23 January 2018

Dr. Malcolm Kendrick's Series on What Causes Heart Disease

Malcolm Kendrick is a very smart guy.

Dr. Kendrick graduated from medical school in Aberdeen and trained as a General Practitioner in Scotland. After ten years he split his time between General Practice and education. On the doctor side, Malcolm currently lives and works in Cheshire in General Practice, Intermediate Care and Out of Hours. On the education side, Malcolm set up the online educational system for the European Society of Cardiology, working with the European Commission and also set up the first website for the National Institute for Clinical Excellence (NICE) in the UK.


Malcolm is an original member of the Centre for Evidence-Based Medicine in Oxford and of The International Network of Cholesterol Sceptics (THINCS). The latter comprises a group of scientists, doctors, and researchers who share the belief that cholesterol does not cause cardiovascular disease. This is the field of medicine for which Malcolm is best known.



"His long-term interest in the epidemiology of cardiovascular disease has resulted in many publications in journals such as the BMJ, Medical Hypotheses, Pulse, and PharmacoEconomics. His breadth and depth of expertise in this area led to his election to Who’s Who in 2009.



"The Great Cholesterol Con was the book that firmly placed Malcolm on the world stage of the ‘diet-cholesterol-heart’ hypothesis and his army of followers are eagerly awaiting his next bout of wit and wisdom. Malcolm blogs at drmalcolmkendrick.org and lectures by invitation. Married with two children and two cats, Malcolm would like more people to challenge the status quo, and never just accept the party line. He likes to ski, golf, sail."



He is a practicing doctor in Scotland and an author.
His website home
His about page
Wikipedia article
His books on Amazon



From the book titles, you can see that he is not a mainstream go-with-the-flow kind of guy.

Please look at his writings, you will see a no-nonsense follow the data approach. It's good reading.

He started a series called What Causes Heat Disease in January 2016. As of January 21, 2018, he is on installment number 44. It is not simple to find all of the links to each of the posts in sequence, so I have made it a project to do that.



