What does HDL measure and how can it be increased?

What HDL Measures and How to Increase It

HDL cholesterol measures the amount of cholesterol carried by high-density lipoproteins, which transport cholesterol from peripheral tissues back to the liver for excretion—functioning as a marker of reverse cholesterol transport and cardiovascular protection. 1

Understanding HDL Cholesterol

HDL cholesterol represents the cholesterol content within high-density lipoproteins that scavenge cholesterol from blood vessel walls and peripheral tissues, transporting it to the liver where it is converted to bile acids and salts or esterified for excretion. 1 Higher HDL levels inversely correlate with coronary artery disease risk, though recent evidence suggests HDL may not be causally protective but rather a marker of metabolic health. 2

Target HDL levels are >40 mg/dL for men and >50 mg/dL for women (with women requiring 10 mg/dL higher targets due to physiological differences). 3, 4

Evidence-Based Strategies to Increase HDL

Exercise: The Most Effective Intervention

Regular aerobic exercise combined with resistance training represents the most effective lifestyle intervention for raising HDL cholesterol. 4, 5

Specific exercise prescription:

• Minimum threshold: 30 minutes of moderate-intensity aerobic exercise, 5 times weekly, targeting 900-1200 kcal energy expenditure per week 4, 5, 6
• For healthy individuals: Prolonged moderate-intensity aerobic exercise at 70-80% heart rate reserve combined with low-intensity resistance training at 50% of 1 repetition maximum (1RM) 4, 5
• For dyslipidemia patients: Progress to 85% maximum heart rate with moderate-to-high intensity resistance training at 75-85% of 1RM 4, 5
• Dose-response relationship: Every 10-minute prolongation per session increases HDL by approximately 1.4 mg/dL, with exercise duration being more important than frequency or intensity 6

The evidence shows exercise can increase HDL by approximately 10-13% when combined with other lifestyle modifications. 7 Meta-analysis demonstrates a modest but significant mean increase of 2.53 mg/dL from aerobic exercise alone. 6

Dietary Modifications

Replace saturated fats with unsaturated fats rather than increasing carbohydrates, as this is critical for HDL optimization. 4, 5

Specific dietary interventions:

• Limit saturated fat to <7% of total daily calories 4
• Completely eliminate trans-unsaturated fatty acids (<1% of energy), which actively lower HDL 4, 5
• Increase monounsaturated fats (olive oil, canola oil) and polyunsaturated fats (corn oil, peanuts) 4, 5
• Minimize refined carbohydrates and added sugars, as high-carbohydrate diets reduce HDL levels—this effect is more pronounced with simple sugars than unprocessed grains 3, 4, 5
• Consume fish at least twice weekly for omega-3 fatty acids 4
• Limit dietary cholesterol to <200 mg/day 4

A critical caveat: Low-fat, high-carbohydrate diets can paradoxically reduce HDL cholesterol, particularly when carbohydrates come from refined sources rather than whole grains. 3

Weight Management and Smoking Cessation

Achieve and maintain BMI 18.5-24.9 kg/m², as excess adiposity adversely affects HDL levels. 4, 5 Weight loss is particularly important for patients with elevated triglycerides and low HDL. 5

Smoking cessation can increase HDL cholesterol by up to 30%—making it one of the single most impactful interventions. 4, 5, 7 This effect typically manifests as a 5-10% increase in HDL levels. 8

Alcohol Considerations

Moderate alcohol consumption (1-2 drinks daily) increases HDL by approximately 12% on average through increased HDL production. 3 However, alcohol is not recommended as a strategy to raise HDL due to associated risks including hypertriglyceridemia (especially in predisposed individuals), increased cancer risk, and potential for abuse. 3, 2 The antioxidant benefits attributed to red wine are unproven and can be obtained from non-alcoholic grape juice and fresh fruits. 3

Pharmacological Options

When Lifestyle Modifications Are Insufficient

After achieving LDL goals, if HDL remains low despite 3-6 months of lifestyle intervention, pharmacological therapy should be considered. 3

Niacin (nicotinic acid) is the most effective drug for raising HDL cholesterol (approximately 20% increase), but carries significant caveats—particularly adverse effects on blood glucose control in diabetic patients. 3, 4, 9 Niacin is FDA-approved to increase HDL-C in primary hyperlipidemia and mixed dyslipidemia, though the AIM-HIGH trial showed no reduction in cardiovascular events when added to statin therapy. 9

Fibrates (gemfibrozil, fenofibrate) effectively increase HDL and reduce triglycerides. 3, 4, 10 Gemfibrozil demonstrated a 34% relative reduction in serious coronary events in the VA-HIT trial among patients with low HDL and prior cardiovascular disease. 4 Fibrates are FDA-approved as adjunctive therapy to increase HDL-C in hypercholesterolemia and mixed dyslipidemia. 10

Statins increase HDL by at least 5% while primarily targeting LDL reduction. 8

Important safety consideration: Combination therapy with statins plus fibrates or niacin may be necessary to achieve targets but carries increased risk of myositis, particularly with gemfibrozil. 3 These combinations have not been adequately evaluated in outcomes studies for either efficacy or safety. 3

Monitoring Strategy

Measure lipid levels annually in adults with diabetes or cardiovascular risk factors, and every 2 years for low-risk individuals (those with LDL <100 mg/dL, HDL >50 mg/dL, and triglycerides <150 mg/dL). 3, 4

Evaluate lifestyle interventions at regular intervals, with consideration of pharmacological therapy at 3-6 months if targets are not achieved. 3, 4

Critical Clinical Pitfalls

Primary target remains LDL cholesterol—HDL raising is a secondary goal. 3 ATP III guidelines do not specify a specific HDL-raising goal, as evidence that pharmacologically raising HDL reduces cardiovascular events remains insufficient. 3 The focus should be on comprehensive cardiovascular risk reduction rather than HDL as an isolated target. 3

For patients with low HDL and high triglycerides (200-499 mg/dL), achieving the non-HDL cholesterol goal (total cholesterol minus HDL cholesterol) takes secondary priority after LDL goals are met. 3