Yogi Berra, the former New York Yankee catcher and coach is one of the most quoted sports figures of all time. One of his famous observations was, "If you don't know where you’re going, chances are you’ll end up somewhere else." It’s a rather astute observation – one that physicians should note.

An individual recently sent me an update on his condition, which can be summarized as follows: “When I went to the cardiologist in October my cholesterol was 192 and I was started on Crestor. I just saw the lipid clinic nurse, who was extremely pleased with my progress. My total cholesterol is down to 102, my HDL cholesterol has dropped from 29 to 15, and my triglycerides have fallen from 162 to 59! Oh, by the way, I’ve developed some weakness in my legs.”

While the nurse at the lipid clinic was pleased with the findings, I was dismayed. She and her physician employer are prime examples of people who do not know where they are going. They cannot, in the words of the old adage, see the forest for the trees. They have become so engaged in driving cholesterol to the lowest achievable level that they have lost sight of the primary goal of health care, which is to keep individuals functioning at the highest level possible for as long as possible. The health of the person in question is declining as a result of their intervention. His leg weakness is a sign that the low cholesterol is adversely affecting muscles throughout his body. He is at risk of dying if the condition progresses.

These and others obsessed with lowering cholesterol have accepted the hypothesis that cholesterol is harmful as fact. In reality, the “cholesterol is harmful” hypothesis is not only unproven, it is now possible to state with certainty that it is false.

The “cholesterol is harmful” hypothesis is but one of several theories that have been advanced over the past 200 years to explain the phenomenon of atherosclerosis (hardening of the arteries). The story of how our understanding of atherosclerosis and coronary heart disease develop is interesting. Current research suggests that a theory first advanced in 1815 may be correct, but it is receiving as little attention today as it did 200 years ago.

The first recorded mention of atherosclerosis is in the writings of Huang Ti, the Yellow Emperor of China in approximately 2650 BC. Huang Ti recorded a “hardened pulse” and suggested that it was associated with a high salt intake.

Hippocrates, considered the Father of Medicine, suggested in about 400 BC that illness was the result of an imbalance of four bodily humours. These he called yellow bile, black bile, blood, and phlegm. It could be argued that the “cholesterol is harmful” hypothesis is an argument that heart attacks arise from an excess of yellow bile, as cholesterol means “solid bile”.

No significant progress was made over the next 2000 years. Around 1500 A.D. Leonardo da Vinci described what we now refer to as atherosclerosis. He stated that blood vessels in the elderly restrict the transit of blood due to thickening of their walls, which he referred to as “tunics”.

The first to specifically advance the “cholesterol is harmful” hypothesis was an English physician, William Heberden, who did so in 1772. He reported that the blood serum of an obese patient who experienced a sudden death was thick like cream.

Coronary artery hardening was first described by another English physician, Caleb Hiller who, in 1799, found a gritty substance in coronary arteries while doing an autopsy. His first impression was that some plaster had fallen from the ceiling, but upon closer investigation he discovered that the plaster-like substance was within the arteries themselves.

In 1815 a London surgeon, Joseph Hodgson, advanced a novel theory of atherosclerosis. Hodgson suggested that inflammation was the underlying cause of the disease rather that a natural part of the aging process. In that same year, however, cholesterol was discovered by a French researcher and Hodgson’s theory was largely ignored.

It was in 1841 that Carl Von Rokitansk, one of the first pathologists, proposed that the deposits he observed in the inner layer of arteries were derived from substances circulating in the blood. The primary component of arterial plaque was shown to be cholesterol just two years later.

The “cholesterol is harmful” hypothesis was advanced in 1949 by J. W. Gofman, an American physician who was researching fats in the bloodstream. He and his team suggested that LDL cholesterol was the cause of atherosclerotic plaque. The hypothesis gained additional support when autopsies of young soldiers killed in the Korean War revealed that 77.3 % had cholesterol deposits in their coronary arteries.

Spurred by the observation that the death rate from heart attacks dropped in areas where the food supply was low during World War II, a University of Minnesota researcher, Dr. Ansel Keys, conducted studies on dietary fat and heart disease beginning in the 1950s. As a result of his studies Dr. Keys became an advocate of what is now known as the Mediterranean Diet, a diet high in vegetable oils and low in saturated fat.

Dr. Keys’ findings were eagerly endorsed by “cholesterol is harmful” advocates, but he himself did not state that cholesterol was the direct cause of heart disease or atherosclerosis. He pointed out that just because cholesterol is present in arterial plaque does not mean that cholesterol is the cause of arterial plaque.

The “cholesterol is harmful” train had left the station, however, and nearly all dieticians, physicians, and medical researchers ran to jump on the bandwagon. The movement steadily picked up momentum during the 1960s and 1970s. By the time an alternative theory was advanced in the late 1980s hardly anyone was willing to listen.

