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GENEMEDICS NUTRITION
Author: Dr. George Shanlikian, M.D. | Last Updated: November 20th, 2024
Also known as niagen, nicotinamide riboside (NR) is an alternative form of vitamin B3. It exerts its anti-aging effects when the body converts it into nicotinamide adenine dinucleotide (NAD+), a helper molecule (coenzyme) that is present in all living cells. NAD+ is essential for several important biological processes including the conversion of food into energy, DNA repair, regulation of immune function, and regulation of the body’s internal clock. Boosting NAD+ levels in the body has been shown to produce several health benefits. [1] Nicotinamide riboside can be found in small amounts in fruits, vegetables, meat, and milk.
The conversion of nicotinamide riboside into nicotinamide adenine dinucleotide (NAD+) allows the body to perform various important biological processes. This includes energy production from food, DNA repair, regulation of immune function, and regulation of the body’s internal clock.
Nicotinamide riboside is converted by the body into nicotinamide adenine dinucleotide (NAD+), a helper molecule (coenzyme) that is present in all living cells and is essential for a broad range of biological functions. To put it simply, nicotinamide riboside is required in order to boost the levels of NAD+ in the body. Studies show that increased NAD+ levels are associated with a longer lifespan. [1-5] This suggests that boosting NAD+ levels through nicotinamide riboside supplementation may help extend lifespan.
Another mechanism that is known to extend lifespan is through increasing sirtuin (SIRT) activity. Increased SIRT activity has been shown to stabilize telomeres (located at chromosomes ends) and attenuate age-related telomere shortening. [6] Interestingly, studies found that individuals with longer telomeres have a longer subsequent lifespan. [7-8] With increased SIRT1 activity, the telomeres are more stable and their length increases which in turn extends lifespan
Nicotinamide riboside-mediated increase in NAD+ activates SIRT1, an enzyme that plays an integral role in the regulation of proteins involved in cellular metabolism and processes associated with longevity, inflammation, and stress. SIRT1 activation removes acetyl groups from transcriptional regulators such as FOXO1 (Forkhead box protein O1) and PGC-1alpha (Peroxisome proliferator-activated receptor-gamma coactivator). This in turn causes metabolic adaptation, a survival mechanism that decreases the resting metabolic rate (number of calories burned at rest). As a result, cells undergo a process called mitochondrial biogenesis, which involves the production of new mitochondria (the powerhouse of cells). Mitochondrial biogenesis is critical for increased longevity since mitochondrial dysfunction in cells is associated with various age-related diseases and a shorter lifespan. [9-10]
A number of studies support that nicotinamide riboside can positively affect longevity mechanisms:
Nicotinamide riboside-mediated increase in NAD+ levels can slow down the signs of aging by preventing mitochondrial dysfunction, which contributes to cellular senescence (also known as biological aging), increased inflammation, decreased stem cell activity, reduced healing rate, and a decline in tissue and organ function. [16] By activating SIRT1, new and healthy mitochondria are formed through a process called mitochondrial biogenesis.
An increasing number of evidence supports the anti-aging effects of nicotinamide riboside:
NAD+ plays an integral role in energy production and regulation of a broad range of biological processes. One of the most important functions of NAD+ is generating a usable form of energy called adenosine triphosphate (ATP). By boosting NAD+ levels, nicotinamide riboside can also help increase energy levels which can improve exercise performance.
Studies suggest that nicotinamide riboside supplementation can help improve exercise performance:
Nicotinamide riboside boosts NAD+ levels which in turn increases energy expenditure. As a result, the body does not store additional fat. Moreover, evidence suggests that increased NAD+ levels are associated with increased metabolism. [27] All of these mechanisms can help promote weight loss.
The fat-burning properties of nicotinamide riboside are backed by a number of studies:
By boosting NAD+ levels, nicotinamide riboside can help attenuate the age-related decline in muscle mass and strength. This is because increased NAD+ levels are associated with enhanced ATP production and mitochondrial function and reduced muscle inflammation. [37] In addition, NAD+ is found to be a major player in skeletal muscle development and regeneration. [38]
Studies suggest that nicotinamide riboside can help prevent muscle degeneration and improve muscle health:
The ability of nicotinamide riboside to improve cognitive function can be attributed to its NAD+-boosting properties. NAD+ can help protect against brain disorders by decreasing the production of reactive oxygen species (ROS), which are linked to a wide array of medical maladies including neurodegenerative diseases. [41] NAD+ can also help prevent degeneration of nerve cells in the brain by regulating the activity of poly adenosine diphosphate-ribose polymerase 1 (PARP1). [42-43] Another mechanism that is important in boosting cognitive health is the ability of NAD+ to regulate the production of brain chemicals called neurotransmitters, such as dopamine, serotonin, and norepinephrine. These brain chemicals play an integral role in different cognitive functions such as memory, motivation, attention, mood, and emotions.
Studies show that nicotinamide riboside can be a therapeutic strategy in improving brain health:
Nicotinamide riboside-mediated increase in NAD+ levels can help promote normal heart function and enhanced cardiac recovery from injury. It has been shown that NAD+ activates SIRT3 which is associated with the prevention of heart enlargement and scarring. [59-61] Moreover, the mitochondrial conservation effects of NAD+ are known to play an integral role in inhibiting heart failure. [62]
Studies show that nicotinamide riboside can help protect against heart disease:
Cancer cells usually exhibit mitochondrial respiration malfunction and increased glucose uptake – both of these mechanisms can be prevented by increasing NAD+ levels. [72] In addition, increased NAD+ levels are known to boost the activity of SIRT1 and SIRT6, both of which are known to exert anti-tumor effects. [73-74] This suggests that nicotinamide riboside-mediated increase in NAD+ levels can help inhibit cancer growth.
The anti-cancer properties of nicotinamide riboside and its ability to treat the side effects of chemotherapy are backed by a number of studies:
Nicotinamide riboside can also be beneficial in people with hypertension because of its blood pressure-lowering effects. By boosting NAD+ levels, SIRT1 activation occurs which in turn increases the production of nitric oxide, a substance that helps widen blood vessels (vasodilation) to allow an increase in blood flow. This process reduces the pressure within the blood vessels.
Studies report that nicotinamide riboside has anti-hypertensive properties:
Nicotinamide riboside can also benefit people suffering from the unpleasant symptoms of diabetes and high blood sugar levels. It does this by boosting the levels of NAD+ which in turn enhances the body’s response to the blood sugar-lowering effects of the hormone insulin.
Evidence shows that nicotinamide riboside has anti-diabetic effects:
NAD+ is essential for brain health and may help protect against various brain injuries. Stroke is a condition wherein the blood supply to the brain is cut off or a blood vessel ruptures. NAD+ is known to improve blood circulation to the brain – a mechanism that may help prevent stroke. Since nicotinamide riboside boosts NAD+ levels, it may offer protective effects against stroke.
A good deal of evidence shows that nicotinamide riboside can help lower the risk of stroke and improve recovery through different mechanisms:
In acute kidney injury, substantial decreases in NAD+ levels are known to impair energy generation and affect the core function of the kidney. [98] In addition, decreased NAD+ levels also decrease sirtuin activity which contributes to the decline in kidney function. Thus, augmentation of NAD+ through nicotinamide riboside supplementation may help protect the kidneys and improve their health.
Nicotinamide riboside has been shown to play an essential role in maintaining optimal kidney function:
Nicotinamide riboside-mediated increase in NAD+ can also help protect against various eye disorders including the age-related decline in visual function. The modulation of sirtuin activity by NAD+ enhances retinal metabolism, reduces the death of eye cells, and improves vision. [103]
A number of convincing pieces of evidence suggest that nicotinamide riboside can help improve eye health:
Nicotinamide riboside side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on nicotinamide riboside. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of nicotinamide riboside. Despite this, it was listed as a side effect associated with nicotinamide riboside even though these associated side effects are very uncommon.
Side effects associated with nicotinamide riboside may include the following:
Nicotinamide riboside (NR) is a form of vitamin B3 that serves as a precursor to nicotinamide adenine dinucleotide (NAD+), a critical molecule involved in cellular energy production and various metabolic processes. NAD+ levels naturally decline with age, and this decrease is associated with aging and various health conditions. NR supplements are designed to increase NAD+ levels, potentially supporting cellular health, energy metabolism, and overall vitality.
Research suggests that boosting NAD+ through NR supplementation may have several health benefits, including improved mitochondrial function, enhanced cognitive performance, and possibly extending lifespan. Some studies have also explored its potential in protecting against neurodegenerative diseases like Alzheimer’s and Parkinson’s by supporting cellular repair mechanisms and reducing oxidative stress.
Despite these promising findings, the effectiveness and long-term safety of NR supplements are still under investigation. While some people report feeling more energized or noticing improvements in their skin and overall well-being, others experience minimal effects. As with any supplement, it is advisable to consult a healthcare professional before starting NR, especially for those with underlying health conditions.
Nicotinamide riboside (NR) supplementation has gained attention for its potential role in enhancing cellular health and supporting healthy aging. NR is a form of vitamin B3 and a precursor to NAD+ (nicotinamide adenine dinucleotide), a critical coenzyme involved in energy production, DNA repair, and cellular metabolism. As we age, NAD+ levels naturally decline, leading to reduced cellular function and increased susceptibility to age-related diseases. Supplementing with NR has been shown to effectively raise NAD+ levels, which may improve mitochondrial function, enhance cognitive health, and promote longevity.
The benefits of NR supplementation extend beyond aging, with research suggesting potential improvements in metabolic health. By increasing NAD+ levels, NR may enhance insulin sensitivity, support weight management, and reduce inflammation. Early studies also indicate that NR could offer neuroprotective effects, making it a promising supplement for those looking to protect against neurodegenerative conditions like Alzheimer’s disease. Additionally, NR is generally well-tolerated, with minimal side effects reported in most clinical trials.
While the long-term effects of NR supplementation are still being studied, the current research is encouraging. Individuals interested in boosting cellular energy, supporting cognitive health, or improving metabolic function may consider NR as a valuable addition to their supplement routine. However, as with any supplement, it’s important to consult with a healthcare provider before beginning NR supplementation, especially for those with existing health conditions or those taking other medications.
Nicotinamide Riboside Chloride (NR) is a form of vitamin B3 that acts as a precursor to nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular metabolism. NAD+ plays a vital role in energy production, DNA repair, and cellular aging. By supplementing with NR, it is believed that one can boost NAD+ levels, potentially enhancing overall cellular function and vitality.
In recent years, NR has gained attention for its potential benefits in age-related health issues and metabolic conditions. Research suggests that increasing NAD+ levels through NR supplementation may support healthy aging, improve metabolic function, and even enhance cognitive performance. However, while preliminary studies are promising, more research is needed to fully understand its long-term effects and benefits.
Nicotinamide Riboside Chloride is available in various dietary supplements and is generally considered safe when used as directed. However, it’s essential to consult with a healthcare provider before starting any new supplement regimen, particularly if you have underlying health conditions or are taking other medications.
Nicotinamide Riboside (NR) powder is a form of Vitamin B3 that has garnered attention for its potential health benefits. As a precursor to nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular metabolism, NR is believed to support various physiological processes. NAD+ is essential for energy production, DNA repair, and cellular maintenance, and its levels tend to decline with age. By supplementing with NR, individuals may aim to boost NAD+ levels and potentially improve overall metabolic health.
Research into Nicotinamide Riboside has suggested several promising benefits. Studies indicate that NR supplementation may enhance mitochondrial function, which can positively affect energy levels and endurance. Additionally, it may have a role in improving cognitive function and promoting healthy aging. Some preliminary research also suggests that NR could have protective effects against age-related diseases, although more extensive human studies are needed to fully understand its long-term impact.
Despite the promising aspects of NR powder, it’s essential to approach supplementation with caution. The effectiveness and safety of NR can vary among individuals, and the long-term effects are still under investigation. Consulting with a healthcare provider before starting any new supplement regimen is advisable, especially for those with underlying health conditions or those taking other medications.
Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN) are both compounds involved in the production of NAD+, a vital molecule for cellular metabolism and energy production. NR is a precursor to NAD+ and is converted into NMN before ultimately being converted into NAD+. Studies have shown that NR supplementation can effectively increase NAD+ levels in the body, potentially offering benefits such as improved mitochondrial function and enhanced cellular repair mechanisms.
NMN, on the other hand, is a direct precursor to NAD+ and is considered to be closer to the final product in the NAD+ biosynthesis pathway. Research suggests that NMN supplementation may offer similar benefits to NR, such as improved metabolic health and potential anti-aging effects. Some studies have indicated that NMN might have a more immediate effect on NAD+ levels due to its direct role in the biosynthesis pathway.
Both NR and NMN have shown promise in preclinical and early clinical studies for their potential to improve various aspects of health, including metabolism, cardiovascular health, and age-related conditions. However, more research is needed to fully understand their long-term effects and optimal dosages. Choosing between NR and NMN often depends on individual health goals and preferences, as both offer valuable benefits in supporting NAD+ levels and overall well-being.
Nicotinamide riboside (NR) is a popular supplement known for its potential to boost cellular NAD+ levels, which can support various aspects of cellular health and longevity. The dosage of NR can vary depending on individual health goals and specific formulations. Typically, daily doses range from 250 mg to 300 mg. Research suggests that this amount is effective in raising NAD+ levels without significant side effects.
For individuals seeking general health benefits or age-related support, a daily dosage of 300 mg is commonly recommended. This dosage is often used in clinical studies and has been shown to enhance NAD+ levels, which may help with cellular repair and metabolic function. However, some users may start with a lower dose, such as 250 mg, to assess tolerance before increasing to the higher end of the spectrum.
It’s important to consult with a healthcare professional before starting nicotinamide riboside supplementation, especially if you have underlying health conditions or are taking other medications. Personal needs and responses can vary, so a tailored approach is often the best way to determine the most appropriate dosage for individual health goals.
Nicotinamide riboside (NR) is a form of vitamin B3, but not all forms of vitamin B3 are the same. Other forms include niacin and nicotinamide. Taking nicotinamide riboside (NR) is a unique precursor to NAD+. Nicotinamide riboside is particularly notable for its potential benefits. Taking nicotinamide riboside can help support cellular health by boosting NAD+ levels.
Nicotinamide riboside is found in small amounts in foods like milk, fish, and yeast, but the levels are very low compared to supplements. However, clinical testing has shown that supplements can provide much higher and more effective doses. Researchers are conducting more clinical testing to determine its potential benefits for various health conditions. Ongoing clinical testing will help establish the safest and most beneficial dosage for daily intake.
