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Roflumilast cream 0.05% (Zoryve) is safe as a treatment for patients aged 3 months to 2 years with atopic dermatitis, new phase 2 findings from the INTEGUMENT-INFANT trial program suggest.¹

These data were presented in a poster during the Dermatology Education Foundation (DERM) 2025 NP/PA CME Conference. Adelaide Hebert, MD—professor and director of pediatric dermatology with McGovern Medical School at UTHealth Houston—spoke with HCPLive about the study and its key takeaways for patients in this age cohort with atopic dermatitis.

“We felt it was critical to include this younger cohort of patients in a special study to better understand their response to roflumilast, and this particular concentration is a bit lower,” Hebert explained. “It’s 0.05% and we know that the skin in an atopic patient is often compromised. The barrier is not as intact as normal skin….It was a four-week study. The patients received the medicine application once daily. There were certain criteria for the patients to be enrolled. They had to have mild to moderate atopic dermatitis, and they were required to have at least 3% body surface area. Patients were not enrolled if they had active infection or if they had another chronic condition, which might have prohibited us from adequately assessing the status of their atopic dermatitis.”

Hebert highlighted that during the course of the study, the patients were enrolled and roflumilast cream 0.05% was provided to the patients aged 3 months to 2 years. Both their progress in terms of atopic dermatitis and any adverse events were recorded by Hebert and coauthors.

Hebert et al’s analysis focused on such endpoints as IGA success as well as percent change from baseline in Eczema Area and Severity Index (EASI), Worst Itch-Numeric Rating Scale (WI-NRS), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI).^1,2 They also looked at sleep disturbances and Caregiver Global Assessment (CGA) results after using roflumilast cream 0.05%.

“One of the things that was determined in this clinical trial was that the outcome was favorable, and that was, of course, what we anticipated, given that we had such good data on older patients in 4-week studies,” Hebert said. “The delta in terms of placebo versus active drug in our older patients was significant, and it was early in onset. So again, we felt very confident using this lower concentration in our younger cohorts, with the expected outcome that we would see positive results. That is indeed what we were able to achieve during this particular clinical trial.”

To find out any further information about roflumilast cream’s use in this population with atopic dermatitis, view Hebert’s full interview video above. For more from DERM 2025, including research on atopic dermatitis therapies, view the latest conference coverage.

The quotes implemented in this interview summary were edited for clarity.

References

1. Hebert A, Eichenfield L, Burnett P, et al. INTEGUMENT-INFANT: A Phase 2, 4-Week Open-Label Safety Study of Roflumilast Cream 0.05% in Infants Aged 3 Months to Less than 2 Years Old With Mild-to-Moderate Atopic Dermatitis. Poster presented at the DERM 2025 NP/PA CME Conference; July 23 – 26, 2025; Las Vegas, Nevada.

2. Hebert A, Eichenfield L, Gonzalez M, et al. INTEGUMENT-INFANT: 4-week open-label safety of roflumilast cream 0.05% in 3-24-month-olds with atopic dermatitis. Poster presented at: The Society for Pediatric Dermatology Meeting 2025. July 23-26, 2025. Seattle, Washington. Accessed August 1, 2025.

A natural compound in chocolate may give “good” cholesterol a slight lift, a new study suggests, though the change is small.

Researchers tested this in people with metabolic syndrome, a cluster of conditions that increase heart disease risk. After 12 weeks of taking theobromine supplements, participants saw a modest rise in HDL cholesterol. However, the increase is considered too small to have a major impact on heart health on its own.

Cocoa has long been studied for its heart-health benefits. Research shows that whether you enjoy it as dark chocolate or take it as a supplement, cocoa can help improve several important health markers—like blood pressure, “bad” LDL cholesterol, total cholesterol and blood sugar. Most of these benefits come from natural antioxidants called polyphenols, especially flavanols, which help reduce inflammation and protect your blood vessels.

