NAD+ Supplementation and Mental Health
Longevity researchers, health professionals, and anti-aging aficionados are aware of the importance of healthy NAD+ concentrations for ensuring physical health and optimal cellular function. Much of the research focuses on the role of NAD+ in preventing and managing age-related chronic diseases, fibromyalgia, ALS, and chronic fatigue, among others.
However, the applications of NAD+ for preventing ailments that primarily affect physical function may just be the beginning. NAD+ also has a vital role in maintaining and promoting mental health, from improving mood, to preventing degenerative brain diseases, to potentially treating anxiety and depression.
This article provides an overview of recent research on how NAD+ therapy, including supplementation with pure NAD+ and NAD+ precursors, may help prevent, manage, or treat mental health-related diseases.
NAD+ is an essential component for the healthy metabolism and function of every cell in the body, including brain cells.
Newly published laboratory research with mice has found that as brain cells age, NAD(P)+ transhydrogenase or NNT, the form of NAD+ found in the mitochondria of cells, is unevenly distributed in different regions in the brain, and overall activity is reduced. The lack of NNT in the brain resulted in depressive behavior and impaired movement (1).
The good news is that other laboratory research has revealed that supplementation with nicotinamide mononucleotide, a precursor of NAD+, reduces depressive behaviors (2). In other words, depression caused by metabolic impairments in brain cells may be treated with supplements that increase NAD+ production.
The available research on the potential role of NAD+ in treating depression is limited, and that which exists has been conducted with animals, not humans. However, initial research is promising, and it is entirely possible that NAD+ therapy will be on the cusp of innovation for the treatment of clinical depression.
NAD+ therapy may help to slow the progression of chronic brain diseases like NAD+ and Alzheimer’s Disease.
Recent research published in the Current Opinion in Clinical Nutrition and Metabolic Care reviewed the existing research on the clinical benefits of using nicotinamide riboside, a precursor to NAD+ to slow cognitive decline caused by Alzheimer’s disease and dementia. Nicotinamide riboside is well known to reduce DNA damage, neuroinflammation, and cell death; and improve the plasticity of the brain’s hippocampus in lab models (3).
The review found that oral supplementation with nicotinamide riboside may be a promising strategy for improving cognitive decline in Alzheimer’s disease models and other cognitive diseases models, as well as during “normal” aging (3).
Other neurodegenerative diseases for which there have been promising applications of NAD+ therapy include Wener syndrome, Charcon-Mari Tooth diseases (CMT), and peripheral neuropathy disorders (4).
More preclinical studies are required to determine if the effects extend to humans.
In the health and wellness world, there has been a growing buzz about the potential for intravenous NAD+ therapy, or NAD+ IV therapy, and other NAD+ therapy types, for treating anxiety.
NAD+ IV therapy for anxiety later in life is based on the knowledge that as humans age, levels of NAD+ decline in regions of the brain where feelings of anxiety originate. One of the first researcher groups to examine the effect of supplementation on hypersensitivity and problems with sensory processing, like those associated with anxiety, found that supplementation with NMN, a NAD+ precursor, can help prevent and treat cognitive impairments like these (5).
A group of researchers published a breakthrough study in 2018, where they tested the effect of intravenous NAD+ therapy on reducing stress and inflammation associated with anxiety, depression, and addiction. They found that NAD+ supplementation helps to reduce inflammation, and there were no significant adverse effects during or after supplementation (6).
While IV NAD+ therapy for treating anxiety in adults is promising, more research is needed.
NAD+ plays a vital protective role in many age-related degenerative diseases, including those directly affecting mental health. Increasing NAD+ concentrations can improve cellular metabolic function, positively influence DNA repair, and support bodily processes that protect the immune system. Additionally, raising NAD+ levels can balance energy needs and protect cells and tissues against oxidative damage and inflammation (7).
While more research is needed to understand the underlying mechanisms and specific effects of NAD+ therapy for preventing and treating different mental and brain health-related diseases, initial research on the potential role of NAD+ in promoting mental health is promising.
Francisco, A., Engel, D., Figueira, T., Rogério, F., de Bem, A., & Castilho, R. (2020). Mitochondrial NAD(P)+ Transhydrogenase is Unevenly Distributed in Different Brain Regions, and its Loss Causes Depressive-like Behavior and Motor Dysfunction in Mice. Neuroscience, 440, 210-229. https://doi.org/10.1016/j.neuroscience.2020.05.042
Xie, X., Yu, C., Zhou, J., Xiao, Q., Shen, Q., & Xiong, Z. et al. (2020). Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice. Journal Of Affective Disorders, 263, 166-174. https://doi.org/10.1016/j.jad.2019.11.147
Braidy, N., & Liu, Y. (2020). Can nicotinamide riboside protect against cognitive impairment?. Current Opinion In Clinical Nutrition & Metabolic Care, 23(6), 413-420. https://doi.org/10.1097/mco.0000000000000691
Kang, B., Choi, J., Stein, S., & Ryu, D. (2020). Implications of NAD+boosters in translational medicine. European Journal Of Clinical Investigation, 50(10). https://doi.org/10.1111/eci.13334
Johnson, S., Wozniak, D., & Imai, S. (2018). CA1 Nampt knockdown recapitulates hippocampal cognitive phenotypes in old mice which nicotinamide mononucleotide improves. Npj Aging And Mechanisms Of Disease, 4(1). https://doi.org/10.1038/s41514-018-0029-z
Braidy, N., Clement, J., Sturges, J., Liu, Y., Poljak, A., & Sachdev, P. (2018). Intravenous NAD+ effectively increased the NAD metabolome, reduced oxidative stress and inflammation, and increased expression of longevity genes safely in elderly humans. Journal Of Cellular Neuroscience And Oxidative Stress, 10(3), 779. Retrieved 18 October 2021, from https://dergipark.org.tr/en/download/article-file/791736.
Braidy, N., & Liu, Y. (2020). NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Experimental Gerontology, 132, 110831. https://doi.org/10.1016/j.exger.2020.110831
