Clinical Context: Patients with LDL-C ≥190 mg/dL and established coronary disease require aggressive management. Current evidence from major cardiovascular organizations (2019-2025) shows that combining high-intensity statin therapy with intensive dietary modification can achieve additive LDL-C reductions of 5-10%, potentially helping patients reach the ESC/EAS very-high-risk target of <55 mg/dL. The Portfolio Diet represents the most potent evidence-based dietary approach, with meta-analyses demonstrating up to 29% LDL-C reduction—comparable to moderate-intensity statin monotherapy.
Latest Evidence (2025): Two major studies published in BMC Medicine and BMC Public Health in May 2025 confirmed the Portfolio Diet’s effectiveness in diverse populations. The BMC Medicine study of 14,835 US adults from NHANES (1988-1994) demonstrated significant cardiovascular disease mortality reduction with higher Portfolio Diet adherence. The BMC Public Health study of 1,507 young adults (mean age 23±3 years) from diverse ethnocultural backgrounds showed meaningful LDL-C reductions even in younger populations.
Quantitative target: <7% of total calories for hypercholesterolemia (ESC/EAS 2019, Class I, Level A); ideally <6% (AHA standard). On a 2,000-calorie diet, this equals approximately 13-15 grams daily.
Expected LDL-C reduction: Each 1% energy reduction from saturated fat replaced with polyunsaturated fat yields 2.1 mg/dL LDL-C reduction. The 2020 Cochrane Review (high-quality evidence) showed that reducing saturated fat for ≥2 years produced −7.3 mg/dL LDL-C reduction and 17% reduction in combined cardiovascular events (RR 0.83, moderate-certainty evidence). A 2024 umbrella review of 21 meta-analyses confirmed these findings with 21% CVD event reduction (RR 0.79, moderate certainty).
Replace saturated fats with monounsaturated fats (olive oil, avocados) and polyunsaturated fats (nuts, seeds, fatty fish). PUFA replacement shows superior LDL-lowering compared to carbohydrate substitution. High levels of physical activity enhance the metabolic benefits of this fat quality shift.
Quantitative target: 0% of calories (ACC/AHA 2019, COR III, LOE B-NR; ESC 2019, Class I, Level A). Trans fats both raise LDL-C and lower HDL-C through dual mechanisms affecting apolipoprotein catabolism.
Clinical impact: The 2024 JACC report documents that trans fat consumption increases CHD death by 28%, CHD risk by 21%, and all-cause mortality by 34%. Complete elimination is the only acceptable target. Check processed food labels vigilantly, though FDA regulations have substantially reduced industrial trans fat exposure in the US.
Current evidence: The 2019 AHA Science Advisory and 2020-2025 US Dietary Guidelines removed the previous 300 mg/day limit. Current guidance: “Keep dietary cholesterol as low as possible without compromising nutritional adequacy.”
Quantitative effect: A 2019 AJCN meta-regression of 55 RCTs (2,652 subjects) found that each 100 mg/day increase in dietary cholesterol raises LDL-C by 1.90 to 4.58 mg/dL depending on the model used. The effect persists after adjusting for saturated fat intake. However, 15-25% of the population are “hyper-responders” showing exaggerated LDL-C increases and may benefit from restriction.
For high-risk patients: Individuals with severe hypercholesterolemia (LDL-C ≥190 mg/dL) and established CAD should consider limiting dietary cholesterol to <200 mg/day (aligned with older NCEP ATP III guidelines still referenced for high-risk patients). The UK NICE guidelines specifically recommend <200 mg/day for familial hypercholesterolemia patients, a principle applicable to patients with very high baseline LDL-C.
Quantitative target: 2-3 g/day (FDA and EFSA approved; Class IIa, Level B across multiple guidelines).
Expected LDL-C reduction: Meta-analysis of 124 RCTs demonstrates dose-response relationships: 2 g/day achieves 8-10% LDL-C reduction, plateauing at 3 g/day with ~12% reduction. For a baseline LDL-C of 220 mg/dL, this translates to approximately 18-26 mg/dL reduction. The European Atherosclerosis Society consensus statement (updated 2023) confirms consistent effects whether using plant sterols or stanols at equivalent doses.
Mechanism: Competes with cholesterol for intestinal micellar incorporation, reducing absorption by approximately 50%. Effects appear within 2-4 weeks and are sustained with continued use.
