Faulty Arguements in Assigning Cholesterol as a Cause of Heart Disease
In reviewing the book “Good Calories, Bad Calories” by Gary Taubes I found pages 62-64,which follow immediately below this discussion, very interesting and worthwhile to think about further and discuss. On these pages Taubes discusses how little one might benefit by lowering cholesterol.
In reviewing the book “Good Calories, Bad Calories” by Gary Taubes I found pages 62-64,which follow immediately below this discussion, very interesting and worthwhile to think about further and discuss. On these pages Taubes discusses how little one might benefit by lowering cholesterol.
The first graph on page 63 shows the heart-disease mortality and serum cholesterol level for men ages 35 to 57[Stamler et al.]. I assume that this population includes people who have had a pre-study heart attack along with people who have not had a heart attack. This curve is often shown by statin proponents except it is usually shown in terms of relative risk, which makes the results seem more impressive.
The first graph can be used to argue that decreasing the cholesterol level can reduce heart disease mortality rates. The assumption is implicitly made that cholesterol is causing heart disease. Down to a certain minimum, the lower the cholesterol levels the better. Thus, one might use a drug to optimally lower the cholesterol level.
By agreeing to frame the discussion this way, Gary Taubes loses an opportunity to emphasize that the high cholesterol levels do not necessarily directly cause heart disease. Rather, high cholesterol levels are positively correlated with age, obesity, high triglyceride levels, increased stress, infection, high blood pressure, raised clotting factors, and increased visceral fat mass. These conditions may exist singly, partially or altogether with high cholesterol levels and are all risk factors, even without the accompaniment of a high cholesterol level. If a drug is given to lower cholesterol, the other risk factors remain unless the drug also lowers the presence of another risk factor. In fact, statins do lower the clotting factor levels. Thus, one cannot make the statement that by lowering the cholesterol level with a statin, heart disease mortality is lowered only by lowering the cholesterol level.
The next graph on page 64 shows total mortality as a function of serum cholesterol. Here it appears that from serum levels of 170 to 260 there is very little difference and the wiggles in the curve only give an idea of the accuracy of the data. As discussed before, the graph presents results for men between 35 and 57 years of age. However, from the Framingham study[Anderson et al] it is shown that the risk is almost independent of the cholesterol level for those men over 47 years old. The risk as a function of cholesterol level would be almost constant and the graph curve would appear as nearly a horizontal line going out to the right. For elderly women the line to the right would be downward sloping [Simon LA et al.]. In other words elderly apparently healthy people would receive no net benefits by only lowering their cholesterol levels.
Above 200, experts recommend statins. According to this graph this recommendation would appear unwarranted and, perhaps, motivated again by greed. In fact, if the cutoff were below 260, one could say the recommendation was unwarranted. Here again, Gary Taubes agrees to frame the argument in terms of how much mortality would be reduced by lowering cholesterol by diet, etc. Again, this argument is not valid because cholesterol levels are interwoven with and sometimes is a function of other risk factors. If the cholesterol were lowered by some method that did not reduce any other risk factor, the mortality rate might even go up. Suppose that one had a chronic infection and this might also raise the cholesterol level. Because cholesterol is involved in fighting infections, lowering the cholesterol level may result in one becoming more vulnerable to the infection.
Above 200, experts recommend statins. According to this graph this recommendation would appear unwarranted and, perhaps, motivated again by greed. In fact, if the cutoff were below 260, one could say the recommendation was unwarranted. Here again, Gary Taubes agrees to frame the argument in terms of how much mortality would be reduced by lowering cholesterol by diet, etc. Again, this argument is not valid because cholesterol levels are interwoven with and sometimes is a function of other risk factors. If the cholesterol were lowered by some method that did not reduce any other risk factor, the mortality rate might even go up. Suppose that one had a chronic infection and this might also raise the cholesterol level. Because cholesterol is involved in fighting infections, lowering the cholesterol level may result in one becoming more vulnerable to the infection.
It may be asked why cholesterol levels rise with the other risk factors, for instance, infection and stress, etc. At least part of the answer, without going into a detailed description of mechanisms (even if I could), has to do with the maintenance of homeostasis. Homeostasis is involved in regulation of levels for cholesterol, temperature and glucose, to name a few of almost innumerable levels. The most obvious manifestation of of homeostasis acting on cholesterol is the relative invariance of cholesterol levels with choice of diet. The level of cholesterol is very insensitive to the dietary intake of cholesterol.
Levels other than cholesterol are often altered by external stimuli such as, for instance, infection. The infection will cause the body temperature to rise in order to fight the infection. A raised temperature becomes the optimal temperature for increased chance of survival. Likewise infection will cause the cholesterol level to rise to enhance the immune response for increased chance of survival. Another example is stress, which causes increased production of cortisol and in turn increased production of cholesterol. This reaction, among others, initially prepares one for fight or flight.
Statins (Lipitor, etc.) are a class of drugs that lower cholesterol levels. Ingestion of statins may interfere with homeostasis although the use of statins may be desirable in some very limited cases, such as might occur for some atherosclerotic conditions. Even though the statin may undesirably lower the levels of cholesterol, COQ10, dolichol,.and pyrroloquinoline quinone (PPQ) [Graveline, D.], it also lowers the clotting factor levels in the blood. The possibly detrimental effect of lowering these other levels may, for people who have coronary heart disease, sometimes be outweighed by the positive effect on the clotting factor levels in the blood. However, when one has coronary heart disease with congestive heart failure the case for prescribing statins is weakened by the deleterious effect of lowering the COQ10 level, which is involved with the mitochondria activity that is needed to furnish fuel for the heart muscle.
