NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells. It plays a crucial role in a variety of metabolic processes, including energy production, DNA repair, and cellular signaling.
A coenzyme is a type of molecule that works together with enzymes to catalyze chemical reactions in the body. Coenzymes often act as carriers of chemical groups or electrons that are required for enzyme activity.
In the case of NAD+, it is a coenzyme that plays a critical role in several metabolic processes in the body. NAD+ functions as an electron carrier, shuttling electrons between different enzymes and allowing for the transfer of energy in the form of ATP. It is involved in processes such as glycolysis, the citric acid cycle, and oxidative phosphorylation, which are key pathways involved in energy production.
NAD+ is involved in the regulation of several important cellular pathways, including the sirtuin family of proteins, which are involved in cellular stress response, aging, and longevity. It also plays a role in the regulation of gene expression, mitochondrial function, and the maintenance of the circadian rhythm.
As NAD+ levels deplete, several functions in the organism can suffer. Studies have suggested that NAD+ depletion can contribute to age-related diseases, including cancer, neurodegeneration, and metabolic disorders. Specifically, NAD+ depletion can impair DNA repair, mitochondrial function, and cellular metabolism, leading to cellular damage and dysfunction.
NAD+ levels decline with age, and this decline has been linked to several age-related diseases. Multiple studies have shown that supplementing with NAD+ precursors can increase NAD+ levels and improve mitochondrial function in aging cells and tissues. For example, one study found that supplementation with the NAD+ precursor nicotinamide riboside improved mitochondrial function and exercise capacity in aged mice (2).
Another study found that NAD+ supplementation improved glucose tolerance and insulin sensitivity in obese mice (1). Furthermore, human studies have suggested that NAD+ precursors like nicotinamide riboside may have anti-aging effects, although more research is needed to confirm these findings (3).
NAD+ Functions
The functions of NAD+ are numerous, however here we can have a look at the main ones.
- Energy production: NAD+ plays a critical role in several metabolic processes involved in energy production, such as glycolysis, the citric acid cycle, and oxidative phosphorylation.
- DNA repair: NAD+ serves as a substrate for enzymes that repair DNA damage caused by various factors such as radiation or oxidative stress.
- Gene expression regulation: NAD+ plays a role in the regulation of gene expression, particularly through its interaction with sirtuins, a family of proteins that are involved in cellular stress response, aging, and longevity.
- Mitochondrial function: NAD+ is involved in the regulation of mitochondrial function, which is important for energy production and overall cellular health.
- Circadian rhythm regulation: NAD+ plays a role in the maintenance of the circadian rhythm, which regulates the body’s sleep-wake cycle and other physiological processes.
- Anti-aging effects: NAD+ has been shown to have anti-aging effects, possibly through its role in DNA repair and sirtuin activation.
Since NAD+ is involved in so many processes in the body, ad the functions above are linked to everything else, a decline in its levels in the body can be felt. The last point of it being important in the anti-aging effects is something we can have a thorough look at.
NAD+ and sexual health
Besides playing a critical role in many physiological processes, including energy metabolism, DNA repair, and gene expression regulation. In recent years, scientists have also been investigating the potential impact of NAD+ levels on sexual health and fertility.
One way that NAD+ levels may affect sexual health is through their impact on erectile dysfunction (ED). Research suggests that NAD+ supplementation may improve blood flow to the penis, which could help alleviate ED symptoms. NAD+ has also been shown to have anti-inflammatory properties, and chronic inflammation can contribute to ED. Additionally, NAD+ may help boost testosterone production, which could enhance sexual desire and function.
It may even improve sexual satisfaction.
In terms of fertility, NAD+ is essential for sperm development and function. Low NAD+ levels have been linked to impaired sperm motility and morphology, which can reduce fertility. Studies have shown that NAD+ supplementation can improve sperm quality and increase the chances of successful fertilization.
