Dr. Charles Brenner, University of Iowa professor and chief scientific advisor at Chromadex took questions from the public on Twitter today. He discovered Nicotinamide Riboside “NR” (FAQs) (Reviews) as an NAD boosting vitamin. Here’s the Q&A:

On COVID-19:

QUESTION: Does NR (TRU Niagen) help against Covid-19? And when can we expect human data on this?

DR BRENNER: Working on this

QUESTION: Does taking NR (TRU Niagen) help suppress COVID?

DR BRENNER: Reasons to think it will: 1) NAD under attack with CoV infection, 2) NMRK genes up, 3) higher NAD allows better PARP functions, which are antiviral, 4) NR shown to depress inflammation markers in small human placebo-controlled trial

QUESTION: Thoughts on this kind of quackery? —> “NAD+ is the key to COVID-19 treatment. Innate immune response depletes NAD+. Increased NAD+ will increase innate immune capabilities to fight virus including preventing viral replication through IFN and PARPs”.

DR BRENNER: His thread is based on a paper of ours that is in peer review. You can read it here — the work is in early days but definitely suggests that higher NAD could promote resistance to establishment of infection. The term for this is innate immunity

QUESTION: How do NAD levels relate to innate immune function?

DR BRENNER: Specific PARPs are induced by CoV infection. See HERE Moreover, activity of these enzymes takes down cellular NAD and is limited by cellular NAD. At higher NAD, we expect PARPs will work better to control viral infection. Being tested with @FehrLab @MichaelNADbio

QUESTION: What you just said here: “Activity of these enzymes {PARPS}…. is limited by cellular NAD”? Would that not also be true for every other disease (including aging) that afflicts humankind?

DR BRENNER: I’m evidence-based. No, I would not say that NAD dysregulation is involved in every disease. Sounds hyperbolic and not helpful.

QUESTION: Can you explain how COVID-19 depletes NAD and why it does so? If it is using NAD and depleting it, is there any danger that increasing NAD may also aid the virus?

DR BRENNER: Interferon turns on expression of a bunch of PARPs. Their increased expression depletes NAD. Genetic evidence says that the PARPs are antiviral and the virus is trying to defeat that. It’s all here.

QUESTION: Are the trials for NR with Corona going to stop at 2g for dosage? I know that is the extent of the safety study but I have been exposed several times and NR always gets me back to symptom free but I have sometime topped out at 4-5g. Are there diminishing returns?

DR BRENNER: Don’t know but suspect NR clinicals will continue at 1-2 g

QUESTION: Does a nicotine transdermal patch provide protection against Covid19?

DR BRENNER: I’d be shocked it if did

On CANCER:

QUESTION: If someone has had or has cancer would you recommend them taking NR?

DR BRENNER: Niagen (NR) is being tested as a molecule to protect against chemotherapeutic neuropathy—work is funded by @theNCI (National Cancer Institute)

QUESTION (THREAD PART #1): What are your thoughts about the controversy regarding NAD precursors promoting/suppressing cancer?

DR BRENNER: Cancer is not one thing. B3 is powerfully protective against cancer in large clinical trials

QUESTION (THREAD PART #2): True, but B3 isn’t touted as a longevity boosting molecule; does it not induce flushing and is it not a less efficient precursor to NAD than, say, NR or NMN? Zhang et al. (2019) warn about “potential detrimental pro-tumorigenic side effects” of supplements

DR BRENNER: In their very peculiar mouse model, they did make such a warning

On NMN (Supplement):

QUESTION (Thread Part #1): Hi! Is there any indication that NMN and NAD+ supplementation in a small dose daily will be of any measurable help in the long run? I began at 30, healthy male, 125mg/daily of each. 34 now, fit & happy, just wondering if I’ll age differently.

DR BRENNER: NMN has not been safety tested and is converted to NR before it can enter cells so I don’t know why you are doing this if you are interested in your health

QUESTION (Thread Part #2): Interesting, thanks for the reply. I’d love to hear you debate @davidasinclair on this topic as it’s his advice/research I’ve followed.

