NAD+ and Niacinamide:
NAD+ and niacinamide are both part of the vitamin B3 family and share a common biosynthetic pathway. Niacinamide is a precursor for the synthesis of NAD. In the body, niacinamide can be converted into nicotinamide mononucleotide (NMN), which is a key intermediate in the biosynthetic pathway leading to the formation of NAD. Both NAD+ and niacinamide influence cellular functions and are involved in maintaining cellular homeostasis. NAD+ is essential for the activity of sirtuins, a class of proteins involved in regulating cellular processes like aging, metabolism, and stress response.
Niacinamide Production:
Tryptophan is an essential amino acid obtained through regular diet is the precursor required for niacinamide biosynthesis. Tryptophan is converted to Niacin and then to Niacinamide by way of an enzyme called nicotinamide phosphoribosyltransferase. The resulting Niacinamide (nicotinamide) then acts as the harbinger for NAD+ production.
NAD as a Coenzyme:
NAD exists in two forms - NAD+ (oxidized) and NADH (reduced). These forms play a crucial role in redox reactions, transferring electrons between molecules in metabolic pathways. NAD+ is involved in accepting electrons during catabolic reactions (such as glycolysis), while NADH donates electrons in anabolic reactions (such as the synthesis of fatty acids). After being used as a cofactor in redox reactions, NAD+ is regenerated to continue its role in cellular processes. The regeneration of NAD+ occurs through the transfer of electrons to an electron acceptor, often in the form of NADH. In the mitochondria, electrons from NADH move through the electron transport chain, leading to the movement of protons and the creation of a proton gradient. This, in turn, drives the synthesis of ATP through oxidative phosphorylation. This process is crucial for maintaining a continuous supply of NAD+ for cellular functions. The NAD+ coenzyme plays a role in energy metabolism, DNA repair, and cellular signaling. It functions as an electron carrier, shuttling electrons during redox reactions.
Topical Application
Topical application of niacinamide has a stabilizing effect on epidermal barrier function, seen as a reduction in trans epidermal water loss and an improvement in the moisture content of the horny layer. Niacinamide leads to an increase in protein synthesis (e.g. keratin), has a stimulating effect on ceramide synthesis, speeds up the differentiation of keratinocytes, and raises intracellular NADP levels. In ageing skin, topical application of niacinamide improves the surface structure, soothes out wrinkles and inhibits photo carcinogenesis. It is possible to demonstrate anti-inflammatory effects in acne, rosacea, and nitrogen mustard-induced irritation. Because of its verifiable beneficial effects, niacinamide is an excellent component in cosmetic products for use in disorders of epidermal barrier function, for aging skin, for improving pigmentary disorders and for use on skin prone to acne.
NAD+ anti-aging properties:
NAD+ production decreases with age. Scientists are unsure if the NAD+ depletion is caused by increased NAD+ consumption and/or decreased synthesis within the body. Replenishment of NAD+ precursors have shown to display beneficial effects against aging. An eight-week randomized, double-blinded, placebo-controlled study in 120 healthy adults (60-80 years old) demonstrated NR (250 mg and 500 mg) induced dose-dependent increase of blood NAD+ level observed after 4-weeks and was sustained till the end of the study. NR is a NAD+ precursor that has been proven to exhibit an increase in NAD+ concentrations found in blood. Importantly, no serious adverse effects were reported, thereby implicating the chronic administration of NR as a safe and effective way to increase NAD+ levels. These findings were reinforced by a 6-week randomized, double-blind, placebo-controlled crossover clinical trial conducted in 55-79 years old individuals that showed NR (oral 500 mg, twice a day) to be well tolerated and able to effectively elevate NAD+ levels in healthy adults. Moreover, it was able to reduce systolic blood pressure and aortic stiffness, which are considered measures of cardiovascular disease. Additional research is currently under way, to better understand NAD+ precursor roles in other illnesses such as such as diabetes, premature aging, and neurodegenerative diseases.
References:
Gehring W. Nicotinic acid/niacinamide and the skin. J Cosmet Dermatol. 2004 Apr;3(2):88-93. doi: 10.1111/j.1473-2130.2004.00115.x. PMID: 17147561.).
Chu, X., & Raju, R. P. (2022). Regulation of NAD+ metabolism in aging and disease. Metabolism, 126, 154923. doi:https://doi.org/10.1016/j.metabol.2021.154923
Anthony, A. S. (2008). NAD<sup>+</sup> and Vitamin B<sub>3</sub>: From Metabolism to Therapies. Journal of Pharmacology and Experimental Therapeutics, 324(3), 883. doi:10.1124/jpet.107.120758
Johannes Wohlrab, Daniela Kreft; Niacinamide - Mechanisms of Action and Its Topical Use in Dermatology. Skin Pharmacol Physiol 1 July 2014; 27 (6): 311–315. https://doi.org/10.1159/000359974
Yahyah Aman, Yumin Qiu, Jun Tao, Evandro F. Fang, Therapeutic potential of boosting NAD+ in aging and age-related diseases, Translational Medicine of Aging,