NAD+ Supplements vs. NAD+ IV Therapy

NAD+ is a central molecule in cellular function. As we age, there is a progressive decline in NAD+ levels in cells that is believed to contribute to many age-related physiological changes that hinder optimal health. Therefore, interest in strategies to boost NAD+ levels to support healthy aging has been growing.

NAD+-boosting supplements and intravenous (IV) NAD+ therapy are two of the main approaches currently available. NAD+-boosting supplementation is the most well-studied, science-backed strategy.* NAD+ IV therapy, usually available in upscale clinics and wellness centers, is a growing trend in wellness treatments and has gained popularity among those seeking cutting-edge biohacking techniques aimed at supporting youthfulness and longevity. Due to its price and relative inaccessibility, NAD+ IV therapy is regarded as a luxury wellness intervention. 

So how does NAD IV therapy compare to the more accessible NAD-boosting supplements? Is it worth the hype? In this article, we’ll learn what science has to say. 

What is NAD+?

NAD+ Defined

NAD+ is the oxidized form of nicotinamide adenine dinucleotide (NAD), a coenzyme form of vitamin B3, colloquially known as niacin. Vitamin B3 is a vitamin family that includes three related compounds (i.e., vitamers): nicotinic acid (niacin), nicotinamide (niacinamide), and nicotinamide riboside. All can be used in the body to produce NAD+.

The Biological Role of NAD+

NAD+ is found in every cell in the body. NAD+ and its reduced form NADH participate in redox reactions (i.e., reactions where electrons are transferred between molecules) with essential roles in cellular signaling and energy metabolism and in maintaining redox homeostasis, i.e., balanced levels of reactive oxygen species (ROS) that can promote oxidative stress [1]. 

As a coenzyme, NAD+ supports the activity of numerous enzymes within cells, including many involved in cellular energy metabolism and cell signaling pathways and processes essential for cellular health, such as sirtuins or poly(ADP-ribose) polymerases (PARPs) [2]. One of the key roles of NAD+ is to carry electrons extracted from nutrients in mitochondrial energy metabolism to the electron transport chain that powers the production of cellular energy as adenosine triphosphate (ATP) [2,3]. 

Some NAD+ can also be found outside of cells, but in normal conditions, extracellular levels are hundreds to thousands of times lower than intracellular levels [4–6]. However, extracellular NAD+ can increase significantly during conditions of cellular stress and may act as a “danger signal” that alerts the immune system to tissue damage and triggers immune responses [5,7,8].* 

Natural Sources of NAD+

As a coenzyme form of vitamin B3, NAD+ levels are contingent on the vitamin B3 status of the body. Dietary compounds that contribute to the body’s vitamin B3 status, and consequently to NAD+ production, are known as niacin equivalents or vitamin B3 equivalents. These include the different vitamers of vitamin B3—niacinamide, nicotinic acid, and nicotinamide riboside (NR). Niacin equivalents are found in all animal, plant, and fungal foods because these organisms also require NAD for life. Red meat, chicken, fish, shrimp, dairy, eggs, and whole grains are the best sources of vitamin B3 [9].

The Science Behind NAD+: Longevity Research

As we age, cellular and tissue levels of NAD+ tend to decline, a process that may start by our early 30s. Most people in their 40s already have relatively low levels of NAD+ compared to a healthy 20-year-old and the decline accelerates progressively as decades pass [10,11]. 

Low NAD+ levels can impact the myriad cellular processes in which NAD+ takes part, including mitochondrial function, cellular energy metabolism, and cellular growth and repair, among many others [10]. Another impactful consequence is a poorer redox balance that may allow for the development of oxidative stress, which is a key driver of aging through the oxidation of cellular molecules and structures. 

Slowly, the progressive decrease in cellular NAD+ starts to affect the optimal function of every tissue and organ in the human body and may promote many of the physiological changes typical of aging [3,12–14]. In fact, NAD+ has been linked to most of the 12 hallmarks of aging, including loss of mitochondrial function, genomic instability, epigenetic modifications, disabled autophagy, and cellular senescence [2,3].* 

Therefore, longevity research has taken an interest in the role of NAD+ in aging, not only from the perspective of how the decline in NAD+ levels may promote the aging process, but also of how replenishing NAD+ in cells may help delay the development of age-related features, maintain cellular youthfulness, promote physiological resilience, and support healthspan.* 

