Cracked porcelain doll face representing aged skin.

5-Fluorouracil Cream: Can This Acne Treatment Really Fight Photoaging?

Nico Varela in Health & Wellness December 2025 • 4 min read.

"New research sheds light on whether this common topical treatment can reverse sun damage and reduce wrinkles."

Photoaging, or premature skin aging caused by prolonged exposure to ultraviolet (UV) radiation, is a growing concern for many. As individuals seek to maintain youthful appearances, the market for anti-aging solutions has exploded. From over-the-counter creams to laser therapies, various treatments promise to reverse the effects of sun damage, but how effective are they?

Among the many treatments available, topical fluorouracil, a medication primarily used for actinic keratosis (scaly, crusty skin patches), has garnered attention for its potential to improve skin texture and reduce wrinkling. However, the evidence supporting its use as an anti-aging treatment has been limited and somewhat conflicting.

A recent study published in JAMA Dermatology investigated the effectiveness of topical fluorouracil, 5%, cream in reversing photoaging. This article breaks down the study's findings, exploring whether this common treatment can truly turn back the clock on sun-damaged skin.

The Fluorouracil Face-Off: What the Research Reveals About Anti-Aging?

Cracked porcelain doll face representing aged skin.

Specifically, the dermatologists assessed 3,042 photographs from 281 participants, evaluating them at baseline, 6 months, 12 months, and 18 months. The photonumeric scales used included:

Griffiths scale (global assessment of photodamage)
Allergan forehead lines scale
Melomental folds scale
Crow's feet scale

The study found no statistically significant changes in photodamage between baseline and any of the follow-up time points (6, 12, and 18 months). These results suggest that a standard course of topical fluorouracil, 5%, cream does not lead to detectable improvements in photoaging as measured by these specific photonumeric scales.

Beyond Wrinkles: Why Current Photoaging Scales Might Miss the Bigger Picture?

The study's authors suggest that the lack of improvement in photoaging may be due to the limitations of the photonumeric scales used, emphasizing their primary focus on rhytides (wrinkles) and overlooking other manifestations of photoaging.

The development of more comprehensive photonumeric scales that incorporate factors such as lentigines (age spots), hyperpigmentation, and telangiectasias (spider veins) could provide a more accurate assessment of photoaging and the effectiveness of treatments like topical fluorouracil.

While this study indicates that topical fluorouracil may not significantly improve photoaging as measured by existing scales, it's important to consider that the treatment's effects on other aspects of skin damage might warrant further investigation. As research evolves, a more holistic approach to evaluating photoaging could reveal the true potential of various treatments.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1001/jamadermatol.2017.2578, Alternate LINK

Title: Effect Of Topical Fluorouracil Cream On Photodamage

Subject: Dermatology

Journal: JAMA Dermatology

Publisher: American Medical Association (AMA)

Authors: Kaveri Korgavkar, Kachiu C. Lee, Martin A. Weinstock

Published: 2017-11-01

Everything You Need To Know

What is 5-Fluorouracil cream, and why is it relevant to skin health?

5-Fluorouracil cream is a topical medication primarily used to treat actinic keratosis, which manifests as scaly, crusty skin patches. Its significance in the context of skin health lies in its potential to address skin damage, specifically the effects of photoaging. While initially developed for other conditions, its properties have led to investigation into its use as an anti-aging treatment because it can improve skin texture and reduce wrinkling. Its implications include the possibility of reversing sun damage and improving the overall appearance of the skin, providing a potential solution for individuals concerned about the visible signs of aging.

What is photoaging, and why is it a growing concern?

Photoaging is the premature aging of the skin caused by prolonged exposure to ultraviolet (UV) radiation from the sun. It is important because it leads to visible signs of aging, such as wrinkles, and other skin damage. This is a growing concern because people are more exposed to the sun. The implications of photoaging are both cosmetic and health-related, as it not only affects appearance but can also increase the risk of skin cancer. Understanding photoaging is crucial for taking preventative measures and seeking effective treatments to maintain healthy, youthful-looking skin.

What was the study's methodology involving 5-Fluorouracil cream?

The study, a secondary analysis of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, involved 932 US veterans with a history of keratinocyte carcinomas. Researchers examined the chemopreventive effects of topical fluorouracil by analyzing photographs taken at baseline and at various time points over four years. Two independent dermatologists graded the photographs using four validated photonumeric scales to assess the degree of photoaging. This study is significant because it provides evidence regarding the efficacy of 5-Fluorouracil cream in treating photoaging. The implications are that a standard course of topical 5-Fluorouracil cream does not lead to improvements in photoaging as measured by specific photonumeric scales.

What were the photonumeric scales used in the study?

The photonumeric scales used in the study were the Griffiths scale, the Allergan forehead lines scale, the Melomental folds scale, and the Crow's feet scale. These scales are used to assess the degree of photoaging, but are limited in their scope. These scales are important because they provide a way to measure and compare the effects of treatments on the skin. The implications are that these scales mainly focused on rhytides (wrinkles) and overlooking other manifestations of photoaging. This may lead to an incomplete understanding of the treatment's effectiveness as they do not capture all aspects of photoaging, such as changes in skin texture or the presence of sunspots.

What were the overall findings regarding the effectiveness of 5-Fluorouracil cream in treating photoaging?

The study found that a standard course of topical 5-Fluorouracil cream did not lead to detectable improvements in photoaging as measured by the specific photonumeric scales. This is important because it shows that the treatment may not be as effective in reversing photoaging as previously thought, specifically according to the used measures. The implications suggest the need for further research to determine if other assessment methods or treatments may be more effective in addressing the effects of sun damage.