Aside from the indication that it is beneficial to replace saturated fat with unsaturated fat, the cohort and intervention studies fail to provide much guidance. It is instructive to turn to the relationship between fat consumption and serum (blood) cholesterol levels. It appears to be an uncontested fact that the consumption of saturated fat increases the levels of low-density lipoprotein (LDL) cholesterol, which is regarded as the bad lipoprotein. However, life is never simple, since saturated fat also increases the high- density lipoprotein (HDL) cholesterol fraction as well, and HDL is considered very beneficial. The extent to which this results in a draw, so to speak, is not clear, but the conventional wisdom ignores the increase in HDL, focuses on the increase in LDL, and thus concludes that saturated fat as bad. However, if an individual had a normal level of LDL and a low level of HDL, raising the HDL might on balance be beneficial even if the LDL level also went up. The percentage decrease in risk is 3% for every 1% increase in HDL, whereas there is only a 1% increase in risk for each 1% increase in LDL (8). The changes in both LDL and HDL with the ingestion of saturated fat will depend on the nature of the fat, that is, the actual saturated fats involved, and as well, will depend on the individual, since there is considerable variation. Perhaps it is because of the combination of good and bad effects of saturated fats, coupled with individual variation, that the studies discussed above provided no definitive guidance as to the question of saturated fat increasing the risk of CHD, but only inconsistent findings.

Both monounsaturated fats (olive oil is high in monounsaturates) and polyunsaturated fats turn out to be beneficial in the context of cholesterol levels. They raise HDL and lower LDL. The interplay between diet and HDL, LDL, total cholesterol, and the other important blood lipids, the triglycerides, merits further discussion, not only since it relates the "bad" label attached to saturated fat and the "good" label associated with the mono- and polyunsaturates, but also because it relates to the question of high vs. low fat diets which can modify these blood lipid levels.

Studies far too numerous to list have established, probably beyond reasonable doubt, that high levels of total cholesterol and LDL cholesterol present a risk for the development of CHD. Since LDL cholesterol represents typically more than 50% of the total cholesterol, this total is considered a surrogate for LDL. Thus the studies that measured only total cholesterol remain valid today and are part of the case for high serum cholesterol being a risk factor. Four quite different and more or less independent approaches to lowering both total cholesterol and LDL produce reduced risk of CHD (surgery, sequesterant drugs, statin drugs and diet). This is one of the cornerstones of the argument that LDL is bad and that lowering it represents a beneficial intervention. There is also considerable literature indicating that low HDL carries added risk for CHD and that raising HDL decreases the risk (9-12).

However, there are some disturbing aspects to this picture. In fact, Ravnskov (4,7) and a few others have been very vocal critics of the hypothesis connecting cholesterol, fat and CHD, but their views are perhaps a bit extreme. Nevertheless, as any doctor involved with heart patients will tell you, something like 50% of all heart attacks occur in individuals who have a normal blood lipid profile, i.e. LDL is not elevated and HDL is not low. In addition, there is frequently no correlation between the extent of LDL lowering and the decrease in risk, and the decrease in risk in some studies is independent of the level of risk in the subjects studied (13,14). This latter phenomenon is also seen in the diet intervention studies, as discussed above. In addition, a significant decrease in CHD risk is found by lowering LDL in individuals that are already at low risk as judged by their blood lipid profile (15,16).

It does not help that the details of the mechanism of the adverse action of LDL is poorly understood, as is the overall mechanism of the formation of atherosclerotic plaques, from their beginnings as fatty streaks in arteries to large, unstable plaques, the rupture of which is thought to be related to heart attacks. In fact, the conventional wisdom that atherosclerosis is caused by high cholesterol has recently been challenged by Ravnskov in the Quarterly Journal of Medicine. He documents the following points (17):

• Serum cholesterol does not predict the degree of atherosclerosis at autopsy.
• Serum cholesterol does not correlate with the degree of coronary atherosclerosis on angiography.
• Serum cholesterol does not correlate with the degree of coronary calcification.
• Serum cholesterol does not correlate with the degree of peripheral atherosclerosis.
• Changes in serum cholesterol concentrations are not followed by parallel changes in atherosclerosis growth--i.e. there is no exposure response.

