, or perhaps some other environmental factor they sought out, could possibly affect their genetic material. There is so much we don’t know. But none of it requires an intelligent designer.
Personally, I think there’s too much information about nutrition/heart disease available and it’s unclear how much of it is scientifically sound. For instance, above, people say not to take vitamin D3 unless you’re taking vitamin K2. One of the best sources of vitamin K2 is cheese. However, the author of Wheat Belly (and I’ve read this book and think he’s likely correct that modern wheat is bad for us or at least for me) wants us not to eat dairy, because of the proteins dairy has. I never ate cheese while on low fat (heaven forbid! Cheese has FAT in it!), and now I’m on a low carb diet, I find I really like cheese, it fits into my low carb diet (can be 80%+ fat), yet I can’t eat it.
Also, I note that some of the vitamin K2 studies are epidemiological, which means they could be true but most likely aren’t. (The same can be said for pretty much anything, including evidence for and against dairy.)
Yikes! Will it never end? Whom should be believed? And why?
The best thing to do might be to ignore it all. Keep on a low carb diet, get sun when you can, and don’t read anything.
No, don’t ignore it all. Obviously have extra salt with the epidemiological stuff, but when there is something clear going on with the biochemistry (e.g. K2 carboxylating Matrix GLA), I’m sure we should give that extra credence.
BobM
Nice comment. Your last sentence says it all. Ignore all epidemiology studies unless they actually meet the late Prof Bradford Hill’s criteria. (most don’t), ignore most meta-analyses as they select studies to get the “right” answer and eat HF and fresh food and limited food containing glucose and fructose.
Whenever I hear of a meta-analysis, I ask myself why this was necessary. I mean properly designed studies have the power to answer questions in themselves, and if a meta-analysis is called for, it probably means the effect is too small to really matter – like the ‘benefits’ of taking statins.
I no longer believe in diet epidemiology. If they could get saturated fats and salt so wrong, why believe them about anything. I mean, you just can’t find matching populations, some of whom eat a lot of SF’s and some very little, and as the word gets out that X might be bad for you, health conscious individuals would (but maybe less and less) avoid X – thus skewing the studies even more.
Eat a variety of things that are tasty, but not to excess.
re: …the author of Wheat Belly … wants us not to eat dairy, because of the proteins dairy has.
Not quite (speaking as the guy who answers the routine questions on the WB blog). Bovine diary elimination is suggested in cases of weight loss stall, and of course as a means of detecting any diary intolerance. The considerations include:
• insulinotrophic response to the whey fraction,
• reaction to the beta casein A1 common in North America herds, and
• good old lactose intolerance (which I lately read was found in Ötzi the Iceman)
Humans are likely not yet fully adapted to bovine dairy.
Aged cheeses are the least troublesome for nearly everyone. General dairy from A2 cows is a solution for many reactive to dairy. Caprine (goat) dairy appears to be the most benign, and is what my family uses, as one person is quite reactive to unfermented bovine diary (which is all A1 around here).
Dr. K’s comment “which of the many rabbit holes………” is so apt. It is impossible to follow or believe all the info out there, so at some point we just have to go with what makes sense to us, hold our nose and jump off a cliff and hope to God. Your comment Bob “stay low carb, get sun, and don’t read anything” gave me a good laugh. There is some truth in that for sure! However although there are different opinions out there in “low carb land”, regarding dairy products I think it’s very important to go with what suits us. For example Paleo is quite strict re dairy, because some people don’t tolerate certain milk proteins, they can be inflammatory. But others can tolerate them, myself and husband for example and we eat loads….not straight milk, but yoghurt, kefir, cheeses. My two adoptive daughters who originate in southern India, have trouble with some dairy, but can eat high carb, although not much bread, mostly rice, I don’t think they would do well eating low carb. When I started out looking into all this it was overwhelming….eat so much of this a day, take this or that supplement every day. One person can’t do all that, you’d be eating and popping pills all day. For example Dr. Terri Wahls, who has had great success curing her own and others m.s., recommends 8 cups of veggies a day. I couldn’t eat that much if I tried. I certainly respect what she says, and what she has accomplished and for many her advice can be a life saver, but we have to modify things to suit ourselves and not get our knickers in a twist about it.
