CYP3A4 and P-gp supplement–drug interactions
Reference table of supplement interactions affecting CYP3A4 and P-glycoprotein in oncology care.
This reference summarises CYP3A4 and P-glycoprotein (P-gp) interaction considerations for supplements.
Strong CYP3A4 inhibitors can markedly increase exposure of these drugs, while strong CYP3A4 inducers can markedly decrease exposure and risk under‑dosing.
For palbociclib and other individual drugs, always cross‑check the prescribing information for exact AUC change data and dose‑adjustment guidance, and review any planned combinations with an oncology pharmacist or treating oncologist.
Be sure to read the 'Drug and Supplements Interactions overview page before using this page.
Supplements — Quick Risk Tier Reference
This table supports integrative oncology discussions. Evidence varies substantially. In vitro findings may not predict clinical effects. Liposomal formulations can increase bioavailability and require added caution.
🔴 High concern — avoid or specialist supervision
Supplement | Direction | Key reason |
|---|---|---|
Citrus Bergamot (high dose) | ↑ Exposure | Furanocoumarins resemble grapefruit. Avoid with CYP3A4-substrate oncology drugs. |
Grapefruit (any form) | ↑ Exposure | FDA label warning. Potent intestinal CYP3A4 inhibitor. |
Long Pepper / Piperine (>10 mg) | ↑ Exposure | Potent CYP3A4 and P-gp inhibitor. Well-characterised clinical concern. |
Danshen (Salvia miltiorrhiza) | ↑↓ Unpredictable | Induces CYP3A4 in vivo, reducing exposure about 27%. Potently inhibits in vitro. |
Super Artemis / Artemisia annua | ↑ + Complex | About 70% CYP3A4 inhibition in vitro. Repeat dosing may cause auto-induction. |
Ashwagandha (therapeutic doses) | ↓ Exposure risk | CYP3A4 modulation or induction appeared in a 2025 study. Similar concern to St. John’s Wort. |
🟡 Moderate concern — use with monitoring and oncologist awareness
Supplement | Direction | Key reason |
|---|---|---|
Berberine (Pure / Liposomal) | ↑ Exposure | Inhibits CYP3A4, CYP2D6, and P-gp in vivo at 300 mg three times daily. |
Chrysin (Pro Liposomal) | ↑ Exposure | Strong flavone CYP3A4 inhibitor in vitro. Liposomal delivery raises exposure concerns. |
Curcumin C3 (especially Liposomal) | ↑ / Dual | CYP3A4 and P-gp inhibition is plausible. Monitor complete blood count. |
Scutellaria / Baicalein | ↑ Exposure | Contains several CYP3A4-active flavones at 500 mg. |
Trans Resveratrol (Liposomal) | ↑ Exposure | CYP3A4 inhibition and possible mechanism-based inactivation. |
Polydatin (Liposomal) | ↑ Exposure | Resveratrol prodrug with similar CYP3A4 inhibition concerns. |
Luteolin (Liposomal) | ↑ Exposure | CYP3A4 IC50 of 4.62 µM. Liposomal dosing increases significance. |
Apigenin (Liposomal) | ↑ Exposure | Moderate CYP3A4 inhibitor in vitro. Monitor at 200 mg liposomal doses. |
Genistein Ultra | ↑ Exposure + ER | CYP3A4 inhibition plus phytoestrogenic activity. Consider ER-positive relevance. |
Withaferin A (Liposomal) | ? ↓ Risk | Apply ashwagandha caution. CYP3A4 modulation is possible. |
Milk Thistle (Silymarin) | ↔ CYP3A4; ⚠ UGT | CYP3A4 interaction is minimal clinically. Strong UGT inhibition may raise palbociclib exposure. Humans Milk Thistle CYP enzyme study details unpacked here |
🟢 Low concern — standard monitoring; no specific dose adjustment