DR BRENNER: NMN as a supplement is expensive NR & it will never be a drug. Derivatized NMN kills neurons & other cells by activating SARM1 (link) — surely not a “longevity molecule.” SIRT activators abandoned by @GSK ages ago. All of this is well known

QUESTION (Thread Part #3): So that suggests the NMN supplement negates the NAD+ supplement or even worse. Contradictory to claims I’ve heard that it does the exact opposite. Thanks for the info, this is something to consider. I’m simply interested in maintaining my good health. @ALIVE_BY_NATURE

DR BRENNER: NMN supplements won’t activate SARM1–they are just not safety tested and make no scientific sense. Derivatized NMN is dangerous and, as I have said here before, is not going to be a drug. #NADtwitter

QUESTION: Does NMN really reverse the age?

DR BRENNER: NMN isn’t safety tested. NMN converts to NR. NR gets into cells and is converted to NAD+, NADH, NADP+ & NADPH, which are required for the function of all cells and tissues. Helps tissues under conditions of metabolic stress the most. Stressed cells induce NMRK genes to use NR

QUESTION: Thank you! There are studies saying NMN is better at increasing NAD than NR. What is your take on it?

DR BRENNER: Show me one

On DIET and NAD+:

QUESTION: What is the impact of diet on NAD+ sparing? Would low carb, high fat tend to utilize more NAD+ sparing oxphos pathways?

DR BRENNER: All macronutrients use the NAD system for metabolism. There aren’t enough data on how different diets influence the NAD metabolome in different tissues. Easy to correct NAD deficiencies though: 3 forms of vitamin B3… our form doesn’t flush & has advantages over others

On NR and NAD+ CONVERSION:

QUESTION: Is it possible that NR is only found in trace amounts in nature because it is converted into NAD+ by most organisms? Just curious.

DR BRENNER: In food, most of the NAD precursor is NAD+ itself. In digestion, NAD breaks down to NR, NAM & NA, which enter cells and are built back up to NAD+, NADH, NADP+ & NADPH. I could have just said YES. Great question

On NAD+ DECLINE:

QUESTION: Do you think that SASP is a primary cause of NAD decline during aging, or is secondary to a larger process? If secondary, what do you think is primary cause? If primary, what is your thoughts about the potential use of senolytics for enhancing age related declines of NAD?

DR BRENNER: I think NAD declines are largely episodic and caused by conditions of metabolic stress. I don’t think ppl have thought through the senolytic thing, especially with respect to fighting infection

On NR taken SUBLINGUALLY:

QUESTION: Is there any additional benefit in taking Nicotinamide Riboside (NR) sublingually (under the tongue)?

DR BRENNER: conceivably but there are no good data

On NAD+ and HORMONE REPLACEMENT:

QUESTION: What do you think of NAD+ concomittend to other anabolic interventions such as bioidentical hormone replacement therapy in aged people (50+) in order to improve the outcome of attempts of tissue regeneration? Thymus regeneration could be an example for discussion.

DR BRENNER: Open question. Hormone replacement is complicated….

On CURRENT NR TRIALS for HEALTHY ADULTS:

QUESTION: Are there any clinical trials underway for longevity gains from NR supplementation for healthy adults?

DR BRENNER: Don’t know how to do that. Have an upcoming editorial in which I describe smart trial designs for improvement in body composition & fatty liver—specific enrollment with evidence-based primary endpoints is the way to go. I will tweet the editorial upon publication

On NR for SCHIZOPHRENIA:

QUESTION: The protocol of HOFFER and OSMOND on schizophrenia, they suggest 3 grams per day of NIACIN and VITAMIN C (tablets or injection). Is NR or NMN as effective as niacin for that genetic disease?

DR BRENNER: Schizophrenia has not been shown genetically to be one disease—almost certainly why some ppl respond & others don’t. There’s hasn’t been a clinical for NR in this indication. I’ve discussed NMN extensively

QUESTION: Bioinformatic analyses and cellular and zebrafish gene expression studies implicate NAPRT1 as a novel susceptibility gene. Given this gene’s role in niacin metabolism and the evidence for niacin deficiency provoking schizophrenia like symptoms

DR BRENNER: One of my favorite genes…. it is downregulated in particular malignancies. Thanks for this

On NAD+ PRESSING QUESTIONS:

QUESTION: What do you think are the most pressing questions for the NAD metabolism field to answer in the immediate future?

