The benefits of high cholesterol

(A shortened excerpt from Fat and Cholesterol are GOOD for You!)

Most people ‘know’ that high cholesterol is something to be afraid of and that the most important thing to do to avoid a heart attack is to lower one’s cholesterol as much as possible. But did you know that high cholesterol protects you against infectious diseases, which most probably explain that high cholesterol is associated with longevity? With these facts min mind, why should we care about high cholesterol?   

Old people with high cholesterol live the longest. This statement seems so incredible that it takes a long time to clear one´s brainwashed mind, at least for those who haven’t read this book, to fully understand its importance. Yet the fact that people with high cholesterol live the longest emerges clearly from many scientific papers.1 

Why High Cholesterol Is Good  
In certain aspects low cholesterol is worse than high cholesterol. Already fifteen years ago American researchers found that low cholesterol predicts an increased risk of dying from diseases of the stomach, the intestines and the lungs.2
      Most of such diseases are infectious. Therefore, a relevant question is whether it is the infection that lowers cholesterol or the low cholesterol that predisposes to infectious diseases You have probably already guessed what the directors of the cholesterol campaign have said, but is it true?     
To answer that question the same researchers followed more than 100,000 healthy individuals in the San Francisco area for fifteen years. At the end of the study they noted that those who had low cholesterol at the start of the study had been admitted more often to hospital because of an infectious disease.3,4 This finding cannot be explained away with the argument that the infection had caused cholesterol to go down, because how could low cholesterol, recorded when these people had no evidence of infection, be caused by a disease they had not yet encountered? Isn’t it much more likely that low cholesterol in some way made them more vulnerable to infection? Much evidence exists to support that interpretation. 

Low Cholesterol Predisposes To HIV And AIDS
Young, unmarried men with a previous sexually transmitted disease or liver disease run a much greater risk of becoming infected with HIV virus than other people. This was what a group of Minnesota researchers found by following such people for several years. Those who had low cholesterol at the beginning of the study were twice as likely to test positive for HIV compared with those with the highest cholesterol.5
                     
Similar results came from another study of more than 300,000 young and middle-aged men.  After sixteen years four times more in the low-cholesterol group had died from AIDS compared with the high-cholesterol group.6

Smith-Lemli-Opitz Syndrome
The benefit of high cholesterol also appears from studies of children with the Smith-Lemli-Opitz syndrome. They are born with very low cholesterol because an enzyme that is necessary for the body’s synthesis of cholesterol does not function properly. Most children with this syndrome are either stillborn or they die early because of serious malformations of the brain. Those who survive are imbecile or autistic, they have extremely low cholesterol, and they suffer from frequent and severe infections. However, if they are given extra cholesterol or eggs in their diet, their cholesterol goes up, their infections become less serious and less frequent, and their autistic and aggressive behavior improves.7 

The lipoproteins  
One of the many reasons not to name LDL as bad is that the lipoproteins have other important functions. One of them is to take care of microorganisms and their toxic products.  
      Staphylococcus aureus α-toxin is the most toxic substance produced by strains of the disease-promoting bacteria called staphylococci. It is able to destroy all kinds of human cells, including red blood cells. For instance, if minute amounts of the toxin are added to a test tube with red blood cells dissolved in salt water, the blood is hemolyzed, that is, the membranes of the red blood cells burst and hemoglobin from the interior of the cells leaks out into the solvent. Dr. Bhakdi and his team mixed purified α-toxin with human serum (the fluid in which the blood cells reside) and now the toxic effect of  α-toxin almost disappeared. By various complicated methods they identified the protective substance in human serum as LDL, the carrier of the “bad” cholesterol. In accordance, nothing happened when they mixed α-toxin with purified human LDL. 
      Dr. Willy Flegel and his co-workers at Heidelberg University in Germany studied bacterial toxins in another way. As mentioned above, one of the effects of bacterial toxins is that they stimulate white blood cells to produce cytokines, hormones that start the inflammatory processes. The German researchers found that this effect disappeared almost completely if the toxin was mixed with purified LDL before they added the white blood cells to the test tubes.8,9 Obviously, LDL was able to neutralize the bacterial toxins. 