Supplement | Direction | Key reason |
|---|---|---|
AHCC | ↔ | No clinically relevant CYP3A4 interaction. |
Agaricus Extract | ↔ | No established CYP3A4 interaction. |
Astragaloside IV (isolated) | ↔ | Low risk at isolated astragaloside doses. |
Calcium AKG | ↔ | No CYP3A4 interaction. |
CoQ10 (Liposomal) | ↔ | No CYP3A4 interaction. Antioxidant considerations are separate. |
Cordyceps | ↔ | No established CYP3A4 interaction. |
Coriolus / Turkey Tail | ↔ | Polysaccharides do not affect CYP3A4. |
EGCG / Super Green Tea Extract | ↔ (CYP3A4) | No significant CYP3A4 effect in clinical review. Use transporter caution at high doses. |
HCA Garcinia | ↔ | No CYP3A4 interaction. |
Honokiol (all forms) | ↔ (CYP3A4) | Weak CYP3A4 effect. Stronger inhibition affects CYP1A2, CYP2C9, and CYP2C19. |
Hydroxytyrosol | ↔ | No established CYP3A4 interaction. |
Lycopene Plus | ↔ | No CYP3A4 interaction. |
Magnesium (all forms) | ↔ | No CYP interaction. |
Maitake | ↔ | Polysaccharides do not affect CYP3A4. |
Mega Flaxseed Lignans | ↔ (PK) | No CYP3A4 concern. Phytoestrogenic pharmacodynamic concern remains. |
Modified Citrus Pectin | ↔ | Water-soluble polysaccharide with no CYP interaction. |
NAC | ↔ | No CYP3A4 interaction. |
Nattokinase | ↔ | No CYP3A4 interaction. |
NMN (Liposomal) | ↔ | No CYP3A4 interaction. |
Omega-3 Fish Oil | ↔ | No CYP3A4 interaction. |
PEA | ↔ | No CYP3A4 interaction. |
R-Lipoic Acid | ↔ | No CYP3A4 interaction. |
Reishi | ↔ | Minimal concern. Polysaccharide component is safe. |
Shiitake (Liquid) | ↔ | Polysaccharides do not affect CYP3A4. |
Spermidine (Liposomal) | ↔ | No CYP3A4 interaction. |
TUDCA | ↔ | No CYP3A4 interaction. |
Urolithin A | ↔ | No established CYP interaction. |
Vitamin C (Liposomal) | ↔ | No CYP3A4 interaction at oral doses. |
Vitamin D3 / K2 | ↔ | D3 is a CYP3A4 substrate, not an inhibitor. |
⚪ Insufficient data — cannot currently assess
Supplement | Direction | Key reason |
|---|---|---|
Andrographis (Andrographolide) | ? ↑ Mild–moderate | Inhibits CYP3A4 and P-gp in vitro. No human pharmacokinetic data confirms significance. |
Betulinic Acid (Liposomal) | ? ↑ Weak | Limited data. Possible weak CYP3A4 inhibition. Monitor. |
Black Cumin / Thymoquinone | ? ↑ Moderate | Thymoquinone has CYP-inhibitory properties. Use standard monitoring. |
Boswellia / AKBA / Inflasanum | ↔ | No significant CYP3A4 data. Likely low risk. |
Fisetin (Liposomal) | ? ↑ Mild | Moderate CYP3A4 inhibition in vitro. Liposomal exposure raises concern. |
Grape Seed Extract | ? ↑ Mild | Proanthocyanidins show mild CYP3A4 inhibition in vitro. |
Green Propolis | ? ↑ | Contains CYP3A4-active flavonoids. Monitor. |
Olive Leaf Extract | ? ↑ Mild | Mild in vitro evidence only. |
Quercetin & Bromelain | ↑ Mild–moderate | Moderate CYP3A4 inhibition in vitro. Monitor at 400 mg. |
Rosmarinic Acid (Liposomal) | ↑ Mild–moderate | CYP-inhibitory properties. Liposomal delivery increases concern. |
Shikonin (Liposomal) | ↑ Preclinical | CYP inhibition in vitro. Evidence remains limited. |
Sulforaphane (Broccoli Ultra) | ↔ / ? | Complex Nrf2 and Phase II induction. Minimal CYP3A4 effect at standard doses. |
Ultra-TQ Thymoquinone | ↑ Moderate | Similar to black cumin, but at a higher concentration. |
CYP3A4 and P-gp Supplement - Drug Interactions in more detail.
