It has long been known that when swallowed, NAD+, NMN and NR are mostly hydrolyzed to NAM in the stomach.
This study showed supplementation with NAM increases NAD+ levels just as much as NR and NMN, and it is not known how much more effective an oral supplement of NR, NMN or NAD+ is as compared to regular old NAM.
More surprising, was the Liu study published in Mar 2018 that clearly proved nearly all supplements of NR and NMN are digested to NAM in the stomach or liver, with very little reaching past the liver.
So while researchers have had success using oral supplementation with NAD+ precursors such as NR and NMN to increase NAD+ levels inside the body, they are all clearly degraded when passing through the stomach.
Taken sublingually (under the tongue) NAD+, NMN and NR may be more effective as they can be rapidly absorbed directly to the bloodstream, bypassing the GI tract entirely.
THE PROBLEM with CAPSULES – DIGESTED TO NAM
This research published in 2018 confirms that most oral supplements of NMN and NR are digested to NAM in the GI tract or the liver.
At 50Mg/Kg of body weight, NO NR or NMN made it out of the liver intact.
Future pharmacological and nutraceutical efforts to boost NAD will need to take into account the minimal oral bioavailability of NR and NMN (R)
Unlike in cell culture where NR and NMN are readily incorporated into NAD, oral administration fails to deliver NR or NMN to tissues (R)
Interestingly, we found that neither compound was able to enter the circulation intact in substantial quantities when delivered orally (R)
That question is totally irrelevant if a molecule NEVER REACHES THE BLOODSTREAM.
This study used a small dose – 50 Mg/Kg of bodyweight (equivalent to 250 Mg for a 70 kg human), vs the 300-400 Mg/Kg commonly tested in other research. Perhaps higher dosages allow NAD+ precursors to make it past the Liver to other tissues.
It is clear that for Oral Supplements (Capsules), the bioavailability of any NAD+ precursor is very poor outside of the Liver.
SUBLINGUAL DELIVERY BYPASSES THE STOMACH AND LIVER
The absorption of the different molecules delivered through the sublingual route can be 3 to 10 times greater than oral route and is only surpassed by direct IV injection (r).
SUBLINGUAL CAN BE MORE BIOAVAILABLE THAN IP INJECTION !
With intraperitoneal injection, the primary route of absorption is via the mesenteric vessels, which drain into the portal vein and pass through the liver before reaching the bloodstream.
This means, IP avoids the GI tract, but is still sent directly to the Liver, where much of it is converted to NAD+. Elevated NAD+ in the liver is good, but its far better to reach the bloodstream with intact NMN.
Sublingual delivery is not filtered by the Liver and can reach systemic circulation intact, so can actually result in greater bioavailability that direct injection! Some examples are:
- A sublingual formulation of zol… exhibited a faster rate of absorption and higher drug exposure as compared to subcutaneous injection (r)
- sublingually administered epin… results in more rapid absorption and a higher peak plasma concentration compared to injected epin… .(r)
- 40mg of sublingually administered pir.. was found to be as effective as a 75 mg intramuscular injection of dicl… (r)
NAD+ METABOLISM IN HUMANS
NAD+ can be synthesized in humans from several different molecules (precursors), thru the De Novo and Salvage Pathways.
Nampt is the rate-limiting step in the salvage process (97).
As we age, Nampt enzyme activity is lower, resulting in less NAM recycling, less NAD+, more disease and aging (97,101).
SUBLINGUAL NMN AND NAD+ BYPASSES THE NAMPT BOTTLENECK
Restoring NAD+ in the Liver does not solve NAD+ deficiency throughout the body.
In the Liver, the CD38 enzyme metabolizes NAD+ to NAM, which is excreted to the rest of the body (r).
Sublingual delivery of NMN or NAD+ directly to the bloodstream bypasses the liver and the Nampt bottleneck that is the root cause of NAD+ deficiency in many tissues.
NAD+ DOES CROSS THE BLOOD BRAIN BARRIER AND ENTERS CELLS INTACT
There are claims that both NMN and NAD+ are “TOO LARGE”, and cannot enter cells directly, but must first be broken down to NR.
We recently wrote this article refuting that theory.
On September 1 2018, more proof was published proving that NAD+ crosses the blood brain barrier, enters the hypothalamus INTACT, and raises NAD+ levels.
