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NAD+, NADH and Cell Energy: How Your Cells Gain Energy
You will learn how your cells produce energy, the role that NAD⁺ and NADH play in this process, and why nicotinamide riboside (NR), as a precursor to NAD⁺, is increasingly becoming a subject of scientific research.
- Introduction
- NAD⁺ & NADH in energy metabolism
- NADH simply explained
- NADH & FADH
- Mitochondria & their connection
- Metabolic flexibility
- NAD⁺, Sirtuins / PARP's)
- NR & NAD⁺
- Balanced NAD⁺/ NADH ratio
- NAD⁺, NADH & NR working together
- Table: NR, NAD⁺ & NADH
- Table: NR & other precursors
- NAD⁺ & Aging
- NAD⁺ & CaAKG
- Sources & Bibliography
Themen dieses Blogartikels:
Why energy doesn't simply come from your food
Perhaps you have asked yourself why a balanced diet alone does not automatically mean that you always feel full of energy.
The reason is simple: the energy from carbohydrates, fats, or proteins is not immediately available to your body. Before your cells can use them, these nutrients must first be processed step by step.¹
For this, your body uses various metabolic pathways, including glycolysis, pyruvate oxidation, the citric acid cycle, and the mitochondrial respiratory chain. They interlock like gears, ensuring that the energy stored in food is gradually converted into a form that your cells can use.¹
The result of this process is ATP (adenosine triphosphate). ATP is considered the universal energy carrier of cells and powers almost all energy-dependent processes – from muscle movement and signal transmission between nerve cells to countless metabolic reactions.¹
For ATP to be produced, electrons must be continuously transferred between different molecules. This is exactly where NAD⁺ and NADH come in.¹`²
How NAD⁺ and NADH Work Together in Energy Metabolism
NAD⁺ (nicotinamide adenine dinucleotide) is a coenzyme found in almost every cell in the body that transports electrons between various metabolic processes.¹² A coenzyme supports enzymes in their work and enables numerous biochemical reactions.
NAD⁺ and NADH are not different substances, but two forms of the same coenzyme.¹ They constantly switch between their oxidized and reduced states – and it is precisely this change that makes them so important for energy metabolism.¹'²
NADH – NAD⁺'s reduced form, simply explained
When NAD⁺ accepts electrons during glycolysis, pyruvate oxidation, or the citric acid cycle, NADH—the reduced form of the coenzyme—is formed.¹³
NADH transports these electrons to the mitochondrial respiratory chain and transfers them to Complex I.¹⁴ In this process, NADH is oxidized back to NAD⁺ and is then available again for the next cycle of energy metabolism.¹
One can imagine both molecules as a shuttle: NAD⁺ accepts electrons in the various metabolic pathways, and NADH transports them to the respiratory chain, where their energy is used for the formation of ATP.¹'³ The energy released in this process contributes to building a proton gradient. This gradient functions similarly to a dammed water flow in a hydroelectric power plant. The stored energy is then used to produce ATP (adenosine triphosphate).⁴ Afterward, the cycle begins anew.
Watch our video on NAD⁺ and NADH
In the video, Cosmo Bulasikis, an expert in functional medicine and a specialist in general medicine, explains what NAD⁺ and NADH are and what function they fulfill in cellular energy metabolism.
NADH and FADH₂
FAD works on the same principle. When the coenzyme accepts electrons, FADH₂ is formed. This then transfers its electrons to Complex II in the respiratory chain and is subsequently re-oxidized to FAD.¹
Brief explanation¹'³'⁴
- Food provides the raw materials.
- NAD⁺ accepts electrons.
- NADH transports them further.
- They are used in the mitochondria for ATP production.
What do mitochondria have to do with NAD⁺ and NADH?
By now you know that NAD⁺ accepts electrons and NADH transports them further. But where do these processes actually take place?
The final steps of energy production occur in the mitochondria.³ As soon as cellular energy is discussed, these small cellular organelles – the mitochondria – become the focus. They are found in most body cells and play a central role in energy metabolism. That's why they are often referred to as the "powerhouses of the cells."³
For NAD⁺ and NADH to fulfill their tasks within the mitochondria, NAD metabolism within the cell must be precisely regulated. For a long time, it was not fully understood how NAD⁺ enters the mitochondria. Recent research has identified SLC25A51 (also called MCART1) as a transport protein that plays an important role in the import of NAD into the mitochondria.⁹,¹⁰ This discovery has significantly contributed to expanding the understanding of mitochondrial NAD metabolism.¹⁰
If you want to learn more about mitochondria as the powerhouses of cells and their function, read our blog article "What are Mitochondria".