Safety: EFSA recommends not exceeding 3 g/day without medical supervision. Well-tolerated in clinical trials; contraindicated only in sitosterolemia (extremely rare genetic condition). Can be safely combined with statins through complementary mechanisms (absorption vs. synthesis inhibition).
Food sources: Typical dietary intake (160-500 mg/day) falls far short of therapeutic targets. Fortified foods required: sterol-enriched margarine/spreads (20-25 g providing 2 g), fortified yogurt drinks (1-2 servings), or supplements. Read labels carefully as sterol content varies.
Clinical application: For Portfolio Diet adherents consuming plant sterols, consistent achievement of the 2 g/day target is essential. This intervention works additively with statin therapy through complementary mechanisms.
Quantitative target: 3 g/day (FDA CFR 101.81; EFSA Article 14 approved health claim).
Expected LDL-C reduction: 5-10% reduction. The 2022 systematic review in British Journal of Nutrition confirms that each gram of viscous fiber reduces LDL-C by approximately 0.045 mmol/L (1.7 mg/dL). For a baseline of 220 mg/dL, 3 g/day could lower LDL-C by 11-22 mg/dL.
Mechanism: Increases GI viscosity, binds bile acids, increases fecal excretion, upregulates hepatic LDL receptors.
Food sources to achieve 3 g beta-glucan:
Practical tip: A bowl of oatmeal made with ¾ cup dry oats provides approximately 3 g beta-glucan. Check labels on fortified products for exact beta-glucan content.
Quantitative target: 7-10 g/day (FDA minimum 7 g/day; median effective dose 10.2 g/day from meta-analyses).
Expected LDL-C reduction: Meta-analysis of 28 trials (1,924 participants) showed −0.33 mmol/L (95% CI: −0.38 to −0.27), approximately 12.7 mg/dL or 5-12% reduction. Also significantly reduced non-HDL-C (−0.39 mmol/L) and apolipoprotein B (−0.05 g/L).
Comparison: Psyllium requires higher doses (7 g vs. 3 g) than beta-glucan but may offer slightly greater LDL-C lowering at therapeutic doses. Evidence quality: moderate to high (AJCN 2018).
Administration: Must be consumed with 8-10 oz water per dose to prevent choking risk, particularly important for older adults. Take medications 2-4 hours before or after psyllium to avoid interference with drug absorption, including statins.
Food sources: 7-10 g requires 2-3 tablespoons psyllium husk powder mixed in water or smoothies, or fortified cereals (check labels).
Quantitative target: 25-35 g/day total fiber, with 5-10 g/day soluble fiber minimum (referenced across ACC/AHA guidelines). Average American intake of 15-17 g/day falls substantially short.
Portfolio Diet context: The original Portfolio Diet protocol included 20 g/day viscous soluble fiber from multiple sources (oats, barley, psyllium, eggplant, okra, berries, apples). High adherence to this component is critical for achieving the portfolio’s 17-29% LDL-C reduction.
Quantitative targets vary by clinical context:
For secondary prevention: ESC 2019 recommends 1 g/day n-3 PUFA (EPA+DHA) for established CVD (Class IIa, Level B). However, recent evidence suggests more nuanced dosing.
Optimal dose range: The 2022 Frontiers meta-analysis of 14 RCTs identified 0.8-1.2 g/day as the “sweet spot” for reducing MACE, cardiovascular death, and MI in CHD patients. Lower (<0.8 g) and higher (>1.2 g) doses showed no significant advantage.
Expected cardiovascular benefit:
EPA vs. EPA+DHA: The 2021 eClinicalMedicine meta-analysis (38 RCTs) found EPA monotherapy superior to EPA+DHA combinations: 28% MI reduction (RR 0.72) and 22% revascularization reduction (RR 0.78) for EPA alone. The REDUCE-IT trial with high-dose icosapent ethyl (EPA 4 g/day) showed 25% cardiovascular event reduction in high-risk patients.
LDL-C effects: Omega-3s have minimal direct LDL-C lowering effect (non-significant in most trials). Primary mechanism is triglyceride reduction (15-30% at therapeutic doses) and pleiotropic effects on endothelial function, inflammation, and plaque stability.
Safety considerations:
Food sources: 2-3 fish/seafood servings per week (AHA 2021, Class I recommendation). To achieve 1 g EPA+DHA: ~3.5 oz salmon, 5 oz sardines, or 6 oz herring. Non-fried preparation essential. Supplements (molecularly distilled for purity) offer consistent dosing.