It is provocative, super-interesting, and need I say it is also quite different from what your cardiologist will tell you. I got up to 10, then decided to catalog this. I'm going to reread from the start and put a little about the content of each as I progress.
  1. What Causes Heart Disease I, 01/18/2016, Introduction. Everything causes heart disease; nothing causes heart disease. What is heart disease (Cardiovascular disease or CVD)? CVD is caused by a process, not a thing. "My simple credo is that, if your hypothesis cannot explain everything about CVD you cannot explain anything."
  2. What Causes Heart Disease II, 01/21/2016, Framing the problem. Start with "What kills people?" There are many complications and variations. The "reverse hypothesis," i.e. the primary cause of a heart attack is simply a blood clot blocking a coronary artery, has two contradictions. An infarction does not mean that a clot develops, and collateral circulation develops. Ischemic stroke and MI have the same underlying disease process. It is very complex.
  3. What Causes Heart Disease III, 01/25/2016, Data from different countries used different standards so is unreliable. Starting at the end--the formation of the final, often fatal, blood clot. Surprisingly, he adds statins to the list of things that reduce the risk of blood clots (although not by much). But not because of their impact on cholesterol, but rather because of anti-coagulant effects--like aspirin. He hints at another effect statins have. Now the controversy--the two steps to CVD are considered to be 1. formation of an atherosclerotic plaque, and 2. clot formation on top of the plaque. But it's strange that the two processes share many risk factors. Perhaps they "are simply two different manifestations of exactly the same underlying disease process." Occam's razor.
  4. What Causes Heart Disease IV, 02/08/2016, Lots of causes of CVD, but only 1 underlying process. He covers the first of four stages that culminate in the development of an atherosclerotic plaque that culminates in the final fatal blood clot--endothelial damage. He looks at three aspects: Nitric Oxide synthesis, consequences of endothelial damage, and tissue factor (a clotting agent). NO is created in the endothelium. It relaxes blood vessels and is an anti-coagulant. Perhaps the single most powerful single factor to increase NO synthesis is sunlight. Wow! The implications of this alone are tremendous. Biomechanical stress (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) is thought to be the highest damaging factor. Tissue factor is inside all blood vessel walls and immediately forms a clot if there is damage. Once the damage is covered, the clot stops. Then what happens to it? To be continued in the next part.
  5. What Causes Heart Disease V, 02/13/2016, Start with some background about how the hypotheses of CVD developed and changed. How does the clot get inside the arterial wall? Endothelial cells grow over the clot. But now you just have a clot in the wall of the blood vessel. This doesn't seem too smart. What happens to the clot? If your body is working right, some of the new endothelial cells convert into macrophages and clear up the clot itself as the new endothelium is forming. But if the damage/clot process happens too rapidly or repeatedly in the same place, the body simply can't keep up with the cleanup. Then the clot turns into "a pulpy mass containing cholesterol crystals and fatty globules."
  6. What Causes Heart Disease VI, 02/21/2016, Recapping, there is a four-step process that happens with CVD. Endothelial damage, clot formation/dysfunctional clot formation, clot repair/dysfunctional clot repair, the final fatal blood clot. Plasminogen in clots causes the destruction of the clot by slicing apart the fibrinogen (good). Plasminogen activation inhibitor (PAI) prevents that. Triglycerides enhance PAI and therefore impair breakdown of the clots! Therefore hypertriglyceridemia is bad. Fibrinogen. From the Scottish Heart study, High cholesterol has no effect, but "‘Fibrinogen is a strong predictor of coronary heart disease, fatal or non-fatal, new or recurrent, and of death from an unspecified cause, for both men and women."  The study found that "Unexpectedly, individuals with low plasma fibrinogen had a low incidence of coronary events even when serum LDL cholesterol was high."  Smoking, stress, sleep apnea, diabetes and depression all raise fibrinogens. Lp(a) is a type of LDL, but with a "backward-threaded" plasminogen molecule. So Lp(a) folded into a blood clot blocks plasminogen, preventing a clot from breaking itself down. Aside, LP(a) is found in mammals that do not produce their own Vitamin C, it is to provide a permanent plug for holes in tissue because scurvy prevents collagen production. Lp(a) level in the blood is thought to be largely genetic, but there is evidence that ensuring more than minimum vitamin C and fish oil (2)/flaxseed can reduce Lp(a).
  7. What Causes Heart Disease VII, 03/01/2016, Yes heart disease is multifactorial, i.e. many things can cause it, but they all trigger the same process. If you can't do this, your hypothesis is off. IT's not the cholesterol. He focused on blood clotting factors and found that factors that increased clotting were bad and vice versa. HDL inhibits platelet activation in the endothelium and increases NO production. ‘Plaques are clots, and clots are plaques. It is all due to blood clotting.’  It is staring you in the face. It has been staring humanity in the face for over a hundred and sixty years. Ever since Rokitansky and Virchow started to look closely. There is no cholesterol in the story. It's something that just happens to be there.
  8. What Causes Heart Disease VIII, 03/10/2016,  The body can heal plaques. (Probably not once calcified, but that is another issue). This chapter relates to the third step--Clot repair / dysfunctional clot repair. Endothelial progenitor cells (EPCs, repair stem cells) are an important part of the picture. Exercise, l-arginine/citrulline, ACE inhibitors and statins all increase NO levels and EPCs. "...statins do have some benefits in CVD. Not enough, in my opinion, to overcome the damage that they can do. However, the benefit is there, it is real.I knew it could be nothing to do with the impact of statins on lowering LDL, as LDL has nothing to do with CVD (well, almost nothing). So there had to be another effect. And that effect is, in my opinion, almost entirely to do with the ability of statins to increase nitric oxide (NO) production..." Many people saw that statins reduced cholesterol and improved CVD outcomes. Therefore, there was an assumption that correlation = causation and low cholesterol is the key.
  9. What Causes Heart Disease IX, 03/16/2016, Modern medicine's disease paradigm has forced the shoe onto the wrong foot. Confirmation bias and cognitive dissonance take over and researchers make excuses for contradictory data. "Me; ‘The French have higher cholesterol levels than the Russians and one-tenth the rate of CVD.' A.N. Expert: ‘The French are protected by drinking red wine and eating lightly cooked vegetables and eating garlic.’ is an example of an ad hoc hypothesis. A new type of study called a teleoanalysis was brought in to try to legitimize ad hoc hypotheses. In a nutshell, they create a hypothesis, assume a study has been done and declare victory. In other words, they make shit up. "...teleoanalysis provides the answer to questions that would be obtained from studies that have not been done and often, for ethical and financial reasons, could never be done.’ Lol.
  10. What Causes Heart Disease X, 03/22/2016, Calcification in arteries. Coronary Artery Calcium (CAC). The best way to look at calcification is as an end stage of plaque development. It may actually be a protective mechanism that puts a hard cap on top of the plaque to prevent it from escaping into the bloodstream and clogging other blood vessels. Not all plaques calcify. Vitamins K and D seem to be protective, Warfarin seems to increase calcification. Calcification seems to have the effect of making plaques more stable. Conclusions: 1. After the age of 40-50, if your CAC score is zero, your risk of CVD is low. 2. If your CAC score is high, it means you have been developing plaques for quite a while, and your risk is higher. "[However, bear in mind that CAC represents your history, not necessarily your future]." 3. Calcification can reverse. Vitamin K2 seems to help this. 4. Calcification is not a cause of CVD. Rather it seems to be an end state of the process. 5. There is no evidence that reversing calcification improves CVD risk. "But it seems likely there would be benefit."
  11. Sunbathing is Good for You, 3/23/2016, ‘Results: Sunburn, high intermittent sun exposure, skin awareness histories and solar elastosis were statistically significantly inversely associated with death from melanoma.’‘Conclusion: Sun exposure is associated with increased survival from melanoma.’
  12. What Causes Heart Disease XI, 03/26/2016, A new study has come out about people with coronary artery disease (CAD). The headline says "Depressed CAD Patients May be at Higher Risk For MI, Death"  CAD patients with depression are much more likely to die. Depression creates a dysfunction in hormonal response to stress (HPA-axis). Abnormal cortisol levles--low in the morning, high the rest of the time. Cortisol is a direct antagonist to insulin, and severe depression can actually cause T2 diabetes! IT can also cause clotting abnormalities: higher fibrinogen, higher Plasminogen Activator Inhibitor, which prevents clot repair. "Diabetes/raised blood sugar levels are directly damaging to the endothelium. Raised fibrinogen and PAI-1 are very powerful risk factors for CVD, primarily because they make the blood more likely to clot, and the clot more difficult to clear up." 
  13. Lower Cholesterol Has No Effect On Heart Disease, 4/24/2016, Hope3 trial for rosuvastatin. Showed no difference between treatment and placebo group. Accelerate trial tested evacetrapib. "Despite reducing levels of low-density lipoprotein (LDL, or “bad” cholesterol) by 37 percent and raising levels of high-density lipoprotein (HDL, or “good” cholesterol) by 130 percent, the drug failed to reduce rates of major cardiovascular events, including heart attack, stroke, angina or cardiovascular death." "Researchers, looking at those living in Framingham, in the US, found that younger men with high cholesterol levels were more likely to die from CVD. From this they concluded. Raised cholesterol causes CVD. ACCELERATE clearly falsifies their simplistic hypothesis. It is a black swan." The evidence is very clear: increased cholesterol is not a cause nor associated with CVD. Greater cholesterol lowering using polyunsaturated fat, increases the risk of death. Yet here's what the British Heart Foundation, as well as other heart disease associations, say. "Here is what the BHF currently say about saturated fats: ‘Swap these for unsaturated fats. Eating too much saturated fat increases the amount of cholesterol in your blood.’"
  14. What Causes Heart Disease XII, 04/25/2016, The four-step process is really overlapping processes. Now, the role of lipoproteins. Bottom Line: High levels of LDL increase the risk of blood clots forming (oxidized LDL is really bad), High levels of HDL reduce the risk of blood clots forming, VLDL/triglycerides increase the risk of blood clots forming. All this is not because cholesterol clogs the arteries, but rather because of their impact on clotting. So lipoproteins do have a role in this. Kendrick apparently  believes the role is small (supported by research as well, see links below.)
  15. What Causes Heart Disease XIII, 05/07/2016, Heart Disease and Inflammation - Take nothing at face value. Many leading researchers have enormous financial stakes in drug trials--often undisclosed. Inflammation as a cause of CVD is not an unreasonable hypothesis, but... There seems to be an association, but is it causal. Inflammation is actually a healing process. If you sprain your ankle, the damage causes an injury and healing process that results in swelling and pain. The swelling and pain did not cause the swollen ankle. "Whenever I see anyone stating that inflammation is a cause of anything I simply change the word inflammation to the word ‘healing,’ to see how sensible it then sounds." Autoimmune disease, e.g. rheumatoid arthritis and asthma are the result of runaway inflammation, and anti-inflammatory can help. RICE for injuries is now thought to be misguided because "‘Anything That Reduces Inflammation Also Delays Healing [I cannot resist stating that, this is because inflammation is healing]"   People who take corticosteroids may get "iatrogenic Cushing's syndrome." This anti-inflammatory regime increase CVD risk. "In short, if CVD is primarily a disease of inflammation, then potent anti-inflammatory agents ought to reduce the risk. Instead, they increase it massively. There is no doubt that inflammation is associated with CVD. Equally, if you measure C-reactive protein (a marker of inflammation), a high level is associated with a higher risk of CVD. However, it is not a cause, and if you try to reduce inflammation you will almost certainly increase the risk of CVD, not decrease it. Ergo. Inflammation is a sign of active CVD."
  16. What Causes Heart Disease XIV, 05/18/2016, Age and sex are two of the most prominent risk factors associated with CVD. There is no doubt that there is an association and a strong one. The calculators used by doctors generally overstate CVD risk. "...if the two most powerful risk factors you have for CVD, cannot be explained, are not explained, then you really have a major problem. Even if you cannot even comprehend that you do."If you cannot explain why age, and gender, cause CVD… you cannot explain CVD."
  17. What Causes Heart Disease XV, 05/31/2016, Everyone "knows" pizza is bad for you.But there was a study assessing the impact of pizza on heart disease. It showed that pizza helps. Upon discovery that the study was done by Italians, the expert said, "Oh yes, but Italian pizzas are much healthier than those in the UK." Pulled straight out of thin air, ad hoc hypotheses like these are extremely common. "There was no point in saying what things may, or may not, cause CVD – and compiling an ever-lengthening list of ‘risk’ factors. I had to work out the process through which any factor may operate, both causal and protected." HE questioned, "Can you link any and all factors, known to cause CVD by their impact on one of two things: Endothelial damage (which triggers blood clot formation) or Increasing blood coagulability (making clots more like to form, become bigger and/or less easy to break down). For all the lists of the usual suspects, he had a "reasonable" view of the mechanism associated with clotting. Warfarin was one of his potential black swans because despite functioning as an anticoagulant, it appeared to have little or no impact on CVD risk. His belief is through its connection with Vitamin K, Warfarin inhibits normal "intrinsic" clotting, whereas the clots that occur in CVD starts with the damage to the endothelium and subsequent exposure of blood to the tissue factor, so no effect. This is an extrinsically driven clotting mechanism. But Warfarin also inhibits the cleanup of clots through the Vitamin K channel. E4E query: It is possible that this explanation of Warfarin is just another ad hoc hypothesis? A "just-so" story? Who knows. Kendrick goes on to say " in the spirit of true scientific endeavour, I welcome as many attacks/contradictions as people can think of. What does not kill a scientific hypothesis can only make it stronger."
