Lipid Metabolism
LDL Particle Size
Let’s look at the LDL particle size, testing methods, and how LDL differs from Lp(a) in clinical management.
Below, you will find practical insights into cholesterol-related health risks and management
1. LDL Particle Size
LDL particles vary in size and density, which impacts their cardiovascular risk:
- Types:
- Large, Buoyant LDL (Pattern A): Good! Larger particles (~25-28 nm) with lower density are less likely to penetrate arterial walls. These are considered less atherogenic (lower risk for atherosclerosis).
- Small, Dense LDL (Pattern B): Bad! Smaller particles (~18-22 nm) with higher density are more prone to oxidation and penetration of the arterial wall. These are more atherogenic, increasing the risk of coronary artery disease, especially in metabolic syndrome or diabetes.
- Why It Matters: Small, dense LDL particles are associated with a 3-7 times higher risk of heart disease, even if total LDL cholesterol levels are normal. Their higher apolipoprotein B-100 (ApoB-100) content relative to cholesterol makes them more harmful.
- Factors Influencing Size: Genetics, high triglyceride levels, insulin resistance, and poor diet (e.g., high refined carbs) promote small, dense LDL. Exercise, weight loss, and low-carb diets can shift LDL toward larger, less risky particles.
- Takeaway: LDL particle size matters as much as total LDL cholesterol.
Small, dense LDL is a hidden risk, detectable through advanced testing.
2. Testing Methods for LDL
Several methods assess LDL and its associated risks, providing actionable data for clinical management:
- Standard Lipid Panel:
- Measures LDL cholesterol (LDL-C), typically calculated using the Friedewald equation: LDL-C = Total Cholesterol – HDL-C – (Triglycerides/5). Direct LDL-C measurement is used if triglycerides are high (>400 mg/dL).
- Normal range: <100 mg/dL (optimal); 100-129 mg/dL (near optimal); >130 mg/dL (elevated, per guidelines like AHA/ACC).
- Limitations: Doesn’t assess particle size or number, missing risks in some patients (e.g., those with normal LDL-C but high small, dense LDL).
- Apolipoprotein B (ApoB) Testing:
- Measures ApoB-100, the protein on each LDL particle, reflecting total LDL particle number.
One ApoB-100 per LDL particle makes this a direct marker of atherogenic particles. - Normal range: <90 mg/dL (optimal); higher levels indicate increased risk, even if LDL-C is normal.
- Advantage: Captures risk from small, dense LDL better than LDL-C.
- Measures ApoB-100, the protein on each LDL particle, reflecting total LDL particle number.
- LDL Particle Size and Number (Advanced Lipid Testing):
- NMR Lipoprofile: Uses nuclear magnetic resonance to measure LDL particle size and number (LDL-P).
High LDL-P (>1000 nmol/L) or a predominance of small, dense LDL indicates higher risk. - Gel Electrophoresis: Separates LDL particles by size to identify Pattern A (large) vs. Pattern B (small, dense).
- Use: Recommended for patients with metabolic syndrome, diabetes, or family history of heart disease.
- NMR Lipoprofile: Uses nuclear magnetic resonance to measure LDL particle size and number (LDL-P).
- Non-HDL Cholesterol:
- Calculated as Total Cholesterol – HDL-C, capturing all atherogenic lipoproteins (LDL, VLDL, Lp(a)). Useful when triglycerides are high or LDL-C is unreliable.
- Takeaway: Standard LDL-C testing is a start, but ApoB and advanced tests like NMR reveal hidden risks from small, dense LDL.
3. How LDL Differs from Lp(a) in Clinical Management
LDL and Lp(a) share structural similarities but differ significantly in clinical management due to their distinct properties and responses to treatment:
- Structural Differences:
- LDL: Composed of cholesterol (cholesteryl esters and free cholesterol), triglycerides, phospholipids, and ApoB-100.
Its primary role is cholesterol delivery to tissues. - Lp(a): An LDL-like particle with an additional apolipoprotein(a) (apo(a)) bound to ApoB-100.
Apo(a)’s kringle structures resemble plasminogen, contributing to prothrombotic and proinflammatory effects.
- LDL: Composed of cholesterol (cholesteryl esters and free cholesterol), triglycerides, phospholipids, and ApoB-100.
- Risk Profile:
- LDL: High LDL-C or ApoB levels drive atherosclerosis by depositing cholesterol in arteries. Small, dense LDL is particularly risky.
- Lp(a): High levels (>50 mg/dL or ~125 nmol/L) increase atherosclerosis and thrombosis risk due to cholesterol deposition and apo(a)’s interference with clot breakdown. Lp(a) is an independent risk factor, less influenced by lifestyle.
- Genetic vs. Lifestyle Influence:
- LDL: Levels are influenced by genetics, diet (saturated fats, trans fats), exercise, and obesity.
It is modifiable with lifestyle changes and medications. - Lp(a): Levels are primarily genetic, determined by the LPA gene, and minimally affected by diet or exercise.
This makes Lp(a) harder to manage.
- LDL: Levels are influenced by genetics, diet (saturated fats, trans fats), exercise, and obesity.
