I read all [18] NMN Human Studies – 4 Key Findings
Summary
TLDRThis script delves into the efficacy of NMN supplements, exploring their potential to improve muscle performance, energy levels, and metabolic health. The excitement around NMN was sparked by a 2016 study on mice, but human studies have been limited and mixed. While short-term safety is established, long-term effects are uncertain. The script reviews 18 human studies, revealing that most measures show no significant benefits beyond a placebo. It raises concerns about high doses of NMN, suggesting that a healthy diet and regular exercise might be more effective in maintaining NAD levels and overall health.
Takeaways
- 🧬 The initial excitement around NMN supplements was due to a 2016 study suggesting they slowed down age-associated decline in mice, not for lifespan extension.
- 🔍 The first human NMN study was published in 2020, a year after the excitement began, indicating early adoption despite limited research.
- 🐁 Mouse studies on a similar molecule, NR, showed no lifespan extension, which tempers expectations for NMN's impact on lifespan.
- 🚫 No human study has shown NMN supplements to be more effective than a placebo in improving muscle performance or other health measures.
- 💊 The placebo effect can significantly influence perceived benefits of supplements, highlighting the importance of randomized clinical trials.
- 🔑 Short-term safety studies on NMN show no significant concerns, but long-term safety is still uncertain.
- 🩺 Blood NAD levels were increased by NMN supplements in all studies measuring it, but muscle NAD levels did not change, questioning the supplements' impact on muscle performance.
- 💪 Most measures of fitness and muscle performance showed no improvement beyond a placebo effect from NMN supplementation.
- 🏋️♂️ Exercise appears to be a natural way to maintain muscle NAD levels, suggesting it might be more beneficial than supplementation.
- 📉 Metabolic health markers, such as body composition and insulin sensitivity, mostly showed no effect from NMN supplementation.
- ⚠️ High doses of vitamin B3, similar to the doses recommended by many NMN supplement companies, have been linked to increased mortality rates.
- 🏠 The author recommends focusing on a healthy diet and regular exercise rather than supplementation and suggests not exceeding 50 mg of vitamin B3.
Q & A
What sparked the initial excitement for NMN supplements?
-The initial excitement for NMN supplements was sparked by a 12-month long study of inbred mice in 2016, which suggested that NMN supplements effectively slowed down the age-associated decline in mice, leading to improved muscle performance and movement.
Why did people start taking NMN supplements before any human studies were published?
-Despite the lack of human research, many people started taking NMN supplements based on the exciting results from the mice studies, which suggested potential benefits such as improved energy levels, muscle performance, and resiliency against disease.
What is the significance of the Interventions Testing Program in mice research?
-The Interventions Testing Program is significant because it uses genetically diverse mice, making the results more applicable to humans. It also ensures that the same experiments are run at three separate labs simultaneously, verifying the reproducibility of the results.
What was the outcome of the study on genetically altered mice with accelerated aging?
-The 2024 study on genetically altered mice with accelerated aging showed a lifespan extension effect, indicating that NMN might have potential benefits in slowing down aging.
Why are randomized clinical trials important in evaluating the effectiveness of supplements?
-Randomized clinical trials are important to determine if there is a true benefit from treatment or if the perceived improvements are merely a placebo effect, which can be quite powerful and misleading.
What was the first takeaway from the human studies on NMN supplements?
-The first takeaway from the human studies is that NMN supplements appear to be safe over the short term, with no significant safety concerns reported in any of the studies.
What is the role of NAD in the context of NMN supplementation?
-NAD is central to our metabolism, and the idea behind supplementing with NMN is to support and increase NAD levels in the body, which is believed to have various health benefits.
Why did the study of muscle biopsies show a disappointing finding regarding NMN supplements?
-The study of muscle biopsies showed a disappointing finding because despite taking NMN supplements, the muscle NAD content did not change, which raises questions about the expected improvement in muscle performance.
