# Luteolin (3',4',5,7-tetrahydroxyflavone)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/luteolin-3457-tetrahydroxyflavone
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-02
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** 3',4',5,7-tetrahydroxyflavone, Luteoline, C.I. Natural Yellow 2, Digitoflavone, Luteolol

## Overview

Luteolin is a polyphenolic flavonoid (C15H10O6) that exerts anti-inflammatory and anticancer effects primarily by inhibiting NF-κB, AP-1, and STAT3 transcription factor pathways, suppressing [pro-inflammatory cytokine](/ingredients/condition/inflammation)s TNF-α and IL-6, and inducing apoptosis via caspase activation with concurrent ERK/Akt inhibition. In preclinical models, luteolin demonstrates an IC50 of 22.2 µM against HT-29 colon cancer cell viability and 16.2 µM against α-glucosidase activity, though robust large-scale human clinical trial data confirming these effects remain limited.

## Health Benefits

- **[Anti-Inflammatory](/ingredients/condition/inflammation) Activity**: Luteolin inhibits LPS-induced production of TNF-α and IL-6 and blocks NF-κB and AP-1 activation, reducing the transcription of downstream pro-inflammatory mediators including inducible nitric oxide synthase (iNOS) and COX-2.
- **Anticancer Potential**: Luteolin suppresses proliferation of cancer cell lines such as Lewis lung carcinoma and HT-29 colon cancer cells (IC50 ≈ 22.2 µM) by activating caspase-dependent apoptosis and inhibiting survival kinases ERK and Akt.
- **Antioxidant and Free Radical Scavenging**: The catechol moiety on the B-ring of luteolin donates hydrogen atoms to neutralize [reactive oxygen species](/ingredients/condition/antioxidant) (ROS), and its chelation of transition metal ions further limits oxidative stress in cellular environments.
- **Antidiabetic and Antiglycation Effects**: Luteolin inhibits α-glucosidase with an IC50 of 16.2 µM, slowing postprandial glucose absorption, and inhibits sugar-induced BSA glycation with IC50 values ranging from 19.6 µM (fructose) to 58 µM (ribose), potentially reducing advanced glycation end-product formation.
- **[Neuroprotective Effect](/ingredients/condition/cognitive)s**: By suppressing neuroinflammatory NF-κB signaling in microglia and reducing oxidative damage to neurons, luteolin has demonstrated protective effects against neurodegeneration in preclinical cell and animal models.
- **NAD+ [Metabolism](/ingredients/condition/weight-management) Support**: Luteolin inhibits CD38, a major NAD+-consuming enzyme, thereby preserving intracellular NAD+ levels and supporting [mitochondrial](/ingredients/condition/energy) bioenergetics and [sirtuin](/ingredients/condition/longevity)-dependent cellular maintenance pathways.
- **[Antimicrobial](/ingredients/condition/immune-support) Activity**: Luteolin disrupts bacterial membrane integrity and inhibits key microbial enzymes, exhibiting broad-spectrum antimicrobial activity against both gram-positive and gram-negative organisms in in vitro assays.

## Mechanism of Action

Luteolin inhibits the NF-κB pathway by targeting Src kinase and IκB kinase, preventing nuclear translocation of NF-κB and reducing transcription of [inflammatory](/ingredients/condition/inflammation) genes encoding TNF-α, IL-6, IL-1β, iNOS, and COX-2; it simultaneously suppresses AP-1 via MAPK pathway inhibition and blocks STAT3 activation through upregulation of SOCS3. In cancer cell models, luteolin inhibits the PI3K/Akt and ERK1/2 survival signaling cascades, triggering [mitochondrial](/ingredients/condition/energy) apoptotic pathways with downstream caspase-3 and caspase-9 activation and cytochrome c release. As a direct [antioxidant](/ingredients/condition/antioxidant), the ortho-dihydroxy (catechol) group on luteolin's B-ring provides electron donation for ROS quenching, and chelation of redox-active iron and copper ions further suppresses Fenton-type oxidative reactions. Luteolin also acts as a CD38 inhibitor, reducing NAD+ catabolism, and moderately inhibits CYP enzymes including CYP1A2, CYP2C8, CYP2C9, and CYP3A4, which has implications for drug [metabolism](/ingredients/condition/weight-management) and potential interactions.

## Clinical Summary

Human clinical trials specifically isolating luteolin as a single intervention are sparse; most clinical observations derive from formulations containing luteolin alongside other flavonoids or polyphenols, making it difficult to attribute outcomes solely to luteolin. One referenced clinical study using a luteolin-containing compound reported therapeutic benefit in [inflammation](/ingredients/condition/inflammation)-related conditions through multi-pathway modulation, but did not disclose participant numbers, randomization methodology, or quantified effect sizes, precluding meaningful effect size estimation. Bioavailability studies conducted in rats indicate that oral luteolin achieves peak plasma concentrations within 1–2 hours, with absolute bioavailability ranging from approximately 17.5% (free form) to 53.9% (total including conjugated metabolites), suggesting that standard oral dosing in humans may yield highly variable systemic exposure. Confidence in clinical recommendations for luteolin supplementation remains low-to-moderate pending adequately powered, well-controlled human intervention trials with pre-specified primary endpoints.

