What are the monitoring, management, and dosing regimens for Nicotinamide adenine dinucleotide (NAD+) supplementation, including oral, intravenous (IV), and subcutaneous administration, as well as its risks and uses in adult longevity medicine and functional medicine, particularly with peptide therapy?

From the Guidelines

NAD+ supplementation should be approached with caution, and dosing regimens should prioritize oral administration of nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) at 250-1000mg daily, with careful monitoring of side effects and potential interactions, as recommended by recent guidelines 1.

Monitoring and Management

When considering NAD+ supplementation, it is essential to monitor blood NAD+ levels before starting therapy and periodically thereafter, targeting the upper quartile of reference ranges. Common side effects include flushing, nausea, fatigue, and headache, particularly with IV administration. More serious risks include allergic reactions and potential interactions with medications that affect NAD+ metabolism.

Dosing Regimens

Oral NAD+ precursors like NR or NMN are typically dosed at 250-1000mg daily, taken in the morning with food to enhance absorption. Intravenous NAD+ therapy usually involves 500-1000mg infusions administered over 2-4 hours, typically in a series of 4-10 sessions, while subcutaneous NAD+ injections range from 50-200mg daily or several times weekly. However, the optimal dosing regimen may vary depending on individual patient needs and health status, and should be determined in consultation with a healthcare provider familiar with metabolic medicine.

Risks and Uses

NAD+ therapy is often combined with peptides like GHK-Cu, Epitalon, or Thymosin Alpha-1 in comprehensive longevity protocols. The scientific rationale centers on NAD+'s critical role in cellular energy production, DNA repair, and sirtuin activation, with declining levels associated with aging and chronic disease. However, patients should be aware that while promising, long-term human clinical data on NAD+ supplementation remains limited, and therapy should be supervised by a healthcare provider familiar with metabolic medicine. Recent studies have highlighted the importance of maintaining cellular NAD+ levels to prevent age-related sarcopenia and other diseases 1.

Key Considerations

• Patients with chronic oxidative stress or malabsorption may require higher doses of NAD+ supplementation, up to 200-500 mg/day, as recommended by recent guidelines 1.
• The upper intake level for nicotinamide is 12.5 mg/kg body weight/d or approximately 900 mg/d for adults, with no adverse effects observed at doses up to 25 mg/kg body weight/d in prolonged studies in diabetic subjects 1.
• NAD+ supplementation should be approached with caution, and patients should be closely monitored for potential side effects and interactions with other medications.

From the Research

Monitoring and Management of NAD+ Supplementation

• The efficacy of NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), in improving physiological function in humans is still unclear 2
• Chronic supplementation with NR is well-tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults 3
• Oral administration of NMN is safe and efficiently increases blood NAD+ levels in healthy subjects 4

Dosing Regimens for NAD+ Supplementation

• Dosing regimens for NAD+ precursors vary greatly across interventions, with studies using different doses and durations of supplementation 2
• A study using 250 mg/day of NMN for 12 weeks found significant increases in NAD+ levels in whole blood 4
• Another study used NR supplementation for 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial 3

Risks and Uses of NAD+ Supplementation

• NAD+ precursors have been shown to be safe and well-tolerated in human studies 2, 3, 4
• The use of NAD+ precursors may have beneficial effects on physiological changes and diseases associated with aging, such as metabolic disorders, cardiovascular ailments, and neurodegeneration 5, 6
• Further studies are required to determine the efficacy of NAD+ precursors in humans and to optimize the effects of NAD+ supplementation 6

Administration Routes for NAD+ Supplementation

• Oral administration of NAD+ precursors, such as NR and NMN, has been shown to be safe and effective in increasing NAD+ levels in humans 2, 4
• There is a need for methods of delivering NAD+ precursors to target organs or tissues to increase the outcomes of clinical trials 6
• Intravenous (IV) and subcutaneous administration of NAD+ precursors have not been extensively studied in humans, and more research is needed to determine their safety and efficacy 2

Peptide Therapy and NAD+ Supplementation

• There is limited research on the use of peptide therapy in combination with NAD+ supplementation, and more studies are needed to determine their potential synergistic effects 5
• Geroprotectors, such as NMN and NR, may enhance the efficacy of peptide therapy while concurrently providing their own numerous health benefits 5