NAD+ is essential for energy production, DNA repair, and overall cellular health, yet its levels naturally decline as we age—by as much as 50% by middle age. To counter this, molecules like NMN and NR have gained attention for their potential to boost NAD+ levels.
In this article, you’ll learn about NMN and NR’s structures, mechanisms, and roles in vitality and longevity.
What is NAD+
Nicotinamide Adenine Dinucleotide (NAD+) is essential for cellular health and energy production. It acts as a coenzyme in the “salvage pathway,” recycling NAD+ to maintain cellular levels.
NAD+ fuels critical reactions in cellular metabolism, enabling mitochondria to convert nutrients into energy. Made from precursors like nicotinic acid, NAD+ supports biosynthesis, helping cells maintain optimal function. Without enough NAD+, cells struggle with energy production, repair, and overall vitality. To naturally support NAD+ levels, consider incorporating foods high in NAD into your diet.
Importance of maintaining adequate NAD+ levels:
- Powers cellular energy, keeping cells active.
- Promotes repair to combat aging and damage.
- Increases resilience to stress and oxidation.
- Ensures effective DNA repair, protecting against long-term damage.
What is NMN?
Nicotinamide Mononucleotide (NMN) is a molecule made of nicotinamide (a form of vitamin B3) and ribose sugar, acting as a direct NAD+ precursor.
Synthesis pathway of NMN:
- NMN is created from NAD+ precursors like nicotinamide.
- The NMN transporter (SLC12A8) moves NMN into cells efficiently.
- Inside cells, NMN is converted to NAD+ by NMNAT.
- This increase in NAD+ levels promotes DNA repair processes.
- Rising NAD+ levels boost sirtuin activity, specifically sirt1 and sirt3, which protect cells from oxidative stress.
How NMN Boosts NAD+ Levels
NMN boosts NAD+ levels by entering cells via the SLC12A8 transporter and converting to NAD+ through NMNAT. This process restores NAD+ in aging cells, activating sirtuins that promote DNA repair and reduce oxidative stress.
Recent research on the effectiveness of NMN supplementation suggests that:
- It promotes DNA repair, enhancing processes essential for cell health.
- It boosts sirtuin activity, increasing sirt1 and sirt3 to protect cells.
- It restores NAD+ in aging cells, replenishing levels in older cells.
- It protects against oxidative stress, shielding cells from long-term damage.
- It benefits mammals, as studies by scientists like David Sinclair show NMN aids in the health of mice.
- It may benefit women, with Elysium Health research suggesting specific health advantages.
What is NR?
Nicotinamide Riboside is a form of vitamin B3 that serves as a precursor to NAD+. Chemically, NR consists of a nicotinamide base linked to a ribose sugar.
How the body uses NR to produce NAD+:
- Absorption: After ingestion, NR is absorbed into the bloodstream.
- Cellular Uptake: NR enters cells through specific transporters.
- Phosphorylation: Inside the cell, NR is phosphorylated by nicotinamide riboside kinases (NRKs) to form nicotinamide mononucleotide (NMN).
- Conversion to NAD+: NMN is then converted into NAD+ by NMN adenylyltransferase (NMNAT) enzymes.
How NR Boosts NAD+ Levels
Once inside cells, NR undergoes two simple steps to become NAD+. First, it’s converted to NMN, which is then quickly transformed into NAD+ through enzymes.
Studies demonstrating NR’s impact on NAD+ levels in humans:
- Nature Communications found NR supplements increased NAD+ levels in middle-aged and older adults.
- Research in Cell Reports showed NR supplements improved mitochondrial function and energy metabolism in aged mice.
- GeroScience published a pilot study suggesting NR might improve cognitive function in older adults.
Nicotinamide Mononucleotide (NMN) vs. Nicotinamide Riboside (NR)
Differences between NMN and NR:
- Molecular structure: NMN has a phosphate group; NR lacks this group, making NR smaller.
- Cellular uptake: NR enters cells directly; NMN requires conversion to NR or a specific transporter.
- Conversion to NAD+: NR converts to NAD+ via NMN; NMN is a direct NAD+ precursor.
NMN converts into NAD+ more efficiently than NR, as it is a direct precursor. However, NR’s smaller size allows for easier cellular uptake. Both supplements boost NAD+ levels, and the choice depends on individual health goals.
Efficiency in Raising NAD+ Levels
Clinical studies have examined the efficacy of NMN and NR in elevating NAD+ levels, with varying effectiveness. Some research suggests NMN converts into NAD+ more efficiently than NR, leading to higher NAD+ levels post-supplementation.
Other studies suggest both supplements similarly increase NAD+ levels, varying by study design and individual response.
Conflicting results and scientific consensus:
- Some studies show NMN is more effective; others find NR equally potent.
- Genetics, health status, and metabolism can influence how individuals respond to these supplements.
