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The Dangers of Low Blood Cholesterol
MORRIE BRICKMAN
We have all heard the claims that a high blood cholesterol level is harmful: it increases the risk of a heart attack. We hear and see this message in news bulletins, magazine articles, advertisements for cholesterol-lowering foods — even breakfast cereals — and drugs several times every day. But is the evidence to clear?
Cholesterol is an essential chemical in our bodies with a wide range of uses and application. Just as our body temperature is held within very fine limits for the whole of our lives, so are hundreds of other processes and chemicals. We don't need to measure and 'correct' even one of them; our bodies can and do regulate these automatically within fine limits and with great accuracy. Unlike body temperature, cholesterol rises naturally as we age and the idea that everyone, young or old, male or female, should all have exactly the same amount of cholesterol in their blood is, frankly, ridiculous.
So, isn't it conceivable that if cholesterol isn't available in sufficient quantity, that deficiency could have catastrophic effects? Or that changing our levels of cholesterol artificially might be detrimental to our health?
Low cholesterol increases overall risk of death
After all that you have heard about cholesterol, you may be surprised to learn that as you age, your chances of an early death rise if your total cholesterol falls. This disturbing finding was published in the respected Journal of the American Medical Association.[1] What it showed clearly was that after the age of 50, heart death rates increased by 14% for every 1 mg/dL (.026 mmol/L) drop in total cholesterol levels per year. The data showed that an individual whose total cholesterol levels dropped 14 mg/dL (0.364 mmol/L) during 14 years would be expected to have an 11% higher death rate than if his cholesterol level had remained the same or risen. To put this into a British context, if your cholesterol level drops from, say, 6 to a 'healthy' 5 mmol/L, your relative risk of an early death are increased by an enormous 3700%
But that isn't all: if you are already suffering from heart failure, lowering cholesterol will increase the time it takes for you to recover. In an analysis of 1,134 patients with heart disease, another recent study found that low cholesterol was associated with worse outcomes in heart failure patients and lower survival rates, while high cholesterol improved survival rates.[2] This study is interesting from another perspective as it also showed that high cholesterol among patients was not associated with high blood pressure, diabetes, or coronary heart disease.
So if you approaching or above the age of 50 and your doctor tells you that your cholesterol is high and he wants to put you on cholesterol-lowering drugs, you might like to reflect on the fact that high cholesterol is actually protective.[3]
Which all rather makes a nonsense of the 'cholesterol myth'.
High cholesterol protects against heart disease risk
Strengthening the evidence against the 'cholesterol myth' are other findings which suggest that high cholesterol levels protect against atherosclerosis, the clogging up of the coronary arteries which is thought to cause heart attacks. There is a growing amount of evidence for a hypothesis that the first step in the formation of atherosclerosis is an inflammatory response to some injury of the arterial wall caused by an infectious bacterium or virus. As we will see later in the chapter, low levels of cholesterol harm the body's immune system. Putting these two factors together suggests that a high cholesterol level would be protective against atherosclerosis. If this is true, it would explain why, although most cardiovascular diseases are seen after the age of 60, studies of the elderly find that those with high cholesterol levels have fewer heart attacks than those with low cholesterol.
Low cholesterol increases stroke risk
Stroke is defined as the sudden rupture or blockage by clotting of a blood vessel to or within the brain. Symptoms depend greatly on which blood vessel is affected. They can range from minor dizziness or momentary temporary loss of function that is barely perceptible to paralysis or death. Strokes were generally confined to the very elderly, but recently are being increasingly seen in younger people.
Asians traditionally eat a diet which is poor in animal products; they have low levels of cholesterol in their blood — and have a very high level of strokes. Japanese scientists believed that their diet could be the cause of their high stroke risk. United States scientists, on the other hand, were sceptical of the possibility, believing that there were few if any risks associated with low blood cholesterol. This difference in viewpoint was thought worthy of further investigation to resolve the question.
