What causes heart disease part IV

I have entitled this little series ‘What causes heart disease?’ But I have been at pains to point out that you cannot possibly establish potential causes heart disease, until you are clear about the underlying process.

By this I mean you can say that smoking causes heart disease – and you would be right. You can also say that Systemic Lupus Erythematosus (SLE) causes heart disease – and you would also be right. You can say that type II diabetes causes heart disease – and you would be, guess what, right. You could say that obstructive sleep apnoea causes heart disease and you would be… right again. Steroids…right again. High levels of fibrinogen…right once more. Cushing’s disease…right. Depression… bang on the button.

But you have to be able to answer the question, how can these very different things lead to the same disease? Or, perhaps you are going to argue they all cause different diseases, that look exactly the same? If so we are doomed, as this would mean that there are a hundred different types of heart disease each with their own individual cause. (I believe this to be unlikely, and am not further discussing it as a possibility).

In short, you cannot simply go around stating that you have identified cause after cause, after cause after cause. Or you can, but it does not help in the slightest with understanding what is going on. It just becomes increasingly confusing. You must establish the process, or processes, that can link all of these potential causes together. Until you can answer this, you are basically just floundering about.

I spent thirty years floundering about in this unending kaleidoscope of risk factors before I decided that it was mission critical to work out what was the actual disease process underpinning CVD. In the end, it came down to this.

The four stage process

Heart disease – or the development of atherosclerotic plaques, followed by the final, fatal, blood clot – consists of four stages. These stages obviously overlap, and interact, and separating them out is a somewhat artificial process. However, I think a degree of separation is necessary for understanding. You can jumble them all around again afterwards.

I should also say that; in this particular blog, I am only going to look at the first stage of the four stage process. And the first stage is endothelial damage.

The endothelium

The endothelium is a single layer of cells that lines all arteries, and veins. At one time endothelial cells were believed to be essentially inert. They just sat there, lining the blood vessels, and not doing much. But, of course, these cells are gigantically, mind-bogglingly, complex.

However, for the sake of this discussion, I am only going to look at three aspects of endothelial cells.

  • Nitric oxide synthesis
  • What happens when endothelial cells are damaged
  • Tissue factor

Nitric oxide synthesis

A critical role of endothelial cells is to manufacture nitric oxide (NO). When it comes to CVD, this little molecule is absolutely key. First, it relaxes the smooth muscle in artery walls, causing them to relax, which opens up the surrounding artery. This then lowers blood pressure.

Within conventional medicine various ‘nitrates’ are given to people with angina, which opens up the coronary arteries, improves blood flow and the oxygen supply improves. The first of these to be discovered was nitro-glycerine. Renamed glyceryl tri-nitrate, and put into tablets to dissolve under the tongue.

NO is also a very powerful anticoagulant – it stops the blood clotting. This is clearly essential as you do not want clots forming on normal blood vessel walls, and when NO levels fall, accidental blood clotting becomes a real possibility.

Healthy endothelial cells produce lots of NO. Stressed and damaged endothelial cells do not. Which means if you have stressed or ‘dysfunctional’ endothelial cells, your arteries are narrower ‘constricted’ and the blood within them more likely to clot.

In recent years it has been recognised that damage to endothelial cells is an early marker of atherosclerosis, as made clear in this paper, entitled: ‘Endothelial dysfunction: the early predictor of atherosclerosis.’

‘Endothelial dysfunction, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis.’ 1

Which means that damaged, or dysfunctional, endothelial cells can be recognised by their failure to produce NO. On the flip side, if there is abundant NO in the body this seems, in reverse, to keep endothelial cells healthy.

There are some drugs, supplements, and activities, that can actually increase NO synthesis in endothelial cells, and also the rest of the body. Possibly the most powerful single factor that can do this is sunlight. As highlighted in this paper, where the rather snappy title actually says all that needs to be said: ‘Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates.2

Essentially, if you sunbathe, NO is released throughout the body, and your blood pressure drops (as your arteries open wider). Other studies have found many other major benefits of sun exposure on lung, breast, prostate and colo-rectal cancer, but that is a story for another day.

For now, the focus here is simple. Endothelial cells produce NO, this chemical is vital for CVD health. Any factor that reduces NO synthesis is unhealthy, any factor that increases NO synthesis will protect against CVD.

What happens when endothelial cells are damaged

I am not looking in any great detail here at how endothelial cells are damaged, although there are many, many, things that have a negative impact on the health and wellbeing of endothelial cells. High blood sugar, low blood sugar, steroids, smoking, cocaine, SLE, Obstructive Sleep Apnoea (OSA), and suchlike.

Perhaps the single most important factor that can damage endothelial cells is this – biomechanical stress. By biochemical stress I mean turbulent blood flow, stretching and bending of the blood vessel, high shear stress, high blood pressure, rapid blood flow, points where the blood has to change direction violently.

Violent direction occurs where smaller arteries branch off from larger one e.g. where carotid arteries (that supply blood to be brain) branch from the aorta at the base of the neck. Such points are called bifurcations, and bifurcations are where the biggest and most ‘vulnerable’ atherosclerotic plaques are almost always to be found.

In reality, extreme biomechanical stress only takes place in the larger arteries in the body, where the pressure is high and there are great forces for the endothelium to deal with. A raging white water river. Place a pebble on the side of this maelstrom and it will soon be ripped off and dragged downstream. Veins and the arteries in your lungs, on the other hand, are more like the lazy rivers of East Anglia, slowly meandering along through flat fields.

It is almost certain that the massive difference in the biomechanical stress that endothelial cells have to deal with, in arteries, in comparison to veins and pulmonary blood vessels (the blood vessels in the lungs) fully explains why atherosclerotic plaques never develop in veins and never develop in the pulmonary blood vessels (blood vessels in the lungs). Despite that fact that these blood vessels are exposed to exactly the same ‘risk factors’ as the arteries.

Moving on. It is possible to do more than simply stress endothelial. They can simply be stripped off. If and when this does happen, not only is there no NO at that location, something else far more important comes into play….

Tissue factor

Sitting within all artery walls (and all vein walls too) is a substance called Tissue Factor (TF). It is by far the most powerful clotting agent known to nature. If you expose blood to it, a clot will immediately form, right on top.

This makes sense. If a large blood vessel is damaged, you will bleed to death very rapidly, unless a very strongly constructed blood clot forms right on top of the damaged area, to block the hole. Another point to mention is that TF triggers the ‘extrinsic’ clotting system which simply bypasses a large part of the blood clotting system. Clot right here, right now!

In truth, the system of blood clotting is incredibly complex, and I have not the slightest intention of covering it all here. Probably because I don’t fully understand it myself. However, at its simplest, blood clots consist of two key components. Platelets and fibrin.

Platelets are small ‘sticky’ cells. They are activated by exposure to Tissue Factor (TF), at which point they start clumping together to get the clot started. Whilst doing this they release about five hundred other substances that further activate the entire ‘clotting cascade.’ Then all hell breaks loose.

The end result of all of these clotting factors activating is that small strands of protein called fibrinogen are stuck together for form a long, very strong, string of protein called fibrin. This wraps round platelets, and anything else floating past, and binds everything together in a tight and very strong blood clot.

This clot then sticks very firmly to the site of damage, and grows, until all the damage is covered up. At which point the other five hundred factors that are designed to stop blood clots forming and/or getting too big, stop the clotting process in its tracks.

After the clotting process has been whipped into action, then brought to a halt, we have a blood clot stuck to the inside of the artery wall. Obviously if it grew too big it will have completely blocked the artery – resulting in a heart attack, or suchlike. Assuming, however, that it stopped growing, before completely blocking the artery. What then happens to it?

To be continued.

References:
1: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721957/
2: http://www.ncbi.nlm.nih.gov/pubmed/19797169

193 thoughts on “What causes heart disease part IV

  1. David Bailey

    Do I take it that the NO only lasts a short amount of time in the body because it reacts with oxygen in the blood? Does it actually take it from the haemoglobin, or is it free oxygen in the blood that destroys it?

    Reply
  2. ismacau

    Dr. Malcolm, would it be accurate (or at least a good idea) to view NO as a potential key to avoiding CVD? That is, if you eat right, exercise daily, get some sun and generally try to boost your bodies natural production of NO, you *may* be able to miss most or all of the destruction that occurs with low NO? I know there are no guarantees in life, but this seems pretty close to a true Cause/Effect relationship… screw up your body’s NO and CVD results; keep the NO production where it should be and you prevent so many bad things. I know this is a simplistic view and I know you absolutely can’t give medical advice here and I know there are caveats to all advice you find online about healthcare, but this one seems pretty safe with little downside: Take care of your Nitric Oxide and it’ll take care of you.

    PS: I love your work. Please keep up the good fight!

    Reply
  3. Dr. Göran Sjöberg

    By God!

    I havn’t even touched the nitrospray I was given 16 years ago.

    And to the horror of my last cardiologist I told him that I used alcohol as my heart medicine instead and this information promptly entered into his records.

    Perhaps I should have worked the other way .

    Reply
      1. Dr. Göran Sjöberg

        David,

        I guess I have done my ‘homework’ on this point.

        The cardiologist I met considered everything I had been up to as complete nonsense and I couldn’t resist the temptation to ask him if he considered my couple of drinks each day together with a large scotch to relieve any acute angina attack also was complete nonsense.

        To my surprise he reluctantly admitted that it made cardiological sense.

        Cardiologists are nowadays my ‘favourites’ and the chronicle by one of them I read in a Swedish medical journal a week ago was almost incredible. He was bitterly complaining about how many hours he had to spend to discuss statins with well read patients. (Mine was though refusing.) The last complaint from the cardiologist in the chronicle was that each patient who used his rights to refuse the statins costed him personally “quality points” in some national register. He had to convince 95% to take them – otherwise he would be in a very awkward position.

      2. mikecawdery

        David

        Many thanks for the link. Unfortunately money and status (professorships, honours, knighthoods, etc) do not flow from bucking the “OFFICIAL ADVICE”. Though as for most things too much of a good thing ain’t good; moderation is everything.

        But I agree with you regarding Govt. advice; it is frequently based on commercial or professional interests. “Evidence-based medicine” is thrown about for astrotufing/agnotological reasons!

      3. mikecawdery

        David

        To support you re corruption:

        and

        BMJ 2016;352:i674 doi: 10.1136/bmj.i674 (Published 4 February 2016)

        It just goes on and on. Data hiding

      4. Dr. Göran Sjöberg

        Mike,

        Thank you for the link to the lecture by Peter Wimshurst – I had never heard of him before.

        Having already lost all my faith in the the health care system and of medicine as having any similarities with the natural science I am familiar with it is still almost unbelievable for me how such a complete corruption as revealed in this lecture is allowed to continue in a discipline so important in our society.

