I want you to look at this. Black pepper. Piper nigrum. The most widely consumed spice on Earth. Used by billions of people every single day. In every cuisine, on every continent. Completely safe. Completely unrestricted.
The active constituent in black pepper — piperine — has been added to the EU's list of substances to be prohibited or restricted in food supplements.
And I want to make the case that this is the single most revealing proportionality failure in this entire regulatory process. Because if you understand piperine, you understand exactly what is wrong with how these decisions are being made.
The concern.
Piperine inhibits two proteins in your intestine and liver: CYP3A4 — a major drug-metabolising enzyme — and P-glycoprotein — a drug efflux transporter. By inhibiting these, piperine increases the blood levels of drugs and nutrients that are metabolised by CYP3A4 or transported out of cells by P-glycoprotein.
At 20 milligrams per day of isolated piperine, clinical studies have demonstrated pharmacokinetic drug interactions. Specific papers — including a 2021 systematic safety review in PMC and a 2024 analysis in PMC — document that interactions in humans were observed at bolus doses of 20 milligrams per day piperine. If you are taking a drug with a narrow therapeutic window — ciclosporin, phenytoin, methotrexate — and you take a 20-milligram piperine supplement alongside it, there is a plausible clinical risk.
This is a real pharmacokinetic signal. I am not dismissing it. Practitioners should be aware of it.
But now let me tell you why restricting piperine while ignoring grapefruit juice is the most devastating single illustration of regulatory inconsistency available to this campaign.
The grapefruit juice argument
Grapefruit and grapefruit juice contain furanocoumarins; compounds that inhibit CYP3A4 by the same basic mechanism as piperine. The CYP3A4/P-glycoprotein inhibitory effect of grapefruit juice is documented in clinical pharmacology. It is the reason that patient information leaflets for statins, certain calcium channel blockers, ciclosporin, and other drugs contain warnings about grapefruit. The drug interactions are real. Some are clinically significant.
Grapefruit juice is not restricted. Grapefruit juice is not on any list of 117 dangerous substances. Grapefruit juice is in every supermarket, next to the orange juice, sold without a prescription, without an age limit, without a safety consultation.
If a drug interaction signal in a food is sufficient to restrict piperine in supplements, why is grapefruit juice free to sit on shelves next to toothpaste?
The answer is not science. The answer is that grapefruit is a food. We have decided as a society that foods are not prohibited on the basis of their drug interaction potential because we manage drug interactions through prescriber guidance and patient information, not through prohibition of foods.
Piperine is a constituent of a food. Black pepper. The decision to treat isolated piperine in supplements differently from piperine in black pepper, and to restrict piperine in supplements while leaving grapefruit juice entirely unregulated, is a regulatory inconsistency that cannot be defended on scientific grounds.
The dose context.
Typical dietary intake from culinary use of black pepper is approximately 1 to 2 milligrams of piperine per day. The standard "BioPerine" dose used in supplement formulations as a bioavailability enhancer is 5 to 10 milligrams. The interaction threshold documented in clinical studies is 20 milligrams per day. At 5 to 10 milligrams the standard supplement dose the interaction risk is low to moderate, not zero, for highly sensitive CYP3A4 substrates. The response to this is labelling requirements and prescriber awareness not restriction.
No hepatotoxicity from piperine itself.
Piperine has no hepatotoxicity signal. None. The hepatotoxicity concern discussed in the turmeric context arises from the piperine-curcumin combination where piperine increases curcumin bioavailability approximately 20-fold, producing a pharmacological entity that behaves very differently from either constituent alone. That is a combination product formulation issue. It is not a piperine toxicity issue in isolation.
What proportionate regulation looks like.
Clear product labelling stating piperine content. Drug interaction warnings on labels. Prescriber guidance documents for practitioners recommending piperine-containing products alongside narrow-therapeutic-window medications. GRAS status for black pepper as a food is entirely consistent with supplement dose labelling requirements. This is proportionate. Prohibition is not.
Grapefruit juice has the same mechanism. It is not restricted. Piperine is on a European restriction list. That is not science. That is a category error dressed as precaution.
The UK Government has committed to align UK supplement law with EU law under the SPS Agreement without parliamentary approval. That commitment is published at www.gov.uk/government/news/uk-eu-sps-agreement-legislation-in-scope .
Write to your MP at writetothem.com. Sign the petition. Respond to the EU consultation. Ask Parliament to vote before piperine is restricted in the United Kingdom.
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