  18. What Causes Heart Disease XVI, 06/08/2017, He discusses how sickle cell anemia and migraine headaches both cause CVD through their link with the clotting system. From an article in BMJ, "Cardiovascular disease was 50% more likely among the women with migraine. Heart attack was 39% more likely, stroke 62% more likely, and these women were 73% more likely to have a revascularization procedure." There's not much research in the area, but he found that migraine is associated with, or causes, blood clotting abnormalities – and also damage to the endothelium in one study. He also cites a case in which Warfarin was successfully used to treat migraines. He challenges the reader to suggest another mechanism besides clotting that is consistent with this set of information. Sickle cell disease (SCD) is the other topic of this post. There is a strong association between SCD and CVD. The abnormal shape of the red blood cells causes both clotting problems and increased endothelial damage. "...sickling process leads to vascular occlusion, tissue hypoxia and subsequent reperfusion injury, thus inducing inflammation and endothelial injury. This causes a blunted response to nitric oxide (NO) synthase inhibition." "In one short section on SCD we have virtually everything I have been writing about in this series so far. There is: Reduced NO synthesis, Damage to the endothelium, Increased risk of blood clotting in general, Increased platelet activation and adhesion, Inhibition of endothelial cell repair and proliferation, Increased risk of CVD and accelerated atherosclerotic plaque development." Sickling also causes hypertension in the pulmonary arteries which is extremely rare. Therefore SCD must be a very powerful contributor to CVD.
  19. What Causes Heart Disease XVII, 06/19/2016, Epidemiology of CVD. In 1948, the World Health Organization (WHO) came up with standard codes for the International Classification of Disease (ICD). Although the codes were standardized, it is not clear if the standards used were the same everywhere. In fact, it's certain they weren't. At least it was a step in the right direction and it is [probably improving over time. The MONICA project attempted to standardize this. CVD deaths have been declining in the UK since 1980, the introduction and increasing use of statins had little or no impact on the decrease. OTOH, Latvia and Russia had CVD death charts that map well onto social and political upheaval.
  20. What Causes Heart Disease XVIII, 07/12/2016, Talking about cholesterol. Here's the bottom line: a. LDL is pro-coagulant and – at very high levels e.g. in FH – increases the risk of CVD [though it is difficult to disentangle this from intertwined genetic pro-coagulant factors]. b. VLDL (triglycerides) are pro-coagulant, and increases the risk of CVD. c. HDL is anticoagulant and protects against CVD. Which then brings onto statins, and how they work. First to re-iterate that statins do reduce the risk of CVD [Something, I have never disputed]. However, they do it not by lowering LDL, but because they have anticoagulant effects. Not that potent, about the same as aspirin, but the effect does exist.
  21. What Causes Heart Disease XIX, 07/31/2016, Ancel Keys and the diet heart hypothesis. Sixty years ago Keys proposed that consuming cholesterol raised blood cholesterol, which then caused heart disease. He later changed his story to saturated fat raising cholesterol, thereby... Many did not agree with him, but he was very influential and his view became accepted as dogma, and set the agenda for discussion of CVD. Kendrick does noit see any eating behavior that powerfully links diet to CVD. "The only link that I can see is that people who eat a higher carbohydrate diet are more likely to become obese and develop diabetes. Or, perhaps I should say, develop diabetes and become obese." "...[Keys] certainly succeeded in anchoring almost all discussions within the wider hypothesis that CVD is primarily due to diet. It is not." A lot of people in the comments to this post insist that CVD does have to do with diet. e4e take: I believe that Kendrick deliberately overstated the case against diet being a cause of CVD. I think there is a subtle distinction at play: unless you are eating poison, the specifics of what you eat have little to do with the process of CVD. At the same time, deficiencies of certain nutrients can and do enhance the CVD process. Changing your dietary patterns may change your overall health and shift your nutrient intake patterns. He did state in an earlier post that lack of vitamin C causes scurvy and can impact Lp(a) expression. If I were to attempt a slightly more pedantic statement, perhaps something like, "Assuming you have adequate intakes of important nutrients and are meeting your body's needs at a reasonable calorie balance, the specifics of your food intake have little impact on CVD health at a population level."
  22. What Causes Heart Disease XX, 08/21/2016, Stress/strain. Stress is what creates a response, strain is the biologic and chemical processes that result in the body from stress. Strain can be measured by dysfunction  in the HPA axis (hypothalamic, pituitary, adrenal).  A normal cortisol secretion rises in the morning, goes down, rises at lunch, goes down and up quite a lot for the rest of the day. It is, basically, flexible. An unhealthy cortisol secretion is more of a flat line. It does not peak in the morning, then it does not fall so much. "...hypothesis being that if someone is exposed to repeated activation of the HPA-axis it eventually becomes unable to cope. The system becomes damaged/inflexible." If you are exposed to constant negative stressors, you are likely to burn out your HPA-axis, you will end up with abnormal cortisol secretion, and suchlike. You will then develop central obesity, high blood pressure, high VLDL levels, low HDL levels, high levels of fibrinogen, and many other clotting factors. All of these things will increase endothelial damage, stimulate blood clotting and impair the repair systems. Country level data on Latvia and Lithuania may be good evidence for the impact of strain on CVD.
  23. What Causes Heart Disease XXI, 09/21/2016, Use of proton pump inhibitors (PPIs) increase the risk of CVD. There are two known effects. 1. PPIs tend to cause platelets to aggregate or clump more. But this does not seem to be the important mechanism. More damning is #2: PPIs tend to inhibit the excretion of NO. Here's what Kendrick says. "...PPIs inhibit NO production, through a biochemical system that is well known, and has been clearly established. NO is probably the vital molecule in heart health. It protects the endothelium, it prevents blood clots, it stimulates the production of endothelial progenitor cells. Therefore, anything that damages NO synthesis will – inevitably – increase the risk of CVD."
  24. What Causes Heart Disease XXII, No XXII exists
  25. What Causes Heart Disease XXIII, 12/24/2016, The dietary guidelines are under attack. The Minnesota Coronary Experiment proved that the hypothesis that "saturated fat causes heart disease" is invalid. In fact replacement of saturated fat with polyunsaturated vegetable oils actually increased death from all causes. This study is important because it was the largest trial to test this, it was run by Ancel Keys, it was finished before the nutritional guidelines were developed, the results were not published until MANY years later. Kendrick says "a bunch of liars hid the results." Which may be true. I tend to take the more generous view that well-meaning people were blinded by confirmation bias and cognitive dissonance. This is not an excuse. Shame on the people who hid the results and contributed directly or indirectly to an enormous amount of human suffering and chronic diseases. "The McGovern hearings which set the entire direction of nutritional thinking, and guidelines, took place in 1977. The MCE trial ran from 1968 to 1973. Had the data from this study been made available, the dietary guidelines in the US, the UK and the rest of the world (In their current form, demonising saturated fat) simply could not have been written." It comes back to three things: Protect the endothelium (lining of blood vessels) from harm, Reduce the risk of blood clots forming – especially over areas of endothelial damage, Reduce the size and tenacity (difficulty of being broken down) of the blood clots that develop. How to protect the endothelium? number one agent that protects the endothelium is nitric oxide (NO). Thus, anything that stimulates NO synthesis will be protective against CVD. Which brings us to sunshine and vitamin D. Sunlight on the skin directly stimulates NO synthesis, which has been shown to reduce blood pressure, improve arterial elasticity, and a whole host of other beneficial things for your cardiovascular system, not least a reduction in blood clot formation. Sunlight on the skin also creates vitamin D, which has significant impact on NO synthesis in endothelial cells, alongside many other actions. It also prevents cancer, so you get a double benefit. "avoiding the sun is a bad for you as smoking. In my opinion ordering people to avoid the sun, is possibly the single most dangerous and damaging piece of health prevention advice there has ever been." See the post for more details about why sun exposure is not dangerous.
  26. What Causes Heart Disease XXIV, 01/16/2017, A refresher on Vitamin C and Lp(a). Humans lost the ability to generate Vitamin C 60 million years ago. High levels of glucose prevent Vitamin C from entering cells in the body, especially immune cells. Scurvy from lack of Vitamin C has many symptoms, but focus on bleeding in this post. Vitamin C is an important piece of collagen synthesis. Collagen repairs damaged blood vessels. As blood vessels "crack", Lp(a)) fixes the damage. Lp(a) is very resistant to removal and eventual repair. Thrombolysis is the word for the ordered breakdown of clots. (‘lyse’ means to break down). But, Lp(a) is inert to the chemicals that break down clots. So if you have high levels of Lp(a), your clots will be resistant to breaking down. G. C. Willis did scurvy studies on guinea pigs (which also do not produce vitamin C). Withholding Vitamin C formed plaques, feeding them Vitamin C reversed plaques. But the longer you wait, the more resistant the plaques become. Here's what we know: A high level of Lp(a) is associated with a higher risk of CVD, There is a probable causal mechanism linking Lp(a) to CVD death, Lp(a) is synthesized in animals that cannot make their own Vitamin C, A lack of vitamin C causes blood vessels to crack open – and potentially leads to atherosclerotic plaques development, Animal models have shown that a lack of vitamin C does lead to rapid atherosclerotic plaque development, and that replacement of vitamin C causes rapid regression of atherosclerosis, Some evidence from humans suggest that vitamin C supplementation causes regression of atherosclerotic plaques, Vitamin C supplementation does seem to lead to a reduction in Lp(a) levels, L-carnitine supplementation does lead to a reduction in Lp(a) levels, L-carnitine supplementation may reduce overall mortality.  l-carnitine is a protein found in beef. There is little good research on therapeutic or maintenance levels of most vitamins, and there is no profit motive to do so at this point. An interesting note from the comments: "Relative Ascorbate deficiency is almost universal, and scurvy is very much a drastic almost complete deficiency . The joke of RDA will certainly prevent this drastic end stage disease, but not more insidious chronic consequences of weak collagen.. Pauling recommended 6-18 G of vit c per day. nothing heals without vitamin C. Including I would guess, microscopic vascular defects. Many long term conditions are quite possibly a result of the weak collagen caused by non-catastrophic ascorbate deficiency."
  27. What Causes Heart Disease XXV, 02/13/2017, The cholesterol hypothesis of heart disease is blown away by one graph heart disease vs cholesterol level in Russia and Switzerland. Switzewrland has cholesterol of 248 and death rate of 35; Russia has lower cholesterol at 197 and a death rate of about 270--834% higher. The establishment calls it a paradox and makes something up, but the reality is cholesterol is simply not the problem. CVD has been falling in most advanced Western countries for decades--well before statins, hypertension medications, stents, etc. This is probably largely due to reductions in smoking. Emergency medical interventions have also improved significantly. Other factors include the clean air laws passed in past decades and the removal of lead from motor fuel, pipes, and paints. "Lead causes endothelial dysfunction by binding and inhibiting endothelial nitric oxide synthase and decreasing nitric oxide production." The TACT study (Trial to Assess Chelation Therapy) was hoped to disprove the idea that chelation took lead out of the system and improved health. But oops,"...we found that we had about a 40% reduction in total mortality, a 40% reduction in recurrent MI, and about a 50% reduction in mortality [in patients with diabetes],"
  28. What Causes Heart Disease XXVI, 02/15/2017, A mainstream cardiology professor, Salim Yusuf has a youtube presentation where he says, "1. Saturated fat does raise LDL, a bit, but has no effect on CVD – maybe slightly beneficial. Monounsaturated fats are slightly beneficial. Polyunsaturated fats are neutral, 2. Carbohydrate intake is most closely associated with CVD. 3. Fruit and vegetable intake has little or no impact on CVD – nor does fish intake [He wonders where the five portions of fruit and vegetable intake recommendations actually came from]. Vegetables in particular have no benefit.4. Legumes – beans and suchlike – are beneficial. 5. The recommendations on salt intake are completely wrong, and set far too low. For those who do not have high blood pressure, low salt intake increase mortality. On the other hand, high salt intake does no harm. 6. He recommends higher potassium intake. 7. He criticizes Ancel Keys and lauds Nina Teicholz [Author of big fat surprise]. Yay.
  29. What Causes Heart Disease XXVII, 03/06/2017, In which Malcolm makes the imaginary elevator pitch to Bill Gates. ‘Blood clots can form and stick to the inside of artery walls. They then get absorbed into the artery wall itself where, normally, they are cleared away by specialised white blood cells. But if blood clots keep forming rapidly, at the same point, or the blood clots are bigger and more difficult to shift when they form, they cannot be cleared away quickly enough and so end up stuck inside the artery wall. This leads to a build-up of blood clot residue, and remnants, in the artery wall itself. Which means that repeated episodes of clotting, over time, build into thickenings, and narrow the larger arteries, mainly in the heart and the neck, growing somewhat like tree rings. These areas of damage are usually called atherosclerotic plaques.      In time, the process of blood clotting, over a vulnerable area, leads to heart attacks and strokes as the final, fatal blood clot forms over an area of the artery that is already thickened and narrowed. In short, atherosclerotic plaques are the remnants of blood clots. Heart attacks and strokes are the end result of the same processes that caused plaques to form in the first place. Heart disease is a disease of abnormal blood clotting. It is as simple as that. The end.’ The blood clotting hypothesis has been proposed and worked many times and for decades by different people. Kendrick believes it is the only hypothesis that reasonably fits all known facts about CVD. "Sometimes the truth stares us in the face, but we just choose not to look." Gil Lewis. It appears that the money and therefore research has all been funneled into the cholesterol hypothesis--which is clearly and demonstrably quite flawed. Pfizer was pursuing the clotting branch in their research and had a promising drug in development called doxazosin. Then they bought Warner Lambert which made Lipitor (a statin). "The focus became Lipitor and lipids, lipids, lipids. Lo it came to pass that Pfizer never mentioned blood clotting ever again, lest it interfere with the LDL story. Pity really, because mighty Pfizer got it right in 1992." "At some point this, the blood clotting hypothesis, the correct hypothesis will win. Maybe that time will be now."