When I was diagnosed with Idiopathic Pulmonary Fibrosis nearly five years ago, I would have taken any advice, any pills that my doctor would have ordered, out of fear. My prognosis was 2 to 3 years. But I gave myself permission to hold off, I had nothing to lose as none of the treatments suggested were proven, or held hope of a cure. So I started researching. I now eat a low carb/ketogenic diet, no processed food, quality grass fed meets when possible, fermented foods and so on and a few supplements. I am amazingly healthy still with some limitations, easy to manage and I credit my health to the diet, and having had the courage to refuse conventional (useless) treatment that comes with significant side effects.
Why can’t you eat cheese?
I am able to get raw, grass fed dairy, so I suppose I’m getting my vitamin K. I take a bit of cod liver oil. I don’t take vitamin K.
Anna, I believe there is no reason not to eat cheese if you tolerate it. The Paleo folks are very strict about avoiding dairy because in some people it causes inflammation. But if you aren’t one of these people then it’s not a problem. Other low carb regimes such as Atkins, Primal, Drs Steve Finney and Jeff Volek (The Art and Science of Low Carb Living) are more flexible.
I’m not so sure “the Paleo folks” are “so strict” about anything. There are literally hundreds of versions of “Paleo”. Some of them try to be scientific about it, like acknowledging there is very robust scientific evidence that man has been eating grains (ground, cooked grains) for well over 30,000 years. Other versions reflect some book-promoting bodybuilder’s personal preferences and have little science behind them. As wild animals consume the milk of other species when they can get it (no, you don’t want to challenge me on this, I have the reference close at hand and have answered the doubters dozens of times on numerous comment boards), and it’s likely Paleo humans did likewise, it makes little sense to forego dairy if you don’t have a sensitivity to it and you like it. Besides, isn’t good health about eating what works best for your body, not adhering to some self-styled guru’s label as if it were a religious affiliation?
Annielaurie,
I think we have been eating grains for probably 100 000 years.
Problem with most diets today is carb in sugar form, overload.
You hit the nail on the head. Especially disconcerting is that today, we have weird, unnatural forms of sugar that the American populace (and maybe others) is consuming in ever-growing amounts. The USDA now estimates that sugar-laden carbonated beverages (that we in the US refer to as “soda”) now make up the largest single source of calories in the American diet. And it’s HFCS. Paleo humans, at least for thousands of years, were eating grains in the same manner they ate all the other foods they consumed — pretty much on a seasonal basis, not year round. It wasn’t until they started settling down, as a precursor to adopting an agricultural lifestyle, that they even started storing the wild grains they gathered. And they sure as heck weren’t treating said grains with acid to produce fake sugars, even after going fully ag.
Mr Chris, I would also say the white flour used in an array of products such as pizzas, burger buns, pastry products (sausage rolls, pasties, pies, pasta) is also to blame. Cheap, filling lazy food. Doesn’t have to be sweet.
I found this article doing further Internet research on the connection between Lp(a) and CVD. I realize the author is associated with vitamin supplements but so much of what he says ties into this Dr. Kenrick article so I am passing it on:
http://knowledgeofhealth.com/something-huge-is-going-on-in-cholesterol-world/
I have a history of high Lp(a), ranging from a high of 906 mg/L to a low of 401mg/L. It currently bounces around 550 which is high. My father died of a heart attack at age 65; I am now 75. I’d like to get my Lp(a) lower and I’m considering Vitamin C. I already take low dose aspirinplus I take 3000mg of Niacin a day and it did lower my reading from 600 to 450 within 2 years of starting.
I have had two electrocardiograms, the second showing some improvement in my blocked arteries compared to the first one. Because of this, my cardiologists has recomended I take 10mg of Lipitor a day which I do now but I may stop that in favour of this Vitamin C therapy.
These aricles have been very helpful and I have noticed a change in the attitude towards statins and CVD in recent years. I thank Dr. Kenrick for his determination and dedication to bring clarity and truth to this important subject.
