Luteolin

Luteolin (3',4',5,7-tetrahydroxyflavone) is a flavone found in celery, parsley, chamomile, artichoke, and green peppers. It is one of the most extensively studied dietary flavonoids, with 492+ publications in 2024-2026 alone and a rich preclinical evidence base spanning anti-inflammatory, neuroprotective, metabolic, and immunomodulatory pathways.

What it does well in the lab: Luteolin is a potent inhibitor of NF-κB, NLRP3 inflammasome, MAPK, and COX-2 pathways. It activates Nrf2 (antioxidant defense), AMPK (metabolic regulation), and stabilizes mast cells. It inhibits CD38 (NAD+ consumer), making it relevant to longevity research. Recent work shows ferroptosis regulation, PANoptosis inhibition, and epigenetic modulation (histone acetylation, DNA methylation).

The problem: Oral bioavailability is 5-10%. Extensive first-pass metabolism by UGT and SULT enzymes converts >90% to inactive conjugates. Achievable plasma concentrations (0.1-3 µmol/L) are often 10-100× below the IC50 values used in cell studies. This pharmacokinetic gap is the single biggest obstacle to clinical translation.

What has human evidence: Only the PEA+luteolin combination (ultra-micronized palmitoylethanolamide 700 mg + luteolin 70 mg) has meaningful RCT support — for post-COVID olfactory dysfunction (3 RCTs, N~300) and frontotemporal dementia (1 Phase 2 RCT, N=50). A 2024 critical evaluation (PMID 38861957) questioned the clinical meaningfulness of olfactory benefits. A 2026 cohort study (PMID 41493853) found luteolin supplementation associated with reduced kidney damage progression in diabetic patients — the first real human outcomes data for metabolic applications.

Who uses it: MCAS/mast cell activation syndrome patients (Theoharides NeuroProtek protocol), biohackers stacking for NAD+ preservation (CD38 inhibition), allergy sufferers, and longevity-focused individuals. The MCAS community is the largest user base.

Bottom line: A compound with exceptional preclinical credentials stuck in the clinical translation gap. The unpatentable nature of a natural flavonoid means no pharma company will fund the large RCTs needed. For now, only the PEA+luteolin combination for olfactory/neuroinflammatory conditions has defensible clinical evidence.

Reading this table: Stars = evidence volume. Type = what kind of evidence (see legend). BH = Bradford Hill causal strength (/9). Safety = FAERS/trial signals for THIS specific indication. One row = one decision.

Hard rule: Star rating cannot exceed the causal taxonomy ceiling for its Type. E.g., Type=AHE (animal→human) caps at 2/5 regardless of how many animal studies exist.

Type codes: DC=Direct causation | PC=Probable | UCC=Unreplicated causal | BC=Biomarker correlation | SE=Surrogate endpoint | ME=Mechanistic extrapolation | AHE=Animal→human | OA=Observational | RC=Reverse causation | CF=Confounded | FA=Folk/anecdotal | NE=No evidence BH: Bradford Hill criteria met (of 9). 7-9=strong causal | 5-6=moderate | 3-4=weak | 1-2=speculative | 0=none Safety flags: -- No signals | MON Monitor (known AEs, manageable) | WARN FAERS or trial safety signal — see Safety section | AVOID Contraindicated for this specific indication

Star rating legend:

Dosing Table

Formulation Table

Absorption essentials: Always take with 10-15g dietary fat (2-3× absorption improvement). Avoid high-fiber meals within 2 hours. Split dosing saturates conjugation enzymes more efficiently than single bolus. No cycling needed — no tolerance develops.

Post-COVID persistent olfactory dysfunction (PEA+luteolin combo)

Evidence: 4/5 probable causal — multiple Italian / European trials, N~300 (PMID 37380908).

• Combination formulation: Palmitoylethanolamide (PEA) 700 mg + Luteolin 70 mg, ultra-micronized, BID
• Adjunct: olfactory training (OT)
• Duration: 8–12 weeks
• Outcome: 20–30% better recovery vs OT alone in adults with anosmia persisting >6 months
• Caveats: the trial article is a fixed PEA+luteolin combo, not luteolin monotherapy. Standalone luteolin has not been tested in this indication. Use ultra-micronized PEA-LUT formulations only.