  30. What Causes Heart Disease XXVIII, 03/17/2017, Holy crap! This one blindsided me. He tells the story of a drug trial to treat angina by Pfizer. After the trials, the subjects refused to give back their extra medications, it was a PDE5i inhibitor. It turns out the drug had a surprising side-effect--it helped men maintain erections. Yes, this is about Viagra. It turns out that even besides the erectile dysfunction angle, it has other positive effects. For one, it helps prevent pulmonary edema at high altitudes. It also treats Reynaud's syndrome as well as reducing high blood pressure in the lungs. "How does it do all these things? The answer is that it increases Nitric Oxide (NO) synthesis in endothelial cells. When it does this in the penis, it stimulates erections. In the heart, it opens up coronary arteries. In the lungs, it dilates the blood vessels, in fingers and toes it opens up arteries. So, all of the many different effects, are all due to exactly the same process – increased NO synthesis. Viagra also lowers blood pressure – as you would expect." Here are the statistics from one study: 4.7% reduction in overall mortality, 38% reduction in MI (relative risk reduction), 14.6% reduction in death after an MI. Compared to stents, Viagra is even more impressive--stents give a 2% absolute reduction in mortality, Viagra gives about 15%. Men with heart failure were 36% less likely to die (relative risk) if the took a PCE5i. It reduces congestive heart failure probably by increasing angiogenesis. l-arginine/l-citrulline, direct sunlight on the skin, potassium, meditation, Vitamins D and C all have a positive impact on NO in endothelial cells.  Viagra could probably save or improve milions of lives, but... Once ED became the prescription focus, research stopped on the CVD side. Now that Viagra is off-patent, there seems little hope that that avenue will ever be pursued. e4e note: there is a daily Cialis available. I believe it is for the treatment of ED. Off-label use of prescriptions is frowned upon by the medical establishment.
  31. Cholesterol lowering – proven or not?, 03/20/2017, PCSK9 trials Repatha. evolcumab trials. This drug was highly successful in lowering cholesterol, yet if anything, mortality was worse. The trial was stopped in the middle to protect patients. Another nail in the cholesterol-causes-CVD-coffin. Tom Naughton of FatHead fame did a post about PCSK9 trials too. "Overall, no significant change was observed in all‐cause mortality or cardiovascular mortality.
  32. What Causes Heart Disease XXIX, 04/01/2017, Alcohol and lifestyle: 1: Do not smoke cigarettes (to which I would now add  – or anything else). 2: Take exercise – that you enjoy. Don’t try to drive yourself into the ground. Walking outside is particularly good, especially on a sunny day. 3: If you don’t drink alcohol, start. If you do drink, drink regularly – don’t binge drink – and make sure that you enjoy what you drink. Drink with friends, drink sociably, don’t drink to get drunk. 4: If you hate your job, get another one – don’t feel trapped. 5: Make a new friend, join a club, find an area of life that you enjoy. Praise other people and try to compliment other people more often. 6: Look forward to something enjoyable every day, every month, and longer term. His take on alcohol "... alcohol – as a chemical – is not protective against CVD. It is protective because, in the various forms that humans drink it, it is relaxing, reduces stress/strain, and when it is drunk with friends, it is part of a lifestyle that is protective. ...In short, I do not believe drinking alcohol is a true ‘drug’ effect. The lifestyle around drinking has a major part to play. However, I may be wrong. Researchers have studied the effects of different types of drink on factors that I consider key for CVD. Endothelial function, and blood clotting factors. It seems that red wine and beer are the most beneficial." There are also studies that show that high levels of alcohol consumption can negative a negative impact on clotting stickiness. There seems to be a therapeutic window beyond which alcohol can be harmful. Non-drinkers and very heavy drinkers have similar outcomes. Where does heavy drinking start? Hm. The research did not test for this. They called heavy drinking anything more than two glasses a day. So they would have lumped those who drink 2.1 glasses of wine each day with those who drink 2.1 bottles of gin. Safe to say though that having two drinks or so per day is likely to be beneficial.  By the way, red beer and wine are the alcohols in the studies discussed.
  33. What Causes Heart Disease XXIXb, 04/16/2017, Alcohol--Kendrick defends his claims about alcohol. One important objection is that the studies are observational/epidemiological, not randomized controlled placebo-controlled. That's true. It's also true that many things we know and believe have never had RCTs. The observational studies are the best that we have. But it's not definitive. Some readers also expressed concern that if Kendrick encourages people to drink in moderation, some will get carried away and become alcoholics, thereby causing them more harm than not drinking. While yes, this is a possibility, he believes that more people would benefit than would be harmed by the recommendation, so the total benefit favors moderate drinking even though, there will be some people that get worse. Cheers!
  34. What Causes Heart Disease XXX, 06/06/2017, On the hypothesis that inflammation causes CVD. A follow-on to XIII. According to Kendrick, inflammation is generally a healing result of damage, not a cause of damage. Reducing inflammation inhibits damage repair, so the I in RICE may actually slow down healing. In some cases, e.g. autoimmune diseases, inflammation is the body malfunctioning with inflammation actually causing damage, so in those cases, powerful anti-inflammatories are justified. But corticosteroids, a very potent anti-inflammatory do not reduce CVD risk. Hm. I fact many agents that reduce inflammation and suppress the immune system increase CVD risk. Even non-aspirin NSAIDS are beefing up their warnings.
  35. What causes heart disease – part thirty one (XXXI), 06/21/2017, What is the final action in CVD? "The final event in most heart attacks, and strokes, is the development of a large, and often fatal, blood clot. If this happens in an artery in the heart, a coronary artery, it cuts off blood supply to an area of heart muscle and can lead to a myocardial infarction (MI) [myocardium = heart muscle, infarction = death of tissue due to lack of oxygen]. There is a related, but different mechanism of action, in most, strokes. In this case a blood clot that has formed in an artery in the neck (carotid artery), breaks off and travels to the brain where it gets stuck, blocking an artery. This leads to a cerebral infarction." This is a simplified view. There are studies, and evidence from people who develop plaque extremely rapidly that the clotting function is the underlying cause.  "There is only one process. Atherosclerotic plaque are simply blood clots, in various stages of growth and/or repair. Plaque growth represents the formation of a new blood clot, at the same point, which is not cleared away properly. The final ‘thrombotic’ event is just a big enough clot forming to do real damage." There is ample evidence that plaques are formed by multiple episodes of clot and repair. "Was it possible, I asked myself, that blood clotting was not just responsible for the final clot, but also for the entire process of atherosclerosis? I believe that the evidence is out there, and clearly supportive, if you choose to look at it this way round. I suppose you could say that I do not believe in atherothrombosis. I believe in thromboatherosis (you’re right, I just made that word up). In thromboatherosis, plaques start and grow, through repeated thrombus formation at the same spot in an artery. In the end, a clot gets big enough to cause a stroke or heart attack. Sometimes the clot can be big enough to kill, without any underlying plaque, but normally it will form over an already existing plaque – where plaque rupture can be the trigger. In short, there is only one process in CVD. It is the development of atherosclerotic plaques through repeated thrombus formation, followed by the final thrombus formation. As you can see this is actually very close to mainstream thinking. The only difference is that you have to flip your thinking through one hundred and eighty degrees, to see it upside down." e4e comment: IMHO this hypothesis is really clean. It is predicated on only one (albeit complicated) process. There is lots of evidence for it, and alternate hypotheses, e.g. cholesterol theory, have lots of contradictory evidence and are clouded by commercial interests and the usual suspects of confirmation bias and cognitive dissonance. I am confident that it is not perfect in every way; there are too many variables. when looked at from a human evolutionary perspective, it just. makes. sense.
  36. What Causes Heart Disease XXXII, 07/12/2017,  for years Kendrick believed that stress was a main driver of CVD but he had not identified the mechanism by which it occurs. In his words, "Negative psychological and/or physical stress → HPA-axis dysfunction → abnormal cortisol secretion → metabolic syndrome/type II diabetes → atherosclerosis → increased risk of CVD. Now, I think that this model is still perfectly usable, and it explains a lot. However, although I drew a simple arrow from metabolic syndrome/type II diabetes → atherosclerosis, this is the bit that Paul Rosch was talking about. What is actually happening here? It is all very well to state that something causes something else, but you still need to explain how."
  37. What Causes Heart Disease XXXIII, 07/29/2017, Viagra again. The idea that CVD begins with damage to the endothelium completely negates the cholesterol hypothesis of CVD. He follows with a letter from the mainstream that claims that "cholesterol deniers" are killing people. Kendrick shows evidence that debunks the cholesterol hypothesis and reiterates some of his arguments supporting the atherothrombosis hypothesis. But he goes on to say that statins do have some positive effects--just not because of the cholesterol lowering. There is a study of atorvastatin that showed positive effects on nitric oxide and endothelial protection. He concludes with "If you decide to look more closely at the process of CVD, and more closely at the actions of statins, a different picture emerges. One which fully supports endothelial damage as the first step in plaque formation. Because statins do many more things than LDL lowering. It could be said that statins are simply the poor man’s Viagra (other PDE5 inhibitors are available)."
  38. What causes heart disease part XXXIV (part thirty-four), 08/09/2017, Looking for contradictions. Refuting hypotheses in the health field is very difficult. There are always ad hoc hypotheses and variables of variables. Just in cholesterol, if you factor in all the types of cholesterol, there could be 25! combinations to test. Even setting "Safe" levels of any single variable is difficult and mostly illogical. Effectively with the paradigm of the lower the better, everyone has high cholesterol. "When confronted with logic like this, the cholesterol hypothesis is perfectly protected from attack. It is a non-refutable hypothesis. As Karl Popper said, if you cannot construct your hypothesis in such a way that it can be refuted, it is not science a.k.a. nonsense." Which is why he looked for an entirely different pathway.
  39. What causes heart disease part XXXV (thirty five), 08/19/2017, The beginning of the end--bringing it all together.  Point 1. Lots of things seem to cause CVD, but there are so many that it is clear that there must be some underlying factor that ties them all together. Point 2. The evidence base is flawed and extremely complicated. It's impossible to control for all the possible and known factors, but you can't just throw out research that contradicts your prejudices or dismiss data as a paradox. Nor can you ignore the effects of conflict of and vested interest on studies. And by the way, peer review doesn't fix it. Studies are flawed and judging them is very difficult one result is that many of us let our preconceived notions and biases color our interpretations. The first step to fix those biases is to know and acknowledge them. Here's what Kendrick says about his biases, "I am almost entirely anti-statin. I am not a great believer in blood pressure lowering – at least not at current levels. I do not believe in the cholesterol hypothesis and I think that the anti-saturated fat dogma is completely bonkers and has no evidence to support it – at all. I believe that salt is good for and, in most people, protects against CVD. I believe that a high carbohydrate low-fat diet is utterly bonkers – especially in those with diabetes. And suchlike. In short, I believe that almost everything we are told is good for you, is bad for you, and vice-versa. With the exception of smoking (bad) and exercise (good).
  40. What causes heart disease part XXXVI (part thirty-six), 09/05/2017, Continuing to sum up. This is a really important post. Remember that atherosclerotic plaques develop only in large arteries, and never develop in veins. Why is that though?There are many possibilities, but most can be rejected easily. You find that as "...plaques develop, you find that they most often occur at [points of] maximum biomechanical stress." A research paper observed this, but then attributed it to a leaky endothelium permitting LDL to pass through into the arterial wall. But wait, why in the world would an intact endothelium do this? Bottom line is that it doesn't unless the endothelium is damaged, which brings us back to square 1; CVD does not start with cholesterol, but rather with a damaged endothelium. There are people who believe that cholesterol can force its way through undamaged endothelium by various mechanisms. Kendrick proposes "a thought experiment if you like. Why would endothelial cells allow LDL to pass through them, to then allow LDL to be oxidised in the arterial wall behind? This process serves no physiological purpose, other than to kill you from cardiovascular disease! The idea that endothelial cells simply cannot prevent this from happening is, frankly bonkers. ...the idea that an endothelial cell cannot prevent a relatively massive LDL molecule from entering the side facing the bloodstream, then passing straight through, then ejecting itself out the other side, is complete nonsense." Quick summary: "1: It is impossible for LDL to pass straight through a living endothelial cell. 2: Endothelial cells are tightly bound together, and will not allow anything to pass between them." He talks about fenestrations in capillaries which do allow nutrients to pass through the blood vessels, and how the brain manufactures its own cholesterol for brain cells, (it doesn't get it from the blood) as further evidence of difficulty in penetrating the endothelium. Finally, he discusses the vasa vasorum, which are vessels that feed blood and other nutrients into the large veins and arteries. There is no need for the endothelium to leak; the vessels get everything they need from the vasa vasorum. At this point you "...realise that the cholesterol hypothesis, whilst it sounds superficially reasonable, requires mechanisms of action that just do not exist." 
