The standard medical paradigm says that eating saturated fats contributes to higher LDL cholesterol in the blood, and that higher LDL is associated with greater risk of CVD (cardiovascular disease = heart attack and stroke). \u00a0The mystery which I identified last month is that there is\u00a0strong evidence both for and against<\/i><\/b> this hypothesis in the mainstream medical literature.<\/p>\n
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Why the disparity?<\/strong><\/p>\n Certainly one reason there is so much difficulty obtaining agreement in the field is that the majority of scientists doing research on cholesterol are funded by drug companies that have billions riding on the results. \u00a0This is not a question of \u201chonest\u201d science vs \u201ccorrupt\u201d science. \u00a0It is simply unreasonable to expect that a scientist working for a statin manufacturer feels free to pursue his study objectively, and to follow the data wherever it leads. \u00a0It is hard to know the extent to which drug money has corrupted the science of cholesterol, but we can be assured that it is substantial.<\/p>\n Despite this major bias, I don\u2019t think that the relationship between cholesterol and heart disease is entirely a mistake or a fraud. \u00a0Even the harshest critics of the cholesterol establishment (Fred Kummerow, Stephanie Seneff, John Abramson, Sally Fallon) admit that there is some correlation between saturated fat in the diet and cholesterol in the bloodstream. \u00a0Similarly, there is good evidence that risk of heart disease is correlated with LDL cholesterol. \u00a0A new test based on the size of the LDL particles is much more predictive – see below<\/a>.)<\/p>\n <\/p>\n Correlation and Causation<\/strong><\/p>\n If A<\/b> is correlated with B<\/b> and B<\/b> is correlated with C,<\/b> it does not follow that A<\/b> must be correlated with C<\/b>. \u00a0Furthermore, even if A<\/b> is correlated with C<\/b>, it may be that A<\/b> does not cause B<\/b>, or B<\/b> does not cause C<\/b>, so that changing A<\/b> may have no effect (or the wrong effect) on C<\/b>.<\/p>\n To be concrete: It may be true that saturated fat in the diet is correlated with high LDL, and high LDL is correlated with high CV mortality, and still cutting saturated fat does not affect CV mortality.<\/p>\n Most studies linking saturated fats with LDL cholesterol have been positive [ref<\/a>], and most studies linking LDL cholesterol with risk of CVD have been positive [ref<\/a>]. \u00a0But studies attempting to link saturated fats in the diet with a higher risk of CVD have mostly been negative [ref<\/a>]. \u00a0This suggests that we don\u2019t understand the underlying mechanism behind heart disease very well, and that much of what we have done in the name of prevention may have been misdirected at intermediate targets that were not causally related to heart disease.<\/p>\n What is true of saturated fat reduction is even more true of statin drugs. \u00a0It is certain that statin drugs improve the cholesterol profile. \u00a0It is less clear that statin drugs save lives, and it is certainly not true that statin drugs are the best prevention strategy.<\/p>\n It is very convenient to have an intermediate measure (like LDL cholesterol) so that you can tell whether an intervention is working without having to wait for large numbers of people to die. \u00a0If we look for the effect of some new treatment on LDL, we can test a small number of patients and know within a few months whether it is working; but if we are looking all the way to the bottom line (how many people taking this new treatment are dying of heart disease?) \u00a0then the study must involve large numbers of subjects, followed over many years.<\/p>\n Almost all of what we thought we knew about saturated fats, cholesterol and CVD has been based on indirect inference. \u00a0We may have to start over, using the more costly and rigorous approach based on counting CV events in large numbers of people.<\/p>\n <\/p>\n <\/a>Blood Tests<\/strong><\/p>\n In the 1960s, people were tested for total cholesterol in the blood, which was certainly the wrong indicator. \u00a0So bad, in fact, that total cholesterol is inversely correlated<\/a>\u00a0<\/i><\/b>with all-cause mortality risk. \u00a0In recent decades, the standard test has been the ratio of LDL to HDL cholesterol. \u00a0These are not two different kinds of cholesterol, but rather variations in the chemistry of the droplets that transport cholesterol in the bloodstream. \u00a0Cholesterol is not water-soluble, so it is carried through the blood to all the places it is needed packaged in little droplets, \u00a0These droplets come in low-density and high-density, large and small. \u201cLDL\u201d is \u201cbad cholesterol\u201d and it refers to the low-density droplets. \u00a0\u201cHDL\u201d is \u201cgood cholesterol\u201d and it refers to the high-density droplets.<\/p>\n Just in the last few years, there is a new blood test, which is a much better indicator of risk of heart disease and stroke than were LDL and HDL. It is a subset of the LDL droplets, the small ones, that are the basis of the new test. [Early article, 1997<\/a>. \u00a0large Scandinavian study, 2014<\/a>.]<\/p>\n (I don\u2019t want to say the small droplets are the culprit, or the cause of heart disease. It is still unclear whether relationship between the blood test and heart disease is a causal one. In other words, if we target therapies to reduce the scoe on the small particle test.)<\/p>\n You may want to make sure that small particle LDL is reported the next time you get a health check-up and blood test. \u00a0It is sometimes reported as LDL III, or LDL-B. \u00a0But the larger significance of this new, more accurate test is that it should make future research studies quicker and more efficient. \u00a0Assuming that causality can be established, we will have, for the first time, a way of knowing whether a preventive therapy is working without having to wait ten years and see how many people have heart attacks.