In vitro (cell culture) studies provide evidence that vitamin B3 (niacin) coenzyme NAD content influences the cellular response to DNA damage, an important risk factor in cancer development (4, 5, 6).
However, little is known regarding cellular NAD levels and the prevention of DNA damage or cancer in humans (7, 8). Neither the cellular NAD content nor the dietary intake of NAD precursors (niacin and tryptophan) necessary for optimizing protective responses following DNA damage has been determined.
Research on biochemical and cellular aspects of DNA repair has stimulated an interest in the relationship between vitamin B3 (niacin) intake and cancer risk in human populations (9). A large case-control study found increased consumption of niacin (5.2–6.2 mg), along with antioxidant nutrients, to be associated with about a 40% decreased incidence of oral (mouth), pharyngeal (throat), and esophageal cancers (10, 11).
Insulin-dependent diabetes mellitus in children, often called ‘type I diabetes’, is known to result from the autoimmune destruction of insulin-secreting cells in the pancreas. Evidence from in vitro and animal research indicates that high levels of vitamin B3 (nicotinamide) protect insulin-producing pancreas cells from inflammatory white blood cells and reactive oxygen species. Thus, nicotinamide might help to delay the onset of insulin dependence in individuals with type 1 diabetes.
An analysis of ten published trials, including five randomized placebo-controlled trials, found evidence of improved insulin-producing cell function after one year of treatment with vitamin B3 (nicotinamide), but the analysis failed to find any clinical evidence of improved blood glucose (‘glycemic’) control (12).
Unlike nicotinamide, nicotinic acid has not been found effective in the prevention of type 1 diabetes.
NAD content influences genomic stability and loss of genomic stability is a hallmark for cancer (29). The pool of NAD is decreased during niacin deficiency and that affects the activity of NAD-consuming enzymes. Among NAD-dependent reactions, poly ADP-ribosylations catalyzed by PARP enzymes are critical for the cellular response to DNA injury. After DNA damage, PARPs are activated. The subsequent poly ADP-ribosylations of a number of signaling and structural molecules by PARPs were shown to facilitate DNA repair at DNA strand breaks. Cellular depletion of NAD has been found to decrease levels of the tumor suppressor protein p53, a target for poly ADP-ribosylation, in human breast, skin, and lung cells (30).
Niacin deficiency was found to decrease bone marrow NAD and poly-ADP-ribose levels and increase the risk of chemically induced leukemia in rats (31). Conversely, a pharmacologic dose of niacin was able to increase NAD and poly ADP-ribose in bone marrow and decrease the development of leukemia in rats (32). However, little is known regarding cellular NAD levels and the prevention of DNA damage or cancer in humans. One study in two healthy individuals involved elevating NAD levels in blood lymphocytes by supplementation with 100 mg/day niacin for eight weeks. Compared to non-supplemented individuals, the supplemented individuals had reduced DNA strand breaks in lymphocytes exposed to free radicals in a test tube assay (33). However, niacin supplementation of up to 100 mg/day in 21 healthy smokers failed to provide any evidence of a decrease in cigarette smoke-induced genetic damage in blood lymphocytes compared to placebo (34). More recently, in an observational study, the rate of chromosome aberrations (used to evaluate DNA damage in peripheral blood lymphocytes of 82 pilots chronically exposed to ionizing radiation) was significantly lower in subjects with high (28.4 mg/day) compared to low (20.5 mg/day) dietary niacin intake (35).
A large case-control study found increased consumption of niacin, along with antioxidant nutrients, to be associated with decreased incidence of oral (mouth), pharyngeal (throat), and esophageal cancers in northern Italy and Switzerland (36, 37). An increase in daily niacin intake of 6.2 mg was associated with about a 40% decrease in cases of cancers of the mouth and throat, while a 5.2 mg increase in daily niacin intake was associated with a similar decrease in cases of oesophageal cancer.
Niacin deficiency can lead to severe sunlight sensitivity in exposed skin. Given the implication of NAD-dependent enzymes in DNA repair, there has been some interest in the effect of niacin on skin health. In vitro and animal experiments have helped gather information, but human data on niacin/NAD status and skin cancer are severely limited.
Several pilot studies for the prevention of insulin dependent diabetes mellitus (IDDM) in Inslet cells Antibodies (ICA)-positive relatives of patients with IDDM yielded conflicting results. A large, multicenter randomized controlled trial of nicotinamide in ICA-positive siblings of IDDM patients between 3 and 12 years of age also failed to find a difference in the incidence of IDDM after three years (38). A randomized, double-blind, placebo-controlled, multicentre trial of nicotinamide (maximum of 3 grams/day) was conducted in 552 ICA-positive relatives of patients with IDDM. The proportion of relatives who developed IDDM within five years was comparable whether they were treated with nicotinamide or placebo (39).
Authored by Dr Peter Engel in 2010, reviewed by Giorgio La Fata on 06.06.2017