What does the human research suggest about the impact of NMN supplements on muscle performance?
-The human research suggests that there is only a possible improvement in muscle performance from NMN supplements, but it is unlikely based on the current studies, as most measures showed no improvement beyond a placebo.
What are the concerns regarding the long-term safety of NMN supplements?
-There are concerns that long-term use of NMN supplements, particularly in high doses, may have negative health effects. A study suggests that high doses of vitamin B3 (including NMN) may increase death rates due to cardiovascular disease, and another study indicates that excessive vitamin B3 metabolites may worsen blood vessel inflammation.
What is the fourth takeaway regarding NMN supplements based on the video script?
-The fourth takeaway is that while NMN supplements appear to be safe in the short term, there are safety concerns over the long term, and until long-term research is conducted, it is advised not to supplement with vitamin B3 in any form beyond 50 mg.
Outlines
🧬 Initial Enthusiasm and Research on NMN Supplements
The speaker delves into the initial excitement surrounding NMN supplements, sparked by a 2016 study on mice that suggested potential benefits such as slowed age-related decline, improved muscle performance, and increased resilience against disease. Despite the lack of human studies at the time, the enthusiasm was fueled by a Harvard professor's appearance on a popular podcast. The first human study was published in 2020, and the speaker outlines the journey of research and personal decisions made regarding NMN supplements, emphasizing the importance of clinical trials over anecdotal evidence due to the placebo effect.
🔍 Analyzing NMN's Impact on NAD Levels and Muscle Performance
This section focuses on the effects of NMN supplements on NAD levels, a crucial component of metabolism. The studies indicate that NMN does increase blood NAD levels, but the hoped-for increase in muscle NAD, which was expected to improve muscle performance, was not observed. The speaker also discusses the potential mechanisms by which NMN might improve muscle function and reviews various human studies, revealing mixed results with most measures showing no significant improvement beyond a placebo effect. The importance of exercise in maintaining muscle NAD levels is highlighted, suggesting that NMN supplements may not be necessary for those who exercise regularly.
🚫 Limited Evidence for Metabolic and Other Health Benefits of NMN
The speaker examines the impact of NMN supplements on metabolic health, energy levels, cognition, and arterial stiffness. The findings across various studies are largely inconclusive, with most measures showing no significant effect from NMN supplementation. A few studies suggest possible benefits, but these are not supported by a consistent body of evidence. The speaker also addresses concerns about the reliability of study results, cautioning against interpreting improvements without proper comparison to placebo groups. The overall message is that while there is some hope for NMN's potential benefits, the current human research does not strongly support its use for these purposes.
⚠️ Safety Concerns and Long-Term Implications of NMN Supplements
In the final paragraph, the speaker discusses safety concerns related to long-term NMN supplementation. While short-term studies indicate that NMN appears safe, there are worries about the long-term effects, especially considering that high doses of vitamin B3, of which NMN is a form, have been linked to increased mortality rates. The speaker shares personal decisions regarding NMN supplementation, opting for a moderate dose of vitamin B3 based on preclinical studies but warning against higher doses due to potential risks. The emphasis is on the need for further research before recommending NMN supplementation and the importance of focusing on healthy lifestyle choices such as exercise and diet.
Mindmap
Keywords
💡NMN (Nicotinamide Mononucleotide)
💡Supplements
💡Aging
💡Muscle Performance
💡Metabolism
💡Placebo Effect
💡Clinical Trials
💡Safety
💡Exercise
💡Vitamin B3
💡Insulin Sensitivity
Highlights
Extensive review of 18 human studies on NMN supplements to evaluate their benefits.
Initial excitement for NMN supplements due to a study suggesting slowed age-associated decline in mice.
No human NMN studies at the time of a prominent interview on The Joe Rogan Experience.
First human study on NMN published in 2020, a year after the interview.
Mice studies on a similar molecule, NR, showed no lifespan extension.
A study on genetically altered mice showed lifespan extension effects.