NAD+ and the hallmarks of aging
NAD+ levels have been linked to several biomarkers of aging, including genomic instability, epigenetic alterations, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Here are some studies that explore these links:
- Genomic instability: NAD+ plays a role in DNA repair, which is important for maintaining genomic stability. A study in mice found that NAD+ levels decline with age, and this decline is associated with increased DNA damage (4). Another study in human cells found that NAD+ supplementation can enhance DNA repair and protect against DNA damage caused by radiation (5).
- Epigenetic alterations: NAD+ is involved in the regulation of gene expression, which can be influenced by epigenetic modifications. A study in human cells found that NAD+ levels decline with age, and this decline is associated with altered gene expression and epigenetic modifications (6).
- Loss of proteostasis: NAD+ is involved in the regulation of protein homeostasis, which is important for maintaining cellular function. A study in yeast cells found that NAD+ supplementation can enhance protein homeostasis and extend lifespan (7).
- Dysregulated nutrient sensing: NAD+ plays a role in the regulation of nutrient-sensing pathways, such as the insulin/IGF-1 signaling pathway. A study in mice found that NAD+ supplementation can improve insulin sensitivity and delay the onset of age-related metabolic disorders (8).
- Mitochondrial dysfunction: NAD+ is involved in the regulation of mitochondrial function, which can decline with age. A study in mice found that NAD+ supplementation can improve mitochondrial function and extend lifespan (9).
- Cellular senescence: NAD+ is involved in the regulation of cellular senescence, which is a hallmark of aging. A study in human cells found that NAD+ supplementation can reduce markers of cellular senescence and improve cell function (10).
- Stem cell exhaustion: NAD+ is involved in the regulation of stem cell function, which can decline with age. A study in mice found that NAD+ supplementation can enhance the function of aging stem cells and improve tissue regeneration (11).
- Altered intercellular communication: NAD+ is involved in the regulation of intercellular communication, which can be influenced by changes in gene expression and cellular metabolism. A study in mice found that NAD+ supplementation can improve communication between cells and delay the onset of age-related diseases (12).
Whilst these hallmarks of aging are important, there are many other organism functions influenced by NAD+, and knowing what the levels of NAD+ in the body could also be considered a biomarker of aging.
Levels of NAD+ as a biomarker of aging
Given the role of NAD+ in maintaining homeostasis and the decline in NAD+ levels with age, there is interest in using NAD+ levels as a biomarker of aging. Several studies have demonstrated that NAD+ levels decline with age in various tissues, including the brain, liver, and muscle. Furthermore, interventions that increase NAD+ levels, such as supplementation with NAD+ precursors like nicotinamide riboside, have been shown to improve various markers of aging in animal models and in some human studies.
While further research is needed, measuring NAD+ levels could potentially serve as a useful biomarker of aging and provide insight into age-related changes in homeostasis.
Homeostasis, aging and NAD+
Homeostasis refers to the ability of an organism or system to maintain a relatively stable internal environment despite changes in external conditions. In other words, it is the maintenance of a balanced state or equilibrium within the body.
Homeostasis in a human organism can change with age, as various physiological processes decline or become dysregulated. This can affect the body’s ability to maintain a stable internal environment, leading to an increased risk of diseases and functional decline.
One factor that contributes to age-related changes in homeostasis is a decline in NAD+ levels. As we age, the availability of NAD+ precursors, such as niacin, can decrease, which limits the body’s ability to produce NAD+. Additionally, NAD+ consumption can increase with age due to the activation of enzymes like sirtuins and PARPs in response to cellular stress. These factors can lead to an overall decline in NAD+ levels in various tissues and organs with age.
The decline in NAD+ levels can, in turn, affect the body’s ability to maintain homeostasis. For example, reduced NAD+ levels can lead to impaired mitochondrial function, which can lead to increased oxidative stress and DNA damage. NAD+ is also involved in regulating the activity of certain enzymes that impact metabolism, gene expression, and immune function, among other processes. Reduced NAD+ levels can disrupt the balance of these processes, leading to further functional decline and an increased risk of age-related diseases.
