HDL Cholesterol

Why HDL Cholesterol Testing Matters

1. Exercise - Most Effective HDL Intervention

Aerobic exercise:150-300 min/week moderate to vigorous intensity. Raises HDL 3-9 mg/dL (5-15%). Running, cycling, swimming most effective

High-intensity interval training:May increase HDL more than moderate intensity. 20-30 min sessions 2-3x/week

Resistance training:Weight lifting 2-3x/week modestly raises HDL, especially combined with aerobic exercise

Duration matters:HDL increase proportional to exercise duration. Need consistent 3-4 months to see maximal HDL rise

Mechanism:Exercise increases lipoprotein lipase and hepatic lipase, enzymes that remodel lipoproteins and raise HDL

2. Weight Loss and Body Composition

Weight loss:Each 6 lbs lost raises HDL ~1 mg/dL. Effect most pronounced if overweight/obese

Visceral fat reduction:Abdominal fat lowers HDL more than subcutaneous fat. Measure waist circumference—target <40"men, <35"women

Build muscle mass:Higher lean body mass associated with higher HDL. Resistance training helps

Avoid crash dieting:Severe caloric restriction transiently lowers HDL. Gradual weight loss (1-2 lbs/week) preferred

Maintain weight loss:HDL improvements sustained only if weight loss maintained

3. Dietary Strategies

Mediterranean diet:Olive oil, nuts, fish, vegetables. Raises HDL 3-5 mg/dL and improves HDL function

Omega-3 fatty acids:2-4g EPA+DHA daily. Modest HDL increase (2-3 mg/dL) but improves particle function

Monounsaturated fats:Olive oil, avocados, nuts. Replace saturated fats with MUFA to raise HDL

Avoid trans fats:Trans fats lower HDL. Eliminate partially hydrogenated oils

Moderate alcohol:1-2 drinks daily raises HDL 3-5 mg/dL. However, also raises triglycerides. Not recommended solely to raise HDL

Purple/blue foods:Anthocyanins in berries, red wine, purple vegetables may improve HDL function

4. Address Metabolic Dysfunction

Improve insulin sensitivity:Low HDL often reflects insulin resistance. Metformin 1000-2000 mg daily, weight loss, exercise improve insulin sensitivity and raise HDL

Treat diabetes:Optimal glycemic control (HbA1c <7%) improves HDL. GLP-1 agonists and SGLT2 inhibitors modestly increase HDL

Lower triglycerides:TG >150 mg/dL suppresses HDL. Reduce simple carbs, lose weight. If TG >200 mg/dL, fibrate therapy raises HDL 10-20%

Thyroid optimization:Hypothyroidism lowers HDL. Ensure TSH 0.5-2.5 mIU/L

Testosterone:Low testosterone in men associated with low HDL. Consider evaluation if HDL <35 mg/dL with low muscle mass

5. Lifestyle Factors

Smoking cessation:Quitting raises HDL 3-10 mg/dL within weeks. Smoking makes HDL dysfunctional even if level is normal

Adequate sleep:7-9 hours nightly. Sleep deprivation lowers HDL

Stress management:Chronic stress lowers HDL via cortisol. Meditation, mindfulness help

Medications that lower HDL:Beta-blockers, thiazide diuretics, anabolic steroids. Discuss alternatives with doctor if HDL low

Don't use niacin:Niacin raises HDL 15-35% but doesn't reduce cardiovascular events and causes flushing, hyperglycemia. No longer recommended for low HDL

Low HDL Cholesterol

• Low HDL itself causes no direct symptoms. Symptoms relate to associated conditions:
• Metabolic syndrome:Abdominal obesity, fatigue, acanthosis nigricans (dark skin patches)
• Diabetes:Polyuria, polydipsia, blurred vision if poor control
• Coronary disease:Angina if low HDL contributed to atherosclerosis over years
• Tangier disease:Orange tonsils, hepatosplenomegaly, neuropathy if genetic severe HDL deficiency (<10 mg/dL)

Note: Low HDL is asymptomatic. It increases cardiovascular risk silently over decades. Screen regularly and address underlying causes.

