Aging and Energy Improvement: Should I Take NR and NMN Supplements as NAD Boosters?
Have you heard about NAD booster supplements that are being researched for anti-aging and cellular energy? Here’s the 101 on NR (nicotinimide riboside) and NMN (nicotinamide mononucleotide).
It’s no secret the wellness and anti-aging industry is a global multi-trillion dollar industry. With research published daily, it can be overwhelming to sort out the mediocre from the life-changing (and I say this as someone in the industry). While research on aging, and especially NAD booster supplements including NR and NMN, have been available for years, Chris and I began to get curious in early 2019 after hearing an interview with Dr. David Sinclair. As I started to dig into research and look at available supplements, the topic popped up again for me at the 2019 Revitalize mindbodygreen conference where we talked about NR and the concept of “aging as a disease” extensively.
NR as a topic sounds very much like it fits into the ‘magic pill’ quick fix category, which is why we researched a long time before taking the supplement and then waited months before we brought it to you. The skeptics that we are, anything that sounds too good to be true is highly suspicious, but based on current research as well as personal experience (and the fact you’ll be hearing a lot about this in the coming years), I wanted you to be informed and knowledgeable.
After taking an NR supplement for months, we decided it was time we simplified the science on this topic to bring you another deep-dive science wellness post. This post will remain a ‘living document’ as research and new products come to market.
If you like this post, be sure to read other deep dives on:
As always remember that this article is not meant to provide personalized wellness advice and you should always talk with your health care team members before embarking on a new wellness journey.
Definitions:
NAD: nicotinamide adenine dinucleotide- in all living cells, plays a vital role in cell functioning and metabolism
NR: Nicotinamide riboside- a compound the body uses to make NAD
NMN: Nicotinamide mononucleotide- a larger compound the body uses to make NAD that is first broken down into NR
What is aging? Is aging a disease?
Aging is often defined as the biological physiological plateau and decline of functions as time progresses. Generally, aging is not defined as a disease (the argument being it happens to everyone) although scientists like Dr. David Sinclair disagree. Sinclair is one of the most well-known researchers in the rejuvenation and genetics field. His lab is known for reporting findings showing that NAD precursors (more on this later) made the mitochondria of elderly mice seem youthful after one week.
What happens during aging? What is NAD and why do we need it?
As a species ages, the mitochondria (say it- the powerhouse of the cell) lose their ability to function effectively as NAD production (the energy for mitochondria) decreases. Between the ages of 40 and 60, up to 50% of NAD is lost. Beyond the progression of time, these functions can also decline with environmental factors like sun damage, bad air quality, high cortisol levels, etc.
NAD (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells. Without it, you die. Period. It plays a vital role in cell functioning and metabolism. A mitochondria that is working sub-optimally is thought to play a role in diseases like heart disease, diabetes and Alzheimer’s. As NAD production declines it causes poor cell communication, meaning signals and instructions within the body don’t work as they should.
Why do sirtuins matter? How does NAD affect sirtuin function?
More NAD means sirtuins work hard in their anti-aging activities in the body. Sirtuins are a grouping of seven genes (at least in humans) that play a role in preventing aging-related activities. They’re activated by a lack of amino acids or through a boost in NAD. If there’s more NAD, these seven genes do helpful things (each one does many different functions). SIR2 is especially worth noting since it is an epigenetic regulator (gene expression) and repairer of cell damage. As aging progresses it causes a loss of epigenetic function which means cells don’t know which genes should be turned on or off.
By increasing NAD, other sirtuin related benefits are activated including maintaining the length of telomeres (the end of a chromosome that protects it from deterioration) or producing effects that mimic the life-extending effect of a level of calorie restriction.
How can you ‘fix’ low NAD levels?
Whether it’s a NAD production decline from aging or other factors, studies show using the supplement precursor of NAD called NR (the ‘ingredients’ the body needs to produce NAD+), can boost NAD levels.
It’s important to note that while NMN is also a NAD precursor, it doesn't have current studies available to provide the same proven statement. However, hypothetically it could also provide the same benefits (although there are no studies to show us right now).
Can you boost NAD without a supplement?