This table lists each supplement, its primary CYP3A4 effect, and its P-gp effect. It also covers other affected CYPs, the likely exposure change for CYP3A4-substrate drugs, the evidence level, and practical dose guidance..
Substance / compound | CYP3A4 effect | P-gp effect | Other CYPs affected | Net effect on CYP3A4-substrate drug exposure | Evidence level and source | Clinical notes / dose guidance |
|---|---|---|---|---|---|---|
Agaricus Extract ↔ / ? | Not well characterised. Likely minimal at typical doses. | Not established. | No data. | Likely minimal. Insufficient data. | Preclinical, in vitro, and expert opinion. | No significant CYP3A4 interaction is reported. Beta-glucans are unlikely to substantially affect CYP pathways. Use general monitoring. |
AHCC (Active Hexose Correlated Compound) ↔ | Minimal or negligible at typical doses. | Not established. | Possible mild CYP1A2 effects. | Likely minimal pharmacokinetic interaction. | Limited clinical studies. | Standardised mushroom extract. Human studies report no clinically relevant CYP3A4 inhibition. Used in oncology without documented CYP3A4-substrate drug-specific interactions. |
Andrographis (andrographolide) ↑ | Weak–moderate inhibitor in vitro (Ki ≈25.4 μM). May down-regulate CYP3A4 mRNA and protein expression. | Inhibits transport concentration-dependently. May down-regulate P-gp overexpression and increase P-gp substrate absorption. | Weak CYP1A2, CYP2B6, CYP2C9, and CYP2E1 inhibition. Potent CYP2C9 inhibition also reported. | May increase exposure through combined CYP3A4 and P-gp inhibition. | Human liver microsomes and Caco-2 studies; rat preclinical data. | Clinical relevance at typical oral doses remains unconfirmed. Monitor CBC and toxicity signs if combined. Discuss timing with the oncologist. |
Apigenin (Pro Liposomal) ↑ | Moderate inhibitor in vitro for standard extracts (IC50 ≈6.25–6.5 μM). | Possible weak inhibition. | Inhibits CYP1A2 and CYP2C9. | High supplement doses may moderately increase exposure. | Human microsome studies. | Liposomal formulations increase systemic exposure. Use caution at liposomal doses of 200 mg or more. Monitor for increased toxicity, including neutropenia. |
Ashwagandha Pure (Withania somnifera) ↓ | Potential CYP3A4 inducer. Modulates CYP3A4 expression. | Not well established. | May affect CYP2D6. | May decrease exposure. Avoid or use with monitoring. | In vitro evidence and conflicting clinical case reports. | Some evidence suggests CYP3A4 induction. Newer work reports expression modulation. Consider avoiding during active treatment with CYP3A4-substrate oncology drugs. |
Astragaloside IV ↔ / ? | Minimal direct effect from isolated astragaloside. Root extracts may weakly induce CYP3A4. | Not established. | No significant data. | Likely minimal at isolated doses. | In vitro evidence limited to root extracts. | No established interaction data at a 50 mg isolated dose. Full astragalus extracts have weak-induction data. Isolated astragaloside likely presents low risk. |
Baicalein (Pro Liposomal) ↑ | Moderate CYP3A4 inhibitor in vitro. | Possible inhibition. | Inhibits CYP1A2, CYP2C9, and CYP2C19. | May moderately increase exposure at supplement doses. | Human microsome studies. | Liposomal delivery may increase systemic concentrations. Monitor for toxicity. Closely related to Scutellaria (skullcap). |
Berberine (Pro Liposomal and Pure) ↑ | Low doses may weakly induce. Clinical doses inhibit CYP3A4. Repeated 300 mg three-times-daily dosing decreased activity in vivo. | Inhibits P-gp and may increase drug absorption. | Inhibits CYP2D6 and CYP2C9 in vivo. | Likely increases exposure. Use caution. | Human clinical study. | Guo et al. (2011) reported decreased CYP2D6, CYP2C9, and CYP3A4 activity. Monitor CBC closely. Liposomal formulations may amplify the effect. |