Thank you again for sharing your knowledge with us.
Dr Kendrick,
Another instructive and brilliant review – just what is needed but ignored by the medical establishment.
Two points:
warfarin is very poor at preventing CVD, but very good at preventing stokes caused by atrial fibrillation, and can prevent dearth from DVT.
The efficacy of warfarin is low circa 4% and is 70% better than aspirin (ie 4% and 2.35% efficacy respectively). This is an estimate that I found from EU guidelines confirmed by a NHS consultant (MD and MPS) a difference of 1.65% which is a 1 in 40 better chance of benefiting the individual. However, from the MHRA DAPs warfarin has more deaths reported than aspirin despite the fact that the gross weight of aspirin used in humans vastly exceeds the weight of warfarin used in humans over much the same time span. This is basically confirmed by http://thennt.com but is given the green light.
The new drugs are equally effective and there is no need for continual checking BUT if something goes wrong there is no antidote like Vit K for warfarin
The probability of benefit is too significantly unlikely with too many problems of “getting it right” for me
‘Hypertriglyceridemia is associated with an increased risk of coronary heart disease (CHD). Impaired endogenous fibrinolytic function is a frequent finding in subjects with hypertriglyceridemia.’
Re triglycerides and VLDL your association of these and “heart attack” emphasizes the increasing interest and relevance of these molecules in the diagnosis of heart disease risk in recent research. However in my local NHS trust neither the trig/HDL ratio or VLDL are ever considered in the “standard lipid profile”. Incidentally a US cardiologist told me that VLDL estimate was triglycerides divided by 5.
Stephan T (Feb 22),
Vitamin K2 and vitamin A still required. Obtaining vitamin D (and other substances not provided by oral supplementation – have a look at https://people.csail.mit.edu/seneff/ for lots of info ) from the sun exposure is by far the best as your body will control the production so no risk of over dosing. I eat plenty of cheese that should contain ample vitamin K2, but I also supplement in case it doesn’t contain as much as I think it does. I also aim to get vitamin A from natural sources. I think you are aware of the confusion over animal sourced vitamin A and carotenoids but for those that are not please see http://philmaffetone.com/vitamin-a-and-the-beta-carotene-myth/ .
Dr Kendrick – thank you for such a great blog I’m totally hooked and can’t wait for the next one. I found an interesting article on P.emblica extract on endothelial dysfunction and thought I’d share.
http://www.ncbi.nlm.nih.gov/pubmed/23935377
What do you think?
May be of interest.
Dr Lown Nobel prize winner
Mike,
This is good simple stuff, everyone should read and digest it. Not the first time I hear it , but banging away at a nail, gets it in.
Thanks
Mike,
Thank you for the link – very encouraging for someone like me who “dared” refuse.
Fascinating and absorbing reading. The whole series is like a ‘ Vascular Nordic Noir ‘. Stocking up with vit C for the final episode.
A simply stunning explanation for CVD. There would not be a single other person in the cardiology world who could refute, or best you, on this outstanding description. Superb!
Cause – the endothelial cells have no GLUT4 (glucose transporter). As I posted the link but not the words a week or 2 ago: the endothelium, if it is working properly controls (among other things) if blood clots properly. The endothelium is vulnerable (due to one cell thick) to injuries. What causes the injury – Postprandial hyperglycemia. Why – because the endothelium can’t resist having a high intracellular sugar. This causes OX damage and can kill the cells, then letting white blood cells get under the endothelium, the “I” word. Note: this is a quick summary. http://www.ncbi.nlm.nih.gov/pubmed/9027391 https://www.youtube.com/watch?v=E5jgrB2RblY
Dr. Kendrick. Thanks for such an interesting series. Regarding your warning of the tendency of medical professionals to focus on one cause and one cure, have you heard about the doctor who went to an Italian restaurant and had a delicious dish of pasta. He took some home and separated it into its components to find the source of the goodness. Noodles, no. Oil, no. Garlic, yes!! He then invited all his friends over for pasta. Imagine their surprise when there was nothing but the active ingredient, garlic, on their plates.