Yes. You can likely boost NAD through fasting and exercise, although taking a supplement appears to provide a more impactful benefit on the NAD levels.
With that said, exercise and a safe form/length of fasting are far less expensive than supplements. But if you’re looking to get a helping hand in the NAD department, an NR supplement may be for you.
What is NR?:
Nicotinamide riboside (NR), a form of vitamin B3, is a compound that the body uses to create NAD. In 2004 it was discovered that NR could increase “levels of a vital cellular resource. This resource is a central regulator in energy metabolism and is believed to play an important role in healthy human aging.”
Studies have shown that taking NR (specifically the trademarked compound of NR that has FDA GRAS status called TruNiagen produced by ChromaDex) increased serum NAD in subjects by 40–50% after 8 weeks.
At this point NR is thought to:
Increase autophagy (cell clean up)
Support cellular energy production
Support brain function including neuroplasticity
Support normal liver function
Promote healthy aging
Have cardiovascular and arterial plaque benefits
There are over 130 published clinical trials, preclinical studies, and review articles that cover NR and NAD in health support. There are currently 5 published human trials to show the safety and effectiveness of NR on increasing NAD levels.
While NR is a form of vitamin B3, unfortunately, there’s not enough of it in the food supply to make an impact. The amount of NR in a 250-mg supplement is more than 1,000 times the amount in an 8-ounce glass of milk.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
What Is NMN?
NMN (Nicotinamide mononucleotide), like NR, is a NAD precursor and claims the same benefits as NR. NMN is known because Dr. Sinclair is often quoted as saying he takes NMN and is currently working on a pharmaceutical approval approach to this compound, rather than a supplement route.
Is NR or NMN better?
Currently, NR is much, much more studied on humans than NMN. There’s no published data to show how NMN can affect human NAD levels. And because of this, there are no trials that directly compare NR to NMN in humans (yet).
NR has 3 FDA safety notifications, 5 published human trials with several more registered on the Clinical trials.gov page. These studies confirm that NR is both safe and effective for increasing NAD in humans. Current NMN studies are only on mice.
There is also data showing that NR uses a unique set of transporters and enzymes to convert directly into NAD within the cell, while NMN is broken down into NR first, outside of cells, before being used to increase NAD. This seems to be an inefficient process although, without the human data for NMN, it’s impossible to know for sure.
NR is also a smaller, less complex molecule than NMN which may affect bioavailability. There is also a known transporter for NR at the gut barrier level in humans although an NMN transporter has been recently found in mice.
What kind of NR should I buy?
The company Chromodex produces the only FDA GRAS (generally recognized as safe) approved NR on the market called NIAGEN®. This compound is used in a few products on the market. When deciding which NR product to take, always look at the sourcing and ingredients (as you should with all supplements).
What do you personally take?
(2021 update) Pre-pregnancy I was taking mbg’s nr+ which they have since stopped producing. Before that, I originally took the FDA GRAS product produced by Chromodex (which contains only the NIAGEN compound).
What have you personally noticed while taking NR?
As with all supplements, it’s important to remember someone may experience something you may not. Chris and I have personally experienced:
An energy boost without feeling jittery-caffeinated (although we have both gotten used to this feeling)
A much higher alcohol tolerance level with zero hangovers. (Everyone around us at an event was drunk and we were dead sober). Always drink responsibly, blah blah you know the drill. Worth noting, this doesn’t fix the dehydration feeling, but other side effects are not as bad.
I’ve experienced unintentional weight loss that became noticeable to me, and to Chris, (I don’t weigh myself) after about three months. The dietitian in me has been looking for other reasons why this would occur, but I’ve had no increase in physical activity and have continued my eating patterns of a 12-hour window fast (7-7) several days of the week to date.
How much NR should I take?
The most recent human clinical trial of NR showed that a dose of 1000 total mg/day was well-tolerated and likely safe. Most dosages of NR products on the market are 250-300 mg/day.
Do I need to take more NR as I age?
When I asked a member of the science team at the lab of a producer, this question they said it's a reasonable assumption since, in studies of NAD and aging, NAD decreases with age. If you take NR which boosts NAD, one would think that increasing NR levels to boost the increased loss of NAD production logical. However, all clinical trials to date have been conducted on subjects from age 30-79 and the constant recommendation for dosage has remained the same regardless of age. It sounds like we need to wait for more research to know the exact proportion of the increase in dosage.