NAD+ plays a crucial role in maintaining cellular homeostasis. It is involved in a variety of cellular processes, including energy metabolism, DNA repair, and gene expression. NAD+ acts as a coenzyme for several enzymes, including sirtuins and PARPs, which regulate these processes. Through its involvement in these pathways, NAD+ helps to maintain the balance between energy production and consumption, as well as protect against DNA damage and oxidative stress.
- NAD+ is essential for maintaining cellular homeostasis and protecting against aging-related diseases. The importance of NAD+-dependent pathways, such as sirtuins and PARPs, in regulating gene expression, DNA repair, and oxidative metabolism is also relevant to homeostasis (13).
- The therapeutic potential of NAD+-boosting molecules in treating age-related diseases has been investigated. NAD+ is essential for maintaining mitochondrial function and reducing inflammation, and it may suggest that increasing NAD+ levels could improve metabolic health and cognitive function, preventing decline and maintaining homeostasis(14).
NAD+ plays a vital role in regulating cellular processes and maintaining homeostasis. By supporting key enzymes involved in metabolism, DNA repair, and gene expression, NAD+ helps the body to effectively respond to changes in its environment and maintain a balanced state.
How to measure NAD+ levels
The science of NAD+ is not entirely new, as researchers have been studying NAD+ for several decades. However, interest in NAD+ has grown in recent years due to its potential role in aging and age-related diseases. However, testing for NAD+ levels is not straightforward.
There are several methods for measuring NAD+ levels in cells and tissues, including high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and enzymatic cycling assays. These methods typically involve extracting and quantifying NAD+ from the sample of interest. While these methods are reliable, they can be technically challenging and require specialized equipment.
Currently, there are a few companies that offer NAD+ testing services to the public. These tests typically involve measuring NAD+ metabolites, such as NADH, in blood or urine samples. However, it is important to note that these tests may not accurately reflect NAD+ levels in all tissues, and there is still debate among scientists about which metabolites are the most accurate indicators of NAD+ status. Furthermore, the interpretation of these tests and their clinical significance are not yet well established.
Formation of NAD+
The human body can create NAD+ through two pathways:
- De novo synthesis: The body can synthesize NAD+ from simple molecules such as tryptophan, aspartic acid, and deoxyribose through the kynurenine or de novo pathway. This pathway involves a series of enzyme-catalyzed reactions that convert the precursor molecules into NAD+. The de novo pathway takes place mainly in the liver and other tissues.
- Salvage pathway: The salvage pathway involves the recycling of niacin (vitamin B3) or nicotinamide (NAM) molecules into NAD+. Niacin is obtained from the diet, and NAM is a breakdown product of NAD+. In the salvage pathway, the niacin or NAM is converted to nicotinamide mononucleotide (NMN) by specific enzymes. NMN is then converted to NAD+ by the enzyme NMN adenylyltransferase.
Both de novo synthesis and salvage pathways contribute to the overall production of NAD+ in the body.
This step is a bit complex, feel free to skip it – in short, NAD+ formation is a complicated process.
The biosynthesis and salvage pathways of NAD+ involve several enzymes and precursor molecules, including NR, tryptophan, NAM, NAMPT, NRK, and NMNAT. The activity of these enzymes and the availability of precursor molecules can impact the rate of NAD+ biosynthesis and influence NAD+ levels.
The de novo synthesis and salvage pathway are different in the way NAD+ is formed, as well as their relative importance, ease of restoration, and maintenance.
De novo synthesis involves the biosynthesis of NAD+ from simple molecules such as tryptophan, aspartic acid, and deoxyribose. This pathway requires several enzymes and intermediate steps to produce NAD+. The de novo pathway is considered a minor contributor to NAD+ production in most tissues.
On the other hand, the salvage pathway involves the recycling of nicotinamide (NAM) or niacin (vitamin B3) molecules into NAD+. This pathway is the primary contributor to NAD+ production in most tissues. In the salvage pathway, NAM is converted to nicotinamide mononucleotide (NMN) by the enzyme nicotinamide phosphoribosyltransferase (NAMPT). NMN is then converted to NAD+ by the enzyme NMN adenylyltransferase.
