HRT may stop a cholesterol-lowering diet working

Dietary approaches to lowering cholesterol may be a side effect-free alternative to statin drugs for patients with moderately high cholesterol, but a new study at Pennsylvania State University shows that in patients with high levels of C-reactive protein (CRP) they may actually increase cholesterol, writes Jess Halliday.

CRP is an acute phase protein that occurs in the blood in increased quantities during systemic inflammation. High levels of CRP are associated with the build-up of fatty deposits in the arteries, and testing CRP has been flagged as a new way to assess the risk of cardiovascular disease.

What is more, CRP is increased by the intake of oral estrogen, hormone replacement therapy (HRT) commonly used to alleviate menopause symptoms.

The Penn State study, funded by The Solae Company and published in the Journal of Nutrition (135:1075-1079), involved 14 men and 18 women, six of whom were receiving HRT. All the participants were overweight and had moderately elevated cholesterol of between 124 and 211 mg/dl.

For the first three weeks of the study, all the participants ate only foods on the National Cholesterol Education Program Step 1 diet - in which total fat is restricted to 30 percent of calories, with saturated fat less than 10 percent - prepared in the research kitchen.

They were then randomly divided into two groups, and for the next six weeks one group received the Step 1 diet with 25 g of soy protein each day, and the other the Step 1 diet with 25g of milk protein.

Following a two week break during which participants reverted to their normal diet, the eight week process was repeated, but this time the Step 1 plus soy group ate Step 1 plus milk, and vice versa.

Lipids and lipoproteins, CRP, and interleukin-6, another protein, were measured at the end of each phase and participants were categorized as having high (more than 3.5 mg/L) or low CRP.

Lead researcher Kirsten Hilpert found that those with high CRP levels did not lower their cholesterol levels with the Step 1 diet, even when they also ate soy protein, which carries an FDA-approved heart health claim.

Regardless of whether they received soy or milk protein, those with low CRP decreased their LDL cholesterol levels by an average of 3.5 percent and their LDL:HDL cholesterol ratio by 4.8 percent.

But in those with high CRP, LDL cholesterol actually increased by 4.8 percent, as did the LDL:HDL cholesterol ratio by 5.2 percent, apolipoprotein B by 3.8 percent and lipoprotein(a) by 13.5 percent.

"These results suggest that habitual consumption of a Step 1 diet may beneficially affect individuals with CRP levels less than 3.5 mg/L, the median level of the study, and may have deleterious effects in patients with elevated levels," said Hilpert.

She added that if the results are confirmed in other studies, the next step will be to test whether lowering CRP improves diet response.