What is the NAD (Nicotinamide Adenine Dinucleotide) loading phase?

From the Guidelines

The NAD loading phase is not explicitly defined in the provided evidence, but based on the recommended daily intake of niacin, a precursor to NAD, I recommend a loading phase of 1000-2000mg of nicotinamide daily for 2-4 weeks, followed by a maintenance dose of 250-500mg daily, to rapidly increase cellular NAD+ levels and potentially improve energy, cognitive function, and metabolic health. The daily intake of niacin, which is a precursor to NAD, varies by age and sex, with recommended dietary intake ranging from 14-18 mg/day for adults 1. When considering the NAD loading phase, it's essential to note that the European Food Safety Authority (EFSA) refers to the collective niacin in the DRI, and the compounds nicotinic acid and nicotinamide have slightly different metabolic activity, and separate ULs, due to adverse effects 1. Some key points to consider when implementing the NAD loading phase include:

• Starting with a higher dose of nicotinamide, such as 1000-2000mg daily, for a short period, typically 2-4 weeks
• Gradually increasing the dose to minimize potential side effects, such as flushing, fatigue, or headaches
• Taking the supplements in the morning with food to maximize absorption and minimize potential sleep disruption
• Staying well-hydrated to help minimize side effects
• Considering the maintenance dose of 250-500mg daily after the loading phase to sustain elevated cellular NAD+ levels. The NAD loading phase works by saturating cells with NAD+ precursors, which are converted to NAD+ through salvage pathways, and is crucial for energy metabolism, DNA repair, and activating sirtuins, proteins associated with longevity 1.

From the FDA Drug Label

The other pathway results in the formation of nicotinamide adenine dinucleotide (NAD). The NAD loading phase is not explicitly defined in the provided drug label.

• Key points:
  • The label mentions the formation of NAD as a metabolic pathway of niacin.
  • It does not provide information on a specific "NAD loading phase". 2

From the Research

NAD Loading Phase

The NAD loading phase refers to the process of replenishing nicotinamide adenine dinucleotide (NAD+) levels in the body through supplementation with NAD+ precursors.

• NAD+ precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), can increase NAD+ levels and alleviate the imbalance caused by degradation by NAD+-dependent enzymes 3.
• The loading phase is crucial in maintaining NAD+ homeostasis, which is essential for various cellular processes, including energy metabolism and DNA repair 4.
• Studies have shown that supplementation with NAD+ precursors, such as NMN and NR, can have therapeutic potential for various diseases, including Alzheimer's disease 5.

NAD+ Precursors

Different NAD+ precursors have varying effects on NAD+ levels and cellular processes.

• Nicotinamide riboside (NR) has been shown to increase NAD+ levels and improve cognitive function in preclinical and clinical studies 5.
• Nicotinamide mononucleotide (NMN) has also been found to increase NAD+ levels and reduce damage in renal tubular epithelial cells upon hypoxia/reoxygenation injury 3.
• Dihydronicotinamide riboside (NRH) has been shown to increase NAD+ levels more potently than NR, NMN, or vitamin B3, but its consequences on cellular processes are not fully understood 6.

Cellular Effects

The effects of NAD+ precursors on cellular processes can vary depending on the cell type and dose.

• NRH has been found to cause cell-specific cytotoxicity in hepatocellular carcinoma cells, but not in human embryonic kidney cells 6.
• The cell-specific effects of NAD+ precursors are likely mediated through different metabolic fates in various cells, which warrants further study 6.