NMN supplements typically show noticeable effects, such as increased energy and focus, within a few days to weeks, while long-term benefits like improved metabolism and anti-aging effects may take months.
NAD+ vs. NADH: Differences, Benefits & Best Choice
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Key takeaways:
- NAD+ and NADH are two forms of NAD that act as “energy transporters” in cell metabolism.
- NAD+ and NADH synthesis are interconnected but require different conditions and thus help alleviate different symptoms.
- NAD+ is more beneficial for longevity and general health, while NADH is better for issues like chronic fatigue.
The Nicotinamide Adenine Dinucleotide (NAD) molecule was discovered in the early nineteen hundreds, but only a few decades ago, its use as a longevity supplement was widely accepted. The spark in scientific studies around NAD proved its benefits in enhancing mitochondrial function and promoting cellular health.
It’s also been established that NAD levels decline as we grow older, which might be one of the reasons for various age-related diseases. The two forms of NAD – NAD+ and NADH – are at the center of these longevity discoveries. Which one should you choose for longevity?
What Are NAD+ and NADH?
Cellular energy production might be the most important process in our bodies. Various nutrients, mainly glucose, are transformed into adenosine triphosphate (ATP) for energy storage. This energy is used in all essential biological processes—from muscle contractions to DNA repair and gene expression.
Once cells cannot produce enough ATP, they run out of energy, start to die, and the body grows old. Nicotinamide adenine dinucleotide (NAD) is crucial for energy production by supplying mitochondria with electrons. It does so by switching between two forms.
- NAD+ is the oxidized form that has a positive charge and does not carry electrons, so it can act as an electron acceptor in redox reactions.
- NADH is the reduced form as it has accepted hydrogen atoms (H⁻), which makes its charge neutral and allows it to participate in the electron transport chain.
The main function of NAD+ is to accept electrons during redox reactions that transform it into NADH. When transformed, electrons are donated and transferred using special shuttle systems to pass the mitochondrial membrane (1).
Simply put, NAD+ and NADH are two forms of NAD crucial for energy production. Their role is to transport electrons in the electron transport chain and aid various pathways crucial for cellular metabolism.
We can think of both NAD forms as energy transporters that help fuel the mitochondria via the electron transport chain. Other molecules participate in this process too, but they are often related to the interplay between NADH and NAD+. For example, vitamin B3 includes precursors to NAD+ but plays a much smaller role in energy metabolism.
How Do NAD+ and NADH Work in the Body?
Various cellular processes, such as cellular respiration, transform NAD+ to NADH and vice versa, but it does not mean that taking one form of supplement provides the body with the other. Certain conditions for the needed cellular processes must be met.
- NAD+ is reduced to NADH when there are electrons and a proton it can accept, which happens during various oxidative reactions in metabolic pathways, such as amino acid oxidation, glycolysis, or the Krebs cycle.
- NADH is oxidized into NAD+ during various enzymatic reactions, most notably oxidative phosphorylation, where NADH passes electrons from its hydrogen atoms into the electron transport chain.
The interplay between NAD+ and NADH enables electrons to pass through the mitochondrial membrane and fuel the ATP production process, which is crucial for cellular energy production. NAD therapy, when taking supplements, can restore the NAD+ or NADH levels in your body to help slow down the aging process.
The Biological Role of NAD+ and NADH
NAD+ and NADH play different roles in the same biological processes, so it’s important to understand how their impact differs before taking oral NAD supplements. While many effects overlap, there are a few major differences in key areas.
Aging & longevity
NAD+ activates various sirtuins and enzymes involved in DNA repair. Supplementation of NAD+ precursors is being tested as an aid for age-related decline (2). NADH supplements impact cellular energy production more directly, but the impact on lifespan or health isn’t widely supported by evidence.
Brain function & mental clarity
Both NAD+ and NADH supplementation can be associated with improved brain function and protection against neurodegenerative diseases, such as Alzheimer’s. However, some studies argue that NADH is more directly related to cognitive capabilities, as NAD+ supplementation has difficulties reaching the brain due to its chemical structure (3).
Muscle recovery & athletic performance
By increasing cellular health more directly, NAD+ supplements support skeletal muscle and heart function. Some studies suggest that it improves the performance of runners, for example (4). For NADH, studies have found promising results for physical performance in animals, but there is a lack of tests on humans (5).