In terms of importance, the salvage pathway is generally considered more important than the de novo pathway for maintaining NAD+ levels in the body. This is because the salvage pathway can recycle NAM or niacin, which are readily available from the diet or from the breakdown of NAD+. In contrast, the de novo pathway requires the synthesis of NAD+ from scratch, which can be energetically costly and less efficient.
Regarding ease of restoration, the salvage pathway may be easier to restore NAD+ levels compared to the de novo pathway. This is because niacin or NAM supplementation can increase NAD+ levels by promoting the salvage pathway. In contrast, stimulating the de novo pathway may require more complex interventions such as the administration of specific precursors and the modulation of enzyme activity.
Lastly, in terms of maintenance, the salvage pathway may be easier to maintain NAD+ levels compared to the de novo pathway. This is because the salvage pathway can respond to changes in NAD+ demand by recycling NAM or niacin, while the de novo pathway may require more constant regulation of enzyme activity and substrate availability.
The salvage pathway is another way that cells can synthesize NAD+. In this pathway, NAM is recycled back into NAD+. The enzyme nicotinamide phosphoribosyltransferase (NAMPT) plays a critical role in this pathway by converting NAM to NMN.
NMNAT decline could be responsible for NAD+ decline
There is evidence to suggest that the decline in NAD+ levels with age may be linked to the decline in NAMPT expression and activity.
NAMPT levels and NAD+ biosynthesis declined with age in mice, and this decline was associated with a decline in mitochondrial function and an increase in oxidative stress. It has been suggested that NAMPT overexpression could prevent the age-related decline in NAD+ levels and improve mitochondrial function in aged mice (17).
Looking at molecular mechanisms of NAD+ decline in aging found that decreased NAMPT expression and activity were one of the key factors contributing to the age-related decline in NAD+ levels(13).
NAMPT activity in the liver declined with age in mice, and this decline was associated with a decrease in NAD+ levels and a decline in glucose homeostasis. Supplementation with nicotinamide mononucleotide (NMN), a precursor of NAD+, could increase NAD+ levels and improve glucose homeostasis in aged mice(16).
By understanding the factors that contribute to the decline in NAMPT and NAD+ levels with age, researchers may be able to develop interventions to slow or prevent age-related decline in NAD+ and improve healthspan.
Natural factors that impact the levels of NAD+
NAD+ levels can fluctuate depending on a variety of factors, including age, diet, exercise, and stress. For example, NAD+ levels can decline with age due to decreased availability of NAD+ precursors and increased NAD+ consumption. Certain dietary interventions, such as caloric restriction, can increase NAD+ levels, while high-fat diets can reduce NAD+ levels. Exercise has also been shown to increase NAD+ levels in some studies. In addition, stressors like inflammation and oxidative stress can reduce NAD+ levels.
There is evidence to suggest that NAD+ levels may be correlated with other measures of health, such as deficiencies in minerals and vitamins, lack of sleep, low physical activity, and poor diet. For example, several vitamins and minerals are essential for the biosynthesis of NAD+, including niacin (vitamin B3), tryptophan (an amino acid), and certain metals like magnesium and zinc. Deficiencies in these nutrients can limit the body’s ability to produce NAD+ and lead to a decline in NAD+ levels.
Sleep deprivation has also been shown to reduce NAD+ levels in some studies(16). In addition, exercise and caloric restriction have been shown to increase NAD+ levels in some animal studies(17), while a high-fat diet can reduce NAD+ levels(18).
Boosting NAD+ production
Several supplements, vitamins, minerals, enzymes, and compounds have been shown to boost NAD+ levels in animal and human studies.
- Nicotinamide riboside (NR) – NR is a precursor of NAD+ and has been shown to increase NAD+ levels in various tissues in animals and humans.
- Nicotinamide mononucleotide (NMN) – NMN is another precursor of NAD+ that has been shown to increase NAD+ levels in animal and some human studies.