Betulinic Acid (Pro Liposomal) ↑ | Weak–moderate inhibition reported in vitro. | Not well established. | May inhibit CYP2C9. | Potential mild increase. Data are limited. | Limited in vitro evidence. | Clinical significance at 50 mg is uncertain. Liposomal delivery may increase systemic exposure. Use monitoring. |
Black Cumin Seed Oil (thymoquinone) ↑ | Moderate CYP3A4 inhibition from thymoquinone. | Possible weak inhibition. | May inhibit CYP2D6 and CYP1A2. | May moderately increase exposure. | In vitro and limited preclinical evidence. | At 500 mg, interaction potential may be clinically relevant. Monitor for increased adverse effects. |
Boswellia MEGA AKBA (Liposomal) and Inflasanum AKBA ↔ | Weak or no direct inhibition at standard doses. | Not well established. | No major CYP inhibition reported. | Likely minimal pharmacokinetic interaction. | In vitro and preclinical evidence. | No significant CYP3A4 interaction is reported at supplement doses. |
Broccoli Ultra — sulforaphane ↔ / ? | Complex. Induces phase II pathways through Nrf2. May weakly inhibit CYP450 at high doses. | P-gp is not significantly affected. | Induces GSTs, UGTs, and SULT. May affect CYP1A2. | Uncertain. High doses may alter metabolism through phase II pathways. | Preclinical and mechanistic evidence. Lubelska et al. 2012 (PMID 23238480). | Dietary-dose CYP3A4 impact appears minimal. High supplement doses may matter. Sulforaphane may enhance phase II conjugation of palbociclib metabolites. |
Chrysin (Pro Liposomal) ↑ | Strong inhibitor in vitro (IC50 ≈0.6 μM). | May inhibit at higher concentrations. | Strong CYP1A2 inhibitor. | May significantly increase exposure. Use caution at 250 mg. | Human microsomes. Kondža et al. 2024; Ho et al. 2001. | Liposomal delivery raises plasma concentrations. Clinical relevance is uncertain, but the in vitro signal warrants caution. Monitor for neutropenia and fatigue. |
Citrus Bergamot ↑ | Contains bergamottin and naringenin, which inhibit CYP3A4. | May inhibit through naringenin. | Moderate CYP2C9 inhibition from bergapten. | May increase exposure. Avoid or use very cautiously. | In vitro evidence and grapefruit analogy. DrugBank; Dayyih et al. 2024. | Bergamot contains grapefruit-related furanocoumarins. Avoid concurrent supplement use with CYP3A4-substrate oncology drugs. |
Cordyceps (Liquid Extract) ↔ / ? | Minimal interaction at dietary doses. | Not established. | No established CYP data for Cordyceps sinensis extract. | Likely minimal pharmacokinetic interaction. | Preclinical evidence and expert opinion. | Contains cordycepin and polysaccharides. No significant clinical CYP3A4 interaction is established. Use standard monitoring. |
Coriolus / Turkey Tail (PSK/PSP) ↔ | No significant interaction at standard doses. | Not established. | None established. | Likely negligible pharmacokinetic interaction. | Clinical adjunct-chemotherapy trials. Berretta et al. 2022 (PMC9657145). | Water-soluble polysaccharides are unlikely to affect CYP enzymes. Concurrent chemotherapy studies report no pharmacokinetic interactions. |
Curcumin C3 (Pro Liposomal and Standard) ↑ / ? | Moderate inhibitor in vitro. May induce CYP3A4 at lower doses or after longer exposure. | Inhibits P-gp and BCRP. | Inhibits CYP2C9 and CYP1A2. Weak CYP2D6 inhibition. May affect SULT. | Acute use may increase exposure. Chronic use may decrease exposure. | Conflicting in vitro and preclinical evidence. Basheer and Kerem 2015; Berretta et al. 2022. | Standard curcumin has poor bioavailability. Liposomal and C3 formulations increase plasma concentrations. Monitor for toxicity and neutropenia. |
