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Nicotinamide Mononucleotide (NMN): Difference between revisions
Nicotinamide Mononucleotide (NMN) (view source)
Revision as of 03:30, 3 November 2023
, 3 November 2023→MIB-626
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MIB-626, developed by MetroBiotech, is a microcrystalline form of NMN. This formulation may offer enhanced stability, solubility, or bioavailability compared to the regular crystalline form of NMN, potentially optimizing the efficacy of NMN supplementation. | MIB-626, developed by MetroBiotech, is a microcrystalline form of NMN. This formulation may offer enhanced stability, solubility, or bioavailability compared to the regular crystalline form of NMN, potentially optimizing the efficacy of NMN supplementation. | ||
== Potential Benefits == | ===Reduced NMN (NMNH)=== | ||
[[Reduced Nicotinamide Mononucleotide (NMNH)]] is a potentially more effective [[NAD+ Precursor|NAD+ precursor]]. | |||
==Potential Benefits== | |||
NMN supplementation has been associated with several potential benefits, primarily due to its role as a precursor to NAD+, a crucial coenzyme involved in various cellular processes. Here are some potential benefits based on preliminary research: | NMN supplementation has been associated with several potential benefits, primarily due to its role as a precursor to NAD+, a crucial coenzyme involved in various cellular processes. Here are some potential benefits based on preliminary research: | ||
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*'''DNA Repair''': Enhanced NAD+ levels through NMN supplementation can support DNA repair mechanisms, potentially reducing DNA damage and the risk of mutation, which are associated with aging and cancer. | *'''DNA Repair''': Enhanced NAD+ levels through NMN supplementation can support DNA repair mechanisms, potentially reducing DNA damage and the risk of mutation, which are associated with aging and cancer. | ||
*'''Insulin Sensitivity''': NMN has been shown to improve insulin sensitivity, potentially reducing the risk of type 2 diabetes and metabolic syndrome, contributing to overall metabolic health. | *'''Insulin Sensitivity''': NMN has been shown to improve insulin sensitivity, potentially reducing the risk of type 2 diabetes and metabolic syndrome, contributing to overall metabolic health. | ||
== Considerations for NMN Supplementation == | ==Considerations for NMN Supplementation== | ||
When considering NMN supplementation, it is crucial to understand the potential interactions and impacts of NMN. Here are some considerations based on current knowledge and research. | When considering NMN supplementation, it is crucial to understand the potential interactions and impacts of NMN. Here are some considerations based on current knowledge and research. | ||
=== Dosage and Effects === | ===Dosage and Effects === | ||
Human studies have indicated that a dosage of 1000 mg over 10 days can raise NAD levels about two-fold, and dosages as high as 2000 mg can triple the amount. However, the long-term safety, efficacy, and optimal dosage of NMN are still under investigation, and more comprehensive studies are needed to establish concrete guidelines for NMN supplementation. {{Citation needed}} | Human studies have indicated that a dosage of 1000 mg over 10 days can raise NAD levels about two-fold, and dosages as high as 2000 mg can triple the amount. However, the long-term safety, efficacy, and optimal dosage of NMN are still under investigation, and more comprehensive studies are needed to establish concrete guidelines for NMN supplementation. {{Citation needed}} | ||
[[Dr. David Sinclair's Supplement Protocol|David Sinclair]] takes 1000 mg/day NMN in the morning. | [[Dr. David Sinclair's Supplement Protocol|David Sinclair]] takes 1000 mg/day NMN in the morning. | ||
=== Types of NMN Administration === | ===Types of NMN Administration=== | ||
Nicotinamide Mononucleotide (NMN) can be administered in various forms, each with its unique considerations. Below is a breakdown of the common types of NMN administration: | Nicotinamide Mononucleotide (NMN) can be administered in various forms, each with its unique considerations. Below is a breakdown of the common types of NMN administration: | ||