  41. What causes heart disease part XXXVII (Part thirty-seven), 09/16/2017, Begin with the end in mind. What is the end-member of CVD. "the final event in cardiovascular disease is, in most cases, pretty much accepted... The formation of a blood clot." There's a ton of documentation that anything that reduces blood clotting also reduces CVD risk, while anything that increases clotting increases CVD risk. But the official party line was that development of the blockage in the first case was not related to the final clotting event. This just doesn't seem right. Why in the world do you need two separate processes for this when one will suffice? The clotting system is extremely important and incredibly complex. Because of its importance, it is always ready to go from zero to 100 at a moment's notice. But it also has to be able to stop before it gets carried away. His analogy is like having one foot mashing the accelerator to the floor while the other is standing on the brake. The most powerful clotting mechanism is "tissue factor," which sits under the endothelium. Exposure of blood to TF sets up a clot instantaneously. This makes sense--bleeding kills if unchecked. The only way a clot forms in arteries is damage to the endothelium. Once it forms, enzymes int he blood moderate the growth, and begin to break the clot down. But it's not like a scab on your skin. Obviously, if a scab broke off in an artery it would cause damage downstream. Rather, once the clot forms, moderates, and begins to clear, your body grows a new layer of endothelium over the old clot.  The new cells are created by endothelial progenitor cells, which actually have a function in addition to the endothelium. They can also convert themselves into macrophages, which clean away tiny pieces of the old "scab" and carry them to the lymph system for elimination. He calls this process healing, but others call in inflammation. Believing that inflammation causes CVD is like believing that firemen cause fires. Another note of importance is that one of the most stubborn constituents of the clot is a factor called apolipoprotein(a) or Lp(a). It is almost identical to LDL particles but with a single molecule difference that makes all the difference and makes it resistant to breaking down. He contemplates that the Lp(a) content may be a part of the belief that cholesterol is a problem, when in fact it is a very similar molecule. 
  42. What causes heart disease part XXXVIII (part thirty-eight), 09/24/2017, What is this biomechanical stress? However you define it, it is clear that the plaques develop at spots of transition or change within the arteries and at those spots, the initial damage happens to the endothelium. Here are some factors that are known to damage the endothelium: Smoking, Air pollution Diabetes, Cocaine use, Dehydration, Infections/sepsis, Systemic Lupus Erythematosus (SLE), Lead, Stress hormones, Avastin, Omeprazole, Cushing’s disease, Kawasaki’s disease. They all also are identified causes of CVD. A young woman with lupus has an increased CVD risk of 5000%. Sickle cell anemia is even worse. Not only does it increase clotting but by itself damages the endothelium. One of the challenges with this series is that in order to demonstrate how these completely disparate causes are related, you have to understand and identify their role within the underlying process. "There is no point in saying that, yes, they all cause heart disease, and that’s that, just add them to the list. There is a requirement to fit them within a single process, and it must make sense. It also has to be supported by the facts – as far as that is possible. Equally, there is no point in saying CVD is ‘multifactorial’, which is the normal defence of the mainstream when pressed on why many people, with no risk factors for CVD, still get CVD. The word “multifactorial” explains nothing, it is just an escape route for those pressed to explain the many ‘paradoxes’ or refutations that keep on appearing." Where are we now then, "...demonstrate[d] that the trigger factor for CVD is damage to the endothelium. If you don’t damage the endothelium nothing else happens. The damage happens at well-recognised places where the biomechanical stress is at its greatest. Which means that, with no biomechanical stress, there can be no atherosclerotic plaques. However, it takes more than just biomechanical stress. You also have to have at least one extra factor present to trigger endothelial dysfunction. " See you in the next post. Same bat-time, same bat-channel.
  43. What causes heart disease part XXXIX (thirty nine), 10/09/2017, There are four types of myocardial infarction: A myocardial infarction with no obstructive arterial disease, A myocardial infarction caused by stress, with no obstructive arterial disease, myocardial infarction that happens weeks after the thrombus forms, the ‘classic’ myocardial infarction with thrombus formation followed rapidly by infarction.  This "...leads to the inevitable conclusion that something else must be going on. Perhaps it is true that the infarction, due to extreme stress and build of lactic acid does come first. Then, as a consequence, the clot forms in the artery." But now we have to ..."dig even deeper, to find the man that isn’t there. Banksy, a man who paints on walls, is never seen, but we know he was there because, otherwise, you can’t explain the painting."
  44. What causes heart disease part XL (part forty), 10/27/2017, On the importance of reducing stress in your life and having close family and community ties. France and Scotland have similar diets (Scotland is slightly lower in saturated fat and vegetables) and similar BMI and blood pressure The French smoke more, exercise less. Rates of diabetes and total cholesterol levels are identical. If you enter all the data into a CVD Risk calculator they come out very similar in terms of risk. Yet the reality is that Scots have five times the rate of CVD as the French. This is typically called the French paradox. However, there is no such thing as a paradox, just bad hypotheses. Ad hoc theories say the French drink more wine or eat more garlic. This is pure horse pucky. Kendrick says the French paradox should actually be called the "French refutation of the diet-heart hypothesis and the LDL hypothesis, and all other hypotheses about cardiovascular disease you can think of." One difference is not in what they eat, but rather how they eat. Scots tend to treat mealtimes as refueling stops on the way to the next thing, whereas the French "Time is taken, food is appreciated, families tend to eat together..." So Kendrick studied the effect of stress on metabolism. Cushing's disease is a disorder where stress hormones are pushed high by the adrenal glands. People with Cushing's are in perpetual fight or flight state. It also increases CVD risk by 600%. Time after time, we see high-stress events, like social and political upheaval followed by increases in CVD. It seems that reduction of stress, and close family and community links may be the silver bullet.
  45. What causes CVD part XL1 (Part forty-one), 11/12/2017, Discussion of the ORBITA study. Stents don't work. BMJ article with a double-blind, randomized, controlled trial comparing an operation to emplace stents with an operation that does nothing. Wow! Here are the results. "‘Percutaneous coronary intervention (PCI) is not significantly better than a placebo procedure in improving exercise capacity or symptoms even in patients with severe coronary stenosis, research has found." To be clear, this was about stents in a non-acute situation. Years ago, the standard of care was to graft a vein where there was blockage in the coronary artery. As with stents, before the procedure was common and became the standard of care, there was virtually no research on efficacy. "Common sense " dictates that open artery = good, closing artery = bad. But there was no actual research demonstrating that their preferred solution did much beyond lining the pockets of the medical establishment. DOctors used phrases like " “You have a time bomb in your chest” and its variant “You are a walking time bomb.” Or, “...This narrowed coronary is a widow maker.” And if patients wish to delay an intervention, a series of fear-mongering expressions hasten their resolve to proceed: “We must not lose any time by playing Hamlet.” Or, “You are living on borrowed time.” Or, “You are in luck — a slot is available on the operating schedule.” Maiming words can infantilize patients, so they regard doctors as parental figures to guide them to some safe harbour." I personally had a doctor tell me that high blood pressure is "the silent killer" in order to bully me into blindly accepting his advice. Dr. Kendrick ends the post with this, "Those who have read my endless blog on the causes of on CVD will know I have long been highly sceptical of stenting as the answer to anything very much. Other than the removal of large sums of money from person A, to hospital B, and interventional cardiologist C. Why does it not work? How can it possibly not work? Because the heart is not simply a pump, arteries are not simply pipes, and humans are not inanimate objects whereby our function, or lack thereof, is purely dependant on some form of medical or surgical intervention. Thus endeth the lesson on stenting."
  46. What Causes Heart Disease XLII, 12/09/2017, More on stress/strain. Stress and other mental health issues drive numbers like a 1300% increase of risk of CVD, whereas factors like diet and cholesterol change risk by 10%. "Chronic stress → dysfunction of the hypothalamic pituitary adrenal axis (HPA-axis) → sympathetic overdrive + raised stress hormones → metabolic syndrome (raised BP, raised blood sugar, raised clotting factors, raised cortisol, raised all sorts of things) → endothelial damage + increased blood clotting → plaque formation and death from acute clot formation." Where should we be focusing?"And if you want to close this loop further, stress also increases LDL levels, in some studies by over 60%. So, when you see raised LDL, in association with increased CVD, it is not the LDL causing the CVD. It is stress, causing both."
  47. What causes heart disease part 43, 12/29/2017, What is stress? You have to separate stress from a person's body response to stress (strain). Some people have little response to stressful events, while others can have a massive response to seemingly minor events. "The hypothesis here is reasonably straightforward. It is as follows. Long-term negative stressors (or one overwhelming acute event) can create damage to the neurohormonal system that coordinates the physiological reaction to strain. This, in turn, has negative physiological effects that can lead to serious disease e.g. CVD, or diabetes, or both." When you go into fight or flight modes, "The blood pressure goes up, sweat glands are activated, blood clotting factors are released..." Measurement of stress hormones is tricky, with clear diurnal patterns putting noise into the data. Per Bjorntorp, a Swedish researcher demonstrated a strong linkage between stress hormones and metabolic syndrome (which in turn links to CVD). It turns out Cushing's disease in people pump lots of stress hormones into people and those people have much higher rates of Metabolic syndrome and CVD. We do not give people cortisol, but corticosteroids have many of the same effects on hormones. Guess what. If you take corticosteroids long-term, "The risk of CVD is increased by, up to, 600%."
  48. What Causes Heart Disease part 44, 01/12/2018, How to remain healthier and live longer, Actions that reduce CVD risk. Taking a statin for 30 years gives you a statistical extra 24 days of life--best case. Regular exercise gives you an extra four and a half years. Which makes exercise at least fifty-four times more effective than statins. The only CV medicines that make a major difference are anti-coagulants (blood thinners) such as warfarin, rivaroxaban, and apixaban. So here is the prescription: Exercise, Stop smoking, Get sunshine and enjoy it. "These three things alone can add around sixteen years to your healthy lifespan."
  49. What Causes Heart Disease part forty-five, 1/27/2018, There are periodic studies that show that taking vitamins is bad. There is little economic benefit to studying the effects of vitamins. They're all off patent. Optimal doses are also unclear; typically we know the minimum dose to prevent disease. Nobody died in 2010 from taking vitamins; OTOH, 328,000 people died from prescribed medicines. Supplements to consider include Vitamin K2 5µg, Thiamine 7mg, Folic acid 7µg, Potassium 50mg, Magnesium 50mg, L-arginine 600mg, L-carnitine  50mg, L-citrulline 7mg, Co-enzyme Q10 3mg, then add Vitamin D and Vitamin C and multiply everything by 4x per day.
  50. What Causes Heart Disease part forty-five B - an addendum, 1/29/2018, Oops. A new paper just came out about Magnesium. It is much more important than he believed.
  51. What causes heart disease part 46, 2/14/20018, The mind and poor social interactions.
  52. What causes heart disease part forty-seven, 3/13/2018, Raised cholesterol is not a factor for stroke. Statins reduce the risk of both heart attacks and stroke. Therefore, the cholesterol hypothesis is not correct. "...the beneficial effect of statins on the risk of stroke, flatly contradicts the cholesterol hypothesis." 
  53. What causes heart disease part forty-eight (48), 3/22/2018, Lead causes endothelial damage! Chelation therapy, which he had written off as "woo-woo medicine," actually works. Thalidomide and avastin both hamper the generation of endothelial cells/angiogenesis, both are used to treat cancer, and avastin leads to higher incidence of CVD. There is no evidence that Thalidomide does. There is a paper that studies this, but he hasn't figured it out yet.
  54. Statins and Amyotrophic Lateral Sclerosis, 4/9/2018, Amyotrophic Lateral Sclerosis, aka Lou Gehrig's disease affects 2-3 people per 100,000 in the US and Europe. It is a disease of the nervous system, in which although you remain alert and able to think clearly, the ability to control your muscles deteriorates until you die of suffocation. A recent paper in the journal Drug Safety indicates that statins can greatly increase the risk of developing ALS. They researchers established an association, but the association was so large that it is believed to represent a causal relationship. The "safest" statin reported was linked to an 800% increase in ALS (so that 2-3 number would increase to about 20). The worst statin reported was Lovastatin with an increase of over 10,000% (the 2-3 number goes to 200-300/100,000). In terms of risk to an individual, the odds are still very greatly in your favor that you will not develop ALS, even with statin use--for Lovastatin, the ration fes from about 1 person per 50,000 to 1 in 500. However, given what Kendrick believes to be the relatively low efficacy of statins in reducing total mortality, is this a risk you want to take? This new information emphasizes the absolute criticality of cholesterol to the human body. There are signals in data that ALS is increasing in a number of countries, but the data is not reliable, as few countries accurately track ALS in mortality statistics.
  55. Very high LDL and no cardiovascular disease – at all, 5/12/2018, We seem to be past the main series on what causes heart disease, but Dr. Kendrick continues to put out interesting analysis of studies. This one is about a case study of a guy who has familial hypercholesterolemia--a genetic condition that drives very high blood cholesterol. He starts with discussion of black swans. Essentially, if you believe that high cholesterol is the key driver of heart disease, the presence of someone with very high cholesterol and no heart disease should make you think about your hypothesis. Here's what he says: "Unfortunately, but predictably, the authors of the paper have not questioned the LDL approach. Instead, they fully accept that LDL does cause CVD. So, this man must represent ‘a paradox’. They have phrased it thus:"‘Further efforts are underway to interrogate why our patient has escaped the damaging consequences of familial hypercholesterolemia and could inform future efforts in drug discovery and therapy development.’