Danshen (Salvia miltiorrhiza) ? | Tanshinones inhibit CYP3A4 in vitro (IC50 0.5 μM). Multiple-dose tablets induce intestinal CYP3A4 in vivo. | Not well established. | Inhibits CYP1A2, CYP2C9, and CYP2E1 in vitro. | Uncertain. Single doses may increase exposure. Repeated doses may decrease exposure by about 27%. | Human clinical and in vitro data. Qiu et al. 2010; Wang et al. 2010 and 2022. | Bidirectional effects make this interaction unpredictable. Discuss use with the oncologist before combining. |
EGCG 80% (epigallocatechin gallate) ↔ | Clinical reviews do not expect clinically significant CYP3A4 inhibition. | In vitro inhibition is reported but not confirmed in vivo. | Inhibits OATP1B1, OATP1B3, OCT1, and OCT2 in vitro. | Likely minimal through CYP3A4. High-dose transporter effects remain possible. | Clinical review and in vitro evidence. Knop et al. 2015 and 2018; Wanwimolruk et al. 2001. | Generally low risk for CYP3A4. Use caution with transporter effects at doses of 400 mg or more. |
Fisetin (Pro Liposomal) ↑ | Moderate inhibitor in vitro (IC50 ≈41–136 μM). | Not well established. | May inhibit CYP1A2. | May mildly increase exposure at a 150 mg liposomal dose. | Human CYP3A4 assays. Wanwimolruk et al. 2001; Ho et al. 2001. | Liposomal delivery increases bioavailability. Monitor CBC if combined. |
Genistein Ultra ↑ | Moderate CYP3A4 inhibitor in vitro. | May inhibit P-gp. | Inhibits CYP1A2 and CYP2C9. Has estrogenic activity. | May moderately increase exposure and modulate estrogen receptors. | In vitro and pharmacological evidence. | Discuss with the oncologist, particularly for ER-positive disease or concurrent endocrine therapy. Both pharmacokinetic and pharmacodynamic concerns apply. |
Glutathione (Pro Liposomal) ↔ | No direct inhibition or induction established. | No established interaction. | No significant CYP data at physiological doses. Phase II substrate. | Negligible pharmacokinetic interaction. | No relevant CYP3A4 data. MSKCC. | Antioxidant concerns during chemotherapy are pharmacodynamic rather than pharmacokinetic. |
Grape Seed Extract (OPC / proanthocyanidins) ↑ | Moderate inhibition in vitro. | May inhibit at higher concentrations. | May inhibit CYP2C9. | May mildly increase exposure at 400 mg. | In vitro polyphenol literature. | Clinical concern is generally low, but CBC monitoring is reasonable. |
HCA Garcinia Pure ↔ | No significant interaction established. | No established interaction. | No significant data. | Likely negligible pharmacokinetic interaction. | No relevant published data. | Hydroxycitric acid has no established CYP interactions. Oncology-specific data are limited. |
Honokiol (Pro Liposomal and Pure Honokiol) ↔ | Weak inhibitor (IC50 97.3 μM). Does not affect CYP3A4 mRNA at typical doses. | Not established. | Strong CYP1A2, CYP2C8, CYP2C9, CYP2C19, and UGT1A9 inhibitor. | Minimal CYP3A4-specific interaction expected. Other pathways may affect co-administered drugs. | Human microsomes. Jeong et al. 2013; Cho et al. 2014; MSKCC. | Liposomal formulations increase systemic concentration. Use standard monitoring for interactions through other CYPs and UGTs. |
Hydroxytyrosol ↔ | No significant interaction at typical doses. | Not established. | No major CYP data. | Likely negligible pharmacokinetic interaction. | Limited published data. | No established CYP3A4 interaction at 50 mg. Generally considered safe alongside oncology treatment. |