Even better, just 1 Mg/kg a day decreased hunger, increased energy expenditure and fat burning for up to 24 hours after dosage.
For reference, most research providing mice with NMN or NR in drinking water uses 300 to 400 Mg/kg a day.
This study found both IV and IP injections had similar results. The results with 1-3 Mg/Kg by IP is extremely promising, as we note that sublingual delivery can be even more effective than IP delivery.
NAD+ IV clinics have been treating patients for decades.
IV Injections avoid the digestion problem that limits the effectiveness of NAD+ Booster capsules.
They have found that an IV drip which provides a slow, constant supply of NAD+ directly to the bloodstream over a long period of time is the most effective delivery method.
Treatment plans are often 8-14 days, cost $1,000-$1,300 a day, and require the patient to sit for 8 hours or more hooked up to an IV drip.
In the last ten years, NAD+ has been more widely used to help detoxify from other types of chemical dependencies, including benzodiazepines, methadone, suboxone, methamphetamines and stimulants.
Below are some of the most well known clinics:
BR+ NAD Minimizes the Cravings and Withdrawal Symptoms of Addiction Detox through Brain Restoration
Our proprietary BR+ NAD IV treatment restores brain function while minimizing withdrawal symptoms and reducing or eliminating cravings. It further enhances brain function by improving clarity, well-being, and impulse control: your life is your own again.
Improves Brain Function
We are the leading provider of this breakthrough treatment in the US. We provide treatment for a growing list of conditions, beginning with addiction recovery and extending to Parkinson’s, Alzheimer’s & other degenerative diseases.
NAD Treatment Center™ is a provider of Brain Restoration Therapy, using intravenous NAD+. The therapy assists in alleviating brain-destroying diseases of alcoholism, addiction, chronic stress, depression and anxiety. Combining innovation and compassion, our medical team provides healing and hope for people who are affected by substance abuse and addiction. NAD+ supports the detoxification process and brain function to help your ongoing treatment and aftercare
Researchers investigating brain health and longevity have found NAD+ is an essential coenzyme that promotes cellular regeneration. Studies have found replenishing cellular levels of NAD+ can repair DNA, protect brain cells from damage, reduce inflammation and turn on enzymes that help prevent aging.
Intravenous NAD+ has been used since the 1960s to help individuals detoxify from alcohol and opioid dependencies. In the last ten years, NAD+ has been more widely used to help detoxify from other types of chemical dependencies, including benzodiazepines, methadone, suboxone, methamphetamines and stimulants.
Many chronic conditions, including chronic fatigue syndrome, neurodegenerative disease and mental health disorders have been linked to cellular dysfunction and dysregulation. NAD+ therapy may help reduce the symptoms of many chronic conditions, and may help individuals suffering from chronic conditions regain their vitality and strength.
What if there was a compound that could turn back time, restore energy, improve athletic performance, bring back clarity of thought, reverse depression and help cure cravings for alcohol and drugs even in the most addicted individuals?
There is such a substance. It is called NAD+, and it occurs naturally in every cell in your body.
Compelling research has shown that supplementing with NAD+ may help you withdraw from addictive substances safely, overcome anxiety and depression, handle acute and chronic stress more effectively, and cope better with PTSD.
In fact, clinics across the US are starting to use IV infusions of NAD+ to help people withdraw from drug and alcohol addiction with minimal symptoms in as little as 7-14 days of treatment. These individuals report feeling calm and content and say they lost their “cravings” after a full course of treatment.
And NAD+ may actually prolong life, protect DNA, slow down aging and help restore function in neurodegenerative illness due to its effects on the genes that govern aging.
Dr. Starr prescribes Nicotinamide Adenine Dinucleotide (NAD+) for intravenous administration under the supervision of our trained registered nurses. NAD+ treatments are performed in our outpatient infusion rooms. While each infusion session typically takes a full 6-8 hours, the duration of NAD+ treatment typically requires 10 (or more) sessions to ensure complete results. For treatment for a non-addiction disorder, such as stress or anxiety, your treatment course may be shorter, and is ultimately determined during your medical assessment with Dr. Starr.
