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What Is the Role of NAD+ in the Body?

Figure 14.1 shows what we know of the many functions that NAD+ performs in healthy cells. NAD+ is essential in cell energy production—without which cells cannot do their work. It is involved in DNA repair and gene expression—the process by which genes are turned on and off. It is included in cell signaling, immune function, and the production of vital enzymes. It probably is involved in increasing the length of telomeres, which has anti-aging benefits. NAD+ is also thought to be a neurotransmitter. Any one of these functions would make NAD+ necessary, but the fact that NAD+ is involved in so many of them highlights the significance of this molecule and shows that prolonged depleted NAD+ levels can have profound health consequences. By the same token, as many of these functions consume NAD+, it is easy to see how, with accumulating stress, age, illness, and other factors, NAD+ levels can become depleted. Just how the body prioritizes which NAD+ functions it will carry out if levels are insufficient for them all is a fertile area for additional research.

Current Clinical Applications of Intravenous NAD+

At Springfield Wellness Center, located in Springfield, Louisiana, psychotherapist Paula Norris Mestayer and Dr. Richard Mestayer developed the American protocols for intravenous use of NAD+ to treat addiction, alcoholism, depression, post-traumatic stress disorder (PTSD), and even neurode- generative diseases such as Alzheimer’s, Parkinson’s, and CTE. However, because the preponderance of their experience with intravenous NAD+ in the treatment of addiction and alcoholism, we are confining our remarks to this application.

What is NAD+ used for?

FIGURE 14.1 What is NAD+ used for?

NAD reduces cravings

FIGURE 14.2 NAD reduces cravings.

At the November 2014 Society of Neuroscience meeting in Washington, D.C., a group of Springfield Wellness colleagues presented the results of a study involving 60 adult patients (both male and female) detoxing from addiction (primarily to opiates and alcohol), who were treated over an average of 10 consecutive days with a proprietary formulation of BR+NAD™. This formulation was composed primarily of intravenous infusions of NAD+, along with oral amino acids and N-acetyl cysteine (NAC). The treatment was administered from 5 to 10 hours daily at a dose range of 500-1500 mg each day. Subjects reported that their cravings stopped or were significantly diminished by Day 2-Day 4 of treatment. Specifically, cravings dropped from an average rating of five or six (on a zero to ten scale) on Day 1 to a rating of two by Day 5 and an average of one or less by Day 10.12

In addition to significantly reduced cravings, study subjects also reported a dramatic reduction in withdrawal symptoms. These vary according to the addiction: for opiate withdrawal they typically include nausea, vomiting, and muscle spasms; for alcohol withdrawal tremors (DTs), and for crystal meth withdrawal the primary symptom is deep depression. They generalized from their experience with these and more than 1000 other patients that withdrawal symptoms are reduced by 60 to 75%. They have found this to be true no matter what patients have been addicted to—even methadone or Suboxone.

Intravenous NAD+ treatment for addiction also appears to be effective in reducing or eliminating post-acute withdrawal syndrome (PAWS), which, along with cravings, is a common reason for relapse. While PAWS can complicate opiate withdrawal for a year or more under conventional addiction treatment protocols, NAD+ detox treatment appears to eliminate PAWS initially and, if patients feel a return, they can be effectively re-treated for a day or two, after which PAWS again subside (Figure 14.2).

In addition to intravenous NAD treatment for addiction detox and PAWS remediation, we have utilized oral NAD supplements, nasal sprays, patches, and creams to extend the NAD boost provided intravenously. Moreover, although excellent research is now' being done by David Sinclair and others on the role of NAD precursors such as NMNB in boosting cellular NAD levels, thus far intravenous NAD has given our patients the most robust clinical response.

Basic Research into the Mechanisms of NAD+ Effectiveness

Although the clinical results of intravenous NAD+ therapy for addiction detox are now well-established, the biochemical mechanisms for its effectiveness are still being studied.