Human trials aim to determine if NMN can improve muscle performance and metabolic health.
Placebo effect is a significant factor in evaluating supplement efficacy.
All 18 NMN studies were short-term and showed no significant safety concerns.
NMN supplements were found to increase blood NAD levels in all studies measuring it.
Only one study measured muscle NAD content, which did not change despite NMN supplementation.
Exercise may be as effective as NMN supplements in maintaining muscle NAD levels.
Most measures of fitness and muscle performance showed no improvement beyond a placebo.
Some metabolic health markers showed no effect or a possible benefit from NMN supplements.
One study showed a possible improvement in energy levels, but with controversial data.
Long-term safety concerns exist for high doses of NMN supplements.
High doses of vitamin B3 may increase mortality rates, as suggested by a 2018 meta-analysis.
A new study suggests that excessive vitamin B3 metabolites may worsen blood vessel inflammation.
Recommendation against taking NMN supplements beyond 50 mg due to long-term safety concerns.
Emphasis on the importance of regular exercise for maintaining NAD levels and overall health.
Transcripts
I read all 18 human studies of inmen
supplements to figure out if there are
any proven benefits this took many hours
of work but it was so worth it because I
found four key takeaways Plus at the end
I'll share what I do regarding enimine
supplements after looking at all of
these studies the excitement for en
supplements accelerated when Davidson
CLE a professor at Harvard appeared on
The Joe Rogan Experience over 5 years
ago so I take NN every morning what is
nmn good question the excitement was not
about lifespan extension there wasn't a
single n Mouse study examining lifespan
at that stage instead a 12-month long
study of inbred mice in 2016 suggested
that enmen supplements effectively slow
down the age Associated decline in mice
so the enmen treated mice appeared to
have greater muscle performance and
movement that's what was so exciting
that maybe by using enimine supplements
humans could also have improved energy
levels muscle performance and resiliency
against disease but it's important to
note that there wasn't a single NN human
study published when Davidson Clair
appeared on the Joe Rogen experience it
was very very early on the research
Journey the first human study was
published a year later in February 2020
but despite the lack of human research
many people made the decision to start
taking enem supplements based on the
exciting mice studies so what's happened
since that Sinclair Joe Rogan interview
we'll start by covering three important
my studies and then go through the human
trials in in 2021 a very similar
molecule to nmn called NR was tested by
the meticulous interventions testing
program this program is the creme de
Creme of mice research instead of using
inbred mice this program uses
genetically diverse mice so the results
are far more applicable to humans plus
the same experiments are run at three
separate Labs at the same time making
sure that the results are true and
reproducible but there was no lifespan
extension seen the second notable study
was published in December last year it
was a study of inbred mice that's
currently undergoing peer review but
just like the 2016 paper that we looked
at it suggests that any men treated mice
delay the onset of Frailty in both males
and females but interestingly there was
a lifespan extension seen of 8.5% in the
female mice not male mice finally a 2024
study looked at mice who were
genetically altered to have accelerated
aging and again there was a lifespan
extension effect seen so hopefully the
interventions testing program will also
trial NN just like they did NR but given
the existing disappointing NR results
I'm not particularly hopeful of a
lifespan extension effect overall the
mice research still suggests that
there's a lot of hope that enmen can
help slow down the age related decline
even if enmen doesn't increase lifespan
that leads us nicely into looking at the
inmen human research now remember the
hope is that inmen will improve muscle
performance help us become more
resilient against illness and infection
Boost energy levels and improve measures
of metabolic Health such as insulin
sensitivity so how do we work out if
enmen Works in humans because if you
look at the review section of enmen
supplement companies the reviews are
amazing other people on social media
will sing any men's Praises saying that
it improves the energy levels and muscle
function so why do we need clinical
trials when customer reviews of inem
supplements are one
well there's a powerful effect known as
the placebo effect where a person
experiences an actual Improvement in
their health despite the fact that the