## Nutritional Profile

Luteolin is a pure flavonoid compound (molecular weight 286.24 g/mol) and is not a macronutrient source; it contributes negligible caloric value when consumed at supplemental doses. As a polyphenol, it is categorized within the flavone subclass of flavonoids, characterized by a 2-phenylchromen-4-one backbone with hydroxyl groups at positions 5, 7, 3', and 4'. In whole food sources, luteolin co-occurs with related flavonoids (apigenin, chrysoeriol), carotenoids, and vitamins C and E, which may act synergistically to enhance its [antioxidant activity](/ingredients/condition/antioxidant). Bioavailability is substantially influenced by the food matrix, gut microbiome composition (which hydrolyzes glycoside conjugates to release the active aglycone), and co-ingestion of lipids; free luteolin aglycone has an estimated oral bioavailability of 17.5–26% in animal models, with significant interindividual variability anticipated in humans due to [microbiome diversity](/ingredients/condition/gut-health) and CYP enzyme polymorphisms.

## Dosage & Preparation

- **Pure Powder (≥98% HPLC purity)**: Used in research at 5–50 mM stock solutions in DMSO or NaOH; no universally established human supplemental dose has been validated in large RCTs.
- **Oral Capsules/Tablets**: Commercially available supplements typically provide 50–200 mg per serving, though these doses are empirically derived and not confirmed by phase II/III clinical trials.
- **Standardized Plant Extracts**: Formulations standardized to luteolin content (e.g., celery seed extract, chamomile extract) at 20–40% luteolin by weight are used in nutraceutical products to deliver consistent doses.
- **Traditional Herbal Preparations**: Consumed indirectly via dietary sources such as parsley, thyme, celery, and chamomile tea; typical dietary intake of luteolin from food is estimated at 1–3 mg/day in Western diets.
- **Bioavailability Enhancement Forms**: Luteolin-7-O-glucoside (cynaroside) and phospholipid complexes (phytosomes) have been investigated to improve oral bioavailability beyond the 17.5–26% reported for the free aglycone form.
- **Timing Note**: Administration with a lipid-containing meal may modestly enhance absorption given luteolin's lipophilic character; enterohepatic recycling contributes to a secondary plasma peak observed several hours post-dose.

## Safety & Drug Interactions

Luteolin has not been subjected to formal human safety dose-escalation trials establishing a maximum tolerated dose or no-observed-adverse-effect level (NOAEL) in clinical populations, and most available safety data are derived from animal toxicology studies or in vitro assays. Its moderate inhibition of CYP1A2, CYP2C8, CYP2C9, and CYP3A4 enzymes presents a clinically relevant concern for drug interactions: co-administration with CYP-metabolized drugs such as warfarin (CYP2C9), theophylline (CYP1A2), cyclosporine (CYP3A4), or statins (CYP3A4) could theoretically alter plasma drug concentrations, though in vivo human pharmacokinetic interaction studies confirming this risk are lacking. Luteolin's inhibition of aromatase and weak phytoestrogenic activity raise a theoretical contraindication in individuals with hormone-sensitive conditions such as estrogen receptor-positive breast cancer, and it should be used with caution in these populations until further data are available. Pregnancy and lactation safety has not been established; given the absence of controlled human data, luteolin supplementation beyond dietary food-based intake is generally not recommended for pregnant or breastfeeding individuals.

## Scientific Research

The preponderance of luteolin research consists of in vitro cell-based assays and animal model studies, with limited and methodologically heterogeneous human clinical data available as of the current literature. Preclinical studies consistently demonstrate [anti-inflammatory](/ingredients/condition/inflammation), anticancer, and [antioxidant activity](/ingredients/condition/antioxidant) across diverse cell lines and murine models, with quantified IC50 values reported across multiple biological targets (e.g., HT-29 colon cancer IC50 = 22.2 µM; α-glucosidase IC50 = 16.2 µM); however, translation to human clinical outcomes has not been rigorously established. One clinical report cited efficacy of a luteolin-containing multi-compound formulation in inflammatory disease management via NF-κB/STAT3/AP-1 modulation, but the publication lacked randomized controlled trial design, defined sample size, or reported effect sizes, substantially limiting its evidentiary weight. Overall, luteolin's evidence base warrants an honest classification as predominantly preclinical, and well-powered, placebo-controlled human RCTs are needed before definitive clinical recommendations can be made.

## Historical & Cultural Context

Luteolin-containing plants have been utilized in traditional medicine systems for millennia, most notably in Traditional Chinese Medicine (TCM), where herbs such as Lonicera japonica (honeysuckle) and Scutellaria baicalensis (Chinese skullcap) — both luteolin sources — were prescribed for fever reduction, detoxification, and respiratory inflammation. In European herbal tradition, weld (Reseda luteola), one of the richest botanical sources of luteolin, was historically valued as a yellow textile dye plant, though its medicinal use for inflammatory conditions was also documented in medieval European herbalism. Ayurvedic practitioners incorporated luteolin-rich plants such as tulsi (Ocimum sanctum) and ginger into formulations intended for [anti-inflammatory](/ingredients/condition/inflammation) and digestive applications, though luteolin itself was not isolated and identified as the active constituent until the development of modern phytochemical analysis in the 19th and 20th centuries. The compound's name derives from Reseda luteola ('little yellow'), reflecting its role as a natural dye constituent before its pharmacological properties were systematically characterized.

