Latest revision as of 09:48, 11 December 2023

NAD+ boosters are substances or interventions designed to increase levels of NAD+ (Nicotinamide Adenine Dinucleotide), a critical coenzyme found in every cell, essential for cellular energy production, metabolism, and repair processes. Boosting NAD+ levels is of significant interest in the fields of health and longevity, as declining levels of NAD+ are associated with aging and various age-related diseases.

Overview of NAD+ Boosters

NAD+ Precursors

NAD+ precursors are compounds that serve as substrates in the biosynthesis of NAD+. They can be converted into NAD+ within the body, thus serving as effective NAD+ boosters.

Nicotinamide Mononucleotide (NMN): A compound that can directly stimulate NAD+ synthesis, playing a crucial role in energy metabolism and cell vitality.
Nicotinamide Riboside (NR): Another precursor that is converted into NMN in the body before participating in the synthesis of NAD+.
Nicotinamide (NAM): A form of vitamin B3, acts as an NAD+ precursor via the NAD+ salvage pathway.

Boosting NAD+ by Inhibiting NAD+ Consumers

NAD+ consumers (NADase) are enzymes that use NAD+ as a substrate, reducing the available NAD+ in the cell. By inhibiting these consumers, more NAD+ remains available for other cellular processes.

Sirtuins: A family of proteins that deacetylate proteins and consume NAD+ in the process. Compounds like resveratrol can activate sirtuins and the subsequent cellular effects can create an environment where cells might maintain or produce NAD+ more efficiently, which could indirectly support NAD+ availability.
PARPs (Poly(ADP-ribose) polymerases): Enzymes involved in DNA repair that also consume NAD+. Inhibiting PARP activity can help maintain NAD+ levels.
CD38: A glycoprotein that uses NAD+; reducing CD38 levels or activity can potentially elevate NAD+ levels.

Other NAD+ Boosting Compounds

Beyond precursors and inhibitors of NAD+ consumers, several other supplements claim to boost NAD+ levels or improve NAD+ metabolism.

Resveratrol: While primarily known as a sirtuin activator, it might also have indirect effects on NAD+ levels and metabolism.
Quercetin: A flavonoid that can inhibit CD38 and may, therefore, increase NAD+ levels indirectly.
Pterostilbene: A polyphenol, similar to resveratrol, purported to have beneficial effects on NAD+ metabolism and sirtuin activation.
Apigenin: A natural compound found in various fruits and vegetables, apigenin is studied for its potential to inhibit CD38 and may, therefore, increase NAD+ levels indirectly.

Interventions to Boost NAD+

Apart from supplements, certain lifestyle and dietary interventions may also support NAD+ levels.

Exercise: Regular physical activity has been shown to increase NAD+ levels, likely due to enhanced energy metabolism and increased demand for ATP.
Caloric Restriction: Reducing calorie intake without malnutrition can elevate NAD+ levels, potentially through the activation of sirtuins and improved metabolic efficiency.
Intermittent Fasting: This dietary approach can also elevate NAD+ levels, likely through mechanisms similar to caloric restriction, such as increased stress resistance and metabolic adaptations.

NAD+ Infusions

NAD+ infusions represent a direct method of increasing NAD+ levels in the body. This intervention involves intravenous administration of NAD+, allowing for higher bioavailability compared to oral supplements.

Effectiveness: NAD+ infusions have been reported to quickly elevate NAD+ levels, potentially offering immediate benefits such as enhanced energy, improved mood, and reduced withdrawal symptoms in addiction treatment.
Uses: This method is utilized primarily in clinical settings and is explored for its potential benefits in addressing conditions like chronic fatigue, addiction, and age-related cognitive decline.
Safety and Accessibility: While generally considered safe when administered under medical supervision, the accessibility, long-term effects, and optimal dosing of NAD+ infusions require further research and standardization.

