Clean Label Supplements: What We Leave Out, and Why

By Jack Zheng, MS Pharmacy — Founder of MIHIYO Labs

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Summary

"Clean label" has no legal definition, so the claim is only as meaningful as the ingredients a brand excludes. Artificial FD&C dyes, titanium dioxide, and talc draw the most current scrutiny. The FDA revoked FD&C Red No. 3 in January 2025 after high-dose studies showed cancer in male rats through a rat-specific mechanism, and the EU has banned titanium dioxide from food since 2022 over an unresolved genotoxicity concern. A 2019 study found over 90 percent of oral medications contain an inactive ingredient associated with adverse reactions. An oral dissolving strip (ODS), cast and dried rather than compressed, needs fewer such excipients. MIHIYO Labs formulates around that advantage.

What does "clean label" actually mean for a supplement?

The direct answer is: nothing fixed. The FDA has never issued a regulatory definition of "clean label," and there is no single universally accepted certification that gives the term one fixed meaning across supplements. In practice, it is a shorthand a brand uses to describe which specific ingredients it has chosen not to include, and the value of the claim depends entirely on how concrete that list is. A supplement can carry a "clean label" sticker while still containing a full stack of excipients — the inactive materials, a term covering anything besides the active ingredient, that hold a formulation together, control its release, or ease manufacturing. Most formulations, including MIHIYO's, need some. The question worth asking is not whether excipients are present, but which ones, and why.

From a formulation-design perspective, I hold every ingredient decision — active or inactive — to a simple test: does it serve a function I can defend with a mechanism, or is it just conventional. Artificial dyes, titanium dioxide, and talc are the three excipients that fail that test most often in the supplement aisle, and each has a documented reason to be treated carefully rather than banned outright.

Why do these three excipients show up in supplements in the first place?

Each of the three plays one specific, non-therapeutic role, and understanding that role is what makes the safety data meaningful rather than alarming.

Artificial FD&C dyes exist purely for visual appearance — they carry no functional role in dissolution, stability, or absorption. Synthetic colors like Red 3, Red 40, Yellow 5, and Yellow 6 are cheaper and more heat-stable than most natural pigments, which is why they became the default in mass-market tablets, capsules, and gummies. The safety picture around this category has shifted twice in recent years. A large 2007 randomized, double-blinded, placebo-controlled crossover trial from the University of Southampton tested mixtures of artificial food colors plus the preservative sodium benzoate in 153 three-year-olds and 144 eight- and nine-year-olds drawn from the general population, and found the additive mixtures increased hyperactive behavior compared with placebo.¹ Separately, the FDA revoked authorization for FD&C Red No. 3 in food and ingested drugs in January 2025, specifically citing the Delaney Clause, which bars any color additive shown to induce cancer in humans or animals — the petition data showed Red 3 caused cancer in male rats.² FDA also noted that this is a rat-specific hormonal mechanism not believed to occur in humans, and that the available evidence does not support a claim that Red No. 3 poses a cancer risk to people at typical exposure levels.² Manufacturers have until January 2027 (food) or January 2028 (ingested drugs) to reformulate. State regulators have moved in the same direction: California's AB-418, the California Food Safety Act, bans Red No. 3 outright in food sold in the state starting January 1, 2027, alongside brominated vegetable oil, potassium bromate, and propylparaben — though titanium dioxide was removed from the bill's final language before passage, a distinction worth noting given the next section.⁸

Titanium dioxide (TiO2, listed as E171 in the EU) plays a different role: it is an opacifier and whitener, used to make a tablet coating or capsule shell opaque and uniformly colored rather than translucent or blotchy. In most supplement uses, it is not part of the active ingredient's intended physiological effect; its role is primarily visual or coating-related. In 2021, the European Food Safety Authority reviewed the available scientific evidence, including thousands of studies, and concluded that titanium dioxide "can no longer be considered safe when used as a food additive," because a concern for genotoxicity — DNA damage — could not be excluded, which meant no acceptable daily intake could be established.³¹⁰ The European Commission acted on that opinion with Regulation (EU) 2022/63, which withdrew authorization for TiO2 as a food additive from August 7, 2022.⁴ The picture in medicines is more complicated, and worth stating plainly: an Article 57 database analysis in EMA's Annex I industry feedback found that, as of June 2021, products containing titanium dioxide accounted for 62.55 percent of tablets and 95.04 percent of capsules with EEA marketing authorizations,¹¹ and the EMA's own September 2021 opinion concluded TiO2 could not be replaced across that installed base without risking medicine shortages.⁵ As of the latest EU medicines review, that distinction still holds: an August 2025 European Commission staff working document reaffirmed that titanium dioxide's use as a colorant in medicinal products should be maintained, based on EMA findings, while its food-additive use remains withdrawn. The document also states EMA considered the carcinogenicity risk from medicine exposure negligible, based on the limited data set submitted.⁹ That is a very different regulatory bar than a discretionary use in a food or supplement product, where an alternative format can simply avoid the ingredient rather than replace it at scale.

