Got Milk (fat globule membrane)?

Cardiovascular disease (CVD) is a general term for any pathological condition that involves the heart or blood vessels. Many of these diseases, and certainly those most commonly associated with Western societies, are a result of atherosclerosis – the thickening of artery walls through the buildup of plaques of fatty material. Although CVD was once thought to be primarily due to elevated cholesterol levels, it is now recognized^[1] that inflammation of the arteries is a necessary prerequisite for plaque formation.

That said, LDL infiltration of the artery walls is a major cause of inflammation^[2], and there is little debate among the medical community that high levels of LDL-cholesterol (LDL-c) is a risk factor for CVD. Two recent meta-analyses support this view. The first looked at over 38,000 patients taking statins^[3] and found a significant reduction in risk as LDL-c levels moved from above 175 mg/dL to below 50 mg/dL. Achieving an LDL-c below 100 mg/dL through statin therapy was associated with a 44% reduced risk of having a major CVD event, while levels below 50 mg/dL were associated with a 56% reduced risk. The second analysis looked at data from over 10,000 patients enrolled in 24 randomized, placebo-controlled trials of PCSK9 inhibitors^[4] and found that treatment reduced LDL-c by nearly half while simultaneously reducing the number of heart attacks by 51% and the odds of death from any cause by 55%.

What these studies serve to illustrate is that we now have two completely different drug therapies, statins and PCSK9 inhibitors, which reduce LDL-c by different methods and reduce the risk of CVD-related events. It stands to reason that other methods that reduce LDL may also reduce the risk of CVD. A first line of defense for the management of blood cholesterol levels is dietary intervention.

Dairy fat is typically around 70% saturated fat^[5] and makes up about a fifth of total saturated fat intake^[6] in the U.S. diet, making it a prime target for nutritional interventions. However, results from observational and experimental trials that evaluate the impact of dairy products on blood cholesterol levels are not conclusive. Notably, there is a lot of evidence^[6] from randomized controlled trials that diets high in saturated fat derived largely from butter fat increases LDL-c, whereas cheese intake results in lower LDL-c compared with butter of equal fat content, and may not increase LDL compared with a diet lower in saturated fat. Similarly, the results are fairly consistent in showing that whole milk increases LDL-c more than low-fat or skim milk, while whole-fat yogurt may reduce LDL-c.

The inconsistent findings with regard to dairy fat’s effects on blood cholesterol have been hypothesized to be owed, at least in part, to the milk-fat globule membrane^[7] (MFGM) – a three-layered membrane composed of proteins, lipids, and numerous minor bioactive sterols that encloses the milk fat globules. Figure 1 shows the basic processes used to make different dairy products. The MFGM is a very fragile compound that is preserved in cream and cheese, but destroyed during mechanical processing, such as the churning required to make butter or the homogenization of milk. It has been suggested to have numerous health benefits^[8], including cholesterol-lowering effects. The current study was an attempt to test the hypothesis that the effect of dairy fat on serum cholesterol levels is mediated by the presence (or absence) of the MFGM.

Figure 1: Dairy products in a nutshell

Observational and experimental evidence investigating the effect of dairy fat on serum cholesterol levels is conflicting and depends on the dairy product consumed. An intact milk-fat globule membrane (MFGM) present in some dairy foods, such as non-homogenized cream and cheeses, may explain the inconsistencies. The study under review tested this hypothesis.