Formulated by experts, built on scientific research, and made without additives.
Every Nullure product uses ingredients sourced from trusted partners, is third-party tested in Germany for purity and carefully manufactured in small batches in Spain funder strict EU GMP standards.
Nicotinamide riboside replenishes NAD+ — the coenzyme your cells rely on for energy, repair, and healthy aging — which declines naturally over time.
More Energy
Nicotinamide riboside fuels NAD+, the coenzyme that drives ATP production in your mitochondria — the energy your cells run on. It supports normal energy metabolism and helps reduce tiredness and fatigue.
Supports Healthy Aging
NAD+ levels fall as we get older. By replenishing NAD+, NR resupplies the coenzyme that DNA repair, cellular energy, and everyday maintenance processes depend on, helping support healthy cellular function over time.
Skin Health
Skin is one of the body's hardest-working tissues, relying on NAD+ for energy, repair, and defence against daily stress. By raising NAD+ from within, NR helps support skin health at the cellular level.
Antioxidant & Inflammatory Balance
By raising NAD+, NR helps your cells manage oxidative stress and keeps inflammatory signalling in balance.
A single-ingredient formula built around nicotinamide riboside — an NAD+ precursor — to support energy, healthy aging, and everyday cellular repair.
• Busy, active adults who want steady energy to keep up with demanding days.
• Adults over 40 who feel their energy, recovery, and vitality slipping with age.
• People wanting to support skin health and a healthy complexion from within.
• Anyone taking a proactive approach to how they age, from the inside out.
Take 1 capsule daily with water, preferably on an empty stomach for improved absorption.
How long to take it?
Nicotinamide riboside works best as part of a consistent daily routine. NAD+ levels begin to rise within the first couple of weeks and stay elevated with continued use, so NR is designed for ongoing, everyday support rather than a short course.
Third-Party Testing:
Every batch of Nicotinamide Riboside is independently tested by a third-party laboratory for microbiological contaminants, yeast, and moulds, and verified GMO-free. In addition, NR undergoes annual independent testing with AGROLAB LUFA for purity and to verify every capsule delivers the full 300 mg of nicotinamide riboside.
Certifications:
Nicotinamide Riboside carries Clean Label Project certification — one of the most rigorous independent purity standards in the industry, testing off-the-shelf products for hundreds of environmental contaminants against some of the strictest thresholds in the world. It's a benchmark few supplements meet. NR is also certified by the Vegan Society.
Gluten-Free · Allergen-Free · Made Without Additives.
Nicotinamide riboside (NR) is a biosynthetic precursor to nicotinamide adenine dinucleotide (NAD+), key metabolism molecule necessary for the creation of cellular energy (ATP) but also cellular repair, DNA repair, calcium signalling and mitochondrial biogenesis and function. (1,2)
Levels of NAD+ decrease with age due to diminishing rates of de novo synthesis from tryptophan coupled with increased utilization. (3)
NAD+ depletion plays a key role in the aging process of human cells via decreased DNA repair function. (4) NAD depletion is associated with age-related diseases (metabolic disorder, cancer, neurodegenerative diseases) and replenishing NAD+ levels may slow down or even reverse some aspects of aging. (5)
NR supplementation boosts NAD+ in humans
Human trials demonstrate that supplementing with NR (dose 100 – 1000 mg) successfully raises levels of NAD+. (6,7,8,9)
Benefits of NR – data from human studies
NR augments skeletal muscle and has an anti-inflammatory effect in humans. A 21-day supplementation with NR was shown to decrease levels of circulatory cytokines - one of NR´s pro-longevity mechanisms. (10)
Improved muscle mitochondrial biogenesis (creation of new mitochondria), stem cell differentiation and gut microbiota diversity in a 2023 twin study. (11)
NR supplementation changed body composition and resulted in increased lean mass and improved metabolic rate during sleep in a 2020 randomized, double-blinded, placebo-controlled, crossover intervention study. (12)
NR supplementation improves oxidative stress markers and exercise endurance (VO2max, muscle strength & muscle fatigue). (13)
NR supplementation had a positive effect of NR on vascular endothelial function. (14)
Potential neuroprotective effects most via anti-inflammatory effect on the brain. (15)
May support the treatment of infections including COVID-19. (3)
Reference link
1. Yoshino J, Baur J, Imai S. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar; 27(3): 513-528
2. Fang E, Lautrup S, Hou Y, Demarest T, Croteau D, Mattson M, et al. NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med. 2017 Oct; 23(10): 899-916.
