Good Calories, Bad Calories

This process is easier to understand if we picture what’s actually happening in the liver. After we eat a carbohydrate-rich meal, the bloodstream is flooded with glucose, and the liver takes some of this glucose and transforms it into fat—i.e., triglycerides—for temporary storage. These triglycerides are no more than droplets of oil. In the liver, the oil droplets are fused to the apo B protein and to the cholesterol that forms the outer membrane of the balloon. The triglycerides constitute the cargo that the lipo-proteins drop off at tissues throughout the body. The combination of cholesterol and apo B is the delivery vehicle. The resulting lipoprotein has a very low density, and so is a VLDL particle, because the triglycerides are lighter than either the cholesterol or the apo B. (In the same way, the more air in the hold of a ship, the less dense the ship and the higher it floats in the water.) For this reason, the larger the initial oil droplet, the more triglycerides packaged in the lipoprotein, the lower its density.

The liver then secretes this triglyceride-rich VLDL into the blood, and the VLDL sets about delivering its cargo of triglycerides around the body. Throughout this process, known poetically as the delipidation cascade, the lipoprotein gets progressively smaller and denser until it ends its life as a low-density lipoprotein—LDL. One result is that any factor that enhances the synthesis of VLDL will subsequently increase the number of LDL particles as well. As long as sufficient triglycerides remain in the lipoprotein to be deposited in tissues, this evolution to progressively smaller and denser LDL continues. It’s this journey from VLDL to LDL that explains why most men who have high LDL cholesterol will also have elevated VLDL triglycerides. “It’s the overproduction of VLDL and apo B that is the most common cause of high LDL in our society,” says Ernst Schaefer, director of the lipid-metabolism laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. None of this, so far, is controversial; the details are described in recent editions of biochemistry textbooks.

How this process is regulated is less well established. In Krauss’s model, based on his own research and that of the Scottish lipid-metabolism researcher Chris Packard and others, the rate at which triglycerides accumulate in the liver controls the size of the oil droplet loaded onto the lipoprotein, and which of two pathways the lipoprotein then follows. If triglycerides are hard to come by, as would be the case with diets low in either calories or carbohydrates, then the oil droplets packaged with apo B and cholesterol will be small ones. The ensuing lipoproteins secreted by the liver will be of a subspecies known as intermediate-density lipoproteins—which are less dense than LDL but denser than VLDL—and these will end their lives as relatively large, fluffy LDL. The resulting risk of heart disease will be relatively low, because the liver had few triglycerides to dispose of initially.

If the liver has to dispose of copious triglycerides, then the oil droplets are large, and the resulting lipoproteins put into the circulation will be triglyceride-rich and very low-density. These then progressively give up their triglycerides, eventually ending up, after a particularly extended life in the circulation, as the atherogenic small, dense LDL. This triglyceride-rich scenario would take place whenever carbohydrates are consumed in abundance. “I am now convinced it is the carbohydrate inducing this atherogenic [profile] in a reasonable percentage of the population,” says Krauss. “…we see a quite striking benefit of carbohydrate restriction.”