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NAD+ and NADH are two forms of the coenzyme: nicotinamide adenine dinucleotide (NAD). NAD+ supports over half of all biological processes. Low NAD+ levels are associated with age-related physical disability and disease.1
NAD+ depletion is detected in major neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, cardiovascular disease, and muscle atrophy.2 NAD+ deficiency has been identified in the skin, muscle, and brain tissue.3 NAD+ supplementation can improve energy metabolism and insulin sensitivity, as well as protect against neurodegeneration and improve cognitive function.4,5
The NAD+ salvage pathway using NAD+ precursors is the primary way NAD+ is supplemented. Both nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), two forms of water-soluble vitamin B3, have been studied as supplements to treat disease in humans. Research suggests that either NR or NMN supplementation could increase cellular NAD+ levels in a dose-dependent manner.6-8 A quick search on ClinicalTrials.gov yields over 1,000 clinical trials investigating the role of NAD+ in preventing and treating disease. Researchers are studying the many potential health benefits possible with NAD+ supplementation.
” NMN could open up a new horizon in modern therapeutics.”Poddar et al. (2019)
NMN has shown promise in treating:1,8-10
NMN supplementation improves physical activity, energy expenditure, and neuronal (brain cell) function in a dose-dependent manner by increasing NAD+ and SIRT signaling.11,12 Exercise improves aerobic capacity, cardiovascular health, metabolic health, and physical function. Many of these benefits may be NAD+/sirtuin-related. Exercise increases the expression of nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage pathway, as well as NAD+ levels and sirtuin activity.13,14When comparing NAD+ levels in middle age and college adults before and after ten weeks of training, Lamb et al. (2020) found that resistance exercise:14
In another study, researchers compared aerobic capacity in middle-aged and young recreationally trained runners taking various doses of NMN. The four groups in the study included:
The results suggested that NMN increased the aerobic capacity of humans during exercise training in a dose-dependent manner. This effect is likely because of enhanced oxygen utilization.15
Results reported from an animal study suggested that using an 18-day series of NMN injection or nine weeks of exercise had similar benefits for reversing metabolic dysfunction and showed that NMN had stronger effects on liver fat metabolism than did exercise.15
The amount of NAD+ that is injected will depend on the specific treatment being used and the individual needs of the patient. NAD+ is being studied as a potential treatment for various conditions, including addiction, depression, and age-related cognitive decline.
In general, NAD+ is administered through intravenous (IV) infusions, in which the NAD+ is injected into a vein using a needle. The typical dosage of NAD+ used in clinical studies ranges from 100 to 300 mg per day, given as one or more infusions over a period of several days.15
Subcutaneous injection, which is the injection of a substance just under the skin, is an alternative method of administering NAD. Subcutaneous NAD+ injections require a prescription. The injections are self-administered and are similar to insulin injections. The dosage range varies but is typically between 20 mg and 100 mg NAD+.
Intramuscular (IM) injection, which is the injection of a substance directly into a muscle, is not a common method of administering NAD+. Limited information is available on the safety and effectiveness of NAD+ intramuscular injection.
The duration of a NAD injection will depend on the specific treatment used and the patient’s individual needs. NAD is being studied as a potential treatment for a variety of conditions, including addiction, depression, and age-related cognitive decline. Experts have not yet worked out how each of the NAD precursors acts in human body tissues because the pathways used to make NAD+ vary by cell type, which makes it difficult to determine an effective dose or recommended treatment length.
It is important to note that NAD is still being studied as a potential treatment for various conditions, and it is not yet approved by regulatory agencies such as the US Foods and Drug Administration (FDA) for use as a treatment. Therefore, it is important to consult with a qualified healthcare professional before considering NAD therapy and to follow the recommended treatment regimen. Invigor Medical’s treatment specialist can help you determine whether NAD+ supplementation is right for you. NAD+ requires a prescription for subcutaneous injection. Your Invigor Medical healthcare provider will determine your dosage during your consultation.
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While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice.
1. Johnson S, Imai SI. NAD (+) biosynthesis, aging, and disease. F1000Res. 2018;7:132. doi:10.12688/f1000research.12120.1
2. Fang EF, Lautrup S, Hou Y, et al. NAD(+) in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med. Oct 2017;23(10):899-916. doi:10.1016/j.molmed.2017.08.001
3. Zapata-Pérez R, Wanders RJA, van Karnebeek CDM, Houtkooper RH. NAD+ homeostasis in human health and disease. https://doi.org/10.15252/emmm.202113943. EMBO Molecular Medicine. 2021/07/07 2021;13(7):e13943. doi:https://doi.org/10.15252/emmm.202113943
4. Braidy N, Liu Y. Can nicotinamide riboside protect against cognitive impairment? Curr Opin Clin Nutr Metab Care. Nov 2020;23(6):413-420. doi:10.1097/mco.0000000000000691
5. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985
6. Custodero C, Saini SK, Shin MJ, et al. Nicotinamide riboside—A missing piece in the puzzle of exercise therapy for older adults? Experimental Gerontology. 2020/08/01/ 2020;137:110972. doi:https://doi.org/10.1016/j.exger.2020.110972
7. Trammell SAJ, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications. 2016/10/10 2016;7(1):12948. doi:10.1038/ncomms12948
8. Hong W, Mo F, Zhang Z, Huang M, Wei X. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Review. Frontiers in Cell and Developmental Biology. 2020-April-28 2020;8doi:10.3389/fcell.2020.00246
9. Poddar SK, Sifat AE, Haque S, Nahid NA, Chowdhury S, Mehedi I. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. 2019;9(1):34.
10. Mehmel M, Jovanović N, Spitz U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients. May 31 2020;12(6)doi:10.3390/nu12061616
11. Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism. 2016;24(6):795-806. doi:10.1016/j.cmet.2016.09.013
12. Park JH, Long A, Owens K, Kristian T. Nicotinamide mononucleotide inhibits post-ischemic NAD+ degradation and dramatically ameliorates brain damage following global cerebral ischemia. Neurobiology of Disease. 2016/11/01/ 2016;95:102-110. doi:https://doi.org/10.1016/j.nbd.2016.07.018
13. de Guia RM, Agerholm M, Nielsen TS, et al. Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiological Reports. 2019/06/01 2019;7(12):e14139. doi:https://doi.org/10.14814/phy2.14139
14. Lamb DA, Moore JH, Mesquita PHC, et al. Resistance training increases muscle NAD+ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals. Aging. 2020;12(10):9447-9460. doi:10.18632/aging.103218
15. Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. Jul 8 2021;18(1):54. doi:10.1186/s12970-021-00442-4