Animal Experiments
The immune systems in various mammals including human beings have many similarities. Therefore, it is interesting to see what experiments with rats and mice can tell us. Professor Kenneth Feingold and his group at the University of California have published some interesting studies. In one of them they lowered LDL-cholesterol in rats by drugs with the result that they died much easier after an injection of bacterial toxins. The high mortality was not due to the cholesterol-lowering drug because, if they gave the animals an injection of human lipoproteins just before the experiment, they survived10
     
In another experiment, researchers from the Netherlands injected bacteria or their toxins into normal mice, and into mice with high cholesterol. Whereas all normal mice died, most of the mice with high cholesterol survived.11
    
Many of the roles played by the lipoprotein LDL are shared by HDL as well. This should not be too surprising considering that high HDL-cholesterol is associated with cardiovascular health and longevity. But there is more.     
Triglycerides, molecules consisting of three fatty acids linked to a molecule named glycerol, are insoluble in water and are therefore carried through the blood inside lipoproteins, just as cholesterol. All lipoproteins carry triglycerides, but most of them are carried by the VLDL, the largest lipoprotein in our blood.
     
     For many years it has been known that patients suffering from sepsis, a life-threatening condition caused by bacterial growth in the blood, have high levels of triglycerides. The serious symptoms of sepsis are due to bacterial toxins, most often produced by gut bacteria. Now to the interesting point. Solutions rich in triglycerides are also able to protect experimental animals from the dangerous effects of bacterial toxins, which means that the high level of triglycerides seen in sepsis is not a bad thing, but a normal response to infection.12 Usually sepsis bacteria come from the guts. It is therefore fortunate that the blood draining the guts is especially rich in triglycerides.
 

High cholesterol protects against allergy
Children with allergic problems, such as asthma and hay fever, have lower cholesterol than healthy children. As allergic diseases have become more common and is still increasing in the Western world it is tempting to suggest that the cause is the increasing consumption of the polyunsaturated vegetable oils of the omega-6 type, because these oils are known to stimulate inflammatory processes, and allergy is a kind of inflammation. But there is room for another explanation.
     At the Skin and Allergy Hospital in Helsinki, Finland Dr.Maria Pesonen and her co-workers followed 200 children from their birth to their 20 year anniversary.13 They found that the children with allergic disorders had lower total and LDL cholesterol than the others. The difference was obvious already at a time where all the children were breastfed. Thus, the difference could not be explained by their dietary habits. The researchers had no explanation for their observation, but if the lipoproteins are able to bind microbial products, it seems not too far-fetched to assume that they can bind other molecules as well, for instance allergens, those molecules that starts the allergic reactions. 

Is familial hypercholesterolemia a disease?
“The more LDL there is in the blood, the more rapidly atherosclerosis develops.”
     This was the main conclusion of the American Nobel Price-winners, Joseph Goldstein and Michael Brown.14 They discovered that the cells of people with familial hypercholesterolemia had difficulties taking in cholesterol from the blood because of a defect in the LDL-receptor, the mechanism that transports these vital molecules into the cells. This was the reason why cholesterol was much higher than normal in these people. People with familial hypercholesterolemia also have more atherosclerosis than normal and some of them do die early in life from heart disease. It was therefore not too far-fetched for Goldstein and Brown to draw the conclusion they did, and also to assume that it was applicable to the rest of mankind. They were awarded the Nobel Prize in 1985 for their discovery, and many other researchers share their view.
     Their finding is certainly interesting, a result of careful scientific work. Unfortunately, the conclusion they drew was too hasty. In fact, there are benefits associated with this condition, which is why I deliberately refer to individuals with familial hypercholesterolemia as people, not as patients. What is even more surprising is that the reason why some of them die at a young age from heart disease is not their high cholesterol, but something else. I shall come back to that. 
     In England The Simon Broome Familial Hyperlipidaemia Register Group have followed almost 3000 people with familial hypercholesterolemia for many years.  At the most recent control they found that 102 of them, or 3.6 % had died from a heart attack. By analyzing mortality of the same age group in the English population they calculated that the expected number should have been 40, or 1.4 %. On the other hand, fewer had died from other causes, 112 against the expected number 193, or 4 % against 6.8 %. For instance, only half as many had died from cancer.30 If you add the figures and compare them you will see that people with familial hypercholesterolemia live at least as long as other people, if not longer. A little more die from heart disease, but fewer die from cancer and other diseases.
     The authors of the scientific report stressed that the participants in their study were admitted because all of them had close relatives who had died at a young age. Cholesterol screening often identifies old people with familial hypercholesterolemia who have no such relatives. The authors therefore suggested that if the participants had been representative for all people with familial hypercholesterolemia, their mortality would have been even lower.
     In Finland, Professor Tatu Miettinen and Dr. Helena Gylling studied about one hundred individuals with familial hypercholesterolemia.16 Fourteen to seventeen years later, 30 had died, 26 because of a heart attack and four of other causes. On average, initial LDL cholesterol was the same among those who had died and those who still were alive. If high LDL cholesterol was the most important cause of atherosclerosis and heart disease, as postulated by Nobel Award winners Goldstein and Brown, then we should have expected higher cholesterol in those who died, but that wasn’t the case. Many other researchers have confirmed the Finnish findings.17-23
    
