Maintaining optimal NAD⁺ levels in the body can be a constant battle. As we age, our NAD⁺ levels naturally decline by approximately 50% every 20 years. This is due to the activity of three enzymes: NNMT (Nicotinamide N-methyltransferase), CD-38 (Cluster of Differentiation 38), and PARP (Poly (ADP-ribose) polymerase). These enzymes act like leaky buckets, constantly consuming NAD⁺ and depleting its availability for crucial cellular functions. Some NAD⁺ in the body is used, but much of it is lost.
NNMT, CD-38, and PARP play crucial roles in NAD⁺ metabolism and cellular processes. NNMT methylates nicotinamide, potentially reducing the NAD⁺ precursor pool. CD-38 is a major NADase (an enzyme that breaks down NAD⁺) that consumes NAD⁺ to produce signaling molecules. PARP enzymes use NAD⁺ as a substrate for DNA repair and other cellular functions. These enzymes can contribute to NAD⁺ depletion, especially with age or under cellular stress. Their activities are interconnected and impact various aspects of cellular health, making them important targets for research in aging, metabolism, and disease prevention. If we can reduce these enzymes, we can boost NAD⁺ levels in the body and increase health at the same time. Blocking the NNMT enzyme is a critical way to increase NAD⁺ levels.
Promising Interventions: 1-MNA and 5-amino-1MQ
Understanding these NAD⁺-depleting enzymes has led to the discovery of two promising compounds: 1-methylnicotinamide (1-MNA) and 5-amino-1-methylquinolinium (5-amino-1MQ). 1-MNA, a metabolite of NNMT, plays a dual role by providing feedback inhibition on NNMT activity and offering anti-inflammatory benefits. It shows particular promise in cardiovascular health, exercise performance, and blocking harmful inflammation through the NLRP3 inflammasome. While essential for host defense and metabolic regulation, aberrant activation of the NLRP3 inflammasome is associated with various inflammatory disorders, making it an important target for therapeutic interventions in diseases such as Alzheimer’s, diabetes, and rheumatoid arthritis.
Enter 5-Amino-1MQ, a synthetic compound that has emerged as a powerful solution to this challenge. As a potent and selective inhibitor of the NNMT enzyme, 5-Amino-1MQ prevents the methylation of nicotinamide (NAM), preserving the NAD⁺ precursor pool. This allows cells to increase NAD⁺ synthesis through the salvage pathways, leading to a cascade of beneficial metabolic changes.
Metabolic and Weight Management Benefits
Studies have demonstrated that 5-Amino-1MQ can improve metabolic parameters associated with obesity and diabetes. Elevated levels of NNMT can significantly impede the body’s ability to metabolize fat cells, creating a vicious cycle where excess weight increases NNMT production, further slowing fat metabolism and promoting additional weight gain. By inhibiting NNMT, it helps break the cycle of excess weight gain by enhancing the body’s ability to burn fat through lipolysis and improving the efficiency of fat cell metabolism. This may be very promising for patients who have had problems with GLP-1s.
Comprehensive Health Improvements
Beyond its metabolic effects, 5-Amino-1MQ offers a range of other potential health benefits such as:
- Increased muscle growth & repair
- Improved cholesterol levels
- Enhanced blood sugar regulation
- Anti-inflammatory properties
- Potential impact on longevity & healthspan
- May reduce cellular senescence
- Potential enhancement of stem cell function & tissue regeneration
- Increased vitality & focus
Targeting Other NAD⁺-Consuming Enzymes
While 5-Amino-1MQ focuses on inhibiting the NNMT enzyme, addressing the activity of other NAD⁺-consuming enzymes, such as CD-38, can also significantly increase NAD⁺ levels. CD-38 is a significant consumer of NAD⁺, converting it into signaling molecules like cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). By reducing CD-38 activity, more NAD⁺ remains available for other critical cell processes. Compounds like the natural flavonoid Apigenin have shown promise in lowering CD-38 activity.
A Holistic Approach to Maintaining Healthy NAD⁺ Levels
Maintaining optimal NAD⁺ levels requires a comprehensive strategy that considers the balance of NAD⁺ synthesis, consumption, and the regulation of key enzymes like CD-38 and NNMT. At PUR-FORM, we offer intravenous NAD⁺ to boost your natural stores. Stay tuned for more information on 5-Amino-1MQ and how you may be able to incorporate it into your longevity routine.
-Dr. P
