Cholesterol is a waxy, fat-like substance present in all cells and in the blood. Cholesterol is carried through the blood on lipoproteins (e.g., low-density lipoprotein (LDL), high-density lipoprotein (HDL). High amounts of LDL particles cause plaque (i.e., fatty deposits) to build up in the arteries.^[1] Plaque hardens and narrows arteries, which restricts blood flow to areas of the body like the heart or brain and can cause a heart attack or stroke.

There are usually no signs or symptoms of high cholesterol. People with severely elevated LDL levels due to a genetic disorder may present with fatty skin deposits called xanthomas over parts of the hands, elbows, knees, ankles, or around the cornea of the eye.

High cholesterol is diagnosed using a blood test. Generally, LDL isn’t measured directly, but is instead estimated using LDL-cholesterol (LDL-C), which is a measure of the total amount of cholesterol contained within LDL particles and is highly correlated with LDL particle number.^[1] Blood samples can be collected in a fasted or nonfasted state.^[2] For people at low cardiovascular risk, an LDL-C goal of <116 mg/dL is recommended.^[3]

Pharmacotherapy typically begins with a statin prescribed up to the highest tolerated dose to reach the LDL-C goal set for the individual.^[2] If the LDL-C goal is not achieved with the maximum tolerated dose of a statin, combination therapy with ezetimibe is recommended.^[2] If the LDL-C goal is still not met, the addition of a PCSK9 inhibitor is recommended.^[2]

The supplement with the largest effect on LDL-C is red yeast rice, which is an inhibitor of endogenous cholesterol synthesis and works via the same mechanism of action as statins.^[4] Other supplements that can improve LDL-C are garlic,^[5] plant sterols and stanols,^[6] and beta-glucan (a soluble fiber primarily found in oats and barley).^[7]

Diet directly influences blood cholesterol levels. trans fats and saturated fats have the greatest effect on LDL-C, so replacing foods rich in these nutrients with foods rich in polyunsaturated or monounsaturated fat, and to a lesser extent whole-grain carbohydrates (especially ones rich in soluble fiber), reduces LDL-C.^[2]

Plant-based dietary patterns, including the Mediterranean diet, Portfolio diet, and Dietary Approaches to Stop Hypertension (DASH) diet, can reliably improve LDL-C.^[8]

Because excess body weight and abdominal fat contribute to high cholesterol, 150–300 minutes of moderate-intensity physical activity plus ≥ 2 resistance exercise sessions per week are recommended to support weight loss (5–10% of initial body weight), and more importantly, the maintenance of a healthy body weight.^[2] Other lifestyle modifications include limiting alcohol consumption (≤ 10 grams of pure alcohol per day) and quitting smoking.^[2]

High cholesterol is often caused by lifestyle habits, such as an unhealthy dietary pattern. However, genetics also strongly influence cholesterol levels. In people with familial hypercholesterolemia (FH), for example, there is typically a defect in the LDL receptor, which reduces the rate of LDL removal from the blood.^[9] FH is treated with pharmacotherapy, as lifestyle modifications alone are insufficient to achieve a healthy LDL-C level.