    "To rephrase their statement. We know that high LDL causes CVD. This man has extremely high LDL, with no CVD, so something must be protecting him. I have an alternative, and much simpler explanation: LDL does not cause CVD. My explanation has the advantage that it fit's the facts of this case perfectly, with no need to start looking for any alternative explanation."
  56. Eggs are Good for You - who knew!?, 5/28/2018, A little off the CHD track, but relevant to cholesterol. A large study of 500,000 people with this conclusion. ‘Among Chinese adults, a moderate level of egg consumption (up to <1 associated="" cvd="" day="" egg="" em="" factors.="" independent="" largely="" lower="" of="" other="" risk="" significantly="" was="" with="">
  57. What causes heart disease? – part 49 (nearly there), 6/15/2018, Flashback to university when a lecturer said that ‘cholesterol cannot get past the endothelium.’ She also said (heretically) ‘In this talk I have concentrated mainly on the factors that may be involved in the progression of the early, low-lipid gelatinous lesion into the typical fibrous plaque with lipid-rich centre that is generally accepted as the significant lesion in occlusive vascular disease and have tried to emphasize the key role that may be played by fibrin.’ He talks about how heart attacks can happen whether or not there is a clot and how sometimes even with a clot, the attack doesn't happen. Finally, he recaps his main hypothesis--that plaques occur when the endothelial damage process occurs faster than the healing process, lists 14 causes of CHD that have nothing to do with cholesterol, then tells about a case of sickle cell anemia in a child.
  58. Why saturated fat cannot raise cholesterol levels (LDL levels), 7/3/2018,
  59. What causes heart disease - Part fifty, 7/23/2018, Malcolm goes through the criteria that help us understand causation from analytical and epidemiological studies. The postulates for lab work are (Robert Koch, 1882): The microorganism must be found in abundance in all organisms suffering from the disease but should not be found in healthy organisms, The microorganism must be isolated from a diseased organism and grown in pure culture, The cultured microorganism should cause disease when introduced into a healthy organism, The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent. As well as Bradford Hill's Cannons [sic] of Causation (1965). from Wikipedia. Strength (effect size): A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal. Consistency (reproducibility): Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect. Specificity: Causation is likely if there is a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship. Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay). Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence. Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge). Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations". Experiment: "Occasionally it is possible to appeal to experimental evidence". Analogy: The effect of similar factors may be considered. Nothing is black or white, but very few of all the criteria above apply to the standard factors normally cited for CHD. The "flat paradigm" says that disease can be multi-factorial, but this is probably too granular. Rather, look at the underlying process involved. CHD is not from smoking in one person, lupus in another and sickle cell in a third. All of those factors trigger a specific underlying process.
  60. What causes heart disease part 51 – ‘Athero-thrombosis’, 8/6/2018 - Recap: The mainstream view is that cardiovascular disease is caused by two completely different and unrelated processes. The first process is the development of plaque, where cholesterol pokes its nose under your endothelium; the second is development of a blood clot on top of that plaque, perhaps from something inside the plaque, or like a boil bursting or something like that. Malcolm HATES this view. It creates a lot of issues and complications in looking for causes and cures of heart disease. "For one thing I do not like having to invoke two completely essentially unrelated processes to explain a single disease. Mainly though, even if it wasn’t deliberately designed to protect the ‘LDL-hypothesis,’ that is exactly what it does." Most atherosclerotic plaques contain cholesterol crystals. But those crystals can only come from red blood cells, not from LDL. So "Repeated blood clotting occurs first, followed by intra-plaque rupture." This is the opposite of the mainstream view, where the blood clot is just some end member state. Thus heart disease should really be described as thrombo-atherosis, not athero-thrombosis. "Blood clotting is not simply the final event in the CVD. It is the only event, and it is how atherosclerosis starts, grows and eventually kills you. Or, to put it another way, there are not two processes in cardiovascular disease, there is only one."
  61. What causes heart disease part 52, 8/16/2018 - The beginning of atherosclerotic plaque development. The idea that cholesterol simply "leaks" past the endothelium has never made any sense. Partial list of issue: 1. If it is leaking due to a pressure gradient, why is it not seen in all arteries, but rather only in some places? 2. Why does LDL never leak into vein walls? 3. Larger arteries have their own blood supply, why don't those vessels have the same problems as the arteries themselves? 4. Endothelium is seen everywhere to be impermeable to cholesterol as exemplified by the blood-brain barrier. The tight junctions in the endothelium prevents molecules and ions from penetrating. Cholesterol doesn't stand a chance. 5. It is possible to get past the endothelial layer if the endothelium allows it through transcytosis. "The idea that an endothelial cell would be programmed to absorb LDL from the bloodstream, then actively transport it through itself, then deposit it in the artery wall behind – for no reason whatsoever – defies all laws of biology and physiology..." He could on but stops here. It's sufficient. The counter argument has always been, "well the plaques contain cholesterol, som they must have leaked through the endothelium." To which Malcolm say, yes, after the endothelium was damaged by other factors. One argument against the clotting hypothesis is that the early stage of atherosclerosis, i.e. the fatty streaks are not related to clotting. He presents evidence that the fatty streaks are a completely different phenomenon not related to CVD. Fatty streaks do not turn into plaques. "...fatty streaks exist, but these ‘lesions’ are not the things that become atherosclerotic plaques. Plaques form in a completely different way." But, until the mid-90s, nobody knew about the existence of the epithelial progenitor cells, which "scab" over damaged endothelium, encrusting whatever is in there. This gave the LDL hypothesis time to take root and become the leading paradigm. "They couldn’t explain how massive molecules that are normally found in the bloodstream, could get inside the artery wall. So, they were defeated by the facile, impossible, ridiculous, LDL hypothesis. A great pity, because the encrustation theory explains what the LDL hypothesis cannot." Even statins, when they work, "...they increase nitric oxide synthesis in endothelial cells, and nitric oxide protects the endothelium, stimulates the growth of endothelial progenitor cells, and is also the most powerful anticoagulant agent known to nature."
  62. What cause heart disease part 53 – diabetes, 8/21/2018 - Diabetes increases CVD risk 3-500%. This does not make any real sense at all in the cholesterol theory. So how does high blood sugar cause endothelial damage? We go to another level of complexity now. Lining the endothelium is a layer of molecules referred to as the glycocalyx. The glycocalyx is composed of hairlike strands of protein and sugars bound together (it's about 1 micrometer thick, so very thin). You know that slimy feel that fish have? That's their glycocalyx. Of course there's a paper, ‘Loss of Endothelial Glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo.’ Function of the glycocalyx: Protects the underlying endothelium from damage, Maintains the endothelial barrier function, Acts as a mechanical sensor for stress/shear stress, Mediates nitric oxide (NO) release, Anticoagulant (stops blood clotting) – many anticoagulant factors live here, including NO, Prevents adhesion of white blood cells and platelets. So this is what diabetes does. Still holding together.
  63. What causes heart disease part 54, 8/31/2018 - Health research is hard because of the "First do no harm" dictum. So the focus has always been to test interventions that will help make people better, not prove that something causes harm. This is a really good thing, although somewhat inconvenient in terms of demonstrating causality. That's part of the reason we rely on epidemiological studies to help us. Bradford Hill laid out the nine criteria to help determine the information that can be extracted from those studies and their validity. (See item 59 above for more detail). Sometimes we have a natural experiment that can be used to extract meaning. The most familiar example is the impact of smoking on people. There are also examples of drugs thought to be beneficial actually causing unintended harm. Thalidomide is a common example. There's another one quite relevant to this topic though--Proton pump inhibotrs (PPIs). These are drugs like omeprazole and other "-zole" medications created to help prevent heartburn. It turns out that PPIs inhibit NO synthesis. If you believe Kendrick's hypothesis of heart disease, you would expect therefore to see heart disease go up with usage of PPIs. And it turns out that PPIs double heart disease risk. (See number 23 above). There are other drugs that have far worse impacts. Avastin, the generic name is Bevacizumab is a case in point.  It is a vascular endothelial growth factor inhibitor (VEGF-inhibitors). Its impact is in preventing or inhibiting repair of blood vessels as they try to build a new endothelial layer, as well as slowing the healing by inhibiting the macrophages that heal the damage site. Endothelial progenitor cells (EPCs) were once thought to be useful only in the development of the foetus, but more recently have been found to have a role in healing arteries as well. Arterial adverse events 2.40 (1.64–3.52), P<0 .001="" attack="" cardiac="" heart="" ischemia="" nbsp="" strong="">5.16 (0.91–29.33), P=0.06, Cerebral ischemia (stroke), 12.39 (1.62–94.49), P=0.02, Venous adverse events 1.37 (1.11–1.68), P=0.03, Bleeding 2.96 (2.46–3.56), P<0 .001="" arterial="" hypertension="" nbsp="" strong="">4.81 (3.10–7.46), P=0.001. The bold numbers represent the risk factor. So the 5.16 on heart attacks means you have a 5.16 times increased probability of a heart attack. A 3% probability goes to 15%+. Avastin easily satisfies all of the Bradford Hill criteria. But here's the thing--Avastin can increase CVD, only if Kenrick's hypothesis of heart disease is correct. It has no impact on LDL or any other cholesterol. So Avastin becomes the black swan in this. "The blackest of black swans. An agent, that is perfectly designed to create endothelial mayhem, causes CVD, with no explanation available within the LDL/cholesterol hypothesis."
  64. What causes heart disease, part 55 - albumin, 9/17/2018 - Maybe you have seen albumin listed on your blood tests and wondered what that was about. Maybe you haven't. You know those pictures of starving children with their bellies distended? That is one of the impacts of having low serum albumin. It also happens to alcoholics because as liver damage increases they are unable to produce sufficient albumin. There's also a link between albumin and CVD. Albumin is a protein that circulates in the blood and, among other things, helps maintain the glycocalyx. Deficiencies in albumin are a causal factor in CVD. ’This study unequivocally confirms the important association between SA (serum albumin) and individuals with chronic stable CAD’. There may not be too much you can do to raise your serum albumin, but eating sufficient protein is a start. "At this point, however, the main point that I want to make here – again – is that, once you start to understand CVD as a process that is triggered by endothelial damage, you can start to look at the research on CVD in a completely different light. You can make associations where, using the LDL hypothesis, none exist. It also makes sense."
  65. What causes heart disease part 56 – a new paper, 9/23/2018 - The paper is called ‘Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia.’ And you can see it here . It will be free access for a very limited time, so go fast. I can see only the abstract, not sure if I'm doing something wrong. Anyway, the summary is that people with Familial hypercholesterolemia live as long as others on average, LDL-C in FH people with and without heart disease is the same, and there is questionable benefit from cholesterol-lowering drugs (statins). Dr. Kendrick and Uffe Ravsnikov are both authors, as well as Michel de Logeril and David M. Diamond.
  66. What causes heart disease – part 57, 10/11/2018 - Blood pressure as a cause of CVD is complicated. Average is not the same as normal. Mortality calculators let you take the systolic down to 90, with CVD risk decreasing at every step. However, below 90 you have hypotension, so exactly 90 is the best level. Lol. CVD risk from blood pressure rises, but only very slowly until systolic of 160--then it increases faster. It is clear that blood pressure is a cause of arterial damage. Blood vessels in normally low-pressure areas like the lungs can develop atherosclerosis if blood pressure is elevated. Only blood vessels in high-pressure areas develop atherosclerosis. a 2000 paper called 'There is a non-linear relationship between mortality and blood pressure' concludes that the reported linearity between blood pressure and mortality is not in the data, but rather the analysis of the data. EmotionsForEngineers wrote on blood pressure in 2014. We'll see what the next installment holds.
  67. What causes heart disease part 58 – blood pressure, 11/1/2018 - Cause of high blood pressure is mostly not known by doctors (e4e comment: Apparently you have to be an engineer to understand pressure in a tube). But Malcolm seems to be on it. He focuses on the narrowing of the pipes, I suspect there's also a stiffening component as well--pulses into a balloon will just expand the balloon, whereas inlead it would cause hammering. One issue that high blood pressure does cause is enlarging of the two ventricles, which can lead to congestive heart failure (a completely different animal than what Malcolm has been discussing in this series). He discusses causality, he says that cardiovascular disease probably causes hypertension rather than the reverse and talks about the biochemical basis for that view. The issue is that lowering blood pressure may be lowering blood flow to places where it is needed. "...dealing with the elderly can turn into a battle between the heart and the kidneys. Get one under control and the other one goes off." He has liked ACE inhibitors for hypertension control in the past because they also increase NO synthesis. However, there is evidence that they can increase the risk of lung disease.
Notes, Comments and Other

