Trans Fatty Acids: Unhealthy or Undebated 3

It goes without saying we avoid trans fat to avoid heart disease. The natural question to come from that simple observation is how strong is the evidence that consuming foods with trans fat, in substantial quantities, will lead to heart disease? The answer isn’t at all easy as only a handful of epidemiologic studies have been conducted to answer that question. And based upon the world’s paranoia regarding trans fat, those few studies are probably all we’ll ever have to draw conclusions from.

A Brief Description of Atherosclerosis
First and most important is the fact that heart disease or coronary artery disease is a cumulative disease (developing over twenty to forty years in most cases). In that time frame, atherosclerotic (fatty) plaques form in the artery wall, leading to potential occlusion of the artery (usually when a plaque ruptures). Tissues downstream and served by that artery describe the damage from the disease; thus an acute coronary occlusion leads to a heart attack and a carotid artery occlusion leads to an ischemic stroke.

Damage to those two end-organs is the focus of cardiovascular disease, although renal artery occlusions can occur. The fat in the fatty plaque comes primarily from circulating LDL-C particles that migrate into the artery wall and become trapped in the intimal layer. After being trapped, the rapidly oxidizing LDL-C particle signals a response similar to an inflammatory signal, which incites circulating monocytes to enter the artery wall. As the monocytes enter the artery wall they become tissue macrophages which function to consume the trapped, oxidized, LDL-C particles. Consuming the LDL-C particles en mass, the tissue macrophages become themselves overwhelmed and eventually die in the artery wall. As more die, the fatty goo builds up and the bump of fat starts to occlude the artery. Thus goes a simplified and quick version of how atherosclerosis develops.

How does that Relate to Trans Fatty Acid?
From the last blog, remember that trans fats can elevate LDL-C and lower HDL-C if consumed in quantities greater than roughly 5% of total daily calories. That increase has been cited as the physiologic basis for the relationship between trans fat intake and the development of atherosclerosis and heart disease.

The ultimate study of trans fat would take a population of representative citizens and randomize them to either receive trans fat or not, usually in a double blind fashion. Follow that group for roughly twenty to forty years and assess the development of atherosclerosis at the end of the study in all participants. That assessment, of course, would be blinded to the intake of trans fat. If this seems a little far-fetched, it’s because it is. The closest thing we have to the above definitive study is the epidemiologic approach to approximate the above study (if conducted rigidly).

Epidemiologic Evidence that Trans Fat intake Leads to Heart Disease
The closest thing to a real randomized and blinded trial over the time frame of disease development is as stated above, the epidemiologic study. It’s sometimes called an observational study because instead of controlling the study, one observes the participants. The observational study seeks to replace what we simply can’t do in the real world.

In the case of trans fat, the typical epidemiologic study follows a large group of participants (called a cohort) over a long period of time—usually five to ten years—and reports the average dietary intakes (derived from periodic questionnaires), relating that intake to some endpoint like heart attack or death. One of the most famous of all cohorts is the Framingham Study, which spun off numerous epidemiologic analyses of environmental exposures as they relate to disease. Other well recognized cohort studies are for example the Health Professionals Follow Up Study and the Nurses Health Study, both utilizing a large group of health care professionals.

Typically, at the outset the groups are asked to report their usual food intake from a very detailed questionnaire, then followed-up after a variable period of time with more questionnaires and possibly physical and laboratory analyses. At the end of some pre-specified time frame, the entire cohort is examined to see how many have died, how many had heart attacks and what the repeated food intake questionnaires revealed about the relationship between what they ate and the rate of heart attacks or cancer or some other specified endpoint.

The studies and the analyses are expensive and complex, but model as closely as possible the effect of a particular food or environmental factor relating exposure to disease. In the case of trans fat intake, the number of studies have been somewhat limited and have generated variable results.

For the sake of brevity I will continue this blog with an analysis of the actual studies. Each has strengths and weaknesses, but as I will show, there is no real evidence to condemn the usual (2.6% of energy) intake of trans fat.