Despite its popularity, the “cholesterol is harmful” theory remains unproven. After tens of thousands of studies and billions of dollars invested in research, the best answer advocates can give to the question, “Is lowering cholesterol beneficial?” remains, “We think so.” Conclusive proof does not exist. While lowering cholesterol has been shown to decrease the number of deaths from heart attacks in some age groups, evidence that lowering cholesterol increases longevity and prolongs vitality is lacking.

Since fifty years of pursuing the “cholesterol is harmful” hypothesis has produced few tangible results perhaps it is time to ask, “Is lowering cholesterol harmful, and, if so, do the risks involved outweigh the observed benefit?” Does having the technology to cut cholesterol levels in half mean that an individual’s cholesterol should be lowered from 192 to 102 or, for that matter, from 280 to 180?

It has been nearly forty years since Atromid-S, the first drug approved for the lowering of cholesterol, appeared in the United States. Released in 1967, it was withdrawn from the market in 2000. While the drug was never proven to decrease the risk of heart attacks or shown to lower the mortality rate, it was found to increase the incidence of gallstones, cancer, liver disease, and a severe inflammation of the pancreas called pancreatitis. Individuals who took the drug reported nausea, diarrhea, loss of sexual ability, headache, weakness, abdominal pain, muscle pain, and other side effects. Some died of a severe muscle disease called rhabdomyolysis.

Currently available cholesterol-lowering drugs are promoted as safer and more effective, but most studies have failed to demonstrate a decrease in the death rate in those taking them and the risks and side-effects appear to be similar to those seen with earlier medications.

I entered medical school in an age when total cholesterols of 250 mg/dL or even 300 mg/dL were considered to be within the normal range. As drug therapy to reduce cholesterol became available the “normal” levels were dropped to 240 mg/dL or less and then to 220 mg/dL.

When treatment failed to demonstrate the anticipated benefits, researchers refused to abandon the “cholesterol is harmful” hypothesis. Instead, they directed their efforts at finding ways to lower cholesterol more effectively. As the ability to drive cholesterol to previously unobtainable levels was achieved, “ideal” values were lowered to promote the use of the new technology.

The National Cholesterol Education Program’s expert panel, heavily weighted by individuals with ties to the pharmaceutical industry, currently recommends that TC be less than 200 mg/dL, and than low-density lipoprotein cholesterol (LDL) be less than 100 mg/dL. In an attempt to reduce the LDL to the 100 mg/dL level, many physicians today are seeking to lower total cholesterol to less than 160 mg/dL.

When confronted with a disease, physicians innately want to do something. Just because it is possible to do something, however, does not mean that one should do something.

Qualifying speeds for IndyCars routinely exceed 200 miles per hour. Therefore it is possible to manufacture cars capable of traveling at 200 mph and raise the speed limits on our highways accordingly.

Raising the speed limit to 200 mph and mass producing vehicles capable of traveling at that speed should enable travelers to reach their destinations in less time, which would be a good thing. On the other hand, injuries and fatalities from motor vehicle accidents would almost certainly increase, which would be a bad thing. Before increasing the speed limit to accommodate the available technology officials asked, “Does the benefit of reaching one’s destination more quickly outweigh the risks involved in doing so?” They determined that it did not.

Before lowering the acceptable levels (the “speed limit”) of cholesterol it would have been wise to ask, “Does the benefit of lowering one’s cholesterol outweigh the risks involved in doing so?”

The answer, I believe, is a resounding NO! A number of epidemiologic studies (analyses of the characteristics of groups of people) have demonstrated that the cholesterol-lowering benefits are seen primarily in men under the age of fifty who have other risk factors for having a heart attack. When those risk factors, such as cigarette smoking, high blood pressure, and inactivity, are addressed a much greater reduction in heart attacks is seen than when cholesterol-lowering is the focus of prevention.

While some studies purportedly do so, it is very difficult to demonstrate a cholesterol-lowering benefit in women and in either sex over the age of fifty. Rather than showing that high cholesterol levels are dangerous in people over sixty, studies have repeatedly found that senior citizens with high cholesterol levels tend to live longer than their peers with low cholesterol values. You didn’t misread the last sentence. As a group, elderly people with high amounts of cholesterol outlive those with low levels of cholesterol.

Unfortunately, physicians have been taught for the past four decades that cholesterol is dangerous and that it must be lowered at all costs. The “cholesterol is harmful” hypothesis, although never proven, has come to be accepted as fact by physicians and patients alike. Any suggestion that cholesterol is beneficial and not harmful tends to fall upon deaf ears. Those who will listen, however, should carefully weigh the benefits and risks before taking measures to lower their body cholesterol.

