The evidence for this appears to be mostly in vitro studies on intestinal cells or recombinant enzyme, with a small amount of supportive animal data. Human studies do not appear to support it:
A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). …
Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma C(max), AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05-0.08 μM and 0.6 μM, respectively).
Conclusion: The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes.
Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers - PubMed
Dextromethorphan (DEX) was used as common probe for CYP2D6 and CYP3A4 enzymes. Metabolic activity of CYP2D6 and CYP3A4 was evaluated through in vitro study; where microsomes were incubated with NADPH in presence and absence of Curcuma extract. In clinical study phase-I, six healthy human subjects received a single dose (30 mg) of DEX syrup, and in phase-II DEX syrup was administered with Curcuma powder. The enzyme CYP2D6 and CYP3A4 mediated O- and N-demethylation of dextromethorphan into dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. Curcuma extract significantly inhibited the formation of DOR and 3-MM, in a dose-dependent and linear fashion. The 100 ÎĽg/ml dose of curcuma extract produced highest inhibition, which was about 70 % for DOR and 80 % for 3-MM. [This is the in vitro result: see the full text].
Therefore, the clinical study was conducted to confirm the results obtained from in vitro investigations. To determine in vivo inhibitory effects, the urinary metabolic ratio of DEX/DOR and DEX/3-MM as well as the amounts of DOR and 3-MM excreted in urine was used to assess the metabolic activities of CYP2D6 and CYP3A4, respectively. …
The inhibitory effect of curcuma on the formation of 3-MM was weak (about 28 % inhibition was recorded), as indicated by insignificant changes in urinary metabolic ratio of DEX/3- MM (Table 1). … C. longa remarkably reduced the level of DOR and 3-MM metabolites excreted in urine and enhanced DEX/ DOR at statistically significant level, while the increased in DEX/3-MM metabolic ratios was statistically insignificant
Present findings suggested that curcuma significantly inhibits the activity of CYP2D6 in in vitro as well as in vivo; which indicates that curcuma has potential to interact with CYP2D6 substrates.
Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects - PubMed
It’s a bit odd that they describe the effect on 3-MM (28% inhibition) as “weak” but also say that it “remarkably reduced the level of DOR and 3-MM metabolites”. A 28% inhibition does sound meaningful, but, they clearly think the effect on DYP2D6 is important and the effect on CYP3A4 as not. The ratios for DEX alone vs. DEX with curcuma extract are 5.959 and 8.290, respectively. The other caveat is that this is anethanolic extract not standardized for curcumin, so it’s not clear how much this one reflects a standard 95% curcumin extract.
In Vitro metabolism of imatinib and bosutinib were investigated in pooled human liver microsomes and recombinant CYP3A4 enzyme in the presence and absence of curcumin and curcumin glucuronide…The potential effects of curcumin coadministration on systemic exposures of imatinib and bosutinib were predicted in silico using PBPK simulations.
PBPK model simulations of curcumin pharmacokinetics given as a single oral dose (SLN formulation containing 160 mg of curcumin) was performed to replicate trial designs (number of people, age range, proportion of male to female) matched to the corresponding published clinical studies (Table 2). A total of 100 virtual trials were carried out. The clinical pharmacokinetic data were taken from a study in healthy people of Indian geographic ancestry receiving the SLN formulation of curcumin [PMID 20092313 — Longvida curcumin nanoparticle]
Results: Curcumin demonstrated potent reversible inhibition of cytochrome P450 (CYP)3A4-mediated N-demethylation of imatinib and bosutinib and CYP2C8-mediated metabolism of imatinib with inhibitory constants (ki,u) of ≤1.5 μmol. L-1… PBPK model simulations predicted that at recommended dosing regimens of SLN curcumin, coadministration would result in an increase in systemic exposures of imatinib and bosutinib of up to only 10%.
Although curcumin possesses a strong In Vitro inhibitory activity towards CYP3A4 and CYP2C8 enzymes, its interactions with imatinib and bosutinib were unlikely to be of clinical importance due to curcumin’s poor bioavailability.
Physiologically-Based Pharmacokinetic Predictions of the Effect of Curcumin on Metabolism of Imatinib and Bosutinib: In Vitro and In Vivo Disconnect - PubMed
This last is only a model, but it’s a much better model than the typical crude 1:1 extrapolation and is recognized by FDA. And the dose is lower than standard curcumin extract, though it’s of a high-bioavailability formulation.
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