The Complex Relationship Between Dietary Cholesterol and Blood Cholesterol Levels

The impact of dietary cholesterol on blood cholesterol levels is a complex topic that has been debated for decades.

What Happens to Cholesterol We Eat

• Most dietary cholesterol is consumed in an “esterified” form bound to a fatty acid. This large molecule cannot be directly absorbed by the intestine.
• A minority of cholesterol in food is in an “unesterified” form that can potentially be absorbed.
• In the gut, the enzyme lipase can break down some of the esterified cholesterol into unesterified cholesterol, making it absorbable.
• Therefore, some of the cholesterol we eat can influence blood cholesterol levels, but for most people this effect is modest.

Cholesterol Absorption in the Intestine

• Cholesterol absorption occurs in the proximal small intestine through receptor proteins called Niemann-Pick C1-like 1 (NPC1L1). This pulls cholesterol from the gut lumen into intestinal cells.
• However, only unesterified or “free” cholesterol can bind to NPC1L1. Cholesterol bound to fatty acids cannot be absorbed through this mechanism.
• Most cholesterol in the gut lumen (~75-90%) comes not from food but from bile secreted by the liver. The body tries to eliminate excess cholesterol through bile, but some gets reabsorbed.
• People with genetic defects in NPC1L1 absorb far less cholesterol. This protects them from high blood cholesterol and heart disease.

Regulation of Cholesterol Absorption

• Another intestinal protein called ABCG5/G8 can pump excess cholesterol in the gut cell back into the intestinal lumen, limiting absorption.
• People with lower ABCG5/G8 function absorb more cholesterol. Blocking absorption with drugs like ezetimibe is an effective treatment for them.
• After absorption into gut cells, cholesterol enters the bloodstream packaged inside chylomicrons. It is then delivered mainly to the liver.
• Bacteria in the gut can convert cholesterol into other molecules like cholestanol that cannot be absorbed, reducing cholesterol uptake.

Individual Variation in Absorption

• On average, around 50% of cholesterol in the gut lumen is absorbed. But there is wide variability between people.
• Roughly 20-25% of people are “hypo-absorbers” who absorb very little dietary cholesterol due to genetic factors like low NPC1L1 function. Their blood cholesterol levels tend to be 15-25% lower over a lifetime.
• Another 20-25% are “hyper-absorbers” with high NPC1L1 function and low ABCG5/G8. They absorb more cholesterol, tend to have higher LDL and higher risk for heart disease.
• Doctors can tailor dietary advice based on a person’s absorber status. Limiting cholesterol has a bigger impact on hyper-absorbers.

Tests for Absorption Status

• HDL cholesterol level. Levels above 60 mg/dL may indicate a hyper-absorber. But this test is non-specific.
• LDL cholesterol or APOB response to a dietary cholesterol challenge. If levels increase substantially, may suggest hyper-absorption.
• Blood phytosterols. Elevated sitosterol and campesterol levels indicate cholesterol hyper-absorption and can guide treatment.

Implications for Dietary Recommendations

• For most people, dietary cholesterol has a minor impact on blood cholesterol levels compared to other factors like saturated fat. Analyses estimate that each additional egg per day increases LDL cholesterol by around 5-10 mg/dL.
• However, for the ~20% of people who are hyper-absorbers, limiting dietary cholesterol can have a more significant impact on LDL and heart disease risk.
• Knowing your absorber status through tests can help personalize dietary advice. Hypo-absorbers need not worry about dietary cholesterol, while hyper-absorbers may want to limit intake.
• Population-level recommendations to limit cholesterol intake are warranted given that hyper-absorbers are common enough. But individual variability should be considered.

High Cholesterol And Heart Disease Risk

In summary, dietary cholesterol can raise blood cholesterol levels, but the magnitude of effect varies considerably between people based on genetic factors that influence intestinal absorption. Understanding this nuance can help reconcile conflicting opinions and research on this topic.

While moderate limitation of cholesterol intake is prudent advice for the general public, individualized recommendations based on absorber status may enable more effective management of high cholesterol and heart disease risk.