Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review

Purpose: NAD+ is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including oxidative phosphorylation and production of adenosine triphosphate, DNA repair, calcium-dependent secondary messenger and gene expression. The purpose of this systematic review is to examine whether the coenzyme formulae NAD+ and NADH are safe and effective when acting as a supplement to humans. Methods: This systematic review of randomized clinical trials performed a search in six electronic databases. Two reviewers assessed and extracted the studies independently. The risk of bias in studies was performed using the version 2 of the Cochrane risk of bias tool for randomized trials. Results: This review includes 10 studies, with a total of 489 participants. The studies included different clinical conditions, such as chronic fatigue syndrome (CFS); older adults; Parkison disease; overweight, postmenopausal prediabetes and Alzheimer disease. Based on studies, the supplementation with NADH and precursors was well tolerated and observed clinical results such as, a decrease in anxiety conditions and maximum heart rate was observed after a stress test, increased muscle insulin sensitivity, insulin signaling. Quality of life, fatigue intensity and sleep quality among others were evaluated on patients with CFS. All studies showed some side effects, thus, the most common associated with NAD's use are muscle pain, nervous disorders, fatigue, sleep disturbance, headaches. All adverse events cataloged by the studies did not present a serious risk to the health of the participants. Conclusion: Overall, these findings support that the oral administration of NADH can be associated to an increase in general quality of life and improvement on health parameters ( e.g., a decrease in anxiety, maximum heart rate). NADH supplementation is safe and has a low incidence of side effects. Future investigations are needed to evidence the clinical benefits regarding specific diseases and doses administered.