Clinical application: For patients with CAD on statin therapy, 1 g/day EPA+DHA or EPA alone provides added cardiovascular protection beyond LDL-C lowering through distinct anti-inflammatory and anti-thrombotic mechanisms. This is particularly relevant for patients with elevated triglycerides.
Quantitative target: 30-60 g/day (approximately 1-2 oz) based on clinical trial data. The AHA 2021 guideline recommends regular nut consumption.
Expected LDL-C reduction: Meta-analysis of 61 trials (2,582 participants) showed that 1 serving (28.4 g/day) reduces LDL-C by 4.8 mg/dL (95% CI: −5.5 to −4.2), total cholesterol by 4.7 mg/dL, and apolipoprotein B by 3.7 mg/dL. The dose-response is non-linear, with stronger effects at ≥60 g/day, translating to 3-7% LDL-C reduction.
Nut type comparison: A 2023 comprehensive review of 19 meta-analyses found:
Mechanisms: Displace saturated fats, provide polyunsaturated fats (especially walnuts’ ALA), contain phytosterols, fiber, plant protein, and favorable effects on lipoprotein particle size/distribution.
Practical serving sizes:
Portfolio Diet component: Original protocol specifies 45 g/day tree nuts or peanuts (~1.5 oz). Unsalted, unroasted preferred; can be incorporated into meals, salads, or as snacks.
Clinical application: For patients with optimal BMI and high physical activity levels, liberal nut consumption (up to 60 g/day, ~380 calories) can be easily accommodated. A 2022 Mayo Clinic case report documented a highly trained athlete achieving 43% LDL-C reduction with Portfolio Diet plus exercise, suggesting that athletic profiles may amplify dietary benefits through synergistic effects.
Quantitative target: 25 g/day soy protein (FDA standard from 1999 health claim, maintained despite 2017 proposed revocation).
Expected LDL-C reduction: 2019 Journal of Nutrition meta-analysis of 46 FDA-reviewed trials found median 25 g/day for 6 weeks reduced LDL-C by 4.76 mg/dL (95% CI: −6.71 to −2.80), representing 3-4% reduction. Earlier meta-analysis with higher doses (47 g/day) showed 12.9% reduction, suggesting dose-response relationship.
Evidence quality: Moderate; FDA considered revoking health claim but evidence supports modest effect comparable to other approved functional foods (nuts, viscous fibers).
Food sources to achieve 25 g soy protein:
Isoflavone consideration: Soy enriched in isoflavones shows enhanced LDL-C reduction (additional 3-5%), but even isoflavone-depleted soy protein remains effective, indicating the mechanism is partially independent of phytoestrogens.
Portfolio Diet component: Original protocol includes 50 g/day plant protein from soy products or dietary pulses (beans, peas, chickpeas, lentils). You can achieve this through soy, legumes, or combination.
Quantitative target: 1 serving (130-180 g or ¾-1 cup cooked) daily based on meta-analyses. Portfolio Diet specifies this as part of the 50 g plant protein target.
Expected LDL-C reduction: Meta-analysis of 26 RCTs (1,037 participants) with median 130 g/day pulses showed −0.17 mmol/L LDL-C (95% CI: −0.25 to −0.09), representing ~5% reduction. A separate meta-analysis of 10 non-soy legume RCTs found LDL-C reduction of 7.98 mg/dL.
Clinical relevance: The 2019 Advances in Nutrition systematic review notes that 5% LDL-C reduction translates to 5-6% reduction in major vascular events. A 2022 RCT with 1 cup (180 g) canned beans daily showed significant total and LDL cholesterol reductions after just 4 weeks, demonstrating practical feasibility.
Mechanisms: Soluble fiber, plant protein (displacing animal protein), phytochemicals, resistant starch, and low glycemic index contribute to cholesterol lowering and improved insulin sensitivity.
Bean types: Kidney, navy, pinto, black beans, lentils (red, green, brown), chickpeas, split peas. Canned beans (drained, rinsed) are convenient and equally effective.
Practical implementation: 1 cup cooked beans ≈ 1 can (15 oz drained) ≈ ½ cup dry beans. Add to soups, salads, chilis, tacos, or as side dishes.
Quantitative target: 3+ servings per day (general recommendations); 48-80 g/day whole grains used in studies. Prioritize oats and barley for beta-glucan content.
