I Analyzed EVERY NMN Human Study (Including MIB-626). The Facts (‼️2024‼️)

Joe Cannon
1 Jun 202428:30

Summary

TLDRThis video script delves into the efficacy of NMN, an anti-aging supplement, through a comprehensive review of 16 clinical trials. It highlights the lack of significant impacts on health metrics such as blood sugar, cholesterol, and blood pressure, despite increasing NAD levels. The script also discusses the potential benefits on exercise performance and sleep quality in older adults, while expressing skepticism about NMN's geroprotective claims due to mixed and inconclusive results.

Takeaways

  • 🧪 NMN (Nicotinamide Mononucleotide) is a popular anti-aging supplement with various human clinical trials investigating its effects.
  • 🔍 The speaker is not affiliated with any supplement or pharmaceutical company, ensuring unbiased review.
  • 🏥 Initial safety studies on NMN showed it raised NMN metabolites without affecting heart rate or blood pressure, indicating short-term safety.
  • 📈 A peculiar finding was a 51% increase in bilirubin levels in some subjects, though still within normal range, and not consistent across studies.
  • 🚫 No negative side effects were reported in a larger safety study involving 31 participants given 1,250 mg of beta-NMN daily for 4 weeks.
  • 💊 Beta-NMN did not lower cholesterol, LDL, or triglyceride levels, despite the dosage, suggesting no impact on these health markers.
  • 🚶‍♂️ A 2-month study with 66 participants found no side effects from the Uthever brand of NMN, but it also did not improve walking distance or well-being significantly.
  • 🩸 A clinical trial with diabetic patients showed a 25% increase in muscle insulin sensitivity with NMN but no significant improvement in blood sugar levels.
  • 💉 A study involving NMN infusions (not supplements) in healthy individuals showed a temporary drop in triglyceride levels, suggesting different mechanisms of action.
  • 🏃‍♀️ Among amateur runners, NMN supplementation improved ventilatory threshold but not VO2 Max, muscle strength, or endurance.
  • 👴 In older adults, chronic NMN supplementation showed mixed results with some reporting improved sleep and daytime function, but no significant impact on cognitive tests or physical performance.

Q & A

  • What is Nicotinamide mononucleotide (NMN) and why is it popular?

    -Nicotinamide mononucleotide, known as NMN, is an anti-aging supplement that has gained popularity due to its potential to increase levels of NAD+ in the body, which is associated with various health benefits and slowing the aging process.

  • What was the outcome of the first safety study on NMN involving 10 healthy men?

    -The first safety study found that NMN raised metabolites of NMN without affecting heart rate or blood pressure. However, it reported a 51% increase in bilirubin, which remained within the normal range, and this increase was not observed in other studies.

  • What was the dosage and duration of the safety study involving 31 healthy individuals?

    -In the safety study with 31 healthy individuals, they were given 1,250 mg of beta-NMN or a placebo daily for 4 weeks.

  • What were the effects of the Uthever brand of NMN on the NAD to NADH ratio in a 2-month study?

    -The Uthever brand of NMN increased the NAD to NADH ratio by about 40% in the 2-month study involving 66 healthy men and women.

  • Did NMN show any significant improvements in blood sugar levels in the clinical trial involving 35 overweight women with elevated blood sugar levels?

    -No, the clinical trial showed that while NMN increased insulin sensitivity by about 25%, there were no significant improvements in blood sugar levels.

  • What was the result of the 3-month study involving 11 healthy men and women taking 250 mg of NMN daily?

    -The study found that NMN raised plasma NMN levels but failed to lower blood sugar, hemoglobin A1c, cholesterol, LDL cholesterol, or triglyceride levels. Interestingly, it reported a doubling of triglyceride levels after one month, which returned to higher than normal levels by the end of the study.

  • What was the focus of the cardiovascular disease study involving 34 men and women in their late 40s?

    -The study aimed to determine if NMN could improve the health and functioning of blood vessels, but it found no significant differences in arterial stiffness between the placebo and supplement groups.

  • What were the findings of the study on NMN and exercise performance in amateur runners?

    -The study found that NMN supplementation improved the ventilatory threshold, indicating that runners could exercise harder before feeling difficulty. However, it did not improve VO2 Max, oxygen saturation, muscle strength, muscle endurance, or flexibility.

  • What was the observation regarding telomere length in the small study involving 8 individuals taking NMN for 3 months?

    -The study reported a significant increase in the length of telomeres in white blood cells after 3 months of NMN supplementation, suggesting a potential impact on aging at the cellular level.

  • What was the outcome of the study involving 80 middle-aged men taking different dosages of beta-NMN for 2 months?

    -The study showed that 600 mg of beta-NMN was more effective at raising NAD levels than 300 mg, but 900 mg did not outperform 600 mg. Participants reported improved quality of life, with those on 600 and 900 mg doses noticing benefits within 30 days.

  • What is the general consensus on the side effects of NMN based on the clinical trials presented in the script?