Talc functions as a lubricant, glidant, and anti-caking agent — it reduces friction so powder blends flow evenly into a tablet press or a capsule-filling machine, and keeps a compressed tablet from sticking to the die. Pharmaceutical-grade talc must meet USP/EP purity specifications that require it to test negative for asbestos, because talc and asbestos are both naturally occurring mineral silicates that can co-occur in the same deposits. That matters because asbestos-contamination risk is real in less-regulated grades: FDA's year-long sampling assignment testing of talc-containing cosmetic powder products in 2019 found 9 of 52 samples positive for asbestos fibers by transmission electron microscopy, prompting voluntary recalls — though FDA itself cautioned that this targeted sample was not drawn randomly from the market, and that the positive rate should not be read as the asbestos-contamination prevalence across the entire cosmetics market.⁶ Cosmetic-grade sourcing controls aren't automatically as tight as pharmaceutical-grade controls, which is why some formulators avoid talc entirely rather than rely on a purity test to catch contamination after the fact.

How common are these ingredients, and what happens when a product carries fewer of them?

The honest data point behind all three ingredients is the same: a supplement or medication rarely contains just one inactive ingredient, and the cumulative load is what a 2019 Science Translational Medicine study set out to measure. Reker and colleagues analyzed the inactive-ingredient lists of more than 42,000 oral medications in the FDA's database and cross-referenced them against 38 excipients with documented allergic or intolerance associations — including lactose, gelatin, dyes, aluminum compounds, and polysorbates. They found more than 90 percent of oral medications contained at least one such adverse-reaction-associated inactive ingredient, and a substantial share contained several at once.⁷ That paper was analyzing prescription and over-the-counter drugs, not supplements specifically, but the mechanism generalizes: any solid oral dosage form assembled from a stack of conventional excipients accumulates exposure risk one ingredient at a time, independent of the active compound's own safety profile.

The pattern across all four rows is that none of these ingredients is acutely dangerous at typical exposure levels — the EFSA opinion on titanium dioxide, for example, describes an unresolved uncertainty, not a demonstrated harm in humans at food-additive doses. What has changed is the margin of confidence regulators are willing to accept for an ingredient that serves no functional purpose beyond appearance or manufacturing convenience. An ingredient that earns its place through a real function — a film-forming polymer controlling dissolution time, for instance — would have that same uncertainty weighed against an actual benefit. Dyes, TiO2, and talc mostly offer no such benefit to a supplement buyer.

What this means for MIHIYO's own formulation choices

None of the studies above were run on MIHIYO's products — they establish the mechanism and the regulatory trend for the ingredient classes, and I want to be explicit about that distinction before connecting it to what we do differently.

The reason our Energy-Focus, Mood-Boost, and Sleep-Support strips can go without titanium dioxide and talc is mostly structural, not a special formulation trick. A film is cast from a polymer solution and dried, not compressed under pressure or filled as a loose powder into a shell. That process does not need a lubricant to prevent sticking in a tablet die, because there is no die — and it does not need an opacifier to hide an uneven fill, because the film's own thin, uniform cast already gives it a consistent appearance. The excipients a compressed tablet or a two-piece capsule needs to solve manufacturing problems are, for a cast film, problems that mostly do not arise in the first place. The ODS format sidesteps the need rather than replacing the ingredient with an equivalent one.

Color is the one place we made an active choice rather than inheriting a structural advantage. Instead of an FD&C synthetic dye, each strip's color and flavor profile come from the functional ingredients and approved flavoring agents already in the formulation, so we are not adding a dye whose only job is visual. That is a deliberate exclusion, not a byproduct of the film format. Related: see how HPMC and pullulan film-forming polymers are chosen for the upstream decisions that make the film matrix itself the main functional excipient in a MIHIYO strip, and how that ties into the moisture-control packaging that protects it afterward.

Where the clean-label argument falls short

It would be dishonest to imply "clean label" means excipient-free, or that removing three specific ingredient categories eliminates every formulation risk. A film still requires functional excipients — a film-forming polymer, a plasticizer to keep it from turning brittle, and typically a sweetener or flavor-masking agent — and each of those carries its own individual safety profile that has to be evaluated on its own terms, not assumed safe by association with what the product excludes.

It is also worth being direct that "clean label" is not an independently audited claim category the way "USP Verified" or "NSF Certified" is. Any brand can define it however it wants, with no enforcement mechanism tying that definition to what is actually in the product — which is why this article names the specific three excipients rather than treating "clean label" as a stand-in for a safety claim.