Expected LDL-C reduction: Meta-analysis of 25 RCTs found whole-grain oats significantly reduced total cholesterol (SMD −0.54) and LDL-C (SMD −0.57). Benefits extend beyond lipids to include improved HbA1c and reduced C-reactive protein (inflammation marker).
Serving definitions:
Strategy: Replace refined grains with whole grains systematically. Choose whole grain bread, brown rice, quinoa, farro, barley, whole wheat pasta. The soluble fiber in oats and barley provides the cholesterol-lowering effect.
Component breakdown (per 2,000 kcal/day):
Expected LDL-C reduction: Meta-analysis by Chiavaroli et al. (2018, 7 trials, 439 participants) showed −0.73 mmol/L (−28 mg/dL), approximately 17% reduction (95% CI: −0.89 to −0.56) with high-certainty evidence (GRADE assessment). Early metabolically controlled trials achieved −29% reduction, comparable to lovastatin 20 mg (−31%). Real-world dietary advice trials showed −15% reduction with 43% average adherence.
Additional cardiovascular benefits:
Long-term outcomes: The landmark 2023 Circulation study by Glenn et al. followed 210,240 participants in three prospective cohorts (Nurses’ Health Study, NHS II, Health Professionals Follow-up Study). Higher Portfolio Diet Score was associated with 14% lower total CVD risk (HR 0.86), 16% lower CHD risk (HR 0.84), and 18% lower stroke risk (HR 0.82). Benefits were consistent across age, sex, and race/ethnicity.
Real-world effectiveness: Approximately 33% of participants achieve ≥20% LDL-C reduction and 31% achieve ≥15% reduction. Inverse associations with LDL-C observed even with partial adherence, making it accessible for varying commitment levels.
Clinical implementation: For optimal results, meticulous adherence to all Portfolio Diet components is essential: 2 g plant sterols daily, 20 g viscous fiber (from multiple sources), 45 g nuts, 50 g plant protein, and olive oil as primary fat. With perfect adherence combined with regular exercise, patients may achieve the upper range (25-29%) of LDL-C reduction, providing substantial additional benefit on top of statin therapy.
Operational definition (PREDIMED protocol):
Expected LDL-C reduction: Modest but consistent −0.15 mmol/L (95% CI: −0.27 to −0.02) or approximately 3-5% reduction (2019 Cochrane Review, moderate-quality evidence). Also reduces total cholesterol (−0.13 mmol/L) and triglycerides (−0.09 mmol/L).
Cardiovascular outcomes—the strongest evidence: The PREDIMED trial (7,447 participants, 4.8 years) demonstrated 30% reduction in major cardiovascular events (stroke, MI, cardiovascular death). Most dramatically, stroke reduction was 40% (HR 0.60, 95% CI: 0.45-0.80, moderate-quality evidence). Type 2 diabetes incidence decreased 29% (HR 0.71).
A 2020 meta-analysis of 84 articles (57 trials, 36,983 participants) confirmed 39% CVD incidence reduction (RR 0.61) and 33% stroke reduction (RR 0.67). The 2023 ATTICA Study showed Mediterranean diet superior to DASH for 10-year CVD outcomes in Mediterranean populations: 3.1% CVD rate in highest adherence quartile vs. 33% in lowest.
Comparison to Portfolio: Mediterranean provides modest LDL-C reduction (3-5%) but superior cardiovascular outcome data from randomized controlled trials. Portfolio achieves greater LDL-C lowering (17-29%) but has only observational outcome data. Combining elements (Portfolio-Mediterranean hybrid) may optimize both lipids and long-term events.
Nutrient targets (2,000 kcal/day):
Food group targets:
Expected LDL-C reduction: Umbrella review of 33 trial comparisons (4,479 participants) showed −0.10 mmol/L (95% CI: −0.20 to −0.01) or 3-6% reduction, with total cholesterol −0.20 mmol/L (moderate-quality evidence). A 2021 meta-analysis of 17 RCTs (2,218 participants) confirmed LDL-C reduction of 3.53 mg/dL (p=0.041).
Primary benefit—blood pressure: Systolic BP reduction of 5.2 mmHg (95% CI: −7.0 to −3.4) and diastolic BP reduction of 2.6 mmHg (clinically meaningful, high-quality evidence). A 2022 study documented progressive reduction in high-sensitivity troponin I and CRP over 12 weeks, indicating reduced subclinical myocardial injury and inflammation.