treatment has no effect on the body one
of the best examples of this is a study
that looked at the combination of
glucosamine and condroitin supplements
for knee arthritis in the glucosamine
and condroitin group roughly 60% of them
experienced a significant Improvement in
their pain which sounds wonderful the
only problem was that the group who
received the placebo or the dummy
medication 60% of them also experienced
a marked improvement in their pain this
is why the clinical guidelines don't
recommend glucosamine and condroitin
supplements for NE arthritis because
those supplements are no better than a
placebo and that's a perfect example of
why randomized clinical trials are done
to figure out if there's a true benefit
from treatment or whether it's just a
placebo effect so let's go through the
18 human studies and figure out if
there's strong evidence of benefit
Beyond a placebo like cre creting
supplements for example now when ever
testing a supplement we first start with
safety and that's the first takeaway
inmen supplements appear safe over the
shortterm so all 18 nmn studies were
short-term studies they lasted a few
months and there were no significant
safety concerns in any of them but we're
going to come back to safety later in
the video because some new research has
come out of the 18 studies four of them
were not randomized control trials so
remember we're trying to figure out if
there's an Improvement Beyond a placebo
so in this analysis I've excluded those
studies the next point is whether enan
supplements increase blood NAD so NAD is
Central to our metabolism and the idea
behind supplementing with nmn is to
support and increase NAD now all of the
studies that measured blood NAD showed
that yes enmen supplements improve blood
NAD so things are looking good so far
but it's not only blood NAD that we want
to support we also want to support
muscle NAD and hopefully improve muscle
performance that was one of the big
hopes from the mice studies there was
only one study that took muscle biopsies
and measured the NAD content and
unfortunately the muscle NAD content did
not change despite any in supplements
that's a very disappointing finding and
it's the same for NR supplements which I
mentioned earlier in the video a 2020
study also found that NR does not
increase muscle NAD remember NN
supplements are taken to support NAD
levels so if any men supplements aren't
increasing muscle NAD can they really be
expected to improve muscle performance
and that leads us on to the next
question do our muscles need that extra
NAD support because in February 2022 a
human study showed that older adults who
exercised had a similar muscle NAD level
compared to younger adult and it was
only when the old adults didn't exercise
that they had lower muscle NAD so it's
likely that just through a healthy diet
and regular exercise we can support our
muscle NAD levels but coming back to nmn
supplements maybe they work via a
different mechanism to improve muscle
function and multiple human studies
looked at this across the human studies
there were 16 different measures of
fitness and muscle performance 12
measures showed no improvement Beyond a
placebo three did suggest a benefit and
one measure was incredibly controversial
so let's spend a bit of time on that one
the controversy comes from the 10th NN
human study which was performed in IND
that study suggested that the groups who
took inim supplements could walk
significantly further during the
6-minute walking test compared to the
placebo group but looking at the raw
data something really odd was going on
these people were middle-aged but they
had such a slow walking speed to the
point where it looked like they were 80y
olds because of these strange numbers
the results were struck down by other
researchers in the space such as
Professor Matt caline the graphs also
appear to be a bit too perfect so we
don't know exactly how how to interpret
these results overall when it comes to
in supplementation and muscle
performance most of the measures show no
improvement so that's the second out of
four takeaways there's a possible
improvement from enn supplements
regarding muscle performance but it's
unlikely based on the human research we
have so far one final point on exercise
the 17th NN study which was an
observational study suggested that blood
NAD levels can go up via exercise so
it's likely that both both our blood and
muscle NAD levels will be absolutely
fine so long as we have a healthy diet
and regularly exercise the next Hope
from the mice studies was that enmen
supplements can improve our metabolic
Health looking at the markers of
metabolic Health such as body
composition LDL cholesterol insulin and
glucose just like the muscle performance
measures most of the metabolic measures
showed no effect from inim supplements
out of the 28 measures across the
