NAD+ IV Therapy

What is NAD+ IV Therapy?

NAD+(nicotinamide adenine dinucleotide) is a widely present coenzyme in organisms, playing a crucial role in cellular metabolism. NAD+exists in all living cells and participates in various biochemical processes. The main functions of NAD+include energy production, DNA repair, and activation of longevity genes. Due to the importance of NAD+and its decreasing trend with age, some studies are exploring the possibility of supplementing NAD * precursors such as NMN (nicotinamide mononucleotide) or NR (nicotinamide ribose) to increase NAD+levels in the body, thereby activating anti-aging related pathways such as the SIRT protein family, as a potential anti-aging strategy.

• NAD+ decreases with age, peaking in the teens.
• It turns out that NAD+ plays an important role in DNA repair and preventing aging.

→ The lack of NAD+ in the body will not only lead to rapid aging, but also one of the causes of lifestyle diseases such as diabetes.

Activation of Sirtuin Gene By NAD+

• The sirtuin gene is also known as a longevity gene or anti-aging gene.
• The sirtuin gene is closely related to aging and lifespan.
• According to research, activating the sirtuin gene can prolong the lifespan of organisms.
• Activating the sirtuin gene can improve and restore bodily functions such as repairing skin cells, enhancing physical strength, and relieving fatigue.

Expected effects of NAD+ Drip Therapy

• Aging care
• Improvement of fatigue
• Cognitive function and memory
• Liver function and renal function
• Reduction of wrinkles and improvement of skin quality
• Weight control to prevent weight gain
• Improvement of sleep quality by cycle control of sleep and wakefulness
• Enhancing immunity
• Inflammation and pain reduction
• Improving motor ability
• Muscle function recovery
• Cardiovascular function recovery

Difference between NAD+ and NMN

NAD+ (nicotinamide adenine dinucleotide) and NMN (B-nicotinamide mononucleotide) play different roles in organisms, and there is a direct precursor product relationship between them. In Japan, NMN drip is a hot topic in anti-aging. NMN is a precursor substance of NAD + , which generates NAD+ through biotransformation pathways. NAD+ drip therapy is very common in the United States. By using NAD+ drip therapy, direct injection of NAD+ components into the body can quickly reach various parts of the body.

Injecting NAD+ for Anti-Aging Purposes

Suggested solution: (It is not necessary to strictly follow the protocol. The doctor's assessment of the patient's health and vitality is a prerequisite for determining and adjusting the dosage and frequency).

Attention: NAD+ infusion takes a long time. Excessive infusion speed may lead to side effects, so please adjust the infusion time according to the concentration of NAD+, or consider spending slightly longer than the recommended infusion time.

※ During the NAD+ drip, you may feel mild chest tightness. Some patients may also experience mild nausea and headaches, but these symptoms can be alleviated by slowing down the infusion rate.

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NAD+ drip capacity, required time, and dilution amount (physiological saline)

100mg 1 hour Minimum (200ml～250ml)
200mg 1.5～2 hours Standard (200ml～250ml)

Drip method: Firstly, 100ml of physiological saline is intravenously injected into the left or right arm. (About 15 minutes) Then, administer the NAD+ containing formulation intravenously to the left or right arm.

※ The first infusion takes a longer time to observe for any side effects.

※ When there are fewer adverse reactions, the infusion time can be shortened during the second infusion.

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Drip Frequency

Intensive (集中) ★★★
After a daily session of 3-10 consecutive days (intravenous infusion of 100-250mg), switch to Standard or Minimum Treatment Course

Standard (標準) ★★
Once every 2 weeks to 1 month (intravenous infusion of 100-250mg)

Minimum (最低限) ★
Once a month (intravenous infusion of 100mg once)

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For the general healthy population, once a month drip therapy can provide sufficient ingredients (NAD) to maintain optimal health and performance. But in many cases, it may be necessary to have an intravenous drip every other week (once every two weeks). The reason is that the components ingested through intravenous NAD+ usually stay in the body for 2 to 3 weeks. Once the equilibrium state is reached, many customers need to receive NAD+ infusions once a month to maintain their physical health. In addition, there are also patients who receive intravenous infusion when experiencing fatigue or other clinical problems. Most people can feel significant effects after receiving a single treatment, but if they continue with intravenous infusion, they can see better results after about a month. The effect of the first drip is considered to last up to two weeks.