Today there seems to be a ‘unified theory’ about the danger of sugar contrasting the still prevailing one about the danger of saturated fat and cholesterol.
I don’t know it is appropriate to forward two links to the two videoclips I recieved from Mercola this morning. In their opposing messages the clips are really chilling by exposing the double standards hidden behind the ‘curtains’ of corporate business.
Anyway – enjoy or get horrified!
Lovely.
But Yudkin back in the 1960s and early 1970s showed that sucrose was disastrous; he was ignored at the time and recently some “genius” has refound that fact. If the medical establishment had listened to him back then we may have avoided the epidemics of metabolic syndrome, obesity, diabetes and Alzheimer’s, all of which have rocketed since 1960.
Alas, not only was Prof. Yudkin’s work ignored – he was villified by the establishment on both sides of the Atlantic. It is thanks to Prof Lustig, the UCSF endocronologist , that Yudkin’s work has now been acknowledged. Up until recently, Yudkin’s books were out of print; they are now available and are well worth reading. I read Pure White & Deadly back in the early 70’s, and reread it a couple of years ago after listening to a lecture by Prof. Lustig. 40 years later, it still is incredibly relevant.
Cripes!
If I may ask. Why do you equate VLDL to triglycerides? Typical tests list them separately, and usually assigns them different values.
I don’t! It is simply a rough way of estimating VLDL based on an answer from an imminent US cardiologist. My local NHS Trust has not yet caught up with the importance of the trigs/HDL ratio.
Personally, I am more interested in the light “fluffy” LDL and its roll in immune response.
Very interesting article I’ve read this morning – and about time ..
http://www.dailymail.co.uk/health/article-3460321/How-Big-Pharma-greed-killing-tens-thousands-world-Patients-medicated-given-profitable-drugs-little-proven-benefits-leading-doctors-warn.html
B. This is a brilliant and brave piece of journalism. Worth reading everyone.
B
Many thanks for the link. To everyone I would recommend reading it. While I was well aware of all the points made by Dr. Malhotra (and indeed by Dr Kendrick over the years) it really is something that should be trumpeted round the world – not hidden as the pharmaceutical giants and their KOLs would have it.
Mike/Sue … It’s was also on Radio 4 today.. Going to try and listen later … maybe it will get picked up by others …I would love to see a documentary about this on TV ….Dr Kendrick???
Anna – yes you put it better than I. It’s clear that there is natural adaptation and evolvement within species, I have no difficulty in that. I thought of adding another comment to that effect but didn’t want to go any further off tangent on the blog and possibly start an entirely different discussion! Thanks for clearing it up. One thing is sure – the more we find out about the human body, the more amazing it reveals itself to be.
.
May be of interest
VLipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data
Prof Naveed Sattar, et al
DOI: http://dx.doi.org/10.1016/S2213-8587(16)00003-6 |
Summary
Background
Patients with type 2 diabetes have increased cardiovascular risk. PCSK9 monoclonal antibodies have been shown to reduce LDL cholesterol and other lipids, but specific efficacy for patients with diabetes is unknown.
We compared the effect of the PCSK9 inhibitor evolocumab on lipid parameters in patients with and without type 2 diabetes.
Methods etc can be downlooaded – whole paper costs $31.50
Interpretation
Evolocumab markedly reduces atherogenic lipoproteins in patients with type 2 diabetes, an effect that is consistent across subgroups and similar to that seen in patients without type 2 diabetes. Results from ongoing cardiovascular outcome trials of PCSK9 inhibitors will provide additional data to inform the use of these drugs in patients with type 2 diabetes.
Funding Amgen ????
I would love to get the details of this letter. It relates to an alternative of warfarin.
Letters Rivaroxaban: can we trust the evidence?
Questions about the reliability of ROCKET-AF anticoagulation data
BMJ 2016; 352 doi: http://dx.doi.org/10.1136/bmj.i1039 (Published 23 February 2016) Cite this as: BMJ 2016;352:i1039
In the study, which compared Xarelto with warfarin, the INR device was used to measure blood clotting in patients taking warfarin. Because of the defect, there were concerns that the INR device could have provided lower INR values in some patients in the warfarin group. The lower values could in turn have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and so giving a false impression of the comparative safety of Xarelto.
