HDL Cholesterol (High‑Density Lipoprotein): Understanding Your Blood Test Series

1. Overview: What this test reveals and why it is important

HDL cholesterol is often called the "good" cholesterol. This oversimplification refers to the fact that high‑density lipoprotein particles transport cholesterol from peripheral tissues—including artery walls—back to the liver for excretion or recycling. This process, reverse cholesterol transport, is anti‑atherogenic.

However, HDL is more than just a carrier of cholesterol. HDL particles contain apolipoprotein A1 (APO A1) and numerous enzymes that confer antioxidant, anti‑inflammatory, anti‑thrombotic, and endothelial‑protective properties.

A low HDL cholesterol level is a well‑established, independent risk factor for atherosclerotic cardiovascular disease (ASCVD). It is a component of the metabolic syndrome and is strongly influenced by lifestyle. However, raising HDL pharmacologically has not consistently translated into cardiovascular benefit, indicating that HDL function—not just cholesterol cargo—matters. Therefore, HDL cholesterol remains a risk marker, not a therapeutic target in isolation.

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2. What does it measure

a. Units of measurement

· Milligrams per decilitre (mg/dL) – standard in the United States

· Millimoles per litre (mmol/L) – used in many other countries (divide mg/dL by 38.67)

b. Normal Range and Risk Stratification

(Reference ranges vary by laboratory and sex; cardiovascular risk categories are based on epidemiological data.)

Adults:

· Optimal (low risk):

· Men: ≥40 mg/dL (≥1.0 mmol/L)

· Women: ≥50 mg/dL (≥1.3 mmol/L)

· Low (increased risk):

· Men: <40 mg/dL (<1.0 mmol/L)

· Women: <50 mg/dL (<1.3 mmol/L)

· Very high HDL (≥80–100 mg/dL):

· May be associated with U‑shaped risk – extremely high HDL is sometimes linked to dysfunctional HDL particles or genetic variants and does not confer additional protection.

Children:

· 30–50 mg/dL (0.8–1.3 mmol/L); lower in pre‑pubertal children, rises slightly after puberty.

Interpretation notes:

· HDL cholesterol is higher in women than men throughout life, likely due to oestrogen.

· Lifestyle factors (exercise, diet, smoking, alcohol) have a greater impact on HDL than most medications.

· Isolated low HDL without other lipid abnormalities or ASCVD risk factors may not warrant pharmacotherapy; global risk assessment guides treatment.

· Very high HDL (>100 mg/dL) warrants investigation for cholesteryl ester transfer protein (CETP) deficiency or other genetic disorders; often benign.

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3. Other factors connected to this

a. Direct correlation (factors that directly lower or raise HDL cholesterol)

Factors that lower HDL:

· Smoking – dose‑dependent reduction; normalises with cessation.

· Physical inactivity – sedentary lifestyle reduces HDL.

· Obesity / insulin resistance / metabolic syndrome / type 2 diabetes – central obesity and hypertriglyceridaemia lower HDL via increased CETP activity.

· Hypertriglyceridaemia – triglyceride‑rich lipoproteins promote cholesterol transfer from HDL to VLDL, leading to HDL particle remodelling and accelerated catabolism.

· Genetic:

· Familial hypoalphalipoproteinaemia (APO A1 mutations, ABCA1 deficiency, LCAT deficiency, Tangier disease).

· CETP gene variants (some lower, some raise HDL).

· Medications:

· Androgens, anabolic steroids, progestins, danazol.

· Beta‑blockers (non‑vasodilating, e.g., propranolol, metoprolol – modest effect).

· Thiazide diuretics (modest reduction).

· Benzodiazepines, some antipsychotics (minor effects).

· Diet:

· High intake of refined carbohydrates, added sugars, trans fats.

· Very low‑fat diets may reduce HDL.

· Inflammation / infection – HDL falls as a negative acute phase reactant.

· Chronic kidney disease, nephrotic syndrome.

