HDL cholesterol is often known as good cholesterol. Early on, research showed that HDL may protect against heart disease.
But, trials in drugs that raise HDL failed to show any benefit. Furthermore, a recent paper found that people with high HDL(>80mg/dL) have higher rates of all-cause and cardiovascular disease mortality.
Many people who undertake a low carb or keto diet notice that their HDL levels rise on the diet. We chalk this up to the saturated fat intake. Evidence strongly suggests that saturated fat increases HDL.
So, this begs the question: Why does saturated fat raise HDL? Furthermore, is this even a good thing?
Why does saturated fat raise HDL?
This story actually begins in a place that is clearly a favorite topic here: The gut. Evidence overwhelmingly shows that saturated fat acutely increases metabolic endotoxemia more than polyunsaturated fats, which are protective. Note: Metabolic endotoxemia is an excessively leaky barrier, in this case the gut, that allows bacterial components in to the blood causing inflammation.
However, over a longer timeline, the metabolic endotoxemia caused by saturated fat returns to normal. This must be related to some adaptation occurring with prolonged high saturated fat intake.
Earlier evidence indicates that there is a moderate association(0.43) between HDL cholesterol and intestinal permeability in healthy men with normal glucose levels. Thus, higher saturated fat intake may increase HDL by increasing intestinal permeability, aka leaky gut.
But, is there another model that suggests greater intestinal permeability increases HDL to give us more confidence? Yes, alcohol is another dietary factor that increases both intestinal permeability and HDL.
But why does this happen?
Why HDL increase with “leaky gut”?
So, what’s the purpose of raising HDL when intestinal permeability is greater? Well, first off, we have to quash a major myth. Most people believe that the liver makes HDL, but the gut actually makes it too. In fact, in mice, intestinal derived HDL makes up 30% of total serum HDL.
Interestingly, this intestinal HDL is dumped into the portal vein, which travels directly to the liver. There must be a purpose for this.
As it turns out, there is. When the gut becomes more permeable, LPS, aka endotoxin, enters the portal vein and binds to something called lipopolysaccharide-binding protein(LBP). On its own, this LBP-LPS complex would enter the liver, bind to toll-like receptor-4, and induce high levels of inflammation.
This is where intestinally-derived HDL comes in. HDL made by the intestine enters the portal vein and binds to this LBP-LPS complex. When HDL gets in on the action, it masks LPS from the liver, and prevents inflammation.
Therefore, intestinally-derived HDL increases to protect the liver when gut permeability increases. This mechanistic data strongly supports the established idea that saturated fat increases intestinal permeability.
Furthermore, this provides a logical explanation for the link between higher saturated fat intake and higher HDL. Higher saturated fat intake increases HDL because it increases intestinal permeability.
It is clearly beneficial to increase HDL under higher saturated fat intake to protect the liver. But, it’s almost certainly not a good idea to increase intestinal permeability when you don’t have to.
This idea supports the notion that high saturated fat intake may not be the best idea for health and wellness assuming calories, BMI, etc are all held constant.