Medical trials are expensive. For this reason, they tend to involve only a relatively small number of people. But there can be exceptions. One such arose after World War II, when Japan's eating habits, influenced by American dietary habits, changed dramatically: from 1958 to 1995 fat consumption increased fourfold; animal protein intake increased by 22%. Most of this increase was attributable to an increased intake of meat, eggs and dairy products. At the same time, carbohydrate intake from rice went down. Not unexpectedly, cholesterol levels rose — by an average 0.57 mmol/L (22 mg/dL) in men and 0.75 mmol/L (29 mg/dL) in women. Although Japan had very low rates of heart disease before the change of diet took place, it did suffer a large death rate from strokes and cerebral haemorrhage. The change of circumstances after the war was a perfect opportunity for scientists to witness any changes in disease patterns that this change of diet would bring. They found that it brought dramatic benefits. During the period cholesterol levels rose from 3.9 mmol/l to 5.0 mmol/l;[4] and the rate of stroke of both types fell by 85 % from 1344 to 205 per 100,000 per year.[5] Investigators attributed this decline in death rates to an increase in blood cholesterol levels over the period. Here are the figures:[6]
- Stroke deaths declined by 61% for men aged 40-69
- Deaths from cerebral haemorrhage declined by 65% in men and 94% in women aged 40-69.
- Even though blood cholesterol went up, there was no increase in heart disease deaths in either sex.
The authors conclude that the benefits to health in Japan were a result of blood pressure fall and a rise in total cholesterol.
A follow study by the Institute of Community Medicine, University of Tsukuba, Japan, over a 30-year period confirmed the earlier findings. By that time, stroke deaths were down by 30% and heart disease deaths had also fallen by 20%.[7]
A later study of both men and women aged 35 to 89 years over the period 1984 to 2001 showed clearly that the really beneficial part of the Japanese diet was the animal fat and cholesterol.[8] In this study, the risk of a stroke was reduced by almost two-thirds (63%) in those who had the highest intake of animal fat and cholesterol, compared to those with the lowest. Animal protein was not significant, just the fat and cholesterol. In their conclusions, the authors say: 'This study suggests that in Japan, . . . a high consumption of animal fat and cholesterol was associated with a reduced risk of cerebral infarction death.'
The results of the trials in Japan were not confined to that country or even to Asia. In 1997, the results of a follow-up of 350,000 men screened for the Multiple Risk Factor Intervention Trial in the United States showed that the excess risk of death from cerebral haemorrhage was raised by 600% in middle-aged men with low blood cholesterol levels.[9]
Scientists at the Cardiovascular Health Research Unit, Washington University, conducted an analysis of 13 randomised controlled trials to look at the effects of lowering serum cholesterol on diseases other than CHD.[10] They found that while lowering cholesterol resulted in a slight lowering of non-fatal strokes, fatal strokes were increased by 32%, and where cholesterol was lowered by the cholesterol-lowering drug, the death rate from stroke rose by a huge 264%.
Strokes and cerebral haemorrhages normally affect the elderly. Because these are rare in younger people, there has been little research done at these lower ages. However, cerebral haemorrhages are now affecting people younger than 40. Doctors at the Stroke Clinic, Instituto Nacional de Neurologia y Neurocirugia, Mexico City, looked into this new phenomenon.[11] They found a number of 'risk factors' including smoking, drinking alcohol and raised blood pressure. You might expect that high blood pressure posed the most risk, but no, that only accounted for 13%. The highest risk, at 35%, was low blood cholesterol levels.
The connection between low cholesterol levels and haemorrhagic stroke cannot be dismissed.
Low cholesterol increases ischaemic stroke risk
There is no doubt the risk of haemorrhagic stroke is increased by low cholesterol levels, but that still leaves the ischaemic stroke. Although the effect is similar to a haemorrhagic stroke, the cause is different. Instead of a blood vessel leaking in the skull, in this case, an artery is blocked by a clot. For the same reason that heart attacks are blamed on cholesterol blocking coronary arteries, so are ischaemic strokes blamed on a fatty diet. But this theory, that eating too much fat or the wrong type of fat increases the risk of a stroke, also seems to have no foundation.
In 1997, we got a Christmas present from the long-running Framingham study. On Christmas Eve of that year, the Journal of the American Medical Association (JAMA) published a study on fats and stroke risk.[12] It found that for every 3% more calories from fat, stroke risk went down by 15%.
Confirmation came six years later in another study. This time, scientists at the Department of Nutrition, Harvard School of Public Health, studied 43,732 men aged 40-75 years who were free from cardiovascular diseases and diabetes in 1986 and followed them for 14 years.[13] During that period they studied intakes of every conceivable type of fat — animal fat, fish oil, vegetable oil, saturated, mono-unsaturated, polyunsaturated, trans fat — as well as the amounts of each that were consumed. They found that none of them made any difference whatever to the likelihood of a stroke and say in their conclusions 'These findings do not support associations between intake of total fat, cholesterol, or specific types of fat and risk of stroke in men.'
