Study to Evaluate the Effect of Nicotinamide Riboside on Immunity
Condition: Atherosclerosis; Diabetes; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Atherosclerosis
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Nicotinamide riboside (NR); Placebo
Intervention type(s): Dietary Supplement; Drug
Intervention description(s): NR at dose of 1000mg/day will be given for a period of 7 days in a double blinded fashion either from the start of tx or after 1 week of placebo pills.; Placebo capsule daily for a period of 7 days in a double blinded fashion either from the start of tx or after 1 week of NR at a dose of 1000mg/day.
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Inflammasome; Sirt3; Nicotinamide Riboside; Fasting