Long Pepper / Piperlongumine (Pro Liposomal) ↑ | Contains piperine, a moderate-to-potent inhibitor. Doses over 10 mg may be clinically significant. | Inhibits P-gp and BCRP. | Inhibits CYP1A2, CYP2D6, UGTs, and SULT. | Likely increases exposure. Avoid high-dose piperine. | Clinical evidence. Medsafe NZ 2014; Lund et al. 2014. | Piperine is a recognised bioenhancer. Avoid concurrent supplement use with CYP3A4-substrate oncology drugs, or monitor very closely. |
Luteolin (Pro Liposomal) ↑ | Moderate-to-potent inhibitor in vitro (IC50 ≈4.62 μM). | May inhibit at higher concentrations. | Inhibits CYP1A2 and CYP2C9. | May moderately increase exposure at a 150 mg liposomal dose. | Human microsomes. Kondža et al. 2024. | Liposomal delivery increases systemic bioavailability. Monitor CBC for neutropenia. |
Lycopene Plus ↔ | No significant inhibition or induction at typical doses. | No established interaction. | No relevant CYP data. | Negligible pharmacokinetic interaction. | Limited published data. | No established CYP3A4 interaction at 38 mg. |
Maitake Extract (Pure and Liquid) ↔ | No significant interaction at standard doses. | Not established. | Immune polysaccharides are unlikely to affect CYP pathways. | Likely negligible pharmacokinetic interaction. | No relevant published data. | Beta-glucans are water-soluble immune modulators. No documented CYP3A4-substrate drug-specific interaction. |
Mega Flaxseed Lignans (secoisolariciresinol) ↔ | No direct interaction at typical doses. | Not established. | Mild estrogenic or anti-estrogenic lignan activity. | Likely negligible pharmacokinetic interaction. Consider ER-modulatory pharmacodynamic effects. | Limited data. | Converted to enterolignans by gut bacteria. Discuss use with the oncologist when taking letrozole, fulvestrant, or related endocrine therapy. |
Milk Thistle — silymarin ↔ | Inhibits CYP3A4 in vitro, but clinical evidence is weak. Most studies show no significant CYP3A4 effect. | Inhibits P-gp in vitro. No clinical digoxin effect established. | Possible weak CYP2C9 inhibition. Potent UGT inhibition reported in vitro. | CYP3A4 effect is likely minimal. UGT effects warrant attention. | Multiple clinical studies. Xie et al. 2019; Pharmacy Times 2021. | UGT inhibition could affect glucuronidated metabolites, including palbociclib M22. Monitor CBC. Lower concern than CYP3A4-active flavonoids. |
Modified Citrus Pectin (Powder and Capsules) ↔ | No interaction expected. | No interaction expected. | No CYP interaction. | Negligible pharmacokinetic interaction. | No relevant data. | Water-soluble dietary fibre and galectin-3 inhibitor. No established CYP enzyme interactions. |
N-Acetyl-L-Cysteine (NAC) ↔ | No direct inhibition or induction established. | No established interaction. | No significant CYP data. Glutathione precursor and phase II substrate. | Negligible pharmacokinetic interaction. | No relevant CYP data. MSKCC. | Potential antioxidant effects are a separate pharmacodynamic question. |
Nattokinase 4000 FU ↔ | No interaction established. | No interaction established. | No relevant CYP data. | Negligible pharmacokinetic interaction. | No relevant data. | Consider anticoagulant and antiplatelet effects when patients use anticoagulants. |
Olive Leaf Extract (oleuropein) ↑ | Possible mild inhibition. | Not established. | Possible mild CYP2C9 inhibition. | Likely minimal. High doses may mildly increase exposure. | Limited in vitro evidence. | Clinical significance at 500 mg is uncertain. Use general monitoring. |