Low cholesterol increases cancer risk
Countries with diets high in saturated fats also tend to have high levels of colon cancer. In 1974 a review of the Framingham data and those from Keys' 'Seven Countries' study was expected to show that the cancer could also be blamed on high blood cholesterol. However, the baffled researchers found the opposite; those with the cancer had cholesterol levels which were lower than average. In 1989, the Renfrew and Paisley Survey, which was studying the lowering of cholesterol levels to prevent heart disease, found the numbers of cancers rose as cholesterol levels fell, such that any reduction in heart deaths was more than offset by an increase in cancers, mainly lung cancer.[14] This was also the case in the World Health Organisation's Cooperative Trial of the cholesterol-lowering drug, clofibrate, which was published in the same year.
We should remember that cholesterol is a vital building block in cell membranes; it is essential for their integrity and stability. It is not, as seems to be suggested, an alien substance that must be reduced at all costs. Professor Michael Oliver pointed to the part that cholesterol played in the integrity of body cell membranes, saying:
'Normal cell activity depends . . . on membrane function and permeability. This is partly dependent on the balance . . . between cholesterol and saturated and polyunsaturated fatty acids. The possibility that normal membrane function is impaired when there is a disproportionate decrease in cholesterol, with resulting loss of resistance to cancerous change, has to remain on the agenda of the risk/benefits of lowering plasma cholesterol.'[15]
Many epidemiological studies have shown consistently that cancer deaths rise in number as blood cholesterol levels fall.
A German study conducted at the Medizinische Universitatsklinik II, Tubingen, investigated blood cholesterol values at the time of diagnosis in patients with Hodgkin's lymphoma and found that they were significantly lower in these patients than in age- and sex-matched people without the disease. They also noted that patients with normal cholesterol values had a five-year survival rate which was two-and-a-half times higher than in patients with low blood cholesterol.[16]
Another study published in 1990 showed that colon cancer was preceded over a ten-year period by a fall in blood cholesterol levels. That doesn't mean the lower cholesterol caused the cancer; there are three possibilities: that the drop in cholesterol caused the cancers, that the drop in cholesterol was a result of the cancers or that the fall in cholesterol and the appearance of cancer at that time was merely a coincidence. The scientists looked meticulously at these three possibilities and, ruling out two of them, say:
'We conclude that individuals in whom colorectal cancer develops share the same level of serum cholesterol as the general population initially, but during the 10 years preceding the cancer demonstrate a decline in serum cholesterol level that is opposite to the rising level seen with age in the general population.'[17]
Their observations support the hypothesis that the onset of cancer was caused by the drop in serum cholesterol levels — not that the decline in cholesterol was a result of the cancer. The figures are the interesting aspect of this study because the average level at diagnosis of cancer was 5.56 mmol/L (214 mg/dL), yet doctors are trying still to reduce population levels to below 5.2 mmol/L (200 mg/dL). Interestingly, this study also specifically attributed the cancers to low levels of LDL, which reinforces other evidence that the so-called 'bad' cholesterol is not so bad after all.
Specific cancers linked to low cholesterol levels include squamous cell and small cell lung cancers,[18] liver cancer,[19] multiple myeloma,[20] adrenal cancer,[21] blood cancers including lymphoma, acute leukaemia, chronic myeloid leukaemia, chronic myelomonocytic leukaemia, policytemia vera, myeloma, chronic lymphoid leukaemia,[22] hairy cell leukemia,[23] brain cancers,[24] and gastrointestinal cancers.[25]
So what is a dangerously low cholesterol level? Well, it's almost certainly higher than you think. Scientists at the Department of Clinical and Experimental Medicine, University of Padua, Italy, analysed cancer deaths in 3282 elderly men and women aged 65 years or over taking part in the 12-year CASTEL (CArdiovascular STudy in the ELderly).[26] The study's analysis showed clearly an increase in cancers in people 'with very low cholesterol'. 'Very low' was defined as a level below 4.63 mmol/L (178 mg/dL). This level is similar to that found in a study of middle-aged men published four years earlier in which 'Serum cholesterol concentrations below 4.8 mmol/l were associated with the highest all cause mortality. . .'[27]
Incidentally, CASTEL showed that men whose Body Mass Index (BMI) was 22.7 or lower also had an increased cancer risk. A BMI of 22.7 is right in the middle of the 'healthy' weight range.
