Triglycerides: Atherosclerotic or SAD-context Biomarker?

Something that's been on my mind a lot over the past couple of years is the meaning of fasting triglycerides in the context of a low carbohydrate diet.  Many, myself included, tend to look at fasting triglycerides and HDL as more important biomarkers and these two both tend to improve rather greatly on a low carbohydrate diet.  But I've always wondered if the reduced triglycerides of LC really indicate a "reduced risk" compared to the generally higher fasting triglycerides of healthy people eating a higher carbohydrate diet.

I blogged recently about triglycerides increasing on a high carb/low fat diet.  Basically, the elevated VLDL in the high carbers was attributed to reduced clearance and not overproduction in the liver.  So I got to asking if it's the triglycerides themselves that are atherogenic or if they are merely indicative of an underlying pathology.

An elevation of triglycerides reflecting decreased triglyceride clearance may not be pathogenic – relevance to high-carbohydrate diets

The fact that carbohydrate-rich diets often increase plasma triglycerides has led some to question the wisdom of such diets. This increase is primarily attributable to a decrease in the efficiency of triglyceride clearance -- whereas the elevation of triglycerides observed in insulin-resistant subjects stems mainly from increased hepatic production of VLDL particles. There is growing reason to suspect that the increased coronary risk associated with elevated triglycerides in Western epidemiology reflects the fact that high triglycerides are a marker for insulin resistance syndrome, rather than any inherent pathogenic role of triglycerides per se. Thus, endothelial dysfunction is seen only in those hypertriglyceridemic subjects who are insulin resistant, and is absent in patients whose markedly elevated triglycerides reflect genetically defective lipoprotein lipase activity. Triglyceride levels are relatively high in certain Third World societies which are virtually immune to coronary disease so long as they persist in their traditional very-low-fat diets; in Ornish's celebrated study, a moderate rise in triglycerides coincided with a marked reduction in coronary events. Although the particle size of both LDL and HDL tends to decrease when triglyceride levels are high, it is questionable whether this effect has a major pathogenic impact.

The author does, to this reader, appear to be biased in favor of low fat diets, and works for a diagnostics company - not sure what that might mean.

The one clear drawback of high-carbohydrate diets is a decrease in HDL particle number, resulting from decreased hepatic production of apoA-I; this effect is seen whether or not triglycerides increase. The very favorable effects of very-low-fat, whole food, quasi-vegan diets on LDL cholesterol, insulin sensitivity, and body weight appear to more than compensate for this decrease in HDL; it is notable that HDL levels tend to be quite low in Third World cultures at minimal risk for coronary disease. On the other hand, this decrease in HDL may be of more significance in the context of omnivore diets only moderately low in fat, as suggested by the fact that diets higher in unsaturated fats emerge as more protective in Western prospective epidemiology. The tendency of high-carbohydrate diets to boost triglycerides can be minimized by exercise training, supplemental fish oil, an emphasis on fiber-rich, low-glycemic-index whole foods, and the "spontaneous" weight loss often seen with ad libitum consumption of such diets -- measures which are highly recommendable whether or not triglycerides are a concern.

I am sharing the full text through Google docs:  HERE

The first reference in that article is, no surprise, Parks & Hellerstein on a similar topic:

Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms

Current trends in health promotion emphasize the importance of reducing dietary fat intake. However, as dietary fat is reduced, the dietary carbohydrate content typically rises and the desired reduction in plasma cholesterol concentrations is frequently accompanied by an elevation of plasma triacylglycerol.  We review the phenomenon of carbohydrate-induced hypertriacylglycerolemia, the health effects of which are among the most controversial and important issues in public health nutrition today. We first focus on how seminal observations made in the late 1950s and early 1960s became the basis for subsequent important research questions and areas of scientific study. The second focus of this paper is on the current knowledge of biological mechanisms that contribute to carbohydrate-induced hypertriacylglycerolemia. The clinical rationale behind mechanistic studies is this: if carbohydrate-induced hypertriacylglycerolemia shares a metabolic basis with endogenous hypertriacylglycerolemia (that observed in subjects consuming high-fat diets), then a similar atherogenic risk may be more likely than if the underlying metabolic mechanisms differ. The third focus of the paper is on both the positive metabolic changes that occur when high-carbohydrate diets are consumed and the potentially negative health effects of such diets. The review concludes with a summary of some important research questions that remain to be addressed. These issues include the level of dietary carbohydrate that induces carbohydrate-induced hypertriacylglycerolemia, whether the phenomenon is transient or can be avoided, whether de novo lipogenesis contributes to the phenomenon, and what magnitude of triacylglycerol elevation represents an increase in disease risk.

I encourage my readers to read both of these papers.  I'll be blogging a bit on ... you guessed it ... those pesky NEFA's in all of this sometime soon.  Please do add your thoughts in the comments!!

I am tending to believe that very elevated triglycerides are probably indicative of a problem (like the over 300 crowd), but the normal "risk assessment" marker for triglycerides need to be taken into account in the context of one's diet.  In this retard, hypertriglyceridemia is not necessarily pathologic.  The flip side of this is that the very low triglyceride levels celebrated in the VLC community may not be as indicative of improved health per se.