Category Archives: plant sterols

Plant sterol controversy discussed in JAMA

Oliver Weingartner and colleagues have a letter in the current issue of JAMA, responding to the publication of a trial of the “portfolio diet” of cholesterol-lowering foods, including margarine fortified with plant sterols.

To the Editor: In their study on dietary strategies to reduce serum cholesterol levels, Dr Jenkins and colleagues concluded that a dietary portfolio including plant sterols resulted in greater reductions in low-density lipoprotein cholesterol (LDL-C) levels during a 6-month follow-up compared with low-saturated-fat dietary advice. Although a significant LDL-C lowering achieved by a dietary portfolio including plant sterols may be beneficial, we believe the results do not necessarily support a heart health benefit. In Table 3 of the article, the plant sterol–fortified dietary portfolio reduced serum cholesterol levels at the expense of an increase of plasma plant sterol levels (10.7 μmol/L at baseline and 13.3 μmol/L at week 24). (To convert phytosterols to mg/dL, multiply by 0.04.)

Our research group has previously assessed the effect of lipid lowering with ezetimibe or phytosterols in apolipoprotein E (apoE) −/− mice. We found that plasma plant sterol concentrations were strongly correlated with increased atherosclerotic lesion formation (r = 0.50), suggesting that plant sterols may be atherogenic. Based on a rare inherited disease called phytosterolemia, characterized by overabsorption of phytosterols and premature coronary artery disease, and several epidemiological studies that have shown a correlation between increased plant sterol plasma levels and cardiovascular risk, the role of plant sterols in the management of hypercholesterolemia has become controversial. Studies assessing hard cardiovascular end points are needed before conclusions that a diet enriched with plant sterols reduces cardiovascular risk can be drawn. (citations omitted)

The essential point, as made by many people in recent years (see, e.g., this commentary), is that it is not enough to show that an intervention lowers LDL (or raises HDL, etc.).  Before we can be sure that the intervention is beneficial, we need evidence that it lowers the risk of heart attacks and strokes.

In their reply, Vanu Ramprasath and colleagues note that some epidemiological and animal studies have not found risk associated with increased plant sterol levels and the fact that statins may increase absorption of plant sterols.  In summary, they state that “based on evidence from both humans and animal models, we believe that plant sterol levels in plasma are not related to increased CHD risk.” 

A comment about this summary statement.  There really is no controversy about whether high levels of plant sterols cause heart disease:  because of the association of premature heart disease with the rare genetic disease sitosterolemia, everyone agrees that they do.  The issue is whether more moderate increases in plant sterol levels are harmful.

So the controversy continues.

Sunday links

David Rind recently revived his blog Evidence in Medicine and has a post up on the SHARP trial.  The SHARP trial, which I discussed recently on this blog and on Gooznews, is the basis for Merck’s application for a new indication for its drugs Vytorin (ezetimibe/simvastatin) and Zetia (ezetimibe).  David explains why the results in SHARP are consistent with previous evidence on the effect of statins in patients with chronic kidney disease, both pre-dialysis and on dialysis.

Kevin Lomangino has an article up on the “portfolio diet,” which is a diet that emphasizes foods that lower cholesterol.  Kevin explains that most of the cholesterol-lowering from this diet comes from the inclusion of foods containing added plant sterols.  As I previously discussed on this blog, while plant sterols lower LDL, their effect on cardiovascular events is unknown, making the portfolio diet a bit of a crapshoot healthwise.

Plant sterols for cholesterol-lowering

In a recent post on the Science-Based Medicine blog, Dr. Harriet Hall reviewed The Mayo Clinic Book of Home Remedies. For elevated cholesterol, the book recommends trying “natural products,” including plant sterols. Plant sterols (aka phytosterols) are sold as supplements or in functional foods, such as certain margarines. It is true that plant sterol supplements will usually lower LDL (“bad”) cholesterol by a small amount, in the range of 5-15%. Unfortunately, there is no good evidence that plant sterols lower the risk of heart disease. In fact, it is possible that plant sterols actually promote heart disease.

1. There is a rare genetic disorder called sitosterolemia, characterized by very high serum plant sterols, in which patients develop premature heart disease. It is similar to homozygous familial hypercholesterolemia, except with very high plant sterols instead of very high LDL. The unfortunate victims develop xanthomas containing plant sterols and arteries clogged by plant sterols.

2. Plant sterol supplements have been shown to increase serum plant sterols in healthy people.

3. The safety of these elevated levels of plant sterols has not been established.

4. No clinical trials have been done to test whether plant sterol supplements reduce the risk of heart attacks and, so far as I know, no such trials are planned.

5. There are studies that have found plant sterols in atherosclerotic plaque (e.g., from people who have had endarterectomies) and in aortic valves of patients with aortic stenosis.

6. There are animal studies showing harm from plant sterol supplementation.

For the above reasons, plant sterol supplements cannot be recommended at the present time.


Weingartner, et al. Vascular effects of diet supplementation with plant sterols. Journal of the American College of Cardiology, 2008;51:1553-1561, doi:10.1016/j.jacc.2007.09.074

Teupser, et al. Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease. Circulation: Cardiovascular Genetics. 2010;3:331-339, doi:10.1161/CIRCGENETICS.109.907873

O. Weingartner, M. Bohm, and U. Laufs
Controversial role of plant sterol esters in the management of hypercholesterolaemia
European Heart Journal, February 2, 2009; 30(4): 404–409.