The European Medicines Agency (EMA) has concluded that a defect with the international normalised ratio (INR) device used in the ROCKET study does not change its conclusions on the overall safety or benefit-risk balance of Xarelto (rivaroxaban).
You can find the entire response here: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2016/02/news_detail_002465.jsp&mid=WC0b01ac058004d5c1
Stipectic,
Many thanks for the link but neither have a particularly good efficacy rate an d both have similar incidence of ARs. My gut decided it did not like it at all with the usual effective response .
Dr Dr Kendrick,
you commented that CVD is a multi-factor disease, and that diet was just one aspect, as well as genetic.
My father, and his two brothers, all scots from the Glasgow area all died of CVD. My lipids specialist looks at my profile, says, your LDL is too high and you have genetic antecedents, as above, therefore Ezetrol for you my boy. I know Scotland has a very high rate of CVD and this is attributed often to diet. However my relations all left sScotland before they were twenty and presumably ate diets that were markedly different. In your blog on this subject until now, you have mentionned the mechanics, and not the genetic aspects, which I would imagine are very difficult to tease out of the overall picture. Do you see genetic predisposition to CVD? I have to admit to quite a lot of scepticism, there may be some but in most cases largely overshadowed by diet and lifestyle factors.
Chris:
I think there may be genetic components to CVD, but genes can be turned off, and turned on, via lifestyle, diet, drugs, the environment, etc. See: epigenetics.
That is, your genes are not your destiny.
Hi Joe,
Thanks for your reply. I tend to agree with you, CVD is a multifactorial thing, and the different factors are in such a mix, that you cannot say which will be dominant in a particular person.
My lipidist, is quite a big cheese in the world of lipids and is not a textbook follower by any means. For example on lp (a) he is relaxed, my score at 50 is well above the naughty threshhold. He said this is not an important factor, in the 100 s yes.
We shall see. Perhaps Dr K deals with all this ine coming episodes.
Anyway, I see no pount in taking Ezetrol.
Of course they are. Once you take out the environmental extremes it becomes a narrow field of randomness which is always clustered, so do what you can but luck will find you.
I know a number of people are interested in the work of Professor Seyfried on cancer and the related book by Travis Christofferson. Christofferson is both articulate and interesting, so I thought some might appreciate this recent interview with Dr Mercola.
Travis Christofferson’s book “Tripping over the Truth” is one of the best books I have read about this issue. It is addressing a more lay public than Thomas Seyfried’s who is given full credit. I strongly recommend “Tripping over the Truth” – a solid piece of work with a strong nerve.
Göran, agreeing of what you say of those books – I have them both and must confess, that Seyfried’s Cancer as a Metabolic Disease needs a reader of professional background (not like me, a layperson). Though this theme is off topic of this blog, those who are interested of cancer management / cure, could Google 3-bromopyruvate, Yvar Verhoeven, Young Ko, Peter L. Pedersen, Valter Longo and Warburg effect. Stunning results!
I just finished Travis Christofferson’s book
Tripping over the Truth. It is well written
and interesting. I recommend it to all, but
especially anyone who has cancer or is
close to someone with cancer.
Thanks again to Stephen T for posting
this video.
Unified Theory of Nutrition: Eat only real food, as much as you like.
Stipetic: Yes, I heard Dr. Seneff speak about cholesterol sulfate in Dallas in 2011. Vitamin D sulfate is made from cholesterol sulfate (the cholesterol and Vitamin D molecules are remarkably similar in their chemical formula and structure) in the skin, rendering it both lipophilic and hydrophilic, enabling it to travel in the bloodstream to where it is needed. All of this provided there is sufficient sulfur in the diet. The sulfate molecule plays many crucial roles in metabolism.
I think we can shut down the Internet now, because there will not be a better blog post ever.
Stephen T:
Thanks for posting that video.
Bill, you’re welcome. I have the feeling that his work is going to be significant, although I think the current cancer ‘industry’ will resist for as long as they can. A cheap effective treatment is no use to them.
