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

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Abstract

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 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.

Section snippets

Carbohydrate-induced hypertriglyceridemia – a genuine risk?

Adoption of a high-carbohydrate diet – especially a diet high in sugars and high-glycemic-index starches – often leads to an elevation of fasting triglyceride level, typically associated with a decrease in HDL cholesterol and, in many individuals, a reduction in LDL particle size [1], [2]. This fact has led to much “revisionist” commentary questioning the appropriateness of carbohydrate-rich diets from the standpoint of their impact on vascular health [3], [4], [5], [6]. It is demonstrably true

The impact of LDL and HDL size

The above considerations suggest that, even if carbohydrate-induced hypertriglyceridemia is not totally benign from the standpoint of vascular risk, the attendent risk is likely to be trivial compared to that associated with insulin resistance syndrome. However, what about the impact of elevated triglycerides on the size of LDL and HDL particles? Transfer of cholesterol esters from these lipoproteins to VLDL or chylomicrons, catalyzed by cholesterol ester transfer protein (CETP), reduces the

Clinical experience with fibrate therapy

An overview of controlled clinical trials with fibrate drugs is reasonably consistent with this interpretation. These drugs can increase the rate of triglyceride clearance by inducing LPL while suppressing hepatic production of apolipoprotein C-III, a physiological LPL inhibitor; they thus tend to lower serum triglycerides while boosting LDL particle size and HDL cholesterol [67]. The latter increase also reflects up-regulation of hepatic production of apoA-I [68]; another potentially

High-carbohydrate diets decrease HDL particle number

Which brings us to the one clear drawback of high-carbohydrate diets – whether or not they raise triglycerides, they usually induce reductions in HDL cholesterol and apoAI [40], [41]. This reflects the fact that saturated fat, by a mechanism that remains to be defined, increases the translatability of apoA-I mRNA in hepatocytes – thereby increasing hepatic secretion of apo-Al [74], [75]. The results of clinical feeding studies suggest that oleic acid shares this property, albeit to a lesser

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