NAD+ vs. NADH: Key Differences
NAD+ | NADH | |
Role in Redox Reactions | Electron acceptor (oxidizing agent) | Electron donor (reducing agent) |
Function in Metabolism | Involved in cellular homeostasis reactions like glycolysis and the Krebs cycle by accepting electrons | Donates electrons to the electron transport chain for ATP production |
Energy State | Positive, low-energy molecule | Neutral, high-energy molecule |
Primary Role | Supports oxidative reactions and DNA repair | Fuels ATP synthesis via oxidative phosphorylation |
Biological Importance | Activates sirtuins and other enzymes essential for cell repair and longevity pathways | Crucial for energy production and maintaining redox balance |
Conversion | Reduced to NADH during metabolic reactions | Oxidized back to NAD+ in oxidative phosphorylation |
Benefits of NAD+ and NADH Supplements
Despite their differences, both nicotinamide adenine dinucleotide forms share multiple benefits related to the aging process, brain function, and energy metabolism.
Energy Boost
Certain NAD+ precursors, such as NMN, are known to provide an energy boost after intake. This is due to cells receiving more NAD+ to transport electrons for cellular respiration and other mitochondrial processes.
Similar effects are likely to be more noticeable after taking NADH supplements for a longer period of time. Some studies suggest that both NADH and NAD+ supplements may be used to treat certain metabolic disorders.
Cognitive Function & Memory
There is a lack of studies quantifying the improvement of human cognitive performance after NAD supplementation (6). Such studies are quite costly, but the general functioning of NADH and NAD+ suggests that they can improve energy metabolism in brain cells and protect from age-related cognitive decline.
Anti-Aging & Longevity
While, as mentioned, NADH supplements support cellular health and metabolism more directly than NAD+, both have shared benefits for longevity and fighting age-related illnesses.
- Mitochondrial processes, such as cellular respiration, require both NADH and NAD+ to function.
- Improves cellular repair as energy metabolism becomes more efficient, the body has more resources to heal itself.
- Anti-inflammatory effects are supported by NADH and NAD+ indirectly by improving mitochondrial health.
- Both NADH and NAD+ help alleviate cardiovascular diseases that come in later years when cells start to lack energy.
- Indirect antioxidant effects help to neutralize free radicals that damage cellular structures as we age.
Who Should Not Take NAD+ or NADH?
NAD+ and NADH supplements are generally safe, with only some minor side effects, such as slight nausea or fatigue right after intake being reported. Choosing the right dose is crucial to avoid them. NMN, for example, is recommended in doses of up to 500 mg or one capsule.
As with all supplements, there are cases where it’s better to avoid taking NAD+ or NADH-containing supplements. You should consult your healthcare provider in the following cases:
- If you are a pregnant or breastfeeding woman
- If you have severe allergies to NAD supplements
- If you take medications that might interact with NAD supplements
- If you have a medical history of liver or kidney issues
In some cases, especially related to kidney and liver function, NAD supplementation might even improve their functioning. However, if you already have a preexisting condition, it’s better to consult a doctor before starting NAD therapy.
NAD+ vs. NADH: Which One Should You Take?
NAD+ is better for those who want to slow down or at least mitigate the negative effects of the aging process. Its effects are better suited to increase the overall metabolic health of your cells and the whole organism. There’s even an immediate energy boost that can be felt after taking supplements like NMN.
Supplements containing NAD+ precursors activate sirtuins, a family of enzymes crucial for various metabolic pathways related to age-related illnesses. It also has a more direct impact on your physical and cognitive performance, especially for avoiding diseases like Parkinson’s or Alzheimer’s.
Due to the hydrogen atoms attached to it, NADH can provide electrons that pass into the inner membrane of the mitochondria. As such, it almost directly participates in the ATP synthesis that produces energy.
There may not be as many varied benefits as with NAD+, but it is very beneficial when treating or alleviating certain conditions, such as Chronic Fatigue Syndrome. NADH is also used when you need to recover energy resources after immediate physical stress, but studies have yet to provide conclusive evidence.
Conclusion
Comparing NAD+ vs NADH seems challenging as both oral NAD supplement forms bring many of the same benefits. Yet, the biological role and chemical structure of these NAD forms are different. In the end, NAD+ is better for general health and longevity, while NAD+ is better for improving lack of energy or fighting chronic fatigue.
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