What is the effect of oral Nicotinamide adenine dinucleotide (NAD+)?

From the Guidelines

Oral NAD+ supplements are not recommended due to their poor bioavailability and limited scientific evidence supporting their effectiveness. NAD+ (nicotinamide adenine dinucleotide) is a coenzyme important for cellular metabolism and energy production, but when taken orally, it is largely broken down in the digestive system 1. Instead, consider precursors like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), which are more effectively absorbed and converted to NAD+ in the body.

Key Points to Consider

• Typical dosages range from 250-500mg daily for NR and 250-1000mg daily for NMN, taken with food to improve absorption 1.
• These precursors work by providing the building blocks needed for your body to produce its own NAD+, potentially supporting cellular energy production, DNA repair, and metabolic functions.
• Lifestyle factors like regular exercise, intermittent fasting, and consuming foods rich in niacin (vitamin B3) may naturally support NAD+ levels in the body more effectively than supplements.
• The administration of 'supraphysiological' doses of vitamin B3 (≥500 mg/kg) has been demonstrated to prevent specific events and the subsequent loss of cellular NAD+ levels 1.

Important Considerations

• Niacin deficiency can lead to a variety of clinical symptoms, including diarrhea, dermatitis, and dementia, collectively known as “pellagra” or “the three D disease” and even death (four D) if not recognized and treated promptly 1.
• Certain populations are at risk of niacin deficiency, including the elderly, pregnant women, and cancer patients undergoing treatments that induce DNA damage 1.
• The oral/enteral route should be used whenever the gastrointestinal tract is functional 1.

From the Research

Oral NAD+ Supplementation

• Oral NAD+ supplementation has been studied as a potential therapeutic approach for various diseases and conditions, including neurological degeneration, Candida glabrata infection, and reverse cholesterol transport 2.
• Nicotinamide riboside (NR) has been identified as a potential NAD+ precursor that may support neuronal NAD+ synthesis, with studies suggesting its potential health benefits in treating cardiovascular, neurodegenerative, and metabolic disorders 3.
• Chronic oral supplementation with NAD+ precursors, such as NR and nicotinamide mononucleotide, has been shown to be safe and tolerable, with potential benefits for improving physiological function in humans, particularly in older adults and those with cardiometabolic disease risk factors 4.

Safety and Effectiveness

• A systematic review of randomized clinical trials found that NAD+ supplementation was well-tolerated and associated with improved clinical outcomes, including decreased anxiety and maximum heart rate, increased muscle insulin sensitivity, and improved quality of life 5.
• However, common side effects associated with NAD+ supplementation include muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches, although these adverse events were not considered serious 5.
• Another study suggested that NAD+ deficiency is a common central pathological factor in various diseases and aging, and that restoring NAD+ levels may have therapeutic potential 6.

Potential Therapeutic Applications

• Oral NAD+ supplementation may have potential therapeutic applications for various diseases and conditions, including:
  • Neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease 3, 5.
  • Cardiovascular disease, including hypertension and atherosclerosis 3, 4.
  • Metabolic disorders, such as diabetes and obesity 3, 4.
  • Infectious diseases, including SARS-CoV-2 3.