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*'''Sublingual Powder:''' This form of NMN is taken by placing the powder directly under the tongue, allowing it to dissolve and be absorbed through the mucous membranes in the mouth. The general guideline is to hold the substance under the tongue for approximately 1 to 5 minutes to allow for adequate absorption through the sublingual gland. Some individuals believe sublingual administration offers better bioavailability due to direct absorption into the bloodstream, bypassing the digestive system. However, while this method is promoted in many YouTube videos, there is no evidence of any positive or negative effects and there is currently no clinical study utilizing sublingual administration. Furthermore, this method is relatively inconvenient, especially for those who might find the taste of sublingual powder too strong. | *'''Sublingual Powder:''' This form of NMN is taken by placing the powder directly under the tongue, allowing it to dissolve and be absorbed through the mucous membranes in the mouth. The general guideline is to hold the substance under the tongue for approximately 1 to 5 minutes to allow for adequate absorption through the sublingual gland. Some individuals believe sublingual administration offers better bioavailability due to direct absorption into the bloodstream, bypassing the digestive system. However, while this method is promoted in many YouTube videos, there is no evidence of any positive or negative effects and there is currently no clinical study utilizing sublingual administration. Furthermore, this method is relatively inconvenient, especially for those who might find the taste of sublingual powder too strong. | ||
=== Optimal Timing for Supplementation === | ===Optimal Timing for Supplementation=== | ||
Our body has a natural rhythm where NAD levels fluctuate throughout the day rather than remaining constant, closely tied to our circadian rhythms. A study by Shin Imai and his team highlighted that NAD plays a crucial role in regulating our body's internal clock. The Sirt-1 gene, which is influenced by NAD, signals our body when it's time to eat or sleep. | Our body has a natural rhythm where NAD levels fluctuate throughout the day rather than remaining constant, closely tied to our circadian rhythms. A study by Shin Imai and his team highlighted that NAD plays a crucial role in regulating our body's internal clock. The Sirt-1 gene, which is influenced by NAD, signals our body when it's time to eat or sleep. | ||
For those considering NMN supplementation, it's suggested to take NMN in the morning when the natural rise in NAD and [[SIRT1|Sirt-1]] activity should happen. Taking NMN e.g. at night might disrupt the NAD cycle and potentially affecting the sleep or hunger. This can be especially beneficial for frequent travelers trying to adjust to a new time zone, as a morning dose of NMN can help reset the body's internal clock and reduce jet lag. <ref>[[2021-12-27 - Interview Dr. David Sinclair - Huberman Lab Podcast - The Biology of Slowing & Reversing Aging]]</ref> | For those considering NMN supplementation, it's suggested to take NMN in the morning when the natural rise in NAD and [[SIRT1|Sirt-1]] activity should happen. Taking NMN e.g. at night might disrupt the NAD cycle and potentially affecting the sleep or hunger. This can be especially beneficial for frequent travelers trying to adjust to a new time zone, as a morning dose of NMN can help reset the body's internal clock and reduce jet lag. <ref>[[2021-12-27 - Interview Dr. David Sinclair - Huberman Lab Podcast - The Biology of Slowing & Reversing Aging]]</ref> | ||
=== Combining NMN with Methyl Donors === | ===Combining NMN with Methyl Donors=== | ||
There's a theoretical concern regarding the consumption of NMN (nicotinamide mononucleotide) and its potential to use up methyl groups in the body. The reasoning is as follows: | There's a theoretical concern regarding the consumption of NMN (nicotinamide mononucleotide) and its potential to use up methyl groups in the body. The reasoning is as follows: | ||
