Diet & Nutrition for Longevity
Evidence-based dietary approaches centered on the Mediterranean diet to reduce inflammation, extend lifespan, and promote healthy aging
Why Diet Matters for Longevity
Your dietary choices profoundly impact lifespan and healthspan. The Mediterranean diet stands out as the most extensively researched dietary pattern for longevity, with over 50 years of evidence showing it reduces all-cause mortality by 20-25% and cardiovascular disease by 30%.
This page explores the Mediterranean diet and specific foods that combat inflammation by reducing HMGB1—a key aging biomarker linked to chronic disease and cellular senescence.
Want the complete Mediterranean diet implementation guide?
Our comprehensive guide includes a 4-week transition protocol, 3-day meal plans, HMGB1-reducing food lists, and evidence-based strategies from the PREDIMED trial.
Read the Complete Mediterranean Diet Guide →EGCG from green tea represents the most potent natural HMGB1 inhibitor with an IC50 below 1.0 μM—placing it among the most effective compounds identified.
Practical Recommendation:
2-3 cups daily provides approximately 10 μL/ml equivalent (75 mL per person for therapeutic effect). EGCG remains effective even when consumed 2-6 hours after inflammatory stimulus.
At concentrations of 10-15 μM, EGCG dramatically attenuates HMGB1 secretion through a unique mechanism: it induces HMGB1 aggregation near Cys106, triggering autophagy-mediated cytoplasmic degradation. Animal studies using 3-4.5 mg/day green tea extract suppressed HMGB1 in cigarette smoke exposure, and EGCG rescued mice from lethal sepsis when given 24+ hours after onset.
Berries: Quercetin Powerhouses
Berries rank among the highest dietary quercetin sources, with quercetin preventing LPS-induced HMGB1 translocation and release at clinically achievable concentrations.
- Bog whortleberry158 mg/kg
- Lingonberry74-146 mg/kg
- Cranberry83-121 mg/kg
- Chokeberry89 mg/kg
- Blueberry99.9 mg/kg
Evidence:
Quercetin at 100 mg/kg attenuated serum HMGB1 at 20 hours post-endotoxin in animal models. Consuming 100 g/day of berries increased plasma quercetin by 50% over 2 months in humans.
Recommendation: 1-2 cups of mixed berries daily
Omega-3 Fatty Acids
Omega-3 polyunsaturated fatty acids reduce endotoxin, inflammatory cytokines, and lymphatic HMGB1. They attenuate microglial inflammation by inhibiting HMGB1/TLR4/NF-κB pathway and modulate SIRT1-mediated deacetylation of HMGB1.
Studies using 1.1-2.1 g EPA + DHA daily showed efficacy. A 12-week study with 2.1 g EPA + 1.1 g DHA per day demonstrated incorporation into blood cells with functional effects. Higher doses exceeding 2.6 g/day lowered inflammatory biomarkers like CRP.
Best Sources:
- • Salmon, mackerel, herring, tuna, sardines, anchovies
- • Flaxseeds (2 tablespoons ground daily)
- • Chia seeds, walnuts, canola oil
Recommendation: 2 servings (8 oz) of fatty fish weekly or 1-3 g EPA+DHA supplement
Mediterranean Diet: The Gold Standard for Longevity
The Mediterranean diet is the most extensively researched dietary pattern for longevity, backed by over 50 years of evidence including the landmark PREDIMED trial with 7,447 participants.
- ✓20-25% reduction in all-cause mortality (largest meta-analysis of 1.5M people)
- ✓30% reduction in cardiovascular disease (PREDIMED trial)
- ✓Anti-inflammatory effects including down-regulation of cell adhesion molecules and reduced inflammatory markers
- ✓Improved autophagy (cellular cleanup mechanism critical for longevity)
- ✓Lower morbidity and mortality from diabetes, cancer, and neurodegenerative disease
- •Extra virgin olive oil as main fat source (3-4 tablespoons daily—contains oleocanthal with strong anti-inflammatory activities)
- •Fatty fish providing omega-3s (2+ servings/week, 8oz total)
- •Abundant vegetables and fruits (9+ servings daily, especially quercetin-rich options like berries, onions, leafy greens)
- •Whole grains for sustained energy (3+ servings daily)
- •Legumes/beans (at least 3 servings per week)
- •Nuts and seeds as daily snacks (1 oz/day)
- •Limited red meat (≤1 serving per week)
- •Moderate wine consumption (optional, 1 glass daily with meals)
PREDIMED Trial (7,447 participants, 4.8 years):
Mediterranean diet with extra virgin olive oil or nuts reduced major cardiovascular events by 30% compared to low-fat diet. Superior results for stroke prevention (39% reduction).
Rheumatoid Arthritis Study:
Produced significant improvement in disease activity after 12 weeks—approximately one-third the benefit of methotrexate—with less pain and morning stiffness persisting 6 months after 6-week intervention.
Meta-Analysis (1.5M+ participants):
Strongest evidence for all-cause mortality reduction (20-25%) and cardiovascular disease prevention across diverse populations.
Ready to implement the Mediterranean diet?
Our comprehensive guide provides a 4-week transition protocol, detailed shopping lists, meal prep strategies, and specific HMGB1-reducing food combinations backed by the latest research.
Get the Complete Mediterranean Diet Implementation Guide →Other Key Foods
Provide among the highest dietary quercetin concentrations, with quercetin concentrated in outer layers. Prevents LPS-induced HMGB1 translocation and release.
Supply lycopene with antioxidative and anti-inflammatory properties that inhibit ICAM-1 expression, NF-κB activation, and HMGB1-mediated pro-inflammatory responses.
Broccoli and kale rank among top three food sources for quercetin and are staples of anti-inflammatory Mediterranean diet.
At 200 mg/kg in mice attenuates HMGB1 expression through inhibition of acetylation. Practical dose: 500-1,000 mg curcumin supplements daily, with bioavailability dramatically enhanced by co-administration with black pepper (piperine).
Daily Anti-HMGB1 Diet Template
Breakfast
Green tea (2 cups) with oatmeal topped with 2 tablespoons ground flaxseeds, 1 cup berries (blueberries or mixed), and walnuts
Lunch
Large salad with dark leafy greens (kale, spinach), red onions, tomatoes, extra virgin olive oil dressing, accompanied by fatty fish (salmon/sardines, 3-4 oz) and whole grain bread
Dinner
Cruciferous vegetables (broccoli, cauliflower), legumes/beans (chickpeas, lentils), turmeric-spiced dishes, and small portions of lean protein or fish
Snacks
Fresh berries, dark chocolate (small amount), nuts, and green or black tea
Foods to Limit or Avoid
- • Refined carbohydrates and added sugars
- • Processed meats
- • Trans fats (margarine, processed foods)
- • Fried foods
- • High-fat dairy
- • Excessive alcohol
- • Advanced glycation end products from grilled/charred meats
All of these increase inflammation and potentially HMGB1.