Best wishes.
Dr. Kenrick: I do love the word unexpectedly. Mainly, because, here is where scientific truths hide.
Isaac Asimov: The most exciting phrase to hear in science, the one that heralds new discoveries, is not “Eureka!” but “That’s funny…”
Off topic but right good laugh!
Dear Dr Kendrick,
Before we get to the exciting bits, I note you refer to good and Cholesterol. Is this a valid distinction, if my body is churning the stuff out in different proportions, is it not possible that that is what my body needs?
Sadly, I’m very disappointed with this conclusion.
There’s a whole line of evidence about the causes of metabolic syndrome and CVD that doesn’t appear here at all, and that, to me, is far more convincing both due to it’s demonstrated cause-and-effect relationship with many of the symptoms, and to its corrlation with the increase of such diseases. You touch on it, with your discussion of lp(a) and vit. C, but those are just symptoms of the more proximate cause. Why worry about the effects of oxidative damage when we know what the cause and the cure are?
It also explains why not just humans, but all the animals that subsist on human-produced foods, are suffering from the same set of diseases.
This is probably an excellent place to start, as it covers the mechanisms and the multiple effects:
“High levels of HNE have been associated with diseases involving redox imbalance: NDD,21 macular degeneration,22 cardiovascular diseases, atherosclerosis,23 metabolic syndrome24 and cancers.25 In these diseases, HNE is not only a simple marker of oxidative stress but also a causative agent. The modalities of HNE involvement in these oxidative stress-related diseases are detailed below and summarizedin the Table 1.”
“Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance” Cell Death and Differentiation (2013) 20, 1615–1630
We also know the source of HNE and the other oxidative metabolites, and that they can be reduced in vivo in humans through simple dietary manipulation.
“Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans.” Prostaglandins Leukot Essent Fatty Acids. 2012 Oct-Nov;87(4-5):135-41. doi: 10.1016/j.plefa.2012.08.004. Epub 2012 Sep 5
My own experience of Vit C supplementation, being a low carb eater and fan of saturated fats I find i can take no more than 100 – 200mg total per day in any processed form without ‘titrating out’ ie spending more time in the toilet. Real sources such as parsley and other fresh green leaves, fruits seem to be more palatable, innately slow release and trustworthy. Not so many artificial nano-particles etc. Some suggest that the loss of the ability to synthesize vit C may have happened as long ago as 60 million years so im sure proto-human evolution had moved on since then. The wikipedia article on the ins and outs of vit c and scurvy etc seems quite balanced to me.
lp(a) – some of the papers published about this look like another wild tangent in support of the cholesterol family of pseudo-hypotheses and this new class of pcsk9 inhibitors will probably make many people more ill if they come to be widely accepted. Mike, the article you discuss there has all of the language and hidden assumptions of the same old same old! Lp(a) certainly seems like part of an important and multipurpose repair kit without which one would be much worse off so preventing or minimising the damage that it helps to fix looks like a better strategy than lowering it. Btw centenarians have relatively high levels of lplittlea, and as it is for cholesterol there seem to be optimal levels in younger people, not too much, not too little, just right.
Then there is the tight relationship between lplittlea and oxLDL to contemplate. What, more cholesterols?
Craig,
Thanks for the encouraging news, I have above norm, for lp(a) and lots of cholesterol so should be set for being a centenarian.
Seriously though, how is anyone supposed to come to a conclusion on these things, you find everything and the contrary on any of these subjects, just look at the widely disparate set of views you find in the comments to Dr K’s blog. My policy is to avidly read the n+? Issues of the blog and try and follow its conclusions.
Craig,
On lp(a) I suspect you are right – as Dr Graveline said many years ago when TC was in full swing “they’ll move the goal posts”. They have.
Another good book to read is Henry Lorin’s “Alzheimer’s: Solved”. In short, it shows that low cholesterol is present in most Alzheimic patients and the reason for it.
Tuck, that was heavy stuff! Wow and Thanks! It explains why easily oxidized omega-6 vegetable oils are so harmful and especially in oxidative bodily environment eg. under high-carbohydrate diet. Serial killer, indeed!