Comparison

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Booster	Mechanism of Action	Relative Strength	Notes
Nicotinamide Mononucleotide (NMN)	NAD+ Precursor	High	Well-researched, direct precursor to NAD+
NR (Nicotinamide Riboside)	NAD+ Precursor	High	Converted to NMN in the body before participating in NAD+ synthesis
Nicotinamide (NAM)	NAD+ Precursor via the salvage pathway	Medium	More research needed on optimal dosing and long-term effects
Resveratrol	Sirtuin activator; may have indirect effects on NAD+ levels and metabolism	Low to Medium	Effectiveness may be influenced by individual metabolic differences and supplement formulation
Quercetin	Inhibits CD38; may increase NAD+ levels indirectly	Low to Medium	More research needed to quantify the impact on NAD+ levels
Pterostilbene	Similar to resveratrol; purported to have beneficial effects on NAD+ metabolism and sirtuin activation	Low to Medium	Requires more rigorous studies to confirm efficacy
Exercise	Increases NAD+ levels likely due to enhanced energy metabolism and increased demand for ATP	Medium to High	Effectiveness may depend on exercise type, intensity, and individual fitness level
Caloric Restriction	Elevates NAD+ levels potentially through the activation of sirtuins and improved metabolic efficiency	High	Sustained caloric restriction may have compliance challenges
Intermittent Fasting	Elevates NAD+ levels through mechanisms similar to caloric restriction	Medium to High	Impact may vary depending on the specific fasting protocol employed
NAD+ Infusion	Direct intravenous administration of NAD+	High	Rapid elevation of NAD+ levels; primarily used in clinical settings; requires further research on long-term effects and optimal dosing

Conclusion

NAD+ boosters, encompassing NAD+ precursors, inhibitors of NAD+ consuming enzymes, and various other supplements, along with non-supplemental measures like exercise and dietary modifications, offer promising avenues to enhance cellular vitality, metabolism, and potentially, longevity. While the science is evolving, understanding the diverse approaches to boost NAD+ highlights the multifaceted nature of cellular health and provides multiple pathways to explore for maintaining optimal health and combating age-related decline.

Todo

2022, A systems-approach to NAD+ restoration ^[1]
2022, Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies ^[2]

References

↑ Conlon N & Ford D: A systems-approach to NAD+ restoration. Biochem Pharmacol 2022. (PMID 35134387) [PubMed] [DOI] A decline in NAD+ is a feature of ageing and may play a causal role in the process. NAD+ plays a pivotal role in myriad processes important in cellular metabolism and is a cosubstrate for enzymes that play key roles in pathways that modify ageing. Thus, interventions that increase NAD+ may slow aspects of the ageing trajectory and there is great interest in pharmacological NAD+ restoration. Dietary supplementation with NAD+ precursors, particularly nicotinamide riboside, has increased NAD+ levels in several human intervention studies and arguably been the most robust approach to date. However, consistency and reliability of such approaches to increase NAD+, and also impact on markers of efficacy to slow or reverse features of ageing, has been inconsistent. We argue that a major element of this variability may arise from the use of single-target approaches that do not consider the underlying biological complexity leading to NAD+ decline. Thus, a systems approach - targeting multiple key nodes in the NAD+ interactome - is likely to be more efficacious and reliable.
↑ Poljšak B et al.: Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies. Antioxidants (Basel) 2022. (PMID 36139711) [PubMed] [DOI] [Full text] Precursors of nicotinamide adenine dinucleotide (NAD+), modulators of enzymes of the NAD+ biosynthesis pathways and inhibitors of NAD+ consuming enzymes, are the main boosters of NAD+. Increasing public awareness and interest in anti-ageing strategies and health-promoting lifestyles have grown the interest in the use of NAD+ boosters as dietary supplements, both in scientific circles and among the general population. Here, we discuss the current trends in NAD+ precursor usage as well as the uncertainties in dosage, timing, safety, and side effects. There are many unknowns regarding pharmacokinetics and pharmacodynamics, particularly bioavailability, metabolism, and tissue specificity of NAD+ boosters. Given the lack of long-term safety studies, there is a need for more clinical trials to determine the proper dose of NAD+ boosters and treatment duration for aging prevention and as disease therapy. Further research will also need to address the long-term consequences of increased NAD+ and the best approaches and combinations to increase NAD+ levels. The answers to the above questions will contribute to the more efficient and safer use of NAD+ boosters.