Studies typically suggest that doses up to 300 mg per day of endogenous nr are safe for most healthy overweight adults, though higher doses of endogenous nr have been used in research with few side effects. It is important to note that the safety of endogenous nr at higher doses continues to be evaluated, especially in healthy overweight adults. Ongoing research aims to determine the long-term effects of higher doses on healthy overweight adults and other populations.
NR chloride may be worth taking for those interested in supporting cellular energy, healthy aging, and overall metabolic health. However, more research, including molecular evaluation, is needed to fully validate its benefits. Molecular evaluation can help clarify the precise mechanisms through which NR chloride impacts cellular functions. Continued studies and molecular evaluation are essential to understand its potential fully with NR chloride.
Nicotinamide riboside is primarily known for boosting NAD+ levels, which can enhance cellular repair, improve mitochondrial function, support cognitive health, and potentially slow aging processes. The benefits have been explored in double-blind, placebo-controlled studies, demonstrating its potential. Further double-blind, placebo-controlled research could help validate its effectiveness in slowing aging. Overall, double-blind, placebo-controlled trials are essential for confirming these effects.
Popular brands include Tru Niagen and Elysium Basis, both of which offer high-quality, third-party tested NR supplements. Both products have been evaluated in placebo-controlled clinical trials, ensuring their effectiveness and safety. In fact, when considering NR supplements, it’s crucial to choose brands that have undergone rigorous testing in placebo-controlled clinical trials. Tru Niagen and Elysium Basis are both known for adhering to these standards, highlighting the importance of selecting supplements that are supported by placebo-controlled clinical trials.
NAD supplements like NR are generally considered safe, but some individuals may experience mild side effects like nausea, fatigue, headaches, or high blood pressure. Long-term safety is still under study, especially for those with high blood pressure. It’s advisable to consult a healthcare provider if you have concerns about potential interactions with conditions like high blood pressure.
Taking NR could be beneficial if you are interested in supporting healthy aging, improving metabolic health, or boosting energy levels. In the field of biochemical sciences, NR is often discussed for its potential benefits in cellular energy production and longevity. However, consult with a healthcare provider to determine if it’s right for you, as the application of biochemical sciences to individual health requires personalized advice. For those involved in biochemical sciences, understanding the mechanisms of NR can be key to exploring its therapeutic potential.
Foods like milk, fish, and yeast naturally contain small amounts of nicotinamide riboside. A placebo-controlled clinical trial might examine the benefits of these foods in boosting NAD+ levels and their potential impact on blood lipids. Understanding the effects through a placebo-controlled clinical trial could be crucial in determining their role in health, particularly concerning blood lipids. Finally, more research, especially via a placebo-controlled clinical trial, could further validate these findings and their implications for blood lipids.
Nicotinamide riboside chloride is used as a supplement to increase NAD+ levels, supporting cellular energy, metabolism, and potentially healthy aging. Being orally bioavailable, nicotinamide riboside chloride influences biosynthetic pathways to help enhance these processes. The compound, which is orally bioavailable, plays a role in various biosynthetic pathways, contributing to overall cellular health and longevity.
Research shows that nicotinamide riboside, a dietary supplement, effectively increases NAD+ levels, and early studies suggest benefits in areas like nature metabolism, cognitive function, and blood nad lipids. However, more long-term studies on this dietary supplement and its impact on nature metabolism and blood nad lipids are needed. Overall, the potential of this dietary supplement in relation to nature metabolism, blood nad, and blood lipids remains promising but requires further investigation.
No, NAD is not vitamin B3; it’s a molecule derived from vitamin B3 (including forms like NR) that plays a crucial role in energy production and cellular processes. The human oral availability of NAD precursors, such as NR, is essential for their clinical efficacy in boosting NAD levels. Understanding the human oral availability of these supplements is key to evaluating their clinical efficacy and potential benefits. Moreover, research continues to explore how enhancing NAD through human oral availability could impact health and aging, contributing to our understanding of their clinical efficacy.
No, nicotinic acid riboside and NMN (nicotinamide mononucleotide) are different compounds, though both are precursors to NAD+. The observed adverse effect level of nicotinic acid riboside and NMN may vary due to their distinct properties, especially when studied in animal models. Understanding the observed adverse effect level for each nicotinic acid riboside through research involving animal models can help in determining safe usage guidelines. Animal models are essential for gaining insights into the potential risks and benefits of these compounds before human application.
NR’s benefits include increasing NAD+ levels and related metabolites, supporting cellular energy production, improving mitochondrial function, promoting healthy aging, and potentially enhancing cognitive health. By boosting NAD+ levels and related metabolites, NR may also contribute to maintaining healthy systolic blood pressure. Furthermore, improving mitochondrial function with NR and related metabolites can help in managing systolic blood pressure levels effectively.
Yes, NR is generally considered safe for most people when taken at recommended doses, though consulting with a healthcare provider is advised. Hematopoietic stem cell regeneration can be an important consideration in discussions about overall health. It’s also beneficial to explore how hematopoietic stem cell regeneration might interact with NR supplementation. A placebo-controlled clinical trial could provide valuable insights into these interactions. Additionally, another placebo-controlled clinical trial focusing on hematopoietic stem cell regeneration and NR supplementation might offer clearer understanding. Evaluating results from a placebo-controlled clinical trial would help guide recommendations on NR’s safety and efficacy.
Individuals with certain health conditions, those taking specific medications, or those with allergies to niacin-related compounds should consult with a doctor before taking nicotinamide or NR, as highlighted in six clinical trials. This is particularly important for those who have conditions affecting peripheral blood mononuclear cells, which have been studied in six clinical trials. Additionally, since peripheral blood mononuclear cells can be influenced by various treatments, it is crucial to discuss any potential interactions with your healthcare provider, as noted in six clinical trials. Ensuring that peripheral blood mononuclear cells are not adversely affected will help in managing overall health effectively.
NR powder is used as a supplement to increase NAD+ levels, potentially benefiting energy metabolism, cellular health, and aging. Dietary intake of NR powder can play a role in improving NAD+ levels, which helps mitigate the effects of metabolic stress on cellular functions. This dietary intake can be particularly beneficial in reducing the impact of metabolic stress associated with aging and other health conditions. By focusing on proper dietary intake, users can enhance the effectiveness of NR powder in supporting overall cellular health.
Both nutritional supplement nicotinamide riboside (NR) and NMN are effective at increasing NAD+ levels, but nutritional supplement nicotinamide riboside (NR) has more research supporting its safety and effectiveness in humans. The choice often depends on individual preferences and goals, and nutritional supplement nicotinamide riboside (NR) is frequently recommended for those seeking a well-researched option. Additionally, nutritional supplement nicotinamide riboside (NR) offers a viable alternative to NMN, especially for those interested in the benefits of nutritional supplement nicotinamide riboside (NR) based on current evidence.
Both NMN and NR are effective nutritional supplements in the field of human nutrition, but NR has better stability and more clinical data backing its use as a nutritional supplement for age-associated diseases. Some prefer NR as a nutritional supplement in human nutrition due to its easier absorption, which is particularly beneficial for managing age-associated diseases. Overall, NR’s proven effectiveness and stability make it a preferable choice in the context of human nutrition and age-associated diseases.
David Sinclair advocates for NMN because he believes it is more directly converted into NAD+ within skeletal muscle cells and other cells, though both NMN and NR have shown efficacy as nutritional supplements. Sinclair’s preference for NMN as a nutritional supplement stems from its potential advantages over other options in skeletal muscle cells. The debate continues among experts about the effectiveness of different nutritional supplements like NMN and NR in improving skeletal muscle cells’ function. Nevertheless, Sinclair’s focus on NMN highlights the growing interest in nutritional supplements for enhancing cellular function.
The controversy around NMN involves regulatory issues, patent disputes, and debates over nicotinic acid’s bioavailability compared to NR, as well as the varying quality among different NMN products. Nicotinic acid plays a role in these discussions, as it is a precursor to NMN and its presence can influence NMN efficacy. The varying quality of NMN products may also reflect differences in the nicotinic acid used in their production. Additionally, regulatory challenges often involve the evaluation of nicotinic acid forms and their impact on NMN’s effectiveness. Understanding the interplay between nicotinic acid and NMN is crucial in navigating these controversies.
Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502. doi: 10.1016/s0092-8674(04)00416-7. PMID: 15137942.
Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans
NAD+ is essential for life in all organisms, both as a coenzyme for oxidoreductases and as a source of ADPribosyl groups used in various reactions, including those that retard aging in experimental systems. Nicotinic acid and nicotinamide were defined as the vitamin precursors of NAD+ in Elvehjem’s classic discoveries of the 1930s. The accepted view of eukaryotic NAD+ biosynthesis, that all anabolism flows through nicotinic acid mononucleotide, was challenged experimentally and revealed that nicotinamide riboside is an unanticipated NAD+ precursor in yeast. Nicotinamide riboside kinases from yeast and humans essential for this pathway were identified and found to be highly specific for phosphorylation of nicotinamide riboside and the cancer drug tiazofurin. Nicotinamide riboside was discovered as a nutrient in milk, suggesting that nicotinamide riboside is a useful compound for elevation of NAD+ levels in humans.
You can read the full article at https://www.cell.com/cell/fulltext/S0092-8674(04)00416-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867404004167%3Fshowall%3Dtrue.
Yang, N. C., Cho, Y. H., & Lee, I. (2019). The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirtuin-Saturating Concentrations. International journal of molecular sciences, 21(1), 142. https://doi.org/10.3390/ijms21010142.
The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirtuin-Saturating Concentrations
Calorie restriction extends lifespan by increasing NAD+ and activating sirtuins. Nicotinic acid (NA) can be metabolized to NAD+, but its potential as a calorie restriction mimetic (CRM) is unclear. This study showed NA increases NAD+ in both human Hs68 cells and C. elegans, but extends lifespan only in C. elegans. Lifespan extension by NA depends on NAD+ levels being below the sirtuin-saturating concentration, indicating that NA’s CRM potential is limited to individuals with lower intracellular NAD+.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982340/.
Hashimoto, T., Horikawa, M., Nomura, T., & Sakamoto, K. (2010). Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16. Biogerontology, 11(1), 31–43. https://doi.org/10.1007/s10522-009-9225-3.
Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16
The NAD-dependent deacetylase sirtuin (sir2) is crucial for lifespan extension under caloric restriction, but its activation mechanism is unclear. In nematodes, caloric restriction requires the sir2 ortholog sir-2.1 for lifespan extension, independently of DAF-16. However, NAD-induced lifespan extension requires both sir-2.1 and DAF-16, suggesting different pathways for caloric restriction and NAD. NAD increases expression of daf-16 target gene sod-3, oxidative-stress resistance, and adiposity, indicating that NAD activates DAF-16 through a distinct insulin-like signaling pathway.
You can read the full article at https://link.springer.com/article/10.1007/s10522-009-9225-3.
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell metabolism, 27(3), 529–547. https://doi.org/10.1016/j.cmet.2018.02.011.
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Nicotinamide adenine dinucleotide (NAD) is essential for redox reactions and acts as a signaling molecule, modulating enzymes involved in key processes like energy metabolism and cell survival. NAD+ levels decline with age, leading to metabolic changes and increased disease risk. Restoring NAD+ in older or diseased animals can improve health and extend lifespan, driving the search for safe NAD-boosting molecules to enhance overall resilience and healthy lifespan in humans.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515/.
Yaku, K., Okabe, K., & Nakagawa, T. (2018). NAD metabolism: Implications in aging and longevity. Ageing research reviews, 47, 1–17. https://doi.org/10.1016/j.arr.2018.05.006.
NAD metabolism: Implications in aging and longevity
Nicotinamide adenine dinucleotide (NAD) is crucial for metabolism, protein modification, and DNA repair, with its levels regulated by a balance between production and degradation. NAD levels decline with age, contributing to aging-associated diseases like metabolic and neurodegenerative disorders, and cancers. Enhancing NAD metabolism, including through dietary supplementation, can prevent this decline and has shown beneficial effects against aging and related diseases. Studies indicate that activating NAD metabolism genetically or nutritionally can extend lifespan in various organisms, highlighting its role in aging and longevity, despite ongoing research challenges.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S1568163718300060?via%3Dihub.
Palacios, J. A., Herranz, D., De Bonis, M. L., Velasco, S., Serrano, M., & Blasco, M. A. (2010). SIRT1 contributes to telomere maintenance and augments global homologous recombination. The Journal of cell biology, 191(7), 1299–1313. https://doi.org/10.1083/jcb.201005160.
SIRT1 contributes to telomere maintenance and augments global homologous recombination
Yeast Sir2 deacetylase, part of the SIR complex, is essential for telomere regulation, and its mammalian counterpart, SIRT1, plays a similar role. Studies using mouse models show that SIRT1 positively regulates telomere length and reduces age-related telomere shortening, dependent on telomerase activity. SIRT1 also interacts with telomeric repeats and enhances homologous recombination across the genome. These findings connect SIRT1 to telomere biology and DNA repair, offering insights into its role in protecting against DNA damage and age-related diseases.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010065/.
Monaghan, P., & Haussmann, M. F. (2006). Do telomere dynamics link lifestyle and lifespan?. Trends in ecology & evolution, 21(1), 47–53. https://doi.org/10.1016/j.tree.2005.11.007.
Do telomere dynamics link lifestyle and lifespan?
Understanding the variation in lifespan among species involves studying the rate and causes of aging, linking evolutionary ecology to cell biology and gerontology. Telomere erosion, a key aging process, is influenced by various factors. This discussion explores telomere regulation and its relationship to lifestyle and lifespan.
You can read the abstract of the article at https://www.cell.com/trends/ecology-evolution/abstract/S0169-5347(05)00371-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS016953470500371X%3Fshowall%3Dtrue.
Monaghan P. (2010). Telomeres and life histories: the long and the short of it. Annals of the New York Academy of Sciences, 1206, 130–142. https://doi.org/10.1111/j.1749-6632.2010.05705.x.
Telomeres and life histories: the long and the short of it
Telomeres, repetitive DNA sequences at chromosome ends, limit cell division and influence cell loss and renewal. While telomere length generally declines with age, it varies significantly within species and is of interest to evolutionary biologists due to its impact on lifespan. Most research focuses on human disease, but there’s growing interest in telomere dynamics in healthy organisms. This field explores how variations in telomere loss relate to life history evolution and trade-offs, and how telomere length might indicate aging and biological state.
You can read the abstract of the article at https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05705.x.
Wang, Y., Oxer, D., & Hekimi, S. (2015). Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis. Nature communications, 6, 6393. https://doi.org/10.1038/ncomms7393.
Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis
A mouse model with controllable ubiquinone (UQ) biosynthesis shows that global UQ loss leads to gradual mitochondrial dysfunction, disease, and shortened lifespan, but does not act as an antioxidant in vivo. Surprisingly, vital organs tolerate lower-than-expected UQ levels for electron transport. Partial UQ restoration reverses severe disease and lifespan shortening, suggesting that aging-related degenerative phenotypes are not secondary to gradual mitochondrial dysfunction.
You can read the abstract of the article at https://www.nature.com/articles/ncomms7393.
Lanza, I. R., & Nair, K. S. (2010). Mitochondrial function as a determinant of life span. Pflugers Archiv: European journal of physiology, 459(2), 277–289. https://doi.org/10.1007/s00424-009-0724-5.
Mitochondrial function as a determinant of life span
Human life expectancy has increased due to advancements in nutrition, vaccination, and medical treatments, while maximal life span has remained mostly unchanged. Caloric restriction (CR) has shown to increase maximal life span in animals through improved mitochondrial function, but this is impractical for humans. Physical activity promises to enhance healthy life expectancy by preserving mitochondrial function, though its effect on maximal life span is unclear. Age-related declines in mitochondrial content and function are linked to reduced physical function and life span regulation. Aerobic exercise and a healthy diet may extend life expectancy by maintaining mitochondrial health.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801852/.
Sun, C., Wang, K., Stock, A. J., Gong, Y., Demarest, T. G., Yang, B., Giri, N., Harrington, L., Alter, B. P., Savage, S. A., Bohr, V. A., & Liu, Y. (2020). Re-equilibration of imbalanced NAD metabolism ameliorates the impact of telomere dysfunction. The EMBO journal, 39(21), e103420. https://doi.org/10.15252/embj.2019103420.
Re-equilibration of imbalanced NAD metabolism ameliorates the impact of telomere dysfunction
Short telomeres in telomere biology disorders, such as dyskeratosis congenita (DC), result in lower NAD levels and an imbalance in the NAD metabolome. This affects various biological pathways, leading to telomere damage, mitochondrial issues, and cellular senescence. Supplementing with nicotinamide riboside and inhibiting CD38 can improve NAD homeostasis, alleviating these issues in DC fibroblasts. This highlights the critical role of NAD dysregulation in telomere-related diseases and its potential for therapeutic interventions.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604620/.
Belenky, P., Racette, F. G., Bogan, K. L., McClure, J. M., Smith, J. S., & Brenner, C. (2007). Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell, 129(3), 473–484. https://doi.org/10.1016/j.cell.2007.03.024.
Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+
Exogenous nicotinamide riboside, a newly discovered NAD(+) precursor, extends lifespan in yeast without calorie restriction by promoting Sir2-dependent functions through increased NAD(+) synthesis via two pathways: the Nrk1 pathway and the Urh1/Pnp1/Meu1 pathway. This enhances gene silencing and recombination repression, demonstrating that nicotinamide riboside elevates NAD(+) levels similarly to calorie restriction.
You can read the full article at https://www.cell.com/cell/fulltext/S0092-8674(07)00390-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS009286740700390X%3Fshowall%3Dtrue.
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., Schoonjans, K., Menzies, K. J., & Auwerx, J. (2016). NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science (New York, N.Y.), 352(6292), 1436–1443. https://doi.org/10.1126/science.aaf2693.
NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice
Nicotinamide riboside (NR), a precursor of NAD(+), rejuvenates muscle stem cells (MuSCs) in aged mice by enhancing mitochondrial activity and the unfolded protein response, leading to increased prohibitin protein synthesis. NR also prevents MuSC senescence in a muscular dystrophy mouse model, delays senescence of neural and melanocyte stem cells, and extends mouse lifespan. Maintaining cellular NAD(+) levels may reprogram dysfunctional stem cells and improve lifespan in mammals.
You can read the full article at https://www.science.org/doi/10.1126/science.aaf2693?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A. A., & Auwerx, J. (2012). The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838–847. https://doi.org/10.1016/j.cmet.2012.04.022.
The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity
Nicotinamide riboside (NR), a precursor of NAD(+), rejuvenates muscle stem cells (MuSCs) in aged mice by enhancing mitochondrial activity and the unfolded protein response, leading to increased prohibitin protein synthesis. NR also prevents MuSC senescence in a muscular dystrophy mouse model, delays senescence of neural and melanocyte stem cells, and extends mouse lifespan. Maintaining cellular NAD(+) levels may reprogram dysfunctional stem cells and improve lifespan in mammals.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616313/.
Ryu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A., Mouchiroud, L., Marshall, P. L., Campbell, M. D., Ali, A. S., Knowels, G. M., Bellemin, S., Iyer, S. R., Wang, X., Gariani, K., Sauve, A. A., Cantó, C., Conley, K. E., Walter, L., Lovering, R. M., Chin, E. R., … Auwerx, J. (2016). NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Science translational medicine, 8(361), 361ra139. https://doi.org/10.1126/scitranslmed.aaf5504.
NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation
Neuromuscular diseases, often caused by inherited mutations, lead to progressive muscle weakness and degeneration. In normal mice, mRNA related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and NAD+ synthesis correlates with muscle health. In patients with Duchenne muscular dystrophy (DMD) and other muscle diseases, the transcriptomes are enriched for NAD+-consuming enzymes (PARPs and NNMT) associated with inflammation. In the mdx mouse model of DMD, NAD+ levels are reduced, and PARP activity is increased. Dietary nicotinamide riboside supplementation restores NAD+ levels, improving muscle function and reducing pathology through enhanced mitochondrial function and reduced inflammation and fibrosis. These findings suggest NAD+ replenishment could benefit patients with muscular dystrophies.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535761/.
Sun, N., Youle, R. J., & Finkel, T. (2016). The Mitochondrial Basis of Aging. Molecular cell, 61(5), 654–666. https://doi.org/10.1016/j.molcel.2016.01.028.
The Mitochondrial Basis of Aging
A decline in mitochondrial quality and activity is linked to normal aging and age-related diseases. This review discusses how impaired mitochondrial function contributes to aging through cellular senescence, chronic inflammation, and reduced stem cell activity. It highlights the mitochondrial unfolded protein response and mitophagy as key regulatory pathways that may influence longevity. Improving mitochondrial quality and function could have broad beneficial effects on aging and related diseases.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779179/.
Khan, N. A., Auranen, M., Paetau, I., Pirinen, E., Euro, L., Forsström, S., Pasila, L., Velagapudi, V., Carroll, C. J., Auwerx, J., & Suomalainen, A. (2014). Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3. EMBO molecular medicine, 6(6), 721–731. https://doi.org/10.1002/emmm.201403943.
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
Nutrient availability regulates life and reproduce
tion, with cellular signaling networks adapting organisms to fasting. Mitochondrial respiratory chain disease affects NADH utilization and ATP production. Nicotinamide riboside (NR), a vitamin B3 and NAD(+) precursor, boosts NAD(+) levels and induces mitochondrial biogenesis. In mitochondrial myopathy mice, NR delayed disease progression by inducing mitochondrial biogenesis, preventing abnormalities, and stimulating the mitochondrial unfolded protein response, suggesting NR as a promising treatment for mitochondrial myopathy.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203351/.
Brown, K. D., Maqsood, S., Huang, J. Y., Pan, Y., Harkcom, W., Li, W., Sauve, A., Verdin, E., & Jaffrey, S. R. (2014). Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell metabolism, 20(6), 1059–1068. https://doi.org/10.1016/j.cmet.2014.11.003.
Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss
Intense noise exposure causes hearing loss by damaging spiral ganglia neurites in the cochlea. Nicotinamide riboside (NR), a precursor to NAD(+), can increase cochlear NAD(+) levels and prevent noise-induced hearing loss (NIHL) and neurite degeneration when administered even after noise exposure. This protective effect is mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, as SIRT3-overexpressing mice resist NIHL, and SIRT3 deletion nullifies NR’s protective effects, revealing an NR-activated NAD(+)-SIRT3 pathway that mitigates neurite degeneration.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940130/.
Harlan, B. A., Killoy, K. M., Pehar, M., Liu, L., Auwerx, J., & Vargas, M. R. (2020). Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models. Experimental neurology, 327, 113219. https://doi.org/10.1016/j.expneurol.2020.113219.
Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models
Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron degeneration. Enhancing NAD+ availability or increasing NAD+-dependent deacylases SIRT3 and SIRT6 in cell cultures reduces astrocyte-induced motor neuron death. In ALS mouse models, NAD+ enhancement via CD38 ablation had no survival effect, but supplementation with nicotinamide riboside (NR) delayed motor neuron degeneration, reduced neuroinflammation, altered muscle metabolism, and modestly increased survival. ALS patients showed altered NAD+ synthesis enzymes and decreased SIRT6 expression, indicating a deficit in this neuroprotective pathway. Boosting NAD+ levels with bioavailable precursors like NR shows therapeutic potential for ALS.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089832/.
Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e6. doi:10.1016/j.celrep.2019.07.043.
Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures
Nicotinamide adenine dinucleotide (NAD+) declines with age, and nicotinamide riboside (NR) supplementation has shown metabolic benefits in rodents. In a study with 12 aged men, daily NR supplementation for 21 days increased the muscle NAD+ metabolome and reduced inflammatory cytokines but did not alter mitochondrial bioenergetics. This establishes NR’s bioavailability to aged human muscle and its potential anti-inflammatory effects.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702140/.
Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., Chonchol, M., & Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature communications, 9(1), 1286. https://doi.org/10.1038/s41467-018-03421-7.
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
In a 2×6-week randomized, double-blind, placebo-controlled, crossover clinical trial, chronic supplementation with the NAD+ precursor nicotinamide riboside (NR) was found to be well-tolerated and effectively increased NAD+ metabolism in healthy middle-aged and older adults. The study suggests that NR supplementation may have potential benefits for reducing blood pressure and arterial stiffness, warranting further clinical trials to assess these effects.
You can read the abstract of the article at https://www.nature.com/articles/s41467-018-03421-7.
Frederick, D. W., Loro, E., Liu, L., Davila, A., Jr, Chellappa, K., Silverman, I. M., Quinn, W. J., 3rd, Gosai, S. J., Tichy, E. D., Davis, J. G., Mourkioti, F., Gregory, B. D., Dellinger, R. W., Redpath, P., Migaud, M. E., Nakamaru-Ogiso, E., Rabinowitz, J. D., Khurana, T. S., & Baur, J. A. (2016). Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle. Cell metabolism, 24(2), 269–282. https://doi.org/10.1016/j.cmet.2016.07.005.
Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle
Depleting the essential NAD salvage enzyme Nampt in murine skeletal muscle caused an 85% decline in NAD, leading to muscle fiber degeneration, loss of strength, and endurance. Nicotinamide riboside supplementation quickly restored muscle function and mass, despite modest NAD increases. Lifelong Nampt overexpression maintained muscle NAD levels and exercise capacity in aged mice, highlighting the importance of NAD homeostasis in muscle health.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985182/.
Sun, P., Qie, S., & Pan, B. (2022). Nicotinamide Riboside will Play an Important Role in Anti-aging Therapy in Humans, Especially in the Face Skin Anti-aging Treatment. Aesthetic plastic surgery, 46(Suppl 1), 192–194. https://doi.org/10.1007/s00266-021-02335-y.
Dolopikou, C. F., Kourtzidis, I. A., Margaritelis, N. V., Vrabas, I. S., Koidou, I., Kyparos, A., Theodorou, A. A., Paschalis, V., & Nikolaidis, M. G. (2020). Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. European journal of nutrition, 59(2), 505–515. https://doi.org/10.1007/s00394-019-01919-4.
Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study
A study investigated the effect of nicotinamide riboside (NR) supplementation on redox homeostasis and physical performance in young and old men. While young individuals showed no significant changes, older individuals, who initially had lower NAD(P)H levels and higher oxidative stress, experienced increased NAD(P)H levels, reduced oxidative stress, and improved muscle performance after NR supplementation. The findings suggest that NR supplementation may benefit older adults with antioxidant deficiencies.
You can read the abstract of the article at https://link.springer.com/article/10.1007/s00394-019-01919-4.
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A. A., & Auwerx, J. (2012). The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838–847. https://doi.org/10.1016/j.cmet.2012.04.022.
The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity
As a rate-limiting cosubstrate for sirtuin enzymes, NAD(+) modulation can regulate sirtuin function and oxidative metabolism. Decreasing NAD(+) consumption by PARP-1 or CD38 increases NAD(+) availability, activating SIRT1 and protecting against metabolic disease. Supplementing with nicotinamide riboside (NR), a natural NAD(+) precursor, raises NAD(+) levels, activates SIRT1 and SIRT3, enhances oxidative metabolism, and protects against diet-induced metabolic issues in mammalian cells and mice. This suggests NR could be a useful supplement for metabolic and age-related disorders linked to mitochondrial dysfunction.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616313/.
Schaefer, P. M., Huang, J., Butic, A., Perry, C., Yardeni, T., Tan, W., Morrow, R., Baur, J. A., & Wallace, D. C. (2022). Nicotinamide riboside alleviates exercise intolerance in ANT1-deficient mice. Molecular metabolism, 64, 101560. https://doi.org/10.1016/j.molmet.2022.101560.
Nicotinamide riboside alleviates exercise intolerance in ANT1-deficient mice
ANT1-deficiency in mice, characterized by exercise intolerance and muscle weakness, is linked to impaired skeletal muscle mitochondrial respiration and reduced complex I activity. This results in NAD+ depletion during exercise, stalling the TCA cycle and mitochondrial function. Supplementing ANT1-deficient mice with nicotinamide riboside increases NAD+ levels, improving exercise capacity and mitochondrial respiration, suggesting NAD+-stimulating compounds as potential therapies for mitochondrial myopathies.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411682A.
Pham, T. X., Bae, M., Kim, M. B., Lee, Y., Hu, S., Kang, H., Park, Y. K., & Lee, J. Y. (2019). Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis. Biochimica et biophysica acta. Molecular basis of disease, 1865(9), 2451–2463. https://doi.org/10.1016/j.bbadis.2019.06.009.
Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosisNicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis
Nicotinamide riboside (NR) supplementation in a diet-induced mouse model of liver fibrosis significantly reduced liver collagen accumulation and hepatic stellate cell (HSC) activation, though it did not affect liver steatosis, inflammation, or serum alanine aminotransferase levels. NR also increased energy expenditure by upregulating β-oxidation in skeletal muscle and brown adipose tissue, indicating its potential as a preventative treatment for human liver fibrosis.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614025/.