Increasing evidence has demonstrated the efficacy of boosting NAD+ levels to support health as we age. Boosting NAD+ levels through supplementation with NAD+ precursors, such as nicotinic acid, niacinamide, nicotinamide mononucleotide (NMN), and nicotinamide riboside (NR), has therefore emerged as a promising approach to enhance the cellular NAD+ pool and support cell and tissue function and healthy aging [2,15,16].*

Types of NAD+ Support

Oral Supplementation with NAD+ Precursors

NAD+ is a large electrically charged molecule that requires a transporter to move across cellular membranes [17,18]. Whether or not NAD+ transporters are present in the human gastrointestinal tract, and if, or to what extent direct absorption of NAD+ occurs, is still unclear. It is believed that NAD+ taken orally is broken into its constituent, smaller molecules, in the gut by extracellular enzymes and gut microbes [19,20]. 

Because it does not survive digestion intact, the NAD+ molecule is not commonly used for oral supplementation. Instead, metabolic precursors for NAD+ are used as NAD+-boosting supplements. These include niacinamide, NMN and NR, used for NAD+ synthesis through the salvage pathway; nicotinic acid, used in the Preiss-Handler pathway; and the amino acid L-tryptophan in the de novo synthesis pathway [16,21].* 

In addition to metabolic precursors, NAD+ levels can also be promoted by compounds that support the activity of crucial enzymes in these pathways. For example, resveratrol supports the activity of the rate-limiting enzyme in the salvage pathway (NAMPT). Furthermore, ATP is required for all the enzymatic steps that convert nicotinic acid, niacinamide, NR, and NMN to NAD+ [22]. ATP must be bound to a magnesium ion and form an ATP-magnesium complex to be biologically active [23,24]. Therefore, magnesium can indirectly support NAD+ synthesis by facilitating the activity of ATP.* 

The primary benefit of NAD+-boosting supplements is to support healthy intracellular NAD+ levels, and consequently, all the cellular roles of NAD+ that underlie many NAD+ benefits to health and well-being, as we’ll see below. NAD precursors are usually well tolerated when taken at recommended amounts.* 

IV NAD+ Infusions

NAD+ IV infusions, also known as NAD+ IV therapy, is a procedure where NAD+ (i.e., the actual molecule, not a precursor) is administered intravenously through an IV line connected to a saline drip containing NAD+. The procedure typically takes place in specialized wellness centers or clinics, as it requires a healthcare provider to administer the infusion and ensure safety during the process. 

IV infusion bypasses the need for intestinal absorption and delivers NAD+ directly into the bloodstream. Therefore, NAD+ IV therapy offers a direct route to the systemic circulation for NAD+. Its main feature is that it quickly elevates plasma NAD+ levels, i.e., extracellular NAD+. IV therapy providers claim that users report improved energy levels, mental clarity, and physical stamina after IV therapy.

The protocol usually entails several IV infusion sessions followed by periodic maintenance sessions. Each session takes several hours as it is kept at a very slow pace to minimize any side effects that can occur if NAD+ is administered too quickly and its plasma levels rise too much. Prices may range from several hundred to over a thousand dollars per session. 

Other Methods

Other methods of NAD+ delivery include: 

• NAD+ injections, which consist of the delivery of NAD+ through self-administered intramuscular or subcutaneous injections; 

• NAD+ nasal sprays, which deliver NAD+ through the nasal passages; 

• NAD+ patches and other topical forms, which deliver NAD+ through the skin. 

These methods are being marketed as effective approaches to administering NAD+ to the body. It is claimed that they allow for rapid absorption of NAD+ into the bloodstream at a lower price relative to NAD+ IV infusions. However, there are no studies in humans assessing whether they are able to increase intracellular NAD+ levels or if they provide actual benefits. 

NAD+ Supplements vs NAD IV Therapy 

A major difference between NAD+-boosting supplementation and IV therapy is the type of NAD+ support they provide. Supplementation provides metabolic precursors that can be absorbed and taken up by tissues and used to produce NAD+ within cells, i.e., it supports intracellular NAD+ levels. IV therapy, on the other hand, delivers NAD+ molecules to the bloodstream and therefore primarily supports extracellular NAD+ levels.* 

Not enough research has been published on NAD+ IV infusions to paint a clear picture of what happens to NAD+ after it reaches the bloodstream. A pilot study that monitored a six-hour IV infusion revealed that, for the first two hours, neither plasma nor urine levels of NAD+ or its metabolites increased as much as would be expected given the amount of NAD+ molecules infused. From 2h onwards, both plasma and urine levels of NAD+ and metabolites rose at a higher rate until the end of the infusion (6h) [25]. This suggests that there may have been a rapid uptake of NAD+ and/or its metabolites into cells or extravascular compartments (e.g., interstitial fluid or cerebrospinal fluid) during the initial part of the infusion, followed by a saturation in NAD+ uptake that resulted in the progressive increase in plasma levels and urinary elimination of NAD+ and its metabolic products [25]. 