    -The general consensus from the clinical trials is that NMN does not report any significant negative side effects.

  • What is the author's overall stance on NMN as a geroprotective supplement after reviewing the clinical trials?

    -The author remains skeptical of the claims for NMN as a geroprotective supplement based on the results of the clinical trials presented.

Outlines

00:00

🧪 Initial Safety and Metabolism Study on NMN

The first paragraph introduces the focus on human clinical trials of NMN, an anti-aging supplement. It discusses an initial safety study involving 10 healthy men, who were given varying doses of NMN. The study found that NMN increased its metabolites without affecting heart rate or blood pressure. However, it noted a 51% increase in bilirubin, which, despite being within normal range, was an unexpected finding. The speaker also mentions being unbiased, not affiliated with supplement or pharmaceutical companies.

05:01

🔎 Expanded Safety Studies and Beta-NMN Effects

This section continues the safety discussion with a larger study involving 31 participants receiving 1,250 mg of beta-NMN daily for four weeks. No negative side effects were observed, and there were no changes in cholesterol, LDL, or triglyceride levels. Another study with 66 participants taking 300 mg of NMN daily showed no side effects and a 40% increase in the NAD to NADH ratio but did not improve walking distance or overall well-being significantly. A clinical trial with diabetic patients showed a 25% increase in insulin sensitivity but no significant improvements in blood sugar levels, blood pressure, body fat, or weight.

10:06

🏃‍♂️ NMN's Impact on Exercise Performance and Long-Term Supplementation

The paragraph explores NMN's effects on exercise performance in a study with 48 middle-aged runners. It found that NMN supplementation improved the ventilatory threshold at higher doses but did not affect VO2 Max, muscle strength, endurance, or flexibility. An interesting note was the improvement in balance at a 600 mg dose. The paragraph also discusses long-term supplementation in 34 participants, noting no improvements in arterial stiffness or blood sugar levels, and a study on NMN infusions in 10 middle-aged individuals that showed a temporary drop in triglyceride levels.

15:12

👴 Effects of NMN on Older Adults and Telomere Length

This section examines NMN's effects in older populations, with a study involving 40 older men showing no significant improvements in fat reduction, insulin sensitivity, cholesterol, blood pressure, or cognitive function. However, it did report an increase in gate speed. Another small study on telomere length in 8 individuals found a significant increase in telomere length after 3 months of NMN supplementation, suggesting potential anti-aging effects.

20:14

🛌 Sleep and Daytime Functioning with NMN Supplementation

The paragraph discusses a study involving 80 middle-aged men given varying doses of beta-NMN, reporting improved quality of life and quicker perceived benefits at higher doses. No significant changes in cholesterol, LDL, triglycerides, or bilirubin were observed. Another study with 60 older adults reported improved walking distance and self-reported better sleep and daytime functioning with NMN supplementation.

25:17

💊 Evaluation of MIB-626 and NMN Effects in Older Diabetic Men

This section presents data on MIB-626, a proprietary form of beta-NMN, showing increased NAD levels in overweight individuals at dosages of 1,000 to 2,000 mg daily. Another study reported reductions in body weight and cholesterol with MIB-626 but no improvements in muscle strength, aerobic capacity, insulin resistance, or fat reduction. A long-term study with older diabetic men found no improvements in grip strength, walking speed, or diabetes management with NMN supplementation.

🕒 Timing of NMN Intake and Its Overall Effectiveness

The final paragraph discusses a study on the timing of NMN intake in older adults, with no clear impact on sleep quality but suggestions that longer-term use may improve sleep and daytime function. A potential difference was observed between afternoon and morning intake regarding drowsiness. The speaker concludes by summarizing the findings from 16 clinical trials, expressing skepticism about NMN's effectiveness as a geroprotective supplement.

Mindmap

Keywords

💡NMN (Nicotinamide Mononucleotide)

NMN, or Nicotinamide Mononucleotide, is a molecule that has gained popularity as an anti-aging supplement. It is a precursor to NAD+, a coenzyme essential for cellular metabolism and energy production. In the video, various clinical trials on NMN are discussed to evaluate its safety and efficacy in improving health outcomes. The script mentions that NMN supplementation has been studied in different dosages and populations to understand its potential benefits, such as increasing NAD+ levels and its effects on blood pressure, cholesterol, and insulin sensitivity.

💡Anti-Aging Supplement

An anti-aging supplement is a product that claims to slow down or reverse the aging process, often targeting aspects such as appearance, cognitive function, or metabolic health. In the context of the video, NMN is considered an anti-aging supplement due to its potential to boost NAD+ levels, which decline with age and are associated with various age-related diseases. The video critically examines clinical trials to assess whether NMN lives up to its anti-aging claims.

💡Clinical Trial

A clinical trial is a research study that investigates the safety and effectiveness of medical interventions, such as drugs, devices, or supplements. The script refers to numerous clinical trials to explore the impact of NMN on various health parameters. These trials are essential for understanding the potential benefits and risks of NMN supplementation in different populations, including its effects on blood sugar, cholesterol, and physical performance.