[pmid35134387-1] Conlon N & Ford D: A systems-approach to NAD+ restoration. Biochem Pharmacol 2022. (PMID 35134387) [PubMed] [DOI] A decline in NAD+ is a feature of ageing and may play a causal role in the process. NAD+ plays a pivotal role in myriad processes important in cellular metabolism and is a cosubstrate for enzymes that play key roles in pathways that modify ageing. Thus, interventions that increase NAD+ may slow aspects of the ageing trajectory and there is great interest in pharmacological NAD+ restoration. Dietary supplementation with NAD+ precursors, particularly nicotinamide riboside, has increased NAD+ levels in several human intervention studies and arguably been the most robust approach to date. However, consistency and reliability of such approaches to increase NAD+, and also impact on markers of efficacy to slow or reverse features of ageing, has been inconsistent. We argue that a major element of this variability may arise from the use of single-target approaches that do not consider the underlying biological complexity leading to NAD+ decline. Thus, a systems approach - targeting multiple key nodes in the NAD+ interactome - is likely to be more efficacious and reliable.

[pmid36139711-2] Poljšak B et al.: Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies. Antioxidants (Basel) 2022. (PMID 36139711) [PubMed] [DOI] [Full text] Precursors of nicotinamide adenine dinucleotide (NAD+), modulators of enzymes of the NAD+ biosynthesis pathways and inhibitors of NAD+ consuming enzymes, are the main boosters of NAD+. Increasing public awareness and interest in anti-ageing strategies and health-promoting lifestyles have grown the interest in the use of NAD+ boosters as dietary supplements, both in scientific circles and among the general population. Here, we discuss the current trends in NAD+ precursor usage as well as the uncertainties in dosage, timing, safety, and side effects. There are many unknowns regarding pharmacokinetics and pharmacodynamics, particularly bioavailability, metabolism, and tissue specificity of NAD+ boosters. Given the lack of long-term safety studies, there is a need for more clinical trials to determine the proper dose of NAD+ boosters and treatment duration for aging prevention and as disease therapy. Further research will also need to address the long-term consequences of increased NAD+ and the best approaches and combinations to increase NAD+ levels. The answers to the above questions will contribute to the more efficient and safer use of NAD+ boosters.

[1]

[2]