Fluharty, N. T., & Brenner, C. (2020). Fat mobilization without weight loss is a potentially rapid response to nicotinamide riboside in obese people: it’s time to test with exercise. The American journal of clinical nutrition, 112(2), 243–244. https://doi.org/10.1093/ajcn/nqaa109.
Fat mobilization without weight loss is a potentially rapid response to nicotinamide riboside in obese people: it’s time to test with exercise
Nicotinamide riboside (NR), a precursor of NAD+, has been shown to reduce weight gain and improve metabolic parameters in high-fat diet (HFD) mouse models by restoring the NAD metabolome, particularly NADP+ and NADPH, which are crucial for biosynthesis and oxidative stress control. While NR’s benefits in mice include lower hepatic steatosis, improved glycemic control, and preserved nerve function, the exact mechanisms remain unclear, and it is uncertain whether these effects can be replicated in human obesity treatments. Despite this, the established safety of NR has spurred human trials to explore its potential as an obesity intervention.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398765/.
de Castro, J. M., Assumpção, J., Stein, D. J., Toledo, R. S., da Silva, L. S., Caumo, W., Carraro, C. C., da Rosa Araujo, A. S., & Torres, I. (2020). Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction. Life sciences, 263, 118596. https://doi.org/10.1016/j.lfs.2020.118596.
Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction
The study investigated the effects of nicotinamide riboside (NR), alone and combined with caloric restriction (CR), on obesity and heart disease in rats fed a cafeteria diet. NR alone reduced body weight gain, adiposity, and improved insulin resistance and cardiometabolic factors, while also enhancing cardiac antioxidant capacity and reducing pro-oxidant enzymes. Combined with CR, NR further improved these parameters. However, NR treatment induced hyperglycemia, hypertriglyceridemia, and elevated TBARS levels in the heart, suggesting state-dependent adverse effects. This is the first study to show NR’s positive modulation of cardiac oxidative stress in an obesity model, highlighting its potential anti-obesity and cardiometabolic benefits.
You can read the full article at https://www.sciencedirect.com/science/article/pii/S0024320520313497?via%3Dihub.
Lozada-Fernández, V. V., deLeon, O., Kellogg, S. L., Saravia, F. L., Hadiono, M. A., Atkinson, S. N., Grobe, J. L., & Kirby, J. R. (2022). Nicotinamide Riboside-Conditioned Microbiota Deflects High-Fat Diet-Induced Weight Gain in Mice. mSystems, 7(1), e0023021. https://doi.org/10.1128/msystems.00230-21.
Nicotinamide Riboside-Conditioned Microbiota Deflects High-Fat Diet-Induced Weight Gain in Mice
The study examines how nicotinamide riboside (NR), a vitamin B3 derivative and NAD+ precursor, affects the gut microbiome and its role in weight management for diet-induced obesity. NR supplementation in mice fed a high-fat diet reduced weight gain and increased energy expenditure. The study found that NR alters gut microbial composition, enriching butyrate-producing Firmicutes. Fecal material transfer (FMT) from NR-treated mice to naive mice also deflected weight gain, suggesting that microbial factors contribute to NR’s benefits. These findings highlight NR’s potential for treating obesity and type 2 diabetes by modifying the gut microbiome, aiding the development of precision medicine.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788325/.
de Castro, J. M., Stein, D. J., Medeiros, H. R., de Oliveira, C., & Torres, I. (2021). Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation. Frontiers in nutrition, 8, 648893. https://doi.org/10.3389/fnut.2021.648893.
Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation
This study investigates the effects of calorie restriction (CR) and nicotinamide riboside (NR) supplementation on skeletal muscle tissue (SMT) and neuroinflammation in obese rats. Obese rats, induced by a cafeteria diet, experienced muscle wasting and increased hypothalamic TNF-α levels under CR. NR supplementation, whether alone or with CR, enhanced weight loss, increased SMT relative weight, and reduced hypothalamic TNF-α levels in CR rats. These findings suggest that NR can mitigate muscle loss and neuroinflammation associated with CR in obesity, highlighting its potential as an adjuvant in weight loss treatments.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475757/.
Kim, M. B., Pham, T. X., vanLuling, M., Kostour, V., Kang, H., Corvino, O., Jang, H., Odell, W., Bae, M., Park, Y. K., & Lee, J. Y. (2022). Nicotinamide riboside supplementation exerts an anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice. The Journal of nutritional biochemistry, 107, 109058. https://doi.org/10.1016/j.jnutbio.2022.109058.
Nicotinamide riboside supplementation exerts an anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice
Nicotinamide riboside (NR), a precursor of NAD+, was tested for its effects on obesity-induced inflammation and fibrosis in the liver and white adipose tissue (WAT) of female mice. While NR had minor effects on young female mice, it significantly reduced body weight gain, fat mass, glucose intolerance, and serum cholesterol in older females. NR decreased inflammation and fibrosis in gonadal WAT and increased metabolic rates, physical activity, and energy expenditure in older females, indicating an anti-obesity effect and prevention of inflammation and fibrosis in older, but not younger, female mice with diet-induced obesity.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0955286322001292?via%3Dihub.
Ear, P. H., Chadda, A., Gumusoglu, S. B., Schmidt, M. S., Vogeler, S., Malicoat, J., Kadel, J., Moore, M. M., Migaud, M. E., Stevens, H. E., & Brenner, C. (2019). Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring. Cell reports, 26(4), 969–983.e4. https://doi.org/10.1016/j.celrep.2019.01.007.
Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring
Metabolic stress dysregulates the NAD metabolome, but nicotinamide riboside (NR) can restore it, providing resistance. Postpartum mothers show depressed liver NAD but increased NAD metabolites in blood to support mammary NAD+. NR supplementation in postpartum mothers enhances lactation, nursing behaviors, and nutrient transmission to milk, benefiting offspring with improved glycemic control, size, and synaptic pruning. Adult offspring of NR-supplemented mothers retain advantages in physical performance, anti-anxiety, spatial memory, and hippocampal neurogenesis, indicating lasting benefits from maternal micronutrition during nursing.
You can read the full article at https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30015-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719300154%3Fshowall%3Dtrue.
Shi, W., Hegeman, M. A., van Dartel, D., Tang, J., Suarez, M., Swarts, H., van der Hee, B., Arola, L., & Keijer, J. (2017). Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet. Molecular nutrition & food research, 61(8), 1600878. https://doi.org/10.1002/mnfr.201600878.
Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet
Nicotinamide riboside (NR) supplementation enhances metabolic health and flexibility, particularly at a dose of 30 mg/kg diet, in nine-week-old male mice on a mildly obesogenic diet. This dose improves the switch between carbohydrate and fatty acid oxidation and upregulates key genes in white adipose tissue related to adipogenesis and antioxidant defense, indicating it is the most beneficial for maintaining metabolic health.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573990/.
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A. A., & Auwerx, J. (2012). The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838–847. https://doi.org/10.1016/j.cmet.2012.04.022.
The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity
Nicotinamide riboside (NR) supplementation increases NAD(+) levels and activates SIRT1 and SIRT3, enhancing oxidative metabolism and protecting against high-fat diet-induced metabolic abnormalities in mammalian cells and mouse tissues. These findings suggest that NR, a natural NAD(+) precursor, could serve as a nutritional supplement to improve metabolic and age-related disorders linked to mitochondrial dysfunction.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616313/.
Crisol, B. M., Veiga, C. B., Lenhare, L., Braga, R. R., Silva, V., da Silva, A., Cintra, D. E., Moura, L. P., Pauli, J. R., & Ropelle, E. R. (2018). Nicotinamide riboside induces a thermogenic response in lean mice. Life sciences, 211, 1–7. https://doi.org/10.1016/j.lfs.2018.09.015.
Nicotinamide riboside induces a thermogenic response in lean mice
Nicotinamide Riboside (NR) supplementation increases NAD+ levels and induces thermogenic response in lean mice by enhancing brown adipose tissue (BAT) metabolism. NR supplementation reduced visceral fat, increased body temperature, and elevated UCP1 protein and Pgc1α mRNA levels in BAT. These effects suggest that NR positively affects glucose and lipid homeostasis and supports thermogenesis, contributing to metabolic health.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0024320518305605?via%3Dihub.
Gomes, A. P., Price, N. L., Ling, A. J., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., Mercken, E. M., Palmeira, C. M., de Cabo, R., Rolo, A. P., Turner, N., Bell, E. L., & Sinclair, D. A. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624–1638. https://doi.org/10.1016/j.cell.2013.11.037.
Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging
During aging, there is a specific loss of mitochondrial-encoded, but not nuclear-encoded, oxidative phosphorylation (OXPHOS) subunits, which leads to mitochondrial dysfunction. This is caused by a decline in nuclear NAD(+) and the accumulation of HIF-1α under normoxic conditions, disrupting nuclear-mitochondrial communication through a PGC-1α/β-independent pathway. Deleting SIRT1 accelerates this process, while raising NAD(+) levels in old mice restores mitochondrial function in a SIRT1-dependent manner, indicating that this decline in mitochondrial function with age is reversible.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076149/.
Goody, M. F., & Henry, C. A. (2018). A need for NAD+ in muscle development, homeostasis, and aging. Skeletal muscle, 8(1), 9. https://doi.org/10.1186/s13395-018-0154-1.
A need for NAD+ in muscle development, homeostasis, and aging
NAD+ is crucial for skeletal muscle function, impacting metabolism, energy production, mitochondrial biogenesis, transcription, and extracellular matrix organization. It plays a significant role in muscle development, regeneration, aging, and disease, with higher NAD+ levels generally enhancing muscle health. However, the detailed mechanisms of NAD+ function across different cellular compartments remain unclear. Recent research aims to uncover these mechanisms, focusing on muscle lysosome function, calcium mobilization, and the interplay between NAD+ signaling targets, to develop precise interventions for boosting NAD+ levels and improving muscle health in both normal and disease states.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840929/#:~:text=Skeletal%20muscle%20cells%20can%20contain,is%20important%20for%20muscle%20function..
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., Yoshino, J., & Imai, S. I. (2016). Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell metabolism, 24(6), 795–806. https://doi.org/10.1016/j.cmet.2016.09.013.
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
In a 12-month study on wild-type C57BL/6N mice, oral administration of nicotinamide mononucleotide (NMN), an NAD+ precursor, significantly mitigated age-associated physiological decline. NMN enhanced NAD+ biosynthesis, suppressed age-related weight gain, boosted energy metabolism, physical activity, insulin sensitivity, and plasma lipid profiles, and improved eye function without toxicity. NMN also prevented age-related gene expression changes in key metabolic organs, enhancing mitochondrial oxidative metabolism and addressing mitonuclear protein imbalance in skeletal muscle. These findings suggest the potential of NAD+ intermediates as effective anti-aging interventions in humans.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668137/.
Remie, C., Roumans, K., Moonen, M., Connell, N. J., Havekes, B., Mevenkamp, J., Lindeboom, L., de Wit, V., van de Weijer, T., Aarts, S., Lutgens, E., Schomakers, B. V., Elfrink, H. L., Zapata-Pérez, R., Houtkooper, R. H., Auwerx, J., Hoeks, J., Schrauwen-Hinderling, V. B., Phielix, E., & Schrauwen, P. (2020). Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. The American journal of clinical nutrition, 112(2), 413–426. https://doi.org/10.1093/ajcn/nqaa072.
Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
A 6-week study on 13 overweight or obese individuals found that nicotinamide riboside (NR) supplementation (1000 mg/day) increased NAD+ metabolites and acetylcarnitine concentrations in skeletal muscle, as well as body fat-free mass and sleeping metabolic rate. However, it had no significant effects on insulin sensitivity, mitochondrial function, lipid accumulation, cardiac function, blood pressure, inflammation markers, or overall energy metabolism. The trial was registered at clinicaltrials.gov as NCT02835664.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398770/.
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019). NAD+ in Brain Aging and Neurodegenerative Disorders. Cell metabolism, 30(4), 630–655. https://doi.org/10.1016/j.cmet.2019.09.001.
NAD+ in Brain Aging and Neurodegenerative Disorders
NAD+ is essential for cellular energy, genomic stability, mitochondrial function, stress response, and cell survival, influencing synaptic plasticity and neuronal stress resistance. Recent studies highlight NAD+’s role in helping neurons adapt to stress and counteract neurodegenerative diseases like Alzheimer’s, Parkinson’s, Huntington’s, and ALS. Understanding NAD+’s mechanisms in neuronal resilience could lead to new treatments for neurological disorders and promote healthy brain aging.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787556/.
Mao, K., & Zhang, G. (2022). The role of PARP1 in neurodegenerative diseases and aging. The FEBS journal, 289(8), 2013–2024. https://doi.org/10.1111/febs.15716.
The role of PARP1 in neurodegenerative diseases and aging
Neurodegenerative diseases like Alzheimer’s and Parkinson’s, characterized by memory loss and motor impairment, are closely linked to aging and pose a significant socioeconomic burden. Traditionally associated with mitochondrial dysfunction and DNA damage, recent research highlights the roles of neuroinflammation, autophagy dysregulation, and SIRT1 inactivation in their pathogenesis. Poly (ADP-ribose)-polymerase-1 (PARP1) has emerged as a key player, connecting stress signals from inflammation and autophagy dysregulation. This review summarizes recent findings on PARP1’s involvement in neurodegenerative diseases and aging and explores potential treatments targeting PARP1.
You can read the full article at https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15716.
Ying W. (2007). NAD+ and NADH in brain functions, brain diseases and brain aging. Frontiers in bioscience: a journal and virtual library, 12, 1863–1888. https://doi.org/10.2741/2194.
NAD+ and NADH in brain functions, brain diseases and brain aging
NAD+ and NADH are crucial regulators of various biological processes, including calcium homeostasis, energy metabolism, mitochondrial functions, cell death, and aging. They significantly influence calcium homeostasis and brain functions, such as neurotransmission, learning, and memory. NAD+ and NADH are also implicated in brain aging and various brain diseases, with evidence suggesting their potential to decrease ischemic brain injury. As fundamental mediators of brain functions and aging, further research into NAD+ and NADH may uncover key mechanisms underlying these processes.
You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/17127427/.
Available from https://www.pnas.org/content/115/8/E1876.
NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency
Compromised cellular bioenergetics and DNA repair contribute to Alzheimer’s disease (AD) pathogenesis. In a DNA repair-deficient mouse model (3xTgAD/Polβ+/−), which exacerbates AD features such as phosphorylated Tau (pTau) pathologies, synaptic dysfunction, neuronal death, and cognitive impairment, a reduced cerebral NAD+/NADH ratio was observed. Nicotinamide riboside (NR) treatment normalized this ratio, reduced pTau pathology, decreased DNA damage, neuroinflammation, and apoptosis, increased SIRT3 activity, and improved cognitive function and hippocampal synaptic plasticity. These findings suggest that NAD+ depletion is upstream of several AD pathologies, indicating the therapeutic potential of boosting NAD+ levels.
You can read the full article at https://www.pnas.org/content/115/8/E1876.
Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2617713/.
Nicotinamide Restores Cognition in Alzheimer’s Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau
Memory loss in Alzheimer’s disease (AD) could be mitigated by preventive strategies, such as histone deacetylase (HDAC) inhibitors that enhance memory and synaptic plasticity. In 3xTg-AD mice, nicotinamide, a sirtuin inhibitor, was found to restore cognitive deficits by selectively reducing phospho-Thr231 tau, associated with microtubule depolymerization, and increasing acetylated α-tubulin and MAP2c, linked to microtubule stability. The reduction of phospho-Thr231 tau also decreased monoubiquitin-conjugated tau, suggesting improved tau clearance. These findings suggest that nicotinamide may be a safe treatment for AD and other tauopathies, highlighting the role of Thr231 phosphorylation in tau stability.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2617713/.
Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., Wang, J., Sastre, M., Ono, K., Sauve, A. A., & Pasinetti, G. M. (2013). Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiology of aging, 34(6), 1581–1588. https://doi.org/10.1016/j.neurobiolaging.2012.12.005.
Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models
Nicotinamide adenine dinucleotide (NAD+), a key coenzyme in mitochondrial electron transport, has lifespan-extending effects and reduces beta-amyloid (Aβ) toxicity in Alzheimer’s disease (AD). Nicotinamide riboside (NR), an NAD+ precursor, boosts PGC-1α expression, which regulates Aβ generation by promoting β-secretase (BACE1) degradation. In Tg2576 AD mice, dietary NR treatment significantly improved cognitive function, increased NAD+ levels in the brain, restored synaptic plasticity, and reduced Aβ production through enhanced PGC-1α-mediated BACE1 degradation. These findings suggest NR could benefit AD by mitigating cognitive decline and synaptic dysfunction.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632303/.
Braidy, N., & Liu, Y. (2020). Can nicotinamide riboside protect against cognitive impairment?. Current opinion in clinical nutrition and metabolic care, 23(6), 413–420. https://doi.org/10.1097/MCO.0000000000000691.
Can nicotinamide riboside protect against cognitive impairment?
Oral supplementation with nicotinamide riboside (NR), a precursor to NAD+, has shown clinical benefits in reducing age-related cognitive decline. In murine models of Alzheimer’s disease and dementia, NR inhibits pathological hallmarks, improves learning and memory, reduces DNA damage, neuroinflammation, and apoptosis, and enhances hippocampal synaptic plasticity. NR also maintains blood-brain barrier integrity and gut microbiota health in specific disease models. Additionally, NR modulates cognitive benefits through upregulation of PGC-1α-mediated BACE-1 ubiquitination and degradation, preventing Aβ production. It is bioavailable, well-tolerated, and has fewer adverse effects in humans compared to other NAD+ precursors.
You can read the abstract of the article at https://journals.lww.com/co-clinicalnutrition/abstract/2020/11000/can_nicotinamide_riboside_protect_against.8.aspx.
Larrick, J. W., & Mendelsohn, A. R. (2021). Modulation of cGAS-STING Pathway by Nicotinamide Riboside in Alzheimer’s Disease. Rejuvenation research, 24(5), 397–402. https://doi.org/10.1089/rej.2021.0062.
Modulation of cGAS-STING Pathway by Nicotinamide Riboside in Alzheimer’s Disease
Studies show that NAD+ levels decline with aging, contributing to hallmarks of aging like reduced mitophagy and neuroinflammation, which are significant in Alzheimer’s disease (AD). Oral nicotinamide riboside (NR), a NAD+ precursor, reduces cell senescence, DNA damage, and neuroinflammation in the AD murine model APP/PS1. NR normalizes elevated cGAS-STING signaling, a pathway linked to brain inflammation and senescence in AD, and enhances mitophagy, improving cognition and behavior in these mice. Modulating the cGAS-STING pathway through NR supplementation may benefit AD patients and other disorders with impaired mitophagy and neuroinflammation.
You can read the abstract of the article at https://www.liebertpub.com/doi/10.1089/rej.2021.0062?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed.
Xie, X., Gao, Y., Zeng, M., Wang, Y., Wei, T. F., Lu, Y. B., & Zhang, W. P. (2019). Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer’s disease model mice. Metabolic brain disease, 34(1), 353–366. https://doi.org/10.1007/s11011-018-0346-8.
Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer’s disease model mice
Nicotinamide ribose (NR), a safe NAD precursor, has shown promise in treating Alzheimer’s disease (AD) and age-related dementia by improving mitochondrial function. In a study, NR-supplemented food improved cognitive function in both APP/PS1 AD model mice and aged mice, inhibited astrocyte activation, reduced Aβ accumulation, and prevented weight gain. These results suggest that NR supplementation could prevent the progression of dementia and offer selective benefits for AD and aging.
You can read the full article at https://link.springer.com/article/10.1007/s11011-018-0346-8.
Hou, Y., Lautrup, S., Cordonnier, S., Wang, Y., Croteau, D. L., Zavala, E., Zhang, Y., Moritoh, K., O’Connell, J. F., Baptiste, B. A., Stevnsner, T. V., Mattson, M. P., & Bohr, V. A. (2018). NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proceedings of the National Academy of Sciences of the United States of America, 115(8), E1876–E1885. https://doi.org/10.1073/pnas.1718819115.
NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency
Compromised cellular bioenergetics and DNA repair are implicated in Alzheimer’s disease (AD). In a DNA repair-deficient AD mouse model, nicotinamide riboside (NR) treatment normalized impaired cerebral energy metabolism, reduced phosphorylated Tau (pTau) pathology, DNA damage, neuroinflammation, and apoptosis, while improving cognitive function and synaptic plasticity. These findings suggest that cellular NAD+ depletion plays a key role in AD pathogenesis, and enhancing NAD+ levels could be a promising therapeutic strategy for AD.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828618/.
Ryu, W. I., Shen, M., Lee, Y., Healy, R. A., Bormann, M. K., Cohen, B. M., & Sonntag, K. C. (2022). Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer’s disease. Aging cell, 21(7), e13658. https://doi.org/10.1111/acel.13658.
Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer’s disease
Nicotinamide adenine dinucleotide (NAD) declines with age, contributing to dysfunctional energy metabolism in late-onset Alzheimer’s disease (LOAD). Nicotinamide riboside (NR), a dietary NAD precursor, and caffeine, which boosts NAD production, were studied in LOAD patients and controls. NR and caffeine increased the NAD pool and transiently enhanced mitochondrial respiration or glycolysis but did not alter the inherent bioenergetic phenotype associated with LOAD. Although NR and caffeine can restore NAD availability, increasing NAD alone may not be enough to improve energy metabolism in brain aging or LOAD, but they might be beneficial in combination with other treatments for age-associated dementia.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282847/.
Lee, H. J., & Yang, S. J. (2019). Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice. International journal of molecular sciences, 20(17), 4196. https://doi.org/10.3390/ijms20174196.
Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice
This study investigated whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. Mice were fed a high-fat diet to induce hyperglycemia and then treated with NR. NR significantly reduced inflammatory markers like IL-1, TNF-α, and IL-6, decreased amyloid-β precursor protein and presenilin 1, and reduced amyloid-β in the brain. NR also improved hippocampus functions, spatial recognition memory, and locomotor activity. These results suggest that NR may help treat cognitive impairment by reducing amyloidogenesis and neuroinflammation in diabetic conditions.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747453/.
Schöndorf, D. C., Ivanyuk, D., Baden, P., Sanchez-Martinez, A., De Cicco, S., Yu, C., Giunta, I., Schwarz, L. K., Di Napoli, G., Panagiotakopoulou, V., Nestel, S., Keatinge, M., Pruszak, J., Bandmann, O., Heimrich, B., Gasser, T., Whitworth, A. J., & Deleidi, M. (2018). The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson’s Disease. Cell reports, 23(10), 2976–2988. https://doi.org/10.1016/j.celrep.2018.05.009.
The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson’s Disease
Alpers’ syndrome is a fatal early-onset neurodegenerative disorder caused by mutations in the POLG gene, essential for mitochondrial DNA replication. It leads to intractable epilepsy and developmental regression. Using induced pluripotent stem cells (iPSCs) from an Alpers’ patient, researchers created cortical organoids and neural stem cells to study the disease. These models showed mitochondrial dysfunction and neural loss similar to patient brain tissue. The NAD+ precursor nicotinamide riboside (NR) significantly improved mitochondrial function in these organoids, suggesting NR as a potential treatment for Alpers’ and similar mitochondrial diseases.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878163/.
Li, C. C., Chen, W. X., Wang, J., Xia, M., Jia, Z. C., Guo, C., Tang, X. Q., Li, M. X., Yin, Y., Liu, X., & Feng, H. (2020). Nicotinamide riboside rescues angiotensin II-induced cerebral small vessel disease in mice. CNS neuroscience & therapeutics, 26(4), 438–447. https://doi.org/10.1111/cns.13276.
Nicotinamide riboside rescues angiotensin II-induced cerebral small vessel disease in mice
Nicotinamide riboside (NR) shows promise as a treatment for hypertension-induced cerebral small vessel disease (CSVD). In a study with C57BL/6 mice infused with angiotensin (Ang), NR supplementation for 28 days improved short-term memory, protected blood-brain barrier integrity, reduced vascular and white matter damage, and decreased neuroinflammation. These findings suggest NR can alleviate CSVD-related cognitive impairment and vascular injury.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080427/.
Available from https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.044746.
Results from a pilot study: The effects of nicotinamide riboside on mild cognitive impairment
Nicotinamide riboside (NR) supplementation in older adults with mild cognitive impairment (MCI) significantly increased blood NAD(+) levels and improved brain function and physical measures over a 10-week period, though cognitive improvements were not observed. This Phase 2 trial suggests NR is well-tolerated and may help maintain brain structure and function, warranting further investigation.
You can read the abstract of the article at https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.044746.
Nkrumah-Elie, Y., Erickson, A., Idoine, R., Ishtiaq, Y., Kwon, J., Rosene, M., & Shao, A. (2022). Nicotinamide Riboside Supports Brain Health: Assessing the Evidence. Current Developments in Nutrition, 6(Suppl 1), 798. https://doi.org/10.1093/cdn/nzac064.017.
Nicotinamide Riboside Supports Brain Health: Assessing the Evidence
The review evaluates the effectiveness of nicotinamide riboside (NR) in improving brain function and neurobiology across various preclinical models, including Alzheimer’s Disease, ALS, and Autism Spectrum Disorder. NR has been shown to increase NAD+ levels, improve cognitive performance, behavior, and slow disease progression, primarily by reducing neuroinflammation, amyloid-β, and neuronal degradation, and enhancing brain-derived neurotrophic factor and sirtuins. Given its safety and efficacy in preclinical models, NR shows promise for clinical evaluation to support brain health.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194035/#:~:text=Conclusions,a%20support%20for%20brain%20health.
Cheng, Y. H., Zhao, J. H., Zong, W. F., Wei, X. J., Xu, Z., Yuan, Y., Jiang, Y. F., Luo, X., Wang, W., & Qu, W. S. (2022). Acute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury. Neurochemical research, 47(8), 2244–2253. https://doi.org/10.1007/s11064-022-03610-3.
Acute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury
In a study of mice with middle cerebral artery occlusion, acute treatment with nicotinamide riboside chloride (NRC) improved cognitive recovery, reduced hippocampal infarct volume, and decreased neuronal loss and apoptosis. NRC treatment also increased hippocampal NAD levels, activated Sirtuin-1 and AMP-activated protein kinase, and boosted ATP production, ultimately enhancing the energy supply and promoting cognitive function recovery after acute brain ischemia.
You can read the abstract of the article at https://link.springer.com/article/10.1007/s11064-022-03610-3.
Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., & Duplus, E. (2017). Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 31(12), 5440–5452. https://doi.org/10.1096/fj.201700221RR.
Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration
Nicotinamide riboside (NR), a form of vitamin B3, provides stronger neuroprotection against excitotoxicity-induced axonal degeneration (AxD) compared to NAD+. In a study, intracortical administration of NR, but not NAD+, reduced brain damage from NMDA injection. NR delayed NMDA-induced AxD more effectively than NAD+, a benefit attributed to NR’s ability to maintain intracellular NAD+ homeostasis.
You can read the abstract of the article at https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.201700221RR.
Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009). Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. The Journal of clinical investigation, 119(9), 2758–2771. https://doi.org/10.1172/JCI39162.
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
Sirtuin 3 (SIRT3), a longevity-associated protein, protects the mouse heart by inhibiting cardiac hypertrophy and interstitial fibrosis. Sirt3-deficient mice exhibited cardiac issues by 8 weeks, while Sirt3-expressing mice resisted hypertrophic stimuli. SIRT3 blocks cardiac hypertrophy by activating Foxo3a-dependent antioxidant genes, reducing reactive oxygen species (ROS) levels, and suppressing Ras activation. This downregulates the MAPK/ERK and PI3K/Akt pathways, and decreases activity of transcription and translation factors involved in cardiac hypertrophy development, thereby serving as an endogenous negative regulator of cardiac hypertrophy.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735933/.
Hafner, A. V., Dai, J., Gomes, A. P., Xiao, C. Y., Palmeira, C. M., Rosenzweig, A., & Sinclair, D. A. (2010). Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging, 2(12), 914–923. https://doi.org/10.18632/aging.100252.
Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy
Cardiac failure, a major age-related cause of death, is linked to mitochondrial dysfunction from increased mitochondrial permeability transition pore (mPTP) opening. The NAD+-dependent deacetylase SIRT3 deacetylates cyclophilin D (CypD), a regulatory component of mPTP, preventing its excessive opening. Mice lacking SIRT3 show age-dependent mitochondrial swelling, cardiac hypertrophy, and fibrosis, which cyclosporine A can rescue. These mice also display heightened sensitivity to heart stress and increased mortality. This study reveals that SIRT3 is essential for preventing mitochondrial dysfunction and cardiac hypertrophy during aging, suggesting potential pharmacological targets for cardiac and other post-mitotic tissue diseases.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034180/.
Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009). Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. The Journal of clinical investigation, 119(9), 2758–2771. https://doi.org/10.1172/JCI39162.
