I read all [18] NMN Human Studies – 4 Key Findings

Summary

This 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

00:00

🧬 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.

05:02

🔍 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.

10:03

🚫 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.

Keywords

💡NMN (Nicotinamide Mononucleotide)

NMN, or Nicotinamide Mononucleotide, is a molecule that is a precursor to NAD+, which is essential for cellular metabolism. In the context of the video, NMN supplements are being discussed as a potential means to slow down the aging process and improve health outcomes such as muscle performance and metabolic health. The script mentions various studies on NMN and its effects on mice and humans, highlighting the excitement and controversy surrounding its use.

💡Supplements

Supplements in this video refer to dietary or nutritional additives that are intended to provide health benefits. The main supplement discussed is NMN, which is taken to potentially increase NAD+ levels in the body. The video explores the efficacy of these supplements based on various studies and the potential benefits they may offer, such as improved energy levels and muscle performance.

💡Aging

Aging is a natural biological process characterized by a gradual decline in various bodily functions. The video discusses the potential of NMN supplements to slow down age-related decline, referencing studies that suggest improvements in muscle performance and metabolic health in mice. The script also addresses the hope that NMN could delay the onset of frailty and possibly extend lifespan.

💡Muscle Performance

Muscle performance refers to the efficiency and effectiveness of muscle function. The video script discusses the hypothesis that NMN supplements could enhance muscle performance in humans, as suggested by studies on mice. However, the human studies reviewed in the script show mixed results, with most measures indicating no significant improvement beyond a placebo effect.

💡Metabolism

Metabolism is the set of life-sustaining chemical reactions in the body that allow it to grow, maintain and reproduce itself. The video explores the potential of NMN supplements to improve metabolic health, as indicated by markers such as body composition, LDL cholesterol, insulin, and glucose levels. The studies mentioned in the script show inconclusive results regarding the metabolic benefits of NMN supplementation.

💡Placebo Effect

The placebo effect is a psychological phenomenon where a person experiences an improvement in their condition due to their belief in the effectiveness of a treatment, even if the treatment has no therapeutic effect. The video emphasizes the importance of randomized clinical trials to distinguish the actual benefits of NMN supplements from the placebo effect, highlighting the need for scientific rigor in evaluating health claims.

💡Clinical Trials

Clinical trials are research studies that aim to determine the safety and effectiveness of medical interventions, such as drugs, devices, or supplements. The script discusses the necessity of clinical trials for NMN supplements to validate their benefits and to account for the placebo effect. It also mentions the importance of randomized control trials in establishing the efficacy of a treatment.

💡Safety

Safety in the context of the video refers to the potential risks or side effects associated with the long-term use of NMN supplements. While short-term studies indicate that NMN supplements appear safe, the script raises concerns about long-term safety, citing research suggesting that high doses of vitamin B3, of which NMN is a form, may be associated with increased mortality rates.

💡Exercise

Exercise is a physical activity that helps maintain and improve health. The video script suggests that regular exercise may be a more effective way to support NAD levels in the body than NMN supplementation. It implies that exercise could be a safer and more natural alternative to achieve the health benefits that NMN supplements are purported to offer.

💡Vitamin B3

Vitamin B3, also known as niacin, is a nutrient that plays a key role in converting food into energy and maintaining healthy skin, nerves, and brain function. In the video, NMN is discussed as a form of vitamin B3, and the script raises concerns about the recommended dosages of NMN supplements, which can be significantly higher than the recommended daily intake of vitamin B3.

💡Insulin Sensitivity

Insulin sensitivity refers to the body's ability to respond to the hormone insulin, which regulates blood sugar levels. The video script mentions insulin sensitivity as one of the metabolic health markers that NMN supplements were hypothesized to improve. However, the studies reviewed in the script show mixed and inconclusive results regarding the impact of NMN on 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