Dr. James Watson is a well-respected surgeon on the clinical faculty of UCLA Medical School as well as the author of a website and blog on the molecular biology of aging.14 As a result of his own research into NAD+, Dr. Watson was selected as one of the keynote speakers at the first 2015 Brain Restoration Summit, where he presented his analysis that the same processes that overwhelm the body’s stress response systems and result in the degeneration associated with aging are also implicated in the disease of addiction.

In his summit presentation, Dr. Watson outlined three factors responsible for addiction: genetics (DNA), epigenetics (DNA regulation), and environment. Genes that have been identified as potential risk factors for addiction include those responsible for the brain’s “reward” pathway, those responsible for ethanol (alcohol) stimulation or depression, those responsible for the “relief’ pathway, and more.

Epigenetics (DNA regulation), though inherited, are also influenced by environmental factors such as stress, aging, disease, and drug use, that can turn gene expression off and on.

The third factor in addiction is environmental. A healthy diet plus regular exercise, for example, can confer positive epigenetic changes; w'hereas regular alcohol consumption, trauma, toxins, illness, or chronic stress adversely impacts a number of genetic switches.

Together, these three factors—genetics, epigenetics, and environment—could result in addiction due to the functioning of a single molecule: NAD+.

NAD+ plays a critical role in all three addiction risk factors, Watson explained. It repairs DNA, which can be damaged by oxidative stress, including drug use. It restores healthy epigenetic functioning—the turning off of epigenetic risk factors related to addiction—and it restores the brain to healthy functioning—including dopamine and endorphin production—so that the addict doesn’t need a drug to get midbrain relief. Watson calls this the gene-environmental interaction (GEI or GXE). The environmental factor of oxidative stress triggers the epigenetic factor to turn on the expression of the genetic factor (DNA).

Watson notes that, although NAD+ is not the only epigenetic mechanism at the body’s disposal, it is involved in several of the pathways implicated in addiction. His analysis also helps to explain how and why intravenous NAD+ given to detoxing patients confers such positive and immediate results: it starts to return the body to normal functioning, with positive genes turned on, negative genes turned off, oxidative stress better managed, mitochondrial energy production returned to normal, and DNA under repair.

Another research team, led by Corinne Lasmezas, has underscored the importance of NAD+ in DNA repair. Lasmezas and colleagues at the Scripps Research Institute showed that depletion of NAD+ drives neuronal death.15

Another research team, at the Linus Pauling Institute, Oregon State University, summarized some of the various implications of niacin—and its co-enzyme, NADh—deficiency. Most notably, they wrote, “NAD+ is the sole substrate for PARP enzymes involved in DNA repair activity in response to DNA strand breaks; thus, NAD+ is critical for genome stability.”16

Yet another researcher, Dr. Ross Grant of the University of New South Wales School of Medical Sciences, has published more than 50 papers on NAD+ metabolism—particularly NAD+’s role in aging and oxidative stress. His research shows that NAD+ levels in our bodies decline with age, triggering changes in certain genetic functions associated with maintaining cell health.17

Still other researchers are investigating the role of NAD+ in DNA repair—an ongoing process given the constant onslaught our bodies are subjected to via stress, environmental toxins, EMFs and RFs, poor diet, and more.

Human trials on NAD+ are underway around the world. These clinical trials are being led by Dr. Grant in Sydney, Australia; the staff at Springfield Wellness Center; Dr. David Lefer, Dr. David Polhemus, and Dr. Tom Sharp through NAD+ Research, Inc., and scientists at many other institutions.

For example, pilot studies conducted by NAD Research, Inc., in collaboration with Dr. Ross Grant, Dr. Jade Berg, and Nady Braidy, PhD, at the Australasian Research Institute, show that intravenous BR+NAD™ treatment reduces biomarkers reflective of inflammation in both alcohol and opiate detox patients, while increasing NAD+ levels and improving the NAD+/NADH ratio in plasma, which increases NAD+ effectiveness.

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