HDL: is higher really better?

We usually refer to LDL (low-density lipoprotein) as “bad cholesterol”, and HDL (high-density lipoprotein) as “good cholesterol”.  Observational studies, such as the Framingham Heart Study, have shown that low HDL is a risk factor for cardiovascular disease.1  Thus it is thought that raising HDL may reduce risk, but it’s not that simple.  

Cholesterol is packaged into lipoproteins when circulated in the blood – LDL transports cholesterol to the cells, and HDL picks up excess cholesterol and delivers it back to the liver where it can be broken down.  Theorectically, having more HDL would mean that more cholesterol would be disposed of, and as a result LDL would decrease, and therefore cardiovascular risk would decrease.  So raising HDL when LDL is high would make sense, but what about raising HDL when LDL is not high?  Would there be any benefit?

Pills. Flickr: melloveschallah

High-dose niacin (vitamin B3), is one substance that can raise HDL, and a government funded clinical trial (the AIM-HIGH trial) was undertaken in 2006 evaluating the use of niacin together with an LDL-lowering drug (a statin) for preventing heart attacks and strokes. The individuals selected for the trial had favorable LDL levels (below 80 mg/dl; due to the statin drugs), but were considered to be at risk for heart attack and stroke based on low HDL levels, high triglyceride levels, and a history of cardiovascular disease.   This study sought to determine whether raising HDL would decrease their risk.

The subjects that took niacin in addition to a statin drug indeed did experience an increase in HDL and decrease in triglycerides.  However, the clinical trial was stopped early because the subjects taking niacin plus the statin were just as likely to have a cardiovascular event as those taking a statin plus placebo.  Furthermore, the subjects who were taking niacin had a small increase in the rate of strokes.2 Niacin is not the first drug that has raised HDL levels and failed to reduce the risk of cardiovascular events. A few years ago, an HDL-elevating drug called torcetrapib was found to increase the risk of cardiovascular events, presumably because it raised blood pressure and impaired endothelial function.3 Pfizer’s development of the drug was halted during clinical trials.

This is yet another study showing that raising HDL does not reduce risk in patients with already favorable LDL levels.  Often, adopting a healthful diet reduces both HDL and LDL, and this is often a source of concern.  But the truth is that it is not harmful – there is simply less need for HDL when LDL decreases, and the body adapts to this change by producing less HDL.

LDL and HDL numbers on a blood test are simply markers that indicate the development of cardiovascular disease.  They are not necessarily an accurate depiction of the extent of the disease, and they are not the only factors that take part in the disease process. The development of atherosclerotic plaque is complex, involving elements of inflammation and oxidative stress in addition to cholesterol.  Manipulating cholesterol levels with drugs is simply not enough to resolve cardiovascular disease and prevent future heart attacks and strokes.  This 52 million dollar study has confirmed what we already know: drugs don’t restore cardiovascular health.  Only healthy living can restore health.



1. Castelli WP, Garrison RJ, Wilson PW, et al: Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986;256:2835-2838.

2. NIH stops clinical trial on combination cholesterol treatment. 2011. NIH News. http://www.nih.gov/news/health/may2011/nhlbi-26.htm. Accessed June 14, 2011.

3. Connelly MA, Parry TJ, Giardino EC, et al: Torcetrapib produces endothelial dysfunction independent of cholesteryl ester transfer protein inhibition. J Cardiovasc Pharmacol 2010;55:459-468.


Trackbacks (0) Links to blogs that reference this article Trackback URL
Comments (9) Read through and enter the discussion with the form at the end
jen - August 5, 2011 12:17 PM

Good info as I have a cholesterol of 228 at age 46 and am working on a nutritarian diet in support of lowering it. Does anyone have a link to a good site with realiable information on cholesterol's good and bad effects on the body? I know we need it to function but too much can be bad. I have also read that as you get older you need more cholesterol to keep functioning properly. I have also read that high cholesterol is a sign of inflammation that the body is trying to heal. Get rid of the inflammation and the numbers will go down. My head is spinning with all the info out there. What to believe??

Johnny Bourdeaux - August 5, 2011 9:18 PM

Your stance on HDL is unsubstantiated. There are many trials on niacin that did not show adverse effects. HATS for example reduced events 90%. The effect of niacin is perhaps more because it reduces small LDL than HDL boosting effect anyway.

Torcetrapib was a failure probably because of multitude of reasons - it's a strech to believe it was because of the 50% rise in HDL since coronary regression was demonstrated in animal studies. One possible explanation may be that artificially inhibiting CETP and ignoring PLTP activity caused the excess mortality. Nutritional interventions and niacin generally do not do that but maintain the equilibrium better.

HDL acts as an anti-inflammatory agent and an antioxidant. It binds harmful substances in the blood, stimulates endothelial cell movement, decreases multiple clotting functions, protects red blood cells, stimulates the synthesis of prostacyclin (an important substance involved in arterial relaxation), and increases the half life in the circulation of this prostacyclin. HDL reduces growth factor synthesis in the vascular smooth muscle cells, stimulates the production of nitric oxide, modulates endothelial function and is antithrombotic. In addition, HDL subfractions are not trivial but perhaps quite important, as are different LDL forms too.