💡Safety Study

A safety study is a type of clinical trial that specifically focuses on evaluating the safety of a substance or intervention, monitoring for side effects and adverse reactions. In the video, early safety studies on NMN are mentioned, which looked at its effects on healthy men in their late 40s and reported no changes in heart rate or blood pressure, suggesting a good safety profile. However, one study noted an increase in bilirubin levels, which was still within the normal range but raised for further investigation.

💡Metabolites

Metabolites are the intermediates and products of metabolism. In the context of the video, NMN metabolites refer to the substances produced as NMN is broken down and utilized in the body. The script mentions that an increase in NMN metabolites was observed after supplementation, which is a positive sign of its bioavailability and metabolic activity.

💡Cholesterol and LDL Levels

Cholesterol is a waxy substance found in the blood, and LDL, or low-density lipoprotein, is often referred to as 'bad cholesterol' because high levels can lead to plaque buildup in the arteries. The video discusses clinical trials that investigated the effects of NMN on cholesterol and LDL levels, with results indicating no significant changes, suggesting that NMN may not have a direct impact on these lipid profiles.

💡Insulin Sensitivity

Insulin sensitivity refers to the ability of cells to respond to the hormone insulin, which regulates blood sugar levels. In the context of the video, the script mentions studies that looked at NMN's potential to improve insulin sensitivity, particularly in individuals with elevated blood sugar levels. However, the results were mixed, with one study showing a 25% increase in muscle insulin sensitivity but no significant improvements in blood sugar levels.

💡Ventilatory Threshold

The ventilatory threshold is a point during exercise when an individual's breathing becomes more labored, and there is an increase in lactic acid production. The video mentions a study where NMN supplementation appeared to increase the ventilatory threshold, suggesting that it might allow individuals to exercise more intensely before experiencing difficulty in breathing, although it did not improve VO2 Max or oxygen saturation.

💡Telomeres

Telomeres are the protective caps at the ends of chromosomes that shorten as cells divide and age. The video discusses a study where NMN supplementation led to a significant increase in telomere length in white blood cells, which could suggest a potential anti-aging effect by slowing cellular aging. However, the study was small and further research is needed to confirm these findings.

💡MIB-626

MIB-626 is a proprietary form of beta-nicotinamide mononucleotide developed by Metro International Biotech. The video mentions studies on MIB-626, which showed increased NAD levels in the blood but did not demonstrate significant benefits on blood pressure, cholesterol, or insulin resistance. The video emphasizes the need for further research and comparison with regular NMN.

💡Geroprotective

Geroprotective refers to substances or interventions that protect against the effects of aging. The video's main theme revolves around the evaluation of NMN as a geroprotective supplement. The script expresses skepticism about the geroprotective claims of NMN based on the mixed results from various clinical trials presented.

Highlights

NMN is a popular anti-aging supplement with ongoing human clinical trials to assess its safety and efficacy.

Initial safety studies on NMN showed no changes in heart rate or blood pressure, indicating good tolerability.

An increase in bilirubin levels was observed in one study, but it was within normal range and not replicated in other studies.

A larger safety investigation found no negative side effects from 1,250 mg of beta-NMN daily for 4 weeks.

NMN supplementation did not lower cholesterol, LDL, or triglyceride levels in studied populations.

A 2-month study showed no side effects from a specific brand of NMN called Uthever, and a 40% increase in the NAD to NADH ratio.

NMN did not improve walking distance or overall well-being in a well-being test according to one study.

In a study with diabetic patients, NMN increased insulin sensitivity by 25% but did not significantly improve blood sugar levels.

A 3-month study showed NMN raised plasma NMN levels but did not decrease them after stopping the supplement.

NMN supplementation in one study doubled triglyceride levels temporarily, but this effect was not consistent across studies.

Long-term NMN supplementation showed no significant improvements in arterial stiffness or cardiovascular health.

A study on NMN infusions in healthy individuals showed a temporary drop in triglyceride levels, but the effect was not sustained.

NMN supplementation in amateur runners improved ventilatory threshold but did not affect VO2 Max or muscle strength.

Chronic NMN supplementation in older adults showed nominal improvements in grip strength and walking speed.

A small study suggested that NMN supplementation may increase telomere length in white blood cells.

MIB-626, a proprietary form of NMN, raised NAD levels but did not improve muscle strength, endurance, or insulin resistance in short-term studies.

The longest NMN study conducted in older men with diabetes showed no improvements in grip strength, walking speed, or diabetes management.

A study on the timing of NMN supplementation suggested potential benefits for sleep and daytime function, but results were inconclusive.

Overall, the clinical trials presented do not strongly support the claims of NMN as a geroprotective supplement.