        And I am so happy that I have had the courage to keep away from these truly disgusting people involved in cardiology and today being able to chop my firewood without any angina.

    1. Anna

      I can’t decide you much you are joking here. In what way would alcohol be your heart medicine, or do you mean that it maketh the heart merry?

      Reply
      1. Dr. Göran Sjöberg

        Anna

        As far as I have understood the effect of alcohol.

        1. Makes your arteries relax in acute angina situation – you need a stiff drink then
        2. Relax your autonomous nervous system i.e. is reduces stress
        3. Increase your life span with 5 years if taken in moderation – not a drop more than three drinks a day!
        4. Reduce your life span with 5 years when taken in excess

  4. Mr chris

    Dr Kendrick
    This is fantastic, we are all waiting to know
    what we can do apart from eating beetroot, to beef up the NO.

    Reply
    1. JanB

      Oh, no, not beetroot. Anything but beetroot. Ugh.
      Great post, Dr. K. You have us all on the edge of our seats. This is better than any detective series on the TV and I can’t wait for the next episode.

      Reply
  5. annielaurie98524

    Oh, Dr. Kendrick, your articles are like those old serial adventure movies my mother watched as a child — you know, where the kids had to wait for a week to find out if the hero was able to rescue the damsel in distress as she lost her grip and began sliding off the edge of the cliff? Only your readers sometimes have to wait several weeks. As an engineer/scientist that has had to deal with the problems associated with various flow regimes in piping systems, I am finding your description of arterial flow/damage fascinating. I wonder if we might not gain some insights by modeling the body’s “piping system”? With all the sophisticated computer models available today, that would be very interesting, and might lead to some observations that could be difficult to make in a living body.

    Reply
  6. Tuck

    “I am not looking in any great detail here at how endothelial cells are damaged…”

    But if endothelial cells can be damaged by an exogenous factor, and removing that factor reduces the damage, wouldn’t that be the “cause” of heart disease?

    Reply
  7. Gert van der Hoek

    Again a great bone for the dogs, a true box of Pandora: 1 more answer leaves many questions open. Let me ask this: what could trigger TF? Apparently a severely damaged bloodvessel. They are “stripped off” by ……. ? Accumulation of mithochondrial damage, or even cell death with a dozen causes?

    Reply
  8. Danny Evatt

    “What then happens to it?” Hmm.. I assume calcification then occurs, covering up the damaged blood tissue. This is the calcification that one sees during a CAC scan. Or are there steps in between…

    Reply
      1. JDPatten

        And then… the clot, now trapped under the new endothelium, becomes plaque?
        If true, seems a stupidly “designed” 🙂 healing process.

  9. Patrick Scully

    Brilliant article Malcolm. Explains the missing links brilliantly Yes, it all begins with endothelial damage. And biomechanical stress P Scully.

    Sent from my iPad

    >

    Reply
  10. Stephen Rhodes

    “Assuming, however, that it stopped growing, before completely blocking the artery. What then happens to it?”

    Only started reading around this last week so not sure how valid the argument is but
    http://www.ncbi.nlm.nih.gov/pubmed/24335500 talks about the development of a close packing polyhedral structure of erythrocytes in clots that effectively seal the ‘rupture/bleed’ – become ‘waterproof’ – , and that suppression of fibrinolysis results from the change in the shape of the erythrocytes preventing too early removal of the clot.

    If fibrinolysis is suppressed for longer, for some reason, might this give a greater period of risk of mechanical displacement of the clot before it is dissolved naturally?

    Or, if the clotting process doesn’t create the polyhedral erythrocyte structure due to insufficiency of fibrin then might clotting continue unabated without binding properly to the area of damaged endothelium until the clot is mechanically moved to cause a blockage.

    Needs more research methinks.

    Reply
    1. Dr. Malcolm Kendrick Post author

      Clots do not entirely dissolve naturally. If they did, they would just expose the blood to TF again, and another clot would form. A significant ‘core’ of the clot will remain untouched. Look up plasminogen and apolipoprotein A1 and Lp(a). You will find much here to ponder.

      Reply
      1. Stephen Rhodes

        Are we back to the evolutionary loss of the ability to produce Vitamin C and the ‘creation’ of Lp(a) as a surrogate repair in conjunction with the ApoA isomorph of plasminogen? And is the ApoA1 isoform a clot sticker rather than a cell sticker?

      1. Kevin O'Connell

        ‘The clot thickens…’ ‘Nice one’ …
        Does that mean that Nice is full of thick clots?

  11. Andrew Ward

    Dr Kendrick, wonderful article, yet again. I am puzzled as to why nature hasn’t recognized the significance of the dynamic stresses at the artery branches and reinforced the arteries at those points? I realize that this is a simplistic idea, but perhaps when we could produce our own vitamin C it wasn’t an issue? Lots to ponder.

    Reply
    1. Christopher Palmer

      ‘I am puzzled as to why nature hasn’t recognized the significance of the dynamic stresses at the artery branches and reinforced the arteries at those points? I realize that this is a simplistic idea, . . . ‘

      No. Not at all simplistic, Andrew, for nature has, for the greater part, evolved to cope – but crucially to cope with conditions that prevailed before some of the present ones.

      The natural conditions that prevailed over the time that nature was evolving the human, and developing the structural integrity necessary for healthy coronary arteries in the human, differ from the largely man-made conditions the modern human typically lives and operates under.

      Challenger was the shuttle mission that failed catastrophically when an ‘O’ ring failed.

      NASA had proceeded with a launch at a time when low temperatures prevailed. Condensation and icing is a problem the engineering must face while the rocket stands ready and waiting, yet on this day NASA ignored the very evident fact that temperatures were low and the level of icing was far in excess of that deemed usual. The ‘O’ ring had not been engineered nor tested to endure such low temperatures. It failed under the stress of low temperature.

      Perfection is rare in engineering nor even in manufacture. Expect that that ‘O’ ring was manufactured to the highest standards while also expecting that its structural integrity may not have been uniform perfection all the way round. In this scenario the point of failure could have been at a point of minor imperfection normal operating stresses would not have found, but more severe operating pressures did.

      In another scenario such an ‘O’ ring could have been old stock, and old stock can suffer assimilated degradation from attack by ozone in the air. Such oxidative stress can diminish the structural integrity and operational reliability of an ‘O’ ring.

      Degradation by oxidative stress is fairly ubiquitous risk and phenomenon in an oxygen rich atmosphere. Almost unavoidable if you breath air – which is why creatures that breath air have systems that deploy (and need a supply of) antioxidants to counter oxidative stress and limit the tissue damage it can give rise to.

      Quite possibly the systemic process at work behind CAD includes chronic aggravation of bio-mechanical stress while arising at a site where chronic oxidative stress could be a factor giving rise to a compromise of the structural integrity of the vessel whose job it is to be a channel for the flow.

      The reasons being that there are more endocrine disruptors, arguably, present in the modern age than in the age in which we evolved. These could have bearing upon flow, the stresses associating with flow, and upon the extent to which oxidative stress can compromise the health of cells and tissues. Indeed I think it likely that they do.

      We readily think the conditions we live under are ‘normal’, when from a suitably inclusive and evolutionary perspective they are not. Aspects of conditions which we readily consider to be normal are actually putting weaker aspects of our natural ‘design’ to the test. We operate beyond our design limitations, trending further as we go, and increasingly finding the weaknesses of ‘design’ as we progress. And there are prominent endocrine disruptors that have escaped common attention and understanding.

      Reply
      1. mikecawdery

        Christopher,

        Many thanks for some very interesting thoughts!, I am particularly interested in your views on antioxidants – something most experts seem to ignore with aplomb; CoQ10 being a classical example.

        It also underlines the current environment in which we are exposed daily to active and very unnatural chemicals. Today’s news that those who reach 65 can expect to live a further 19-20 years (according to gender) must be based on those born in the 1920s who have lived through the “Rise of Modern Medicine…………..” (J. LeFanu) and benefited by the introduction of anti-bacterials, new and improved surgical techniques.

        It remains to be seen whether this continues for those born in the age of hicarb/lofat, obesity, diabetes, lifetime pharmaceuticals, multiple vaccines to the immunolgically incompetent etc.

    2. BobM

      Probably because we’re really only supposed to live to be able to reproduce. So, maybe 40 years old or so. After that, there’s no “need” for us. So, the body doesn’t have to reinforce the arteries to live that long.

      Reply
      1. Lebret

        I suppose you phrase it so for the sake of keeping simple.
        But no one , nothing is planning we should live just to reproduce (believers from various religions will have a different mileage).
        It just happens that once we’ve reproduced we have reproduced. If we die therafter id does not change the natural selection process. We can even feed the worms and their own natural selection cycle. Irk ! 😉
        My oversimplistc view.

  12. Gary Ogden

    Thank you, Dr. Kendrick. Those of who love the sun are happy today. On this side of the pond the dermatologists have very effectively frightened the sheep into avoiding sun exposure entirely, or covering up with sunblock, which blocks both UVA and UVB. Not a good idea. When I cycle to the sawbones to have my BP checked it is always lower than when I drive.

    Reply
    1. Craig

      Excellent. A great piece of exposition!

      So perhaps while (low) vit D is predictive of cvd, it is just a surrogate marker for uv exposure? Uv destroys vit a also and damages skin collagen – another place where vit C may enter the picture. If skin tone is any indicator of vascular health, or vascular health capacity, then anecdotally one of the best things that ever happened to my skin was giving up wheat, beans and sugar.

      C.

      Reply
      1. BobM

        I think modern wheat is very bad for many people, including me. Not sure about beans, though (although I rarely eat these, as I’m on a low carb diet, but they do have relatively high amounts of “resistant starch”). I’m still experimenting with einkorn wheat, which is an “ancient”, unhybridized wheat. If I eat modern wheat, I develop symptoms such as chest congestion, digestion problems, acid reflux, etc. I haven’t found that einkorn wheat causes those problems (though I’m still testing), but it is a high carb food which is bad for me, as I become much hungrier after eating high carb. So, I limit even einkorn wheat to once a month or less, and I only started making it because our kids were complaining about not having bread and eating too many eggs for breakfast (“Eggs again?!”). I thought I’d make one bread and one set of waffles once per month, and that has worked out OK — except for the high carbs for me.

  13. Randall

    “NO is very definitely very important” but what if your arteries are coated with calcium how can NO interact with the endothelial cells? In my case even though 20% calcium in the tree arteries my condition as improved over 10 years

    Reply
  14. Kathy S

    There’s a large colored poster in my heart doc’s exam rooms that seeks to explain how our arteries clog up and cause a heart attack. It’s printed by one of the large pharma companies and emphasizes how cholesterol floating around in the arteries clogs things up. I think the next time I see my doc, I’ll ask him to take that thing down!

