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.
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.