Precursors of nicotinamide adenine dinucleotide (NAD+), modulators of enzymes of the NAD+ biosynthesis pathways and inhibitors of NAD+ consuming enzymes, are the main boosters of NAD+. Increasing public awareness and interest in anti-ageing strategies and health-promoting lifestyles have grown the interest in the use of NAD+ boosters as dietary supplements, both in scientific circles and among the general population. Here, we discuss the current trends in NAD+ precursor usage as well as the uncertainties in dosage, timing, safety, and side effects. There are many unknowns regarding pharmacokinetics and pharmacodynamics, particularly bioavailability, metabolism, and tissue specificity of NAD+ boosters. Given the lack of long-term safety studies, there is a need for more clinical trials to determine the proper dose of NAD+ boosters and treatment duration for aging prevention and as disease therapy. Further research will also need to address the long-term consequences of increased NAD+ and the best approaches and combinations to increase NAD+ levels. The answers to the above questions will contribute to the more efficient and safer use of NAD+ boosters.

Compositions of stainless steel, nickel-titanium, cobalt-chromium and β-titanium orthodontic alloys were simulated with mixtures of Fe, Ni, Cr, Co, Ti and Mo metal ions as potential oxidative stress-triggering agents. Wild-type yeast Saccharomyces cerevisiae and two mutants ΔSod1 and ΔCtt1 were used as model organisms to assess the cytotoxicity and oxidative stress occurrence. Metal mixtures at concentrations of 1, 10, 100 and 1000 µM were prepared out of metal chlorides and used to treat yeast cells for 24 h. Every simulated orthodontic alloy at 1000 µM was cytotoxic, and, in the case of cobalt-chromium alloy, even 100 µM was cytotoxic. Reactive oxygen species and oxidative damage were detected for stainless steel and both cobalt-chromium alloys at 1000 µM in wild-type yeast and 100 µM in the ΔSod1 and ΔCtt1 mutants. Simulated nickel-titanium and β-titanium alloy did not induce oxidative stress in any of the tested strains.

The aim was to assess the composition of released metal ions from fixed orthodontic appliances both in an in vitro and in vivo setting and to compare their quantities to evaluate any possible health risks associated with them. For the in vitro setting, a set of 24 as-received sterile SS brackets, 2 SS sterile archwires, and 2 NiTi sterile archwires were aged for 90 days in artificial saliva, and released metal ion concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS), using matrix-matched standards for calibration. For the in vivo setting, 15 brackets, 15 SS, and 15 NiTi archwires were retrieved after 90 days of intraoral exposure in 15 subjects. Debris composition on each part of the orthodontic appliance was assessed using scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). The present study evidenced a difference in the composition of released metal ions from fixed orthodontic appliances detected in an in vitro and in vivo setting. Generally, the relative content of metal ions was higher in the retrieved debris than that released in artificial saliva. The concentration of released metal ions from all tested alloys was below the upper recommended limit of daily intake; however, possible local effects in terms of hypersensitivity due to their accumulation in the debris cannot be excluded even with such concentrations.