Factors that raise HDL:

· Physical activity – aerobic exercise (≥30 minutes, most days) increases HDL by 5–15%.

· Weight loss – particularly loss of visceral fat.

· Smoking cessation – HDL increases within weeks.

· Diet:

· Monounsaturated fats (olive oil, nuts, avocados).

· Polyunsaturated fats (omega‑3 fatty acids, especially from algae).

· Soluble fibre (oats, barley, psyllium, legumes).

· Moderate alcohol consumption – raises HDL by 10–20%; not recommended as intervention due to net health risks.

· Medications:

· Niacin (nicotinic acid) – most potent HDL raiser (15–30%), but limited by side effects and lack of outcome benefit added to statins.

· Fibrates (fenofibrate, gemfibrozil) – modest HDL increase (5–15%).

· Statins – minimal HDL increase (3–8%).

· CETP inhibitors (e.g., anacetrapib) – raise HDL markedly but cardiovascular benefit modest/uncertain; not in routine use.

· Oestrogen – hormone replacement therapy raises HDL; not used for this purpose due to overall risks.

· Alcohol – as above.

· Genetic:

· CETP deficiency (very high HDL, often benign).

· APO A1 Milano (rare variant, dysfunctional HDL despite high levels).

b. Indirect correlation (factors that influence HDL interpretation or cause artefactual changes)

· Fasting status: HDL is minimally affected by recent meals; non‑fasting samples acceptable.

· Pregnancy: HDL rises in mid‑pregnancy, falls slightly in third trimester.

· Age: HDL remains relatively stable; slight decline in elderly men.

· Ethnicity: South Asians have lower HDL for same degree of insulin resistance.

· Seasonal variation: small, clinically insignificant.

· Medications:

· Raise HDL: carbamazepine, phenytoin (enzyme inducers) – mild effect.

· Lower HDL: as above.

· Laboratory assay: direct homogeneous assays are standard; ultracentrifugation reference method rarely used.

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4. Disorders related to abnormal values

a. When HDL is low (clinically significant – increased ASCVD risk)

· Metabolic syndrome / insulin resistance / type 2 diabetes – most common cause.

· Obesity – particularly visceral adiposity.

· Hypertriglyceridaemia – any cause (familial, dietary, alcohol).

· Cigarette smoking.

· Physical inactivity.

· Genetic:

· Familial hypoalphalipoproteinaemia.

· Tangier disease (ABCA1 mutation) – extremely low HDL, cholesterol ester accumulation in macrophages, neuropathy, splenomegaly.

· LCAT deficiency – low HDL, corneal opacities, anaemia, proteinuria.

· Chronic inflammatory diseases – rheumatoid arthritis, SLE, psoriasis – HDL may be low and dysfunctional.

· Chronic kidney disease / end‑stage renal disease.

· Infections – HIV, hepatitis C (associated with low HDL).

· Medications – as above.

b. When HDL is high (usually not pathological, but context matters)

· Genetic:

· CETP deficiency – very high HDL (often >100 mg/dL), no increased ASCVD risk; paradoxically, some studies suggest increased risk at extreme levels.

· Hepatic lipase deficiency.

· APO A1 mutations (some raise, some lower).

· Alcohol use disorder – chronic heavy intake raises HDL.

· Oestrogen therapy / hormone replacement.

· Exercise‑induced – endurance athletes often have HDL >70 mg/dL.

· Primary biliary cholangitis – elevated HDL in early disease due to LCAT inhibition.

· Hyperthyroidism.

· Familial longevity – associated with high HDL in some cohorts.

Important: Very high HDL (>90–100 mg/dL) is not protective if HDL particles are dysfunctional. Consider HDL function assays if available, though not routine.

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5. Best way to address aberrant levels

Important principle: HDL cholesterol is a risk marker, not a direct therapeutic target. There is no evidence that pharmacologically raising HDL cholesterol in isolation reduces cardiovascular events. The INTERHEART study and numerous RCTs (ILLUMINATE, AIM‑HIGH, HPS2‑THRIVE) have shown that raising HDL with niacin or torcetrapib does not improve outcomes when LDL is optimally controlled. Treatment should focus on global cardiovascular risk reduction: LDL lowering, glycaemic control, blood pressure management, and lifestyle modification.

