Polyphenols in Korean health supplements: safety review flags regulatory gaps

A sweeping review of South Korea’s health functional food (HFF) industry has found that roughly one in five of the country’s major supplement ingredients relies on polyphenolic compounds as its official quality marker, and it warns that the regulatory system built around those markers is not equipped to handle the high-bioavailability formulations and multi-product consumption patterns now dominating the market. The review, published in Applied Biological Chemistry, examined all 68 notified ingredients registered in the Health Functional Foods Code and the top 50 individually recognized ingredients by sales volume, a set that together accounts for more than 90 percent of the domestic market.

The analysis comes at a moment of rapid commercial expansion. As of 2025, the South Korean HFF market had grown into a KRW 6.5 trillion industry, expanding 1.9 percent over the previous year, with more than eight out of ten consumers purchasing these products. More than 393 ingredients had been recognized across 57 functional categories, the majority derived from plant sources. That growth has accelerated the launch of products with enhanced bioavailability or high contents of bioactive ingredients, creating what the authors describe as a consumer environment susceptible to overlapping or multiple intakes.

Within the Korean regulatory system, every functional ingredient must designate one or more marker compounds: analytically identifiable substances that characterize the source material, represent its physiological activity, and support manufacturing standardization and quality control. The review found that 10 of the 68 notified items (14.7 percent) and 16 of the top 50 individually recognized items (31.4 percent) use polyphenolic compounds as their standardized quality markers. After accounting for overlaps between regulatory categories, 31 distinct polyphenolic entities were identified across the system, spanning flavonoids, lignan glycosides, hydrolyzable tannins, phenolic acids, and diarylheptanoids.

The problem, the authors argue, is that the same chemical properties that make polyphenols beneficial at dietary concentrations can produce harm under different exposure conditions. At levels encountered through habitual consumption of fruits, vegetables, and beverages, polyphenols act largely as antioxidants and modulators of inflammatory signaling. At supradietary concentrations delivered by concentrated supplements, they can show pro-oxidant activity, genotoxic effects in laboratory tests, organ-specific toxicity, and clinically significant pharmacokinetic interactions. The review highlights this concentration-dependent transition through three case studies: curcumin, epigallocatechin gallate (EGCG), and quercetin, all of which have recently been or are currently being re-evaluated by Korea’s Ministry of Food and Drug Safety (MFDS).

Curcumin, the primary curcuminoid in turmeric, illustrates the stakes. Although standard curcuminoid preparations at 1,500 milligrams per day for up to 12 months have been well tolerated in clinical studies, and the European Food Safety Authority has set an acceptable daily intake of 3 milligrams per kilogram of body weight, clusters of acute liver injury linked to curcumin supplements have recently been reported in Italy, Australia, and the United States. The Drug-Induced Liver Injury Network noted that many hepatotoxicity cases involved co-administration with piperine or the use of bio-enhanced formulations deliberately engineered to increase curcumin absorption. Genetic susceptibility factors, particularly the HLA-B*35:01 and HLA-DRB1*13 alleles, have been strongly implicated. Curcumin also inhibits the efflux pumps BCRP and P-glycoprotein, raising systemic exposure to substrate drugs, and a clinical case report described markedly elevated tacrolimus concentrations and subsequent nephrotoxicity after high-dose turmeric intake.

International regulators have responded unevenly. The German Federal Institute for Risk Assessment suggested the current acceptable daily intake framework may not adequately account for the amplified systemic exposure of bio-enhanced products. The French agency ANSES identified bio-enhanced formulations as a major risk factor for hepatitis and advised caution for people taking anticoagulants, anticancer drugs, or immunosuppressants. Australia’s Therapeutic Goods Administration mandated precautionary labeling instructing consumers to stop use and seek medical attention if symptoms such as jaundice, fatigue, or dark urine appear. Canada regulates bio-enhanced curcumin formulations separately under its higher-risk Class III category, requiring comprehensive pre-market safety assessment. South Korea, by contrast, manages curcumin primarily through quantitative standardization of marker content in turmeric-derived ingredients, an approach the review characterizes as leaving a gap around modern bio-enhanced formulations.