Thus an important question: why does high cholesterol predict cardiovascular disease if LDL levels and changes in LDL do not correlate with the degree of atherosclerosis or with atherosclerosis growth? As Ravnskov points out, there can be many reasons for these observations. One is that high LDL or total cholesterol may be secondary to other factors that promote cardiovascular disease (17). On-going research will no doubt eventually produce a more satisfactory picture.

It seems clear that LDL is bad cholesterol and HDL is good cholesterol. Saturated fat consumption raises both and might be viewed as neutral. Eating mono- or polyunsaturated fat decreases LDL and raises HDL. From this one might conclude that it is pointless to worry about fat. However, to not worry about fat at all would be to ignore the apparently beneficial effects of the unsaturated fats and the studies that demonstrated a significant decrease in the risk of CHD when saturated fat is replaced with unsaturated fat-- a benefit that does not appear to prove that the reduction of saturated fat was indeed beneficial, but that merely the combined action has merit. In this context, it is important to understand that if one merely increases the consumption of unsaturated fat and does not decrease the saturated component, there may be a risk of adversely disturbing the energy balance with an associated weight gain, unless other macronutrients such as protein or carbohydrate are decreased.

LOW-FAT DIETS

Once the "fat is bad" religion was firmly established and supported by the US government, the medical profession, the nutritionist community, the media, and, with great enthusiasm, the food industry, the so- called low-fat or very low-fat diet was a natural result. Since most people tend to maintain a certain level of caloric intake, low fat in fact meant a dietary change that involved replacing fat with carbohydrate. Protein in general was not viewed as a candidate since most common protein sources contained lots of fat. Carbohydrate has roughly half the calories per gram as compared to fat (4 vs. 9 kcal/gram), so the low fat diet was also a high carbohydrate diet, and this was embraced by millions as the path to health and longevity. Lack of knowledge among the general public as to the various types of carbohydrates and their relative effects on blood glucose, insulin, and the development of insulin resistance led to the indiscriminate consumption of increased amounts of carbohydrates, in many cases carbohydrates from sources such as potatoes, white rice, ordinary pasta, white bread, bagels, baked goods, sugar-rich deserts, non-diet soft drinks and juices, etc. Much of the carbohydrate that replaced fat was of the type that was rapidly digested to yield large increases in post-meal (called postprandial) blood glucose and insulin, which frequently leads to insulin resistance and eventually the so-called metabolic syndrome or Syndrome-X (18). Carbohydrate not needed for energy was turned into fat and stored--something the general public was probably not aware of, since the "fat is bad" religion did not include information on the metabolism of carbohydrates. The notion that eating fat made one fat, and avoiding fat therefore would result in weight stability or weight loss, was part of the conventional wisdom of the masses.

The replacement of fat with carbohydrate has been studied a great deal since the "fat is bad" religion became commonplace. In many individuals, such a change in diet results in a significant decrease in serum HDL, an equally significant increase in serum triglycerides, and eventually the development of insulin resistance, where the body requires larger and larger amounts of insulin to manage the load of serum glucose that arises from the heavy carbohydrate component of the diet. Insulin resistance frequently leads to type 2 diabetes, which in turn results in a whole host of serious health problems and a well documented huge increase in the risk of heart disease. Most diabetics in fact die of heart disease. The above-described changes in HDL and triglycerides also are in the direction of increasing the risk of CHD. It actually turns out to be difficult to separate the effects on CHD risk of high triglycerides and low HDL, since these two conditions frequently occur together, but there are studies that indicate that high triglycerides can be viewed as an independent risk factor (19). Suffice to say that there are a number of studies in the recent literature that indicate a very high level of increased risk when HDL is low and triglycerides are high (9-12). Interestingly enough, men with conventional risk factors for CHD actually have low risk if they have low triglycerides and high HDL (11). Some investigators think that in fact low HDL and high triglycerides can present a greater risk than either high total cholesterol or high LDL (8). In some individuals, low HDL and high triglycerides are accompanied by a change to smaller LDL particles. There is considerable evidence that these are more dangerous in the context of heart disease than large, less dense LDL particles (20). In fact, this is one of the frequently encountered arguments against the low-fat high-carbohydrate diet. However, not all studies find that CHD risk higher when the serum concentration of small, dense LDL particles predominates (21).

