Topical caffeine plus exercise protects more effectively against skin cancer

Key Points

National report - Caffeine and exercise together may be up to four times as protective against ultraviolet light-induced skin cancer than either alone, according to a recent study from Rutgers University, New Brunswick, N.J.

Each of these factors is known to reduce the risk of skin cancer and reduce the amount of tissue fat that is associated with the risk for internal cancers. This new research shows that combining the two can have a more-than-additive effect for enhancing the ability to eliminate UVB-damaged epidermal cells, at least in mice.

The latest study looked at four groups of animals that were exposed to UVB radiation in a controlled setting. One group's water was laced with a low dose of caffeine (0.1 mg/ml), the equivalent of one to two cups of coffee a day in humans. Another group had access to a running wheel for voluntary exercise; a third had access to both the wheel and caffeinated water; and the control group had access to neither.

The work was conducted at the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers University and published in the July 31 issue of the Proceedings of the National Academy of Sciences (PNAS).

"I think that our studies in mice will be extrapolatable to humans, but we really won't know that until we do a careful study," senior author Allan H. Conney, Ph.D., tells Dermatology Times.

Other factors

He acknowledges it is difficult to translate the findings to humans, in part because, "Mice metabolize caffeine quite rapidly - it has a half-life of about 45 minutes - while humans have an average half-life of about five hours."

There also is great genetic variability in humans and the rate of metabolism of caffeine can range down to two to three hours or up to 10 hours. Smoking cigarettes is a confounding factor that can increase the metabolism of caffeine up to threefold.

Dr. Conney has done extensive work with both topically and orally administered caffeine.

"Caffeine and caffeine sodium benzoate are, to the best of my knowledge, the first examples of substances that have both a sunscreen effect and also enhance apoptosis in DNA damaged epidermis," he says.

Topical application of caffeine or caffeine sodium benzoate 30 minutes before UVB irradiation inhibited the formation of thymine dimers by 70 percent to 80 percent, and the formation of UVB-induced thymine dimers is the genetic basis for UVB-induced cancerous growth.

One recent and counterintuitive finding from a parallel study using a larger dose of caffeine (0.4 mg/ml) showed that "The response goes downhill with the larger doses of caffeine. The higher dose of caffeine was less effective than the lower dose in terms of getting a greater-than-additive response. I don't have an explanation for it," Dr. Conney says.

He is still seeking to ascertain caffeine's mechanism of action in preventing cancer.

One observation is that "Caffeine inhibits the ATR/Chk1 pathway by inhibiting the phosphorylation of Chk1, and this results in a premature increase in cyclin ±, premature mitosis and cell death."

Another mechanism appears to be that caffeine enhances UVB-induced p53 upregulation, which also is involved with apoptosis. However, this appears to be more the case with orally rather than topically administered caffeine.