How to lower Low-Density Lipoprotein (LDL) cholesterol?

How to Lower LDL Cholesterol

Start with therapeutic lifestyle changes (TLC) focusing on limiting saturated fat to <7% of total energy intake, adding plant stanols/sterols (2 g/day), and increasing soluble fiber (10-25 g/day), which together can lower LDL-C by approximately 20-30%. 1

Dietary Modifications (First-Line Approach)

Primary Fat Modifications

• Limit saturated fatty acids to <7% of total energy intake (ideally from <10% baseline), which represents the single most effective dietary intervention 1
• Eliminate trans-unsaturated fatty acids completely from the diet 1
• Restrict dietary cholesterol to <200 mg/day (avoid egg yolks, organ meats, high-fat dairy) 1

Fat Replacement Strategy

• Replace saturated fats with monounsaturated fats (olive oil, canola oil) or polyunsaturated fats (corn oil, nuts) rather than high-carbohydrate foods 1
• Replacing saturated fat with carbohydrates lowers LDL-C by approximately 0.21 mmol/L but raises triglycerides by 0.17 mmol/L, creating a neutral cardiovascular effect 2
• Replacing 1% of energy from saturated fat with polyunsaturated fat lowers LDL-C by 0.05 mmol/L; moving from highest to lowest quintile of saturated fat intake (approximately 7% difference) should lower LDL-C by 0.35 mmol/L or about 10% 2

Enhanced LDL-Lowering Additions

• Add plant stanols/sterols at 2 g/day, which lowers total cholesterol by 10-32 mg/dL and LDL-C by 8-29 mg/dL (approximately 10% reduction) 1, 2
  • Available in fortified margarine spreads, sesame seeds, peanuts, and soybeans 1
• Increase soluble (viscous) fiber to 10-25 g/day, which lowers LDL-C by approximately 5-10% 1, 3
  • Each gram of soluble fiber lowers LDL-C by approximately 2.2 mg/dL 1
  • Best sources: oat products, psyllium, pectin, guar gum, and konjac glucomannan (most effective per gram, lowering LDL-C by 0.2-0.35 mmol/L at 3.5-7.0 g/day) 1, 2

Weight Management and Physical Activity

• Achieve modest weight loss if overweight or obese, as this independently lowers LDL-C and improves the overall lipid profile 1
• Engage in regular aerobic physical activity, which reduces triglycerides and improves insulin sensitivity, contributing to overall lipid improvement 1

Timeline for Dietary Intervention

• Evaluate LDL-C response after 6 weeks of initial dietary changes 1
• If LDL-C goal not achieved after 6 weeks, intensify dietary modifications by reinforcing saturated fat and cholesterol reduction, adding plant stanols/sterols, and increasing soluble fiber 1
• Monitor adherence every 4-6 months once therapeutic lifestyle changes are established 1
• The ATP III guidelines recognize dietary limitations by reducing the trial period from 6 months to 12 weeks before considering medication 1

When to Add Drug Therapy

Drug therapy should be considered based on cardiovascular risk category and LDL-C levels after adequate trial of TLC 1:

High-Risk Patients (CHD or CHD equivalents)

• LDL-C goal: <100 mg/dL 1
• Initiate TLC at LDL-C ≥100 mg/dL 1
• Consider drug therapy at LDL-C ≥130 mg/dL (at 100-129 mg/dL, drug therapy is optional) 1

Moderate-Risk Patients (2+ risk factors, 10-year risk <20%)

• LDL-C goal: <130 mg/dL 1
• Initiate TLC at LDL-C ≥130 mg/dL 1
• Consider drug therapy at LDL-C ≥130 mg/dL for 10-year risk 10-20%, or ≥160 mg/dL for 10-year risk <10% 1

Low-Risk Patients (0-1 risk factor)

• LDL-C goal: <160 mg/dL 1
• Initiate TLC at LDL-C ≥160 mg/dL 1
• Consider drug therapy at LDL-C ≥190 mg/dL (at 160-189 mg/dL, drug therapy is optional) 1

Pharmacologic Options

First-Line: Statins

• Statins are the drug of choice for elevated LDL-C, particularly in patients with established cardiovascular disease or familial hypercholesterolemia 4, 5, 6
• Simvastatin inhibits HMG-CoA reductase, accelerating LDL-receptor expression and LDL-C uptake by the liver 5
• Maximum LDL-C reduction typically achieved by 4 weeks and maintained thereafter 5

Second-Line: PCSK9 Inhibitors

• Alirocumab (PRALUENT) is indicated to reduce myocardial infarction, stroke, and unstable angina in adults with established cardiovascular disease 4
• Recommended starting dosage: 75 mg every 2 weeks or 300 mg every 4 weeks subcutaneously 4
• LDL-lowering effect measurable as early as 4 weeks after initiation 4

Adjunctive Therapies

• Bile acid sequestrants lower LDL-C and are often used to augment statins and niacin 1, 6
• Niacin is particularly useful for combined hyperlipidemia with low HDL-C 1, 6

Common Pitfalls to Avoid

• Avoid replacing saturated fat with high-glycemic carbohydrates, as this raises triglycerides and lowers HDL-C, potentially negating cardiovascular benefits 1, 2
• Do not recommend fish oil for LDL-C lowering, as it may actually increase LDL-C despite lowering triglycerides (requires monitoring if used for hypertriglyceridemia) 1
• Ensure adequate trial of dietary intervention before declaring failure—comprehensive dietary changes can achieve 13-20% LDL-C reduction with good adherence 3, 7
• Do not underestimate cumulative dietary effects: Step 1 diet (-10%), dietary fibers (-5 to -10%), plant sterols/stanols (-10%), nut consumption (-8%), and soy protein (-3 to -10%) can sum to substantial LDL-C reduction 3