Low HDL is addressed by treating the underlying metabolic disturbance, not by chasing the number.

a. Quick ways or using Medications

No medication is FDA‑approved specifically to raise HDL for cardiovascular risk reduction. The following agents affect HDL but are used for other indications:

· Statins:

· Primary indication: LDL lowering.

· HDL effect: +3–8% (minor, not clinically meaningful).

· Preferred: plant‑based fermentation‑derived statins (e.g., simvastatin, atorvastatin – synthetic, not ecological concern).

· Fibrates:

· Primary indication: hypertriglyceridaemia (particularly when triglycerides >500 mg/dL to prevent pancreatitis).

· HDL effect: +10–20% in hypertriglyceridaemic patients.

· Fenofibrate preferred over gemfibrozil in combination with statins (safer).

· No proven cardiovascular benefit in primary prevention when added to statin.

· Niacin (nicotinic acid):

· Most potent HDL raiser (+15–35%), but no longer recommended due to lack of outcome benefit, significant side effects (flushing, hepatotoxicity, hyperglycaemia), and increased risk of serious adverse events in trials.

· Avoid – especially over‑the‑counter sustained‑release formulations (hepatotoxic).

· PCSK9 inhibitors:

· Primary indication: potent LDL lowering.

· HDL effect: minor increase (+5–10%).

· Not used for low HDL alone.

· CETP inhibitors:

· Markedly raise HDL (up to +100%) but failed to show consistent cardiovascular benefit; anacetrapib showed modest benefit in subgroup analysis but not approved in most countries.

· Not in routine use.

· Insulin sensitizers (pioglitazone):

· Modestly raises HDL (+5–15%) in type 2 diabetes.

· Used for glycaemic control, not for HDL.

Do not self‑prescribe any lipid‑modifying medication. All require medical supervision.

b. Using Supplements or Holistic medicine

For low HDL – supporting metabolic health and HDL function:

· Omega‑3 fatty acids (EPA/DHA):

· Modest HDL increase (+3–5%) in some studies; more effective for triglyceride reduction.

· Preferred source: Algae oil – sustainable, plant‑based, direct EPA/DHA, no marine contaminants.

· Avoid conventional fish oil (overfishing, ocean pollution, ethical concerns).

· Dose: 2–4 g/day EPA/DHA for triglyceride effect; lower doses for general health.

· Form: re‑esterified triglyceride for optimal absorption.

· Niacin (nicotinic acid):

· Effective but not recommended as a supplement due to side effect profile and lack of outcome benefit.

· If prescribed by a physician, immediate‑release niacin is preferred over sustained‑release (less hepatotoxic). Flushing can be managed with aspirin and taking with food.

· Do not self‑administer.

· Berberine:

· Improves insulin resistance, modestly raises HDL (+5–10%) in some trials.

· Preferred source: Standardised berberine (≥97%) from Berberis aristata or Phellodendron amurense.

· Dose: 500 mg twice daily.

· Caution: GI side effects, drug interactions (statins, cyclosporine, anticoagulants); avoid in pregnancy.

· Plant sterols and stanols:

· Lower LDL‑C; minimal effect on HDL.

· Not for HDL raising.

· Soluble fibre (psyllium, beta‑glucans):

· Lowers LDL; minimal effect on HDL.

· Curcumin (turmeric):

· Anti‑inflammatory; some small studies show HDL improvement.

· Use phytosomal, liposomal, or with piperine for bioavailability.

· Green tea catechins (EGCG):

· Modest HDL increase in some meta‑analyses.

· Use beverage (2–3 cups/day) rather than concentrated extracts (hepatotoxicity risk).

· Vitamin D:

· Deficiency linked to low HDL; supplementation may modestly increase HDL in deficient individuals.

· Preferred: D3 (cholecalciferol) from lichen.