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
Sirtuin 3 (SIRT3), a longevity-associated protein, protects the mouse heart by inhibiting cardiac hypertrophy and interstitial fibrosis. Sirt3-deficient mice exhibited cardiac issues by 8 weeks, while Sirt3-expressing mice resisted hypertrophic stimuli. SIRT3 blocks cardiac hypertrophy by activating Foxo3a-dependent antioxidant genes, reducing reactive oxygen species (ROS) levels, and suppressing Ras activation. This downregulates the MAPK/ERK and PI3K/Akt pathways, and decreases activity of transcription and translation factors involved in cardiac hypertrophy development, thereby serving as an endogenous negative regulator of cardiac hypertrophy.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735933/.
Yuan, Y., Liang, B., Liu, X. L., Liu, W. J., Huang, B. H., Yang, S. B., Gao, Y. Z., Meng, J. S., Li, M. J., Ye, T., Wang, C. Z., Hu, X. K., & Xing, D. M. (2022). Targeting NAD+: is it a common strategy to delay heart aging?. Cell death discovery, 8(1), 230. https://doi.org/10.1038/s41420-022-01031-3.
Targeting NAD+: is it a common strategy to delay heart aging?
Heart aging significantly increases the risk of coronary heart disease and heart failure, especially with ischemia-reperfusion injury. NAD+ supplementation has shown promise in anti-aging treatments, but a comprehensive review of its role in cardiac aging has been lacking. This review summarizes studies on NAD+ signaling in delaying heart aging, its interactions with other cardiac aging-related pathways, and its therapeutic potential. NAD+ is crucial in delaying heart aging, but factors like altered metabolism, oxidative stress, and calcium overload can affect its function. Understanding these mechanisms is essential for developing effective therapies to prevent age-related heart diseases.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042931/.
de Castro JM, Assumpção JAF, Stein DJ, Toledo RS, da Silva LS, Caumo W, Carraro CC, da Rosa Araujo AS, Torres ILS. Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction. Life Sci. 2020 Dec 15;263:118596. doi: 10.1016/j.lfs.2020.118596. Epub 2020 Oct 17. PMID: 33080243.
Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction
Nicotinamide riboside (NR) alone or combined with caloric restriction (CR) was studied for its effects on obesity and cardiometabolic factors in rats fed a high-calorie diet. NR alone reduced body weight, adiposity, insulin resistance, and improved cardiac health by increasing antioxidant enzymes and reducing pro-oxidant complexes. However, NR also induced hyperglycemia, hypertriglyceridemia, and elevated TBARS in the heart. This study highlights NR’s anti-obesity and cardiometabolic benefits, marking the first report of its effects on cardiac oxidative stress in an obesity model.
You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/33080243/.
Diguet, N., Trammell, S., Tannous, C., Deloux, R., Piquereau, J., Mougenot, N., Gouge, A., Gressette, M., Manoury, B., Blanc, J., Breton, M., Decaux, J. F., Lavery, G. G., Baczkó, I., Zoll, J., Garnier, A., Li, Z., Brenner, C., & Mericskay, M. (2018). Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy. Circulation, 137(21), 2256–2273. https://doi.org/10.1161/CIRCULATIONAHA.116.026099.
Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy
Nicotinamide riboside (NR) supplementation can improve myocardial metabolic impairment in heart failure by stabilizing NAD+ levels. This study found a 30% reduction in NAD+ in failing hearts of mice with dilated cardiomyopathy (DCM) and transverse aorta constriction, linked to decreased nicotinamide phosphoribosyltransferase and increased nicotinamide riboside kinase 2 (NMRK2). NR supplementation restored NAD+ synthesis, stimulated glycolysis, and attenuated heart failure development, especially in DCM. These results suggest NR as a promising treatment for heart failure, particularly DCM.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954688/.
Emerging potential benefits of modulating NAD+ metabolism in cardiovascular disease, Daniel S. Matasic, Charles Brenner, and Barry London, American Journal of Physiology-Heart and Circulatory Physiology 2018 314:4, H839-H852.
Emerging potential benefits of modulating NAD+ metabolism in cardiovascular disease
Nicotinamide adenine dinucleotide (NAD+) is essential for fuel oxidation, bioenergetics, and the activity of enzymes regulating cellular processes in cardiomyocytes. Recent studies highlight its role in cardiovascular diseases, suggesting that NAD+ precursors like nicotinamide riboside may be cardioprotective. This review discusses molecular physiology and preclinical data on NAD+ precursors in heart failure, ischemic-reperfusion injury, and arrhythmias, and explores alternative NAD+-boosting strategies and their potential systemic effects on cardiovascular health.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966770/.
Ma, S., Feng, J., Lin, X., Liu, J., Tang, Y., Nie, S., Gong, J., & Wang, L. (2021). Nicotinamide Riboside Alleviates Cardiac Dysfunction and Remodeling in Pressure Overload Cardiac Hypertrophy. Oxidative medicine and cellular longevity, 2021, 5546867. https://doi.org/10.1155/2021/5546867.
Nicotinamide Riboside Alleviates Cardiac Dysfunction and Remodeling in Pressure Overload Cardiac Hypertrophy
The study investigated the protective effects of nicotinamide riboside (NR) on myocardial hypertrophy induced by transverse aortic constriction (TAC) in mice. NR treatment improved cardiac structure and function, reduced oxidative stress and inflammatory cytokines, and inhibited NLRP3 inflammasome activation. These benefits were linked to the regulation of the NAD+-Sirtuin3-MnSOD signaling pathway, highlighting NR’s potential in mitigating pathological cardiac hypertrophy and dysfunction.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463245/.
Abdellatif, M., Trummer-Herbst, V., Koser, F., Durand, S., Adão, R., Vasques-Nóvoa, F., Freundt, J. K., Voglhuber, J., Pricolo, M. R., Kasa, M., Türk, C., Aprahamian, F., Herrero-Galán, E., Hofer, S. J., Pendl, T., Rech, L., Kargl, J., Anto-Michel, N., Ljubojevic-Holzer, S., Schipke, J., … Sedej, S. (2021). Nicotinamide for the treatment of heart failure with preserved ejection fraction. Science translational medicine, 13(580), eabd7064. https://doi.org/10.1126/scitranslmed.abd7064.
Nicotinamide for the treatment of heart failure with preserved ejection fraction
Heart failure with preserved ejection fraction (HFpEF), associated with diastolic dysfunction, is linked to a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction in animal models by enhancing myocardial bioenergetics and reducing systemic comorbidities. Nicotinamide also improved cardiomyocyte function through increased deacetylation of titin and calcium ATPase. A human cohort study showed high dietary intake of NAD+ precursors was associated with lower blood pressure and reduced cardiac mortality, suggesting NAD+ precursors, especially nicotinamide, as potential therapies for HFpEF.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611499/.
Ahmad, F., Tomar, D., Aryal A C, S., Elmoselhi, A. B., Thomas, M., Elrod, J. W., Tilley, D. G., & Force, T. (2020). Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling. Biochimica et biophysica acta. Molecular basis of disease, 1866(3), 165609. https://doi.org/10.1016/j.bbadis.2019.165609.
Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling
Nicotinamide riboside kinase-2 (NRK-2), primarily expressed in skeletal muscle, shows increased expression in ischemic heart tissue. Using NRK-2 knockout (KO) mice, researchers found that NRK-2 deficiency exacerbates cardiac dysfunction, hypertrophy, and fibrosis following myocardial infarction (MI). KO mice exhibited increased mortality, extensive scarring, and left ventricular dilation. Mechanistically, NRK-2 loss enhances p38α activation, promoting fibroblast activation and cardiomyocyte death. These findings suggest that NRK-2 plays a critical role in mitigating heart failure progression post-ischemic injury by regulating p38α activation and reducing fibrosis.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954964/.
Shahzadi, S. K., Marzook, H., Qaisar, R., & Ahmad, F. (2022). Nicotinamide riboside kinase-2 inhibits JNK pathway and limits dilated cardiomyopathy in mice with chronic pressure overload. Clinical science (London, England : 1979), 136(2), 181–196. https://doi.org/10.1042/CS20210964.
Nicotinamide riboside kinase-2 inhibits JNK pathway and limits dilated cardiomyopathy in mice with chronic pressure overload
Nicotinamide riboside kinase-2 (NRK-2) is crucial for cardiac remodeling. NRK-2 knockout (KO) mice subjected to trans-aortic constriction (TAC) showed significant cardiac dysfunction, hypertrophy, and heart failure (HF) during maladaptive remodeling. KO hearts exhibited extensive left ventricular dilatation, cardiomyopathy, and fibrosis. Overexpression of NRK-2 in cardiomyocytes reduced fetal gene expression, cardiomyocyte death, JNK activation, and mitochondrial dysfunction. These findings suggest NRK-2 protects against pressure overload-induced dilatative remodeling, and its deficiency worsens dilated cardiomyopathy and cardiac dysfunction post-TAC.
You can read the abstract of the article at https://portlandpress.com/clinsci/article-abstract/136/2/181/230683/Nicotinamide-riboside-kinase-2-inhibits-JNK?redirectedFrom=fulltext.
Zheng, D., Zhang, Y., Zheng, M., Cao, T., Wang, G., Zhang, L., Ni, R., Brockman, J., Zhong, H., Fan, G. C., & Peng, T. (2019). Nicotinamide riboside promotes autolysosome clearance in preventing doxorubicin-induced cardiotoxicity. Clinical science (London, England : 1979), 133(13), 1505–1521. https://doi.org/10.1042/CS20181022.
Doxorubicin (DOX) is a common chemotherapy drug that causes severe cardiotoxicity, primarily through oxidative stress and disrupted autophagic flux in cardiomyocytes. This study found that nicotinamide riboside (NR), a precursor to NAD+, alleviates DOX-induced cardiac injury by restoring autophagic flux and reducing oxidative stress. NR increased NAD+ levels, improved cardiac function, and reduced autolysosome accumulation in DOX-treated mice and cardiomyocytes. These protective effects involve the NAD+/SIRT1 signaling pathway, highlighting NR’s potential to mitigate DOX-induced cardiotoxicity.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705112/.
Hu, L., Guo, Y., Song, L., Wen, H., Sun, N., Wang, Y., Qi, B., Liang, Q., Geng, J., Liu, X., Fu, F., & Li, Y. (2022). Nicotinamide riboside promotes Mfn2-mediated mitochondrial fusion in diabetic hearts through the SIRT1-PGC1α-PPARα pathway. Free radical biology & medicine, 183, 75–88. https://doi.org/10.1016/j.freeradbiomed.2022.03.012.
Nicotinamide riboside promotes Mfn2-mediated mitochondrial fusion in diabetic hearts through the SIRT1-PGC1α-PPARα pathway
Myocardial dysfunction in diabetic patients is linked to imbalanced mitochondrial dynamics. This study found that nicotinamide riboside (NR) supplementation improved mitochondrial function and reduced oxidative stress in diabetic hearts by increasing NAD+ levels and promoting mitochondrial fusion through elevated Mfn2 levels. NR reduced mitochondrial fragmentation, suppressed H2O2 and O2•- production, and decreased cardiomyocyte apoptosis in diabetic mice. Mechanistically, NR activated SIRT1, leading to deacetylation of PGC1α and enhanced Mfn2 transcription. These results suggest that NR supplementation could delay cardiac complications in diabetes by promoting mitochondrial fusion.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0891584922001071?via%3Dihub.
Wu, L. E., Gomes, A. P., & Sinclair, D. A. (2014). Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis. Cancer cell, 25(1), 12–19. https://doi.org/10.1016/j.ccr.2013.12.005.
Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis
Cancer risk increases with age, often attributed to the multi-hit hypothesis and the accumulation of genomic mutations over time. This study suggests that a decline in oxidative metabolism during aging is an early and crucial factor driving tumorigenesis. The sirtuins, a family of NAD+-dependent deacylases, play a central role in these metabolic changes by coordinating responses to nutrient intake and energy demand. Modulating sirtuins could potentially reverse age-related metabolic changes and reduce cancer risk.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970212/.
Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., Hahn, W. C., Guarente, L. P., & Sinclair, D. A. (2008). The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PloS one, 3(4), e2020. https://doi.org/10.1371/journal.pone.0002020.
The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth
Numerous longevity genes, when altered, prolong lifespan in model organisms, but in mammals, these alterations might increase cancer risk by boosting cell survival. The Sir2/SIRT1 family of NAD(+)-dependent deacetylases is linked to the health benefits of calorie restriction (CR), which broadly suppresses cancer in mammals. CR doubles SIRT1 expression in rodents’ intestines, and SIRT1 induction in a beta-catenin-driven mouse model of colon cancer significantly reduces tumor formation and proliferation without CR. SIRT1 deacetylates beta-catenin, suppressing its transcriptional activity and promoting its cytoplasmic localization, which correlates inversely with nuclear beta-catenin in human colon tumors. Thus, SIRT1 suppresses intestinal tumors and may be a therapeutic target for beta-catenin-driven cancers.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2289879/.
Sebastián, C., Zwaans, B. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., Cosentino, C., Greenson, J. K., MacDonald, A. I., McGlynn, L., Maxwell, F., Edwards, J., Giacosa, S., Guccione, E., Weissleder, R., Bernstein, B. E., … Mostoslavsky, R. (2012). The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell, 151(6), 1185–1199. https://doi.org/10.1016/j.cell.2012.10.047.
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
SIRT6 is identified as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Loss of SIRT6 leads to tumor formation without activation of known oncogenes, and transformed SIRT6-deficient cells show increased glycolysis and tumor growth. In vivo SIRT6 deletion increases tumor number, size, and aggressiveness. SIRT6 regulates ribosome metabolism by repressing MYC transcriptional activity and is selectively downregulated in several human cancers, predicting prognosis and tumor-free survival rates. Thus, SIRT6 is a critical modulator of cancer metabolism and acts as a potent tumor suppressor.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526953/.
Nikas IP, Paschou SA, Ryu HS. The Role of Nicotinamide in Cancer Chemoprevention and Therapy. Biomolecules. 2020;10(3):477. Published 2020 Mar 20. doi:10.3390/biom10030477.
The Role of Nicotinamide in Cancer Chemoprevention and Therapy
Nicotinamide (NAM), a form of Vitamin B3 and precursor of NAD+, regulates cellular energy metabolism and acts as an inhibitor of SIRT1 and PARP1. Evidence suggests NAM’s role in cancer prevention and therapy, with Phase III trials confirming its efficacy for non-melanoma skin cancer chemoprevention and as an adjunct to radiotherapy for head, neck, laryngeal, and bladder cancers. Although promising, further preclinical studies and clinical trials are necessary to fully establish its value in cancer treatment.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175378/.