# NMN is converted into NAD+ in the body. | #NMN is converted into NAD+ in the body. | ||
# NAD+ can be broken down into nicotinamide. | #NAD+ can be broken down into nicotinamide. | ||
# Nicotinamide is then methylated by the liver to form N1-methylnicotinamide, which can be excreted in the urine. This methylation process consumes a methyl group from [[S-adenosylmethionine (SAMe)]], the primary methyl donor in the body. | #Nicotinamide is then methylated by the liver to form N1-methylnicotinamide, which can be excreted in the urine. This methylation process consumes a methyl group from [[S-adenosylmethionine (SAMe)]], the primary methyl donor in the body. | ||
The potential concern is that excessive NMN supplementation might lead to a decrease in the body's available methyl groups, which play crucial roles in various biological processes including DNA methylation and neurotransmitter synthesis. | The potential concern is that excessive NMN supplementation might lead to a decrease in the body's available methyl groups, which play crucial roles in various biological processes including DNA methylation and neurotransmitter synthesis. | ||
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However, there are a few important points to consider: | However, there are a few important points to consider: | ||
# '''No clear evidence yet''': While the pathway is known, the actual significance of NMN supplementation on global methyl group status is not well-established in humans. It's a theoretical concern, and it would require substantial NMN consumption to have a significant impact. | #'''No clear evidence yet''': While the pathway is known, the actual significance of NMN supplementation on global methyl group status is not well-established in humans. It's a theoretical concern, and it would require substantial NMN consumption to have a significant impact. | ||
# '''Compensatory mechanisms''': The human body has various feedback mechanisms. If methyl groups were being depleted at a concerning rate, the body would likely slow down the conversion of NMN to NAD+ or the methylation of nicotinamide. | #'''Compensatory mechanisms''': The human body has various feedback mechanisms. If methyl groups were being depleted at a concerning rate, the body would likely slow down the conversion of NMN to NAD+ or the methylation of nicotinamide. | ||
# '''Methyl donors in diet''': Many people consume methyl donors like choline, betaine, and folate in their diets. These can help replenish methyl groups. | #'''Methyl donors in diet''': Many people consume methyl donors like choline, betaine, and folate in their diets. These can help replenish methyl groups. | ||
===Risks of NMN Supplementation=== | ===Risks of NMN Supplementation=== | ||
While NMN supplementation holds promise due to its potential anti-aging benefits and ability to enhance cellular metabolism, it is crucial to be aware of the potential risks involved. Here are some risks and considerations based on current knowledge and research: | While NMN supplementation holds promise due to its potential anti-aging benefits and ability to enhance cellular metabolism, it is crucial to be aware of the potential risks involved. Here are some risks and considerations based on current knowledge and research: | ||
* '''Limited Human Studies:''' Most of the studies on NMN have been conducted in animal models, and there is limited data on its effects in humans. Therefore, the safety and efficacy of NMN supplementation in humans are not fully understood, and caution is advised until more research is conducted. | *'''Limited Human Studies:''' Most of the studies on NMN have been conducted in animal models, and there is limited data on its effects in humans. Therefore, the safety and efficacy of NMN supplementation in humans are not fully understood, and caution is advised until more research is conducted. | ||
* '''Potential Interaction with Medications''': The interaction of NMN with various medications is not well studied, and there could be potential risks when combined with certain drugs. Individuals on medication should consult with a healthcare professional before considering NMN supplementation. | *'''Potential Interaction with Medications''': The interaction of NMN with various medications is not well studied, and there could be potential risks when combined with certain drugs. Individuals on medication should consult with a healthcare professional before considering NMN supplementation. | ||