Frontotemporal dementia (PEA-LUT 770 mg combo)

Evidence: 3/5 unreplicated causal — Italian Phase 2 (PMID 40046339), N=50 FTD patients age 40–80.

• Combination formulation: PEA-LUT 770 mg, BID
• Duration: 24 weeks
• Outcome: improved frontal-lobe function; GABAergic normalization on MRS
• Caveats: unreplicated single trial; same combo-product caveat as olfactory protocol. Not a substitute for FTD-specific care.

Allergic rhinitis / mast-cell stabilization (seasonal adjunct)

Evidence: 3/5 mechanistic extrapolation — 30–60% reduced histamine release in vitro / animal allergy models (PMID 33368702); limited human data.

• Dose: 100–200 mg/day oral luteolin
• Timing: start 2 weeks before allergy season; continue through season
• Co-formulation: with Piperine 20 mg or as liposomal for enhanced absorption
• Status: adjunct only, NOT monotherapy. Use alongside standard antihistamines / nasal steroids per allergy specialist.

Inflammatory bowel disease (active flare adjunct)

Evidence: 2/5 animal-to-human — rodent DSS colitis 40–60% reduced severity (PMID 40808687); zero human RCTs.

• Formulation: liposomal luteolin (absorption is impaired in active IBD inflammation)
• Dose: 200–400 mg/day split BID with meals
• Duration: 8–12 weeks
• Status: adjunct to standard IBD therapy (5-ASA / biologics / immunomodulators). NOT a primary therapy. Discuss with gastroenterologist before combining with biologics.

General anti-inflammatory (oral, mechanistic + biomarker)

Evidence: 3/5 mechanistic extrapolation — 20–40% CRP / TNF-α reduction in animals; sparse human biomarker data (PMID 29801717).

• Dose: 100–300 mg/day, divided BID–TID with fat-containing meals
• Duration: 4–12 weeks for biomarker shift
• Caveats: evidence is largely preclinical. Reasonable as part of a broader anti-inflammatory stack (e.g., omega-3 + curcumin + luteolin) but not validated as standalone disease-modifying therapy.

Interactions Table

Contraindications

• Absolute: Known hypersensitivity to luteolin/flavonoids; active bleeding disorder; scheduled surgery within 2 weeks
• Relative: Pregnancy/lactation (insufficient data); severe hepatic impairment (Child-Pugh C); severe renal impairment (GFR <30); active chemotherapy; hormone-sensitive cancers (weak estrogenic effects)

Adverse Effects

• Common (>1%): GI upset (nausea, bloating) 5-10% — take with food, reduce dose; Headache 2-5% — transient, resolves 1-2 weeks
• Uncommon (0.1-1%): Dizziness 1-2% (mild BP lowering); fatigue/drowsiness 1-2%; allergic skin reactions <1% — discontinue
• Rare (<0.1%): Elevated liver enzymes — isolated case reports, causality uncertain, monitor LFTs if >300 mg/day for >6 months; menstrual changes — theoretical estrogenic effects, anecdotal only
• Serious (very rare): Bleeding events — primarily with anticoagulant co-use, no spontaneous reports from luteolin alone; DILI — extremely rare, more common with herbal combos
• Photosensitivity — 1 FAERS report (report 21169941), non-serious, with pregabalin as primary suspect; not established as luteolin-caused
• Animal toxicity note: 200 mg/kg caused liver/kidney toxicity in mice — equivalent to ~16g in 80kg human, far above any supplement dose (100-400 mg/day)

FAERS Signal Table (from BioMCP)

Reading FAERS data: Of 29 total reports mentioning luteolin, only 1 listed luteolin as sole suspect drug (report 21169941: photosensitivity, rash, pain — non-serious). The remaining reports are from MCAS patients where luteolin was co-administered with other medications. The dominant FAERS signal is "drug ineffective" in MCAS patients — reflecting treatment failure for the underlying condition, not adverse effects from luteolin. Per FAERS supplement noise principles, these counts are heavily inflated by concomitant medication listings.

Monitoring Table

Special Populations

Renal Impairment

Hepatic Impairment

Sex-Specific Considerations

Genetic Modifiers

Disclaimer: This section captures real-world user reports from online communities. None of this constitutes clinical evidence. N-sizes are approximate. Selection bias, placebo effect, and recall bias are inherent. Presented for completeness, not as medical guidance.

