Study to Evaluate the Effect of Nicotinamide Riboside on Immunity

Overview

Background: The immune system controls how the body responds to infection or injury. Researchers want to see what effect a dietary supplement called nicotinamide riboside (NR) has on the immune system. A study showed that fasting has a good effect on immune cell health in healthy people. And when immune cells were exposed to NR they had a similar positive response as with fasting. Researchers want to see if healthy people have the same effects from NR and fasting, and if those effects last. Objectives: To see if taking nicotinamide riboside will have the same healthy immune system effects as fasting. To see if these good effects continue even after eating again. Eligibility: Healthy volunteers ages 18 - 39 years Design: Participants will be screened with medical history, physical exam, and blood tests. Women will have a urine pregnancy test. Participants will take 4 pills of either NR or a placebo once a day for 1 week. On day 6, they will not eat or drink anything. On day 7, they will have a study visit to give a blood sample before and after eating a meal at the clinic. They will also give a urine sample. Participants will stop taking the pills for 1 2 weeks. Participants will take either NR or a placebo once a day for 1 week. They will repeat day 6 and day 7 of the first week. Participants will get NR once and placebo once, but will not know which they are taking.

Intermittent caloric restriction or fasting has numerous health effects including the reduction in numerous cardiovascular disease risk factors. The cellular programs activated by caloric restriction are similarly turned on in preclinical studies in response to a 24-hour fast. We have found that a beneficial effect of 24-hour fasting is that it blunts the activation of a component of the immune system, termed the Nod-like receptor family protein 3 (NLRP3) Inflammasome. This inflammasome, as a mediator of sterile inflammation, is associated with the development of diabetes and atherosclerosis. At the same time, we found that refeeding after the 24-hour fast significantly increased NLRP3 protein levels, IL-1Beta, and TNF signaling, and that fasting blunted the NLRP3 inflammasome response, in association with the activation of a fasting sensing protein called SIRT3. Interestingly, a recently discovered naturally occurring form of vitamin B3, called nicotinamide riboside (NR), has been found to activate SIRT3. We found that NR reproduces the NLRP3 inflammasome blunting effect of fasting when administered to primary human monocytes/macrophages in culture. Putting this together, it would be interesting to evaluate whether the administration of NR to human subjects would replicate the fasting blunting effect on the NLRP3 inflammasome. Interestingly, at the same time, it has recently been found, in a preclinical study, that the NLRP3 protein can orchestrate differentiation of naive T- cells into Th2 cells. We therefore propose to more broadly examine the effects of NR administration on myeloid and lymphoid cell biology in healthy volunteers.