Omega-3 (DHA and EPA Fish Oil) ↔ | No significant inhibition or induction at typical doses. | No established interaction. | EPA may mildly affect CYP2C9. | Negligible pharmacokinetic interaction. | Well-established clinical evidence. | No clinically significant CYP3A4 interaction is established. Consider antiplatelet activity. |
PEA (palmitoylethanolamide) ↔ | No significant interaction established. | Not established. | No significant CYP data. | Likely negligible pharmacokinetic interaction. | Limited data. | No established CYP3A4 interaction data. |
Polydatin (Pro Liposomal — resveratrol glucoside) ↑ | Inhibits CYP3A4 through its resveratrol moiety. May inhibit PXR-induced CYP3A4 expression. | Inhibits P-gp. | May inhibit CYP2E1 and affect OATP transporters. | May moderately increase exposure. | In vitro and preclinical evidence. Li et al. 2016; Guthrie et al. 2017; Poór et al. 2022. | Liposomal polydatin increases plasma concentrations. Monitor for increased CYP3A4-substrate drug exposure. |
Quercetin and Bromelain ↑ | Moderate inhibitor in vitro (IC50 ≈41 μM). | Inhibits at higher concentrations. | Inhibits CYP1A2 and CYP2C9. | May mildly to moderately increase exposure at 400 mg. | Human microsomes. Wanwimolruk et al. 2001; Ho et al. 2001; Kondža et al. 2024. | Bromelain has no established CYP3A4 interaction. Monitor CBC for neutropenia. |
R-Lipoic Acid ↔ | No direct inhibition or induction established. | No established interaction. | No significant CYP data. | Likely negligible pharmacokinetic interaction. | Limited data. | No established CYP3A4 interaction at supplement doses. |
Reishi (Extract and Liquid) ↔ / ? | Minimal direct interaction at standard doses. | Not established. | Ganoderic acids may weakly inhibit some CYPs. | Likely minimal at standard doses. | Preclinical evidence. | Polysaccharides are unlikely to affect CYP pathways. Clinical significance of weak triterpene effects is likely minimal. |
Rosmarinic Acid (Pro Liposomal) ↑ | Moderate inhibition in vitro. | May inhibit. | Inhibits CYP1A2. Possible CYP2C9 effects. | May mildly to moderately increase exposure. | In vitro polyphenol literature. | Liposomal formulations increase bioavailability. Monitor for increased adverse effects. |
Scutellaria Extract (Skullcap / Baicalin) ↑ | Contains baicalein and wogonin, which inhibit CYP3A4. | May inhibit. | Inhibits CYP1A2, CYP2C9, and CYP2C19. | May moderately increase exposure. | Human microsomes. Basheer and Kerem 2015. | A 500 mg extract dose could meaningfully inhibit CYP3A4. Monitor CBC closely. |
Shiitake (Liquid Extract) ↔ | Minimal direct interaction. | Not established. | No significant data for standard extract. | Likely negligible pharmacokinetic interaction. | No relevant data. | Lentinan and beta-glucan extracts are unlikely to affect CYP pathways. Used alongside chemotherapy in clinical trials. |
Shikonin (Pro Liposomal) ↑ | CYP3A4 and CYP2D6 inhibition reported in vitro. | May inhibit drug-efflux transporters. | CYP2D6 and CYP1A2 inhibition reported in vitro. | May increase exposure. Liposomal delivery increases concern. | In vitro preclinical evidence. | Liposomal delivery may achieve higher plasma concentrations. Monitor for toxicity. |
Spermidine (Pro Liposomal) ↔ | No established interaction. | Not established. | No significant CYP data. | Likely negligible pharmacokinetic interaction. | No relevant data. | No established CYP3A4 interaction data. |
Super Artemis (artemisinin / Artemisia annua) ↑ / ? | Artemisinin inhibits CYP3A4 in vitro. Repeated dosing auto-induces its metabolism. | Not well established. | Inhibits CYP2B6 in vitro. Repeated dosing auto-induces metabolism. | Short-term use may increase exposure. Chronic patterns may alter exposure unpredictably. | Strong in vitro and clinical pharmacokinetic evidence. Kondža et al. 2023; Pernaute-Lau et al. 2022. | Discuss with the oncologist before combining. The net effect on co-administered CYP3A4 substrates is unpredictable. |