@@ Line 1: / Line 1: @@
-==NAD Boosters: Enhancing Cellular Metabolism and Longevity==
+NAD+ boosters are substances or interventions designed to increase levels of [[Nicotinamide Adenine Dinucleotide (NAD)|NAD+ (Nicotinamide Adenine Dinucleotide)]], a critical coenzyme found in every cell, essential for cellular energy production, metabolism, and repair processes. Boosting NAD+ levels is of significant interest in the fields of health and longevity, as declining levels of NAD+ are associated with aging and various age-related diseases.
-'''NAD''', or Nicotinamide Adenine Dinucleotide, is a crucial coenzyme found in every cell in our bodies. It plays a vital role in energy metabolism and maintaining proper cell function. As we age, the levels of NAD in our body decline, which can contribute to the aging process and the development of age-related diseases. NAD boosters have therefore garnered significant attention for their potential to mitigate aging and enhance cellular health.
+== Overview of NAD+ Boosters ==
-===Understanding NAD:===
+=== NAD+ Precursors ===
-NAD is pivotal in cellular metabolism, aiding in the conversion of nutrients into energy. It is involved in various metabolic pathways and cellular processes, like the citric acid cycle, and it's essential for maintaining cellular integrity and function.
+[[NAD+ Precursor|NAD+ precursors]] are compounds that serve as substrates in the biosynthesis of NAD+. They can be converted into NAD+ within the body, thus serving as effective NAD+ boosters.
+* '''[[Nicotinamide Mononucleotide (NMN)]]:''' A compound that can directly stimulate NAD+ synthesis, playing a crucial role in energy metabolism and cell vitality.
+* '''[[Nicotinamide Riboside (NR)]]:''' Another precursor that is converted into NMN in the body before participating in the synthesis of NAD+.
+* '''[[Nicotinamide (NAM)]]:''' A form of vitamin B3, acts as an NAD+ precursor via the NAD+ salvage pathway.
-===The Importance of NAD Boosters:===
+=== Boosting NAD+ by Inhibiting NAD+ Consumers ===
-NAD boosters, like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), are supplements designed to increase the levels of NAD in the body. These boosters are important for enhancing cellular energy, repairing DNA damage, modulating immune-system functions, and optimizing lifespan and health span.
+NAD+ consumers ([[NADase]]) are enzymes that use NAD+ as a substrate, reducing the available NAD+ in the cell. By inhibiting these consumers, more NAD+ remains available for other cellular processes.
+* '''[[Sirtuins]]:''' A family of proteins that deacetylate proteins and consume NAD+ in the process. Compounds like resveratrol can activate sirtuins and the subsequent cellular effects can create an environment where cells might maintain or produce NAD+ more efficiently, which could indirectly support NAD+ availability.
+* '''PARPs (Poly(ADP-ribose) polymerases):''' Enzymes involved in DNA repair that also consume NAD+. Inhibiting PARP activity can help maintain NAD+ levels.
+* '''CD38:''' A glycoprotein that uses NAD+; reducing CD38 levels or activity can potentially elevate NAD+ levels.
-===Scientific Studies and Clinical Trials:===
+=== Other NAD+ Boosting Compounds ===
-Numerous studies have demonstrated the efficacy of NAD boosters in improving cellular health and delaying the aging process in animals. However, research on humans is in the early stages, and more clinical trials are needed to substantiate the benefits and understand the long-term effects and optimal dosages of NAD boosters in humans.
+Beyond precursors and inhibitors of NAD+ consumers, several other supplements claim to boost NAD+ levels or improve NAD+ metabolism.
+* '''[[Resveratrol]]:''' While primarily known as a sirtuin activator, it might also have indirect effects on NAD+ levels and metabolism.
+* '''[[Quercetin]]:''' A flavonoid that can inhibit CD38 and may, therefore, increase NAD+ levels indirectly.
+* '''[[Pterostilbene]]:''' A polyphenol, similar to resveratrol, purported to have beneficial effects on NAD+ metabolism and sirtuin activation.
+* '''[[Apigenin]]:''' A natural compound found in various fruits and vegetables, apigenin is studied for its potential to inhibit CD38 and may, therefore, increase NAD+ levels indirectly.
-===Benefits of NAD Boosters:===
+=== Interventions to Boost NAD+ ===
-* '''Improved Energy Levels:''' NAD boosters enhance cellular metabolism, thus improving energy levels and combating fatigue.
+Apart from supplements, certain lifestyle and dietary interventions may also support NAD+ levels.
-* '''Enhanced Longevity:''' By mitigating age-associated cellular decline, NAD boosters may contribute to an increase in lifespan.
+* '''[[Exercise]]:''' Regular physical activity has been shown to increase NAD+ levels, likely due to enhanced energy metabolism and increased demand for ATP.
-* '''Cognitive Enhancement:''' Boosting NAD levels has been linked to improved cognitive function and a potential reduction in the risk of neurodegenerative diseases.