Transcripts

play00:00

Nicotinamide mononucleotide, better known as  NMN, continues to be one of the most popular  

play00:06

anti-aging supplements on the market today. Get  comfy because now we're going to take a deep  

play00:11

dive into every human clinical trial on NMN I was  able to locate oh and by the way I don't work for  

play00:19

any supplement company and I don't work for big  Pharma either. Okay, so before we go any further,  

play00:24

there have been some safety studies of NMN to  make sure it's safe, so let's begin our discussion  

play00:30

by looking at those. so we have this paper which  is probably the first safety study ever done it  

play00:35

was involved 10 healthy men they're in their late  40s and they're given between 100, 250 and 500 mg  

play00:43

of NMN each day or a placebo. 5 hours later they  give these guys some tests and they notice that  

play00:50

the NMN did in fact raise metabolites of NMN and  that's good however there were no changes in heart  

play00:56

rate or blood pressure. that's good as well;  didn't make heart rate go up and didn't make  

play01:01

blood pressure go up so that's a good thing. now  one oddity of this paper that I wanted to call  

play01:05

your attention to is that this paper also reported  that bilirubin increased by about 51% in those who  

play01:14

took NMN supplements although the increase in  bilirubin was still within the normal range.  

play01:20

now I bring that up in case you have your blood  test done and this happens to you although I do  

play01:24

think this is going to probably be a fluke because  having looked at all the other studies that were  

play01:30

about to talk about I don't see a rise in  bilirubin in any of those studies that actually  

play01:34

measured that compound. next up we have this  safety investigation which was a bit larger.  

play01:39

we have 31 healthy men and women they're in their  mid 30s and they're given a whopping 1,250 mg of  

play01:47

beta NMN or a placebo each day for 4 weeks oh and  by the way if you're wondering, beta-NMN is often  

play01:54

said to be the active form of this compound. so  the good news here is that after 4 weeks of use  

play02:00

beta NMN did not cause any negative side effects  there were also no changes in cholesterol levels  

play02:06

or bad cholesterol LDL levels or triglycerides  either. And while that is good that the values  

play02:12

did not increase it is also true from this  paper that 1250 mg of beta n NMN did not lower  

play02:20

these values either. next up is this next safety  investigation which has a very wordy title as you  

play02:26

can see where 66 healthy men and women they're  in their late 40s and they're given 300 mg of  

play02:33

nicotinamide mononucleotide or placebo and they  take the supplement or the placebo every day after  

play02:39

breakfast and the study lasts 2 months. oh and by  the way in this study they're actually testing a  

play02:44

specific brand of NMN called Uthever which is a  pretty catchy name if you ask me. now the good  

play02:51

news here is that there were no side effects  reported from the Uthever supplement .that's  

play02:55

really good and if we drill down further, we also  see that this supplement increased the NAD to NADH  

play03:02

ratio by about 40%. that's good too. However on  the flip side, the NMN supplement did not increase  

play03:10

walking distance when people did what was called  the six-minute walk test. now these people were  

play03:15

also given a well-being test called the S-36 test  and while some of them appeared to show that their  

play03:23

overall well-being appeared to improve, when they  were taking the NMN supplement the differences  

play03:29

be between the supplement takers and the placebo  takers again was not clinically meaningful. As for  

play03:35

blood pressure, the supplement did not lower blood  pressure any better than a placebo. there were no  

play03:40

significant differences there and additionally,  there were no significant improvements in insulin  

play03:46

sensitivity, in other words how well insulin can  lower blood sugar levels. However, these people  

play03:51

were generally healthy and so I wouldn't expect it  to have a significant effect in people who don't  

play03:57

have diabetes for example. Speaking of diabetes,  we have this clinical trial that investigated the  

play04:02

effects of NMN supplements in people who had  elevated blood sugar levels for 10 weeks 35  

play04:08

overweight women who were in their 60s who also  had elevated blood sugar levels were given 250  

play04:14

milligrams of NMN or a placebo each day and as  they do state in the title of this investigation  

play04:22

the insulin sensitivity of muscles was increased  by about 25% and that is good; however, there were  

play04:30

no significant improvements in blood sugar levels.  Furthermore, there were also no reductions in  

play04:36

blood pressure or body fat or body weight either.  here's a sample of some of the before and after  

play04:42

results that occurred in this investigation feel  free to stop the video at this point and zoom in  

play04:48

and take a closer look at what happened. They also  gave these people before and after grip strength  

play04:54

test to gauge how well NMN might have made these  people stronger however it didn't. ironically too,  

play05:01

there were no improvements in muscle mitochondrial  function either. I bring that up because one of  

play05:07

the things that NMN is supposed to do is help  the mitochondria work better. in this paper, it  

play05:14

didn't. next up is this study that lasted 3 months  it involved 11 healthy men and women they took 250  

play05:22

milligrams of NMN or a placebo each day in the  morning and as the title does indeed tell us  

play05:30

NMN supplements did raise plasma NMN levels that's  good. However those levels began to decline after  

play05:40

about a month of not taking the supplement any  longer and that's to be expected once you stopped  

play05:45

taking these things, your NAD levels would be  expected to go back down again as we can see from  