Not surprisingly, there have been several reviews of the cholesterol-cancer connection. This is of greater concern in cases where cholesterol has been lowered artificially with drug treatment as, in an increasingly litigious society, the person administering the drugs could be blamed and sued for causing the cancer. Drs T.B. Newman and S.B. Hulley of the School of Medicine, University of California, San Francisco, reviewed the findings and implications of studies of cancer and cholesterol-lowering drugs in trials involving both rodents and humans, and list the drugs and types of tumour found. They note in their review that 'all members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed for humans.' But they add that 'Evidence of carcinogenicity [cancer-causing properties] of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up.'[28] Because the evidence here is sketchy, Newman and Hulley conclude that longer term surveillance needs to be carried out over the next few decades; in the meantime 'the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.'
You might like to consider this: while this surveillance is conducted, anyone taking cholesterol-lowering drugs is effectively being used as a guinea pig in an uncontrolled trial in which a likely outcome is an increased risk of cancer.
Low blood cholesterol compromises immune function
As I have mentioned, there is a substantial amount of evidence that relatively low cholesterol levels in apparently healthy individuals is associated with increased subsequent mortality from cancer. It is also associated with other, non-heart related deaths. A group at the Center for Clinical Pharmacology, University of Pittsburgh, Pennsylvania, tested whether the effectiveness of their immune systems differed in individuals with high and low levels of blood cholesterol.[29] The low cholesterol group's cholesterol averaged 3.9 mmol/L (151 mg/dL); the high cholesterol group averaged 6.8 mmol/L (261 mg/dL). The immune systems of the men in the low cholesterol group were significantly less effective than those of the high cholesterol group. This finding was not surprising as several studies have shown that cholesterol is necessary for the proper functioning of blood cells — macrophages and lymphocytes — that form part of our immune systems. For this reason low blood cholesterol undoubtedly adversely affects our bodies' ability to fight infection. This could well be another reason why infectious diseases are becoming more prevalent in our society.
Tuberculosis (TB), a disease thought to have been conquered decades ago, is returning. It has been noticed that low levels of cholesterol are common in patients suffering from TB. TB patients with low cholesterol also have higher death rates, particularly those cases with small (military) nodules. A hospital for respiratory diseases tested whether giving TB patients high-cholesterol meals would effective in treating their condition.[30] They split patients into two groups. One had meals containing 800 mg of cholesterol per day; the other had 250 mg of cholesterol per day. The trial was a success. By the second week, the numbers of TB bacteria in sputum was reduced 80% in the high-cholesterol group; it was only reduced by 9% in the low-cholesterol group. High-cholesterol diets now form part of the treatment for TB.
Infections and deaths in surgical patients
Low cholesterol is also linked to increased susceptibility to infection, including development of postoperative infection,[31] and it predicts death and adverse outcomes in hospitalised patients.[32] While some of this could be due to illness causing lower cholesterol, it may also be that low cholesterol contributes to illness; indeed, animal studies suggest lipoproteins may serve to protect against bacterial infection-induced death.[33]
It has been suggested in cases of critical surgical illness that a low cholesterol level is more likely to lead to the development of organ failure and death
A study of patients undergoing surgery for gastrointestinal diseases at the Universita di L'Aquila in Italy, found that 'Hypocholesterolemia [low blood cholesterol] seems to represent a significant predictive factor of morbidity and mortality in critically ill patients.'[34] Of the patients studied, 35.1% contracted a postoperative infection. The highest incidence of postoperative septic complications (72.7%) was encountered in patients with cholesterol levels below 2.73 mmol/L (105 mg/dl). The authors say 'The results of this study seem to indicate a significant relationship between preoperative hypocholesterolemia and the incidence of septic complications after surgery. Moreover, evaluation of blood cholesterol levels before major surgery might represent a predictive factor of septic risk in the postoperative period.'
Low cholesterol levels have also been associated clinically with the development of hospital infections. A study conducted at the Department of Surgery, Weill Medical College of Cornell University, New York, set out to verify this. They found that lower levels of total cholesterol, and of LDL and HDL occurred early in the course of critical illness; this led to the development of a hospital infection; and with or without the infection, lower cholesterol was independently associated with a higher death rate.[35] The authors conclude: 'Decreased serum cholesterol concentration is an independent predictor of mortality in critically ill surgical patients. Repletion of serum lipids is a feasible therapeutic approach for the management of critical illness.'