    Reply
  15. JDPatten

    So, if one is taking warfarin or one of the NOACs to avoid a clotted valve or a clotted atrium, mightn’t that mean that he is then less able to form a strong protective clot on a “stripped” bifurcation?
    Sounds dangerous.

    Reply
    1. Tuck

      Yeah, the anticoagulants lead to strokes from bleeding, rather than clots. This is what happened to the President of Israel, as I recall.

      Reply
      1. JDPatten

        I was taking 100 mg twice daily. Have backed off to 150 once daily. ($!) No change in BP after 6 months. How would improvements in endothelial function make themselves obvious anyway? Dunno.

  16. stcrim

    Since NO is important look how important Carbon Dioxide is! This is really not a reach, people who have heart disease over-breathe way above the norm. They have less circulating Co2 and thus less NO as a result of over-breathing. Stress? Maybe! Over-breathe on any level and you drive the Co2 out of your system and as a result you drive NO down. Think about it!!! No Co2 no NO.

    Reply
  17. MIchael DeSocio

    Dr. McKendrick said: “Vitamin C is, of course, a big clue.” [from “Responses” to Part One of “What Causes Heart Disease?”]. Here are some notes on inflammation and epithelial dysfunction caused by diabetes and hyperglycemia as contributing factors in heart disease, and some of the ways that Vitamin C might be a “big clue”.

    1. Hyperglycemia is associated with increased glycation of proteins, e.g., in membranes of epithelial cells lining the arteries (most crucially at focal points of “mechanical” pressure), initiating a cascade of biological repair responses, involving, among other things, Apolipoprotein A and clotting factors.

    Quote: “The experimental evidence gathered so far unequivocally demonstrates that AGEs can alter vessel wall homeostasis in a pro-atherogenic fashion through multiple mechanisms: alterations of extracellular matrix permeability, release of inflammatory cytokines and growth factors, alterations of antithrombotic properties of the endothelium and of the ability of the vessel wall to modulate vascular tone, and the increased expression of adhesion molecules and chemokines on vascular cells. Once initiated, a state of chronic vascular inflammation ensues, sustained by the migration and activation of inflammatory cells—mostly mononuclear phagocytes and T cells—that infiltrate the altered vessel wall. These processes thus trigger a cycle of ongoing cellular injury and vascular dysfunction….” Giuseppina Basta, et al., “Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes”, Cardiovascular Research 63 (2004) pp. 582– 592. http://www.ncbi.nlm.nih.gov/pubmed/15306213.

    2. There is evidence that Vitamin C may play a role in inhibiting glycation of proteins:

    Quote: “In healthy human subjects, supplementation of vitamin C significantly decreased serum protein glycation.” Paraskevi Gkogkolou and Markus Böhm, “Advanced glycation end products: Key players in skin aging?”, Dermato-endocrinology, 2012, July 1; 4(3): 259–270. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583887/

    3. Under conditions of hyperglycemia, excess glucose appears to obstruct vitamin c from entering cells (where vitamin c is needed not just to perform antioxidant functions but also to support collagen synthesis), perhaps as a result of evolutionarily-determined preference for glucose uptake to clear dangerous glucose out of the blood. Collagen, which requires Vitamin C for its synthesis, is vital to ensure blood vessel function, integrity and tissue repair. Vitamin C is chemically similar in structure to Glucose. (Humans, guinea pigs and apes supposedly lost the ability to synthesize Vitamin c from glucose about two million years ago due to a mutation.)

    Quote: “DHA [oxidized form of Vitamin C] and glucose share the same GLUT transporters leading to a competitive inhibition particularly secondary to pathologies that alter serum glucose levels and attenuate the bioavailability of vitamin C, for instance under hyperglycemic conditions caused by diabetes”. Giuseppe Grosso, et al., “Effects of Vitamin C on health: a review of evidence”, Frontiers in Bioscience 18, June 1, 2013, pp. 1017-1029. “Recently, several studies observed a decrease in plasma vitamin C levels in both type I and type II diabetes….” ibid. [When DHA enters cells it is reconverted to an antioxidant form of Vitamin C.] http://www.ncbi.nlm.nih.gov/pubmed/23747864.

    4. Nitric Oxide Synthase production may also be adversely affected due to antagonistic effects of hyperglycemia on Vitamin C, as referred to above.

    Quote: “… vitamin C enhances the NO synthase activity by maintaining tetrahydrobiopterin, an essential co-factor for the enzyme, in its reduced and active form, normally inhibited by ROS that oxidize and thus deplete the co-factor. By increasing NO production, vitamin C may indirectly protect the vascular endothelium due to its actions, namely smooth muscle cell relaxation, downstream vasodilatation, and inhibition [of] the effects of pro-inflammatory cytokines and adhesion molecules important in atherosclerosis”. Grosso, et al., ibid.

    5. Insulin resistance leads to increased production of inflammatory cytokines such as Tumor Necrosis Factor (TNF) and the inflammatory marker, C-Reactive Protein.

    6. When fat is deposited in visceral fat depots, which are associated with Diabetes-related obesity and dyslipidemia, these visceral fat depots express pro-inflammatory signaling compounds and hormones, thus setting in motion a “positive feedback” mechanism leading to more systemic inflammatory damage and the further exacerbation of pathological processes outlined above.

    Reply
    1. mikecawdery

      Christopher,

      Many thanks for some very interesting thoughts!, I am particularly interested in your views on antioxidants – something most experts seem to ignore with aplomb; CoQ10 being a classical example.

      It also underlines the current environment in which we are exposed daily to active and very unnatural chemicals. Today’s news that those who reach 65 can expect to live a further 19-20 years (according to gender) must be based on those born in the 1920s who have lived through the “Rise of Modern Medicine…………..” (J. LeFanu) and benefited by the introduction of anti-bacterials, new and improved surgical techniques.

      It remains to be seen whether this continues for those born in the age of hicarb/lofat, obesity, diabetes, lifetime pharmaceuticals, multiple vaccines to the immunolgically incompetent etc.

      Reply
  18. michael goroncy

    Two thoughts on this current topic.

    (1) Many years ago, I read the work of Louis Ignarro (Nobel Laureate) on the signalling properties of ‘Nitric Oxide’.
    I adopted his protocol for 7-8 years (although lapsed in the past year).

    Combo: To boost nitric oxide
    *must be taken together and  do not exceed dose. Safe maximum.
    :with or without food..OK
    (A)          L-arginine………..6 grams
    (B)          L-citrulline…         1 gram
    (C)          Alpha lipoic acid…50mg
    (D)          Vitamin C…………500mg
    (E)           Vitamin E………….200iu
    (F)           Folate………………800mcg    

    (2) On the subject of ‘Nitrate medications’ for angina. My thought process is either terribly wrong or right.
    Although all my ‘Coronary arteries’ are totally occluded, and rely on ‘Collateral circulation’. Been this way for the last 27 years, after CABG.
    My reasoning is (although contrary to medical advice’ is as such: Nitrates force the heart muscle to be lazy. Without them, the heart is forced to grow and strengthen ‘Collateral circulation’…..’The cloud with a silver lining’
    (3) BTW: I think our host (Malcolm) will be introducing ‘Blood Viscosity’

    Reply
    1. Dr. Göran Sjöberg

      Michael,

      My daily protocol says

      1600 IU Natural E-vitamin (no problem with angina any more!)
      8000 mg Vitamin C (I love Linus Pauling’s 40 years old writing about this subject)
      1 g fishoil
      5000 IU Vitimin D3 and K2 to make it work

      And then of course the strict LCHF regime at the bottom – here they are after Professor Tim Noakes these days again in South Africa.

      And I am still alive ‘kicking’ and like you with all my arteries clogged since 16 years but no CABG and no medicines.

      Life is wonder!

      Reply
      1. Dr. Göran Sjöberg

        Joe,

        I take a betacarotene supplement which is a precursor to vitamin A.

        By having grassfed liver quite often and other organ meat I probably am overcautiously stocking up on fat soluble vitamins. Especially the the heart as ground beef is a treat. All this organ meat was valued among inuits and indians who fed their dogs the lean muscle meat.

        The seal liver was shared raw on the spot by the inuit hunting team. Myself, I have cultural prejudices against cutting in on raw liver – deep culture resistance I guess – no logic involved. I am though carful not to overcook liver.

      2. annielaurie98524

        I am surprised that more people in the US do not eat liver. Perhaps they did not get it growing up? “Liver and onions” was a staple in my family. A suggestion I give to people that cringe at the thought of eating liver is to fix it in the Asian “pepper steak” style: slice the liver thin, lightly sautee it with sliced green onions, sliced hot and/or sweet peppers, sliced mushrooms, a bit of organic soy sauce, a little chopped ginger, chopped garlic, a spoon of tahini and a sprinkle of sesame seeds. I also like to throw in a sprinkle of 5-spice powder. Don’t overcook or the meat will get tough. People always think they are eating sliced round steak with this recipe.

      3. JanB

        Hi – I was made to eat liver as a child and to this day (I’m now 73) I shudder at the look of it and the very thought of it makes me gag. HOWEVER, I have recently discovered Ardenne Pate which I really enjoy and am wondering if it counts. Too good to be true?

      4. Joe

        “By having grassfed liver quite often and other organ meat I probably am overcautiously stocking up on fat soluble vitamins”

        Thanks! You’re good to go!

  19. wdmeans

    I love reading your posts! I can’t get enough especially when you really get into physiology!!! I could read that for hours!!! Thank you!!

    Reply
  20. wdmeans

    I love reading your posts, especially when you really dive into the physiology!! I could read it for hours!! Thank you so much. Of course I learn a lot besides the physiology but that was my favorite subject in nursing school!

    Reply
  21. Diana

    Tissue factor. Where from?

    “Fungal Invasion of Normally Non-Phagocytic Host Cells” (Filler, 2006)
    http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.0020129

    “A. fumigatus conidia and hyphae can invade the luminal surface of endothelial cells by inducing their own endocytosis in vitro [49,57,58]. The significance of conidial invasion of endothelial cells is uncertain because it is highly probable that the organism has formed hyphae by the time it invades endothelial cells in vivo [53]. Hyphae are endocytosed by the luminal surface of human umbilical vein endothelial cells more slowly than are conidia. Endocytosis of hyphae causes endothelial cell damage as well as up-regulation of endothelial cell–tissue factor expression [57]. It is likely that the expression tissue factor contributes to the vascular thrombosis at sites of A. fumigatus angioinvasion.”

    “The endocytosis of live hyphae caused significant endothelial cell damage. Interestingly, killed hyphae induced a similar extent of endothelial cell damage, suggesting that a factor associated with the fungal cell wall is toxic to these cells. Damage to endothelial cells results in exposure of vascular smooth muscle cells, which can release large quantities of tissue factor and cause intravascular thrombosis [62]. Thus, induction of endothelial cell damage during angioinvasion may contribute to thrombosis and tissue infarction, which are characteristic of mucormycosis.”