* '''Theoretical Concerns''': There are theoretical concerns regarding NMN’s potential to deplete methyl groups in the body, which could impact various biological processes, including DNA methylation and neurotransmitter synthesis. While this is a theoretical concern and not substantiated by concrete evidence, it is important to consider when evaluating the potential risks of NMN supplementation.{{Citation needed}} | *'''Theoretical Concerns''': There are theoretical concerns regarding NMN’s potential to deplete methyl groups in the body, which could impact various biological processes, including DNA methylation and neurotransmitter synthesis. While this is a theoretical concern and not substantiated by concrete evidence, it is important to consider when evaluating the potential risks of NMN supplementation.{{Citation needed}} | ||
* '''Over-Supplementation Risks''': Excessive supplementation of NMN may lead to unknown side effects due to the lack of long-term human studies. Over-supplementation might also disrupt the natural balance of NAD+ and its related compounds in the body, potentially leading to unforeseen consequences. | *'''Over-Supplementation Risks''': Excessive supplementation of NMN may lead to unknown side effects due to the lack of long-term human studies. Over-supplementation might also disrupt the natural balance of NAD+ and its related compounds in the body, potentially leading to unforeseen consequences. | ||
* '''Purity and Quality Concerns''': The purity and quality of NMN supplements can vary, and impurities or contaminants in the supplements pose additional risks. It is essential to choose high-quality, reputable brands and sources for NMN supplements to minimize risks associated with impurities and contaminants. | *'''Purity and Quality Concerns''': The purity and quality of NMN supplements can vary, and impurities or contaminants in the supplements pose additional risks. It is essential to choose high-quality, reputable brands and sources for NMN supplements to minimize risks associated with impurities and contaminants. | ||
== Clinical Trials == | ==Clinical Trials== | ||
{| class="wikitable" | {| class="wikitable" | ||
|+ | |+ | ||
!Study | !Study | ||
!Design | !Design | ||
!Participants | !Participants | ||
!Outcome | !Outcome | ||
|- | |- | ||
|{{pmid_text|31685720}} | |{{pmid_text|31685720}} | ||
| | | | ||
* singe admission of up to 500 mg | *singe admission of up to 500 mg | ||
* oral admission at 9 AM | *oral admission at 9 AM | ||
| | | | ||
* 10 healthy men | *10 healthy men | ||
* 40-60 years | * 40-60 years | ||
| | | | ||
* admission was safe and well-tolerated | *admission was safe and well-tolerated | ||
|- | |- | ||
|{{pmid_text|33888596}} | |{{pmid_text|33888596}} | ||
|[[RCT]], 10 weeks | |[[RCT]], 10 weeks | ||
* placebo (n=12) | *placebo (n=12) | ||
* 250 mg/day (n=13) | * 250 mg/day (n=13) | ||
| | | | ||
* 25 postmenopausal women with prediabetes | *25 postmenopausal women with prediabetes | ||
* overweight or obese (BMI 25.3 - 39.1) | *overweight or obese (BMI 25.3 - 39.1) | ||
* 56 - 66 years | *56 - 66 years | ||
| | | | ||
* increase in skeletal muscle insulin signaling, insulin sensitivity, and muscle remodeling | *increase in skeletal muscle insulin signaling, insulin sensitivity, and muscle remodeling | ||
* improvement in muscle insulin sensitivity is clinically relevant and is similar to the improvement observed after ~10% weight loss | *improvement in muscle insulin sensitivity is clinically relevant and is similar to the improvement observed after ~10% weight loss | ||
|- | |- | ||
|{{pmid_text|34238308}} | |{{pmid_text|34238308}} | ||
|[[RCT]], 6 weeks | |[[RCT]], 6 weeks | ||
* placebo (n=12) | *placebo (n=12) | ||
* 300 mg/day (n=12) | * 300 mg/day (n=12) | ||
* 600 mg/day (n=12) | *600 mg/day (n=12) | ||
* 1200 mg/day (n=12) | *1200 mg/day (n=12) | ||
| | |||
*48 young and middle-aged recreationally trained runners | |||
*35 years in average | |||
| | | | ||
*The combination of NMN supplementation and exercise further improves ventilatory threshold even among healthy young and middle-aged people. | |||
*The improvement of aerobic capacity is in a dosage-dependent, large dosage of NMN with exercise has better effects. | |||
*The improvement is muscle, not cardiac, related. | |||
* The combination of NMN supplementation and exercise further improves ventilatory threshold even among healthy young and middle-aged people. | |||
* The improvement of aerobic capacity is in a dosage-dependent, large dosage of NMN with exercise has better effects. | |||
