How Nicotinamide Riboside Relates to Exercise Recovery
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Exercise increases energy demand and activates pathways involved in mitochondrial adaptation and NAD metabolism. In this clip from the FoundMyFitness episode with Dr. Charles Brenner, he and Dr. Rhonda Patrick discuss nicotinamide riboside, or NR, as an NAD precursor. Dr. Brenner is Chief Scientific Advisor to Niagen Bioscience. An eight-week dose-ranging trial in 140 healthy adults with overweight found that 100, 300, and 1,000 milligrams per day were generally well tolerated and increased blood NAD-related metabolites in a dose-dependent manner. [1]
Human studies suggest that NR can affect redox biology and selected performance measures differently across populations. In a double-blind crossover study of 12 young and 12 older men, one acute dose raised blood NADH and NADPH in both groups. Among the older men, it also lowered an oxidative-stress marker and improved isometric peak torque and a fatigue index, while VO2 max and concentric peak torque did not improve. [2]
Dr. Brenner and Dr. Patrick also discuss athlete interest, dosing, and supplement combinations. In eight young men, seven days of 1,000 milligrams of NR per day changed selected muscle NAD metabolites but did not alter substrate use, mitochondrial respiration, or signaling involved in adaptation to one hour of endurance exercise. This keeps regular training at the center of recovery while identifying NR as a supplement that warrants more targeted study. [3]
- ^ 10.1038/s41598-019-46120-z
- ^ Dolopikou CF; Kourtzidis IA; Margaritelis NV; Vrabas IS; Koidou I; Kyparos A, et al. (2020). Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Eur J Nutr 59, 2.
- ^ Stocks B; Ashcroft SP; Joanisse S; Dansereau LC; Koay YC; Elhassan YS, et al. (2021). Nicotinamide riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise. J Physiol 599, 5.
Dr. Rhonda Patrick: For me, exercise is always at the top of everything. So, I'd love to start there. How does exercise affect NAD, and what type of exercise would be better for increasing NAD? Would it be aerobic, strength training, resistance training, or both? I can come up with rationales for why I think either or both would work.
Dr. Charles Brenner: The exercise that you do is infinitely better than the exercise that you plan to do or wish you did, right? Anything is better than nothing. We do have some clinical evidence showing that exercise leads to an increase in the gene expression of NAD biosynthetic enzymes. I recently published that with a group in Germany. I can't remember what kind of exercise they did, but there is evidence that exercise boosts transcription and gene-expression pathways associated with youth and vitality. I hate the word rejuvenating, but those pathways are associated with youth and vitality.
Dr. Rhonda Patrick: Mitochondrial biogenesis goes up when you exercise. That's rejuvenating. Some buzzwords can become overplayed.
Dr. Charles Brenner: When it's true, it's true, right?
Dr. Rhonda Patrick: It's true. Does mitochondrial biogenesis play a role in some of the NAD increases as well? If you're making more mitochondria, is it an adaptation where the body responds, "We need more NAD around"?
Dr. Charles Brenner: A transcription factor responds to the NAD system, and then you make more mitochondria and have better beta oxidation. You would imagine that NAD helps with the repair involved in exercise recovery. Sports trainers and the heads of professional football clubs and college athletic programs that buy Niagen by the tub swear by it. There is not much rigorous placebo-controlled data, but there is trainer data.
Dr. Rhonda Patrick: Anecdotal data.
Dr. Charles Brenner: Yes. There are photos of two Niagen advisors, Dr. Rudolph Tanzi and me, with Bill Belichick when he coached the New England Patriots and a 40-year-old Tom Brady. It is well known that the Patriots took Niagen for many years. I don't know whether they are still taking it post-Belichick, but it is in many training rooms for recovery. Have any exercise physiologists become interested in studying this?
Dr. Rhonda Patrick: I think it needs to be studied in an exercise-physiology laboratory because you can do those kinds of trials. You can work people really hard on a bicycle and see whether they can work as hard the following day.