3. Mehmel M, Jovanovic N, Spitz U. Nicotinamide Riboside—The Current State of Research and Therapeutic Uses. Nutrients .2020 Jun; 12(6): 1616.
4. Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin G. Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue. Plos One [Internet]. 2012 Jul [cited 2023 Aug 24]; 7(7): e42357.
5. Aman Y, Qiu Y, Tao J, Fang E. Therapeutic potential of boosting NAD+ in aging and age-related diseases. Transl Med Aging. 2018 Jan; 2: 30-37.
6. Trammell S, Schmidt M, Weidemann B, Redpath P, Jaksch F, Dellinger R, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun [Internet]. 2016 Oct [cited 2023 Aug 24]; 7: 12948.
7. Airhart S, Shireman L, Risler L, Anderson G, Gowda G, Raftery D, et al. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. Plos One [Internet]. 2017 Dec [cited 2023 Aug 24]; 12(12): e0186459.
8. Dellinger R, Santos S, Morris M, Evans M, Almanina D, Guarente L, et al. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis. 2017 Nov; 3: 17.
9. Martens C, Denman B, Mazzo M, Armstrong M, Reisdorph N, McQueen M, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018 Mar; 9(1): 1286.
10. Elhassan Y, Kluckova K, Fletcher R, Schmidt M, Garten A, Doig C, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019 Aug; 28(7): 1717-1728
11. Lapatto H, Kuusela M, Heikkinen A, Muniandy M, van der Kolk M, Gopalakrishnan S. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci Adv [Internet]. 2023 Jan [cited 2023 Aug 24]; 9(2): eadd5163. 10.1126/sciadv.add5163
12. Remie C, Roumans K, Moonen M, Connell N, Havekes B, Mevenkamp J, et al. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. Am J Clin Nutr. 2020 Aug; 112(2): 413-426.
13. Dolopikou C, Kourtzidis I, Margaritelis N, Vrabas I, Koidou I, Kyparos A, et al. Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Eur J Nutr. 2020 Mar; 59(2); 505-515.
15. Brakedal B, Dolle C, Riemer F, Ma Y, Nido G, Skeie G. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. 2022 Mar; 3483): 396-407.
Expert-Formulated
Third-Party Tested
No Additives
Trusted Ingredients
Made in Spain
Expert-Formulated
Third-Party Tested
No Additives
Trusted Ingredients
Made in Spain
Ingredients You Can Trust
Every formula is built on ingredients backed by human clinical studies, dosed at effective levels, and chosen for bioavailability — how well your body absorbs and uses them. Each ingredient is rigorously vetted and sourced from trusted partners who standardize and batch-test for potency, ensuring quality and real, consistent results.
Nicotinamide Riboside
Nicotinamide riboside (NR) is a mononucleotide (a molecule that is c...
The formulas our customers come back to, month after month. Developed in-house by nutrition experts, dosed for real results, and tested beyond industry standards. Rooted in research, confirmed by the people who take them every day.
Boost NAD+
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Frequently Asked
Nicotinamide riboside is a form of vitamin B3 and functions as a precursor to nicotinamide adenine dinucleotide (NAD+). NAD+ is crucial for converting food into energy, repairing DNA, strengthening cellular defenses, and maintaining your internal clock. Notably, NAD+ levels decrease with age, which can contribute to aging and chronic illnesses such as diabetes and heart disease. NR supplements are effective in boosting NAD+ levels, potentially slowing down some aspects of aging and improving energy and vitality.
Nicotinamide riboside is naturally present in trace amounts in certain foods. It can be found in cow’s milk, yeast, and beer. However, the concentrations in these foods are typically low, which is why supplements are considered a more effective way to increase NAD+ levels in the body. For those looking to naturally increase their intake, focusing on these foods might provide some benefit, albeit minor compared to supplementation.
Each capsule of nicotinamide riboside is absorbed through the intestines and is transported to the cells, where it is used to create NAD+, which is then used to create cellular energy (ATP). Having more energy available to the body is the main pro-longevity mechanism of NR as it means more resources for cellular, DNA and tissue repair.