Summa summarum, HDL is something you want more of, largely regardless of LDL level.

Steve - August 6, 2011 6:56 AM

It seems to me that there are other things that need consideration [besides merely HDL, LDL Niacin and drugs] that may not have been included in the studies such as magnesium and gluathione levels for starters. How can you do an accurate study if all the variables are not included in the study? For instance if all the subjects were magnesium deficient this may have caused the effect. If they were not magnesium deficient the results may have been different. We won;t know if those variables were not included.

Mike Rubino - August 8, 2011 3:40 PM

How is the position not substantiated when its right from the report cited ?

Marie Krieger - August 9, 2011 9:41 AM

Dr. Fuhrman is right on point. Artificially manipulating HDL or LDL with "natural" niacin or with synthetic drugs has questionable and relative bearing on cardiovascular health with the mixed results that Mr. Bordeaux cites. Many studies show that too much niacin has very deleterious effects on the liver. So you may be improving the cardio picture and wrecking a liver. The most salient point of Dr.Fuhrman's post is that overall healthful diet and lifestyle choices are the best and most positive determinants for cardiovascular health and overall health in general. Think of all the people popping lipitor and cheeseburgers. They would do the same with niacin and cheeseburgers and sorry to say to the same effect. The sad thing is that these people and their well meaning but misguided doctors think they have been given a get out of jail free card by virtue of their "low cholesterol numbers". They remain ignorant of what generates proper health and do not have the opportunity to learn how a whole foods diet is a piece of an wholistic life that is supportive of the whole planet and not only of their body.

Joel Fuhrman, M.D. - August 10, 2011 8:57 AM

I have cared for and influenced hundreds of patients with advanced coronary artery disease who were able to reverse their condition and open up their obstructed arteries. Many of these individuals have given their stories here in this blog. I have often observed as their body fat gets very low and atherosclerotic plaque has been effectively reduced, the LDL can be low and the HDL can get very low. When there is no plaque left to remove many people simply do not make much HDL. Obviously, LDL is the more important marker than HDL, but the blood test does not tell the whole story. Plus many people following my nutritarian diet with clean disease-free vessels have very low HDL. Since HDL's major function is to remove excess cholesterol, and extremely low LDL cholesterol means that less HDL is needed, the body adapts to this reduced need. You don’t need snow shovels if you live in Florida. It is true that HDL has some additional beneficial effects (antioxidant and anti-inflammatory) in those who do not eat an ideal diet, however, if HDL levels have dropped as a result of following a high-nutrient, cardioprotective diet, there is no need to think that a higher HDL would be any better. Certainly you would not want to address that with medication. Oxidative stress, inflammation, LDL levels, and cardiovascular risk will be reduced by a healthful eating style, regardless of the corresponding decrease in HDL. Populations around the world with more cardio-protective diets and extremely low heart disease risk, have very low HDLs.

(Fan WX, Parker R, Parpia B, et al. Erythrocyte fatty acids, plasma lipids, and cardiovascular
disease in rural China. Am J Clin Nutr. 1990 Dec;52(6):1027-36.)

Even the results from the JUPITER trial showed HDL levels were predictive of cardiovascular risk in the placebo group, but in those who maintained low LDL levels with a statin drug, there was no significant relationship between HDL and risk of cardiovascular events.

(Ridker PM, Genest J, Boekholdt SM, et al. JUPITER Trial Study Group. HDL cholesterol and residual risk of first cardiovascular events after treatment withpotent statin therapy: an analysis from the JUPITER trial. Lancet. 2010 Jul 31;376(9738):333-9.)

MIke Rubino - August 10, 2011 10:19 PM

Right on Dr F. Too bad that you cant take all your succesfull patients, line them up and give them stress tests in front of a group from the heart section of the AMA . Then say you want substantiation ? Here it is. Id voulunteer/

SkepticalHealth - February 28, 2012 9:12 AM

I agreed with you up until you wrote that "medications can not help with cholesterols."

Statins are indisputably proven to decrease LDLs and decrease risk of cardiovascular events in a dose-response relationship. Diet can yield decent decreases in LDL, but only 20% of our LDLs come from the diet.

You have some nice information, but vastly overestimate the role of diet in cholesterol management.

Brandon Beard - October 29, 2012 10:22 AM

When signing up for medical insurance, I did a lipid profile and complete metabolic panel.

I weigh around 115 (I am working on gaining weight the nutritarian way).

I do not eat meat much at all, maybe a meal or two on weekends. My creatine levels were flagged as LOW at 0.74 and my HDL was flagged as being too low at 38. (But, my LDL is only 53). Is this really something to worry about? the notes say "According to ATP-III Guidelines, HDL-C>59 mg.dL is considered a negative risk factor for CHD.

Your Thoughts?

Post A Comment / Question Use this form to add a comment to this entry.

Remember personal info?