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- Contains NADH – the reduced form of the body's own coenzyme NAD⁺ – the electron shuttle of the mitochondria
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- Sublingual application – let 1 lozenge dissolve under the tongue daily
- With D-Biotin for energy metabolism¹
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Metabolic Flexibility – Why Adaptability Matters
The human organism is designed to respond flexibly to different demands.
Depending on the situation, cells can:
- Utilize carbohydrates
- Metabolize fatty acids
- Integrate amino acids into the metabolism
This ability is referred to as metabolic flexibility.
An important prerequisite for this is a functional interplay between:
- Mitochondria
- NAD+/NADH system
- Citric acid cycle
- Respiratory chain³
The better these systems work together, the more efficiently cells can respond to different energy demands.
NAD⁺ as a versatile coenzyme (sirtuins/PARPs)
Why NAD⁺ is the subject of such intensive research today
NAD⁺ performs far more functions in the cell than just electron transport in energy metabolism.¹'² Furthermore, NAD⁺ serves as a cofactor for various enzymes, including sirtuins and PARPs. These enzymes are involved in processes such as gene regulation, DNA repair, and the cellular stress response, among others.²'⁵
For this reason, scientists no longer view NAD⁺ metabolism solely in terms of energy production. Rather, it is considered an important component of various cellular regulatory mechanisms.²'⁵ Scientists are investigating, among other things, the role NAD⁺ metabolism might play in normal cell function and age-related changes.²'⁵'¹⁵
Why the NAD⁺/NADH ratio is important
You might be asking yourself now: Is the amount of NAD⁺ truly the only decisive factor for cell energy?
It's not that simple. It's not just the concentration of NAD⁺ that's crucial, but primarily its interplay with NADH. NAD⁺ accepts electrons, while NADH releases them later in the energy metabolism. Both molecules therefore form a so-called redox pair.¹,³
Current review articles show that not only the absolute concentration of NAD⁺, but especially the ratio of NAD⁺ to NADH, is important for numerous metabolic processes. Scientists refer to this as the NAD⁺/NADH ratio or the redox balance of the cell.³,⁸
A higher proportion of NAD⁺ is associated with a more oxidative metabolic environment, while a higher proportion of NADH can indicate a more reduced metabolic situation.³
Both molecules are not distributed evenly throughout the cell but are located in separate NAD pools, for example, in the cytoplasm and in the mitochondria. These compartments are functionally separated from each other but are connected via metabolic pathways such as the malate-aspartate shuttle.³,⁸
These findings illustrate how precisely NAD metabolism is regulated within the cell and why the entire NAD⁺/NADH system is currently the focus of much research.³
The role of NR and how your body can create new NAD⁺ from vitamin B3
Your body uses various starting materials to maintain NAD⁺ metabolism. This is where Nicotinamide Riboside (NR) comes in.
NR is a naturally occurring form of vitamin B3 and serves as a precursor for the body's production of NAD⁺.¹¹ This means that NR is not directly used as NAD⁺ but is first converted in several steps.¹¹
The Salvage Pathway – Recycling for NAD⁺
The Salvage Pathway – recycling for NAD⁺. A crucial pathway for the body's own NAD⁺ formation is the so-called salvage pathway. Here, Nicotinamide Riboside (NR) is first converted into Nicotinamide Mononucleotide (NMN) by the enzymes NRK1 and NRK2 (the so-called NR kinases). ¹¹'¹² Subsequently, NAD⁺ is formed from it.¹¹'¹² Studies also show that NR kinases play a central role in this conversion process.¹²
NR → (with the help of NRK1/NRK2) → NMN → NAD⁺
Why NR is the focus of many studies
Nicotinamide riboside (NR) is the focus of many studies because it serves as a precursor for the body's production of NAD⁺. Furthermore, NR is orally bioavailable and is converted into NAD⁺ via a well-researched metabolic pathway.¹¹,¹³
Human studies show that orally ingested NR can increase the concentration of various NAD metabolites in the blood. Preclinical studies describe corresponding changes in other tissues as well.¹³,¹⁴
How efficiently various NAD⁺ precursors are absorbed and utilized by the body is still a subject of ongoing research. However, NR stands out because its metabolic pathway and oral bioavailability are comparatively well-studied.¹³,¹⁴
How NAD⁺, NADH, and NR work together
Up to this point, you've learned about the individual components. Only their interaction shows how NAD⁺ metabolism works.
