Medium-chain triacylglycerols may not raise cholesterol.

Although medium-chain triacylglycerols (MCTs; 8:0 and 10:0) historically have been considered nonlipemic for most individuals, the report by Asakura et al (1) suggests that MCTs may be hypercholesterolemic in subjects with hypertriglyceridemia. Although the authors emphasized the hypercholesterolemia induced when MCTs progressively replaced corn oil in the carefully manipulated diet of these subjects, an alternative conclusion would be that the removal of dietary linoleic acid (18:2) was the primary cause of the plasma cholesterol elevation. Patients were adapted to a low-fat diet (containing 22% of energy as fat) in which 100% corn oil represented about one-half (12%/22%) of the total fat energy, including 8% of energy from 18:2. Progressive replacement of corn oil with MCTs resulted in <2% of energy from 18:2 in the final diet period (estimated as 20% of the intrinsic dietary fat) when 100% MCT was the added fat. This exchange progressively increased total cholesterol and triacylglycerol, with VLDL cholesterol and LDL cholesterol contributing equally to the elevation in total cholesterol, even though the increase in triacylglycerol was not significant. Thus, MCTs increased cholesterol in apolipoprotein B–rich lipoproteins as dietary 18:2 was reduced from 8% of energy to <2% of energy, the rise in total cholesterol being significant only when all the corn oil was removed. The background carbohydrate and other intrinsic fatty acids were constant and tended not to complicate interpretation here, which was a nice aspect of the study design. The failure to alter plasma triacylglycerol values in this study likely reflects the fact that high-carbohydrate diets (22% of energy as fat in this case) are hypertriglyceridemic in their own right. Had the total fat provided 30–40% of energy, MCTs might have had a more favorable effect on triacylglycerol. More important is the fact that 18:2 is the principle dietary fatty acid responsible for reducing hepatic fatty acid and triacylglycerol synthesis as well as VLDL secretion induced by carbohydrate, and presumably, induced by MCTs acting like carbohydrate (2). It is well appreciated that 18:2 also can enhance impaired LDL receptor activity (3), and carefully controlled fatty acid exchanges showed that progressive decreases in 18:2 per se raise total cholesterol when diet saturated fatty acids (SFAs) are high but stable, ie, when 18:1 replaces 18:2 (4). In the relative absence of dietary cholesterol, the resulting increase in LDL reflects an overproduction of LDL more than impaired clearance (5). We described these fatty acid interrelations previously in terms of the 18:2 threshold, wherein a specific amount of 18:2 is required to protect against total cholesterol elevation during consumption of SFAs and cholesterol (6). Examples of these fatty acid interrelations specifically involving MCTs were shown in normolipemic women (7) and hamsters (8). In fact, even when women were fed a low-18:2 diet (3% of energy), MCTs proved less cholesterolemic than a source of longer-chain SFAs (trilaurin). Futhermore, the hamster study found MCTs to be as cholesterol lowering as safflower oil in a cholesterol-free diet when 18:2 intake was adequate at 5% of energy. Although the current data support the 18:2 threshold concept, they are not definitive because, as is often the case in such experiments, 2 important variables (MCTs and 18:2) were altered simultaneously in opposite directions. Thus, it is not clear which is to blame, rising MCTs or declining 18:2. But substantial evidence would argue the latter is most critical (6). A more definitive design would have kept 18:2 constant at 5–6% of energy and exchanged MCTs for 18:1 or carbohydrate, which are considered neutral. Furthermore, the clinical data cited in support of the cholesterol-raising nature of MCTs (9, 10), like the comparison in normolipemic women (7), suffer the same shortcoming as the present study, ie, 18:2 was lower (and below threshold) in the MCT diet period than in the control diet period. The clinically relevant point is that an adequate source of 18:2 needs to be supplied when MCTs, or even carbohydrate, replace other longchain SFAs and monounsaturated fatty acids (5). In summary, MCTs should not be considered as SFAs that raise total cholesterol and LDL. Nor do they represent a substitute for 18:2 that will effectively reduce circulating apolipoprotein B–rich lipoproteins in the absence of 18:2.