Do I need to increase the NR dosage the longer I take it?
The one dose and the 8-week studies of NR indicate the effects on NAD plateau at the higher dose of about 1,000 mg/day (remember, most NR on the market indicates a day to day dosage of 250/300 mg/day). In these studies those subjects who were assigned the 300 mg/day dosage as well as those in the 1000 mg/day dosage had a significant increase in whole blood NAD+ and maintained this increase throughout the study. For maintenance, there does not appear to be a need to continue escalating dosages beyond a certain point.
Do I need to take a different amount of NR if I’m male or female? What about if I weigh more/less than an average person?
There is no current evidence that biological sex NR needs are different. Men and women have been test subjects in various published trials. However, as with many supplements, there is some difference in weight and dosage according to scientists. In general, with an increase in weight, more NR would be needed however there is no specific study on this yet. That's why if you look at the back of NR packaging, there is no dosage differential from male to female or by weight at this time. The dosages may become more specific as we gather additional information.
What’s the best time of day to take NR?
Studies have shown NR taken once or twice daily, however with conditions like Crohn’s, it may be beneficial to switch to dosing twice a day. In general, the best time to take the supplement is at a time when you can build a routine and remember to take it.
What are the potential negative side effects of NAD boosters?
It might not help with anti-aging or increasing life span. Extremely long studies showing an effect over decades are unknown at this time. With a very high promise of excellent results, and what seems like a ‘the only negative is it may not help with lengthening life span’ that we’ll only know after several decades, the negative side effects are few. While NR is shown to increase NAD in the body, we just don’t know if it truly slows down aging quite yet.
Taking NR might be a lot like wearing sunscreen: the results aren’t immediately noticeable until decades later…when you look at side by side comparisons of twins who wore sunscreen, and those who didn’t
With that said, the downside is the cost for something that may take a while to show the overt benefits. For me after the initial energy boost feeling, I didn’t see or feel any additional changes until three months out.
There’s also a percentage of the population who are ‘poor methylators’. If someone takes NR and feels ‘bad’, they may need to take methyl folate or betaine along with NR to avoid this. This occurs because the ultimate ‘metabolic fate’ of the NR compound is Methylnicotinamide which requires methyl donors from the body. Methyl donors include compounds like B 12, folate, betaine, choline, etc. By taking a methyl donor with NR, this side effect can potentially be resolved.
Lastly, although a 2014 was published raising the question of whether or not nr would feed cancer cells as well as regular cells, there is no convincing data, animal or human, that it increases the incidence or progression of cancer. In fact, there’s no data that shows raising NAD levels would do so either- and obviously, inhibiting NAD levels is bad (because you know…you can’t live without NAD).
Should you take NR if you’re pregnant?
There’s a very small look into mutations of NAD related genes and how taking vitamin B3 (aka NR) could help pregnant mothers. This article goes into the possibility of creating a B3 recommendation for pregnancy. It’s still WAY too early to say this is beneficial or safe. Articles following that scientific document release specifically warned against pregnant women supplementing with vitamin B3. Always check with your OB/GYN care team before taking supplements.
I personally did not take NR while pregnant.
Can I absorb NR if I have Crohn’s disease/digestive issues?
The absorption of vitamin B3 can be impaired in those who suffer from Crohn’s but there’s no current information if NR absorption is impaired. With that said, NR scientists have indicated there is a “strong mechanistic hypothesis” (but no direct study) that NR may be helpful within the intestinal wall cells themselves without the NR being taken into the systemic circulation.
Why are NAD boosters (NR and NMN) talked about in conjunction with resveratrol?
There is a current theory that NR and/or NMN may work synergistically with resveratrol or pterostilbene (resveratrol like compound). Dr. Sinclair hypothesizes that antioxidants from plants (resveratrol) interact with SIR2.
Does NR interact with other supplements or medications?
There are no known interactions at this time but it’s always important to connect with your health professional before starting a new supplement.
(note: *These below statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.)
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