How can I raise my high‑density lipoprotein (HDL) cholesterol?

How to Raise HDL Cholesterol

The most effective strategy to raise HDL cholesterol is regular aerobic exercise combined with weight loss, which together can increase HDL-C by 10-13%, while pharmacologic options like niacin or fibrates should be reserved for patients who fail lifestyle modifications after 3-6 months. 1, 2

Lifestyle Modifications: First-Line Approach

Exercise (Most Effective Single Intervention)

• Engage in at least 150 minutes per week of moderate-intensity aerobic exercise, which increases HDL-C by 3.1-6 mg/dL (0.08-0.15 mmol/L) 3, 1
• Aerobic exercise totaling 1,500-2,200 kcal/week of energy expenditure provides the greatest HDL benefit 1
• Exercise is more effective at raising HDL than dieting alone, as it positively affects HDL metabolism enzymes including increased lipoprotein lipase activity and reduced hepatic triglyceride lipase clearance 4
• Resistance training can be combined with aerobic exercise, though aerobic activity provides superior HDL elevation 3

Weight Loss

• Each kilogram of sustained weight loss increases HDL-C by 0.4 mg/dL (0.01 mmol/L) 1
• Target a 5-10% body weight reduction, which when combined with exercise can increase HDL-C by 10-13% 2
• Weight loss achieved through exercise is more effective at raising HDL than weight loss through dieting alone 4
• Visceral adiposity (intra-abdominal fat) is particularly important to target, as it correlates negatively with HDL-C levels 4

Dietary Modifications

• Replace saturated fats with monounsaturated fats from sources like olive oil, avocados, and nuts—this has a neutral or minimal effect on HDL-C but improves overall lipid profile 1
• Ensure sufficient unsaturated fat intake (15-20% of calories) while keeping saturated fat low (7-10% of calories) 2
• Limit refined carbohydrates and sugars, especially those high in fructose/sucrose, as replacing fat with carbohydrates decreases HDL-C by 0.1 mmol/L for every 10% energy substitution 1
• Increase soluble fiber intake to >10 g/day 3

Alcohol and Smoking

• Moderate alcohol consumption (up to 20-30 g/day in men, 10-20 g/day in women) is associated with increased HDL-C levels compared to abstainers 1
• Smoking cessation can increase HDL levels by up to 30% 3

Pharmacologic Therapy: When Lifestyle Fails

Timing of Pharmacologic Intervention

• Consider pharmacological therapy between 3-6 months if lifestyle modifications are insufficient to achieve target HDL-C levels 1
• The magnitude of HDL-C increase from lifestyle changes alone is typically only 3-6 mg/dL, which may be inadequate for high-risk patients 1

Niacin (First-Line Pharmacologic Option)

• Nicotinic acid (niacin) is the most effective pharmacological treatment currently available for elevating HDL-C, increasing levels by 25-35% at the highest doses 1, 5, 6
• Low doses (≤2 g/day) have minimal effect on glycemic control in diabetic patients 1
• However, raising HDL cholesterol pharmacologically in diabetic patients is very difficult since niacin is relatively contraindicated in this population 3
• Extended-release formulations combined with laropripant reduce flushing side effects 5

Fibrates (Second-Line Option)

• Fibrates (gemfibrozil, fenofibrate) can raise HDL cholesterol levels significantly without affecting glycemic control 3, 1
• Gemfibrozil demonstrated a 24% decrease in cardiovascular events in diabetic subjects with prior cardiovascular disease and low HDL in the VA-HIT trial 1
• The combination of statins with fibrates (especially gemfibrozil) has been associated with increased risk of myositis, so fenofibrate is preferred when combining with statins 1

Emerging Therapies

• Novel agents in clinical trials include cholesterol ester transfer protein (CETP) inhibitors, apolipoprotein A-I Milano, D4F, dual peroxisome proliferator-activated receptor (PPAR) agonists, and rimonabant 5, 6
• These agents carry the potential to markedly reduce coronary disease incidence when used alone or in combination with existing therapies 6

Target Goals

• Aim for HDL-C >40 mg/dL (1.02 mmol/L) in men and >50 mg/dL (1.28 mmol/L) in women 3, 1
• Women may require HDL goals 10 mg/dL higher than men due to baseline differences 1

Critical Considerations

For Diabetic Patients

• Raising HDL cholesterol pharmacologically in diabetic patients is very difficult since the most effective agent (nicotinic acid) is relatively contraindicated 3
• Fibrates become the preferred pharmacologic option in this population as they can raise HDL significantly without affecting glycemic control 3
• Improved glycemic control should be the first priority, as optimizing diabetes management can improve the entire lipid profile 3

Combined Approach

• Combining a healthy diet with weight loss and physical activity can increase HDL-C by 10-13%, which when combined with interventions affecting other cardiovascular risk factors contributes to overall cardiovascular disease risk reduction 2
• The specific HDL subfractions that improve with lifestyle interventions include HDL2, apolipoprotein A-I, and pre-beta1 subfractions 4

Important Limitations

• Although HDL cholesterol is a powerful predictor of cardiovascular disease, it is difficult to raise HDL cholesterol levels without pharmacological intervention 1
• Even with optimal LDL-lowering using intensive statin therapy, substantial residual cardiovascular risk remains, making HDL elevation an important complementary strategy 5, 7