NAD+ Therapy involves a high dose intravenous infusion of NAD+ that goes straight into the bloodstream. IV therapy allows NAD+ to bypass the digestive system for better absorption. NAD+ works rapidly to repair cells throughout the body and neurons in the brain. When your NAD+ levels are increased, your cells produce more energy, your good genes are “turned on”, DNA is repaired, and many other functions are optimized. Since NAD+ is such a powerful and prolific molecule in the body, high dose IV therapy can be helpful for many different conditions.
CONDITIONS SUCCESSFULLY TREATED WITH NAD OR BRAIN RESTORATION THERAPY BR+
Reflex Sympathetic Dystrophy
Chronic Migraine Headaches
Depression / Anxiety
NAD is short for Nicotinamide Adenine Dinucleotide. NAD is a coenzyme of Niacin, which is vitamin B3. Niacin produces energy in the body which is needed for its proper function and well-being. However, people that are involved in drug and alcohol abuse are deficient in NAD making it hard for them to get over their addictions. It is no wonder high-end drug rehabs used it to detox heavily addicted patients from tranquilizers, alcohol and stimulants among others.
NAD IV Drips Brain Restoration Therapy
A majority of people that are addicted to alcohol and other harmful drugs usually suffer from a severe form of neurotransmitter imbalance. This imbalance results in them experiencing insomnia, depression and anxiety among others. Apart from this imbalance, their bodies also absorb nutrients poorly leading to other mineral imbalances and their capability in forming neurotransmitters is also negatively affected. However, when amino acids are introduced into the body along other vitamins and coenzymes the proper levels are re-established and neurotransmitters begin to be properly circulated in the body, thus eliminating or at least reducing the withdrawal effects a drug addict would have otherwise experienced.
NAD IV Drips Brain Restoration Therapy is based on the supplementing of amino acids in the body so that it can be able to produce its own neurotransmitters and utilize them properly as well. When the production and utilization are done well through exercise and proper nutrition, the drug addict begins to get closer to being completely cured other than the suppression of symptoms as other conventional therapies have been known to do.
In general, the use of NAD amino acid IV drips to repair the brain of drug addicts has been quite successful. For those considering signing up for the treatment in any of the drug rehab centers run by professionals, it is important to note that:
The treatment only works when followed as described by a health worker at an accredited facility. Also, the length of treatment varies from one person to another thus making it important to exercise patient while seeking this kind of treatment for addiction. For example, alcohol addiction can be overcome much faster when compared to other hard drugs. Patients interested in NAD amino acid IV Drips should expect to be discouraged by medical experts on the use of this addiction treatment but with the proper administration, the results are likely to be successful. Finally, NAD IV Drips for Addiction Treatment can be a bit costly but the benefits are worth it in the long run.
How is NAD Therapy Used?
NAD Therapy Requires The Use Of An IV DripIn NAD Therapy, the co-enzyme is placed in an IV and slowly dripped into the blood stream. This allows the substance to bypass the stomach (where analgesic medication breaks down) and travel directly to the brain. This provides the individual with a boost of energy, providing enhanced mood and awareness, as the energy they get is now from their natural sources, not other substances. It has also been claimed to slow the aging process. These benefits have opened the door for clinics to use it as a luxury, like a spa treatment.
Advertising it as an all-natural, mood-elevating, no-crash, anti-aging energy booster, clinics are selling to people who have not suffered an addiction of any kind. It is advertised as a therapeutic treatment to give them more energy and reverse aging. This procedure isn’t as lengthy as someone looking for rehabilitation and can be sold as a regular treatment appointment, receiving a “top off” every 6 to 8 weeks.
Why Use NAD Therapy to Treat Addiction?
It has been determined that the excessive use of drugs and alcohol will deplete the body’s natural stores of NAD. Because of this, the brain cannot receive the same energy it usually would from breaking down food. NAD Therapy floods the brain with the co-enzyme to replenish its stores, providing three key effects.
It flushes out all of the drugs that are still in the user’s system.
It curbs the cravings for alcohol and Opioids and lessens the pain of withdrawal, making recovery easier physically and mentally.
It allows the body to produce energy more naturally, without a crash or jitters like caffeine and sugar or the negative effects that come with other substances.
Length of sessions vary depending on severity of the addiction and what the clinic recommends. After the initial session, follow ups will be scheduled 1 to 2 months later. These sessions can continue at the discretion of the prescribing clinic.