Tuck,
“We also know the source of HNE and the other oxidative metabolites, and that they can be reduced in vivo in humans through simple dietary manipulation.”
Evidently this is not a new insight.
The greek historian (the first?) Herodotus had a lot to say about medicine, diets and health.
He noted, among many other things, that in the first meeting between the persians envoys and the ethiopians the latter, who basically subsisted on cooked meat, lamented the persian people who had to subside on bread and who would hardly live longer than 80 years due to this fact while the ethiopians themselves claimed to reach the age of 140 years. You may doubt the actual numbers but the ethiopians made their point and added that they thought the only reason for the persians to be able to reach the age of 80 most probably was because they not only had the bread but drank wine as well.
Also Platon in his Republic discuss the fact the greek city dwellers who were indulging pastries in excess went sick and then had to frequent the doctors to ask for medical remedies while on the other hand people living the austere life in the countryside remained healthy and in no need of any doctors.
“Evidently this is not a new insight.”
I’m uncertain about what your point is… I’m also a history student, and you’ve left a few more-pertinent examples out.
But as far as the discussion of modern CVD causes goes, this has far more explanatory value than the one offered in the OP.
“Collectively, these observations suggest that lipid peroxidation products, such as 4-HNE, mediate the effect of foam cells on VEC [vasuclar endothelial cell] senescence. Among the known properties of 4-HNE is its biphasic activity: at low concentrations it presents a signalling function via activation of the nuclear factor PPARδ, whereas at high concentrations it acts as a cytotoxic agent [31, 42, 43]. Interestingly, our previous studies showed that endothelial cells do not produce detectable amounts of 4-HNE [44]. Therefore, it appears that exogenous 4-HNE that diffuses from foam cells is involved in VEC senescence.”
“Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner”
http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12561/full
This is a much better overview, although it misses some key points about what we know about OXLAM production and effects… It’s been demonstrated that dietary manipulation of OXLAM production is possible, and one common aspect of the metabolic syndrome (fatty liver disease) was demonstrated to have a 100% cure rate upon reduction of OXLAMs in vivo.
“Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease”
http://www.sciencedirect.com/science/article/pii/S2213231713000396
tuck,
“I’m uncertain about what your point is… I’m also a history student, and you’ve left a few more-pertinent examples out.”
My point was that I basically agreed with your general statement about the importance of the diet when considering our “western” diseases, and about possible homeostatic ‘cures’ by taking away the actual ’cause’ in general terms and that this has been well acknowledged among our ancestors.
Even among us LCHF-adherents we have noted this ‘curing’ effect, not least myself with my serious CVD and my wife with her severe DM. Of course, I could have dwelled on the Hippocratic aspects of medicine, “Let the food be your medicine and the medicine your food”, or the fact the most ‘colonial’ doctors noted the absence of most of our present day diseases among the ‘natives’ before they were exposed to our ‘junk’ food.
I also agree that there are more than a “few” examples to be added from an historical point of view, not least relating to the specific subject of this post.
Besides, I see a certain danger in turning categorical when going into physiological details about PUFA peroxidation although I suspect that you may be all right in that the importance of this subject have been strongly overlooked.
Personally, I keep away from the omega-6 PUFA’s out of precaution.
As always, the “devil” dwells in the details.
I’ve been taking Lysine with Vitamin C for 6 months now – and no longer take Statins – my Triglycerides have lowered by 50% and HDL has increased 13% – I also take Q10 and K2 .. Diet has altered massively and I’ve lost 21 pounds – I’m also training for the London Marsthon this year – and am feeling positive – I read this today which I found interesting ..
Lp(a) and the Lysine Binding Sites
“Many investigators contributed to demonstrating that it is lipoprotein(a) that is deposited in plaques, not merely LDL, but lipoprotein(a), or Lp(a) for short. If you have more than 20 mg/dl in the blood it begins to deposit plaques and causes atherosclerosis. The question then is: What causes Lp(a) to stick to the wall of the artery and form these plaques?