various studies 23 showed no Effect one
measurement showed worsening of insulin
and only four showed a benefit with one
of those measures being extremely odd in
the sixth nmn study the placebo group
worsened The insulin sensitivity by 30%
over the 60-day trial period so what on
Earth were they doing to worsen their
health by that much in 60 days it's very
difficult to interpret these results
then because if you compare that
worsening of insulin sensitivity to the
nmn group where the insulin sensitivity
didn't change you can be tricked into
thinking that Inman improves insulin
sensitivity when in reality these
results are uninterpretable so be
careful when you go through these
studies like this so will enem
supplements improve our metabolic Health
well it's not overly convincing based on
the trials we have so far and that's the
third out of the four takeaways there's
a possible metabolic benefit but it's
unlikely moving forward one study looked
at sleep and fatigue and when reading
these studies here's another classic
example of being aware of trickery so
remember we need to compare to the
placebo it's exactly the same at looking
at fatigue scores there was improvements
in every group so there was no
difference between the different groups
so you can't just rely on what the
abstract or summaries of these studies
say you have to look at the raw numbers
and you need to make sure that the
groups are being compared against one
another now many of the reviews of Inn
will say that there's a significant
Improvement in energy levels so
well-being and energy levels were
measured in three studies two showed no
improvement and the one study that did
show an improvement is one of the papers
that we've already gone through that's
got some issues so that was the 10th Inn
study there were no improvements in
hearing and cognition and the final
measure was arterial stiffness or blood
vessel stiffness one study showed no
effect and the other showed a trend
towards Improvement but this didn't
reach statistical significance so before
we address safety again looking at the
overall table that combines the current
inum studies together most measures show
no effect Beyond a placebo compare this
to creatine supplements for example
where study after study shows an
improvement in exercise performance
compared to a placebo plus from the
observational human studies it appears
that both our blood and muscle NAD
levels will be absolutely fine if we
regularly exercise so what am I going to
do regarding Enimen supplements
considering these studies and then we'll
get to the fourth takeaway well some of
the preclinical mice studies are
intriguing and enmen is a form of
vitamin B3 so when I designed microv
vitamin I elected to have a higher dose
of vitamin B3 of 50 mg because of those
exciting preclinical studies but just
because I'm taking the supplement does
not in anyway mean that you should as
well now for context the recommended
daily intake of vitamin B3 is 1616 mg so
I'm taking
33% of the recommended daily intake but
I would not want to take more than 50
milligrams of vitamin B3 we do have
evidence from a metaanalysis in 2018
that high doses of vitamin B3 in the
form of nasin so between 1 to 3 G A Day
increased mortality or death rates by
10% this is very different to the mice
studies because mice typically don't die
of cardiovascular disease instead they
die of other causes such as cancer for
humans however cardiovascular disease is
the number one killer most enemy
supplement companies suggest dosing with
1,000 mg which is
6,250 of the recommended daily intake
and that's a problem because from the
mice research and this hasn't been done
yet in humans most of the NN is
converted into nin by the gut microbiome
and then absorbed so it's possible that
by taking these extraordinarily high
doses of vitamin B3 you might be doing
damage particularly when considering
that a new study came out this year
suggesting that when there's excessive
vitamin B3 metabolites called 2py and
4py go up those metabolites appear to
worsen blood vessel inflammation and may
explain why highd do vitamin B3 in the
form of niin appears to increase death
rates the authors note that it's all
forms of vitamin B3 that increase these
metabolites including nmn and NR overall
there's limited evidence that enmen
supplements offer benefits Beyond a
placebo over the short term enmen
supplements appear to be safe but over
the long term there's a concern and
that's the fourth takeaway there are
safety concerns with anyen supplements
over the long term and until we have
that long-term research I would not
supplement with vitamin B3 in any form
Beyond 50 mg instead we should be
focusing on exercise so check out this
video here that explains how I built the
perfect home gym for only $250
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