NAD+ drip therapy is suitable for daily maintenance of the human body, so in most cases, a monthly dose is sufficient. However, if necessary, NAD+ infusion is also a safe therapy that can be treated multiple times within a month. The treatment plan varies from person to person. The subjective reactions of patients are crucial in determining the frequency of maintenance treatment. For example, after receiving intravenous NAD+, many patients report increased cognitive function (increased brain clarity).

Adverse Reactions / Side Effects

NAD+ drip is considered a safe and highly tolerated treatment method. The side effects of NAD+ infusion include but are not limited to symptoms such as headache, shortness of breath, constipation, increased plasma bilirubin, decreased levels of gamma glutamatyltransferase, lactate dehydrogenase, and aspartate aminotransferase.

The case report on the use of NAD+ to treat drug addiction provides preliminary detailed information on side effects and safety. A report in 1961 described that drugaddicts reported "no pain" at slower drip rates (less than 35 drops per minute). However, at a faster drip rate, patients may experience symptoms of headache and shortness of breath. In this report, the patient received 500- 1000mg intravenous infusion every day for four days, and then changed to once every two weeks for one month, receiving two intravenous infusions per month. One of the two patients reported experiencing constipation symptoms during the treatment process.

In 2019, a group of healthy male subjects aged 30-55 (n=11, NAD+n=8, control group n=3) underwent liver function testing (serum, total bilirubin, alkaline phosphatase, alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, aspartate aminotransferase adverse reactions) for clinical observation, and the safety of intravenous infusion of NAD+ was studied. During the 6-hour infusion process, there were no adverse reactions observed in both the NAD+ and control (saline) groups. In NAD+ infusion, a significant decrease in liver function enzymes (gamma glutamatyltransferase, lactate dehydrogenase, and aspartate aminotransferase) and a significant increase in plasma bilirubin were observed. However, these changes are considered to have nosignificant clinical significance.

The author acknowledges that the sample size is relatively small, especially in the control group. Therefore, caution should be exercised when interpreting these results.

Taboos / Precautions

※ At present, there have been no reports of serious adverse reactions to intravenous NAD+. Patients with a history of allergies are not suitable for intravenous administration of NAD+.

Pregnancy / Lactation Period

※ The safety of NAD + drip is not evaluated for pregnant women. Avoid pregnant nad drip becaus e there is no data on safety.

※ Safety of NAD + drip infusion to women and children during lactation is not evaluated. Because there is no safety data, women and children during lactation avoid nad injection.

Regarding The Free Treatment of Unrecognized Medical Drugs

• It is necessary to disclose that this product is an unrecognized medical drug and the way it was purchased

The NAD+ preparation used in this treatment has not yet been recognized in pharmaceutical and medical device laws. In Japan, unapproved pharmaceuticals and medical devices cannot be used without the responsibility of a physician.

• ‍Is there a recognized similar pharmaceutical product in Japan

There is currently no recognized pharmaceutical product in Japan that has the same performance as the one used in this treatment.

• Current information on security in various countries

At present, there have been no reports of significant side effects.

Summary of Nicotinamide Adenine Dinucleotide (NAD+) Injection Drug

Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous intracellular electron transporter, coenzyme, and signaling molecule in all cells of living organisms, essential for cellular function and survival. NAD+ and its reducing molecules (NADH), as well as phosphorylated molecules (NADP+ and NADPH), all play important roles. NAD+ and its reducing molecule (NADH) are indispensable in the production of energy (ATP) in all parts of cellular respiration, including glycolysis in the cytoplasm, tricarboxylic acid cycle in mitochondria, and electron transfer reactions.