Dominant Sentiment

Mixed across ~200-500 reports. Polarized between MCAS community (frequent users, mixed results) and nootropic/longevity community (theoretical interest, fewer actual users).

What Users Report

Community Dosing vs Clinical

Popular Stacks (Community)

Red Flags & Skepticism Notes

• Theoharides conflict of interest: Theoharis C. Theoharides is Scientific Director and shareholder of Algonot LLC, which manufactures NeuroProtek (the leading luteolin supplement). He holds US Patent No. 8,268,365 and 30+ patents/trademarks. His prolific publication record (hundreds of papers on mast cells and luteolin) creates a single-researcher dependency where much of the luteolin clinical narrative flows through one person with direct financial interest.
• MLM involvement: None detected. Luteolin is not MLM-distributed.
• Influencer concentration: Moderate — Dr. Theoharides is the dominant voice. Biohacker/longevity channels mention it occasionally but no single influencer drives hype.
• Astroturfing signals: No clear patterns detected. Community sentiment is genuinely mixed, which argues against coordinated promotion.
• "All that glitters" editorial: Theoharides himself published an editorial titled "Luteolin supplements: All that glitters is not gold" (2020) acknowledging quality and bioavailability problems — a point of intellectual honesty despite commercial interest.

Folk vs Clinical Reality Check

Community experience largely aligns with clinical data in one key area: the PEA+luteolin combination for brain fog and olfactory issues generates the most positive reports, consistent with RCT evidence. The biggest divergence is in MCAS: the community treats luteolin as a first-line mast cell stabilizer based on in vitro data, but FAERS data shows "drug ineffective" as the top reaction — many MCAS patients find it doesn't help. The nootropic/PDE4 inhibition use case (artichoke extract + forskolin) has theoretical mechanistic support but zero clinical validation. The CD38/NAD+ use case is mechanistically plausible but one biohacker's n=1 experiment with 400mg daily showed no biological age impact, consistent with the bioavailability problem limiting real-world efficacy.

Key Mechanisms with Clinical Translation Status

Clinical Trials (from BioMCP / ClinicalTrials.gov)

Regulatory Status (from BioMCP)

• FDA: Not approved as drug. Dietary supplement status. DrugBank ID: DB15584.
• EMA: Not approved as drug. No monograph.
• Regulatory context: Natural flavonoid — unpatentable, no commercial incentive for pharma to pursue drug approval. GRAS as food constituent. The clinical translation gap is primarily economic, not safety-driven.

Evidence Classification (Mode 5: Evidence Classifier)

Quality Concerns

• Hasty generalization (HIGH): Animal/in-vitro findings extrapolated to human supplementation throughout. "30-50% reduced neuronal death" in rodents presented alongside human dosing recommendations without acknowledging the species gap.
• Composition fallacy (MEDIUM): PEA+luteolin combination shows clinical benefit, but luteolin alone gets credited. The file previously rated "luteolin alone (extrapolated)" at 3/5 based on combo evidence.
• Appeal to mechanism (MEDIUM): "NF-κB inhibition, AMPK activation, Nrf2 activation" — mechanistic plausibility treated as evidence of clinical effect. Thousands of compounds inhibit NF-κB in vitro; very few produce human benefit.
• Cherry-picking (MEDIUM): Cancer section emphasizes extensive in vitro anti-cancer effects while the pharmacokinetic impossibility (IC50 10-100× above achievable plasma) makes oral supplementation for cancer essentially moot.

Evidence Gaps

1. Zero human PK study establishing tissue-level concentrations at standard supplement doses
2. Zero head-to-head formulation comparison in humans (aglycone vs liposomal)
3. Zero IBD human clinical trial despite preclinical meta-analysis demanding it
4. Zero metabolic syndrome RCT despite 400+ animal studies
5. Zero pharmacogenomic stratification study (UGT1A1 effects on bioavailability unknown in humans)
6. Zero long-term safety study >12 months
7. No data on whether oral luteolin meaningfully crosses the blood-brain barrier

Bias Flags (Mode 4: First Principles)

• Unexamined assumption #1: "Oral supplementation at 100-300mg achieves therapeutic tissue concentrations" — with 5-10% bioavailability and >90% conjugation, actual free luteolin at target tissues may be negligible. This is the load-bearing assumption for the entire supplement category.
• Unexamined assumption #2: "Anti-inflammatory mechanisms translate to clinical benefit" — most NF-κB inhibitors fail clinically. Being a potent in vitro inhibitor is necessary but nowhere near sufficient.
• Unexamined assumption #3: "Luteolin works as monotherapy" — ALL clinical evidence is for combination therapy (PEA+luteolin). Standalone supplement recommendations are extrapolation.

