Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans

Abstract

Cutaneous immunity, which is a key defence against the development of skin cancers, is suppressed by even small doses of ultraviolet (UV) radiation. Preventing this UV-induced immunosuppression may therefore reduce the incidence of skin cancer. Nicotinamide (vitamin B3) has immune-protective and cancer-preventive effects against UV radiation in mice, and we have shown previously that topical nicotinamide is immune protective in humans. Using the Mantoux model of skin immunity in healthy volunteers, we compared oral nicotinamide to placebo (both administered for 1 week) in a randomized, double-blinded, crossover design against the effects of solar-simulated ultraviolet (ssUV) radiation on delayed-type hypersensitivity to tuberculin purified protein derivative. Discrete areas of the back were irradiated with low doses of ssUV daily for three consecutive days. Immunosuppression, calculated as the difference in Mantoux-induced erythema of irradiated sites compared with unirradiated control sites, was determined in volunteers taking oral nicotinamide and placebo. Significant immunosuppression occurred in an UV dose-dependent manner in the presence of placebo. Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight.

Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair

“…Using the Mantoux model of delayed-type hypersensitivity (DTH) in healthy volunteers, we have shown that nicotinamide protects from UV-induced immunosuppression in humans [63, 64]. 5% topical nicotinamide, applied 15 minutes before or after each of 3 daily exposures to low-dose solar-simulated (ss) UV (equivalent to less than ~8 minutes exposure to Sydney spring sunlight [65]), prevented UV-induced suppression of Mantoux reactions [63].…”

Nicotinamide enhances repair of ultraviolet radiation‐induced DNA damage in primary melanocytes

“…Nicotinamide enhances DNA repair in UVirradiated human HaCaT keratinocytes and ex vivo human skin (7), likely by preventing UV-induced ATP depletion (8). The immunosuppressive effects of UV radiation are also reduced by nicotinamide (9,10). In phase 2 clinical trials, it reduced premalignant actinic keratoses and significantly reduced new non-melanoma skin cancers, although this was not a primary endpoint (11).…”

Nicotinamide and resveratrol regulate bovine adipogenesis through a SIRT1-dependent mechanism

“…Nicotinamide, an inhibitor of SIRT1, plays an essential role in many cellular processes such as increasing DNA replication, modulating mitochondrial quantity and quality, and reducing ultraviolet radiation-induced immunosuppression (Jang, Kang, & Hwang, 2012;Sandler & Andersson, 1988;Yiasemides, Sivapirabu, Halliday, Park, & Damian, 2009). It is an inexpensive and non-toxic compound and currently used for a variety of skin ailment applications.…”