Many patients in hospitals have or acquire infections during or after major abdominal surgery. The Department of Surgery at the Catholic University, Rome, Italy, conducted a study to identify factors that influenced mortality in patients who are affected by such infections.[36] The hospital records of patients who had had a variety of abdominal operations and who had acquired an infection such as peritonitis were reviewed. Checking deaths against a battery of blood measurements, the authors of the study found that low cholesterol levels and low protein levels were both 'strongly and independently associated with the outcome'.
Professor Uffe Ravnskov would not be at all surprised. He found that: 'There is much evidence that blood lipids play a key role in the immune defence system. Bacterial endotoxin and Staphylococcus aureus α-toxin bind rapidly to and become inactivated by low-density-lipoprotein (LDL).'[37] (Staphylococcus aureus is what the 'SA' in MRSA stands for.) Ravnskov also pointed out that 'Total cholesterol is inversely associated with mortality caused by respiratory and digestive disease, the aetiologies of which are mostly infectious. Total cholesterol is also inversely associated with the risk of being admitted to hospital because of an infectious disease.' In other words, if you have low cholesterol, you are more likely to end up in hospital and more likely to contract an infection while there.
Low cholesterol increases depression
Men with low cholesterol have higher mortality from injury. Although cholesterol-lowering tends to reduce CHD mortality in certain age groups, there is no evidence that it reduces total mortality. In populations with naturally low blood cholesterol there is also a significant death rate from 'non-medical' causes. Why is there this association?
A pilot study into blood cholesterol and depression in schizophrenics found a highly significant interaction between low levels of cholesterol and depression. Extreme lowering of cholesterol with drugs altered the functional state of the 'feel good' hormone, seratonin. The authors suggest that 'the degree of the low cholesterol combined with its duration might be a risk factor for the development of an abnormal mental state.'[38] Dr A Ryman, writing in the British Medical Journal says:
'Our current understanding of the relation between cholesterol metabolism and psychiatric illness is poor . . . The possibility that a low or falling cholesterol concentration is a marker of risk merits further study.'[39]
A large study at the Cholesterol Center, Jewish Hospital, Cincinnati, Ohio aimed to assess the relation between cholesterol levels and affective disorders such as depression, bipolar disorder and schizophrenia disorder.[40] Cholesterol concentrations below 4.16 mmol/L (160 mg/dL) were much more common in patients with affective disorders. When paired with healthy people of a similar sex and age, patients with affective disorders had much lower total cholesterol, LDL and HDL. Cholesterol levels in patients hospitalized with affective disorders was also markedly lower. Dr M Law added confirmation two years later. He writes: 'treating depression has been shown to increase serum cholesterol concentration. . . . Low seratonin concentrations (which accompany and may cause depression) are, not surprisingly, also associated with low cholesterol, people who attempt suicide have low serum cholesterol concentrations, . . . men with declining serum cholesterol concentrations are particularly likely to commit suicide.'[41]
Low cholesterol increases suicide risk
Depression is the main psychiatric illness leading to suicide and there is an observed increase in suicides among those undertaking cholesterol-lowering dietary regimes. In 1992, Dr H Engleberg proposed a hypothesis to explain this. He suggested that decreases in blood cholesterol affected the balance of the metabolism of fats within the brain and that this could have profound effects on brain function.[42] He showed that low blood cholesterol was found in aggressive people and those with antisocial personality. These averaged typically 5.04 mmol/L (194 mg/dL). Mental patients with high blood cholesterol (7.55mmol/L) were less regressed and withdrawn than those with lower (4.80mmol/L). And a French study concluded: 'Both low serum cholesterol concentration and declining cholesterol concentration were associated with increased risk of death from suicide in men.'[43]
There are many other such studies.
There is also a large number of clinical studies showing that total cholesterol levels below 4.7 mmol/L (180 mg/dL) are associated with depression, accidents, suicide, homicide, antisocial personality disorder in criminals and Army veterans, cocaine and heroin addicts. It is also associated with high relapse rates after detoxification and rehabilitation.[44]
Low cholesterol and resistance to authority by adults
I talked about cholesterol levels and suicides above. Low blood cholesterol is also associated with aggression and antisocial behaviour. Typically, people whose cholesterol was 'healthily' below 5.04 mmol/L were significantly more antisocial compared to others whose cholesterol was above 6.02 mmol/L.[45] And mental patients with blood cholesterol around 7.55 mmol/L were less regressed and withdrawn than those whose cholesterol levels were around 4.80 mmol/L.