Peter Attia's view. Dr. Attia is another very smart guy. His view is somewhat different than Dr. Kendrick's view. Attia focuses on the end stage as being the infarction, rather than the clot breaking. There are also other differences.

Kendrick's view is that the clot occurs mainly (although not exclusively) because of physical damage to the endothelium. In "normal" circumstances, most of the clot will get cleaned up by the body, perhaps leaving behind some scar tissue. But if the clot has some malformation, or the person has an imbalance in some of the important blood factors, the cleanup either does not occur or is poorly done. At that point, the vessel will become blocked, or the clot may break loose because of defects in the clot.

Attia, on the other hand, seems to regards CVD as simply an inevitable outcome of age. Oxidation and damage happen inside the intima (the artery wall itself, behind the endothelium), then essentially spills over through the endothelium, where it clots, etc.

For me, Kendrick's view seems to hold together better. It contains both a pathology as well as a mechanism for reversing it if everything is working properly. Attia presents the damage as something that happens that cannot repair itself. I don't think that's the way the body usually works. Kendrick's view is that overall the body is doing its best to protect itself, but when it gets overloaded it simply can't keep up. This can be compared to the view that CVD is a horrible pathology.

In all likelihood, I am misinterpreting much (and perhaps they are saying something quite similar but explaining it differently), but Kendrick's view seems more biologically consistent with the way the body usually works.

Other posts during the series on What Causes Heart Disease.