+* '''[[Caloric Restriction]]:''' Reducing calorie intake without malnutrition can elevate NAD+ levels, potentially through the activation of sirtuins and improved metabolic efficiency.
-* '''Optimized Cellular Repair:''' NAD is crucial for DNA repair processes, and elevated levels may optimize the body's ability to repair damaged cells.
+* '''[[Intermittent Fasting]]:''' This dietary approach can also elevate NAD+ levels, likely through mechanisms similar to caloric restriction, such as increased stress resistance and metabolic adaptations.
-===Possible Side Effects:===
+=== NAD+ Infusions ===
-While NAD boosters are generally considered safe, some people may experience side effects like nausea, fatigue, headaches, or insomnia. Consultation with a healthcare professional is advisable before incorporating NAD boosters into one's routine, especially for those with underlying health conditions or those on medication.
+[[NAD+ Infusion|NAD+ infusions]] represent a direct method of increasing NAD+ levels in the body. This intervention involves intravenous administration of NAD+, allowing for higher bioavailability compared to oral supplements.
+* '''Effectiveness:''' NAD+ infusions have been reported to quickly elevate NAD+ levels, potentially offering immediate benefits such as enhanced energy, improved mood, and reduced withdrawal symptoms in addiction treatment.
+* '''Uses:''' This method is utilized primarily in clinical settings and is explored for its potential benefits in addressing conditions like chronic fatigue, addiction, and age-related cognitive decline.
+* '''Safety and Accessibility:''' While generally considered safe when administered under medical supervision, the accessibility, long-term effects, and optimal dosing of NAD+ infusions require further research and standardization.
-===Consumer Awareness:===
+== Comparison ==
-Given the increasing popularity of NAD boosters, consumers should exercise caution and prioritize purchasing from reputable brands and suppliers. It is also vital to stay informed about the evolving scientific understanding of the efficacy and safety of NAD boosters.
+{{Citations Needed}}
+{| class="wikitable"
+! Booster
+! Mechanism of Action
+! Relative Strength
+! Notes
+|-
+| [[Nicotinamide Mononucleotide (NMN)]]
+| NAD+ Precursor
+| High
+| Well-researched, direct precursor to NAD+
+|-
+| NR (Nicotinamide Riboside)
+| NAD+ Precursor
+| High
+| Converted to NMN in the body before participating in NAD+ synthesis
+|-
+| [[Nicotinamide (NAM)]]
+| NAD+ Precursor via the salvage pathway
+| Medium
+| More research needed on optimal dosing and long-term effects
+|-
+| [[Resveratrol]]
+| Sirtuin activator; may have indirect effects on NAD+ levels and metabolism
+| Low to Medium
+| Effectiveness may be influenced by individual metabolic differences and supplement formulation
+|-
+| [[Quercetin]]
+| Inhibits CD38; may increase NAD+ levels indirectly
+| Low to Medium
+| More research needed to quantify the impact on NAD+ levels
+|-
+| [[Pterostilbene]]
+| Similar to resveratrol; purported to have beneficial effects on NAD+ metabolism and sirtuin activation
+| Low to Medium
+| Requires more rigorous studies to confirm efficacy
+|-
+| [[Exercise]]
+| Increases NAD+ levels likely due to enhanced energy metabolism and increased demand for ATP
+| Medium to High
+| Effectiveness may depend on exercise type, intensity, and individual fitness level
+|-
+| [[Caloric Restriction]]
+| Elevates NAD+ levels potentially through the activation of sirtuins and improved metabolic efficiency
+| High
+| Sustained caloric restriction may have compliance challenges
+|-
+| [[Intermittent Fasting]]
+| Elevates NAD+ levels through mechanisms similar to caloric restriction
+| Medium to High
+| Impact may vary depending on the specific fasting protocol employed
+|-
+| [[NAD+ Infusion]]
+| Direct intravenous administration of NAD+
+| High
+| Rapid elevation of NAD+ levels; primarily used in clinical settings; requires further research on long-term effects and optimal dosing
+|}
-===Conclusion:===
+= Conclusion =
-NAD boosters, specifically NR and NMN, hold immense promise in enhancing cellular metabolism, combating aging, and improving overall well-being. While animal studies have shown encouraging results, more extensive and long-term human studies are essential to validate these outcomes and determine appropriate dosages. As science continues to evolve in this field, NAD boosters could potentially become a cornerstone in preventive healthcare and longevity science.
+NAD+ boosters, encompassing NAD+ precursors, inhibitors of NAD+ consuming enzymes, and various other supplements, along with non-supplemental measures like exercise and dietary modifications, offer promising avenues to enhance cellular vitality, metabolism, and potentially, longevity. While the science is evolving, understanding the diverse approaches to boost NAD+ highlights the multifaceted nature of cellular health and provides multiple pathways to explore for maintaining optimal health and combating age-related decline.
+== Todo ==
+* {{pmid text|35134387}}
+* {{pmid text|36139711}}
+== References ==
+<references />
+[[Category:Lifespan Extending]]