While NR is absorbed after the very first serving, increasing NAD+ levels takes time and some beneficial effects like better energy, stronger immunity, improved skin tone can be expected over a few months. Even if not immediately visible, there are long-term benefits in maintaining higher NAD+ levels overtime, which is why prolonged use of NR is recommended for optimum results.
Both NR and NMN are biosynthetic precursors of NAD+ and their molecular structures are very similar. Ultimately, their purpose as dietary supplements is the same - to increase NAD+ levels. NR in the form of nicotinamide riboside chloride is currently the only NAD+ booster approved by the EFSA (European Food Safety Authority) to be sold as a food supplement in the EU.
There are no known interactions with other food supplements or medications. However, we always advise you to consult your doctor before taking a new dietary supplement.
The product is good I feel very well and have great energy. I use it in combination with NMN and I feel great.
JL
Jose L.
Verified Buyer
I recommend this product
How old are you? 55-64
What is your gender? Male
Rated 5 out of 5 stars
2 years ago
Buena calidad precio
El tratamiento de 3 meses es mucho más rentable, y la certificación de un laboratorio externo me da tranquilidad sobre su pureza y contenido. Tras años tomando NR por sus beneficios para la salud y la longevidad, he cambiado a Nullure por su precio más asequible.
CG
Clara G.
Verified Buyer
I recommend this product
How old are you? 25-34
What is your gender? Female
Rated 5 out of 5 stars
2 years ago
Prolonged energy boost
Highly recommend! In just a month I have felt an increase in energy levels that last me all day without being “too much”, like I used to feel with caffeine. I also felt a difference when waking up in the mornings, feeling more refreshed and not as lethargic as I used to be in mornings and early afternoon. I also felt a difference in the gym, being able to work out more efficiently, and just an overall improvement in my well-being. I love that it doesn’t contain toxic ingredients and will continue taking it!
TC
Thomas C.
Verified Buyer
I recommend this product
How old are you? 35-44
What is your gender? Male
Rated 5 out of 5 stars
2 years ago
I am satisfied with my purchase
The NR is certified by a German laboratory, which gives me confidence in its purity and content. The previous one I was taking did not work for me, and I think it is because it was not tested and could have less purity
OS
Oriol Salat M.
Verified Buyer
I recommend this product
How old are you? 25-34
What is your gender? Male
Rated 5 out of 5 stars
2 years ago
Mejor precio del mercado para 90 capsulas
He incluido esta Nicotinamide Riboside en mi rutina por 3 razones: 1) Mejor Precio en el mercado por cápsula 2) Producto testado por laboratorio independiente 3) No hay additivos artificiales como en otros productos de la competencia
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The Nullure Journal
We write about health and wellness the way we formulate — starting from the research. Every article is written by qualified experts in nutrition, health, and human performance and based on peer-reviewed science. If you're curious about nutrition, supplements, and how your body works, the Nullure Journal might be just the thing for you.
There’s a strong connection between neuroinflammation and chronic diseases. Persistent brain inflammation contributes to neurodegenerative diseases like Parkinson’s and Alzheimer’s, as well as mental health challenges such as depression and anxiety.
Conditions like diabetes and heart disease, which cause systemic inflammation, can also trigger brain inflammation, creating a harmful cycle. By reducing inflammation, we can support brain health and potentially prevent or slow chronic disease progression.
In this article, we delve into key aspects of these interconnected systems. Explore what neuroinflammation is, its link to chronic disease, and practical ways to manage it. Additionally, we’ll examine the gut-brain axis, highlighting how gut health affects mental wellness and discussing dietary and supplementary support for improved outcomes.
Why Neuroinflammation Matters and How to Manage It
What is Neuroinflammation?