    Reply
  22. John Scott

    So good…
    I think I should move to your catchment area.
    It would be great to have you as my GP.
    Although I would miss my West coast Scottish fishing village, perhaps you could move back to Scotland.
    I think the UK flooding problems could be eased by those trying to manage the problem, by reading your blog.
    Swollen rivers that have no flexibility due to narrow culverts and building on flood plains.
    Let the rivers expand when swollen to catchment areas, resevoirs etc.

    Reply
  23. Nigella P

    This is the best series of articles I have read in a long time. Thank you so much Dr Kendrick – you clearly could have been a detective in another life. Particularly interested in your references to sunshine / Vit D given the 38 pages of NICE guidelines on being in the sunshine issued today!

    Reply
  24. vjadams2014

    So Mediterranean sunshine may be at east as important as the “Mediterranean diet” in whatever form in protecting heart health? That sounds like a good reason to head south!

    Reply
  25. Ek!mdn0b

    Amidst much discussion about vitamin C, Linus Pauling may have got it right all those years ago but, of course, nobody had a vested interest in doing the trials. And Buteyko also has a point – breathing in through the nose stimulates NO production via the sinuses and exhaling through the nose slows down the exhalation allowing more CO2 to be retained, so stimulating O2 circulation.

    Reply
    1. Dr. Göran Sjöberg

      I actually pulled Pauling’s book from 1976 “Vitamin C, the Common Cold and the Flu” from my shelf today to refresh my memory.

      A striking effect of my (and my wife’s) strict LCHF is that I have not had any cold or flu since I ‘converted’ six years ago, nor my wife. Before that I have, for as long as I can remember, had a number of them each year and often severe – I didn’t miss anything that passed me.

      Reply
      1. Gary Ogden

        Dr. Sjoberg: I ,too, haven’t had any illness since making a dietary change eleven years ago. I simply stopped eating all industrial food, and gradually have refined it, first to WAPF, then, a couple of years ago, giving up grains and legumes, to something resembling what is here called Primal, but I just call it mighty good garden produce, pastured animal foods, high-quality seafood and sea vegetables, and nuts. I feel wonderful at 67.

      2. Colombo

        I’ve heard the explanation that vitamin C gets recycled because of CoQ10 and Glutathione, so if you have a diet rich in organ meat (CoQ10) and all the precursors of GSH in the diet, perhaps the rate of depletion of vitamin C is much slower, allowing to wait to find the ocassional tart berries. On the other hand, but as long as many (I mean very many) raw leaves are also present in the diet, or some part of an animal high in C (like the eyes), then the paleo diet should have enough ascorbate in it. This is the explanation I was given. I don’t know if it is true.

        I suspect the conundrum could be that the whole idea that humans cannot make vitamin C is just a hasty generalization, a wrong assumption, and that, perhaps, in some people, with the adequate environment and diet, the “dormant” genes for its synthesis could be awakened. This is just a wild speculation on my part.

        Has anyone studied whether the inuit (or other peoples from very cold places with very little vegetation and, therefore, living with an obligate animal-foods based diet) have those genes dormant too? If so, this is a remarkable mystery. (Perhaps more vitamin C is needed in warmer climates, because of a higher chance of infections?)

        What do you think, Dr. Sjöberg?

      3. Tuck

        “…perhaps the rate of depletion of vitamin C is much slower, allowing to wait to find the ocassional tart berries…”

        Fresh meat contains all the vitamin C that’s necessary for human life. Vitamin C degrades over time, however, hence sailors on long voyages eating C-deficient stored meat would suffer from scurvy.

        When Vilhjalmur Stefansson did his all-meat diet experiment in NYC after returning from his Arctic voyages, one of the bad outcomes the experimenters looked for was scurvy. It did not appear.

        (One interesting question would be if freezing meat, as is common now, and I presume in the Arctic, prevents the C from degrading. Meat stored on sailing ships was preserved with salt, of course.)

      4. Dr. Göran Sjöberg

        Colombo,

        Good questions!

        As far as my understanding goes when we parted from the chimpanzees 5 million years ago this fundamental C-genetics was already set up in us being mainly vegetarians at that time so there was no evolutionary need for converting dextrose into vitamin C. When we turned more carnivorous around 1 million years ago we where still getting enough from the vegetables.

        Talking eskimos or inuits, living exclusively on meat, they got enough vitamin C from the meat. I think they were pretty cautious in their traditional attitudes towards their the food available. Some organs were preferred due to higher contents of vitamins as far as I remember.

        By the way , the ability to live on meat exclusively was carefully examined through a one year experiment carried out by the end of the 1920th at the Bellevue hospital in New York on two explorers who had been living among the inuits for several years, Vilhjalmur Stefansson and dr. Andersson. When they came back to New York around 1920 and claiming that they had exclusively been eating the usual inuit meat fare there was mistrust around.This was the time of the great vitamin discoveries and their claims where contested since it was believed that they couldn’t avoid getting scurvy if only eating meat with the minimal C-vitamin content.

        However the one year experiment was successfully showing that their health state actually improved on such a purely meat diet. It seems as, as long as you avoid the carbohydrates, your cells preserve the available vitamin C and that the amount in meat is adequate. As always the physiology turns complex when you start digging into it as you indicate.

        My own approach is today a very broad and very cautious one due to my precarious metabolic health state. Keeping away from all kind of processed food as far as possible, mostly organic, and especially working on restoring my insulin sensitivity by avoiding all carbs. When people ask me for advice I usually say “Don’t eat more carbs than you can take!” When you are young and healthy you can probably sustain a lot of carbs but probably as me pay a high price. If asking for more advice I often state: “Up with omega-3, down with omega-6 and in with the saturated fats.”

      5. Craig

        Göran, another part of the vitamin C pre-history is that perhaps in the same epoch, the human ancestor also lost uricase functionality. One of these mutations might have led to the other . Uricase is the enzyme that breaks down uric acid in many other animals. Uric acid news makes up maybe 1/2 of the antioxidant capacity of human blood and it has a complex relationship with vit C. I am painfully aware of this because I have suffered from gout in the past. One relevant aspect of uric acid to this current discussion is that a prolonged high uric acid level may lead to kidney damage such that the kidneys become hypersensitive to sodium levels and a type of salt driven high blood pressure results.

        Having a high uric acid level seems to reduce the chance of developing Parkinson’s disease almost to zero. Thank goodness there is this consolation prize.

  26. Jude

    Thank goodness for you! Clever & common sense – what a combination:-) Love the way you write. You are direct, specific, factual and funny. I hope your candour and bravery makes other ‘professionals’ think twice before just going with the flow in a sheeplike manner.

    Reply
  27. JanB

    Thank you, Dr. K. I find your posts so informative and mentally stimulating that they make me wish to be 40 or 50 years younger so that I could study biochemistry or some branch of medicine.
    I look forward to each and every post.

    Reply
  28. mikecawdery

    Dr Kendrick

    Brilliant once again. It gets more informative at each step. Congratulations.

    One thing caught my eye on first perusal.

    Possibly the most powerful single factor that can do this is sunlight

    and

    Any factor that reduces NO synthesis is unhealthy, any factor that increases NO synthesis will protect against CVD.

    The two cited papers are very interesting. However, the second citation:
    http://www.ncbi.nlm.nih.gov/pubmed/19797169

    the abstract is available at Pubmed with a “Free full text” label but attempting to download it gets the the following response:

    “Not Found

    The page you were trying to reach could not be found. I wonder why. I am adding it to my long list of items and reports that have unaccountably disappeared.

    Please check the address for the page you were trying to reach. If you believe you have reached this page in error, you may contact us with any questions”.

    In view of the news today claiming that virtually and sun exposure without sunscreen is BAD one begins to wonder if this “BAN” is essentially more agnotology and astroturfing by the sunscreen manufacturers!

    Reply
  29. Sylvia

    So impressive Dr Kendrick. Sunlight, something so relaxing and life giving and of which in Northern Europe we are so lacking in winter. So to live in wonderful climes, eat a so called healthy diet, have enough money to pay the bills gives you a head start. But to live in the sun in Sicily in a poor socio economic group is another story. Your article is fantastic, the deep mysterious mechanisms of how the body works is quite wonderful.

    Reply
  30. Albert

    You clearly think that sunlight is important for health saying: “Possibly the most powerful single factor that can do this is sunlight … Essentially, if you sunbathe, NO is released throughout the body, and your blood pressure drops (as your arteries open wider). Other studies have found many other major benefits of sun exposure on lung, breast, prostate and colo-rectal cancer, but that is a story for another day.”

    Do you think that taking vitamin D3 as a supplement works similarly to getting sun exposure, or should we be ditching our vitamin D3 and instead buying sunlamps that mimic the spectrum of the sun? (Obviously it is preferable to get our sunlight in natural form, but that is not possible during winter in the northern latitudes.)

    Reply
      1. Albert

        I agree with you. If the sun is available, it is a better choice than supplements. However in the winter, there is very little sunlight. Do you think Vitamin D is adequate, or should you get in front of a sunlamp that mimics the spectrum of the sun?

      2. Craig

        So are there good data to suggest that Europeans now living closer to the equator have significantly lower rates of vascular disease?

        C.

      3. Dr. Malcolm Kendrick Post author

        UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase.
        Liu D1, Fernandez BO2, Hamilton A3, Lang NN4, Gallagher JM5, Newby DE4, Feelisch M2, Weller RB6.
        Author information
        Abstract
        The incidence of hypertension and cardiovascular disease (CVD) correlates with latitude and rises in winter. The molecular basis for this remains obscure. As nitric oxide (NO) metabolites are abundant in human skin, we hypothesized that exposure to UVA may mobilize NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers, irradiation of the skin with two standard erythemal doses of UVA lowered blood pressure (BP), with concomitant decreases in circulating nitrate and rises in nitrite concentrations. Unexpectedly, acute dietary intervention aimed at modulating systemic nitrate availability had no effect on UV-induced hemodynamic changes, indicating that cardiovascular effects were not mediated via direct utilization of circulating nitrate. UVA irradiation of the forearm caused increased blood flow independently of NO synthase (NOS) activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labeled with the NO-imaging probe diaminofluorescein 2 diacetate revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent manner, with the majority of the light-sensitive NO pool in the upper epidermis. Collectively, our data provide mechanistic insights into an important function of the skin in modulating systemic NO bioavailability, which may account for the latitudinal and seasonal variations of BP and CVD

      4. Craig

        Maybe mad dogs and Englishmen are not as well evolved as some. 😉

        Thanks for providing the deailed response to my question earlier. One of the articles that branched off from the one you quoted mentions that melanoma is a more serious problem amongst people who don’t get regular moderate exposure to sunlight ie less than you would need to get sunburn, and this also strengthens their resistance to sunburn. I guess you could say that sunburn is there to warn us not to get too much sun. Evolution doesn’t much care if you die a horrible death from skin cancer so long as you have passed on your genes beforehand and everyone dies of something eventually.