Low cholesterol and mental illness and crime in children
In the Third National Health and Nutrition Examination Survey (NHANES III) conducted in the USA between 1988 and 1994, blood cholesterol levels were measured in 4,852 children aged 6-16 years.[46] Psychosocial development was evaluated by interviewing the mother regarding her child's history of school suspension or expulsion and difficulty in getting along with others.
What the survey showed was that children whose cholesterol concentration was below 3.77 mmol/L (145 mg/dL) were almost three times more likely to have been suspended or expelled from schools than their peers with higher cholesterol levels. The authors concluded that low total cholesterol may be a risk factor for aggression or a risk marker for other biologic variables that predispose to aggression.
Low cholesterol and Alzheimer's disease
The low cholesterol we are all supposed to strive for is one likely cause of the increase in Alzheimer's disease. Work in the 1950s found that as we get older, the level of cholesterol in our brains declines.[47] Later studies suggested that this decline may be the cause of brain disorders such as Alzheimer's. In 1991, a paper discussing the relief of Alzheimer's Disease, asked that 'strategies for increasing the delivery of cholesterol to the brain should be identified' and recommended increasing fat intake.[48]
The Framingham Study added weight to this proposition when it examined the relationship between total cholesterol and cognitive performance.[49] Participants were 789 men and 1105 women who were free of dementia and stroke and who received biennial cholesterol checks over a 16- to 18-year surveillance period. Cognitive tests were administered four to six years after the surveillance period. The researchers found a significant linear association between the level of blood cholesterol and measures of verbal fluency, attention, concentration, abstract reasoning, and a composite score measuring multiple cognitive domains. Participants with 'desirable' cholesterol levels of less than 5.2 mmol/L (200 mg/dL) performed significantly less well than participants with cholesterol levels higher than 6.25 mmol/L (240 mg/dL). Dr. Penelope K. Elias from Boston University said that 'It is not entirely surprising that lower cholesterol levels were associated with moderately lower levels of cognitive function, given [that] cholesterol is important in brain function.'
Low cholesterol and Parkinson's disease
There is much evidence that suggests a link between low levels of cholesterol and Parkinson's disease. The Rotterdam Study, involving 6,465 people aged over 55 examined over an average follow-up period of 9.4 years showed that this higher levels of total cholesterol in the blood were associated with a significantly decreased risk of Parkinson's disease; those with low levels were much more likely to contract the disease. [50] The highest risk was found with cholesterol levels below 6.1 mmol/L. Using that as a reference, they found that the risk dropped to 58% in the cholesterol range 6.1 and 6.8; it dropped to 46% between 6.8 and 7.4; and with a cholesterol level above 7.4 the risk was down to only 16%. Strangely, however, this link was only seen in women.
Low cholesterol, diabetes and obesity
Because of a heightened interest in people with very low cholesterol levels, several studies have looked at possible effects. One unexpected finding was that diabetics tended to have lower cholesterol levels than non-diabetics. Those with the lowest cholesterol levels were also more likely to be obese and to have higher triglyceride levels.[51]
Low cholesterol increases kidney disease risk
Low cholesterol and protein levels in the blood also portend a higher death rate in kidney disease patients according to a study conducted at the Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia in 1999.[52] While age, gender, and underlying chronic medical conditions were not predictive of mortality, both low protein and low cholesterol levels were. This finding was reinforced four years later in another study at the Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, and School of Medicine, University of California, Los Angeles of kidney dialysis patients.[53] This study found that conventional 'risk factors' such as obesity, high blood cholesterol and high blood pressure appeared to be protective features that are associated with a greater survival among dialysis patients.