Another conflicting observation is the fact that people with familial hypercholesterolemia have normal cerebral arteries, even though the same cholesterol-rich blood flows through their brain as through the rest of their body.25 

A missing link  
The genetic aberrations in people with familial hypercholesterolemia are more complicated than Brown and Goldstein assumed. For instance, in a study of 2400 such individuals, Dr. Angelique Jansen at the University of Amsterdam  found that variations of the prothrombin gene were associated with an increased risk of heart disease in these people.26 Prothrombin is a substance necessary for blood coagulation and an abnormal prothrombin gene may lead to the production of too much of this substance. The result is an increased tendency to coagulation and clot formation. Thus, some individuals with familial hypercholesterolemia may form arterial clots more easily than other people, not because of their high cholesterol, but because of an abnormal coagulation system.

Heart patients with familial hypercholesterolemia more often have high concentrations of fibrinogen and factor VIII in their blood than healthy people with familial hypercholesterolemia. Also these substances participate in the coagulation process, and too much of them may stimulate to clot formation. And again, whereas the heart patients had much higher concentrations of fibrinogen and factor VIII, their total and LDL cholesterol did not differ from those measured in healthy people with familial hypercholesterolemia.27

In earlier times, people with familial hypercholesterolemia lived longer than other people! Dutch researchers tracked the ancestors of people with familial hypercholesterolemia and identified 412 individuals with a 50 percent chance of having this genetic abnormality. They also searched official records of deaths and found that the longevity of those with a family history of this genetic aberration was not lower before the year 1900; in fact, on average they lived longer than other people. As the most common cause of death at that time was infectious disease, the authors suggested that high cholesterol protects against infection.28

 

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Notes

    1. Kozarevic D et al. Serum cholesterol and mortality: the Yugoslavia Cardiovascular Disease Study. Am J Epidemiol. 1981 Jul;114(1):21-8.
      Rudman D et al et. Antecedents of death in the men of a Veterans Administration nursing home. J Am Geriatr Soc. 1987 Jun;35(6):496-502.  
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      Casiglia E et al. Predictors of mortality in very old subjects aged 80 years or over. Eur J Epidemiol. 1993 Nov;9(6):577-86. 
      Krumholz HM et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994 Nov 2;272(17):1335-40.  
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      Weverling-Rijnsburger AW et al. High-density vs low-density lipoprotein cholesterol as the risk factor for coronary artery disease and stroke in old age. Arch Intern Med. 2003;163(13):1549-54.
      Onder G et al. Serum cholesterol levels and in-hospital mortality in the elderly. Am J Med. 2003;115(4):265-71.
      Casiglia E et al. Total cholesterol and mortality in the elderly. J Intern Med. 2003 Oct;254(4):353-62.
      Psaty BM et al. The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study. J Am Geriatr Soc. 2004 Oct;52(10):1639-47.
      Ulmer H et al. Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality.J Womens Health 2004 Jan-Feb;13(1):41-53.  
      Schupf N et al. Relationship between plasma lipids and all-cause mortality in nondemented elderly. J Am Geriatr Soc. 2005 Feb;53(2):219-26
      Akerblom JL et al. Relation of plasma lipids to all-cause mortality inC aucasian, African-American and Hispanic elders. Age Ageing. 2008;37:207-13.
      Newson RS et al. Association between serum cholesterol and noncardiovascular mortality in older age. J Am Geriatr Soc. 2011;59:1779-85.
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© Uffe Ravnskov       Updated January 2, 2010