      5. JDPatten

        There’s not enough sun for anyone in Massachusetts to make their own D for almost half the year. British Isles are even farther North. What do we all do for the sake of our NO and BP?

        Sun lamps?

      6. JDPatten

        Sun lamp. Is that what you do yourself Dr Malcolm?
        (The proof is in what the Dr prescribes for himself. 🙂 )

      7. Dr. Malcolm Kendrick Post author

        I tend to believe that evolution works. We can get enough sun in the summer to tide us over – so long as we get a decent amount of exposure. I suspect we are all running pretty short by mid-March. Perhaps sun lamps could be a good thing, but I am not sure.

    1. Bob Niland

      re: Do you think that taking vitamin D3 as a supplement works similarly to getting sun exposure,…

      That’s a crucial question, and my general impression is that for most things, including CVD, the answer is yes. What target is also important. The consensus view is very likely too low. In the US, both Drs. Davis & Perlmutter encourage achieving a titer of 60-70ng/ml, which might appear high, but not as high as, say, an Israeli lifeguard just getting sun.

      re: …or should we be ditching our vitamin D3 and instead buying sunlamps that mimic the spectrum of the sun?

      a. that still won’t work well for people over 40
      b. matching the exact SPD (spectral power distribution) of the sun may not be trivial
      c. there are major circadian considerations to light exposure
      But expect much more attention to this as time goes on.

      re: (Obviously it is preferable to get our sunlight in natural form, but that is not possible during winter in the northern latitudes.)

      And Vitamin D synth from sunlight declines with age.

      On the consensus advice to hide from the sun, I’m inclined to think that the resulting pathologies from “excess” exposure say less about sunlight than they do about the DIET that the sunbathers follow.

      I used to sunburn, easily and badly, on a full-time glycemic diet (SAD or Zone). Since switching to a grain-free LCHF diet high in DHA&EPA, as well as other elements, I no longer do. And that concludes my anecdote for the day.

      Reply
      1. mikecawdery

        Dr Holick suggests that exposure to direct sun for a few minutes (10-20) is a good way to naturally get Vit D3. But the sunscreen manufacturers objected to ADA (dermatology) and he lost his research grant. In my local Trust hospital, the dermatology clinic notice board is covered exclusively with warnings about the sun, use of sunscreens etc. Not a word about Vit D. and this despite the CMO’s advice.

      2. annielaurie98524

        I’ll second your anecdote. As a medium-light complected redhead, i used to burn quite easily. Since going to an 80+% ancestral diet (drastically reducing my grain consumption, eating only real food, removing refined sugar, eating organic as much as possible, getting plenty of Vite D through diet and supplements), I find I can stay in the summer sun for many times longer than I used to –even at nearly 70 years old, and probably thus having thinner, more fragile skin than in my youth.

      3. Marijke

        In winter at higher latitudes, the sunlight does contain UV-A but no UV-B. The latter is needed for vitamin D. The former for NO, so the sun could still provide NO in winter.

      4. Patrick Snook

        I recall reading that the sun’s effectiveness for producing Vit-D via *UVB* radiation, which depends on the sunlight’s angle of incidence with the Earth (hence the seasonal and latitude variability), can be estimated by checking that your shadow is shorter than your height.

        Where I live, NE USA, that translates to no UVB from October-ish to May-ish.

  31. Lebret

    Dr K Sayeth:
    “By this I mean you can say that smoking causes heart disease – and you would be right. You can also say that Systemic Lupus Erythematosus (SLE) causes heart disease – and you would also be right. You can say that type II diabetes causes heart disease – and you would be, guess what, right. You could say that obstructive sleep apnoea causes heart disease and you would be… right again. Steroids…right again. High levels of fibrinogen…right once more. Cushing’s disease…right. Depression… bang on the button.

    But you have to be able to answer the question, HOW can these very different things lead to the same disease?”

    But but …. t’is obvious !
    They raise the Ugly cholesterol you stupid ! THAT’S WHY !
    Tongue-in-cheekingly yours.

    Reply
  32. Tony

    Several contributors to this blog have mentioned low levels Vitamin C, D etc., being a factor not just of heart disease, but of our overall health in the environmentally challenging lifestyle that we live today. In researching my own health issues T2 diabetes was easily sorted (LCHF diet), I am now concentrating on the vitamin (or lack of) side of things, plus cancer as a metabolic disease, (early colorectal) and Linus Pauling & Otto Warburg played an early part of this research, which is ongoing. (slightly off blog, Artesumate and 3BP seem to the cancer hopes to a metabolic cure)

    A well researched presentation on causes of heart disease (and cancer) was presented by Suzanne Humphries http://artimus.se/en/productions/vitamin-c.php about a year ago, covering in depth studies and summaries of Vitamin C and disease, that is both layperson and professional friendly…..(apologies if posted elsewhere) for me this lecture is a game changer and confirmation of Linus Pauling’s Vitamin C thesis.

    Reply
    1. mikecawdery

      Tony,

      Many thanks for the link. Artemisinin/artesunate is well known for its use in malaria; I was intrigued by its possible use in cancer

      I am not sure whether Artemisinin/artesunate is authorised for use in UK for any purpose but can be used with a special icense. The reason for this goes back many decades.

      Reply
      1. Tony Gaskell

        Hi Mike,
        here are the relevant links for the recent UK trials of Artesunate:
        http://theconversation.com/could-leading-anti-malarial-be-used-as-an-experimental-treatment-for-bowel-cancer-34893
        http://www.sciencedirect.com/science/article/pii/S2352396414000346
        As you say, artesunate is an effective anti- malaria drug, with very few side effects. Emerging evidence suggests that it could be effective in slowing / preventing cancer growth, and in preventing liver met’s in colorectal cancer, 3BP could be an adjuvant to this treatment. Artesunate / Artemisia can be bought in uk (made in Germany)

      2. mikecawdery

        Tony,

        Many thanks for the links. I find that these excellent articles by Dr. Kendrick also provide a vast amount of information by other contributors. Anti-malarials are of interest as I have had it many times, luckily long before resistance developed. Its use in cancer in association(?) with 3BP is of interest since I was introduced to the metabolic theory of cancer on this blog.

    2. Stephen T

      Tony, thank you for the link to the interesting talk on vitamin c. The opposition to vitamins is curious when you look at the colossal death toll from prescribed drugs that barely gets a mention. I think drug companies detest the idea that vitamins help people, so they insist that the daily recommended amounts are barely enough to ward off rickets and scurvy.

      Reply
      1. Mr chris

        Hello
        Big pharma aversion to vitamins surely springs from inability to patent them.
        There are many grandmother style natural remedies that are effective and without side effects, but alas carry no patent protection.
        I know my banging on about beetroot and blood-pressure amuses many, but it works.

  33. Maggie

    This explains why my blood pressure shot up after I moved from a southern U.S. state to the dark and rainy Pacific Northwest

    Reply
  34. Colombo

    I have a few tangential questions about the “biomechanical stress” point you make as prime factor associated with damage in endothelial cells. Is aerobic exercise related in any way with this stress? I suspect so.
    This “high intensity training” that is in vogue these days (anaerobic, slow weight lifting or pushing), is as stressful to endothelial cells? I’ve heard the reassuring “no” by its proponents, but I tend to disbelieve reassuring answers.
    I’ve also heard that people with varicose veins should be very careful with weight-lifting. If a patient has to exercise, but aerobic exercise is bad for his arteries, and anaerobic exercise is bad for his veins, then what exercise can he make?
    I guess we’ll end up in that ancient recommendation (perhaps spurious) by Hippocrates of “just walk, there’s no better medicine”.

    Reply
    1. Tuck

      “This “high intensity training” that is in vogue these days (anaerobic, slow weight lifting or pushing), is as stressful to endothelial cells? I’ve heard the reassuring “no” by its proponents, but I tend to disbelieve reassuring answers.”

      One of the best prospective studies we have on exercise and health is the Stanford Running Study, which followed a cohort of older runners and matched non-runners until death (still underway, last update was after 21 years), and then determined cause of death. Runners suffered half the rate of disability and half the per-annum death rate (all cause!) of non-runners. The runners were in a marathon club and trained at pretty high levels of activity.

      So no, there’s no evidence I’m aware of that running is harmful. If it was a pill, it would be a super drug.

      (Oh, and the study started as to track the higher rates of osteoarthritis they expected to find in old runners. It too was much lower.)

      I really hope Dr. Kendrick’s answer to this whole series doesn’t come down to mechanical stress from blood flowing…

      Reply
      1. JDPatten

        You can always have too much of a good thing. Research suggests that marathoners are two to seven times more likely to present with atrial fibrillation that the general public (whoever that might be!).

      2. Tuck

        “You can always have too much of a good thing.”

        Sure, but we don’t yet know what “too much” running is.

        “Regular exercise is associated with substantial health benefits; however, little is known about the health impact of extreme levels of exercise. This study examined the prevalence of chronic diseases, health-care utilization, and risk factors for exercise-related injuries among ultramarathon runners. Retrospective, self-reported enrollment data from an ongoing longitudinal observational study of 1,212 active ultramarathon runners were analyzed. The most prevalent chronic medical conditions were allergies/hay fever (25.1%) and exercise-induced asthma (13.0%), but there was a low prevalence of serious medical issues including cancers (4.5%), coronary artery disease (0.7%), seizure disorders (0.7%), diabetes (0.7%)…”

        “Health and Exercise-Related Medical Issues among 1,212 Ultramarathon Runners: Baseline Findings from the Ultrarunners Longitudinal TRAcking (ULTRA) Study”
        http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083867

        Injury rate went down as time in the sport increased, which implies experience is important.

        “Ultramarathon runners, compared with shorter distance runners, have a similar annual incidence of exercise-related injuries but higher proportion of stress fractures involving the foot, and it is the younger and less experienced ultramarathoners who appear most at risk for injury.”

        An ultramarathon is something longer than a marathon, often 50k, 50 miles, or 100 miles.

        If there was a negative effect for running, you’d think it would start to appear here. I expected it to, and was quite surprised by these results.

        “Research suggests that marathoners are two to seven times more likely to present with atrial fibrillation that the general public (whoever that might be!).”

        If you have a higher rate of AF, and half the per-annum death and disability rate, isn’t that a good trade? 🙂 I suspect the AF incidence is related to the diet runners usually follow, as AF is closely associated with fibrosis, and fibrosis can be induced by a high glucose level. All that carbo-loading may be a bad idea.