Cardiovascular outcomes (observational): Prospective cohort studies (942,140 participants) found 20% CVD incidence reduction (RR 0.80), 21% CHD reduction (RR 0.79), 19% stroke reduction (RR 0.81), and 18% type 2 diabetes reduction (RR 0.82).
Clinical context: For patients with excellent blood pressure control from physical activity, DASH offers less lipid benefit than Portfolio, making it a secondary choice for LDL-C-focused management. However, DASH principles (high potassium, low sodium, abundant produce) can complement the Portfolio approach.
Operational definitions: Spectrum from vegan (no animal products) to lacto-ovo-vegetarian (includes dairy and eggs) to plant-based (emphasizes plants with minimal animal products).
Expected LDL-C reduction: Major 2023 European Heart Journal meta-analysis of 30 RCTs found −0.30 mmol/L LDL-C (95% CI: −0.40 to −0.19; p=4×10⁻⁸), approximately 7-10% reduction. Total cholesterol reduced −0.34 mmol/L and apolipoprotein B reduced −12.92 mg/dL (14% reduction). Effects were consistent across age, geographic regions, health status, and vegetarian subtypes.
Mechanisms: Lower saturated fat intake, higher fiber (especially soluble), presence of plant sterols/stanols, soy protein effects, lower body weight, and improved insulin sensitivity.
Cardiovascular outcomes: Observational studies show lower ischemic heart disease incidence in vegetarians/vegans. A 2020 comparative analysis estimated 3% reduction in fatal CVD and 6% reduction in CVD events based on LDL-lowering effects alone.
Practical consideration: Plant-based eating provides the foundation for the Portfolio Diet—they’re complementary, not competing approaches. Ensure nutritional adequacy (vitamin B12, iron, zinc, omega-3s) with strict vegetarian/vegan patterns.
Treatment targets: ESC/EAS 2019 classifies established coronary artery disease as very high risk: LDL-C goal <55 mg/dL AND ≥50% reduction from baseline (Class I, Level A). For a baseline of 223 mg/dL, this requires ≥112 mg/dL reduction to 111 mg/dL or lower, then further reduction to <55 mg/dL.
High-intensity statin contribution: High-intensity statin (rosuvastatin 20-40mg or atorvastatin 40-80mg) typically achieves ≥50% LDL-C reduction (Class I, Level A), potentially reducing 223 mg/dL to approximately 112 mg/dL—halfway to the <55 mg/dL target.
Dietary contribution on top of statin: Portfolio Diet meta-analysis shows additional 17% LDL-C reduction when added to background lipid-lowering diet. For a baseline of 223 mg/dL on statin (reduced to ~112 mg/dL), this could provide an additional 19-38 mg/dL reduction, potentially bringing patients to 74-93 mg/dL. Perfect Portfolio adherence with high physical activity may achieve the upper range (29% dietary reduction), potentially reaching 65-80 mg/dL.
Remaining gap: Many patients will need ezetimibe (additional ~20-25% reduction from current level) to reach <55 mg/dL. The ACC/AHA 2018 guideline recommends adding ezetimibe for very-high-risk ASCVD patients on maximal statin with LDL-C ≥70 mg/dL (Class IIa, Level B).
Intensive lifestyle evidence in secondary prevention:
Optimal treatment strategy for established ASCVD:
Guidelines: ACC/AHA 2018 classifies LDL-C ≥190 mg/dL as requiring high-intensity statin therapy immediately (Class I, Level B) with goal of ≥50% LDL-C reduction. If <50% reduction on maximal statin, add ezetimibe (Class IIa, Level B).
Dietary role: A 2022 Mayo Clinic case report documented a highly trained 29-year-old man with LDL-C 135 mg/dL who achieved 43% reduction to 76 mg/dL with Portfolio Diet + 30g flaxseed + intense exercise over 10 months—similar magnitude to rosuvastatin 20mg in the JUPITER trial (50% median reduction). This suggests that athletic profiles combined with dietary diligence could achieve exceptional synergistic results.
Limited RCT data: Few studies specifically target baseline LDL-C >200 mg/dL with diet alone. FH studies show 10-20% dietary reduction, confirming diet is helpful but inadequate as monotherapy for very high LDL-C. Clinical guidelines universally recommend statin therapy with diet as essential adjunct.
