Summary

This study shows that a high-fat meal causes increased plasma levels of bacterial endotoxin; this may represent one way that atherosclerosis originates or develops.

Introduction

The effect of meals on the body's metabolism has been well studied, and has led to number of 'corrective' medications over the years - carminatives such as peppermint, antacids, and, more recently, the meglitinides that are used for suppressing postprandial glucose levels (e.g. Starlix^®, Prandia^®). But now attention has turned to the role of certain types of meal (i.e. high-fat content) in increasing low-grade inflammatory changes in the body.

High-fat meals lead to lipemia (raised fat levels in the blood, in particular in the form of very low density lipoprotein or as chylomicrons), which has been shown to increase several inflammatory markers in the blood; perhaps the best known one is tumor necrosis factor-alpha (TNF-alpha).

To investigate further the cause of postprandial inflammation, Scottish scientists have studied the role of bacterial endotoxin, a lipopolysaccharide (LPS) that is normally present in the intestines in large quantities; it's potentially an inflammatory antigen. The findings of this study are published in the American Journal of Clinical Nutrition.

What was done

Twelve healthy volunteers (average age 32) were recruited - they were all 'occasional smokers'. They were selected because smoking may contribute to the circulating endotoxin via absorption of small quantities of smoke-derived LPS in the lung.

On 4 separate visits one week apart, each participant received either: no meal; a high-fat meal; no meal and 3 cigarettes; or a high-fat meal and 3 cigarettes. The individual participants were allocated to these treatments in random order.

The high-fat meal consisted of a cup of tea and 3 slices of toast spread with 50 grams of butter. Blood was taken for estimation of plasma LPS at baseline (twice), and ½, 1, 1½, 2, 3, and 4 hours after treatment. Triglycerides and C-reactive protein (CRP, another inflammatory marker) were measured at 2 and 4 hours.

What was found

Plasma endotoxin levels at baseline averaged 8.2 picograms/mL (pg/mL). At 30 minutes they increased temporarily (up to 20-25 pg/mL), but by 1 hour they leveled off for the rest of the 4-hour period.

Using the average of all time points after the treatment, the values for the 4 groups were: no meal - 8.2 pg/mL (same as baseline); after high-fat meal - 12.3 pg/mL; after cigarettes - 10.3 pg/mL; and after high-fat meal and cigarettes - 12.6 pg/mL. The values for both high-fat meal groups were significantly greater than the baseline and 'no meal' values.

Because of the fluctuating nature of plasma endotoxin, the researchers added another test, the 'endotoxin neutralization capacity' of the blood. This provided confirmation of the first test, showing that a high-fat meal with or without cigarettes significantly reduced plasma endotoxin neutralization capacity, while 'no meal' and smoking alone had no such effect.

What the Findings May Mean

Increased plasma endotoxin has been found after colonoscopy, major surgery, extreme physical exertion, and acute exposure to large amounts of alcohol (which breaks down the natural intestinal barrier). So the concept of fluctuating endotoxin levels is not entirely new. But this study links LPS increases to high-fat meals, suggesting that postprandial inflammation is a possibility under these circumstances. And such low-grade inflammation may be sufficient to contribute to 'activation' of the endothelial cells (the cells that line the arteries), the first step in the process of atherosclerosis. It's interesting to note that both olive oil and resveratrol, which have well-known anti-atherosclerotic properties, are powerful inhibitors of bacterial endotoxin in lab tests.

Whether you have followed the scientific results and arguments above or not, the practical conclusion supports what we know from other studies - high-fat meals should be avoided if one intends to keep healthy.