      3. JDPatten

        Tuck:
        Whew. I guess you don’t know about atrial fibrillation.
        “If you have a higher rate of AF, and half the per-annum death and disability rate, isn’t that a good trade?”
        Good? No. You have to understand what it is you’re trading.
        First, AF IS a disability. You can’t have it both ways.
        Imagine: You’re working hard. Suddenly you feel faint. Gasping, you can’t get enough air in your lungs. You realize that your heart is slamming into your ribs at an erratic rate. This is incapacitating.
        If you have the presence of mind to go in deep and pay close attention, you realize there’s also trembling or quivering going on in there. The atria are going wild and the ventricles are picking up part of the crazy signal being passed along in a haphazard fashion. Circulation is just not working very well at all. Blood chemistry changes and, over time, changes in the atrial endocardium promote clotting. The clot can build in the stagnant flow areas of the left atrium and/or the left atrial appendage. A bit of that massive clot breaking loose means stroke. Unless you take warfarin and all the horror that involves. Or one of the NOACs. Don’t let anyone tell you that this is not life threatening. 😦
        This is a description of paroxysmal AF. Living with repeated bouts of this, particularly when you’ve always participate in an active lifestyle, is extremely disheartening. QUALITY of life counts in the equation.

      4. Tuck

        “Whew. I guess you don’t know about atrial fibrillation.”

        I know a great deal, in fact, as my father has had it for the last three decades, is on warfarin, and got a stroke when his idiot doctor attempted to “reset” his heart electrically to “cure” it. The stroke followed a couple days later when his “normal” heartbeat reasserted itself. So I’ve researched it extensively.

        You’re missing the point in your response. If running gives you atrial fibrillation, but you suffer the consequences (stroke) at half the rate of the normal population, and much later, than that’s a good trade-off, surely. Most runners are not the professional endurance athletes who’ve shown the higher risk for AF, at any rate.

        You’re also making the “correlation equals causation” mistake. I think a far more likely explanation for increased AF in endurance athletes is that they’ve been told for decades that they need to fuel their activities with glucose, and hyperglycemia is a well-recognized risk factor for AF. Additionally, oxidation products can induce AF, and these are well-demonstrated to be diet related.

        “Oxidized Ca2+/Calmodulin-Dependent Protein Kinase II Triggers Atrial Fibrillation”
        http://circ.ahajournals.org/content/128/16/1748.short

        But at any rate, since the larger studies have failed to show any negative effects from running, it’s kind of tough to make the argument that it’s bad for you…

      5. Ray Davies

        Surely if one was in poor health and arthritic, one would not be indulging in marathon running, (ergo, marathon runners are healthier than the more sedentary).

        In other words, the running doesn’t make them healthy it just enables them to do it.

        Ray

      6. JDPatten

        Tuck:
        My heart goes out to your father. Do you have any idea what caused/triggered his AF? Lone AF has been given that name when the cause can’t be figured out, but, surely, there’s always something/s that lead to it?
        I’ll grant you that carb loading is probably doing all sorts of nasty things to runners, but the valid ‘“correlation equals causation” mistake’ applies to this idea as well. You just can’t tell without lots of RCT. That’ll never get done.
        Hm. If you run, reducing your risk of stroke, then get AF (From the running? Whatever. There is a correspondence), your risk of stroke has just gone way up. “They” are now conservatively estimating that 30% of unexplained strokes can now actually be explained as the result of AF that no one knew the patient had.
        Again, the catch phrase is “too much”. As applied to running or anything else, the borderline is an individual’s variable that only he can discover.

      7. JDPatten

        Tuck:
        Also: Might I presume that you were describing a cardioversion performed on your father?
        I would mention a couple of observations, having gone through this myself.
        Anticoagulation is required (according to protocol, with good reason, I think) for a number of weeks before the procedure, and during and after the procedure. Then, a sticky “paddle” under you, one on top, propofol for a couple minutes of sleep… and zap. That stops the arrhythmia on the spot. Or not. Did me. Though sometimes they’ll give it two or three tries in that session.
        You say the stroke happened a few days later. When normal rhythm returned. There could well have been a bit of earlier clot dislodged only after a few days, but the normal rhythm would have been in place at the time immediately after the procedure – if the procedure actually did anything at all.
        Warfarin is really pretty bad stuff. Really difficult to keep your INR on track. You can’t take a vacation from it without risk. The risk of stroke with warfarin is only a reduction anyway.
        It works by countering vitamin K. Of course, without K1 and K2 your bones weaken and your vessels calcify. Warfarin seems to be doing this. Actual cause? Hm…
        Does all this ring true at all?

        BTW, that description of paroxysmal AF above was of me, before three ablations. I follow my father who died of a massive stroke after three years refusing treatment for his AF.

      8. Tuck

        “Does all this ring true at all?”

        Yep. My Dad’s had two strokes in his 82 years (that we know of): the kidney last year, and the brain a few days after the electrical therapy. So I think it’s fair to assign the brain stroke to the procedure.

        Warfarin’s a lousy drug, agreed, but he’s been on it 30 years with, well, I won’t say “no ill effects”, but it’s been tolerable.

        He did need a bunch of stents (for angina), this was done *after* the paper came out showing they were ineffective, but very profitable. The doctor (the previous cardio’s son-in-law) commented on how much calcification he had. I pointed out to my father that he’d been on rat poison, so of course he did. Asked him if the doctor had prescribed k2 supps to prevent it, of course he hadn’t.

        “BTW, that description of paroxysmal AF above was of me, before three ablations. ”

        Yes, I figured. Not fun, I’m sure. Hope you’re better.

        BTW, my father track in high school, but not since. Giving up running didn’t help him…

        The notion, IMHO, that running can cause AF is the worst sort of what I call “doctor-think”. One of the unique attributes of our species is our ability as endurance runners. How unlikely is it that our hearts aren’t well evolved to support that attribute? (And no, cavemen didn’t live until 30, unlike us. They lived just as long.) And when you read papers observing that runner’s hearts are “abnormally large”, one wants to shout: “no, the sedentary people’s hearts are abnormally small!”.

  35. DBM

    Fantastic as always Dr K, I am really enjoying this current series and am eagerly anticipating the next instalment.

    NO is very important and and very powerful but before everyone gets too excited about finding ways to increase their NO levels they might want to consider the following;

    http://www.sciencedirect.com/science/article/pii/S0531556598000503
    or
    http://onlinelibrary.wiley.com/doi/10.1196/annals.1356.064/abstract

    These articles outline the Nitric oxide hypothesis for ageing. This essentially states that excessive amounts of NO can promote or accelerate ageing and causes damage in every organ especially the brain and the heart. In the presence of infection or expose to LPS
    ( endotoxin) the body releases high amounts of NO which is toxic to bacteria and viruses but also harmful to human cells. This hypotheses states that recurrent infections over the course of a lifetime play a significant role in the ageing process via release of toxic quantities of NO.

    Lots of interesting stuff within these articles;

    ‘NO my be a major factor for the development of Coronary heart disease…stress inflammation and infection have all been shown to induce iNOS and it likely that this triad of events is very important in the progression of coronary heart disease.’

    “…At the Third International Symposium on the Neurobiology and Neuroendocrinology of Aging, I (McCann, 1997) presented evidence to suggest that excessive production of the free radical, nitric oxide (NO), in the central nervous system (CNS) and its related glands, such as the pineal and anterior pituitary, may be the most important factor in aging of these structures. Evidence for this hypothesis has been accruing rapidly. Because of the fact that the synthesis of inducible NO synthase (iNOS) following injection of bacterial lipopolysaccharide (LPS) in the rat was much greater outside the blood– brain barrier (Wong et al., 1996), for example, in the anterior pituitary and pineal gland, than inside this barrier, it occurred to us that NO might play a role in aging of every organ system of the body. The evidence for this concept is particularly well developed to explain the pathogenesis of coronary arteriosclerosis.”

    “…These findings provide an explanation for the high incidence of early onset Parkinsonism in many people who served in World War I and developed influenza. There was a major epidemic of influenza with encephalitis, which presumably led to generation of large amounts of NO in the region of the substantia nigra that then caused loss of dopaminergic neurons and eventual development of Parkinsonism many years before it would have appeared as a result of normal aging. The appearance of Parkinsonism with age is probably related to the quite rapid decline, beginning at age 45, in dopaminergic neurons in this region even in normal individuals (Knoll, 1997), which may also be caused by enhanced NO generation during infections.”

    “…In conclusion, although much work needs to be done, it is already known that treatment of patients with antioxidants, vitamin C and E, which would reduce the toxic effects of NO, is of value in patients with CHD. This is probably the mechanism of their protective effects against CHD. Finally, compounds that inhibit the production of NO directly, such as inhibitors of NOS or agents that inhibit the production of NOS, such as corticoids, the tetracyclines, and a-MSH may prove useful in slowing the aging process. Aspirin blocks cyclooxygenase I, thereby reducing production and toxicity of prostanoids produced by NO, accounting for its protective effect in CHD.”

    Is NO good or bad? I think you have to strike the right balance

    Reply
    1. TS

      Newtonian physics may not be applicable in the quantum world but in the macro world it works. But “Every action has an opposite and equal reaction” seems to apply to more than physical forces.
      What happens if hormone therapy for oestrogen receptive breast cancer is continued for too long? – why, it can have the opposite effect. So just what other drugs does this apply to?
      Why does a person suffering from mania become depressed afterwards? Why do we have withdrawal mixed with hypersensitivities, allergies, agitation, panic attacks and mania? Isn’t there a tendency for the body to respond to an extreme reaction by initiating another extreme reaction in the opposite direction?
      At least the body apparently knows when to shut down vitamin D production from sunlight so that we cannot overdose, even if we damage our skin. Perhaps it also knows when to switch off NO production,
      Does anyone know?

      Reply
      1. Dr. Malcolm Kendrick Post author

        I know that NO is a vital substance. I would rather risk too much, rather than too little. When increased NO is associated with long term problems, it is usually because of underlying illness. Who knows if it was actually the NO causing the problem, or some other factor associated with the illnes. Association does not mean causation, unless you have controlled for all other variables.

    2. mikecawdery

      DBM,

      I thank you for raising the issue of NO imbalance. It clearly is of importance in that normal control can be disrupted by many factors which contribute to CVD.

      My reading of the abstracts (The nitric oxide hypothesis of aging an “revisited”) suggests that the imbalance of NO is due to:

      Stress, inflammation, and infection have all been shown to cause induction of iNOS in rats, and it is likely that this triad of events is very important in progression of coronary arteriosclerosis leading to coronary occlusion

      and that

      Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play important roles in reducing or eliminating the oxidant damage produced by NO..

