In recent years, there has been growing interest in NAD+ supplements as a potential way to improve brain health and cognitive function. NAD+, or nicotinamide adenine dinucleotide, is a molecule that is involved in many cellular processes in the body, including energy production, DNA repair, and cellular signaling. As we age, our levels of NAD+ naturally decline, which has been linked to various health issues, including cognitive decline.
NAD+ is an essential component of cellular energy metabolism, playing a critical role in the electron exchange from the tricarboxylic acid (TCA) cycle through the electron transport chain (ETC) for the generation of ATP by oxidative phosphorylation. Furthermore, it is also a key substrate for ADP-ribosylation by poly-ADP-ribose polymerase (PARP) enzymes, protein deacetylation by sirtuins, and cyclic ADP-ribose (cADPR) production by CD38 and CD157. Due to its involvement in several critical cellular processes, declining NAD+ levels have been identified as a likely cause of cognitive decline in aging and age-related diseases such as Alzheimer's.
Multiple mechanisms have been proposed to explain how NAD+ precursor supplementation can help support NAD+ levels and achieve neuroprotection. Several studies have demonstrated that NAD+ precursor supplementation can reduce oxidative stress, lower protein aggregation, have anti-inflammatory effects, stimulate neuroprotective HCA2 macrophages, and ameliorate mitochondrial damage and dysfunction.
A recent systematic review of NAD+, its derivatives, and Alzheimer’s disease in rodent models identified eleven studies that had been published up to December 2020. The synthesis of their findings supported the conclusion that treatment with NAD+ precursors did restore its levels in the brain, with consequent improvements in learning and memory. The results of the included studies supported the involvement of several mechanisms, including reduced oxidative stress, inflammation, and apoptosis, as well as improved mitochondrial function.
Additional studies have found promising results, including one by Hou et al. (2021), who showed that treating APP/PS1-mutant mice with the NAD+ precursor NR for 5 months improved learning and memory. Rehman et al. (2021) induced neuronal dysfunction in an Alzheimer’s disease model and showed that NAM treatments prevented memory deficits. Yao et al. (2017) showed that NMN greatly ameliorated cognitive impairment in a transgenic mouse model of Alzheimer’s disease.
One study published in 1996 by Birkmayer found that the treatment of 17 Alzheimer’s disease patients with open-label 10 mg/day NADH disodium salt resulted in improved cognitive function based on the mini-mental state examination (MMSE) and global deterioration scale (GDS) over a treatment period of 8–12 weeks without side effects or adverse events.
In conclusion, our cognitive abilities are precious, and we should do everything we can to maintain and improve them. As we've seen, NAD+ supplementation can be an effective way to support and enhance cognitive health, particularly as we age. By taking action today to invest in our mental well-being, we can enjoy the benefits of better focus, memory, and clarity, allowing us to achieve our goals and live a more fulfilling life. So why not take that first step and explore the many ways you can incorporate NAD+ supplements into your daily routine? With the right approach, you can empower yourself to elevate your cognitive performance and live your best life.
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