· Magnesium:

· Deficiency associated with low HDL; supplementation may improve lipid profile.

· Preferred forms: glycinate, citrate, malate.

· Chromium:

· Controversial; may improve insulin sensitivity; weak HDL effect.

· Form: chromium picolinate or polynicotinate.

· Coenzyme Q10 (CoQ10):

· No consistent evidence for HDL raising.

· Ayurvedic approaches:

· Arjuna (Terminalia arjuna) – bark extract; modest evidence for HDL improvement.

· Guggulu (Commiphora mukul) – standardised guggulsterones; may improve lipid profile but efficacy modest and hepatotoxicity concerns.

· Garlic (Allium sativum) – aged garlic extract; small LDL‑C reduction, minimal HDL effect.

· Always use standardised extracts from GMP‑certified manufacturers.

· Consult a qualified practitioner; herbs can interact with statins and anticoagulants.

For high HDL:

· No supplements are indicated. Very high HDL is rarely pathological; investigate underlying cause if extreme (genetic testing, CETP activity).

· Moderate alcohol intake – if high HDL is due to alcohol excess, reduction may lower HDL; not recommended as intervention.

c. Using Diet and Foods (following a plant‑forward, ecologically sustainable approach)

Diet is the cornerstone of lifestyle‑mediated HDL improvement. However, dietary effects on HDL are modest compared to exercise and smoking cessation. The primary goal of dietary intervention in low HDL is improving overall cardiometabolic health – reducing triglycerides, improving insulin sensitivity, and achieving weight loss.

Core dietary pattern – what to emphasise:

· Mediterranean‑style plant‑forward diet – strongest evidence for cardiovascular risk reduction; modestly raises HDL.

· Replace saturated fats with unsaturated fats:

· Extra virgin olive oil – principal fat source.

· Nuts and seeds: walnuts, almonds, pistachios, flaxseeds, chia seeds, hemp seeds.

· Avocado.

· Increase soluble fibre:

· Oats, barley, psyllium, eggplant, okra, legumes (lentils, chickpeas, beans).

· Target 25–40 g fibre daily.

· Emphasise whole grains – quinoa, brown rice, whole wheat, millets.

· Limit refined carbohydrates and added sugars – reduce VLDL/triglycerides; HDL rises as triglycerides fall.

· Avoid trans fats – completely.

Specific foods with evidence for HDL raising / cardiometabolic benefit:

· Monounsaturated fat‑rich foods:

· Olive oil, canola oil, nuts, avocados.

· Omega‑3 fatty acids:

· ALA sources: ground flaxseeds, chia seeds, hemp seeds, walnuts.

· Direct EPA/DHA: microalgae (spirulina, chlorella – limited amounts); algae oil supplements for therapeutic doses.

· Legumes: lentils, chickpeas, black beans, kidney beans – improve glycaemic control, reduce triglycerides.

· Soy protein: tofu, tempeh, edamame – modest HDL benefit.

· Dark chocolate (≥70% cocoa): flavonoids may modestly raise HDL; limit added sugar.

· Green tea: 2–3 cups/day.

· Fruits and vegetables: particularly berries, citrus, leafy greens.

· Fermented foods: kimchi, sauerkraut, kombucha – support gut microbiome; indirect metabolic benefits.

What to avoid:

· Refined carbohydrates: white bread, white rice, sugary cereals.

· Added sugars: soft drinks, fruit juices, sweets, pastries.

· Trans fats: partially hydrogenated oils (banned in many countries but still present in some processed foods).

· Excess saturated fats: butter, cream, fatty meats, palm oil, coconut oil.

· Excess alcohol: moderate intake raises HDL, but heavy intake harms liver and overall health. Alcohol is not recommended as a therapeutic intervention.

Protein sources (hierarchy adhered):

· Plant‑based: legumes, soy products (tofu, tempeh, edamame), seitan – primary.

· Fungi / algae: mycoprotein (Quorn), spirulina, chlorella – encouraged.

