How can HDL (High-Density Lipoprotein) levels be increased in a healthy adult?

How to Increase HDL Cholesterol

Start with lifestyle modifications as the foundation: engage in at least 150 minutes per week of moderate-intensity aerobic exercise, achieve a 5-10% weight loss if overweight, quit smoking immediately, and modify your diet to reduce saturated fats while incorporating monounsaturated fats. 1

Lifestyle Interventions (First-Line Approach)

Exercise - The Most Effective Single Intervention

• Aerobic exercise totaling 1,500-2,200 kcal/week of energy expenditure increases HDL-C by 3.1-6 mg/dL (0.08-0.15 mmol/L) 1
• A minimum threshold of 1,100 kcal of energy expenditure per week is required to elicit significant HDL increases 1
• This translates to approximately 150 minutes per week of moderate-intensity activity (brisk walking, cycling) or 75 minutes per week of vigorous activity 1
• Exercise enhances skeletal muscle's ability to utilize lipids and increases enzymes responsible for HDL metabolism 1
• The effect is dose-dependent—more exercise produces greater HDL increases 1

Weight Management

• Each kilogram of sustained weight loss increases HDL-C by 0.4 mg/dL (0.01 mmol/L) 1
• Target a 5-10% reduction in body weight, which also decreases triglycerides by 20-30% when maintained 1
• Weight loss is particularly effective when combined with exercise 2

Smoking Cessation

• Stop smoking immediately, as cessation directly contributes to HDL-C elevation 1
• This is a non-negotiable intervention with proven benefit 3

Dietary Modifications

Fat Quality Matters More Than Quantity:

• Replace saturated fats with monounsaturated fats (MUFAs) from sources like olive oil, avocados, and nuts 1
• Keep saturated fat intake to <7% of total energy 4
• This substitution has neutral or minimal effect on HDL-C but improves overall lipid profile 1

Carbohydrate Considerations:

• Limit refined carbohydrates and sugars—high-carbohydrate diets (especially high in fructose/sucrose) decrease HDL-C by 0.1 mmol/L for every 10% energy substitution from fat 1
• When consuming carbohydrates, choose low glycemic index foods with high fiber content to minimize HDL-C reduction 1
• Incorporate dietary fiber (particularly soluble fiber) from legumes, fruits, vegetables, and whole grains 1

Alcohol (With Important Caveats):

• 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
• However, this must be balanced against other health risks and is not recommended as a primary intervention 3

Pharmacological Interventions (When Lifestyle Modifications Are Insufficient)

When to Consider Medications

• Lifestyle modifications should be evaluated at regular intervals, with consideration of pharmacological therapy between 3-6 months if targets are not achieved 1
• The magnitude of HDL-C increase from lifestyle changes alone is modest (typically 3-6 mg/dL), and raising HDL-C without pharmacological intervention is difficult 4, 1

Medication Options (In Order of Priority)

1. Nicotinic Acid (Niacin):

• First-line pharmacological option for HDL raising 4
• Low doses of nicotinic acid (≤2 g/day) may not significantly affect glycemic control in diabetic patients 4
• Any deterioration in glucose control may be easily remediable by adjustment of hypoglycemic medications 4
• FDA-approved to increase HDL-C in patients with primary hyperlipidemia and mixed dyslipidemia 5
• Important caveat: Should be used with caution in patients with diabetes 4

2. Fibrates (Gemfibrozil, Fenofibrate):

• Second-line option for HDL raising 4
• Gemfibrozil demonstrated a 24% decrease in cardiovascular events in diabetic subjects with prior cardiovascular disease and low HDL in the VA-HIT trial 4
• Can effectively increase HDL cholesterol levels 4
• Critical safety consideration: Combination of statins with fibrates (especially gemfibrozil) may carry increased risk of myositis 4

3. Statins (Adjunctive Benefit):

• While primarily LDL-lowering agents, statins provide modest HDL increases 6
• The increase in HDL-C levels associated with statin treatment is a significant predictor for reduction in cardiovascular events 6

Target Goals

• Aim for HDL-C >40 mg/dL (1.02 mmol/L) in men 4
• Aim for HDL-C >50 mg/dL in women 4, 1
• Women may require HDL goals 10 mg/dL higher than men 4, 1

Important Considerations and Pitfalls

Gender Differences

• HDL-C response to lifestyle interventions shows gender differences, with men demonstrating more consistent improvements than women in some studies 1

Realistic Expectations

• The magnitude of HDL-C increase from lifestyle changes alone is typically only 3-6 mg/dL 1
• Combining a healthy diet with weight loss and physical activity can increase HDL-C by 10-13% 2
• Although HDL cholesterol is a powerful predictor of cardiovascular disease, it is difficult to raise HDL cholesterol levels without pharmacological intervention 4

Behavioral Interventions Are Essential

• Weight loss, increased physical activity, restricted intake of saturated fats, incorporation of monounsaturated fats, reduction of carbohydrate intake, and reduction of alcohol consumption are essential in managing dyslipidemia 4
• Smoking cessation and increased physical activity may increase HDL cholesterol 4

Combination Therapy Considerations

• In some cases, combined lipid therapy may be initiated 4
• The combination of statins with nicotinic acid, fenofibrate, and especially gemfibrozil has been associated with increased risk of myositis 4
• The risk of myositis may be increased with the combination of gemfibrozil and a statin or in patients with renal disease 4