In a nutshell:
- NR serves as a precursor for the body's own production of NAD⁺.¹¹
- NAD⁺ accepts electrons in various metabolic pathways.¹
- This creates NADH.¹
- NADH transports the electrons to the mitochondrial respiratory chain.³,⁴
- There, their energy is used to form ATP – the most important energy carrier in your cells.³,⁴
All these steps continuously interlock and ensure that your cells can continuously provide energy.
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- Holistic formula for the NAD system in mitochondrial energy metabolism
- Contains nicotinamide riboside (NR), NAD⁺ and NADH – building blocks of various areas of the NAD system
- Supplemented with coenzyme Q10 & alpha-ketoglutarate – building blocks of the citrate cycle & the respiratory chain
- Supplemented with antioxidant micronutrients and polyphenols
- Developed with doctors and experts
NR, NAD⁺ and NADH Table by Function and Significance in Energy Metabolism
| Molecule | Function | Significance in Energy Metabolism |
|---|---|---|
| NR (Nicotinamide Riboside) | Serves as a precursor for the body's own production of NAD⁺. | Provides the starting material for the body to continuously produce new NAD⁺. |
| NAD⁺ | Accepts electrons during various metabolic processes. | Connects the breakdown of nutrients with mitochondrial energy production and is reduced to NADH in the process. |
| NADH | Transports the accepted electrons to the mitochondrial respiratory chain and releases them there. | Contributes to the energy of the electrons being used for the production of ATP – the most important energy carrier in cells. |
All information is based on the studies listed in the bibliography.
NR Compared to Other NAD⁺ Precursors
| Precursor | Role in NAD⁺ Metabolism | Special Feature |
|---|---|---|
| Nicotinamide Riboside (NR) | Is first converted to NMN via NRK enzymes and then to NAD⁺. | Naturally occurring form of vitamin B3. |
| NMN (Nicotinamide Mono nucleotide) | Intermediate product in the salvage pathway. | Formed, among other things, from nicotinamide riboside (NR). |
| Nicotinamide (NAM) | Also a component of NAD⁺ metabolism. | Uses a different metabolic pathway than NR. |
| Nicotinic Acid (NA) | Is incorporated into NAD⁺ metabolism via the Preiss-Handler pathway. | Classic form of vitamin B3. |
All information is based on the studies listed in the bibliography.
Good to know:
NR is a form of vitamin B3. NMN and NAD⁺ themselves are not considered sources of vitamin B3.¹⁴ NMN¹¹,¹², however, is classified as a Novel Food in the European Union and is subject to the corresponding regulatory requirements.¹⁶
Why NAD⁺ is being extensively researched in old age
With increasing age, numerous metabolic processes change – including NAD⁺ metabolism.²,⁷,¹⁵
Studies describe that NAD⁺ levels may tend to decrease with increasing age. The biological mechanisms behind this and the significance of these changes for humans are currently being intensively investigated.²,⁷,¹⁵
For this reason, various NAD⁺ precursors – including Nicotinamide Riboside (NR) – are increasingly becoming the focus of research.¹¹,¹³,¹⁴
Scientific classification is important here: A large part of the current knowledge comes from cell culture and animal models. Although initial human studies are now available, further high-quality clinical investigations are necessary to better classify many of the observed correlations.¹³–¹⁵
Why CaAKG is also frequently mentioned in this context
NAD⁺ and calcium alpha-ketoglutarate (CaAKG) are often mentioned together because both substances play a role in cellular energy metabolism. However, they perform different functions and do not act as substitutes for each other.¹⁶
While NAD⁺ transports electrons as a coenzyme between various metabolic processes, alpha-ketoglutarate is an intermediate product of the citric acid cycle. There, it helps to ensure that energy metabolism can run continuously.¹⁶
For this reason, scientists are investigating both substances, among other things, in connection with metabolic processes and age-related changes. However, these are two different fields of research that should not be equated.¹⁶,¹⁷
If you would like to learn more about calcium alpha-ketoglutarate, you can find a detailed blog article about it.
