Despite this new therapeutic proposal, the clinical translational relevance of this study seems to be limited. That’s because the condition related to ‘macrophage-specific NAMPT depletion’ is not expected to be encountered easily in a clinical setting.
Nevertheless, Hong and colleagues emphasize that NAD+ is critical in the cleaning up activity of macrophages and in the subsequent resolution of inflammation. In cells, including macrophages, NAD+ is made mainly from nicotinamide (a form of vitamin B3, also known as niacin), with various dietary sources like fish, meat, and mushroom. Without proper supplementation, people can suffer from its deficiency, a condition known as pellagra.
Meanwhile, patients with IBD commonly have trouble eating or taking anything orally because they frequently go through abdominal pain, diarrhea, or decreased appetite. Malabsorption is another common problem in IBD patients. So, these challenges often result in nutritional imbalance or deficiency. The reported prevalence of malnutrition in IBD patients ranges between 20% and 85%. Furthermore, malnutrition is one of the most critical factors associated with a poor clinical outcome in IBD patients. Thus, this collective information implies that NAD+ deficiency may occur in immune cells – which is equivalent to NAMPT depletion in macrophages in our study – of chronic IBD patients with malnutrition.
In addition, aging is accompanied by a gradual decline in tissue and cellular NAD+ levels in multiple organisms, including humans. This decline in NAD+ levels is tied to numerous aging-associated diseases, such as cognitive decline, cancer, and metabolic disease. Remarkably, it has been reported that NAMPT levels also decrease in many tissues during organismal aging.
Thus, it seems that a decrease in NAD+ is ascribed to the reduced NAMPT levels in aged cells, at least in part. Taken together, supplementation of NMN (or nicotinamide) seems to be an effective treatment strategy that helps to reduce the severity and the duration of inflammation in patients with IBD, in particular those who are old or suffer from malnutrition.