      With many other factors (nitric oxide synthase; cyclic GMP; cyclooxygenase; bacterial lipopolysaccharide; cytokines; hypothalamus; brain; pituitary gland; pineal gland; degenerative diseases) contributing to this disruption of normal control of NO. One might also add pharmaceuticals to the list of disruptants but, of course, that was avoided.

      I note too, that these papers were hidden behind a pay wall which at $3 a page one needs deep pockets to read.

      Reply
    3. DBM

      It seems pretty obvious that keeping your vessels dilated and elastic is much better for you than having tight contracted and non-compliant ones. But what is the best way to achieve this?Certainly one of the beneficial actions of NO is to cause vasodilation but it might come at a cost if is activated for prolonged periods of time. Cortisol and insulin are both essential hormones for life but no-one here would argue that prolonged high levels of either of these is healthy.

      Another more benign way to induce vasodilation is via Co2. Higher Co2 levels can also result in vasodilation. This probably explains some of the health benefits associated with meditation and yoga, the controlled breathing that is part of these practices prevent/counteract hyperventilation and results in higher Co2 levels and this leads to increased vasodilation. Stress, however is often associated with hyperventilation and therefore lower Co2 levels. In this context in order keep vessels dilated NO is produced as a stop gap ,useful in the short term but may not be so beneficial in the long term.

      This is explained in more detailed in the following discussion that delves into the biochemistry of NO further

      Also discussed in the above is Methylene blue which is quite an interesting substance. Its a dye and is more commonly used for treating infected gold fish but also has some clinical applications including treatment of septic shock, malaria, cancer, alzheimers disease and priapism. Its action is via inhibiting NO synthase i.e. reducing toxic levels of NO.

      Reply
      1. mikecawdery

        Methylene blue. Many years ago I did a Part 2 preclinical expert report for methylene blue eye drops; something one does not forget.

      2. mikecawdery

        DBM

        Indeed, Apparently improves the glamour of the eyes – a French use.

        Methylene blue has many uses; probably far more than it is credited with, but then it is not patentable and like Vit C might actually cure rather than ameliorate.

  36. mikecawdery

    Just to remind everyone of the “official view” that it is cholesterol and the following that shows that their own data destroys their hyypothesis.

    The WHO produced a graph that shows that compares cholesterol levels (BHF-HEARTSTATS) with WHO All cause mortality age standardized per 100,000 (source WHO Mortality ) for various conditiations. This graph showed a series of J-curves. The cholesterol levels with the lowest mortality for three conditions are as follows:
    All Cause mortality 222 mg/dl 5.75 mmol/L
    Non-communicable disease 210 mg/dl 5.49 mmol/L
    Cardiac Disease 208 mg/dl 5.44 mmol/L
    These levels a way higher than the current medically approved target levels

    http://www.heartstats.org/documents/download.asp?nodeib=6797 This URL no longer exists?

    Just another fact that was removed because it did not fit the “gospel”

    Hurray found it again on:

    https://renegadewellness.files.wordpress.com/2011/02/cholesterol-mortality-chart.pdf

    Reply
  37. Alan

    Did NICE read this before deciding no level of sunlight is safe? I suspect they are trying to get rid of us earlier to save the NHS some cash!

    Reply
    1. David

      You might like to ponder this from NICE.

      1.1.5 Use existing community health promotion programmes or services to raise awareness of the risks and benefits of sunlight exposure.
      1.1.6 Offer one‑to‑one or group‑based advice, as appropriate, tailored to the type of risks the person or group faces.
      1.1.7 Encourage and support people at increased risk of low vitamin D status or skin cancer to contribute to awareness‑raising activities.

      https://www.nice.org.uk/guidance/ng34/chapter/1-recommendations
      NICE are not some all purpose baddie.

      Reply
  38. annielaurie98524

    I just now got this in an AARP e-newsletter , and it contradicts what I have read on statin use. I have not been able to track down any study that shows they are “effective at preventing heart attacks” in general. The newsletter did not give a link to the cited “new” JAMA article that purportedly shows benefits from wider use of statins. The article states, “If you’ve been prescribed statins, take them as directed. Studies show they’re effective in preventing heart attacks, particularly for those with a genetic predisposition or who have survived a heart attack. A new study published in the Journal of the American Medical Association confirms that when statin use is widened to include people at medium risk, this further reduces deaths from heart disease.” Thanks for any insight anyone can provide.

    Reply
    1. mikecawdery

      Just a thought.
      NO is an important, naturally produced molecule which is controlled by normal processes, but when these control processes become disrupted by various factors (infections, chemicals {including pharmaceuticals} etc) it can become a dangerous and cause problems in excess or deficiency.(see DBM’s comments above)

      In a normal healthy human it would seem desirable to avoid these disruptive factors insofar as they can be avoided. Indeed it would seem that this logic should apply to all natural processes and this in turn prompts the question: What are these disruptive processes and which can be avoided?

      Nowadays, many if not most drugs do not cure. They simply modify, ameliorate, manipulate or simple reduce signs and/or symptoms. They simply have to be taken for life; which of course is ideal for Big Pharma. They have a captive consumer base, a commercially ideal situation for them.

      However, many of these lifetime drugs have adverse reactions and the drugs themselves for various reasons are causing the incidence of iatrogenic deaths to increase to a level that competes with chronic diseases for importance as Starbridge pointed out in her report (JAMA, July 26, 2000—Vol 284, No. 4 http://www.jhsph.edu/research/centers-and-institutes/johns-hopkins-primary-care-policy-center/Publications_PDFs/A154.pdf Seem as if another report has gone “missing”)

      Back in 1975, Henry Gadsden, chief executive of the drug company Merck, expressed in a candid interview his frustration that the potential market for his company’s products was limited to those with some treatable illness – as to ‘sell to everyone’. Three decades on, medical commentator Roy Moynihan observes, ‘Henry Gadsden’s dream has come true (Le Fanu, James (2011-11-03). The Rise And Fall Of Modern Medicine)

      And how many of these “lifetime” drugs are actually disrupting basic metabolic processes that have been evolved over the millennia to protect health?

      Reply
      1. mikecawdery

        Annielaurie

        May be that is why I am regularly having to change my email password because of warnings of illegal attempts to access it. Twice this week!

      1. annielaurie98524

        Thanks for the link. I had seen a similar analysis, by Chris Kresser I think. He was a bit more generous, and estimated the “extension” as 2-3 weeks, if I am remembering correctly. Seems a bad trade-off to risk neurological and muscle damage, diabetes and cancer for even 3 more weeks.

      2. Mr chris

        Hello mike,
        There was a follow up to the original article which suggested the three or four extra days was the result of a statistical quirk, whereby the cut off in the studies had been set at six years. Extending the cutoff gives a more hopeful extra three years life I seem to remember. You can find the comments in the BMJ open in the mfollowing month’s edition

      3. mikecawdery

        Mr Chris.

        If one extends/extrapolates outside the data range one can sometimes extend the “prediction”. Why was this not done in the original article or am I wrong to assume that “pressures” were brought to bear? As Stephen points out, the fact of the MI might well result in a major change in life style. Having had an MI and five stents it certainly had an effect on me and my approach to Big Pharma and its KOLs astroturfing and agnotology!

      4. mikecawdery

        Mr Chris,

        Incidentally I did not see any mention of levels of Total Anti-oxidant Capacity (TAC) in blood. I would have thought that this measurement is of importance where anti-oxidants are low. An old colleague of mine has a test for TAC (Knightscientific.com) and has shown that diabetics have substantially lower levels than normal healthy individuals. Dr Jan Knight is the person to contact. My own level is above the normal mean and at the very top of the diabetic distribution; but then I take a lot of anti-oxdants

    2. Stephen Rhodes

      Just a thought.

      The cohort that has been ‘found’ to have a genetic predisposition or has survived a heart attack is now ‘aware’ of their condition and – unless suicidal or stupid – will moderate their behaviour as a result.

      Maybe this group, by modifying their behaviour – diet, exercise, stress reduction, would suffer fewer heart attack and stroke events as a result.

      And maybe they would suffer fewer heart attack and stroke events than those taking ‘pills’ and not modifying their behaviour.

      Unethical maybe, but such a trial would be very illuminating.

      Reply
      1. Mr chris

        Hello
        That seems very interesting. Am I right in understanding that there are good and bad clots, and some get some people and others don’t?,
        Why would this be so. I had thought it was like drains, treat them badly and they block?

  39. Randall

    its the undetected plaque causes 85 percent of all heart attacks that got my attention. IMO that’s why calcium score test is important

    Reply
  40. Dr. Göran Sjöberg

    Vitamin C doesn’t seem to be off topic since it clearly relates to CVD due to it is importance in healing wounds and helping the endothelial cells stick better together if I should believe Linus Pauling which I am very inclined to do when rereading his book on vitamin C from 1976. Evidently I must just have briefed through the book when I got it a couple of years ago.

    Now I am though reading the book with care and am amazed by the scientific rigour and logic that permeates the book. Well, he is perhaps not without reason a double nobel price laureate. With my present view upon ‘evidence based medicine’ as a huge corrupt scam and really a quack enterprise it is not at all mysterious to me why Pauling by this same enterprise has been nominated as the ‘biggest quack ever’.

    Well it is so obvious to me that this attitude towards Pauling as well as to all cholesterol sceptics is driven be fear. And it is a fear that people get healthy on their own with equally obvious result for the whole enterprise. Think about 500 000 000 diabetics with no need for medicine.

    Pauling is advocating what he calls “Orthomolecular Medicine” and I realise now that it is just this I have been up to during16 years – treating the cause by improving my immune system by natural means, carrying no side effects, to improve my physiological defence mechanisms rather than accepting dubious treatments, to say the least, of the manifestations of my CVD.

    Read the book and get ‘converted’ 🙂

    Your Swedish “woodchopper” – Göran

    Reply
    1. Dr. Malcolm Kendrick Post author

      I have followed the vitamin C Lp(a) correlation for many years. Once again, you find blood clotting sitting at the centre of it all. Apolipoprotein A1 (the apolipoprotein attached to Lp(a)) is chemically identical to plasminogen. This is not a coincidence. Animals that cannot manufacture vitamin C, synthesize Lp(a). It keeps the blood vessel cracks of scurvy at bay…. at a price.

      Reply
      1. Dr. Göran Sjöberg

        Malcolm, you are for sure far more read than myself on this subject. Still I find Pauling’s writings from 1976 interesting not least by his scientific attitude. He seemed to be very updated on this issue at that time and also brought a clear historical perspective on the subject along.

    2. Barry

      Dr. Göran,
      Pauling followed up Vitamin C, the Common Cold and the Flu with How to Live Longer and Feel Better in 1986 (sixth reprint 2015) which draws from the previous two books on health and integrates information from a book Pauling co-authored with Dr. E. Cameron in the late 1970s titled Cancer and Vitamin C. If you haven’t read it you may find it interesting.