DR BRENNER: two fundamental questions are 1) how are nicotinic acid & nicotinamide riboside made available from one cell to another; 2) how are the NAPRT, NMRK1 & NMRK2 genes regulated as a function of key NAD metabolites & conditions of metabolic stress

On NR and HAIR COLOR:

QUESTION: Stepping back from survival, I understand that hair whitening is caused by the buildup of H2O2 in hair follicles and that NAD has some role in the regulation of H2O2 in cells. Is it possible NR can reverse hair whitening? I understand not really a concern for you. Thanks.

DR BRENNER: People have shown me pictures of hair that is dark at the ROOTS and white at the ends. The data are anecdotal but commonly experienced…. virtually everyone on NR reports faster hair and nap growth, which should be easily measurable

On NAD+ ENTERING BLOOD:

QUESTION: How does NAD/NADH get to the blood? Do serum concentrations reflect tissue concentrations?

DR BRENNER: Serum NAD is close to zero. Coenzymes are in the cellular fraction of blood and tissue NAD can be different. Watch this space for more in a common human affliction

On NR and METHYLATION:

QUESTION: I’m taking TRU Niagen. Do I need to worry about methylation?

DR BRENNER: No evidence that you do

On NR and HCQ:

QUESTION: I take HCQ (400 mg/day)+ Methotrexate for RA treatment, which works. I take NAD precursor as well. HCQ is an autophage inhibitor & NAD precursor is meant to enhance autophagy? Is NAD precursor reduced by HCQ? Thanks.

DR BRENNER: NAD has a role in autophagy and 999 other cellular processes. Beware “narratives”

On NR DOSING & TIMING:

QUESTION: My question is: Apart from the cost, is there a downside to taken higher doses (e.g. 1,000mg/day vs 500mg/day). Can this downregulate the NAD salvage pathway? Thanks!

DR BRENNER: No evidence for downregulation of NAMPT or NRKs under these conditions

QUESTION: Hello! Do you recommend taking it first thing in the morning before food or later in a day? Also, are there any benefits of taking more that 300mg pill a day?

DR BRENNER: Most ppl take NR first thing, with or without food. There are dose-dependent increases in NAD. Quite a lot of therapeutic trials are at 1-2 grams per day. At higher doses, it makes some sense to split into 2 doses per day

QUESTION: A. The label suggests “for use beyond 12 weeks consult a health care professional”. Why is that? B. When using NR regularly does the body reach a saturation point and one should tapper off use as a new baseline is reached? I am 62, athletic condition. C. Why is it so expensive?

DR BRENNER: Longest human trials published to date. Within two weeks blood NAD gets to higher levels that are dose dependent. I don’t see a reason to stop. Costs have come down & have been passed to consumer. I’d like to see that continue

QUESTION: What do you do or take to boost your own NAD?

DR BRENNER: I was the first person in the world to take NR. Initially it was to figure out time course for human NAD metabolomics. I continue to take @truniagen — as you know, I am chief sci adviser for the company…

QUESTION: At what dose do you personally take?

DR BRENNER: I’m not your doc & I don’t see any upside in answering questions about my dose. I do tell everyone to stay mentally & physically active etc etc bc I am confident that will help everyone. Someone taking more or less than I take may clearly benefit in measurable ways

QUESTION: If most cellular repair is done while sleeping, wouldn’t before sleeping be best time to have it?

DR BRENNER: Maybe

On REMARKABLE NAD+ / ANIMAL STUDY RESULTS:

QUESTION: In animal experiments involving NAD+, what is the largest known increase in average lifespan of a single organism? For example, are there anecdotes of a mouse who doubled or tripled (or greater) the average lifespan of mice?

DR BRENNER: Not useful dealing in anecdotes. Effects are profound in mouse model of heart failure for example.

On MARKETING NR:

QUESTION: Ha! My doc hasn’t even heard of NR, he probably graduated med school in 1995. He told me to maybe only take a multivitamin, but anything else isn’t recommended. Which brings up, what is ChromaDex doing to reach out to general pract. about benefits of NR?

DR BRENNER: They publish http://aboutNAD.com — one can always do more

RELATED:

  • FAQs on taking NAD boosting vitamin supplement Nicotinamide Riboside (NR) can be found HERE.
  • NR supplementation may have helped sufferers of these diseases & conditions (Consumer Reviews)

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