Neuroinflammation refers to the immune system’s response within the central nervous system (CNS), particularly the brain and spinal cord. While inflammation is a natural mechanism to combat infections or injuries, chronic inflammation in the brain can lead to significant issues. It is driven by overactivation of microglia, the brain’s resident immune cells, which release inflammatory molecules such as cytokines and chemokines. (1, 2)
This prolonged inflammatory state disrupts the balance of brain health, impairing neuronal communication and damaging brain tissue. Over time, it can lead to cognitive health problems, including memory loss and a decline in mental sharpness. Understanding what neuroinflammation is and why it matters is crucial to mitigating its impact. (2)
Link Between Neuroinflammation and Chronic Disease
There’s a strong connection between neuroinflammation and chronic diseases. Research indicates that persistent brain inflammation is a contributing factor to neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. It also exacerbates cognitive decline, depression, and anxiety, showcasing its far-reaching effects on mental and physical health. (3, 4, 5)
Chronic diseases, including diabetes, cardiovascular conditions, and autoimmune disorders, often involve systemic inflammation, which can spill over into the CNS. This bidirectional relationship highlights the importance of managing inflammation at both the systemic and neuronal levels. (3, 4)
Triggers of Neuroinflammation
Neuroinflammation can be triggered by various factors, many of which are linked to modern lifestyles. Understanding these causes and triggers of brain inflammation is critical for prevention and management.
Chronic Stress: Persistent stress overstimulates the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated cortisol levels. Over time, this can activate microglia and contribute to brain inflammation. (6, 7)
Poor Diet: Diets high in refined sugars, trans fats, and processed foods promote systemic inflammation, which can cross into the brain. These foods that cause neuroinflammation often disrupt the gut microbiome, worsening the gut-brain connection. (8, 9)
Infections: Viral, bacterial, or fungal infections can spark an immune response in the central nervous system, leading to prolonged inflammation if not resolved. (10)
Environmental Toxins: Exposure to pollutants, heavy metals, and pesticides can induce oxidative stress and damage neurons, further fueling neuroinflammation symptoms. (11, 12)
Sleep Disorders: Poor sleep quality or chronic insomnia disrupts the brain’s natural detoxification process, allowing inflammatory compounds to accumulate. (13)
Chronic Diseases: Conditions like obesity, diabetes, and cardiovascular disease often involve systemic inflammation that can exacerbate brain inflammation. (14, 15)
Practical Tips to Manage Neuroinflammation
Reducing neuroinflammation naturally involves lifestyle adjustments and targeted strategies. Here’s how we can take control:
Adopt an Anti-Inflammatory Diet: Focus on a diet for brain health rich in whole foods, such as leafy greens, berries, fatty fish, and nuts. These provide antioxidants and omega-3 fatty acids that combat inflammation. Avoid highly processed foods and excessive sugar. (16, 17)
Incorporate Anti-Inflammatory Supplements: Supplements like curcumin, omega-3 fatty acids, and saffron are known to reduce inflammation. Adding top supplements for reducing brain inflammation can support long-term cognitive health. (18, 19)
Prioritize Gut Health: Maintaining a balanced gut microbiome with probiotics for mental health and prebiotics can help reduce systemic and brain inflammation. A healthy gut fortifies the gut-brain connection, preventing inflammation from spreading to the brain. (20)
Manage Stress: Practicing mindfulness, meditation, or yoga can regulate the HPA axis and reduce cortisol levels. A calm mind supports better brain health and minimizes inflammation. (21)
Improve Sleep Hygiene: Ensure 7–9 hours of quality sleep each night. Deep sleep helps the brain clear waste products and inflammatory compounds. (22, 23)
Exercise Regularly: Moderate physical activity reduces systemic inflammation and improves blood flow to the brain, supporting both brain health and the vagus nerve for improved communication between the gut and brain. (24)
Limit Exposure to Toxins: Minimize contact with environmental pollutants and opt for organic foods when possible to reduce toxin-induced brain inflammation. (25)
The Gut-Brain Connection: A Deeper Dive
The gut-brain connection is a two-way communication network between the central nervous system and the gut, often referred to as the "second brain." This connection is vital for regulating mood, cognition, and overall mental health. Let’s explore the gut-brain axis and its profound impact on our well-being. (26)
Understanding the Gut-Brain Axis
The gut-brain axis is the bidirectional link between the gut and the brain, mediated by the vagus nerve, hormones, and the immune system. The gut houses trillions of microorganisms collectively known as the gut microbiome, which play a pivotal role in brain and cognitive health.