Exogenous NAD+ crosses the BLOOD BRAIN BARRIER intact, increases NAD content in Hypothalamus, increases energy and decreases appetite
In this study, administration of LABELED NAD+ by IP and IV injection demonstrated that exogenous NAD+ crosses the blood brain barrier to enter the hypothalamus INTACT, reduces hunger and weight gain, and increases energy expenditure and fat burning in mice.
This study shows that NAD+ levels in the blood have a direct effect on the levels of metabolic activity in the body.
They also show that NR and NMN can not utilize the cd43 gap to cross the blood brain barrier.
This might explain why NAD+ clinics have found success treating addictions and other brain imbalances, but NR and NMN have not been used in similar fashion.
In mice, exogenous NAD may be transported to the hypothalamus via Cx43 at the blood-brain barrier  thereby increasing hypothalamic NAD content and decreasing food intake and weight gain.
Increasing evidence suggests that boosting NAD+ levels could be clinically beneficial, as it activates the NAD+/sirtuin pathway which yields beneficial effects on multiple metabolic pathways
Exogenous NAD+ crosses the plasma membrane intact, increases NAD content, and mitochondrial bioenergetics.
Although the canonical view considers NAD unable to permeates lipid bilayers (Di Lisa and Ziegler, 2001), several studies report evidence for exogenous NAD (eNAD) uptake by different cells “
These findings are at odds with the hypothesis that eNAD increase iNAD contents because of extracellularly-formed NAD precursors
mitochondria do not synthesize NAD at all, but rather take it up intact from the cytosol, which in turn, can take up NAD from the extracellular space
While mammalian mitochondria are generally considered to be impermeable to pyridine nucleotides (32,33), at least two studies have previously reported evidence for uptake of NAD
leading the authors to propose that intact NAD crosses the plasma membrane and subsequently enters the mitochondria directly
Protects against liver damage
NAD+ at the doses of 100 or 200 mg/kg was also injected intraperitoneally 1 h before the DOX administration.
NAD(+) is capable of increasing the antioxidation capacity of tissues.
NAD(+) can significantly decrease DOX-induced liver damage
can also selectively decrease tumor cell survival, NAD(+)
Treat Multiple Sclerosis autoimmune-related neurodegeneration
NAD(+) could be an effective and promising agent to treat multiple sclerosis
Prevents heart disease
Mice were simultaneously treated with NAD at 1 mg/kg/day for 2 weeks
NAD treatment was capable of maintaining cellular NAD levels
Exogenous supplementation of NAD restores the intracellular levels of NAD and blocks the cardiac hypertrophic response.
These results indicated that NAD treatment prevented the development of cardiomyocyte hypertrophy
NAD treatment restored the cellular NAD levels
NAD treatment may become a panacea for prevention and cure of many diseases in the future
Prevents heart damage from Stroke
NAD+ produced 85% decrease in the infarct size
NAD+ is one of the drugs that have greatest capacity to decrease myocardial ischemia
NAD+ dose dependently decreased infarct formation
Decreased brain damage
The profound protective effects of the intranasal NAD+ administration were also observed at 72 hrs after ischemia.
intranasal administration with 10 mg / kg NAD+, but not with 5 mg / kg NAD+, significantly attenuated the ischemia / reperfusion-produced neurological deficits
NAD+ administration can profoundly decrease brain damage under certain pathological conditions
Investigated as a potential anti-aging treatment
Promotes mitochondrial health,
Enhances fat oxidation
Protects against metabolic disease
It is imperative there is no doubt the finished product is free from harmful impurities and includes the quantity of NMN specified on the label. The 3 step quality certification process we use entails:
1. ACCEPTANCE TESTING:
Our initial acceptance testing ensures the raw ingredient does not include harmful amounts of heavy metals, alcohol (solvent) or microbials and is > 99% purity.
2. PRODUCT ASSURANCE TESTING:
After bottling, we send a random bottle to a second lab for product assurance testing that verifies the finished product has at least the quantity of Mg per capsule specifed on the label.
3. QUALITY CERTIFICATION:
Lastly, we ship a random sealed bottle to a third laboratory to verify the finished product meets the standards for strength and purity specified on the label.
We use 3 DIFFERENT LABS to certify the strength and quality of every batch of our NMN products.
This product is not intended to diagnose, treat, cure, or prevent any disease.