Finally, avoiding titanium dioxide, talc, and dyes still leaves every other excipient in the Reker dataset unaddressed — lactose, gelatin, and certain preservatives among them — and a customer's individual sensitivities may have nothing to do with any of the three ingredients discussed here.

The bottom line

A clean label supplement claim is only as trustworthy as the specific exclusions behind it, because the term itself carries no regulatory weight. Artificial dyes, titanium dioxide, and talc have each drawn documented safety scrutiny in the past two decades — a hyperactivity signal, an unresolved genotoxicity concern, and a mineral-contamination risk, respectively — for ingredients that exist to solve appearance or manufacturing problems rather than to help an active ingredient work. MIHIYO Labs' oral dissolving strips leave out titanium dioxide and talc largely because the cast-film manufacturing process does not create the problems those ingredients exist to solve, and leave out synthetic dyes by deliberate choice. That is the honest version of a clean label claim: named exclusions, tied to a mechanism, not a blanket promise that the product carries no risk at all.

References

1. McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, Kitchin E, Lok K, Porteous L, Prince E, Sonuga-Barke E, Warner JO, Stevenson J. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. The Lancet. 2007;370(9598):1560-1567. PMID: 17825405. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61306-3/abstract
2. U.S. Food and Drug Administration. FDA to Revoke Authorization for the Use of Red No. 3 in Food and Ingested Drugs. FDA, January 2025. https://www.fda.gov/food/hfp-constituent-updates/fda-revoke-authorization-use-red-no-3-food-and-ingested-drugs
3. European Food Safety Authority. Titanium dioxide: E171 no longer considered safe when used as a food additive. EFSA, May 6, 2021. https://www.efsa.europa.eu/en/news/titanium-dioxide-e171-no-longer-considered-safe-when-used-food-additive
4. European Commission. Commission Regulation (EU) 2022/63 of 14 January 2022 amending Annexes II and III to Regulation (EC) No 1333/2008 as regards the food additive titanium dioxide (E 171). Official Journal of the European Union, 2022. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32022R0063
5. European Medicines Agency. Final feedback from the European Medicines Agency (EMA) to the EU Commission's request to evaluate the impact of removal of titanium dioxide from the list of authorised food additives on medicinal products. EMA, September 2021. https://www.ema.europa.eu/en/documents/report/final-feedback-european-medicine-agency-ema-eu-commission-request-evaluate-impact-removal-titanium-dioxide-list-authorised-food-additives-medicinal-products_en.pdf
6. U.S. Food and Drug Administration. FDA Releases Data from the Agency's Year-Long Sampling Assignment to Test Talc-Containing Cosmetic Products for the Presence of Asbestos. FDA, March 2020. https://www.fda.gov/food/hfp-constituent-updates/fda-releases-data-agencys-year-long-sampling-assignment-test-talc-containing-cosmetic-products
7. Reker D, Blum SM, Steiger C, Anger KE, Sommer JM, Fanikos J, Traverso G. "Inactive" ingredients in oral medications. Science Translational Medicine. 2019;11(483):eaau6753. PMID: 30867323. DOI: 10.1126/scitranslmed.aau6753. https://www.science.org/doi/10.1126/scitranslmed.aau6753
8. California Legislative Information. AB-418 California Food Safety Act (bans brominated vegetable oil, potassium bromate, propylparaben, and FD&C Red No. 3 in food sold in California, effective January 1, 2027; titanium dioxide removed from the final bill by amendment). California State Legislature, 2023. https://leginfo.legislature.ca.gov/faces/billTextClient.xhtml?bill_id=202320240AB418
9. European Commission. Commission Staff Working Document on the Use of Titanium Dioxide in Medicinal Products. SWD(2025) 244 final, August 6, 2025. https://health.ec.europa.eu/document/download/34542b69-8507-4fc2-b106-bd15b481e40d_en?filename=mp_working-doc-titanium-dioxide_en.pdf
10. European Commission. Re-evaluation of Food Additives — Titanium Dioxide (E171). European Commission Food Safety. https://food.ec.europa.eu/food-safety/food-improvement-agents/additives/re-evaluation_en
11. European Medicines Agency. Annex I — Use of Titanium Dioxide as Excipient in Human Medicines: Industry Feedback to QWP Experts / EMA Questions. EMA, October 2021. https://www.ema.europa.eu/en/documents/other/annex-i-use-titanium-dioxide-excipient-human-medicines-industry-feedback-qwp-experts-ema-questions_en.pdf

By Jack Zheng, MS Pharmacy — Founder of MIHIYO Labs. Focused on the R&D of high-bioavailability, fast-absorption oral dissolving strips.