Vagus Nerve Communication: This nerve acts as a highway, transmitting signals between the gut and the brain. For example, inflammation in the gut can send stress signals to the brain, affecting mood and cognition. (27, 28)
Gut Microbiome’s Role: A balanced gut microbiome supports the production of neurotransmitters like serotonin and dopamine, which are crucial for emotional and mental stability. (29)
Leaky Gut and Inflammation: A compromised gut lining, often called "leaky gut," allows harmful substances to enter the bloodstream. This can trigger systemic inflammation, which ultimately affects brain health. (30, 31)
Understanding the gut-brain axis and its role in health is key to improving mental and physical resilience.
How Gut Health Affects Mental Health
A healthy gut is essential for maintaining a balanced mind. Here’s how:Supports Serotonin Production:
About 90-95% of serotonin, the "feel-good" hormone, is produced in the gut. An unhealthy gut can disrupt its production, contributing to anxiety and depression. (32, 33, 34, 35)
Reduces Systemic Inflammation: A healthy gut limits systemic inflammation, protecting the brain from inflammatory damage that can impair cognitive health and emotional regulation. (36, 37)
Regulates Stress Responses: A balanced gut microbiome helps regulate the HPA axis, minimizing stress responses and supporting the vagus nerve for better mental health. (33)
Protects Against Depression: Studies have shown a direct link between gut microbiome and depression, highlighting the need to prioritize gut health for mental wellness. (32, 38)
Top Dietary and Supplementary Support for Gut Health
To strengthen the gut-brain connection and promote mental well-being, consider these dietary and supplementary approaches:
Probiotics: Foods like yogurt, kefir, and fermented vegetables introduce beneficial bacteria to the gut. Adding probiotics for mental health can improve mood and reduce anxiety. (39, 40)
Prebiotics: Found in a variety of fiber-rich foods, such as fruits, vegetables, and legumes, prebiotics serve as nourishment for beneficial gut bacteria, fostering a healthy and robust microbiome. The more variety you get, the better for supporting your microbiome diversity. (41, 42)
Anti-Inflammatory Foods: Include foods rich in omega-3 fatty acids (e.g., salmon, walnuts) and polyphenols (e.g., berries, green tea) to reduce inflammation and protect both gut and brain health. (17, 43)
Gut Health Supplements: Supplements such as L-glutamine, zinc, and digestive enzymes repair the gut lining and support a healthy microbiome, enhancing the gut-brain axis. (44, 45)
Targeted Herbal Supplements: Certain herbs and natural extracts can play a significant role in supporting the gut-brain connection. For example ashwagandha helps regulate stress by balancing cortisol levels, reducing inflammation, and improving gut resilience to stress. Rhodiola Rosea enhances serotonin production, reduces fatigue, and supports mental resilience, positively influencing the gut-brain axis. (45, 47, 48, 49, 50, 51)
Hydration: Staying hydrated aids digestion and supports a healthy gut lining. (52)Limit Trigger Foods: Avoid foods high in sugar, trans fats, and artificial additives, which disrupt the microbiome and contribute to leaky gut. (53, 54)
By adopting these strategies, we can nurture the gut-brain connection and foster better mental health, resilience, and cognitive performance.
Nullure's Suggestion for Supporting Brain and Gut Health:
To further enhance your brain and gut health, we recommend the following Nullure products:
Memory-Focus-Nootropic: Our Memory & Focus supplement is formulated to boost cognitive performance through a powerful blend of ingredients like Cognizin, Ginseng, and B Vitamins. It enhances memory, focus, and attention while supporting overall brain health by maintaining healthy levels of protective neurotransmitters and ensuring a balanced neuronal growth and neuroprotection. This supplement is essential for anyone looking to fuel brain energy, support neurotransmitter balance, and promote healthy aging.
Ashwagandha KSM-66: Ashwagandha KSM-66 is a premier adaptogen that enhances mental and physical wellness by modulating stress responses and supporting overall homeostasis. It significantly reduces stress and anxiety, improves sleep quality, and boosts memory and cognition. Additionally, it enhances energy levels and physical performance, making it an excellent choice for those looking to increase endurance and manage daily stressors effectively. This supplement also acts as a potent antioxidant and anti-inflammatory agent, bolstering the immune system and promoting long-term health.
Critical findings on NAD+
NAD+ is an essential molecule for life that primarily acts as a “coenzyme”: a cofactor for enzymes in oxidation-reduction (redox) reactions, facilitating the transfer of hydrogen atoms. This transfer is crucial in enabling cells to adapt to changes such as DNA damage, daily rhythm disruptions, infections, inflammation, exposure to foreign chemicals and one of the most important: nutrient availability and the production of ATP, the cell's main energy currency, essential for proper functioning of all cells in the body.