Marketing Red Flags

• Industry marketing: Moderate. NeuroProtek/Algonot LLC markets luteolin supplements for MCAS, autism, and brain fog. Claims are qualified but the single-researcher pipeline (Theoharides → Algonot → NeuroProtek) creates a closed loop where the researcher, manufacturer, and brand are the same entity.
• Influencer economics: Low-moderate. Dr. Theoharides dominates the luteolin narrative through 30+ patents and hundreds of publications. No major social media influencer drives hype.
• Counter-narrative manipulation: No significant anti-luteolin actors detected. The compound is too small-market for pharma suppression.

Practical Considerations

• Health utility score: 5/10 — broad preclinical anti-inflammatory profile with universal theoretical relevance, but weak bioavailability (5-10%), no validated human monotherapy dose, and sparse independent clinical data limit real-world utility.
• Opportunity cost: $15-45/month for a compound with 5-10% bioavailability and no validated human dose. Could be spent on better-validated options (Omega-3, Curcumin with human RCTs, Quercetin with some clinical data).
• Verdict: WATCH LIST
• Conditions (revisit when): (a) A human dose-response trial is published for any indication as monotherapy, (b) bioavailability solutions (P-gp inhibition SMEDDS, PMID 41570979) reach commercial market, (c) FTD Phase 2 results are independently replicated, (d) the NCT06718452 tinnitus trial or NCT06777680 stroke trial report results
• Exception: PEA+luteolin combination for post-viral olfactory dysfunction — this specific use is CONDITIONAL (only if dealing with persistent anosmia/parosmia >6 months post-infection)

Bottom Line

Luteolin has one of the richest preclinical portfolios of any dietary flavonoid — 492+ publications in 2024-2026, mechanisms spanning NF-κB to ferroptosis to epigenetics, and a safety profile that appears favorable. But the compound is trapped in the supplement industry's most common failure mode: extraordinary lab promise, inadequate clinical proof. The 5-10% bioavailability means most of what you swallow never reaches its targets as free compound. The only validated clinical application is the PEA+luteolin combination for olfactory dysfunction and neuroinflammation, and even that is being questioned by independent groups. The unpatentable nature of a natural flavonoid means the large RCTs needed to move the needle will likely never be commercially funded. For biohackers willing to accept that calculated uncertainty: the safety profile supports self-experimentation at 100-200 mg/day, monitoring is minimal, and the downside risk is primarily wasted money. For evidence-based decision-makers: WATCH LIST until human monotherapy data emerges.

Brands & Product Selection

• Third-party tested: Life Extension, Swanson, Jarrow Formulas, Doctor's Best, Bulk Supplements
• PEA+luteolin: Guna (ultra-micronized, used in clinical trials), Epitech Group
• Quality markers: >98% luteolin by HPLC; heavy metals <10 ppm; CoA available on request
• Red flags: Proprietary blends, "100% absorption" claims, no CoA, <$10/month pricing

Storage & Handling

• Standard capsules: room temp (15-25°C), opaque container, away from humidity. Shelf life 2-3 years unopened.
• Liposomal: refrigerate after opening, 6-12 month shelf life opened. Phospholipids oxidize.
• Luteolin degrades with UV exposure — always store in amber/opaque container.

Palatability & Compliance

• Powder is slightly bitter — capsules preferred for most users
• Can mix into smoothies, nut butter, or full-fat yogurt if using powder
• Avoid mixing with hot liquids >60°C (degrades luteolin)
• Split dosing improves compliance vs 3x daily

Exercise & Circadian Timing

• No strong circadian effects identified; consistency > timing
• Pre-exercise (1-2h before): theoretical anti-inflammatory benefit, no human exercise data
• One animal study suggests luteolin-7-glucoside enhances sleep via GABAergic modulation (PMID 41276885) — evening dosing may have marginal benefit, but unvalidated
• NCT07280520 (athletic performance trial, enrolling) will be first human exercise data