- Treatment Approaches:
- LDL:
- Nutrition and Lifestyle:
A healthy fat diet that is moderate and excludes any vegetable oils and seed oils (promoted heavily today as healthy). Avoid these processed oils, high in Omega 6 and trace chemicals. They are proinflammatory and very bad for you.
Replace processed seed oils and hydrogenated oils, such as margarine-type products, with extra-virgin olive oil, coconut oil, avocado oil, ghee, butter, lard, or any other saturated animal fats, which are more stable and much healthier than vegetable oils.
Consumed in moderation, they provide satiety and vitamins. Our ancestors have used these natural products for thousands of years! Sugar and lack of exercise, combined with chronic stress and possibly the modified and ultraprocessed dairy, may raise your LDL.
Moderate daily exercise and weight loss can lower LDL-C and shift LDL toward larger, less dense particles.
Lose weight by consuming low GI (glycemic index) foods. Avoid frying! Instead, use steaming and oven roasting, baking and broiling. Fried foods are much higher in calories and the oils are bad for you they oxidize through heat. Never eat fast food – it lacks nutritional value, is high in bad fats, and is super high in calories.
Think that someone who eats a cheeseburger would have to run 15 km to consume those 800+ calories.
Increase the amount of plant-based foods, such as legumes, leafy green vegetables, sweet potatoes, squashes, green beans, asparagus, tomatoes, and cruciferous vegetables, along with clean protein sources.
Add clean spices (turmeric, ginger, pepper, cinnamon, cloves, saffron, allspice, juniper berries, etc.
Add herbs: onions, garlic, pepper. Use apple cider vinegar, or fresh citrus juices combined with a good oil and a bit of honey or raw sugar to make a dressing that helps with nutrient absorption.
Herbs are rich in nutrients and antioxidants. Use wild arugula, fennel, dill, parsley, chives, sage, rosemary, cilantro, and other herbs.
These are also helping you with heavy metal excretion and filling the gap of nutrients, vitamins, and minerals you cannot get from regular food.
Clean protein refers to wild-caught fish, smaller fish, such as those like tuna and swordfish, which have high mercury levels, as well as grass-fed meat and cage-free eggs.
Replacing enriched flours with whole grains will not only feed your microbiome but will also make you feel less food cravings and digest better.
Eat a large amount of plant-based foods and clean protein.
Do not starve your body!
When you starve, your body lowers its metabolism, and you cannot lose weight. Additionally, you can lose some of your important microbiome species, develop leaky gut, and increase your risk of autoimmune diseases.
Eat to feel satisfied but remove all processed foods from your diet and replace white sugar and salt with raw sugar or honey, and opt for raw, mineral-rich salt. Introduce home-made fermented foods like sourkraut, yoghurt, kefir, etc.
reduce - Medications: Statins (e.g., atorvastatin) lower LDL-C by 20-50% by inhibiting cholesterol synthesis. PCSK9 inhibitors (e.g., evolocumab), ezetimibe, or bile acid sequestrants further reduce LDL-C. Niacin or fibrates may target small, dense LDL in specific cases.
- Goal: LDL-C <100 mg/dL (or <70 mg/dL for high-risk patients, per guidelines).
- Nutrition and Lifestyle:
- Lp(a):
- Lifestyle: Limited impact; diet and exercise have minimal effect on Lp(a) levels.
- Medications: Statins don’t lower Lp(a) and may slightly increase it. PCSK9 inhibitors can reduce Lp(a) by ~20-30%, but this is not their primary use. Emerging therapies like antisense oligonucleotides (e.g., pelacarsen, in clinical trials) specifically target Lp(a).
- Current Approach: Focus on reducing overall cardiovascular risk (e.g., lowering LDL-C, controlling blood pressure, quitting smoking) since Lp(a) is hard to target directly.
- LDL:
- Testing in Clinical Practice:
- LDL: Routine lipid panels (LDL-C) and ApoB testing are standard. Advanced tests (NMR, electrophoresis) are used for high-risk patients.
- Lp(a): Measured via blood tests (in mg/dL or nmol/L) in patients with a family history of heart disease, premature atherosclerosis, or normal LDL-C but unexplained cardiovascular events. Not routinely screened due to limited treatment options.
- Takeaway: LDL is manageable with lifestyle and drugs like statins, while Lp(a)’s genetic basis and resistance to standard treatments make it a unique challenge. Both require monitoring, but Lp(a) often needs a broader risk-reduction strategy.
- Lipid Metabolism: LDL particle size explains why “bad cholesterol” varies in risk (small, dense LDL is more dangerous due to higher ApoB-100 content).
- Diseases: doctors assess LDL-related risks using the lipid panel, ApoB, NMR testing methods.
High LDL and Lp(a) both drive atherosclerosis, but Lp(a)’s genetic nature and prothrombotic effects require distinct management. - Reader-Friendly Angle: advanced tests reveal hidden risks (e.g., small, dense LDL or high Lp(a)). Discuss these with your doctor.
Note that while LDL can be lowered through diet and medication, Lp(a) management focuses on controlling other risk factors until new therapies emerge.