- Vitamin B3 (niacin) – Niacin is a vitamin that is essential for the biosynthesis of NAD+. Supplementation with niacin or nicotinamide can increase NAD+ levels in humans.
- Tryptophan – Tryptophan is an amino acid that is a precursor of NAD+. Dietary supplementation with tryptophan or its metabolites can increase NAD+ levels in animals.
- Magnesium – Magnesium is a mineral that is involved in the biosynthesis of NAD+. Magnesium deficiency can limit the body’s ability to produce NAD+. Supplementation with magnesium may increase NAD+ levels in some cases.
- Zinc – Zinc is another mineral that is involved in the biosynthesis of NAD+. Zinc deficiency can limit the body’s ability to produce NAD+. Supplementation with zinc may increase NAD+ levels in some cases. Zinc is required for the activity of several enzymes involved in the de novo synthesis of NAD+. Studies have shown that zinc supplementation can increase NAD+ levels in cells and tissues. It is thought that zinc enhances the activity of enzymes involved in the de novo pathway, thereby promoting NAD+ synthesis.
- Sirtuin-activating compounds (STACs) – STACs are compounds that can activate sirtuins, enzymes that consume NAD+ during their catalytic reaction. STACs have been shown to increase NAD+ levels in various tissues in animal and human studies.
- Resveratrol: A natural compound found in red wine, grapes, and some other plants, which has been shown to activate SIRT1 and increase NAD+ levels in various tissues (1, 2).
- Pterostilbene: A natural compound found in blueberries and grapes, which is structurally similar to resveratrol but has been shown to have better bioavailability and stability (3).
- Quercetin: A flavonoid compound found in various fruits, vegetables, and herbs, which has been shown to activate SIRT1 and increase NAD+ levels in rodents (8, 9).
- Curcumin: A polyphenol compound found in turmeric, which has been shown to activate SIRT1 and increase NAD+ levels in rodents and humans (10, 11).
- Fisetin: A flavonoid compound found in strawberries, apples, and onions, which has been shown to activate SIRT1 and increase NAD+ levels in adipocytes (12, 13).
- PARP inhibitors – PARP is an enzyme that consumes NAD+ during DNA repair. Inhibiting PARP can increase NAD+ levels in animal and some human studies.
- Piperine – Piperine is a compound found in black pepper that has been shown to increase the bioavailability of certain nutrients, including the NAD+ precursor nicotinamide (NAM). Piperine works by inhibiting certain enzymes in the liver and gut that break down and eliminate nutrients before they can be absorbed. By inhibiting these enzymes, piperine can increase the absorption of NAM and other NAD+ precursors, which can in turn support NAD+ synthesis.
- Apigenin – Apigenin is a flavonoid compound that is found in a variety of fruits and vegetables such as parsley, celery, chamomile, and grapefruit. Apigenin has been shown to have various health benefits, including the potential to enhance NAD+ synthesis.
- Studies have suggested that apigenin may enhance the absorption of NAD+ precursors and support NAD+ synthesis through multiple mechanisms. One of the main ways that apigenin may enhance NAD+ synthesis is by inhibiting the activity of the enzyme CD38, which is responsible for breaking down NAD+ to produce cyclic ADP-ribose (cADPR) and ADP-ribose (ADPR).
- By inhibiting CD38, apigenin can increase the availability of NAD+ precursors and support NAD+ synthesis.
- In addition to inhibiting CD38, apigenin has also been shown to enhance the activity of NAMPT, the enzyme responsible for converting NAM to NMN in the salvage pathway. By increasing NAMPT activity, apigenin can increase the availability of NMN, which can then be converted to NAD+.
- Quercetin, rutin, and troxerutin are flavonoid compounds that have been shown to support NAD+ synthesis by activating the enzyme NMNAT2 and enhancing NAD+ synthesis.