NADP and NADPH are involved in the synthesis of cholesterol and nucleic acids, the extension of fatty acids, and the regeneration and assimilation of glutathione, a substance with important antioxidant effects in the body. In other cellular processes, NAD+ and other forms of NAD+ are used as substrates for protein post-translational modifications by enzymes that rely on NAD+ /consume NAD+. NAD+ is also a precursor of cyclic ADP ribose, which is a crucial secondary messenger molecule for calcium signaling.

NAD+ is synthesized in the body through natural synthesis pathways of tryptophan (De Novo pathway/Ky nurenine pathway, KP) or through biosynthetic intermediates such as niacin and nicotinamide, which are collectively known as vitamin B3 or niacin precursors (Nam salvage pathway). In the rescue pathway, NAD+ continuously circulates within cells and converts with other forms of substances. Cell culture studies have also shown that mammalian cells can absorb extracellular NAD+ .

The NAD+ content in newborns is the highest and steadily decreases with age; After the age of 50, the NAD+ content is about half of that of young adults. The question of why NAD+ levels decrease with age has been studied in model organisms. During redox reactions, NAD+ and NADH are not consumed but continuously recycled. However, in other metabolic processes, NAD+ dependent enzymes consume NAD+ , and over time, NAD+ may be depleted, leading to increased DNA damage, age-related symptoms and diseases, and mitochondrial dysfunction. The health and function of mitochondria decrease with age, which is prominent in the theory of aging and senescence. Research on NAD+ consumption and subsequent oxidative damage and stress also confirms these views.

A study conducted on mice in 2016 showed that the age-related decrease in NAD+ levels in mice was similar to what was observed in humans. The study revealed that the age-related decrease in NAD+ levels was caused by an increase in CD38, a membrane-bound NAD+ enzyme that can break down NAD+ and its precursor nicotinamide mononucleotide. The study also found that the expression level of CD38 gene is increased in the adipose tissue of elderly people (average age 61) compared to young people (average age 34). However, other studies on mice have shown that inflammation and oxidative stress caused by aging can reduce the biosynthesis of NAD+ . Therefore, the age-related (aging) reduction of NAD+ in humans may involve a complex mechanism.

The clinical importance of maintaining NAD+ levels was established as early as the early 20th century, when it was discovered that foods containing NAD+ precursors (especially vitamin B3) could cure pellagra characterized by diarrhea, dermatitis, dementia, and death. It is worth noting that supplementing with vitamin B3 (niacin) can cause skin redness, while injecting NAD+ does not have this side effect. In recent years, the decrease of NAD+ level has been confirmed to be related to many aging related diseases and diseases with increased oxidative/free radical damage, including diabetes, heart disease, vascular dysfunction, ischemic brain damage, Alzheimer's disease and visual impairment.

NAD+ intravenous injection has been used for many years, originating from Dr. Paul O'Horalen's 1961 research report at Shaddell Hospital in Seattle, Washington, and widely used to treat addiction. Dr. Ohoran uses intravenous injection of NAD+ to prevent, alleviate, and treat acute and chronic symptoms of various drugs, including alcohol, heroin, opium extract, morphine, dihydromorphine, methylprednisolone, codeine, cocaine, amphetamine, barbiturates, and sedatives, and has presented over 100 successful cases. However, so far there have been no clinical trials evaluating the safety and efficacy of NAD+ in treating addiction.

NAD+ supplementation therapy can promote mitochondrial health and balance, genomic stability, neuroprotection, healthy aging, and longevity, and can help treat dependency disorders. However, clinical trials evaluating the therapeutic effect of NAD+ intravenous therapy on individuals have not yet been officially published. However, many clinical trials have recently been completed to evaluate the efficacy and safety of NAD+ supplementation or enhancement therapy for human diseases and aging, and there are still many ongoing trials.