The argument for statins to treat high cholesterol levels is somewhat analogous to that for using Tylenol to treat a fever. When infection occurs, the body temperature is raised in order to more efficiently fight the infection. However, when the body temperature goes above a maximum value, Tylenol may be needed to forestall convulsions, etc.. Likewise when the cortisol levels are high, which causes the clotting factors to rise along with cholesterol levels, statins may be prescribed to lower the clotting factors to forestall CHD from worsening even though the rise in cholesterol level may have a beneficial effect.
Below is Taubes text.
Levels other than cholesterol are often altered by external stimuli such as, for instance, infection. The infection will cause the body temperature to rise in order to fight the infection. A raised temperature becomes the optimal temperature for increased chance of survival. Likewise infection will cause the cholesterol level to rise to enhance the immune response for increased chance of survival. Another example is stress, which causes increased production of cortisol and in turn increased production of cholesterol. This reaction, among others, initially prepares one for fight or flight.
Statins (Lipitor, etc.) are a class of drugs that lower cholesterol levels. Ingestion of statins may interfere with homeostasis although the use of statins may be desirable in some very limited cases, such as might occur for some atherosclerotic conditions. Even though the statin may undesirably lower the levels of cholesterol, COQ10, dolichol,.and pyrroloquinoline quinone (PPQ) [Graveline, D.], it also lowers the clotting factor levels in the blood. The possibly detrimental effect of lowering these other levels may, for people who have coronary heart disease, sometimes be outweighed by the positive effect on the clotting factor levels in the blood. However, when one has coronary heart disease with congestive heart failure the case for prescribing statins is weakened by the deleterious effect of lowering the COQ10 level, which is involved with the mitochondria activity that is needed to furnish fuel for the heart muscle.
The argument for statins to treat high cholesterol levels is somewhat analogous to that for using Tylenol to treat a fever. When infection occurs, the body temperature is raised in order to more efficiently fight the infection. However, when the body temperature goes above a maximum value, Tylenol may be needed to forestall convulsions, etc.. Likewise when the cortisol levels are high, which causes the clotting factors to rise along with cholesterol levels, statins may be prescribed to lower the clotting factors to forestall CHD from worsening even though the rise in cholesterol level may have a beneficial effect.
Below is Taubes text.
Page 62 THE FAT-CHOLESTEROL HYPOTHESIS
One striking fact about this evolution is that the low-fat diets now being recommended for the entire nation had only been tested twice, as I've said, once in Hungary and once in Britain, and in only a few hundred middle- aged men who had already suffered heart attacks. The results of those trials had been contradictory. The diets tested since then had been exclusively cholesterol-lowering diets that replaced saturated fats with unsaturated fats.
The rationale for lowering the total fat content of the diet to 30 percent was the tangential expectation that such a diet would help us control our weight. In 1984, the year of the NIH Consensus Conference, Robert Levy and Nancy. Ernst of the NHLBI had described the state of the science this way: "There has been some indication that a low-fat diet decreases blood cholesterol levels," they wrote. "There is no conclusive proof that this lowering is independent of other concomitant changes in the diet (for example, increased dietary fiber or complex carbohydrate. . . or decreased cholesterol or saturated fatty acid level).... It may be said with certainty, however, that because 1 g fat provides about 9 calories—compared to about 4 calories for 1 g of protein or carbohydrate—fat is a major source of calories in the American diet. Attempts to lose weight or maintain weight must obviously focus on the content of fat in the diet." Though this was an untested conjecture (however obvious it might seem), the official healthy diet of the nation was now a low-fat diet. A new generation of diet doctors, the most influential of whom was Dean Ornish, were even prescribing io-percent-fat diets, if not lower.
Another striking aspect of the low-fat diet recommendations is how little any individual might benefit from lowering his cholesterol.* Keys and others had argued that heart disease had to be prevented because its first symptom was often a fatal heart attack. But in twenty-four years of observation, the Framingham Heart Study had detected no relationship between cholesterol and sudden cardiac death. The likelihood of suffering a fatal first heart attack was no less for those with a cholesterol level of 18o mg/dl than for those with 250. "The lack of association between serum cholesterol level and the incidence of sudden death suggests that factors other than the atherosclerotic process may be of major importance in this manifestation of coronary artery disease," explained Thomas Dawber.
* Though women were clearly meant to adhere to the low-fat guidelines, they had not been included in any of the clinical trials. The evidence suggested that high cholesterol in women is not associated with more heart disease, as it might be in men, with the possible exception of women under fifty, in whom heart disease is exceedingly rare.
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Page 63
There is also little to gain from lowering cholesterol even in less catastrophic manifestations of the disease. This was made clear in 1986, when Stamler published a reanalysis of his MRFIT data in JAMA. As Stamler reported it, the MRFIT investigators had continued to track the health of the 362,000 middle-aged men who had originally been screened as potential candidates for MRFIT, including death certificates. Stamler reported that the cholesterol/heart-disease association applied at any level of cholesterol, and so anyone would benefit from lowering cholesterol.
Using the MRFIT data, however, it is possible to see how large or small that benefit might be (see chart, below). For every one thousand middle- aged men who had high cholesterol—between, say, 240 and 250 mg/dlight could expect to die of heart disease over any six-year period. For every housand men with cholesterol between 210 and 220, roughly six could expect to die of heart disease. These numbers suggest that reducing choesterol from, say, 250 to 220 would reduce the risk of dying from a heart attack in any six-year period from .8 percent (eight in a thousand) to .6 percent (six in a thousand). If we were to stick rigorously to a cholesterol-lowering diet for thirty years—say, from age forty to seventy, at which point