High HDL Cholesterol

• Very high HDL (>100 mg/dL) is generally benign:
• Usually reflects genetic variation (CETP deficiency)
• No symptoms
• Paradoxically, extremely high HDL (>90-100 mg/dL) may not be protective—U-shaped relationship in some studies

Note: Extremely high HDL (>120 mg/dL) rarely indicates a problem but offers no additional benefit over 60-80 mg/dL.

Low HDL Cholesterol:

• Low HDL (<40 men, <50 women) causes:
• Metabolic syndrome:Insulin resistance, abdominal obesity, hypertriglyceridemia (most common)
• Sedentary lifestyle:Physical inactivity is primary modifiable cause
• Smoking:Lowers HDL and impairs function
• Obesity:Especially visceral adiposity
• Diabetes:Poorly controlled diabetes lowers HDL
• Hypertriglyceridemia:Inverse relationship—high TG lowers HDL via lipid exchange
• Genetic:Familial low HDL, Tangier disease (homozygotes have HDL <5 mg/dL), LCAT deficiency
• Medications:Beta-blockers, thiazide diuretics, anabolic steroids, progestins

High HDL Cholesterol:

• High HDL (>60 mg/dL) causes:
• Exercise:Regular aerobic exercise is primary cause of elevated HDL
• Leanness:Low body fat percentage
• Genetics:CETP deficiency, cholesterol ester transfer protein variants
• Moderate alcohol:1-2 drinks daily (not recommended to start drinking for HDL)
• Estrogen:Women have higher HDL premenopause. Estrogen replacement therapy raises HDL
• Medications:Fibrates, statins (modest 5-10% HDL increase)
• Extreme HDL (>100 mg/dL):Usually genetic (CETP deficiency). May not be additionally protective

HDL and Cardiovascular Risk - Observational Data

Framingham and other cohort studies show inverse relationship between HDL and cardiovascular risk. Each 1 mg/dL increase in HDL correlates with 2-3% lower cardiovascular risk. HDL <40 mg/dL in men and <50 mg/dL in women approximately doubles cardiovascular risk. However, this is association, not proven causation.

Source:Gordon DJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Circulation. 1989;79(1):8-15.

HDL-Raising Therapy Fails to Reduce Events

Multiple trials of HDL-raising therapies (niacin, CETP inhibitors) failed to reduce cardiovascular events despite successfully raising HDL 20-40%. AIM-HIGH, HPS2-THRIVE (niacin) and dal-OUTCOMES (dalcetrapib CETP inhibitor) all showed no benefit. This proved raising HDL pharmacologically doesn't reduce cardiovascular risk—HDL is a marker, not a target.

Source:Boden WE, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.

HDL Functionality vs Quantity

HDL cholesterol efflux capacity (ability to remove cholesterol from macrophages) predicts cardiovascular events independent of HDL level. Patients with high efflux capacity have lower risk even with low HDL, while those with low efflux have higher risk despite high HDL. This suggests HDL function is more important than quantity, but efflux testing is not widely available.

Source:Rohatgi A, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014;371(25):2383-2393.

Exercise and HDL

Meta-analyses of exercise interventions show aerobic exercise raises HDL 3-9% (typically 2-8 mg/dL). Effect is dose-dependent—more exercise, greater HDL increase. Combination of aerobic and resistance training is most effective. HDL increase occurs within 3-4 months and requires ongoing exercise to maintain. This makes exercise the most effective HDL-raising intervention.

Source:Kodama S, et al. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol:a meta-analysis. Arch Intern Med. 2007;167(10):999-1008.

Very Low HDL and Metabolic Syndrome

HDL <40 mg/dL is a component of metabolic syndrome and strongly associated with insulin resistance. Low HDL in metabolic syndrome reflects underlying metabolic dysfunction rather than being causal. Treatment focuses on weight loss, exercise, and treating insulin resistance (metformin, GLP-1 agonists) which secondarily raise HDL. Fibrates raise HDL but don't reduce cardiovascular events unless triglycerides >200 mg/dL.

Source:Grundy SM, et al. Diagnosis and management of the metabolic syndrome:an AHA/NHLBI scientific statement. Circulation. 2005;112(17):2735-2752.

Frequently Asked Questions About HDL Cholesterol