      As vitamin C is essential to the production of collagen which, in turn, is essential to the structural integrity of the whole body it follows that a deficiency of vitamin C will adversely affect the body in many ways – one of which is the strength of the arterial wall. Any weakness here will make it more susceptible to damage and any damage that does occur will take longer to repair or be repaired inadequately setting the stage for further problems. It is well known that wound healing is massively influenced by vitamin C to the extent that wounds will not heal if somebody is deficient. Plenty of information in Pauling’s book plus, as an example: http://www.surgerysupplements.com/the-role-of-vitamin-c-in-wound-healing/.

      Given that the RDA for vitamin C is so ridiculously low, and that whatever is available in the modern diet is depleted by storage and cooking, it is not much of a leap to realize that unless will ingest optimal amounts of vitamin C (grams rather than milligrams) the structural integrity of our CVD will be adversely affected plus, of course, our ability to fight infections and free radicals. There are obviously many other factors including AGE and associated free radical damage from, in particular, processed omega-6 heavy vegetable oils, hyperglycaemia and hyperinsulinemia all of which will cause damage to the arterial wall (which Dr Kendrick is explaining in detail).

      It would appear that, in general, we ingest sufficient vitamin C to avoid the signs of clinical deficiency overall but an inadequate amount to maintain optimum arterial integrity and, as a result, our CVS is prone to damage. Not saying this is the only reason – far from it – but I do think it is a major factor.

      Reply
      1. Dr. Göran Sjöberg

        Barry,

        I am fully aware of the sucessful work, with high doses of intravenous ascorbate, which Pauling carried out together with Dr. Cameron on cancer patient in terminal states and consider it a real scientific sham how the Mayo clinic ‘duplicated’ the trial with much lower doses to ‘prove’ that Pauling was a quack. In Pauling’s book “How to Live Longer and Feel Better” the details of this scam is revealed in detail.

        What is though troubling my mind is when I recently specifically asked Thomas Seyfried about this issue he actually avoiding my question. There seems to be a controversy relating to ROS and the mitochondria and cancer involving antioxidants as ascorbic acid which I am not able to grasp at the moment. Well, in thirty years that has passed sin Pauling published his book the understanding of the molecular biology of our cells has undoubtedly taken leaps forward.

      2. Dr. Göran Sjöberg

        Barry,

        i just finished my rereading of Pauling’s book from 1976 of the benefits of vitamin C.

        The last section in the last chapter “Ascorbic Acid and Other Diseases” is ‘Vitamin C and Cancer’ and I find here an interesting hypothesis. Since vitamin C improves our ability to produce collagen fibrils it is reasonable to assume that tumours are better encapsulated when high doses of vitamin C is administered to patients and thus more easily removed by later surgical means. The invasiveness of tumours is reduced. An interesting hypothesis where no side effects could be imagined.

        I think this is really a great book though challenging the medical pharmathutical establishment.

  41. Dr. Göran Sjöberg

    When it comes to ‘success stories’ from ‘converted people’ this has been a ‘trick’ for many thousands of years to get people hooked up on a ‘new religion’ and I realise that LCHF is here no exception.

    I am always ambivalent towards this way of ‘convincing’ people but these stories have still a strong ‘anecdotical’ power, but without the scientific rigour which Pauling represents to me. This is also the reason why I, as an old researcher, am dwelling and commenting here on Malcolm’s blog but still cannot refrain from having a look now and then at sites of more popular types and the most prominent LCHF site is the following one which is now run in a professional way.

    http://www.dietdoctor.com

    I am, as many of the permanent visitors here on Malcolm’s blog probably have noted, a strong ‘believer’ not only in the LCHF way of living but also siding with Malcolm in the fight against the corruption of medicine. The Dietdoctor on the other hand is very carful not to openly challenge the medical establishment but rather to convince by many practical LCHF success stories which are so difficult to refute but at the same time introduce serious interviews with people representing alternative medical views and interviews which carried out with a professional video quality which doesn’t hurt i public. This is his basic business idea of Dietdoctor and I for one am not against any business of ethical nature.

    Mercola is working along the same lines though he differs from Dietdoctor when taking a much more comprehensive fight involving not only for a natural healthy diet but also fights against corrupt medicine and corrupt agricultural. Mercola, however, has the unavoidable tint of doubt attached to his activity since his business rests on marketing supplements of his own mark while Dietdoctor relies on the membership fees which undoubtedly improves the credibility of the message from the latter.

    http://www.mercola.com

    Mercola together with Malcolm belongs to my prime favourites by taking the ‘fight’ while Dietdoctor steadily gains in popularity through his idealistic, philosophical ‘no-fight’ Buddhist approach and as such is more religious in character.

    Reply
    1. Frederica Huxley

      I don’t get upset by Dr Mercola’s business of selling supplements; to me it is a side issue. I have rarely, if ever, felt that he is ‘sellng’ his wares in his articles, and the majority of the subjects he writes about have nothing to do with what he is selling. As Dr Mercola has noted, he has to make money to keep the blog in operation. There are a number of other like minded bloggers who do tie their wares into their articles!

      Reply
      1. Mr chris

        Where I find Mercola interesting is the the fact that he offers an alternative voice on health.
        No one is obliged to believe him, or buy his stuff.

      2. Gary Ogden

        Frederica, I agree. Dr. Mercola gives lots of free information, wonderful interviews, and a lot of good fitness information, that have nothing to do with selling supplements. I have great respect for him. As for myself, I take no supplements. It is possible for most people, most of the time, to get all the nutrients they need to achieve robust health from food, but it takes a great deal of study, and discernment of often conflicting evidence, but it also takes a look at historical evidence of how truly healthy people ate.

  42. goutboy

    Given the evidence in aninmals I am sold on the idea, shame that vit c doesn’t really work on gout but its nice to know there is no real causal relationship between uric acid and CVD. Are you moving us to vit c and lysine supplements. Doctoring Data not bad btw, gives a reason why this theory has no interest in med prof. – there’s no money in it!

    Reply
  43. Henry Fabian

    All this commentary drives me to search for additional information although a fair amount of the research is technical and causes brain strain for me but a useful exercise for us older folks.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018556/#!po=23.0263

    The above article was very interesting with a final conclusion (as I understood it) that certain antioxidants along with caloric restriction may help to protect endothelial function and prevent against vascular diseases. However there was more than one statement in the article that stated additional research was needed. Sigh. After reading Doc Kendrick’s, “Doctoring Data” I wonder how long it takes for this necessary and ultimately definitive study that might prove certain vitamins and supplements are all that’s needed for a healthy life ( plus a little exercise) to occur. When pigs fly comes to mind, but I too want to be more optimistic.

    Reply
  44. Anna

    Goran, did I misunderstand you last comment re vitamin C and Dr. Kendrick’s reply? It seems to me his reply corroborated that lack of vitamin C will increase the chances of cracks in the arterial walls.

    By the way, to someone above, you cannot supplement with vitamin K for people on warfarin. Vitamin K will counteract the warfarin.

    Reply
    1. Dr. Göran Sjöberg

      Anna, to be honest I don’t know enough about the mechanisms Malcolm mentions to fully understand what is involved. What Pauling specifically stresses in his 1976 book is how large doses (5 – 10 g/day) of vitamin C may greatly help our immune system to increase the production of lymphocytes. I don’t know how this relates to what is happening in my artery walls other than such lymphocytes need to slip out between the junctions (tight?) of the endothelial cells to do their ‘job’.

      I get so easily overwhelmed by the complexity of our physiology when I try to dig into any specific health subject that any simple overview map I might have entered with rapidly disappears and leaving me in a more confused state of mind than before.

      Reply
    2. JDPatten

      You can eat plenty of good green produce that has lots of K. You just must “dose” with this kind of food regularly and uniformly. There’s plenty of other good stuff in there you wouldn’t want to cheat yourself of. The trick is to dose yourself with warfarin appropriately, so your INRs are in bounds.
      The pills are dirt cheap, but it costs to get yourself to the clinic often enough and it costs for that service. You could get your own machine and test as often as would satisfy your worry about being in the zone – that costs too.

      Reply
    3. Tuck

      “By the way, to someone above, you cannot supplement with vitamin K for people on warfarin. Vitamin K will counteract the warfarin.”

      There are 2 vitamin Ks, K1 and K2. Warfarin blocks K1, which is converted to K2, so it blocks production of both. K1 controls clotting, K2 controls calcification. So you supplement with K2 to prevent the calcification, while still getting the clotting benefit.

      Demonstrated here:

      “Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats”
      http://www.bloodjournal.org/content/109/7/2823.long?sso-checked=true

      Reply
  45. Dr. Göran Sjöberg

    It struck my mind just now that we have a Swedish professor, Karl Arfors, now retired, who specifically studied the role of NO and the action of lymphocytes in the capillary arteries by having invented some ingenious microscopic technique enabling him to study what happened in the actual streaming blood. He is a strong believer in the benefits of taking NO as food supplement.

    By the way he spent some time at Linus Pauling’s research centre in La Jolla, CA.

    Reply
  46. Craig

    I see that Dr K has moved on to the next exciting episode of this series but I thought it better to tack this link in here

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799034/

    Defocused laser light (or high power l.e.d.) therapy at near infrared wavelengths has some useful therapeutic applications including wound healing. It is essentially the same as narrow band i.e. filtered, high intensity sunlight. You can achieve something similar by just being out in strong sun but to get more of the near infrared wavelengths without much UV you can put water between yourself and raw sunlight. eg clear plastic bags of water over exposed areas.

    Reply
    1. Mike

      Would be really interested to see if high power LED can also trigger NO release in a similar way to sunlight – basically trying to work out whether low-powered sun beds or an alternative LED form would be good through the winter for us Europeans.

      Reply
      1. Craig

        This web site covers the practical basics of leds vs sunlight and references many research papers.

        http://heelspurs.com/led.html

        Leds are very easy to control, cheap as dirt and easily capable of producing energy densities comparable to sunlight over narrow wave-bands. They are available in a wide range of wavelengths too, all the way from low ir to uvb. And if you do find them useful for joint pain and wound healing they are much less systemically hazardous than eg naproxen or ibuprofen. I find them useful.

    1. Craig

      David, very interesting links, thanks!

      Eg. ‘Hyperuricemic rats have impaired endothelial function and hypertension that can be reversed by lowering uric acid or treating with L-arginine or antioxidants (50–52). Hyperuricemia is also associated with endothelial dysfunction in humans, and lowering uric acid with allopurinol improves endothelial dysfunction in asymptomatic hyperuricemia, congestive heart failure, diabetes, chronic kidney disease, obstructive sleep apnea, ‘

      Reply
  47. Frederica Huxley

    There is a school of thought in America that it is prudent to supplement with K2 whilst on Coumadin, to help keep the INR steady.

    Reply

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