* The improvement is muscle, not cardiac, related. | |||
|- | |- | ||
| {{pmid_text|36002548}} | |{{pmid_text|36002548}} | ||
|[[RCT]], 4 weeks | |[[RCT]], 4 weeks | ||
* placebo (n=15) | *placebo (n=15) | ||
* 1250 mg/day (n=16) | *1250 mg/day (n=16) | ||
| | | | ||
* 31 healthy adult men and women | * 31 healthy adult men and women | ||
* 20–65 years | *20–65 years | ||
| | | | ||
* Oral administration of 1250 mg of NMN, when administered once daily for up to 4 weeks, was safe and well-tolerated in healthy adult men and women. | *Oral administration of 1250 mg of NMN, when administered once daily for up to 4 weeks, was safe and well-tolerated in healthy adult men and women. | ||
* Oral administration of NMN in humans has a low adverse effect on renal function. | *Oral administration of NMN in humans has a low adverse effect on renal function. | ||
* Results indicate that NMN can be administered orally to humans at doses 1250 mg once daily for up to 4 weeks without causing hepatotoxicity and vasodilative flushing, and is believed to have a higher upper tolerable limit compared to NAM and NA. | *Results indicate that NMN can be administered orally to humans at doses 1250 mg once daily for up to 4 weeks without causing hepatotoxicity and vasodilative flushing, and is believed to have a higher upper tolerable limit compared to NAM and NA. | ||
|- | |- | ||
| {{pmid_text|36482258}} | |{{pmid_text|36482258}} | ||
|[[RCT]], 8.5 weeks (60 days) | |[[RCT]], 8.5 weeks (60 days) | ||
* placebo (n=20) | *placebo (n=20) | ||
* 300 mg (n=20) | *300 mg (n=20) | ||
* 600 mg (n=20) | *600 mg (n=20) | ||
* 900 mg (n=20) | *900 mg (n=20) | ||
| | | | ||
* healthy males and females | *healthy males and females | ||
* 40-65 (49.3 in average) years | *40-65 (49.3 in average) years | ||
* BMI between 18.5 and 35 | *BMI between 18.5 and 35 | ||
| | | | ||
* Oral administration of NMN up to 900 mg/day for 60 days was safe and well tolerated | *Oral administration of NMN up to 900 mg/day for 60 days was safe and well tolerated | ||
* blood NAD concentration was significantly and dose-dependently increased | *blood NAD concentration was significantly and dose-dependently increased | ||
* significant improvement of six-minute walking test, blood biological age, and SF-36 scores | *significant improvement of six-minute walking test, blood biological age, and SF-36 scores | ||
* 900 mg/day oral dose did not give significantly better efficacy than 600 mg/day dose | * 900 mg/day oral dose did not give significantly better efficacy than 600 mg/day dose | ||
|- | |- | ||
| {{pmid_text|35215405}} | |{{pmid_text|35215405}} | ||
|[[RCT]], 12 weeks | |[[RCT]], 12 weeks | ||
* placebo, before 12 pm | *placebo, before 12 pm | ||
* placebo, after 6 pm | *placebo, after 6 pm | ||
* 250 mg, before 12 pm | *250 mg, before 12 pm | ||
* 250 mg, after 6 pm | * 250 mg, after 6 pm | ||
| | | | ||
* 108 older adults | *108 older adults | ||
* ≥65 years | *≥65 years | ||
| | | | ||
* NMN intake in the afternoon is more effective in improving lower limb function and reducing drowsiness in older adults. | *NMN intake in the afternoon is more effective in improving lower limb function and reducing drowsiness in older adults. | ||
|} | |} | ||
== See also == | ==See also== | ||
* [[Nicotinamide Adenine Dinucleotide (NAD+)]] | *[[Nicotinamide Adenine Dinucleotide (NAD+)]] | ||
* [[NAD+ Boosters]] | *[[NAD+ Boosters]] | ||
* [[NAD+ Precursor]] | *[[NAD+ Precursor]] | ||
* [[NMN Manufacturer]] | *[[NMN Manufacturer]] | ||
* [[Wikipedia:Nicotinamide mononucleotide|Wikipedia article about NMN]] | *[[Wikipedia:Nicotinamide mononucleotide|Wikipedia article about NMN]] | ||
== Todo == | ==Todo== | ||
* {{pmid_text|37619764}} | *{{pmid_text|37619764}} | ||
* {{pmid_text|37718359}}, https://www.nmn.com/news/nmn-lowers-blood-pressure-in-patients-with-hypertension-latest-human-trial | *{{pmid_text|37718359}}, https://www.nmn.com/news/nmn-lowers-blood-pressure-in-patients-with-hypertension-latest-human-trial | ||
* https://www.nmn.com/news/nmn-tablet-blood-nad-levels-humans | *https://www.nmn.com/news/nmn-tablet-blood-nad-levels-humans | ||
==References== | ==References== | ||
<references/> | <references /> | ||
[[Category:Orally Consumable Longevity Molecules]] | [[Category:Orally Consumable Longevity Molecules]] | ||