Interestingly, NAD+ has been identified as a key link connecting oxidative stress, inflammation, caloric restriction, exercise, DNA repair, longevity, and overall health span (1). Maintaining optimal NAD+ levels is thus vital for supporting metabolic health. This is highly relevant in modern societies, where lifestyle factors such as poor dietary habits, chronic stress, sedentarism, lack of sunlight or high exposure to chemicals contribute to an increasing prevalence of impaired metabolic health (2, 3).
Metabolic dysfunction is a root cause of chronic inflammation, which over time can lead to the development of autoimmune diseases—conditions that are increasing at an alarming rate each year (4, 5).
Why is NAD+ considered a hallmark of aging?
Although NAD+ research is dated since the early 1900s, NAD+ has gained a lot of interest in the recent years as it has been identified as a hallmark of aging.
NAD+ levels consistently decline with age due to decreased NAD+ synthesis and increased consumption, driven by NAD+’s increasing demand in essential cellular oxidation-reduction reactions (6). Importantly, NAD+ levels have also been shown to be decreased through overnutrition, alcohol consumption, viral infection and a sedentary lifestyle in clinical and preclinical studies (6,7). Decreased NAD+ levels lead to metabolic alterations and increased disease susceptibility, such as cardiovascular disease, neurodegenerative diseases, and cancer.
Interestingly, studies showed that restoring NAD+ levels in old or diseased animals promoted health and extended lifespan (1). The discovery of NAD+’s crucial role in aging and metabolic health has prompted further research in humans and uncovered its therapeutic potential, driving the growth of a substantial market for NAD-boosting molecules, which have clinically shown promising results in slowing down age-related processes and increasing the body’s resilience to many autoimmune diseases such as Parkinson’s or multiple sclerosis, thereby extending healthy human lifespan (6).
What are NAD+’s main functions in the body?
NAD+ acts in many critical processes in our body (6, 8, 9), including:
Cellular energy production: NAD+ collects hydrogen atoms during glycolysis (breakdown of sugar), fatty acid breakdown, and the subsequent tricarboxylic acid (TCA) cycle - occurring in the mitochondria – which forms NADH. NADH then donates these hydrogens to produce ATP (the cell's main energy currency) through mitochondrial oxidative phosphorylation (OXPHOS). Additionally, NAD+ supports mitochondrial biogenesis, the process of forming new mitochondria, which is critical for energy production and metabolism.
Sirtuin activity and 24-hour daily rhythm cycle (circadian rhythm): NAD+ plays a crucial role in regulating the body's circadian rhythm by directly affecting the transcription of clock genes via enzymes, such as sirtuins (SIRT1/6). Sirtuins act as intracellular NAD+ sensors and have been described to help modulate the circadian clock, influencing metabolism, sleep, and overall health.
DNA repair: NAD+ is essential for activating enzymes known as PARPs (poly(ADP-ribose) polymerases), which are involved in repairing damaged DNA. This function helps maintain genomic stability and prevents the accumulation of DNA damage that contributes to aging and disease development.
How is NAD+ synthesised and regulated?
NAD+ is one of the most common metabolites in the human body and it is in a homeostatic status of biosynthesis, consumption, recycling and degradation at both cellular and systemic levels (Figure 1) (6).
(In agreed, similar figure with information below pending to be generated)
Figure 1. Mammalian cells can synthesize NAD+ de novo from tryptophan by the kynurenine pathway or from NA by the Preiss‐Handler pathway, while most NAD+ is recycled via salvage pathways from nicotinamide (NAM), NA, NR and NMN to maintain the cellular NAD+ levels. NAD+ can be reduced into NADH in the metabolic processes, including glycolysis, fatty acid oxidation and the TCA cycle. As a co-substrate important to various post-synthesis modifications of fundamental macromolecules, NAD+ can be cleaved (“degraded”) by NAD+-consuming enzymes including: PARPs, sirtuins, CD38 and SARM1, to generate NAM and ADP-ribose. The precursor NR is imported by ENTs and transformed to NMN by NRK (6).
