HDL probably does not protect against heart disease.

A meta-analysis of 108 RCTs found that HDL had little appreciable effect on the risk of heart disease or all-cause mortality after controlling for LDL."

http://www.bmj.com/content/338/bmj.b92

http://www.askdoctork.com/is-high-hdl-cholesterol-good-201212193969

"Posted December 19, 2012, 5:00 am

DEAR DOCTOR K:
For years my doctor has been telling me about the benefits of high levels of HDL cholesterol. Now I read that high HDL may not protect against heart disease after all. Is "good" cholesterol still good for you?

DEAR READER:
The HDL cholesterol story is a cautionary tale. It demonstrates once again that even the most persuasive theories about what should make us healthy need to be put to the test.

It has been solidly established that people who have high levels of LDL (bad) cholesterol have a higher risk of developing heart disease. Moreover, it has been solidly established that treatments that lower LDL cholesterol reduce the risk of developing heart disease.

It also has been solidly established that people with HDL levels above 60 milligrams per deciliter (mg/dL) tend to have a lower risk for heart disease. Since HDL cholesterol removes fat from the plaques in arteries, that observation made sense.

Not unreasonably, doctors and scientists assumed that boosting HDL with medication would lower cardiac risk even more. There are several drugs that have been around for 30 years - particularly gemfibrozil and niacin - that modestly raise levels of HDL. These drugs were tested in people with heart disease. They did lower the risk of new heart problems, but it wasn't clear if they achieved that benefit by lowering HDL cholesterol or through some other effect.

Then several different types of drugs were developed that could dramatically raise HDL levels. Most doctors, myself included, bet that such drugs would probably reduce the risk of heart disease. Why? Because all the evidence seemed to point in that direction.

Before such drugs were approved by the Food and Drug Administration, however, the agency required that studies involving large numbers of people be conducted to prove the value of the drugs. To make a long and painful story short, over the past five years these drugs have proved very disappointing. Not only have they not convincingly lowered the risk of heart trouble - in some cases, they have increased the risk.

In addition, a recent Harvard study pooled health information on more than 116,000 people genetically predisposed to produce higher-than-normal amounts of HDL. Surprisingly, this group did not show the predicted lower risk of heart attack.

How can this study be squared with previous studies that have convincingly showed that people with high levels of HDL have a lower risk of heart disease? The most likely conclusion is that it is not the high HDL levels, but rather something else about people who have high HDL levels that protects them from heart disease.

Many lifestyle changes raise HDL cholesterol and indisputably reduce your risk of heart disease: regular exercise, healthy weight, avoiding trans fats, quitting smoking and moderate use of alcohol. These lifestyle changes may not work through their effects on your HDL level, but they surely and powerfully do work."

"Dr. Anthony Komaroff is a practicing physician, Professor of Medicine at Harvard Medical School, and Editor in Chief of Harvard Health Publications."

The Alzheimer's cholesterol connection

Dietary fats and the risk of incident Alzheimer disease.

"Persons in the upper fifth of saturated-fat intake had 2.2 times the risk of incident Alzheimer disease compared with persons in the lowest fifth in a multivariable model adjusted for age, sex, race, education, and apolipoprotein E epsilon4 allele status (95% confidence interval, 1.1-4.7)."

http://www.ncbi.nlm.nih.gov/pubmed/12580703

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Food combination and Alzheimer disease risk: a protective diet.

"RESULTS: Two hundred fifty-three subjects developed AD during a follow-up of 3.9 years. We identified a dietary pattern (DP) strongly associated with lower AD risk: compared with subjects in the lowest tertile of adherence to this pattern, the AD hazard ratio (95% confidence interval) for subjects in the highest DP tertile was 0.62 (0.43-0.89) after multivariable adjustment (P for trend = .01). This DP was characterized by higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter."

http://www.ncbi.nlm.nih.gov/pubmed/20385883

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Alzheimer's disease: the cholesterol connection

"A hallmark of all forms of Alzheimer's Disease (AD) is an abnormal accumulation of B-amyloid protein (AB) in specific brain regions. Both the generation and clearance of AB are regulated by cholesterol. Elevated cholesterol levels increase AB in cellular and most animal models of AD, and drugs that inhibit cholesterol synthesis lower AB in these models...The identification of a variant of the Apolipoprotein E (APOE) gene as a major genetic risk factor for AD is also consistent with a role for cholesterol in the pathogenesis of AD."

http://www2.massgeneral.org/neurology/kovacs/publications/pdf/NN_AD_cholesterol_03.pdf

Since the most effective way to raise cholesterol is by consuming saturated fat, it is not surprising that saturated fat would be associated with increased Alzheimer's disease. BTW, Asian countries that consume a higher percentage of carbohydrates and a lower percentage of saturated fat than Americans have a lower rate of Alzheimer's than Americans. BTW, the apoe4 gene that increases the risk of Alzheimer's disease also raises cholesterol levels.