Enhancement without a rationale? Black pepper extract (piperine) in dietary supplements and the future of formulation: a perspective from Japan
Year: 2026
Type: article
Abstract: Bioavailability enhancers, most notably black pepper extract (piperine), are increasingly added to dietary supplements with claims of "improved absorption." Piperine raises systemic exposure to co-administered compounds not by enhancing absorption but mainly by inhibiting drug-metabolizing systems, including CYP3A4, CYP2C9, and P-glycoprotein, and can therefore alter concentrations of concomitant medications, including drugs with a narrow therapeutic index. This Perspective argues that piperine is frequently included in multi-ingredient products without a defensible formulation rationale and, in the author's observation, now appears in Japan's practitioner-exclusive (clinic-dispensed) supplement market. A structured summary of 22 human pharmacokinetic studies shows that reports of enhanced nutrient absorption derive from manufacturer-affiliated studies of a few chemical forms; that trials without piperine-manufacturer involvement have not confirmed enhancement for curcumin or resveratrol at supplement doses; and that interaction studies with prescription drugs, mostly from groups with no commercial interest, repeatedly demonstrate altered drug exposure. This asymmetry is compounded by inadvertent supplement-supplement combinations and reports of turmeric-piperine-associated liver injury. The conditions under which piperine is a rational formulation choice are defined, and label warnings are endorsed as necessary but insufficient. "Practitioner-exclusive" labeling does not guarantee a sound formulation, and the good manufacturing practice requirements mandatory for Foods with Function Claims in Japan since September 2026 address manufacturing quality, not formulation appropriateness. Supplement formulation should be a deliberate, expert-driven discipline rather than an accumulation of trending ingredients; formulation rationale and interaction risk, not manufacturing quality alone, should become explicit considerations for clinicians, regulators, and industry.
Source: Frontiers in Nutrition
Author: Masaki Kaneko
Institution: Kayaba Industry (Japan)
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222527844