play05:51

this before and after table NMN also significantly  raised insulin levels after just 2 months now  

play05:58

insulin is responsible for lowering blood sugar  however in this paper it is also reported that  

play06:04

NMN failed to lower blood sugar or hemoglobin A1c  likewise NMN supplements did not lower cholesterol  

play06:11

levels or bad LDL cholesterols either however the  weirdest thing in my opinion that was reported in  

play06:17

this study is what happened to triglyceride levels  after just one month; triglyceride levels doubled  

play06:25

from about 80 to 186 mg/dl by the end of the  study the triglycerides had declined a bit down  

play06:32

to 155 mg/dl but that's still higher than when is  normally recommended for healthy people. Now to be  

play06:40

fair, this is the only clinical trial I located  showing that triglyceride levels skyrocket after  

play06:47

taking NMN supplements so it might be a fluke  however if you ask me this finding should have  

play06:54

been in the title of this investigation. next  up is this interesting investigation of what  

play06:58

they call long-term NMN supplementation where we  have 34 men and women they're in their late 40s;  

play07:05

they are given 250 milligrams or placebo each  day for 3 months and they're basically looking at  

play07:11

whether NMN can improve the health and functioning  of the blood vessels. so this is essentially a  

play07:16

cardiovascular disease study although they  did also measure some other things as well  

play07:22

For example these researchers report that NMN  significantly raises nicotinamide levels in the  

play07:27

serum and that makes sense because NMN contains  nicotinamide, which is also known as niacinamide,  

play07:34

the no flush version of niacin. now moving on to  arterial stiffness which I think is the main focus  

play07:41

of the study there were no significant differences  in arterial stiffness between placebo takers and  

play07:47

supplement takers and something else they point  out is that this lack of improvement also seemed  

play07:53

to carry over to whether or not the people had  high blood pressure or not so again you would  

play07:58

think that might not work as well in people  with normal blood pressure but there didn't  

play08:03

appear also to be any significant Improvement in  arterial stiffness in people who had high blood  

play08:09

pressure either. Additionally these researchers  also tell us that NMN supplements also did not  

play08:15

have any Improvement on lowering blood sugar  levels or lowering bad LDL cholesterol levels  

play08:20

it didn't raise HDL levels or triglycerides and it  didn't raise testosterone or other hormones either  

play08:27

however, on the plus side, it's also reported  that there were no increases in liver enzymes  

play08:33

either so that is good. next up is this paper  which tells us from the title that NMN is not  

play08:39

only safely broken down in the body but it also  significantly lowers triglycerides too. now that  

play08:47

statement is bound to get everybody's attention  especially those who have elevated triglycerides;  

play08:53

however there is a word that they did not include  in the title of this study. this clinical trial  

play08:59

in involved 10 healthy middle-aged men and women  they were in their 40s and they were given 300 mg  

play09:05

of NMN that was dissolved in 3.5 ounces of water.  That solution was then injected into these people;  

play09:14

in other words they gave these people infusions  of nicotinamide mononucleotide which is very  

play09:21

different than taking an NMN dietary supplement.  Another limitation of the study in my opinion,  

play09:27

is that they gave these people before and after  blood tests 5 hours before and up to 5 hours after  

play09:33

they gave them the infusion; in other words, this  study only lasted 10 hours. And, as I pointed out  

play09:38

in my original review of this investigation,  the triglyceride levels began to drop quickly  

play09:45

after the NMN infusion. they went from around 80  mg/dl all the way down to 20 mg/dl in about an  

play09:54

hour after getting the infusion. however -and this  is an important point -those triglyceride levels  

play09:59

began to rise again after about 3 or 4 hours. Now  I've heard that people are getting infusions of  

play10:06

NMN and this paper might be one of the reasons  why that's happening however I do want to point  

play10:12

out a few problems with this study .number one,  the people were healthy; in other words, they  

play10:18

didn't have elevated triglyceride levels to begin  with so that's one problem. The othe problem with  

play10:24

this study is that there was only 10 people so it  was a small investigation. There was no placebo  

play10:29

group. Something else is that the NMN infusions  were given to people after an overnight fast,  

play10:36

so what would happen if you had breakfast and then  went and got your infusion? Would the same thing  

play10:41

happen with triglycerides or anything else? We're  not sure yet. And also, because the study lasted  

play10:45

just 10 hours, this can't prove that infusions  of NMN will indeed lower triglyceride levels  

play10:52

long-term. Now let's switch gears and talk about  whether NMN can improve your exercise performance,  

play10:59

and we have this paper, nicotinamide  mononucleotide supplementation enhances  

play11:04

aerobic capacity in amateur runners: a randomized  double-blind study. Here we have 48 middle-aged  

play11:11

men and women; they are runners. They're actually  part of a running group in China and they are  

play11:16

given three different dosages of NMN - 300 mg  600 mg and 1200 mg- or a placebo each day and  

play11:25

the study lasts for 6 weeks. everybody works out  5 to 6 days a week for between 40 and 60 minutes  