Dr. Charles Brenner: And not just recovery, but performance. You would think that if you are taxing NAD and consuming more NAD, your muscles are working harder. As you said, the adaptation is increased transcription. The genes or enzymes important for making NAD will increase because your body recognizes that it is using more and needs to respond. It would be interesting to know whether supplementing with the precursor is also beneficial.
Dr. Rhonda Patrick: It would be, but it would be nice to know.
Dr. Charles Brenner: Right. It would be nice for someone to prove that. The pattern is becoming clear to me: there is room for improvement, particularly in people who are unhealthy because they do not exercise much or have obesity. If you are making lifestyle changes, that is the most important thing.
Dr. Rhonda Patrick: Right. If you can add this to those changes, that may help. As you said about weight loss, you cannot expect someone to take nicotinamide riboside and lose weight in 13 weeks. You have to do something in addition to that.
If there is a healthy individual who is physically active and not overweight or obese but wants to add a supplement, what would you say is the best argument for adding an NAD precursor such as nicotinamide riboside to their routine? I think I already know your answer, but I will ask anyway. What is the best argument for adding it, and what is the best argument for why they do not need it?
Dr. Charles Brenner: Yeah, I think the best argument is probably workout recovery, right? Because it synergizes well with exercise, and exercise makes everything else work better.
Dr. Rhonda Patrick: Amazing. Okay.
Dr. Charles Brenner: Yeah. And I think it's worth a try.
Dr. Rhonda Patrick: Well, full disclosure here, I have been taking TruNiagen for about since August and I take a lot of other things, but my recovery's great. That's why I work out a lot.
Dr. Charles Brenner: Great to hear.
Dr. Rhonda Patrick: So great recovery and then I was going to say inflammation as well, but because there's oh even a healthy individual there's always, maybe a little bit of room for recovery, but I like that. I like that answer. I'd love to talk a little bit about, dosing a little deeper. I know we sort of touched on it a little bit. You talked about some of the clinical trials out there. Typically using 500 mg to 1,000 mg. 1,000, yeah. Right or 1,000.
Yeah. Is there an upper limit? I say this because there's a lot of people that like to go the extreme and so it's really important to talk about like I think I've seen even a 2,000 mg study out there for nicotinamide riboside. So I'd love to know your thoughts like in terms of, obviously there's the evidence and we can talk, you can mention I don't know the 2,000 mg a day what the end points were, but if there's someone like myself, so I'm taking 1,000 mg a day of TruNiagen, nicotinamide riboside. Does that seem like a reasonable dose in your opinion?
Dr. Charles Brenner: Well, I am not your doctor. Based on the evidence, I think that for most people, 500 mg to 1,000 mg is a substantive amount of NR to take. The safety and source of the NR are very important. This material has been safety tested at up to 3 grams per day in certain populations. I do not think people should go beyond that. In certain diseases and conditions, we always say to ask your doctor. Your doctor may or may not have the background to address it, but someone with an unusual condition could potentially have an unusual result.
Dr. Rhonda Patrick: You mentioned stacking nicotinamide riboside with resveratrol, a polyphenol that appeared to negate some benefits in peripheral artery disease, right?
You can find some of these NAD boosters with other combinations, pterostilbene being one. I think the rationale behind that was that it increased the bioavailability or something like that. I remember reading, maybe you can correct me on that, but it also perhaps could potentially raise LDL. I think pterostilbene at least to some degree. I don't know that matters unless you're already someone that has high LDL cholesterol because it wasn't like a huge amount. But I'd love to know your thoughts on can they be mixed?
Dr. Charles Brenner: There is no use case for resveratrol or pterostilbene in my view. Both of those compounds were thought to be sirtuin activators. I don't think that there's an evidence basis for saying that sirtuin 1 is a longevity gene. Pterostilbene and resveratrol don't actually increase the activity of sirtuin anyway, and as you said, pterostilbene shows a dose-dependent increase in LDL cholesterol, which is generally not a good thing for people. So, for people that are interested in just boosting their NAD, This is not necessarily going to help.
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