NAD+
NAD⁺ (nicotinamide adenine dinucleotide) is a vital molecule found in every living cell. Its main job is to help turn food into energy by moving electrons around during metabolic processes. It also supports over 500 enzyme reactions and is essential for healthy mitochondria, the parts of cells that act like power generators. Beyond energy production, NAD⁺ helps repair DNA and keeps cells functioning properly, which protects the body from aging and disease. Without enough NAD⁺, cells wouldn’t survive or work correctly.
Is this used to correct a deficiency or achieve supramaximal levels?
Deficiency
Is it taken for life span or health span?
Both, preventing diseases like CVD and neurodegeneration can extend lifespan
Is it targeting a specific disease? Or general health?
General health and ‘four horsemen: metabolic syndrome, neurodegeneration, cancer and CVD
Any genetic involvement?
N/A
Is there a biomarker to track its effects?
NAD+
MOA of supplement
NAD⁺ is essential for making energy in cells. It carries electrons during glycolysis, the Krebs cycle (which makes ATP, the body's main energy currency), and oxidative phosphorylation. NAD⁺ also powers enzymes like sirtuins and PARPs, which repair DNA and control gene activity. NAD⁺ levels can drop during immune responses because it gets broken down by an enzyme called CD38. To maintain healthy levels, the body recycles NAD⁺ using an enzyme called NAMPT. Problems with this recycling can affect energy production, DNA repair, and the immune system.
Risk vs reward
+ NAD is involved in activating sirtuins, which help reduce oxidative stress and inflammation. This may reduce atherosclerosis
+ Some NAD precursors e.g. NR and NMN may improve endothelial function and arterial stiffness.
+ Niacin, an NAD precursor has shown to reduce triglicerised and apoB liproproteins which may slow CVD progression
+ NR may reduce cancer risk and protect against chemotherapy induced DNA damage and neurotoxicity
+ NR may improve exercise performance
+ NR and NMN have neuron protecting mechanisms and improve motor function in Parkinson's
- NAD precursors can cause flushing of the skin due to vasodilation
- Some precursors also may accelerate the growth of existing cancers as it plays a role in glycolysis (ATP production).
Evidence for it?
In a cross over study with 24 participants (12 young, 12 older adults), each group received either NR supplementation or a placebo. NR supplementation improved muscle strength and reduced fatigue in older adults. However, it did not affect aerobic capacity (VO2max)in either group. NR also increased NAD(P)H levels and reduced oxidative stress, particularly in older adults, suggesting benefits for muscle performance and fatigue reduction in aging individuals.
Systematic review of 10 randomized clinical trials with 489 participants assessed the safety and effectiveness of NAD+ and NADH supplementation. The findings showed improvements in anxiety, heart rate, insulin sensitivity, and quality of life, particularly in conditions like chronic fatigue syndrome, Alzheimer’s disease, and Parkinson’s. Side effects were mild. Additionally, lifestyle factors such as exercise and diet were found to enhance NAD+ levels, potentially amplifying the benefits of supplementation.
This lab study tested whether NAD+ precursors, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) could protect HeLa cells (a cancer cell type) from DNA damage caused by cisplatin, a chemotherapy drug. Both NR and NMN improved cell survival, reduced DNA damage, boosted DNA repair, and restored NAD⁺ levels. NR showed slightly better protection, but overall, both compounds offered similar benefits in reducing cisplatin’s harmful effects.
Evidence against it?
RCT This study tested whether 12 weeks of 2000 mg/day nicotinamide riboside (NR) could improve insulin sensitivity and metabolism in 40 obese, insulin-resistant men aged 40–70. Participants were randomly assigned to NR or placebo. No significant improvements were seen in insulin sensitivity, glucose metabolism, fat oxidation, or body composition in the NR group. However, NR was well tolerated with no safety concerns. The findings suggest that while NR is safe, it may not improve metabolic health in this population, and benefits seen in animal studies may not translate to humans.
Effects of NR supplementation: Most human trials on nicotinamide riboside (NR) supplementation show limited clinical effects, mainly small reductions in inflammation and increased NAD⁺ levels in blood. NR doesn’t consistently raise NAD⁺ in muscle. While early findings suggest NR may have potential in treating inflammation, some severe diseases (such as chronic conditions and hypertension), the results remain mixed. More rigorous studies are needed to fully understand NR’s therapeutic potential, especially in populations with NAD+ deficiency.
Best bioavailable form?
Subcutaneous for NAD+
Advice on taking it?
NAD precursors have higher bioavailability that NAD