play11:31

per exercise session and I also want to point out  that the placebo in the study that was used was a  

play11:37

combination of cranberry powder and maltodextrin,  so kudos to the researchers for telling us what  

play11:43

the placebo is. we'll stick a pin in that for  right now I want to circle back and talk about  

play11:48

that in a moment so the first thing that I would  say is that NMN failed to promote any superior  

play11:53

losses in body fat or body weight. However the  supplement was reported to improve what's called  

play11:59

the ventilatory threshold and higher doses of NMN  appear to increase ventilatory threshold better  

play12:07

than lower doses. And if you're unfamiliar with  that term ventilatory threshold is the point of  

play12:13

exercise when you start breathing harder and  exercise begins to start to feel difficult  

play12:19

for you. It's also associated with the buildup of  lactic acid in the body during exercise in other  

play12:25

words, NMN supplements appeared to help these  runners work harder/ exercise harder before they  

play12:33

started to feel the exercise getting difficult  and that is actually really interesting. However,  

play12:40

I will point out that even though ventilatory  threshold is associated with the buildup of  

play12:45

lactic acid, unfortunately, they did not measure  lactic acid in this study. I also want to point  

play12:51

out that NMN did not improve VO2 Max or oxygen  saturation in these runners either. VO2 Max is  

play12:59

essentially the maximum volume or amount of oxygen  that you can consume into the body and turn that  

play13:05

oxygen into energy and oxygen saturation is  essentially how much oxygen is saturating  

play13:10

your blood. and while no improvement was seen in  the study I really can't fault on this because  

play13:15

we are looking at highly conditioned runners who  already likely have a very high VO2 Max to start  

play13:22

off with and because they're also healthy their  oxygen saturation is also extremely high as well.  

play13:27

Now they also perform some fitness testing on  these runners as well and it's reported that  

play13:32

NMN supplements did not improve muscle strength or  muscle endurance and it didn't improve flexibility  

play13:37

of the muscles either.  One odd result is  that NMN did appear to improve balance,  

play13:44

however that was only seen in those who were  taking the 600 mg dose. Now, I want to circle  

play13:49

back for a moment and talk about that placebo  that was used in this study. if this study is ever  

play13:54

replicated my hope Is that the cranberry powder  is taken out of the placebo and that is because  

play14:01

there is some research suggesting that cranberries  may have an exercise benefit. Let's switch gears  

play14:09

and talk about the effects of NMN in older adults  and let's begin with this paper involving chronic  

play14:15

long-term supplementation which they define as  3 months. Here we're dealing with 40 older men;  

play14:21

they're in their 70s and they're given either  a placebo or 250 mg of NMN each day. Here's  

play14:27

the various tests they did on these people at the  beginning of the study. To me it looks like their  

play14:31

hemoglobin A1c values look a little bit on the  high side, so some of these individuals may be  

play14:38

moving into pre-diabetes. Now the other thing  I want to point out with this paper is that it  

play14:43

does suffer from what I think as a big problem  and that is they began their study originally  

play14:50

with 42 people but only 20 people completed the  investigation and the reason is that after the  

play14:57

study it was recognized that the supplier of the  placebo and the supplements made an error which  

play15:04

resulted in 11 of the supplement takers getting  placebos and 11 of the placebo people getting the  

play15:11

actual NMN supplements. So those 22 people had  to be removed from this study. Okay so all that  

play15:20

said what happened? So no surprise, NMN raises  NAD levels and levels of NMN itself also as well  

play15:29

as its metabolites so that's good one interesting  finding here however is the observation that NMN  

play15:35

also increased levels of nicotinamide riboside.  Nicotinamide riboside is the other big player  

play15:42

in this NAD booster arena and I will link to my  videos on nicotinamide riboside below so you can  

play15:49

see more about the research on that. we see from  the results that NMN supplement did not reduce fat  

play15:54

from either the liver or the spleen and likewise,  there were no improvements in insulin sensitivity  

play16:00

either. Additionally as pointed out in other  studies, NMN failed to produce any improvements  

play16:05

in cholesterol, LDL cholesterol triglyceride blood  sugar hemoglobin A1c or fasting glucose levels  

play16:12

either. Likewise there was no improvement in  blood pressure or blood vessel health and before  

play16:16

and after cognitive tests showed no improvement in  learning or memory either. Now they did point out  

play16:22

that hearing seemed to improve -in the right ear  only -however, it wasn't a clinically significant  

play16:29

effect so it might have just been a fluke.  Now as for the effects of NMN on muscle, well,  

play16:34

there were no improvements in muscle mass in these  people however there was a somewhat Improvement  

play16:39

in grip strength in the left hand only in the  people who were taking the supplements. however  

play16:44

it wasn't clinically significant; it was said to  be a "nominal improvement." On the flip side these  

play16:50

researchers did see a significant improvement in  gate speed where the people taking the supplement  

play16:56

did appear to be able to walk a little faster.  Next up we have this interesting investigation  