Mechanism of action

The exact mechanisms underlying the potential health benefits of supplementing or enhancing NAD+ , such as supporting healthy aging and treating age-related diseases, metabolic and mitochondrial disorders, and addiction, are not yet clear. Supplementing NAD+ can counteract the age-related degradation of NAD+ and its precursor nicotinamide mononucleotide by NAD+ enzymes (especially CD38), prevent mitochondrial dysfunction, and maintain metabolic function/ energy (ATP) production. However, studies on animal models and humans (and/or samples and cell lines) have shown that it also assists several other biological pathways through NAD+ dependent enzymes.

There are several enzymes that rely on NAD+ that are worth noting. CD38 and CD157 are NAD+ enzymes, and their products (cADP ribose, ADP ribose, and nicotinate adenine dinucleotide) are used for Ca ²+ signaling and intercellular immune communication. Sirtuins (Sirt 1-7) are a member of the histone deacetylase family, which can regulate various proteins related to cellular metabolism, cellular stress response, circadian rhythm, and endocrine function. SARM1 is a recently discovered NAD+ hydrolase involved in neuronal degeneration and regeneration.

Through the study of premature aging syndrome, we have gained some understanding of the mechanism of action of NAD+ supplementation. Werner syndrome (WS) is considered to be the syndrome closest to natural aging, characterized by extensive metabolic dysfunction, dyslipidemia, early atherosclerosis and insulin resistant diabetes. WS is caused by a mutation in the gene encoding Werner (WRN) DNA helicase, which regulates the transcription of an important NAD+ biosynthetic enzyme called nicotinamide nucleotide adenylate transferase 1.

A 2019 study showed that the depletion of NAD+ is a key inducing factor for WS metabolic dysfunction caused by mitochondrial imbalance. NAD+ depleted cells extracted from WS patients and WS animal model samples showed impaired mitotic function (selective degradation of defective mitochondria).

Supplementing NAD+ can restore normal mitosis and regulate NAD+ metabolism in WRN mutant human cells, improve fat metabolism, reduce mitochondrial oxidative stress, and improve mitochondrial quality. In animal models, supplementing NAD+ can significantly prolong lifespan and delay accelerated aging, including increasing the number of proliferating stem cells in germ cells. By taking various NAD+ precursor molecules to supplement NAD+ , the results were replicated, confirming that the beneficial effect is attributed to the supplementation of NAD+ .

The irregular mitochondria of mouse cells overexpressing NAD+ enzyme CD38, including low oxygen consumption, elevated lactate levels, and missing or expanded cristae, further demonstrate the role of NAD+ in promoting mitochondrial and metabolic health. Compared with the control group, mitochondria isolated from these cells showed severe loss of NAD+ and NADH; In CD38 deficient mice, NAD+ levels, mitochondrial respiratory rate, and metabolic function are maintained after aging.

Pharmacokinetics

A pharmacokinetic study evaluated the changes in NAD+ and its metabolite concentrations after intravenous injection in a group of healthy male subjects (n=11; NAD+ n=8 and control group n =3). After continuous infusion of NAD+ 6 hours (750mg, 3 ì mol/min), the levels of NAD+ (398%), nicotinamide (409%), and adenosine phosphoribose (ADPR, 393%) in plasma significantly increased compared to baseline at the end of infusion (p<0.0001, p<0.001, p<0.001, andp<0.0001, respectively). There is also a significant difference compared to the control group. After 8 hours, there was still a significant difference in NAD+ levels among the groups, but there was no significant difference in the levels of nicotinamide and ADPR. In both control groups, the levels of these two NAD+ metabolites were significantly correlated within8 hours (=1.0, p<0.001), indicating that NAD+ was cleaved into nicotinamide and ADPR by NAD+ enzymes such as CD38. With the increase of nicotinamide, the plasma levels ofits metabolites methylnicotinamide (350%) and nicotinamide mononucleotide (NMN; 472%) also significantlyincreased compared to baseline (p<0.0001) and the control group (p<0.05) at the end of NAD+ infusion (p<0.0001, p<0.05, respectively).

