Treatment of substance abuse disorders continues to challenge clinicians and the patient’s cravings for the abused substance are often impediments to sobriety. Nicotinamide Adenine Dinucleotide (NAD+) has been used in the past with claims of having anti-craving properties.
NAD+ is in every human cell and is an essential part of hundreds of cellular processes. It’s most documented function is as a pivotal coenzyme in cellular respiration. What this means is that NAD+ is one of the most important parts in generating energy for your cells. While it is not the energy molecule ATP itself, NAD+ is essential to the creation of ATP in every one of the human body’s mitochondria. Two separate, but interrelated, respiratory processes—glycolysis via the Citric Acid Cycle and oxidative phosphorylation—use NAD+ as a reducing agent, and its reduced form NADH, as essential parts of human energy function.
NAD+ is present in each major compartment of the human cell (the nucleus, cytoplasm, and mitochondria), but it was not always clear how NAD(H) pools in each compartment influenced the others. Until recently it was assumed that the inner mitochondrial membrane was impermeable by NAD(H) and that new NAD+ was created de novo (brand new) in the mitochondria. New research has demonstrated that extracellular NAD(H) not only enters into the cytosol of a cell, but can directly and positively influence mitochondrial NAD(H) pools as well. What this means is an intravenous delivery of NAD+ to your body will increase the useable building block, allowing all of your cells to produce more energy. Like a breath of fresh air after being subjected to months of smog, your body will feel revitalized.
It has been demonstrated that adequate amounts of NAD+, NADH, and the maintenance of a proper NAD+ /NADH ratio are all tied to the efficient functioning of the human energy organelles (mitochondria). A small number of the many NAD-dependent enzymatic processes are of potential clinical significance: NAD+ is required for the selective DNA repair enzymes Poly ADP Ribose Polymerase (PARP1) and Sirtuins, silent mating type information regulation homologue 2 1, (SIRT1) in the human nucleolus. PARP1 in particular is the enzyme that triggers DNA repair after DNA is subjected to oxidative stress. These functions cannot happen when NAD+concentrations are low enough to be the limiting factor — therefore DNA goes unrepaired. This means if NAD+ levels are low DNA repair will not occur properly, if we give your body NAD+ certain processes that are not occurring will begin again.
PARP1 and SIRT1 are examples of this type of NAD-dependent process. Therefore, every time one of these enzymes uses NAD+ to fix DNA, it reduces the availability of NAD+ to do the process again. The body can make more NAD+, but this takes time and the available resources. This is where clinical application of NAD+ intravenously comes in.
Indeed, NAD+ deficiency is both necessary enough to cause apoptosis (cell death) in some cells. This is thought to be due to NAD+ concentrations being necessary to the maintenance of the mitochondrial membrane’s polarization. Without enough NAD+ available for oxidative phosphorylation (cellular respiration, or the creation of ATP), the membrane becomes depolarized, the mitochondrial mobility transition pore opens and releases apoptotic inducing factor, which travels to the nucleus and triggers cell death. (Low NAD+ = cell death)
NAD+ either has to be produced by the body or recycled again once it is used. The de novo pathway from the amino acid tryptophan is long, and has many limiting factors. The NAD+ salvage pathway is more direct, but requires metabolites for NAD+ to already be present. NAD+ and NADH actively transitions back and forth between its reduced and oxidative states, but many pathways that use NAD+ consume or cleave the NAD+ into its constituent parts. Therefore, certain NAD-dependent functions and proteins use the NAD+ available, and are selectively turned off when NAD+is deficient.
Peer reviewed application of extracellular NAD(H) have shown positive results in the activation of PARP1 induced genetic repair, increased sirtuin type genetic repair (Human SIRT 1-7), and increased mitochondrial health measured both in mitochondrial efficiency and mitochondrial biogenesis in vitro and in animal administrations. Non-peer reviewed clinical application seems to support the ability of extracellular NAD+ administrations to address patient symptoms wherever a patient can be diagnostically said to have either profound levels of system wide oxidative stress or system wide mitochondrial dysfunction.
There is no diagnosis that is directly characterized by discovering system wide mitochondrial dysfunction. Diagnostic procedure, particularly in the fields of medicine that cover the convergence of mental and general physiological health, look to symptom self-reporting and quantification for diagnosis — they do not rely on microbiological tracking of subcellular function.
However there is an increasing number of afflictions that have both physiological and mental components that seem to share symptoms that could be attributable mitochondrial dysfunction including: alcohol use disorder (alcoholism), opiate use disorder (addiction), chronic fatigue disorder, fibromyalgia, and post treatment Lyme Disease syndrome. Each of these diagnoses can correspond with a physical lack of energy, which is a possible symptom of mitochondrial dysfunction due to the mitochondrion’s role in human energy production.
Also, human neurons, since their discovery, have been typified as a type of cell that has an overabundance of mitochondria — their presence at the terminal end of a neuron’s dendrite is part of what allows for neuronal electro-conductivity and the release of neurotransmitters. Treating the patient with the micronutrient that its body needs to run effectively, efficiently, and repair from oxidative stress has in some cases accelerated recovery from the above mentioned diagnoses.
It should be noted that each of these conditions are chronic in nature, and are subject to fluctuating symptoms. Periods where symptoms present more strongly are often followed by a period of lessening symptom severity. Some of the positive outcomes reported may have been misattributed to the intravenous therapy of NAD+. NAD+ does not present a cure to all mental and physical afflictions, and should be regarded more like a clinical accelerator of the body’s natural ability to mend after exposures to stressors rather than as a cure.
NAD+ is an essential cofactor in processes relating to energy production, cellular maintenance and DNA repair after oxidative damage. Therefore, it is hypothesized that an overabundance of the limiting factor inhibiting cellular maintenance can have therapeutic merit. The body can build NAD+ by consuming tryptophan and vitamin B3 (nicotinamide and nicotinic acid) that are metabolites of NAD+. However, tryptophan can as easily be consumed by the body for the creation of serotonin and melatonin, and is often siphoned away from the long process of creating NAD+ de novo. Also, neither nicotinamide nor nicotinic acid are effectively absorbed by the gastrointestinal tract and are subject to inhibitory factors before they can become NAD+ in the body. Therefore, the application of NAD+ intravenously is the clinical way of applying mega doses of pure coenzyme for therapeutic purposes.
NAD+ is an effective detox therapy for alcohol and opiate addicts as evidenced by a significant reduction in craving ratings.
NAD+ has been effective in reducing and maintaining the number of relapse episodes, as well as severity of drug cravings.
NAD+ shows potential as a long-term therapy in maintaining sobriety through minimizing drug cravings and preventing relapse.
Thank you to Springfield Wellness Center for providing patient data. References for the above research are available upon request.