In an article entitled Needs to Change the Direction of Cholesterol-Related Medication – A Problem of Great Urgency, published in November 2005, Japanese researcher H. Okuyama reported his findings based upon the data available in the medical literature. He concluded, “ . . . reducing the intake of saturated fatty acids and cholesterol and increasing that of polyunsaturated fatty acid are ineffective in reducing total cholesterol in the long run, but rather increase mortality rates from coronary heart disease and all causes . . . high total cholesterol is not positively associated with high coronary heart disease mortality rates among general populations more than 40-50 years of age. More importantly, higher total cholesterol values are associated with lower cancer and all-cause mortality rates among these populations . . . Although the effectiveness of statins in preventing coronary heart disease has been accepted in Western countries, little benefit seems to result from efforts to limit dietary cholesterol intake or to lower TC values to less than approximately 260 mg/dl among the general population and the elderly . . . (These measures) create major risk factors for CHD, cancers, and shorter longevity. Based on the data reviewed here, it is urgent to change the direction of current cholesterol-related medication for the prevention of CHD, cancer, and all-cause mortality.”

Okuyama concludes, on the basis of an exhaustive review of the available data:

• High cholesterol levels are not associated with heart attacks in people over 40 to 50 years of age
• High cholesterol levels are associated with lower cancer and premature death rates
• There is little benefit in lowering cholesterol levels below 260 mg/dL in older people
• Efforts to lower cholesterol increase the risk of developing cancer and shorten life span

He believes that changing the current practice of lowering cholesterol levels is a matter of the utmost urgency. His pleas will almost certainly be ignored, as he is not the first to sound the alarm.

A 1993 analysis of the cholesterol-lowering data available at that time reached the same conclusion. Because of the increased rate of death from causes other than heart disease in people taking cholesterol-lowering drugs the researchers concluded

• Cholesterol-lowering drugs lower the overall mortality rate in only a small subset of people who are at extremely high risk of death from CHD
• Cholesterol screening tests are a waste of money
• Lowering cholesterol in the vast majority of people is harmful, not helpful
• Cholesterol-lowering drugs should be used cautiously, if at all

That same year an analysis of the results of the Honolulu Heart Program revealed a sharp increase in death rates from hemorrhagic stroke, cancer, liver disease, chronic obstructive lung disease (emphysema), and deaths from unknown causes when cholesterol levels dropped below 190 mg./dL. The investigators theorized that lowering cholesterol would not have any substantial impact on total mortality over fifteen years because premature deaths would increase in those individuals with starting cholesterol levels less than 225 mg./dL (approximately 60 % of the population).

One of the largest investigations of all-cause mortality and cholesterol involved nearly half a million Korean men between the ages of 30 and 65. Reported in 2000, the study found that the lowest death rates corresponded to cholesterol levels between 211 and 251 mg./dL., well above currently recommended treatment goals.

Another large study, which looked at nearly 150,000 men and women, was published in 2004. This report, Why Eve is not Adam, concluded that while high cholesterol levels predicted risk of death from heart disease in men of all ages and women under the age of 50, low cholesterol in men of all ages and women over the age of 50 was associated with deaths from cancer, liver disease, and mental diseases.

When confronted with the data that demonstrates the dangers of lowering cholesterol, “Cholesterol is Harmful” advocates are quick to point to the 10 year follow-up of individuals who participated in what is known as the Scandinavian Simvastatin Survival Study, commonly referred to as the 4S study. The 4S study compared a group of individuals who received a cholesterol-lowering drug, simvastatin, with a control group who did not. The follow-up study, Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S), compared the incidence of cancer in the two groups over the ten year period following the conclusion of the original study in 1994. The researchers did not find any difference in cancer incidence between the two groups.

There is a dirty little secret behind the 4S follow-up study, however. Advocates of the extensive use of cholesterol-lowering statin drugs would like people to believe that the study demonstrates that the practice is safe – that there is no difference in the risk of developing cancer whether one is taking the drug or not. This is not the case. What the proponents of statin use do not state is that after the completion of the original study in 1994, most of the patients in both groups were placed on cholesterol-lowering drugs. Therefore, the 4S follow-up study compared people on the drugs with people on the drugs! How could there possibly be a difference in the incidence of cancer and other diseases commonly associated with low cholesterol levels?

Okuyama is correct in stating that there is an urgent need to reconsider the current practice of aggressively lowering cholesterol levels. Cholesterol-lowering drugs seem to reduce the risk of premature death in only a small group of individuals who are at very high risk of death from coronary heart disease. Lowering cholesterol appears to increase the risk of premature death in at least sixty percent of individuals. In the remainder of the population, the net effect of aggressively lowering cholesterol is zero, with the increase in non-cardiac deaths equaling the decrease in deaths from heart disease.