EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR

WAILEA, HAWAII (FRONTLINE MEDICAL NEWS) – Nicotinamide is one of the rare proposed agents for skin cancer chemoprevention distinguished by dirt cheap cost combined with a highly reassuring safety profile plus evidence of efficacy – which, together, make it a reasonable option in high risk patients, according to Daniel M. Siegel, MD.

Other agents that fit into that category include the tropical rainforest fern Polypodium leucotomos and milk thistle, added Dr. Siegel , a dermatologist at the State University of New York, Brooklyn.

Then, there’s rapamycin.

“That’s a really interesting one. I don’t know if, 5 years from now, we’ll all be taking low-dose rapamycin as an antiaging drug, but we might, especially if someone figures out the ideal dose,” he said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.

Nicotinamide

In the case of nicotinamide, the efficacy is actually supported by published level 1 evidence in the form of a highly positive 1-year, double-blind, randomized, placebo-controlled phase III clinical trial.

“You can Google ‘nicotinamide’ and find it at places like Costco and Trader Joe’s for less than 6 cents per day. That makes for a really good risk/benefit ratio. A nickel a day: That’s a cheap one. That’s one where I’d say, ‘Why not?’ It seems to be safe,” Dr. Siegel said.

In the phase III ONTRAC trial, Australian investigators randomized 386 patients who averaged roughly eight nonmelanoma skin cancers in the past 5 years to either 500 mg of oral nicotinamide twice daily or matched placebo for 12 months. During the study period, the nicotinamide group had a statistically significant and clinically meaningful 23% reduction in new nonmelanoma skin cancers, compared with the control group. They also had 13% fewer actinic keratoses at 12 months than controls. And the side effect profile mirrored that of placebo ( N Engl J Med. 2015 Oct 22;373[17]:1618-26 ).

“Nicotinamide is vitamin B3. It’s not niacin. It doesn’t cause flushing and other vasodilatory effects. It’s actually pretty innocuous,” Dr. Siegel said.

In laboratory studies, nicotinamide has been shown to enhance DNA repair following UV exposure, as well as curb UV-induced immunosuppression.

Polypodium leucotomos Samambaia

This plant , commonly known as calaguala in the Spanish-speaking tropics and samambaia in Brazil, has a centuries-long tradition of safe medicinal use. It is commercially available over-the-counter (OTC) as a standardized product called Heliocare, designed to avoid the guesswork involved in topical sunscreen application. Each capsule contains 240 mg of an extract of P. leucotomos. Dr. Siegel said he takes it daily when he’s in a sunny locale, such as Hawaii.

Milk thistle

This plant, known as Silybum marianum, has silymarin as its bioactive compound. Dermatologist Haines Ely, MD , of the University of California, Davis, has reported therapeutic success using it in porphyria cutanea tarda and other conditions. It has been shown to inhibit photocarcinogenesis in animal studies.

Dr. Siegel said that, while Dr. Ely has told him his preferred preparation is a German OTC product, milk thistle seeds can be found in health food stores, ground to a powder using a coffee bean grinder, and used as a food supplement. Like Polypodium leucotomos and nicotinamide, milk thistle is nontoxic.

Rapamycin

This macrolide compound is produced by the bacterium Streptomyces hygroscopicus. Rapamycin is an immunosuppressant used to coat coronary stents and prevent rejection of transplanted organs. It is an mechanistic target of rapamycin signaling pathway inhibitor being studied as a cancer prevention and antiaging agent.

Science magazine called the discovery that rapamycin increased the lifespan of mice one of the top scientific breakthroughs of 2009 . Subsequent animal studies have established that the extended lifespan wasn’t solely the result of rapamycin’s antineoplastic effects but of across-the-board delayed onset of all the major age-related diseases. Thus, rapamycin could turn out to be a true antiaging agent, in Dr. Siegel’s view.

Studies in humans are underway. Researchers at Novartis have reported that a rapamycin-related compound curbed the typical decline in immune function that accompanies aging as reflected in a 20% enhancement in the response to influenza vaccine in elderly volunteers ( Sci Transl Med. 2014 Dec 24;6[268]:268ra179 ).

Dr. Siegel reported serving as a consultant to Ferndale, which markets Heliocare. The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

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