Super Green Tea Extract (EGCG-rich) ↔ | Not expected to significantly inhibit CYP3A4. | OATP inhibition in vitro. P-gp findings conflict. | Not significant for CYP3A4 at normal intake. | Likely minimal at standard doses. Transporter caution at 580 mg. | Clinical review. | Same assessment as EGCG. Higher catechin exposure may increase transporter-related concern. |
Trans Resveratrol (Liposomal) ↑ | Mechanism-based CYP3A4 inhibitor. May inhibit PXR-induced CYP3A4 expression. | May stimulate or inhibit P-gp, depending on context. | Inhibits CYP2E1 and CYP2C9. Affects OATP transporters. | May increase exposure. P-gp stimulation may partly offset this effect. | In vitro and preclinical evidence with conflicting P-gp direction. | At liposomal 250 mg, clinically meaningful inhibition is plausible. Monitor CBC closely. |
TUDCA (tauroursodeoxycholic acid) ↔ | No established interaction. | Not established. | No significant CYP data. | Likely negligible pharmacokinetic interaction. | Limited data. | No established CYP3A4 interaction. |
Turkey Tail — Coriolus (PSK/PSP) ↔ | See Coriolus entry. | Not established. | None established. | Likely negligible pharmacokinetic interaction. | Clinical adjunct-chemotherapy trials. | Duplicate Coriolus entry. PSK and PSP are water-soluble polysaccharides without established CYP3A4 interaction. |
Ultra-TQ Thymoquinone ↑ | See Black Cumin Seed Oil. Thymoquinone is the active component. | Possible weak inhibition. | May inhibit CYP2D6 and CYP1A2. | May moderately increase exposure. | In vitro and preclinical evidence. | Concentrated thymoquinone may raise exposure beyond black cumin oil. Monitor CBC. |
Urolithin A ↔ / ? | No established interaction for urolithin A specifically. | Not established. | Limited CYP data. | Likely negligible pharmacokinetic interaction, but data are limited. | Limited published data. | Emerging mitophagy and longevity compound with limited interaction data. |
Vitamin C (Pro Liposomal) ↔ | No inhibition or induction at typical doses. | No established interaction. | No significant CYP data. | Negligible pharmacokinetic interaction. | Well-established clinical evidence. | Oral or liposomal vitamin C at 500 mg has no established CYP3A4 interaction. High-dose IV vitamin C is a different context. |
Vitamin D3 and K2 / D3 Liquid Drops ↔ | Vitamin D3 is partly metabolised by CYP3A4 but is not a significant inhibitor. | No established interaction. | D3 is mainly a substrate of CYP27A1, CYP2R1, and CYP24A1. | Negligible pharmacokinetic interaction. | Well-established clinical evidence. | Vitamin D3 and K2 are pharmacokinetically safe at standard supplement doses. |
Withaferin A (Pro Liposomal — WFA) ? | Specific CYP3A4 data are limited. Ashwagandha may modulate CYP3A4. | Not established. | Limited data. | Apply the same precaution as ashwagandha. Exposure may decrease. | Limited in vitro evidence. | Withaferin A is a withanolide from ashwagandha. Monitor CYP3A4-substrate oncology drug clinical response. |
Important disclaimer: This reference is for educational purposes in integrative oncology discussions. Evidence levels vary substantially. In vitro findings may not translate to clinical significance. CYP3A4 inhibition at dietary doses does not equal clinical inhibition at supplement doses. Liposomal formulations have greater bioavailability than standard forms and require greater caution.
Generated: July 2026.