Cost

• Standard extract: $0.50-1.50/day ($15-45/month)
• Liposomal: $1.50-2.50/day ($45-75/month)
• PEA+luteolin: $1.50-2.00/day ($45-60/month)
• Dietary sources (celery, parsley, artichoke): essentially free but provide only 1-5mg/day

• Whether oral luteolin supplements achieve therapeutically relevant tissue concentrations in any organ
• The optimal human dose for any indication (all dosing is extrapolated from animals)
• Whether luteolin crosses the blood-brain barrier in meaningful amounts after oral dosing
• Long-term safety beyond 12 months of continuous supplementation
• Whether luteolin-7-glucoside (plant form) is effectively converted to active aglycone by human gut bacteria
• The real contribution of luteolin vs PEA in combination therapy
• Whether UGT1A1 polymorphisms (Gilbert syndrome) meaningfully alter supplement bioavailability
• Whether the CD38 inhibition observed in vitro translates to NAD+ preservation at supplement doses in humans
• Whether newer delivery systems (P-gp inhibition SMEDDS, intranasal nanocomposites) will solve the bioavailability problem
• Whether the hormetic dose-response (PMID 34403687) means lower doses are actually more effective than higher doses
• Whether the new eye health data (photoreceptor protection, vitreoretinopathy, glaucoma) translates to oral supplementation benefits

Systematic Reviews & Meta-Analyses

• Capra AP et al. (2023). PEA+luteolin for post-COVID olfactory dysfunction meta-analysis. Biomedicines. PMID: 37626685
• Shi Y et al. (2026). Anti-neuroinflammatory supplement + OT for post-COVID olfactory disorders SR+MA. Eur Arch Otorhinolaryngol. PMID: 41559316
• Feng Y et al. (2025). Preclinical evidence for luteolin in UC meta-analysis. Front Pharmacol. PMID: 40808687
• Wang Q et al. (2025). Antidepressant activity of flavones meta-analysis. Pharm Biol. PMID: 39996320
• Bischoff S et al. (2024). Treatment of COVID-19 olfactory dysfunction SR. Curr Allergy Asthma Rep. PMID: 39477832
• Guo H et al. (2026). Global research landscape luteolin bibliometric. Front Nutr. PMID: 41684783

Landmark RCTs & Clinical Trials

• Di Stadio A et al. (2023). PEA+luteolin RCT, COVID olfactory, N=202. Eur Arch Otorhinolaryngol. PMID: 37380908
• Cantone E et al. (2024). PEA+luteolin vs ALA, COVID parosmia, N=85. Eur Arch Otorhinolaryngol. PMID: 38492007
• Gellrich J et al. (2024). PEA+luteolin olfactory: clinical meaningfulness questioned. ORL. PMID: 38861957
• Assogna M et al. (2025). Phase 2 PEA+luteolin in frontotemporal dementia, N=50. Brain Commun. PMID: 40046339
• Sultana A et al. (2025). Luteolin herbal Unani vs nitrofurantoin for UTI. Curr Pharm Des. PMID: 40265431
• Li L et al. (2026). Luteolin supplementation and kidney damage in diabetic patients, cohort. Phytother Res. PMID: 41493853
• Yang X et al. (2021). TCM formula with luteolin in HCC, N=291. Phytomedicine. PMID: 33984593

Mechanism Studies (2024-2026 highlights)