## Synergistic Combinations

Luteolin and quercetin exhibit complementary NF-κB and MAPK inhibition with partially overlapping but distinct binding profiles at inflammatory enzyme targets, and their co-administration in preclinical models has been shown to produce additive to synergistic [anti-inflammatory](/ingredients/condition/inflammation) effects at lower individual doses than required for either compound alone. Luteolin combined with piperine (from black pepper) may enhance oral bioavailability by inhibiting intestinal P-glycoprotein efflux transport and first-pass CYP3A4 [metabolism](/ingredients/condition/weight-management), a mechanism well-characterized for structurally similar flavonoids. Pairing luteolin with [NAD+ precursor](/ingredients/condition/longevity)s such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) may produce complementary NAD+ elevation by simultaneously reducing CD38-mediated NAD+ consumption (luteolin) and increasing biosynthetic NAD+ input (NR/NMN), supporting [mitochondrial](/ingredients/condition/energy) and sirtuin-dependent pathways.

## Frequently Asked Questions

### What does luteolin do in the body?

Luteolin acts primarily as an anti-inflammatory agent by blocking NF-κB and AP-1 transcription factor activation, reducing production of pro-inflammatory cytokines TNF-α and IL-6 and the enzyme iNOS. It also functions as a direct antioxidant through free radical scavenging via its catechol B-ring, inhibits cancer cell survival kinases ERK and Akt, and preserves NAD+ levels by inhibiting the CD38 enzyme.

### What is the recommended dosage of luteolin for supplements?

No universally validated human clinical dose has been established in large randomized controlled trials; commercially available supplements most commonly provide 50–200 mg per day of luteolin, an empirically derived range. Bioavailability studies in rats show peak plasma levels within 1–2 hours, but human absorption varies considerably based on gut microbiome composition and formulation, so standardized forms such as luteolin phytosomes or glycoside extracts may improve consistency of systemic exposure.

### Does luteolin have anticancer properties?

Preclinical in vitro and animal studies consistently demonstrate anticancer activity: luteolin inhibits HT-29 colon cancer cell viability with an IC50 of 22.2 µM and suppresses Lewis lung carcinoma proliferation via caspase-dependent apoptosis and ERK/Akt inhibition. However, robust human clinical trial evidence confirming anticancer efficacy in vivo is currently absent, and luteolin should not be considered a substitute for standard oncological treatment based on existing data.

### Does luteolin interact with medications?

Luteolin moderately inhibits CYP enzymes CYP1A2, CYP2C8, CYP2C9, and CYP3A4 in vitro, which raises the theoretical possibility of elevated plasma concentrations of co-administered drugs metabolized by these enzymes — including warfarin, theophylline, cyclosporine, and certain statins. In vivo human pharmacokinetic drug interaction studies confirming the clinical magnitude of these effects are currently lacking, so individuals taking prescription medications should consult a healthcare provider before supplementing with luteolin.

### What foods are high in luteolin?

Luteolin is found in numerous common foods, with the highest concentrations in fresh herbs such as dried thyme (up to ~900 mg/100g dry weight), parsley, and celery, as well as in chamomile tea, artichoke, peppers, and chicory. Typical dietary intake in Western populations is estimated at only 1–3 mg per day from food sources, which is substantially lower than doses studied in preclinical research, underscoring the rationale for concentrated supplement forms in clinical investigation.

### Is luteolin safe during pregnancy and breastfeeding?

There is insufficient clinical data to establish the safety of luteolin supplementation during pregnancy and breastfeeding, so it is generally recommended to avoid supplemental doses during these periods. While luteolin is naturally present in foods, concentrated supplement forms have not been adequately studied in pregnant or nursing women. Consult with a healthcare provider before using luteolin supplements if you are pregnant, planning to become pregnant, or breastfeeding.

### How does luteolin's bioavailability compare to other flavonoids?

Luteolin has relatively low bioavailability when taken orally, with poor absorption in the small intestine and significant first-pass metabolism by the liver and gut microbiota. Co-administration with certain compounds or food components may enhance its absorption, though research on optimal delivery methods is still emerging. Some studies suggest that luteolin glucosides (the glycosylated form found in plants) may have different absorption kinetics than the aglycone form.

### What does current clinical research show about luteolin's anti-inflammatory effects in humans?

Most evidence for luteolin's anti-inflammatory effects comes from in vitro and animal studies demonstrating inhibition of NF-κB signaling and reduction of pro-inflammatory cytokines like TNF-α and IL-6. Human clinical trials are limited, though preliminary studies suggest potential benefits for inflammatory conditions, but larger, well-designed trials are needed to establish efficacy in specific patient populations. The gap between promising laboratory data and clinical human evidence remains significant for this ingredient.

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