· Biotechnology / lab‑grown: precision‑fermented dairy proteins, heme analogues – acceptable emerging options.

· Dairy / eggs: permitted but not emphasised; full‑fat dairy may raise LDL‑C; low‑fat fermented dairy (yoghurt, kefir) may have neutral or favourable effects.

· Meat, poultry, fish: deliberately omitted. Effective plant‑based alternatives exist to support all dietary goals for raising HDL and improving cardiometabolic health. There is no nutritional requirement for meat to achieve optimal HDL levels.

Physical activity – more potent than diet for HDL:

· Aerobic exercise: 30–60 minutes, moderate to vigorous intensity, most days of the week, raises HDL by 5–15%.

· High‑intensity interval training (HIIT): may be even more effective.

· Resistance training: modest HDL benefit.

Weight loss:

· 5–10% reduction in body weight significantly increases HDL, particularly when visceral fat is reduced.

Smoking cessation:

· HDL increases by 5–10% within weeks of quitting.

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6. How soon can one expect improvement and the ideal time frame to retest

For lifestyle interventions:

· Smoking cessation: HDL begins to rise within 2–4 weeks; full effect by 2–3 months.

· Aerobic exercise: HDL changes detectable after 8–12 weeks of consistent training; maximal effect at 6–12 months.

· Weight loss: for every 1 kg of weight lost, HDL increases by approximately 0.35 mg/dL (0.01 mmol/L). A 5–10% weight loss over 3–6 months yields measurable HDL improvement.

· Dietary change: HDL responds slowly; modest increases (3–8%) may be seen in 3–6 months with sustained adherence to Mediterranean‑style diet.

For medications:

· Fibrates: HDL increase detectable within 4–8 weeks.

· Statins: minimal HDL effect; no need to monitor HDL for statin efficacy.

· Niacin: HDL rises within 2–4 weeks, but drug is not recommended.

For supplements:

· Omega‑3 (algae oil): triglyceride reduction in 6–12 weeks; HDL effect modest and delayed.

· Berberine: lipid changes in 4–8 weeks.

Retesting interval:

· Low HDL as part of ASCVD risk assessment: repeat lipid panel every 1–5 years depending on global risk.

· Lifestyle intervention: repeat lipid panel every 3–6 months to monitor progress.

· Medication initiation (for other indications): repeat at 8–12 weeks, then annually.

· Do not retest HDL more often than every 3 months – meaningful change does not occur faster.

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Conclusion

HDL cholesterol is the Gordian knot of lipidology. It is an undeniably powerful risk marker—low HDL predicts events, high HDL predicts longevity in epidemiological studies—yet every attempt to pharmacologically raise HDL has failed to improve outcomes. The lesson is clear: HDL function, not HDL cholesterol, is what matters.

Thus, the approach to low HDL is not to chase the number with niacin or CETP inhibitors, but to address the metabolic terrain that suppresses it. Smoking cessation, exercise, weight loss, and the replacement of refined carbohydrates with unsaturated fats and fibre are the true interventions. They raise HDL modestly, but more importantly, they transform HDL from a dysfunctional particle to a functional one.

A plant‑based, ecologically responsible diet—rich in olive oil, nuts, legumes, whole grains, and algae‑sourced omega‑3s—is perfectly aligned with this goal. Meat is not required; neither are animal‑derived supplements. The same dietary pattern that restores HDL also lowers LDL, reduces triglycerides, improves insulin sensitivity, and lightens humanity's ecological footprint.

Low HDL is a warning. Listen to it—but treat the patient, not the particle.

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Note on dietary recommendations on this site:

For the sake of our environment we adhere to the following dietary preference hierarchy:

1. Plant‑based

2. Fungi / algae / fermented

3. Biotechnology / lab‑grown / cultures

4. Dairy / eggs

5. Meat / fish / poultry (only if no effective alternative exists)

This approach reflects ecological responsibility, antibiotic stewardship, and the urgent need to reduce the environmental footprint of dietary recommendations.

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