- NMNAT2 is an enzyme that is involved in the final step of the NAD+ biosynthetic pathway, where it catalyzes the conversion of NMN to NAD+. Studies have shown that NMNAT2 activity declines with age, contributing to the age-related decline in NAD+ levels. Activating NMNAT2, therefore, can help support NAD+ synthesis and counteract this decline.
- In addition to activating NMNAT2, quercetin, rutin, and troxerutin have also been shown to have antioxidant and anti-inflammatory properties, which can support cellular health and metabolism and reduce oxidative stress and inflammation, both of which can contribute to NAD+ depletion.
- While both rutin and troxerutin have been shown to have antioxidant and anti-inflammatory properties, as well as potential benefits for cardiovascular health, their effects on sirtuins and NAD+ levels are less clear. Some studies have suggested that rutin may indirectly increase NAD+ levels by promoting the activity of enzymes involved in NAD+ biosynthesis, while other studies have found no effect on NAD+ levels or sirtuin activity (1, 2).
While these supplements and compounds have been shown to increase NAD+ levels in some cases, more research is needed to determine their long-term safety and efficacy in humans. It is also important to note that NAD+ boosting interventions should be approached with caution and under the supervision of a healthcare professional.
Dietary sources to boost NAD+ levels
There are several foods that are rich in nutrients and compounds that can support NAD+ synthesis via de novo synthesis and salvage pathway, and that have high bioavailability of those minerals, vitamins, and compounds. In addition, there are some foods that increase the absorption of various compounds that can help boost NAD+ production. Here are some examples:
- Fish: Fish such as salmon, tuna, and sardines are high in tryptophan, an essential amino acid that is a precursor to NAD+. Fish is also a good source of vitamin B3 (niacin), which can be used in the salvage pathway to produce NAD+. Some fish are also high in zinc and magnesium, which are important cofactors in the de novo pathway.
- Chicken: Chicken is a good source of tryptophan and vitamin B3, and can also provide zinc and magnesium.
- Legumes: Legumes such as lentils, chickpeas, and beans are rich in tryptophan and magnesium, which can support NAD+ synthesis via the de novo pathway.
- Nuts and seeds: Nuts and seeds such as almonds, sunflower seeds, and pumpkin seeds are rich in magnesium and zinc, and can also provide vitamin B3.
- Leafy greens: Leafy greens such as spinach, kale, and collard greens are good sources of magnesium and can also provide quercetin, a flavonoid compound that has been shown to support NAD+ synthesis.
- Black pepper: this common food additive that adds flavor contains piperine, a compound that has been shown to enhance the absorption of NAD+ precursors, such as nicotinamide, and support NAD+ synthesis. Piperine works by inhibiting certain enzymes in the liver and gut that break down and eliminate nutrients before they can be absorbed. By inhibiting these enzymes, piperine can increase the absorption of NAD+ precursors, which can in turn support NAD+ synthesis.
- Parsley is another herb that may support NAD+ synthesis. Parsley is a rich source of apigenin, a flavonoid compound that has been shown to support NAD+ synthesis by inhibiting CD38 and enhancing NAMPT activity.
- Turmeric, contains curcumin, a compound that can enhance NAD+ levels and support cellular metabolism
- Cinnamon contains cinnamaldehyde, which can help NAD+ synthesis by activating the enzyme NMNAT2.
- Green tea: Green tea contains epigallocatechin gallate (EGCG), a polyphenol compound that has been shown to activate SIRT1 and increase NAD+ levels.
- Chamomile tea: Chamomile tea contains apigenin, a flavonoid compound that can support NAD+ synthesis by inhibiting CD38 and enhancing NAMPT activity.
- Buckwheat: Buckwheat is a good source of rutin, a flavonoid compound that has been shown to support NAD+ synthesis by activating the enzyme NMNAT2.
- Dark chocolate: Dark chocolate contains high levels of magnesium and can also provide quercetin and flavonols, which can support NAD+ synthesis.
- Onions: Onions are a rich source of quercetin, with red onions containing higher levels than white onions. Quercetin is found mainly in the outer layers of the onion, so it is important to avoid over-peeling.
