What is NAD+?

Nicotinamide Adenine Dinucleotide (NAD) is a vital component in the metabolic processes and reactions that occur within human cells. NAD is crucial for numerous cellular events. This includes glycolysis (the breakdown of glucose into pyruvate and hydrogen), the citric acid cycle (the release of stored energy from carbohydrates, proteins, and fats through the oxidation of acetyl CoA), fatty acid breakdown, DNA repair, and inflammatory responses, to name a few. Without NAD, these processes cannot occur. As it exerts its effects on the body’s metabolic processes, NAD undergoes oxidation or reduction, with the oxidised variant referred to as NAD+.

How NAD+ is Synthesised?

There are two primary mechanisms through which the human body synthesizes NAD+. The kynurenine pathway is one where NAD+ is synthesized from the essential amino acid tryptophan. Enzymes such as tryptophan-2,3-dioxygenase (TDO) and indoleamine-2,3-dioxygenase (IDO) facilitate the oxidative cleavage of tryptophan to form the product formylkynurenine in this pathway. Several enzymatic reactions occur after the formation of formylkynurenine, and it is then converted into NAD+ by various enzymes, including 3-hydroxy anthranilic acid 3, 4-dioxygenase (3-HAAO).

The second pathway, known as the salvage pathway, recycles NAD+ during the consumption of nicotinic acid, nicotine adenine mononucleotide, and nicotinamide. The enzyme nicotinamide phosphoribosyltransferase (Nampt) converts nicotinamide to nicotinamide adenine mononucleotide (NMN), which is then converted into NAD+ using another enzyme called nicotinamide mononucleotide adenylyltransferase (Nmnat). Additionally, nicotinic acid can serve as a precursor for NAD+ synthesis by generating nicotinic acid mononucleotide (NAMN), which is conjugated to NAD+ by means of the enzyme Nampt. The availability of multiple pathways for NAD+ synthesis underscores its critical importance within the human body.

The importance of NAD+ in the human body

As established, NAD+ plays a vital role in various metabolic processes within the human body. A deficiency or disruption in NAD+ homeostasis in the body may impair these physiologic functions.

NAD+ levels decline as we age, leading to a decline in energy levels, impaired cognitive function, and increased susceptibility to disease. Diseases linked to low NAD+ levels include neurodegenerative disorders, metabolic disorders, and cancer. Boosting NAD+ levels through supplementation has shown promise in improving energy levels, cognitive function, and overall health.

Below are some of the many physiologic processes that are dependent on NAD+.

Genomic Stability

Every day, the body releases reactive oxygen species (ROS) and reactive nitrogen species (RNS) that can cause damage to cellular DNA. Exogenous factors such as carcinogens, chemical mutagens, and radiation can also contribute to DNA damage. When this occurs, genomic instability can result, leading to an increased risk of cancer development and accelerated cellular ageing.

To minimise cellular DNA damage, there is a process in the body known as DNA damage response (DDR). This process detects and repairs any damaged DNA in the body. When amounts of NAD+ are low in the body, the DDR process is impaired, resulting in increased damage to the cellular DNA.

Genetic Expression

This refers to the process by which genetic information stored in cellular DNA is utilised to produce specific proteins or substances within the human body. This complex process is responsible for the development of all the physical characteristics that define an individual This includes hair and skin colour, as well as other unique physical attributes. The study of genetic expression is critical to our understanding of human biology and has far-reaching implications for the treatment and prevention of various genetic diseases.

One of the mechanisms by which genetic expression successfully occurs in the body is through modifying a product known as histones. Histone modification is a NAD+ dependent process. A deficiency in NAD+ levels may disrupt histone modification, which may impair genetic expression. NAD+ deficiency may also result in the methylation of cellular DNA so that genes are not expressed appropriately. This is known as genetic silencing.

Immunity and Inflammation

Studies have shown that NAD+ levels in the human body play a critical role in determining the extent and effectiveness of immune responses during infections. Elevated levels of NAD+ during an infection promote oxidative phosphorylation in macrophages, enhancing their ability to neutralise the infectious agent.

Moreover, NAD+ exerts anti-inflammatory effects during an infectious process, as it reduces the expression of inflammatory markers such as Tumor Necrosis Factor alpha (TNF-a) and Interleukin-6 (IL-6) when there are high cellular levels of NAD+ and its precursors. These findings highlight the essential role of NAD+ in regulating immune responses and suggest its potential as a therapeutic target for combating infections.

Energy Metabolism

Several energy metabolic pathways in the human body require NAD+ as a coenzyme to function effectively. NAD+ facilitates the catalytic reactions of key enzymes such as Glyceraldehyde-3-phosphate dehydrogenase (GADPH) and lactate dehydrogenase (LDH) in the glycolytic pathway.