Fania L, Mazzanti C, Campione E, Candi E, Abeni D, Dellambra E. Role of Nicotinamide in Genomic Stability and Skin Cancer Chemoprevention. Int J Mol Sci. 2019 Nov 26;20(23):5946. doi: 10.3390/ijms20235946. PMID: 31779194; PMCID: PMC6929077.
Role of Nicotinamide in Genomic Stability and Skin Cancer Chemoprevention
Nicotinamide (NAM), an amide form of vitamin B3 and NAD+ precursor, is essential for ATP production and cellular metabolism. Vitamin B3 deficiency, leading to NAD+ depletion, causes pellagra, UV sensitivity, impaired DNA repair, and increased cancer risk. NAM replenishment boosts cellular energy, enhances DNA repair, and reduces UV-induced immunosuppression and skin cancer incidence. Clinical studies show that both topical and oral NAM administration can reduce skin aging and non-melanoma skin cancers, making it a promising approach for skin cancer chemoprevention.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929077/.
Hwang ES, Song SB. Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells. Cell Mol Life Sci. 2017 Sep;74(18):3347-3362. doi: 10.1007/s00018-017-2527-8. Epub 2017 Apr 17. PMID: 28417163.
Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells
Nicotinamide (NAM), a form of vitamin B3, is crucial for maintaining NAD+ redox balance and acts as a substrate for sirtuins, which use NAD+ to deacetylate proteins. Although NAM is often used to inhibit SIRT1, it is rapidly converted to NAD+, potentially leading to a temporary inhibition followed by increased SIRT1 activity. Literature reviews suggest that NAM’s inhibitory effect on SIRT1 is often unreliable and may even stimulate SIRT1 activity, raising concerns about the interpretation of studies using NAM as a SIRT1 inhibitor.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11107671/.
Park, J. M., Han, Y. M., Lee, H. J., Park, Y. J., & Hahm, K. B. (2021). Nicotinamide Riboside Vitamin B3 Mitigated C26 Adenocarcinoma-Induced Cancer Cachexia. Frontiers in pharmacology, 12, 665493. https://doi.org/10.3389/fphar.2021.665493.
Nicotinamide Riboside Vitamin B3 Mitigated C26 Adenocarcinoma-Induced Cancer Cachexia
Nicotinamide riboside (NR), a form of vitamin B3, supports nicotinamide adenine dinucleotide (NAD+)-consuming enzymes crucial for various cellular processes, including aging and muscle function. This study examined whether NR could alleviate cancer cachexia, a condition characterized by severe weight loss and muscle atrophy in advanced cancer patients. In a mouse model, preemptive NR administration significantly reduced cancer cachexia, inhibited muscle-specific ubiquitin-proteasome ligases, and reduced inflammation and adipose tissue lipolysis. Additionally, NR increased NAD+ biosynthesis and inhibited the NAD+-sensitive enzyme sirtuin 1 (SIRT1), suggesting its potential as a preventive treatment for cachexia in cancer patients.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273280/.
Hamity, M. V., White, S. R., Blum, C., Gibson-Corley, K. N., & Hammond, D. L. (2020). Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats. Pain, 161(10), 2364–2375. https://doi.org/10.1097/j.pain.0000000000001924.
Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats
Nicotinamide riboside (NR), a vitamin B3 precursor of NAD, alleviates diabetic and chemotherapy-induced peripheral neuropathy in preclinical models. This study investigated NR’s effect on paclitaxel-induced peripheral neuropathy and tumor growth in female rats with mammary gland tumors. Daily NR administration significantly reduced paclitaxel-induced hypersensitivity, loss of intraepidermal nerve fibers, and tumor growth, without affecting tumor growth in non-paclitaxel-treated rats. These findings suggest NR could mitigate peripheral neuropathy and potentially enhance the tumor-suppressing effects of taxane chemotherapy in cancer patients.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508763/.
Hamity, M. V., White, S. R., Walder, R. Y., Schmidt, M. S., Brenner, C., & Hammond, D. L. (2017). Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats. Pain, 158(5), 962–972. https://doi.org/10.1097/j.pain.0000000000000862.
Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats
This study investigates whether nicotinamide riboside (NR), a precursor of NAD, can reduce paclitaxel-induced peripheral neuropathy in rats. Daily NR administration before and during paclitaxel treatment prevented tactile hypersensitivity and escape-avoidance behaviors, effects sustained even after a washout period. NR increased blood NAD levels by 50%, did not interfere with paclitaxel’s myelosuppressive effects, and had no adverse locomotor effects. Post-treatment with NR also reversed established tactile hypersensitivity. These findings suggest NR, as a vitamin B3 precursor of NAD and a nutritional supplement, could be a novel therapeutic approach for chemotherapy-induced peripheral neuropathies.
You can read the abstract of the article at https://journals.lww.com/pain/abstract/2017/05000/nicotinamide_riboside,_a_form_of_vitamin_b3_and.22.aspx.
Vannini, N., Campos, V., Girotra, M., Trachsel, V., Rojas-Sutterlin, S., Tratwal, J., Ragusa, S., Stefanidis, E., Ryu, D., Rainer, P. Y., Nikitin, G., Giger, S., Li, T. Y., Semilietof, A., Oggier, A., Yersin, Y., Tauzin, L., Pirinen, E., Cheng, W. C., Ratajczak, J., … Naveiras, O. (2019). The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance. Cell stem cell, 24(3), 405–418.e7. https://doi.org/10.1016/j.stem.2019.02.012.
The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance
This study shows that nicotinamide riboside (NR), an NAD+-boosting agent, reduces mitochondrial activity in hematopoietic stem cells (HSCs) through increased mitochondrial clearance, promoting asymmetric HSC divisions. NR supplementation significantly enlarges the progenitor pool without exhausting HSCs, improves survival by 80%, and accelerates blood recovery after lethal irradiation and HSC transplantation. Additionally, NR enhances human leucocyte production in immune-deficient mice. This demonstrates the potential of NR to improve recovery in patients with hematological failures, including post-chemo and radiotherapy.
You can read the full article at https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30062-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590919300621%3Fshowall%3Dtrue.
Acklin, S., Sadhukhan, R., Du, W., Patra, M., Cholia, R., & Xia, F. (2022). Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation. Neuro-oncology advances, 4(1), vdac101. https://doi.org/10.1093/noajnl/vdac101.
Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation
This study reveals that nicotinamide riboside (NR), a precursor of NAD+ and activator of SIRT2, can prevent and treat cisplatin-induced peripheral neuropathy (CIPN) in mice without reducing cisplatin’s effectiveness against cancer cells. Using mouse models and cell survival assays, the research shows that NR’s neuroprotective effects are SIRT2-dependent and may even enhance cisplatin’s cytotoxicity in some cancer cells, suggesting NR as a promising therapy for alleviating CIPN.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297957/.
Podyacheva, E., & Toropova, Y. (2021). Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects. Nutrients, 13(10), 3435. https://doi.org/10.3390/nu13103435.
Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy
Despite advancements in cancer treatment, doxorubicin remains a widely used yet cardiotoxic drug with no existing treatments for doxorubicin cardiomyopathy. Nicotinamide riboside, a vitamin B3-like compound and NAD+ precursor, shows promise in addressing this issue. While no studies have specifically examined its effects on cardiomyopathy, its mechanisms in other pathologies suggest potential for preventing doxorubicin-induced heart damage. This review evaluates the experimental evidence on nicotinamide riboside’s effects and explores its potential in preventing doxorubicin cardiomyopathy.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538727/#:~:text=To%20date%2C%20there%20are%20no,as%20a%20precursor%20to%20NAD%2B..
Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. Published 2018 Mar 29. doi:10.1038/s41467-018-03421-7.
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
Doxorubicin, widely used for over 40 years in treating various cancers, remains problematic due to its cardiotoxicity, with no existing treatments specifically for doxorubicin cardiomyopathy. Nicotinamide riboside, a precursor to NAD+ similar to vitamin B3, shows potential in addressing this issue. Although there is no published research on its effects on cardiomyopathy, its mechanisms in other pathologies are well-studied. This review explores nicotinamide riboside’s effects in different experimental models, its role in NAD+ synthesis, and its potential for preventing doxorubicin cardiomyopathy.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876407/.
Bushehri N, Jarrell ST, Lieberman S, Mirdamadi-Zonozi N, Birkmayer G, Preuss HG. Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR). GeriatrNephrol Urol. 1998;8(2):95-100. doi: 10.1023/a:1008242900153. PMID: 9893217.
Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR)
A gradual increase in blood pressure (BP) during aging, known as age-related hypertension, necessitates safe preventive measures. This study explored whether oral B-nicotinamide adenine dinucleotide (NADH), primarily used for neurological disorders, could lower BP and benefit the cardiovascular system, similar to coenzyme Q10. In a blinded, placebo-controlled study with spontaneously hypertensive rats (SHR), NADH significantly reduced systolic BP, lowered total cholesterol and LDL, and decreased renal thiobarbituric acid reactive species (TBARS), indicating reduced lipid peroxidation. These findings suggest NADH supplementation may help prevent age-related BP increases and cardiovascular issues.
You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/9893217/.
Trammell SA, Weidemann BJ, Chadda A, et al. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Sci Rep. 2016;6:26933. Published 2016 May 27. doi:10.1038/srep26933.
Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice
Male C57BL/6J mice on a high-fat diet (HFD) develop prediabetes, insulin resistance, and sensory neuropathy, which progresses to severe insulin resistance and diabetic peripheral neuropathy with low-dose streptozotocin, modeling type 2 diabetes (T2D). Treatment with nicotinamide riboside (NR) improved glucose tolerance, reduced weight gain, liver damage, and hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR significantly reduced blood glucose, weight gain, and hepatic steatosis, and protected against diabetic neuropathy, independent of glycemic control. NR maintained hepatic NADP+ and NADPH levels, suggesting potential benefits for human obesity, T2D, and neuropathies.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882590/.
Shi W, Hegeman MA, Doncheva A, Bekkenkamp-Grovenstein M, de Boer VCJ, Keijer J. High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet. Nutrients. 2019; 11(10):2439. https://doi.org/10.3390/nu11102439.
High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet
High-dose nicotinamide riboside (NR) supplementation in male C57BL/6JRccHsd mice on a mildly obesogenic diet reduced metabolic flexibility, lowered glucose clearance, and aggravated systemic insulin resistance. Molecular and morphological changes in epididymal white adipose tissue (eWAT) included SIRT1-mediated repression of PPARγ, downregulated AKT/GLUT4 signaling, increased crown-like structures and macrophages, and upregulation of pro-inflammatory gene markers. These findings suggest that high-dose NR induces white adipose tissue dysfunction, contributing to deteriorated metabolic health.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835358/.
Carlijn M E Remie, Kay H M Roumans, Michiel P B Moonen, Niels J Connell, Bas Havekes, Julian Mevenkamp, Lucas Lindeboom, Vera H W de Wit, Tineke van de Weijer, Suzanne A B M Aarts, Esther Lutgens, Bauke V Schomakers, Hyung L Elfrink, Rubén Zapata-Pérez, Riekelt H Houtkooper, Johan Auwerx, JorisHoeks, Vera B Schrauwen-Hinderling, Esther Phielix, Patrick Schrauwen, Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans, The American Journal of Clinical Nutrition, Volume 112, Issue 2, August 2020, Pages 413–426, https://doi.org/10.1093/ajcn/nqaa072.
Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
In a study investigating the effects of 6-week nicotinamide riboside (NR) supplementation on metabolic health in overweight and obese individuals, NR increased NAD+ metabolites in skeletal muscle, enhanced acetylcarnitine metabolism, and slightly improved body composition and sleeping metabolic rate. However, NR had no significant impact on insulin sensitivity, mitochondrial function, lipid accumulation, cardiac health, blood pressure, inflammation markers, or overall energy metabolism.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398770/.
Yang, S. J., Choi, J. M., Kim, L., Park, S. E., Rhee, E. J., Lee, W. Y., Oh, K. W., Park, S. W., & Park, C. Y. (2014). Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes. The Journal of nutritional biochemistry, 25(1), 66–72. https://doi.org/10.1016/j.jnutbio.2013.09.004.
Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes
In a study on the effects of nicotinic acid (NA) and nicotinamide (NAM) on glucose metabolism and the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes, NAM at a high dose (100 mg/kg BW/day) significantly improved glucose control and insulin resistance. This treatment increased liver NAD levels, NAD/NADH ratio, and sirtuin activity, alongside enhanced mitochondrial biogenesis markers. NAM was found to be more effective than NA in regulating glucose metabolism and the NAD-sirtuin pathway.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0955286313001988?via%3Dihub.
Lee, H. J., Hong, Y. S., Jun, W., & Yang, S. J. (2015). Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes. Journal of medicinal food, 18(11), 1207–1213. https://doi.org/10.1089/jmf.2015.3439.
Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes
Nicotinamide riboside (NR), a vitamin B3 present in milk and beer, was shown to attenuate low-grade chronic inflammation (metaflammation) linked to metabolic diseases like type 2 diabetes, obesity, and cardiovascular disease. In a study with male KK/HlJ mice, NR treatment (100 mg/kg/day for 7 days) improved glucose control, lowered liver cholesterol levels, and rescued mitochondrial and nuclear integrity in the liver. Additionally, NR significantly reduced hepatic proinflammatory markers (TNF-alpha, IL-6, IL-1) and modulated components of the NLRP3 inflammasome, demonstrating its anti-inflammatory capacity and beneficial effects on metabolic regulation.
You can read the abstract of the article at https://www.liebertpub.com/doi/10.1089/jmf.2015.3439?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed.
Trammell, S. A., Weidemann, B. J., Chadda, A., Yorek, M. S., Holmes, A., Coppey, L. J., Obrosov, A., Kardon, R. H., Yorek, M. A., & Brenner, C. (2016). Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Scientific reports, 6, 26933. https://doi.org/10.1038/srep26933.
Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice
In a study with male C57BL/6J mice on a high-fat diet (HFD), prediabetic mice treated with nicotinamide riboside (NR) showed improved glucose tolerance, reduced weight gain, less liver damage, and protection against sensory neuropathy. In mice with type 2 diabetes (T2D), NR reduced blood glucose levels, weight gain, hepatic steatosis, and protected against diabetic neuropathy, with neuroprotection not solely attributed to glycemic control. NR supplementation preserved hepatic NADP(+) and NADPH levels, degraded in prediabetes and T2D, suggesting NR’s potential for treating obesity, T2D, and related neuropathies in humans.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882590/.