Non-pharmacologic strategies to increase NAD+ bioavailability
Intracellular NAD+ levels can be increased naturally by adopting a series of lifestyle habits, which serve as effective preventive measures to slow the aging process. Thus far, research has shown that NAD+ can be increased by energy stress, including caloric and glucose restriction, as well as exercise (6, 10).
Caloric restriction: Caloric restriction has been shown to help counteract age-related declines in circadian rhythm – the body’s 24-hour cycle – by improving circadian control of NAD+ metabolism and enhancing NAD+/SIRT1-related epigenetic changes. Both long-term and short-term caloric restriction have been shown to reduce artery stiffness and improve endothelial function. Additionally, another study reported that caloric restriction raised NAD+ levels and protected the brain against aging and disease by reducing oxidative stress and cellular damage.
Exercise: Exercise has gained attention for its ability to potentially boost NAD+ levels and SIRT1 activity, by increasing NAMPT. Regular training significantly raises NAMPT protein in the muscles as a way to respond to energy stress, as seen in a study with non-obese sedentary adults.
Boosting NAD+ as a Therapeutic Strategy
NAD+ depletion is a key feature of aging and age-related disorders. Increasing NAD+ levels can slow aging and combat diseases, promoting a longer, healthier life. Therapeutically, NAD+ can be boosted through dietary supplementation of NAD+ precursors such as Trp, NA, NMN and NR, or by inhibition NAD+-consuming enzymes (e.g., PARP1, CD38) (6).
NAD+ precursors, especially the soluble and orally bioavailable molecules NR, NAM, and Niacin, have shown therapeutic potential in human clinical trials. In particular, NR has become one of the most popular options given the high amount of beneficial clinical results in many different NAD+ related diseases (see our article about NR for more detail).
MNM has also been shown to be rapidly absorbed and converted to NAD+ in organs like muscle, liver, and kidney, but its cellular transport mechanisms remain unclear. In addition, MNM has significantly less clinical studies than NR and the other NAD+ precursors and has shown some risks. A study showed that NMN-induced inflammation promoted the development of pancreatic cancer, highlighting the need for long-term safety studies of NMN NAD+ boosters (6, 11, 12).
Conclusions
NAD+ levels regulate many critical processes, including cellular energy balance, genomic stability, metabolism, stress responses, circadian rhythm, inflammation, redox homeostasis and mitochondrial balance. NAD+ levels consistently decline with age, as well as through modern lifestyle poor habits such as overnutrition, alcohol consumption, viral infection and a sedentary lifestyle. Decreased NAD+ levels lead to metabolic alterations and increased prevalence of chronic inflammation leading to autoimmune diseases.
Boosting NAD+ through lifestyle changes such as exercise or caloric restriction can offer a non-pharmacological way to promote healthy aging by improving resilience and extending healthy lifespan. Clinically approved NAD+ pharmacological boosters, NR being the most studied, are uncovering a broad spectrum of health benefits in both healthy and diseased humans, particularly in NAD+ deficiency related pathologies such as aging-related neurodegenerative disorders, cancer, metabolic diseases, acute injury, infection and overall aging.
Nicotinamide riboside (NR) is a safe and effective way to boost NAD+ levels, which is a key factor in anti-aging. NAD+ levels decline naturally with age, and this decline is linked to a number of age-related diseases.
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Gisela Jiménez
Biomedical Researcher & PhD · Gut & Mitochondrial Health Specialist
I have a sensitive gut and a history of digestive issues, so I am careful about what I put into my body. Since using Nullure's Vitamin D3 + K2, Saffron and Skin Collagen, I've noticed real improvements — better gut health, a calmer nervous system, improved sleep, more energy and fewer hormonal PMS symptoms.
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Ultra Endurance Athlete · First Chilean Woman to Run 500 km Solo
Running, lifting, eating plants — Nullure fits how I actually live. As a vegan, the Vegan Multi is my non-negotiable daily base. Training for my last 500km race, I stacked Rhodiola for the explosive sessions and long endurance days, and Shilajit morning and night to keep my energy solid through the hardest weeks."
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Registered Dietitian & Yoga Teacher
As a dietitian, Nullure has become the go-to supplement brand for both me and my clients: clean formulas, transparent ingredients, evidence-based doses, and the kind of rigour I expect from everything I recommend professionally.
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