Crohn's disease in children
Low blood cholesterol was also noted in patients with Crohn's disease as a result of lower LDL-cholesterol concentrations than in control subjects at the Gastroenterology-Nutrition Unit, Centre de Recherche, Hôpital Sainte-Justine, Departments of Pediatrics and Nutrition, Universite de Montreal, Canada.[54]
Low cholesterol and sickle cell anaemia
Sickle cell anaemia is a disease in West Africa in which red blood cells are not the usual round shape but curved like the blade of a sickle. This condition results in haemoglobin, a protein that carries oxygen around the body, not doing its job proper;y. There is some disagreement as to whether sickle cell anaemia also increases the risk of coronary heart disease. Scientists at the Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico, in Albuquerque, analysed the blood serum of children with the disease looking for levels of total cholesterol, HDL, LDL, triglycerides, and homocysteine.[55] They found that both the male and female children with the disease had much lower cholesterol than healthy children of the same ages and sex. Because those with the disease had low levels of cholesterol, the scientists concluded that 'Collectively, these results indicate that children with SCD [sickle cell disease] in northern Nigeria are not at increased risk of CVD.' But they obviously recognised that this low cholesterol was not as healthy as we think it is, because they continued: 'However, their marked hypocholesterolemia should be a cause of concern about the overall mortality and general well-being.'
Low cholesterol increases death rates in young and old alike
In 1991 the US National Cholesterol Education Programme recommended that children over two years old should adopt a low-fat, low-cholesterol diet to prevent CHD in later life. A table showing a good correlation between fat and cholesterol intakes and blood cholesterol in seven to nine-year-old boys from six countries was published to support this advice. What it did not show, however, was the even stronger correlation between blood cholesterol and childhood deaths in those countries.[56] As is clearly demonstrated at Table I, the death rate rises dramatically as blood cholesterol levels fall.
|
Blood Cholesterol (mmol/L) |
Childhood deaths |
|
| Finland | 4.9 | 7 |
| Netherlands | 4.5 | 9 |
| USA | 4.3 | 12 |
| Italy | 4.1 | 12 |
| Philippines | 3.8 | 72 |
| Ghana | 3.3 | 145 |
Two studies, which considered total blood cholesterol levels and mortality in the elderly, were published in the Lancet almost simultaneously in 1997. In the first, scientists working at Leiden University's Medical Centre found that 'each 1 mmol/L increase in total cholesterol corresponded to a 15% decrease in mortality'.[57]
Similarly, doctors at Reykjavik Hospital and Heart Preventive Clinic in Iceland noted that the major epidemiological studies had not included the elderly. They too studied total mortality and blood cholesterol in men over eighty to show that those with blood cholesterol levels over 6.5 mmol/L had less than half the death rate (48%) of those whose cholesterol level was a 'healthy' 5.2 mmol/L.[58]
This relationship between low cholesterol and higher mortality was strengthened by a further study published six years later. The UCLA School of Medicine, Los Angeles, studied the association between blood cholesterol levels and 7-year all-cause mortality.[59] What they found was that people whose cholesterol levels were below 4.4 mmol/L (169 mg/dL) had nearly double the death rate over the period of those with higher levels. While some of this increase was attributed to inflammation and poor diet, the low cholesterol link was still apparent even after these factors had been allowed for.
Studies in Japan added yet more weight to this argument. Japan is reported to have low levels of death from coronary heart disease but Okinawa has the lowest of all. Yet Okinawa's cholesterol levels are similar to those in Scotland — much higher than the average in Japan. In 1992 a paper examined the relationship of nutritional status to further life expectancy and health in the Japanese elderly based on three population studies.[60] It found that Japanese who lived to the age of one hundred were those who got their protein from meat rather than from rice and pulses. The centenarians also had higher intakes of animal foods such as eggs, milk, meat and fish; significantly, their carbohydrate intake was lower than that of their fellow countrymen who died younger.
These comparisons are important, as Japan might not have the low levels of heart disease deaths that are attributed to it. Although heart disease deaths are reportedly low, deaths from stroke and cerebral haemorrhage are very high. Keys attributed the lowest levels of heart deaths to Japan in his studies. These findings have been used to support recommendations that we should adopt Japanese eating patterns based on fish and rice. But vital statistics from death certificates are too unreliable for scientific use. One of the recognized facts about Japanese statistics is that the cause of many deaths was not certified by a qualified doctor. Another is that coronary heart disease was an undesirable cause of death; stroke was a more desirable one as it was thought to be indicative of intelligence in the family. More recent autopsies have revealed that stroke is not as common as once believed and that heart disease is much more common than original figures suggested.[61] This is a good example of why vital statistics used by Keys and others may be unreliable.
However, if we lump deaths from all causes together, we get a figure that cannot be fudged. Comparing average age at death from all causes and food intake, we find that the Japanese who live longest are the ones who eat the most animal products and the least carbs.
