How the Latest Research May Shed Light on Serum Cholesterol

It was such a simple sound bite: Know your number and know your risk. When research emerged in the 1980s implicating dietary and serum cholesterol in the development of heart disease, cholesterol became the nutrient that everybody loved to hate.

Over time, science slowly moved the needle away from this mindset. “Good” and “bad” serum cholesterol were delineated, and more recently, studies determined that eating cholesterol-rich foods didn’t actually increase serum cholesterol like we once thought. And while some still maintain that lower total serum cholesterol is always best, more recent research challenges the validity of measuring cholesterol as a singular marker of cardiovascular health. So where does the medical community stand now on serum cholesterol?

What is Cholesterol?

First, a refresher. Manufactured by the liver, cholesterol’s functions extend well beyond the cardiovascular system. It’s the structural backbone to sex hormones, including testosterone, estrogen and progesterone (in addition to the adrenal hormone cortisol), and is crucial to brain function, both as part of myelin sheath structure and its role in nerve impulse conductivity. Because it is required to synthesize vitamin D from sun exposure, cholesterol is relevant to the immune and skeletal systems. And in cell membranes, cholesterol provides structural support and may also act as an antioxidant.

There’s even evidence that cholesterol may play a role in protecting against bacterial and parasitic infection.

Serum cholesterol travels through the blood stream within lipoproteins, of which the two most abundant are low-density lipoprotein and high-density lipoprotein. LDL carries cholesterol from the liver to peripheral tissues, while HDL carries cholesterol back to the liver for excretion or recycling. Routine cholesterol panels typically include total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. LDL and HDL cholesterol levels measure the amount of cholesterol carried in these lipoproteins, and many health professionals rely on these figures to gauge risk for cardiovascular and coronary artery disease.

What if "Normal" Does Not Equal "Healthy"?

This is where it gets interesting. Studies have found that up to 75 percent of patients hospitalized for heart attacks had normal to optimal serum LDL levels, and in 2013, revised guidelines from the American Heart Association and American College of Cardiology removed LDL cholesterol target levels and recommended that doctors not prescribe cholesterol-lowering medication based on cholesterol levels alone — a significant departure from long-held advice.

The key to understanding LDL cholesterol’s risks and rewards may lie in the size and density of its particles, which range from large, buoyant, cholesterol-rich particles to small, dense particles low in lipids. Since everyone has a mix of different types of LDL particles at any given time, some practitioners are testing for serum cholesterol “phenotype” patterns to discern composition (see sidebar).

Pattern A describes having mostly large, more buoyant LDL particles and is linked with good cardiovascular health, while pattern B refers to having mostly smaller, more dense LDL particles that are more prone to oxidation — and therefore associated with greater risk of atherosclerosis and higher overall cardiovascular disease risk. So whereas a person with low triglycerides, high HDL cholesterol and slightly elevated total and LDL cholesterol with pattern A phenotype (big, buoyant particles) may not be at increased risk for atherosclerosis or cardiovascular disease, a person with low to normal HDL cholesterol and normal total and LDL cholesterol levels with pattern B phenotype (small, dense particles) may indeed be at increased risk.

LDL particle size and density are influenced by genetics, diet and body weight — and dietary interventions have demonstrated measurable effects. More long-term studies are needed to help shape recommendations, but some researchers are exploring the effect of diet and weight loss on LDL patterns.

While the mechanisms are not yet understood, they include:

  • Higher intakes of saturated fat may increase large, buoyant LDL particles.
  • Reducing carbohydrates may reduce small, dense LDL particles.
  • Reducing dietary fat may reduce total LDL cholesterol, but specifically lowers large, buoyant particles.
  • Weight loss has been shown to improve LDL patterns in overweight men.
  • A high-carbohydrate, low-fat diet has been shown to shift study participants from pattern A to pattern B.
  • Study participants who started out as pattern B on a high-fat diet remained pattern B on a low-fat diet.

Although the clinical value of measuring LDL patterns remains hotly debated, many agree that more research is warranted since findings potentially could change the landscape surrounding serum cholesterol. In the meantime, staying up to date on emerging research and new practices is advice that any practitioner can get behind.

Robin Foroutan
Robin Foroutan, MS, RDN, is a National Spokesperson for the Academy of Nutrition and Dietetics who specializes in integrative medicine, functional medicine and holistic healing. She practices privately and at the Morrison Center.