More blog articles on this topic
This article is based on carefully researched sources:
Sources & Bibliography
- Amjad S. et al. (2021). Role of NAD+ in regulating cellular and metabolic signaling pathways. Molecular Metabolism, 49, 101195. https://doi.org/10.1016/j.molmet.2021.101195
- Covarrubias A.J., Perrone R., Grozio A., Verdin E. (2020). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22, 119–141. https://doi.org/10.1038/s41580-020-00313-x
- Waddell J., Khatoon R., Kristian T. (2023). Cellular and Mitochondrial NAD Homeostasis in Health and Disease. Cells, 12(9), 1329. https://doi.org/10.3390/cells12091329
- Okoye C. et al. (2023). Mitochondrial complex I ROS production and redox signaling in hypoxia. Redox Biology, 67, 102926. https://doi.org/10.1016/j.redox.2023.102926
- Imai S., Guarente L. (2014). NAD+ and Sirtuins in Aging and Disease. Trends in Cell Biology, 24(8), 464–471. https://doi.org/10.1016/j.tcb.2014.04.002
- Saqr A.-H.A. et al. (2024). Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research. Frontiers in Medicine, 10. https://doi.org/10.3389/fmed.2023.1278641
- McReynolds M.R., Chellappa K., Baur J.A. (2020). Age-related NAD+ decline. Experimental Gerontology, 134, 110888. https://doi.org/10.1016/j.exger.2020.110888
- Hu Q. et al. (2021). Genetically encoded biosensors for evaluating NAD+/NADH ratio in cytosolic and mitochondrial compartments. Cell Reports Methods, 1. https://doi.org/10.1016/j.crmeth.2021.100116
- Davila A. et al. (2018). Nicotinamide adenine dinucleotide is transported into mammalian mitochondria. eLife, 7. https://doi.org/10.7554/eLife.33246
- Kory N. et al. (2020). MCART1/SLC25A51 is required for mitochondrial NAD transport. Science Advances, 6. https://doi.org/10.1126/sciadv.abe5310
- Alegre G.F.S., Pastore G. (2023). NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health. Current Nutrition Reports. https://doi.org/10.1007/s13668-023-00475-y
- Ratajczak J. et al. (2016). NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nature Communications, 7. https://doi.org/10.1038/ncomms13103
- Braidy N. et al. (2019). Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases. Antioxidants & Redox Signaling, 30, 251–294. https://doi.org/10.1089/ars.2017.7269
- Reiten O.K. et al. (2021). Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing. Mechanisms of Ageing and Development. https://doi.org/10.1016/j.mad.2021.111567
- Yusri K. et al. (2025). The role of NAD+ metabolism and its modulation of mitochondria in aging and disease. npj Metabolic Health and Disease, 3. https://doi.org/10.1038/s44324-025-00067-0
- European Commission. Novel Food Consultation Status – Nicotinamide Mononucleotide (NMN). https://food.ec.europa.eu/system/files/2022-10/novel-food_consult-status_nmn-cz.pdf
- European Commission. Regulation (EU) No 432/2012 establishing a list of permitted other health claims made on foods, other than those referring to the reduction of disease risk and to children’s development and health. https://eur-lex.europa.eu/legal-content/DE/TXT/?uri=CELEX:32012R0432
- Tannous C. et al. (2020). Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases. Acta Physiologica, 231. https://doi.org/10.1111/apha.13551
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Biomolecules & Therapeutics, 24(1), 1–8. https://doi.org/10.4062/BIOMOLTHER.2015.078 - Alberts B., Johnson A., Lewis J., Raff M., Roberts K., Walter P. (2015). Molecular Biology of the Cell. 6th Edition. Garland Science.
- Zdzisińska B., Żurek A., Kandefer-Szerszeń M. (2016). Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use. Archivum Immunologiae et Therapiae Experimentalis, 65(1), 21–36. https://doi.org/10.1007/S00005-016-0406-X
- Asadi Shahmirzadi A., Edgar D., Liao C.Y. et al. (2020). Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metabolism, 32(3), 447–456.e6. https://doi.org/10.1016/j.cmet.2020.08.004