<\/p>\n Stay tuned…<\/p>\n Statins<\/strong> It is probably true that statin drugs have saved millions of lives, if the alternative is defined as inaction in the face of heart risk. \u00a0It is also true that statins are the most over-prescribed medications in the Western world, that their benefits are modest and come at a cost in side-effects that can be devastating in the long run. \u00a0There are better ways to reduce cardiovascular risk, many of which have no side-effects, or side-effects that are wholly beneficial.<\/p>\n The way statins work is by impeding the synthesis of cholesterol. \u00a0This is the wrong target. \u00a0We need cholesterol. \u00a0As I explained in my last post<\/a>, cholesterol is what makes cell membranes in animals pliable. \u00a0Cholesterol is also an intermediate product that the body uses to make essential hormones. \u00a0Cholesterol is necessary for neurons in the brain. \u00a0If we artificially suppress the body\u2019s production of cholesterol, we are asking for trouble.<\/p>\n Statins also have a powerful anti-inflammatory effect, which may be the entire reason for their effectivenesss in lowering mortaliy. \u00a0There are safer antiinflammatory agents available, including fish oil and aspirin, which seem to be the easiest route to lower cardiovascular risk.<\/p>\n Statin side-effects include:<\/p>\n The first item is the most troubling. \u00a0Statin drugs increase blood sugar, and increased blood sugar signals the body to age more rapidly. \u00a0In the long run, this has got to be bad for heart disease risk, and also for all other causes of mortality. \u00a0Trading heart disease for diabetes<\/a> is not a good bargain. \u00a0Blood sugar (particularly fructose) also combines with cholesterol to create the chemical species that is most damaging. \u00a0Stephanie Seneff<\/a> explains:<\/p>\n Worse than that, once LDL particles have finally delivered their contents, they become “small dense LDL particles,” remnants that would ordinarily be returned to the liver to be broken down and recycled. But the attached sugars interfere with this process as well, so the task of breaking them down is assumed instead by macrophages in the artery wall and elsewhere in the body, through a unique scavenger operation. The macrophages are especially skilled to extract cholesterol from damaged LDL particles and insert it into HDL particles. Small dense LDL particles become trapped in the artery wall so that the macrophages can salvage and recycle their contents, and this is the basic source of atherosclerosis. HDL particles are the so-called “good cholesterol,” and the amount of cholesterol in HDL particles is the lipid metric with the strongest correlation with heart disease, where less<\/i> cholesterol is associated with increased risk. So the macrophages in the plaque are actually performing a very useful role in increasing the amount of HDL cholesterol and reducing the amount of small dense LDL.<\/p><\/blockquote>\n Perhaps the clearest message to come out of my reading is that there are better methods of lowering CV risk than statin drugs, and that people taking statin drugs should be looking for ways to replace them with measures that have beneficial<\/i><\/b> side-effects. \u00a0I divide these into two categories:<\/p>\n (1) those whose mechanism is like statins, and may lead to some of the same problems <\/i><\/strong><\/p>\n <\/p>\n (2) those that have a fundamentally different mechanism of action, and are likely to be safer<\/i><\/strong><\/p>\n <\/p>\n Congenital high cholesterol<\/strong><\/p>\n There are a number of genetic defects that can cause high LDL cholesterol. \u00a0Some can be tested, but most cannot. \u00a0The defects are relatively rare (1\/500) but have a substantial effect on life expectancy [ref<\/a>].<\/p>\n There is a particular mutation on chromosome 19 that is responsible for high levels of LDL cholesterol, and experts on both sides of the divide agree that it is associated with a significant decrease in life expectancy and should be treated. \u00a0Traditional treatment is based on extra-high doses of statins. \u00a0Alternative treatments are available that are less well-documented but show indications they may be more effective than statin treatment, with fewer long-term side-effects. \u00a0I recommend this article from Life Extension Magazine<\/a>.<\/p>\n <\/p>\n Separating saturated fats from other factors in a meat-based diet<\/strong><\/p>\n Vegetarians enjoy lower mortality rates<\/a>. \u00a0How much of this is due to lower saturated fats, how much to high fiber, how much to micronutrients from fruits and vegetables? \u00a0And how much is an artifact from the association between vegetarianism and better self-care in other areas? \u00a0In this same study<\/a> , vegetarians who ate fish had 10% lower mortality (over 6 years) than vegetarians who ate cheese and eggs. \u00a0Perhaps this is an indication that saturated fats are bad for you, and fish oil lowers inflammation as well as blood cholesterol. \u00a0This study<\/a> suggests that the difference may be more about benefits of fish than of hazzards of eating eggs and dairy.<\/p>\n (This is the last paradox, I promise!) I began by noting that the correlation between saturated fat in the diet and cardiovascular risk is weak or non-existant [ref<\/a>]. \u00a0But we know that saturated fat intake is highly-correlated with animal foods in the diet, and animal products lead to higher overall mortality. \u00a0This suggests that it is something else<\/i><\/b> about the plant-based diet, besides low sat-fat, that is giving the benefit.<\/p>\n <\/p>\n
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