“Countless biochemists and chemists discovered what in the wall of the artery causes Lp(a) to adhere and form atherosclerotic plaques and ultimately lead to heart disease, strokes, and peripheral arterial disease. The answer is that there is a particular amino acid in a protein in the wall of the artery – lysine – which is one of the twenty amino acids that binds the Lp(a) and causes atherosclerotic plaques to develop. I THINK IT IS A VERY IMPORTANT DISCOVERY”
“Knowing that lysyl residues are what causes Lp(a) to stick to the wall of the artery and form atherosclerotic plaques, any physical chemist would say at once that to prevent that put the amino acid lysine in the blood to a greater extent than it is normally. You need lysine, it is essential, you have to get about 1 gram a day to keep in protein balance, but we can take lysine, pure lysine, a perfectly non toxic substance as supplements, which puts extra lysine molecules in the blood. They enter into competition with the lysyl residues on the wall of arteries and accordingly count to prevent Lp(a) from being deposited, or even will work to pull it loose and destroy atherosclerotic plaques.”
Hurry up Dr Kendrick with the next blog …
“Besides, I see a certain danger in turning categorical when going into physiological details about PUFA peroxidation although I suspect that you may be all right in that the importance of this subject have been strongly overlooked.”
A wisely conservative approach. If one does a bit of reading in Google Scholar, looking up 4-HNE and whatever your favorite aspect of CVD is, and I think you’ll be astonished at what the published research has to say. 4-HNE and the related oxidized linoleic acid metabolites, the only source of which is diet, is found at every step of the way, often in a causative role…
“…Furthermore, CD163 expression and 4-HNE content were considerably higher in unstable than in stable plaques. Interestingly, in the combined patient population, linear relations were found among neovascularization, expression of CD163, and glycophorin A and 4-HNE content….”
https://eurheartj.oxfordjournals.org/content/30/15/1821
Tuck
“CD163 expression and 4-HNE content were considerably higher in unstable than in stable plaques”
CD163 is a scavenger receptor, right? IL10, nice…
There is a research paper that suggests that taking Vit C can lower Lp(a) and I have to say my experience is that this is true. Twice I have stopped taking Vit C and my Lp(a) has shot up to an unacceptable 31 whilst when on Vit C it has been no more than 23 and as low as 18
ONE BIG TRIGGER IS MISSING HERE. THAT IS: THE INFECTION. SINCE THE CLOTTING SYSTEM IS ACTUALLY A PART OF THE IMMUNE SYSTEM. BACTERIA AND EVEN BACTERIAL REMNANTS ARE PERFECT TRIGGERS OF ATHEROSCLEROSIS AND CVD.
I fully agree. (Perhaps you could take off the caps lock in future posts?)
Thanks for posting this stuff. IT is amazing information. I know I’m a year late on this response, but I’m hoping someone has some insight.
I don’t understand something in the section on Lp(a) and Vitamin C. It sounds like the Lp(a) is protective for cases of low Vitamin C. But I didn’t see any reason to think that low C triggers production of Lp(a). Is it that Vitamin C can protect against endothelial damage in even without a deficiency, or is there reason to believe that even with very slightly inadequate levels of C damage will occur, so therefore, just take extra?
The precautionary principle is good, and there’s no harm in taking extra obviously, but it may not help if the arterial or endothelial damage is caused by factors other than low Vitamin C. Does this make sense?
My experience is that with boosting Vit C Lp(a) drops which is in line with some research I had read. When I was at the HeartUK conference a doctor doing research on hear disease said that Lp(a0 was hereditary and nothing could be done to influence it at the moment. When I proposed to him that Vit C could help he swore blind this was not the case. I ended up sending him the research paper which did kindly acknowledge as interesting. My understanding is that Vit C helps with collagen formation and this aids reconstruction of healthy endothelial when damage does occur
Smartersig
Flax seed is also supposed to do the trick on Lp(a). I have it on my porridge with cinnamon.
I did not know that Chris, thanks. I was aware that Niacin is also supposed to lower it
smartersig
here is a reference, its worth what its worth, and as you say, it seems to have no downside
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989356/
Thanks Chris, reading that it is easy to see why Dr Greger raves about flaxseed