Intravenous NAD Therapy: What Clinicians Should Know

Nicotinamide adenine dinucleotide (NAD) is a coenzyme that plays a crucial role in various metabolic processes, including energy production and DNA repair. Unfortunately, NAD levels decrease as we age, which can decrease overall energy levels. Although NAD is not FDA approved and is regulated as a dietary supplement, some studies and various media outlets have suggested that increasing NAD levels via dietary supplementation may have the following beneficial effects on metabolism and overall health:

• Addiction treatment
• Muscle recovery 
• Anti-aging 
• Improvements in neurocognitive functions
• Athletic performance improvements 
• Weight loss

Patients can increase their NAD levels by receiving an intravenous (IV) infusion of NAD for an immediate effect. But to ensure that patients receive a proper dose without experiencing adverse events, it is critical that clinicians understand how to properly administer NAD intravenously. In this blog post, we’ll review the different administration routes as well as the peer-reviewed literature about NAD supplementation. Plus, we’ll cover how to ensure successful and safe IV administration of NAD. 

Oral vs. intravenous NAD administration

NAD is incredibly sensitive to light, moisture, and temperature and may not be stable in capsule form. Also sensitive to pH, NAD may degrade in the stomach if the capsule does not have a slow-release coating. Because of its susceptibility to degradation, oral tablets often contain NAD precursors such as nicotinamide (NAM) and nicotinic acid (NA). These two precursors respectively require two and three enzymatic steps to be converted into NAD, and will become bioavailable more slowly than intravenously administered NAD.¹ Another NAD precursor, nicotinamide mononucleotide (NMN), is currently facing a similar battle as NAC supplements, in which the FDA has prevented it from being marketed as a dietary supplement due to its prior investigation as a drug. 

In contrast, IV NAD infusion bypasses the need to use its precursors and provides the body with a more immediate source of NAD, which has been shown to be completely uptaken by tissues and/or metabolized in the first 2 hours of administration.² 

Here’s what the literature says about the benefits of intravenous NAD 

Compared with oral administration of NAD precursors, the literature discussing intravenous administration of NAD is relatively scarce. However, the literature that is available has suggested that IV infusion of NAD provides the following benefits:

• Alleviating tremors associated with Parkinson’s Disease.^3,4,5
• Improving cognitive performance.⁶
• Managing post-acute COVID-19 syndrome symptoms.⁷
• A potential link between NAD and a reduction in food cravings⁸

The link between NAD and obesity

While there is ongoing research on the potential benefits of NAD supplementation, most of this research has been performed in mouse models and has used NAD precursors such as nicotinamide riboside.⁹ However, evidence suggests that low NAD levels are associated with obesity. In a human study, acquired obesity was associated with a suppressed NAD+/SIRT pathway, and the authors suggested that NAD+ boosters might help prevent decreased metabolism associated with obesity.¹⁰ 

Overall, the impact of NAD supplementation on weight loss is not well-established, and there is scant literature on this topic, making it difficult to make any definitive conclusions. Still, there does appear to be a connection between low NAD+ levels and acquired obesity. 

Intravenous NAD therapy recommendations 

The success of NAD intravenous therapy hinges upon its correct administration, including both a proper dose and drip rate, and should be performed by an experienced professional, such as a licensed Registered Nurse, Physician Assistant, Nurse Practitioner, or more senior-credentialed clinician. Clinicians should have a strong comfort level with administering NAD. Clinicians considering NAD supplementation for their patients should be comfortable and familiar with the proper administration rate and dosage. 

• The minimal dose must be dripped over at least two hours, or the patient may experience adverse events, such as rapid heartbeat, nausea, and anxiousness. 
• NAD IV is typically given as a monotherapy, and many drugs may NOT be added to this IV. If providers wish to add additional meds, they will (likely) need to be dripped via secondary IV or a push. This is because the two forms of NAD are a highly reactive redox couple (NAD+/NADH) that may react with other medications and also rapidly decomposes in acidic or alkaline solutions.
• When initiating NAD therapy, a patient’s tolerance should be built by slowly titrating doses to achieve compliance and successful outcomes. 
• Drug quality is important for any administration route, but especially important with intravenous medications. Although we source our NAD from PCCA (the leader in quality APIs), we still perform quality control testing on all compounded sterile medications.
• At VLS/ New Drug Loft, our NAD is compounded as 50 mg/mL in two 5 mL vials, with a BUD of 7 days or 45 days when frozen, as per USP guidelines. 

Instead of relying on supplements with NAD precursors such as NMN, which may be sourced from unknown vendors and can be pulled from the market at any time due to FDA actions, consider sourcing NAD from a trusted, licensed 503A compounding pharmacy with a USP <797> compliant facility such as VLS Pharmacy.

 

Please comment below with any thoughts or questions. Reach out to our team to learn about best practices and to partner with our experts about our other nutritional IV therapies for your patients. All medications from VLS Pharmacy and New Drug Loft are prepared in a lab that follows safety and quality standards per our status as a 503A pharmacy.

 

References

1. Ito TK, Sato T, Takanashi Y, et al. A single oral supplementation of nicotinamide within the daily tolerable upper level increases blood NAD+ levels in healthy subjects. Translational Medicine of Aging. 2021;5:43-51. doi:10.1016/j.tma.2021.09.001
2. Grant R, Berg J, Mestayer R, et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+. Front Aging Neurosci. 2019;11:257. doi:10.3389/fnagi.2019.00257
3. William Carey University, Sl B. Intravenous Administration Of Nicotinamide Adenine Dinucleotide Alleviates Tremors Associated With Parkinson’s Disease A Case Report. HGGM. 2020;6(1):1-5. doi:10.24966/GGM-8662/100046
4. Birkmayer JGD, Vrecko C, Volc D, Birkmayer W. Nicotinamide adenine dinucleotide (NADH) — a new therapeutic approach to Parkinson’s disease. Acta Neurologica Scandinavica. 1993;87(S146):32-35. doi:10.1111/j.1600-0404.1993.tb00018.x
5. Birkmayer JGD, Birkmayer W. THE COENZYME NICOTINAMIDE ADENINE DINUCLEOTIDE (NADH) AS BIOLOGICAL ANTIDEPRESSIVE AGENT EXPERIENCE WITH 205 PATIENTS.
6. Gibson SB, Mestayer R, Berg J, Grant R, Dyess G. Intravenous Administration of Nicotinamide Adenine Dinucleotide Improves Cognitive Performance in Human Subjects: Implications for Clinical Populations. Archives of Physical Medicine and Rehabilitation. 2021;102(10):e42. doi:10.1016/j.apmr.2021.07.585
7. Block T, Kuo J. Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome. Clin Med�Insights�Pathol. 2022;15:2632010X221106986. doi:10.1177/2632010X221106986
8. Braidy N, Villalva MariaD, Eeden S van. Sobriety and Satiety: Is NAD+ the Answer? Antioxidants. 2020;8(5):425. doi:https://doi.org/10.3390/antiox9050425
9. Cantó C, Houtkooper RH, Pirinen E, et al. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity. Cell Metab. 2012;15(6):838-847. doi:10.1016/j.cmet.2012.04.022
10. Jukarainen S, Heinonen S, Rämö JT, et al. Obesity Is Associated With Low NAD+/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins. The Journal of Clinical Endocrinology & Metabolism. 2016;101(1):275-283. doi:10.1210/jc.2015-3095

 

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