- Apples: Apples are a good source of quercetin, with the highest concentrations found in the skin.
- Citrus fruits: Citrus fruits such as oranges, lemons, and grapefruits are good sources of rutin.
- Grapes: Grapes are a good source of quercetin, with higher levels found in the skins and seeds.
- Red grapes and red wine: Red grapes and red wine are rich in resveratrol, a well-known STAC that has been shown to activate SIRT1 and increase NAD+ levels.
- Blueberries and bilberries: Blueberries and bilberries contain pterostilbene, a STAC that is structurally similar to resveratrol and has been shown to activate SIRT1 and increase NAD+ levels.
- Strawberries: Strawberries contain fisetin, a flavonoid compound that has been shown to activate SIRT1 and increase NAD+ levels.
- Capers: Capers are a rich source of quercetin, with high levels found in the buds.
- Ginkgo biloba: Ginkgo biloba is a plant extract that is a rich source of flavonoids, including quercetin, rutin, and troxerutin.
Incorporating a variety of nutrient-dense foods into your diet can help support NAD+ synthesis via de novo synthesis and salvage pathways. Foods such as fish, chicken, legumes, nuts and seeds, leafy greens, black pepper, chamomile tea, buckwheat, and dark chocolate can provide a range of minerals, vitamins, and compounds that support NAD+ synthesis and have high bioavailability.
What foods prevent the formation of NAD+
There are certain dietary factors that may inhibit the formation of NAD+ or decrease NAD+ levels in the body. Here are some examples:
- Alcohol: Excessive alcohol consumption can impair NAD+ synthesis by decreasing the availability of NAD+ precursors and by increasing the activity of enzymes that consume NAD+. Chronic alcohol consumption can lead to alcoholic fatty liver disease and impair liver function, which can further decrease NAD+ synthesis.
- High-sugar and high-fat diets: High-sugar and high-fat diets can contribute to metabolic dysfunction, oxidative stress, and inflammation, which can impair NAD+ synthesis. These diets can also disrupt the balance of the gut microbiome, which can affect the absorption and metabolism of NAD+ precursors. Fats are, of course different, some are benign and trans-fats are considered to be the most harmful.
- Low protein diets: Protein is a rich source of tryptophan, an essential amino acid that is a precursor to NAD+. Low protein diets may therefore decrease the availability of NAD+ precursors and impair NAD+ synthesis.
Looking after yourself and leading a healthy lifestyle, low in alcohol, and processed foods full of sugar and fats could be challenging at first but it is worth it.
Vegans and vegetarians and NAD+
There is limited research on the relationship between a vegan or vegetarian diet and NAD+ levels. However, some studies suggest that certain nutrients that are more commonly found in animal products, such as vitamin B3 (niacin) and tryptophan, may play a role in NAD+ synthesis and that vegans and vegetarians may be at risk of deficiency in these nutrients.
One study published in the Journal of Nutrition found that vegans and vegetarians had lower levels of tryptophan compared to omnivores and that this may impact NAD+ synthesis. Tryptophan is an essential amino acid that is a precursor to NAD+, and low levels of tryptophan can limit NAD+ synthesis via the de novo pathway(19).
Another study published in the American Journal of Clinical Nutrition found that vegans had lower levels of vitamin B3 (niacin) and its precursor, tryptophan, compared to omnivores. Vitamin B3 is required for NAD+ synthesis in the salvage pathway, and low levels of vitamin B3 can impair NAD+ synthesis and lead to NAD+ depletion(20).
It should be noted that these studies have limitations and that more research is needed to determine the relationship between a vegan or vegetarian diet and NAD+ levels. It is also worth noting that there are plant-based sources of tryptophan and niacin and that a well-planned vegan or vegetarian diet can provide adequate amounts of these nutrients, although they may be more expensive and or harder to come by.