In the NAD+ injection group, the level of NAD+ excreted in urine after injection (6 hours) significantly increased (53.8%) compared to the level measured 30 minutes later (p<0.001), and there was a significant difference compared to the control group (p<0.05). Compared to the peak at 6 hours, the value at 8 hours decreased by 43% (p<0.05).

Excess NAD+ and its metabolites will be excreted from the body through urine. In the NAD+ group, there was no change in urinary excretion of nicotinamide within 8 hours, while methylnicotinamide showed a significant increase after infusion (6 hours) compared to 30 minutes. It is noteworthy that there was no significant increase in NAD+ or its metabolites in plasma or urine during the first 2 hours after injection, indicating rapid and complete tissue absorption and/or metabolism (at least during the first 2 hours).

The intracellular concentration of NAD+ is maintained at 0.2-0.5 mM, and NAD+ is believed to bedistributed in three compartments: the nucleus, cytoplasm, and mitochondria. The NAD+ rescuepathway plays a role according to the needs of each compartment. However, it is currently unclear how injection of NAD+ affects intracellular and intercellular NAD+ levels.

The Advantages of NAD+ Drip Therapy

Nicotinamide adenine dinucleotide (NAD+) was discovered in the early 18th century and is an important component of cellular metabolism and reactions in the human body. Without the presence of NAD, all important cellular activities in the human body cannot take place. The processes that rely on NAD include glycolysis (breaking down glucose into pyruvate and hydrogen), citric acid cycle or tricarboxylic acid cycle (releasing energy stored in carbohydrates, proteins, and fats through the oxidation of acetyl CoA), fatty acid oxidation or degradation, DNA repair, inflammatory response, and many other reactions. NAD is usually oxidized or reduced to affect metabolic processes in the body; The oxidized form of NAD is called NAD+.

How is NAD+ synthesized?

There are two main mechanisms for the synthesis of NAD+ in the human body. One is the natural synthesis pathway De Novo pathway/canine urea pathway, in which NAD+ is synthesized from tryptophan (an essential amino acid). In this pathway, tryptophan undergoes oxidative cleavage to produce formylkynurenine. Tryptophan -2,3-oxygenase (TDO) and indoleamine-2,3-dioxidase (1D0) promote this process. The second pathway for synthesizing NAD+ is called the salvage pathway (Nam salvage pathway). The reason why it is named the salvage pathway is because when niacin, nicotinate adenine mononucleotide, and nicotinamide are consumed, NAD+ is recycled, hence the name. Nicotinamide phosphoribosyltransferase (Nampt) converts nicotinamide to nicotinamide adenine mononucleotide (NMN), which is then converted to another NAD enzyme, nicotinamide adenine transferase (Nmnat). In addition, niacin can be used as a precursor for synthesizing NAD+, producing nicotinate mononucleotide (NAMN), which can be converted to NAD+ by Nampt enzyme. The diversity of NAD+ synthesis pathways indicates the importance of NAD+ for the human body.

As mentioned earlier, NAD+ plays a crucial role in all major processes in the human body, so it is necessary to maintain NAD+ levels at optimal levels. Like pellagra, when symptoms of NAD+ deficiency such as dermatitis, dementia, and diarrhea occur, intravenous injection of NAD+ may be necessary. In addition to symptoms of NAD+ deficiency, there are also some reasons why individuals may consider receiving intravenous injections of NAD+. Some of the reasons are as follows:

1) Addiction Therapy

One of the most common reasons for considering intravenous injection of NAD+ is addiction treatment; Intravenous injection of NAD+ is effective for patients attempting to quit opioid, alcohol, chemical, and prescription drug addiction, and can also minimize the severity of withdrawal symptoms. The mechanism of action of NAD+ is still under study, but it is believed that intravenous injection of NAD+ can help clear drugs and reduce addictive desires.