- Variations in dosages and formulations make direct comparisons challenging.
Safety Profile
- NMN side effects: Generally well-tolerated; some report mild nausea, headaches, or digestive discomfort.
- NR side effects: Typically safe; possible mild effects include nausea, fatigue, headaches, or stomach discomfort.
The FDA has not approved NMN as a dietary supplement, citing its investigation as a new drug. NR is generally recognized as safe and is available as a supplement to support NAD+ production. Always consult your doctor before use.
Bioavailability
Bioavailability refers to how well a substance is absorbed and used by the body. For NMN and NR, it indicates how effectively these supplements increase NAD+ levels after intake.
- NMN: Studies suggest NMN converts into NAD+ more efficiently than NR, indicating higher bioavailability.
- NR: Research shows NR is highly bioavailable, easily absorbed, and quickly metabolized into NAD+.
Long-term Benefits for Aging
NAD+ levels decline with age, leading to reduced cellular energy and increased vulnerability to stress. Therefore, restoring them may slow aging and improve health.
Studies and ongoing research on NMN and NR:
- Long-term NMN supplementation in mice shows lifespan-extending, rejuvenating effects, and improved metabolic health.
- Ongoing trials investigate NMN and NR for their longevity-enhancing potential and safety in humans.
- Studies suggest NMN and NR restore NAD+ levels, giving cells a rejuvenating effect.
Stability & Storage
- Keep supplements away from heat and moisture to maintain potency.
- Exposure to light can degrade the compounds; use opaque containers.
- Ensure containers are airtight to prevent moisture and air exposure.
- While only sometimes necessary, storing in the fridge can extend shelf life.
How NMN and NR Become NAD+ in Cells
Nicotinamide Riboside (NR):
- NR enters cells through specific transporters.
- Inside, it’s changed into NMN by enzymes called NRKs.
- NMN is then converted into NAD+ by NMNAT enzymes.
Nicotinamide Mononucleotide (NMN):
- NMN enters cells directly through a specific transporter (Slc12a8).
- Inside, NMN is quickly converted to NAD+ by NMNAT enzymes.
The enzymes NRKs and NMNATs are crucial in these pathways. NRKs phosphorylate NR to NMN, while NMNATs convert NMN to NAD+. The expression levels of these enzymes can influence the efficiency of NAD+ synthesis. Elevated expression of NRKs and NMNATs enhances NAD+ production, supporting systemic cellular functions.
Why is Boosting NAD+ Important for Aging?
As we age, declining NAD+ levels reduce cellular energy, impair DNA repair, and lower stress resistance, disrupting vital functions and contributing to aging and age-related diseases. Since NAD+ levels decline with age, boosting them through lifestyle and supplements may help support longevity and resilience.
Boosting NAD+ levels may mitigate age-related decline by:
- Improving mitochondrial energy production.
- Activating enzymes for DNA repair and genomic stability.
- Protecting neurons to lower neurodegenerative disease risk.
How to Choose Between NMN and NR
- Effectiveness: Both NR and NMN can increase NAD+ levels, helping keep cells active.
- Cost: NR is usually more budget-friendly than NMN.
- Availability: NR is widely available, while NMN access varies depending on location.
- Personal health needs: Your health situation may affect whether NR or NMN is better.
It’s always wise to check with your doctor before starting supplements to ensure they’re right for you.
How to Tackle Aging with NMN and NR Supplements
Incorporating NMN and NR supplements can help combat aging by boosting NAD+ levels for energy and repair. Always consult your doctor to find the proper dosage and ensure they meet your health needs.
Holistic anti-aging tips:
- Eat nutrient-rich foods.
- Stay active with regular exercise.
- Get enough sleep to recharge.
- Manage stress with relaxation techniques.
Key Takeaways
- NAD+ is crucial for energy, DNA repair, and cellular health, but levels decline with age.
- NMN and NR boost NAD+, supporting cellular energy, repair, and overall vitality.
- NMN is a direct NAD+ precursor, while NR requires conversion but is more easily absorbed.
- Both supplements show potential for reducing inflammation, enhancing cell health, and promoting longevity.
- Consult your doctor to determine the best supplement based on your health needs.
Frequently Asked Questions
Is NR Better Than NMN?
It depends on your goals and response. NMN converts to NAD+ more efficiently, while NR boosts energy and supports mitochondria. Both promote rejuvenation, reduce inflammation and may extend lifespan.
Can I Take Both NMN and NR Together?
Combining NMN and NR is still being studied. As NAD+ declines with age, these supplements may rejuvenate cells and support metabolism—consult your doctor.
Can NMN Delay Aging?
Animal studies suggest NMN may delay aging by restoring NAD+ in cells, improving tissue function, and supporting mitochondrial health. NMN boosts sirtuin activity and optimizes metabolism, helping maintain function as NAD+ declines with age. While promising for longevity, more human research is needed.