In the Krebs cycle, NAD+ acts as a coenzyme for alpha ketoglutarate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase. Similarly, alcohol metabolism in liver cells relies on NAD+ as a cofactor. A deficiency of NAD+ in the body can negatively affect these metabolic processes, including glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, fatty acid oxidation, and ethanol metabolism, leading to impaired energy production.

Circadian Clock

NAD+ levels are closely related to the circadian clock. Also known as the biological clock or circadian rhythm, this 24-hour cycle regulates sleep-wake cycles. This internal clock is a natural, internal process. It responds to light and darkness to synchronise bodily functions with the environment.

The accuracy and effectiveness of the circadian clock are due in part to cellular levels of NAD+. A deficiency of NAD+ may disrupt the circadian rhythm and result in effects such as daytime sleepiness, restless sleep, hormonal imbalances, and mood alterations, among others.

Cardiovascular Function

The heart is the most metabolically active organ in the human body, due to its constant beating. Studies have shown that normal NAD+ levels are essential in maintaining the metabolic activity of the heart. Furthermore, in the event of a significant cardiac event such as a transient ischemic attack or myocardial infarction, normal levels of NAD+ help in the recovery from injury. Other studies have shown that a deficiency in NAD+ may result in cardiac disorders such as cardiac hypertrophy and fibrosis.

Kidney Function

As people age, their renal function tends to decline. This decline in renal function may be linked to a decrease in NAD+ levels in the elderly. Studies have shown that NAD+ supplementation can provide increased protection against acute renal injury. NAD+ supplements also stimulate the release of prostaglandin E2, which can improve renal function following an acute renal injury.

Liver Function

The optimal functioning of the liver is dependent on normal NAD+ levels in the body. Enzymes in the NAD+ pathways play a crucial role in protecting the liver from various conditions like nonalcoholic fatty liver disease, hepatic fibrosis, and nonalcoholic steatohepatitis. Numerous studies have shown that supplementing individuals with NAD+ can enhance the overall health of the liver, protect it from toxic illnesses, and increase its ability to regenerate after a hepatic injury.

Neurological Function

Studies indicate that NAD+ and its precursors play a protective role in brain neurons following significant neurological events like stroke. Maintaining normal NAD+ levels is critical for the proper functioning and survival of cerebral neurons. Furthermore, NAD+ supplements have demonstrated potential in treating and preventing neurodegenerative diseases like Alzheimer’s disease, though ongoing studies are still investigating this possibility.

Benefits of IV NAD therapy

NAD+ plays a vital role in all the body’s major processes. It’s no wonder it’s essential to ensure that NAD+ levels are optimal. Signs of NAD+ deficiency such as in pellagra, which manifests as dermatitis, dementia, or diarrhoea, may require supplemental IV NAD therapy. In addition to signs of NAD+ deficiency, there are other reasons for which an individual may consider receiving intravenous NAD+ supplementation. These may include the following:

Addiction Therapy

IV NAD+ therapy is frequently used to aid in the management of addiction. Patients withdrawing from opioid, alcohol, chemical, or prescription drug dependencies may benefit from IV NAD+ therapy, as it may help alleviate the severity of withdrawal symptoms and reduce cravings. Although the mechanism by which NAD+ works in this capacity is still being researched, it is believed that IV NAD+ aids in flushing drugs out of the body.

Improved Cognition

As mentioned earlier, NAD+ has been found to have both protective and stimulating effects on the brain. Consequently, IV NAD+ therapy may be used to potentially boost memory, enhance concentration and focus, promote brain regeneration, and improve overall neurological function. The exact mechanism by which IV NAD+ supplementation produces these effects is still being investigated through ongoing studies.

Chronic Fatigue

IV NAD+ therapy has been used in the management of individuals with chronic fatigue and low energy levels. NAD+ is an important cofactor in the glycolytic pathway and tricarboxylic acid pathways, which are responsible for producing Adenosine Triphosphate (ATP), the primary energy source in the human body. By administering NAD+ supplements, ATP production is increased, which may lead to an improvement in energy levels and a reduction in fatigue.

Athletic Performance

IV NAD+ therapy has been used by athletes to enhance their athletic performance due to its role in ATP production. NAD+ supplements administered through IV may increase energy levels, improve cognitive function, and improve reaction times during competitions or athletic events. Furthermore, studies suggest that NAD+ supplementation may aid in muscle development and repair, potentially leading to muscle hypertrophy and hyperplasia.

Pain Management

IV NAD+ therapy is being explored as a potential way to manage pain due to its anti-inflammatory effects on the body. Inflammation and pain go hand in hand, and the use of NAD+ may help reduce inflammation and offer some relief. While studies are ongoing, the effectiveness of NAD+ as a pain control method is not yet definitive.