• Liang Q et al. (2025). Luteolin diabetes mechanisms systematic review. Eur J Pharmacol. PMID: 40311831
• Luo L et al. (2026). Luteolin NLRP3 inflammasome inhibition via AMPK in colitis. Cell Prolif. PMID: 41077623
• Xie H et al. (2026). Luteolin endothelial barrier + myocardial I/R injury via FOXP1-NLRP3. Int J Mol Sci. PMID: 41596522
• Zhong X et al. (2026). Luteolin PFKFB3 targeting in doxorubicin cardiotoxicity. Phytomedicine. PMID: 41720006
• Li K et al. (2026). Luteolin autophagy-dependent ferroptosis in HCC via SLC40A1. Eur J Pharmacol. PMID: 41933872
• Liu K et al. (2026). Luteolin attenuates asthma via ALOX15-mediated ferroptosis. Inflammation. PMID: 41547709
• Ouyang X et al. (2026). Luteolin alleviates PCOS via AR/STAT3/NLRP3. J Ovarian Res. PMID: 41580826
• Shi FL et al. (2026). Luteolin targets XIAP to block PANoptosis. Int Immunopharmacol. PMID: 41637826
• Wang X et al. (2026). Luteolin in osteoarticular diseases review. Inflammopharmacology. PMID: 41941072
• Peng R et al. (2026). Luteolin targets CD74+ macrophages in OA via CEBPB/P65. Adv Sci. PMID: 41268703
• Han X et al. (2026). Luteolin + Lycium barbarum protects photoreceptors. Neural Regen Res. PMID: 40817723
• Wu L et al. (2026). Luteolin mitigates proliferative vitreoretinopathy via ERK1/2. Front Pharmacol. PMID: 41710935
• Li J et al. (2026). Luteolin ameliorates skin lipid hypersecretion. J Nutr Biochem. PMID: 40946871
• Li T et al. (2026). Luteolin ameliorates steroid-induced osteonecrosis via gut microbiota. J Transl Med. PMID: 41652636
• Han SH et al. (2026). Luteolin neuroprotection via gut-brain axis. J Agric Food Chem. PMID: 41609616
• Divyajanani S et al. (2026). Luteolin epigenetic modulation Nrf2 in hyperglycemia. Cell Biochem Biophys. PMID: 41649668
• Kim H et al. (2026). Luteolin-7-glucoside enhances sleep via GABAergic modulation. J Sci Food Agric. PMID: 41276885
• Perez-Siles G et al. (2026). Luteolin repurposed for CMTX6 energy production. J Mol Cell Biol. PMID: 41871365
• Zheng Y et al. (2026). P-gp inhibition SMEDDS for luteolin bioavailability. J Adv Res. PMID: 41570979
• Spicer LJ et al. (2026). Luteolin influence on steroidogenesis. J Appl Toxicol. PMID: 41482630
• Binmahfouz LS (2026). Luteolin in female reproductive disorders review. Front Pharmacol. PMID: 41821610
• Poór M et al. (2026). Luteolin sulfate metabolites affect warfarin-albumin binding. ACS Omega. PMID: 41970813
• Jin Z et al. (2026). Luteolin prevents hyperoxaluria renal injury. Int J Biochem Cell Biol. PMID: 41672398
• Yang F et al. (2026). Luteolin attenuates bone destruction via NLRP3/TNF-α. Cell Signal. PMID: 41605374

Foundational Reviews

• Aziz N et al. (2018). Luteolin anti-inflammatory mechanisms review. J Ethnopharmacol. PMID: 29801717
• Nabavi SF et al. (2015). Luteolin neuroprotection review. Brain Res Bull. PMID: 26361743
• Gendrisch F et al. (2021). Luteolin skin inflammation review. Biofactors. PMID: 33368702
• Hostetler GL et al. (2017). Flavones bioavailability review. Adv Nutr. PMID: 28507008
• Zhu M et al. (2024). Luteolin comprehensive multifunctional review. Phytother Res. PMID: 38666435
• Calabrese EJ et al. (2021). Luteolin hormesis review. Mech Ageing Dev. PMID: 34403687
• Ali F & Siddique YH (2019). Luteolin in Alzheimer's review. CNS Neurol Disord Drug Targets. PMID: 30892166
• Imran M et al. (2019). Luteolin anticancer review. Biomed Pharmacother. PMID: 30798142
• Singh D & Shukla G (2025). Luteolin anticancer pathways review. Inflammopharmacology. PMID: 39543054
• Chang XQ & Yue RS (2025). Luteolin diabetes review. Chin J Integr Med. PMID: 39302570
• Zhou J et al. (2025). Luteolin antidepressant review. J Pharm Anal. PMID: 40276566
• Wang Z et al. (2021). Luteolin glycolipid metabolism review. J Agric Food Chem. PMID: 33522240
• Li B et al. (2021). Luteolin gut microbiota UC rats. Life Sci. PMID: 33434535

Food Sources

• Highest dietary sources: celery (leaves), parsley, thyme, peppermint, perilla, chamomile tea, artichoke, green pepper, broccoli, carrots, olive oil
• Typical content: 0.1-10 mg per 100g depending on plant source
• Dietary intake: 0.5-5 mg/day Western; 5-10 mg/day Mediterranean