Clinical approach: For patients with LDL-C ≥190 mg/dL, recognize that diet provides critical but insufficient LDL-C reduction. The combination of high-intensity statin + Portfolio Diet + potential ezetimibe represents evidence-based aggressive management.
For patients with very high baseline LDL-C (≥190 mg/dL), consideration of FH-specific recommendations is warranted even without confirmed FH diagnosis. The 2025 MDPI Review emphasizes that diet remains important supportive treatment even when genetics dominate, though typical dietary effects in FH are 6.6-17% LDL-C reduction.
FH-specific dietary guidance:
Canadian vs. Chinese FH cohort insight: Dietary fat intake (33.5% vs. 20% calories) explained ~70% difference in plasma LDL-C levels despite identical LDLR variants, highlighting that fat quality and quantity matter even with genetic drivers.
Macronutrient foundation:
Functional food targets:
Expected combined dietary effect: With perfect adherence, 17-29% LDL-C reduction (38-65 mg/dL from a 223 mg/dL baseline). Combined with high-intensity statin (~50% reduction), patients could achieve total LDL-C of 65-112 mg/dL depending on statin response and dietary adherence.
If the complete Portfolio protocol feels excessive:
Expected simplified effect: 10-15% LDL-C reduction (22-34 mg/dL)
Timeline for dietary effects:
Recommended monitoring:
Highest quality:
Plant sterols/stanols:
Omega-3 fatty acids:
Psyllium fiber:
Nuts:
Very low LDL-C levels:
| Intervention | Daily Target | LDL-C Reduction | Evidence Level |
|---|---|---|---|
| Plant sterols/stanols | 2-3 g | 8-12% (~18-26 mg/dL at baseline 220 mg/dL) | Level A (124 RCTs) |
| Beta-glucan | 3 g | 5-10% (~11-22 mg/dL at baseline 220 mg/dL) | Level A (FDA/EFSA) |
| Psyllium | 7-10 g | 5-12% (12.7 mg/dL mean) | Level A (28 RCTs) |
| Nuts | 30-60 g | 3-7% (4.8 mg/dL per oz) | Level A (61 trials) |
| Soy protein | 25 g | 3-4% (4.76 mg/dL) | Level B (46 trials) |
| Legumes | 1 cup (180 g) | ~5% (7.98 mg/dL) | Level B (26 RCTs) |
| Saturated fat <7% | <15 g/day | 1.6 mg/dL per 1% reduction | Level A (Cochrane) |
| Portfolio Diet (complete) | All components | 17-29% (~38-65 mg/dL at baseline 220 mg/dL) | Level A (high GRADE) |
| Mediterranean Diet | Pattern adherence | 3-5% (~6-11 mg/dL) | Level A (PREDIMED) |
| Plant-based pattern | Vegetarian/vegan | 7-10% (~15-22 mg/dL) | Level B (30 RCTs) |
| DASH Diet | Pattern adherence | 3-6% (3.53 mg/dL) | Level B (33 trials) |
| High-intensity statin | Rosuvastatin 20-40mg | ≥50% (~112 mg/dL at baseline 220 mg/dL) | Level A (definitive) |
| Ezetimibe (added) | 10 mg | Additional 20-25% | Level A (definitive) |
Example Case Profile: 43-year-old male, LDL-C 223 mg/dL, established CAD (very high risk), on high-intensity statin, Portfolio Diet adherent, high physical activity (200km/month running), BMI 21.6, non-smoker.
Treatment Target: LDL-C <55 mg/dL AND ≥50% reduction (≥112 mg/dL decrease) per ESC/EAS 2019 very-high-risk criteria (Class I, Level A).
Recommended Treatment Pathway:
1. Dietary optimization (first 8-12 weeks):
2. Pharmacologic optimization:
3. Lifestyle maintenance:
4. Monitoring schedule:
Realistic expectations for patients with baseline LDL-C ~220 mg/dL:
Evidence quality: This approach combines Level A evidence (high-intensity statin, Portfolio Diet, saturated fat reduction, plant sterols, soluble fiber) with Level B evidence (omega-3 fatty acids, nuts). This represents state-of-the-art, guideline-concordant management for secondary prevention with severe hypercholesterolemia. The 2022 Mayo Clinic case report of a highly trained athlete achieving 43% LDL-C reduction with Portfolio Diet plus exercise demonstrates that high physical activity levels can amplify dietary benefits through synergistic effects.