play17:02

involving telomere length. It's a small study  involving only 6 men and 2 women; they're between  

play17:08

the ages of 40 and 60 and they take 300 milligrams  of NMN in the morning, 30 minutes after breakfast,  

play17:16

with warm water. They do this each day for 3  months. For me, the most interesting part of  

play17:20

this study was where they report that 3 months  of NMN supplements -again at 300 milligrams a  

play17:26

day - caused a significant increase in the length  of the telomeres in white blood cells. Telomeres  

play17:32

are found at the ends of the chromosomes and as we  get older, telomeres begin to shorten, and so some  

play17:38

associate shorter telomes with increased aging.  Next up is this study which has a really long  

play17:45

title where 80 middle-aged men in their late 40s  are given either 300, 600, or 900 mg of beta NMN  

play17:55

daily versus a placebo and the study lasts for 2  months. oh, and by the way it's pointed out that  

play18:01

they're testing a specific brand called AbinoNutra  NMN.  One of the interesting -and odd- parts of  

play18:08

this study is where they state that NAD levels in  the blood rose more (went higher) when people took  

play18:16

600 mg, more than when they took 300 mg; however  you didn't see this when people took 900 mg of  

play18:24

NMN. in other words 600 mg raised NAD better than  300 mg did but 900 didn't work any better than  

play18:32

600. Everybody who was taking the supplement said  that their quality of life had improved by the end  

play18:38

of the study and those who were taking the 600 and  900 milligram dose actually started feeling better  

play18:44

within just 30 days. moving on to the blood tests  here are some of the before and after values that  

play18:50

were reported in this study and as you can see  there were no significant changes in cholesterol,  

play18:56

LDL, cholesterol, triglycerides, or insulin  resistance. notice here also that bilirubin  

play19:02

did not go up either which contradicts the outcome  of that other study I told you about previously  

play19:08

which stated that bilirubin increased 51%. this  study contradicts that and so again reinforces  

play19:14

my thought that the original finding was a fluke.  Leaving that paper and moving on to the next one,  

play19:19

we have this clinical trial and again involving  beta nicotinamide mononucleotide where 60 older  

play19:25

people took 250 mg of beta NMN or placebo  again the study lasts for 3 months. Results  

play19:32

of this study revealed that there was no  improvement in the step test; in other words  

play19:37

how many times people could step up and down in  a period of time. However the people taking the  

play19:43

supplement could walk a bit further than those  who took placebos. It's also reported that those  

play19:49

who took the supplements stated that they slept  better and that they appeared to function better  

play19:55

during the daytime hours and I thought this was  interesting because several people have told me  

play20:01

privately that NMN seemed to help them sleep  better so this may be some evidence for that  

play20:08

although I do want to point out that I wasn't able  to read this full study when I posted this video  

play20:13

and in the process of getting it now so when I do  get this investigation I will do a follow-up more  

play20:18

in-depth video on this investigation. next up is  what I believe is the very first clinical trial  

play20:24

on MIB 626. MIB-626 is a proprietary version  of beta nicotinamide mononucleotide that was  

play20:34

developed by Metro International Biotech. Here we  have 31 overweight people and they're between the  

play20:40

ages of 55 and 80. They're given 1,000 milligrams  of MIB-626 either once a day or twice a day for  

play20:48

two weeks. So in other words these people are  taking between 1,000 and 2,000 mg of MIB 626  

play20:55

daily. Results show that the 1,000 mg dose of MIB  626 raised blood levels of NAD about 1.7 times  

play21:04

above baseline while those taking the higher dose  of 2,000 milligrams each day saw a bump of about  

play21:11

3.7 times higher NAD relative to what it was a  baseline. And while that is nice do you notice  

play21:17

what they didn't do? In the study, they didn't  compare MIB 626 to regular NMN. Now we also have  

play21:24

another investigation of MIB 626. Here it is 30  overweight people are given either placebo or  

play21:31

1,000 mg of MIB 626 NMN each day for 28 days. Here  they are reporting that not only did NAD levels  

play21:41

rise, but also there were significant reductions  in not only body weight but also cholesterol,  

play21:48

LDL and non-HDL cholesterol as well, and let's  reiterate these benefits showed up after just  

play21:54

28 days. However when they tested these older  adults, they found that MIB 626 failed to improve  

play22:00

muscle strength or muscle endurance; it didn't  help aerobic capacity or stair climbing and it  

play22:05

didn't reduce insulin resistance or liver fat  or abdominal fat either. The next paper I want  

play22:10

to show you is this investigation of NMN in older  men with diabetes 14 men who are in their 80s are  

play22:18

given 250 milligrams of NMN or a placebo for  6 months. To my knowledge this is the longest  

play22:27

NMN supplement study that I was able to find and  while this is indeed a small investigation, I like  

play22:33

it because we're dealing with older, frail people  which is a great population to test an anti-aging  

play22:39

supplement on. results from the study showed that  NMN failed to improve grip strength which is again  

play22:45

a common indicator of muscle strength and it also  didn't help these older people walk faster either.  