ESSENTIAL FATTY ACIDS

By restricting fat consumption, there also arises the risk of a deficiency in the essential fatty acids, which are critical to health. The omega-3 and omega-6 (n-3 and n-6) polyunsaturated fatty acids require a more detailed discussion. They are critically important because they are involved in the production of what are called eicosanoids, which are transient hormones that play key roles in human biochemistry. There are a large number of different eicosanoids, and a detailed discussion (22) is beyond the scope of this review. Suffice to say that the subject can be simplified by thinking in terms of two classes of eicosanoids, which are frequently called "good" and "bad" although this simple pair of labels conceals the fact that good and bad eicosanoids are both necessary. It is thus not a matter of minimizing the bad and maximizing the good, but of keeping the two classes in balance. How they complement one another can be seen from the following table:

These lists are far from complete but nevertheless illustrate the complimentary nature of the two classes as well as the central role they play in essential biochemical processes. The connection with cardiovascular disease is also evident. The relationship between the n-3 and n-6 polyunsaturated fatty acids and the eicosanoids is that the n-3 fats are involved in the production and regulation of the good eicosanoids whereas the n-6 fats come into play with the bad eicosanoids. Since balance is the name of the game, it is important not only to get enough of each type of fat, but also to get them in roughly the correct proportion for optimum functioning of all the systems that depend on eicosanoids and the hormones derived from them. One school of thought on this subject maintains that the n-3 to n-6 ratio should by around 1:2 to 1:4. There is some evidence that our genetic makeup evolved on a diet that had a ratio in this range (23). While the optimum ratio is debatable (24), what is clear is that the typical Western diet is very heavy in the n-6 fats and very light in the n-3s. This is due to the high consumption of vegetable oils that are rich in n-6 fatty acids and the low consumption of fish, nuts, and the oils that are rich in n-3s. There is a great deal of literature on the beneficial effects of increasing the intake of n-3 fats, and most of this is in the context of cardiovascular disease. The typical Western diet has been estimated to have an n-3 to n-6 ratio of 1 to 20. Thus there seems to be little risk associated with dietary modifications that reduce n-6 consumption, and there appears to be considerable room to increase the n-3 content of diets, a move that should prove beneficial.

An interesting twist to the n-3 story is that the parent acid, alpha-linolenic acid, is converted with variable efficiency in humans into two critically important n-3 fatty acids, EPA and DHA. Fish, however, are rich in these two n-3 fats, and they can be found in concentrated form in fish oil. There are dozens of studies that have shown that n-3 fatty acids from fish and other sources are active in preventing heart attacks and sudden cardiac deaths by preventing erratic heart rhythms, reducing the tendency of blood to clot inside arteries (a cause of heart attacks), improving the blood lipid profile (total cholesterol, HDL, LDL, and triglycerides), and favorably influencing inflammation which is thought to play an important role in the development of atherosclerosis (plaque formation). By far the strongest connection between the n-3 fatty acids and heart disease is the reduction of sudden deaths, presumably because of the strong anti- arrhythmic effects of these fats (25). This is very important since for a significant number of victims, sudden death is the first indication of heart disease. It is clear from the above that by reducing the dietary fat content to a very low value, there is a significant danger of insufficient n-3 essential fatty acids and of having a very high ratio of n-6 to n-3, because what fat there is in the low-fat diet will generally be rich in the omega-6 fats.

In the above discussion of the connection between dietary fat and CHD, one study was mentioned that produced an astounding 73% reduction in risk of a second adverse coronary event as compared to the control group in patients who had already experienced one heart attack. The dietary approach in this study was to switch the treated group to a Mediterranean style diet and to add supplementary alpha-linolenic acid in the form of an enriched margarine (free of trans-fats) thus increasing the n-3 content of the diet. This study, known as the "Lyon Diet Heart Study" underscores the importance of the n-3 essential fatty acids in connection with heart disease (26,27).

In summary, many experts in nutrition, who base their views and recommendations on the recent literature, are suggesting that the popular movement to replace fat with carbohydrate was in fact a serious mistake in the context of public health, that the recommendation in fact has no basis in valid scientific studies, and that the general public would be well advised to instead replace some saturated fat with unsaturated fat and limit the consumption of rapidly digested (high glycemic index) foods (24). The consumption of the right mix of fat, protein and slowly digested carbohydrates such as are found in many vegetables, as well as low- glycemic index fruits, is recommended as a prudent approach to a diet that is more in tune with current knowledge regarding the prevention of CHD than the low-fat high-carbohydrate diet.

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