EGCG, the major catechin in green tea, shows how exposure context can dominate toxicity. A systematic review identified the liver as the principal target organ and derived a safe intake of 4.6 milligrams of EGCG per kilogram of body weight per day for a solid green tea extract bolus taken with food, equivalent to 322 milligrams daily for a 70-kilogram adult. Under fasting conditions, that threshold fell to 0.4 milligrams per kilogram, just 32 milligrams daily. Severe liver injury has rarely been reported with brewed tea or beverage preparations, and the authors stress that multi-ingredient weight-management products, in which green tea extract is combined with stimulants and other botanicals, confound causal attribution to EGCG alone. The European Union now restricts green tea extracts so that a single daily portion contains less than 800 milligrams of EGCG, with precautionary labeling warning against empty-stomach consumption and use by pregnant or lactating women and people under 18. Korea’s own re-evaluation, completed in 2017 and implemented in 2018, set an EGCG-specific upper limit of 300 milligrams per day, and a 2025 re-evaluation proposed warning against combining green tea extract with other health functional foods claiming body fat reduction.

Quercetin presents a different profile. Long regarded as safe on the basis of extensive dietary exposure, with routine dietary ingestion showing no association with systemic toxicity or in vivo carcinogenicity, quercetin is now available in supplements at doses up to 1,000 milligrams per day, far above typical dietary intake, while robust data on long-term safety beyond 12 weeks at such doses remain limited. Animal studies have suggested possible nephrotoxicity and estrogen-related tumor-promoting effects under specific high-dose conditions. Quercetin also inhibits CYP2C9, which can elevate plasma concentrations of drugs such as diclofenac, and has been shown to enhance absorption of cyclosporine. Phytosome-based delivery systems have increased systemic quercetin exposure by roughly 20-fold in a human pharmacokinetic study, leading the authors to conclude that historical safety thresholds may not reflect the exposure achievable with advanced formulations. In Korea, quercetin is managed almost entirely as a passive quality marker, for instance in ginkgo leaf extract, where specifications require a minimum flavonol glycoside content of 240 milligrams per gram and a defined quercetin-to-kaempferol ratio.

From these case studies, the review proposes three regulatory considerations. First, ingredients using delivery systems that substantially increase systemic exposure, evidenced by area-under-the-curve or maximum plasma concentration values exceeding a defined threshold relative to conventional formulations, should be required to submit pharmacokinetic bridging data, and safety thresholds should incorporate bioavailability-adjusted exposure rather than nominal intake alone. Second, an integrated post-market network should embed high-risk HFF-drug interaction profiles into electronic clinical decision support and consumer labeling, a concern sharpened by South Korea’s transition to a super-aged society, where older adults are both the largest consumer cohort and the population most exposed to polypharmacy. Third, Korean population-specific factors deserve explicit weight: high frequencies of CYP2C19 and CYP2C9 intermediate or poor metabolizers in the Korean population could amplify interactions when concentrated polyphenols are taken with narrow-therapeutic-index drugs such as warfarin, while baseline dietary polyphenol exposure in Korea differs from that of international reference populations.

The authors also caution that marker compounds should be treated as reference points rather than full proxies for whole-extract safety, since matrix components in botanical extracts can alter the solubility, absorption, metabolism, and toxicity of the marker. They frame the review not as a definitive resolution but as an analytical framework for ongoing policy dialogue, arguing that Korea’s HFF system must move toward a dynamic, lifecycle-based, formulation-stratified approach that evaluates safety at both the marker-compound and whole-extract levels, integrating Korean-specific pharmacogenomic and dietary data while remaining consistent with internationally accepted risk assessment methodologies.

Subject of Research: Safety assessment of polyphenolic marker compounds in South Korean health functional food ingredients and the regulatory gaps surrounding bio-enhanced supplement formulations

Article Title: Safety assessment of selected polyphenolic marker compounds in plant-derived Korean health functional food ingredients and regulatory considerations

Article References: Kim, G.-D., Lee, H.-Y., & Kim, E. (2026). Safety assessment of selected polyphenolic marker compounds in plant-derived Korean health functional food ingredients and regulatory considerations. Applied Biological Chemistry, 69(1), Article 61. https://doi.org/10.1186/s13765-026-01133-x

Image Credits: AI Generated

DOI: 10.1186/s13765-026-01133-x

Keywords: polyphenols, health functional foods, South Korea, curcumin, EGCG, quercetin, hepatotoxicity, drug interactions, bioavailability, food safety regulation, MFDS, dietary supplements