play22:51

Likewise there was no improvement in diabetes  in these people either. by the way I was also  

play22:56

unable to get a hold of this study by the time I  made this video when I do get it I'll make a more  

play23:00

in-depth video on this paper too. And, if you're  still with me fantastic, now we come to the very  

play23:06

last clinical trial that I have for you today and  it involves 108 older men and women they are in  

play23:11

their 70s they take 250 milligrams of NMN each day  or a placebo and this study lasts for 3 months and  

play23:19

to see if it is better to take NMN in the morning  or in the evening they actually broke people up  

play23:26

into am and PM groups and just to be more clear  here they defined the AM group as taking NMN any  

play23:35

time from when they awoke up to 12:00 p.m. and the  PM group was defined as anywhere from 6:00 p.m. on  

play23:43

to bedtime. The results of this study reveal that  the quality of sleep didn't appear to be impacted  

play23:49

by NMN however the longer they took the supplement  the better their sleep was and daytime function  

play23:58

scores were in other words the longer they took  the supplement appeared to play a role in their  

play24:04

sleep and their daytime functioning something  else that's reported that is worth mentioning is  

play24:09

that there may have been a difference in the time  effects here where people taking the supplement  

play24:15

in the afternoon appeared to have less drowsiness  compared to people who took this supplement in the  

play24:22

morning. However it's also reported that there was  a placebo effect that was observed here as well so  

play24:27

what this means is we're still not sure whether  it's better to take NMN in the morning afternoon  

play24:32

or in the evening. Okay if you're still with me  phenomenal we're almost done I know I presented an  

play24:37

awful lot of information here so let's see if we  can make some sense out of the results of all of  

play24:44

these studies now the first thing I would say is  that pretty much all the studies don't report any  

play24:48

negative side effects so that is a good thing and  also pretty much all of them state that when you  

play24:54

take the supplement, NAD levels and metabolites  of NAD also increase as well that's good. However,  

play25:02

I would also point out that the study researchers  usually only measure NAD levels in a couple places  

play25:08

like plasma, blood, skeletal muscle cells, etc.  in other words we still don't know if taking  

play25:16

these supplements increases NAD levels throughout  the body, although that is the assumption. now I  

play25:23

couldn't show you all the studies on the screen  at one time because there's just too many of them,  

play25:26

so let's break this down and begin by looking  at these studies of what I call diabetes and  

play25:31

heart health so if we look at these four clinical  trials that I'm showing you right now we can see  

play25:37

some things in common here such as at dosages  of between 250 and 300 milligrams per day,  

play25:44

NMN does not appear to have any effects on  lowering triglycerides lowering cholesterol or  

play25:51

bad cholesterol levels it doesn't appear to lower  blood pressure it doesn't appear to lower blood  

play25:56

sugar or hemoglobin A1 either. we also see the  same lack of effect in other studies too and so  

play26:03

far only one clinical trial revealed a significant  decline in triglyceride levels but again that was  

play26:10

for intravenously used NMN which is not really  relevant to people who take NMN as a dietary  

play26:19

supplement. now if we move over to the exercise  effects of NMN I found only one clinical trial  

play26:26

involving high-functioning healthy people who were  exercising and taking NMN supplements the study  

play26:34

that you're looking at here does appear to show  that at dosages of between 600 and 1200 milligrams  

play26:40

a day, NMN may improve ventilatory threshold  after several weeks of use. this as well as other  

play26:46

studies also reveal that NMN does not seem to  improve muscle strength or muscle endurance or the  

play26:52

flexibility of muscles either now if we transition  to those studies of older folks who take this  

play26:58

supplement well these also add evidence that at  dosages between 250 and 1,000 mg taken for several  

play27:07

weeks NMN does not appear to have any significant  effects on lowering blood sugar, triglycerides LDL  

play27:14

or improving insulin levels either. Likewise NMN  does not appear to improve muscle mass in older  

play27:22

folks either and from what we know so far this  supplement may or may not improve walking speed  

play27:28

walking distance or grip strength as for the two  studies of the MIB- 626 form of NMN these studies  

play27:35

are ongoing but from the two clinical trials I  was able to find the longest of these studies  

play27:40

lasted just 28 days which is not very long.  neither study revealed any side effects and both  

play27:46

revealed that at dosages between 1,000 and 2,000  mg per day, NAD levels do indeed go up; however,  

play27:53

these short-term studies also reveal that MIB  626 doesn't appear to have any beneficial effect  

play27:58

on blood pressure, cholesterol, LDL cholesterol,  liver fat or insulin resistance. Moving forward  

play28:03

researchers should also compare MIB 626 effects  to regular NMN as well as the already well-known  

play28:11

health benefits of regular exercise. So if I  would have boil this down into one statement  

play28:16

this would be it: based on the results of the  16 different clinical trials I just presented,  

play28:22

I remain skeptical of the claims for NMN as a  geroprotective supplement but what do you think?

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