The generally held belief that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease is clearly wrong. In 2001 by Dr Schatz, professor of medicine at the University of Hawaii, wrote: 'those with cholesterol levels widely assumed to healthy had a roughly 35-40% greater chance of dying from any cause in the following 25 years'.[62] And in 2004 yet another new study suggested that low cholesterol was to a shorter lifespan.[63] So don't worry if yours goes up on the low-carb diet recommended in this book.
Low cholesterol increases total mortality in the middle-aged
Children and the elderly have both been shown to have higher death rate with low cholesterol levels. That leaves the middle aged. Amongst men in their forties there does seem to be a correlation between high cholesterol and greater coronary death rates. But here again we find that total mortality is highest in men whose blood cholesterol is lowest — less than 4.8 mmol/l (185 mg/dL). These deaths are largely due to cancers and other non-cardiovascular causes.[64] In this age group, while the lowest total mortality was seen between 4.8 mmol/l and 5.4 mmol/L (185—208 mg/dL), it rose only slightly as cholesterol concentrations rose above 5.4 but was considerably higher below 4.8.
In 1993 Dr M G Dunnigan wrote that both primary and secondary trials showed a significant number of excess deaths from non-cardiac causes: cancer, violence and suicide. He also pointed out that in a meta-analysis of 35 randomised controlled trials (RCTs) had little relevance to the non-symptomatic person under 65.
'Without definite data on all-cause mortality and with current unresolved concerns about excess deaths from non-cardiac causes in RCTs, decisions to embark on lifelong lipid lowering drug treatment in most patients with primary hypercholesterolaemia depend on the doctor's interpretation of available evidence. As in other situations in which certainty is illusory, this varies from evangelical enthusiasm for lowering lipid concentrations to therapeutic nihilism.'[65]
How physicians are fooled
So, with all this information apparently at their fingertips, you might wonder why there is such widespread acceptance of the cholesterol myth in the medical world, and why it is that doctors insist that everyone should have exactly the same cholesterol level. You might also wonder if their oath to 'first do no harm' means anything any more.
The reason is relatively simple to explain. Firstly, there are some 30,000 medical journals published and no doctor can be expected to read all of them. Secondly, wherever heart disease is mentioned in conjunction with cholesterol, out of the many studies that have been published only a mere handful of the supportive studies are quoted.[66] Those that don't support the myth are rarely mentioned.
This preferential citation has skewed the facts. In addition, pharmaceutical companies who sell cholesterol-lowering drugs produce many publications which broadcast the cholesterol lowering myth to millions. Dr Jerome P Kassirer, a former editor of the New England Journal of Medicine told readers of The Washington Post that major publications such as Lipid Letter, Lipids Online, and Lipid Management are all financed by the makers of cholesterol-lowering drugs.[67] These publications which warn relentlessly of the (false) dangers of cholesterol reach millions of medical doctors; they are designed, of course, to persuade doctors to prescribe their cholesterol lowering drugs. So it isn't really surprising that overworked professionals continue to teach us that cholesterol is dangerous and pharmaceutical companies aggressively push their cholesterol lowering drugs.
Conclusion
Dr A E Dugdale of the Cherbourg Hospital, St Lucia, Queensland, Australia, looked at the costs and benefits of cholesterol-lowering using 1984 Australian mortality statistics.[68] What he discovered was that the main effect of cholesterol lowering 'is to alter the cause of death'. 'When the lowest quintile of cholesterol levels is compared with the highest, the proportion of deaths from heart disease is almost halved, but the proportion from malignancies is almost doubled.' He concluded that:
'A decrease in serum cholesterol of a population by 10%, even if this were possible, would be expensive in money and manpower. The benefits would be small and perhaps not liked by the subjects. We all die and . . . heart disease may be preferable to cancer.'
It's a sobering thought. But when we add all the other adverse effects that low blood cholesterol seems to be responsible for and which increase ill health while we are alive, why would anyone want to lower their cholesterol? It is quite obvious that, while there might (or might not) be an increased risk of a heart attack in a man, if he is in his 40s and if his cholesterol level is very high, for men older than that, and for women of any age, a cholesterol level over 7 looks healthiest.
With so much evidence of the link between low-cholesterol and poor health — particularly in respect of cancer, why on earth can doctors not see it? It's about time, I think, that those profligate GPs who press cholesterol-lowering drugs on their 'patients' were held to account.
Anyone who isn't unaware of all this evidence is at serious risk of becoming a victim of the low cholesterol scam.
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