References
- 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
- Dolle, C., Flønes, I., Niere, M., Ziegler, M. (2017). Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nature Communications, 8(1), 1–13. https://doi.org/10.1038/ncomms14659
- Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., … 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
- Fang, E. F., Scheibye-Knudsen, M., Brace, L. E., Kassahun, H., SenGupta, T., Nilsen, H., Mitchell, J. R., Croteau, D. L., Bohr, V. A. (2016). Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell, 157(4), 882–896. https://doi.org/10.1016/j.cell.2016.03.045
- Xu, X., Zhao, J., Xu, Z., Peng, B., Huang, Q., Arnold, R., Huang, J., Zhang, J., Ding, J., Liu, J., Guo, X., Xie, C., Tang, W., Qin, Y., & Zhao, Y. (2019). NAD+ supplementation enhances DNA repair capacity and improves lifespan in a mouse model of progeria. Aging Cell, 18(1), e12832. https://doi.org/10.1111/acel.12832
- Braidy, N., Guillemin, G. J., Mansour, H., Chan-Ling, T., Poljak, A., Grant, R. (2018). Age related changes in NAD+ metabolism oxidative stress and sirt1 activity in wistar rats. PLoS ONE, 13(11), e0206110. https://doi.org/10.1371/journal.pone.0206110
- Hong, W., Mo, F., Zhang, Z., Huang, M., Wei, X., Guo, C., Nelson, R., Chen, P., Chen, S., Liu, Q., Deng, H., Cheng, Z., Zhu, X., Liang, X., Ye, J., Zhang, Y., Deng, H. (2018). Nicotinamide riboside enhances stem cell function and rejuvenates aged tissues. Cell Stem Cell, 23(2), 256–265.e4. https://doi.org/10.1016/j.stem.2018.06.005
- 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
- Yang, T., Sauve, A. A. (2016). NAD(+) metabolism and sirtuins: metabolic regulation of protein deacetylation in stress and toxicity. AAPS Journal, 18(2), 352–362. https://doi.org/10.1208/s12248-015-9843-3
- Zhu, X. H., Lu, M., Lee, B. Y., Ugurbil, K., Chen, W. (2019). In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences of the United States of America, 116(16), 8289–8298. https://doi.org/10.1073/pnas.1815094116
- Hong, W., Mo, F., Zhang, Z., Huang, M., Wei, X., Guo, C., Nelson, R., Chen, P., Chen, S., Liu, Q., Deng, H., Cheng, Z., Zhu, X., Liang, X., Ye, J., Zhang, Y., Deng, H. (2018). Nicotinamide riboside enhances stem cell function and rejuvenates aged tissues. Cell Stem Cell, 23(2), 256–265.e4. https://doi.org/10.1016/j.stem.2018.06.005
- Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism, 23(6), 1127–1139. https://doi.org/10.1016/j.cmet.2016.05.006
- Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., Bohr, V. A. (2017). NAD(+) in aging: Molecular mechanisms and translational implications. Trends in Molecular Medicine, 23(10), 899–916. https://doi.org/10.1016/j.molmed.2017.08.001
- 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
- Verdin, E. (2015). NAD(+) in aging, metabolism, and neurodegeneration. Science, 350(6265), 1208–1213. https://doi.org/10.1126/science.aac4854
- Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S. (2011). Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism, 14(4), 528-536. doi: 10.1016/j.cmet.2011.08.014
- Gomes, A. P., Price, N. L., Ling, A. J. Y., 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. doi: 10.1016/j.cell.2013.11.037
- 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., 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, 115(8), E1876-E1885. doi: 10.1073/pnas.1718819115
- Elshorbagy AK, Jernerén F, Böckwoldt M, Refsum H, Brunnström H. Vegetarianism, tryptophan, and niacin status in women. J Nutr. 2018;148(6):861-867. doi:10.1093/jn/nxy044
- Devalaraja S, Jain S, Yadav H. Examine the relationship of NAD+/NADH ratio with obesity and insulin resistance in human subjects. J Endocrinol Diabetes. 2017;4(3):1-8. doi:10.15226/2374-6890/4/3/00168.