But cocoa doesn’t just offer polyphenols. It also contains thobromine, a mild stimulant related to caffeine. While theobromine isn’t as famous as those antioxidants, it might have its own heart benefits, possibly by helping to raise levels of “good” HDL cholesterol. Earlier studies have had mixed results, so researchers wanted to dig deeper.

For this study, published in Food Science & Nutrition, researchers focused on theobromine to see if it could boost HDL cholesterol—and even looked at which parts of HDL might be affected. They also explored how theobromine might work in our bodies. While the details aren’t fully understood yet, these advances give researchers new clues to investigate.

How Was This Study Conducted?

Researchers at Kermanshah University of Medical Sciences in Kermanshah, Iran, ran a 12-week study with 72 adults ages 40 to 55 who were living with overweight or obesity and had metabolic syndrome—a condition marked by a combination of high blood pressure, elevated blood sugar, excess visceral fat or low HDL cholesterol levels. About 90% of the participants were women.

Participants were assigned to take either a daily 450 mg theobromine supplement or a placebo. Everyone followed a calorie restricted diet with daily calorie needs tailored to each person based on age, sex, weight, height and physical activity.

In addition, the participants were also asked to avoid foods containing cocoa and limit caffeine intake to no more than four cups of coffee, tea or cola per day, since the body can convert caffeine into theobromine.

The researchers measured overall HDL cholesterol levels as well as specific subtypes, including HDL2 and HDL3, which differ in size and potential heart-protective effects. They also examined changes in the activity of two genes—PPAR-α and Sirt1—both involved in regulating how the body processes fat and energy.

What Did the Study Find?

At the start of the study, the group taking theobromine had an average HDL cholesterol level of 41.3 mg/dL, while the placebo group was slightly higher at 42.4 mg/dL. Both numbers fall near the lower end of what’s considered normal for adults. 

After 12 weeks, participants taking theobromine supplements saw a very small increase in overall HDL cholesterol—about 0.34 mg/dL on average—while the placebo group experienced a decrease of about 1.24 mg/dL.

The increase was more noticeable for the HDL2 subtype, which is a larger, more protective form of HDL. HDL2 levels rose by approximately 0.95 mg/dL in the theobromine group but dropped slightly in the placebo group. The ratio of HDL2 to HDL3 also improved, suggesting a shift toward a healthier HDL balance.

In addition, theobromine appeared to increase activity of the gene PPAR-α, which helps the body break down fat and manage energy. However, another gene studied, Sirt1, did not show meaningful changes. While these findings are statistically significant, the size of the changes is quite small and unlikely to have a major effect on heart health on their own.

How Does This Apply to Real Life?

If you’re hoping to boost your good cholesterol by eating more chocolate, don’t get ahead of yourself—it’s not that simple. The dose of theobromine using the study (450 mg per day) is roughly the equivalent to what you’d get from eating about 2 to 3 ounces of dark chocolate daily. That’s slightly more than a serving per day, which might work against your health goals if you’re trying to cut back on sugar. 

Importantly, the actual increase in HDL cholesterol observed in the study was small—about 0.3 mg/dL—which is unlikely to have a significant impact on heart health on its own. Additionally, the placebo group experienced a slight decrease in HDL levels, making the difference appear more pronounced than it might be in real life.

But since dark chocolate also offers beneficial polyphenols and has even been connected to a lower diabetes risk, dark chocolate is still a great choice when you need to add some sweetness to your day. Just don’t think of it as a magic bullet for your cholesterol levels.

While the study provides some insights into how theobromine might influence cholesterol levels and gene activity, it’s essential to focus on proven lifestyle habits—such as maintaining a balanced diet, staying active and managing blood pressure and blood sugar—to effectively support heart health.

Our Expert Take

Theobromine in chocolate might give your “good” cholesterol a small boost and help your body manage fat more efficiently—but the effect is modest and unlikely to lower heart disease risk on its own. That said, cocoa’s natural antioxidants have been shown to help reduce total cholesterol and support heart health. So while chocolate can be part of a balanced eating plan, your best bet is to stick with proven heart-healthy habits like eating well and staying active.