Duane Graveline, 09/06/2016, Duane was a doctor who trained to be an astronaut. He was prescribed statins and had severe side-effects. He researched and studied these effects and developed the SpaceDoc website. He passed away.
Medical censorship in the twenty first century, 9/11/2016, Medical censorship. Tells stories about how researchers try to quash research and studies contrary to their beliefs and/or interests. This is an interesting read about limitations of studies, especially when researchers have a dog in the hunt. [e4e note: This post is mostly about how confirmation bias and cognitive dissonance destroy even intelligent people's ability to reason.] Read it, but there is little to learn about heart disease. There is interesting information about statin adverse effects.
Buy this new book, 09/26/2016, "There is a group of doctors, scientists and researchers called the International Network of Cholesterol Skeptics (THINCS) www.thincs.org. I am a member, and recently a number of us have contributed chapters to a new book called Fat and Cholesterol Don’t Cause Heart Attacks And Statins are Not the Solution."
Saturated fat and heart disease, 10/20/2016, "Total saturated fat intake was associated with a lower IHD (Ischaemic Heart Disease) risk..." It goes on to say that substituting anything for saturated fat increases heart disease risk. The main point of this post though is that questioning dogma can be professionally and legally risky for doctors and researchers. It is especially bad when the dogma is built on "common sense" and not research. "Made up scientific hypothesis are, I find, very difficult to dislodge with evidence." He talks about a few examples and crazy quotes from people entrenched in the dogma.
Those who promote a high fat low carbohydrate diet are silenced around the world, 11/13/2016, The curious case of Dr. Gary Fettke. Horrible process they have in Australia.
High cholesterol low heart disease – The Sami, 11/29/2016, Another paradox--people whose good health persists despite their efforts to kill themselves with unhealthy habits. The Sami are what we used to call the Lapps in Finland. "...the Sami, despite having very high cholesterol levels, a high level of smoking, a high-fat diet, and almost zero carbohydrate intake – and suchlike – had a very low rate of cardiovascular disease. This was particularly interesting for a couple of reasons. Firstly, most of the Sami live in Finland, and the Finns – at one time – had the highest rate of heart disease in the world. Not only that, but the Sami live in an area of Finland, North Karelia, which had the highest rate of heart disease in Finland. The worst of the worst.In addition, the Sami had considerably worse ‘traditional’ risk factors for heart disease than the surrounding population. Higher cholesterol and LDL, high-fat diet, far more smoking etc."
The diet-heart hypothesis suffers another attack – hoorah!, 12/16/2016, A Group of concerned Canadian Physicians and Allied Health Care providers put together recommendations about Canada's dietary guidelines. Their recommendations are as follows: 1. Clearly communicate to the public and health-care professionals that the low-fat diet is no longer supported, and can worsen heart-disease risk factors. 2. Be created without influence from the food industry. 3. Eliminate caps on saturated fats. 4. Be nutritionally sufficient, and those nutrients should come from real foods, not from artificially fortified refined grains. 5. Promote low-carb diets as at least one safe and effective intervention for people struggling with obesity, diabetes, and heart disease. 6. Offer a true range of diets that respond to the diverse nutritional needs of our population. 7. De-emphasize the role of aerobic exercise in controlling weight. 8. Recognize the controversy on salt and cease the blanket “lower is better” recommendation. 9. Stop using any language suggesting that sustainable weight control can simply be managed by creating a caloric deficit. 10. Cease its advice to replace saturated fats with polyunsaturated vegetable oils to prevent cardiovascular disease. 11. Stop steering people away from nutritious whole foods, such as whole-fat dairy and regular red meat. 12. Include a cap on added sugar, in accordance with the updated WHO guidelines, ideally no greater than 5% of total calories. 13. Be based on a complete, comprehensive review of the most rigorous (randomized, controlled clinical trial) data available; on subjects for which this more rigorous data is not available, the Guidelines should remain silent." Yay!
https://drmalcolmkendrick.org/2017/01/28/vitamin-c-an-update/, 01/28/2017, ‘Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine may prove to be effective in preventing progressive organ dysfunction including acute kidney injury and reducing the mortality of patients with severe sepsis and septic shock. This one has nothing to do with heart disease, but VItamin C continues its march.
https://drmalcolmkendrick.org/2017/04/26/tim-noakes-found-not-guilty-of-something-or-other/
https://drmalcolmkendrick.org/2017/05/08/its-official-statins-do-not-have-any-side-effects/. 05/08/2017, discussion of a study that claims statin side-effects are extremely rare. The study was conducted by companies that sell statins. He doesn't believe it and has comments about the studies. In any case, except in a minority of people, statins help very little.
https://drmalcolmkendrick.org/2017/05/22/cholesterol-lowering-the-end-of-the-beginning/, 05/22/2017, more on the statin side-effect studies and conflicts of interest in the researchers.
https://drmalcolmkendrick.org/2017/05/28/mike-cawdrey-a-tribute/, 05/28/2017, Mike Cawdery was a regular commenter on Kendrick's blog.
https://drmalcolmkendrick.org/2017/06/24/british-society-of-lifestyle-medicine-conference/, 06/24/2017, "This is a great grassroots movement of people, and many doctors, who are trying to achieve a more holistic approach to health. "
https://drmalcolmkendrick.org/2017/07/16/diabetes-unpacked-a-new-book/, He talks about a book that he contributed to that discusses the causal link between diet and diabetes. It should come as no surprise that he favors a low-carb, high-fat (LCHF) diet. This is consistent with e4e recommendations, so beware confirmation bias.
https://drmalcolmkendrick.org/2017/10/19/starting-the-conversation/

Evacetrapib trials fail
https://www.nytimes.com/2016/04/04/health/dashing-hopes-study-shows-cholesterol-drug-has-no-benefits.html
Great quote, "“We had an agent that seemed to do all the right things,” said Dr. Stephen J. Nicholls, the study’s principal investigator and the deputy director of the South Australian Health and Medical Research Institute in Adelaide. “It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?” he said, referring to the 37 percent drop in LDL levels with the drug." Here's the e4e answer to his question. The hypothesis that high LDL and low HDL cause heart disease is a failed hypothesis. Your company should now declare bankruptcy and stop selling statins before you kill more people.

14 comments:

  1. I wish you could do this for the Hyperlipid site! thank you, it is fantastic!

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    1. Hi Shaza, I like Hyperlipid too. So much good info.
      Regards,
      Tony

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  2. Great project! I love Malcolm's blog. You've shared this on Facebook, Ivor. Is this your blog?

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    1. Hello Anonymous, If the share on Facebook was from Tony Kenck, then yes.
      Cheers,
      Tony

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  3. Thank you--this is impressive..can you perhaps remove the colour background..makes screen reading difficult.
    With thanks.
    Johann Slabbert GP RSA

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    1. Thanks Johann, I'll look into it. I am getting tired of the format. Last time I did it, I had to do a bunch of tweaks and it was a bit painful.

      I'll check and see if there's a good way for me to make the change you suggest.

      I appreciate the feedback.

      Tony

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  4. Thank you for this excellent review?

    It should be noted that Malcolm Kendrick, whose ideas on CVD have earned my highest regard, expressed serious doubts that the earth is on a trend of global warming caused by human activity. The lesson I am learning from this is that I should be as skeptical of him as he is of the cholesterol hypothesis. Nothng wrong with being skeptical.

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    1. Hi Anonymous,

      I must confess to significant skepticism about parts of the anthropogenic global warming hypothesis, and more importantly, what should be done about it.

      Fundamentally, I agree that the earth is warming to some extent, although frankly, the data on that is not as good as most people think. But I do believe that the earth has generally been on a warming trend since the early 1800s.
      The AGW hypothesis states that around 1950, the cause changed from natural to manmade CO2. OK.

      I'm not sure I believe that, but it's the next stuff I have a real problem with. Solutions being put forward would have tremendous cost, and if the cause is not absolutely correct it's money wasted and misspent and millions of lives lost for nothing.

      And by the way, the idea that global warming will be catastrophic is not accepted by anyone. Even the IPCC reports make no claims about future catastrophe.

      My suspicion is that there is actually little we can or should do to try to control the climate, but rather harden our infrastructure to cope with the consequences of climate change that are inevitable.

      Notice, I am not denying, but rather questioning the most extreme views and the proposed solutions to the problem.

      Anyway, thsi is out of scope of e4e. I have some posts on the matter at my personal blog, http://kenckar.blogspot.com if you want to engage there.

      By the way, my bachelor's degree is in geophysical engineering and I have an MBA, so earth science and economics are part of my formal training. Listening to Kendrick talk about earth climate processes is kind of like listening to an engineer talk about emotions. Oops.

      Back to your comment though, Kendrick himself says that even he is skeptical of his own hypothesis on CVD and keeps looking for holes in it. Thanks for your comment.

      Regards,
      Tony

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  5. Thanks everyone. For the record, this is not Ivor’s blog.

    As I reached about number 10 of his posts, I realized there was sooooo much good stuuff that I needed to take notes. As long as I was taking notes...

    Anonymous. I am an earth scientist and an economist. The anthropogenic global warming issue is complicated, and made more so by lack of clarity in discussions around it. In one of the posts, Malcolm compares the ad how hypotheses of the French Paradox (red wine and garlic are protective) to the change in hypothesis from global warming to climate change and says something like if it can’t be disproven, then it isn’t science. It is as true for climate as it is for health.

    I believe the climate is changing and man has influenced it. I have a lot of questions about the temperature record, there seems to be a lot of woo there. I’m not at all convinced that the forward models are correct or even reasonable. Finally, in my economist opinion,the proposed solutions are expensive, may not help much if at all, and do not consider the significant negatives that could result, especially to the poor and disadvantaged people in the world.

    I don’t want to dwell on the climate issue here though except to say that much of the science is not strong and the proposed solutions are not robust. If you are interested in a fuller view of my opinions, I have more at my personal blog kenckar.blogspot.com.

    In anyy case, we totally agree that there’s nothing wrong with being skeptical. Without skeptics, no progress is possible.

    Regards,
    Tony e4e

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  6. Dr. Kendrick's posts were enlightening. I learned quite a bit. I think it's safe to call Dr. Attia's hypothesis "child's play" by comparison. It also appears to be wrong from the very start by suggesting LDL can pass through the endothelium. Dr. Kendrick made a convincing argument that such a thing is not possible. Dr. Attia also doesn't seem to have answers for why atherosclerosis happens in arteries and not veins.

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  7. Hi Sean, I couldn't agree more. I read Attia's version a while back and thought it was pretty good, but it just didn't quite all fit. Malcolm's views seem so much more coherent, internally consistent and realistic.

    Thanks for your comments.

    Tony e4e

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  8. Dr. Kendrick certainly has rigorous scientific standards. The nerd/engineer in me appreciates the way he examines every conceivable detail.

    Looking forward to whatever else you dig up on diet and nutrition.

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  9. I was intrigued by this set of posts - thank you Tony for cataloguing - and so I looked into the genetic hints as to the etiology of CVD.

    One of the most unbiased ways to get information is through a genome-wide association study that looks at common variants and tests them for association with a complex (multifactorial) disease like CVD. In theory, if the study is designed well, it should yield associations with genetic regions related to all the different factors involved in the etiology. For example, in dental cavity genetics research, you get signals near genes related to oral antimicrobial peptides, tooth enamel regeneration, and saliva flow - all processes known to be related to cavity formation.

    I looked into the most recent pathway analysis of CVD - essentially a grouping of the biological pathways most related to CVD based on these types of genetic association studies. The number one most related hit was glycosaminoglycan metabolism by a factor of 100000 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5200919/). Apparently glycosaminoglycans on endothelial cells have a strong anti-coagulant activity (https://www.ncbi.nlm.nih.gov/pubmed/8495730).

    I was very pleased to see this hypothesis line up so well with the unbiased genetic study-generated data! Thanks for sharing.

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    1. Hi microkat,

      Really interesting. Thanks for doing this background work.

      I looked at the papers you referenced and they are way beyond any expertise I have, so I will take your word.

      Cheers,
      Tony

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