Wang SN, Miao CY. Targeting NAMPT as a therapeutic strategy against stroke. Stroke Vasc Neurol. 2019;4(2):83-89. Published 2019 Apr 5. doi:10.1136/svn-2018-000199.
Targeting NAMPT as a therapeutic strategy against stroke
Stroke is a leading cause of death worldwide, particularly in China, with few effective therapies. Nicotinamide phosphoribosyltransferase (NAMPT) is crucial for NAD salvage synthesis, influencing NAD-dependent enzymes and offering strong endogenous defense against stress. Studies indicate NAMPT’s neuroprotective effects in stroke. Five potential therapeutic strategies are reviewed: NAMPT overexpression, recombinant NAMPT, NAMPT activators, and NAMPT enzymatic products like nicotinamide mononucleotide (NMN) and its precursors nicotinamide riboside and nicotinamide. These strategies offer promising avenues for developing new stroke treatments, despite some limitations.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613878/.
Fricker RA, Green EL, Jenkins SI, Griffin SM. The Influence of Nicotinamide on Health and Disease in the Central Nervous System. Int J Tryptophan Res. 2018;11:1178646918776658. Published 2018 May 21. doi:10.1177/1178646918776658.
The Influence of Nicotinamide on Health and Disease in the Central Nervous System
Nicotinamide, the amide form of vitamin B3, is crucial for neuronal development, survival, and function in the CNS, offering neuroprotection against traumatic injury, ischemia, stroke, and neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s. It maintains cellular energy levels and inhibits molecules like SIRT1. Its bioavailability is key, as low concentrations cause neurological deficits while high levels may lead to neurotoxicity.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966847/.
Griffin SM, Pickard MR, Hawkins CP, Williams AC, Fricker RA. Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells. PLoS One. 2020 Sep 14;15(9):e0233477. doi: 10.1371/journal.pone.0233477. PMID: 32925933; PMCID: PMC7489539.
Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells
Emerging evidence suggests a significant relationship between brain regenerative therapies and nutrition, particularly emphasizing the role of vitamins in neuron formation and survival. Nicotinamide, a form of vitamin B3, promotes the development of mature catecholaminergic neurons from mouse embryonic stem cells, enhancing tyrosine hydroxylase-expressing and serotonergic neurons while reducing cell proliferation. This study indicates nicotinamide’s potential in driving neuronal differentiation and maturation, highlighting its importance in early brain development and regenerative medicine.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489539/.
Zhao Y, Guan YF, Zhou XM, Li GQ, Li ZY, Zhou CC, Wang P, Miao CY. Regenerative Neurogenesis After Ischemic Stroke Promoted by Nicotinamide Phosphoribosyltransferase-Nicotinamide Adenine Dinucleotide Cascade. Stroke. 2015 Jul;46(7):1966-74. doi: 10.1161/STROKEAHA.115.009216. Epub 2015 Jun 9. PMID: 26060246.
Regenerative Neurogenesis After Ischemic Stroke Promoted by Nicotinamide Phosphoribosyltransferase-Nicotinamide Adenine Dinucleotide Cascade
Nicotinamide adenine dinucleotide (NAD) and its regulatory enzyme nicotinamide phosphoribosyltransferase (Nampt) are crucial for brain regeneration after ischemic stroke. In this study, Nampt transgenic mice exhibited enhanced neural stem cell activity, better neural recovery, and increased survival following stroke, effects not seen in enzymatically inactive Nampt mutant mice. Administering nicotinamide mononucleotide improved neurogenesis post-stroke, although it did not protect against acute brain damage. Nampt-NAD axis promoted neural stem cell proliferation and differentiation, with the involvement of sirtuins (SIRT1, SIRT2, SIRT6). These findings suggest the Nampt-NAD pathway as a promising target for stroke recovery therapies.
You can read the full article at https://www.ahajournals.org/doi/10.1161/STROKEAHA.115.009216?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
Wang P, Miao CY. NAMPT as a Therapeutic Target against Stroke. Trends Pharmacol Sci. 2015 Dec;36(12):891-905. doi: 10.1016/j.tips.2015.08.012. Epub 2015 Nov 1. PMID: 26538317.
NAMPT as a Therapeutic Target against Stroke
Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is crucial for synthesizing nicotinamide mononucleotide (NMN) and maintaining nicotinamide adenine dinucleotide (NAD) levels, which are essential for energy metabolism and signaling. NAMPT’s role in NAD-dependent sirtuin (SIRT) signaling supports its potential as a therapeutic target for ischemic stroke by offering cerebroprotection, aiding vascular repair, and promoting neurogenesis. Research into NAMPT’s mechanisms and its therapeutic potential through NMN and NAMPT activators shows promise for stroke treatment and recovery.
You can read the abstract of the article at https://www.cell.com/trends/pharmacological-sciences/abstract/S0165-6147(15)00182-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614715001820%3Fshowall%3Dtrue.
Wang SN, Xu TY, Li WL, Miao CY. Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis. CNS NeurosciTher. 2016 Jun;22(6):431-9. doi: 10.1111/cns.12539. Epub 2016 Mar 28. PMID: 27018006; PMCID: PMC6492912.
Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis
Adult neurogenesis, the process of generating new neurons in the olfactory bulb and hippocampus, is affected by aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), an enzyme crucial for synthesizing nicotinamide adenine dinucleotide (NAD), plays a key role in this process by supporting neural stem/progenitor cell proliferation and differentiation. Recent research highlights NAMPT as a potential therapeutic target for restoring neurogenesis in conditions such as aging, stroke, and neurodegenerative diseases. Interventions with NMN, NAD, or recombinant NAMPT show promise, particularly with P7C3 compounds that activate NAMPT, offering potential avenues for drug development.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492912/.
Ralto, K. M., Rhee, E. P., & Parikh, S. M. (2020). NAD+ homeostasis in renal health and disease. Nature reviews. Nephrology, 16(2), 99–111. https://doi.org/10.1038/s41581-019-0216-6.
NAD+ homeostasis in renal health and disease
The mammalian kidney, with its high mitochondrial content, requires ample ATP for solute reclamation and various cellular processes. Nicotinamide adenine dinucleotide (NAD+) is crucial for energy production and cellular regulation. In acute kidney injury (AKI), reduced NAD+ levels compromise energy production and kidney function. Conversely, increasing NAD+ can protect renal tubules from stressors such as ischemia-reperfusion and inflammation, and may reduce the risk of chronic kidney disease. Exploring factors affecting NAD+ levels could lead to new strategies for preventing and treating kidney disease.
You can read the abstract of the article at https://www.nature.com/articles/s41581-019-0216-6.
Hershberger KA, Martin AS, Hirschey MD. Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases. Nat Rev Nephrol. 2017;13(4):213-225. doi:10.1038/nrneph.2017.5.
Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases
Nicotinamide adenine dinucleotide (NAD+) is crucial for regulating redox status and energy metabolism, and its depletion is linked to cardiac and renal diseases. Replenishing NAD+ may restore metabolic health and function, particularly by enhancing sirtuin enzyme activity, which influences various metabolic processes. This review explores NAD+’s roles in heart and kidney health, focusing on how boosting NAD+ could be a promising therapeutic strategy for these conditions by modulating the NAD+-sirtuin axis.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508210/.
Ralto, K.M., Rhee, E.P. & Parikh, S.M. NAD+ homeostasis in renal health and disease. Nat Rev Nephrol 16, 99–111 (2020). https://doi.org/10.1038/s41581-019-0216-6.
NAD+ homeostasis in renal health and disease
The kidney’s function relies heavily on mitochondria for ATP production, crucial for solute reclamation and cellular processes. NAD+ is vital for energy production and cellular health, and its depletion during acute kidney injury (AKI) impairs kidney function. Enhancing NAD+ levels may protect against AKI and long-term kidney damage, offering potential new strategies for preventing and treating kidney disease by improving understanding of factors affecting NAD+ production and renal health.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223841/.
Lenglet, A., Liabeuf, S., Guffroy, P. et al. Use of Nicotinamide to Treat Hyperphosphatemia in Dialysis Patients. Drugs R D 13, 165–173 (2013). https://doi.org/10.1007/s40268-013-0024-6.
Use of Nicotinamide to Treat Hyperphosphatemia in Dialysis Patients
In chronic kidney disease (CKD), controlling serum phosphate is crucial for managing complications like cardiovascular issues and vascular calcification. Current treatments for hyperphosphatemia are costly and sometimes poorly tolerated. Nicotinamide, a derivative of vitamin B3, shows promise as a potential alternative to traditional phosphate binders, as it inhibits phosphate transport in the kidneys and intestines. However, more research is needed on its effectiveness, safety, and pharmacokinetics before it can be recommended for managing hyperphosphatemia in end-stage renal disease (ESRD) patients.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784056/.
Simic, P., Vela Parada, X. F., Parikh, S. M., Dellinger, R., Guarente, L. P., & Rhee, E. P. (2020). Nicotinamide riboside with pterostilbene (NRPT) increases NAD+ in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI. BMC nephrology, 21(1), 342. https://doi.org/10.1186/s12882-020-02006-1.
Nicotinamide riboside with pterostilbene (NRPT) increases NAD+ in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI
A study investigated the effects of nicotinamide riboside (NR) and pterostilbene (PT) on NAD+ levels and safety in patients with acute kidney injury (AKI). The randomized, double-blind trial found that NRPT supplementation increased whole blood NAD+ levels significantly at certain doses, with a 37% overall increase compared to baseline. The treatment was safe and well-tolerated, with minimal minor gastrointestinal side effects. Further research is needed to explore the potential therapeutic benefits of NRPT for AKI.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427083/.
Lin, J. B., & Apte, R. S. (2018). NAD+ and sirtuins in retinal degenerative diseases: A look at future therapies. Progress in retinal and eye research, 67, 118–129. https://doi.org/10.1016/j.preteyeres.2018.06.002.
NAD+ and sirtuins in retinal degenerative diseases: A look at future therapies
Retinal degenerative diseases, which lead to significant visual impairment, share a common outcome of photoreceptor death despite their genetic diversity. Recent research suggests that metabolic dysfunction, particularly involving NAD+ and sirtuins, may be a unifying factor in these diseases. Studies indicate that enhancing retinal metabolism and modulating sirtuin activity could potentially reduce photoreceptor loss and improve vision, offering a promising avenue for developing new treatments.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235699/.
Zhang, X., Zhang, N., Chrenek, M. A., Girardot, P. E., Wang, J., Sellers, J. T., Geisert, E. E., Brenner, C., Nickerson, J. M., Boatright, J. H., & Li, Y. (2021). Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage. Pharmaceutics, 13(6), 893. https://doi.org/10.3390/pharmaceutics13060893.
SystemicTreatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage
Systemic administration of nicotinamide riboside (NR), a NAD+ precursor, was tested for its protective effects against retinal ganglion cell (RGC) damage in mouse models of glaucoma. The treatment improved RGC survival, preserved function, and reduced inflammation in both acute and chronic models of RGC degeneration. NR’s high bioavailability and good tolerance in humans suggest its potential for further clinical investigation.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235058/.
Available from https://www.biorxiv.org/content/10.1101/866798v1.full.
Systemic Treatment with Nicotinamide Riboside is Protective in Three Mouse Models of Retinal Degeneration
This study explores the potential of nicotinamide riboside (NR), a precursor to the metabolic cofactor NAD+, as a treatment for retinal degenerative diseases. Using three mouse models of retinal degeneration, the researchers found that NR treatment prevented declines in retinal function and preserved retinal structure by maintaining NAD+ levels. These findings suggest NR could be a promising therapeutic approach for retinal diseases and warrant further clinical investigation.
You can read the full article at https://www.biorxiv.org/content/10.1101/866798v1.full.
Zhang, X., Henneman, N. F., Girardot, P. E., Sellers, J. T., Chrenek, M. A., Li, Y., Wang, J., Brenner, C., Nickerson, J. M., & Boatright, J. H. (2020). Systemic Treatment With Nicotinamide Riboside Is Protective in a Mouse Model of Light-Induced Retinal Degeneration. Investigative ophthalmology & visual science, 61(10), 47. https://doi.org/10.1167/iovs.61.10.47.
Systemic Treatment With Nicotinamide Riboside Is Protective in a Mouse Model of Light-Induced Retinal Degeneration
This study investigates the protective effects of nicotinamide riboside (NR), a NAD+ precursor, in a mouse model of light-induced retinal degeneration. NR treatment maintained retinal NAD+ levels, preventing declines in retinal function, structural damage, and inflammation caused by light exposure. These results indicate that NR could be a promising therapy for retinal degeneration and warrants further clinical exploration.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452859/.
Zhou, B., Zhao, G., Zhu, Y., Chen, X., Zhang, N., Yang, J., & Lin, H. (2021). Protective Effects of Nicotinamide Riboside on H2O2-induced Oxidative Damage in Lens Epithelial Cells. Current eye research, 46(7), 961–970. https://doi.org/10.1080/02713683.2020.1855662.
Protective Effects of Nicotinamide Riboside on H2O2-induced Oxidative Damage in Lens Epithelial Cells
This study examines the protective effects of nicotinamide riboside (NR) against oxidative damage in human lens epithelial cells exposed to hydrogen peroxide (H2O2). NR treatment improved cell viability, reduced apoptosis and reactive oxygen species, and enhanced antioxidant enzyme activities and mitochondrial function. It also modulated key signaling pathways, inhibiting MAPK and activating JAK2/Stat3. These findings suggest NR could be a promising candidate for preventing or treating cataracts.
You can read the full article at https://www.tandfonline.com/doi/full/10.1080/02713683.2020.1855662.
Leung, C., Ren, S. T., Chan, P., Wan, K., Kam, A., Lai, G., Chiu, V., Ko, M., Yiu, C., & Yu, M. (2022). Correction to: Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial. Trials, 23(1), 134. https://doi.org/10.1186/s13063-022-06079-1.
Leung, C., Ren, S. T., Chan, P., Wan, K., Kam, A., Lai, G., Chiu, V., Ko, M., Yiu, C., & Yu, M. (2022). Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial. Trials, 23(1), 45. https://doi.org/10.1186/s13063-021-05968-1.
Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial
This randomized controlled trial aims to determine if nicotinamide riboside (NR) can slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). Over 24 months, 125 patients will receive either 300 mg NR or a placebo, with outcomes measured by rates of retinal nerve fiber layer (RNFL) thinning, visual field progression, and changes in visual sensitivity. The study will assess whether NR provides neuroprotection and enhance feasibility for short-term glaucoma trials by using RNFL thinning as an objective measure.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762963/.
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