2) Improve Cognitive Function

As mentioned above, NAD+ has protective and stimulating effects on the brain. Therefore, intravenous injection of NAD+ is expected to improve memory, enhance attention, promote brain regeneration, and improve overall neurological function. The exact way in which exogenous NAD+ supplements exert these effects is still under investigation.

3) Relieve Chronic Fatigue

Intravenous injection of NAD+ can be used to treat patients with chronic fatigue and lack of energy. NAD+ is an indispensable cofactor in the glycolysis and tricarboxylic acid systems, andthe adenosine triphosphate (ATP) produced by these pathways is the energy source of the human body. Supplementing with exogenous NAD+ is expected to increase ATP levels in the body, thereby increasing energy levels and reducing fatigue.

4) Enhance Athletic Ability

NAD+ participates in the generation of ATP, so athletes also receive intravenous injections of NAD+ to improve their athletic performance and results; NAD+ intravenous injection can increase the energy level, promote cognition, and improve reaction speed of competitive athletes. In addition, studies have shown that supplementing NAD+ can help with muscle repair and development, assist in muscle enlargement and muscle generation.

5) Pain Management

A new reason for intravenous injection of NAD+ is pain treatment. As is well known, NAD+ has significant anti-inflammatory effects in the body and is expected to alleviate pain by reducing inflammation associated with pain. The research on controlling pain by supplementing NAD+ is still ongoing, and there are no definite results so far.

6) Cardiovascular Function

The heart beats constantly and is the most metabolically active organ in the human body. Research has shown that normal NAD+ levels are crucial for maintaining the metabolic activity of the heart. In addition, normal levels of NAD+ are said to aid in post injury recovery in the event of severe heart disease, such as transient ischemic attacks or myocardial embolism. Other studies have shown that a lack of NAD+ can lead to heart diseases such as cardiac hypertrophy and fibrosis.

7) Renal Function

Generally speaking, kidney function decreases with age. Research has shown that supplementing NAD+ can enhance the preventive effect on acute kidney injury. In addition, supplementing NAD+ can promote the release of prostaglandin E2, which plays a role in improving renal function after acute kidney injury.

8) Liver Function

Normal NAD+ levels in the body are crucial for optimizing liver function; Some enzymes in the NAD+ pathway have been shown to prevent liver fibrosis. Research has shown that supplementing NAD+ can improve overall liver health, protect the liver from toxic diseases, and enhance the regenerative capacity of the liver after damage. These research results have also been published in papers.

9) Nervous Function

It has been proven that NAD+ and its precursors have a protective effect on brain neurons after severe neurological events such as stroke. The normal level of NAD+ in the body is crucial for the normal function and survival of brain neurons. In addition, supplementing NAD+ has been shown to be effective in treating and preventing certain neurodegenerative diseases, such as Alzheimer's disease, although these conclusions have not yet been established, there are still multiple studies exploring this possibility.

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Personalized Treatment for Your Needs:

At Artisan Regenerative Centre, we offer personalized NAD+ IV therapy treatments to ensure that you get the right dose based on your health goals. Our licensed medical professionals will work with you to determine the appropriate amount of NAD+ you need, whether it's for a one-time boost or a more comprehensive treatment plan.

Is NAD+ IV Therapy Right for You?

NAD+ IV therapy is a highly effective treatment for those looking to restore energy, enhance cognitive function, and support overall health. Before starting any treatment, we encourage you to consult with one of our licensed healthcare professionals to determine the best course of action based on your unique needs. Whether you're looking for a one-time energy boost or seeking to undergo a comprehensive NAD+ therapy plan, we are here to guide you on your wellness journey.