How We Assess Urolithin A Evidence

Supplements and cosmetics are not the same market

Oral Urolithin A and topical Urolithin A raise different scientific and regulatory questions.

An oral supplement must be lawfully permitted as a food or supplement ingredient in the consumer’s jurisdiction. Its advertising must comply with food and health-claim rules. A cosmetic must meet cosmetic safety and notification requirements, and its claims should remain cosmetic — for example, improving the appearance of skin — rather than implying that it treats disease or changes abnormal physiology.[15-19]

A study of an oral dose cannot be used automatically to support a cream, and a cell-culture experiment cannot establish that a finished cosmetic produces the same result on human skin.

Evidence hierarchy

We generally give the greatest weight to:

1. Systematic reviews of relevant, well-designed human trials.

2. Large, independently replicated randomised controlled trials.

3. Smaller controlled human trials.

4. Prospective observational studies.

5. Mechanistic human studies and biomarker research.

6. Animal studies.

7. Cell and biochemical studies.

8. Expert opinion, testimonials and marketing materials.

The hierarchy is not absolute. A poor systematic review can be less useful than a well-designed trial, and a large observational study cannot establish causation by itself.

Factors that increase confidence

  • pre-registered methods and outcomes;
  • suitable placebo and blinding;
  • adequate sample size;
  • low dropout and transparent missing-data handling;
  • validated and clinically relevant outcomes;
  • correction for multiple comparisons;
  • full reporting of negative findings;
  • independent replication;
  • data and protocol availability;
  • minimal conflict of interest.

Factors that reduce confidence

  • animal or cell evidence presented as a human benefit;
  • preprints without peer review;
  • very small samples;
  • short duration for a long-term claim;
  • many outcomes with selective emphasis;
  • subgroup findings not specified in advance;
  • surrogate markers without functional outcomes;
  • lack of an appropriate control;
  • sponsor control over analysis or publication;
  • testing a branded ingredient but marketing a different finished product.

Commercial sponsorship

Commercial sponsorship does not automatically invalidate research. It increases the importance of transparent protocols, analysis, reporting, data access and independent replication.

Several central Urolithin A studies involved employees, board members or advisers of the ingredient developer and sponsor.[2,3,5,7] We therefore treat independent confirmation as an important evidence gap.