Therefore, this small study suggests that NAD+ IV infusions may provide some degree of immediate support for NAD+ in tissues, but that increasingly more of the infused NAD+ accumulates in the plasma (outside cells) and is eliminated in the urine as the IV session progresses. NAD+ can be taken up by cells directly through a transporter [17,18], but its uptake capacity is still unclear. NAD+ may also be metabolized by extracellular enzymes [26] into smaller molecules (e.g., niacinamide, NR) that can be taken up by cells and used to produce NAD+ intercellularly. But overall, it’s still unknown to what extent IV therapy may support intracellular NAD+ levels and, importantly, if it’s a lasting support.* 

Regardless of a possible intracellular NAD+ support, it is likely that the benefits of IV therapy are primarily due to the extracellular effects of NAD+, as NAD+ also has extracellular functions. Extracellular NAD+ can support immune signaling and immune responses [7,8,27,28] and may even behave as a neurotransmitter in the enteric, peripheral, and central nervous systems [29]. Therefore, it is possible that NAD+ IV infusions affect responses in the immune and/or nervous systems that contribute to the subjective feelings people report during and shortly following IV NAD+ administration.* 

Conversely, the benefits of NAD+ supplements derive primarily from boosting intracellular NAD+ levels over time, which is why they may take longer to produce noticeable effects. However, by supporting optimal NAD+ levels inside cells and tissues, in the long term, benefits may be more sustained and impact cellular functions in different ways than would be expected to occur from a periodic IV infusion.*

Unlike IV therapy, there is extensive research showing that supplementation with NAD+ precursors can boost tissue levels of NAD+. Preclinical studies with oral niacinamide, nicotinic acid, NMN, or NR have shown that NAD+ precursors can promote healthy NAD+ levels in the liver, kidney, adipose tissue, pancreas, lung, heart, skeletal muscle, thyroid, and brain, among others [30–67].*

Studies in humans have shown that NAD+ precursors can boost NAD+ levels in whole blood (i.e., plasma and/or blood cells) [68–78]. A significant, but variable, promotion of cerebral NAD+ levels has also been observed with NR [79]. Our own clinical studies have shown similar benefits for Qualia NAD+, our NAD+-boosting supplement. Our Qualia NAD+ double-blind, placebo-controlled clinical trial, which was completed by 63 participants aged 36 to 77 years, showed that Qualia NAD+ taken daily for one month significantly increased whole blood NAD+ levels by 67%.*† 

†Based on double-blind placebo-controlled studies. Individual results may vary. Full study results at qualialfe.com/nad-clinical2.

These studies show that oral supplements are a simple and effective method for supporting healthy NAD+ levels. Relative to IV therapy, NAD+-boosting supplements are a more accessible, affordable, and convenient approach that can be easily integrated into daily routines. Furthermore, several clinical studies have supported the safety and efficacy of NAD-boosting supplements, unlike IV therapy. Oral supplementation is therefore a scientifically validated approach to gradually promoting NAD+ levels over time.* 

Benefits of NAD+-Boosting Supplements

Healthy Aging 

Preclinical studies have shown that supporting NAD+ levels through oral supplementation with NAD+ precursors such as nicotinic acid, niacinamide, NMN, or NR supports several aspects of cellular function that are often compromised with aging and helps the body resist age-related physiological changes [80–82]. NAD+ precursors have been shown to support healthy mitochondrial function, energy metabolism, DNA integrity, healthy cellular senescence, redox balance, metabolic health, immune responses, cardiovascular health, muscle health, and brain health, for example [83–97].* 

In clinical trials, health-related outcomes have shown mixed results depending on the characteristics and health status of the study population. Still, studies with NR, for example, have shown support for metabolic health, mitochondrial biogenesis in muscle, and gut microbiota composition in adults [78], and enhanced redox homeostasis and exercise performance in older individuals [98].* 

Healthy Brain Function

Mitochondrial health in neurons is an important factor in cognitive health [99]. Age-related reductions in brain NAD+ levels can impact mitochondrial function and energy metabolism and thereby affect the production of ATP, which the brain requires in high amounts to support its energetic demands. Reductions in neuronal NAD+ levels can also affect redox balance, promote oxidative stress, and hinder optimal neuronal communication and synaptic plasticity [100]. Consequently, low NAD+ levels can significantly impact brain function and cognition. 

Replenishing NAD+ levels may help the body resist these age-related changes and support the brain’s resilience as we age, thereby contributing to maintaining healthy brain function and cognition as we age [100].*

Healthy Skin 

The decline of NAD+ levels also contributes to the skin aging process. Therefore, supporting NAD+ levels may help decelerate many features of skin aging to which an NAD+ reduction can contribute [101]. In vitro studies have shown that boosting NAD+ helped restore mitochondrial integrity in aged human fibroblasts [102]. Fibroblasts are the main cells of the dermis and are responsible for the production of structural molecules that provide firmness and elasticity to the skin. Boosting NAD+ may also support skin cells’ defenses from oxidative stress and environmental stressors, which are the main causes of skin aging [103–107]. In humans, supplementation with niacinamide supported uniform skin pigmentation [108].* 

Healthy Muscle Function

Reductions in NAD+ levels impact mitochondrial function, energy production, and redox balance in skeletal muscle. In turn, this affects muscle health, muscle function, and post-exercise regeneration, and influences muscle strength, which is a common feature of aging [14,109]. Boosting NAD+ levels in muscles may help preserve mitochondrial health and the regenerative capacity of muscles [14,109–111]. In humans, boosting NAD+ supported mitochondrial biogenesis in muscles [78], promoted muscle remodeling in overweight women [68], and enhanced physical performance in healthy middle-aged and older adults [69,73,98].* 

Healthy Cardiovascular Function

Similarly to skeletal muscle, NAD+ depletion with aging can affect the optimal health of cardiac muscle due to hindered mitochondrial activity, cell energy production, and redox balance in cardiac cells [14,97,112,113]. Preclinical studies have indicated that boosting NAD+ levels may help maintain heart muscle health and strength by supporting cardiac muscle metabolism with aging [14,62,97,110,111,114]. Boosting NAD+ also supported vascular function in animal studies by attenuating oxidative stress and age-related changes in endothelial function [88], supporting the healthy generation of new blood vessels [115], helping promote capillary density in muscles of old mice [116], and supporting healthy cerebral blood flow [117].*

Frequently Asked Questions

Is NAD+ supplementation safe? 

NAD+ is not usually used as a supplement because of its poor oral bioavailability. Dietary supplementation aimed at boosting NAD+ levels is usually done using NAD+ metabolic precursors. These molecules, which include nicotinic acid, niacinamide, NMN, and NR, are generally well tolerated. The most common side effect is flushing (an experience of tingling, heat or redness in the skin), which can occur with supplementation with nicotinic acid (niacin), particularly when taken in amounts substantially above the daily value (DV) amount. For most people who experience this, it will stop if use is discontinued. The other forms of vitamin B3, niacinamide and NR, do not cause flushing. None of the NAD+ precursors have been associated with serious adverse effects at recommended amounts [19,118].*

Can I combine NAD+ with other supplements? 

NAD+ is not usually used as an oral supplement because the molecule may not be effectively absorbed in the intestines. NAD+ precursors and intermediates such as niacinamide, nicotinic acid, or NR are the molecules used as NAD+ boosting supplements. These can be combined with other oral supplements.*

How Qualia NAD+ Supports NAD+ Levels

Maintaining adequate levels of NAD+ is crucial for good health, particularly as we age and NAD+ levels in tissues naturally decline. NAD+-boosting supplements such as Qualia NAD+ are a simple approach to do so. Qualia believes that the best strategy for long-term well-being and healthy aging is to support the functional redundancy inherent in the human body for NAD+ maintenance. This means that rather than supporting only one pathway of NAD+ production, we developed Qualia NAD+ to support intracellular NAD+ levels through the multiple pathways of NAD+ synthesis. This entails providing several substrates for NAD+ biosynthesis (NIAGEN® Nicotinamide Riboside, niacinamide, and nicotinic acid), along with supporting rate-limiting steps in the different pathways. You can learn more about our formulation approach here: Qualia NAD+ ingredients.*

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. 

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